Syndax Announces Completion of Enrollment in AUGMENT-101 Pivotal Trial Cohort of Patients with Relapsed/Refractory mNPM1 Acute Myeloid Leukemia

On March 28, 2024 Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported completion of enrollment in the AUGMENT-101 pivotal trial cohort of patients with relapsed/refractory (R/R) mutant nucleophosmin (mNPM1) acute myeloid leukemia (AML) (Press release, Syndax, MAR 28, 2024, View Source [SID1234641578]). Topline data is expected in the fourth quarter of 2024 and could support a supplemental New Drug Application (sNDA) filing for revumenib in R/R mNPM1 AML in the first half of 2025.

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"We are thrilled to announce that we are one step closer to potentially expanding the therapeutic reach of revumenib in genetically defined acute leukemias," said Neil Gallagher, M.D., Ph.D., President, Head of Research and Development at Syndax. "We look forward to reporting topline data for this pivotal cohort in the fourth quarter of this year, which will follow closely behind a potential first approval of KMT2A acute leukemia in the third quarter."

Michael A. Metzger, Chief Executive Officer, added, "With revumenib and axatilimab, two first-and best-in-class drugs, expected to launch in 2024 and the potential to expand beyond first approvals and into additional indications, Syndax is well positioned to deliver on its mission to improve the lives of cancer patients and create meaningful long-term value for shareholders."

Sixty-four (64) adult and up to 20 pediatric patients with mNPM1 AML have been enrolled into the pivotal portion of AUGMENT-101, a pivotal trial designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of orally administered revumenib. The primary endpoint for the trial is efficacy as measured by complete remission (CR) or a CR with partial hematological recovery (CRh) rate (CR + CRh) per protocol, with secondary endpoints including duration of response (DOR) and overall survival (OS).

A new drug application (NDA) is under review by the U.S. Food and Drug Administration (FDA) for revumenib in R/R KMT2Ar acute leukemia with a Prescription Drug User Fee Act (PDUFA) action date of September 26, 2024. The NDA submission is supported by positive data from the AUGMENT-101 pivotal trial cohort of revumenib in adult and pediatric patients with KMT2Ar AML and acute lymphoblastic leukemia (ALL).

About Revumenib

Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged, also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and NPM1-mutant AML. Positive topline results from the Phase 2 AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint were presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and data from the Phase 1 portion of AUGMENT-101 in acute leukemia was published in Nature. Revumenib was granted Orphan Drug Designation by the FDA and European Commission for the treatment of patients with AML, and Fast Track designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. Revumenib was granted Breakthrough Therapy Designation (BTD) by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.

About NPM1-Mutant Acute Myeloid Leukemia

NPM1-mutant AML, which is distinguished by mutations in the NPM1 gene that drive the leukemic phenotype, is the most common type of cytogenetically normal adult AML and represents approximately 30% of all adult AML cases. This subtype of AML has a five-year overall survival rate of approximately 50%. Similar to KMT2A-rearranged acute leukemia, NPM1-mutant AML is highly dependent on the expression of specific developmental genes shown to be negatively impacted by inhibitors of the menin-KMT2A interaction. NPM1-mutant AML is routinely diagnosed through currently available screening techniques. There are currently no approved therapies indicated for NPM1-mutant AML.

SELLAS Life Sciences Reports Full Year 2023 Financial Results and Provides Corporate Update

On March 28, 2024 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS’’ or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported financial results for the full year ended December 31, 2023, and provided a corporate update (Press release, Sellas Life Sciences, MAR 28, 2024, View Source [SID1234641577]).

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"We are off to a strong start this year highlighted by progress in our late-stage pipeline, strong data from Phase 2a study of SLS009 in r/r AML, completing enrollment in Phase 3 REGAL study, positive feedback from the REGAL Steering Committee, and the recent FDA Fast Track Designation granted for SLS009 in r/r AML," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "The data from the Phase 2a study of SLS009 in r/r AML patients resistant to venetoclax combination therapies achieved 50% response in the selected optimal dose regimen of 30 mg BIW and 100% response rate in patients with identified biomarkers to date. We were pleased to recently announce enrollment completion in the Phase 3 REGAL trial and we eagerly anticipate the Independent Data Monitoring Committee (IDMC) meeting in late April. We also reported Phase 1 data of SLS009 in AML at ESH demonstrating the first-ever complete response achieved in a relapsed/refractory AML patient through CDK9 inhibition monotherapy. We enter 2024 well-positioned to execute on our goals with the priority of reporting data from the Phase 3 REGAL trial of GPS in AML, additional data from our Phase 2a study of SLS009 in r/r AML, and topline data from the Phase 1b/2 study of SLS009 in PTCL by the end of the second quarter."

Recent Highlights:

Completed enrollment in Phase 3 REGAL study: Reached planned enrollment of patients in the United States, Europe, and Asia, in accordance with the predetermined statistical analysis plan.

Phase 3 REGAL study in AML: The Steering Committee has reviewed the study as of the March 1, 2024 cutoff date, signaling potentially imminent interim analysis of the ongoing global Phase 3 registrational clinical trial (the REGAL study) of GPS in patients with AML who have achieved complete remission following second-line salvage therapy (CR2 patients). The next IDMC meeting is expected in late April 2024.

Reported data from the Phase 2a Study of SLS009 in Relapsed/Refractory AML Patients: 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). The response rate of 10% was achieved in the 45 mg (safety cohort), 20% in the 60 mg QW cohort, and 50% response rate in the 60 mg, 2 x 30 mg BIW, the optimal dose level cohort. Additionally, in the patients with identified biomarkers, a 100% response rate was observed to date at the optimal dose level and a 57% response rate across all the levels tested in patients with those biomarkers. The SLS009 aza-ven treatment was well-tolerated and evoked anti-leukemic effects in 67% of patients across all levels dosed. The median survival rate has not been reached in any of the dose levels. The first patient who achieved a complete response continues on the study and remains leukemia-free 9 months post-enrollment.

Received $20.0 million of gross proceeds from a registered direct offering priced at-the-market under Nasdaq rules: On March 19, 2024, announced the closing of a $20.0 million registered direct offering with two institutional investors before deducting placement agent’s fees and related offering expenses. The net proceeds from the offering strengthen the Company’s financial position and will be used for research and development activities, working capital, and general corporate purposes.

Presented Phase 1 Data in AML at the 2024 European School of Haematology (ESH): All key study objectives regarding pharmacokinetic, pharmacodynamic, safety, and clinical activity were met. Data showed that for the first time, a relapsed/refractory patient achieved complete remission (CR) with a CDK9 inhibitor monotherapy. The CR was achieved after three months of treatment and lasted 8 months with one-year survival at the latest assessment.

Publication in Oncotarget: The preclinical data published revealed the underlying mechanisms of action behind the anti-proliferative effects of SLS009, a highly selective CDK9 small molecule inhibitor, in various hematologic malignancies. The publication, entitled, "The pharmacodynamic and mechanistic foundation for the antineoplastic effects of GFH009, a potent and highly selective CDK9 inhibitor for the treatment of hematologic malignancies", is available online.

Fast Track Designation: The U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to SLS009, for the treatment of r/r AML. The Fast Track Designation is intended to facilitate the development and review of drugs to treat serious conditions and fill an unmet medical need.

2024 Milestones:

Galinpepimut-S (GPS): Wilms Tumor-1 (WT1) targeting immunotherapeutic

Phase 3 REGAL study in AML: Anticipated interim analysis of the ongoing global Phase 3 registrational clinical trial (the REGAL study) of GPS in patients with AML who have achieved complete remission following second-line salvage therapy (CR2 patients) in 1H 2024. Final analysis expected to occur by the end of 2024.

SLS009: highly selective CDK9 inhibitor

Phase 2a clinical trial in r/r AML: Additional data expected in 1H 2024. Initially planned enrollment of approximately 20 patients has been completed and additional patients continue to enroll. Confirmation of safety and further exploration of efficacy in additional patients will be combined with additional biomarkers related data to enable us to plan for further development.
Phase 1b/2 clinical trial in r/r PTCL: Enrollment started in December 2023. Thirty-one sites are active for recruiting and approximately 10 more sites will be initiated. Interim analysis is planned after 20-25 patients are enrolled and have undergone initial follow-up which is projected to occur in 1H 2024. The interim efficacy data will be discussed with regulatory agencies to decide on the continuation of the trial as a pivotal registrational study that would enroll approximately 70-75 additional patients. This study is fully funded by the Company’s partner for SLS009, GenFleet Therapeutics (Shanghai), Inc. ("GenFleet"), and is being conducted in China.
Phase 1b/2 clinical trial in combination with BTK inhibitor, Brukinsa (zanubrutinib), in r/r DLBCL: Genfleet entered into a clinical trial collaboration and supply agreement with BeiGene Switzerland GmbH and the first patient dosed in March 2024. The trial is an open-label single-arm multicenter Phase 1b/2 trial to be conducted in two parts. In the Phase 1b portion, 6-18 patients will be enrolled and in the Phase 2 portion, approximately 45 patients will be enrolled. This study is being conducted in China and is funded by GenFleet.
PIVOT program with the National Cancer Institute (NCI) in multiple pediatric cancer indications continues. Initial safety and efficacy data are expected to be reported throughout 2H 2024.
2023 Highlights:

Galinpepimut-S (GPS): Wilms Tumor-1 (WT1) targeting immunotherapeutic

Positive immunobiological and clinical data from the completed Phase 1/2 clinical trial of GPS in combination with Keytruda (pembrolizumab) in WT1+ platinum-resistant advanced ovarian cancer was presented at the International Gynecologic Cancer Society 2023 annual global meeting in November 2023.
The Company reported positive follow-up immune response and survival data in the fourth quarter of 2023 for the completed Phase 1 clinical trial of GPS combined with Opdivo (nivolumab) in advanced malignant pleural mesothelioma.
In the fourth quarter of 2023, the Company announced that it had concluded a Type C meeting with the U.S. Food and Drug Administration (FDA) regarding the Company’s Chemistry, Manufacturing, and Controls (CMC) sections in a potential biologics license application (BLA) for GPS. SELLAS had submitted a CMC Briefing Package to the FDA which provided an up-to-date overview of the extensive work completed for the GPS CMC program and commercial manufacturing and regulatory plans. The FDA reviewed this package of data and accompanying questions to the agency and responded with favorable guidance.

SLS009: highly selective CDK9 inhibitor

The Phase 1 clinical trial for patients with AML and lymphomas was completed in 2023. For patients with AML, SLS009 demonstrated a favorable tolerability profile with no dose limiting toxicities. Anti-tumor activity and clinical responses across dose levels were observed, indicating a broad therapeutic index. Meaningful cell killing activity, defined as ≥50% reduction in blasts in the bone marrow, was observed at several dose levels. A durable complete remission (CR) with no minimal residual disease (MRD) was observed in one patient with AML who had failed prior venetoclax plus azacytidine (aza/ven) therapy. The patient achieved CR three months after the treatment that lasted 8 months and continues to be alive 12 months following commencement of treatment per last follow-up. The recommended Phase 2 dose for patients with AML was established at 60 mg. For the patients with lymphomas, no off-target safety issues were observed at any dose level and responses were observed across dose levels with a 14.7% clinical response rate overall, 35.3% overall disease control rate, and 36.4% clinical response rate for patients with PTCL. The recommended Phase 2 dose for patients with lymphomas was established at 100 mg administered as a once weekly infusion.
In the second quarter of 2023, the Company announced the dosing of the first patient (45 mg) in an open-label, single-arm, multi-center Phase 2a study that is designed to evaluate safety, tolerability, and efficacy at two dose levels of SLS009 (once weekly 45 mg or 60 mg) in combination with aza/ven in patients with AML. Enrollment in the 45 mg cohort was completed in the fourth quarter of 2023. Also in the fourth quarter of 2023, the Company announced the dosing of the first patients in the 60 mg dose cohort. The patients in the 60 mg dose cohort will be dosed with 60 mg once per week or 30 mg twice per week.
Early topline data from the Phase 2a study in patients with AML dosed at the 45 mg level (n=9) include one patient with a CR and significant anti-leukemic effects (≥50% decrease in bone marrow blasts) were observed in five out of six assessable patients with no significant safety issues to date.
In the fourth quarter of 2023, the Company announced the dosing of the first patient in a Phase Ib/II open-label, single-arm trial in r/r 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 fully funded by the Company’s partner for SLS009, GenFleet Therapeutics (Shanghai), Inc., and is being conducted in China.
The Company received the following regulatory designations from the FDA for SLS009 in 2023:
Orphan Drug Designation (ODD) for the treatment of AML
ODD for the treatment of PTCL
Fast Track Designation for the treatment of r/r PTCL
Financial Results for the Full Year 2023:

R&D Expenses: Research and development expenses for the year ended December 31, 2023, were $24.0 million, compared to $20.3 million for the year ended December 31, 2022. The increase was primarily due to an increase in clinical trial expenses related to the ongoing Phase 3 REGAL clinical trial and our clinical trials of SLS009, increase in clinical and regulatory consulting expenses due to the advancement of our clinical programs

Acquired In-Process Research and Development: There was no acquired in-process research and development for the year ended December 31, 2023, compared to $10.0 million during the year ended December 31, 2022 from the in-licensing of SLS009.

G&A Expenses: General and administrative expenses for the year ended December 31, 2023, were $13.9 million, as compared to $12.6 million for the year ended December 31, 2022. The increase was primarily due to personnel-related expenses and an increase in intellectual property related expenses.

Net Loss: The net loss was $37.3 million for the year ended December 31, 2023, or a basic and diluted loss per share of $1.34, as compared to a net loss of $41.3 million for the year ended December 31, 2022, or a basic and diluted loss per share of $2.13.

Cash Position: As of December 31, 2023, cash and cash equivalents totaled approximately $2.5 million. On January 8, 2024, the Company received gross proceeds of $9.0 million from a public offering. On March 19, 2024, the Company received gross proceeds of $20.0 million from a registered direct offering priced at-the-market under Nasdaq rules.

Revolution Medicines to Deliver Multiple Presentations at the Upcoming American Association for Cancer Research Annual Meeting 2024

On March 28, 2024 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for patients with RAS-addicted cancers, reported the company will deliver multiple presentations at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 being held April 5-10, 2024, in San Diego, California (Press release, Revolution Medicines, MAR 28, 2024, View Source [SID1234641576]).

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Details of the planned presentations are listed below:

Revolution Medicines Oral Presentations:

Title:
Discovery of RMC-9805, an Oral, RAS(ON) G12D-Selective Covalent Tri-Complex Inhibitor
Presenter:
John Knox, Ph.D.
Abstract Number:
ND03
Session: New Drugs on the Horizon: Part 1
Date/Time: 1:45 – 2:00 p.m. PT on April 7, 2024

Title: RMC-6236, a RAS(ON) Multi-Selective Tri-Complex Inhibitor
Presenter: Elena Koltun, Ph.D., Wei Lin, M.D.
Session: KRAS: Broadening the Attack Beyond G12C with Small Molecules and Immuno-Oncology
Date/Time: 1:00 – 1:20 p.m. PT on April 9, 2024

Title: Combination of RAS(ON) G12C-Selective and Multi-Selective Tri-Complex Inhibitors Overcomes Resistance and Prolongs Durability in Preclinical Models of KRASG12C NSCLC
Presenter: Xing Wei, Ph.D.
Abstract Number: 6585
Session: Novel Antitumor Agents 5
Date/Time: 2:35 – 2:50 p.m. PT on April 9, 2024

Revolution Medicines Poster Presentations:

Title:
Potential Biomarkers of Response to the Combination of the RAS(ON) Multi-Selective Inhibitor RMC-6236 Plus Anti-PD-1 Antibody in Preclinical PDAC Models
Presenter:
Lillian Seu, Ph.D.
Abstract Number:
581/4
Session: Immunotherapy
Date/Time: 1:30 – 5:00 p.m. PT on April 7, 2024

Title: RMC-5127, a First-in-Class, Orally Bioavailable RAS(ON) G12V-Selective Tri-Complex Inhibitor, is CNS-Penetrant and Drives Regressions in Intracranially Implanted KRASG12V Xenograft Tumors
Presenter: Zhe Chen, M.B.B.S., Ph.D.
Abstract Number: 3340/28
Session: Novel Antitumor Agents 3
Date/Time: 1:30 – 5:00 p.m. PT on April 8, 2024

Title: The RAS(ON) Multi-Selective Inhibitor RMC-7977 Blocks Downstream MAPK and PI3K Pathway Activation in KRASG12X-Mutant Cancers
Presenter: Priyanka Bapat, Ph.D.
Abstract Number: 4709/2
Session: Other Cellular Mechanisms for Anticancer Drug Action
Date/Time: 9:00 a.m. – 12:30 p.m. PT on April 9, 2024

Collaborator Poster Presentations:

Title:
RTK Signaling and WT RAS Activity as Vulnerabilities in Tumors with Acquired Resistance to GDP-State Selective KRASG12C Inhibitors in Preclinical Models
Lead RevMed Co-Author: Harshit Shah, Ph.D.
Abstract Number:
1924/2
Session: Drug Resistance 2: RAS GTPase
Date/Time: 9:00 a.m. – 12:30 p.m. PT on April 8, 2024

Title: Resistance to RAS-GTP Inhibition in Models of Pancreatic Ductal Adenocarcinoma Arises Downstream of RAS Effectors
Lead RevMed Co-Author: Jingjing Jiang, Ph.D.
Abstract Number: 1927/5
Session: Drug Resistance 2: RAS GTPase
Date/Time: 9:00 a.m. – 12:30 p.m. PT on April 8, 2024

Additional information on the AACR (Free AACR Whitepaper) Annual Meeting 2024 is available through the AACR (Free AACR Whitepaper) website at: View Source

Purple Biotech to Present New Data On its Oncology Drug NT219 at AACR 2024

On March 28, 2024 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that harness the power of the tumor microenvironment to overcome tumor immune evasion and drug resistance, reported it will present data for its oncology candidate NT219, a first-in-class small molecule, dual-inhibitor of IRS 1/2 and STAT3, in two poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting which takes place April 5-11, 2024, in San Diego, California (Press release, Purple Biotech, MAR 28, 2024, View Source [SID1234641575]).

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"The growing body of clinical, biomarker, and preclinical data for NT219 demonstrate its potential not only in the lead indication of recurrent/metastatic squamous cell carcinoma of the head and neck, but also in other solid-tumor cancers. These publications at AACR (Free AACR Whitepaper) 2024 are a result of the progress made last year both in clinical and preclinical work bringing out NT219’s attributes," stated Gil Efron, Chief Executive Officer of Purple Biotech. "We look forward to leveraging these data as we move forward with the clinical evaluation of NT219."

Dr Hadas Reuveni, VP Research and Development at Purple Biotech, added, "At AACR (Free AACR Whitepaper) 2024 we will present new data related to NT219. We show for the first time the potential of NT219 to effectively suppress cancer stem cells (CSC), a critical cell population for tumor propagation, characterized by self-renewal and multipotency, and known to promote resistance and tumor recurrence. In addition, synergistic effect of NT219 and mKRAS inhibitors is demonstrated, suggesting a novel mechanism to combat resistance to both KRASG12C and KRAS KRASG12D inhibitors in lung cancer and pancreatic cancers, respectively, both aggressive diseases with unmet medical need. In another presentation, we show the results of translational research in our Phase 1 study, suggesting activated IGF1R and STAT3 as potential biomarkers for the treatment with NT219. We will further evaluate these biomarkers in the next study."

Poster Details:

Title: NT219, a dual inhibitor of IRS1/2 and STAT3, suppresses cancer stem cell mediated resistance to KRASG12C and KRASG12D inhibitors in solid tumors

Session Category: Experimental and Molecular Therapeutics

Session Title: Drug Resistance 2: Ras GTPase

Session Date and Time: Monday Apr 8, 2024, 9:00 AM – 12:30 PM PST

Published Abstract Number: 1939

Title: Early activity and biomarker evaluation of NT219 in combination with cetuximab in a Phase 1/2 study of recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN)

Session Category: Clinical Research

Session Title: Predictive Biomarkers 4

Session Date and Time: Tuesday Apr 9, 2024, 9:00 AM – 12:30 PM PST

Published Abstract Number: 5181

The abstracts are available on the AACR (Free AACR Whitepaper) Online Program Planner and were published in the online-only Proceedings supplement to the AACR (Free AACR Whitepaper) journal Cancer Research. The presented posters will be available on the Publications section of Purple Biotech’s website, following their presentations at the conference.

Omega Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Strategic Update

On March 28, 2024 Omega Therapeutics, Inc. (Nasdaq: OMGA) ("Omega"), a clinical-stage biotechnology company pioneering the development of a new class of programmable epigenomic mRNA medicines, reported financial results for the fourth quarter and full year ended December 31, 2023, and a strategic prioritization initiative to focus resources on near-term milestones to support long-term shareholder value (Press release, Omega Therapeutics, MAR 28, 2024, View Source [SID1234641574]).

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"2023 was an important year for Omega where we executed to plan and demonstrated clinical validation of an epigenomic controller to regulate c-MYC in humans for the first time. These proof-of-platform clinical data, coupled with our research collaboration with Novo Nordisk in obesity, support the ability of the OMEGA platform to potentially address epigenomic regulation of almost all human genes across broad therapeutic areas including cancer, cardiometabolic conditions and liver regeneration," said Mahesh Karande, President and Chief Executive Officer of Omega Therapeutics. "Initial clinical data from our ongoing Phase 1/2 MYCHELANGELO I trial of OTX-2002 demonstrated controlled modulation of MYC expression levels, one of the most challenging gene targets in oncology, and an encouraging disease control rate and stable disease in heavily pre-treated, late-stage HCC patients. We are within what we believe is a clinically meaningful dose range and, as we continue to see a promising safety profile for OTX-2002, have recently opened enrollment of Cohort 5. We look forward to sharing additional updates from this program throughout 2024."

"Today we also announced a strategic prioritization, implemented to ensure we have sufficient resources to advance our lead program and maximize near- and long-term value creation from our platform. As part of this initiative, we are taking difficult but necessary actions to streamline our team and optimize our R&D efforts and cost structure to extend our cash runway into the first quarter of 2025. These changes will unfortunately affect a number of our colleagues, and we are grateful for their dedication and contributions to our mission," continued Mr. Karande. "As we sharpen our focus, we look forward to the opportunities ahead to generate meaningful clinical data for OTX-2002, continue to demonstrate the broad potential of our platform, and establish additional partnerships. We remain steadfast in our mission to pioneer a new class of programmable epigenomic mRNA medicines to transform the treatment of a broad range of diseases."

Recent Highlights and Key Anticipated Milestones

Development Pipeline and Platform


Advanced the Phase 1/2 MYCHELANGELO I clinical trial evaluating OTX-2002 in patients with hepatocellular carcinoma (HCC):
o
OTX-2002 continues to advance in monotherapy dose escalation.
o
As of March 24, 2024, data from the first three cohorts (0.02 mg/kg – 0.06 mg/kg) showed:

OTX-2002 continued to be generally well tolerated, with no dose-limiting toxicities observed.

Consistent dose-dependent pharmacokinetics with no drug accumulation observed following repeat doses.

All patients demonstrated controlled modulation and downregulation of MYC mRNA expression, an important oncogene regulating cell function and cell death.

The interim disease control rate (DCR) for the target population of HCC patients was 80%, reflecting 4 out of 5 efficacy-evaluable patients having a best overall response of stable disease. These patients had an average of three or more previous therapies and entered the trial with a life expectancy of less than 12 weeks. The DCR for patients with non-HCC solid tumors in the trial (n=5) was 40%, indicating the potential specificity of OTX-2002 for HCC.
o
The Company continues to evaluate patients with HCC in Cohort 4 at the 0.12 mg/kg dose level, which recently cleared the 28-day dose limiting toxicity (DLT) window. Based on preclinical experience and modeling, Omega believes this dose level is within the expected active dose range. In March 2024, the Company opened enrollment for Cohort 5 at a dose level of 0.3 mg/kg.
o
Omega expects to report additional updated clinical data from monotherapy dose escalation in mid-2024.
o
The Company plans for expansion into monotherapy and combination settings in mid-2024.

Announced research collaboration with Novo Nordisk to develop a novel therapeutic for obesity management:
o
The collaboration will leverage Novo Nordisk’s expertise in research and development within cardiometabolic diseases and Omega’s proprietary platform technology to develop an epigenomic controller designed to enhance metabolic activity.
o
Unlike traditional approaches focused on appetite suppression, the program aims to leverage precision epigenomic control to enhance thermogenesis, a naturally occurring metabolic process that burns calories.
o
Under the terms of the agreement, Novo Nordisk will reimburse all R&D costs and has the right to select one target to advance for clinical development.

Omega and Flagship’s Pioneering Medicines are eligible to receive up to $532 million in upfront, development and commercial milestone payments, as well as tiered royalties on annual net sales of a licensed product, which will be split equally between the parties.

Continued to advance and expand OMEGA platform capabilities:
o
Presented new preclinical data supporting the breadth of Omega’s platform capabilities, including bidirectional and multiplexed epigenomic control of gene expression in liver inflammation and fibrosis at the American Association for the Study of Liver Diseases’ (AASLD) The Liver Meeting 2023.

A HNF4A-targeting epigenomic controller led to a durable increase in HNF4α expression, preferential upregulation of HNF4α P1 promoter isoforms, and reduced key measures of fibrosis both in vitro and in vivo, supporting this development candidate’s potential for the treatment of fibrotic liver disease.

In preclinical models, liver-specific multiplexed targeting of CXCL9, CXCL10 and CXCL11 via an epigenomic controller led to a significant reduction in T-cell migration, a critical driver of inflammation-induced liver injury, supporting the potential of this approach as a novel treatment for inflammatory liver diseases.

Corporate


Announced cost reduction and strategic prioritization initiative to maximize near- and long-term value creation opportunities:
o
Following a strategic review, the Company has focused its pipeline and reduced overall headcount by approximately 35%. These fiscally disciplined actions are expected to extend the Company’s cash runway into Q1 2025.
o
Positions the Company to achieve key clinical data readouts from the monotherapy dose escalation and dose expansion stages of the MYCHELANGELO I clinical trial.
o
The Company will prioritize certain preclinical programs and platform efforts:

Prioritized preclinical programs include OTX-2101 for non-small cell lung cancer (NSCLC), the HNF4A program in liver regeneration, and development of an epigenomic controller for obesity in collaboration with Novo Nordisk.

Core work on platform biology, epigenomic controllers, and characterization of LNP delivery to the lung and other tissues will continue.
o
An updated corporate presentation is available on the Investors section of the Company’s website at View Source

Fourth Quarter and Full Year 2023 Financial Results

As of December 31, 2023, the Company had cash, cash equivalents and marketable securities totaling $73.4 million, which is expected to fund operations into Q1 2025.

Research and development (R&D) expenses for the fourth quarter of 2023 were $15.5 million, compared to $26.0 million for the fourth quarter of 2022. R&D expenses for 2023 were $77.2 million compared to $81.2 million in 2022. The $4.0 million decrease in R&D expenses in 2023 compared to 2022 was primarily due to lower external research and manufacturing costs, consulting and professional fees, and lab expenses, partially offset by an increase in personnel-related expenses, including stock-based compensation to support business growth, and facilities and other costs.

General and administrative (G&A) expenses for the fourth quarter of 2023 were $6.2 million, compared to $5.7 million for the fourth quarter of 2022. G&A expenses for 2023 were $26.2 million, compared to $23.7 million in 2022. The $2.5 million increase in G&A expenses in 2023 compared to 2022 was primarily due to higher professional and consulting fees, and facilities and other administrative costs.

Net loss for the fourth quarter of 2023 was $20.2 million, compared to $30.8 million for the fourth quarter of 2022. Net loss for the year ended December 31, 2023, was $97.4 million, compared to a net loss of $102.7 million for the year ended December 31, 2022. The decrease in net loss for 2023 compared to 2022 was primarily due to decreases in R&D expenses.