Proof-of-Concept Data Demonstrates Broad Therapeutic Potential of Company’s Multi-targeted Antibody Therapy Enhancer (MATE™) Platform
NEW HAVEN, Conn., Dec. 07, 2020 (GLOBE NEWSWIRE) — Kleo Pharmaceuticals, Inc., a targeted immunotherapy company developing fully synthetic bispecific therapies to redirect, enhance or replace antibodies, is presenting preclinical data today on KPMW135, a novel CD3 x CD20 bispecific molecule developed with Kleo’s multi-targeted antibody therapy enhancer (MATE™) conjugation platform.
Kleo’s technology was used to create KPMW135 via chemical conjugation of a CD3 binder directly to the anti-CD20 monoclonal antibody rituximab, a drug approved for the treatment of B-cell lymphomas and lymphocytic leukemias. Data showed that KPMW135 increased anti-tumor activity by at least a factor of 10 by adding T cell mediated cytotoxicity to rituximab’s existing mechanism of action. These data are being presented at the 62nd Annual American Society of Hematology (ASH) Meeting, being held Dec 5-8, 2020 in a virtual format.
“Using our proprietary MATE technology, we have built a true ‘biosuperior’ agent by adding an additional mechanism of action – potent and specific activation of anti-tumor T cells to destroy tumors – to an existing approved therapeutic antibody, rituximab, without increasing overall toxicity,” said Doug Manion, MD, CEO. “We believe our technology can rapidly improve product profiles in both approved or investigational antibodies and Fc-containing proteins, and we are actively pursuing strategic collaborations in this space.”
In vitro studies showed that KPMW135:
- maintained the native binding properties of rituximab, with data demonstrating KPMW135’s ability to bind CD16a/FcgRIIIA and FcRn via the Fc domain, as well as CD20 binding on target tumor cells via the Fab domains
- induced functional activation of a number of peripheral blood mononuclear cell (PBMC) effector cell types, including NK cells and T cells
- T cell activation was target cell dependent and robust (100-fold higher)
In vivo cynomolgus study showed that KPMW135:
- activated T cells 2-3 fold with a peak at four hours post-dose, compared to an equivalent dose of rituximab, as shown by increased CD69 and CD44 expression
- induced a rapid and sustained reduction of B cells, demonstrating CD20 target specific engagement without overt toxicity
In addition to KPMW135, Kleo’s oncology and infectious diseases portfolio includes KP1237, a clinical-stage, CD38-targeting therapy in development for the treatment of multiple myeloma, as well as a hyperimmune globulin mimic (HGM) therapy in development to treat COVID-19.
Details of the electronic presentation are as follows:
Title: KPMW135, a Biosuperior CD3 Bispecific Version of Rituximab Created by a Novel Chemical Conjugation Technology Demonstrates Increased Anti-Tumor Activity by Adding T Cell-Mediated Cytotoxicity Activity to the Existing Mechanisms of Rituximab
Presenter: Christian Vidal, PhD
Program: Oral and Poster Abstracts
Session: 625. Lymphoma: Pre-Clinical—Chemotherapy and Biologic Agents: Poster III
Time and Location: Monday, December 7, 2020: 7:00 a.m. – 3:30 p.m. PST
Poster Hall (Virtual Meeting)
About Kleo Pharmaceuticals, Inc.
Kleo Pharmaceuticals is a targeted immunotherapy company that develops fully synthetic bispecific therapies to redirect, enhance or replace antibodies. The company was founded on the groundbreaking research of its scientific founder Dr. David Spiegel at Yale University. Kleo’s synthetic immunotherapy platform uses two chemistry-based approaches – antibody-redirecting molecule (ARM) and multi-targeted antibody therapy enhancer (MATE) – that help redirect and stimulate key components of the immune system to eradicate cancer cells and virulent pathogens. Compared to biologic therapies, Kleo’s compounds are smaller and more versatile, allowing for better tumor/tissue penetration, non-immunogenic for improved safety and higher dose levels, more efficient to produce and potentially orally bioavailable. They can be optimized against specified biological targets or combined with existing cell- or antibody-based therapies. Kleo investors include Biohaven Pharmaceutical Holding Company (NYSE:BHVN) and PeptiDream Inc. (Nikkei:PPTDF). For more information, visit www.kleopharmaceuticals.com.
Susan Kinkead (Media)