Hinge Bio Introduces its GEM-⁠DIMER™ Platform: A Completely New Class of Biotherapeutics

GEM-DIMERs are multivalent, multi-specific antibody-based molecules that project freely into multidimensional space enabling entirely new functionality for superior efficacy and safety

Lead GEM-DIMER is COVICEPT, a tetravalent, biepitopic ACE2 receptor superdecoy, in development for treatment of COVID-19 and is variant agnostic

Co-founded by renowned biotechnology inventor Daniel Capon, Ph.D., venture investor, Carin Mueller Rollins M.B.A., and Miriam Siekevitz, Ph.D., J.D.

Published in <NAME OF PREPRINT SERVER HERE>

Burlingame, Calif., September xx, 2021 – Hinge Bio, Inc., a biotechnology company developing a new class of biotherapeutics based on its proprietary Flex-Hinge™ technology, today introduced its GEM-DIMER™ platform, which generates a completely new class of biotherapeutics. GEM-DIMERs are multivalent, multi-specific antibody-based molecules that project freely into multidimensional space with little or no steric hindrance due to the Company’s proprietary Flex-Hinge technology. This novel approach allows for entirely new functionality and potentially superior efficacy and safety. A manuscript detailing the Company’s GEM-DIMER technology was published online on the preprint server and has been submitted to a high-profile scientific journal.

Hinge Bio was co-founded in 2015 by three highly experienced biotechnology executives with a total of more than 100 years in the industry. Daniel Capon, Ph.D. is an accomplished industry inventor. In his more than 35 years in the industry, he is responsible for well-known biotech products and technologies such as recombinant Factor VIII for hemophilia (Genentech), Fc-fusion proteins (Genentech), chimeric antigen receptors (Cell Genesys), XenoMouse for fully human antibodies (Abgenix), and the PhenoSense HIV drug resistance and susceptibility test (Monogram Biosciences). He adds the GEM-DIMER platform to that list of accomplishments. Carin Mueller Rollins, M.B.A., has more than 25 years of experience as a venture investor, including co-founding 5AM Ventures, and as a management consultant and equity research associate. Miriam Siekevitz, Ph.D., J.D. has more than 35 years in the biotechnology industry, including as Corporate Counsel at PDL BioPharma and its successor company, Facet Biotech Corporation, as an Associate at Heller Ehrman and as an Assistant Professor in the Department of Microbiology at Mount Sinai School of Medicine.

“Antibodies and Fc-fusion proteins have been amazing biotechnology success stories providing breakthrough therapies in oncology, inflammatory diseases, cardiovascular disease and many other therapeutic areas,” said Dr. Capon. “Each of these molecules can bind to their disease target with high specificity and high affinity resulting in impressive efficacy and are generally well tolerated. It might surprise some that the full potential of these molecules remains unrealized due to their challenge of engaging multiple (2 or more) different disease targets given their largely planar structure. GEM-DIMERs solve that problem by enabling multiple (e.g., 6 or more) unencumbered functional domains to project freely into multiplanar, multidimensional space. This enables the potential for new functionalities and dramatically enhanced potency. These features are powerfully demonstrated by in vitro and in vivo data obtained for our lead asset, COVICEPT, which is undergoing IND-enabling studies and is in development as a durable treatment for COVID-19 over the long haul.”

COVICEPT is a first-in-class tetravalent, biepitopic ACE2 receptor “superdecoy” in development to treat and prevent SARS-CoV-2 infection. It is designed to be SARS-CoV-2 variant agnostic, that is to be an effective treatment regardless of the variants circulating today or that emerge in the future. It has shown extremely potent in vitro activity against all of the 12 SARS-CoV-1 and SARS-CoV-2 variants tested including the Delta variant, whereas each of 8 monoclonal antibodies that have received Emergency Use Authorization (EUA) or that are in late stages of clinical trials inhibit only some of the variants.

[COVICEPT was designed by employing Hinge Bio’s proprietary topological engineering platform, which [DESCRIPTION OF TOPOLOGICAL ENGINEERING IN ENGLISH HERE]. COVICEPT is made from three different polypeptide chains: (1) a Fab domain and Fc domain, (2) a second Fab domain and (3) an ACE2 receptor domain and Fc domain. 

The latter ACE2 receptor Fc complex also includes a dimerization domain that enables the complex protein to assemble during secretion in mammalian cell culture to form a 6-chain super-heterodimer (a dimer of a heterodimer). The ACE2 receptor domain replicates the natural dimeric ACE2 receptor that binds to viral spike protein. It also has a single point mutation that ablates the enzyme’s catalytic activity. The Fab domains are antibody domains that bind to a conserved epitope on SARS-CoV-1 and SARS-CoV-2 spike proteins. The Fc domains are inactivated to ensure against antibody-dependent enhancement (ADE) of infection, and Fcγ-mediated inflammation and thrombosis while also prolonging circulation time. Intracellular assembly of the super heterodimer also enables manufacturing that reflects that of therapeutic antibodies.]

In vitro and in vivo data on COVICEPT obtained to date and included in the manuscript provide proof-of-concept that the GEM-DIMER platform enables new functionality and extremely potent biological activity.

  • COVICEPT demonstrates increased cytopathic activity compared to a conventional ACE2 receptor decoy (traditional Fc-fusion protein) with an IC50 of almost 10×10-4 μM compared to approximately 10×10-1 μM for the conventional receptor decoy.
  • COVICEPT neutralizes infection in vitro of 11 different variants of SARS-CoV-2, including the Alpha, Beta, Gamma, Delta, Epsilon and other variants, with IC50s between 0.003 and 0.0113 nM demonstrating that COVICEPT’s activity is variant agnostic.
  • COVICEPT potently neutralizes infection in vitro of all of the SARS-CoV-1 and 11 SARS-CoV-2 variants, whereas each of 8 monoclonal antibodies that have received Emergency Use Authorization (EUA) or that are in late stages of clinical trials, including those from Regeneron, Eli Lilly, Vir Biotechnology, AstraZeneca and Celltrion, inhibit only some of the variants.
  • COVICEPT is highly active against the South African (B.1.351, Beta) SARS-CoV-2 variant in a hamster model of infection.
 

The GEM-DIMER platform has significant potential beyond its use in generating superior anti-viral therapeutic candidates. Hinge Bio is focused on similarly addressing the problems of inadequate efficacy and resistance in a variety of oncology applications with GEM-DIMERS it calls All-In-One antibody therapeutics. These All-In-Ones combine three key anti-tumor functions – multivalent/multi-specific cancer cell engagement, single/multivalent immune cell (e.g., T cell or natural killer cell) engagement, and single/multivalent immune cell (e.g., T cell or natural killer cell) activation – into a single molecule. For example, CD3+ T cells and CD_+ Natural Killer cells require two signals, both engagement and activation, to kill tumor cells. A GEM-DIMER can be designed to provide both signals while also engaging a cancer cell. Currently, one needs either two separate antibodies or a tri-specific antibody to accomplish the same task. A GEM-DIMER can perform all three tasks with a single molecule.

In vitro data obtained to date demonstrate and reported in the manuscript … [ALL IN ONE DATA HERE].

“Hinge Bio’s GEM-DIMER platform, which allows for the incorporation of more functionality into a single molecule than conventional approaches, has extremely broad applicability across a range of diseases because of its flexibility to mix and match target binding domains to address specific disease applications,” said Ms. Rollins. “For this reason, we believe that products emerging from the platform can have significant therapeutic and commercial potential. Although GEM-DIMERs are a new class of biotherapeutics, they are predictable, easy to work with and leverage established and cost-effective manufacturing processes that have been developed for antibody products. We are currently conducting pre-IND work on COVICEPT with the objective of entering first-in-human studies in the first half of 2022. In addition, we are progressing All-in-One antibodies towards IND-enabling studies to address the problems of inadequate efficacy and resistance in oncology. The manuscript posted on [PREPRINT SERVER] provides a description of the platform and proof of concept of its capabilities. We look forward to moving COVICEPT into clinical development and advancing our oncology assets.”

Hinge Bio is a privately held biotechnology company leveraging its powerful GEM-DIMER™ platform to develop therapeutics that address the problems of inadequate efficacy and resistance in oncology and infectious disease.  The GEM-DIMER™ platform creates multivalent, multi-specific antibody-based therapeutics that project freely into multidimensional space and cooperatively bind their disease target(s), enabling entirely new functionality for superior efficacy and safety. Learn more at www.hingebio.com.

Hinge Bio:

Carin Rollins

Chief Executive Officer and Co-Founder

carin.rollins@hingebio.com or info@hingebio.com

Media:

Burns McClellan, Inc.Robert

Flamm, Ph.D. / Harrison Wong

rflamm@burnsmc.com / hwong@burnsmc.com

(212) 213-0006, ext. 364 / 316