Multitude Therapeutics Announces Encouraging Interim Phase I/II Results from Ongoing First-in-Human Study Evaluating its MUC18-directed Antibody-Drug-Conjugate, AMT-253, in Melanoma and Other Advanced Solid Tumors at the 2025 ESMO Annual Meeting

AMT-253 is a potential first-in-class MUC18-directed ADC with a proprietary linker-payload design  

AMT-253 demonstrated a manageable safety profile, consistent with other TOP1-inhibitor based ADCs

Promising antitumor activity was observed in heavily pretreated patients with melanoma and gynecologic cancers without MUC18 preselection

SHANGHAI, Oct. 19, 2025 /PRNewswire/ -- Multitude Therapeutics, Inc., a clinical stage biopharmaceutical company focused on the development of ADC drugs, today announced interim results from its ongoing Phase I/II open-label, multicenter dose escalation and expansion study evaluating AMT-253, a MUC18-directed antibody-drug-conjugate (ADC), in patients with melanoma and other advanced solid tumors. The data are being presented on October 19th at the 2025 European Society for Medical Oncology (ESMO) Annual Meeting being held in Berlin, Germany.

Phase I/II clinical trials are ongoing in both Australia 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-253, 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 September 8th, 2025, safety data are available for 170 patients who have received AMT-253 once every three weeks (Q3W) at doses ranging from 1.6 to 5.6 mg/kg. Primary tumor types are melanoma, endometrial cancer, cervical squamous cancer and uterine leiomyosarcoma. In heavily pretreated melanoma patients, with prior lines of therapy ranging from 1-7, promising efficacy was observed without MUC18 preselection. The overall response rate (ORR) was 28.6% in all melanomas (16/56, 15 confirmed, 1 unconfirmed still on-treatment) across all dose levels. In melanoma patients without prior chemotherapy, ORR was 35% (7/20, all confirmed), 50% (5/10; 4 confirmed, 1 unconfirmed still on-treatment), and 33.3% (1/3, confirmed) for the cutaneous, acral, and mucosal subtypes, respectively; preliminary mPFS was 8.6, 8.3, and 11.0 months. Among 18 cutaneous melanoma patients at the potential expansion doses, ORR was 38.9% (7/18, all confirmed), and preliminary mPFS was 8.6 months. Preliminary antitumor activity was also observed in endometrial cancer, cervical squamous carcinoma and uterine leiomyosarcoma patients. Responses were observed across MUC18 expression levels in all tumor patients evaluated. AMT-253 showed a safety profile consistent with other topoisomerase-1 (TOP1) inhibitor–based ADCs, with manageable hematologic toxicities as the most common treatment-related adverse events. No treatment-related cases of neuropathy or pneumonitis were observed as of the data cutoff.

"We are excited by the durable antitumor activity observed in the early clinical results of AMT-253, particularly in unselected, late-line metastatic melanoma patients, where the unmet medical need remains high," said Dr. Shu-Hui Liu, Co-founder and CSO of Multitude Therapeutics. "These initial data, together with our previously published preclinical findings*, highlight the potential of AMT-253 to offer meaningful outcome improvement to patients who have exhausted standard-of-care options. We look forward to further clinical confirmation of these results and to fully exploring the potential of this novel ADC for greater patient benefit."

*Shi et al., (2023) Cancer Research 83:3783-95

Poster Presentation Details:

Title: Ongoing Phase I trial results of AMT-253, a first-in-class MUC18-targeting antibody-drug conjugate in patients with melanoma and other advanced solid tumors
Session Title: Developmental therapeutics
Date and Time: October 19th – 09:00-17:00
Poster Number: 997P
Location: Hall 25, Level 2

About AMT-253

AMT-253, a MUC18 ADC, is composed of a proprietary antibody with high MUC18 binding affinity, a protease-cleavable linker, and an exatecan payload (a potent and clinically validated topoisomerase-1 inhibitor). The linker is designed to complement the exatecan payload, enabling a stable and homogenous ADC. The payload is a weak substrate for BCRP/P-gp, which are drug efflux pumps that drive chemoresistance to many therapies. In preclinical data, this linker-payload has been shown to have an increased "bystander effect" compared to the equivalent of competitor ADCs**. AMT-253 has a drug-to-antibody ratio of eight. AMT-253 is being evaluated in a Phase I/II study in patients with melanoma and other advanced solid tumors. Additional information on the AUS PhI(NCT05906862) and China PhI/II (NCT06209580) trials can be found at clinicaltrials.gov.

** Weng et al., (2023) Cancer Discovery 13:950–73

About Multitude Therapeutics

Multitude Therapeutics is a clinical-stage company focused on the development of ADC drugs. Multitude Therapeutics utilizes 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

Contact:

Multitude company email
[email protected] 

SOURCE Multitude Therapeutics, Inc.