What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2026-03-03 compared with 2025-03-19 · 194 added, 158 removed, 554 unchanged (39% of the section changed)

We are a clinical-stage targeted oncology company committed to developing targeted therapies designed to improve outcomes for cancer patients.

We are advancing an innovative portfolio of therapeutics, drawing on leadership that previously played key roles in the design, development, and commercialization of cutting-edge targeted cancer therapies, including antibody-drug conjugate therapies, or ADCs.

We believe that the pursuit of novel or underexplored targets will be central to the next generation of transformative therapies, and we are dedicated to developing targeted cancer therapies with first-in-class and best-in-class potential.

Our goal is to establish a broad pipeline of preclinical and clinical assets and develop these assets into approved products for commercialization.

We are advancing a pipeline comprising two clinical assets and four preclinical assets.

Varegacestat, formerly AL102, is an investigational gamma secretase inhibitor, or GSI, currently under evaluation in a Phase 3 clinical trial for the treatment of desmoid tumors.

Our investigational new drug application, or IND, for IM-1021, a receptor tyrosine kinase-like orphan receptor 1, or ROR1, antibody-drug conjugate, received FDA clearance in December 2024, and the Phase 1 trial is ongoing with the first patient dosed in February 2025.

Our other preclinical assets include IM-3050, a fibroblast activation protein, or FAP, targeted radioligand therapy, or RLT, for which we submitted an IND in March 2025, and three solid tumor ADC drug candidates:

IM-1617, IM-1340, and IM-1335, all of which are in IND-enabling activities.

We have six additional ADCs currently undergoing lead optimization in advance of future development decisions.

At present, our internal discovery efforts center on designing ADCs against novel or underexplored targets.

We are a biotechnology company committed to the development of first-in-class and best-in-class targeted oncology therapies.

Our goal is to establish a broad portfolio of differentiated clinical assets to improve the lives of cancer patients.

Key to that strategy is our deep expertise in the discovery, design, development, manufacturing, and ultimately commercialization of antibody-drug conjugates and other oncology therapeutics.

We are advancing a pipeline that includes three clinical assets and three preclinical assets.

Varegacestat, formerly AL102, is an investigational, oral, once-daily gamma secretase inhibitor, or GSI.

In December 2025, we announced positive topline results from the global pivotal Phase 3 RINGSIDE trial of varegacestat in patients with progressing desmoid tumors.

We anticipate submitting a new drug application, or NDA, in the second quarter of 2026.

IM-1021, a receptor tyrosine kinase-like orphan receptor 1, or ROR1, antibody-drug conjugate, is currently under evaluation in a Phase 1 trial.

In November 2025, we reported observed objective responses at multiple dose levels in B-cell lymphoma patients treated with IM-1021, and we plan to share initial data in 2026.

IM-3050, a fibroblast activation protein, or FAP, targeted radioligand therapy, or RLT, received IND clearance in April 2025, and we plan to initiate a Phase 1 trial in early 2026 after delivery of third-party diagnostic radiotracer supply.

Our preclinical assets include three solid tumor ADCs with anticipated 2026 IND submissions:

IM-1617, IM-1340, and IM-1335.

Our pipeline also includes numerous early-stage ADCs produced by our internal discovery efforts, providing opportunities for additional IND submissions in 2027 and beyond.

Our approach to discovery centers on designing ADCs against novel or underexplored targets.

We believe that pursuing differentiated targets provides a path to significant clinical benefit and meaningful market opportunities.

This strategy is supported by HC74, the differentiated, novel topoisomerase 1, or TOP1, inhibitor payload we exclusively licensed from Zentalis Pharmaceuticals, Inc., or Zentalis, in January 2024 and subsequently purchased from Zentalis in October 2024.

We have efforts underway to develop additional linkers and payloads and believe that a broad toolbox of linkers and payloads supports our mission to design and develop a diverse pipeline of ADCs.

HC74, our differentiated, novel topoisomerase 1, or TOP1, inhibitor payload, supports this strategy.

We have efforts underway to develop additional linkers and payloads and believe that a broad toolbox of linkers and payloads supports our mission to design and develop a diverse pipeline of ADCs with differentiated safety, efficacy, and tolerability profiles that address unmet medical need.

To expand and advance our innovative portfolio of therapeutics, we draw on leadership that previously played key roles in the design, development, and commercialization of cutting-edge targeted cancer therapies, including the first ADCs commercialized for Hodgkin and T-cell lymphoma, urothelial cancer and cervical cancer.

Our mission is to build an oncology company committed to developing first-in-class and best-in-class targeted therapies designed to improve outcomes for cancer patients.

Key elements of our business strategy are to:

• Advance varegacestat and prepare for potential commercialization.

We are prioritizing regulatory, clinical, and operational activities to support a potential commercial launch of varegacestat for the treatment of desmoid tumors, subject to regulatory approval.

Our launch readiness approach includes a staged build-out of commercial capabilities and our commercial organization;

patient identification and market education efforts focused on the treating community;

early market access planning intended to support appropriate patient access;

and a build-out of patient support capabilities aligned with the chronic nature of treatment in this population.

We are also making investments intended to support commercial supply readiness for varegacestat.

• Leverage our ADC capabilities to progress additional pipeline assets.

Key to our strategy is our expertise in the discovery, design, development, manufacturing, and ultimately commercialization of ADCs.

We intend to apply these capabilities across our portfolio to efficiently advance additional clinical and preclinical programs, prioritizing programs based on biological rationale, development feasibility, competitive landscape, and potential to address meaningful unmet medical need.

• Pursue selective business development opportunities while retaining flexibility.

We may pursue strategic collaborations, alliances, or other transactions where we believe they can enhance our capabilities, accelerate development timelines, expand our pipeline, support clinical regimens with our pipeline or improve our financial flexibility.

We may also, from time to time, evaluate in-licensing, acquisitions, or investments in complementary businesses, technologies, products, or assets.

Immunome Pipeline

Varegacestat (formerly AL102)

Varegacestat is an oral, once daily GSI therapy that is being evaluated for the treatment of desmoid tumors.

In the Phase 2 RINGSIDE study Part A, varegacestat demonstrated objective response rates, or ORR, of 75% of evaluable patients and 64% in the intent-to-treat population;

median reduction in tumor volume of 88%;

and an 85% reduction in T2 imaging, which is suggestive of a reduction in cellularity.

The Phase 2 data also show that varegacestat has a safety profile consistent with other GSI therapies.

Enrollment in a Phase 3 registrational trial was completed in February 2024, and we expect to report topline data from this trial in the second half of 2025.

Varegacestat is an investigational, oral, once-daily GSI therapy under evaluation for the treatment of desmoid tumors.

In December 2025, we reported positive Phase 3 RINGSIDE (Part B) topline results showing that the study met all primary and key secondary endpoints.

Varegacestat achieved the primary endpoint of progression free survival, delivering an 84% reduction in the risk of disease progression or death versus placebo (HR=0.16, p<0.0001).

The confirmed objective response rate (ORR) based on RECIST v1.1 was 56% with varegacestat vs.

9% with placebo (p<0.0001), as assessed by blinded independent central review.

In an exploratory analysis, varegacestat demonstrated a median best change in tumor volume of -83% vs.

+11% with placebo, as assessed by blinded independent central review.

In addition, the trial met all key secondary endpoints, with varegacestat achieving statistically significant improvements vs.

placebo in landmark tumor volume reduction and worst pain intensity.

The Phase 3 RINGSIDE topline and Phase 2 RINGSIDE (Part A) data also show that varegacestat has a safety profile consistent with other GSI therapies.

We acquired varegacestat from Ayala Pharmaceuticals, Inc., or Ayala, in March 2024.

Disease background

Desmoid tumors, also known as aggressive fibromatosis or desmoid-type fibromatosis, are debilitating, painful and aggressive non-metastatic soft tissue tumors that are prone to recurrence.

Depending on where in the body they occur, desmoid tumors can cause debilitating pain, deformity and, in some cases, life threatening organ damage.

These tumors are rare, with approximately 1,000-1,650 patients diagnosed each year and approximately 5,500-7,500 actively managed patients in the United States.

They typically occur in people between the ages of 15 and 60 and are most common in adults, with a peak around 30 years of age, and they are more common in women than men.

Desmoid tumors, also known as aggressive fibromatosis or desmoid-type fibromatosis, are rare, non-metastatic, locally aggressive sarcomas of fibroblastic origin.

They often strike in young adulthood, with 1,000-1,650 patients diagnosed each year in the United States.

Desmoid tumors can lead to debilitating pain, deformity, and life-threatening organ damage depending on location.

Quality of life is a major challenge for people living with desmoid tumors, and a majority of patients experience chronic pain that can significantly limit physical functioning.

Up to ~60-80% of patients experience recurrence, which can be exacerbated by surgery.

Following progression during initial active surveillance, systemic therapy is recommended for ~75% of tumors based on location.

Desmoid tumors arise in connective tissue and can occur anywhere in the body where connective tissue is found.

22 unchanged sentences

Clinical development

Prior to the initiation of the Phase 3 clinical trial of varegacestat in desmoid tumors (RINGSIDE Part B), varegacestat clinical activity was observed in two clinical trials that enrolled adult desmoid tumor patients.

Prior to the initiation of the Phase 3 RINGSIDE clinical trial of varegacestat in desmoid tumors, varegacestat clinical activity was observed in two clinical trials that enrolled adult participants with desmoid tumors.

A Phase 1 dose-escalation clinical trial was conducted by Bristol-Myers Squibb, or BMS, in patients with solid tumors.

1 unchanged sentence

This patient demonstrated tumor shrinkage of 16.5% while on study.

Based on these data and responses demonstrated with other GSIs, Ayala designed a seamless Phase 2/3 study called RINGSIDE to specifically evaluate the activity of varegacestat in patients with progressing desmoid tumors who required therapy.

RINGSIDE Part A enrolled 42 patients at three different dosing regimens of varegacestat:

Based on these data and responses demonstrated with other GSIs, Ayala designed a seamless Phase 2/3 study called RINGSIDE to specifically evaluate the activity of varegacestat in participants with progressing desmoid tumors who required therapy.

The Phase 2 portion of RINGSIDE enrolled 42 participants at three different dosing regimens of varegacestat:

2 mg once a day for two days every week, 4 mg once a day for two days every week and 1.2 mg once a day daily.

Overall, the ORR in evaluable patients as measured by RECIST v1.1 by an independent radiologist was 64% for all doses tested.

Overall, the ORR in evaluable participants as measured by RECIST v1.1 by an independent radiologist was 64% for all doses tested.

The 1.2 mg daily dosing cohort had an ORR of 75% in the evaluable population.

Among patients in the intention-to-treat population, the overall response rate was 55% across all doses tested and the response rate was 64% for patients in the 1.2 mg daily dosing cohort.

Among participants in the intention-to-treat population, the overall response rate was 55% across all doses tested and the response rate was 64% for participants in the 1.2 mg daily dosing cohort.

In this study, more rapid and deeper responses were achieved with 1.2 mg once-daily dosing compared with the other dosing schedules, as evaluated based on RECIST by blinded independent central review, or BICR, tumor volume, and T2W signal intensity.

These data were reported in a poster presentation at ESMO in 2024.

Safety results from the Phase 2 portion of RINGSIDE show that varegacestat was well tolerated and has an overall safety profile consistent with that reported with other GSIs.

A lower rate of ovarian dysfunction in premenopausal women was observed for varegacestat (55.6%) compared with published data for an approved GSI (75.0%).

Additionally, responses observed in the 1.2mg once-daily cohort in the Phase 2 portion of RINGSIDE compared favorably to nirogacestat across all measures assessed.

Phase 3 RINGSIDE Part B trial in desmoid tumors

Based upon the clinical activity observed in RINGSIDE Part A at the dose of 1.2 mg given once daily, and following consultation with the FDA, RINGSIDE Part B (NCT04871282) was initiated in November 2022.

RINGSIDE Part B is a registrational Phase 3, global, double-blind, randomized, placebo-controlled clinical trial, conducted at clinical sites in North America, Europe, Asia and Australia.

It is designed to evaluate the efficacy, safety and tolerability of varegacestat compared to placebo in patients with progressing desmoid tumors.

One hundred fifty-six patients with histologically confirmed desmoid tumors with progressive disease (defined as tumor growth of at least 20% within the past 12 months as measured by RECIST v1.1) were enrolled.

Enrollment was completed in February 2024 and the study is ongoing.

Enrolled patients were either treatment-naïve with desmoid tumors not amenable to surgery or had refractory or recurrent disease after at least one line of therapy.

Patients in the study were randomized 1:1 to receive either varegacestat at a dose of 1.2 mg given once daily or placebo and evaluated for tumor progression using RECIST v1.1.

Patients who progress while on study are eligible to enter an open-label extension whereby they may receive varegacestat at a dose of 1.2 mg once daily until disease progression or unacceptable toxicity.

The primary endpoint of RINGSIDE Part B is progression-free survival with secondary endpoints of ORR, duration of response and specific patient-reported outcomes.

We expect to share topline data for RINGSIDE Part B in the second half of 2025.

In parallel, we are completing the manufacturing, toxicology and pharmacology work required to support an NDA submission.

Phase 3 RINGSIDE trial in desmoid tumors

The Phase 3 portion of RINGSIDE is a registrational, global, double-blind, randomized, placebo-controlled clinical trial, conducted at clinical sites in North America, Europe, Asia and Australia.

It is designed to evaluate the efficacy, safety and tolerability of varegacestat compared to placebo in participants with progressing desmoid tumors.

One hundred fifty-six participants with histologically confirmed desmoid tumors with progressive disease (defined as tumor growth of at least 20% within the past 12 months as measured by RECIST v1.1) were enrolled.

Enrollment was completed in February 2024.

Enrolled participants were either treatment-naïve with desmoid tumors not amenable to surgery or had refractory or recurrent disease after at least one line of therapy.

Participants in the study were randomized 1:1 and received either 1.2 mg varegacestat or placebo given once daily.

Tumor progression was evaluated by RECIST v1.1 determined blinded independent central review (BICR).

Participants who progress while on study are eligible to enter an open-label extension whereby they may receive varegacestat at a dose of 1.2 mg once daily until disease progression or unacceptable toxicity.

The primary endpoint of Phase 3 RINGSIDE is progression-free survival with secondary endpoints of ORR, duration of response and specific patient-reported outcomes.

In December 2025, we reported positive Phase 3 RINGSIDE topline results showing that the study met all primary and key secondary endpoints.

Varegacestat achieved the primary endpoint of the Phase 3 RINGSIDE trial, delivering an 84% reduction in the risk of disease progression compared with placebo (HR=0.16, p<0.0001).

To our knowledge, this is the lowest hazard ratio reported for a pivotal study in this population.

Kaplan-Meier analysis of PFS demonstrated marked separation of the two arms as soon as the first tumor assessment at 12 weeks, and the separation between the curves continued throughout the course of treatment.

The study met the key secondary endpoint, showing a highly significant ORR benefit (p<0.0001) with varegacestat (56%) compared with placebo (9%).

The waterfall plot shows that none of the study subjects in the varegacestat arm had progressive disease, and tumor shrinkage was observed in the vast majority of participants.

The exploratory endpoint of median best tumor volume also was achieved, with a mediation reduction of 83% in the varegacestat arm compared with an 11% increase in tumor volume in the placebo arm.

Safety results from Phase 3 portion of RINGSIDE show that varegacestat was generally well-tolerated, with a manageable safety profile consistent with the GSI class of medicines.

The most common adverse events for participants in the treatment arm were diarrhea (82%), fatigue (44%), rash (43%), nausea (35%), and cough (34%), and most events were grade 1 or 2.

Ovarian toxicity was reported in 55.6% of premenopausal women.

There were no deaths on study.

We are completing the manufacturing, toxicology and pharmacology work required to support an NDA submission, and expect to submit an NDA to the FDA for varegacestat for the treatment of desmoid tumors in the second quarter of 2026.

We also anticipate presenting the complete Phase 3 RINGSIDE data set at an upcoming medical conference.

IM-1021 (Solid Tumor and B-Cell Lymphoma ADC)

IM-1021 is a ROR1 ADC that incorporates HC74, our proprietary TOP1i payload.

ROR1 is expressed in both hematologic malignancies and solid tumors with limited normal tissue expression, and previous ADCs targeting ROR1 have demonstrated clinical activity.

In preclinical studies, IM-1021 showed sustained tumor regression in preclinical models, including a mouse model of triple-negative breast cancer, or TNBC, and a mouse model of mantle cell lymphoma, or MCL.

ROR1 is expressed in both hematologic malignancies and solid tumors with limited normal tissue expression.

Previous ADCs targeting ROR1 have demonstrated clinical activity.

We believe that IM-1021 may provide improved therapeutic index as compared to other ROR1-targeted ADCs in development.

IM-1021 received IND clearance in December 2024, and the phase 1 clinical trial is ongoing with a starting dose of 2 mg/kg of adjusted ideal body weight.

We expect dose escalation to include patients both with solid tumors and with B-cell lymphoma.

The Phase 1 clinical trial is ongoing, with objective responses observed in patients with B-cell lymphomas at multiple dose levels.

ROR1 is a clinically validated target in B-cell lymphoma

High or moderate expression of ROR1 has been demonstrated in a variety of hematopoietic malignancies, particularly in B-cell lymphomas, and clinical results have validated it as a target in these tumors.

Preliminary Phase 1 data from zilovertamab vedotin (also known as MK-2140 or VLS-101), a ROR1-targeted ADC with a vedotin payload, in heavily pre-treated patients (median prior lines of therapy = 4, range 1-9), showed objective tumor responses in participants with mantle cell lymphoma, or MCL, and diffuse large B-cell lymphoma, or DLBCL.

Subsequent evaluation in a Phase 2 study by Merck in DLBCL showed that of 103 patients treated at 2.5 mg/kg, 15 participants had complete responses, or CRs, 14 had partial responses, or PRs, and 17 had stable disease, or SDs.

Preliminary Phase 1 data from zilovertamab vedotin (also known as MK-2140 or VLS-101), a ROR1-targeted ADC with a vedotin payload, in heavily pre-treated patients (median prior lines of therapy = 4, range 1-9), showed objective tumor responses in patients with mantle cell lymphoma, or MCL, and diffuse large B-cell lymphoma, or DLBCL.

Subsequent evaluation in a Phase 2 study by Merck in DLBCL showed that of 103 participants treated at 2.5 mg/kg, 15 participants had complete responses, or CRs, 14 had partial responses, or PRs, and 17 had stable disease, or SDs.

Of 37 participants treated at 2.25 mg/kg, there were 7 CRs, 2 PRs, and 7 SDs.

Both of these dose levels were associated with a high degree of toxicity.

In February 2025, Merck announced the initiation of waveLINE-010 (ClinicalTrials.gov, NCT06717347), a pivotal Phase 3 clinical trial evaluating zilovertamab vedotin in combination with rituximab plus cyclophosphamide, doxorubicin and prednisone, or R-CHP, compared to rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone, or R-CHOP, alone, for the treatment of patients with previously untreated DLBCL.

In addition, CStone Phamaceuticals has shared Phase 1 data demonstrating activity in both Hodgkin and non-Hodgkin lymphoma for CS5001, their ROR1-targeted ADC.

In February 2025, Merck announced the initiation of waveLINE-010 (ClinicalTrials.gov, NCT06717347 ), a pivotal Phase 3 clinical trial evaluating zilovertamab vedotin in combination with

rituximab plus cyclophosphamide, doxorubicin and prednisone, or R-CHP, compared to rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone, or R-CHOP, alone, for the treatment of patients with previously untreated DLBCL.

In addition, CStone Pharmaceuticals has shared Phase 1 data demonstrating activity in both Hodgkin and non-Hodgkin lymphoma for CS5001, their ROR1-targeted ADC.

ROR1 is an attractive target for select solid tumors

7 unchanged sentences

In October 2024, we presented preclinical data demonstrating robust anti-tumor activity for IM-1021 at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics.

IM-1021 showed superior activity compared to zilovertamab vedotin 1 at both dose levels in both the Jeko-1 mantle cell lymphoma model and the MDA-MB-468 TNBC model.

In the MDA-MB-468 study, five out of eight animals achieved complete responses after three 5 mg/kg doses.

1 The head-to-head data is based on our synthesized version of MK-2140, which we believe is structurally equivalent to MK-2140.

IM-1021 showed superior activity compared to zilovertamab vedotin 1 at both dose levels in the Jeko-1 mantle cell lymphoma, or MCL, model.

In a patient-derived NSCLC xenograft model, eight out of eight animals achieved complete responses after three 2.5 mg/kg doses IM-1021.

We received IND clearance for IM-1021 in December 2024 and began dosing patients in our Phase 1 clinical trial in February 2025 with a starting dose of 2 mg/kg of adjusted ideal body weight.

Our clinical strategy is designed to efficiently evaluate dose escalation in patients with solid tumors and lymphoma, followed by potential expansion into specific indications.

Dose escalation will evaluate B-cell lymphomas, including diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma and small lymphocytic lymphoma, as well as solid tumor indications like non-small cell lung cancer triple-negative breast cancer, ovarian cancer, liposarcoma, mesothelioma, and pancreatic cancer.

1 The head-to-head data is based on our synthesized version of MK-2140, which we believe is structurally equivalent to MK-2140.

We received IND clearance for IM-1021 in December 2024 and began dosing participants in our Phase 1 clinical trial in February 2025 with a starting dose of 2 mg/kg of adjusted ideal body weight.

Our clinical strategy is designed to efficiently evaluate dose escalation in participants with solid tumors and lymphoma, followed by potential expansion into specific indications.

Dose escalation is primarily focused on B-cell lymphomas, including diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma and small lymphocytic lymphomas.

We are developing an in vitro diagnostic that could help identify solid tumor participants most likely to respond to IM-1021 in indications like non-small cell lung cancer, triple-negative breast cancer, ovarian cancer, liposarcoma, mesothelioma, and pancreatic cancer.

Expansion cohorts may include any of the above-mentioned tumor types.

We are also evaluating the need and benefit of developing a potential companion diagnostic(s) that could help identify patients most likely to respond to IM-1021.

Our strategy is to pursue pivotal clinical studies in indications that have shown compelling clinical outcomes in early-stage trials, present significant commercial opportunities, and offer a potential accelerated path to approval.

The Phase 1 clinical trial is ongoing, with objective responses observed in participants with B-cell lymphomas at multiple dose levels.

We expect to present initial data for IM-1021 in 2026.

IM-3050 (FAP Radioligand Therapy)

17 unchanged sentences

Two targeted radiotherapies have been approved by the FDA in the past few years:

Lu ta thera® for gastroenteropancreatic neuroendocrine tumors, or GEP-NETs, that express the somatostatin receptor;

Lutathera® for gastroenteropancreatic neuroendocrine tumors, or GEP-NETs, that express the somatostatin receptor;

and Pluvicto® for metastatic castration-resistant prostate cancer, or mCRPC that expresses PSMA.

5 unchanged sentences

by Eli Lilly and Company;

and a $50 million upfront payment from Novartis AG to license FAP-2286, a FAP-targeted radiotherapy Phase 1 clinical candidate originally developed by Clovis Oncology , Inc.

and license by BMS in 2025 from Philochem for a early clinical stage radioligand therapy for $350 million upfront, approximately $1.1 billion in potential development, regulatory and commercial milestones and royalties on product sales.

Published clinical results from FAP-targeted RLT product candidates have demonstrated both the potential therapeutic benefits of this class of therapeutics and the limitations of current candidates.

Among eleven patients with advanced or metastatic solid tumors treated with 177 Lu-FAP-2286, one patient achieved a PR after six treatments, and that patient’s disease did not progress for more than 12 months after their first dose.

However, most patients did not achieve a response, highlighting the need for FAP-target ed therapies with improved activity.

In the early Phase I LuMIERE trial among eleven participants with advanced or metastatic solid tumors treated with 177Lu-FAP-2286, one patient achieved a PR after six treatments, and that patient’s disease did not progress for more than 12 months after their first dose.

However, most participants did not achieve a response, highlighting the need for FAP-targeted therapies with improved activity.

Additional early stage clinical results are expected for FAP targeted radiotherapeuties in development with varied radio isotopes such as lead‑212 (212Pb), actinium‑225 (Ac‑225) and lutetium-177, Lu-177 are expected between 2026 to 2028.

IM-3050 is a FAP-targeted RLT with best-in-class potential

2 unchanged sentences

a small molecule FAP-specific ligand, a linker tuned to drive tumor-specific uptake, an albumin-binding domain to improve tumor retention, and a chelator to deliver the radionuclide.

Over the last three years, we have evaluated over 80 FAP-targeted RLTs that use different combinations of ligands, linkers, and albumin binders while still maintaining the four-domain structure.

We have evaluated over 80 FAP-targeted RLTs that use different combinations of ligands, linkers, and albumin binders while still maintaining the four-domain structure.

An example of the impact that a change in a single domain can impart on the therapeutic potential of a product candidate is the effect of specific albumin-binding domains.

6 unchanged sentences

Use of 177Lu-IM-3050 in a mouse model of glioblastoma demonstrated substantial tumor regression with no meaningful weight loss observed.

We submitted an IND for this program to the FDA in March 2025, and expect to initiate a Phase 1 clinical trial in the second half of 2025.

We received IND clearance for this program in April 2025 and plan to initiate a Phase 1 trial in early 2026 after delivery of third-party diagnostic radiotracer supply.

We believe that our team’s ADC expertise positions us to develop the next generation of transformative ADCs.

6 unchanged sentences

Another is their challenging development and commercialization pathways.

Additionally, with multiple therapies in development against them, these highly prevalent targets provide reduced opportunity to address unmet need — which is an essential component of our mission.

With multiple therapies in development against them, these highly prevalent targets provide reduced opportunity to address unmet need — which is an essential component of our mission.

Instead, we are focusing on targets with no approved therapeutics.

3 unchanged sentences

ADCs with these payloads generally show greater tolerability and achieve higher doses than earlier ADCs.

For example, a third-party randomized controlled clinical trial found that a HER2-targeted ADC with a TOP1 inhibitor payload, Enhertu, showed a significant progression-free survival benefit compared with a HER2-targeted ADC with an emtansine payload.

Additionally, ADCs containing TOP1 inhibitors have achieved higher DARs and have the ability to achieve higher clinical doses compared to ADCs with microtubule payloads, allowing for potential increased payload delivery.

For example, a third-party randomized controlled clinical trial found that a HER2-targeted ADC with a TOP1 inhibitor payload, Enhertu ® , showed a significant progression-free survival benefit compared with a HER2-targeted ADC with emtansine, a microtubule inhibtor payload.

Additionally, ADCs containing TOP1 inhibitors have achieved higher DARs and have the ability to achieve higher clinical doses compared to ADCs with microtubule inhibitor payloads, allowing for potential increased payload delivery.

These attributes may allow for a higher clinical dose of TOP1 inhibitor-containing ADCs, enabling an increased therapeutic index.

In October 2024, we presented preclinical data at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics demonstrating that, compared to deruxtecan, or DXd, HC74 demonstrated superior potency measured across 89 cell lines while retaining potency in chemotherapy-resistant cell lines.

HC74 also shows increased permeability that may lead to superior bystander effect, reduced efflux that may lead to avoiding certain mechanisms of resistance, and rapid hepatocyte clearance that may improve tolerability.

Our proprietary HC74 TOP1 inhibitor payload is designed with best-in-class attributes

Existing TOP1 inhibitors, such as deruxtecan (DXd), have several limitations, including high efflux potential, which leads to primary and acquired payload resistance when cancer cells “pump” the payload out of the cell before it can trigger cell death, and low permeability, which leads to poor bystander activity by preventing uptake of cytotoxic payloads by nearby target-negative cells.

Efflux transporters, such as P-glycoprotein, or P-gp, and multidrug resistance associated protein 1, or MRP1, actively remove ADC payloads from cells.

HC74 was designed to overcome these limitations and to incorporate the attributes of a potential best-in-class ADC payload.

These attributes include:

• Overcoming payload resistance:

HC74 is designed to have a lower efflux potential, which is intended to overcome payload resistance mediated by transporters such P-gp and MRP1).

• Increased bystander activity:

HC74 is designed to have higher permeability, which increases killing of nearby tumor cells that do not express the target of the ADC via bystander activity.

• Superior cytotoxicity:

HC74 has demonstrated superior cytotoxic activity across 89 tumor cell lines compared with DXd.

With this combination of attributes, we believe HC74 ADCs have the potential for greater frequency and duration of benefit compared with DXd and other TOP1 inhibitor payloads.

Preclinical studies have demonstrated that our HC74 TOP inhibitor payload and HC74 ADCs showed superior properties when compared with DXd and DXd ADCs.

The lower efflux potential of HC74 resulted in increased payload cytotoxicity in cells that overexpress efflux transporters, compared with DXd.

HC74 also showed increased permeability compared with DXd, resulting in significantly greater cytotoxicity.

We believe these results support the potential for superior bystander activity with HC74 compared with DXd.

We believe the reduced efflux ratio observed with HC74 in preclinical studies has the potential to provide clinical benefit because sensitivity to efflux meaningfully limits the clinical efficacy of existing TOP1 inhibitor ADCs.

High P-gp expression has been shown to correlate with significantly lower ORR and progression-free survival (PFS) in patients with HER2-positive colorectal cancer treated with T-DXd.

Preclinical data presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2025 also support the potential for HC74 ADCs to provide clinical benefit in the treatment of tumors with primary or acquired resistance to other TOP1 inhibitor therapies.

In these studies, a tumor model using a colorectal cancer cell line that expresses high levels of P-gp (HCT-15) was refractory to T-DXd or irinotecan but sensitive to HC74 ADCs.

We believe the superior bystander activity observed with HC74 ADCs compared with DXd ADCs supports the potential for greater HC74 activity in tumors with target heterogeneity.

Within a tumor, the target of the ADC may not be expressed on all cancer cells.

Cells lacking the target will not be killed directly by the ADC but may be killed through bystander activity that occurs when target-expressing cells killed by the ADC release payload that enters and kills neighboring target-negative cells.

Such effects cannot be discerned in tumor models that use cell lines in which every cell expresses the ADC target.

The NCI-H292 bystander mode comprises cells that are positive for TROP2 (a validated ADC target) as well as cells that lack TROP2 expression.

In this model, a TROP2-HC74 ADC significantly reduced tumor volume compared with a TROP2-DXd ADC.

Our unique combination of ADC expertise, novel targets, proprietary payload, and novel linkers enables us to pursue a differentiated ADC development strategy, which is focused on targets that have no approved ADCs and on indications with substantial unmet need.

2 unchanged sentences

Executing on this strategy, we have screened more than 1,000 targets, and this effort has to-date yielded more than 40 targets evaluated in vitro and more than 15 targets evaluated in vivo.

This has yielded three novel solid tumor ADCs for which IND-enabling studies are ongoing and six additional ADCs currently undergoing lead optimization.

This has yielded three novel solid tumor ADCs for which IND-enabling studies are ongoing and multiple additional ADCs currently undergoing lead optimization.

Continued execution of this ADC development strategy is anticipated to yield multiple new and highly differentiated ADC candidates each year.

6 unchanged sentences

Preclinical in vivo efficacy studies have shown tumor regression after a single, clinically relevant dose of IM-1617 in tumor models derived from melanoma, esophageal cancer, CRC, NSCLC, and other carcinomas.

IND-enabling work for IM-1617 was initiated in the fourth quarter of 2024.

IND-enabling work for IM-1617 is ongoing and we expect to submit an IND for this program to the FDA in early 2026.

IM-1340 (Solid Tumor ADCs)

8 unchanged sentences

An initial study in NHPs found a highest non-severely toxic dose of 40 mg/kg, indicating potential for a robust therapeutic window.

IND-enabling work for IM-1340 was initiated in the fourth quarter of 2024.

IND-enabling work for IM-1340 is ongoing and we expect to submit an IND for this program to the FDA in mid-2026.

IM-1335 (Solid Tumor ADCs)

6 unchanged sentences

As shown below, IM-1335 shows in vivo preclinical efficacy in a solid tumor indication.

IND-enabling work for IM-1335 was initiated in the fourth quarter of 2024.

IND-enabling work for IM-1335 is ongoing and we expect to submit an IND for this program to the FDA in late 2026.

Management Team

We are led by Clay Siegall, Ph.D., President and Chief Executive Officer.

Siegall previously served as CEO of Seagen, Inc., which he co-founded in 1997 and led for nearly 25 years.

During his tenure, Seagen earned FDA approvals for four cancer therapies.

Pfizer purchased Seagen in December 2023.

Siegall joined us in connection with our merger with Morphimmune, a preclinical biotechnology company led by Dr.

Siegall, in October 2023.

Bob Lechleider, M.D.

serves as our Chief Medical Officer.

Lechleider was most recently the Chief Medical Officer of OncoResponse, Inc.

and previously worked with Dr.

Siegall at Seagen, where he was responsible for directing the development of early and late-stage portfolios.

Jack Higgins, Ph.D., is our Chief Scientific Officer.

Most recently, he was Chief Scientific Officer at Morphimmune.

Previously, he was the Chief Development Sciences Officer at Molecular Templates, Inc., where he led discovery and development efforts for multiple clinical candidates and co-invented the company’s Engineered Toxin Body platform.

Phil Tsai, Ph.D., serves as our Chief Technical Officer.

Prior to joining Immunome, Dr.

Tsai spent 21 years at Seagen and then Pfizer (following the acquisition of Seagen in December 2023) in positions of increasing responsibility.

Most recently, he was the SVP of Technical Development, responsible for end-to-end development of biologics and drug-linker manufacturing processes, analytics, and drug products.

Max Rosett, our Chief Financial Officer, most recently served as Acting Chief Operating Officer at Morphimmune and joined Immunome as Senior Vice President, Operations.

Rosett previously served as a Principal at Research Bridge Partners, where he led Research Bridge Partners’ investment in Morphimmune’s Series A financing.

Sandra Stoneman, J.D., serves as our Chief Legal Officer.

She joined us from Duane Morris LLP, where she was an equity partner.

Kinney Horn serves as our Chief Business Officer.

He previously served in the same role at Olema Oncology, Inc.

and spent more than 15 years at Genentech, Inc.

Roee Shahar is our Executive Vice President, Commercial.

Shahar served as Vice President and Franchise Lead for Pfizer, where he managed the combined hematology portfolio resulting from the December 2023 acquisition of Seagen.

Before the acquisition, he served as Vice President and Franchise Lead for Seagen overseeing all commercial activities for hematology.

We believe that our team’s expertise positions us to develop the next generation of transformative targeted therapies including ADCs.

This expertise comprises executive leadership with a proven record of success, an ADC-focused discovery team with deep experience in ADC design, and a seasoned development team whose members spearheaded the development of multiple FDA-approved therapies.

Strategic Transactions

2 unchanged sentences

Under the Ayala Purchase Agreement, we paid Ayala approximately $20.0 million in cash and issued 2,175,489 shares of our common stock with an aggregate fair value of $50.6 million on the date of issuance.

We are also obligated to pay Ayala up to $37.5 million in the aggregate upon the achievement of certain development, regulatory and commercial milestones.

In December 2025, the Company achieved a $10.0 million development milestone pursuant to the Ayala Purchase Agreement associated with reporting positive topline results for the Phase 3 RINGSIDE trial of varegacestat.

We are also obligated to pay Ayala up to an additional $27.5 million in the aggregate upon the achievement of certain future regulatory and commercial milestones.

Acquisition of Assets from Zentalis Pharmaceuticals, Inc.

5 unchanged sentences

The $5.0 million developmental milestone was achieved in the fourth quarter of 2024 and paid in the first quarter of 2025.

Merger with Morphimmune

On October 2, 2023, we completed our merger with Morphimmune.

Under the terms of the Agreement and Plan of Merger and Reorganization dated as of June 28, 2023, or the Merger Agreement, among us, Morphimmune and Ibiza Merger Sub, Inc., a wholly owned subsidiary of the Company, or Merger Sub, Morphimmune merged with and into Merger Sub, with Morphimmune surviving as a wholly-owned subsidiary of us, or the Merger.

In connection with the Merger, on October 2, 2023, we issued and sold 21,690,871 shares of our common stock pursuant to the subscription agreements in a private investment in public equity, or PIPE, transaction which provided us with gross proceeds of $125.0 million.

Strategic Collaborations, License Agreements and Other Material Agreements

15 unchanged sentences

BMS has the right to terminate the BMS License in its entirety upon written notice to us (a) for insolvency-related events involving us, (b) for our material breach of the BMS License if such breach remains uncured for a defined period of time, (c) for our failure to fulfil our obligations to develop or commercialize the BMS Licensed Compounds and/or BMS Licensed Products not remedied within a defined period of time following written notice by BMS, or (d) if we or our affiliates commence any action challenging the validity, scope, enforceability or patentability of any of the licensed patent rights.

We have the right to terminate the BMS License (a) for convenience upon prior written notice to BMS, the length of notice dependent on whether a BMS Licensed Product has received regulatory approval, (b) upon immediate written notice to BMS for insolvency-related events involving BMS, (c) for BMS’s material breach of the BMS License if such breach remains uncured for a defined period of time, or (d) on a BMS Licensed Compound-by-BMS Licensed Compound and/or BMS Licensed Product-by-BMS Licensed Product basis upon immediate written notice to BMS if we reasonably determine that there are unexpected safety and public health issues relating to the applicable BMS Licensed Compounds and/or BMS Licensed Products.

events involving BMS, (c) for BMS’s material breach of the BMS License if such breach remains uncured for a defined period of time, or (d) on a BMS Licensed Compound-by-BMS Licensed Compound and/or BMS Licensed Product-by-BMS Licensed Product basis upon immediate written notice to BMS if we reasonably determine that there are unexpected safety and public health issues relating to the applicable BMS Licensed Compounds and/or BMS Licensed Products.

Upon termination of the BMS License in its entirety by us for convenience or by BMS, we grant an exclusive, non-transferable, sublicensable, worldwide license to BMS under certain of our patent rights that are necessary to develop, manufacture or commercialize BMS Licensed Compounds or BMS Licensed Products.

22 unchanged sentences

We expect our future contractual manufacturing organizations to have successful track records of producing products for other companies under applicable compliance regulations, such as cGMP compliance in the case of the FDA.

Commercialization

In preparation for the potential regulatory approval of varegacestat for the treatment of desmoid tumors, we are in the process of establishing a commercial organization, which is led by a leadership team with experience in the successful launch of pharmaceutical products for oncology and rare disease indications.

The objectives of our commercial organization include developing and executing market development and commercialization strategies for any products that receive regulatory approval.

In furtherance of these objectives, we are continuing to build our commercial capabilities and infrastructure.

We currently hold global commercial rights for varegacestat, our product candidate for the treatment of desmoid tumors.

Subject to obtaining the necessary regulatory approvals, we plan to lead the global commercial strategy and commercialization efforts for this product.

In the United States, we expect to commercialize the product through a focused internal commercial organization, which would include capabilities in marketing, analytics, market access, and a targeted sales force designed to reach specialized treatment centers.

Outside of the United States, we anticipate pursuing a flexible commercialization strategy.

In certain key markets, including Europe, we may retain commercial rights and build a focused internal commercial team to support commercialization activities, subject to obtaining marketing approvals.

Alternatively, we may seek to commercialize the product through strategic collaborations, distribution arrangements, or other marketing partnerships with third parties.

The development and commercialization of new product candidates is highly competitive.

2 unchanged sentences

Our competitors also may obtain marketing approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market.

We expect to compete with oncology companies advancing antibodies, ADCs, small molecules, targeted radiotherapies, and other therapeutic modalities.

We are aware of competitors who are developing ADCs, including, but not limited to, ADC Therapeutics SA, Ipsen SA, Exelexis, Inc., and Zymeworks Inc.

and competitors based overseas, including, but not limited to, Hansoh Pharmaceutical Group, Ltd., Jiangsu Hengrui Pharmaceuticals Company Ltd.

and LaNova Medicines.

We also expect to compete with companies pursuing targeted radiotherapies, including, but not limited to, RayzeBio, (acquired by BMS), Fusion Pharmaceuticals (acquired by AstraZeneca), Point Biopharma (acquired by Eli Lilly and Company), Aktis Oncology, Actinium Pharmaceuticals, and Yantai LNC Biotechnology.

In addition, we expect to compete with large, multinational pharmaceutical companies that discover, develop and commercialize antibodies, ADCs, small molecules, targeted radiotherapies, and other therapeutics for use in treating cancer such as Immunogen (acquired by AbbVie Inc.);

Daiichi Sankyo;

We expect to compete with oncology companies advancing small molecules, ADCs, targeted radiotherapies, antibodies, and other therapeutic modalities.

This may include large, multinational pharmaceutical companies such as Immunogen (acquired by AbbVie Inc.), AstraZeneca;

Bayer AG, BMS;

Eli Lilly and Company;

2 unchanged sentences

Seagen (acquired by Pfizer) and Johnson & Johnson.

If any future product candidates identified through our current lead programs are eventually approved for sale, they will likely compete with a range of treatments that are either in development or currently marketed for use in those same disease indications.

If any of our current or future product candidates are eventually approved for sale, they will likely compete with a range of treatments that are either in development or currently marketed for use in those same disease indications.

With respect to varegacestat, we expect to compete with companies advancing treatments for desmoid tumors, including, but not limited to, SpringWorks Therapeutics, Inc.

(acquired by Merck KGaA in July 2025).

In November 2023, Springworks received FDA approval for its oral gamma secretase inhibitor, OGSIVEO ® (nirogacestat), for the treatment of adult patients with progressing desmoid tumors who require systemic treatment.

Desmoid tumors treatments also include surgery, hormonal therapy, targeted therapy and chemotherapy.

We believe that IM-1021, our preclinical ROR1 ADC program, has the potential to address hematologic and solid tumor indications.

There are several other companies developing antibodies, ADCs, and targeting ROR1, and they may represent the most direct competition to our ROR1 ADC program.

Merck has an ADC program (zilovertamab vedotin) in a Phase 3 clinical trial for B-cell lymphoma.

CStone Pharmaceuticals , Inc.

has an ADC program in a Phase I trial.

CSPC Pharmaceutical Group Limited and Radiance Biopharma have received clearance from Chinese regulatory authority clearance to initiate clinical trials for SYS6005, a ROR1 ADC.

There are several other companies developing FAP-targeted radioligand therapies which may represent the most direct competition to our IM-3050 program.

Novartis is advancing a FAP-targeted radioligand therapy (177Lu-FAP-2286) that was acquired from Clovis Oncology and is currently in Phase 2.

Yantai LNC Biotechnology has also initiated a Phase 1 trial for another FAP-targeted radioligand therapy (LNC1004).

IM-1021 is a ROR1 ADC program with the potential to address hematologic and solid tumor indications.

We are aware of several other companies developing therapeutics, including ADCs, targeting ROR1, and they may represent direct competition to our ROR1 ADC program.

For example, Merck has a ROR1 ADC program (Zilovertamab vedotin) in a Phase 3 clinical trial for diffuse large B-cell lymphoma, and CStone Pharmaceuticals, Inc.

has disclosed a ROR1 ADC program in clinical development.

Regarding IM-3050, we are aware of several other companies developing FAP-targeted radioligand therapies, which may represent direct competition to that program.

For instance, Novartis, Ratio Therapeutics, Perspective Therapeutics and Sinotau Pharmaceutical Group have disclosed FAP-targeted radioligand therapies in clinical development.

Additionally, our IM-3050 program faces competition from competitors who may have superior access to a consistent supply of radioactive isotopes.

Many of our competitors have significantly greater financial resources and expertise in research and development, manufacturing, preclinical studies, conducting clinical studies, obtaining regulatory approvals and marketing approved products than we have.

Many of our competitors have significantly greater financial resources and expertise in research and development, manufacturing, preclinical studies, conducting clinical studies, integrating assets into their portfolio, obtaining regulatory approvals and marketing approved products than we have.

These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical study sites and patient registration for clinical studies, as well as in acquiring technologies complementary to, or necessary for, our programs.

14 unchanged sentences

We believe our current layered patent estate, together with our efforts to develop and patent next generation technologies, provides us with substantial intellectual property protection.

As of December 31, 2024, we own or exclusively in-license 141 issued or granted patents and 117 pending applications on a world-wide basis (including major commercial and manufacturing jurisdictions of the United States, Europe, Japan and China) covering our varegacestat, IM-1021, IM-3050, IM-1617, IM-1340 and IM-1335 product candidates.

As of December 31, 2025, we own or exclusively in-license 170 issued or granted patents and 155 pending applications on a world-wide basis (including major commercial and manufacturing jurisdictions of the United States, Europe, Japan and China) covering our varegacestat, IM-1021, IM-3050, IM-1617, IM-1340 and IM-1335 product candidates and other technologies.

The US composition of matter patent covering varegacestat will expire in 2038, which includes 5 years of expected patent term extension.

107 unchanged sentences

Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product development, nonclinical studies and clinical trials, along with information relating to the product’s chemistry, manufacturing, and controls and proposed labeling, are submitted to the FDA as part of an NDA or BLA requesting approval to market the product for one or more indications.

To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and efficacy of the investigational drug (or safety, purity and potency of the investigational biologic product) to the satisfaction of the FDA.

Under the Prescription Drug User Fee Act, as amended, or PDUFA, each NDA or BLA must be accompanied by a significant user fee, and the sponsor of an approved application is also subject to an annual program fee.

57 unchanged sentences

Pediatric Trials

Under the Pediatric Research Equity Act, or PREA, certain NDAs or BLAs or supplements thereto must contain data to assess the safety and efficacy of the drug candidate (or safety, purity and potency of the biologic candidate) for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.

Under the Pediatric Research Equity Act, or PREA, certain NDAs or BLAs or supplements thereto must contain data to assess the safety and efficacy of the drug candidate (or safety, purity and potency of the biologic candidate) in relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.

The FDA may grant deferrals for submission of such data or full or partial waivers.

13 unchanged sentences

Orphan exclusivity does not prevent the FDA from approving a different drug or biological product for the same disease or condition, or the same product for a different disease or condition.

A comparable program of orphan drug designation and exclusivity is offered in the European Union, Japan and other jurisdictions.

Post-Approval Requirements

Any products that we may manufacture or distribute pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, monitoring and record-keeping requirements, reporting of adverse experiences with the product, periodic reporting requirements, providing the FDA with updated safety and efficacy information, product sampling and distribution requirements, as well as advertising and promotion requirements, which include, among others, standards for direct-to-consumer advertising, restrictions on promoting products for uses or in patient populations that are not described in the product’s approved uses (known as off-label use), limitations on industry-sponsored scientific and educational activities, and requirements for promotional activities involving the Internet.

Any products that we may manufacture or distribute pursuant to FDA approvals are subject to pervasive and continuing regulation, including, among other things, monitoring and record-keeping requirements, reporting of adverse experiences with the product, periodic reporting requirements, providing updated safety and efficacy information, product sampling and distribution requirements, as well as advertising and promotion requirements, which include, among others, standards for direct-to-consumer advertising, restrictions on promoting products for uses or in patient populations that are not described in the product’s approved uses (known as off-label use), limitations on industry-sponsored scientific and educational activities, and requirements for promotional activities involving the Internet.

After approval, most changes to the approved product, such as adding new indications or other labeling claims, are subject to prior FDA review and approval of a new application or supplement, which may require the applicant to develop additional data or conduct additional pre-clinical studies and clinical trials.

13 unchanged sentences

Examples of these consequences include, without limitation, the following:

may result in revisions to the approved labeling to add new safety information;

revisions to the approved labeling to add new safety information;

imposition of post-market studies or clinical studies to assess new safety risks;

or imposition of distribution restrictions or other restrictions under a REMS program;

imposition of distribution restrictions or other restrictions under a REMS program;

complete withdrawal of the product from the market or other limits on marketing or manufacture of the product;

51 unchanged sentences

Among other things, the passage of HITECH made HIPAA’s privacy and security standards directly applicable to business associates and their covered subcontractors.

Additionally, the federal Physician Payments Sunshine Act, or the Sunshine Act, within the Patient Protection and Affordable Care Act, or ACA, and its implementing regulations, require that certain manufacturers of drugs, devices, biological and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) report annually to CMS information related to certain payments or other transfers of value made or distributed to physicians, as broadly defined by such law, certain advanced non-physician health care practitioners, and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, such individuals or entities, and to report annually certain ownership and investment interests held by physicians and their immediate family members.

Additionally, the federal Physician Payments Sunshine Act, or the Sunshine Act, within the Patient Protection and Affordable Care Act, or ACA, and its implementing regulations, require that certain manufacturers of drugs, devices, biological and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) report annually to the Centers for Medicare & Medicaid Services, or CMS, information related to certain payments or other transfers of value made or distributed to physicians, as broadly defined by such law, certain advanced non-physician health care practitioners, and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, such individuals or entities, and to report annually certain ownership and investment interests held by physicians and their immediate family members.

In order to distribute products commercially, we must comply with state laws that require the registration of manufacturers and wholesale distributors of drug and biological products in a state, including, in certain states, manufacturers and distributors who ship products into the state even if such manufacturers or distributors have no place of business within the state.

21 unchanged sentences

Limited coverage and less than adequate reimbursement may reduce the demand for, or the price of, any product for which we obtain regulatory approval.

Moreover, there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug products.

For example, the U.S.

Department of Health and Human Services, or HHS, has been empowered to (1) negotiate drug prices annually for a select number of single source Part D drugs and biologics that have been on the market for at least seven (7) years for drugs and eleven (11) years for biologics without generic or biosimilar competition, and (2) impose rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

Each year up to twenty (20) products will be selected by HHS for the Medicare Drug Price Negotiation Program.

Products subject to the Medicare Drug Price Negotiation Program are expected to experience a significant reduction in reimbursement from the Medicare program on a per unit basis.

Third-party payors are increasingly challenging the price, examining the medical necessity, and reviewing the cost-effectiveness of medical products, therapies, and services, in addition to questioning their safety and efficacy.

24 unchanged sentences

There have been judicial and Congressional challenges and amendments to certain aspects of the ACA.

For example, on August 16, 2022, the Inflation Reduction Act of 2022, or the IRA, was signed into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.

The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and creating a new manufacturer discount program.

For example, narrowed access to ACA marketplace exchange enrollment and declined to extend the ACA enhanced advanced premium tax credits that expired at the end of 2025, which, among other provisions in the law, are anticipated to reduce the number of Americans with health insurance.

The OBBBA also is expected to reduce Medicaid spending and enrollment by implementing work requirements for some beneficiaries, capping state-directed payments, reducing federal funding, and limiting provider taxes used to fund the program.

Congress is considering proposed legislation intended to further reduce healthcare costs with alternatives to replace the expired ACA subsidies.

Further legislative and regulatory changes under the ACA remain possible, but it is unknown what form any such changes or any law would take, and how or whether it may affect the biopharmaceutical industry as a whole or our business in the future.

2 unchanged sentences

These changes include aggregate reductions to Medicare payments to providers pursuant to the Budget Control Act of 2011, which began in 2013 and, due to subsequent legislative amendments, will remain in effect through 2032, unless additional Congressional action is taken.

For example, the IRA has multiple provisions that may impact the prices of drug products that are both sold into the Medicare program and throughout the United States.

Starting in 2023, a manufacturer of a drug or biological product covered by Medicare Parts B or D must pay a rebate to the federal government if the drug product’s price increases faster than the rate of inflation.

This calculation is made on a drug product by drug product basis and the amount of the rebate owed to the federal government is directly dependent on the volume of a drug product that is paid for by Medicare Parts B or D.

Additionally, starting in payment year 2026, CMS will negotiate drug prices annually for a select number of single source Part D drugs and biologics that have been on the market for at least 7 years for drugs and 11 years for biologics without generic or biosimilar competition.

On August 15, 2024, the agreed-upon prices for the first ten drugs that were subject to price negotiations was published, although the Medicare drug price negotiation program is currently subject to legal challenges.

On January 17, 2025, CMS selected fifteen additional products covered under Part D for price negotiation in 2025.

Each year thereafter more Part B and Part D products will become subject to the Medicare drug price negotiation program If a drug product is selected by CMS for negotiation, it is expected that the revenue generated from such drug will decrease.

Additionally, on December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights.

While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework.

The current Trump administration is pursuing policies to reduce regulations and expenditures across government including at HHS, the FDA, CMS and related agencies.

These actions presently directed by executive orders or memoranda from the Office of Management and Budget, may propose policy changes that create additional uncertainty for our business.

These actions may, for example, include directives to reduce agency workforce, rescinding a Biden administration executive order tasking the Center for Medicare and Medicaid Innovation (“CMMI”) to consider new payment and healthcare models to limit drug spending and eliminating the Biden administration’s executive order that directed HHS to establishing an AI task force and developing a strategic plan.

For example, the current Trump administration has announced agreements with pharmaceutical companies that require the drug manufacturers to offer, through a direct-to-consumer platform, U.S.

patients and Medicaid programs prescription drug Most-Favored Nation pricing equal to or lower than those paid in other developed nations, with additional mandates for direct-to-patient discounts and repatriation of foreign revenues.

Other recent actions, for example, include (1) directives to reduce agency workforce and cut programs;

(2) directing HHS and other agencies to lower prescription drug costs through a variety of initiatives, including by improving upon the Medicare Drug Price Negotiation Program and establishing Most-Favored-Nation pricing for pharmaceutical products;

(3) imposing tariffs on imported pharmaceutical products;

and (4) as part of the Make America Healthy Again Commission’s recent Strategy Report, working across government agencies to increase enforcement on direct-to-consumer pharmaceutical advertising.

Additionally, the current administration recently called on Congress to enact "The Great Healthcare Plan," to codify and expand Most-Favored Nation pricing, lower government subsidies to private insurance companies, increase healthcare price transparency, expand pharmaceutical drugs available for over-the-counter purchase, and enact restrictions on pharmacy benefit manager, or PBM, payment methodologies, among other things.

These actions and policies may significantly reduce U.S.

drug prices, potentially impacting manufacturers’ global pricing strategies and profitability, while increasing their operational costs and compliance risks.

Additionally, in its June 2024 decision in Loper Bright Enterprises v.

Raimondo (“Loper Bright”), the U.S.

Supreme Court overturned the longstanding Chevron doctrine, under which courts were required to give deference to regulatory agencies’ reasonable interpretations of ambiguous federal statutes.

The Loper Bright decision could result in additional legal challenges to current regulations and guidance issued by federal agencies applicable to our operations, including those issued by the FDA.

Congress may introduce and ultimately pass health care related legislation that could impact the drug approval process and make changes to the Medicare Drug Price Negotiation Program created under the IRA.

Raimondo, the U.S.

Supreme Court’s decision greatly reduced judicial deference to regulatory agencies, which could increase successful legal challenges to federal regulations affecting our operations.

Congress may introduce and ultimately pass health care related legislation that could impact the drug approval process and make changes to the Medicare Drug Price Negotiation Program.

Individual states in the United States have also increasingly passed legislation and implemented 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.

For example, on January 5, 2024, the FDA approved Florida’s Section 804 Importation Program, or SIP, proposal to import certain drugs from Canada for specific state healthcare programs.

It is unclear how this program will be implemented, including which drugs will be chosen, and whether it will be subject to legal challenges in the United States or Canada.

Other states have also submitted SIP proposals that are pending review by the FDA.

Any such approved importation plans, when implemented, may result in lower drug prices for products covered by those programs.

We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative or executive action, either in the United States or abroad, particularly in light of the recent U.S.

Presidential and Congressional elections.

We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative or executive action, either in the United States or abroad.

We expect that additional state and federal health care reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for health care products and services, including any future drug products for which we secure marketing approval.

7 unchanged sentences

We may incur significant costs to comply with such laws and regulations now or in the future.

Additionally, we are, or may in the future become, subject to numerous data privacy and security obligations, including federal, state, local, and foreign laws, regulations, guidance, and industry standards related to data privacy, security, and protection.

Such obligations may include, without limitation, the Federal Trade Commission Act, state consumer health data laws, the European Union’s General Data Protection Regulation, the United Kingdom’s General Data Protection Regulation, Australia’s Privacy Act 1988, and Israel’s Protection of Privacy Law.

These and other such laws that have been enacted or proposed impose numerous compliance requirements and potential penalties on covered businesses, and as a result increase compliance costs and complexity for companies such as ours.

Employees and Human Capital Resources

As of December 31, 2024, we had 118 full-time employees, including 71 who hold advanced degrees.

Of these 118 employees, 87 were engaged in research and development activities and 31 were engaged in general and administrative activities.

As of December 31, 2025, we had 177 full-time employees, 133 of whom were engaged in research and development activities.

None of our employees are represented by labor unions or covered by collective bargaining agreements.

1 unchanged sentence

Our human capital resources objectives include, as applicable, identifying, recruiting, and retaining a diverse pool of qualified talent as well as training, incentivizing, and integrating our new and existing employees, advisors, and consultants.

We offer a competitive total rewards package, updated in 2024 based on market research.

We offer a competitive total rewards package, updated regularly based on market research.

We incentivize high performers through an annual bonus program based on our company and individual performance for which all employees are eligible.

10 unchanged sentences

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