• AMT-676 is a potential first-in-class CDH17-directed ADC with a proprietary exatecan-based linker-payload design
• AMT-676 demonstrated a favorable safety profile, similar to other TOP1-inhibitor based ADCs with reduced hematological toxicities
• Promising antitumor activity was observed in heavily pretreated CRC patients
Shanghai,
China, July 2nd, 2026 – Multitude Therapeutics Co., Ltd., a clinical stage
biopharmaceutical company focused on the development of ADC drugs, today
announced interim results from its ongoing Phase I open-label, multicenter dose
escalation and expansion study evaluating AMT-676, a CDH17-directed antibody-drug-conjugate
(ADC), in patients with advanced colorectal cancer (CRC) and other GI cancers. The
data are being presented on July 2nd at the 2026 ESMO Gastrointestinal Cancers
Congress (ESMO GI) Annual Meeting being held in Munich, Germany.
The
Phase I clinical trial is ongoing in Australia, the United States, 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-676, in patients
with advanced solid GI tumors. The study design consists of both dose
escalation and backfilling/dose expansion portions.
As of May 22nd, 2026, 246
patients have been treated with AMT-676 without CDH17 preselection across AUS
(63.0%), CN (27.6%) and US (9.3%). Patients received AMT-676 once every three
weeks (Q3W) at doses ranging from 1.6 to 12 mg/kg. Primary tumor type is CRC.
In heavily pretreated CRC patients, with a median of 3 prior treatment lines (range:
1-9), promising efficacy was observed. Across efficacy-evaluable CRC patients
treated at doses of 7.2–12 mg/kg, the overall response rate (ORR) was 20%
(20/100), including 17 confirmed responses and 3 unconfirmed responses in
patients who remain on treatment, while the disease control rate (DCR) was 91%.
At the 8 mg/kg dose, the ORR was 26% (12/47), with 25 patients remaining on
treatment. Notably, patients with RAS wild-type tumors achieved higher ORRs
(36% at 7.2 mg/kg and 38% at 8 mg/kg) than those with RAS-mutant tumors.
AMT-676 showed a favorable safety
profile consistent with other topoisomerase-1 (TOP1) inhibitor–based ADCs, with
gastrointestinal and hematologic toxicities as the most common
treatment-related adverse events, mostly at grade 1 and 2 and clinically
manageable. Hematological toxicities were generally mild, reflecting the
benefit of the lower DAR (4) design. MTD was not reached after escalating to 12
mg/kg. The low Gr3+ TRAE rates further support dose selection/optimization and future
combination strategies including chemotherapies.
“We
are very encouraged by the durable antitumor activity and disease control rate observed
in the early clinical results of AMT-676, particularly in unselected, late-line
metastatic CRC patients, where the unmet medical need remains high,” said Dr. Xun
Meng, CEO of Multitude Therapeutics. “These initial data highlight the
potential of AMT-676 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.”
Poster
Presentation Details:
Title: Phase I study of
AMT-676, an anti-CDH17 antibody-drug conjugate, in patients with advanced CRC
and other GI tumors Date
and Time:
July 2nd – 15:30 Poster
Number:
112P
About
AMT-676 AMT-676,
a CDH17 ADC, is composed of a proprietary antibody with high CDH17 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-676 has a drug-to-antibody ratio of 4.
AMT-676 is being evaluated in a Phase I study in patients with CRC and other
advanced solid tumors. Additional information on the Phase I (NCT06400485) trial
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 en.multitudetherapeutics.com
Contact: Multitude company email info@multitudetherapeutics.com
