On October 17, 2023 Biomea Fusion, Inc. ("Biomea" or "the company") (Nasdaq: BMEA), a clinical-stage biopharmaceutical company dedicated to discovering and developing novel covalent small molecules to treat and improve the lives of patients with genetically defined cancers and metabolic diseases, reported that the first patient has been dosed in COVALENT-103, the company’s Phase I trial of BMF-500, an investigational covalent FLT3 inhibitor developed using the proprietary FUSIONTM System, in adult patients with relapsed or refractory acute leukemia (Press release, Biomea Fusion, OCT 17, 2023, View Source [SID1234636056]).

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"Despite several late stage and approved therapies targeting FLT3, the majority of patients with AML harboring FLT3 mutations have not achieved durable remissions. We believe that BMF-500, which is designed to have key attributes of covalency, potency, and selectivity, has the capacity to fully extinguish FLT3-driven disease and the potential to combine with other targeted therapies and standard-of-care agents," said Steve Morris, MD, Biomea’s Chief Development Officer.

"Today, we have taken another important step to bring novel covalent drug candidates into the clinic by exploring the potential of BMF-500, an investigational covalent FLT3 inhibitor, in treating adult patients with relapsed or refractory acute leukemia. BMF-500 is designed to be a potent molecule and is the second covalent inhibitor we have developed in-house, demonstrating the potential of the FUSIONTM platform and our team in bringing novel assets to the clinic. Beyond single agent studies of BMF-500 we are planning combination studies with various approved therapies and therapy candidates, including BMF-219, to explore the potential of this powerful dual-mechanistic approach to provide deeper and more durable treatment responses," said Thomas Butler, Biomea’s CEO and Chairman of the Board.

About COVALENT-103

COVALENT-103 is a multicenter, open-label, non-randomized trial seeking to evaluate the safety and efficacy of BMF-500, a twice daily oral treatment, in adult patients with relapsed or refractory acute leukemia with FMS-like tyrosine kinase 3 (FLT3) wild-type and FLT3 mutations. Additional information about the Phase I clinical trial of BMF-500 can be found at ClinicalTrials.gov using the identifier NCT05918692.

About BMF-500

BMF-500, an investigational, novel, orally bioavailable, highly potent and selective covalent small molecule inhibitor of FLT3, was discovered and developed in-house at Biomea using the company’s proprietary FUSION System and has demonstrated encouraging potential based on extensive preclinical studies. The kinase inhibitory profile of BMF-500 showed high target selectivity, suggesting the potential for reduced off-target liabilities. BMF-500 was designed to have a therapeutic profile to allow for combinations with standard of care and/or novel targeted agents like BMF-219, Biomea’s investigational covalent menin inhibitor currently in clinical development for solid and liquid tumors as well as diabetes.

Previous data presented at the 2022 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting showed BMF-500’s picomolar affinity for inhibition of activating FLT3 mutations, including FLT3-ITD and various tyrosine kinase domain (TKD) mutations. BMF-500 demonstrated multi-fold higher potency and increased cytotoxicity than the commercially available non-covalent FLT3 inhibitor gilteritinib. These data also showed complete tumor regression in mouse models of FLT3-ITD AML, with no tumor regrowth even after treatment cessation.

Data presented at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting exhibited the potential utility of combination strategies to achieve higher antileukemic cell killing with reduced concentrations of BMF-500 and BMF-219. Additionally, Biomea has shown the potential of combinatorial approaches of BMF-500 and BMF-219 with MEK and BCL2 blockade in other preclinical studies. These data provide preclinical evidence for combining pathway-specific inhibitors as a promising therapeutic strategy for further investigation in acute leukemia.

About FLT3 in AML

FLT3 is a receptor tyrosine kinase (RTK) that plays a central role in the survival, proliferation, and differentiation of immature blood cells. FLT3 gene mutations are common in patients with AML and are associated with a poor prognosis. Nearly 30% of AML patients have a FLT3 mutation, representing more than 6,000 incident patients in the U.S. each year. In addition, academic literature suggests that >50% of AML patients with an NPM1 mutation also harbor a FLT3 mutation. While FLT3-specific and pan-tyrosine kinase inhibitors are approved by the FDA across various lines of therapy in AML, these agents have produced relatively low rates of durable responses and overall survival remains an unmet need.

On October 17, 2023 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, reported that the Phase 3 RATIONALE 315 study met its dual primary endpoints of major pathological response (MPR) by Blinded Independent Pathology Review (BIPR) and event-free survival (EFS) by Blinded Independent Central Review (BICR), demonstrating statistically significant and clinically meaningful improvements in patients with resectable Stage II or IIIA NSCLC treated with tislelizumab in combination with chemotherapy before surgery and as a single agent after surgery versus neoadjuvant chemotherapy plus placebo followed by placebo after surgery (Press release, BeiGene, OCT 17, 2023, View Source [SID1234636055]). The tislelizumab plus chemotherapy regimen also showed a statistically significant improvement in pathological complete response (pCR), the key secondary endpoint, after neoadjuvant therapy versus chemotherapy. The MPR and pCR data will be featured as a late-breaking mini oral presentation on October 23 at 2:55 p.m. CEST at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 (Abstract #LBA58).

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In the study, 56.2% of NSCLC patients treated with tislelizumab in combination with chemotherapy before surgery achieved MPR, compared to 15.0% of patients treated with chemotherapy alone (difference: 41.1%; 95% CI: 33.2-49.1, p<0.0001). MPR is defined as less than 10% residual viable tumor after neoadjuvant therapy. Additionally, 40.7% of patients on the tislelizumab-based regimen achieved pCR, defined as no viable residual tumor after neoadjuvant therapy, compared to 5.7% of patients treated with chemotherapy alone (difference: 35.0%; 95% CI: 27.9-42.1, p<0.0001). Tislelizumab plus chemotherapy was generally well tolerated, with no new safety signals identified.

Additionally, at a recent prespecified interim analysis conducted by the independent data monitoring committee (IDMC), the tislelizumab-based regimen demonstrated a statistically significant improvement in EFS per assessment by BICR. Detailed results will be submitted for presentation at an upcoming medical conference.

"Lung cancer remains the most common type of cancer and the leading cause of cancer-related death worldwide. Despite available treatment options, rates of recurrence within five years remain unacceptably high, underscoring the need for innovative new neoadjuvant and adjuvant interventions to help improve patient outcomes," said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. "The data from RATIONALE 315 are encouraging and demonstrate that early integration of tislelizumab into the treatment paradigm may help both improve responses at the time of surgery and reduce the recurrence risk for these patients. These results add to the growing evidence suggesting the potential benefits of tislelizumab in treating patients with NSCLC."

About RATIONALE 315 (NCT04379635)

RATIONALE 315 is a randomized, double-blind, placebo-controlled, Phase 3 trial evaluating the efficacy and safety of neoadjuvant tislelizumab plus platinum-based doublet chemotherapy, followed by surgery and subsequent adjuvant tislelizumab, compared to placebo plus neoadjuvant platinum-based doublet chemotherapy followed by surgery and subsequent adjuvant placebo in patients with resectable Stage II or IIIA NSCLC. The primary endpoints are MPR rate by BIPR and EFS by BICR. The key secondary endpoint is pCR. Other secondary endpoints included overall survival (OS), objective response rate (ORR), disease-free survival (DFS) as assessed by BICR, and investigator assessed EFS. A total of 453 patients were enrolled and randomized 1:1 to receive either tislelizumab or placebo in combination with chemotherapy.

About Tislelizumab

Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody, with high affinity and binding specificity against PD-1, specifically designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors. In pre-clinical studies, binding to Fcγ receptors on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.i,ii,iii,iv

The tislelizumab development program encompasses 21 registration-enabling clinical trials in more than 30 countries and regions. To date, BeiGene has announced positive readouts from 10 Phase 3 pivotal studies across multiple tumor types and disease settings, such as NSCLC, small cell lung cancer, gastric cancer, ESCC, hepatocellular cancer, and nasopharyngeal cancer. More information on the clinical trial program for tislelizumab can be found at: View Source

Tislelizumab is currently under review by the U.S. Food and Drug Administration (FDA) and received approval by the European Commission for advanced or metastatic ESCC after prior chemotherapy. Additionally, the FDA recently accepted for review a Biologics License Application for tislelizumab as a first-line treatment for patients with unresectable, recurrent, locally advanced, or metastatic ESCC. The European Medicines Agency (EMA) is reviewing a marketing authorization application for tislelizumab as a treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy, and in combination with chemotherapy for previously untreated locally advanced or metastatic NSCLC.

Regulatory submissions for tislelizumab are also under review by authorities in Australia, Brazil, China, Korea, Israel, New Zealand, Singapore, Switzerland, and the U.K. Tislelizumab is approved for 11 indications in China and is the leading PD-1 inhibitor in the country.

On October 17, 2023 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, reported that the Phase 3 RATIONALE 315 study met its dual primary endpoints of major pathological response (MPR) by Blinded Independent Pathology Review (BIPR) and event-free survival (EFS) by Blinded Independent Central Review (BICR), demonstrating statistically significant and clinically meaningful improvements in patients with resectable Stage II or IIIA NSCLC treated with tislelizumab in combination with chemotherapy before surgery and as a single agent after surgery versus neoadjuvant chemotherapy plus placebo followed by placebo after surgery (Press release, BeiGene, OCT 17, 2023, View Source [SID1234636054]). The tislelizumab plus chemotherapy regimen also showed a statistically significant improvement in pathological complete response (pCR), the key secondary endpoint, after neoadjuvant therapy versus chemotherapy. The MPR and pCR data will be featured as a late-breaking mini oral presentation on October 23 at 2:55 p.m. CEST at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 (Abstract #LBA58).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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In the study, 56.2% of NSCLC patients treated with tislelizumab in combination with chemotherapy before surgery achieved MPR, compared to 15.0% of patients treated with chemotherapy alone (difference: 41.1%; 95% CI: 33.2-49.1, p<0.0001). MPR is defined as less than 10% residual viable tumor after neoadjuvant therapy. Additionally, 40.7% of patients on the tislelizumab-based regimen achieved pCR, defined as no viable residual tumor after neoadjuvant therapy, compared to 5.7% of patients treated with chemotherapy alone (difference: 35.0%; 95% CI: 27.9-42.1, p<0.0001). Tislelizumab plus chemotherapy was generally well tolerated, with no new safety signals identified.

Additionally, at a recent prespecified interim analysis conducted by the independent data monitoring committee (IDMC), the tislelizumab-based regimen demonstrated a statistically significant improvement in EFS per assessment by BICR. Detailed results will be submitted for presentation at an upcoming medical conference.

"Lung cancer remains the most common type of cancer and the leading cause of cancer-related death worldwide. Despite available treatment options, rates of recurrence within five years remain unacceptably high, underscoring the need for innovative new neoadjuvant and adjuvant interventions to help improve patient outcomes," said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. "The data from RATIONALE 315 are encouraging and demonstrate that early integration of tislelizumab into the treatment paradigm may help both improve responses at the time of surgery and reduce the recurrence risk for these patients. These results add to the growing evidence suggesting the potential benefits of tislelizumab in treating patients with NSCLC."

About RATIONALE 315 (NCT04379635)

RATIONALE 315 is a randomized, double-blind, placebo-controlled, Phase 3 trial evaluating the efficacy and safety of neoadjuvant tislelizumab plus platinum-based doublet chemotherapy, followed by surgery and subsequent adjuvant tislelizumab, compared to placebo plus neoadjuvant platinum-based doublet chemotherapy followed by surgery and subsequent adjuvant placebo in patients with resectable Stage II or IIIA NSCLC. The primary endpoints are MPR rate by BIPR and EFS by BICR. The key secondary endpoint is pCR. Other secondary endpoints included overall survival (OS), objective response rate (ORR), disease-free survival (DFS) as assessed by BICR, and investigator assessed EFS. A total of 453 patients were enrolled and randomized 1:1 to receive either tislelizumab or placebo in combination with chemotherapy.

About Tislelizumab

Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody, with high affinity and binding specificity against PD-1, specifically designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors. In pre-clinical studies, binding to Fcγ receptors on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.i,ii,iii,iv

The tislelizumab development program encompasses 21 registration-enabling clinical trials in more than 30 countries and regions. To date, BeiGene has announced positive readouts from 10 Phase 3 pivotal studies across multiple tumor types and disease settings, such as NSCLC, small cell lung cancer, gastric cancer, ESCC, hepatocellular cancer, and nasopharyngeal cancer. More information on the clinical trial program for tislelizumab can be found at: View Source

Tislelizumab is currently under review by the U.S. Food and Drug Administration (FDA) and received approval by the European Commission for advanced or metastatic ESCC after prior chemotherapy. Additionally, the FDA recently accepted for review a Biologics License Application for tislelizumab as a first-line treatment for patients with unresectable, recurrent, locally advanced, or metastatic ESCC. The European Medicines Agency (EMA) is reviewing a marketing authorization application for tislelizumab as a treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy, and in combination with chemotherapy for previously untreated locally advanced or metastatic NSCLC.

Regulatory submissions for tislelizumab are also under review by authorities in Australia, Brazil, China, Korea, Israel, New Zealand, Singapore, Switzerland, and the U.K. Tislelizumab is approved for 11 indications in China and is the leading PD-1 inhibitor in the country.

On October 17, 2023 Akoya Biosciences, Inc. (Nasdaq: AKYA) ("Akoya"), The Spatial Biology Company, reported that researchers from Akoya Biosciences and The University of Queensland’s Frazer Institute have comprehensively mapped the spatial proteome of head and neck squamous cell carcinoma (HNSCC) using ultrahigh-plex spatial phenotyping (Press release, Akoya Biosciences, OCT 17, 2023, View Source [SID1234636053]). Spatial phenotyping consists of whole-slide imaging of tissue sections at single-cell resolution to visualize and quantitate biomarker expression and reveal how cells interact and organize across the entire tissue landscape.

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The study, published in GEN Biotechnology in an article titled "Mapping the Spatial Proteome of Head and Neck Tumors: Key Immune Mediators and Metabolic Determinants in the Tumor Microenvironment" identified a high degree of intra- and inter-tumoral heterogeneity intrinsic to head and neck cancers and advances the understanding of the mechanistic basis of variable clinical responses.

The study analyzed head and neck cancer tissues from a patient with varying responses to immune checkpoint inhibitor (ICI) therapy. The analysis was conducted using a panel of 100+ biomarkers to measure key cancer hallmarks of tumor and immune biology with Akoya’s PhenoCycler-Fusion system. The PhenoCycler-Fusion is the fastest spatial biology solution available which enables rapid imaging of whole slides at single-cell resolution.

"This study represents a significant advancement in multiplexed imaging and, to our knowledge, is the first single-cell spatial proteomic dataset integrating information from immune, metabolic and stress pathways to provide a holistic view into the biology of heterogenous HNSCC tumors" noted Niyati Jhaveri, PhD, Head of Applications at Akoya Biosciences. "It provides an analytical framework for future spatial studies leveraging the resolution, plex and speed of Akoya’s solution to decipher the complex nuances of human tissues in homeostasis and disease."

A pivotal discovery in the study highlighted the divergent enrichment of functionally specialized immune cell subsets, as well as distinct metabolic and stress signatures organized within specific spatial domains in the tumor. This overarching observation in the paper underscored the existence of heterogeneous niches and competitive microenvironments, potentially serving as defining factors for clinical response and resistance.

"Immune checkpoint inhibitors have shown promising results in recurrent and metastatic cases of HNSCC," said Dr. Arutha Kulasinghe, of The University of Queensland’s Frazer Institute, leader of the Clinical-oMx Lab, and one of the paper’s authors. "Durable treatment results, however, are observed in only 30% of patients, indicating that new biomarkers for stratification of responders and non-responders are needed. The dichotomy of immune activation-induced death and tumor progression we observed in an individual patient’s tissue sample correlated with the partial response seen with ICI therapy. We believe that the approach outlined in this study will pave the way towards a new understanding of tumor microenvironment features associated with response and sensitivity to immune checkpoint inhibitor therapies in head and neck cancer and other solid malignancies."

On October 17, 2023 AIM ImmunoTech Inc. (NYSE American: AIM) ("AIM") reported that it has entered into an agreement with Azenova, LLC ("Azenova"), a professional business development (BD) consulting firm, to support efforts to partner AIM’s pipeline programs with a particular focus on the company’s lead asset, Ampligen, for the treatment of various malignant solid tumors (Press release, AIM ImmunoTech, OCT 17, 2023, View Source [SID1234636052]).

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Azenova has been engaged to assist AIM with its BD efforts with the goal of entering into a partnership, out-license or other transaction whereby a biopharmaceutical company takes on the further development and commercialization of Ampligen with the goal of maximizing value to AIM. This process may not result in any transaction and the company does not intend to disclose additional details unless and until it has entered into a definitive agreement.

"With our growing body of compelling clinical data, we believe Ampligen has significant potential to provide a therapeutic solution for a wide range of cancers, immune disorders and viral diseases. We believe the timing of our engagement with Azenova perfectly aligns their BD expertise with our strategic vision to maximize the opportunities for our Ampligen pipeline programs and to unlock significant value in the asset," commented AIM Chief Executive Officer Thomas K. Equels.

Azenova provides a wide range of services to support clients in their partnership, licensing, and other transactional activities. This includes determining opportunities for partnership (assets and technologies), identification and assessment of potential partners and leading all steps involved in engaging partners and establishing definitive BD transaction agreements. Azenova’s principals, Jeff Southerton, PhD, MBA, and Stacy Evans, MD, MBA, have more than 50 years of combined BD experience in the biopharmaceutical industry leading transactions across a wide range of deal structures in multiple therapeutic areas, including significant experience in oncology.

"With AIM’s emerging data showing the promise of Ampligen as a therapeutic across a pipeline of malignant and often end-stage solid tumors, Azenova is excited to be formally engaged by AIM to assist the company with materializing a potential value inflecting BD transaction for the company," commented founder of Azenova, Jeff Southerton.