What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2026-03-18 compared with 2025-03-21 · 382 added, 279 removed, 778 unchanged (46% of the section changed)

Business Summary

We are a late-stage pharmaceutical development company currently conducting a pivotal Phase 3 trial evaluating Annamycin, a non-cardiotoxic anthracycline, in combination with Cytarabine for the treatment of subjects with relapsed/refractory acute myeloid leukemia (AML).

This Phase 3 trial should have an interim unblinding of data by the end of 2025, less than a year from its commencement, and an additional unblinding in the first half of 2026.

We believe such early visibility for a pivotal registration-enabling trial is highly unique in that stakeholders will receive preliminary safety and efficacy data in the “MIRACLE” trial (derived from Moleculin R/R AML AnnAraC Clinical Evaluation) within one year of dosing the first subject.

Additionally, we have two portfolios of technologies for hard-to-treat cancers and viruses with clinical and preclinical research funded by investigators at academic institutions.

Each of our three core technologies is based substantially on discoveries made at and licensed from the University of Texas MD Anderson Cancer Center (MD Anderson) in Houston, Texas, and features one or more drugs that have successfully completed a Phase 1 clinical trial.

Three of our six drug candidates have shown human activity in clinical trials and are currently or have been in Phase 1B/2 or Phase 2 clinical trials.

One is currently beginning a Phase 2B/3 trial.

Since our inception, our drug candidates have completed, are currently in, or have been permitted to proceed in, fourteen clinical trials.

Annamycin is in a class of drugs referred to as Anthracyclines, which are an inhibitor of topoisomerase II, enabling them to cause DNA damage in rapidly replicating tumor cells.

Annamycin, in a unique multilamellar lipid formulation, is our lead molecule and we have recently concluded one Phase 1B/2 clinical trial for treating AML and are embarking on a Phase 3 clinical trial for the treatment of AML, which we believe will be pivotal.

Annamycin was also in two Phase 1B/2 clinical trials for treating Soft Tissue Sarcoma metastasized to the lungs (STS lung metastases, STS lung mets, or Advanced STS).

We believe that our lead drug candidate Annamycin has summarily:

Demonstrated significant efficacy in Phase 1 and 2 cancer clinical trials – specifically relapsed and refractory (R/R) AML with complete remission rates significantly above currently approved second line therapies and STS lung mets with overall survival as a median seventh line therapy comparable to overall survival seen with approved first line monotherapies;

Shown encouraging activity in five different clinical trials (most of which are now complete), funded both internally and externally (through investigator initiated trials);

Shown in its clinical trials to be non-cardiotoxic (N=84) with some patients being safely dosed at five times the typical lifetime maximum allowed anthracycline dose, which potentially enables repeated dosing and consolidation;

Demonstrated in preclinical models, to be more potent than and to avoid cross resistance with some of the most common drugs used to treat AML (as well as many other cancers), including currently approved anthracyclines, Cytarabine and Venetoclax;

Composition of matter patent protection thru 2040 and has orphan drug and fast track status;

No vesicant activity, making it safer to handle and administer as compared to other anthracyclines;

Shown a complete response (CR) rate of 50%, a composite complete response (CRc) rate of 60%, durability of CRc’s of approximately 9 months (and climbing), and an overall survival (OS) rate of approximately 11 months (and climbing) (N=10) in combination with Cytarabine for the treatment of R/R AML as second line therapy to date, which is higher than other currently approved second line therapies for R/R AML

One of our core management beliefs is that anthracyclines represent one of the most important treatments for AML and Advanced STS, and we believe Annamycin may, for the first time ever, allow a majority of these patients to benefit from this treatment.

We believe that such a benefit would be disruptive to the competitive landscape for these markets.

We are a late-stage pharmaceutical development company currently evaluating Annamycin, also known as L-Annamycin and by its generic name “naxtarubicin”, which we believe is a “next-generation” anthracycline and, with it, are conducting a pivotal Phase 3 trial in combination with cytarabine for the treatment of subjects with relapsed/refractory (R/R) acute myeloid leukemia (AML).

We call this the “MIRACLE” trial (derived from Moleculin R/R AML AnnAraC Clinical Evaluation).

A blinded preliminary data readout has been released for the MIRACLE trial, and we expect to have an interim unblinding of data in mid-2026 and an additional unblinding in the second half of 2026, thereby concluding Part A of the two-part trial.

We believe such early visibility for a pivotal registration-enabling trial is unique in that stakeholders will receive preliminary safety and efficacy data long before the conclusion of the trial.

We have two additional portfolios of technologies for hard-to-treat cancers and viruses with clinical and preclinical research funded by investigators at academic institutions.

One of these portfolios has an ongoing investigator-initiated trial, another one planned and additional active preclinical testing.

Since our inception, drug candidates from each of the three core portfolios are in active planning for, have approval to begin, are currently in or have successfully completed eighteen clinical trials.

Each of our three core technologies is based substantially on discoveries made at, made in conjunction with, and/or licensed from the University of Texas MD Anderson Cancer Center (MD Anderson) in Houston, Texas.

For each of the core technologies, one or more drug candidates have successfully completed a Phase 1 or greater clinical trial.

Three of our drug candidates have shown human activity in clinical trials and are currently or have been in Phase 1B/2, Phase 2, or Phase 2B/3 clinical trials.

One of those drug candidates is Annamycin, which is currently in the MIRACLE trial.

We believe Annamycin is the first of its kind DNA binding agent, a “next-generation” anthracycline.

Whereas first- and second-generation anthracyclines are currently used to treat approximately half of all cancers, they carry with them the burden of dangerous cardiotoxicity and efficacy limitations associated with multidrug resistance mechanisms and poor tissue/organ distribution.

Later generation anthracyclines are comprised mainly of attempts to reduce cardiotoxicity or enhance anticancer activity but we believe have failed to deliver the necessary safety and efficacy profiles to win approval or gain market acceptance.

Annamycin is an entirely new chemical entity integrating a new molecular structure intended to enhance its ability to selectively kill cancer cells and reduce toxic side effects.

Annamycin possesses a unique and innovative multilamellar lipid-based delivery system designed to improve bioavailability and to increase the therapeutic window.

The result is a next-generation anthracycline that we believe effectively addresses critical problems associated with currently used anthracyclines.

It is our lead drug candidate, and we have concluded a Phase 1B/2 clinical trial for treating AML and are now conducting a Phase 3 clinical trial for R/R AML, which we believe will be registration enabling.

We have also sponsored two Phase 1B/2 clinical trials of Annamycin for treating Soft Tissue Sarcoma metastasized to the lungs (STS lung metastases, STS lung mets, or Advanced STS), the results of which we believe supports the initiation of a pivotal approval trial in this additional indication.

We believe that our lead drug candidate Annamycin has:

The following advantages over early-generation anthracyclines which in their totality support Annamycin’s classification as a “next-generation” anthracycline:

1) demonstrated across five clinical trials to be non-cardiotoxic (n=90) with some patients being safely dosed at five times the typical lifetime maximum allowable anthracycline dose, (which potentially enables repeated dosing, consolidation and even use as a maintenance therapy);

2) exhibits no vesicant activity as well as greater tolerability, making it safer to handle and administer and easier on patients;

3) shown in preclinical models to circumvent multidrug resistance by avoiding MDR1 mechanisms and also to avoid cross-resistance with some of the most commonly used drugs for the treatment of AML (as well as many other cancers), including currently approved early-generation anthracyclines, cytarabine and venetoclax and, 4) exhibited in preclinical models substantially improved tissue/organ distribution;

Demonstrated a complete remission (CR) rate of 50% and a composite complete remission (CRc) rate of 60% in combination with Cytarabine for the treatment of R/R AML as second line therapy (n=10).

On an all comer's basis (no limit on prior lines of therapy), the population of subjects who achieved a CR (n=8) demonstrated durability of approximately 13 months with median overall survival of 15 months and developing at the time of analysis, with 4 of 8 subjects (50%) censored;

Shown promising blinded safety and efficacy data for the first 30 subjects treated in the MIRACLE trial as we head towards the planned interim unblinding of data for the first 45 subjects treated with efficacy data in Part A of the MIRACLE trial in mid-2026;

Shown encouraging activity in a total of five different clinical trials (most of which are now complete), funded both internally and externally (through investigator-initiated trials);

specifically including relapsed and refractory AML with complete remission rates significantly above currently approved second line therapies and STS lung mets with overall survival as a median seventh line therapy comparable to overall survival seen with approved first line monotherapies;

Obtained composition of matter patent protection through 2040 with the potential to extend as far as 2045 as well as Orphan Drug and Fast Track designation.

One of our core management beliefs is that anthracyclines represent one of the most important treatments available for AML and Advanced STS, as well as many other cancers, and we believe Annamycin may, for the first time ever, allow a majority of these patients to benefit from Annamycin’s improved safety and efficacy by allowing increased dosing (and even maintenance dosing), improved tolerability and allowing access for patients who otherwise would not be eligible for an anthracycline (including the elderly and those with impaired cardiac function).

We believe that such benefits will be disruptive to the competitive landscape for these markets.

This belief, coupled with our limited resources, leads us to currently focus mainly on the development of Annamycin.

We intend to advance our other drug candidates via investigator led studies – both clinically and preclinically.

Focus and Core Technologies

We are focused on internally funded (“internally” and “externally” funded trials are defined in the Funding Strategy section below) development of our core technologies:

1) Annamycin:

In combination with Cytarabine (also known as Ara-C, the combination with Annamycin of which is referred to as AnnAraC) for the treatment of R/R AML, and

For the treatment of STS metastasized to the lungs.

2) WP1066 IV:

A better formulation for delivery intravenously of a molecule from the WP1066 portfolio to possibly further support for future externally funded oncology clinical trials.

Such a formulation will require additional preclinical work prior to a clinical trial.

We have established a Recommended Phase 2 Dose for WP1122 to potentially enable future externally funded oncology and virology trials.

Beyond this, we support development of our core technologies through several externally funded clinical trials and primarily externally funded non-clinical research, with the potential for further studies in the future.

We seek to advance our other drug candidates via investigator led studies, both clinically and preclinically, and as available resources will allow.

Core Technologies and Focus

Our core technologies consist of the following programs:

a) Annamycin or L-Annamycin is a “next generation” anthracycline (one of the most widely used classes of chemotherapy), designed to be different than currently approved anthracyclines, which are limited in utility because of cardiotoxicity risks and their susceptibility to multidrug resistance mechanisms.

Annamycin was designed to avoid multidrug resistance and to be non-cardiotoxic and, with intensive cardiac monitoring, has shown no cardiotoxicity in subjects treated in our five Annamycin clinical trials to date.

Furthermore, we have demonstrated safe dosing significantly beyond the dose limitations imposed by regulatory authorities upon commonly prescribed anthracyclines due to their inherent cardiotoxicity.

a) Annamycin is what we believe to be a “next-generation” anthracycline (one of the most widely used classes of chemotherapy), designed to be different than currently approved anthracyclines, which are limited in utility because of cardiotoxicity risks, tolerability, their susceptibility to multidrug resistance mechanisms and a lack of efficacy in certain tumor models.

b) Our WP1066 Portfolio includes WP1066, WP1193 and WP1220, three of several Immune/Transcription Modulators in the portfolio designed to inhibit p-STAT3 (phosphorylated signal transducer and activator of transcription) among other transcription factors associated with tumor activity.

2 unchanged sentences

We believe such compounds may provide an opportunity to cut off the energy supply of tumors by taking advantage of their high degree of dependence on glucose in comparison to healthy cells, as well as viruses that also depend upon glycolysis and glycosylation to infect and replicate.

In all our discussions, clinical data (where a CSR or its equivalent has not been published), are considered preliminary and subject to change.

Our Current Clinical Trial Focus

We are focused on Annamycin and WP1066 program’s internally and externally funded (“internally” and “externally” funded trials are defined in the Funding Strategy section below) development of our core technologies as follows:

Internally funded – In combination with Cytarabine (also known as Ara-C, the combination with Annamycin of which is referred to as AnnAraC) for the treatment of R/R AML, and

Externally funded – Advancing beyond our initial Phase 1B/2 internally funded trial for the treatment of STS metastasized to the lungs.

Externally funded – Based on sponsored research, we intend to begin in 2026 a Phase 1B/2 clinical trial with Annamycin as a monotherapy treating 3 rd line pancreatic cancer.

Internally funded – MB-109 utilizing AnnAraC for R/R AML as 3 rd line therapy in adults is planned for 2027.

Externally funded – MB-110 utilizing AnnAraC for R/R AML as 2 nd line therapy in pediatrics is planned for 2027.

We are researching potential sites for a grant funded trial.

Externally funded - An improved formulation for delivery intravenously (IV) of a molecule from the WP1066 portfolio to possibly further support future externally funded oncology clinical trials.

Such a formulation requires additional preclinical work prior to a clinical trial.

Externally funded - Phase 1B/2 trial for WP1066 oral formulation in combination with radiation treating glioblastoma (GBM) both in adults and pediatrics.

An adult clinical trial is in process, and a pediatric trial is in the planning stage.

We have established a Recommended Phase 2 Dose for WP1122 to potentially enable future externally funded oncology and virology trials.

Beyond this, we support development of our core technologies through sponsored (internally funded) non-clinical research at MD Anderson.

Clinical Trials Summary

As summarized on the next page, we and our external investigators have multiple active INDs/CTAs (Investigational New Drug authorization in the US or Clinical Trial Authorization in Europe).

Under these INDs/CTAs, we have under development, approved, have in progress, or have completed fourteen internally and externally funded clinical trials.

Below in Table 1 we are summarizing those clinical trials that have concluded, are in progress, or are approved/allowed by the FDA or its European equivalent.

See the notes below and the detailed discussion in the sections following Table 1 for more information.

We have multiple active INDs/CTAs (Investigational New Drug authorization in the US or Clinical Trial Authorization in Europe).

These INDs/CTAs are under development, approved, in progress, or completed comprising a total of eighteen clinical trials, internally and externally funded.

With Annamycin, we currently have active one AML clinical trial, MB-108 (also referred to as the MIRACLE trial), which is a Phase 2B/3 pivotal clinical trial studying AnnAraC for the treatment of R/R AML in 2 nd line subjects for which recruitment began in March 2025.

MB-106, which was a Phase 1B/2 trial treating AML with AnnAraC has achieved data lock, and the clinical study report (CSR) is in process and should be published in late March 2026.

Data is preliminary and subject to change.

was published in early March 2026.

We also had one internally funded Phase 1B/2 trial– MB-107 – and one externally funded trial – both treating STS with Annamycin as monotherapy.

The externally funded trial is closed and the CSR or its equivalent is being drafted.

With WP1066, we have an externally funded phase 1B/2 in combination with radiation treating GBM at Northwestern University that is actively recruiting.

We are currently planning an externally funded Phase 1B/2 trial to study Annamycin as a monotherapy for the treatment of 3rd line subjects with pancreatic cancer at Atlantic Health System in New Jersey.

This trial is expected to begin in 2026.

This is summarized in Table 1 below.

In all our discussions, clinical data, where a CSR or its equivalent has not been published, are considered preliminary and subject to change.

We denote where a CSR or its equivalent has been published.

See the notes below Table 1 and the detailed discussion in the sections following Table 1 for more information.

Table 1 - Clinical Summary as of this filing

20 unchanged sentences

Annamycin in Combination with Cytarabine

MB-106 / R/R AML / Europe

22 subjects intent to treat.

MB-106 / AML / Europe (7)

22 subjects' safety evaluable.

2 subjects had an allergic reaction and did not receive full dose.

Enrollment closed.

Trial continues with long-term follow-up.

CSR is in process and should be published in late March 2026.

Seven sites recruited in Poland and Italy.

6 unchanged sentences

CR 50% & CRc 60% 2 nd Line;

Durability of all CR’s~12 mos & climbing;

Durability of all CR’s 13.14 mos ;

CR’s in Multiple genotypes/mutations;

and post 2 nd line post Venetoclax therapy (60% CRc)

and 60% CRc in 2L subjects previously treated with venetoclax therapy)

MB-107 / STS Lung Metastases / US

1 unchanged sentence

Phase 2 completed;

CSR finalized not yet submitted.

CSR finalized

RP2D of 330 mg/m 2 identified

No cardiotoxicity reported

CSR finalized but not submitted.

Final data to be presented by the end of April.

Preliminary OS ~10 mos as median 4 th line.

Median OS 13.5 mos (n=36) as median 7 th line therapy

Annamycin in Combination with Cytarabine

MB-108 / 2 nd Line R/R AML / Global (MIRACLE)

First site initiated

Over 20 sites with Site Initiation Visits (SIVs) across nine countries in Europe and the US;

35 subjects treated as of February 10, 2026.

Global trial Annamycin plus cytarabine vs control arm of cytarabine plus placebo

No data to date

Too early for Expert to review data.

No significant cardiac events reported to date for blinded subjects.

Preliminary blinded CRc 40%, CR 30% (n=30) w/ randomized three arms – AraC, AraC+190 mg/m 2 Annamycin, AraC+230 mg/m 2

MB-109/ 3 rd Line R/R AML/ Global

2027 target start

MB-110/ Pediatric R/R AML/ US

External (intended)

2027 target start

IIT / STS Lung Metastases / Poland

Study closed to further enrollment.

Study closed.

CSR or its equivalent in process

Investigator led trial weekly dosing regimen versus traditional chemotherapy dosing

No cardiotoxicity reported

8 subjects enrolled and treated.

More detail below.

No evidence of

cardiotoxicity noted by our independent expert

No efficacy data reported to date.

IIT/ 3 rd Line Pancreatic Cancer/ US

(exploring IIT)

2026 planned start

Monotherapy once every three weeks with correlative biomarker assessment planned

IIT /Adult GBM / US

6 unchanged sentences

Open to an investigator to lead a study

WP1066 in combination with radiation

IND allowed for Adult GBM / US

WP1066 in combination w/ radiation therapy

2 nd protocol under IND allowed for Adult GBM / US

Open to an investigator to lead a study

2 unchanged sentences

IND allowed for IIT led Adult GBM / US

Site initiation visit was in May 2024

4 subjects enrolled and treat with 1 subject currently on active treatment

Enrolling and treating

4 subjects enrolled and treated with 1 subject currently on active treatment

No safety data reported to date

No efficacy data reported to date

WP1066 in combination with radiation therapy

IIT led Pediatric Brain Tumors / US

Planned 2026 start

IIT / Pediatric Brain Tumors / US

Concluded in February 2023 with a dose level at 8mg/kg;

CSR in process.

Concluded 10 subjects enrolled and treated over 3 dose levels up to 8 mg/kg

11 unchanged sentences

N/A as in healthy volunteer subjects

IND approved for GBM

IND allowed for GBM;

1B/2 External

Exploring for an investigator to lead a study

Trial has not begun

Open to an investigator to lead a study

Notes for Table 1 :

1) This is a summary of the detailed clinical discussion below and does not include compassionate use/right-to-try usage of our drug candidates;

2) Complete Response Composite (CRc) includes CRs and CRi’s;

2) Complete Remission ("Response" for STS) Composite includes Complete Remission and CR with incomplete hematologic recovery (CRi or CRh);

3) Overall Response Rate (ORR) includes CRc and Partial Response (PR);

4) “Met safety endpoints” means that no drug-related serious and no unexpected adverse event (only one serious in MB-105) occurred as defined in the trial protocol 5) All data presented are preliminary (and subject to change) unless a CSR or an investigator's final report has been issued for the trial referenced;

4) “Met safety endpoints” means that the studies achieved their safety objectives and refers to the overall safety profile observed in the study, which did not preclude continued clinical development.

Serious adverse events were reported, including one considered related to study drug and unexpected.

5) All data presented are preliminary (and subject to change) unless a CSR or its equivalent has been issued for the trial referenced;

6) With regard to safety and human activity summaries please see the detailed discussion below;

1 unchanged sentence

Our Drug Candidate Programs

In the US and Europe, since our inception, we or independent investigators have approval to begin, are currently conducting or have completed fourteen internally or externally funded clinical trials for four of our drug candidates – Annamycin, WP1066, WP1220, and WP1122, as listed above.

In the US and Europe, since our inception, we or independent investigators are actively planning, have approval to begin, are currently conducting or have completed eighteen internally or externally funded clinical trials for our drug candidates – Annamycin, WP1066, WP1220, and WP1122, as listed above.

All of the clinical trials are or were in the Phase 1 or 2 stage with the exception of MB-108 which is a Phase 2B/3.

Starting in 2021 through 2024, there have been eight "right-to-try" (or their foreign equivalent) uses of Annamycin and WP1066.

Starting in 2021 through 2024, there have been eight "right-to-try" or “compassionate use” (or their foreign equivalent) uses of Annamycin and WP1066.

Our clinical trials focused on Annamycin in 2024 with two internally funded and one externally funded Phase 1B/2 clinical trials.

We concluded recruitment and treatment in the MB-107 Phase 1B/2 all comers clinical trial using Annamycin as a single agent for the treatment of STS lung mets in 2023 and followed for progression free survival (PFS) and OS during 2024.

In our MB-106 Phase 1B/2 all-comers clinical trial using Annamycin in combination with Cytarabine for the treatment of AML, we concluded recruitment and treatment with 22 subjects recruited on an Intent-To-Treat (ITT) basis.

The CSR was published in 2025.

In our MB-106 Phase 1B/2 all-comers clinical trial using Annamycin in combination with Cytarabine for the treatment of AML, we concluded recruitment and treatment with 23 subjects recruited on an Intent-To-Treat (ITT) basis (22 subjects' safety evaluable with one subject enrolled but never treated).

The term "all-comers" for this trial indicates that we did not limit the number of prior therapies for subjects entering the trial in the Phase 1 portion of MB-106.

1 unchanged sentence

We utilized the MB-106 data for an End of Phase 2 (EOP2) meeting with the U.S.

Food and Drug Administration (FDA) in July 2024.

Food and Drug Administration in July 2024.

The CSR for MB-106 is in process and should be published in late March 2026.

Data is preliminary and subject to change.

In July 2024, we announced the completion of our EOP2 meeting with the FDA for our Phase 1B/2 clinical trial evaluating Annamycin in combination with Cytarabine for the treatment of subjects with AML as both first line therapy and for subjects who are refractory to or relapsed after induction therapy (MB-106).

We believe that this meeting, based upon the FDA minutes, was a positive discussion and resulted in the design and implementation of a Phase 2B/3 pivotal trial for the treatment of AML patients who are refractory to or relapsed after induction therapy (R/R AML).

The MIRACLE trial will be a global trial, including sites in the US, Europe, Western Asia and the Middle East.

The MIRACLE trial is a global trial, including sites in the US, Europe or the European Union (EU), and Eastern Europe.

The FDA’s Divisions of Hematologic Malignancies I and Cardiology and Nephrology, as well as related divisions, were involved in the review of the data showing no cardiotoxicity in MB-106 and prior clinical trials.

Consistent with the FDA’s recommendations, in the adaptive MIRACLE trial we plan to utilize a double-blind, placebo-controlled design, where we will compare AnnAraC versus a control arm of high dose cytarabine (HiDAC) plus placebo and we will rely solely on CR (complete remission) at approximately one month as the primary endpoint.

The FDA also wanted to see the durability of response (DoR) as a secondary endpoint and overall survival as an exploratory endpoint, as well as data for patients beyond 2nd line, which is why our plan includes a follow-on MIRACLE2 trial in 3rd line patients starting once the optimum dose is established in the MIRACLE trial.

Consistent with the FDA’s recommendations, in the adaptive MIRACLE trial we are utilizing a double-blind, placebo-controlled design, where we will compare two arms of AnnAraC, with two different strengths of Annamycin, versus a control arm of high dose cytarabine (HiDAC) plus placebo and we will rely solely on CR (complete remission) after a single cycle of treatment (at approximately one month) as the primary endpoint.

The FDA also wanted to see overall survival (OS) as a secondary endpoint and durability of response (DoR) as an exploratory endpoint, as well as data for patients beyond 2nd line, which is why our plan includes a follow-on MIRACLE2 trial in 3rd line patients starting once the optimum dose is established in the MIRACLE trial.

Based on our discussions with the FDA, we amended in September 2024 our MB-104 investigational new drug application or IND for MB-108.

In the amendment with the new MIRACLE protocol, the trial will, for the first time ever in the US for an AML trial, allow dosing above the lifetime maximum allowable dose (LTMAD) for currently prescribed anthracyclines.

The MIRACLE study, subject to appropriate future filings with and potential additional feedback from the FDA and their foreign equivalents, utilizes an adaptive design whereby the first 75 to 90 subjects will be randomized (1:1:1) in Part A of the trial to receive high dose cytarabine (HiDAC) combined with either placebo, 190 mg/m2 of Annamycin, or 230 mg/m2 of Annamycin, which Annamycin doses were specifically recommended by the FDA in the Company’s end of Phase 1B/2 meeting.

The amended protocol allows for the unblinding of preliminary primary efficacy data (Complete Remission or CR) and safety/tolerability of the three arms once 45 subjects have been evaluated, in addition to unblinding at the conclusion of Part A (at a total of 75 to 90 subjects).

The first unblinding will yield 30 subjects treated with Annamycin (190mg/m2 and 230/m2) and HiDAC compared with 15 subjects from the control arm.

The Company expects to reach the first unblinding (45 subjects) in the second half of 2025, in addition to the second unblinding, which is expected in the first half of 2026.

For Part B of the trial, approximately 220 additional subjects will be randomized to receive either HiDAC plus placebo or HiDAC plus the optimum dose of Annamycin (randomized 1:1).

The selection of the optimum dose will be based on the overall balance of safety, pharmacokinetics and efficacy, consistent with the FDA’s new Project Optimus initiative.

In the amendment with the new MIRACLE protocol, the trial, for the first time ever in the US, allowed for dosing in an AML trial above the lifetime maximum allowable dose (LTMAD) for currently prescribed anthracyclines.

The MIRACLE study, subject to appropriate future filings with and potential additional feedback from the FDA and their foreign equivalents, utilizes an adaptive design whereby the first 90 subjects will be randomized (1:1:1) in Part A of the trial to receive five days of HiDAC combined with three days of either placebo, 190 mg/m2 of Annamycin, or 230 mg/m2 of Annamycin, which Annamycin doses were specifically recommended by the FDA in the Company’s end of Phase 1B/2 meeting.

This “5+3” regimen differs from the traditional 7+3 regimen which is considered the gold standard for first line AML therapy whereby patients receive seven days of HiDAC plus three days of a currently prescribed anthracycline.

We believe 5+3 not only improves tolerability for patients but also reduces cost and strain on hospital staff by not having to schedule infusions over a weekend.

The amended protocol allows for an interim unblinding of data of the first 45 subjects treated with efficacy data across the three arms.

In addition, there is an unblinding of data at the conclusion of Part A (at a total of up to 90 subjects) for all three arms.

The first interim unblinding should yield approximately 30 subjects treated with Annamycin (190mg/m2 and 230/m2) and HiDAC compared with approximately 15 subjects from the control arm.

The use of the word “approximately” is due to randomization of these 45 subjects between the three arms.

The Company expects to reach the first interim unblinding (45 subjects) in mid-2026 with the expected second unblinding of the full 90 subjects in Part A in the second half of 2026.

For Part B of the trial, 222 additional subjects will be randomized to receive either HiDAC plus placebo or HiDAC plus the optimum dose of Annamycin (randomized 1:1).

The selection of the optimum dose will be based on the overall balance of safety, pharmacokinetics and efficacy obtained from Part A, consistent with the FDA’s new Project Optimus initiative.

Additionally, recruiting and treatment concluded in 2024 for the externally funded Phase 1B/2 clinical trial studying an alternative dosing schedule of Annamycin for the treatment of STS lung mets in Poland.

The investigator is expected to issue a publication in 2025 on this study.

In February 2023, the externally funded Phase 1 clinical trial with WP1066 for the treatment of pediatric brain tumors concluded.

An externally funded Phase 1B/2 clinical trial for WP1066 in combination with radiation for the treatment of GBM began treating subjects in 2024.

Preclinical studies have begun on an intravenous formula of WP1066 to determine which molecule within the WP1066 portfolio will be best suited for future trials.

Internally funded preclinical studies at MD Anderson were initiated in 2023 and ongoing thru 2025.

The investigator is expected to issue a publication or CSR in 2026 on this study.

In February 2023, the Emory physician-sponsored clinical trial for the treatment of pediatric brain tumors with an oral formulation of WP1066 concluded.

Final positive results were announced in December 2025 from the Emory‘s physician-sponsored Phase 1 clinical trial.

The results of this first-in-child trial show some encouraging signals of activity in a highly aggressive chemotherapy resistant brain cancer, such as partial tumor response in a diffuse intrinsic pontine glioma (DIPG) patient and clear anti-tumor immune changes.

Additionally, externally funded preclinical work is being performed at Emory University and along with the data from the clinical trial at Northwestern University, should set the stage for additional pediatric studies at Emory University in the future.

We have a National Institutes of Health (NIH) funded preclinical study with WP1096 (from the WP1122 portfolio) for the treatment of the Tacaribe Arenavirus at University Texas Medical Branch.

We successfully completed a Phase 1 clinical study of WP1122 in 2023.

Annamycin Program

We consider Annamycin to be a "next generation" anthracycline, unlike any currently approved anthracyclines, as it is designed to avoid multidrug resistance mechanisms and cardiotoxicity, recognizing that the efficacy of all currently approved anthracyclines is limited by both multidrug resistance and cardiotoxicity.

We believe Annamycin can be a safer and more efficacious "next-generation" anthracycline, unlike any currently approved anthracyclines.

We believe its design 1) avoids cardiotoxicity, 2) improves safety and tolerability, 3) overcomes multidrug resistance (MDR), 4) avoids cross resistance with commonly used first line therapies, 5) provides improved tissue/organ distribution and uptake, and 6) demonstrates a unique ability to target key sites of cancer metastasis.

We believe Annamycin has the potential to be highly significant and disruptive as current anthracyclines are used to treat approximately half of all cancers and 60% of all childhood cancers.

The latter statistic is particularly important since it is estimated that more pediatric cancer patients will suffer cardiovascular disease later in life as a result of their treatment than a recurrence of the cancer for which they were treated.

Our preclinical studies and clinical trials support this intended design.

1 unchanged sentence

Based upon the efficacy and safety data to date, we believe that Annamycin has potential to fill an unmet need as a second line therapy (2 nd line) in AML and potentially as a first line therapy (1 st line) in both AML and Advanced STS.

Furthermore, preclinical studies indicate that Annamycin has the potential to be not only safer and more effective than currently prescribed anthracyclines in a wide range of additional cancer indications, but also to be effectively used to treat primary and metastatic cancers resistant to other anthracyclines or cancers where no effective therapies or only limited therapeutic options are available, including:

Pancreatic cancer

Pancreatic cancer metastasized to the liver

Colorectal cancer metastasized to the liver

Colorectal cancer metastasized to the lungs

RCC metastasized to the lungs

Endometrial cancer metastasized to the lungs

Hepatocellular carcinoma

Triple negative breast cancer metastasized to the lungs

Sarcoma metastasized to the lungs

The FDA and the EMA (European Medicines Agency) have granted Orphan Drug Designation (ODD) to Annamycin for the treatment of AML.

1 unchanged sentence

Such designation means, in part, these agencies believe we have established a medically plausible basis for using the drug for those indications.

The FDA also granted Fast Track-Designation (FTD) for Annamycin for both the treatment of AML and Soft Tissue Sarcoma.

The FDA also granted Fast Track-Designation for Annamycin for both the treatment of AML and Soft Tissue Sarcoma.

A drug that receives Fast Track-Designation (FTD) is eligible for some or all of the following:

3 unchanged sentences

Rolling review by FDA of the NDA, rather than waiting until every section of the NDA is complete before beginning review of the application, which is the typical process.

Annamycin – the Next-Generation Anthracycline

Our description of Annamycin as a next-generation anthracycline stems from how significantly different it is from any anthracyclines that have preceded it.

First-generation anthracyclines are the “classic” agents such as daunorubicin and doxorubicin, which were among the earliest anthracyclines developed and widely adopted in oncology.

Second-generation anthracyclines are later structural analogs designed to modify toxicity and/or spectrum of activity;

commonly cited examples include epirubicin and idarubicin.

Annamycin is an entirely new chemical entity integrating a new molecular structure with a unique and innovative multilamellar lipid delivery mechanism designed to address the problems associated with early-generation anthracyclines.

While it incorporates molecular structure changes found in second-generation anthracyclines the molecule also benefits from the addition of an iodine atom that dramatically changes the physical structure as compared with all prior generations of anthracyclines.

Among other things, iodine facilitates a significant increase in lipophilicity and when integrated into our unique multilamellar vesicle never before used with existing anthracyclines, preclinical research has demonstrated Annamycin to be a safer and more effective alternative in a wide range of tumor models.

Annamycin’s unique next-generation design also results in substantive differences in pharmacokinetics when compared with currently used anthracyclines.

Preclinical models comparing Annamycin with doxorubicin show a significant increase in cellular uptake and retention, as well as what we believe are highly beneficial changes in tissue/organ distribution.

These changes also result in a profound “organotropism” enabling Annamycin to accumulate in certain organs that are particularly important when targeting cancer cells.

The Importance of Lower Cardiotoxicity and Multi-Drug Resistance for 2 nd Line Therapy

5 unchanged sentences

In the case of acute leukemia, anthracyclines are typically used in “induction therapy,” where the goal is often to induce sufficient remission of patients’ bloodborne tumor cells to allow for a potentially curative bone marrow transplant.

Two key factors limit the safety and effectiveness of anthracyclines:

cardiotoxicity and multidrug resistance.

We believe Annamycin may significantly reduce the impact of these two factors.

If early clinical data of efficacy are borne out in subsequent clinical trials, of which there can be no assurance, Annamycin may ultimately provide clinically meaningful benefits over currently approved anthracyclines in treating certain cancers, especially as a 2 nd line therapy.

Several key factors limit the safety and effectiveness of anthracyclines:

cardiotoxicity, multidrug resistance and tissue/organ distribution and uptake.

We believe Annamycin represents a significant improvement over currently prescribed anthracyclines in each of these areas.

While we believe this is especially the case as a 2 nd line therapy in R/R AML, we also believe there is a significant opportunity for Annamycin to become a first line standard of care.

The potential for cardiotoxicity in pediatric leukemia patients, whose life spans can be severely shortened by the induction therapy intended to cure them of acute leukemia, represents a significant risk.

2 unchanged sentences

This would be especially valuable in the case of pediatric acute leukemia (both AML and acute lymphoblastic leukemia or ALL) because of the potential impact of cardiotoxicity on long-term survival.

In addition, the effectiveness of currently approved anthracyclines is limited by their propensity for succumbing to “multidrug resistance.” This can occur where, as a natural defense mechanism, transmembrane proteins acting as transporters (one type of which is referred to as a “P-glycoprotein pump” or an “ABCB1 transporter”;

otherwise referred to as “MDR1 mechanisms”) develop on the outer surface of cells to expel perceived threats like anthracyclines.

In many instances, the likelihood of cardiotoxicity (and other serious side effects) prevents increasing the dosing of current therapies in order to overcome multidrug resistance.

As a result, most patients cannot receive current anthracyclines in doses that are adequate to produce lasting remission and thereby qualify for a bone marrow transplant.

A laboratory study has suggested that Annamycin may resist being expelled by P-glycoprotein pumps and similar multidrug resistance transporters, which may mean the drug circumvents multidrug resistance.

Although significant further study is necessary, this characteristic has been shown in pre-clinical testing to allow for higher drug uptake in diseased cells, which we believe could allow for more effective induction therapy with less risk to the patient, especially in relapsed patients.

We believe that the encouraging preliminary efficacy being demonstrated in our clinical trials in 2 nd line AML therapy may, in part, be the result of Annamycin's ability to avoid MDR1 mechanisms.

As part of our Annamycin clinical trials, we have engaged an independent expert at the Cleveland Clinic to assess cardiotoxicity associated with chemotherapy (Expert or Independent Expert).

6 unchanged sentences

In our discussions regarding the lack of Annamycin's cardiotoxicity, we rely on the Expert's assessment.

Annamycin in preclinical studies has shown a lack of cardiotoxicity and this also has been shown in our clinical trials to date, as reported by our Expert.

Our Expert has issued and will continue to issue periodic reports as additional data are provided in batches of subject data.

To date, we have received several independent assessments for the absence of cardiotoxicity in subjects treated with Annamycin.

We now have independent assessments covering 84 subjects that have been treated with Annamycin in five different clinical trials in the U.S.

We have not seen evidence of cardiotoxicity in over 100 subjects that have been treated with Annamycin in our clinical trials to date.

Within in that population, we now have independent assessments covering 90 subjects that have been treated with Annamycin in five different clinical trials in the U.S.

and Europe with no evidence of cardiotoxicity.

To date of the 77 subjects treated in our internally funded trials, 56 were treated above the FDA’s lifetime maximum anthracycline limit of 550 mg/m 2 , with one subject having been treated with 3420 mg/m 2 (or roughly five times the FDA approved lifetime anthracycline exposure) of standard anthracyclines and there has been no evidence of cardiotoxicity.

To date, of the 90 subjects treated in our internally funded trials, 65 were treated above the FDA’s lifetime maximum anthracycline limit of 550 mg/m 2 , with one subject having been treated with 3420 mg/m 2 (combined doses of prior anthracyclines plus Annamycin) of anthracyclines and there has been no evidence of cardiotoxicity.

The 3420 figure converts to 6534 mg/m 2 on a combined basis of prior anthracyclines plus Annamycin expressed as a daunorubicin-equivalent estimate based on the conversion factor described in Zamorano et al.

After review of the data provided, the Independent Expert, in their most recent report and as stated in previous reports, concluded that there was no evidence of cardiotoxicity.

6 unchanged sentences

We believe that the potential for such future incidences, however, does not outweigh the significant elimination of cardiotoxicity to date as reflected in the Expert’s reports.

otherwise referred to as “MDR1 mechanisms”) develop on the outer surface of cells to expel perceived threats like anthracyclines.

In many instances, the likelihood of cardiotoxicity (and other serious side effects) prevents increasing the dosing of current therapies in order to overcome multidrug resistance.

As a result, most patients cannot receive current anthracyclines in doses that are adequate to produce lasting remission and thereby qualify for a bone marrow transplant.

We believe that the encouraging preliminary efficacy being demonstrated in our clinical trials in 2 nd line AML therapy may, in part, be the result of Annamycin's ability to avoid MDR1 mechanisms.

The Organotropic Nature of Annamycin

Nonclinical research at MD Anderson has indicated that Annamycin has an organotropic nature enabling it to hyperaccumulate in certain key organs, including the liver, spleen, pancreas and lungs as compared with existing anthracyclines such as doxorubicin.

This could prove to be especially valuable for primary tumors in or tumors that eventually metastasize to these organs.

As an example, animal models have shown a 39-fold increase in the concentration of Annamycin over doxorubicin (one of the most commonly used anthracyclines) in the spleen, which is considered a sanctuary site for residual disease in AML patients.

In these same models, we see a 31-fold increase in uptake to the lungs where sarcoma metastases are most commonly found and an 11-fold increase in uptake to the pancreas where drug uptake is notoriously difficult.

We announced in April 2019 that our ongoing sponsored nonclinical research at MD Anderson demonstrated that Annamycin may improve survival in an aggressive form of triple negative breast cancer metastasized to the lungs in animal models.

Annamycin was previously shown to be significantly more potent than doxorubicin in both Lewis lung carcinoma in animal models and in small cell lung cancer in vitro models.

In addition to seeing activity in animal models of triple negative breast cancer metastasized to the lungs, we have also seen activity in colon cancer metastasized to the lungs.

The particular animal models used in our testing are considered to represent very aggressive forms of cancer.

Furthermore, a poster entitled, "Liposomal annamycin inhibition of lung localized breast cancer," was presented at the San Antonio Breast Cancer Symposium held in December 2019.

The published poster (https://www.moleculin.com/san-antonio-bc-symposium-poster/) shows substantially increased survival in both triple negative breast cancer and colon cancer lung metastases animal models.

It should also be noted that treatment with Annamycin resulted in long-term survival of a significant number of animals, even when cancer was reintroduced into the animals post initial treatment, suggesting the development of beneficial immune memory.

A reduction in tumor growth was demonstrated as well as a reversal of tumor activity resulting in an almost complete reduction of tumor burden.

Such preclinical results may not be replicated in human clinical trials.

We announced in early 2021 that Annamycin demonstrated consistently high antitumor activity in tested animal models of different types of lung-localized cancers, including sarcoma.

These promising findings correlate with a high uptake of Annamycin to the lungs in animal models.

We found in our studies that Annamycin uptake to the lungs is over 30-fold higher than that of doxorubicin, the primary first-line chemotherapy for advanced soft tissue sarcoma.

The limited pulmonary uptake of doxorubicin in animal models may help explain its limited activity against STS lung metastases in humans.

Additionally, our clinical data to date show no cardiotoxicity associated with the use of Annamycin, and the published research demonstrate Annamycin’s ability to avoid multidrug resistance mechanisms, both of which are often treatment-limiting effects of anthracyclines (which includes doxorubicin) in this setting.

Taken together, these factors suggest that Annamycin could represent an important treatment to help address a significant unmet need in patients with STS lung metastases.

In February 2021, we also announced that a preclinical study in animals had suggested a possible significant therapeutic benefit of Annamycin against metastatic osteosarcoma.

As of day 130 of the study, the survival rate for animals treated with Annamycin was 100%, compared with only 10% for untreated animals.

Computerized tomography scans demonstrated that animals treated with Annamycin exhibited suppression of tumor growth and not a single death was observed in the treated animals, whereas observed tumor burden was believed to have contributed to the rapid death of 90% of untreated animals.

We believe these data are a promising indication of the possibility of Annamycin’s impact on other cancers metastasized to the lungs.

We caution that these are preclinical animal data and we can provide no assurance that we will see similar results in our clinical trials, let alone ultimately obtain approval of Annamycin for this use.

The Importance of the Unmet Need in 2 nd Line Therapies for AML

There are approximately 160,000 people with AML worldwide with about 20,000 newly diagnosed patients annually in the U.S.

Anthracyclines are an important class of first line tools for physicians and while effective, their maximum lifetime dose in patients is limited due to concerns over cardiotoxicity.

The following discussion, which includes estimates based on current literature and our discussions with key opinion leaders, suggests that approximately 60% of AML patients continue to have a significant unmet need for new therapies.

There are approximately 150,000 people with AML worldwide with over 20,000 newly diagnosed patients annually in the U.S.

(https://www.cancer.org/cancer/types/acute-myeloid-leukemia/about/key-statistics.html).

Anthracyclines are an important class of first line tools for physicians and while effective, their rate of relapse is very high and their maximum lifetime dose in patients is limited due to concerns over cardiotoxicity.

This is based on the reality that effective treatment options are limited.

We estimate that only around 40% of AML patients are afforded an opportunity to overcome their disease through a curative bone marrow transplant or through lasting remission.

We believe this aligns with the published statistic that the 5-year survival rate for AML is only 29%.

We believe this aligns with the published statistic that the 5-year survival rate for AML is roughly 30% (https://seer.cancer.gov/statfacts/html/amyl.html).

While the standard of care treatment can be complex, regionally variable (especially since not all current AML drugs are approved in all countries), and highly individualized (based on a range of factors including gene mutations), all AML patients are initially categorized based on their ability to undergo intensive chemotherapy.

As a result, we estimate around 50% of patients are deemed “Fit” for standard intensive first-line treatment and the other 50% are deemed “UnFit.”

As a result, we estimate around 50% of patients are deemed “Fit” for standard intensive first-line treatment and the other 50% are deemed “Unfit.” This delineation is most often based primarily on age with those over 65 years of age commonly deemed to be Unfit, however younger patients with comorbidities and especially cardiac impairment may also be deemed to be Unfit.

Those who are deemed “Fit” are most often treated with the “standard” induction therapy of three days of intravenous daunorubicin or equivalent anthracycline, and seven days of intravenous cytarabine.

This first line regimen is often referred to as “7+3.” We estimate that only about 36% of these patients, or approximately 18% of overall AML patients, will have a durable CR as a result of first line therapy, meaning the cancerous cells in their bone marrow have been reduced to 5% or less.

At this point, they either qualify for a bone marrow transplant or hope for the remission to become long lasting.

6 unchanged sentences

Additionally, a study of AML subjects who were refractory to or relapsed after receiving venetoclax plus a hypomethylating agent regimen (such as azacitidine) as 1 st line therapy demonstrated a dismal outcome upon failure of this regimen with a median OS of just 2.4 months.

Of those subjects that, upon Venetoclax regimen failure and received salvage therapy, only 12.5% and 4% achieved a CRc and a CR, respectively (A.

Of those subjects, that, upon venetoclax regimen failure received salvage therapy, only 12.5% and 4% achieved a CRc and a CR, respectively (A.

Cortes, Et al, “Outcomes of relapsed or refractory acute myeloid leukemia after frontline hypomethylating agent and venetoclax regimens, Haematologica online, vol.

2 unchanged sentences

Unfortunately, we believe success here has been relatively limited.

Five such drugs have been approved to date, but each is only relevant to a subset of AML patients who happen to have the requisite genetic mutation and response rates are relatively low.

Six such drugs have been approved to date, but each is only relevant to a subset of AML patients who happen to have the requisite genetic mutation and response rates are relatively low.

We estimate that only about 21% of those 2nd line patients who happen to have the requisite genetic profile will achieve a durable CR, which means only another 18% of the AML population is given a chance to beat their disease with a successful bone marrow transplant or lasting remission.

1 unchanged sentence

We believe this is not an acceptable outcome and are advancing Annamycin for the treatment of AML via our clinical trials.

In multiple clinical studies, subjects treated with Annamycin have shown no signs of cardiotoxicity, allowing physicians to dose higher than the currently set limits for other anthracyclines or potentially treat traditionally "Unfit" subjects.

In multiple clinical studies, subjects treated with Annamycin have shown no signs of drug-related cardiotoxicity, allowing physicians to dose higher than the currently set limits for other anthracyclines or potentially treat traditionally "Unfit" subjects.

The subjects treated to date have included those who were initially deemed unfit for intensive chemotherapy and the initial, preliminary data suggest that Annamycin’s safety and tolerability profile may make the product suitable for those patients, too.

2 unchanged sentences

These trials are MB-104, MB-105, and MB-106.

In MB-105 and MB-106, we saw what we believe to be potentially significant efficacy in AML.

In MB-105 and MB-106, we saw what we believe to be potentially significant efficacy in AML using Annamycin as a monotherapy.

With that data in July 2024, we announced the completion of our EOP2 meeting with the FDA for our Phase 1B/2 clinical trial evaluating Annamycin in combination with Cytarabine (also known as “Ara-C” and for which the combination of Annamycin and Ara-C is referred to as AnnAraC) for the treatment of subjects with AML as both first line therapy and for subjects who are refractory to or relapsed after induction therapy (MB-106).

Based upon the FDA minutes, we designed and began implementation of a Phase 2B/3 pivotal trial for the treatment of AML patients who are refractory to or relapsed after induction therapy.

This MIRACLE trial will be a global trial, including sites in the US, Europe, Western Asia and the Middle East.

Based upon the FDA minutes, we designed and began implementation of a Phase 2B/3 pivotal trial, dubbed the MIRACLE trial, for the treatment of AML patients who are refractory to or relapsed after a single induction therapy.

MIRACLE is a global trial, including sites in the US, Europe, Western Asia and the Middle East.

The MIRACLE study is a Phase 2B/3 clinical trial whereby data from the 2B portion will be combined with the Phase 3 portion.

This trial is more fully discussed below.

It should be noted that periodically throughout the trials below up to and excluding MB-108, our Expert reviewed cardiotoxicity, as discussed above.

A Phase 1 clinical trial of Annamycin as a single agent for the treatment of R/R AML in the US was successfully completed in 2020.

10 unchanged sentences

neutropenia 65%, thrombocytopenia 50%, anemia 40%, febrile neutropenia 30%, pancytopenia 10%, and leukopenia, hepatocellular injury, hepatotoxicity, anaphylactic reaction, sepsis, and hypotension 5% each.

Additionally, our Expert noted that after review of the data for nineteen of the twenty subjects in this trial there were no signs of cardiotoxicity.

One subject who received a partial dose of Annamycin and left the trial had no post-treatment evaluations performed.

Additionally, 15 subjects were taken over the LTMAD and exposed as high as 1800 mg/m 2 as allowed by the protocol.

In the final cohort, five subjects received a full course of Annamycin and demonstrated an ORR of 80% with one CRi and three PRs.

However, in two of the PRs, as noted by the site, subjects' bone marrow blast counts were successfully decreased to below 5%, however these subjects were still designated as a PR by the sub-investigator at that site.

Our Expert noted no cardiotoxicity in subjects in this trial.

As a part of our ongoing sponsored research at MD Anderson, animal testing indicated that the combination of Annamycin with Ara-C provides a synergistic effect that is more effective in AML mouse models than either drug alone.

4 unchanged sentences

We believe these experiments supported initiation of clinical development of the combination of Annamycin and Ara-C in AML patients.

This combination was achieved via a promising advancement in lipid enabled drug delivery developed in collaboration with and exclusively licensed from MD Anderson.

The unique patented lipid composition allows us to combine a new concept in chemotherapeutic agents within a lipid structure that helps target the delivery of the payload and reduce the potential for toxicity.

In the case of Annamycin, our unique use of lipid technology enables improved tissue/organ distribution and, as demonstrated in multiple clinical trials, dramatically reduced toxicity, including avoiding cardiotoxicity.

Although Annamycin had already shown human activity as a single agent in its two Phase 1 AML clinical trials and had shown no signs of cardiotoxicity, the observed synergy in vitro and confirmatory in vivo data suggested that the AnnAraC could be more effective in a clinical setting than Annamycin as a single agent.

This would be consistent with the current practice to use Ara-C in combination with other anthracyclines in AML patients.

This would also be consistent with the current practice to use Ara-C in combination with other anthracyclines in AML patients.

The most common first-line therapy for fit AML patients currently is the combination of an anthracycline and Ara-C in a regimen referred to as "7+3" where Ara-C is administered daily for 7 days in parallel with 3 daily doses of an anthracycline.

Simply substituting Annamycin for the currently used anthracycline in a similar 7+3 (or as is the case in MB-106, 5+3) regimen would therefore represent a familiar and well-practiced treatment modality.

Simply substituting Annamycin for the currently used anthracycline in a similar 7+3 regimen would therefore represent a familiar and well-practiced treatment modality.

In the case of MB-106 and MB-108, however, we utilized a 5+3 regimen, which was consistent with our preclinical animal testing and which our advising clinicians believed would not only be better tolerated by patients but would also reduce cost and hospital staffing burden by not extending the infusion period over a weekend.

Beyond that, we believed it would have the added advantages that Annamycin has been shown in published research to be active against tumor cells resistant to doxorubicin and, importantly, has the potential to remove the concern for cardiotoxicity, a significant toxic side effect currently limiting the use of anthracycline-based intensive chemotherapy.

Thus, we focused our efforts on a clinical trial studying AnnAraC for the treatment of AML in Europe.

Below in Table 2 is a summary of the preliminary responses in the MB-106 combination therapy trial to date.

Table 2 - Summary of Annamycin Responses in MB-106 AML Studies as of March 1, 2025

Below in Table 2 is a summary of the responses demonstrated in the MB-106 combination therapy trial to date.

Table 2 - Summary of Annamycin Responses in MB-106 AML Studies Per Draft CSR

Study MB-106 Combination Therapy – Phase 1B/2 All Lines (Range As 1 st -7 th Line)

Study MB-106Combination Therapy – Phase 1B/2 (As 2 nd & 3 rd Line)

Study MB-106Combination Therapy – Phase 1B/2 (As 2 nd Line Only)

1 unchanged sentence

Ara-C + Annamycin “ 5+3"

Recruited & Dosed

Subjects Evaluable Not Dosed Per Protocol

Median Age - Years (Range)

Complete Responses

CR with incomplete recovery (CRi)

Total Complete Response(s)

Partial Responses (PRs)

Durability of CRc’s to date (mos)

Median OS to date (mos)

Notes for Table 2 :

1) Data from MB-106 is for intent to Treat subjects;

2) Data from MB-106 is preliminary and subject to change;

3) Durability and OS are developing;

and, 4) Durability is measured from the date of CR assessed to relapse date or date of the last update to the database.

2) Data from MB-106 is per the current draft CSR.

The final CSR is in process and should be published in late March 2026.

Data is preliminary and subject to change.

Median OS for CR responders (n=8) was 15.2 months at study close and was developing.

In such cases the median at study close is based on a theoretical sensitivity analysis.

Median OS for second line subjects (n=10) was 12.39 months and the median OS for first thru seventh line subjects (n=22) was the same 12.39 months.

DoR for the CR responders was 13.14 months.

In May 2023, we announced successful completion of the first cohort in our Phase 1B portion of our Phase 1B/2 clinical trial using Annamycin in combination with Cytarabine for the treatment of AML.

This study utilized a “5+3” regimen where Annamycin is administered with three days of infusion along with the five days of infusion of Cytarabine.

As we noted, this combination strategy is similar to the familiar “7+3” induction therapy that is considered to be a standard of care in AML, where seven days of Cytarabine infusions are paired with three days of an approved anthracycline (typically, daunorubicin).

In the first cohort, 3 subjects were treated, all of whom were relapsed from multiple prior therapies.

2 unchanged sentences

In August 2023, we successfully completed the second cohort at 230 mg/m 2 of Annamycin in this combination study.

Four subjects were treated in this cohort, one is believed to be relapsed from one or more prior therapies and three are believed to be refractory to up to three prior therapies.

One subject was replaced due to a Serious Adverse Event (SAE) experienced on first day of dosing.

The SAE was determined to be unrelated to Annamycin and definitively related to Cytarabine:

an allergic reaction to the Cytarabine infusion.

Of the four subjects treated in this cohort, one is believed to be relapsed from one or more prior therapies and three are believed to be refractory to up to three prior therapies.

At the recommendation of the safety review committee, we deemed the second cohort dose as safe and as the recommended expansion phase dose and opened recruitment, including for both first line therapy and for subjects who are refractory to or relapsed after induction therapy, to the Phase 2 portion of the trial.

1 unchanged sentence

In addition, we expanded the MB-106 study protocol to include 1st line subjects to provide data to enable the designing of a potential confirmatory Phase 3 post-approval study.

Our current planned pathway for approval for Annamycin in combination with Cytarabine for the treatment of AML is as a 2 nd line therapy.

Therefore, our focus is primarily on securing an accelerated approval pathway for the treatment of 2 nd line subjects (those who were relapsed from or refractory to a 1st line AML therapy, regardless of whether the subject was deemed “fit” or “unfit”).

Later in 2024, we closed all recruitment.

We continue to follow subjects that remain in the study for OS and durability of CR/CRc’s, as well as safety data.

As mentioned previously, the Phase 1b portion of the MB-106 clinical trial with Annamycin in combination with Cytarabine for the treatment of AML was an “all-comers” (as discussed above) trial, accepting subjects with a wide range of prior therapies.

2 unchanged sentences

The results of the trial to date are shown in Table 2 above.

These data are preliminary and subject to change once the CSR is published.

These data are per the draft CSR.

The final CSR is in process and should be published in late March 2026.

No evidence of cardiotoxicity was noted by the Expert following assessments of the MB-106 data.

In all subjects enrolled to date (n=22) in MB-106 adverse events (Grade < 3) are as follows:

thrombocytopenia 47.4%;

neutropenia 31.5%;

anemia 21.1%;

and infections (pneumonia, sepsis, septic shock and staphylococcal bacteremia) 10.5%.

Two subjects experienced adverse events and were not dosed per protocol with one having an allergic reaction to Annamycin, the first we have seen in over 70 subjects dosed in our multiple Annamycin clinical trials;

Grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 21 of 22 subjects (95.5%) in the safety population.

The most frequently reported Grade ≥3 TEAEs (≥20% of subjects) were hemoglobin decreased (10 subjects, 45.5%), platelet count decreased (9 subjects, 40.9%), and pneumonia (5 subjects, 22.7%).

Additional Grade ≥3 TEAEs reported in more than two subjects included neutrophil count decreased (4 subjects, 18.2%) and febrile neutropenia (3 subjects, 13.6%).

Two subjects experienced adverse events and were not dosed per protocol with one having an allergic reaction to Annamycin;

the second adverse event was due to an allergic reaction to cytarabine.

2 unchanged sentences

We believe the FDA minutes reflect a positive discussion and the meeting resulted in the design and implementation of a Phase 2B/3 pivotal trial for the treatment of AML patients who are refractory to or relapsed after induction therapy.

This MIRACLE trial will be a global trial, including sites in the US, Europe, Western Asia and the Middle East.

The FDA’s Divisions of Hematologic Malignancies I and Cardiology and Nephrology, as well as related divisions, were involved in the review of the data showing no cardiotoxicity in MB-106.

Consistent with the FDA’s recommendations, in the adaptive MIRACLE trial we plan to utilize a double-blind, placebo-controlled design, where we will compare AnnAraC versus the control arm of high dose cytarabine (HiDAC) plus placebo and we will rely solely on CR (complete remission) at approximately one month as the primary endpoint.

The FDA also wanted to see the durability of response (DoR) and overall survival as secondary endpoints, as well as data for patients beyond 2nd line, which is why our plan includes a follow-on MIRACLE2 trial in 3rd line patients starting once the optimum dose is established in the MIRACLE trial.

Consistent with the FDA’s recommendations, in the adaptive MIRACLE trial we plan to utilize a double-blind, placebo-controlled design, where we will compare AnnAraC versus the control arm of HiDAC plus placebo and we will rely solely on CR (complete remission) after a single cycle of treatment (at approximately one month) as the primary endpoint.

The FDA also wanted to see overall survival as a secondary endpoint and the DoR as an exploratory endpoint.

The FDA also wanted data for patients beyond 2nd line, which is why our plan includes a follow-on MIRACLE2 trial in 3rd line patients starting once the optimum dose is established in the MIRACLE trial.

The MIRACLE trial is a global trial as described above – across nine countries including the US, Spain, Italy, Poland, Ukraine, Czechia, Romania, Georgia, and Lithuania with 25 sites targeted for Part A and more sites and countries targeted for Part B, as described above and below.

Based on our discussions with the FDA, we amended in November 2024 our MB-104 investigational new drug application or IND for MB-108.

In the amendment with the new MIRACLE protocol, the trial will allow, for the first time in the US for AML subjects, dosing above the lifetime maximum allowable dose for currently prescribed anthracyclines.

Subsequently, in February 2025 we received FDA feedback and guidance on our IND amendment, noted above, that allowed a reduction in the size of our Phase 3 pivotal trial protocol to 220.

In the amendment with the new MIRACLE protocol, the trial allows, for the first time in the US, for AML subjects to be dosed above the lifetime maximum allowable dose for currently prescribed anthracyclines.

Subsequently, in February 2025 we received FDA feedback and guidance on our IND amendment, noted above, that allowed a reduction in the size of Part B of the trial to 222 subjects.

With their feedback and our response, all the major aspects of the trial remain unchanged.

Guidance from FDA included a recommendation to alter the statistical plan that reduced the initially proposed size of Part B of our trial by approximately 10%.

Moreover, the nature of the feedback helps us move forward quickly to open sites in the US, in addition to the non-US sites we are expecting to open.

Any reduction in recruitment helps to shorten the time to completion of the trial.

On February 3, 2025, and February 27, 2025, we received additional comments and information requests from the FDA about the amended IND.

We believe that we addressed those issues in our responses on February 17, 2025 and March 6, 2025, respectively.

On March 14, 2025, we received an additional information request, with a requested response date of March 28, 2025.

We cannot be assured that our responses will be adequate for the FDA to continue to allow the amended IND to proceed, or that there will not be additional requests for information.

During 2025, we received various comments and requests from the FDA on the MIRACLE trial and we may continue to receive comments and requests from the FDA in the future.

We responded to each in a timely manner.

While we believe that we responded adequately, we cannot be assured that our responses or that our future responses will be adequate for the FDA to continue to allow the amended IND to proceed, or that there will not be additional requests for information.

Because we are amending an existing IND, there is no required time for the FDA to respond to our submissions, but neither is a response required for us to proceed with the MIRACLE trial.

As with all clinical trials, if at any time the FDA believes there is a safety issue that merits it, the agency may put the MIRACLE trial on clinical hold.

The amended protocol allows for the unblinding of preliminary primary efficacy data (Complete Remission or CR) and safety/tolerability of the three arms at 45 subjects, in addition to the conclusion of Part A (at 75 to 90 subjects).

This early unblinding will yield 30 subjects having received Annamycin (190 mg/m2 and 230 mg/m2) and HiDAC and 15 subjects receiving HiDAC plus placebo.

The Company expects to reach the first unblinding (45 subjects) in the second half of 2025, in addition to the second unblinding, which is expected in the first half of 2026.

This accelerated estimated timeline is due to the positive response the Company received in meetings during December with potential investigators regarding recruitment for the trial.

For Part B of the trial, approximately 220 additional subjects will be randomized to receive either HiDAC plus placebo or HiDAC plus the optimum dose of Annamycin (randomized 1:1).

In the first half of 2025, we submitted clinical trial applications or their equivalent in the EU and the non-EU countries listed above.

Our first approval to proceed with MIRACLE occurred in Ukraine in February 2025 and we dosed the first subject in March 2025.

We received EU approval to commence the MIRACLE trial in May 2025.

Soon after, we then received the approval for the other non-EU countries in 2025.

The MIRACLE study, subject to appropriate future filings with and potential additional feedback from the FDA and their foreign equivalents, utilizes an adaptive design whereby the first 90 subjects will be randomized (1:1:1) in Part A of the trial to receive HiDAC (or AraC) combined with either placebo, 190 mg/m2 of Annamycin, or 230 mg/m2 of Annamycin, which Annamycin doses were specifically recommended by the FDA in the Company’s end of Phase 1B/2 meeting.

The amended protocol allows for an interim unblinding of data of the three arms for the first 45 subjects with efficacy data and then an unblinding at the conclusion of Part A (full 90 total subjects).

This early unblinding will yield approximately, due to randomization, 30 subjects having received Annamycin (190 mg/m2 and 230 mg/m2) and HiDAC and approximately 15 subjects receiving HiDAC plus placebo.

The Company expects to reach the first unblinding in mid-2026, in addition to the second and final unblinding of Part A, which is expected in the second half of 2026.

In February 2026 we reported a blinded preliminary composite complete remission rate of 40% in the MIRACLE trial’s first 30 subjects treated and with blinded, preliminary efficacy data.

This CRc rate is comprised of a complete remission rate of 30% and complete remission with partial hematological recovery (CRh or CRi) of 10%.

MIRACLE is randomizing 1:1:1 the three different arms described above.

This includes the control arm of cytarabine plus placebo.

Even with the control arm included, these preliminary, blinded results substantially outperform historical outcomes for CR with cytarabine alone in the treatment of R/R AML.

Of particular note is that roughly 35% of the subjects treated to date are relapsed or refractory from a venetoclax regimen, a subject population that is generally considered among the most challenging to address with 2 nd line therapies.

The subjects treated to date presented with a high degree of genetic markers that are considered predictive of poor treatment response.

These efficacy rates were observed across six different countries.

As previously mentioned, the Company expects to have the first interim unblinding in mid-2026.

As such, the preliminary blinded data discussed above may differ from the final locked data in the first and second unblinding.

Recruitment of the second group of 45 subjects in Part A will continue uninterrupted while the first 45 subjects’ data are being analyzed by the Data Safety Monitoring Committee for MIRACLE.

Unblinding for the full 90 subjects in Part A may require more time than for the first interim unblinding as it involves more data to support the transition from Part A to Part B.

For Part B of the trial, 222 additional subjects will be randomized to receive either HiDAC plus placebo or HiDAC plus the optimum dose of Annamycin (randomized 1:1).

The selection of the optimum dose will be based on the overall balance of safety, pharmacokinetics and efficacy, consistent with the FDA’s new Project Optimus initiative.

Data from the control arm and the optimum dose of Annamycin in the Phase 2B portion of the trial will be combined with the data for the Phase 3 portion of the trial in determining efficacy and safety.

The Organotropic Nature of Annamycin

Nonclinical research at MD Anderson has demonstrated that Annamycin has an organotropic nature enabling it to hyperaccumulate in certain key organs, including the liver, spleen, pancreas and lungs as compared with existing anthracyclines such as doxorubicin.