What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2026-03-26 compared with 2025-03-13 · 1227 added, 1709 removed, 545 unchanged (84% of the section changed)

Class-Leading GSK-3β Inhibitor

We are a clinical stage biopharmaceutical

1 unchanged sentence

synthase kinase-3 (“GSK-3”).

We are developing elraglusib (formerly 9-ING-41), an ATP-competitive small molecule that is designed to enter

cancer cells and block the function of the enzyme glycogen synthase kinase-3 beta (“GSK-3β”), a master regulator of complex

We are developing elraglusib, an ATP-competitive small molecule that is designed to enter cancer

cells and block the function of the enzyme glycogen synthase kinase-3 beta (“GSK-3β”), a master regulator of complex

biological signaling cascades, including those mediated by oncogenes, that lead to tumor cell survival, growth, migration, and invasion.

We believe that the blockade of GSK-3β signaling ultimately results in the death of the cancer cells and the regulation of anti-tumor

We have exclusively licensed a

portfolio of GSK-3 inhibitors developed in a collaboration between The Board of Trustees of the University of Illinois-Chicago (“UIC”)

and Northwestern University (“NU”).

Elraglusib is the lead drug in our portfolio and is being evaluated in a randomized Phase 2

trial in patients with metastatic pancreatic ductal adenocarcinoma (“mPDAC”), our most advanced clinical indication to date.

We are also advancing a Phase 1/2 clinical trial in refractory pediatric malignancies, including Ewing sarcoma (“EWS”).

Elraglusib represents a broad

opportunity for us to potentially initiate and advance multiple drug development programs around our lead asset based on data emerging

from completed or ongoing Phase 1/2 trials and non-clinical biological, cellular, and animal data.

Animal tumor model data, Phase 1/2

clinical data and AI-based computational approaches have identified a number of areas of unmet clinical need in cancer treatment where

elraglusib may play an interventional role, including pancreatic, metastatic melanoma, lung, colon, breast, renal, and ovarian cancer,

leukemias and lymphomas, as well as some pediatric cancers including Ewing sarcoma, neuroblastoma and pediatric leukemias.

Elraglusib Injection

Our lead clinical program, referred

to as Actuate-1801, is an intravenous (“IV”) injection solution of elraglusib (“Elraglusib Injection”) that we

are evaluating for the treatment of first-line mPDAC.

There are no approved high-affinity inhibitors of GSK-3β and we believe elraglusib is one of the most advanced GSK-3β

inhibitors in clinical development.

Elraglusib was originally known as 9-ING-41 but was granted the elraglusib International Nonproprietary

Names (“INN”) and United States Adopted Names (“USAN”) generic name in 2021.

Exclusive Rights

We have exclusively licensed

elraglusib, a proprietary and patent protected GSK-3 inhibitor developed in a collaboration between The Board of Trustees of the University

of Illinois-Chicago (“UIC”) and Northwestern University (“NU”).

Broad Therapeutic Potential

We believe elraglusib represents

a “pipeline in a molecule” with a broad opportunity for us to potentially initiate and advance multiple drug development programs

around our lead asset based on its multimodal mechanisms of action, data emerging from completed or ongoing clinical trials and non-clinical

biological, cellular, and animal data.

Animal tumor model data, clinical trial data and AI-based computational approaches have identified

a number of areas of unmet clinical need in cancer treatment where elraglusib may play an interventional role, including pancreatic, metastatic

melanoma, lung, colon, breast, renal, and ovarian cancer, leukemias and lymphomas, as well as some pediatric cancers including Ewing sarcoma,

neuroblastoma and pediatric leukemias.

Figure 1 shows the broad therapeutic

potential of elraglusib where evidence of preclinical and clinical activity has been observed.

GSK-3β inhibitors and elraglusib’s

potential to treat numerous cancer histologies.

Significant Clinical Experience and Promising

Phase 2 Data in mPDAC

To date, we have treated over

500 patients with Elraglusib Injection in Phase 1 and Phase 2 studies.

Elraglusib Injection is currently being evaluated in a Phase 2

study (as part 3B of our Actuate 1801 protocol) as a weekly IV infusion in combination with gemcitabine/nab-paclitaxel (“GnP”).

Overall survival (“OS”) has been summarized throughout the study by following and reporting 1 year survival rate.

endpoint at the end of the study will be summarized as median overall survival (“mOS”).

The study completed enrollment in

January 2024, and top-line results are expected to be presented in the second quarter of 2025.

As further described below, we conducted

a preliminary analysis of interim data in the pre-specified safety population as of November 15, 2024, at the point when >70% of death

events occurred in the GnP control arm.

Log-rank analysis will be used to determine statistical significance when comparing the elraglusib/GnP

and GnP arms of the study.

The analysis of interim data demonstrated

that treatment with elraglusib in combination with GnP resulted in statistically significant increases in 1-year survival rate (p-value

of 0.002) and mOS (hazard ratio of 0.63, p-value of 0.016) versus treatment with GnP alone.

The combination treatment also resulted in

increased Objective Response Rates (“ORR”) and Disease Control Rates (“DCR”) in the elraglusib/GnP combination

arm versus the GnP control arm.

As depicted in Figure 1 and below, interim data highlights from the predefined safety population as of

the November 15, 2024 cutoff date include:

· The interim data met the primary endpoint with

a 1-year survival rate of 43.6% in the elraglusib/GnP combination arm versus 22.5% in the GnP control arm (p-value of 0.002).

· 18- and 24-month survival rates also demonstrated

benefit of 20.9% vs 0% and 16.7% vs 0% in the elraglusib/GnP combination vs GnP arms, respectively.

· In the elraglusib/GnP combination arm, 38% of

subjects were still alive vs 19% in the GnP control arm.

· A statistically significant 37% reduction in

risk of death and increased mOS were observed in the elraglusib/GnP combination arm (mOS of 9.3 months) vs the GnP control arm (mOS of

7.2 months), (hazard ratio of 0.63, p-value of 0.016).

· The trial also met its primary safety endpoint.

Treatment-emergent adverse events (“TEAEs”) and Serious Adverse Events (“SAEs”) in the elraglusib/GnP combination

arm were similar to those observed in the GnP arm, indicating a favorable risk-benefit profile for the elraglusib/GnP combination.

· The ORR was 27.7%, DCR was 42.6 %, and PFS was

5.6 months in the elraglusib/GnP combination arm versus 20.5%, 33.3% and 4.9 months in the GnP arm, respectively.

· Two patients in the elraglusib/GnP combination

arm with previously inoperable metastatic lesions with noted reductions in target lesions were referred for successful resection, one

of which resulted in 100% reduction in total tumor burden after surgery.

In addition, there have been one Complete Response (“CR”)

and one Partial Response (“PR”) with 100% reduction in target lesions in the elraglusib/GnP combination arm versus none in

the control arm.

Actuate-1801 Part 3B:

Draft unaudited Phase 2 data of elraglusib in mPDAC (as of November 15, 2024).

As with all preliminary analyses

of interim data, this data should not be relied upon as a final analysis and is subject to change once full data analysis is complete.

At the completion of this Phase

2 study, we plan to meet with the U.S.

Food and Drug Administration (the “FDA”) and discuss the design and execution of a

Phase 3 registration study.

In addition, we plan to discuss the use of the Phase 2 data to support potential registration.

As discussed in more detail below

under “History of Elraglusib Clinical Development,” the Phase 2 trial followed the evaluation of Elraglusib Injection in a

Phase 1 dose escalation study (Actuate-1801 Part 1) in 238 adult patients with refractory advanced cancers when given as a single

agent (n=67) or in combination with chemotherapy (n=171).

The objective of this study was to establish the safety profile of elraglusib

when used alone or in combination with chemotherapy and to identify either a maximum tolerated dose (“MTD”) or recommended

Phase 2 dose (“RP2D”) to then inform the design of exploratory efficacy studies in Phase 2.

Subjects in this study were

diagnosed with a variety of cancer types and most patients had received two or more previous lines of chemotherapy prior to enrollment

in the study.

Objective responses and durable disease control were observed in both the single agent and combination treatment arms of

The most common TEAEs attributed to elraglusib were transient visual disturbance (patients described lights as brighter and

skin tones as darker, which resolved spontaneously) and fatigue across both study parts.

The majority (>99%) of TEAEs that occurred

in ≥ 20% of patients were reported as Grade 1 or 2 (mild or moderate).

In combination with chemotherapy, no new safety signals

were observed.

While the elraglusib/GnP combination appears to be well-tolerated and well-managed in the clinic, we do not yet know whether

any increase in the number or severity of toxicities will be attributable to elraglusib and thus the elraglusib/GnP combination will have

its own safety profile that will need to be evaluated and discussed with regulators.

Based on the results of the Phase 1

study, we initiated a single arm Phase 2 study (“Actuate-1801 Part 3A” or “Part 3A”) in patients with

previously untreated mPDAC.

This study was originally designed as a single arm exploratory Simon two-stage trial (and therefore not designed

or powered to demonstrate statistical significance).

The elraglusib dose was started at the RP2D evaluated in the latter part of the Phase

1 trial (15 milligrams of drug per kilogram of body weight (mg/kg) administered twice weekly).

No new safety signals were observed with

the elraglusib/GnP combination, but investigators observed that GnP toxicities may have occurred earlier and may have been more intense

in some patients than would be anticipated for GnP alone.

For these reasons, the dose of elraglusib was proactively reduced near the end

of the Part 3A study to 9.3 mg/kg administered twice weekly.

After an analysis conducted following the completion of Part 3A, which showed

an mOS of 15.3 months in the efficacy evaluable (n=29) patient population, we amended and expanded the second stage of the study

to a randomized, controlled trial now powered for statistical significance (“Actuate-1801 Part 3B” or “Part 3B”)

that would allow a comparison of the safety and efficacy of the combination of Elraglusib Injection plus GnP versus GnP alone in 286 patients.

In addition, Elraglusib Injection

is also being evaluated in pediatric cancer patients with recurrent/refractory solid cancers.

This study, Actuate-1902, is a Phase 1/2

study that evaluated escalating doses of elraglusib as a single agent as well as in combination with irinotecan or cyclophosphamide/topotecan

in the Phase 1 portion.

This study was based off the RP2D from the Actuate-1801 adult cancer study using twice weekly dosing of elraglusib.

Patients in this Actuate-1902 study also experienced a number of objective responses in the combination chemotherapy arms, and based on

this data, we identified Ewing sarcoma as a potential second indication for further development of Elraglusib Injection.

Currently, the

Actuate-1902 study is open but only accruing patients with refractory Ewing sarcoma into the Phase 1 portion of the study.

to future funding, we plan to further investigate the activity of elraglusib in the Ewing sarcoma patient population.

Elraglusib Oral Tablet Development Plans

We have developed several oral

dosage forms of elraglusib, which we believe will allow us to expand the number of cancer indications that we are able to target and allow

us to further explore more convenient dose delivery options for patients.

A clinical candidate tablet, the Elraglusib Oral Tablet, has

been selected for further development and we are planning a Phase 1 study (Actuate-2401) to identify the MTD and RP2D for Elraglusib Oral

Tablet in adult patients with advanced, refractory cancers, subject to future funding.

Subject to additional funding, several Phase 2

studies have been identified for further clinical development of Elraglusib Oral Tablet based on data from the Actuate-1801 study in indications,

including but not limited to, refractory, metastatic melanoma and refractory, metastatic colorectal cancer.

Our Market Opportunity

Treatment of Metastatic Pancreatic Ductal

Adenocarcinoma (“mPDAC”)

According to the American Cancer

Society, the annual incidence of pancreatic cancer is expected to exceed 67,000 patients in the United States in 2025 and approximately

70% of these patients will present with metastatic disease.

A recent review of clinical trials in Future Oncology 1

showed that the mOS in patients with mPDAC treated with GnP ranged from approximately 3.6 to 9.8 months with an unweighted mOS of 6.9

Therefore, we believe the ability to extend survival by even a few months would be considered meaningful in this patient

We are developing elraglusib

for patients with mPDAC who have not previously received systemic treatment for their metastatic disease.

Due to lack of early symptoms,

approximately 80-90% of all patients with pancreatic cancer are unresectable, and present with advanced or metastatic disease.

80-90% of PDAC cases do not have a high tumor mutational burden in general, and are unlikely to respond to checkpoint inhibitors such

as pembrolizumab.

Pembrolizumab has been approved for patients with metastatic solid cancer with high tumor burden but is rarely used

in metastatic pancreatic cancer for this reason.

However, frequent mutations in KRAS and TP53 oncogenes drive pancreatic tumor growth

and treatment resistance, often making PDAC refractory to chemotherapy.

Current first-line therapies

for mPDAC consist of GnP, FOLFIRINOX, or irinotecan liposomal injection given with oxaliplatin, fluorouracil, and leucovorin (“NALIRIFOX”).

NALIRIFOX was recently approved (February 2024) and may provide an alternative to FOLFIRINOX with a somewhat improved safety profile.

The mOS in mPDAC patients

is 11.1 months with NALIRIFOX, 11.2 months with FOLFIRINOX and 7 to 10 months with GnP, respectively, in the first-line setting.

demonstrated superiority to GnP in the NAPOLI-3 trial (mOS 11.1 vs 9.2 months).

However, safety profiles between these three chemotherapy

backbones are quite different:

FOLFIRINOX leads to higher rates of neutropenia and nausea, NALIRIFOX has more gastrointestinal and constitutional

toxicity such as nausea, diarrhea and fatigue, and GnP treatment leads to increased myelosuppression and neurotoxicity.

An analysis of

an insurance claims database indicated that first-line treatment from 2014-2018 was split between FOLFIRINOX and GnP.

We believe it is

too early to predict how NALIRIFOX will fit into clinical use in patients with mPDAC.

Our management believes

elraglusib may improve outcomes in first-line mPDAC regardless of the chemotherapy backbone used.

Patients with mPDAC are often resistant

or become resistant to the first-line chemotherapy backbones currently used to treat them.

Part of elraglusib’s mechanism of action

is the ability to enhance chemotherapy activity even in resistant tumors and we believe this has been demonstrated in multiple animal

tumor models.

In addition, elraglusib has shown the ability to enhance the activity of several chemotherapy drugs that comprise the current

first-line backbones in mPDAC including gemcitabine, nab-paclitaxel and irinotecan, suggesting the potential for elraglusib to be used

in combination with multiple first-line mPDAC treatments.

In addition to the activity observed in our 1801 Part 3B study evaluating the

activity of elraglusib/GnP combination in mPDAC, an additional exploratory Phase 2 study is ongoing through an investigator initiated

trial (“IIT”) in patients with mPDAC evaluating the combination of elraglusib/FOLFIRINOX/losartan combination in up to 65

Early evidence of increased clinical activity in patients receiving this combination was recently presented at the AACR Special

Conference on Advances in Pancreatic Cancer Research.

This trial is being led by Dr.

Colin Weekes at Massachusetts General Hospital (“MGH”)

and is supported by the Lustgarten Foundation as well as Actuate.

Additional sites participating in the study include The University of

Colorado and the University of Washington’s Fred Hutchinson Cancer Center.

Thus, our plan, subject to available funding, is to develop

elraglusib in combination with the present first-line chemotherapy regimens used in the treatment of mPDAC, as exemplified by our lead

program of elraglusib/GnP combination and later moving to combinations with either FOLFIRINOX or NALIRIFOX pending results of the FOLFIRINOX

combination trial.

If shown to be clinically active, elraglusib/chemotherapy combinations could eventually be used to treat a large segment

of mPDAC patients.

Elraglusib has been granted Fast

Track and Orphan Drug Designations from the FDA for pancreatic cancer in the United States and Orphan Drug Designation for soft tissue

sarcomas in the United States.

Elraglusib received Orphan Medicinal Product Designation (“OMPD”) for both pancreatic cancer

and sarcoma from the European Medicines Agency (“EMA”).

Actuate is planning a Type D meeting with the FDA to discuss Phase

3 design and an End of Phase 2 (Type B) meeting to discuss future development plans in 2025.

____________________

1 Cockrum P, Dennen S, Brown A, Briggs

Real-world clinical outcomes and economic burden of metastatic pancreatic ductal adenocarcinoma:

a systematic review.

10.1080/14796694.2024.2435253.

Epub 2024 Dec 8.

Treatment of Ewing Sarcoma

An estimated 9,550 children (ages

0-14 years) and 5,140 adolescents (ages 15-19 years) are expected to be diagnosed with cancer in the United States in 2025.

estimated that 1,050 children and 600 adolescents will die from the disease in the United States in 2025.

While death rates for pediatric

and adolescent cancers have declined by more than 50% over the last five decades due to improved treatment options, there is still room

for improvement.

Despite the improved survival offered by current therapies, approximately 40% of childhood cancer survivors have severe,

life-threatening or fatal complications within 30 years of diagnosis and up to 90% of survivors will have a chronic health condition by

the age of 45.

These long-term effects are related to the type of treatment used such as chemotherapy and radiation which can have a material

adverse impact on developing organs.

Work is ongoing to determine how to more effectively identify underlying mechanisms of pediatric

cancers in an effort to develop and administer more targeted, more effective and less toxic treatments.

Based on extensive preclinical

work in pediatric malignancies showing excellent synergy between elraglusib and standard of care chemotherapy in neuroblastoma, sarcoma,

glioma and others, we initiated the Actuate-1902 Phase 1 study to evaluate the safety of elraglusib +/- chemotherapy in pediatric patients

with refractory malignancies in 2020.

The dose escalation part of the study assigned patients to elraglusib alone, elraglusib/irinotecan

or elraglusib/cyclophosphamide and topotecan (“CT”).

As of December 31, 2024, 40 patients had been enrolled and received at

least one dose of elraglusib.

No SAEs were observed with elraglusib monotherapy at the first two dose levels and positive results were

observed for some patients as discussed under “Our Solution – Current Elraglusib Development - Developing Elraglusib IV for

the Treatment of Ewing Sarcoma – Actuate 1902” below.

Upon determination of RP2D for monotherapy and combination therapy,

we had originally intended to initiate a Phase 2 study in neuroblastoma.

However, recently approved anti-GD2 antibodies have shown considerable

improvement of response rate, progression-free survival (“PFS”), and survival, making development in this population much

more challenging.

Based on the positive response

from a Ewing sarcoma patient further discussed below under “Developing Elraglusib Injection for the Treatment of Ewing Sarcoma –

Phase 1 and Phase 2 Plans – Actuate-1902,” six additional patients with metastatic, refractory Ewing and Ewing-like sarcoma

were enrolled in the elraglusib/CT combination arm.

There are currently no known treatment regimens that meaningfully extend life in Ewing

sarcoma patients with metastatic, refractory disease.

The five-year survival rate for patients who have recurrent (relapsed) disease is

Patients who are refractory and have metastases and disease progression despite two or more chemotherapy regimens generally have

a very short survival of 3-8 months.

Twelve patients including ten Ewing sarcoma patients, one patient with desmoplastic small round cell

tumors (“DSRCT”) and one patient with CIC rearranged sarcoma were enrolled in our Actuate-1902 trial.

All twelve patients

appear to have metastatic disease and had disease progression prior to joining the study despite undergoing previous treatment combinations

including chemotherapy, radiation, and/or surgical procedures.

Eight patients received two or more previous chemotherapy regimens, prior

to entering the 1902 study.

All patients received the combination of elraglusib and cyclophosphamide/topotecan.

We believe this exploratory

Ewing sarcoma data, discussed further under “Developing Elraglusib IV for the Treatment of Ewing Sarcoma – Actuate 1902”

below, is sufficiently positive in this orphan pediatric cancer indication to consider additional development in Ewing sarcoma.

The Actuate-1902

Phase 1 arm of the study is open to enrollment, focusing on recruitment of patients with refractory Ewing sarcoma.

The FDA has granted Rare

Pediatric Disease Designation (“RPDD”) to elraglusib for our treatment of EWS.

Rare Pediatric Disease Designation is granted

by the FDA for serious or life-threatening diseases that affect fewer than 200,000 people in the United States and in which the serious

or life-threatening manifestations primarily affect individuals less than 18 years of age.

If, in the future, a New Drug Application (“NDA”)

for elraglusib for the treatment of Ewing sarcoma is approved by the FDA, we may be eligible to receive a Priority Review Voucher (“PRV”)

that could be utilized by us or potentially sold to another company for its use.

Our Pipeline and Development Timeline

Our initial focus is on the development

of GSK-3 inhibitors for the treatment of cancers with ineffective treatment options and poor overall survival.

Given our ability to formulate

elraglusib in both the Elraglusib Injection and Elraglusib Oral Tablet forms, if adequate funding is secured, and given the potential

to use it in different ways depending on the cancer type, we believe that elraglusib represents a pipeline in a molecule, as shown in

the Figure 2 below.

We are currently focused on advancing our trials in mPDAC with Elraglusib Injection.

Our ability to advance our ongoing

and planned clinical trials listed in Figure 2 will depend on whether we have or raise sufficient capital to support those trials.

Ongoing and planned clinical trials.

Our Strengths

500 patients with elraglusib as an IV injection (“Elraglusib Injection”) in Phase 1 and Phase 2 studies.

Our most advanced clinical

indication is first-line metastatic pancreatic ductal adenocarcinoma (“mPDAC”).

Our Phase 2 study in mPDAC, known as Actuate-1801

Part 3B study, is a randomized, controlled Phase 2 trial that enrolled 286 patients with no prior systemic treatment for metastatic disease.

The primary endpoint for this study was median overall survival (“mOS”), with overall survival (“OS”) summarized

throughout the study by estimates of 1-year survival.

Updated data results presented at the American Society of Clinical Oncology (“ASCO”)

Genitourinary Cancers Symposium (“ASCO GI”) in January 2026 utilizing a data cutoff as of November 22, 2025 showed that the

trial met its primary endpoint, demonstrating a statistically significant improvement in mOS with elraglusib plus gemcitabine/nab-paclitaxel

(“GnP”) versus GnP alone.

Data presented at ASCO GI

· Statistically significant benefit in mOS in the

elraglusib/GnP arm vs GnP control arm (mOS 10.1 months vs.

7.2 months, p=0.02, HR=0.62);

· Near doubling of the 12-month survival rate,

from 22.3% in the GnP arm to 44.4% in the elraglusib/GnP arm;

· Almost fivefold increase in 24-month survival

rate, from 2.6% in the GnP control arm to 12.9% in the elraglusib/GnP arm, emphasizing the potential for long-term clinical benefit.

Elraglusib Injection Shows Promise in the Treatment

of Pediatric Cancers

In addition to mPDAC, Elraglusib

Injection is also being evaluated in pediatric cancer patients with recurrent/refractory solid cancers.

This study, Actuate-1902, is a

Phase 1/2 study that evaluated escalating doses of elraglusib as a single agent as well as in combination with irinotecan or cyclophosphamide/topotecan

in the Phase 1 portion of the trial.

Patients in this Actuate-1902 study also experienced a number of objective responses in the combination

chemotherapy arms, and based on this data, we identified Ewing sarcoma and neuroblastoma as new indications for further development of

Elraglusib Injection, further expanding the potential of elraglusib.

Elraglusib Oral Dose Tablet Allows Us to Expand

into New Indications

We have developed several

oral dosage forms of elraglusib, which we believe will allow us to expand the number of cancer indications that we are able to target

and allow us to further explore more convenient dose delivery options for patients.

A clinical candidate tablet, the Elraglusib Oral Tablet,

has been selected for further development and, subject to future funding, we are planning a Phase 1 study to identify the maximum tolerated

dose and recommended Phase 2 dose (“RP2D”) for Elraglusib Oral Tablet in adult patients with advanced, refractory cancers.

Once we have determined a RP2D, several Phase 2 studies have been identified for further clinical development of Elraglusib Oral Tablet,

subject to additional funding, based on data from previous studies, including but not limited to, refractory, metastatic melanoma and

refractory, metastatic colorectal cancer, and non-small cell lung cancer.

Pancreatic Cancer Represents a High Unmet Need

with Limited Treatment Options for Patients

According to the American

Cancer Society, the annual incidence of pancreatic cancer is expected to exceed 67,000 patients in the United States in 2026.

ductal adenocarcinoma (“PDAC”) is considered one of the most aggressive malignancies, with approximately 90% of patients presenting

with advanced disease.

Despite advances in the treatment therapies over the last 30 years, the 5-year survival rate for Stage IV disease

is less than 5%.

The standard of care for first-line treatment of mPDAC generally includes one of the following two chemotherapy regimens:

· FOLFIRINOX:

A combination of 5-fluorouracil,

irinotecan, and oxaliplatin, which has been established as the new standard of care for advanced or mPDAC.

It achieved a mOS of 11.1 months

in the ACCORD/PRODIGE Phase 3 trial.

This regimen achieved a mOS of 8.5 months

with GnP compared to 6.7 months with gemcitabine alone in the MPACT Phase 3 trial.

A recent review of clinical

trials in Future Oncology 1 showed that the mOS in patients with mPDAC treated with GnP ranged from approximately 3.6

to 9.8 months with an unweighted mOS of 6.9 months.

Therefore, we believe the ability to extend survival by even a few months would be

considered meaningful in this patient population.

Our Strategy and Strengths

We believe that we have several

2 unchanged sentences

· Advancing a potentially class-leading GSK-3β

inhibitor, elraglusib with a novel, multimodal mechanism of action (“MOA”), in multiple advanced trials for the treatment

· Broad potential with clinical responses (CRs/PRs) and disease control observed

across multiple cancer histologies.

· Extended survival and increased responses are observed in mPDAC and relapsed/refractory

Ewing sarcoma.

· Preliminary evidence of clinical benefit has also been observed in patients

with metastatic melanoma and relapsed/refractory colorectal and lung cancer.

· Oral version of elraglusib successfully evaluated in a Healthy Volunteer

Phase 1 study.

· Phase 1 dose escalation study planned in advanced

cancer patients.

· Broad composition of matter intellectual property protection and development

inhibitor, elraglusib with a novel, multimodal mechanisms of action (“MOA”) profile, in multiple advanced trials for the treatment

· Broad potential with clinical responses (complete

responses and partial responses) and extended disease control observed across multiple cancer histologies.

· Extended survival and increased responses observed

in mPDAC, relapsed/refractory Ewing sarcoma, and neuroblastoma.

· Preliminary evidence of clinical benefit has

also been observed in patients with metastatic melanoma and relapsed/refractory colorectal and lung cancer.

· Elraglusib Oral Tablet developed and ready for

Phase 1/2 study in advanced cancer patients.

· Broad composition of matter intellectual property

protection and development incentives.

· Orphan Drug Designations for pancreatic and other

1 unchanged sentence

Fast Track Designation for pancreatic cancer.

Our Business Strategies

Subject to available financing,

we intend to develop elraglusib in a broad list of advanced cancer indications, initially in patients with refractory disease and with

an initial focus on metastatic pancreatic cancer.

We believe that our two product candidates, Elraglusib Injection and Elraglusib Oral

Tablet, will provide us with two different dosage forms of drug product with different attributes that will allow us to tailor each dosage

form to a specific cancer type to potentially improve outcomes and compliance.

Key elements of our strategy to accomplish this objective

· Build a sustainable oncology company.

vision is to build a leading oncology company with a sustainable pipeline of target indications revolving around a patented, active product

candidate, elraglusib, that can be delivered in different ways to potentially treat a wide variety of cancers.

To accomplish this, we

are focused on rapid advancement of our currently active clinical trials while curating and preparing additional indications for future

expansion of elraglusib development.

This effort is led by Daniel Schmitt, our chief executive officer and founder, and Dr.

Mazar, our scientific co-founder and chief operating officer, who have more than 60 years of combined experience in the management

of biotechnology companies and healthcare investing.

Schmitt has led and contributed to the successful development and launch

of multiple pharmaceutical and health technology products and executed over approximately $1.0 billion in milestone value through

licensing, acquisition, and development deals.

Mazar has founded seven start-ups and is the co-founder, former chief scientific

officer and director, of Monopar Therapeutics, Inc.

MNPR) as well as the former chief scientific officer of Attenuon, LLC.

has shepherded eleven drugs from discovery stage through Phase 2 and Phase 3 trials.

Our board of directors (the “Board”)

is comprised of experienced entrepreneurs, scientists, business leaders and investors in the biotechnology industry .

· Advance our lead product candidate, elraglusib,

through clinical trials.

We have generated clinical data from over 500 patients who have been dosed with elraglusib to date.

Under the innovative seamless study design of our Actuate-1801 Phase 1/2 clinical trial ( Figure 14:

Actuate-1801 Master

Protocol Study Design ), we have initiated a Phase 2 trial testing Elraglusib Injection in combination with chemotherapy in mPDAC

under this Master Protocol (Actuate-1801 Part 3B).

We are also advancing an opportunity in Ewing sarcoma as part of the Actuate-1902

Phase 1/2 study in pediatric refractory malignancies.

Currently, the Phase 1 portion of the Actuate-1902 study is open but only

accruing patients with refractory Ewing sarcoma and we are working to amend the Phase 2 portion of this trial to focus on Ewing sarcoma,

which will require additional funding.

We also intend to explore strategically identified IITs that may identify additional indications

and standard of care products to combine with elraglusib in indications that go beyond those already identified in Actuate 1801-Part 1

and 2, which allows us to further leverage our pipeline in a molecule.

By collaborating with our network of oncology Key Opinion Leaders

(“KOLs”), we anticipate partnering to access non-dilutive funding for our IITs through both federal (e.g.

NIH) and non-federal

cancer-specific foundations, pharma partners) sources, to the extent available.

For example, Actuate collaborated with Dr.

Weekes to obtain Lustgarten Foundation grant support for the IIT currently being run at MGH.

Actuate provides financial and resource support

for IITs in exchange for rights to the trial data but Actuate has no control over the design, conduct or timeline of an IIT.

· Advance our lead product candidate, elraglusib,

by obtaining regulatory development incentives to accelerate path to approval.

One of our strategic objectives is to obtain

development incentives in the United States and in other countries that we believe may accelerate our path to drug approval:

Designation (“ODD”), Fast Track Designation (“FTD”) and Breakthrough Therapy Designation (“BTD”) in

the United States;

Our strategy is to develop

elraglusib for multiple advanced cancer indications with high unmet medical need and significant commercial potential, initially in patients

with metastatic pancreatic cancer, pediatric cancers, and metastatic melanoma, subject to available financing and/or funding from potential

strategic collaborations.

We believe that our two product candidates, Elraglusib Injection and Elraglusib Oral Tablet, will provide us

with two different dosage forms of drug product with different attributes that will allow us to tailor each dosage form to a specific

cancer type to potentially improve outcomes and compliance.

Key elements of our strategy to accomplish this objective include:

a Sustainable Oncology Company.

Our vision is to build a leading oncology company with a sustainable pipeline of target

indications revolving around a patented, active product candidate, elraglusib, that can be delivered in different ways to potentially

treat a wide variety of cancers.

To accomplish this, we are focused on rapid advancement of our currently active clinical trials while

curating and preparing additional indications for future expansion of elraglusib development.

This effort is led by Daniel Schmitt, our

president, chief executive officer and founder, and Dr.

Andrew Mazar, our scientific co-founder and chief operating officer.

they bring more than 60 years of combined experience in biotechnology management and healthcare investing.

Schmitt has led and

contributed to the successful development and launch of multiple pharmaceutical and health technology products and executed licensing,

acquisition, and development transactions totaling over approximately $1.0 billion in milestone value.

Mazar has founded

seven start-ups and is the co-founder, former chief scientific officer and director of Monopar Therapeutics, Inc.

MNPR) as well

as the former chief scientific officer of Attenuon, LLC.

Mazar has shepherded eleven drugs from discovery stage through Phase 2

and Phase 3 trials.

Our Lead Product Candidate, Elraglusib, Through Clinical Trials.

We have generated clinical data from over 500 patients

who have been treated with elraglusib to date.

Under the innovative seamless study design of our Actuate-1801 Master Protocol, we have

reported promising top-line data from our Phase 2 trial testing Elraglusib Injection in combination with GnP in mPDAC.

considering advancing the development of elraglusib in pediatric cancers, including Ewing sarcoma and neuroblastoma, based on promising

data from the Phase 1 portion of the Actuate-1902 study, pending additional internal or external funding support.

We also intend

to explore strategically identified investigator-initiated trials (“IITs”) that may identify additional indications and standard

of care products to combine with elraglusib in indications that go beyond those already identified, which would allow us to further leverage

our pipeline in a molecule.

By collaborating with our network of oncology Key Opinion Leaders (“KOLs”), we anticipate partnering

to access non-dilutive funding for our IITs, to the extent available.

_______________________

1 Cockrum P, Dennen S, Brown A,

Briggs J, Paluri R.

Real-world clinical outcomes and economic burden of metastatic pancreatic ductal adenocarcinoma:

a systematic review.

Future Oncol.

10.1080/14796694.2024.2435253.

Epub 2024 Dec 8.

Regulatory Development Incentives to Accelerate the Path to Potential Approval of Elraglusib.

One of our strategic objectives

is to obtain development incentives in the United States and in other countries that we believe may accelerate our path to drug approval:

Orphan Drug Designation (“ODD”), Fast Track Designation (“FTD”) and Breakthrough Therapy Designation (“BTD”)

in the United States;

Orphan and priority medicines (“PRIME”) designations in the EU;

and Orphan designations in Japan and Australia.

There is no guarantee that any such designation, if received, will lead to a faster development, regulatory review or approval process;

and Orphan designations in Japan and

There is no guarantee that any such designation, if received, will lead to a faster development, regulatory review or approval

or increase the likelihood that a product candidate will receive FDA approval.

· Explore strategic partnerships that can

accelerate and maximize the potential of GSK-3 inhibitors.

We will evaluate potential strategic (pharma) partnering opportunities

which could further help us to accelerate development of elraglusib by providing expertise, guidance, and funding to expand the pipeline

into different tumors and other disease areas that could benefit from GSK-3 inhibitor therapy, as discussed in more detail below.

also broaden the reach of our platform by selectively in-licensing technologies or novel product candidates.

In addition, we will consider

potentially out-licensing certain geographic rights to elraglusib or other product candidates in our target indications or for indications

and industries that we are not currently pursuing ourselves.

· Leverage our academic and research partnerships.

are actively engaging with regulators, KOLs, advocates and other stakeholders early and throughout the development process in each cancer

indication being considered for development to enhance the probability of technical success.

We currently have clinical partnerships with

investigators conducting IITs with elraglusib at MGH and Dana-Farber Cancer Institute (“DFCI”).

The trials are partially financially

supported by grants from us in amounts ranging from $500,000 to $700,000 depending on the study, to be paid on an enrollment milestone

basis, with the balance of study funds provided by the institutions or with grants from government or research institutions.

We also provide

elraglusib for the study and input into study design.

We retain the rights to any preexisting intellectual property and the right for

exclusively licensing any joint inventions resulting from the studies.

The studies may be terminated by either party with 30 days’

notice (subject to appropriate offboarding and follow up care for enrolled patients).

We expect to expand these pending additional funding

to explore indications beyond pancreatic cancer.

We also have a research and development collaboration with Lantern Pharma to leverage

Strategic Partnerships That Can Accelerate and Maximize the Potential of GSK-3 Inhibitors.

We will evaluate potential strategic

partnering opportunities with pharmaceutical companies which could further help us to accelerate development of elraglusib by providing

expertise, guidance, and funding to expand the pipeline into different tumors and other disease areas that could benefit from GSK-3 inhibitor

We may also broaden the reach of our platform by selectively in-licensing technologies or novel product candidates, pending

the availability of the necessary funding.

In addition, we will consider potentially out-licensing certain geographic rights to elraglusib

or other product candidates in our target indications or for indications and industries that we are not currently pursuing ourselves.

Our Academic and Research Partnerships.

We are actively engaging with regulators, KOLs, advocates and other stakeholders

early and throughout the development process in each cancer indication being considered for development to enhance the probability of

technical success.

We currently have clinical partnerships with investigators conducting IITs where we provide elraglusib drug product

and input into study design while retaining the rights to any preexisting intellectual property and the right for exclusively licensing

any joint inventions resulting from the studies.

We also have a research and development collaboration with Lantern Pharma Inc.

their artificial intelligence platform to further understand the effects of elraglusib and identify patient subtypes that are particularly

2 unchanged sentences

and development efforts.

About Elraglusib (9-ING-41)

There are no approved high-affinity

inhibitors of GSK-3β and we believe elraglusib is one of the most advanced GSK-3β inhibitors in clinical development.

was originally known as 9-ING-41 but was granted the elraglusib International Nonproprietary Names (“INN”) and United States

Adopted Names (“USAN”) generic name in 2021.

The known major mechanisms of action of elraglusib are summarized in Figure 4

and emphasize the therapeutic potential of this drug in multiple cancer types.

For these reasons, elraglusib represents a “pipeline

in a molecule” depending on the dosage form and how it is used in a particular cancer type.

Our lead development program is seeking

to treat mPDAC in combination with GnP.

Our clinical data to date and the development plan are also further discussed below.

Elraglusib may exert anticancer

activity through a variety of mechanisms that may be context and cancer type specific.

For example, GSK-3β mediates signaling of

oncogenic PI-3K but if this oncogene is not expressed in a particular tumor, this would not be a pathway that could be targeted by elraglusib

in that tumor.

Potential antitumor activity through GSK-3β inhibition may occur through the following six mechanisms of action (see

Figure 3 below):

(1) Immune modulation;

(2) Inhibiting cell proliferation;

(3) Reducing tumor fibrosis;

(4) Decreasing immune evasion;

(5) Increasing apoptosis and disrupting DNA damage repair;

(6) Inhibition of epithelial-mesenchymal transitions (“EMT”).

Elraglusib mechanisms

(1) Immune modulation and inhibition of immune evasion

GSK-3β plays an important

role in immune cell function, as inhibition of GSK-3β can facilitate immune cell expansion, differentiation and activation including

T and natural killer (“NK”) cells.

GSK-3β inhibition increases the ability of effector T cells to kill tumors in vivo

through the induction of effector proteins granzyme B and FasL in gastric cancer models.

Additionally, inhibition of GSK-3β, with

both small molecules and small interfering RNA (“siRNA”), downregulates programmed cell death protein 1 (“PD-1”)

expression in CD8 and cytolytic T cells and enhances their function.

GSK-3β inhibition also lowers PD-1 expression and promotes long-term

survival and generation of memory CAR-T cells in vivo.

These memory T cells enabled 100% clearance of cancer cells after rechallenging

during tumor remission.

Recently, inhibition of GSK-3β with small molecules was shown to reduce the expression of T cell immunoreceptor

with immunoglobulin and ITIM domain (“TIGIT”) and lymphocyte activation gene-3 (“LAG-3”), additional immune system

suppressing molecules that work in concert with PD-L1 (Programmed Death-Ligand 1) to reduce anti-tumor surveillance by the system.

GSK-3β inhibition and LAG-3 blockade significantly enhanced clearance of melanoma tumors compared to either treatment alone.

was recently validated as a cancer therapeutic target when the first anti-LAG-3 antibody, relatlimab, was approved in March 2022

by the FDA for treatment of patients with unresectable or metastatic melanoma.

Blocking GSK-3 in NK cells leads

to enrichment of mature NK cells and primes them for enhanced cytokine production and anti-tumor function in vivo.

GSK-3β expression

was increased in the NK cells of patients with acute myeloid leukemia (“AML”) and inhibition of GSK-3β led to increased

cell directed cytotoxicity in these patient-derived samples.

Inhibition of GSK-3 also decreased LAG-3 expression on NK cells.

GSK-3β activity has also

been tied to transforming growth factor β (“TGF-β”) expression.

TGF-β released by cancer cells, stromal fibroblasts

and other cells in the tumor microenvironment further promotes cancer progression by shaping the architecture of the tumor and by suppressing

the anti-tumor activities of immune cells, thus generating an immunosuppressive environment that prevents or attenuates the efficacy of

anticancer immunotherapies.

Therefore, blocking GSK-3β may reduce TGF-β-mediated immunosuppression.

Elraglusib has now been demonstrated

to decrease expression of PD-1, TIGIT and LAG-3 and to enhance the anti-tumor effects of anti-PD-1 checkpoint inhibition in animal tumor

Thus, elraglusib blockade of GSK-3β activity may improve immune response to tumors by augmenting the responsiveness of a

patient’s immune system in addition to the direct anti-tumor effects of elraglusib within the cancer cells themselves.

(2) Inhibiting cell proliferation

Inhibition of GSK-3β leads

to inhibition of tumor cell proliferation.

This has been shown in multiple tumor model systems using elraglusib.

A number of pathways

have been implicated in the inhibition of cell proliferation mediated by GSK-3 inhibitors including MYC, Cyclin D1, TGFα, epidermal

growth factor receptor, Ras, PI3K/Akt, and NF-κB.

Given GSK-3’s role as an adapter of multiple signaling pathways, elraglusib

may exert its antiproliferative effects through the inhibition of one or more of these pathways.

(3) Reducing tumor fibrosis and (4) decreased immune evasion

A chronic inflammatory microenvironment

is conducive to tumorigenesis (e.g., pancreatitis patients are known to have increased risk of pancreatic cancer) and tumors can undergo

EMT, leading to increased metastasis, under inflammatory conditions.

Moreover, several profibrotic cytokines (e.g., TGF-β, TNF-α

and IL-1) are secreted by inflammatory cells and tumor cells and converge to activate pathways that regulate EMT.

Further, GSK-3β

has also been demonstrated to be a mediator of EMTs.

Therefore, the inflammatory response designed to fight tumor progression also ends

up promoting metastasis and tumor-associated fibrosis.

Tumor fibrosis presents multiple challenges to drug delivery and tumor immune recognition

and contributes to drug resistance by presenting physical barriers in the tumor microenvironment to drug and immune cell access.

has been shown to reduce the inflammation and signaling that contribute to immune system evasion in multiple animal models, including

lung and liver, suggesting another mechanism through which elraglusib may interfere in cancer growth.

(5) Increasing apoptosis and disrupting DNA damage repair

GSK-3 inhibits apoptosis pathways.

A number of studies have suggested that the primary mechanism of GSK-3-mediated apoptosis is through the NF-κB pathway.

is a mechanism of cell death that is often suppressed in cancer cells leading to cancer cell survival and resistance even after treatment

with chemotherapeutic drugs or radiation.

Studies have shown that eliminating or inhibiting GSK-3β in cancer cells is able to restore

apoptosis to cells, leading to tumor cell death.

These findings support GSK-3β as a potential therapeutic target to potentiate apoptosis

in cancer cells.

In addition to GSK-3β’s

role in regulating NF-κB activity, it has also been shown to modulate DNA damage repair (“DDR”) pathways.

are integral in both normal and cancer cells to maintain genomic integrity by sensing and responding to DNA damage.

In normal cells, DDR

helps to identify and repair mutations or breaks in DNA and restore the normal, intact sequence.

If the cell is unable to repair a DNA

lesion, these DDR pathways can then initiate cell death signaling to prevent neoplastic growth.

In cancer, DNA repair has been subverted

to protect tumor cells from repairing DNA damage that would otherwise lead to spontaneous apoptosis.

Cancers will often have mutations

in at least one DNA repair pathways leading to dysregulated cell growth and replication.

Our collaborators have shown that elraglusib

inhibition of GSK-3β sensitizes pancreatic cancer cells to gemcitabine by disrupting TopBP1/ATR mediated cell-cycle arrest and DNA

GSK-3β’s emerging role in regulating DDR pathways supports its use in combination with DNA damaging chemotherapy.

Inhibition of DDR pathways have

also been shown to enhance tumor immune recognition by immune checkpoint inhibitors such as anti-PD-1, creating neoantigens in tumors

that lead to recruitment of tumor infiltrating immune cells, decreased immune evasion and increased anti-tumor immune response.

This provides

the link that couples the various elraglusib-related mechanisms of action through the targeting of GSK-3.

(6) Inhibition of epithelial-mesenchymal transition (EMT)

GSK-3β has been shown to

be a mediator of a number of signaling pathways that regulate the transition of tumor cells from an epithelial to mesenchymal phenotype

potentially contributing to tumor progression, a process known as EMT.

Signaling through Wnt, Notch, TGF-β and Snail are known mediators

of EMT and their signaling is regulated through GSK-3β.

Several toolkit GSK-3β inhibitors have been shown to inhibit EMT in

tumor models suggesting that this is a class effect and highlighting a similar mechanism for elraglusib.

Our Solution – Current Elraglusib Development

Elraglusib represents a broad

2 unchanged sentences

Our lead program is developing Elraglusib Injection for the first-line treatment of mPDAC.

mPDAC remains one of the highest unmet needs in oncology as the 5-year survival rate for PDAC (<10%) is one of the lowest of any cancer

Despite advances in the treatment therapies over the last 30 years, the 5-year survival rate for Stage IV mPDAC remains at less than 5%,

representing one of the lowest of any cancer type.

Our Advancing Pipeline

Our initial focus is on the

development of GSK-3 inhibitors for the treatment of cancers with ineffective treatment options and poor overall survival.

Given our ability

to formulate elraglusib in both the Elraglusib Injection and Elraglusib Oral Tablet forms, and given the potential to administer this

molecule as an IV or oral formulation depending on the cancer type and existing standard of care, we believe that elraglusib represents

a pipeline in a molecule that can be broadly developed if adequate funding is secured.

We are focused on advancing trials in mPDAC, Ewing

sarcoma, and neuroblastoma with Elraglusib Injection while also advancing the Elraglusib Oral Tablet in a Phase I trial in advanced solid

Our ability to advance our ongoing and planned clinical trials listed in Figure 2 will depend on whether we can raise sufficient

capital to support those trials, including potential support from strategic collaborations.

Ongoing and planned clinical trials.

Developing Elraglusib Injection for the Treatment

of mPDAC – Phase 2 Studies

Actuate-1801 Part 3B

We are currently evaluating elraglusib

through the second part of a Phase 2 study, referred to as Actuate-1801 Part 3B, which was initiated under the Actuate-1801 Master

Protocol in patients with mPDAC who had not previously received systemic treatment for their metastatic disease.

This study was designed as a randomized,

controlled study with a run-in to explore two different dosing schedules of elraglusib/GnP (once weekly vs.

twice weekly) in the hope

of potentially providing clinical support for moving to a more convenient, commercially viable elraglusib schedule.

Pharmacokinetics were

also included in this study to address the potential for drug-drug interactions (“DDI”) between elraglusib and gemcitabine

or nab-paclitaxel.

Management believes that confirmation of the Actuate-1801 Part 3A result discussed below in an adequately powered,

randomized study, would compare favorably with the recently approved irinotecan liposomal injection and would complement the other first-line

regimens currently used to treat mPDAC and provide a basis for approval for use in patients with mPDAC who had not previously received

systemic treatment for their metastatic disease.

Actuate-1801 Part 3B enrolled

its first patients in October 2021 and the run-in part of the trial demonstrated the weekly dosing of elraglusib was equivalent to

twice weekly dosing of elraglusib.

All patients randomized to the elraglusib/GnP arm now receive weekly elraglusib in addition to GnP.

The trial accrued more readily than projected and enrollment was completed in January 2024.

Below are the key inclusion criteria

and clinical endpoints in the study:

Inclusion Criteria:

· ≥ 18 years old with metastatic pancreatic

adenocarcinoma

· Participants must have measurable disease as

defined by RECIST1.1

· No prior therapy

· Total enrollment:

· Primary endpoints:

1 year OS/mOS

· Secondary endpoints:

ORR, DCR, PFS

· Sample size based on projected increase in 1-year survival from 35% in GnP

to 55% in elraglusib/GnP with α=0.05;

232 patients needed for 80% power

We conducted a preliminary analysis

of interim data in the pre-specified safety population as of November 15, 2024.

As with all preliminary analyses of interim data, this

data should not be relied upon as a final analysis and is subject to change once full data analysis is complete.

For this preliminary

analysis, we used data based on a cut-off date corresponding to the date when >70% of death events occurred in the GnP control arm.

The analysis of interim data demonstrated

treatment with elraglusib in combination with GnP resulted in statistically significant increases in 1-year survival rate (p-value of

0.002) and mOS (hazard ratio of 0.63, p-value of 0.016) versus treatment with GnP alone.

The combination treatment also resulted in increased

ORR and DCR in the elraglusib/GnP combination arm versus the GnP control arm.

Interim data highlights include the following:

· The interim data met the trial primary endpoint

with a 1-year survival rate of 43.6% in the elraglusib/GnP combination arm versus 22.5% in the GnP control arm (p-value of 0.002).

· 18-and 24-month survival rates also demonstrated

benefit of 20.9% vs 0% and 16.7% vs 0% in the elraglusib/GnP combination vs GnP arms, respectively.

· As of the November 15, 2024 cutoff, 38% of subjects

were still alive in the elraglusib/GnP combination arm vs 19% in the GnP control arm.

· A statistically significant 37% reduction in

risk of death and increased mOS were observed in the elraglusib/GnP combination arm (mOS 9.3 months) vs the GnP control arm (mOS 7.2 months),

(hazard ratio of 0.63, p-value of 0.016).

· The trial also met its primary safety endpoint.

TEAEs and SAEs in the elraglusib/GnP combination arm were similar to those observed in the GnP arm, indicating a favorable risk-benefit

profile for the elraglusib/GnP combination.

(See Figure 11 for a summary of TEAEs of any grade reported in >20% of patients treated

with elraglusib).

· At the interim cutoff of November 15, 2024, the

ORR was 27.7%, DCR was 42.6 %, and PFS was 5.6 months in the elraglusib/GnP combination arm versus 20.5%, 33.3% and 4.9 months in the

GnP arm, respectively.

· As of November 15, 2024, two patients in the

elraglusib/GnP combination arm with previously inoperable metastatic lesions with noted reductions in target lesions were referred for

successful resection, one of which resulted in 100% reduction in total tumor burden after surgery.

In addition, there have been one CR

and one PR with 100% reduction in target lesions in the elraglusib GnP combination arm versus none in the control arm to date.

Figure 4 provides additional details

regarding the demographics and disease history of the enrolled patient population (draft unaudited data as of November 15, 2024).

+ GnP (n=155)

Black or African American

Unknown/Not Reported

Hispanic or Latino

Not Hispanic or Latino

Unknown/Not Reported

Body Surface Area (BSA) (m2)

Eastern Cooperative Oncology Group Performance Status

Disease Status

Metastatic at Initial Diagnosis

Metastatic at Study Entry

Site of Metastases

Actuate-1801 Part 3B:

for patients in study (as of November 15, 2024).

Additional data from the preliminary

analysis of interim data as of November 15, 2024 are shown in Figures 5 – 11.

These figures represent draft unaudited data

as of November 15, 2024 and the final data and results may change as the study continues through completion.

As with all interim data,

this data should not be relied upon as a final analysis and is subject to change once full data analysis is complete.

Figure 5 summarizes primary

and secondary endpoints and patients remaining on study for each treatment arm as well as landmark OS endpoints of 18- and 24-months.

A large number of patients are still on treatment with 38% still remaining on the elraglusib/GnP combination arm versus 19% still remaining

on the GnP only arm as of November 15, 2024.

This is also shown at the patient level for each treatment cohort in the swim plots in Figure

9 that show patients still on treatment, patients with a response including stable disease, and patients still on study as well as those

that have reached an event.

Interim safety data is shown in Figure 11.

Our lead clinical program

is focused on evaluating Elraglusib Injection for the treatment of first-line mPDAC.

The Phase 2 trial is a randomized, controlled Phase

2 trial of elraglusib in combination with GnP versus GnP alone in first-line mPDAC.

The trial enrolled 286 patients with mPDAC and no

prior systemic treatment for metastatic disease.

Patients were randomized 2:1 to the elraglusib/GnP combination arm or the GnP arm, respectively.

This study included a run-in to explore two different dosing schedules of elraglusib/GnP (once weekly versus twice weekly) to evaluate

the potential of moving to a more convenient, commercially viable elraglusib dosing schedule.

The Phase 2 trial enrolled its first patient

in October 2021 and the run-in part of the trial demonstrated that the weekly dosing of elraglusib was equivalent to twice weekly dosing

of elraglusib with no meaningful clinical difference in safety or efficacy.

After the dose run-in part of the trial, all patients that

were randomized to the elraglusib/GnP arm received weekly elraglusib in addition to GnP.

Last patient was enrolled in the first quarter

Key inclusion criteria included

patients that were 18 years or older with metastatic pancreatic adenocarcinoma and no prior therapy with measurable disease as defined

by RECIST1.1.

The primary endpoint for this

study was mOS, with OS summarized throughout the study by estimates of 1-year survival.

Secondary endpoints were overall response rates

(“ORR”), median progression-free survival (“mPFS”), disease control rate (“DCR”) and adverse events.

Updated study results were

presented at the ASCO GI conference in January 2026 utilizing a data cutoff of November 22, 2025.

Log-rank analysis was used to determine

statistical significance when comparing the two arms of the study.

Data presented in the pre-specified safety population showed that the

trial met its primary endpoint of improved mOS in patients in the elraglusib/GnP arm versus the GnP control arm.

The analysis of updated

data demonstrated treatment with elraglusib/GnP resulted in statistically significant increases in 1-year survival rate (p-value of 0.0004)

and mOS (10.1 months vs 7.2 months, HR=0.62, log-rank p=0.02) with a 38% reduction in the risk of death versus treatment with GnP alone.

The following table provides

additional Phase 2 study results as of the November 22, 2025 cutoff date:

Safety Population

Elraglusib/GnP

Primary Endpoint:

1 Year OS (%)

Primary Endpoint:

log-rank p=0.02*

Events (% events)

12-month OS (%) p=0.0004*

Number (%) of death events

18-month OS (%)

24-month OS (%)

_____________________

*statistically significant

In addition, updated data showed there were numerically

improved ORR, mPFS, and DCR in the elraglusib/GnP combination arm versus the GnP arm as noted in the below table.

Safety Population

Elraglusib/GnP

mPFS (months)

Events (% events)

Actuate-1801 Part 3B:

secondary study endpoints (as of November 15, 2024).

Figure 6 below represents interim

Kaplan-Meier estimate for mOS.

The administrative analysis of interim data indicates that >80% of the patients in the GnP control arm

progressed and were no longer receiving GnP.

Actuate-1801 Part 3B:

Kaplan-Meier Estimate for mOS (as of November 15, 2024).

Figure 7 below depicts the best overall response

(“BOR”) of patients enrolled in the Phase 2 study (Actuate-1801 Part 3B) in the GnP control arm who received at least one

radiographic scan.

Actuate-1801 Part 3B:

GnP Best Overall

Response (as of November 15, 2024).

Figure 8 below depicts the BOR of patients enrolled

in the Phase 2 study (Actuate-1801 Part 3B) in the elraglusib/GnP combination arm who received at least one radiographic scan.

Actuate - 1801 Part 3B:

GnP/Elraglusib

combination Best Overall Response (as of November 15, 2024).

Figure 9 below is a graphical

representation of survival (“mOS Swim Plot’”) of patients enrolled in the Phase 2 study (Actuate-1801 Part 3B) in the

elraglusib/GnP combination arm compared to the GnP control arm.

Actuate-1801 Part 3B:

Administrative Analysis

of mOS Swim Plot (as of November 15, 2024).

This is an open-label study and

therefore, the study could not be used to support accelerated approval which would be based on evaluation of surrogate endpoints.

Management expects top-line data

will be presented in the second quarter of 2025 based on the completion of enrollment in January 2024.

At the conclusion of Phase 2 trial

(Actuate-1801 Part 3B), we expect to have survival data on the elraglusib/GnP combination arm and GnP arm in patients with mPDAC

who had not previously received systemic treatment for their metastatic disease.

At the completion of this study, we plan to meet with

the FDA and discuss the design and execution of a Phase 3 registration study, if justified by the results this study.

we plan to discuss the use of the Actuate-1801 Part 3B data for regulatory support and to support possible registration if the study

achieves its primary endpoint of showing improved survival over GnP alone.

Moreover, while the elraglusib/GnP combination appears to be

well-tolerated and well-managed in the clinic, we do not yet know whether any increase in the number or severity of toxicities will be

attributable to elraglusib and thus the elraglusib/GnP combination will have its own safety profile that will need to be evaluated and

discussed with regulators.

Figure 11 is a summary of the safety events reported as of November 15, 2024.

Actuate-1801 Part 3A

Actuate-1801 Part 3A is a single

arm Phase 2 trial that was initiated in patients with mPDAC who had not previously been treated with any systemic chemotherapy including

GnP (first-line study) and which built on the results of Actuate-1801 Part 2 described below, allowing a comparison of the safety

and efficacy of the combination of Elraglusib Injection plus GnP as compared to GnP alone.

By moving our development into the first line

setting, we increased our ability to deliver the elraglusib/GnP combination to many more patients since more than 70% of patients with

mPDAC never go on to a second-line treatment once they have progression on first-line treatment.

In addition, we believe that the safety

profile of elraglusib/GnP provides a strong basis for testing this combination in first-line patients.

We also received a number of commercialization

incentives (e.g.

ODD, FTD) through registration for pancreatic cancer including mPDAC.

Results from the Actuate-1801 Part 3A study formed

the basis for the initiation of Actuate-1801 Part 3B trial.

In Part 3A of the Phase 2

study under the Actuate-1801 Master Protocol, the efficacy evaluable (“EE”) patient population was pre-defined as the efficacy

analysis population and the modified intent to treat (“mITT”) was the safety population.

The elraglusib dose was started at

the RP2D evaluated in Part 2 (15 mg/kg dosed twice weekly).

The original study design proposed

to enroll 23 consecutively evaluable patients who met the definition for the EE.

These patients could be replaced at the discretion of

the independent data monitoring committee (“IDMC”).

Consequently, six patients were replaced such that there were 29 EE patients

in the study.

No new safety signals were observed with the elraglusib/GnP combination, but investigators observed that GnP toxicities

may have occurred earlier and may have been more intense in some patients than would be anticipated for GnP alone.

For these reasons,

the dose of elraglusib was proactively reduced near the end of the study to 9.3 mg/kg dosed twice weekly, with the final four patients

enrolled being treated at this dose.

Figure 10 below is a summary of

the response of patients with mPDAC treated with the elraglusib/GnP combination in Part 3A (data cutoff as of March 2023) in the

29 EE patients.

SD ≥16 weeks, n (%)

SD <16 weeks, n (%)

Progressive disease, n (%)

Disease control rate (CR+PR+SD ≥16 weeks), n (%)

5.4 months (4.9 months ITT)

15.3 months (11.9 months ITT)

Confidence Interval (“CI”);

Stable Disease (“SD”)

Response of EE patients

with mPDAC treated with elraglusib/GnP combination in Part 3A (data cutoff as of March 2023).

The mOS for the EE and ITT were

15.3 months and 11.9 months, respectively.

These compare favorably with the mOS for GnP alone of 8.5 months in the MPACT

trial or more recently 9.2 months in NAPOLI-3 trial, which evaluated irinotecan liposomal injection (Onivyde®) in combination

compared to GnP, in the first-line mPDAC setting.

Elraglusib Injection was initially

evaluated in Actuate-1801 Part 1/2, a dose escalation study in adult patients with refractory advanced cancers when given as a single

agent or in combination with chemotherapy.

The objective of this study was to establish the safety profile of elraglusib when used alone

or in combination with chemotherapy and to identify either an MTD or RP2D to then inform the design of exploratory efficacy studies in

Figure 14, which shows the study design process, and additional information regarding Actuate 1801 Master Protocol and potential

future development opportunities (for which funding would need to be raised) identified through Actuate 1801 Parts 1 and 2 are set forth

under “History of Elraglusib Clinical Development” below.

Overview of Interim Safety Profile from Phase 2 Trial (Actuate-1801

Figure 11 provides safety

data as of November 15, 2024 from the Actuate-1801 Part 3B trial.

TEAEs broadly encompass all adverse events observed while a patient

is on study and could be due to the drug or drugs (if used in combination), the disease or something specific to a particular patient

such as other diseases or illness.

It is then up to individual clinical investigator to decide which toxicities are due to elraglusib.

The most common TEAEs attributed to elraglusib were transient visual disturbance and fatigue across both study parts, and the majority

of TEAEs that occurred in ≥ 20% of patients were reported as Grade 1 or 2 (Figure 11).

Visual disturbance affected 66.5% of patients

(n=103/155) receiving elraglusib plus GnP and 9.0% of patients (n=7/78) receiving GnP alone.

Commonly reported symptoms were darkened

vision, where patients described lights as brighter and skin tones darker.

Greater than 99% of visual disturbance cases were reported

as mild or moderate (Grade 1 or 2).

These visual disturbances were considered dose-dependent, occurring more frequently and lasting longer

at higher doses.

All cases of visual disturbance were transient, resolved completely, and lacked any associated retinal, ocular, or systemic

Fatigue, while also observed in ≥ 20% of patients, was also reported as mild or moderate (Grade 1 or 2) and did not interfere

with daily life.

Some of the key findings from the interim safety analysis

as of November 15, 2024 include:

· Overall rates of TEAEs and/or SAEs observed were

similar in the elraglusib + GnP-treated patients as compared to GnP-treated patients.

· Treatment discontinuation due to TEAEs were similar

across the treatment groups.

· Visual impairment and fatigue were major TEAEs

attributed to elraglusib as a single agent in 1801 Part 1 and were mild to moderate.

o Transient visual impairment described as transient alterations in color and skin tones under fluorescent

o No permanent changes to eye structure or vision.

Figure 11 below is a summary of

TEAEs of any grade reported in >20% of patients treated with elraglusib as of November 15, 2024 in Actuate 1801 Part 3B (trial

Figure 3 depicts the interim

Kaplan-Meier estimate for mOS as of November 22, 2025 cutoff and other endpoints in the study, including primary and secondary endpoints

and patients remaining on study for each treatment arm as well as landmark OS endpoints at 18- and 24-months.

Unaudited Phase 2 data of elraglusib

in mPDAC (data as of November 22, 2025 cutoff).

As with all preliminary analyses

of interim data, this data should not be relied upon as a final analysis and is subject to change once full data analysis is complete.

Treatment-emergent adverse

events (“TEAEs”) and Serious Adverse Events (“SAEs”) in the elraglusib/GnP combination arm were similar to those

observed in the GnP arm, indicating a favorable risk-benefit profile for the elraglusib/GnP combination.

TEAEs broadly encompass all

adverse events observed while a patient is on study and could be due to the drug or drugs (if used in combination), the disease or something

specific to a particular patient such as other diseases or illness.

It is then up to the individual clinical investigator to decide which

toxicities are due to elraglusib.

The most common TEAEs attributed to elraglusib were transient visual disturbance and fatigue across

both study parts, and the majority of TEAEs that occurred in ≥ 20% of patients were reported as Grade 1 or 2 (Figure 4).

Visual disturbance

affected 68.4% of patients (n=106/155) receiving elraglusib/GnP and 9.0% of patients (n=7/78) receiving GnP alone.

Commonly reported

symptoms were darkened vision, where patients described lights visually appearing brighter and skin tones visually appearing darker.

Greater than 99% of visual disturbance cases were reported as mild or moderate (Grade 1 or 2).

All cases of visual disturbance were transient,

resolved completely, and lacked any associated retinal, ocular, or systemic toxicity.

Fatigue, while also observed in ≥ 20% of patients,

was also reported as mild or moderate (Grade 1 or 2) and did not interfere with daily life.

Figure 4 below is a summary

of TEAEs of any grade reported in ≥20% of patients treated with elraglusib/GnP versus GnP alone as of November 22, 2025 data cutoff.

Adverse Event

1 unchanged sentence

Leading to Stoppage of Any Study Drug

Leading to death

Resulting in death

of any Grade in ³ 20%

6 unchanged sentences

Peripheral sensory neuropathy

1 Carneiro et al.

Clin Cancer Res 2024 Feb 1;30(3):522-531

*Includes Preferred Terms (PT) neutropenia and neutrophil count decreased

** Includes PT anemia and hemoglobin decreased

***Includes PT thrombocytopenia and platelet count decreased

TEAEs of Any Grade Reported in >20% of Patients Treated with Elraglusib.

Investigator-Initiated Trial – PDAC

Elraglusib is also currently being

evaluated in an IIT focusing on adults with untreated metastatic pancreatic adenocarcinoma.

IND 157435, a Phase 2 study of FOLFIRINOX

combined with elraglusib and the TGF-β inhibitor losartan in patients with untreated metastatic adenocarcinoma is being conducted

Colin Weekes (the “Weekes IIT”).

This study administers elraglusib by intravenous infusion twice weekly in combination

with FOLFIRINOX administered once every 14 days and daily losartan in adults with pancreatic cancer who have not received any prior

systemic therapy for advanced disease.

As of December 31, 2024, 57 patients have been enrolled in the Weekes IIT and the study is ongoing.

We will receive all final data

from this study, which is considered exploratory and may inform future development of elraglusib.

For additional information regarding

other IITs involving elraglusib, see additional information below.

Developing Elraglusib Injection for the Treatment of Ewing Sarcoma

– Phase 1 and Phase 2 Plans – Actuate-1902

As discussed under “Our

Market Opportunity” above, based on extensive preclinical work in pediatric malignancies showing excellent synergy between elraglusib

and standard of care chemotherapy in neuroblastoma, sarcoma, glioma and others, we initiated the Actuate-1902 Phase 1 study to determine

the safety of elraglusib +/- chemotherapy in pediatric patients with refractory malignancies in 2020.

Based on the response from the Ewing

sarcoma patient, additional patients with metastatic, refractory Ewing and Ewing-like sarcoma were enrolled in the elraglusib/CT arm of

the 1902 Phase 1 study.

Twelve patients including ten

Ewing sarcoma patients, one DSRCT patient and one CIC rearranged sarcoma patient have been treated in the Actuate-1902 Phase 1 trial with

a combination of elraglusib and cyclophosphamide/topotecan.

All twelve patients appeared to have metastatic disease and had disease progression

prior to joining the study despite undergoing previous treatment combinations including chemotherapy, radiation, and/or surgical procedures.

Eight patients received two or more previous chemotherapy regimens, prior to entering the 1902 study.

The following represents the status

of Actuate-1902 Phase 1 trial as of December 31, 2024:

· One Ewing sarcoma patient with the CR stopped

all treatments after Cycle 5 and patient was reported alive as of December 31, 2024 (OS of 1,138 days).

· A second Ewing sarcoma patient had a PR of their

target lesion and a Complete Metabolic Response (“CMR”) of two secondary lesions by FDG-PET.

This patient received treatment

for 10.5 cycles before transitioning to monotherapy in August 2024.

This patient continues on monotherapy with no change in tumor status

or response as of February 4, 2025.

· A third patient had a partial response with a

52% reduction in tumor burden compared to baseline and the patient ended treatment after 3 cycles with OS of 368 days.

· Three Ewing sarcoma patients had best overall

response as stable disease, two patients were removed from treatment prior to week two and four patients were reported as having progressive

· As of December 31, 2024, three of twelve patients

remain alive and one patient continues on monotherapy treatment with elraglusib.

We believe that this exploratory

Ewing sarcoma data is sufficiently positive in this orphan pediatric cancer indication to consider additional development and treatment

options in Ewing sarcoma.

The Actuate-1902 Phase 1 arm of the study is open to accrual.

With future funding, and pending

1902 data review at the end of Phase 1, we plan to evaluate additional treatment options focusing on patients with Ewing sarcoma.

Given that Ewing sarcoma is a

very rare pediatric cancer, an international consortium of investigators and sites will be needed to advance this program to registration.

Neuropathy peripheral

of Any Grade Reported in ≥ 20% of Patients Treated.

Additional updated data

as of November 22, 2025 are shown in Figures 5 and 6.

As with all interim data, this data should not be relied upon as a

final analysis and is subject to change once full data analysis is complete.

Figure 5 summarizes

additional details regarding the demographics and disease history of the enrolled patient population in each arm of the study.

Black or African American

Unknown/Not Reported

Hispanic or Latino

Not Hispanic or Latino

Unknown/Not Reported

Body Surface Area (BSA) (m2)

Eastern Cooperative Oncology Group Performance Status

Disease Status

Metastatic at Initial Diagnosis

Metastatic at Study Entry

Site of Metastases

Patient demographics and disease history

as of November 22, 2025 cutoff.

Figure 6 below is a

graphical representation of survival (“mOS Swim Plot’”) of each patient enrolled in the Phase 2 study in the

elraglusib/GnP arm versus the GnP control arm.

mOS Swim Plot as of November 22, 2025.

During the first half of 2026,

we plan to meet with the FDA and EMA to discuss the design and execution of a Phase 3 global registration study to support potential

product registration.

Elraglusib Injection for the Treatment of Pediatric

Elraglusib Injection is also

being evaluated in pediatric cancer patients with recurrent/refractory solid cancers.

The Actuate-1902 study was an open-label, multicenter

Phase 1/2 study evaluating the safety and efficacy of elraglusib in 40 pediatric patients ages 3 – 21 with relapsed (>2 remissions)/refractory

cancers, including EWS, neuroblastoma, Central Nervous System (“CNS”) tumors, non-EWS sarcomas, and other refractory pediatric

malignancies.

This trial evaluated escalating doses of elraglusib as a single agent as well as in combination with irinotecan or cyclophosphamide/topotecan

in the Phase 1 portion of the trial.

The Phase 1 dose escalation portion of the trial was designed primarily to determine the maximum

tolerated dose (“MTD”) and/or RP2D of elraglusib as a single agent and in combination with chemotherapy.

While an MTD was

not reached, initial evidence of anti-tumor activity was observed, particularly when elraglusib was administered with a standard cyclophosphamide

and topotecan regimen.

Two Complete Metabolic Responses (“CMRs”) were observed in patients with relapsed/refractory metastatic

EWS and one Complete Response (“CR”) was observed in a patient with relapsed/refractory metastatic neuroblastoma.

1 portion of this study was closed in July 2025.

Key highlights from the Actuate-1902 study include:

Elraglusib in combination with cyclophosphamide

and topotecan regimen:

· Clinical responses and disease control observed

in 10 of 19 patients with relapsed/refractory EWS or neuroblastoma.

o One patient with six prior treatments for EWS achieved a CMR with a 60% reduction in tumor size of a lung

target lesion.

This patient completed 30 weeks (Cycle 10) on treatment with long term treatment with elraglusib monotherapy continuing

without disease progression outside of the study.

o One patient with four prior treatments for EWS (+EWSR1 translocation or Ewing sarcoma breakpoint region

1) was identified as a CR (BOR) at week 9 (Cycle 3) with CT scan showing a 100% decrease in piriformis muscle tumor compared to baseline

(CMR by Positron Emission Tomography or PET).

o One patient with six prior treatments for unfavorable neuroblastoma histology (Indeterminate MYCN, ALK

(anaplastic lymphoma kinase), and ploidy) had a first response at week 9 (Cycle 3) of stable disease (“SD”), with a BOR of

a complete bone marrow response identified at week 27 (Cycle 9).

o One patient with 10 prior treatments for DSRCT (Desmoplastic Small Round Cell Tumor) achieved a PR (52.6%

decrease in liver/lung target lesions compared to baseline).

Non-target lesions included multiple lung and liver lesions, which were not

present at the end of treatment.

o Six patients with prior treatments ranging from 2 to 11, achieved a BOR of stable disease.

Elraglusib in combination with irinotecan regimen:

· Four patients (neuroblastoma, ganglioneuroblastoma

(a high-risk variant with an unfavorable prognosis)) achieved BOR of stable disease.

· One patient with neuroblastoma achieved a 35%

reduction in tumor burden between baseline and week 9 (Cycle 3).

· One patient with ependymoma experienced stable

disease with a prolonged time to progression of 54 weeks.

Based on these data, we identified

Ewing sarcoma and neuroblastoma as new indications for further development of Elraglusib Injection.

Given that Ewing sarcoma and neuroblastoma

are very rare pediatric cancer indications, an international consortium of investigators and sites will be needed to advance this program

to registration.

In addition, we plan to pursue a number of development incentives in the United States and parallel programs in the EU.

In July 2024,

we received ODD from the FDA for elraglusib for the treatment of soft tissue sarcomas in the United States and Orphan Medical Product

Designation from the EMA for the treatment of sarcoma.

In October 2024, we received RPDD from the FDA for the treatment of Ewings sarcoma.

The ability to engage in further development in pediatric cancers will depend on our ability to raise sufficient additional capital to

support this path.

We believe that pursuing this development could be an efficient and rapid path to registration in the United States

and Marketing Authorization in the EU.

Elraglusib Oral Tablet Development - Actuate-2203 and Actuate-2401

We have been developing several

oral dosage forms of elraglusib in addition to Elraglusib Injection that will potentially allow for further dose exploration and potentially

allow us to evaluate elraglusib as a single agent and in combination with additional chemotherapy backbones.

We believe that we will be

able to administer the Elraglusib Oral Tablet daily, which may allow the drug to achieve steady state levels in plasma in patients resulting

in continuous inhibition of the target GSK-3 in tumor and tumor-associated cells.

Preclinical studies have shown

that persistent exposure of tumor cells (>12 hours but longer exposures work better) is required to observe induction of apoptosis

in these tumor cell line models.

Both the liquid and solid oral dosage forms of elraglusib are highly bioavailable.

However, we have chosen

to advance the Elraglusib Oral Tablet into clinical development based on an assessment of potential compliance, convenience of use and

taste that favor the Oral Tablet.

Investigational product has already been manufactured under Good Manufacturing Practice (“GMP”)

standards, and we are planning a First in Human (“FIH”) Phase 1 clinical trial (Actuate-2401).

Subject to additional

funding, we plan to initiate a dose escalation Phase 1 trial in patients with advanced solid cancer to identify the MTD/RP2D for

the Elraglusib Oral Tablet.

Our development plan would then be to pursue Phase 2 indications such as metastatic melanoma, metastatic

colorectal cancer and/or non-small cell lung cancer (“NSCLC”) using the oral tablet.

We would require additional funds to

initiate and complete these Phase 2 studies.

An oral liquid was evaluated for

bioavailability in a Phase 1 healthy volunteer study (Actuate-2203) at a single dose using a cross-over design such that each subject

on the study received IV, oral liquid after fasting and oral liquid with food.

Elraglusib oral liquid was approximately 50% bioavailable

when given with food and was very well tolerated by healthy volunteers, as depicted in Figure 12.

Bioavailability of Elraglusib Oral

Liquid in Phase 1 Human Healthy Volunteer Study.

The oral liquid and several oral

tablets formulations were also evaluated for bioavailability in dogs and an oral tablet candidate was identified that was greater than

95% orally bioavailable when given with food.

For the first time, an MTD was identified with any formulation or dosing schedule of elraglusib.

In the past, elraglusib had been given up to 3 times a week in animal toxicology studies to cover twice weekly and once weekly dosing

of Elraglusib Injection in the Actuate-1801 and Actuate-1902 studies, but never daily.

In July 2024, we received ODD from the FDA for elraglusib for the treatment of soft tissue sarcomas in the United States and Orphan Medical

Product Designation from the EMA for the treatment of sarcoma.

In October 2024, we received Rare Pediatric Disease Designation (“RPDD”)

from the FDA for the treatment of EWS.

The ability to engage in further development in pediatric cancers will depend on our ability to

raise sufficient additional capital to support this path.

We believe that pursuing this development could be an efficient and rapid path

to registration in the United States and Marketing Authorization in the EU.

Elraglusib Oral Tablet for the Treatment of

We initially developed an

oral liquid that was evaluated for bioavailability in a Phase 1 healthy volunteer study (Actuate-2203) in a single dose cross-over

design such that each subject on the study received IV, oral liquid after fasting and oral liquid with food.

Elraglusib oral liquid was

greater than 50% bioavailable when given with food and was very well tolerated by healthy volunteers.

Consequently, we developed several oral tablet prototype formulations that were evaluated for bioavailability in dogs, and an oral tablet

candidate was identified with greater than 95% orally bioavailable when given with food.

In the study, the oral drug had an AUC24 (Area

1 unchanged sentence

time curve for 0-24 hours) of 77,000 ng•h/mL (nanograms times hours per milliliter) after a single

250 mg oral tablet and 137,000 ng•h/mL after oral administration of 500 mg (2 x 250 mg tablets) as shown in Figure 13.

dose demonstrated toxicity and was not tolerated by dogs but the 250 mg dose was well-tolerated when given daily for 28 days in this

exploratory study.

This simulated the expected daily dosing that we would plan to use in our FIH Phase 1 study.

The 25 mg/kg daily

dose in dogs corresponds to approximately the 9.3 mg/kg weekly dose currently being used in the Actuate-1801 Part 3B study when scaled

from dog to humans.

Our management expects that steady state exposures of 77,000 ng•h/mL or greater will be possible with the Elraglusib

Oral Tablet at well-tolerated doses in humans.

Based on these observations, we would expect to also reach MTD in the Elraglusib Oral Tablet

Phase 1 study in patients with refractory advanced cancer.

We believe this will allow for

additional opportunities to explore the anti-tumor activity of elraglusib with the oral tablet that could not be achieved with Elraglusib

While the weekly dosing of the Elraglusib Injection pairs well with GnP since both are given once per week, the oral tablet

may be more amenable to use with other, less convenient chemotherapies, as well as a single agent.

Bioavailability of Elraglusib Injection

compared to Oral Tablet in Dogs.

History of Elraglusib Clinical Development

Figure 14 is a graphical depiction

of the Actuate-1801 Master Protocol and study design process, followed by a discussion of the history of elraglusib clinical development

that led to finding that elraglusib plus GnP was well-tolerated in pre-treated cancer patients and selecting previously untreated mPDAC

as our lead indication.

Master Protocol Study Design

Actuate-1801 Phase 1/2 Clinical Study

We developed an innovative Phase 1/2

adaptive design “basket” clinical study to efficiently evaluate elraglusib safety and initial anti-tumor activity across multiple

This trial design facilitated the rapid advancement of elraglusib through dose escalation and safety cohorts while later

establishing a process for transition into Phase 2 efficacy studies in patient populations that showed evidence of anti-tumor activity

during the safety portion of the study.

Elraglusib has been dosed in over 500 patients to date both as a single agent and in combination.

The study design consists of three

Part 1 and Part 2 consist of the evaluation of the safety and tolerability of elraglusib to determine the MTD and RP2D

as both a monotherapy and in combination with various chemotherapy regimens.

Part 1 and 2 involve dose escalation of elraglusib to

identify either the MTD or RP2D if an MTD cannot be achieved.

These were run in tandem and interdigitated.

Initial dose escalation was

performed using single agent elraglusib (Part 1), but once Part 1 opened the fourth dose level, Part 2 was allowed to open

at the third dose level in combination with the chemotherapy backbones evaluated.

Dose escalation was then continued for Part 1 and

2 in tandem until MTD or RP2D were identified, with Part 2 always being one dose level behind Part 1.

A key design element of

Part 2 is that all subjects enrolled in a chemotherapy basket must have previously failed that chemotherapy such that each patient

was re-challenged by a drug to which they are resistant.

Thus, each patient acts as their own control since any disease control must be

due to the combination.

In Part 2, six dose levels of elraglusib were evaluated across eight different chemotherapy baskets.

is designed to assess the clinical benefit of elraglusib at the RP2D from Part 2 in combination with chemotherapy in specific cancer

Between January 2019 and

August 2021, patients participating in the Actuate-1801 Part 1 and Part 2 study received at least one dose of elraglusib as monotherapy

Part 1) or in combination with chemotherapy (n=171;

Twenty-one different cancer types were enrolled in Part 1.

On average, patients had received and failed at least three previous lines of chemotherapy regimens.

No dose-limiting toxicities (“DLTs”)

related to elraglusib occurred in either Part 1 or Part 2.

Since the MTD was not reached in either part of the study, 15 mg/kg,

the pre-specified highest dose evaluated in both Actuate-1801 Part 1 and 2, was named the RP2D.

The chemotherapy backbone and cancer

types involved in the study included:

Type – Number of Patients Treated

Doxorubicin (n=10)

Adrenal gland – 1

Esophageal – 1

Irinotecan (n=34)

Colorectal – 20

Pancreas – 11

Gallbladder – 1

Any carboplatin group (n=50)

Esophageal – 4

Head and Neck – 4

Colorectal – 3

Endometrial – 2

Mesothelioma – 2

Gallbladder – 1

Merkel Cell – 1

Fallopian tube – 1

Pancreas – 26

Osteosarcoma – 1

Lomustine (n=14)

Glioblastoma – 5

Astrocytoma – 1

Gliosarcoma – 1

Anaplastic oligodendroglioma – 1

Parts 1 and 2 comprised the Phase 1

portion of the Actuate-1801 trial and the results of this study were recently published in Clinical Cancer Research (Carneiro

Despite the fact that the patients

enrolled on the Actuate-1801 study had previously received and failed multiple chemotherapy regimens, the mOS was 7.7 months (95%

CI, 5.1-9.7) for elraglusib monotherapy (Part 1) and 6.9 months (95% CI, 5.7-8.9) for the combination of elraglusib and chemotherapy

(Part 2) across all the different chemotherapy baskets.

The mOS of 7.7 months in Part 1 benchmarks favorably with mOS 8-10 months

for other active single agents evaluated in Phase 1.

CR, PR and stable disease (“SD”) were determined using RECIST 1.1.

Only evaluable patients as defined per the Actuate-1801 Master Protocol experiencing stable disease ≥4 cycles of treatment are counted

as “stable.” Our management believes that 51.6% of patients in Actuate-1801 Part 1 and 49.3% in Actuate-1801 Part 2

with a response or stable disease who are able to stay on for at least four cycles of treatment is encouraging given the advanced and

treatment-refractory nature of their cancers.

Figure 15 below is a summary of

the best overall response of elraglusib as monotherapy (Part 1) and in combination with chemotherapy (Part 2).

Part 1 (n=62)

with chemotherapy

Part 2 (n=138)

OS, median (95% CI), month(a)

7.7 (5.1, 9.7)

6.9 (5.7, 8.4)

PFS, median (95% CI), month(a)

1.6 (1.3, 2.2)

2.1 (2.0, 2.6)

Best overall response, n (%)

Complete response

Partial response

Stable disease

Progressive disease

Abbreviations:

CI - confidence interval

Best overall response of elraglusib

as monotherapy (Part 1) and in combination with chemotherapy (Part 2)

To further demonstrate that elraglusib

shows single agent anti-tumor activity, an analysis was conducted regarding tumor size reduction and tumor tissue for the expression (presence)

of GSK-3β (as the target for elraglusib) using a validated immunohistochemical method.

Of the patients evaluated for

a tumor size reduction response, 15 out of 51 demonstrated tumor size reduction even if they did not reach a level of reduction associated

with a RECIST response.

Our management believes that the reason for this response is the administration of elraglusib since it is the

only anticancer drug given in this part of the trial.

Of the enrolled patients in Part 1, 16 patients had rapid clinical deterioration

related to their disease.

These patients were unable to stay on treatment long enough to reach their first tumor assessment and are therefore

not included in the Part 1 analyses as per the protocol.

Several tumor types are represented with clinical data in Part 1 including

melanoma, colorectal, appendix, and lung, providing initial rationale for future studies in these cancer types.

Tumor tissues from both Actuate-1801

Part 1 and Part 2 were analyzed for the expression (presence) of GSK-3β using a validated immunohistochemical method.

and fresh pre-dose samples of tumor tissue were analyzed with 59.4% of tumor samples in Part 1 and >80% of samples in Part 2

immunostaining positive for GSK-3β, demonstrating that the target for elraglusib is present in a large portion of tumors across all

the cancer types enrolled in this study.

Our management believes that this broad expression of GSK-3β supports the development of

elraglusib in several different cancer types.

As the Actuate-1801 study was

ongoing, studies in preclinical tumor models from several collaborating laboratories that were evaluating elraglusib reported that elraglusib

was also able to regulate expression of immune checkpoints such as PD-1/PD-L1, LAG-3 and TIGIT.

The data further credentialed GSK-3β

as a novel target for mediating anti-tumor immunity, which had been reported by a number of groups over the past decade, and demonstrated

the potential for immune checkpoint modulatory activity for elraglusib.

These were novel observations for elraglusib in addition to previously

described roles in attenuating anti-apoptotic activity, NF-κB and DDR mediated drug resistance and enhancing chemotherapy and suggested

that elraglusib may inhibit tumor progression through multiple mechanisms of action.

Circulating tumor cells isolated

from a patient with adult T cell leukemia/lymphoma (“ATLL”) in the Actuate-1801 study (Part 1) who experienced a durable

PR (406 days) while on single agent elraglusib also exhibited robust cytokine changes when treated with elraglusib ex vivo.

Huntington et al 2 showed that plasma from elraglusib-treated patients in the Actuate-1801 Part 1 clinical study

demonstrated reduced VEGF and BAFF and elevated IL-1β, CCL22, and CCL4 concentrations that correlated with longer survival.

paired tumor biopsies from patients in the Actuate-1801 study, Huntington et al also showed that tumor-infiltrating immune cells

had reduced expression of inhibitory immune checkpoints (VISTA, PD-1, PD-L2) and elevated expression of T cell activation markers (CTLA-4,

OX40L) after elraglusib treatment.

Taken together, our management

believes that these early studies further support elraglusib’s multimodal mechanism of action including immune modulation and inhibition

of immune evasion.

Given that a number of recent reports have highlighted that drugs that modulate anti-tumor immune response may improve

mOS with little or no effect on ORR, we re-analyzed all the Actuate-1801 Part 1 and 2 data with respect to OS.

Support for planned Phase 2

indications is provided by data extracted from Actuate-1801 Part 1 in patients with metastatic melanoma.

Actuate-1801 Part 1

enrolled 11 patients with metastatic melanoma who received only single agent elraglusib and demonstrated an mOS of 9.1 months, which

compares favorably to the mOS of 6.9 months for salvage chemotherapy in a similar patient population.

Our management believes that

we have potentially identified a method for enriching patients diagnosed with metastatic melanoma who are refractory to checkpoint inhibitors

but may benefit from elraglusib.

Patient selection and enrichment could improve the probability of success in a future Phase 2 trial

These 11 Actuate-1801 Part 1 patients were refractory to several lines of treatment including immune checkpoint inhibitors

and would typically be candidates for chemotherapy salvage with an expected mOS of 6.9 months based on a meta-analysis of many different

chemotherapy regimens tested in the salvage setting in this patient population.

In Actuate-1801 Part 1, one metastatic melanoma patient

with widely metastatic disease to the brain, lungs, bones, muscles, stomach, lymph nodes, pancreas and adrenal glands received Elraglusib

Injection as a single agent.

This patient was refractory to all FDA-approved standard therapies, including several checkpoint inhibitors

and a BRAF/MEK inhibitor.

This patient reported a partial response at 6 weeks and after 12 weeks on elraglusib, the patient’s brain

MRI showed a CR by RANO criteria and a PET scan showed CMR for other lesions.

This patient continues to have a durable CMR ongoing (>5.5 years

as of November 15, 2024) and continues to receive the investigational drug elraglusib.

A second melanoma patient who received single agent

elraglusib has ongoing stable disease and was still alive for 3.1 years as of last documented alive date.

This patient also failed

all FDA-approved standard therapies including immune checkpoint inhibitors and several experimental treatments.

These are extraordinary

results and should not be considered representative of all patients or all outcomes.

Similarly, Actuate-1801 Part 2

data in the irinotecan chemotherapy basket identified metastatic colorectal (in combination with irinotecan) as another potential Phase 2

indication for elraglusib based on mOS of 6.9 months for patients who were heavily pre-treated and refractory to chemotherapy.

compares favorably with expected mOS of less than 3 months for this same patient population treated with salvage chemotherapy or

best supportive care.

Safety in Actuate-1801 Part 1 and 2

In both Parts 1 and 2, all patients

experienced TEAEs.

TEAEs broadly encompass all adverse events observed while a patient is on study and could be due to the drug or drugs

(if used in combination), the disease or something specific to a particular patient such as other diseases or illness.

It is then up to

the individual clinical investigator to decide which toxicities are due to elraglusib.

The most common TEAEs attributed to elraglusib

were transient visual disturbance and fatigue across both study parts, and the majority of TEAEs that occurred in ≥ 20% of patients

were reported as Grade 1 or 2.

Visual disturbance affected 50.7% of patients (n=34/67) receiving elraglusib monotherapy and 60.8% of patients

(n=104/171) receiving elraglusib with chemotherapy.

Commonly reported symptoms were darkened vision, where patients described lights as

brighter and skin tones appearing darker.

Greater than 99% of visual disturbance cases were reported as mild or moderate (Grade 1 or 2).

These visual disturbances were considered dose-dependent, occurring more frequently and lasting longer at higher doses.

All cases of visual

disturbance were transient, resolved completely, and lacked any associated retinal, ocular, or systemic toxicity.

Fatigue, while also

observed in ≥ 20% of patients, was also reported as mild or moderate (Grade 1 or 2) and did not interfere with daily life.

____________________

2 Huntington KE, Louie AD, Srinivasan PR, Schorl C, Lu S, Silverberg

D, Newhouse D, Wu Z, Zhou L, Borden BA, Giles FJ, Dooner M, Carneiro BA, El-Deiry WS.

GSK-3 Inhibitor Elraglusib Enhances Tumor-Infiltrating

Immune Cell Activation in Tumor Biopsies and Synergizes with Anti-PD-L1 in a Murine Model of Colorectal Cancer.

Int J Mol Sci.

29;24(13):10870.

In addition to the company sponsored

trials and the Weekes IIT referenced above, elraglusib is currently being evaluated in an additional IIT.

We track patient accrual and

SAEs in these trials and report these to our IND.

IND 156280 is a Phase 2 study

of elraglusib plus carboplatin in patients with advanced, metastatic salivary gland carcinoma being conducted by Dr.

study administered elraglusib by intravenous infusion twice weekly in combination with carboplatin administered once every 21 days

in adults with incurable, recurrent or metastatic salivary gland carcinomas.

A total of 32 patients were enrolled and this study is now

Final data analysis is ongoing and the study has been submitted for presentation at the AACR Annual Meeting 2025 with a final

data report anticipated by the end of 2025.

The elraglusib dose used in this study is lower than the levels recommended by our studies.

250 mg oral tablet and 137,000 ng•h/mL after oral administration of 500 mg (2 x 250 mg tablets).

We expect that steady state exposures

of 77,000 ng•h/mL or greater will be possible with the Elraglusib Oral Tablet at well-tolerated doses in humans.

We believe that

we will be able to administer the Elraglusib Oral Tablet daily, which may allow the drug to achieve steady state levels in plasma in

patients resulting in continuous inhibition of the target GSK-3 in the tumor and tumor-associated cells.

Based on the potential for daily

dosing, we believe this will allow for additional opportunities to explore the anti-tumor activity of elraglusib with the oral tablet

that could not be achieved with Elraglusib Injection.

Our lead clinical candidate

tablet, the Elraglusib Oral Tablet, has been selected for further development, and we are planning a Phase 1/2 dose escalation study to

identify the MTD and RP2D for Elraglusib Oral Tablet in adult patients with advanced, refractory cancers, subject to future funding.

we have determined a RP2D, several Phase 2 studies have been identified for further clinical development of Elraglusib Oral Tablet based

on data from the Actuate-1801 study in indications, including but not limited to, refractory, metastatic melanoma and refractory, metastatic

colorectal cancer, and non-small lung cancer.

Investigator-Initiated Trials

In addition to company-sponsored

trials, we have collaborated with a number of investigators through investigator-initiated trials (“IIT”) to evaluate elraglusib

in new indications and with new drug combinations.

Two of these IITs will provide exploratory data on the combination of elraglusib and

FOLFIRINOX as a first-line treatment for mPDAC and may provide a rationale for developing elraglusib in combination with FOLFIRINOX or

NALIRIFOX as another first-line treatment for mPDAC.

Since either GnP or FOLFIRINOX are currently used to treat the majority of patients

with mPDAC, we believe that elraglusib has the potential to treat a large segment of patients diagnosed with mPDAC.

In August 2025, we supported

commencement of a Phase 1b IIT with UPMC Hillman Cancer Center.

The trial is evaluating elraglusib in combination with Incyte’s

PD-1 inhibitor, retifanlimab, and modified FOLFIRINOX (“mFOLFIRINOX”) as front-line therapy in advanced pancreatic adenocarcinoma

in up to 12 patients.

This IIT is an open-label, single-arm RiLEY (NCT06896188) trial, led by Anwaar Saeed, MD, Associate Professor of

Medicine, and Chief of the Gastrointestinal Medical Oncology at UPMC Hillman Cancer Center.

The primary objective of the trial is to determine

the RP2D for the combination regimen, while the secondary objectives include evaluation of ORR, DCR, mPFS, OS, and assessment of safety

and tolerability.

The trial is currently open for enrollment, and four patients have been enrolled as of February 28, 2026.

In February 2022, we supported

commencement of a Phase 2 IIT to determine the safety, tolerability, and progression-free survival of the combination of elraglusib with

FOLFIRINOX and losartan in adults with untreated metastatic pancreatic adenocarcinoma.

The IIT is being led by Colin Weekes, MD Ph.D.

at Massachusetts General Hospital and is supported by us and the Lustgarten Foundation.

Additional sites participating in the study include

The University of Colorado and the University of Washington’s Fred Hutchinson Cancer Center.

This study administers elraglusib by

IV infusion twice weekly in combination with FOLFIRINOX administered once every 14 days and daily losartan in adults with pancreatic

cancer who have not received any prior systemic therapy for advanced disease.

A total of 49 patients have been enrolled in the study.

We expect to receive all final data from this study, which is considered exploratory and may inform future development of elraglusib in

Our Market Opportunity

Treatment of Metastatic Pancreatic Ductal Adenocarcinoma

According to the American

Cancer Society, the annual incidence of pancreatic cancer is expected to exceed 67,000 patients in the United States in 2026, and the

majority of these patients will present with metastatic disease.

The Pancreatic Cancer Treatment Market Size Report, 2030 by Grand View

Research, estimates the current global market for treating pancreatic cancer was approximately $2.9 billion in 2024 and is expected to

grow to $5.8 billion by 2030 based on the growing aging population and associated rise in lifestyle-related diseases.

Current first-line therapies

for mPDAC consist of GnP, FOLFIRINOX, or irinotecan liposomal injection given with oxaliplatin, fluorouracil, and leucovorin (“NALIRIFOX”).

NALIRIFOX was approved in February 2024 and may provide an alternative to FOLFIRINOX with a somewhat improved safety profile.

We are developing elraglusib

for patients in mPDAC who have not previously received systemic treatment for their metastatic disease.

Due to lack of early symptoms,

approximately 80-90% of all patients with pancreatic cancer are unresectable, and present with advanced or metastatic disease.

80-90% of PDAC cases do not have a high tumor mutational burden in general, and are unlikely to respond to checkpoint inhibitors such

as pembrolizumab.

Pembrolizumab has been approved for patients with metastatic solid cancer with high tumor burden but is rarely used

in metastatic pancreatic cancer for this reason.

However, frequent mutations in KRAS and TP53 oncogenes drive pancreatic tumor growth

and treatment resistance, often making PDAC refractory to chemotherapy.

A recent review of real-world

clinical trials in Future Oncology showed

that the mOS in patients with mPDAC treated with GnP ranged from approximately 3.6 to 9.8 months with an unweighted mOS of 6.9 months.

Therefore, we believe the ability to extend survival by even a few months would be considered meaningful in this patient population.

We believe elraglusib may

improve outcomes in first-line mPDAC regardless of the chemotherapy backbone used by doctors.

Patients with mPDAC are often resistant

or become resistant to the first-line chemotherapy backbones currently used to treat them.

One of the mechanisms of action of elraglusib

is the ability to enhance chemotherapy activity even in resistant tumors, and we believe this has been demonstrated in multiple animal

tumor models.

Elraglusib has shown the ability to enhance the activity of several chemotherapy drugs that comprise the current first-line

backbones in mPDAC including gemcitabine, nab-paclitaxel and irinotecan, suggesting the potential for elraglusib to be used in combination

with multiple first-line mPDAC treatments.

Treatment of Pediatric Cancers

EWS is a rare malignancy that

occurs primarily in the bone or in the soft tissue around a bone.

The tumor is most common in older children and adolescents, but it can

occur at any age.

According to American Cancer Society, Ewing sarcoma accounts for about 1% of all childhood cancers and approximately

200 children and adolescents in the United States are diagnosed annually with EWS.

Treatment options include surgery, radiotherapy, chemotherapy,

and tyrosine kinase inhibitors.

The response to therapy is dependent on the stage of the tumor.

Overall, the 5-year survival rates range

from 81% for patients with localized disease to 41% for patients with metastatic disease.

The five-year survival rate for patients who

have recurrent (relapsed) disease is <30% with no known treatment regimens that meaningfully extend life in Ewing sarcoma patients

with metastatic, refractory disease.

Neuroblastoma is a rare cancer

of the early nerve cells, called neuroblasts, that make up the nerves in our bodies.

According to American Cancer Society, neuroblastoma

is the most common cancer in infants who are less than 1 year old.

There are about 600 to 800 new cases of neuroblastoma each year in

the United States.

The 5-year survival rates range from 95% for lower risk patients to 60% for patients with higher risk disease per the

American Cancer Society, and neuroblastoma claims more lives of children under the age of 5 than any other cancer.

The FDA has granted RPDD to

elraglusib for our treatment of EWS and neuroblastoma.

Rare Pediatric Disease Designation is granted by the FDA for serious or life-threatening

diseases that affect fewer than 200,000 people in the United States and in which the serious or life-threatening manifestations primarily

affect individuals less than 18 years of age.

If, in the future, a New Drug Application (“NDA”) for elraglusib for the treatment

of Ewing sarcoma or neuroblastoma is approved by the FDA, we may be eligible to receive a Priority Review Voucher (“PRV”)

that could be utilized by us or potentially sold to another company for its use.

There are no approved high-affinity

inhibitors of GSK-3β, and we believe elraglusib is one of the most advanced GSK-3β inhibitors in clinical development.

GSK-3β inhibition may

exert anticancer activity through a variety of mechanisms that may be context and cancer type specific.

For example, GSK-3β mediates

signaling of oncogenic PI-3K but if this oncogene is not expressed in a particular tumor, this would not be a pathway that could be targeted

by elraglusib in that tumor.

Potential antitumor activity through GSK-3β inhibition may occur through multimodal mechanisms of action,

(1) Immune modulation;

(2) Inhibiting cell proliferation;

(3) Reducing tumor fibrosis;

(4) Decreasing immune evasion;

(5) Increasing apoptosis and disrupting DNA damage repair;

(6) Inhibition of epithelial-mesenchymal transitions (“EMT”).

GSK-3β plays an important

role in immune cell function, as inhibition of GSK-3β can facilitate immune cell expansion, differentiation and activation including

T and natural killer (“NK”) cells.

Inhibition of GSK-3β leads to inhibition of tumor cell proliferation as shown in multiple

tumor model systems using elraglusib.

A number of pathways have been implicated in the inhibition of cell proliferation mediated by GSK-3β

inhibitors including MYC, Cyclin D1, TGFα, epidermal growth factor receptor, Ras, PI3K/Akt, and NF-κB.

Also, a chronic inflammatory

microenvironment is conducive to tumorigenesis (e.g., pancreatitis patients are known to have increased risk of pancreatic cancer), and

tumors can undergo EMT, leading to increased metastasis, under inflammatory conditions.

Further, GSK-3β has also been demonstrated

to be a mediator of EMTs.

Therefore, the inflammatory response designed to fight tumor progression also ends up promoting metastasis and

tumor-associated fibrosis.

In addition, a number of studies have suggested that the primary mechanism of GSK-3β -mediated apoptosis

is through the NF-κB pathway.

Studies have shown that eliminating or inhibiting GSK-3β in cancer cells is able to restore apoptosis

to cells, leading to tumor cell death.

These findings support GSK-3β as a potential therapeutic target to potentiate apoptosis in

cancer cells.

GSK-3β has been shown to be a mediator of a number of signaling pathways that regulate the transition of tumor cells

from an epithelial to mesenchymal phenotype potentially contributing to tumor progression, a process known as EMT.

Signaling through Wnt,

Notch, TGF-β and Snail are known mediators of EMT, and their signaling is regulated through GSK-3β.

Several toolkit GSK-3β

inhibitors have been shown to inhibit EMT in tumor models suggesting that this is a class effect and highlighting a similar mechanism

for elraglusib.

License Agreements

Northwestern University License Agreement

We licensed the exclusive worldwide

rights to materials and non-exclusive rights to certain know-how relating to the use for therapeutic, diagnostic and commercial research

purposes of elraglusib and related compounds in cancer and combination therapies from NU pursuant to that certain royalty-free license

agreement between us and NU dated March 31, 2015, as amended on April 29, 2019 (as amended, the “NU License Agreement”).

Pursuant to the NU License Agreement,

NU granted us (i) a nonexclusive license to certain technical information developed in the laboratory of Dr.

Mazar, and (ii) an

exclusive license to all results obtained by Dr.

Mazar and his collaborators at NU on the use of the GSK-3β inhibitor 9-ING-41

and related compounds used for the treatment of cancer and combination therapies.

The term of the NU License Agreement continues in effect

until the expiration of the last to expire of patent rights covering 9-ING-41 and related GSK-3 inhibitors (see the discussion under “ Intellectual

Property” below for a discussion of our expected patent terms), unless earlier terminated by NU due to our making a general

assignment for the benefit of creditors, initiation of bankruptcy proceedings by or against us or the appointment of a receiver or trustee

to take possession of our property, or by either party following 90 days’ notice of a material breach of the NU License Agreement

that is not then cured.

The NU License Agreement terms are subject to the provisions of the Bayh-Dole Act, including requiring us to substantially

manufacture products related to the license in the United States, unless waived.

While the drug substance (“DS”) for elraglusib

is manufactured by a supplier in China, the end drug product is substantially manufactured in the United States.

We licensed the exclusive

worldwide rights to materials and non-exclusive rights to certain know-how relating to the use for therapeutic, diagnostic and commercial

research purposes of elraglusib and related compounds in cancer and combination therapies from NU pursuant to that certain royalty-free

license agreement between us and NU dated March 31, 2015, as amended on April 29, 2019 (as amended, the “NU License Agreement”).

Pursuant to the NU License

Agreement, NU granted us (i) a nonexclusive license to certain technical information developed in the laboratory of Dr.

and (ii) an exclusive license to all results obtained by Dr.

Mazar and his collaborators at NU on the use of the GSK-3β

inhibitor 9-ING-41 and related compounds used for the treatment of cancer and combination therapies.

The term of the NU License Agreement

continues in effect until the expiration of the last to expire of patent rights covering 9-ING-41 and related GSK-3 inhibitors (see the

discussion under “ Intellectual Property” below for a discussion of our expected patent terms), unless earlier

terminated by NU due to our making a general assignment for the benefit of creditors, initiation of bankruptcy proceedings by or against

us or the appointment of a receiver or trustee to take possession of our property, or by either party following 90 days’ notice

of a material breach of the NU License Agreement that is not then cured.

The NU License Agreement terms are subject to the provisions

of the Bayh-Dole Act, including requiring us to substantially manufacture products related to the license in the United States, unless

While the drug substance (“DS”) for elraglusib is manufactured by a supplier in China, the end drug product is substantially

manufactured in the United States.

In consideration of the license

11 unchanged sentences

The following summarizes the key terms set forth in the UIC License Agreement.

Pursuant to the UIC License Agreement,

UIC granted us (i) an exclusive, nontransferable license, with the right to sublicense under UIC’s rights in the Patent Rights,

and (ii) a non-exclusive, non-transferable license, with the right to sublicense, to use UIC’s rights in the Technical Information

within the specified territory (which is where the Patent Rights exist for such rights and worldwide for the Technical Information) for

all uses other than rights reserved by UIC for non-commercial purposes, including teaching, research and public service and publishing

information included in the Patent Rights and the Technical Information.

The term of the UIC License Agreement continues in effect until

the later of (x) expiration of the last to expire of the Patent Rights, (y) notice from us that the use of the Technical Information

has ceased, and (z) the expiration of the last form of market exclusivity for products using the licensed technology.

The UIC License

Agreement may also be earlier terminated by UIC in the event of certain breaches of its terms that are not cured following a notice period

or initiation of bankruptcy proceedings by or against us or the imposition of any lien or encumbrance on the licensed technology.

also terminate the UIC License Agreement for any reason following 90 days’ notice.

Pursuant to the UIC License

Agreement, UIC granted us (i) an exclusive, nontransferable license, with the right to sublicense under UIC’s rights in the

Patent Rights, and (ii) a non-exclusive, non-transferable license, with the right to sublicense, to use UIC’s rights in the

Technical Information within the specified territory (which is where the Patent Rights exist for such rights and worldwide for the Technical

Information) for all uses other than rights reserved by UIC for non-commercial purposes, including teaching, research and public service

and publishing information included in the Patent Rights and the Technical Information.

The term of the UIC License Agreement continues

in effect until the later of (x) expiration of the last to expire of the Patent Rights, (y) notice from us that the use of the

Technical Information has ceased, and (z) the expiration of the last form of market exclusivity for products using the licensed technology.

The UIC License Agreement may also be earlier terminated by UIC in the event of certain breaches of its terms that are not cured following

a notice period or initiation of bankruptcy proceedings by or against us or the imposition of any lien or encumbrance on the licensed

We may also terminate the UIC License Agreement for any reason following 90 days’ notice.

In consideration of the license

2 unchanged sentences

of which, up to $0.25 million is due upon the progress of clinical trials and $1.0 million is due upon the initiation of commercial

sales (ii) annual minimum royalty payments of $5,000 beginning on the three-year anniversary of the UIC License Agreement and increasing

to $15,000 in year four, $35,000 in year five, and $50,000 in year six and thereafter, (iii) royalty on net sales for product covered

under the Patent Rights in the low single digits with a 50% reduction in royalties for products solely utilizing Technical Information,

(iv) a declining percentage of sublicensing revenue based on the escalating stage of development upon a sublicensing event,

and (v) the reimbursement of all patent and related expenses incurred by UIC covering the Patent Rights.

We also agreed to customary

confidentiality and progress update obligations, to indemnify UIC for any claims arising from our use of the licensed rights under the

UIC License Agreement.

The UIC License Agreement obligates

us or a sublicensee to commercialize the licensed technology, including to achieve the development events specified in the agreement,

sales (ii) increasing annual minimum royalty payments reaching $50,000 in year six and thereafter, (iii) royalty on net sales

for product covered under the Patent Rights in the low single digits with a 50% reduction in royalties for products solely utilizing Technical

Information, (iv) a declining percentage of sublicensing revenue based on the escalating stage of development upon a sublicensing

event, and (v) the reimbursement of all patent and related expenses incurred by UIC covering the Patent Rights.

We also agreed to

customary confidentiality and progress update obligations, to indemnify UIC for any claims arising from our use of the licensed rights

under the UIC License Agreement.

The UIC License Agreement

obligates us or a sublicensee to commercialize the licensed technology, including to achieve the development events specified in the agreement,

including progress through clinical trials and achieving commercialization.

11 unchanged sentences

drug product is substantially manufactured in the United States.

In addition, we entered into a

sublicense and collaboration agreement dated August 28, 2017 with an unrelated entity that was covered under the UIC License Agreement,

In addition, we entered into

a sublicense and collaboration agreement dated August 28, 2017 with an unrelated entity that was covered under the UIC License Agreement,

which sublicense agreement was later terminated on January 31, 2018.

6 unchanged sentences

The Deferred Amount is treated as debt and continues to accrue interest at a rate of five percent (5%) per annum, representing

the prime rate as of the date of the agreement plus 1%.

On July 16, 2024, the Company and UIC entered an amendment to the UIC License

Agreement (“UIC Amendment”).

Pursuant to the UIC Amendment, accrued interest is due and payable in two installments:

was due within 30 days following the closing of the Company’s IPO;

and (ii) 50% is due within 30 days following the first anniversary

of the closing of the IPO.

Thereafter, interest will be paid annually within 30 days following the second anniversary of the closing of

the IPO and annually thereafter.

In addition, the UIC Amendment provides for payment of the Deferred Amount and any accrued interest thereon

upon the sooner of (i) termination of the UIC License Agreement by the Company, (ii) the Company ceases development of the licensed UIC

technology, (iii) the Company consummates a Change in Control (as defined in the UIC License Agreement), (iv) the Company sublicenses

the licensed technology or the developed product, (v) the one-year anniversary following approval of a NDA of a licensed product, or (vii)

the Company executes a partnership agreement with any entity resulting in the payment to us above a specified milestone amount or the

Company secures cumulative financing equal to or exceeding $200 million.

In addition, the UIC Amendment provides that to the extent the

Company secures equity financing equal to or exceeding $85 million through its IPO or otherwise, 50% of the Deferred Amount is due and

payable within 30 days.

The remaining 50% of the Deferred Amount shall be due and payable upon the first to occur of any of the events

noted above in clauses (i) through (vii).

Finally, the UIC Amendment provides that for as long as the Company or a sublicensee is selling

the licensed product, the Company will pay all consideration provided for in the original UIC License Agreement and described above until

the last to expire market exclusivity date, the period of which for all products in a jurisdiction will not exceed a total of seven (7)

years beginning with the date regulatory approval is granted for the first licensed product in the jurisdiction, and such obligation will

survive termination of the UIC License Agreement.

Interest payable to UIC was $77,725

as of December 31, 2024, of which $70,957 is classified as current and $6,768 is classified as non-current, and are included in the accompanying

consolidated balance sheet.

At December 31, 2023, accrued interest to UIC was $130,041, which is included in the accompanying consolidated

balance sheet.

the prime rate as of the date of the agreement plus 1%, payable annually within 30 days following the second anniversary of the closing

of the IPO and annually thereafter.

On July 16, 2024, the Company and UIC entered an amendment to the UIC License Agreement (“UIC

Pursuant to the UIC Amendment, the payment of the Deferred Amount and any accrued interest thereon is due upon the

sooner of (i) termination of the UIC License Agreement by the Company, (ii) the Company ceases development of the licensed UIC technology,

(iii) the Company consummates a Change in Control (as defined in the UIC License Agreement), (iv) the Company sublicenses the licensed

technology or the developed product, (v) the one-year anniversary following approval of a NDA of a licensed product, or (vii) the Company

executes a partnership agreement with any entity resulting in the payment to us above a specified milestone amount or the Company secures

cumulative financing equal to or exceeding $200 million.

In addition, the UIC Amendment provides that to the extent the Company secures

equity financing equal to or exceeding $85 million through its IPO or otherwise, 50% of the Deferred Amount is due and payable within

The remaining 50% of the Deferred Amount shall be due and payable upon the first to occur of any of the events noted above in

clauses (i) through (vii).

Finally, the UIC Amendment provides that for as long as the Company or a sublicensee is selling the licensed

product, the Company will pay all consideration provided for in the original UIC License Agreement and described above until the last

to expire market exclusivity date, the period of which for all products in a jurisdiction will not exceed a total of seven (7) years beginning

with the date regulatory approval is granted for the first licensed product in the jurisdiction, and such obligation will survive termination

of the UIC License Agreement.

Collaboration Agreement

5 unchanged sentences

shares if results from the collaboration are utilized in future development efforts.

Our former director, Les Kreis, Jr., was a director

of Lantern Pharma until June 8, 2022.

Certain affiliates of the Bios Equity Affiliated Funds (as defined below), which is our largest

stockholder, beneficially owned greater than 10% of Lantern Pharma’s common stock as of December 31, 2024.

Through December 31,

2024, no revenue has been recognized by either party under this agreement.

Kreis was not involved in the negotiation of this

agreement and the negotiations were conducted at arm’s length.

Certain affiliates of the Bios Equity Affiliated

Funds (as defined below), which is our largest stockholder, beneficially owned greater than 10% of Lantern Pharma’s common stock

as of December 31, 2025.

Through December 31, 2025, no revenue has been recognized by either party under this agreement.

Intellectual Property

The proprietary nature of, and

protection for, our product candidates and their methods of use and compositions of matter are an important part of our strategy to develop

and commercialize novel medicines, as described in more detail below.

The proprietary nature of,

and protection for, our product candidates and their methods of use and compositions of matter are an important part of our strategy to

develop and commercialize novel medicines, as described in more detail below.

Our policy is to file patent applications to protect technology,

7 unchanged sentences

As of December 31, 2025,

we own or have licensed 88 issued patents and pending patent applications worldwide, including two pending international Patent Cooperation

Treaty (“PCT”) patent applications and four U.S.

provisional patent applications, which are material to the programs described

in this Report.

Three of these issued worldwide patents are owned by UIC, which has granted us exclusive license rights to the technology.

we own or have licensed 119 issued patents and pending patent applications worldwide, including four pending international Patent Cooperation

Treaty (“PCT”) patent applications, which are material to the programs described in this Report.

Three of these issued worldwide

patents are owned by UIC, which has granted us exclusive license rights to the technology.

With respect to our elraglusib

6 unchanged sentences

Actuate subsequently discovered

that elraglusib exists as one of only two polymorphs and filed composition of matter patents covering both polymorphs.

The patent family

covering “Polymorph I” is based on PCT/US2018/046203 9-ING-41 Polymorph I Composition of Matter and includes two granted patents

(US 11,136,334 and 12,145,943) and Mexico, one granted patent in each of Australia, China, Europe (with validation in 18 countries),

Japan, Israel, and South Korea, and pending patent applications in Australia, Brazil, Canada, China, Hong Kong, Israel, Japan, Macao,

South Korea, South Africa and the U.S., which are directed to a polymorph of a GSK-3β inhibitor, compounds, pharmaceutical compositions,

methods of preparing and uses for treating cancers.

patent is expected to expire in 2038.

that elraglusib exists as only two polymorphs and filed composition of matter patents covering both polymorphs.

The patent family covering

“Polymorph I” is based on PCT/US2018/046203 9-ING-41 Polymorph I Composition of Matter and includes two granted patents in

(US 11,136,334 and 12,145,943) and three granted patents in Mexico, and two granted patents in Australia and Japan, one granted

patent in each of China, Europe (with validation in 18 countries), Israel, and South Korea, and pending patent applications in Australia,

Brazil, Canada, China, Hong Kong, Israel, Japan, Macao, South Korea, South Africa and the U.S., which are directed to a polymorph of a

GSK-3β inhibitor, compounds, pharmaceutical compositions, methods of preparing and uses for treating cancers.

expected to expire in 2038.

The patent family we own that

covers elraglusib “Polymorph II” is based on PCT/US2018/056083 9-ING-41 Polymorph II Composition of Matter and includes two

patents (US 11,407,759 and 12,116,374), one granted patent in each of Australia, China, Mexico and Macao, and pending patent

applications in Brazil, Canada, the European Patent Office, Israel, Japan, South Korea, South Africa and the U.S., which are directed

to a polymorph of a GSK-3β inhibitor, compounds, pharmaceutical compositions, methods of preparing and uses for treating cancers.

patents (US 11,407,759 and 12,116,374), one granted patent in each of Europe (validated in France, Austria, Belgium, Switzerland,

Germany, Denmark, Spain, Finland, the United Kingdom, Greece, Ireland, and Italy) Australia, China, Mexico and Macao, South Korea, Japan,

and Israel, and pending patent applications in Brazil, Canada, the European Patent Office, Japan, South Africa and the U.S., which are

directed to a polymorph of a GSK-3β inhibitor, compounds, pharmaceutical compositions, methods of preparing and uses for treating

patent is expected to expire in 2038.

We intend to file additional patent

applications for the liquid and solid formulations of these elraglusib compositions covering the liquid and solid oral dosage forms of

elraglusib that we expect to develop.

The patent family we own that

covers oral dosage forms of elraglusib is based on PCT/US2023/069158.

Patent applications are pending in Australia, Brazil, Canada, China,

Europe, Israel, India, Japan, South Korea, Mexico, Hong Kong, South Africa, and the U.S.

The term of individual patents

44 unchanged sentences

institutions, government agencies and public and private research institutions, among others.

Any product candidates that we

successfully develop and potentially commercialize will compete with currently approved therapies and new therapies that may become available

in the future.

Key product features that would affect our ability to effectively compete with other therapeutics include the efficacy,

safety and convenience of our products.

Our most advanced clinical program

is being evaluated in a Phase 2 clinical trial as a first line treatment for mPDAC.

The current standard first-line chemotherapies for

mPDAC include GnP, FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) or NALIRIFOX (liposomal irinotecan, 5-fluorouracil,

leucovorin and oxaliplatin), and are associated with modest overall survival benefit.

We are presently developing elraglusib

Any product candidates that

we successfully develop and potentially commercialize will compete with currently approved therapies and new therapies that may become

available in the future.

Key product features that would affect our ability to effectively compete with other therapeutics include the

efficacy, safety and convenience of our products.

Our most advanced clinical

asset, Elraglusib Injection (“elraglusib”) is being evaluated in a Phase 2 clinical trial as a first-line treatment for mPDAC.

The current standard first-line treatments for mPDAC include GnP, FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin)

or NALIRIFOX (liposomal irinotecan, 5-fluorouracil, leucovorin and oxaliplatin), and are associated with modest overall survival benefit.

We are developing elraglusib

in combination with GnP as a first-line treatment for mPDAC.

In addition, we are also supporting an ongoing IIT that may provide exploratory

In addition, we are also supporting an ongoing IIT that will provide exploratory

data on the combination of elraglusib and FOLFIRINOX as a first-line treatment for mPDAC.

2 unchanged sentences

Patients with mPDAC either have primary

resistance to these chemotherapy backbones (e.g., do not respond at all when treated) or develop resistance quickly (responses with GnP,

FOLFIRINOX and NALIRIFOX are transient and not very durable).

resistance to these chemotherapy backbones (e.g., do not respond when treated) or develop resistance quickly (responses with GnP, FOLFIRINOX

and NALIRIFOX are transient and not very durable in most patients).

Our management believes that elraglusib may improve outcomes in first-line

1 unchanged sentence

Nevertheless, since

either GnP or FOLFIRINOX are used to treat >90% of patients with mPDAC and there is potential for combining elraglusib with either

of these chemotherapy backbones based on our ongoing clinical studies, our management believes that elraglusib has the potential to treat

either GnP or FOLFIRINOX are currently used to treat the majority of patients with mPDAC and there is potential for combining elraglusib

with either of these chemotherapy regimens based on our ongoing clinical studies, we believe that elraglusib has the potential to treat

a large segment of patients diagnosed with mPDAC.

2 unchanged sentences

FOLFIRINOX or NALIRIFOX pending results of the IIT.

If shown to be clinically meaningful, elraglusib chemotherapy combinations could eventually

be used to treat a large segment of patients with mPDAC.

If shown to be clinically meaningful, elraglusib plus standard of care chemotherapy

combinations could eventually be used to treat a large segment of patients with mPDAC.

In addition, we are also supporting a recently

initiated Phase 1b IIT trial of elraglusib in combination with Incyte’s PD-1 inhibitor, retifanlimab, and modified FOLFIRINOX (“mFOLFIRINOX’)

as a frontline therapy in advanced PDAC, representing another combination therapy that could expand the potential of elraglusib in first-line

Several other targeted therapies

6 unchanged sentences

untreated mPDAC.

Both of these studies have only recently been initiated.

There are other studies combining immune checkpoint inhibitors,

PARP inhibitors, various chemotherapies and other RAS inhibitors in patients with mPDAC including second-line studies.

However, many of

the targeted agents besides elraglusib are only able to target a small percentage of mPDAC patients based on the presence of the target

or other genomic information.

Ongoing studies with many of these agents in mPDAC are generally non-randomized at one or a limited number

of sites, are too early to assess for commercial potential and would not be considered as a competitor to elraglusib because of their

lack of broad suitability for most mPDAC patients.

For example, the PARP inhibitor Lynparza (olaparib) was recently approved as a maintenance

therapy as it has been shown to significantly improve PFS and duration of response in patients with BRCA-mutated mPDAC who have not progressed

following first-line platinum-based chemotherapy.

However, BRCA mutations are only present in 4-7% of all PDAC patients.

Olaparib is currently

being evaluated as a therapeutic intervention in combination with a checkpoint inhibitor, pembrolizumab, in patients with mPDAC in BRCA1

mutated patients.

Similarly, many of the RAS mutations targeted by clinical RAS inhibitors are only present in a low percentage of

all PDAC and thus, of the current PDAC inhibitors available in the clinic, few PDAC patients would be expected to benefit from their treatment.

Thus, the vast majority of mPDAC

patients still do not have an approved targeted therapy that can treat their tumor.

If successful, we believe the elraglusib/chemotherapy

combination would introduce the first broadly targeted agent, elraglusib, as a treatment option for patients with mPDAC and would have

the potential to treat the majority (80-90%) of patients with mPDAC.

A review of clinicaltrials.gov reveals that there are only a few

randomized studies for any novel drug or drug combination (not just targeted) in patients with mPDAC previously untreated for metastatic

There are other studies combining immune checkpoint inhibitors, PARP inhibitors, various chemotherapies and other RAS

inhibitors in patients with mPDAC including second-line studies.

Ongoing studies with many of these agents in mPDAC are generally non-randomized

at one or a limited number of sites, are too early to assess for commercial potential and may not represent a substantial competitive

threat to elraglusib because of their lack of broad suitability for most mPDAC patients.

For example, the PARP inhibitor Lynparza (olaparib)

was recently approved as a maintenance therapy as it has been shown to significantly improve PFS and duration of response in patients

with BRCA-mutated mPDAC who have not progressed following first-line platinum-based chemotherapy.

However, BRCA mutations are only present

in 4-7% of all PDAC patients.

Olaparib is currently being evaluated as a therapeutic intervention in combination with a checkpoint inhibitor,

pembrolizumab, in patients with mPDAC in BRCA1 mutated patients.

Despite these efforts, the

vast majority of mPDAC patients still do not have an approved targeted therapy that can treat pancreatic cancer.

If successful, we believe

the elraglusib/chemotherapy combination would introduce the first broadly targeted agent, elraglusib, as a treatment option for patients

with mPDAC and would have the potential to treat the majority of patients with mPDAC.

A review of clinicaltrials.gov reveals that there

are several randomized studies for any novel drug or drug combination (not just targeted) in patients with mPDAC previously untreated

for metastatic disease, including the following:

· Onivyde® (Ipsen Pharma):

Recently approved

for first-line mPDAC when used as part of the NALIRIFOX regimen based on a survival improvement of 1.9 months (NALIRIFOX 11.1 months

vs GNP 9.2 months).

for first-line mPDAC when used as part of the NALIRIFOX regimen based on an improvement in mOS of 1.9 months (NALIRIFOX mOS of 11.1 months

vs GnP mOS of 9.2 months).

· SBP-101 (Panbela Therapeutics, Inc.):

A randomized,

double-blind, placebo-controlled, multicenter study of standard treatment with nab-paclitaxel and gemcitabine with or without SBP-101

in subjects previously untreated for mPDAC.

· Zolbetuximab (Astellas):

A phase 2, open-label,

randomized study to assess the efficacy and safety of zolbetuximab (IMAB362) in combination with nab-paclitaxel and gemcitabine as first-line

treatment in subjects with claudin 18.2 (cldn18.2) positive, metastatic pancreatic adenocarcinoma.

double-blind, placebo-controlled, multicenter study (ASPIRE) of standard treatment with GnP with or without SBP-101 in subjects previously

untreated for mPDAC.

· Zolbetuximab and setidegrasib (Astellas):

A randomized , open-label, Phase

2 study (8951-CL-5201) to assess the efficacy and safety of zolbetuximab (IMAB362) in combination with GnP as first-line treatment in

subjects with claudin 18.2 (cldn18.2) positive, metastatic pancreatic adenocarcinoma.

Astellas is also planning a Phase 3 trial in 2026

of setidegrasib combined with mFOLFIRINOX in first-line mPDAC.

· Mitazalimab (Alligator Pharmaceuticals):

1b/2 study (OPTIMIZE-1) primary analysis was recently reported at ASCO 2024 (June 4, 2024).

Mitazalimab is a CD40 agonist hypothesized

to overcome the suppressive immune environment in PDAC.

OPTIMIZE-1 evaluated the combination of mitazalimab with mFOLFIRINOX in a single

arm study in patients with previously untreated mPDAC and met its ORR threshold >30% with an mOS of 14.3 months.

Previous clinical

studies using the CD40 agonist sotigalimab combined with GnP in patients with previously untreated mPDAC did not meet its primary endpoint

of 1 year OS compared to a historical 1-year OS of 35%.

· RASolute- daraxonrasib (Revolution Medicines,

To be determined (Not yet listed on the website www.clinicaltrials.gov).

· PRISM-1- quemliclustat (Arcus Biosciences, Inc.):

A randomized, placebo-controlled, double-blind, Phase 3 trial of quemliclustat and chemotherapy versus placebo and chemotherapy in patients

An open-label,

multi-center Phase 1b/2 study (OPTIMIZE-1) to assess the clinical efficacy of mitazalimab in combination with chemotherapy in patients

Mitazalimab is a CD40 agonist hypothesized to overcome the suppressive immune environment in PDAC.

OPTIMIZE-1 evaluated the

combination of mitazalimab with mFOLFIRINOX in a single arm study in patients with previously untreated mPDAC and met its primary endpoint

with an ORR of 42.1% and OS of 14.9 months.

Previous clinical studies using the CD40 agonist sotigalimab combined with GnP in patients

with previously untreated mPDAC did not meet their primary endpoint of 1 year OS compared to a historical 1-year OS of 35%.

· Daraxonrasib (Revolution Medicines, Inc.):

randomized Phase 3 trial (RASolute 303) in patients with first-line mPDAC that will evaluate daraxonrasib monotherapy and the combination

of daraxonrasib plus GnP, each compared to a control arm with GnP treatment.

This study was recently initiated in the fourth quarter of

· Quemliclustat (Arcus Biosciences, Inc.):

A randomized,

placebo-controlled, double-blind, Phase 3 trial (PRISM-1) of quemliclustat and chemotherapy versus placebo and chemotherapy in patients

with treatment-naive mPDAC.

This study was only recently initiated.

There are several treatments in

development for locally advanced or mPDAC.

· Atebimetinib (Immuneering Corporation):

A randomized,

Phase 3 trial (MAPKeeper 301) of atebimetinib in combination with modified gemcitabine and nab-paclitaxel.

This study is set to dose the

first patient in mid-2026.

· Certepetide (Lisata Therapeutics):

A randomized,

placebo-controlled, Phase 2b trial (ASCEND) to measure the effect of adding certepetide ,

compared to placebo, to chemotherapy (gemcitabine and nab-paclitaxel) in patients who have untreated mPDAC.

· Zabilugene almadenorepvec (Theriva Biologics):

A multicenter, open label, randomized, 2-parallel arm, Phase 2b trial (VIRAGE) evaluating intravenous zabilugene almadenorepvec in combination

with first-line standard of care chemotherapy in patients with newly-diagnosed mPDAC.

· Pelareorep (Oncolytics

An open label, multi-indication biomarker, safety, and efficacy Phase 2 trial (GOBLET Cohort 5) to explore the safety and efficacy

of pelareorep and mFOLFIRINOX with or without atezolizumab in patients with mPDAC.

There are several other treatments

in development for locally advanced or mPDAC.

The information cited above focuses only on select first-line treatments that are in clinical

1 unchanged sentence

Quite a few of these are very early stage and therefore little information is available on clinical activity to date.

With the initial success of biomarker driven and targeted therapies, there is an effort to test additional targeted agents in mPDAC patients

With the initial success of biomarker-driven targeted therapies, there is an effort to test additional targeted agents in mPDAC patients

to determine if there is any synergy with standard chemotherapy regimens in the first-line setting.

1 unchanged sentence

90% of pancreatic cancer patients and there are several KRAS targeted agents in development.

however, several agents are specifically

targeting the G12C mutation which only accounts for 1-2% of KRAS mutations in pancreatic cancer.

Other agents are being tested in KRAS

mutant cancers more broadly by targeting other MAPK pathway members such as MEK and ERK1/2, though treatment-related toxicity has been

reported with these agents.

Other agents are being tested in KRAS mutant

cancers more broadly by targeting other MAPK pathway members such as MEK and ERK1/2, though treatment-related toxicity has been reported

with these agents.

Additionally, these MAPK targeted agents are currently being evaluated in second-line and later settings.

In the future, targeted/ immunotherapy agents may be able to be combined or used in series to provide a more flexible and tailored therapeutic

approach for each individual patient.

Additionally, the multifaceted and differentiated mechanism of action of elraglusib is likely to

be synergistic with both cytotoxic and immunomodulatory therapeutics that may be approved in the future.

Our management believes that

this potential for combining elraglusib with future multi-therapy regimens is also feasible given favorable safety profile of elraglusib

as a single agent.

Mechanistically, some of the targets inhibited by competitors (e.g., KRAS) intersect with the GSK-3 pathways and provide

a rationale for potentially prioritizing these combinations with elraglusib in the future.

In the future,

targeted agents may be able to be combined or used in series to provide a more flexible and tailored therapeutic approach for each individual

Additionally, the multifaceted and differentiated mechanism of action of elraglusib is likely to be synergistic with both cytotoxic

and immunomodulatory therapeutics that may be approved in the future.

Our management believes that this potential for combining elraglusib

with future multi-therapy regimens is also feasible given the favorable safety profile of elraglusib as a single agent observed to date.

Mechanistically, some of the targets inhibited by competitors (e.g., KRAS) intersect with the GSK-3 pathways and provide a rationale for

potentially prioritizing these combinations with elraglusib in the future.

The above information includes

13 unchanged sentences

Government Regulation and Product Approval

Government authorities in the

United States, at the federal, state and local level, and other countries extensively regulate, among other things, the research, development,

testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval

monitoring and reporting, marketing and export and import of products such as those we are developing.

The pharmaceutical product candidates

that we develop must be approved by the FDA before they may be legally marketed in the United States.

See “Risk Factors — Risks

Related to Clinical Development and Regulatory Approval.”

Government authorities in

the United States, at the federal, state and local level, and other countries extensively regulate, among other things, the research,

development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution,

post-approval monitoring and reporting, marketing and export and import of products such as those we are developing.

The pharmaceutical

product candidates that we develop must be approved by the FDA before they may be legally marketed in the United States.

Pharmaceutical Product Development Process

In the United States, the FDA

regulates pharmaceutical products under the Federal Food, Drug and Cosmetic Act (“FDCA”) and implementing regulations.

Pharmaceutical

products are also subject to other federal, state and local statutes and regulations.

The process of obtaining regulatory approvals and

the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial

time and financial resources.

In the United States, the

FDA regulates pharmaceutical products under the Federal Food, Drug and Cosmetic Act (“FDCA”) and implementing regulations.

Pharmaceutical products are also subject to other federal, state and local statutes and regulations.

The process of obtaining regulatory

approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure

of substantial time and financial resources.

Failure to comply with the applicable U.S.

requirements at any time during the product development process,

approval process or after approval, may subject an applicant to administrative or judicial enforcement.

Any regulatory enforcement action

could have a material adverse effect on us.

The process required by the FDA before a non-biological pharmaceutical product may be marketed

in the United States generally involves the following:

· Completion of preclinical laboratory tests, animal

studies and formulation studies according to Good Laboratory Practices (“GLP”), and other applicable regulations;

· Submission of an Investigational New Drug application

(“IND”), which must become effective before human clinical studies may begin;

· Conduct of adequate and well-controlled human

clinical studies according to current Good Clinical Practices (“GCP”), to establish the safety and efficacy of the proposed

pharmaceutical product for its intended use;

· Submission to the FDA of an NDA for a new pharmaceutical

· Satisfactory completion of an FDA inspection

of the manufacturing facility or facilities where the pharmaceutical product is produced to assess compliance with current Good Manufacturing

Practice standards (“cGMP”), to assure that the facilities, methods and controls are adequate to preserve the pharmaceutical

product’s identity, strength, quality and purity;

· Potential FDA inspection of the preclinical and

clinical study sites that generated the data in support of the NDA;

· FDA review and approval of the NDA.

The lengthy process of seeking

required approvals and the continuing need for compliance with applicable statutes and regulations require the expenditure of substantial

resources and approvals are inherently uncertain.

requirements at any time during the product development

process, approval process or after approval, may subject an applicant to administrative or judicial enforcement.

Any regulatory enforcement

action could have a material adverse effect on us.

The process required by the FDA before a non-biological pharmaceutical product may

be marketed in the United States generally involves the following:

of preclinical laboratory tests, animal studies and formulation studies according to Good Laboratory Practices (“GLP”), and

other applicable regulations;

of an Investigational New Drug application (“IND”), which must become effective before human clinical studies may begin;

of adequate and well-controlled human clinical studies according to current Good Clinical Practices (“GCP”), to establish

the safety and efficacy of the proposed pharmaceutical product for its intended use;

to the FDA of an NDA for a new pharmaceutical product;

· Satisfactory

completion of an FDA inspection of the manufacturing facility or facilities where the pharmaceutical product is produced to assess compliance

with current Good Manufacturing Practice standards (“cGMP”), to assure that the facilities, methods and controls are adequate

to preserve the pharmaceutical product’s identity, strength, quality and purity;

FDA inspection of the preclinical and clinical study sites that generated the data in support of the NDA;

review and approval of the NDA.

The lengthy process of seeking required

approvals and the continuing need for compliance with applicable statutes and regulations require the expenditure of substantial resources

and approvals are inherently uncertain.

Before testing any pharmaceutical

18 unchanged sentences

that, once begun, issues will not arise that can lead to suspension or termination of such clinical studies.

During the development of a new

drug, sponsors are given opportunities to meet with the FDA to discuss progress.

These meetings may occur prior to submission of an IND,

at the end of Phase 2 clinical development, and before an NDA is submitted.

During the development of

a new drug, sponsors are given opportunities to meet with the FDA to discuss progress.

These formal meetings may occur prior to submission

of an IND, at the end of Phase 1 clinical development (for certain investigational products), at the end of Phase 2 clinical development,

and before an NDA is submitted.

Meetings at other times may be requested.

These meetings

can provide an opportunity for the sponsor to share information about the data gathered to date, for the sponsor to ask specific questions

of the FDA, for the FDA to provide advice, and for the sponsor and FDA to reach agreement on the next phase of development.

Sponsors typically

use the end of Phase 2 meeting to discuss their Phase 2 clinical results and present their plans for the pivotal Phase 3

clinical (registration) trial(s) that they believe will support approval of the new drug.

A sponsor may be able to request a Special Protocol

Assessment (“SPA”), the purpose of which is to reach agreement with the FDA on the Phase 3 clinical trial protocol design

and analyses that will form the primary basis of an efficacy claim.

These meetings can provide an opportunity for the sponsor to

share information about the data gathered to date, for the sponsor to ask specific questions of the FDA, for the FDA to provide advice,

and for the sponsor and FDA to reach agreement on the next phase of development.

Sponsors typically use the end of Phase 2 meeting

to discuss their Phase 2 clinical results and present their plans for the pivotal Phase 3 clinical (registration) trial(s) that

they believe will support approval of the new drug.

A sponsor may be able to request a Special Protocol Assessment (“SPA”),

the purpose of which is to reach agreement with the FDA on the Phase 3 clinical trial protocol design and analyses that will form

the primary basis of an efficacy claim.

Conducting Clinical Studies

16 unchanged sentences

or her legal representative and will also monitor the clinical study to ensure patient safety until completed.

Human clinical studies are typically

conducted in three sequential phases that may overlap or be combined:

Human clinical studies are

typically conducted in three sequential phases that may overlap or be combined:

The pharmaceutical product

55 unchanged sentences

already provided in the submission within the last three months before the PDUFA goal date.

After the NDA submission is accepted

for filing, the FDA reviews the NDA application to determine, among other things, whether the proposed product is safe and effective for

its intended use, and whether the product is being manufactured in accordance with cGMP to assure and preserve the product’s identity,

strength, quality and purity.

The FDA may refer applications for novel pharmaceutical products or pharmaceutical products which present

difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for

review, evaluation and a recommendation as to whether the application should be approved and under what conditions.

The FDA is not bound

by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

During the pharmaceutical

product approval process, the FDA also will determine whether a risk evaluation and mitigation strategy (“REMS”), is necessary

to assure the safe use of the pharmaceutical product.

If the FDA concludes that a REMS is needed, the sponsor of the NDA must submit a

proposed REMS;

After the NDA submission is

accepted for filing, the FDA reviews the NDA application to determine, among other things, whether the proposed product is safe and effective

for its intended use, and whether the product is being manufactured in accordance with cGMP to assure and preserve the product’s

identity, strength, quality and purity.

The FDA may refer applications for novel pharmaceutical products or pharmaceutical products which

present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts,

for review, evaluation and a recommendation as to whether the application should be approved and under what conditions.

The FDA is not

bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

pharmaceutical product approval process, the FDA also will determine whether a risk evaluation and mitigation strategy (“REMS”),

is necessary to assure the safe use of the pharmaceutical product.

If the FDA concludes that a REMS is needed, the sponsor of the NDA

must submit a proposed REMS;

the FDA will not approve the NDA without a REMS, if required.

Before approving an NDA, the FDA

will inspect the facilities at which the product is manufactured.

The FDA will not approve the product unless it determines that the manufacturing

processes and facilities are in compliance with cGMP requirements and adequate to ensure consistent production of the product within required

specifications.

Before approving an NDA, the

FDA will inspect the facilities at which the product is manufactured.

The FDA will not approve the product unless it determines that the

manufacturing processes and facilities are in compliance with cGMP requirements and adequate to ensure consistent production of the product

within required specifications.

Additionally, before approving

4 unchanged sentences

In addition, the FDA will require the review and approval of product

The NDA review and approval process

is lengthy and involved and the FDA may refuse to approve an NDA if the applicable regulatory criteria are not satisfied or may require

additional clinical data or other data and information.

Even if such data and information are submitted, the FDA may ultimately decide

that the NDA does not satisfy the criteria for approval.

Data obtained from clinical studies are not always conclusive and the FDA may

interpret data differently than the sponsor interprets the same data.

The FDA will issue a complete response letter if the agency decides

not to approve the NDA.

The complete response letter usually describes all of the specific deficiencies in the NDA identified by the FDA.

The deficiencies identified may be minor, for example, requiring labeling changes, or major, for example, requiring additional clinical

Additionally, the complete response

letter may include recommended actions that the applicant might take to place the application in a condition for approval.

If a complete

response letter is issued, the applicant may either resubmit the NDA, addressing all of the deficiencies identified in the letter, or

withdraw the application.

The NDA review and approval

process is lengthy and involved and the FDA may refuse to approve an NDA if the applicable regulatory criteria are not satisfied or may

require additional clinical data or other data and information.

Even if such data and information are submitted, the FDA may ultimately

decide that the NDA does not satisfy the criteria for approval.

Data obtained from clinical studies are not always conclusive and the

FDA may interpret data differently than the sponsor interprets the same data.

The FDA will issue a complete response letter if the agency

decides not to approve the NDA.

The complete response letter usually describes all of the specific deficiencies in the NDA identified

The deficiencies identified may be minor, for example, requiring labeling changes, or major, for example, requiring additional

clinical studies.

Additionally, the complete

response letter may include recommended actions that the applicant might take to place the application in a condition for approval.

a complete response letter is issued, the applicant may either resubmit the NDA, addressing all of the deficiencies identified in the

letter, or withdraw the application.

If a product receives regulatory

7 unchanged sentences

Expedited Development and Review Programs;

Breakthrough Therapy Designation

Fast-Track Designation

(“FTD”) and Breakthrough Therapy Designation (“BTD”)

The FDA has a Fast Track program

8 unchanged sentences

determines that the schedule is acceptable and if the sponsor pays any required user fees upon submission of the first section of the

Any product submitted to the FDA

for marketing approval, including a Fast Track program, may also be eligible for other types of FDA programs intended to expedite development

and review, such as priority review and accelerated approval.

Any product is eligible for priority review if it has the potential to provide

safe and effective therapy where no satisfactory alternative therapy exists or a significant improvement in the treatment, diagnosis or

prevention of a disease compared to marketed products.

The FDA will attempt to direct additional resources to the evaluation of an application

for a new pharmaceutical product designated for priority review in an effort to facilitate the review.

Additionally, a product may be

eligible for accelerated approval.

Pharmaceutical products studied for their safety and effectiveness in treating serious or life-threatening

illnesses and that provide meaningful therapeutic benefit over existing treatments may receive accelerated approval, which means that

the products may be approved on the basis of adequate and well-controlled clinical studies establishing that the product has an effect

on a surrogate endpoint that is reasonably likely to predict a clinical benefit, or on the basis of an effect on a clinical endpoint other

than survival or irreversible morbidity.

As a condition of approval, the FDA may require that a sponsor of a pharmaceutical product receiving

accelerated approval perform adequate and well-controlled post-marketing clinical studies.

In addition, the FDA currently requires as

a condition for accelerated approval pre-approval of promotional materials, which could adversely impact the timing of the commercial

launch of the product.

Fast Track designation, priority review and accelerated approval do not change the standards for approval but may

expedite the development or approval process.

The FDA is also required to expedite

the development and review of the application for approval of drugs that are intended to treat a serious or life-threatening disease or

condition where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies

on one or more clinically significant endpoints.

Under the breakthrough therapy program, the sponsor of a new product candidate may request

that the FDA designate the product candidate for a specific indication as a breakthrough therapy concurrent with, or after, the filing

of the IND for the product candidate.

The FDA must determine if the product candidate qualifies for breakthrough therapy designation within

60 days of receipt of the sponsor’s request.

Elraglusib IV and elraglusib oral dosage forms may all be eligible for breakthrough

therapy designation depending on the indication and pending additional data.

Any product submitted to the

FDA for marketing approval, including a Fast Track program, may also be eligible for other types of FDA programs intended to expedite

development and review, such as priority review and accelerated approval.

Any product is eligible for priority review if it has the potential

to provide safe and effective therapy where no satisfactory alternative therapy exists or a significant improvement in the treatment,

diagnosis or prevention of a disease compared to marketed products.

The FDA will attempt to direct additional resources to the evaluation

of an application for a new pharmaceutical product designated for priority review in an effort to facilitate the review.

Additionally,

a product may be eligible for accelerated approval.

Pharmaceutical products studied for their safety and effectiveness in treating serious

or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may receive accelerated approval,

which means that the products may be approved on the basis of adequate and well-controlled clinical studies establishing that the product

has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit, or on the basis of an effect on a clinical

endpoint other than survival or irreversible morbidity.

As a condition of approval, the FDA may require that a sponsor of a pharmaceutical

product receiving accelerated approval perform adequate and well-controlled post-marketing clinical studies.

In addition, the FDA currently

requires as a condition for accelerated approval pre-approval of promotional materials, which could adversely impact the timing of the

commercial launch of the product.

Fast Track designation, priority review and accelerated approval do not change the standards for approval

but may expedite the development or approval process.

The FDA is also required to

expedite the development and review of the application for approval of drugs that are intended to treat a serious or life-threatening

disease or condition where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing

therapies on one or more clinically significant endpoints.

Under the breakthrough therapy program, the sponsor of a new product candidate

may request that the FDA designate the product candidate for a specific indication as a breakthrough therapy concurrent with, or after,

the filing of the IND for the product candidate.

The FDA must determine if the product candidate qualifies for breakthrough therapy designation

within 60 days of receipt of the sponsor’s request.

Elraglusib IV and elraglusib oral dosage forms may all be eligible for

breakthrough therapy designation depending on the indication and pending clinical additional data.

Orphan Drug Designation

Under the Orphan Drug Act, the

FDA may grant orphan designation to a drug intended to treat a rare disease or condition affecting fewer than 200,000 individuals in the

United States, or in other limited cases.

ODD provides for seven years of market exclusivity, independent of patent protection, to

the company with ODD that brings a particular product to market.

In addition, companies developing orphan drugs are eligible for certain

incentives, including tax credits for qualified clinical testing.

To gain exclusivity, if a product

that has ODD subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product

is entitled to the orphan drug exclusivity, which means that the FDA may not approve any other applications to market the same active

moiety for the same indication for seven years, except in limited circumstances, such as another drug’s showing of clinical

Under the Orphan Drug Act,

the FDA may grant orphan designation (“ODD”) to a drug intended to treat a rare disease or condition affecting fewer than

200,000 individuals in the United States, or in other limited cases.

ODD provides for seven years of market exclusivity, independent

of patent protection, to the company with ODD that brings a particular product to market.

In addition, companies developing orphan drugs

are eligible for certain incentives, including tax credits for qualified clinical testing.

To gain exclusivity, if a

product that has ODD subsequently receives the first FDA approval for the disease or condition for which it has such designation, the

product is entitled to the orphan drug exclusivity, which means that the FDA may not approve any other applications to market the same

active moiety for the same indication for seven years, except in limited circumstances, such as another drug’s showing of clinical

superiority over the drug with orphan exclusivity.

2 unchanged sentences

for the same active moiety for the same indication before we do, unless we are able to demonstrate that our product is clinically superior.

A sponsor may request ODD of a

previously unapproved product or new orphan indication for an already marketed product.

In addition, a sponsor of a product that is otherwise

the same product as an already approved orphan drug may seek and obtain ODD for the subsequent product for the same rare disease or condition

if it can present a plausible hypothesis that its product may be clinically superior to the first, approved product.

More than one sponsor

may receive ODD for the same product for the same rare disease or condition, but each sponsor seeking ODD must file a complete request

for designation, and only the first sponsor that obtains approval for that drug for the orphan indication will obtain market exclusivity,

effectively preventing the FDA from approving products under development by competitors for the same drug and same indication, unless

the competitor is able to demonstrate that the product under development is clinically superior to the approved product or the approved

product is not available in sufficient quantities.

To permit the FDA to end another manufacturer’s orphan exclusivity period, the

FDA must determine that the manufacturer has demonstrated clinical superiority by showing the later drug is safer, more effective, or

otherwise makes a major contribution to patient care.

We may plan to pursue ODD and

exclusivity for some of our product candidates in the United States, the EU, and other geographies of interest for specific products.

A sponsor may request ODD

of a previously unapproved product or new orphan indication for an already marketed product.

In addition, a sponsor of a product that

is otherwise the same product as an already approved orphan drug may seek and obtain ODD for the subsequent product for the same rare

disease or condition if it can present a plausible hypothesis that its product may be clinically superior to the first, approved product.

More than one sponsor may receive ODD for the same product for the same rare disease or condition, but each sponsor seeking ODD must file

a complete request for designation, and only the first sponsor that obtains approval for that drug for the orphan indication will obtain

market exclusivity, effectively preventing the FDA from approving products under development by competitors for the same drug and same

indication, unless the competitor is able to demonstrate that the product under development is clinically superior to the approved product

or the approved product is not available in sufficient quantities.

To permit the FDA to end another manufacturer’s orphan exclusivity

period, the FDA must determine that the manufacturer has demonstrated clinical superiority by showing the later drug is safer, more effective,

or otherwise makes a major contribution to patient care.

We may plan to pursue ODD

and exclusivity for some of our product candidates in the United States, the EU, and other geographies of interest for specific products.

ODD neither shortens the development time or regulatory review time of a drug nor gives the drug any advantage in the regulatory review

5 unchanged sentences

Regulation Outside the United States

In order to market a pharmaceutical

product outside of the United States, a company must also comply with numerous and varying regulatory requirements of other countries

and jurisdictions regarding quality, safety and efficacy that govern, among other things, clinical trials, marketing authorization, commercial

sales and distribution.

Whether or not we obtain FDA approval for a pharmaceutical product, we would need to obtain the necessary approvals

by the comparable non-U.S.

regulatory authorities before it can commence clinical trials or marketing of the product in those countries

or jurisdictions.

The approval process ultimately varies between countries and jurisdictions and can involve additional product testing

and additional administrative review periods.

The time required to obtain approval in other countries and jurisdictions might differ from

and be longer than that required to obtain FDA approval.

Regulatory approval in one country or jurisdiction does not ensure regulatory

approval in another, but a failure or delay in obtaining regulatory approval in one country or jurisdiction may negatively impact the

regulatory process in others.

Regulation and Marketing Authorization in the EU

The EMA is the scientific agency

of the EU that coordinates the evaluation and monitoring of new and approved medicinal products such as drugs and biologics.

It is responsible

for the scientific evaluation of applications for EU marketing authorizations, as well as the development of technical guidance and the

provision of scientific advice to sponsors.

The process regarding approval

of medicinal products in the EU follows roughly the same lines as in the United States and likewise generally involves satisfactorily

completing each of the following:

· preclinical laboratory tests, animal studies

and formulation studies all performed in accordance with the applicable EU Good Laboratory Practice regulations;

· submission to the relevant regulatory agencies

in EU member states, or national authorities, of a clinical trial application (“CTA”) for each clinical trial, which must

be approved before human clinical trials may begin;

· performance of adequate and well-controlled clinical

trials to establish the safety and efficacy of the product for each proposed indication;

· submission to the relevant national authorities

of a Marketing Authorization Application (“MAA”), which includes the data supporting safety and efficacy as well as detailed

information on the manufacture and composition of the product in clinical development and proposed labeling;

· satisfactory completion of an inspection by the

relevant national authorities of the manufacturing facility or facilities, including those of third parties, at which the product is produced

to assess compliance with cGMP;

· potential audits of the non-clinical and clinical

trial sites that generated the data in support of the MAA;

· review and approval by the relevant national

authority of the MAA before any commercial marketing, sale or shipment of the product.

Preclinical Studies

Preclinical tests include laboratory

evaluations of product chemistry, formulation and stability, as well as studies to evaluate the potential efficacy and toxicity in animals.

The conduct of the preclinical tests and formulation of the compounds for testing must comply with the relevant EU regulations and requirements.

The results of the preclinical tests, together with relevant manufacturing information and analytical data, are submitted as part of the

CTA when seeking approval to start a clinical trial, and with the MAA when seeking marketing authorization.

Clinical Trial Approval

Requirements for the conduct of

clinical trials in the EU including GCP, are implemented in the current Clinical Trials Directive 2001/20/EC and the GCP Directive 2005/28/EC.

Pursuant to Directive 2001/20/EC and Directive 2005/28/EC, as amended, a system for the approval of clinical trials in the EU has been

implemented through national legislation of the EU member states.

Under this system, approval must be obtained from the competent national

authority in which a trial is planned to be conducted, or in multiple member states if the clinical trial is to be conducted in a number

of member states.

To this end, a CTA is submitted, which must be supported by an investigational medicinal product dossier (IMPD) and

further supporting information prescribed by Directive 2001/20/EC and Directive 2005/28/EC and other applicable guidance documents.

a clinical trial may only be started after a competent ethics committee has issued a favorable opinion on the clinical trial application

in that country.

On January 31, 2022, the

Clinical Trials Regulation (EU) No.

536/2014 repealed the Clinical Trials Directive 2001/20/EC.

To ensure that the rules for clinical

trials are identical throughout the EU, the Clinical Trials Regulation (EU) No.

536/2014 was passed as a regulation which is directly

applicable in all EU member states.

The Clinical Trials Directive 2001/20/EC will, however, still apply three years from the

date of entry into application of the Clinical Trials Regulation to (i) clinical trials applications submitted before the entry into

application and (ii) clinical trials applications submitted within one year after the entry into application if the sponsor opts

for the old system.

Regulation (EU) No 536/2014 aims

to simplify and streamline the approval of clinical trial in the EU.

The main characteristics of the regulation include:

· a streamlined application procedure via a single

entry point, known as the Clinical Trials Information System;

· a single set of documents to be prepared and

submitted for the application as well as simplified reporting procedures which will spare sponsors from submitting broadly identical information

separately to various and different national authorities;

· harmonized procedure for the assessment of applications

for clinical trials, which is divided in two parts;

· strictly defined deadlines for the assessment

of clinical trial application;

· the involvement of the ethics committees in the

assessment procedure in accordance with the national law of the member state concerned but within the overall timelines defined by the

Regulation (EU) No 536/2014.

Marketing Authorization

Authorization to market a product

in the member states of the EU proceeds under one of four procedures:

a centralized procedure, a mutual recognition procedure, a decentralized

procedure or a national procedure.

Centralized Procedure

The centralized procedure enables

applicants to obtain a marketing authorization that is valid in all EU member states based on a single application.

Certain medicinal

products, including products developed by means of biotechnological processes, must undergo the centralized authorization procedure for

marketing authorization, which, if granted by the European Commission, based on the opinion of the EMA, is automatically valid in all

EU member states.

Sponsors may elect to file an MAA through the centralized procedures for other classes of products.

The centralized procedure is mandatory

for certain types of products such as medicines derived from biotechnology processes (e.g., genetic engineering), advanced-therapy medicines

(e.g., gene-therapy, tissue engineered medicine), orphan medicines, and medicinal products containing a new active substance indicated

for the treatment of HIV, AIDS, cancer, diabetes, neurodegenerative disorders, autoimmune and other immune dysfunctions, and viral diseases.

The centralized authorization

procedure is optional for other medicinal products if they contain a new active substance, if the applicant shows that the medicinal product

concerned constitutes a significant therapeutic, scientific or technical innovation, or that the granting of authorization is in the public

interest of the EU.

Administration Procedure

Under the centralized procedure,

the EMA’s Committee for Human Medicinal Products (“CHMP”) serves as the scientific committee that renders opinions about

the safety, efficacy and quality of medicinal products for human use on behalf of the EMA.

The CHMP is composed of experts nominated by

each member state’s national authority for medicinal products, with one of them appointed to act as Rapporteur for the coordination

of the evaluation with the possible assistance of a further member of the Committee acting as a Co-Rapporteur.

After approval, the Rapporteur(s)

continue to monitor the product throughout its life cycle.

The CHMP has 210 active days, to adopt an opinion as to whether a marketing

authorization should be granted.

The process usually takes longer in case additional information is requested, which triggers clock-stops

in the procedural timelines.

The process is complex and involves extensive consultation with the regulatory authorities of member states

and a number of experts.

When an application is submitted for a marketing authorization in respect of a drug which is of major interest

from the point of view of public health and in particular from the viewpoint of therapeutic innovation, the applicant may, pursuant to

Article 14(9) Regulation (EC) No 726/2004, request an accelerated assessment procedure.

If the CHMP accepts such request, the time-limit

of 210 days will be reduced to 150 days, but it is possible that the CHMP can revert to the standard time-limit for the centralized

procedure if it considers that it is no longer appropriate to conduct an accelerated assessment.

Once the procedure is completed, a European

Public Assessment Report (“EPAR”) is produced.

If the opinion is negative, information is given as to the grounds on which

this conclusion was reached.

After the adoption of the CHMP opinion, a decision on the MAA must be adopted by the European Commission,

after consulting the EU member states, which in total can take more than 60 days.

After a drug has been authorized and launched,

it is a condition of maintaining the marketing authorization that all aspects relating to its quality, safety and efficacy must be kept

under review.

To market any medicinal product

outside of the U.S., similar regulatory requirements, including adherence to GLP, Good Clinical Practices (“GCP”) and Good

Manufacturing Practice (“GMP”), collectively referred to as GxP to initiate clinical trials and, subsequently, to obtain marketing

approval of a new pharmaceutical product are in place in each jurisdiction and vary country to country.

Each regulatory jurisdiction will

apply these regulations in their assessment of clinical trial applications and marketing authorization applications.

The foreign regulatory

approval process includes all the risks associated with FDA approval set forth above, as well as additional country-specific regulation.

Failure to comply with applicable foreign regulatory requirements may be subject to, among other things, fines, suspension or withdrawal

of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.

Non-clinical Studies, Clinical Trials, and

Manufacturing

Similarly to the United States,

the various phases of non-clinical and clinical research in the European Union (“EU”), United Kingdom (“UK”) and

Canada are subject to significant regulatory controls.

Non-clinical studies are performed

to demonstrate the health or environmental safety of new biological substances.

Non-clinical studies (pharmaco-toxicological) must be

conducted in compliance with the principles of GLP, as set forth in EU Directive 2004/10/EC.

Non-clinical studies, both in vitro and in

vivo, must be planned, performed, monitored, recorded, reported and archived in accordance with the GLP principles, which define a set

of rules and criteria for a quality system for the organizational process and the conditions for non-clinical studies.

These GLP standards

reflect the Organization for Economic Co-operation and Development requirements.

Clinical trials of medicinal

products humans must be conducted in accordance with national regulations and the International Council for Harmonization of Technical

Requirements for Pharmaceuticals for Human Use (“ICH”) guidelines on GCP as well as the applicable regulatory requirements

and the ethical principles that have their origin in the Declaration of Helsinki.

Clinical trials involve the administration of the investigational

new drug or biological product to healthy volunteers or patients under the supervision of a qualified investigator.

Clinical trials must

be conducted:

(i) in compliance with federal regulations;

(ii) in compliance with GCP, which is an international standard meant to protect

the rights and health of patients and to define the roles of clinical trial sponsors, administrators and monitors;

as well as (iii) under

protocols detailing the objectives of the trial, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated.

Each protocol involving testing on patients and subsequent protocol amendments must be submitted to regulatory authorities for review

and approval.

Medicines used in clinical trials must be manufactured in accordance with regulatory requirements under GMP.

Legislation in EU, UK, and Canada

In the EU, the EMA conducts

the scientific evaluation, supervision and safety monitoring of our innovative medicinal products that are eligible for the centralized

marketing authorization procedure.

Through the centralized procedure, pharmaceutical companies may submit to the EMA a single application

for a marketing authorization valid in all the EU and the European Economic Area (“EEA”) countries.

The European Community

(“EC”) makes a legally binding decision based on the EMA’s recommendation.

The centralized procedure is mandatory for certain

new products and optional for others.

In the UK, we are subject

to rigorous and evolving regulation and standards in the UK, overseen primarily by the Medicines and Healthcare products Regulatory Agency

In 2026, the UK will require a new, independent framework for the authorization and surveillance of medicinal products.

This includes mandatory compliance with revised standards governing clinical trials, patient protections and the new International Reliance

Framework for marketing authorizations.

In April 2026, clinical trials

in the UK will be subject to the Medicines for Human Use (Clinical Trials) Amendment Regulations 2025, which introduced revised classification

for trial modifications, enhanced transparency, and extended data retention requirements.

We are also subject to ICH E6(R3) standards

and, the UK’s Cyber Security and Resilience Bill.

The regulations are intended to protect the rights, safety and wellbeing of research

participants and to simplify and harmonize regulatory processes.

They apply to trials designed to generate information on the efficacy

or safety of medicine.

In Canada, we are subject

to rigorous and evolving regulation and standards by Health Canada under the Food and Drugs Act and the Food and Drug Regulations.

receiving marketing authorization, we must conduct extensive preclinical and clinical trials, demonstrating safety, efficacy, and quality

to Health Canada.

The regulatory approval process is lengthy, expensive, and uncertain.

Even if we obtain approval, our products remain

subject to ongoing post-marketing surveillance, and failure to comply with Health Canada requirements, such as GMP and GCP, could result

in product recalls, suspension of approvals, or penalties.

Marketing Authorization in the EU

The EMA is the scientific

agency of the EU that coordinates the evaluation and monitoring of new and approved medicinal products such as drugs and biologics.

is responsible for the scientific evaluation of applications for EU marketing authorizations, as well as the development of technical

guidance and the provision of scientific advice to sponsors.

In the EU, we are required

to apply for marketing authorizations under the centralized procedure to the EMA as the centralized procedure is mandatory for certain

medicines, such as t orphan medicinal products, and advanced therapy medicinal products and those containing a new active substance indicated

for the treatment of cancer.

The marketing authorization granted under the centralized procedure by the EMA will be valid in all EEA Member

The evaluation of a marketing authorization application by the EMA’s Committee for Medicinal Products for Human Use (“CHMP:)

takes up to 210 “active” days (excluding all “clock stops” for an applicant to address questions by the EMA–there

are usually one or two clock stops that last three to six months and one to two months, respectively) but can be extended, should additional

information be required by the CHMP.

The European Commission makes the final decision to grant a marketing authorization, which is issued

within 67 days of receipt of the EMA’s positive opinion.

An accelerated assessment

procedure of 150 days may be implemented for drugs considered to be of major public health interest.

There is also an internal re-examination

procedure available in case the applicant disagrees with the CHMP opinion.

Regulatory Submissions

The EU Clinical Trials Regulation

(“CTR”) which was adopted in April 2014 and repeals the EU Clinical Trials Directive and went into full effect on January

Unlike directives, the CTR is directly applicable in all EU member states without the need for member states to further implement

it into national law.

The CTR harmonizes the assessment and supervision processes for clinical trials throughout the EU via a Clinical

Trials Information System, which contains a centralized EU portal and database.

The CTR introduces a centralized

process and only requires the submission of a single application for multi-center trials.

The CTR allows sponsors to make a single submission

to both the competent authority and an ethics committee in each member state, leading to a single decision per member state.

trial application (“CTA”) must include, among other things, a copy of the trial protocol and an investigational medicinal

product dossier containing information about the manufacture and quality of the medicinal product under investigation.

The assessment

procedure of the CTA has been harmonized as well, including a joint assessment by all member states concerned, and a separate assessment

by each member state with respect to specific requirements related to its own territory, including ethics rules.

Each member state’s

decision is communicated to the sponsor via the centralized EU portal.

Conditional Approval

In specific circumstances, EU

legislation (Article 14(7) Regulation (EC) No.

In specific circumstances,

EU legislation (Article 14(7) Regulation (EC) No.

726/2004 and Regulation (EC) No.

507/2006 on Conditional Marketing Authorizations

for Medicinal Products for Human Use) enables applicants to obtain a conditional marketing authorization prior to obtaining the comprehensive

507/2006 on Conditional Marketing Authorizations for

Medicinal Products for Human Use) enables applicants to obtain a conditional marketing authorization prior to obtaining the comprehensive

clinical data required for an application for a full marketing authorization.

Such conditional approvals may be granted for products (including

medicines designated as orphan medicinal products), if (1) the risk-benefit balance of the product is positive, (2) it

is likely that the applicant will be in a position to provide the required comprehensive clinical trial data, (3) the product fulfills

unmet medical needs, and (4) the benefit to public health of the immediate availability on the market of the medicinal product concerned

outweighs the risk inherent in the fact that additional data are still required.

A conditional marketing authorization may contain specific

obligations to be fulfilled by the marketing authorization holder, including obligations with respect to the completion of ongoing or

new studies, and with respect to the collection of pharmacovigilance data.

Conditional marketing authorizations are valid for one year,

and may be renewed annually, if the risk-benefit balance remains positive, and after an assessment of the need for additional or modified

conditions and/or specific obligations.

The timelines for the centralized procedure described above also apply with respect to the review

by the CHMP of applications for a conditional marketing authorization.

medicines designated as orphan medicinal products), if (1) the risk-benefit balance of the product is positive, (2) it is likely

that the applicant will be in a position to provide the required comprehensive clinical trial data, (3) the product fulfills unmet medical

needs, and (4) the benefit to public health of the immediate availability on the market of the medicinal product concerned outweighs the

risk inherent in the fact that additional data are still required.

A conditional marketing authorization may contain specific obligations

to be fulfilled by the marketing authorization holder, including obligations with respect to the completion of ongoing or new studies,

and with respect to the collection of pharmacovigilance data.

Conditional marketing authorizations are valid for one year, and may be

renewed annually, if the risk-benefit balance remains positive, and after an assessment of the need for additional or modified conditions

and/or specific obligations.

The timelines for the centralized procedure described above also apply with respect to the review by the

CHMP of applications for a conditional marketing authorization.

Marketing Authorization Under Exceptional Circumstances

As per Article 14(8) Regulation

(EC) No 726/2004, products for which the applicant can demonstrate that comprehensive data (in line with the requirements laid down in

Annex I of Directive 2001/83/EC, as amended) cannot be provided (due to specific reasons foreseen in the legislation) might be eligible

for marketing authorization under exceptional circumstances.

This type of authorization is reviewed annually to reassess the risk-benefit

The fulfillment of any specific procedures/obligations imposed as part of the marketing authorization under exceptional circumstances

is aimed at the provision of information on the safe and effective use of the product and will normally not lead to the completion of

a full dossier/approval.

Pediatric Studies

Prior to obtaining a marketing

authorization in the EU, applicants have to demonstrate compliance with all measures included in an EMA-approved Pediatric Investigation

Plan (“PIP”) covering all subsets of the pediatric population, unless the EMA has granted (1) a product-specific waiver,

(2) a class waiver, or (3) a deferral for one or more of the measures included in the PIP.

The respective requirements for all

marketing authorization procedures are laid down in Regulation (EC) No 1901/2006, the so-called Pediatric Regulation.

This requirement

also applies when a company wants to add a new indication, pharmaceutical form or route of administration for a medicine that is already

The Pediatric Committee of the EMA (“PDCO”) may grant deferrals for some medicines, allowing a company to delay

development of the medicine in children until there is enough information to demonstrate its effectiveness and safety in adults.

may also grant waivers when development of a medicine in children is not needed or is not appropriate, such as for diseases that only

affect the elderly population.

Before a marketing authorization

application can be filed, or an existing marketing authorization can be amended, the EMA determines that companies actually comply with

the agreed studies and measures listed in each relevant PIP.

Marketing Authorization Under

Exceptional Circumstances is a regulatory pathway in the EU allowing early access to medicines for rare diseases, emergencies, or ethical

constraints preventing comprehensive data collection.

It enables approval without a full efficacy/safety dossier, provided the benefit-risk

balance is positive.

Per Article 14(8) Regulation (EC) No 726/2004, products for which the applicant can demonstrate that comprehensive

data (in line with the requirements laid down in Annex I of Directive 2001/83/EC, as amended) cannot be provided (due to specific reasons

foreseen in the legislation) might be eligible for marketing authorization under exceptional circumstances.

This type of authorization

is reviewed annually to reassess the risk-benefit balance.

The fulfillment of any specific procedures/obligations imposed as part of the

marketing authorization under exceptional circumstances is aimed at the provision of information on the safe and effective use of the

product and will normally not lead to the completion of a full dossier/approval.

Accelerated Approval Pathways

The EU and UK operate accelerated

evaluation and assessment schemes, which include, at EU level, Priority Medicines (“PRIME”) scheme and, at UK level, the Early

Access to Medicines Scheme (“EAMS”), which may be granted in exceptional cases, often when there is unmet medical need for

a life-threatening or serious debilitating condition and existing data show a positive benefit/risk balance that means the medicinal product

is of a major public health interest.

The CHMP of the EMA or the MHRA (or other national competent authority) will make this determination

on a case-by-case basis and subject to meeting eligibility criteria.

Accelerated assessment takes place within 150 days.

Other regulatory

facilitations for these pathways include additional scientific advice at key development milestones and frequent guidance and discussions

throughout the approval process.

In the UK, the MHRA has launched

the Innovative Licensing and Access Pathway (ILAP), a new accelerated assessment procedure for marketing authorization applications that

enables companies to enter the UK market faster.

The MHRA launched an International Recognition Procedure for Great Britain (England,

Scotland and Wales) marketing authorization applications whereby the MHRA will, when considering such applications, recognize the approval

of medicines by trusted reference regulators in Australia, Canada, Switzerland, Singapore, Japan, United States and EU following its own

abbreviated assessment.

Pediatric Development

In the EEA, MAAs for new medicinal

products must include the results of studies conducted in the pediatric population, in compliance with a pediatric investigation plan

(“PIP”), agreed with the EMA’s Pediatric Committee (“PDCO”).

The PIP sets out the timing and measures proposed

to generate data to support a pediatric indication of the drug for which MA is being sought.

The PDCO can grant a deferral of the obligation

to implement some or all the measures of the PIP until there are sufficient data to demonstrate the efficacy and safety of the product

Further, the obligation to provide pediatric clinical trial data can be waived by the PDCO when these data are not needed or

appropriate because the product is likely to be ineffective or unsafe in children, the disease or condition for which the product is intended

occurs only in adult populations, or when the product does not represent a significant therapeutic benefit over existing treatments for

pediatric patients.

We have received a class waiver for pediatric data in mPDAC.

Orphan Medicinal Products

In the EU and UK, under Regulation

(EC) 141/2000 and the UK Human Medicines Regulations 2012 SI 2012 No.

1916 (as amended), respectively, medicinal products may be granted

an orphan drug designation if they are used to treat or prevent life-threatening or chronically debilitating conditions that affect no

more than five in 10,000 people in the EU/UK and for which there is no satisfactory method of diagnosis, prevention or treatment when

the application is made, or when the medicinal product is of significant benefit to those affected by the condition.

In addition, orphan

drug designation can be granted to drugs used to treat or prevent life-threatening or chronically debilitating conditions which, for economic

reasons, would be unlikely to be developed without incentives.

The application for orphan

designation must be submitted to and approved by the EMA in respect of the EU or to the MHRA for Great Britain before an application is

made for marketing authorization for the product.

Medicinal products which benefit from orphan status can benefit from up to ten years

of market exclusivity in respect of the approved indication.

This prevents regulatory authorities in the EU or Great Britain from granting

marketing authorizations for similar medicinal products for the same therapeutic indication, unless another applicant can show that the

similar medicinal product in question is safer, more effective or clinically superior to the orphan-designated product or if the marketing

authorization holder consents to the second orphan medicinal product application, or were the marketing authorization holder cannot supply

the needs of the market.

The ten-year market exclusivity

may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for orphan

designation, for example, if the product is sufficiently profitable not to justify the maintenance of market exclusivity.

the 10- year exclusivity period can be further extended by two years, when pediatric studies are conducted in accordance with an agreed

pediatric investigation plan (“PIP”) and in completion of all the legal requirements.

Orphan designation does not convey any

advantage in, or shorten the duration of, the regulatory review and approval process.

It is noted that the general

pharmaceutical legislative framework, as well as the framework applicable to orphan and pediatric medicinal products in the EU, is under

On April 26, 2023, the European Commission adopted a proposal for a new Regulation set to replace Regulation (EC) No 726/2004

and a new Directive to replace Directive 2001/83 on the Community Code relating to medicinal products for human use.

Initial framework

agreement was reached in December 2025;

however, final legislation is undergoing final formal review by the European Parliament and Council.

If made into law, this proposal will revise the existing general pharmaceutical legislation with new measures to encourage pediatric research,

including incentives for completing pediatric investigation plans (PIPs) and introducing more flexible paths for pediatric medicines;

however, may reduce applicable regulatory exclusivities which will significantly affect all medicinal products that will be authorized

after the legislative changes have taken effect.

We have received Orphan Designation

from the EMA for mPDAC and sarcoma in pediatric patients.

Period of Authorization and Renewals

A marketing authorization will

be valid for five years in principle, and the marketing authorization may be renewed after five years on the basis of a re-evaluation

A marketing authorization

will be valid for five years in principle, and the marketing authorization may be renewed after five years on the basis of a re-evaluation

of the risk-benefit balance by the EMA or by a national authority.

7 unchanged sentences

member state within three years after authorization will cease to be valid, the so-called “sunset clause.”

Orphan Medicinal Product Designation and Exclusivity

The European Commission can grant

OMPD to products for which the sponsor can establish that it is intended for the diagnosis, prevention, or treatment of (1) a life-threatening

or chronically debilitating condition affecting not more than five in 10,000 people in the EU, or (2) a life threatening, seriously

debilitating or serious and chronic condition in the EU and that without incentives it is unlikely that sales of the drug in the EU would

generate a sufficient return to justify the necessary investment.

In addition, the sponsor must establish that there is no other satisfactory

method approved in the EU of diagnosing, preventing or treating the condition, or if such a method exists, the proposed orphan drug will

be of significant benefit to patients.

OMPD provides a number of benefits,

including fee reductions, regulatory assistance, and the possibility to apply for a centralized EU marketing authorization, as well as

10 years of market exclusivity following a marketing authorization.

During this market exclusivity period, neither the EMA, nor the

European Commission nor the Member States can accept an application or grant a marketing authorization for a medicinal product containing

a similar active substance or substances as contained in an authorized orphan medicinal product, and which is intended for the same therapeutic

The market exclusivity period for the authorized therapeutic indication may be reduced to six years if, at the end of

the fifth year, it is established that the OMPD criteria are no longer met, including where it is shown that the product is sufficiently

profitable not to justify maintenance of market exclusivity.

In addition, a competing similar medicinal product may be authorized prior

to the expiration of the market exclusivity period, including if it is shown to be safer, more effective or otherwise clinically superior

to the already approved orphan drug or if the holder of the marketing authorization for the already approved orphan drug is unable to

supply sufficient quantities of the product.

If the MAA of a medicinal product

designated as an orphan drug includes the results of all studies conducted in compliance with an agreed PIP, and a corresponding statement

is subsequently included in the marketing authorization granted, the 10-year period of market exclusivity will be extended to 12 years.

Regulatory Data Protection

EU legislation also provides for

a system of regulatory data and market exclusivity.

Upon receiving marketing authorization, new chemical entities approved on the basis

of complete independent data package benefit from eight years of data exclusivity and an additional two years of market exclusivity.

EU legislation also provides

for a system of regulatory data and market exclusivity.

Upon receiving marketing authorization, new chemical entities approved on the

basis of complete independent data package benefit from eight years of data exclusivity and an additional two years of market exclusivity.

Data exclusivity prevents regulatory authorities in the EU from referencing the innovator’s data to assess a generic or biosimilar

4 unchanged sentences

The overall 10-year period will be extended to a maximum of 11 years if, during the first 8

8 years of those 10 years, the marketing authorization holder (“MAH”) obtains an authorization for one or more new

therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical

benefit in comparison with existing therapies.

Even if a compound is considered to be a new chemical entity and the innovator is able

to gain the period of data exclusivity, another company nevertheless could also market another version of the drug if such company obtained

marketing authorization based on an MAA with a complete independent data package of pharmaceutical test, preclinical tests and clinical

However, products designated as orphan medicinal products enjoy, upon receiving marketing authorization, a period of 10 years

of orphan market exclusivity.

Depending upon the timing and duration of the EU marketing authorization process, products may be eligible

for up to five years’ supplementary protection certificates (“SPCs”).

Such SPCs extend the rights under the basic

patent for the drug.

Regulatory Requirements After a Marketing Authorization Has Been Obtained

If we obtain authorization for

a medicinal product in the EU, we will be required to comply with a range of requirements applicable to the manufacturing, marketing,

promotion and sale of medicinal products.

We will, for example, have to

comply with the EU’s stringent pharmacovigilance or safety reporting rules, pursuant to which post-authorization studies and additional

monitoring obligations can be imposed.

Other requirements relate to,

for example, the manufacturing of products and active pharmaceutical ingredients in accordance with good manufacturing practice standards.

EU regulators may conduct inspections to verify our compliance with applicable requirements, and we will have to continue to expend time,

money and effort to remain compliant.

Non-compliance with EU requirements regarding safety monitoring or pharmacovigilance, and with requirements

related to the development of products for the pediatric population, can also result in significant financial penalties in the EU.

failure to comply with the EU’s requirements regarding the protection of individual personal data can also lead to significant penalties

and sanctions.

Individual EU member states may also impose various sanctions and penalties in case we do not comply with locally applicable

requirements.

years of those 10 years, the marketing authorization holder (“MAH”) obtains an authorization for one or more new therapeutic

indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in

comparison with existing therapies.

Even if a compound is considered to be a new chemical entity and the innovator is able to gain the

period of data exclusivity, another company nevertheless could also market another version of the drug if such company obtained marketing

authorization based on an MAA with a complete independent data package of pharmaceutical test, preclinical tests and clinical trials.

However, products designated as orphan medicinal products enjoy, upon receiving marketing authorization, a period of 10 years of orphan

market exclusivity.

Depending upon the timing and duration of the EU marketing authorization process, products may be eligible for up

to five years’ supplementary protection certificates (“SPCs”).

Such SPCs extend the rights under the basic patent for

Clinical Trials Regulation and Data Sharing

In the EU/EEA, all initial

clinical trial applications (“CTA”) must be submitted through the Clinical Trials Information System (“CTIS”)

and ethics approval must be sought from an independent Ethics Committee.

Under the EU Clinical Trials Regulation 536/2014, which has been

in effect since January 31, 2022, replacing the EU Clinical Trials Directive 2001/20/EC, suspected unexpected serious adverse reactions

to the drug during the clinical trial must be reported via the EudraVigilance database.

In the EU, Transparency Regulation

No 1049/ 2001, EMA Policy 0043, EMA Policy 0070, as well as the Clinical Trials Regulation No 536/2014 set out the obligation for sponsors

to make publicly available certain information stemming from clinical studies, whether proactively or in response to third party requests.

Interested parties based in the EU may submit a request to the EMA to access information included in the marketing authorization application

for authorized medicinal products.

Commercially confidential information and protected personal data, however, may not be accessed.

The European Health Data Space

Regulations (the “EHDS Regulations”) came into force on March 26, 2025.

The aims of the EHDS Regulations are to provide individuals

with more control over their electronic health data, enable cross-border sharing of European Health Data (EHD) between national EU healthcare

systems and facilitate the sharing of EHD for secondary research purposes.

The EHDS Regulations impose new obligations but also create

opportunities for companies engaged in health-related research to share and access health data on a large scale.

Although the EHDS Regulations

have come into force, key obligations will not apply until March 2029.

We are subject to extensive

privacy and data protection laws and regulations around the world concerning the collection, use and sharing of personal data.

subject to privacy laws in connection with our clinical trial activities outside the United States such as the EU and UK General Data

Protection Regulation (“GDPR”), non-compliance with which could result in administrative fines of up to the greater of 4%

of global annual revenues or €20.0 million (under the EU GDPR) or £17.5m (under the UK GDPR).

The GDPR also confers a private

right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies and

obtain compensation for damages resulting from violations of the GDPR.

We routinely collect and use sensitive personal information relating

The legislative, regulatory and litigation landscape for privacy and data protection requirements is rapidly evolving and changing

and may limit our ability to use data globally or across borders.

Data protection requirements are not universal and can conflict between

jurisdictions.

Compliance with local laws

and regulations is made more complex by the lack of consistent standards, common definitions, or clear regulatory expectations.

same time, enforcement of these laws and regulations is increasing and fines and penalties are also increasing.

Any failure or perceived

failure by us to comply with applicable privacy and data protection laws and regulations, including cybersecurity breaches or incidents,

could subject us to significant fines and penalties, and/or litigation, as well as negatively impacting our reputation.

Regulatory Requirements After a Marketing Authorization

(“MA”) Has Been Obtained

Similar to the United States,

MA holders and manufacturers of medicinal products are subject to comprehensive regulatory oversight by the EMA, the European Commission

and/or the competent regulatory authorities of the EU member states.

The holder of a MA must establish and maintain a pharmacovigilance

system and appoint an individual qualified person for pharmacovigilance (“QPPV”) who is responsible for the establishment

and maintenance of that system and oversees the safety profiles of medicinal products and any emerging safety concerns.

Key obligations

include expedited reporting of suspected serious adverse reactions and submission of periodic safety update reports (“PSURs”).

All new MAA must include a

risk management plan (“RMP”) describing the risk management system that the company will put in place and documenting measures

to prevent or minimize the risks associated with the product.

The regulatory authorities may also impose specific obligations as a condition

Such risk-minimization measures or post-authorization obligations may include additional safety monitoring, more frequent submission

of PSURs, or the conduct of additional clinical trials or post-authorization safety studies.

The manufacturing of authorized

drugs, for which a separate manufacturer’s license is mandatory, must be conducted in compliance with the EMA’s cGMP requirements

drugs, for which a separate manufacturer’s license is mandatory, must be conducted in compliance with the EMA’s GMP requirements

and comparable requirements of other national authorities, which mandate the methods, facilities and controls used in manufacturing, processing

and packing of drugs to assure their safety and identity.

The EMA enforces its cGMP requirements through mandatory registration of facilities

The EMA enforces its GMP requirements through mandatory registration of facilities

and inspections of those facilities.

5 unchanged sentences

action or possible civil and criminal penalties.

The marketing and promotion of

authorized drugs, including industry-sponsored continuing medical education and advertising directed toward the prescribers of drugs and/or

the general public, are strictly regulated in the EU.

The applicable regulations aim to ensure that information provided by holders of

marketing authorizations regarding their products is truthful, balanced and accurately reflects the safety and efficacy claims authorized

by the EMA or by the national authority of the authorizing member state.

Failure to comply with these requirements can result in adverse

publicity, warning letters, corrective advertising and potential civil and criminal penalties.

The advertising and promotion

of medicinal products is also subject to laws concerning promotion of medicinal products, interactions with physicians, misleading and

comparative advertising and unfair commercial practices.

All advertising and promotional activities for the product must be consistent

with the approved summary of product characteristics, and therefore all off-label promotion is prohibited.

Direct-to-consumer advertising

of prescription medicines is also prohibited in the EU.

Reimbursement of Medicines in Europe

In the EU, pricing and reimbursement

methods can differ in each Member State.

Some Member States and the UK may require that health technology assessments (“HTA”)

be completed for the product to be recommended for funding under the NHS.

The outcome of HTAs is decided on a national basis and some

Member States may decide not to reimburse the use of medicines or may reduce the rate of reimbursement.

As of January 12, 2025, EU Health

Technology Regulation No.

2021/2282 has become applicable in respect of new oncology medicines.

Regulation 2021/2282 imposes a new procedure,

a joint clinical assessment at a centralized level, as a mandatory step for the assessment of the pricing and reimbursement of medicinal

products by national authorities.

It requires companies applying for products in scope to make relevant submissions for the joint clinical

assessment, in line with a number of prespecified criteria.

In the UK, NICE is the body

in England and Wales, which conducts HTAs and issues guidance on whether a product is considered to be “cost-effective” and

therefore recommended for use and reimbursement under the national health service.

This means that if a positive recommendation has been

obtained, then the medicinal product will be widely available to patients in England and Wales.

For avoidance of doubt, Scotland and Northern

Ireland have their own HTA bodies which will conduct their own assessment.

Other Healthcare Laws

88 unchanged sentences

to allow us to sell our product candidates on a profitable basis.

In order to secure coverage and

reimbursement for any product that might be approved for sale, we may need to conduct expensive pharmacoeconomic studies in order to demonstrate

the medical necessity and cost-effectiveness of the product, in addition to the costs required to obtain FDA, EMA or other comparable

regulatory approvals.

In order to secure coverage

and reimbursement for any product that might be approved for sale, we may need to conduct expensive pharmacoeconomic studies in order

to demonstrate the medical necessity and cost-effectiveness of the product, in addition to the costs required to obtain FDA, EMA or other

comparable regulatory approvals.

Our product candidates may not be considered medically necessary or cost-effective.

A payer’s decision to

provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved.

Third-party reimbursement may

not be sufficient to enable us to maintain price levels high enough to realize an appropriate return on our investment in product development.

Pricing and reimbursement schemes

vary widely from country to country.

Some countries provide that drug products may be marketed only after a reimbursement price has been

Some countries may require the completion of additional studies that compare the cost-effectiveness of a particular product candidate

to currently available therapies.

The conduct of such studies could be expensive and result in delays in our commercializing efforts.

There can be no assurance that any country that has price controls or reimbursement limitations for drug products will allow favorable

reimbursement and pricing arrangements for any of our products.

A payer’s decision

to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved.

Third-party reimbursement

may not be sufficient to enable us to maintain price levels high enough to realize an appropriate return on our investment in product

Pricing and reimbursement

schemes vary widely from country to country.

Some countries provide that drug products may be marketed only after a reimbursement price

has been agreed.

Some countries may require the completion of additional studies that compare the cost-effectiveness of a particular product

candidate to currently available therapies.

The conduct of such studies could be expensive and result in delays in our commercializing

There can be no assurance that any country that has price controls or reimbursement limitations for drug products will allow

favorable reimbursement and pricing arrangements for any of our products.

The marketability of any products

7 unchanged sentences

Healthcare Reform

In the United States, there have

been and continue to be a number of significant legislative initiatives to contain healthcare costs.

The PPACA contains provisions that

may reduce the profitability of drug products, including, for example, increased rebates for drugs subject to the Medicaid Drug Rebate

In the United States, there

have been and continue to be a number of significant legislative initiatives to contain healthcare costs.

The PPACA contains provisions

that may reduce the profitability of drug products, including, for example, increased rebates for drugs subject to the Medicaid Drug Rebate

Program, extension of Medicaid rebates to Medicaid managed care plans, mandatory discounts for certain Medicare Part D beneficiaries

and annual fees based on pharmaceutical companies’ share of sales to federal health care programs.

Since its enactment, there have

been executive, judicial and Congressional challenges to certain aspects of the PPACA.

Since its enactment, there

have been executive, judicial and Congressional challenges to certain aspects of the PPACA.

On June 17, 2021, the U.S.

Supreme Court dismissed

the most recent judicial challenge to the PPACA brought by several states without specifically ruling on the constitutionality of the

Supreme Court

dismissed the most recent judicial challenge to the PPACA brought by several states without specifically ruling on the constitutionality

of the PPACA.

In addition, other legislative

18 unchanged sentences

on customers for our drugs, if approved, and, accordingly, our financial operations.

Moreover, recently there has been

heightened governmental scrutiny over the manner in which manufacturers set prices for their commercial products.

There have been several

Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more

transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the cost of drugs under

Medicare, and reform government program reimbursement methodologies for drugs.

Moreover, recently there has

been heightened governmental scrutiny over the manner in which manufacturers set prices for their commercial products.

There have been

several recent U.S.

Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring

more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the cost of drugs

under Medicare, and reform government program reimbursement methodologies for drugs.

The FDA published a final rule on October 1,

25 unchanged sentences

although the IRA may be subject to legal challenges.

It is currently unclear how the IRA will be implemented but is likely to have a significant

impact on the pharmaceutical industry.

In addition, in response to the Biden administration’s October 2022 executive order,

on February 14, 2023, HHS released a report outlining three new models for testing by the Center for Medicare and Medicaid Innovation

which will be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care.

It is unclear

whether the models will be utilized in any health reform measures in the future.

Although a number of these and

other proposed measures may require authorization through additional legislation to become effective, Congress has indicated that it will

continue to seek new legislative measures to control drug costs.

It is currently unclear how the IRA will be implemented but it is likely to have

a significant impact on the pharmaceutical industry.

In addition, in response to the Biden administration’s October 2022 executive

order, on February 14, 2023, HHS released a report outlining three new models for testing by the Center for Medicare and Medicaid

Innovation which will be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care.

is unclear whether the models will be utilized in any health reform measures in the future.

Although a number of these

and other proposed measures may require authorization through additional legislation to become effective, Congress has indicated that

it will continue to seek new legislative measures to control drug costs.

CMS issued a final rule, effective

3 unchanged sentences

drugs and biological products that are in violation of these requirements will be included on a public list.

Any adopted health reform measure

could reduce the ultimate demand for our products, if approved, or put pressure on our product pricing.

Individual states in the United

States have also become increasingly active in passing legislation and implementing regulations designed to control pharmaceutical product

pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure

and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products

and which suppliers will be included in their prescription drug and other healthcare programs.

We expect that additional state and federal

healthcare reform measures will be adopted in the future.

Any adopted health reform

measure could reduce the ultimate demand for our products, if approved, or put pressure on our product pricing.

Individual states in the

United States have also become increasingly active in passing legislation and implementing regulations designed to control pharmaceutical

product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing

cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical

products and which suppliers will be included in their prescription drug and other healthcare programs.

We expect that additional state

and federal healthcare reform measures, as well as legal changes by foreign governments, will be adopted in the future, any of which could

limit the amounts that governments will pay for healthcare products and services, which could result in reduced demand for our product

and federal healthcare reform measures will be adopted in the future.

We expect that additional

state and federal healthcare reform measures, as well as legal changes by foreign governments, will be adopted in the future, any of which

could limit the amounts that governments will pay for healthcare products and services, which could result in reduced demand for our product

candidates or additional pricing pressures.

1 unchanged sentence

As of December 31, 2025,

we had 10 full-time employees plus a number of contract workers, who manage and oversee all aspects of our operations, including nonclinical

development, manufacturing, clinical development, and general and administrative functions.

Seven employees were engaged in research and

development activities.

In addition, we currently work with numerous highly experienced consultants and contractors who provide management

and oversight in manufacturing, analytical, clinical supply chain, regulatory, pharmacovigilance and safety, clinical operations, data

management, statistics, non-clinical toxicology, nonclinical and clinical pharmacology, and medical affairs.

Thus, we currently operate

as a semi-virtual pharmaceutical company with expertise in numerous aspects of preclinical and clinical development.

Many of our consultants

and contractors have extensive experience specifically in the development of cancer drugs.

None of our employees are represented

by a labor union or covered under a collective bargaining agreement.

We consider our relationship with our employees to be good.

we had 12 full-time employees plus a number of contract workers, who manage and oversee all aspects of our operations, including

nonclinical development, manufacturing, clinical development, and general and administrative functions.

Nine employees were engaged

in research and development activities.

In addition, we currently work with numerous highly experienced consultants and contractors

who provide management and oversight in manufacturing, analytical, clinical supply chain, regulatory, pharmacovigilance and safety,

clinical operations, data management, statistics, non-clinical toxicology, nonclinical and clinical pharmacology, and medical

Thus, we currently operate as a semi-virtual pharmaceutical company with expertise in numerous aspects of preclinical and

clinical development.

None of our employees are

represented by a labor union or covered under a collective bargaining agreement.

We consider our relationship with our employees to be

Corporate Information

7 unchanged sentences

The information contained on our website or connected to our website is not incorporated

by reference into this annual report on Form 10-K and should not be considered part of this Report.

Our annual reports on Form 10-K,

quarterly reports on Form 10-Q, current reports on Form 8-K, and amendments to those reports, filed or furnished pursuant to Section 13(a)

or 15(d) of the Securities Exchange Act are available free of charge on or through our website at www.actuatetherapeutics.com under the

"SEC Filings" heading on the "Investors" page as soon as reasonably practicable after such reports have been filed

by reference into this Annual Report and should not be considered part of this Report.

Our annual reports on Form

10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, and amendments to those reports, filed or furnished pursuant to Section

13(a) or 15(d) of the Securities Exchange Act are available free of charge on or through our website at www.actuatetherapeutics.com under

the “SEC Filings” heading on the “Investors” page as soon as reasonably practicable after such reports have been filed

with or furnished to the SEC.

They are also available for free on the SEC’s website at www.sec.gov.

In addition, we use our website

www.actuatetherapeutics.com as a means of disclosing material non-public information and for complying with our disclosure obligations

under the Regulation FD.

Such disclosures will be included on the Company’s website under the heading “Investors.” We

also use social media accounts as a means of disclosing material non-public information, including accounts at:

· X account (formerly Twitter):

@ActuateThera or https://x.com/ActuateThera

https://www.linkedin.com/company/actuate-therapeutics-inc./

· Facebook profile:

https://www.facebook.com/profile.php?id=61572431561095

Accordingly, investors should

monitor such portions of the Company’s website and social media accounts, in addition to following the Company’s press releases,

SEC filings, corporate presentations, and public conference calls and webcasts (if any).

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business