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Item 1. Business

2025-03-20 compared with 2024-03-28 · 272 added, 206 removed, 1150 unchanged (29% of the section changed)

We are a late-stage clinical biopharmaceutical company focused on the development of novel therapeutics for a broad range of cancer indications.

Our product candidates currently include galinpepimut-S, or GPS, a peptide immunotherapy directed against the Wilms tumor 1, or WT1, antigen, and SLS009 (formerly, GFH009), a highly selective small molecule cyclin-dependent kinase 9, or CDK9, inhibitor.

Our product candidates currently include galinpepimut-S, or GPS, a peptide immunotherapy directed against the Wilms tumor 1, or WT1, antigen, and SLS009 (tambiciclib), a highly selective small molecule cyclin-dependent kinase 9, or CDK9, inhibitor.

Galinpepimut-S:

Highly Novel and Engineered Immunotherapy Targeting the WT1 Antigen

Our lead product candidate, GPS, is a cancer immunotherapeutic agent licensed from Memorial Sloan Kettering Cancer Center, or MSK, that targets the WT1 protein, which is present in 20 or more cancer types.

Based on its mechanism of action as a directly immunizing agent, GPS has potential as a monotherapy or in combination with other immunotherapeutic agents to address a broad spectrum of hematologic, or blood, cancers, and solid tumor indications.

In January 2020, we commenced in the United States an open label randomized Phase 3 clinical trial, the REGAL study, for GPS monotherapy in patients with acute myeloid leukemia, or AML, in the maintenance setting after achievement of second complete remission, or CR2, following successful completion of second-line antileukemic therapy.

We have an ongoing open label randomized Phase 3 clinical trial, the REGAL study, for GPS monotherapy in patients with acute myeloid leukemia, or AML, in the maintenance setting after achievement of second complete remission, or CR2, following successful completion of second-line antileukemic therapy.

Patients are randomized to receive either GPS or best available treatment, or BAT.

We expect this study will be used as the basis for submission of a Biologics License Application, or BLA, subject to a statistically significant and clinically meaningful data outcome and agreement with the U.S.

We expect this study will be used as the basis for submission of a Biologics License Application, or BLA, subject to a statistically significant and clinically meaningful trial outcome and agreement with the U.S.

Food and Drug Administration, or the FDA.

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In March 2024, we announced the completion of enrollment.

Under our current assumptions with respect to enrollment and the estimated survival times for both the treated and control groups in the study, we believe, after discussions with our external statisticians and experts, that the planned interim analysis after 60 events (deaths) per the protocol will occur in the first half of 2024 and the final analysis after 80 events will occur by the end of 2024.

Because these analyses are event driven, they are difficult to predict with any certainty and may occur at a different time than currently expected.

In December 2020, we entered into an exclusive license agreement with 3D Medicines Inc., or 3D Medicines, a China-based biopharmaceutical company developing next-generation immuno-oncology drugs, for the development and commercialization of GPS, as well as the Company’s next generation heptavalent immunotherapeutic GPS+, which is at preclinical stage, across all therapeutic and diagnostic uses in mainland China, Hong Kong, Macau and Taiwan, which we refer to as Greater China.

In December 2024, we announced that the pre-specified threshold of 60 events (deaths) per the protocol had been reached, triggering the interim analysis to be conducted by the Independent Data Monitoring Committee, or IDMC.

In January 2025, we announced that the IDMC had completed pre-specified interim analysis of the REGAL study and had recommended that the study continue without modifications.

The next and final analysis will be conducted once 80 events (deaths) are reached.

We anticipate that 80 events will be reached this year.

Because the final analysis is event driven, it is difficult to predict with any certainty and it may occur at a different time than currently expected.

In December 2020, we entered into an exclusive license agreement, or the 3D Medicines Agreement, with 3D Medicines Inc., or 3D Medicines, a China-based biopharmaceutical company developing next-generation immuno-oncology drugs, for the development and commercialization of GPS, as well as the Company’s next generation heptavalent immunotherapeutic GPS+, which is at preclinical stage, across all therapeutic and diagnostic uses in mainland China, Hong Kong, Macau and Taiwan, which we refer to as Greater China.

We have retained sole rights to GPS and GPS+ outside of Greater China.

In November 2022, we announced that we had agreed with 3D Medicines for 3D Medicines to participate in the REGAL study through the inclusion of approximately 20 patients from mainland China.

In December 2022, we entered into a Side Letter Agreement with 3D Medicines, or Side Letter, which together with the 3D Medicines Agreement, details the terms and conditions of 3D Medicines' participation in the REGAL study.

Although the REGAL study has completed enrollment as announced in March 2024, in accordance with the predetermined statistical analysis plan, 3D Medicines may still enroll patients in mainland China.

The timing of such participation and patient enrollment by 3D Medicines, if at all, cannot be predicted with certainty.

As of March 15, 2025, we have received an aggregate of $10.5 million in upfront and milestone payments under our license agreement with 3D Medicines, or the 3D Medicines Agreement, and a total of $191.5 million in potential future development, regulatory and sales milestones, not including future royalties, remains under the license agreement, which milestones are variable in nature and not under our control.

In December 2023, we announced that we had commenced a binding arbitration proceeding against 3D Medicines to resolve a dispute regarding, among other things, the trigger and payment of relevant milestone payments due to us under the 3D Medicines Agreement.

Legal Proceedings .

As of March 15, 2024, we have received an aggregate of $10.5 million in upfront and milestone payments under our license agreement with 3D Medicines, or the 3D Medicines Agreement, and a total of $191.5 million in potential future development, regulatory and sales milestones, not including future royalties, remains under the license agreement, which milestones are variable in nature and not under our control.

In December 2018, pursuant to a Clinical Trial Collaboration and Supply Agreement, we initiated a Phase 1/2 multi-arm "basket" type clinical study of GPS in combination with Merck & Co., Inc.’s anti-PD-1 therapy, pembrolizumab (Keytruda ® ).

In 2020, we, together with Merck, determined to focus on ovarian cancer (second or third line).

In November 2022, we reported topline clinical and initial immune response data from this study, which showed that treatment with the combination of GPS and pembrolizumab compared favorably to treatment with anti-PD-1 therapy alone in a similar patient population.

In November 2023, additional immunobiological and clinical data from the

study was presented at the International Gynecologic Cancer Society 2023 Annual Global Meeting which showed a correlation between immune response and progression free survival, or PFS.

In February 2020, a Phase 1 open-label investigator-sponsored clinical trial of GPS, in combination with Bristol-Myers Squibb’s anti-PD-1 therapy, nivolumab (Opdivo ® ), in patients with malignant pleural mesothelioma, or MPM, who harbor relapsed or refractory disease after having received frontline standard of care multimodality therapy was commenced at MSK.

Enrollment of a target total of 10 evaluable patients was completed at the end of 2022.

We reported positive topline safety and efficacy data from this study in June 2023 and positive follow-up immune response and survival data in December 2023.

GPS was granted Orphan Drug Designations, or ODD, from the FDA, as well as orphan medicines designations from the European Medicines Agency, or EMA, for GPS in AML, MPM, and multiple myeloma, or MM, as well as Fast Track designations for AML, MPM, and MM from the FDA.

GPS was granted Orphan Drug Designations, or ODD, from the FDA, as well as orphan medicines designations from the European Medicines Agency, or EMA, in AML, malignant pleural mesothelioma, or MPM, and multiple

myeloma, or MM, as well as Fast Track designations for AML, MPM, and MM from the FDA.

In October 2024, the FDA granted Rare Pediatric Disease, or RPD, designation to GPS for the treatment of pediatric AML.

Highly Selective Next Generation CDK9 Inhibitor

On March 31, 2022, we entered into an exclusive license agreement, or the GenFleet Agreement, with GenFleet Therapeutics (Shanghai), Inc., or GenFleet, a clinical-stage biotechnology company developing cutting-edge therapeutics in oncology and immunology, that grants rights to us for the development and commercialization of SLS009, a highly selective small molecule CDK9 inhibitor, across all therapeutic and diagnostic uses worldwide, except for Greater China.

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We completed a Phase 1 dose-escalating clinical trial in the United States and China for SLS009 in mid-2023 and reported positive safety and efficacy data for both patient cohorts, that is relapsed and/or refractory AML and refractory lymphoma.

We also established in the trial a recommended Phase 2 dose, or RP2D, of 60 mg for AML and 100 mg for lymphomas.

In the second quarter of 2023, we commenced an open label, single arm, multi-center Phase 2a clinical trial of SLS009 in combination with venetoclax and azacitidine, or aza/ven, in AML patients who failed or did not respond to treatment with venetoclax-based therapies.

The Phase 2a trial is evaluating safety, tolerability and efficacy at two dose levels, 45 mg once weekly, and 60 mg once weekly or 30 mg twice a week.

In the fourth quarter of 2023, we announced the dosing of the first patient in a Phase 1b/2 open-label, single arm trial in relapsed/refractory, or r/r, peripheral T-cell lymphoma, or PTCL, which will enroll up to 95 patients to evaluate safety and efficacy and, based on results, may serve as a registrational study.

This study is funded by GenFleet and is being conducted in China.

In March 2024, we announced positive topline data from the Phase 2a clinical trial of SLS009 in combination with aza/ven in r/r/ AML.

A total of 21 patients were enrolled in the study as of March 15, 2024:

10 in the 45 mg safety cohort and 11 in the 60 mg cohort (30 mg twice a week or 60 mg once a week).

Response rates observed in the three cohorts were 10% in the 45 mg once a week safety dose cohort (dose level below the RP2D), 20% in the 60 mg once a week dose cohort, and 50% in the 30 mg twice a week dose cohort.

Additionally, we observed strong anti-leukemic activity, which is defined as 50% or more bone marrow blast reduction in 67% of patients across all dose levels.

Median OS has not been reached in any of the cohorts and the first patient enrolled in the study who achieved a CR continues on the study and remains leukemia-free 9 months after enrollment.

We also established in the trial a recommended Phase 2 dose, or RP2D, of 60 mg once weekly for AML and 100 mg once weekly for lymphomas.

In the second quarter of 2023, we commenced an open label, single arm, multi-center Phase 2a clinical trial with SLS009 in combination with venetoclax and azacitidine, or aza/ven, in patients with AML who failed or did not respond to treatment with venetoclax-based therapies.

The trial is evaluating safety, tolerability, and efficacy at two dose levels of SLS009, 45 mg once weekly, and 60 mg once weekly or 30 mg twice a week, in combination with aza/ven.

In addition to safety and tolerability of SLS009 in combination with aza/ven, the efficacy endpoints are complete response composite rate and duration of response.

Additional endpoints include event free survival, overall survival, and pharmacokinetic and pharmacodynamic assessments.

In the fourth quarter of 2023, we completed enrollment in the 45 mg (safety) dose cohort in the Phase 2a study and reported positive initial topline data.

At that time, we also commenced enrollment in the 60 mg dose cohort with patients randomized to one of two groups, 60 mg fixed dose once weekly or 30 mg fixed twice weekly.

Each group was planned to enroll five to 10 patients.

During the trial we identified 30 mg fixed twice weekly as our optimal dose level.

During the trial, we identified potential biomarkers currently undergoing testing as predictive markers in the most recent portion of the study.

Patients with the identified biomarkers exhibited significantly higher response rates:

100% response rate at the optimal dose level (30 mg twice a week) and 57% response rate across all dose levels.

Furthermore, we have clarified the proposed biological basis and mechanism of action for SLS009 activity in patients with these biomarkers.

The relevant biomarkers are present in multiple hematologic and solid cancer indications, with a substantial proportion of patients exhibiting them in additional indications, ranging up to ~50% of patients in some indications.

SLS009 was granted ODD for AML and PTCL and Fast Track designations for r/r AML and r/r PTCL by the FDA.

In May 2024, we announced additional preliminary data from the Phase 2a trial of SLS009 in r/r AML and successful filing of a provisional patent application around the ASXL1 mutation and SLS009, including all CDK9 inhibitor drugs.

ASXL1 mutations are associated with poor prognosis in all myeloid diseases, owing to the reduced response to the current treatment options.

We observed a high rate of responses in patients with myelodysplasia-related molecular mutations (AML MRC), as defined by the World Health Organization, and patients with the ASXL1 gene mutation accounted for the most responders across all dose cohorts.

We expanded the ongoing study to include two additional cohorts, one with ASXL1 mutated AML patients and one with patients with myelodysplasia-related molecular abnormalities other than ASXL1 at the optimal dose level of 30 mg fixed twice weekly.

A summary of the positive data from the first 3 cohorts in the Phase 2a trial is as follows as of the December 2024 follow-up, which we announced in December 2024:

Dose Level Evaluable Patients ORR AML MRC ORR mOS AML MRC mOS

45 mg QW 10 10% 17% 5.1 months 5.8 months

60 mg BIW 9 33% 33% 3.9 months 3.9 months

30 mg BIW 9 46% 60% 7.7 months + 8.3 months +

Overall 28 31% 40% 5.1 months + 5.7 months +

leukemia-free status that includes complete response, complete response with incomplete hematologic recovery, and morphologic leukemia-free state.

median overall survival

Additionally, we announced that, as of the December 2024 follow-up, in the expansion cohorts 4 and 5, in patients with AML-myelodysplasia-related changes (AML-MRC) with ASXL1 mutation (cohort 4) and mutations and cytogenic changes other than ASXL1 (cohort 5), the ORR was 56% in 9 patients evaluable for efficacy.

SLS009 was well-tolerated with no new safety signals observed to date as the regimen remains safe in additional patients enrolled to date.

In November 2024, we announced data from preclinical studies identifying ASXL1 mutation as key predictor of SLS009 in response to solid cancers.

SLS009 is also currently being evaluated in pediatric solid tumors and leukemia models through the NCI Pediatric Preclinical in Vivo Testing, or PIVOT, program.

Studies are supported through cooperative agreement grants from the NCI to the PIVOT research centers performing the testing in pediatric tumor models and a centralized coordinating center.

We expect to report relevant data from the program in the first half of 2025.

Our partner, GenFleet, is focusing on lymphoma indications with SLS009 in its Greater China market.

In March 2024, we announced that GenFleet initiated a study of SLS009 in combination with zanubrutinib (Brukinsa®), a BTK inhibitor, in r/r diffuse large B-cell lymphoma, or DLBCL, and the first patient was dosed in the trial.

The study is funded and sponsored by GenFleet and is being conducted in China only.

In February 2025, we announced positive data from the Phase 2a study evaluating SLS009 in combination with zanubrutinib.

The results showed an overall response rate of 67%, more than double the expected ORR of zanubrutinib alone.

For SLS009, the FDA granted Orphan Drug Product designations in AML and peripheral T-cell lymphoma, or PTCL, and Fast Track designations for r/r AML and r/r PTCL.

The FDA granted RPD designation to SLS009 for the treatment of pediatric acute lymphoblastic leukemia, or ALL, in June 2024 and the FDA granted RPD designation to SLS009 for the treatment of pediatric AML in July 2024.

Also, the European Medicines Agency granted Orphan Drug Designation for SLS009 in AML and in PTCL in June 2024 and July 2024, respectively.

The chart below summarizes the current status of our clinical development pipeline:

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The WT1 protein is one of the most widely expressed cancer proteins in multiple malignancies.

A 2009 pilot project regarding the prioritization of cancer antigens (substances that evoke an immune response) conducted by the National Cancer Institute, or NCI, a division of the National Institutes of Health, or NIH, ranked the WT1 protein as a top priority for immunotherapy.

A previous pilot project regarding the prioritization of cancer antigens (substances that evoke an immune response) conducted by the National Cancer Institute, or NCI, a division of the National Institutes of Health, or NIH, ranked the WT1 protein as a top priority for immunotherapy.

WT1 is a protein that resides in the cell’s nucleus and participates in the process of cancer formation and progression.

As such, WT1 is classified as an “oncogene.” WT1 plays a key role in the development of the kidneys in fetal life, but then almost disappears from normal organs and tissues.

In approximately 20 cancer types, WT1

becomes detectable again in at least 50% of tumor pathology specimens in the cells of these cancers.

In approximately 20 cancer types, WT1 becomes detectable again in at least 50% of tumor pathology specimens in the cells of these cancers.

WT1 appears in large amounts ( i.e.

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These mutated peptides are recognized by the immune system as non-self entities and are therefore less likely to induce immune tolerance.

These mutated peptides are designed using artificial intelligence (AI) to elicit strong T-cell response against both mutated peptides and naturally occurring peptides in cancer cells.

These mutated peptides are designed using artificial intelligence, or AI, by researchers at MSK, to elicit strong T-cell response against both mutated peptides and naturally occurring peptides in cancer cells.

This concept is called the heteroclitic principle.

We believe that GPS has a mechanism of action that involves direct activation of the patient’s immune system specifically and solely against the WT1 protein.

We believe that GPS has a mechanism of action that involves direct activation of the patient’s immune system specifically against the WT1 protein.

Although the immune system is designed to identify foreign or abnormal proteins expressed on tumor cells, this process is often defective in cancer patients.

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(i) conversion of some of the activated CD8 cells to memory CD8 cells, and (ii) activation of CD4 cells and the eventual creation of CD4 terminal effector memory cells.

We further believe that cytotoxic CD8 T-cells activated by GPS have been shown to be able to kill up to 10 to 20 WT1-positive cancer cells.

Further, with respect to the activation of CD4 cells, we believe that CD4 cells are stimulated to produce WT1-specific helper T-cells, which are able, in turn, to activate cytotoxic T-cells and B-cells.

The B-cells “helped” by the helper T-cells produce antibodies to specific WT1 epitopes.

The anti-cancer effect is considered to be a result of a combination of all of the above actions, as well as possible additional, less clear, mechanisms involving other immune cell types ( e.g.

, natural killer cells) that are not as widely understood.

The following diagram illustrate GPS’ mechanism of action:

GPS cannot be administered to patients in a water-soluble form, and so it is given under the skin, or subcutaneously.

If administered on its own, GPS would rapidly degrade and would not have the opportunity to activate the immune system.

Therefore, GPS is mixed with Montanide™, a commercially available, non-specific immune adjuvant composed of a natural metabolizable oil and a very refined emulsifier, creating a water in oil emulsion.

The GPS and Montanide emulsion is administered by subcutaneous injection to optimally activate cellular and humoral immune responses in vaccinated patients.

GPS' proposed mechanism of action is based on the induction and stimulation of T-lymphocytes, both cytotoxic CD8 cells – which are attacking the tumor directly – and CD4 cells, which are very important for immunologic memory, maintenance, and helper function of the cellular immune response.

Two of the peptides within the GPS mixture are native, meaning that they contain the exact same amino acid (AA) sequences as the fragments of the wild type (unmutated) WT1 protein they originated from.

The remaining two peptides are by design modified by a single point AA mutation.

In that sense, the heteroclitic WT1 peptide carries a mutation and is presented to the native CD8+ cell through the host’s antigen-presenting cells - macrophages, dendritic cells or B cells.

The CD8+ cell is reprogrammed and activated, thus becoming a cytotoxic T-cell specifically against the target antigen, and now may recognize not only the mutated version of the WT1 peptide (against which the host was immunized, and which does not get expressed naturally), but also the corresponding native WT1 fragment.

The native fragment could get expressed and presented on the membrane of cancer cells in an MHC Class I context.

Similar events occur in CD4+ cells after cross-presentation of the WT1 heteroclitic fragment and eventual activation of the CD4+ cells into effector and memory cells.

The heteroclitic technology mitigates against the emergence of tolerance, as the mutated peptides are classified as ‘non-self’ antigens.

GPS is given under the skin, or subcutaneously, after mixing with Montanide™ an adjuvant, which creates a reservoir of GPS in a water in oil emulsion.

Additionally, prior to the administration of GPS, patients receive another immune adjuvant, granulocyte-macrophage colony-stimulating factor, or GM-CSF, to non-specifically stimulate and activate antigen-presenting cells, or APCs, in the vicinity of the subcutaneously injected GPS.

After subcutaneous injection, the WT1 peptides within GPS disperse locally underneath the injection site and at local lymph nodes and are ingested by APCs.

Digested peptide fragments are then presented on the surface of APCs to CD8 and CD4 T-cells while simultaneously associated on the cell membrane with major histocompatibility complexes, or MHC, human leukocyte antigen, or HLA, molecules.

As mentioned earlier, after subcutaneous injection, the WT1 peptides are ingested by APCs at the local injection sites.

Antigen presenting cells migrate to lymph nodes where the ingested peptide fragments are then presented on the surface of APCs to CD8 and CD4 T-cells though major histocompatibility complex class II, (MHCII), where they can bind to T-cell receptor, (TCR).

This process activates the CD4 and CD8 cells and sensitizes them to the key 25 epitopes of WT1, thus initiating the process of short- and long-term T-cell-mediated immunity against WT1.

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• Phase 1 clinical trial of 3D189 (GPS) in China (our licensee, 3D Medicines is the sponsor)

Enrollment completed;

final results pending

• Phase 1 clinical trial in patients with hematologic and thoracic malignancies with no demonstrable residual/recurrent disease after debulking therapy

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Building on the Phase 2 study in AML CR2 patients, which showed a median OS of 21.0 months, at a median follow-up of 30.8 months, in patients receiving GPS compared to 5.4 months in contemporaneously treated patients

with best standard therapy, in January 2020, we commenced a Phase 3 pivotal registration-enabling study for GPS in AML patients in CR2, including those in complete remission with incomplete platelet recovery.

with best standard therapy, we currently have an ongoing Phase 3 pivotal registration-enabling study for GPS in AML patients in CR2, including those in complete remission with incomplete platelet recovery.

This study, which we refer to as the REGAL study, is a 1:1 randomized, open-label study comparing GPS in the maintenance setting to investigators’ choice of best available treatment, or BAT, in adult AML patients (age >18 years) who have achieved their second or later hematologic (morphological) complete remission, with or without thrombocytopenia, after second-line antileukemic therapy and who are deemed ineligible for, or unable to undergo, allo-HSCT.

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Exploratory endpoints include antigen-specific T-cell immune response dynamics over time.

We expect this study will be used as the basis for a BLA submission, subject to a statistically significant and clinically meaningful data outcome and agreement with the FDA.

We expect this study will be used as the basis for a BLA submission, subject to a statistically significant and clinically meaningful trial outcome and agreement with the FDA.

The REGAL study was expected to enroll approximately 125 to 140 patients (not including potentially 20-25 patients from mainland China) at approximately 95 clinical sites in North America, Europe and Asia.

In the fourth quarter of 2023, we announced that we had exceeded our target enrollment of 105 patients (excluding the approximately 20-25 patients intended for enrollment in mainland China) and exceeded the number of patients needed for the pre-specified interim and final analyses (60/80).

In March 2024, we announced the completion of enrollment.

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The IDMC has met several times to perform these prespecified risk-benefit assessments of unblinded data from the study and have recommended in each instance that the trial continue without modifications.

Based upon our current assumptions with respect to completion of enrollment and the estimated survival times for both the treated and control groups, we believe, after discussions with our external statisticians and experts, that the planned interim analysis after 60 events per the protocol will occur in the first half of 2024 and that the final analysis after 80 events will occur by the end of 2024.

Because these analyses are event driven, they are difficult to predict with any certainty and may become available at different times than currently expected.

In January 2025, we announced that following this interim analysis, the IDMC recommended that the trial continue without modifications.

The interim futility, efficacy, and safety analysis is designed to assess whether the therapy is safe, demonstrates potential efficacy, and merits continuation.

The IDMC’s review of the interim data supports the continuation of the study according to its original protocol.

Based on this positive evaluation, the trial is to advance toward completion.

The next and final analysis will be conducted once 80 events (deaths) are reached, further determining the potential of GPS in addressing the needs of AML patients.

We anticipate that 80 events will be reached this year.

Because the final analysis is event driven, it is difficult to predict with any certainty and it may occur at a different time than currently expected.

We have agreed with our partner in China, 3D Medicines, for 3D Medicines to participate in the REGAL study through the inclusion of approximately 20-25 patients from mainland China.

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Expanded Access Program

At the request of several investigators, in 2022 we instituted an Expanded Access Program that allows qualified physicians to treat patients who do not meet currently required study entry criteria for the ongoing REGAL trial with GPS.

This access is provided on a case-by-case basis to patients in the United States and Germany.

At the request of several investigators, in 2022 we instituted an Expanded Access Program for GPS that allows qualified physicians to treat patients who do not meet currently required study entry criteria for the ongoing REGAL trial with GPS.

This access is provided on a case-by-case basis to patients in the United States.

Patients treated under the Expanded Access Program are not considered participants in the REGAL study.

Currently, our Expanded Access Program is available for GPS only.

GPS Combination Therapy with Checkpoint Inhibitors

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On November 10, 2022, we reported the following confirmatory topline data from 17 evaluable patients in the study.

• Median OS was 18.4 months compared to 13.8 months with pembrolizumab alone in a in a checkpoint inhibitor single agent study in a similar patient population treated with checkpoint inhibitor alone.

• Median OS was 18.4 months compared to 13.8 months with pembrolizumab alone in a checkpoint inhibitor single agent study in a similar patient population treated with checkpoint inhibitor alone.

• Median progression-free survival, or PFS, was 12 weeks compared to 8 weeks in a checkpoint inhibitor single agent study in a similar patient population treated with checkpoint inhibitor alone.

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GPS Combination Therapy with Nivolumab for MPM

A single-center, open-label, single-arm, non-randomized investigator-sponsored Phase 1 trial of concomitant administration of GPS in combination with Bristol-Myers Squibb’s anti-PD-1 therapy, nivolumab (Opdivo) was initiated in February 2020 at MSK in patients with MPM who have previously received treatment with pemetrexed-

based chemotherapy and have measurable disease on imaging, either due to residual disease after prior treatment or recurrent disease.

initiated in February 2020 at MSK in patients with MPM who have previously received treatment with pemetrexed-based chemotherapy and have measurable disease on imaging, either due to residual disease after prior treatment or recurrent disease.

We provided GPS and Bristol-Myers Squibb provided nivolumab for this study.

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• Of the 10 evaluable patients, eight were male and two were female, with a median age of 69 years.

Sixty percent of entered the study as Stage III or IV patients.

Sixty percent entered the study as Stage III or IV patients.

Initial tumor stages were I (one patient), II (three patients), III (two patients) and IV (four patients).

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Higher selectivity :

In preclinical studies, SLS009 has demonstrated higher selectivity for CDK9 than other members of the human kinome when compared to other non-oral CDK9 inhibitors currently in active clinical development in the United States for hematological cancers, including AZD-4573 being developed by AstraZeneca and enitociclib (VIP152) being developed by Vincerx Pharma.

In preclinical studies, SLS009 has demonstrated higher selectivity for CDK9 than other members of the human kinome when compared to other non-oral CDK9 inhibitors in clinical development in the United States for hematological cancers, including AZD-4573 being developed by AstraZeneca and enitociclib (VIP152) being developed by Vincerx Pharma.

The human kinome is a set of all 538 kinases, which are enzymes that play essential functions by catalyzing protein phosphorylation.

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In a mouse AML xenograft model, the lowest tumor growth and the highest AML cell killing was achieved by SLS009.

In this mouse model, there was significantly more toxicity, including weight loss, observed with enitocliclib (VIP152) treated mice.

In this mouse model, there was significantly more toxicity, including weight loss, observed with enitociclib (VIP152) treated mice.

SLS009 IC50 (72h)

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After QW administration, there was no obvious accumulation of SLS009.

Comparison of twice a week and once a week dosing regimens is shown below.

Comparison of pharmacokinetics results in twice a week and once a week dosing regimens at different dose levels is shown below.

Pharmacodynamic, or PD, Data:

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These data are important in that we believe they demonstrate that SLS009 is translating CDK9 inhibition into a meaningful suppression of cancer associated proteins.

MCL1 is a key antiapoptotic protein which is difficult to inhibit directly.

MCL1 is a key antiapoptotic protein.

It is postulated that CDK9 inhibitors can indirectly inhibit MCL1.

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Venetoclax, in combination with hypomethylating agents, is a key component of treatment for AML across all patient categories, especially older patients, who are the vast majority of AML patients.

We believe that SLS009 has potential as a treatment option for AML patients who are r/r to venetoclax.

We believe that SLS009 has potential as a treatment option for AML patients who are refractory to or relapsed after treatment with venetoclax.

We observed in the Phase 1 study that a r/r AML patient achieved a complete response and four additional r/r AML patients achieved greater than or equal to 50% decrease in bone marrow blasts which includes patients who had prior treatment with venetoclax.

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In addition to safety and tolerability of SLS009 in combination with aza/ven, the primary endpoints are complete response composite rate and duration of response.

Additional endpoints include event free survival, OS, and PK and PD assessments.

The trial includes several sites in the United States, will enroll a minimum of 20 patients and, based on initial results, may be expanded into a registrational trial.

Additional endpoints include event free survival, OS, and PK assessments.

The trial includes several sites in the United States, designed to enroll a minimum of 20 patients and based on initial results, may be expanded into a registrational trial.

In the fourth quarter of 2023, we completed enrollment in the 45 mg QW dose cohort in the Phase 2a study and reported positive initial topline data.

We also commenced enrollment of the 60 mg dose cohort with patients

randomized to one of two groups, 60 mg fixed dose QW or 30 mg fixed dose BIW.

We also commenced enrollment of the 60 mg dose cohort with patients randomized to one of two groups, 60 mg fixed dose QW or 30 mg fixed dose BIW.

Each group will enroll approximately five to 10 patients.

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Median age was 70 and 19/21 (90.5%) of patients were older than 60.

A total of 21 patients were enrolled in the study as of March 15, 2024:

10 in the 45 mg safety cohort and 11 in the 60 mg cohort (2 x 30 mg twice a week or 60 mg once a week).

• 10% response rate in the 45 mg QW safety cohort (dose level below the RP2D).

In May 2024, we announced additional preliminary data from the Phase 2a trial of SLS009 in r/r AML.

As of the April 19, 2024 data cutoff, a 57% overall response rate had been achieved in the 30 mg BIW cohort, far surpassing the targeted 20% rate.

4/4 (100%) r/r AML patients with ASXL1 truncating mutations at the selected dose level achieved an overall response (CR/CRi/MLFS) and were alive.

5/8 (63%) of r/r AML patients, across all dose levels, with ASXL1 truncating mutations treated with SLS009 achieved an overall response.

A review of the mutational status of the patient in the Phase 1 trial with SLS009 monotherapy, who achieved a CR lasting 8+ months, revealed that the patient also harbored an ASXL1 mutation.

The ASXL1 mutation was found in both hematological malignancies as well as solid tumors.

In June 2024, we announced the completion of enrollment and additional positive data in the Phase 2a study.

A total of 30 patients were enrolled in the study as of May 25, 2024:

10 in the 45 mg QW safety cohort, 9 in the 60 mg QW cohort, and 11 in the 30 mg BIW cohort.

Among 27 evaluable patients,

• 10% response rate in the 45 mg QW safety cohort

• 33% response rate in the 60 mg QW cohort

• 50% response rate in the 60 mg, 2 x 30 mg BIW cohort.

• 50% response rate in the 30 mg BIW cohort

• Observed strong anti-leukemic activity, defined as 50% or more bone marrow blast reduction in 67% of patients across all dose levels.

• Median survival rate has not been reached in any of the dose levels.

• The first patient enrolled in the study who achieved a complete response (CR) continues on the study and remains leukemia-free 9 months after enrollment.

• Median survival rate had not been reached at the time of analysis in any of the dose levels.

• The first patient enrolled in the study who achieved a complete response (CR) continued on the study and remained leukemia-free 9 months after enrollment.

• During the trial, we identified potential biomarkers currently undergoing testing as predictive markers in the most recent portion of the study.

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• Hematologic toxicities profile was consistent with aza/ven standalone treatment.

In December 2024, we announced additional data from the expansion cohorts in the Phase 2a clinical trial of SLS009 in r/r AML.

As of the December 4, 2024 data cutoff date, 14 patients were enrolled in the 30 mg BIW cohort and 14 patients were enrolled in cohorts 4 (ASXL1 mutated AML patients) and 5 (patients with myelodysplasia-related molecular abnormalities other than ASXL1), of which 9 were evaluable at the time of analysis.

At latest follow-up, the median overall survival, or mOS, had not been reached yet but had exceeded 7.7 months in the 30 mg BIW cohort.

This is particularly significant as the expected mOS for patients in this setting is typically 2.5 months.

In expansion cohorts 4 and 5, in patients with AML-myelodysplasia-related changes (AML-MR) with ASXL1 mutation (cohort 4) and mutations and cytogenic changes other than ASXL1 (cohort 5) the ORR was 56% in 9

evaluable for efficacy patients.

SLS009 was well-tolerated with no new safety signals observed to date as the regimen remains safe in additional patients enrolled to date.

Patients with AML that fail venetoclax-based therapies have limited treatment options and a poor prognosis with a median OS of approximately 2.5 months.

See Current AML Treatment Therapies for more information on the AML treatment landscape.

Additional data from the 60 mg dose cohort are expected in the second quarter of 2024.

Phase 1b/2 in PTCL

The first patient in a Phase 1b/2 trial evaluating SLS009 in r/r PTCL was dosed in the fourth quarter of 2023.

The open-label, single-arm trial will enroll up to 95 patients to evaluate safety and efficacy and, based on the results,

may serve as a registrational study.

This initial PTCL study is fully funded by GenFleet and is being conducted in China.

We expect to report initial topline data from the study in the second quarter of 2024.

The open-label, single-arm trial will enroll up to 95 patients to evaluate safety and efficacy.

This initial PTCL study was fully funded by GenFleet and was conducted in China.

Phase 1b/2 in Combination with Brukinsa ® in Diffuse Large B-Cell Lymphoma (DLBCL)

In March 2024, GenFleet announced that it entered into a collaboration and supply agreement with BeiGene Switzerland GmbH to initiate a combination study of SLS009 and Brukinsa (zanubrutinib), a BTK inhibitor, in r/r DLBCL and the first patient was dosed in the trial.

In March 2024, we announced that GenFleet initiated a combination study of SLS009 and Brukinsa (zanubrutinib), a BTK inhibitor, in r/r DLBCL and the first patient was dosed in the trial.

The open-label, single-arm multi-center trial will be conducted in two parts.

In the Phase 1b portion, 6-18 patients will be enrolled.

In the Phase 2 portion, approximately 45 patients will be enrolled.

This study is funded by GenFleet and is being conducted in China.

In February 2025, we announced positive data from the Phase 2a study evaluating SLS009 in combination with zanubrutinib.

The results showed an overall response rate of 67%, more than double the expected ORR of zanubrutinib alone.

Among responders, one achieved complete response, while three had partial response (PR) with target lesion shrinkages of 89%, 78%, and 56%, respectively.

As of the last follow-up, after the median of 4.6 (range:

1.4 - 7.4) months follow-up, mOS was not reached, and six out of nine patients were alive.

GenFleet will determine the next steps on development around lymphoma as our focus remains on AML and spliceosome–chromatin mutations, including ASXL1 mutations.

Efficacy and Safety

• Among six non-GCB DLBCL (ABC DLBCL) patients, four had an objective response and one patient achieved stable disease (SD) for the disease control rate (DCR) of 5/6 (83%)

• Overall response rate was 4/6 (67%), more than double the expected ORR with zanubrutinib alone

• One patient achieved complete response (CR), and three patients had PR with target lesion shrinkages of 89%, 78%, and 56%, respectively

• As of the last follow-up, after the median of 4.6 (range:

1.4 - 7.4) months follow-up, mOS was not reached

• Six patients were alive as of the last follow-up, including five non-GCB DLBCL and 1 GCB DLBCL.

Adverse events (AEs) grade ≥ 3 AEs were reported in 55.6% of patients, comparable to safety outcomes expected with Zanubrutinib alone.

• Genetic data of six out of nine enrolled patients showed that none of the patients carried MYD88 or CD79B mutations predictive of better response to BTK inhibitors.

The patient who achieved complete response (CR) by CT had MYC amplification, which is expected, but interestingly also harbored TP53 mutations, indicating that CDK9 inhibition with SLS009 could circumvent TP53 mutated cancers drug resistance.

Preclinical Studies

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No significant toxicity or safety concerns were observed in any of the treatment groups.

In November 2024, we announced data from preclinical studies identifying ASXL1 mutation as key predictor of SLS009 in response to solid cancers.

We performed experiments in patient derived cell lines (PDCs), exposing them to SLS009 at various concentrations and determining the inhibitory concentration (IC50) for each cell line.

All cell lines were analyzed for presence of ASXL1 mutations and other genetic markers.

High efficacy was prespecified as IC50 < 100 nM, significantly lower than the standard threshold definition for an effective compound (IC50 < 1,000 nM).

This threshold was chosen based on the observed long-lasting concentrations of SLS009 observed in patients, which were ~400 nM.

Negative controls consisted of untreated cell lines, while active negative control varying concentrations of revumenib (drug used in hematologic malignancies).

Positive controls involved cell lines treated with staurosporine at different concentrations (staurosporine is a standard control compound for kinase inhibitors due to its high broad-spectrum potency in inhibiting most protein kinases at sub-micromolar concentrations).

The results were as follows:

• In CRC MSI-H, ASXL1 mutations were observed in 7/12 (58%) of PDCs, aligning with predicted frequency of ~55%

• In NSCLC, ASXL1 mutations occurred in 2/6 (33%) studied cell lines, higher than predicted 2.6%

• Overall, in 18 studied solid cancer cell lines, ASXL1 mutations were recorded in nine cell lines and no ASXL1 mutations were recorded in 9 cell lines which were designated as control

• In ASXL1 mutated cell lines, high SLS009 efficacy (IC50 <100 nM) was observed in 6/9 (67%) solid cancer cell lines and in non-ASXL1 mutated cancer high SLS009 efficacy was observed in 0/9 (0%) of studied solid cancer cell lines

◦ In CRC MSI-H, high efficacy (IC50 <100 nM) was observed in 4/7 (57%) of ASXL1 mutated cell lines and in 0/5 (0%) of non-ASXL1 mutated cell lines

◦ In NSCLC, high efficacy (IC50 <100 nM) was observed in 2/2 (100%) of ASXL1 mutated cell lines and in 0/4 (0%) of non-ASXL1 mutated cell lines

• No activity was observed in any of the studied cell lines with revumenib (negative control) at any concentration

• Staurosporine activity was confirmed, but interestingly and importantly, SLS009 outperformed positive control staurosporine in 5/9 cell lines

PIVOT Program

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In the second phase, tolerability of the dose and route of administration selected from the PK phase will be determined.

In the last phase, monotherapy in vivo efficacy testing for SLS009 will be performed by PIVOT investigators.

In the last phase, monotherapy in vivo efficacy testing for SLS009 will be performed by PIVOT

investigators.

Studies will be supported through cooperative agreement grants from the NCI to the seven PIVOT research programs performing the testing and a centralized coordinating center.

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Each PIVOT principal investigator has expertise in preclinical testing of childhood cancer in vivo models.

These models utilize patient derived xenografts, many of which are refractory to current standard of care treatments, from

high-risk childhood cancers and have undergone comprehensive genomic characterization to demonstrate close resemblance to genetic alterations seen in the respective human cancers.

These models utilize patient derived xenografts, many of which are refractory to current standard of care treatments, from high-risk childhood cancers and have undergone comprehensive genomic characterization to demonstrate close resemblance to genetic alterations seen in the respective human cancers.

Research strategies are based on a substantial body of data showing that preclinical testing in the appropriate pediatric cancer models, combined with expertise on relative drug exposures tolerated in mice and humans, provides powerful insights into likely clinical utility of investigational agents.

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• Children’s Hospital of Philadelphia for neuroblastoma

The first phase of the program, pharmacokinetics, has been successfully completed and dosing regimens have been developed.

The second phase of the program, tolerability, is currently in progress and is projected to be completed at all sites in the first half of 2024.

The final phase of the program, efficacy, is in progress at certain sites and will have commenced at all sites by the second quarter of 2024.

We expect to report relevant data from the program in the second half of 2024.

The first and second phases of the program, pharmacokinetics and tolerability, respectively, have been successfully completed and dosing regimens have been developed.

The final phase of the program, efficacy, is in progress and we expect to report relevant data from the program in the first half of 2025.

Strategic Collaborations and License Agreements

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Under the terms of the current amended and restated MSK license agreement, we agreed to pay minimum royalty payments in the amount of $0.1 million each year commencing in 2015 and research funding costs of $0.2 million in each year and for three years commencing in January 2016.

We also agreed to pay MSK a mid-six digit amount over a one year period in exchange for MSK’s agreement to further amend and restate the MSK license agreement in October 2017.

We also agreed to pay MSK a mid-six digit amount over a one year period in exchange for MSK’s agreement to further amend and restate the MSK license agreement

in October 2017.

In addition, to the extent certain development and commercial milestones are achieved, we also agreed to pay MSK up to $17.4 million in aggregate milestone payments for each licensed product, and for each additional patent licensed product, up to $2.8 million in additional milestone payments.

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We raised this amount from the proceeds received from the sale of our Series A Convertible Preferred stock in March 2018 and our underwritten public offering of shares of common stock, pre-funded warrants to purchase shares of common-stock, and warrants to purchase shares of common stock in July 2018.

Under the terms of the agreement, we achieved a clinical

development milestone at the end of the fourth quarter of 2018, triggering a $0.5 million payment in the first quarter of 2019.

Under the terms of the agreement, we achieved a clinical development milestone at the end of the fourth quarter of 2018, triggering a $0.5 million payment in the first quarter of 2019.

Unless terminated earlier in accordance with its terms, the MSK license agreement as amended and restated, will continue on a country-by-country and licensed product-by-licensed product basis, until the later, of:

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3D Medicines also agreed to pay tiered royalties based upon a percentage of annual net sales of GPS Licensed Products in the 3DMed Territory ranging from the high single digits to the low double digits.

The royalties are payable on a GPS Licensed Product-by- GPS Licensed Product and region-by-region basis commencing on the first commercial sale of a GPS Licensed Product in a region and continuing until the latest of (i) the date that is 15 years from the receipt of marketing authorization for such GPS Licensed Product in such region and (ii) the date that is 10 years from the expiration of the last valid claim of a licensed patent covering or claiming such GPS Licensed Product in such region.

from the receipt of marketing authorization for such GPS Licensed Product in such region and (ii) the date that is 10 years from the expiration of the last valid claim of a licensed patent covering or claiming such GPS Licensed Product in such region.

The royalty rate is subject to reduction under certain circumstances, including when generic competition for a GPS Licensed Product exists in a particular region.

3D Medicines is responsible for all costs related to developing, obtaining regulatory approval of and commercializing the GPS Licensed Products in the 3DMed Territory.

3D Medicines is required to use commercially reasonable best efforts to develop and obtain regulatory approval for, and upon receipt of regulatory approval, commercialize the

GPS Licensed Products in the 3DMed Territory.

3D Medicines is required to use commercially reasonable best efforts to develop and obtain regulatory approval for, and upon receipt of regulatory approval, commercialize the GPS Licensed Products in the 3DMed Territory.

A joint development committee has been established between 3D Medicines and us to coordinate and review the development, manufacturing and commercialization plans with respect to the GPS Licensed Products in the 3DMed Territory.

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Our sole CMO for GPS drug substance peptides is Polypeptide Group.

Our sole CMO for GPS drug product is Lyophilization Services of New England, Inc., or LSNE.

Our sole CMO for GPS drug product is Lyophilization Services of New England, Inc.

(PCI Pharma Services).

Our CMOs comply with cGMP requirements and manufacture product batches used in ongoing clinical trials.

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Our commercial success depends in part on our ability to avoid infringing the proprietary rights of third parties, our ability to obtain and maintain proprietary protection for our product candidates, technologies and know-how, and our ability to prevent others from infringing our proprietary rights.

We seek to protect our proprietary position by, among other methods, evaluating relevant patents, establishing defensive positions, monitoring European Union, or EU, oppositions and pending intellectual property rights, preparing litigation strategies in view of the U.S.

We seek to protect our proprietary position by, among other methods, evaluating relevant patents, establishing defensive positions, monitoring post grant proceedings in the US and foreign jurisdictions and pending intellectual property rights, preparing litigation strategies in view of the U.S.

legislative framework, filing U.S.

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Patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, and only one patent applicable to an approved drug may be extended.

Similar provisions are available in the EU and certain other foreign jurisdictions to extend the term of a patent that covers an approved drug.

Similar provisions are available in Europe and certain other foreign jurisdictions to extend the term of a patent that covers an approved drug.

In the future, if and when our product candidates receive approval by the FDA or foreign regulatory authorities, we expect to apply for patent term extensions on issued patents covering those products, depending upon the length of the clinical trials for each drug and other factors.

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• Patent application co-owned by us and MSK:

◦ Patent applications covering a heptavalent (7-peptide) immunotherapy composition and methods of use for treating, reducing the incidence of, or inducing an immune response against a WT1-expressing cancer pending in the United States, Australia, Canada, China, Europe, Hong Kong, India, Israel, Japan, South Korea, Mexico and Russia, which, if granted, are expected to expire in 2040.

◦ Patent applications covering a heptavalent (7-peptide) immunotherapy composition and methods of use for treating, reducing the incidence of, or inducing an immune response against a WT1-expressing cancer pending in the United States, Australia, Canada, China, European Patent Office, or EPO, Hong Kong, India, Israel, Japan, South Korea, Mexico and Russia, which, if granted, are expected to expire in 2040.

• Patents and patent applications in-licensed from MSK:

◦ Composition-of-matter patents covering certain WT1-targeting peptides and methods of use in the United States, which are expected to expire in 2034;

and a composition-of-matter patent covering

additional WT1-targeting peptides and methods of use in the United States, which is expected to expire in 2035;

◦ Composition-of-matter patents covering certain WT1-targeting peptides and methods of use in Australia, China, Hong Kong, several countries of the EU and Japan, which are expected to expire in 2034;

◦ Patent applications covering certain WT1-targeting peptides and methods of use pending in the United States, Australia, EU, Canada, China, Hong Kong, and Japan, which, if granted, are expected to expire in 2034;

◦ Patents covering methods for treating, reducing the incidence of, or inducing an immune response against a WT1-expressing cancer, using the peptides of GPS in combination with anti-PD-1 antibody checkpoint inhibitors in the United States, Australia, China, Hong Kong, several countries in the EU and Japan, which are expected to expire in 2037 (United States) and 2036 (Australia, China, Hong Kong, EU and Japan);

◦ Patent applications covering methods for treating, reducing the incidence of, or inducing an immune response against a WT1-expressing cancer, using the peptides of GPS in combination with immune checkpoint inhibitors pending in the United States, Australia, Canada, China, Hong Kong, EU, South Korea, and Japan, which, if granted, are expected to expire in 2036;

◦ Composition-of-matter patents covering the WT1-A1 peptide of GPS in the United States, Canada, Australia, and several countries of the EU, which are expected to expire in the United States in 2026 and elsewhere in 2024;

and a composition-of-matter patent covering additional WT1-targeting peptides and methods of use in the United States, which is expected to expire in 2035;

◦ Composition-of-matter patents covering certain WT1-targeting peptides and methods of use in Australia, China, Hong Kong, several countries in Europe, and Japan, which are expected to expire in 2034;

◦ Patent applications covering certain WT1-targeting peptides and methods of use pending in the United States, Australia, the EPO, Canada, China, and Hong Kong, which, if granted, are expected to expire in 2034;

◦ Patents covering methods for treating, reducing the incidence of, or inducing an immune response against a WT1-expressing cancer, using the peptides of GPS in combination with anti-PD-1 antibody checkpoint inhibitors in the United States, Australia, China, Hong Kong, several countries in Europe and Japan, which are expected to expire in 2037 (United States) and 2036 (Australia, China, Hong Kong, Europe and Japan);

◦ Patent applications covering methods for treating, reducing the incidence of, or inducing an immune response against a WT1-expressing cancer, using the peptides of GPS in combination with immune checkpoint inhibitors pending in the United States, Australia, Canada, China, Hong Kong, the EPO, South Korea, and Japan, which, if granted, are expected to expire in 2036;

◦ Composition-of-matter patents covering the WT1-A1 peptide of GPS in the United States, which are expected to expire in 2026;

◦ Composition-of-matter patent covering the WT1-427 long and WT1-331 long peptides of GPS issued in the United States, which is expected to expire in 2031, and patents covering the methods of use in the United States, which are expected to expire in 2026;

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and a patent application covering peptide conjugates of the WT1-427 long peptide or WT1-331 long peptide pending in the United States, which, if granted, is expected to expire in 2026;

◦ Composition-of-matter patents covering the WT1-427 long peptide of GPS and WT1-331 long peptide of GPS, and methods of use, in Australia and several countries of the EU, which are expected to expire in 2026;

composition-of-matter patent covering the WT1-427 long peptide of GPS and method of use in Canada, which is expected to expire in 2026;

◦ Composition-of-matter patent application covering the WT1-331 long peptide of GPS and the WT1-427 long peptide of GPS and method of use pending in Canada, which, if granted, is expected to expire in 2026;

◦ Composition-of-matter patents covering the WT1-427 long peptide of GPS and WT1-331 long peptide of GPS, and methods of use, in Australia, Canada, and several countries in Europe, which are expected to expire in 2026;

◦ Composition-of-matter patent covering a WT1-specific peptide in the United States, which is expected to expire in 2026;

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and patent application covering the WT1-122A1 long peptide of GPS and methods of use pending in the United States, which, if granted, is expected to expire in 2027;

◦ Composition-of-matter patent covering the WT1-122A1 long peptide of GPS and methods of use in several countries of the EU, which is expected to expire in 2027, and patent applications covering the WT1-122A1 long peptide of GPS and methods of use pending in the EU, Hong Kong and Canada, which, if granted, are expected to expire in 2027.

◦ Composition-of-matter patent covering the WT1-122A1 long peptide of GPS and methods of use in several countries in Europe, which is expected to expire in 2027, and patent applications covering the WT1-122A1 long peptide of GPS and methods of use pending in the EPO, Hong Kong and Canada, which, if granted, are expected to expire in 2027.

Patents and patent applications covering SLS009:

• Patents and patent applications in-licensed from GenFleet:

◦ Composition-of-matter patents covering SLS009 and use thereof in the treatment or amelioration of cancer in the United States, Australia, Canada, Japan, Russia, South Korea, the United Kingdom, and several countries of the EU, which are expected to expire in 2038;

◦ Composition-of-matter patents covering SLS009 and use thereof in the treatment or amelioration of cancer in the United States, Australia, Brazil, Canada, Japan, Russia, South Korea, and several countries in Europe, which are expected to expire in 2038;

and a patent application covering SLS009 and use thereof in the treatment or amelioration of cancer pending in Brazil, which, if granted, is expected to expire in 2038;

◦ Patents covering maleate and fumarate crystal salts and polymorphs of SLS009, syntheses thereof, and use thereof in prevention or treatment of CDK9-related diseases, including cancer, in Australia and Japan, which are expected to expire in 2040;

patent applications covering maleate and fumarate salt forms and polymorphs of SLS009, syntheses thereof, and use thereof in prevention or treatment of CDK9-related diseases, including cancer, pending in the United States, Brazil, Canada, South Korea, the United Kingdom and the EU (via the European Patent Office), and several former Soviet bloc countries, including Russia (via the Eurasian Patent Office), which, if granted, are expected to expire in 2040.

patent applications covering maleate and fumarate salt forms and polymorphs of SLS009, syntheses thereof, and use thereof in prevention or treatment of CDK9-related diseases, including cancer, pending in the United States, Brazil, Canada, South Korea, the EPO, and the Eurasian Patent Office, which, if granted, are expected to expire in 2040.

Oncology in general, and specifically, cancer immunotherapy, is a significant growth area for the biopharmaceutical industry, attracting large pharmaceutical companies as well as small niche players.

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Principal competitors for AML broadly include companies with currently marketed products, such as AbbVie/Genentech (Venclexta), Pfizer (Mylotarg), Daiichi-Sankyo (Vanflyta), Rigel Pharmaceuticals (Rezlidhia) and Bristol Myers Squibb (Vidaza), among others.

There are also companies developing therapies to treat AML in the r/r setting, which are in earlier stages of clinical development, including emavusertib, which is in a Phase 1/2 trial in AML and being developed by Curis, and later-stage clinical development candidates which may enter the market before our potential products, such as GlycoMimetics (uproleselan), Delta-Fly Pharma (DFP-10917), and AROG Pharmaceuticals (crenolanib).

Actinium Pharmaceuticals, which announced in late 2022 / early 2023 positive results in its Phase 3 trial of Iomab-B in adults aged 55 and above with r/r AML, may be a key competitor.

There are also companies developing therapies to treat AML in the r/r setting, which are in earlier stages of clinical development, including emavusertib, which is in a Phase 1/2 trial in AML and being developed by Curis, and later-stage clinical development candidates which may enter the market before our potential products, such as Delta-Fly Pharma (DFP-10917) and AROG Pharmaceuticals (crenolanib).

Actinium Pharmaceuticals, which previously announced in late 2022 / early 2023 positive results in its Phase 3 trial of Iomab-B in adults aged 55 and above with r/r AML, has since announced that the FDA determined that its Phase 3 trial is not adequate to support a BLA filing for Iomab-B.

With respect to WT1-targeting therapies, we do not believe GPS has direct competition in AML in the maintenance setting after CR2 at this time.

While there are companies engaged in the clinical development of WT-1 targeting therapies including Astellas (ASP7517) and Cue Biopharma (CUE-102), they are not currently focused on AML.

With respect to SLS009, we anticipate competition from companies who are currently engaged in the clinical development of selective CKD9-targeting therapies.

MEI Pharma is in Phase 1 clinical development for voruciclib alone and in combination with venetoclax for adults with r/r AML.

Vincerx Pharma may also be a potential competitor in our other indication, PTCL, with enitociclib, its CDK9 inhibitor, as a monotherapy and in combination with venetoclax.

There are other companies which are in early development stages for their CDK9 inhibitors and targeting other hematologic malignancies or solid tumors, including Kronos Bio (KB-0742), Sumitomo Dainippon Pharma (TP-1287), Adastra Pharmaceuticals (zotiraciclib) and Prelude Therapeutics (PRT2527).

With regard to both GPS and SLS009, many of our competitors, either alone or with their strategic partners, have substantially greater resources and expertise in research and development, manufacturing, preclinical testing, obtaining regulatory approvals, and marketing approved products than we have.

While there are companies engaged in the clinical development of WT-1 targeting therapies, they are not currently focused on AML or have since discontinued or paused their development of WT-1 targeting therapies.

With respect to SLS009, we anticipate competition from companies who have been engaged in the clinical development of selective CKD9-targeting therapies.

Vincerx Pharma may be a potential competitor in our other indication, PTCL, with enitociclib, its CDK9 inhibitor, as a monotherapy and in combination with venetoclax.

are other companies which are in early development stages for their CDK9 inhibitors and targeting other hematologic malignancies or solid tumors, including Sumitomo Dainippon Pharma (TP-1287), Cothera Bioscience (zotiraciclib), and Prelude Therapeutics (PRT2527).

With regard to both GPS and SLS009, many of our competitors, either alone or with their strategic partners, may have substantially greater resources and expertise in research and development, manufacturing, preclinical testing, obtaining regulatory approvals, and marketing approved products than we have.

Mergers and acquisitions in the biotechnology, pharmaceutical and diagnostics industries may result in even more resources being concentrated among a smaller number of our competitors.

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Our employees have various backgrounds, experience, and perspectives.

For example, as of March 1, 2024, of our 16 employees, 56% self-identify as women, 25% self-identify as racial or ethnic minorities and 62% have advanced degrees.

In addition, two of our six Board of Director members self-identify as women, including the Chair.

For example, as of March 1, 2025, of our 15 employees, 53% are women, 33% are racial or ethnic minorities, and 53% have advanced degrees.

In addition, two of our six Board of Director members are women.

We believe we have built and continue to build a strong culture of cooperation, respect and acceptance.

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The FDA and other regulatory authorities at federal, state, and local levels, as well as in foreign countries, extensively regulate, among other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring, and post-approval reporting of drugs and biologics such as those we are developing.

Along with our third-party contractors, we will be required to navigate the various preclinical, clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies or seek approval or licensure of its current or future product candidates.

wish to conduct studies or seek approval or licensure of its current or future product candidates.

The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local, and foreign statutes and regulations require the expenditure of substantial time and financial resources.

A company can make

only those claims relating to safety and efficacy, purity and potency that are approved by the FDA and in accordance with the provisions of the approved label.

A company can make only those claims relating to safety and efficacy, purity and potency that are approved by the FDA and in accordance with the provisions of the approved label.

A biologic candidate is licensed by the FDA through approval of a biologics license application, or BLA.

Assuming we receive positive data from our REGAL clinical trial of GPS for monotherapy in patients with AML, we will submit a BLA to the FDA.

Assuming we receive positive data from our REGAL clinical trial of GPS in patients with AML, we will submit a BLA to the FDA.

A drug candidate must be approved by the FDA through a new drug application, or NDA.

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Before testing any drug or biological product candidate, including our product candidates, in humans, the product candidate must undergo rigorous preclinical testing.

Nonclinical studies during the preclinical development stage include laboratory evaluation of product chemistry and formulation and typically include in vitro and animal studies to assess the potential for adverse events and in some cases to establish a rationale for therapeutic use.

Consolidated Appropriations Act for 2023, signed into law on December 29, 2022, (P.L.

Nonclinical studies during the preclinical development stage

include laboratory evaluation of product chemistry and formulation and typically include in vitro and animal studies to assess the potential for adverse events and in some cases to establish a rationale for therapeutic use.

The Consolidated Appropriations Act for 2023, signed into law on December 29, 2022, (P.L.

117-328) amended the Food, Drug, and Cosmetic Act, or the FDCA, and the Public Health Service Act to specify that nonclinical testing for drugs and biologics may, but is not required to, include in vivo animal testing.

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Human clinical trials in support of an NDA or BLA

Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with GCP, which include the requirement that all research subjects provide their informed consent for their participation in any clinical trial.

Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with GCP and other trial-related regulations, which include, among other things, the requirement that all research subjects provide their informed consent for their participation in any clinical trial.

Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated.

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Regulatory authorities, the IRB or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the subjects are being exposed to an unacceptable health risk or that the trial is unlikely to meet its stated objectives.

Some studies also include oversight by an independent data safety monitoring board, or DSMB, organized by the clinical trial sponsor, which at designated check points based on access to certain data from the clinical trial may recommend the sponsor to halt the trial if the DSMB determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.

Some studies also include oversight by an independent data safety monitoring board, or DSMB, organized by the clinical trial sponsor, which at designated check points based on access to certain data from the clinical trial may recommend that the sponsor halt the trial if the DSMB determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.

Information about certain clinical trials, including details of the protocol and eventually study results, also must be submitted within specific timeframes to the NIH for public dissemination on the ClinicalTrials.gov data registry.

Information related to the product, patient population, phase of investigation, study sites and investigators and other aspects of the clinical trial is made public as part of the registration of the clinical trial.

Information related to the product, patient population, phase of investigation, study site locations and other aspects of the clinical trial is made public as part of the registration of the clinical trial.

Sponsors are also obligated to disclose the results of their clinical trials after completion.

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• Phase 1 -The investigational product is initially introduced into healthy human subjects or patients with the target disease or condition.

These studies are designed to test the safety, dosage tolerance, absorption,

metabolism, distribution, and excretion of the investigational product in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness.

These studies are designed to test the safety, dosage tolerance, absorption, metabolism, distribution, and excretion of the investigational product in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness.

• Phase 2 -The investigational product is administered to a limited patient population with a specified disease or condition to evaluate the preliminary efficacy, optimal dosages and dosing schedule and to identify possible adverse side effects and safety risks.

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Our Phase 3 REGAL trial of GPS for AML patients who have achieved CR2 was initiated before this requirement became effective, but for any future Phase 3 trials we plan to conduct, we must submit a diversity action plan to the FDA by the time we submit plans for such Phase 3, or pivotal study, protocol to the agency for review as part of an IND, unless we are able to obtain a waiver for some or all of the requirements for a diversity action plan.

It is unknown at this time how the diversity action plan may affect Phase 3 trial planning and timing or what specific information FDA will expect in such plans, but if FDA objects to a sponsor’s diversity action plan and requires the sponsor to amend the plan or take other actions, it may delay trial initiation.

It is unknown at this time how the diversity action plan may affect Phase 3 trial planning and timing, but if FDA objects to a sponsor’s diversity action plan and requires the sponsor to amend the plan or take other actions, it may delay trial initiation.

Phase 1, Phase 2 and Phase 3 testing may not be completed successfully within a specified period, if at all, and there can be no assurance that the data collected will support FDA approval or licensure of the product.

Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA and more frequently if unexpected serious adverse events, or SAEs, occur.

Progress reports detailing the progress of and safety data from the clinical trials must be submitted at least annually to the FDA and more frequently if unexpected serious adverse events, or SAEs, occur.

The FDA or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk.

Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the clinical protocol, GCP, or other IRB requirements or if the drug has been associated with unexpected serious harm to patients.

Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the clinical protocol, GCP regulations, or other IRB requirements or if the drug has been associated with unexpected serious harm to patients.

Concurrent with clinical trials, companies may complete additional nonclinical studies and develop additional information about the biological characteristics of the product candidate and must finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.

The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things, must incorporate methods for testing the identity, strength, quality and purity of the final product, or for biologics, the safety, purity and potency.

Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

Additionally, appropriate packaging must be selected and tested, and

stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

Marketing Application Submission and Review by the FDA

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The resubmitted application is also subject to review before the FDA accepts it for filing.

Once an NDA or BLA is accepted for filing, the FDA’s goal is to review the application within 10 months after it accepts the application for filing, or, if the application meets the criteria for “priority review”, six months after the FDA accepts the application for filing.

Once an NDA or BLA is accepted for filing, the FDA’s goal is to review the application within 10 months after it accepts the application for filing, or, if the application meets the criteria for “priority review”, within six months after the FDA accepts the application for filing.

The review process is often significantly extended by FDA requests for additional information or clarification after the NDA or BLA has been accepted for filing.

The review process may be extended by the FDA for three additional months to consider new information or in the case of a clarification provided by the applicant to address an outstanding deficiency identified by the FDA following the original submission.

During the review process, the FDA reviews the NDA or BLA to determine, among other things, whether the product is safe, effective, pure and potent and the facility in which it is manufactured, processed, packed, or held meets standards designed to assure the product’s continued safety, purity and potency.

During the review process, the FDA reviews the NDA or BLA to determine, among other things, whether the product is safe, effective, pure and potent and whether the facility in which it is manufactured, processed, packed, or held meets standards designed to assure the product’s continued safety, quality, purity and potency.

The FDA may refer any NDA or BLA, including applications for novel drug or biologic candidates which present difficult questions of safety or efficacy, to an advisory committee to provide clinical insight on application review questions.

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Before approving an NDA or BLA, the FDA will typically inspect the facility or facilities where the product is manufactured.

The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.

Additionally, before approving an NDA or BLA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP and integrity of the clinical data.

within required specifications.

Additionally, before approving an NDA or BLA, the FDA will typically inspect one or more clinical trial sites to assure compliance with GCP and integrity of the trial data.

If the FDA determines that the application, manufacturing process or manufacturing facilities are not acceptable, it will outline the deficiencies as part of the review process and often will request additional testing or information.

Notwithstanding the submission of

any requested additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.

Notwithstanding the submission of any requested additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.

Under the Pediatric Research Equity Act, or PREA, amendments to the FDCA, an NDA or BLA or supplement to such applications must contain data that are adequate to assess the safety and efficacy of the product candidate for the claimed indications in all relevant pediatric populations and to support dosing and administration for each pediatric population for which the product is safe and effective.

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

The PREA requires a sponsor that is planning to submit a marketing application for a product that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration to submit an initial Pediatric Study Plan, or PSP, within sixty days of an end of-Phase 2 meeting or, if there is no such meeting, as early as practicable before the initiation of the Phase 3 or Phase 2/3 clinical trial.

The PREA requires a sponsor that is planning to submit a marketing application for a product that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration to submit an initial Pediatric Study Plan, or PSP, within 60 days of an end of-Phase 2 meeting or, if there is no such meeting, as early as practicable before the initiation of the Phase 3 or Phase 2/3 clinical trial.

The initial PSP must include an outline of the pediatric study or studies that the sponsor plans to conduct, including trial objectives and design, age groups, relevant endpoints and statistical approach, or a justification for not including such detailed information, and any request for a deferral of pediatric assessments or a full or partial waiver of the requirement to provide data from pediatric studies along with supporting information.

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Once approved, the FDA may withdraw the product approval if compliance with pre- and post-marketing regulatory standards is not maintained or if problems occur after the product reaches the marketplace.

The FDA may require one or more Phase 4 post-market studies and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization and may limit further marketing of the product based on the results of these post-marketing studies.

The FDA may require one or more Phase 4 post-market studies and surveillance to further assess and monitor the product’s safety and

effectiveness after commercialization and may limit further marketing of the product based on the results of these post-marketing studies.

After approval, some types of changes to the approved product, such as adding new indications, manufacturing changes and additional labeling claims, are subject to further testing requirements and FDA review and approval.

In addition, new government requirements, including those resulting from new legislation,

may be established, or the FDA’s policies may change, which could delay or prevent regulatory approval of our products under development.

In addition, new government requirements, including those resulting from new legislation, may be established, or the FDA’s policies may change, which could delay or prevent regulatory approval of our products under development.

Fast Track, Priority Review, and Breakthrough Therapy Designations

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In addition, products studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may receive accelerated approval from the FDA and may be approved on the basis of adequate and well-controlled clinical trials establishing that the drug product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit.

The FDA may also grant accelerated approval for such a drug or biologic when it has an effect on an intermediate clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality, or IMM, and that is reasonably likely to predict an effect on IMM or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

As a condition of approval, the FDA may require that a sponsor of a drug or biologic receiving accelerated approval perform post-marketing clinical trials to verify and

describe the predicted effect on IMM or other clinical endpoint, and the product may be subject to expedited withdrawal procedures.

The FDA may also grant accelerated approval for such a drug or biologic when it has an effect on an intermediate clinical endpoint that can

be measured earlier than an effect on irreversible morbidity or mortality, or IMM, and that is reasonably likely to predict an effect on IMM or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

As a condition of approval, the FDA may require that a sponsor of a drug or biologic receiving accelerated approval perform post-marketing clinical trials to verify and describe the predicted effect on IMM or other clinical endpoint, and the product may be subject to expedited withdrawal procedures.

Drugs and biologics granted accelerated approval must meet the same statutory standards for safety and effectiveness as those granted traditional approval.

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As part of the Consolidated

Appropriations Act for 2023, Congress provided FDA additional statutory authority to mitigate potential risks to

Appropriations Act for 2023, Congress provided the FDA additional statutory authority to mitigate potential risks to

patients from continued marketing of ineffective drugs or biologics previously granted accelerated approval.

the act’s amendments to the FDCA, FDA may require the sponsor of a product granted accelerated approval to have a confirmatory trial underway prior to approval.

The sponsor must also submit progress reports on a confirmatory trial every six months until the trial is complete, and such reports are published on FDA’s website.

The amendments also give FDA the option of using expedited procedures to withdraw product approval if the sponsor’s confirmatory trial fails to verify the claimed clinical benefits of the product.

the act’s amendments to the FDCA, the FDA may require the sponsor of a product being considered for accelerated approval to have a confirmatory trial underway prior to approval.

The sponsor must also submit progress reports on a confirmatory trial every six months until the trial is complete, and such reports are published on the FDA’s website.

The amendments also give the FDA the option of using expedited procedures to withdraw product approval if the sponsor’s confirmatory trial fails to verify the claimed clinical benefits of the product.

All promotional materials for product candidates being considered and approved under the accelerated approval program are subject to prior review by the FDA.

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After the FDA grants Orphan Drug Product Designation, the generic identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA.

If a drug or biologic product that has Orphan Drug Product Designation subsequently receives the first FDA approval for a particular active ingredient for the disease for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications, including a full NDA or BLA, to market the same drug or biologic for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan product exclusivity or if FDA finds that the holder of the orphan product exclusivity has not shown that it can assure the availability of sufficient

quantities of the orphan product to meet the needs of patients with the disease or condition for which the drug or biologic was designated.

orphan product exclusivity, which means that the FDA may not approve any other applications, including a full NDA or BLA, to market the same drug or biologic for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan product exclusivity or if FDA finds that the holder of the orphan product exclusivity has not shown that it can assure the availability of sufficient quantities of the orphan product to meet the needs of patients with the disease or condition for which the drug or biologic was designated.

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

Among the other benefits of Orphan Drug Product Designation are tax credits for certain research and a waiver of the BLA application user fee.

Among the other benefits of Orphan Drug Product Designation are tax credits for certain research and a waiver of NDA or the BLA application user fee.

A drug or biologic with Orphan Drug Product Designation may not receive orphan product exclusivity if it is approved for a use that is broader than the indication for which it received Orphan Drug Product Designation.

In addition, orphan product exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.

Recent court cases have challenged FDA’s approach to determining the scope of orphan drug exclusivity;

Court cases have challenged FDA’s approach to determining the scope of orphan drug exclusivity;

however, at this time the agency continues to apply its long-standing interpretation of the governing regulations and has stated that it does not plan to change any orphan drug implementing regulations.

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In 1984, with passage of the Drug Price Competition and Patent Term Restoration Act, or Hatch-Waxman Act, which established an abbreviated regulatory scheme authorizing the FDA to approve generic drugs based on an innovator or “reference” product, Congress also enacted Section 505(b)(2) of the FDCA, which provides a hybrid pathway combining features of a traditional NDA and a generic drug application.

To obtain approval of a generic

drug, an applicant must submit an abbreviated new drug application, or ANDA, to the agency.

To obtain approval of a generic drug, an applicant must submit an abbreviated new drug application, or ANDA, to the agency.

ANDAs are “abbreviated” because they do not include preclinical and clinical data to demonstrate safety and effectiveness.

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Upon approval of an NDA or a supplement thereto, NDA sponsors are required to list with the FDA each patent with claims that cover the applicant’s product or an approved method of using the product.

Each of the patents listed by

the NDA sponsor is published in the Orange Book.

Each of the patents listed by the NDA sponsor is published in the Orange Book.

When an ANDA applicant files its application with the FDA, the applicant is required to certify to the FDA concerning any patents listed for the reference product in the Orange Book, except for patents covering methods of use for which the ANDA applicant is not seeking approval.

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Under the BPCIA, a reference biological product is granted 12 years of data exclusivity from the date of first licensure of the product, which means that the FDA is barred from approving biosimilar applications for 12 years after the reference biological product receives initial marketing approval.

The first approved interchangeable

biological product will be granted an exclusivity period of up to one year after it is first commercially marketed, and as part of the Consolidated Appropriations Act for 2023, Congress amended the PHSA in order to permit multiple interchangeable products approved on the same day to receive and benefit from this one-year exclusivity period.

The first approved interchangeable biological product will be granted an exclusivity period of up to one year after it is first commercially marketed, and as part of the Consolidated Appropriations Act for 2023, Congress amended the PHSA in order to permit multiple interchangeable products approved on the same day to receive and benefit from this one-year exclusivity period.

In addition, the FDA will not accept an application for a biosimilar or interchangeable product based on the reference biological product until four years after the date of first licensure of the reference product.

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The BPCIA is complex and continues to be interpreted and implemented by the FDA.

In addition, recent government proposals have sought to reduce the 12-year reference product exclusivity period.

In addition, some government proposals have sought to reduce the 12-year reference product exclusivity period.

Other aspects of the BPCIA, some of which may impact the BPCIA exclusivity provisions, have also been the subject of recent litigation.

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The manufacturing facilities for our product candidates must meet applicable cGMP requirements to the FDA’s or comparable foreign regulatory authorities’ satisfaction before any product is approved and our commercial products can be manufactured.

We rely, and expect to continue to rely, on third parties for the production of clinical and commercial quantities of our products in accordance with cGMP regulations.

We rely, and expect to continue to rely, on third parties for the

production of clinical and commercial quantities of our products in accordance with cGMP regulations.

These manufacturers must comply with cGMP regulations that require, among other things, quality control and quality assurance, the maintenance of records and documentation and the obligation to investigate and correct any deviations from cGMP.

Manufacturers and other entities involved in the manufacture and distribution of approved

drugs or biologics are required to register their establishments with the FDA and certain state agencies and are subject to periodic prescheduled or unannounced inspections by the FDA and certain state agencies for compliance with cGMP and other laws.

Manufacturers and other entities involved in the manufacture and distribution of approved drugs or biologics are required to register their establishments with the FDA and certain state agencies and are subject to periodic prescheduled or unannounced inspections by the FDA and certain state agencies for compliance with cGMP and other laws.

Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain cGMP compliance.

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The DSCSA mandates phased-in and resource-intensive obligations for pharmaceutical manufacturers, wholesale distributors, and dispensers over a ten-year period, which culminated in November 2023.

Most recently, the FDA announced a one-year stabilization period to November 2024, giving entities subject to the DSCSA additional time to finalize interoperable tracking systems and to ensure supply chain continuity.

After an additional one-year stabilization period to give entities subject to the DSCSA additional time to finalize interoperable tracking systems and to ensure supply chain continuity, the applicable requirements under the DSCSA became fully enforceable as of November 27, 2024.

From time to time, new legislation and regulations may be implemented that could significantly change the statutory provisions governing the approval, manufacturing and marketing of products regulated by the FDA.

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Our sales, promotion, medical education and other activities following product approval will be subject to regulation by numerous regulatory and law enforcement authorities in the United States in addition to FDA, including potentially the Federal Trade Commission, or FTC, the Department of Justice, or DOJ, the Centers for Medicare and Medicaid Services, or CMS, other divisions of the Department of Health and Human Services, or DHHS, and state and local governments.

Our promotional and scientific/educational programs must comply with the federal

Anti-Kickback Statute, the Foreign Corrupt Practices Act, the False Claims Act, or FCA, the Veterans Health Care Act, physician payment transparency laws, privacy laws, security laws, and additional state laws similar to the foregoing.

Our promotional and scientific/educational programs must comply with the federal Anti-Kickback Statute, the Foreign Corrupt Practices Act, the False Claims Act, or FCA, the Veterans Health Care Act, physician payment transparency laws, privacy laws, security laws, and additional state laws similar to the foregoing.

The federal Anti-Kickback Statute prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving, or paying remuneration, directly or indirectly, in cash or in kind, in exchange for or to induce or reward either the referral of patients for, or the purchase, order or recommendation of, any good or service that may be paid for in whole or part by Medicare, Medicaid or other federal health care programs.

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The federal criminal statutes enacted under HIPAA impose criminal liability for knowingly and willfully executing, or attempting to execute, a scheme to defraud any health care benefit program, including private third-party payors, or obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any health care benefit program;

knowingly and willfully embezzling or

stealing from a health care benefit program;

knowingly and willfully embezzling or stealing from a health care benefit program;

willfully preventing, obstructing, misleading, or delaying a criminal investigation of a health care offense;

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The collection, use, disclosure, transfer, or other processing of personal data regarding individuals in the EU, including personal health data, is subject to the EU’s General Data Protection Regulation, or GDPR, which became effective on May 25, 2018.

The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other sensitive data, obtaining

consent of the individuals to whom the personal data relates, providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of data breaches, and taking certain measures when engaging third-party processors.

The GDPR also imposes strict rules on the transfer of personal data to countries outside the EU, including the U.S., and permits data protection authorities to impose large penalties for violations of the GDPR, including potential fines of up to €20 million or 4% of annual global revenues, whichever is greater.

The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other sensitive data, obtaining consent of the individuals to whom the personal data relates, providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of data breaches, and taking certain measures when engaging third-party processors.

The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR.

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Reimbursement rates may vary according to the use of the product and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost products and may be incorporated into existing payments for other services.

Net prices for products may be reduced by mandatory discounts or rebates required by third-party payors and by any future relaxation of laws that presently restrict imports of products from countries where they may be sold at lower prices than in the United States.

In the United States, third-party payors often rely upon CMS coverage policy and payment limitations in setting their own reimbursement policies, but they also have their own methods and approval process apart from CMS coverage and reimbursement determinations.

Net prices for products may be reduced by mandatory discounts or rebates

required by third-party payors and by any future relaxation of laws that presently restrict imports of products from countries where they may be sold at lower prices than in the United States.

In the United States, third-party payors often rely upon CMS coverage policy and payment limitations in setting their own reimbursement policies, but they also have their own methods and approval processes apart from CMS coverage and reimbursement determinations.

Accordingly, one third-party payor’s determination to provide coverage for a product does not assure that other payors will also provide coverage for the product.

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As 340B drug pricing is determined based on AMP and Medicaid rebate data, the revisions to the Medicaid rebate formula and AMP definition described above could cause the required 340B discount to increase.

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.

certain Medicare plans to develop tools to display Medicare Part D prescription drug benefit information in real time, and (3) for group and health insurance issuers to report information on pharmacy benefit and drug costs to the Secretaries of the DHHS, the Department of Labor and the Department of the Treasury.

More recently, in August 2022, President Biden signed into the law the Inflation Reduction Act of 2022, or the IRA.

methodologies for drug products.

For example, the 2021 Consolidated Appropriations Act signed into law on December 27, 2020 incorporated extensive health care provisions and amendments to existing laws, including new requirements for (1) all manufacturers of drugs and biological products covered under Medicare Part B to report the product’s ASP, to the DHHS beginning on January 1, 2022, subject to enforcement via civil money penalties, (2) certain Medicare plans to develop tools to display Medicare Part D prescription drug benefit information in real time, and (3) for group and health insurance issuers to report information on pharmacy benefit and drug costs to the Secretaries of the DHHS, the Department of Labor and the Department of the Treasury.

More recently, in August 2022 the Inflation Reduction Act of 2022, or the IRA, was signed into law.

Among other things, 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.

For example, 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 product-by-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 without generic or biosimilar competition.

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If a drug product is selected by CMS for negotiation, it is expected that the revenue generated from such drug will decrease.

CMS has begun to implement these new authorities and entered into the first set of agreements with pharmaceutical manufacturers to conduct price negotiations in October 2023.

CMS has begun to implement these new authorities and entered into the first set of agreements with drug and biologic manufacturers for negotiated prices of 10 products, which will become applicable for payment year 2026.

However, the IRA’s impact on the pharmaceutical industry in the United States remains uncertain, in part because multiple large pharmaceutical companies and other stakeholders (e.g., the U.S.

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Supreme Court held unanimously that federal law does not preempt the states’ ability to regulate pharmacy benefit managers, or PBMs, and other members of the health care and pharmaceutical supply chain, an important decision that may lead to further and more aggressive efforts by states in this area.

The Federal Trade Commission in mid-2022 also launched sweeping investigations in the practices of the PBM industry that could lead to additional federal and state legislative or regulatory proposals targeting such entities’ operations, pharmacy networks, or financial arrangements.

The FTC in mid-2022 also launched sweeping investigations in the practices of the PBM industry that could lead to additional federal and state legislative or regulatory proposals targeting such entities’ operations, pharmacy networks, or financial arrangements.

Significant efforts to change the PBM industry as it currently exists in the United States may affect the entire pharmaceutical supply chain and the business of other stakeholders, including biopharmaceutical developers like us.

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Some countries provide that drug and biological products may be marketed only after agreement on a reimbursement price has been reached.

Some countries may require additional studies that compare the cost-effectiveness of our product candidate to currently available therapies (so called health technology assessment, or HTA) in order to obtain reimbursement or pricing approval.

Some countries may require additional studies that compare the cost-effectiveness of our

product candidate to currently available therapies (so called health technology assessment, or HTA) in order to obtain reimbursement or pricing approval.

For example, the EU provides options for its member states to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicines.

A member state may approve a specific price for the product or it may instead adopt a

system of direct or indirect controls on the profitability of the company placing the product on the market.

A member state may approve a specific price for the product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the product on the market.

Other member states allow companies to fix their own drug prices but monitor and control prescription volumes and issue guidance to physicians to limit prescriptions.

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As of January 2023, all new clinical trials must comply with the Clinical Trials Regulation.

In addition, any clinical trial that was already under way as of January 1, 2023, and continues for more than three years from the day on which the Clinical Trials Regulation becomes applicable (i.e., January 31, 2025), the Clinical Trials Regulation will at that time begin to apply to the clinical trial.

The requirements and processes governing the conduct of clinical trials, product licensing, pricing and reimbursement in Europe vary from country to country, even though there is already some degree of legal harmonization in the EU member states resulting from the national implementation of underlying EU legislation.

In all cases, the clinical trials are conducted in accordance with GCP and other applicable regulatory requirements.

In all cases, the clinical trials must be conducted in accordance with GCP and other applicable regulatory requirements.

To obtain regulatory approval of a new drug or medicinal product in the EU, a sponsor must obtain approval of a marketing authorization application.

The way in which a medicinal product can be approved in the EU depends on the nature of the medicinal product.

The centralized procedure results in a single marketing authorization granted by the European Commission that is valid across the EU, as well as in Iceland, Liechtenstein and Norway, or the European Economic Area.

The centralized procedure is compulsory for human medicines that are:

(i) derived from biotechnology processes, such as genetic engineering, (ii) contain a new active substance indicated for the treatment of certain diseases, such as HIV/AIDS, cancer, diabetes, neurodegenerative diseases, autoimmune and other immune dysfunctions and viral diseases, (iii) officially designated as orphan medicinal product and (iv) advanced-therapy medicines, such as gene-therapy, somatic cell-therapy or tissue-engineered medicines.

Area, or the EEA, the product constitutes a significant therapeutic, scientific or technical innovation, or where the granting of authorization in the centralized procedure is in the interests of public health in the EEA.

diseases, (iii) officially designated as orphan medicinal product and (iv) advanced-therapy medicines, such as gene-therapy, somatic cell-therapy or tissue-engineered medicines.

The centralized procedure may at the request of the applicant also be used for human medicines which do not fall within the above mentioned categories if the medicinal product contains a new active substance which has not been previously authorized in the EEA, the product constitutes a significant therapeutic, scientific or technical innovation, or where the granting of authorization in the centralized procedure is in the interests of public health in the EEA.

Under the centralized procedure in the EU, the maximum timeframe for the evaluation of a marketing authorization application by the EMA is 210 days (excluding clock stops, when additional written or oral information is to be provided by the applicant in response to questions asked by the Committee for Medicinal Products for Human Use, or CHMP, with adoption of the actual marketing authorization by the European Commission thereafter.

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As in the centralized procedure, this process entails consulting various European Commission Directorates General and the EU member states Standing Committee on Human Medicinal Products.

Only products for which marketing authorizations have been granted may be sold in the EU.

A marketing authorization is valid for five years in principle and the marketing authorization may be renewed after the initial five-year period on the basis of a re-evaluation of the risk-benefit balance by the EMA or by the competent authority of the authorizing member state.

To this end, the marketing authorization holder must provide the EMA, or the applicable competent authority, with a consolidated version of the file in respect of quality, safety and efficacy, including all variations introduced since the marketing authorization was granted, at least six months before the marketing authorization ceases to be valid.

Once renewed, the marketing authorization is valid for an unlimited period, unless the European Commission, or the applicable competent authority, decides, on justified grounds relating to pharmacovigilance, to proceed with one additional five-year renewal.

Any marketing authorization which is not followed by the actual placing of the drug on the market in the EU (in case of centralized procedure) or on the market in the authorizing member state within three years after authorization ceases to be valid (the so-called sunset clause).

In the EU, new chemical entities, sometimes referred to as new active substances, qualify for eight years of data exclusivity upon marketing authorization and an additional two years of market exclusivity.

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(2) either (a) such condition affects no more than five in 10,000 persons in the EU when the application is made, or (b) the product, without the benefits derived from orphan status, would not generate sufficient return in the EU to justify investment;

and (3) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the EU, or if such a method exists, the product will be of significant benefit to those

affected by the condition, as defined in Regulation (EC) 847/2000.

Orphan medicinal products are eligible for financial incentives such as reduction of fees or fee waivers and are, upon grant of a marketing authorization, entitled to ten years of market exclusivity for the approved therapeutic indication.

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We have obtained Orphan Medicinal Product Designations from the EMA for GPS in AML, MPM and MM.

In April 2023, the European Commission issued a proposal that will revise and replace the existing general pharmaceutical legislation.

If adopted and implemented as currently proposed, these revisions will significantly change several aspects of drug development and approval in the EU.

For other countries outside of the United States and the EU, such as countries in Eastern Europe, Latin America or Asia, the requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country.

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In the United States and some foreign jurisdictions, there have been, and continue to be, several legislative and regulatory changes and proposed changes regarding the health care system that could prevent or delay marketing approval of product and therapeutic candidates, restrict or regulate post-approval activities, and affect the ability to profitably sell product and therapeutic candidates that obtain marketing approval.

The FDA’s and other regulatory authorities’ policies may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our product and therapeutic candidates.

The FDA’s and other regulatory authorities’ policies may change and additional government regulations may be enacted that could prevent, limit or

delay regulatory approval of our product and therapeutic candidates.

In addition, future legislative and regulatory proposals may materially impact the ability of the FDA and other regulatory agencies to operate as they have historically operated.

We cannot be sure whether additional legislative changes will be enacted, or whether any of the FDA’s regulations, guidances or interpretations will be changed, or what the impact of such changes on the agency and its scientific review staff, if any, may be.

For example, the next FDA user fee reauthorization package is expected to enter stakeholder negotiations beginning in mid-2025, with any agreement sent to Congress in early 2027 for purposes of initiating the legislative process.

Reauthorization of the prescription drug user fee program would need to be finalized by Congress by the end of September 2027 in order to avoid a disruption in FDA’s review goals for NDAs and other activities supported by user fees assessed against industry.

As previously mentioned, the primary trend in the US health care industry and elsewhere is cost containment.

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Because generic and biosimilar product developers need samples to conduct certain comparative testing required by the FDA, some have attributed the inability to timely obtain samples as a cause of delay in the entry of generic and biosimilar products.

To remedy this concern, the CREATES Act establishes a private cause of action that permits a generic or biosimilar product developer to sue the brand manufacturer to compel it to furnish the necessary samples on “commercially reasonable, market-based terms.” Whether and how generic and biosimilar product developments will use this new pathway, as well as the likely outcome of any legal challenges to provisions of the CREATES Act, remain highly uncertain and its potential effects on our future commercial products are unknown.

The Consolidated

Appropriations Act of 2021 also includes, among other things, a new requirement for patent information to be submitted to the FDA and published in a “Purple Book” that contains detailed information about each FDA-licensed biological product, analogous to the Orange Book that provides information about approved small-molecule drug products and their patent and exclusivity information under the Hatch-Waxman Act.

In addition to the IRA’s drug price negotiation provisions summarized above, President Biden’s Executive Order 14087, issued in October 2022, called for the CMS Innovation Center to prepare and submit a report to the White House on potential payment and delivery modes that would complement the IRA, lower drug costs, and promote access to innovative drugs.

In February 2023, CMS published its report which described three potential models focusing on affordability, accessibility and feasibility of implementation for further testing by the CMS Innovation Center.

As of January 2024 , the CMS Innovation Center continues to test the proposed models and develop implementation plans.

To remedy this concern, the CREATES Act establishes a private cause of action that permits a generic or biosimilar product developer to sue the brand manufacturer to compel it to furnish the necessary samples on “commercially reasonable, market-based terms.” Although lawsuits have been filed under the CREATES Act since its enactment, those lawsuits have settled privately;

therefore, to date no federal court has reviewed or opined on the statutory language and there continues to be uncertainty regarding the scope and application of the law.

The Consolidated Appropriations Act of 2021 also includes, among other things, a new requirement for patent information to be submitted to the FDA and published in a “Purple Book” that contains detailed information about each FDA-licensed biological product, analogous to the Orange Book that provides information about approved small-molecule drug products and their patent and exclusivity information under the Hatch-Waxman Act.

In the EU, many member states have increased the amount of discounts required on pharmaceuticals and these efforts could continue as countries attempt to manage health care expenditures, especially in light of the severe fiscal and debt crises experienced by many countries in the EU.

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Our website address is www.sellaslifesciences.com.

We do not incorporate the information on our website into this Annual Report on Form 10-K, and you should not consider such information part of this Annual Report on Form 10-K.

We do not incorporate the

information on our website into this Annual Report on Form 10-K, and you should not consider such information part of this Annual Report on Form 10-K.

We were incorporated on April 3, 2006 in Delaware as Argonaut Pharmaceuticals, Inc.

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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