On April 22, 2025 Ensem Therapeutics, Inc. (ENSEM) reported the clearance of its Investigational New Drug (IND) application by the U.S. Food and Drug Administration (FDA) for ETX-636, a potential best-in-class novel allosteric pan-mutant-selective PI3Kα inhibitor and degrader, with its first-in-human study anticipated in the second quarter of 2025 (Press release, ENSEM Therapeutics, APR 22, 2025, View Source [SID1234652031]). In addition, ENSEM will present preclinical data on April 28th at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Annual Meeting in Chicago, Illinois, supporting a differentiated profile of ETX-636 and its potential to deliver clinical benefit to patients with tumors harboring activating PI3Kα mutations.

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Mutant PI3Kα is a key and frequent oncogenic driver across a broad spectrum of cancers, including up to 40 percent of hormone receptor-positive (HR+) /HER2-negative advanced breast cancers. However, wildtype PI3Kα is central to glucose homeostasis, and ATP-binding-site inhibitors target both mutant and wildtype PI3Kα, resulting in hyperglycemia which limits the clinical utility of these therapeutics.

"Targeting mutant PI3Kα within tumors while sparing wildtype PI3Kα in normal tissues represents a significant clinical challenge, which ETX-636 overcomes. The IND clearance is an important milestone for the company, and we are laser-focused on driving ETX-636 through clinical development," said Shengfang Jin, PhD, CEO and Co-Founder of ENSEM.

Dr. Jin noted that ETX-636 is the second novel ENSEM compound entering clinical development. ETX-197, an oral selective CDK2 inhibitor licensed to BeOne and being developed as BG-68501, is currently undergoing Phase 1 clinical development in advanced or metastatic solid tumors associated with CDK2 dependency.

Jeffery Kutok, MD, PhD, ENSEM’s Chief Scientific Officer, added, "ETX-636 is a potent pan mutant-specific allosteric PI3Kα inhibitor and degrader, which differentiates it from other compounds in its class. We are excited to evaluate ETX-636’s therapeutic potential in patients in our upcoming clinical trial. ENSEM also eagerly anticipates INDs for additional pipeline programs in 2026."

The initial first-in-human, Phase 1/2 study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of ETX-636 in participants with advanced solid tumors harboring a PI3Kα mutation. ETX-636 will be administered alone and in combination with fulvestrant, a selective estrogen receptor degrader approved for the treatment of advanced hormone receptor HR+/HER2- breast cancer.

Poster Details

Title: ETX-636, a novel allosteric pan-mutant-selective PI3Kα dual inhibitor and degrader with best-in-class potential
Poster ID: 1659
Sessions: Experimental and Molecular Therapeutics – Degraders and Glues 2
Date/Time: Monday, April 28, 2025, from 9am-12pm CT
Location: Poster session 18, Board 19
About ETX-636
ETX-636 was designed to optimally fit into a specific allosteric binding site in p110α, the catalytic subunit of PI3Kα. This allosteric binding site has been shown to selectively inhibit multiple activating mutant forms of PI3Kα, including hotspot kinase and helical domain PI3Kα mutants, while sparing wildtype PI3Kα. The selectivity of ETX-636 for mutant PI3Kα greatly reduces the risk for hyperglycemia and other wildtype PI3Kα-related adverse events compared to non-mutant selective PI3Kα inhibitors. In addition to its potent inhibitory effect on mutant PI3Kα catalytic activity, ETX-636 also leads to proteasome-dependent degradation of mutant PI3Kα, while sparing wildtype protein (a feature not seen with other pan-mutant allosteric inhibitors). This dual mechanism of action results in deep and durable pathway inhibition and induces concordant tumor regression in kinase and helical domain PI3Kα-mutant breast cancer xenograft models as monotherapy and in combination with fulvestrant. In preclinical toxicology studies, blood glucose levels after dosing in multiple species indicate that ETX-636 did not disrupt glucose homeostasis at predicted human efficacious doses.

On April 22, 2025 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:​HCM; HKEX:​13) reported that it has completed enrollment of the registration phase of its Phase II trial of savolitinib in gastric cancer patients with MET amplification (Press release, HUTCHMED, APR 22, 2025, View Source [SID1234652015]).

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This clinical trial is a single-arm, multi-center, open-label, Phase II registration study to evaluate the efficacy, safety and tolerability of savolitinib in treating gastric cancer or gastroesophageal junction ("GEJ") adenocarcinoma patients with MET amplification. Primary endpoint is objective response rate ("ORR") evaluated by the Independent Review Committee ("IRC") (RECIST 1.1). Secondary endpoints include progression free survival (PFS) and incidence of various adverse events (AE), among others. A total of 64 patients have been enrolled in the study. Further details may be found at clinicaltrials.gov using identifier NCT04923932.

As reported at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, interim results from the study showed a 45% ORR confirmed by IRC and a 50% ORR in patients with high MET gene copy number. 4-month duration of response (DOR) rate was 85.7% with median follow up time of 5.5 months. The most common grade 3 or higher treatment-related adverse events ("TRAE") (≥ 5%) were platelet count decreased, hypersensitivity, anemia, neutropenia and hepatic function abnormal. Only one patient discontinued treatment due to grade 4 liver function abnormal (TRAE) and no patient died due to TRAE.

The China’s National Medical Products Administration ("NMPA") has granted Breakthrough Therapy Designation to savolitinib for the treatment of locally advanced or metastatic gastric cancer or GEJ adenocarcinoma patients with MET amplification who have failed at least two lines of standard therapies. If positive, HUTCHMED may initiate plans to apply for marketing authorization of savolitinib for gastric cancer in China in late 2025.

About Gastric Cancer with MET Amplification

MET-driven gastric cancer has a very poor prognosis.1 It is estimated that MET amplification accounts for approximately 4-6% of gastric cancer patients.2,3 The annual incidence of MET amplification gastric cancer is estimated to be approximately 18,000 in China.4 The ongoing registration trial follows multiple Phase II studies conducted in Asia to study savolitinib in MET-driven gastric cancer patients, including VIKTORY.2 The VIKTORY study reported a 50% ORR in patients whose tumors harbored MET amplification and were treated with savolitinib monotherapy.

About Savolitinib

Savolitinib is an oral, potent, and highly selective MET tyrosine kinase inhibitor ("TKI") being jointly developed by AstraZeneca and HUTCHMED and commercialized by AstraZeneca. MET is a tyrosine kinase receptor that has an essential role in normal cell development.5 Savolitinib blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.

Savolitinib is approved in China and is marketed under the brand name ORPATHYS by our partner, AstraZeneca, for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping alteration, representing the first selective MET inhibitor approved in China. It has been included in the National Reimbursement Drug List of China (NRDL) since March 2023.

It is currently under clinical development for multiple tumor types, including lung, kidney, and gastric cancers as a single treatment and in combination with other medicines.

On April 22, 2025 Charles River Laboratories International, Inc. (NYSE: CRL), ahead of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, IL, reported updates to its comprehensive portfolio of products and services supporting the discovery and development of novel oncology drugs (Press release, Charles River Laboratories, APR 22, 2025, View Source [SID1234652032]). Based solely on projected population growth, the number of cancer cases is predicted to increase to 35 million by 2050, and approximately 1 in 5 individuals will develop cancer in their lifetime.

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"Having worked on over 80 percent of the FDA-approved cancer therapies over the last five years, Charles River has a well-established track record of delivering innovative solutions for oncology researchers," said Julia Schueler, DVM, PhD, Therapeutic Area Lead, Oncology, Charles River. "We are consistently looking for ways to leverage new technologies and techniques to enhance our ability to deliver life-changing therapeutics to patients."

Developing a Fully Human Platform
Across several modalities, Charles River is developing and implementing humanized platforms to promote a more effective, translatable way of identifying human-specific drug targets and disease mechanisms, as well as treatments for individual patients. These methodologies include:

3D Tumoroids
Patient-derived xenograft (PDX) models are an increasingly common tool drug developers use when evaluating their new therapies, particularly immunotherapies. Charles River researchers have developed PDX-derived organoids, or tumoroids, which are self-organized 3D cell cultures that aim to mimic the structure, function, and cellular complexity of human organs, making them, in some ways, more translatable than animals.

Julia Schueler is presenting on PDX-derived breast cancer tumoroids on Sunday, April 27, 2025, at 2:00 p.m. and on establishing tumoroids from PDX tissue for in vitro applications on Tuesday, April 29, 2025, at 2:00 p.m.

2D Tumor Killing Assays
Charles River has a range of immune-mediated tumor-killing assays, including cytotoxic T-cell assays and natural killer (NK) cell assays. These assays are analyzed using flow cytometry and live cell imaging with IncuCyte. IncuCyte-based assays quantify the number of viable target cells and can be multiplexed with an apoptotic readout. The selection of target and effector cells can be tailored to the anticipated mechanism of action by selecting from a panel of validated target cell lines.

Ina Rohleff is presenting a comparison of NK-92MI cell line vs. primary NK cells derived from peripheral mononuclear blood cells on Wednesday, April 30, 2025, at 9:00 a.m.

Tumor Microenvironment
Leveraging knowledge of the tumor microenvironment (TME), Charles River is able to target different components of the TME that promote tumor growth and metastasis through anti-tumor immune suppression.

Louise Brackenbury is presenting on leveraging the tumor microenvironment for candidate vaccine screening on Tuesday, April 29, 2025, at 2:00 p.m.

Through a partnership with Cypre, Charles River clients can access Cypre’s 3D tumor models to predict therapeutic efficacy and mechanism of action in an accurate tumor microenvironment model. Utilizing Cypre’s patented 3D hydrogel technology and proprietary methods that synergize with Charles River’s PDX tumor model collection, the platform recreates the tumor microenvironment and enables predictive screening of innovative immune-oncology compounds.

Humanized Models
Charles River offers a comprehensive line of humanized mice models to support researchers in replicating human immune interactions and therapeutics responses in controlled, in vivo environments. Charles River has expanded its offering of humanized mouse models by introducing two new PBMC models that reduce the onset of graft versus host disease (GvHD). Along those lines, the Company offers a PBMC Select Humanization Kit, giving researchers the ability to leverage pre-qualified PMBCs and engraft specific NCG mice for improved study flexibility.

Eva Oswald is presenting on a PDX biobank in humanized mice and Steve Bronson is presenting on PMBC-humanized, MHC-deficient NCG mice that support human tumor xenographs without rapid onset GvHD, both beginning on Monday, April 28, 2025, at 9:00 a.m.

Leveraging AI in Oncology
The influence of artificial intelligence (AI) and machine learning (ML) tools is beginning to impact how researchers analyze cancer research data. Charles River recently collaborated with Revvity, Inc., to determine the feasibility of automatic organ volumetric analysis from 3D ultrasound images of mice using deep learning. Segmentation of 3D imaging data is labor intensive and measurements derived from human-annotated data are prone to inter-user variability and user error. To address these challenges, an AI model was generated to segment spleens from diverse 3D ultrasound images taken from several in vivo models.

David Harris is presenting on longitudinal ultrasound imaging as a novel pharmacodynamic marker of graft versus host disease progression in mice with Revvity on Monday, April 28, 2025, at 2:00 p.m.

Charles River is also partnering with Aitia to develop virtual control groups (VCGs) supported by Charles River’s extensive and well-categorized library of PDX data. VCGs, combined with insights from PDXs, allow researchers to predict tumor evolution over time in a specific model, reducing the need for control animals in future experiments and supporting the principles of the 3Rs (Replacement, Reduction, and Refinement).

Global Support for the RACE Act
As part of our broad oncology portfolio, Charles River, via the ITCC-P4 consortium, offers over 200 annotated, well-characterized, and Research to Accelerate Cures and Equity (RACE) for Children Act-compliant pediatric PDX models to accelerate time to clinic. These are critical models for research, as the U.S. Food and Drug Administration’s RACE Act requires nearly all oncology drugs to be tested for pediatric indications before approval.

"Globally, 400,000 children and adolescents develop cancer each year, and approximately one in four cannot be cured with currently available therapies," added Schueler. "Combined with our comprehensive portfolio of oncology drug discovery and development services, we are positioned to assess the safety and efficacy of new oncology treatments, specifically in this critically important patient population."

Charles River is proud to sponsor the Richi Childhood Cancer Foundation at AACR (Free AACR Whitepaper) 2025. Attendees can stop at Booth #1642 to learn how to actively support the mission to connect, support, and uplift children, youth with cancer, and survivors through the Richi House.

AACR Annual Meeting 2025: Transforming Oncology Drug Development
Charles River’s team has the capability to optimize workflows and maximize success across modalities including small and large molecules, cell and gene therapies, vaccines, and combination therapies. Charles River also recently launched an alliance with NJ Bio to optimize the development and manufacturing of antibody drug conjugates (ADCs.)

During the show, Charles River is presenting a Spotlight on HER2 therapy development on Monday, April 28, 2025 from 3:00-4:00 p.m. Visit Charles River during AACR (Free AACR Whitepaper) at Booth #1642 during the show, and visit criver.com to schedule a meeting, view a full schedule of activities, and explore oncology resources.

On April 22, 2025 OncoSpherix, a biotech company pioneering innovative therapies for tumor hypoxia, reported its participation in Portal Innovations’ ‘Rising Stars in Oncology’ event during the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago (Press release, OncoSpherix, APR 22, 2025, View Source [SID1234652016]).

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The event, taking place on April 25, 2025, will spotlight emerging biotech companies developing breakthrough cancer treatments. OncoSpherix will present its latest advancements in targeting the hypoxia-inducible factor 1 (HIF-1) pathway, thereby disrupting essential processes that fuel tumor growth, metastasis, and resistance to therapy.

"We are honored to be recognized as a rising innovator in oncology," said OncoSpherix CEO, Margaret Offermann, MD, PhD. "This event provides a unique platform to share our mission and engage with leading investors, researchers, and industry experts."

The ‘Rising Stars in Oncology’ event, hosted by Portal Innovations, brings together cutting-edge biotech companies, venture investors, and scientific leaders to showcase promising advancements in cancer therapeutics.

For more details on the event, visit: View Source

On April 22, 2025 OS Therapies (NYSE-A: OSTX) ("OS Therapies" or "the Company"), a clinical-stage immunotherapy and Antibody Drug Conjugate (ADC) biopharmaceutical company, reported that the US Food & Drug Administration ("FDA") granted the Company’s meeting request to gain alignment on the surrogate endpoint to support Breakthrough Therapy Designation & Accelerated Approval of OST-HER2 in the Prevention of Recurrence of Fully Resected, Lung Metastatic Osteosarcoma (Press release, OS Therapies, APR 22, 2025, View Source [SID1234652033]). FDA granted a written response-only meeting and confirmed that its response would be received by mid-June 2025, in time for the Company to present the statistical analysis as part of the keynote presentation closing out major osteosarcoma conference MIB Factor on June 28, 2025 at 3:30pm MDT.

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"We are pleased that FDA agreed to the requested meeting forward and work within the timelines of the meeting type requested so that we would be able to share our analysis with the patient and physician communities that will be represented at MIB Factor in late June," said Robert Petit, Chief Medical & Scientific Officer of OS Therapies.

"We remain on track for an early third quarter submission and are hopeful to receive approval by year-end 2025 in order to bring this life saving treatment to patients in early 2026," said Paul Romness, CEO of OS Therapies.

OST-HER2 has received Rare Pediatric Disease Designation (RPDD) for osteosarcoma from the US FDA, and if it receives a conditional BLA via Accelerated Review prior to September 30, 2026, it will become eligible to receive a Priority Review Voucher (PRV) that it intends to immediately sell. The most recent PRV sale, valued at $150 million, occurred in February 2025.

The osteosarcoma treatment market was estimated at $1.2 billion in 2022 according to Data Bridge Market Research. Approximately 50% of patients are diagnosed with a lung metastasis at some point following surgical resection and chemotherapy. 3-year survival rates in patients who were not diagnosed with a metastasis are 59%. 3-year survival rates in patients who were diagnosed with pulmonary metastasis were 30%. The Company believes the market opportunity for OST-HER2 in the prevention of lung metastases is over $500 million.

OST-HER2, an immunotherapy for osteosarcoma using a HER2 bioengineered form of the bacteria Listeria monocytogenes to trigger a strong immune response against cancer cells expressing HER2, is being featured in the upcoming movie Shelter Me: The Cancer Pioneers. The movie offers a look into canine comparative oncology, a field that compares treatment of cancers in dogs to those in people and covers developing treatments for rare forms of cancer. A trailer for the movie is available here. The movie will air live nationally on PBS and be available via streaming on PBS’ website in early May 2025.