On October 9, 2025 Vividion Therapeutics, Inc. (Vividion), a clinical-stage biopharmaceutical company, and a wholly owned and independently operated subsidiary of Bayer AG, reported the publication of a manuscript in Science describing the discovery and preclinical characterization of small molecules that inhibit RAS-dependent PI3Kα oncogenic signaling by specifically blocking the interaction between RAS and PI3Kα, without disrupting homeostatic signaling (Press release, Vividion Therapeutics, OCT 9, 2025, View Source [SID1234656539]).

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The article, "Covalent inhibitors of the PI3Kα RAS binding domain impair tumor growth driven by RAS and HER2" (Klebba et al., Science, Advanced Online Publication, October 2025), demonstrates the promising potential of RAS-PI3Kα inhibitors as treatments for RAS-driven cancers.

"Vividion’s RAS-PI3Kα inhibitors exemplify a fundamentally new way of addressing RAS-dependent cancers, offering the potential to disrupt one of the most important drivers of human malignancy without the dose-limiting toxicities that have historically hindered similar efforts," said Aleksandra Rizo, M.D., Ph.D., Chief Executive Officer of Vividion. "Now in Phase I, this program underscores our ability to convert deep scientific expertise into therapeutic candidates that could help patients in need of better treatment options."

RAS mutations, which occur in about 20% of human cancers, can lead to uncontrolled cellular growth through the activation of both the MAPK and PI3K pathways. Preclinical models have shown that simultaneously targeting these two pathways can effectively inhibit disease progression, but this approach has been hampered by dose-limiting toxicities. Vividion researchers identified multiple covalent compounds which were validated, in collaboration with the Francis Crick Institute, as selective inhibitors of RAS activation of the PI3Kα pathway. In vivo studies showed one of the compounds successfully inhibited tumor growth without disrupting the pathway’s normal downstream activity, representing a promising new approach for cancer therapy. In addition to blocking RAS-driven activation of PI3Kα, the compounds were also found to block HER2-mediated activation through the same binding site – a previously unrecognized function that could extend their potential to treat a wider range of tumors.

"We’ve been exploring how to stop RAS interactions with cell growth pathways for many years, but side effects have held back the development of treatments," said Julian Downward, Ph.D., Principal Group Leader of the Oncogene Biology Laboratory at the Crick Institute. "Our collaborative effort has overcome this challenge by targeting the PI3Kα and RAS interaction specifically — highlighting the power of understanding chemistry and fundamental biology in designing better cancer therapies."

Taken together, these data represent a new class of covalent inhibitors that can be used to selectively disrupt the RAS-PI3Kα interaction, potentially preventing the growth of RAS-driven tumors in patients without impacting PI3K’s normal role in glucose homeostasis.

"Vividion’s pioneering covalent-first chemoproteomics approach enabled us to discover multiple classes of PI3Kα selective small molecules, including both inhibitors as well as enhancers of RAS interaction, with potential applications in cancer and beyond," said Matt Patricelli, Ph.D., Chief Scientific Officer of Vividion. "Our approach continues to reveal unexpected mechanisms of action targeting well-known targets and cellular pathways, expanding our understanding of cancer dependencies and pointing to new therapeutic opportunities."

On October 9, 2025 Shanghai Henlius Biotech, Inc. (2696.HK) reported that its self-developed innovative anti-PD-1 monoclonal antibody, HANSIZHUANG (serplulimab, Hetronifly in Europe), in combination with chemotherapy for the neoadjuvant/adjuvant monotherapy treatment of gastric cancer, has met the primary endpoint of Event-Free Survival (EFS) in an interim analysis of its phase 3 clinical study (ASTRUM-006) (Press release, Shanghai Henlius Biotech, OCT 9, 2025, View Source [SID1234656542]). This outcome represents a breakthrough, making it the world-first regimen to replace adjuvant chemotherapy with mono-immunotherapy in the perioperative treatment of gastric cancer.

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ASTRUM-006 is a randomized, double-blind, multi-centre phase 3 clinical study among patients with early-stage gastric cancer, aiming to compare the efficacy and safety of HANSIZHUANG or placebo in combination with chemotherapy as a neoadjuvant/adjuvant monotherapy treatment for patients with early-stage gastric cancer. According to the interim analysis conducted by the Independent Data Monitoring Committee (IDMC), the trial met its predefined efficacy criteria. Compared with placebo plus chemotherapy, HANSIZHUANG plus chemotherapy significantly prolonged EFS and achieved a more than threefold higher pathological complete response (pCR) rate compared with the control arm, with a significant reduction in the risk of recurrence. Furthermore, the combination regimen demonstrated a favorable safety profile, with no new safety signals identified. Based on this positive outcome, the IDMC has recommended an early NDA submission.

Professor Jiafu Ji from Beijing Cancer Hospital, a leading principal investigator of the ASTRUM-006 study, commented: "Surgery is the cornerstone of gastric cancer treatment, and perioperative therapy is critical to long-term survival. This study is the first to confirm the feasibility of replacing adjuvant chemotherapy with mono-immunotherapy in the postoperative setting. It not only opens a new path to consolidate surgical outcomes and reduce recurrence risk, but also paves the way for innovation in clinical practice."

Professor Lin Shen from Beijing Cancer Hospital, a leading principal investigator of the ASTRUM-006 study, stated: "The positive results from this study confirm the significant potential of serplulimab in the perioperative setting for gastric cancer. The innovative exploration of a ‘chemotherapy-free, mono-immunotherapy’ regimen during the adjuvant phase tangibly improves patients’ quality of life, offering a new approach for optimizing clinical strategies."

Dr. Jason Zhu, Executive Director, and Chief Executive Officer of Henlius, said: "Gastrointestinal (GI) cancer is a core therapeutic area of dedicated focus for Henlius. The successful achievement of the primary endpoint in the phase 3 perioperative study of HANSIZHUANG in gastric cancer marks a pivotal breakthrough for the company. We are committed to actively advancing the translation of these findings into clinical practice, with the goal of bringing benefits to patients at the earliest opportunity. Concurrently, we will continue to accelerate the in-depth exploration and broad application of more innovative therapies."

Pioneering New Pathways in Gastric Cancer Perioperative Care

Gastric cancer represents a major global public health challenge. According to the latest GLOBOCAN statistics, there were approximately 969,000 new cases and 660,000 deaths worldwide in 2022, ranking it fifth in both incidence and mortality among all cancers. [1] While radical surgery remains the primary treatment modality, optimizing perioperative (neoadjuvant/adjuvant) strategies has become pivotal to improving long-term patient survival. [2]

In recent years, immunotherapy is fundamentally reshaping the treatment landscape for gastric cancer. While the combination of immunotherapy and chemotherapy has become the first-line standard for advanced disease, its potential in the perioperative setting is now a major focus of clinical investigation, with multiple trials underway to evaluate its efficacy and safety in this context. However, the field faces a dual challenge. On one hand, no immunotherapy has yet been formally approved for this specific indication, and only a limited number of phase 3 studies have successfully met their primary endpoints. On the other hand, in clinical practice, factors such as slow postoperative recovery and poor chemotherapy tolerance often prevent patients from completing adjuvant chemotherapy, thereby compromising their long-term survival outcomes. This significant unmet medical need underscores the urgent demand for novel treatment strategies that deliver both superior efficacy and improved tolerability.

As a core oncology asset for Henlius, HANSIZHUANG demonstrates unique advantages in treating various solid tumors via its differentiated mechanism. The drug not only induces stronger PD-1 internalization—reducing PD-1 receptor presence on T cells for rapid and potent immune activation [3]—but also minimizes PD-1-mediated recruitment of the co-stimulatory molecule CD28, thereby preserving CD28 signaling [4-6], enhancing downstream AKT activity [7], and promoting sustained T-cell activation. The ASTRUM-006 study innovatively employed a "chemotherapy-free" serplulimab monotherapy strategy in the adjuvant setting. This approach maintained therapeutic efficacy while effectively circumventing toxicity related to conventional chemotherapy, significantly improved patients’ quality of life, and provided a new clinical option. The success of this trial marks a pivotal shift in perioperative gastric cancer care—from a conventional intensity-driven paradigm toward a more refined "high-efficacy, low-toxicity" treatment model.

Delving into the Frontiers of GI Oncology

GI cancer is a strategically core therapeutic area for Henlius, with dedicated focus and extensive development. The company has built a diversified product portfolio spanning from immunotherapy to targeted agents, and from established targets to novel molecular modalities, addressing high-incidence GI cancers such as esophageal, gastric, and colorectal cancers. This portfolio forms a differentiated treatment system covering various molecular subtypes and disease stages.

In esophageal cancer, HANSIZHUANG received approval in China in September 2023 for the first-line treatment of esophageal squamous cell carcinoma (ESCC). Its efficacy and safety profile have earned it broad clinical recognition, rapidly establishing it as a key therapeutic option in this field. In the gastric cancer segment, Henlius demonstrates strong R&D depth and synergistic advantages. Beyond the positive outcomes achieved with HANSIZHUANG in the neoadjuvant/adjuvant setting, the company’s internally developed, differentiated novel epitope HER2 mAb, HLX22, is challenging the current first-line standard of care for HER2-positive advanced gastric cancer through an international multi-centre, head-to-head phase 3 trial. In colorectal cancer, Henlius is actively advancing an international multi-centre phase 3 clinical study evaluating HANSIZHUANG-based combinations in the first-line treatment of metastatic CRC (mCRC). Concurrently, the company continues to push the boundaries of GI cancer treatment by developing next-generation therapies, such as the PD-L1-targeting ADC HLX43, now in clinical studies for advanced gastric/gastroesophageal junction adenocarcinoma and other tumors.

Looking ahead, Henlius will leverage its robust pipeline of innovative therapies and extensive global multi-centre clinical trial data to solidify its leadership in GI oncology. The company is dedicated to bringing a growing portfolio of high-quality therapeutic options to patients worldwide, addressing significant unmet needs across the globe.

On October 9, 2025 Vivace Therapeutics, Inc., a small molecule discovery and development company developing first-in-class cancer therapies targeting the Hippo pathway, reported that new data from the company’s ongoing Phase 1/2 clinical trial of its first-in-class transcriptional enhanced associate domain (TEAD) autopalmitoylation inhibitor, VT3989, will be featured in an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 (Press release, Vivace Therapeutics, OCT 9, 2025, View Source [SID1234656543]). Timothy A. Yap, M.D., Ph.D., Head of Clinical Development in the Therapeutics Discovery Division at the University of Texas, M.D. Anderson Cancer Center, will deliver the oral presentation at the conference, which is being held October 17-21, 2025, in Berlin, Germany.

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Details of the oral presentation are as follows:

Presentation #920O:

Title: Safety and efficacy of first-in-class, YAP/TEAD inhibitor, VT3989 in refractory pleural and non-pleural mesothelioma: A Phase I/II study

Presenting Author: Timothy A. Yap, M.D., Ph.D., University of Texas, M.D. Anderson Cancer Center

Session: Proffered Paper Session: Mesothelioma and thymic tumours: Targeting and breaking through

Session Date/Time: Sunday, October 19, 2025, 4:30 – 6:00 p.m. Central European Summer Time (CEST)

Presentation Date/Time: Sunday, October 19, 2025, 4:40 – 4:50 p.m. CEST

Location: Hanover Auditorium – Hall 7.2c
Previously reported initial results from the Phase 1/2 trial demonstrated VT3989 to be well tolerated with durable antitumor responses in patients with advanced malignant mesothelioma and other tumors with neurofibromatosis 2 (NF2) mutations. The study (View Source) is a multi-center, open label trial designed to evaluate the safety, tolerability, pharmacokinetics (PK) and biological activity of VT3989 in patients with refractory metastatic solid tumors, including refractory non-pleural and pleural malignant mesothelioma. The study included both a dose escalation and a dose expansion phase.

On October 9, 2025 GlyTR Therapeutics, a biotech company pioneering development of glycan-targeting cancer immunotherapies, reported the publication of its foundational technology in the journal, Cell (Press release, GlyTR Therapeutics, OCT 9, 2025, View Source [SID1234656544]).

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"With the publication in Cell, GlyTR is entering the global spotlight," said Bob Genthert, Co-Founder and Interim CEO. "This is a critical milestone as we advance toward clinical trials and expand partnerships with investors, academic collaborators, and pharmaceutical companies."

The study details Glycan-Dependent T cell Recruiter (GlyTR1 & GlyTR2) therapeutics that have pan-cancer activity by targeting tumor-associated carbohydrate antigens (TACAs). The TACA’s targeted by GlyTR are among the most abundant and widespread cancer antigens known but are largely inert to the immune system and previously un-targetable.

Conventional antigen-targeting immunotherapies like Chimeric Antigen Receptor T cell (CAR-T cell) and bispecific antibodies require cancer-specific antigen expression to avoid "on-target, off-cancer" toxicity to normal tissue. In contrast, GlyTR’s innovative "Velcro-like" density-dependent binding enables discrimination between tumor and normal tissue based on target density, potentially offering unprecedented safety and efficacy in oncology treatment.

GlyTR1 also overcomes a second major roadblock to development of CAR T cells and bi-specific antibodies: immune-suppression driven by the tumor. By binding to an immune-suppressive TACA, GlyTR1 defeats these mechanisms to break the shield of immunosuppression.

"This publication validates more than a decade of research and represents a major step toward making multiple TACAs druggable targets for the first time," said Dr. Michael Demetriou, M.D., Ph.D., Co-Founder and Professor of Neurology and Molecular Genetics at University of California, Irvine. "We believe GlyTR technology could fundamentally reshape the landscape of immuno-oncology by providing a safe pan-cancer therapeutic option in a single drug."

"This work represents a potential paradigm shift from the current antibody-centric approach to cancer cell targeting," said Dr. Raymond Zhou, Ph.D., co-founder and president of GlyTR Therapeutics.

Highlights from the Cell publication:

Demonstrates potent, selective killing of multiple highly diverse tumors in preclinical models, including breast, ovarian, colon, pancreatic, lung, prostate and leukemia.
Shows no toxicity in mice with human-like glycan expression.
Details the unique ability to overcome immunosuppression in hostile tumor microenvironments.
GlyTR technology has been developed in collaboration with the UC Irvine from grants totaling ~$30 million. This includes a Cancer Moonshot award from the National Cancer Institute (NCI), multiple small business grants from NCI, several awards form the California Institute for Regenerative Medicine (CIRM) and a NCI Experimental Therapeutics program award for clinical-grade manufacturing of GlyTR1 for human trials.

Here is a link to the article in Cell: View Source

On October 9, 2025 Adcendo ApS ("Adcendo"), a biotech company focused on the development of first and best-in-class antibody-drug conjugates (ADCs) for the treatment of cancers with high unmet medical need, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to ADCE-D01 for the treatment of soft tissue sarcoma (STS) (Press release, ADCendo, OCT 9, 2025, View Source [SID1234656545]).

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ADCE-D01 is a first-in-class ADC targeting urokinase plasminogen activator receptor-associated protein (uPARAP) conjugated to the Topoisomerase I inhibitor payload P1021. uPARAP is a novel endocytic ADC target that is overexpressed in tumors of mesenchymal origin, such as sarcomas. Preclinically, ADCE-D01 shows strong anti-tumor activity in a range of mesenchymal tumor models including STS and is well tolerated in non-human primate toxicology studies with a favorable safety profile and no evidence of target-specific toxicity.

ADCE-D01 is currently being evaluated in the ADCElerate1 clinical trial, a first-in-human Phase I/II multicenter, open-label, dose escalation and expansion study evaluating ADCE-D01 as a monotherapy in patients with metastatic and/or unresectable STS. The primary objective of the study is to evaluate the safety and tolerability of ADCE-D01. The secondary objectives are to characterize the pharmacokinetics and to evaluate the preliminary efficacy of ADCE-D01. The study is recruiting in the US (NCT06797999) and in Europe. (EUCT number: 2024-516900-41-00).

Dr. Lone Ottesen, Chief Medical Officer of Adcendo, said: "This Fast Track designation is an important recognition of the potential of our uPARAP-targeting drug candidate and marks another meaningful milestone for Adcendo. We are committed to further advancing ADCE-D01 and believe that our uPARAP-targeting approach has the potential to transform the sarcoma treatment landscape and overcome the limitations experienced with existing therapies."

Dr. Victoria Marsh, Global Head of Regulatory at Adcendo, said: "With this Fast Track designation the development of ADCE-D01 will now benefit from more frequent interactions with the FDA. Increased FDA engagement will support and expedite the future regulatory review of ADCE-D01 with the aim of making ADCE-D01 available to patients sooner".