CUSP06 is a CDH6-directed ADC with a differentiated profile and potentially best-in-class activity

CUSP06 demonstrated a manageable safety profile, consistent with other TOP1-inhibitor ADCs

Promising signs of efficacy were observed in patients with heavily pretreated platinum-resistant high-grade serous ovarian cancer (HGSOC) without CDH6 pre-selection

PRINCETON, N.J., June 2, 2025 /PRNewswire/ -- OnCusp Therapeutics, Inc., a clinical-stage biopharmaceutical company dedicated to transforming cutting-edge preclinical innovation into clinically validated treatments for cancer patients, today announced initial Ph1a data from its ongoing Phase 1 open-label, multicenter dose escalation and expansion study evaluating CUSP06, a CDH6-directed antibody-drug conjugate (ADC) with a differentiated profile, in patients with platinum-refractory/resistant ovarian cancer and other advanced solid tumors. The data are being presented today at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting being held in Chicago, Illinois.

"We are excited by the early results, especially in platinum-resistant HGSOC, which demonstrated promising activity in a heavily pretreated population without requiring CDH6 biomarker selection," said Dr. Bing Yuan, Co-Founder and CEO of OnCusp Therapeutics. "These data, together with previously presented preclinical findings, underscore the best-in-class potential of CUSP06. We look forward to observing promising data in the Phase 1b study and to bringing this therapy to patients with ovarian cancer and other CDH6-expressing solid tumors."

The Phase 1 trial is an open-label, multicenter, first-in-human study of CUSP06. The primary objective of the study is to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of CUSP06 in patients with platinum-refractory/resistant ovarian cancer and other advanced solid tumors. The Phase 1a portion will determine the recommended doses for expansion and the Phase 1b portion will focus on further characterizing safety and efficacy in select tumor types.

As of May 13, 2025, data are available for 37 patients who have received CUSP06 once every three weeks (Q3W) at doses ranging from 1.6 to 5.6 mg/kg. These patients were heavily pretreated, with a median of 4 prior lines of therapy. Promising efficacy was observed in patients with heavily pretreated platinum-resistant HGSOC without CDH6 pre-selection. The overall response rate (ORR) was 36% in HGSOC (9/25; 5 confirmed (including 2 responders who had previously received mirvetuximab treatment) and 4 unconfirmed partial responses (PRs)). All patients with unconfirmed PRs remain on treatment. The ORR reached 50% at both 4.0 mg/kg + prophylactic granulocyte colony-stimulating factor (G-CSF) and 4.4 mg/kg + G-CSF cohorts (3/6 and 1/2 patients, respectively); all responders remain on treatment. The clinical benefit rate (CBR) was 92% (23/25). CA-125 responses occurred in 45% of Gynecologic Cancer InterGroup (GCIG)-evaluable HGSOC patients, further supporting clinical activity. Responses were seen in low and high-CDH6-expressing tumors. CUSP06 has been well tolerated, with manageable hematologic toxicities as the most common treatment-related adverse events. These Phase 1a safety and efficacy results support continued evaluation of CUSP06 in platinum-resistant HGSOC and other CDH6-positive tumors in Phase 1b expansion cohorts.

CUSP06 was recently granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of patients with platinum-resistant ovarian cancer.

Poster Presentation Details:

Title: First-in-human (FIH) Phase 1 study of CUSP06, a cadherin-6 (CDH6)-directed antibody-drug conjugate (ADC), in patients with platinum-refractory/resistant ovarian cancer and other advanced solid tumors.Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor BiologyDate and Time: June 2 – 1:30 PM CDTAbstract Number: 3042Poster Number: 357Location: Hall A

About CUSP06

CUSP06, a CDH6 ADC, is composed of a proprietary antibody with high CDH6 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 homogeneous 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 with competitor ADCs. CUSP06 has a drug-to-antibody ratio of eight. OnCusp obtained the exclusive global rights (outside of China) to lead the development and commercialization of CUSP06 from Multitude Therapeutics in 2022. CUSP06 is being evaluated in a Phase 1 study in patients with platinum refractory/resistant ovarian cancer and other advanced solid tumors. Additional information on the CUSP06-1001 (NCT06234423) trial can be found at ClinicalTrials.gov.

About OnCusp Therapeutics

OnCusp Therapeutics, Inc., headquartered in Princeton, New Jersey, is a clinical-stage biopharmaceutical company dedicated to transforming cutting-edge preclinical innovation into clinically validated treatments for cancer patients. OnCusp was co-founded by Dr. Bing Yuan, Dr. Eric Slosberg, and Dr. Andy Fu, and has built a strong team of accomplished veterans with proven track records in building biotech startups, leading successful preclinical and clinical programs, and creating value through global partnerships. The company is committed to accelerating the advancement of globally competitive oncology assets for patients. OnCusp raised an oversubscribed $100 million Series A financing round in January 2024, co-led by Novo Holdings, OrbiMed, and F-Prime Capital.

Contact:

OnCusp Investors & Media:

Argot Partners

OnCusp@argotpartners.com