On December 16, 2024 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported the development candidate nomination of IDE251, a potential first-in-class KAT6/7 dual inhibitor (Press release, Ideaya Biosciences, DEC 16, 2024, View Source [SID1234649145]).

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"We are pleased to announce the nomination of IDE251 as our third development candidate this quarter and 8th development candidate in our precision medicine oncology pipeline. IDE251 has a potential first-in-class product profile and selectively inhibits two epigenetic modulators, KAT6 and KAT7, and based on the preclinical profile we believe there is an opportunity for an enriched response in 8p11 amplified cancers, which occur in 15% of breast cancers patients and in up to 17.5% in squamous NSCLC," said Yujiro S. Hata, President and Chief Executive Officer of IDEAYA Biosciences.

"IDE251 is a promising potential first-in-class molecule designed to selectively target both KAT6 and KAT7 while sparing other structurally similar KAT family members. KAT6 and KAT7 are mechanistically intertwined epigenetic modulators of cell identity and lineage commitment programs corrupted by oncogenic transformation. Dual KAT6/7 inhibition with IDE251 delivers robust and durable anti-tumor activity, superior to KAT6 inhibition alone, in preclinical tumor models with 8p11 amplifications as well as in biomarker selected indications dependent upon lineage-specific transcription factor activity. IND-enabling studies are progressing as planned and we are targeting to bring this program to the clinic next year," commented Michael White, Ph.D., Chief Scientific Officer, IDEAYA Biosciences.

IDE251 is an equipotent, highly selective, small molecule dual inhibitor of the lysine acetyltransferase (KAT) 6 and 7, both of which have been shown to support cancer cell survival. IND-enabling studies to support the potential clinical evaluation of IDE251 monotherapy in patients with breast and lung cancers with 8p11 amplification are ongoing, as well as additional opportunities in the setting of lineage addiction. Based on IDEAYA’s biomarker evaluation, 8p11 amplification prevalence is projected to be approximately 15% in breast cancer and 17.5% in squamous NSCLC.

IDEAYA is targeting an Investigational New Drug (IND) submission to the U.S. Food and Drug Administration (FDA) in 2025 for IDE251, subject to satisfactory completion of ongoing preclinical and IND-enabling studies.

On December 16, 2024 Microbio Co., Ltd. (4128) reported encouraging results from an exploratory clinical trial of MS-20 combined with Keytruda (pembrolizumab) in stage IIIb/IV non-small cell lung cancer (NSCLC) (Press release, Microbio Co, DEC 16, 2024, View Source [SID1234649143]). The trial showed a threefold increase in the objective response rate (ORR) for the MS-20-Keytruda group (75%) compared to Keytruda alone (25%). Additionally, the median progression-free survival (PFS) for MS-20 patients improved from 4.5 months to over 12 months, with a complete response (CR) rate of 12.5%.

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Enhancing Immunotherapy with MS-20

MS-20, developed by Microbio, is a microbiome-based postbiotic designed to improve cancer immunotherapy by modulating the gut microbiome. "The results support MS-20’s potential to reshape the microbiome and enhance Keytruda’s effectiveness in treating advanced NSCLC," said Dr. Wan-Jiun Chen, Executive VP of Research & Development at Microbio. "Currently, hundreds of ongoing trials are aimed to find novel therapeutic agents for improving the efficacy of cancer immunotherapy, and this proof-of-concept trial supports the use of MS-20 in such application."

This randomized, double-blind, placebo-controlled trial involved 15 patients, with 12 analyzed in the modified intent-to-treat (mITT) population (ClinicalTrials.gov ID: NCT04909034). Of the 8 patients receiving MS-20 and Keytruda, 6 (75% ORR) responded positively, including 1 with an ongoing CR lasting over 22 months and 5 with partial responses (PR). In contrast, only 1 of 4 patients in the placebo and Keytruda group showed a PR (25% ORR). The median PFS for the MS-20-Keytruda group was over 12 months, compared to 4.5 months in the placebo group.

Scientific Insights and Next Steps

Preclinical research published in Gut Microbes earlier this year supported these findings, showing that MS-20 enhances immune responses by increasing effector CD8 T cells in the tumor microenvironment. Microbio plans to use these results to pursue global collaborations and further its microbiome-based cancer immunotherapy platform.

On December 16, 2024 SK Biopharmaceuticals, a biotech company focusing on the research, development and commercialization of treatments for disorders of the central nervous system and oncology worldwide, reported a research collaboration agreement with ProEn Therapeutics, a biotech company dedicated to advancing oncology treatments, to further extend its oncology research capability and expand its pipeline of radiopharmaceutical therapies (RPT) (Press release, SK biopharmaceuticals, DEC 16, 2024, View Source [SID1234649142]).

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Under this agreement, both sides seek to advance up to two preclinical candidates for the development of novel radiopharmaceutical drugs by 2027 – the year when SK Biopharmaceuticals aims to become a global leading RPT player, via strengthened internal and external resources.

This joint research builds on a series of SK Biopharmaceuticals’ global strategic partnerships, including the in-licensing of a radiopharmaceutical compound, and a supply agreement to secure actinium-225, an alpha-particle emitting radioisotope, since the company unveiled its "RPT Roadmap" to gain a competitive edge in the rapidly growing field of nuclear medicine.

SK Biopharmaceuticals will leverage ProEn Therapeutics’ ArtBody platform, a dual-target binding technology that incorporates small proteins[1] to identify and target specific tumor antigens – enhancing tumor selectivity – for the development of potential cancer treatments, while minimizing damage to healthy tissues. ArtBody, which has intrinsic advantages of high stability and structural robustness, can be mass-produced using bacteria, making it ideal for industrial applications.

Il-Han Lee, Chief Executive Officer of ProEn Therapeutics, said, "We are pleased to enter this joint research, and positive that the ArtBody platform will generate synergy with and complement SK Biopharmaceuticals’ radiopharmaceutical therapy business. ProEn Therapeutics will push to produce the best possible outcome that can meet not only the two companies’ expectations, but also patients’ needs."

Donghoon Lee, Chief Executive Officer of SK Biopharmaceuticals, said, "This collaboration with ProEn Therapeutics is significant as the platform technology will help overcome the limitations of existing therapies. We will aim to develop more effective, safer treatments, while leading global RPT research and development efforts."

On December 16, 2024 Medigene AG (Medigene or the "Company", FSE: MDG1, Prime Standard), an oncology platform company focused on the research and development of T cell receptor (TCR)-guided therapies for the treatment of cancer, reported the submission of its Clinical Trial Application (CTA) to the European Medicines Agency (EMA) for its MDG1015 program for the treatment of advanced gastric cancer, ovarian cancer, myxoid/round cell liposarcoma and synovial sarcoma in the phase 1 clinical trial EPITOME1015-I (Press release, MediGene, DEC 16, 2024, View Source [SID1234649140]). The CTA submission follows the Company’s receipt of the U.S. Food and Drug Administration (FDA) clearance of the Investigational New Drug (IND) application for EPITOME1015-I earlier this year.

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EPITOME1015-I consists of a dose escalation followed by an expansion segment and aims to assess safety, feasibility and preliminary efficacy of MDG1015 in multiple solid tumor indications.

"We are delighted to announce the submission of the CTA for MDG1015. This milestone is a significant step forward in the development of our differentiated cell therapy. The extensive experience of European clinical sites provides an ideal environment for this trial. The robust infrastructure and strong network of clinical investigators will facilitate efficient patient recruitment once funding is secured, which will enable us to then rapidly progress toward bringing this potentially transformative therapy to patients in need," said Selwyn Ho, CEO at Medigene AG.

MDG1015 is a first-in-class, third generation T cell receptor engineered T cell (TCR-T) therapy targeting the cancer-testis antigen New York esophageal squamous cell carcinoma 1 / L Antigen Family Member-1a (NY-ESO-1/LAGE-1a) in the context of human leukocyte antigen (HLA)-A*02 with a natural and optimal affinity 3S (specific, sensitive and safe) TCR. The TCR-T cells are further armored and enhanced by the addition of the proprietary costimulatory switch protein (CSP) PD1-41BB and have demonstrated significantly enhanced anti-tumor activities against tumor cells expressing varying levels of PD-L1, one of the most immunosuppressive signals emanating from the solid tumor microenvironment. Importantly, compared to first generation TCR-T therapies, MDG1015 will be manufactured with a short, 6-day cell expansion period, leading to younger, fitter cells, with the potential for a markedly reduced number of cells required during dosing and a shorter vein-to-vein time for patients of approximately 20 days. This has also resulted in a drug product with an almost pure CD8+ population and with a very high proportion of cells with stemness-like qualities (~95%) that could lead to improved durability of response, greater efficacy and reduced adverse events.

On December 16, 2024 Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a biopharmaceutical company focused on advancing innovative immuno-oncology technologies addressing hard to treat cancers, reported it has extended its previously announced Research Funding Agreement (the "Agreement") with the University of Virginia ("UVA") to advance the development of its systemic DNase program through 2025 (Press release, Xenetic Biosciences, DEC 16, 2024, View Source [SID1234649139]).

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Xenetic’s DNase-based oncology platform is designed to target neutrophil extracellular traps (NETs), which are weblike structures composed of extracellular chromatin coated with histones and other proteins. In cancer, NETs are expelled by activated neutrophils into the tumor microenvironment (TME) and blood, thereby promoting cancer spread, local and systemic immunosuppression, as well as cancer-associated thrombosis. Reduction of NETs burden via application of Xenetic’s proprietary recombinant human DNase I has been shown to improve efficacy of immunotherapy, adoptive cell therapy and chemotherapy in preclinical animal models.

"Allan Tsung, MD, and the team at UVA continue to be valued partners and we are pleased with the progress under the Agreement in evaluating the potential addition of DNase to available treatment options in areas of significant unmet need. The preclinical and translational data that UVA has accumulated under the initial Scope of Work to the Agreement further strengthens the scientific rationale for investigating combinations of DNase I with immunotherapies and chemotherapies. In the next phase of this partnership, UVA will continue to investigate combinations of DNase I with immunotherapies in models of primary and metastatic colorectal cancer. As a surgical oncologist and scientist, Dr. Tsung is internationally recognized for leading substantial research on the role of NETs in tumor growth, metastasis, and resistance to existing cancer therapies and we look forward to leveraging that expertise as we advance our technology toward the clinic," commented Reid P. Bissonnette, Ph.D., Executive Consultant for Translational Research and Development of Xenetic.

Under the terms of the Agreement, in addition to advancing Xenetic’s existing intellectual property, Xenetic has an option to acquire an exclusive license to any new intellectual property arising from the DNase research program. Allan Tsung, MD, a member of the Company’s Scientific Advisory Board and Chair of the Department of Surgery at the UVA School of Medicine, will continue to oversee the research conducted under the Agreement. Xenetic is working toward its planned first-in-human study to evaluate DNase combined with immune checkpoint inhibitors or chemotherapy.