On December 7, 2023 MBrace Therapeutics, Inc. ("MBrace"), a clinical-stage biopharmaceutical company devoted to improving the lives of cancer patients through the development of antibody-drug conjugates (ADCs) against novel oncology targets, reported new preclinical data supporting ongoing development for lead investigational ADC therapeutic, MBRC-101, at the San Antonio Breast Cancer Symposium taking place December 5-9, 2023, in San Antonio, Texas (Press release, MBrace Therapeutics, DEC 7, 2023, View Source [SID1234638243]).

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"The data presented today further characterize the safety and activity of MBRC-101 and support its potential to effectively treat various solid tumors, including difficult-to-treat breast cancers," said Isan Chen, M.D., co-founder, president, and chief executive officer at MBrace. "We are advancing our clinical evaluation of MBRC-101 in breast cancer, as well as for patients with other EphA5-expressing solid tumor cancers for whom there is a significant need for targeted treatment options."

MBRC-101 is composed of a humanized anti-EphA5 IgG1 antibody conjugated to monomethyl auristatin E (MMAE). In the data presented today, robust and selective EphA5 expression was detected in greater than 80% of triple-negative breast cancer (TNBC) and greater than 80% of HR+ breast cancer tissue samples. EphA5 expression was not detected in adjacent, non-malignant breast tissue or normal breast.

Additionally, extensive in vitro testing showed that MBRC-101 binds to EphA5 exclusively, is rapidly internalized, and is cytotoxic to cells expressing EphA5. Dramatic preclinical efficacy was observed in vivo, with weekly administration of intravenous MBRC-101 showing dose-dependent, robust, and reproducible anti-tumor activity in patient-derived xenograft murine models of TNBC. In addition, in preclinical models, MBRC-101 was well tolerated at doses ranging from 10 mg/kg to 30 mg/kg. Toxicologic findings were attributed to the MMAE payload and not target-related. The highest non-severely toxic dose (HNSTD) was 10 mg/kg (HED = 3.2 mg/kg). At a dosage of 0.5 mg/kg, the safety margin was approximated at 15-fold based on projected human exposures.

The data presented are the results of research conducted both by MBrace, as well as in the laboratories of MBrace co-founders, Renata Pasqualini, Ph.D., Professor at Rutgers Cancer Institute of New Jersey and Chief of the Division of Cancer Biology at Rutgers New Jersey Medical School; and Wadih Arap, M.D., Ph.D., Professor and Chief of the Division of Hematology/Oncology and Director of the Rutgers Cancer Institute of New Jersey at University Hospital.

Details of the poster presentation are as follows:

Abstract Title: MBRC-101: a novel antibody-drug conjugate (ADC) targeting the membrane-associated tyrosine kinase receptor EphA5 in breast cancer

Presenter: Fernanda Staquicini, Ph.D., Director of Research & Development, MBrace Therapeutics

Presentation ID: P03-18-04

Spotlight Session: Poster Session 3

Session Date and Time: Thursday, December 7, 12:00 PM – 2:00 PM CST

Location: Henry B. Gonzalez Convention Center, San Antonio, Texas

Published Abstract Number: 1580268

The poster is also available on the MBrace Therapeutics website at www.mbractetrx.com.

About MBRC-101

MBRC-101 is an investigational antibody-drug conjugate (ADC) that uniquely targets the EphA5 receptor tyrosine kinase, which is present in multiple cancers including, but not limited to, breast, non-small cell lung (NSCLC), colorectal, gastric, and pancreatic cancers. MBRC-101 is currently being evaluated in the MBRC-101-001 Phase 1 clinical trial, a first-in-human, open-label, multicenter, dose escalation and dose expansion study enrolling patients with advanced metastatic solid tumors refractory to standard-of-care treatment. For more information about the MBRC-101-001 clinical trial and to review patient eligibility criteria visit clinicaltrials.gov (NCT06014658).