On July 24, 2025 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a leading precision medicine oncology company, reported that results from a multi-site global Phase 2 study of neoadjuvant darovasertib in primary uveal melanoma was accepted for a Proffered Paper oral presentation at the 2025 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) meeting, taking place on October 17-21 in Berlin, Germany (Press release, Ideaya Biosciences, JUL 24, 2025, View Source [SID1234654508]). A summary of the data from the abstract will be shared at a future date.

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"We are excited to share clinical data at ESMO (Free ESMO Whitepaper) 2025 on the effects of neoadjuvant darovasertib in primary uveal melanoma across both plaque brachytherapy and enucleation cohorts. Its potential to impact the natural history of this disease and its management will be highlighted in the presentation. We continue to advance our clinical strategy for darovasertib in earlier stage disease, with the recent initiation of a randomized Phase 3 neoadjuvant registrational trial in primary uveal melanoma," said Dr. Darrin Beaupre, Chief Medical Officer, IDEAYA Biosciences.

Details of the Proffered Paper Oral Presentation are as follows:

Title (Abstract #5053): Enucleation prevention and vision preservation in primary uveal melanoma (UM): preliminary results from a phase 2 study of neoadjuvant darovasertib

Presenter: Dr. Marcus Butler, MD, Associate Professor, Princess Margaret Cancer Center at the University of Toronto

On July 24, 2025 Nanjing Leads Biolabs Co., Ltd. ("Leads Biolabs" or the "Company") reported that listed on the Main Board of The Stock Exchange of Hong Kong Limited (HKEX) under the stock code "09887" (Press release, Nanjing Leads Biolabs, JUL 24, 2025, View Source [SID1234654507]).

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The clinical-stage biotech company priced its IPO at HKD 35 per share, offering 36.86 million shares (excluding green shoe option). The deal included a Hong Kong public tranche of 16.03 million shares (43% of the total) and an international placement of 20.84 million shares (57%). Morgan Stanley and CITIC Securities acted as joint sponsors of the transaction.

Gross proceeds totaled approximately USD 189 million (including green shoe option). According to Leads Biolabs, the proceeds will be allocated as follows:

~65% for ongoing and planned clinical trials and regulatory affairs;
~15% for advancing preclinical assets, expanding existing pipelines, and optimizing technology platforms
~10% for upgrading manufacturing capacity and commercialization preparedness post-approval;
~10% for working capital and general corporate purposes.
Dr. Xiaoqiang Kang, Founder, Chairman, and CEO of Leads Biolabs, commented:

"Our HKEX debut represents a major leap from laboratory innovation to global capital markets, accelerating our innovation-driven international expansion. For more than a decade, we’ve pursued one goal: becoming a global leader in immuno-oncology therapeutics. At this inflection point, we reaffirm our founding commitment to eradicating disease while maintaining the entrepreneurial vigor that defines us. Through strengthened global execution and accelerated translation of breakthrough therapies from bench to bedside, we will deliver paradigm-shifting treatments to patients across the globe."

Founded in 2012, Leads Biolabs is a clinical-stage biotechnology company dedicated to the discovery, development, and commercialization of innovative therapies to address unmet medical needs in oncology, autoimmune, and other severe diseases both in China and globally. The Company has built a differentiated pipeline of 14 innovative drug candidates, including six clinical-stage drug candidates, of which four lead products are among the top-tier clinically advanced candidates globally.

Leads Biolabs operates an integrated business model encompassing in-house discovery, development and commercialization of innovative tumor immunotherapies. The Company has strategically developed assets in three areas: Immuno-oncology 2.0 (IO 2.0), T-cell engagers (TCEs), and antibody-drug conjugates (ADCs). Its oncology pipeline includes 12 investigational products, including 3 monoclonal antibodies, 5 bispecific antibodies, 3 ADCs and 1 bispecific fusion protein. The Company is also progressing two promising candidates for autoimmune diseases—a bispecific fusion protein and a trispecific antibody.

Leads Biolabs’ R&D is powered by multiple proprietary technology platforms that feature integrated, AI-powered and diversified antibody engineering capabilities, including LeadsBody (a CD3 T-cell engager platform), X-body (a 4-1BB engager platform) and its linker-payload platform for ADC development. These platforms have demonstrated clinical proof-of-concept, particularly with bispecific antibody combinations.

The LeadsBody platform delivers strong technological capabilities for developing CD3-targeted bispecific antibodies. Its innovative molecular design enables precise affinity modulation between TCEs and both CD3 and tumor-associated antigens (TAAs). With spatially optimized steric hindrance architecture, the platform enables conditional T-cell activation exclusively within the tumor microenvironment (TME), significantly lowering the risk of cytokine release syndrome (CRS) and systemic toxicity. This molecular engineering approach is designed to optimize the therapeutic index through customized spatial configurations that reduce treatment interruptions due to toxicity. By minimizing adverse systemic effects, the platform enables extended treatment durations and, ultimately, aims to improve patient quality of life (QoL).

Building on this platform, Leads Biolabs has established a position of leadership in the promising field of solid tumor immunotherapies. The company has developed six differentiated TCE therapeutic candidates, forming a portfolio spanning three major therapeutic areas: hematologic malignancies, solid tumors, and autoimmune diseases.

Hematologic Malignancies:

LBL-034: A GPRC5D/CD3 bispecific antibody for the treatment of multiple myeloma (MM)
LBL-043: A LILRB4/CD3 bispecific antibody targeting acute myeloid leukemia (AML) and multiple myeloma (MM)
Solid Tumors:

LBL-033: A MUC16/CD3 bispecific antibody targeting solid tumors overexpressing MUC16, with a focus on gynecologic cancers including ovarian cancer, cervical cancer, and endometrial carcinoma
LBL-054: A CDH17/CD3 T-cell engager under development for colorectal cancer (CRC), gastric cancer, pancreatic ductal adenocarcinoma (PDAC), and neuroendocrine neoplasms (NENs)
LBL-058: A first-in-class TCE-ADC (antibody-drug conjugate) targeting DLL3, demonstrating encouraging efficacy in DLL3-positive small cell lung cancer (SCLC) and NENs
Autoimmune Diseases:

LBL-051: A first-in- class CD19/BCMA/CD3 trispecific antibody designed to block autoantibody production by B cells and plasma cells while regulating B-cell hyperactivation, differentiation, and plasmacytic transformation. The candidate’s unique mechanism of action enables broad-based B-cell modulation, potentially delivering superior clinical outcomes. The program is being advanced through a strategic collaboration with NewCo, a portfolio company of leading biotech investor Aditum Bio.
The company’s X-body platform utilizes advanced antibody engineering to develop 2:2 bispecific antibody structures. Its lead candidate, LBL-024 (PD-L1/4-1BB), represents a key advance in 4-1BB agonist therapies, becoming the first agent in this class to enter global registrational trials. The platform’s 2:2 configuration is designed to restrict 4-1BB activation to the tumor microenvironment (TME), addressing systemic toxicity issues, particularly hepatotoxicity, that have undermined earlier efforts in this category. This platform-driven approach enables precise control of immune activation within the TME, minimizing off-target adverse effects while reactivating exhausted T cells and driving clonal expansion. The mechanism has shown particular promise in tumors resistant to PD-1/PD-L1 inhibitors, as well as in so-called immunologically "cold" tumors. The successful execution of this strategy with LBL-024 underscores its potential as a best-in-class immunotherapy candidate.

At the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting, Leads Biolabs presented data from a multicenter Phase Ib/II trial evaluating LBL-024 in combination with etoposide and platinum-based chemotherapy in first-line advanced extra-pulmonary neuroendocrine carcinoma (EP-NEC). The study reported a 75.0% objective response rate (ORR) and a 92.3% disease control rate (DCR) among the efficacy-evaluable population (n=52). In the 15 mg/kg cohort, ORR reached 83.3%, with a DCR of 100%. Overall, 57.7% of patients (30/52) achieved tumor reduction exceeding 50%. These results substantially outperformed historical benchmarks for chemotherapy alone, which typically show ORR in the 30–55% range. While progression-free survival (PFS) data were not yet mature at the April 15, 2025 cutoff (median follow-up: 8.2 months), all dose cohorts showed favorable trends compared with historical controls.

EP-NEC is a rare and aggressive cancer with poor advanced-stage outcomes and no approved second-line or later therapies. Recognizing this unmet medical need, China’s National Medical Products Administration (NMPA) granted approval on April 30, 2024 for a pivotal single-arm registrational trial of LBL-024 in EP-NEC, potentially establishing it as the first approved therapy for this indication.

As the world’s first 4-1BB-targeted molecule to have reached registrational stage, LBL-024 could establish 4-1BB as the fourth approved immuno-oncology target following PD-1/L1, CTLA-4 and LAG-3. The candidate has earned Breakthrough Therapy Designation from China’s NMPA for relapsed/refractory EP-NEC and Orphan Drug Designation from U.S. FDA for neuroendocrine neoplasms (NENs).

LBL-024 has also secured regulatory approvals to investigate indications including small cell lung cancer (SCLC), biliary tract cancer (BTC), ovarian cancer (OC), non-small cell lung cancer (NSCLC), esophageal squamous cell carcinoma (ESCC), hepatocellular carcinoma (HCC), and gastric cancer (GC). Early clinical data have shown promising antitumor activity in SCLC, BTC and OC, supporting its potential as a broad-spectrum oncology therapeutic.

On July 24, 2025 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK pathway-driven cancers, reported the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to VS-7375, an oral KRAS G12D (ON/OFF) inhibitor, for the first-line treatment of patients with KRAS G12D-mutated locally advanced or metastatic adenocarcinoma of the pancreas (PDAC) and for the treatment of patients with KRAS G12D-mutated locally advanced or metastatic PDAC who have received at least one prior line of standard systemic therapy (Press release, Verastem, JUL 24, 2025, View Source [SID1234654506]). Fast Track is a process designed to facilitate the development and expedite the review of new drugs intended to treat or prevent serious conditions and address unmet medical needs.

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"The Fast Track Designation for VS-7375 underscores the importance of our potential best-in-class KRAS G12D (ON/OFF) inhibitor. As we continue enrollment in our U.S. Phase 1/2a clinical trial, our goal is to accelerate the program’s development given the lack of FDA-approved, KRAS G12D-targeted treatments for people living with KRAS G12D cancers," said Dan Paterson, president and chief executive officer of Verastem Oncology. "Given the encouraging initial safety and efficacy results in China reported by our partner, GenFleet Therapeutics, at ASCO (Free ASCO Whitepaper) this year, we are excited to be advancing VS-7375 in the U.S. to evaluate it in advanced pancreatic cancer and non-small cell lung cancer and in combination with cetuximab in advanced solid tumors, including colorectal cancer."

VS-7375-101 is a Phase 1/2a study being conducted in the U.S., with plans to expand globally, and will evaluate the safety and efficacy of VS-7375 in patients with advanced KRAS G12D mutant solid tumors, including PDAC. The monotherapy dose escalation phase of the study started at a 400mg QD dose based on an efficacious dose identified in the Phase 1/2 study conducted in China by the Company’s partner, GenFleet Therapeutics. GenFleet announced encouraging initial safety and efficacy results from its Phase 1 dose-escalation phase of its study of VS-7375 (known as GFH375 in China) at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Verastem plans to dose-escalate across dose levels where encouraging initial safety and efficacy were observed in patients with advanced KRAS G12D mutant solid tumor cancers in GenFleet’s study. Upon successful completion of the dose-escalation phase, the Company will select a recommended Phase 2 dose and assess the efficacy and safety of monotherapy VS-7375 in expansion cohorts of patients with advanced pancreatic cancer and non-small cell lung cancer. In parallel with the monotherapy dose escalation, Verastem will evaluate VS-7375 in combination with cetuximab in advanced solid tumors. Subject to the results of the Phase 1 dose escalation combination of VS-7375 and cetuximab, Verastem plans to initiate a combination expansion cohort in colorectal cancer.

About KRAS G12D

KRAS G12D represents 26% of all KRAS mutations, making it the most prevalent KRAS mutation in human cancers. The KRAS G12D mutation occurs most commonly in pancreatic (37%), colorectal (12.5%), endometrial (8%), and non-small cell lung (5%) cancers. Currently, no therapies are approved by the U.S. Food and Drug Administration (FDA) specifically targeting KRAS G12D mutations in cancer.

About VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor

VS-7375 is a potential best-in-class, potent, and selective oral KRAS G12D dual ON/OFF inhibitor. VS-7375 is the lead program from the Verastem Oncology discovery and development collaboration with GenFleet Therapeutics. Verastem announced in April 2025 that the U.S. Investigational New Drug (IND) application for VS-7375 was cleared and initiated a Phase 1/2a clinical trial in June 2025. GenFleet’s IND for VS-7375 (known as GFH375 in China) was approved in China in June 2024, and the first patient was dosed in a Phase 1/2 study in July 2024.

On July 24, 2025 Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical-stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, reported that the European Medicines Agency (EMA) has granted Orphan Designation for CAN-2409 (aglatimagene besadenovec) for the treatment of pancreatic cancer (Press release, Candel Therapeutics, JUL 24, 2025, View Source [SID1234654505]). This designation complements CAN-2409’s existing U.S. Food and Drug Administration (FDA) Orphan Drug Designation and FDA Fast Track Designation for the treatment of pancreatic ductal adenocarcinoma (PDAC) awarded to CAN-2409 in April 2024 and December 2023, respectively, and underscores the significant unmet medical need in this disease beyond the U.S.

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CAN-2409 is an investigational, off-the-shelf, replication-defective adenovirus engineered to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to tumor cells. When administered with a prodrug (valacyclovir or acyclovir), the HSV-tk enzyme converts the prodrug into DNA-incorporating nucleotide analogs, causing immunogenic cell death and the release of tumor (neo)antigens within the tumor microenvironment (TME). This mechanism has the potential to induce an individualized, systemic immune response against multiple therapy-resistant solid tumors, including prostate cancer, non-small cell lung cancer (NSCLC), and PDAC.

The Company previously reported positive overall survival (OS) data from its randomized controlled phase 2a clinical trial of CAN-2409 plus valacyclovir in borderline resectable PDAC, demonstrating remarkable survival benefits with estimated median OS of 31.4 months in the CAN-2409 plus standard of care arm versus 12.5 months in the standard of care control arm, supported by immunological biomarker data. Notably, three of seven patients treated with CAN-2409 were still alive at the time of data cut-off (February 20, 2025) with survival of 66.0, 63.6 and 35.8 months after enrollment, respectively, suggesting a long tail of survival.

"Pancreatic cancer remains one of the most challenging malignancies to treat, particularly in patients whose disease is unresectable," said Garrett Nichols, MD, MS, Chief Medical Officer at Candel. "We observed that CAN-2409 profoundly remodels the tumor microenvironment, transforming it from ‘cold’ (non-inflamed and immunosuppressive) to ‘hot’ (inflamed with active immune infiltration) and extends survival."

The EMA grants Orphan Designation to drugs and biologics intended for the treatment, diagnosis or prevention of rare, life-threatening or chronically debilitating diseases or conditions that affect fewer than five in 10,000 people in the European Union. Orphan Designation allows pharmaceutical companies certain benefits, including reduced regulatory fees, clinical protocol assistance, research grants and up to 10 years of market exclusivity in the European Union, if approved.

"Receiving EMA Orphan Designation for CAN-2409 represents a significant regulatory milestone for CAN-2409 in this disease," said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel. "This designation, alongside our existing FDA Orphan Drug and Fast Track Designations for CAN-2409 in PDAC, underscores the promise of our novel multimodal immunotherapy approach. The notable benefits we’ve observed with CAN-2409, including evidence of a long tail of survival, highlight the transformative potential of this immunotherapy. As we advance our regulatory strategy across global markets, we remain committed to bringing CAN-2409 to patients who face limited therapeutic options. We look forward to continuing our development efforts and working with regulatory authorities across the world to make this innovative therapy available to patients in need."

CAN-2409 has received regulatory designations recognizing its potential across multiple solid tumor indications. In addition to the EMA Orphan Designation announced today and the FDA Orphan Drug Designation and FDA Fast Track Designation for PDAC mentioned above, CAN-2409 has also received FDA Fast Track Designation for NSCLC and localized prostate cancer, as well as FDA Regenerative Medicine Advanced Therapy designation (RMAT) for intermediate-to-high risk, localized prostate cancer.

About CAN-2409

CAN-2409 (aglatimagene besadenovec), Candel’s most advanced multimodal biological immunotherapy candidate, is an investigational, off-the-shelf, replication-defective adenovirus designed to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to a patient’s tumor. After intratumoral administration, HSV-tk enzyme activity results in conversion of prodrug (valacyclovir) into deoxyribonucleic acid (DNA)-incorporating nucleotide analogs, leading to immunogenic cell death in cells exhibiting DNA damage and proliferating cells, with subsequent release of a variety of tumor (neo)antigens in the tumor microenvironment. At the same time, the adenoviral serotype 5 capsid protein promotes inflammation through the induction of expression of pro-inflammatory cytokines, chemokines, and adhesion molecules. Together, this regimen is designed to induce an individualized and specific CD8+ T cell-mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity, based on in situ immunization against a variety of tumor antigens. CAN-2409 has the potential to treat a broad range of solid tumors. Encouraging monotherapy activity as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, and immune checkpoint inhibitors have previously been shown in several preclinical and clinical settings. More than 1,000 patients have been dosed with CAN-2409 with a favorable tolerability profile to date, supporting the potential for combination with standard of care, when indicated.

On July 24, 2025 Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, reported the publication of a peer-reviewed research paper in Science (Press release, Revolution Medicines, JUL 24, 2025, View Source [SID1234654504]). The scientific paper details the discovery and development of zoldonrasib (RMC-9805), a RAS(ON) G12D-selective covalent inhibitor.

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Oncogenic RAS mutations are observed in approximately 92% of pancreatic ductal adenocarcinoma (PDAC), 50% of colorectal cancer, and 30% of non-small cell lung cancer (NSCLC) cases. RAS G12D, an oncogenic variant of RAS that contains an aspartic acid in place of glycine at amino acid 12, is one of the most common RAS mutations in human solid tumors. Historically, it has been particularly challenging to target aspartic acid residues with covalent inhibitors. ​This publication details the novel mechanism of zoldonrasib, a member of the differentiated class of targeted protein binders called tri-complex inhibitors. This natural product-like compound successfully overcomes the challenge of engaging aspartic acid residues by leveraging a neomorphic protein-protein interface between the cellular chaperone cyclophilin A and activated RAS, or RAS(ON), to selectively catalyze covalent bond formation with RAS(ON) G12D proteins. Data reported in this paper demonstrate that this activity drives deep and durable tumor regressions in preclinical models of multiple tumor types with KRAS G12D mutations.

"The tri-complex inhibitor modality has proven to be a productive approach to solving the challenge of developing mutant-selective inhibitors for RAS variants beyond the G12C substitution, as demonstrated by zoldonrasib that targets the G12D variant," said Jan Smith, Ph.D., chief scientific officer of Revolution Medicines. "This report demonstrates the novel features of zoldonrasib that enable it to bind to the active or RAS(ON) state, including a highly novel covalent bond formed selectively with the substituted aspartic acid in this oncogenic variant. The preclinical profile combined with recent clinical data presentations provide an encouraging picture of the therapeutic potential for zoldonrasib in cancers caused by RAS G12D and further validate the broad utility of this drug discovery approach."

The full manuscript, titled "A neomorphic protein interface catalyzes covalent inhibition of RAS G12D aspartic acid in tumors," is available online at Science.

Zoldonrasib is currently undergoing evaluation in several clinical trials, including RMC-9805-001 (NCT06040541), a multicenter, open-label, dose escalation and dose-expansion Phase 1 study designed to evaluate zoldonrasib in patients with advanced solid tumors harboring a KRAS G12D mutation. NSCLC results from this study were presented in April 2025 at the American Academy for Cancer Research annual meeting and PDAC results from this study were presented in October 2024 at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics.