Core Insights - HUTCHMED has initiated a Phase I/IIa clinical trial for HMPL-A580, its second Antibody-Targeted Therapy Conjugate (ATTC), targeting unresectable, advanced, or metastatic solid tumors in China and the US, with the first patient dosed on March 4, 2026 [1] Group 1: Product Overview - HMPL-A580 is a first-in-class ATTC that combines a selective PI3K/PIKK small-molecule inhibitor with an anti-EGFR antibody, designed to enhance anti-tumor activity through simultaneous inhibition of the PAM pathway and EGFR signaling [2][8] - The ATTC platform represents a next-generation approach to precision oncology, aiming to achieve synergistic anti-tumor activity and improved safety compared to traditional cytotoxin-based therapies [4][5] Group 2: Clinical Trial Details - The Phase I/IIa study is a multicenter, open-label trial assessing the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary efficacy of HMPL-A580, consisting of a dose escalation phase followed by a dose expansion phase [3] - The trial aims to determine the maximum tolerated dose and recommended dose for further development in selected solid tumors [3] Group 3: Mechanism of Action - The PAM pathway is critical for cell growth and survival, and its alterations are linked to poor prognosis in various cancers; HMPL-A580 aims to deliver targeted inhibition directly to EGFR-expressing tumor cells, potentially overcoming systemic toxicity associated with existing PAM-targeted therapies [7][8]

Safe harbor statement & disclaimer R&D UPDATES October 31, 2025 HKEX: 13, Nasdaq / AIM:HCM The performance and results of operations of the HUTCHMED Group contained within this presentation are historical in nature, and past performance is no guarantee of future results. The performance and results of operations of the Group contained within this presentation are historical in nature, and past performance is no guarantee of future results of the Group. This presentation contains forward-looking statements w ...

Core Insights - Celcuity Inc. announced preliminary clinical data for gedatolisib in two early phase clinical trials, demonstrating promising efficacy and safety profiles in treating metastatic cancers [1][4][5] Phase 1 Clinical Trial in mCRPC - In the Phase 1 trial evaluating gedatolisib plus darolutamide in men with metastatic castration resistant prostate cancer (mCRPC), the six-month radiographic progression-free survival (rPFS) rate was reported at 66% [1][4] - The trial involved 38 patients, with two arms receiving different doses of gedatolisib (120 mg and 180 mg) alongside darolutamide [2] - No patients discontinued treatment due to treatment-related adverse events (AEs), and less than 3% experienced Grade 3 stomatitis [4][5] Phase 2 Clinical Trial in HER2+ Metastatic Breast Cancer - In the Phase 2 trial for HER2+ metastatic breast cancer (mBC), the objective response rate (ORR) was 43% among 44 patients treated with gedatolisib plus trastuzumab-pkrb [1][6] - The median number of prior anti-HER2 therapies for enrolled patients was four or more, with 86% having received at least three prior treatments [6] - No patients discontinued treatment due to treatment-related AEs, and no Grade 3 hyperglycemia was reported [5][6] Future Directions - The company plans to amend the clinical trial protocol to explore additional dosing options for gedatolisib in the ongoing Phase 1/1b trial [4] - Up to six patients will be enrolled in each of three arms to determine the recommended Phase 2 dose (RP2D), with a total of approximately 30 subjects expected to be treated with the RP2D in the Phase 2 dose expansion study [4][5] - Celcuity is also conducting other clinical trials, including a Phase 3 trial evaluating gedatolisib in combination with fulvestrant for HR+/HER2- advanced breast cancer [7]