Multitude Therapeutics Announces Promising Interim Phase I/II Results from the Ongoing First-in-Human Study Evaluating its CD44v9-directed Antibody-Drug-Conjugate, AMT-116, in Heavily Pretreated EGFR Wild-type Non-Small Cell Lung Cancer (NSCLC) and Other Advanced Solid Tumors at the 2025 ESMO Annual Meeting

AMT-116 is a potential first-in-class CD44v9-directed Topoisomerase I inhibitor-based ADC

AMT-116 demonstrated a favorable safety profile, with manageable hematologic and Gastrointestinal toxicities

Promising efficacies were observed in patients with heavily pretreated EGFR Wild-type NSCLC and other advanced solid tumors without CD44v9 pre-selection

SHANGHAI, Oct. 17, 2025 /PRNewswire/ -- Multitude Therapeutics, Inc., a clinical-stage company focused on the development of antibody-drug-conjugate (ADC) drugs, today announced initial data from its ongoing phase I/II open-label, multicenter dose escalation and expansion study evaluating AMT-116, a CD44v9-directed ADC, in patients with EGFR wild-type NSCLC and other advanced solid tumors. The data are being presented on October 17th at the 2025 European Society for Medical Oncology (ESMO) Annual Meeting being held in Berlin, Germany.

Phase I/II clinical trials are being conducted across Australia, US and China. This first-in-human study will evaluate the Maximum Tolerated Dose (MTD) / the Recommended Phase II Dose (RP2D), safety, tolerability, anti-tumor activity, pharmacokinetics, pharmacodynamics and immunogenicity of AMT-116, in patients with advanced solid tumors. The Phase Ia portion will determine the recommended doses for expansion, and the Phase Ib/II portion will focus on further characterizing safety and efficacy in select tumor types.

As of July 17th, 2025, safety data are available for 164 patients who have received AMT-116 once every two weeks (Q2W) at doses ranging from 1.5 to 5.0 mg/kg. Primary tumor types are NSCLC, NPC (nasopharyngeal carcinoma), anal carcinoma and salivary gland cancer. In heavily pretreated EGFR Wild-type NSCLC patients, with prior lines of therapy ranging from 1-5, promising efficacy was observed regardless CD44v9 expression status. The overall response rate (ORR) was 40% (6/15), and the disease control rate (DCR) was 93% (14/15), in EGFR Wild-type NSCLC at dose levels >3 mg/kg. Among five EGFR Wild-type NSCLC patients at 5.0 mg/kg, ORR was 80% (4/5) and DCR was 100% (5/5). Preliminary antitumor activity was also observed in patients with NPC, anal carcinoma and salivary gland cancer at >3mg/kg, with ORRs of 50% (3/6), 60% (3/5) and 33% (2/6), respectively. Antitumor activity was observed across patients with varying levels of CD44v9 expression. The safety profile of AMT-116 was consistent with that of other Topoisomerase I inhibitor-based ADCs, with manageable hematologic toxicities as the most common treatment-related adverse events. Only low-grade and infrequent mucosal and skin toxicities were observed, demonstrating a favorable tolerability profile.

"We are excited by the impressive and durable efficacy shown in the early results of AMT-116, especially in unselected heavily pretreated EGFR Wild-type NSCLC and several other advanced solid tumors. The efficacies of AMT-116 observed so far are consistent with its broad tumor expression profile observed in preclinical studies, while the greatly reduced mucosal and skin toxicities reflect the desired outcome of a carefully selected linker-payload platform aimed at mitigating potential on-target toxicities from normal tissue expression. With these encouraging results, we are further expanding the clinically efficacious dose levels of 4 mg/kg Q2W and 5 mg/kg Q2W cohorts in select tumor types to explore the full potential of this novel ADC for greater patient benefit in NSCLC and beyond," said Dr. Shu-Hui Liu, co-founder and CSO of Multitude Therapeutics.

Mini Oral Presentation Details:

Title: Updated ongoing Phase I/II clinical trial results of AMT-116, a first-in-class anti-CD44v9 antibody-drug conjugate (ADC), in patients with advanced solid tumors
Mini Oral Session Title: Developmental therapeutics
Date and Time: October 17th – 04:05 PM
Location: Heidelberg Auditorium - Hall 6.2
Presentation number: 922MO

About AMT-116
AMT-116, a CD44v9 ADC, is composed of a proprietary antibody with high CD44v9 binding affinity, a hydrolysable linker, and a belotecan derivative payload (a novel and clinically validated topoisomerase-1 inhibitor, named KL610023, collaborating with Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (6990.HK)). CD44v9 is involved in broad biological pathways and has an implicated role in cancer stem cells. The target is a highly abundant protein and is overexpressed broadly in solid tumors with a restrictive normal tissue expression. AMT-116 has a drug-to-antibody ratio of 7-8. AMT-116 is being evaluated in a phase I/II study in patients with EGFR Wild-type NSCLC and other advanced solid tumors. Additional information on the Australia/US Phase I (NCT05725291) and China Phase I/II (NCT06782334) trials can be found at clinicaltrials.gov. 

About Multitude Therapeutics
Multitude Therapeutics is a clinical-stage company focused on the development of ADC drugs. Multitude Therapeutics has two technology platforms: MabArray™— an antibody platform for discovering novel cell surface tumor antigens to identify first-in-class targets, and T1000- exatecan — a new linker-payload technology for developing ADCs, which allows ADCs prepared with this platform to achieve a better balance of the bystander effect, efficacy, and safety. The combination of MabArray™ and T1000-exatecan generates significant synergistic effects, enabling Multitude Therapeutics to build an ADC "atlas" that is expected to treat malignant tumors with high unmet medical needs and achieve higher and more durable responses.

Based on the above technology platforms, Multitude Therapeutics currently has several ADCs in development, including three potential first-in-class target ADCs. Moreover, several ADCs, including all-new target ADCs, have entered the clinical stage, where they have demonstrated promising safety and efficacy and provided preliminary validation of the company's platform technology. For further information, please visit www.multitudetherapeutics.info

SOURCE Multitude Therapeutics, Inc.