Kleo Pharmaceuticals Presents Preclinical Proof-of-Concept Data on a Novel Chemical Conjugation ...
NEW HAVEN, Conn., Nov. 09, 2020 (GLOBE NEWSWIRE) -- Kleo Pharmaceuticals, Inc., a targeted immunotherapy company developing fully synthetic bispecific therapies to redirect, enhance or replace antibodies, today announced the presentation of proof-of-concept data on KPMW101, an anti-tumor therapeutic agent created with the company’s multi-targeted antibody therapy enhancer (MATE™) conjugation platform. The data were presented at the Society for Immunotherapy of Cancer’s (SITC) 35th Annual Meeting, taking place in a virtual format from November 9-14, 2020.
Kleo’s proprietary technology allows for one-step chemical conjugation to ‘off-the-shelf’ antibodies, enabling greater functionality, for example, in creating bispecific antibodies. The presentation at SITC demonstrates how MATE technology can be applied to commercial-grade intravenous immune-globulin (IVIG) to add target-mediated anti-tumor activity.
The company developed KPMW101, which consists of a CD38-specific binder (from PeptiDream) conjugated to IVIG to create a novel immunotherapy that engages the immune system through IgG subtypes 1, 2 and 4. The anti-tumor activity of KPMW101 was compared directly with the approved anti-CD38 antibody Darzalex® (daratumumab) in in vitro and in vivo studies, validating the platform capabilities and the compound’s ability to kill tumor cells.
Highlights from the presentation include:
In vitro studies using human peripheral blood mononuclear cells (PBMC) demonstrated that KPMW101 activated FcRyIIIa (CD16a) on immune effector cells and elicited CD38+ target cell killing with single nM EC50. Maximum tumor cytotoxicity was similar to daratumumab.
In vivo studies in mouse models showed that KPMW101 resulted in more than a 50% reduction of tumor cells; this antitumor activity was similar to that observed with daratumumab.
- MATE conjugation does not affect the normal functions of immune cell engagement via FcRyIIIa (CD16a) or in vivo half-life via FcRn.
- A pharmacodynamic analysis showed KPMW101 remained stable over the course of a 144-hour study which is comparable to unconjugated IVIG.
“We are pleased to present these data detailing the chemical conjugation capabilities of our MATE platform as demonstrated by KPMW101. By maintaining native binding to FcRs via the Fc domain, our technology ensures the stability of the molecule and retains immune-mediated mechanisms of action,” said Luca Rastelli, PhD, chief scientific officer, Kleo Pharmaceuticals. “Additionally, because the MATE platform allows for chemical engineering of off-the-shelf therapeutic antibodies and IVIG, Kleo is positioned to rapidly produce improved antibodies at a greater scale and in a cost-efficient manner, potentially eliminating the need for protein engineering and recombinant production.”
In addition to oncology applications, the MATE platform is also being used to develop Kleo’s COVID-19 hyperimmune globulin mimic (HGM) therapy which previously received grant funding from the Bill & Melinda Gates Foundation.
Details of the electronic poster presentation are as follows:
Abstract Title: “A novel site-directed chemical conjugation technology confers antitumor activity via native Fc receptor to plasma immunoglobulin by attaching tumor binders.”
Abstract Number: #635
Authors: Christian M. Vidal, PhD; Michael Cukan, PhD; Rajat Varma, PhD; Lawrence Iben, MA; Tanya Berbasova, PhD; Ada Vaill, MS; Anna Bunin, PhD; Ann Marie Rossi, MS; David Trinh, BS; Katy McGrath, BS; Enrique Alvarez, DVM; Matthew Welsch, PhD; Luca Rastelli, PhD
Session Title: Immuno-conjugates and chimeric molecules
Poster Presentations: Wednesday, November 11, from 5:15-5:45 p.m. EST and Friday, November 13, from 4:40-5:10 p.m. EST.
Virtual Poster Hall: Posters will be on display from November 9 at 8 am EST, until the virtual poster hall closes on December 31, 2020.
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)