On March 26, 2024 Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that the U.S. Food and Drug Administration (FDA) has granted Priority Review for its New Drug Application (NDA) for revumenib, the Company’s first-in-class menin inhibitor, for the treatment of adult and pediatric relapsed or refractory (R/R) KMT2A-rearranged (KMT2Ar) acute leukemia (Press release, Syndax, MAR 26, 2024, View Source [SID1234641453]). The NDA filing is being reviewed under the FDA’s Real-Time Oncology Review Program (RTOR) and has been assigned a Prescription Drug User Fee Act (PDUFA) target action date of September 26, 2024. RTOR allows for a more efficient review and close engagement between the sponsor and the FDA throughout the submission process, which historically has led to earlier approvals.

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"The receipt of Priority Review for the revumenib NDA filing is a significant milestone as we transition to a leading commercial-stage oncology company with the planned launches of two first- and best-in class drugs in 2024," said Michael A. Metzger, Chief Executive Officer. "With two regulatory filings now under FDA Priority Review, our team is focused on commercial preparations to enable Syndax’s continued success as we enter this next stage of growth."

The NDA submission is supported by positive data from the pivotal AUGMENT-101 trial of revumenib in adult and pediatric patients with KMT2Ar acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). As previously reported, the trial met its primary endpoint at the protocol-defined interim analysis with a complete remission (CR) or a CR with partial hematological recovery (CRh) rate of 23% (13/57; 95% confidence interval [CI]: [12.7, 35.8, one-sided p-value = 0.0036]) among the 57 efficacy evaluable patients in the pooled KMT2Ar acute leukemia population. 70% of patients who achieved a CR/CRh and were assessed for minimal residual disease (MRD) were MRD negative. Additionally, 63% (36/57) of the efficacy-evaluable patients achieved an overall response, 39% (14/36) of whom underwent hematopoietic stem cell transplant (HSCT), with 50% (7/14) restarting revumenib as post-transplant maintenance at the time of the data cutoff.

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 Real-Time Oncology Review (RTOR)

RTOR provides a more efficient review process for oncology drugs to ensure that safe and effective treatments are available to patients as early as possible, while improving review quality and engaging in early iterative communication with the applicant. Specifically, it allows for close engagement between the sponsor and the FDA throughout the submission process and it enables the FDA to review individual sections of modules of a drug application rather than requiring the submission of complete modules or a complete application prior to initiating review. Additional information about RTOR can be found at: View Source

On March 26, 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 topline data from the Phase 2a study of SLS009 and provides an update on Phase 3 REGAL Study of GPS in AML (Press release, Sellas Life Sciences, MAR 26, 2024, View Source [SID1234641452]). The Company will host a webinar to discuss the data and the REGAL update today at 8:15 am ET.

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"Completion of enrollment in the Phase 3 REGAL trial represents an important milestone in our goal to deliver GPS to AML patients," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "We are extremely grateful to the patients, their families, and investigators who have helped us achieve this significant milestone. Additionally, we are pleased to share that the Steering Committee has reviewed the study as of the March 1, 2024, cutoff date. As of this evaluation, 123 patients were enrolled with 66 of them discontinuing the treatment. In the trial, patients are recorded as having stopped the study treatment in cases of death for any reason, relapse, intolerable toxicity, or treatment completion. Regarding the GPS arm, we are pleased to report that we have not observed any intolerable toxicities in any patient population across all our clinical studies thus far, although toxicities are commonly observed with therapies used in the control arm. Therefore, almost all patients who are off treatment may have most likely either relapsed or passed away. The most frequent cause of death in this patient population is relapse. As the study sponsors, we lack specific information on the outcomes of these 66 patients, hindering our ability to confirm whether the required number of events for interim analysis – 60 – has been reached. The determination of such outcomes, the primary endpoint of the trial, lies within the purview of the IDMC, which is now scheduled to meet by the end of April."

The REGAL Steering Committee met on March 22, 2024, to discuss the study and believes the high number of patients who completed participation in the study signals that the interim analysis requiring 60 events may be imminent. The Committee also expressed its satisfaction with SELLAS’ overall clinical study conduct and complimented SELLAS for addressing such a debilitating and high unmet medical need as no drugs are approved in the AML CR2 maintenance setting.

Dr. Stergiou continued: "We are extremely excited to share positive topline data from the Phase 2a trial of SLS009 in AML patients resistant to venetoclax combination therapies. In the selected optimal dose regimen of 30 mg BIW a 50% response rate was achieved, far surpassing the targeted 20% rate. Notably, we identified promising biomarkers and observed a 100% response rate 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 first patient who achieved a complete response continues on the study and remains leukemia-free 9 months post-enrollment. These compelling results from the Phase 2a reinforce our belief that SLS009 represents a potential breakthrough for relapsed and/or refractory AML patients, addressing one of the most urgent unmet medical needs."

Summary of Topline Data from Phase 2a data of SLS009 in AML

Patients Characteristics

As of March 15, 2024 data cutoff, 21 patients were treated
All patients were diagnosed with AML refractory to or relapsed after venetoclax containing regimens
20 out of 21 (95%) enrolled patients had adverse/high-risk cytogenetics and 1 patient (5%) had intermediate cytogenetics
Median age was 70 and 19/21 (90.5%) of patients were older than 60
Safety

SLS009 in combination with aza/ven has been well-tolerated at all tested dose levels
No dose-limiting toxicities (DLT) at any of the studied dose levels and no treatment-related high-grade (≥G3) toxicities were observed
Hematologic toxicities profile was consistent with aza/ven standalone treatment

Efficacy

A total of 21 patients were enrolled in the study as of March 15, 2024: 10 in the 45 mg safety cohort, 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 recommended Phase 2 dose, RP2D)
20% response rate in the 60 mg QW cohort
50% response rate in the 60 mg, 2 x 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
Biomarkers

During the trial the Company 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 BIW)
57% response rate across all dose levels
Furthermore, the Company has 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
The Phase 2a clinical trial of SLS009 is an open-label, single-arm, multi-center study designed to evaluate the safety, tolerability, and efficacy of SLS009 in combination with aza/ven at two dose levels, 45 and 60 mg. In the 60 mg dose cohort patients were randomized into either a 60 mg dose once per week or a 30 mg dose two times per week. The target response rate at the optimal dose level is 20% with a target median survival over 3 months. In addition, the study aims to identify biomarkers for the target patient population and enrichment for further trials.

On March 26, 2024 The Swedish biotech company Neogap Therapeutics reported to have received SEK 5 million from Eurostars in a collaboration project with the French biotech company Okomera (Press release, Neogap Therapeutics, MAR 26, 2024, View Source,c3951209 [SID1234641451]). The funding aims to enhance the development of an analysis method for T-cell activity against the patient’s tumour.

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Neogap is developing pTTL, personalised Tumour Trained Lymphocytes, a tailored cell therapy that utilises modified proteins, known as neoantigens, to activate the immune system specifically against cancer cells. The therapy is currently being assessed in phase I/II clinical trials for the treatment of colorectal cancer.

As part of the Eurostars-funded project, Neogap collaborates with the French biotech company Okomera, which has developed an innovative method to analyse cell interactions. The method allows for the analysis of how T-cells kill tumour cells in what is known as a killing assay, requiring only a minimal quantity of the cell product. This analysis is set to deepen the understanding of the interactions between T-cells and tumour cells, potentially enabling predictions about the efficacy of Neogap’s cell therapy products. The goal is to develop a system that can easily and reliably measure the capability of Neogap’s T-cell product, pTTL, in eradicating cancer cells.

"We are very grateful for Eurostars’ backing, which not only recognises the scientific potential of our company but also reinforces our role as an innovator in analysis methods for next-generation cell therapies. The funding enables further research that is essential for advancing our cell therapy product to later clinical phases," says Samuel Svensson, CEO of Neogap Therapeutics.

"Through our collaboration with Neogap, we’re afforded the opportunity to integrate Okomera’s technology into developing analytical methods for their pioneering cancer therapies. We eagerly anticipate the advancements this partnership will bring to the field of precision medicine," says Sidarth Radjou, CEO of Okomera.

On March 26, 2024 Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company developing novel, investigational engineered cytokine therapies designed to address areas of unmet need for patients with a variety of cancers, reported its financial results for the fourth quarter and year ended December 31, 2023, and provided a business update (Press release, Mural Oncology, MAR 26, 2024, View Source [SID1234641450]).

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"We have made significant progress since becoming an independent company during the fourth quarter of 2023. We have amplified the company’s strong talent by bringing in world-class leaders in immuno-oncology. To date, nemvaleukin has generated promising data with durable responses both in monotherapy and in PD-1 combination across a range of solid tumor types. We expect our current cash reserves to fund our operations, including multiple clinical development programs, into 4Q 2025 and we are selectively exploring partnerships to further investigate the significant potential of both nemvaleukin and our preclinical programs," said Caroline Loew, Ph.D., Chief Executive Officer of Mural Oncology. "This year, we plan to continue to advance our late-stage clinical trials, including evaluating less frequent IV dosing for nemvaleukin. We also look forward to presenting pre-clinical data from our IL-18 and IL-12 programs at multiple oncology conferences and nominating candidates for each this year."

Recent Corporate Highlights and Upcoming Milestones

Mural Oncology spun out of Alkermes and became an independent, publicly traded immuno-oncology company in November 2023. Now led by an experienced and highly accomplished oncology-focused leadership team and board of directors, the company is leveraging its core competencies in immune cell modulation and protein engineering to develop a portfolio of investigational cytokine therapies designed to address areas of unmet need for patients with solid tumors.

Mural Oncology has completed evaluation of the less frequent IV (LFIV) dosing regimen of nemvaleukin in ARTISTRY-3, and determined the recommended phase 2 dose selection to be 30 µg/kg, to be evaluated in cohort 3 of ARTISTRY-6:

The new dosing regimen, a shift from five daily infusions (days 1-5) per three-week cycle to two infusions (on days 1 and 8) per three-week cycle, did not result in additional observed tolerability issues compared to previous studies of nemvaleukin. Notably, there were no dose-limiting toxicities at any dose tested and the desired pharmacodynamic effects were seen with twice per cycle dosing.
The company plans to evaluate the LFIV nemvaleukin dosing regimen in the open-label cohort 3 of ARTISTRY-6, the company’s ongoing phase 2 trial, to explore the safety and efficacy of this new dosing regimen in a homogeneous patient population.
The company looks forward to presenting data from ARTISTRY-3 at an upcoming medical conference.
Enrollment in ARTISTRY-6 and ARTISTRY-7 is ongoing:

Cohort 2 of ARTISTRY-6 is a potentially registrational, phase 2 trial evaluating nemvaleukin as a monotherapy in 90 mucosal melanoma patients. The company expects to report top-line data results from cohort 2 of ARTISTRY-6 in the first half of 2025.
Cohort 3 of ARTISTRY-6 is an open label extension of the trial that will evaluate the recommended phase 2 LFIV dosing regimen from ARTISTRY-3 as a monotherapy and in combination with pembrolizumab in approximately 50 patients with cutaneous melanoma. The company expects to report top-line data for monotherapy from cohort 3 of ARTISTRY-6 in the first half of 2025 and for the pembrolizumab combination in the second half of 2025.
ARTISTRY-7 is a potentially registrational, phase 3 trial evaluating nemvaleukin in combination with pembrolizumab compared to investigators’ choice chemotherapy in 448 patients with platinum-resistant ovarian cancer. Mural expects to report interim overall survival (OS) results based on approximately 75% of events in the first quarter of 2025 and final OS results in the second quarter of 2026.

Mural Oncology will present preclinical IL-18 and IL-12 data for the first time at the upcoming AACR (Free AACR Whitepaper) conference.

The company intends to nominate development candidates for these engineered IL-18 and IL-12 therapies later this year.
Financial Results for the Quarter Ended December 31, 2023

Cash Position: As of December 31, 2023, cash and cash equivalents were $270.9 million.

R&D Expenses: Research and development expenses were $42.2 million for the fourth quarter of 2023 and were primarily due to employee-related expenses and expenses related to ARTISTRY-7. These expenses included $5.6 million of non-cash, share-based compensation expenses.

G&A Expenses: General and administrative expenses were $16.3 million for the fourth quarter of 2023, including $9.7 million in non-cash, share-based compensation expenses.

Net Loss: Net loss was $59.5 million for the fourth quarter of 2023. This included $15.2 million non-cash, share-based compensation, of which approximately $11.7 million was driven by one-time charges related to the separation from Alkermes and conversion of employee equity during the fourth quarter of 2023.
Financial Guidance

The company’s cash resources are expected to fund its operations into the fourth quarter 2025.
After the spin out from Alkermes on November 15, 2023, the company incurred certain non-cash, share-based compensation, most of which was one-time in nature, and this is reflected in today’s reported results. Furthermore, the company’s 2023 financial results reflect carve-out financials until the date of the spin out. The company anticipates reporting lower operating expenses in the quarters going forward.
About Nemvaleukin
Nemvaleukin is a novel, engineered cytokine designed to leverage antitumor effects of the IL-2 pathway while mitigating its hallmark toxicities that limit its use. Nemvaleukin selectively binds to the intermediate-affinity IL-2 receptor (IL-2R) and is sterically occluded from binding to the high-affinity IL-2R. Because of this molecular design, nemvaleukin treatment leads to preferential expansion of antitumor CD8+ T cells and natural killer cells, with minimal expansion of immunosuppressive regulatory T cells. Nemvaleukin is currently being evaluated in two potentially registrational late-stage trials.

On March 26, 2024 Immunome, Inc. (Nasdaq: IMNM), a biotechnology company focused on developing first-in-class and best-in-class targeted cancer therapies, reported the successful completion of its purchase of AL102 and related drug candidate AL101 from Ayala Pharmaceuticals, Inc (Press release, Immunome, MAR 26, 2024, View Source [SID1234641448]).

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"AL102 is a high-quality asset that complements our existing pipeline of targeted cancer therapies," said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Immunome. "We believe that AL102 can establish a new standard of care for the treatment of desmoid tumors. In parallel, we are excited to advance our preclinical programs towards Phase 1 trials."

AL102 is an investigational small molecule gamma secretase inhibitor currently being evaluated in the randomized Phase 3 RINGSIDE international trial for the treatment of desmoid tumors – a debilitating soft tissue malignancy. AL102 is a potential once-daily oral treatment for desmoid tumors. Data from clinical trials have shown AL102 may be more effective in treating desmoid tumors than OGSIVEO (nirogacestat), which recently became the first treatment approved for desmoid tumors by the U.S. Food and Drug Administration in November 2023.