On October 24, 2025 Alphamab Oncology (stock code: 9966.HK) reported that the first patient has been successfully dosed at Sun Yat-sen University Cancer Center in the phase I clinical study (Study ID: JSKN022-101) of JSKN022, an independently developed innovative bispecific antibody-drug conjugate (ADC) targeting PD-L1 and integrin αvβ6, for the treatment of advanced malignant solid tumors (Press release, Alphamab, OCT 24, 2025, View Source [SID1234656982]). JSKN022 is the Company’s fourth ADC candidate entering clinical development, as well as the world’s first PD-L1/αvβ6 bispecific ADC to advance into clinical trials.

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JSKN022 innovatively combines immuno-oncology (IO) mechanisms with ADC approaches, utilizing Alphamab Oncology’s proprietary glycan-specific conjugation platform and linker-payload (Alphatecan) to significantly improve stability and homogeneity. The molecule is designed to bind to PD-L1 and/or integrin αvβ6 on the surface of tumor cells. After binding to either target, JSKN022 enters the lysosome through target-mediated endocytosis. The linker is hydrolyzed by proteolytic enzymes, releasing cytotoxic topoisomerase I inhibitor, which then induces apoptosis of PD-L1 and/or integrin αvβ6 positive tumor cells. In addition, the inhibitor can block TGFβ signaling to modulate immune function, and kill antigen-negative cells through the bystander effect, thereby achieving multiple anti-tumor activity. Preclinical data presented at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, demonstrated that JSKN022 effectively inhibited the proliferation of cancer cells and demonstrated greater tumor suppression than single-target ADCs.

JSKN022-101 is an open-label, multi-center, phase I clinical trial of JSKN022, including dose-escalating and dose-optimization phases. This study aims to evaluate the safety, tolerability, pharmacokinetics (PK)/pharmacodynamics (PD), and antitumor activity of JSKN022 in patients with advanced malignant solid tumors, and determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D).

At present, no ADC targeting integrin αvβ6 or PD-L1 has been approved for marketing worldwide, with all related investigational candidates remaining in clinical development stages. JSKN022 will potentially bring in novelty in the therapeutic approach for cancers that are refractory or resistant to PD-1/PD-L1 inhibitors.

About JSKN022

JSKN022 is a first-in-class ADC targeting both PD-L1 and integrin αvβ6. Based on independently developed Envafolimab, Alphamab integrates immuno-oncology (IO) mechanisms with ADC approaches. This novel drug molecule utilizes proprietary glycan-specific conjugation technology and linker-payload (Alphatecan) to enhance both stability and homogeneity. The molecule is designed to bind to PD-L1 and/or integrin αvβ6 on the surface of tumor cells. After binding to either target, JSKN022 enters the lysosome through target-mediated endocytosis. The linker is hydrolyzed by proteolytic enzymes, releasing cytotoxic topoisomerase I inhibitor, which then induces apoptosis of PD-L1 and/or integrin αvβ6 positive tumor cells. In addition, the inhibitor can block TGFβ signaling to modulate immune function, and kill antigen-negative cells through the bystander effect, thereby achieving multiple anti-tumor activity. JSKN022 is expected to provide a novel therapeutic option for cancers that are refractory or resistant to PD-1/PD-L1 inhibitors. The Phase I clinical study of JSKN022 in patients with advanced malignant solid tumors has been conducted in China.

On October 24, 2025 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of cancer and autoimmune diseases, reported initial results from the ongoing Phase 1 dose-escalation study of XmAb819, a ENPP3 x CD3 T-cell engaging bispecific antibody, in patients with advanced clear cell renal cell carcinoma (ccRCC). The results were presented in a poster at the AACR (Free AACR Whitepaper)-NCI-EORTC Conference on Molecular Targets and Cancer Therapeutics in Boston, Massachusetts.

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"We are excited to be developing XmAb819 as a novel first-in-class ENPP3 T-cell engager that could potentially offer a much-needed new therapeutic modality for patients with advanced clear cell renal cell carcinoma and clinicians. In our first clinical presentation of dose-escalation data, XmAb819 demonstrated compelling anti-tumor activity and a well-tolerated safety profile in very heavily pre-treated patients," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "We are on-track with our first dose-expansion cohort now selected and are enrolling patients as we continue to dose escalate. We are confident that we will be able to select a recommended Phase 3 dose during 2026 to support the initiation of our first pivotal study in advanced ccRCC during 2027."

The poster will be archived under "Events & Presentations" in the Investors section of the Company’s website located at www.xencor.com.

Phase 1 Study of XmAb819 in Advanced ccRCC

The Phase 1 clinical trial is a multicenter, open-label, dose-escalation and dose-expansion study designed to evaluate XmAb819 as monotherapy in patients with advanced ccRCC. As of the September 19, 2025 data cut-off, 69 patients received XmAb819 across 10 intravenous (IV) dose cohorts and 5 subcutaneous (SC) dose cohorts. Patients received a median of 4 prior lines of therapy (range 1-8). All patients received prior anti-PD1 therapy and prior VEGF-TKI therapy, and 36% of patients were previously treated with a HIF2α inhibitor. Efficacy was assessed by investigators using RECIST v1.1.

XmAb819 demonstrated evidence of anti-tumor activity and an acceptable safety profile that was generally well tolerated across dose levels. Of the 20 efficacy-evaluable patients treated at the dose levels that were preclinically predicted to be within the target dose range, 25% achieved a partial response (PR) as best response (n=5, 4 confirmed PRs and 1 unconfirmed PR), with a 70% disease control rate (DCR, 14/20). All five responders remain on treatment, and 50% (10/20) of all efficacy-evaluable patients within the target dose range remain on treatment. For one patient with a first-scan assessment of progressive disease, a subsequent 47% reduction in target lesions was reported, and the patient remains on-treatment as of the data cut-off (treatment week 30). All 6 patients within the target dose range with greater than 30% reduction in lesion size remain on treatment as of the data cut-off.

The most common treatment-emergent adverse events (TEAE) were cytokine release syndrome (CRS), rash and gastrointestinal-related toxicities that were primarily Grade 1 or 2 in severity and predominantly associated with prime-step dosing in the first four weeks of treatment. Grade 3 TEAEs related to treatment were rash (16%), liver enzyme elevations (7%) and CRS1 (4%). One dose-limiting toxicity of Grade 4 elevated liver enzymes was deemed related to treatment. No cases of treatment-related immune effector cell-associated neurotoxicity syndrome (ICANS) were observed. No Grade 5 events were reported. Four patients (6%) were dose-reduced due to treatment-related AEs, and three patients (4%) discontinued treatment due to treatment-related AEs, which includes two patients who experienced elevated liver enzymes and one patient who experienced a non-fatal myocardial infarction in the presence of hypotension and CRS.

1 While 51 patients received the correct priming dose of XmAb819, higher than expected serum levels of XmAb819 were observed in 18 patients, which was investigated during early 2025 and linked to priming dose preparation errors that resulted from use of certain ports and syringes during drug dilution. Of the 51 patients receiving the correct priming dose, 2 (4%) experienced Grade 3 CRS. Of the 18 patients that were found to have a 3- to 8-fold higher than expected concentration of study drug post-priming dose, 5 (28%) experienced Grade 3 CRS. Mitigation of dosing errors through site retraining is complete, and the root cause of these errors will be eliminated through the introduction of a low concentration formulation to be implemented during the first half of 2026.

Webcast Details

Xencor will host a webcast today at 1:30 a.m. ET (10:30 a.m. PT) to discuss the initial results outlined in this news release. The live webcast may be accessed through this link and through "Events & Presentations" in the Investors section of the Company’s website, located at investors.xencor.com. A recording will be available for at least 30 days.

About XmAb819

XmAb819 is a first-in-class, tumor-targeted, T-cell engaging XmAb 2+1 bispecific antibody in development for patients with clear cell renal cell carcinoma (ccRCC). XmAb819 engages the immune system and activates T cells for highly potent and targeted lysis of tumor cells expressing ENPP3, an antigen highly expressed on kidney cancers. ENPP3 is a differentially expressed target, with high level expression in renal cell carcinoma (RCC) and low-level expression on normal tissues. With two tumor-antigen binding domains and one T-cell binding domain, Xencor’s XmAb 2+1 format enables antibodies to bind more avidly and selectively kill tumor cells with higher antigen density, potentially sparing normal cells. Xencor is conducting a Phase 1 study to evaluate XmAb819 in patients with advanced ccRCC.

(Press release, Xencor, OCT 24, 2025, View Source [SID1234656984])

On October 24, 2025 Xencor presented its corporate presentation.

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(Presentation, Xencor, OCT 24, 2025, View Source [SID1234656985])

On October 24, 2025 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported updated preclinical data from the company’s potent and selective pan KRAS(ON) inhibitor in a poster presentation at the 2025 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) taking place in Boston, MA, October 22-26, 2025.

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"We are excited today to share updated data from our pan KRAS(ON) program which demonstrates a potential best-in-class profile for our lead molecule," said Andrew Robbins, Cogent’s President and Chief Executive Officer. "We look forward to advancing this program with the goal of filing an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) in 2026."

Poster Details
The poster will be accessible on the ‘Posters and Publications’ page of Cogent’s website.

Title: Identification of CGT1263, a Potent KRAS Inhibitor with Selectivity for Mutant KRAS over HRAS and NRAS
Session Date and Time: Poster Session B, Friday, October 24, 2025 – 12:30 p.m. – 4:00 p.m. ET
Poster Number: B024
Abstract Number: B024

Mutations in KRAS are among the most prevalent mutations found in cancer, occurring most often in colorectal cancer, non-small cell lung cancer and pancreatic cancer. The poster presented today describes Cogent’s internally developed KRAS(ON/OFF) inhibitor CGT1263, showing clear selectivity over HRAS and NRAS, with picomolar (pM) activity across a broad panel of KRAS mutant cell lines. In addition, the poster also characterizes CGT1815 (the prodrug of CGT1263), which is designed to optimize human pharmacokinetic performance, supported by pharmacokinetics data from both CGT1815 and CGT1263 across multiple species. Finally, the poster highlights that CGT1815 demonstrates superior efficacy in KRASG12D and KRASG12V tumor growth inhibition studies when compared to RMC-6236.

(Press release, Cogent Biosciences, OCT 24, 2025, View Source [SID1234656987])

On October 24, 2025 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported updated preclinical data from the company’s potent and selective pan KRAS(ON) inhibitor in a poster presentation at the 2025 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) taking place in Boston, MA, October 22-26, 2025.

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Discover why more than 1,500 members use 1stOncology™ to excel in:

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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"We are excited today to share updated data from our pan KRAS(ON) program which demonstrates a potential best-in-class profile for our lead molecule," said Andrew Robbins, Cogent’s President and Chief Executive Officer. "We look forward to advancing this program with the goal of filing an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) in 2026."

Poster Details
The poster will be accessible on the ‘Posters and Publications’ page of Cogent’s website.

Title: Identification of CGT1263, a Potent KRAS Inhibitor with Selectivity for Mutant KRAS over HRAS and NRAS
Session Date and Time: Poster Session B, Friday, October 24, 2025 – 12:30 p.m. – 4:00 p.m. ET
Poster Number: B024
Abstract Number: B024

Mutations in KRAS are among the most prevalent mutations found in cancer, occurring most often in colorectal cancer, non-small cell lung cancer and pancreatic cancer. The poster presented today describes Cogent’s internally developed KRAS(ON/OFF) inhibitor CGT1263, showing clear selectivity over HRAS and NRAS, with picomolar (pM) activity across a broad panel of KRAS mutant cell lines. In addition, the poster also characterizes CGT1815 (the prodrug of CGT1263), which is designed to optimize human pharmacokinetic performance, supported by pharmacokinetics data from both CGT1815 and CGT1263 across multiple species. Finally, the poster highlights that CGT1815 demonstrates superior efficacy in KRASG12D and KRASG12V tumor growth inhibition studies when compared to RMC-6236.

(Press release, Cogent Biosciences, OCT 24, 2025, View Source [SID1234657021])