Preclinical In Vivo Models Demonstrate Blockade of FcRn-Albumin Interactions May Have Application in Protecting the Liver from Hepatotoxins
SYNT002 Program to Commence IND-Enabling Studies in 2017
NEW YORK–(BUSINESS WIRE)–Syntimmune, Inc., a clinical-stage biotechnology company and the leader in FcRn biology, today announced the peer-reviewed publication of research findings for SYNT002, the Company’s second most advanced pipeline program and lead monoclonal antibody therapy targeting albumin-FcRn interactions. SYNT002 is in active preclinical development by Syntimmune for a number of indications and is expected to enter IND-enabling studies in 2017. The study, led by Syntimmune scientific founder Dr. Richard Blumberg in collaboration with multiple members of the Company’s Scientific Advisory Board, appears in the journal Proceedings of the National Academy of Sciences (doi: 10.1073/pnas.1618291114 PNAS March 20, 2017). These research findings demonstrate that inhibition of FcRn (neonatal Fc receptor) provides protection against toxin-induced liver injury and causes removal of toxins from circulation via a newly described mechanism that is engaged by SYNT002. Among the key results are:
- While FcRn in the liver maintains albumin homeostasis, inhibition of albumin-FcRn binding caused clearance of albumin from the circulation via transport into the bile.
- Using acetaminophen poisoning as a preclinical model of an albumin-bound hepatotoxin, FcRn inhibition was shown to increase albumin-mediated transport of acetaminophen out of the circulation and into the bile where it is excreted from the body, protecting the liver and other organs from this toxin.
- In addition to inducing sequestration of albumin-bound toxins in bile, FcRn blockade caused albumin accumulation within hepatocytes, exerting important anti-oxidant effects to protect liver cells from acetaminophen damage.
- Multiple therapeutic modalities, including SYNT002 and a peptide mimetic inhibitor of FcRn, engaged this mechanism to provide robust protection from acetaminophen-induced liver toxicity
“There are two important aspects of this research. First, FcRn is shown to be critical for directing albumin into the blood, allowing albumin’s normal functions for health,” stated David E. Cohen, Chief of Division of Gastroenterology and Hepatology at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center. “Second, this article also underscores a broad therapeutic opportunity. Substances such as acetaminophen can literally act as hitchhikers by attaching to albumin and this allows them to build up toxic levels in the body. I find it a very exciting possibility that we may be able to decrease these toxic levels by selectively inhibiting FcRn so that albumin and the toxin it is carrying can be shunted out of the bloodstream and into the bile. I look forward to the continued progress of this promising research.”
“Syntimmune has built a commanding intellectual property (IP) estate covering therapeutic blockade of FcRn-albumin interactions, including key IP licensed from Brigham and Women’s Hospital. The findings published this week in PNAS bring together over a decade of research on modulation of FcRn-albumin interactions. The results of this study support the high potential of SYNT002 and related molecules to treat a wide range of conditions involving exo- and endo-toxins that bind to albumin. These include toxins associated with renal disease and drug induced liver injury as well as certain severe metabolic diseases and many forms of chemical poisoning. In addition to promoting liver clearance of albumin-bound toxins, we envision an opportunity to also effect the clearance of toxins through the kidney by extrapolation from these innovative studies,” stated David de Graaf, Ph.D., Syntimmune’s President and Chief Executive Officer. “The immediate goal for our SYNT002 program is to progress our lead molecule to the IND stage in important indications where this novel mechanism of action has potential to transform therapy. We are excited with the progress of this program, which could have a far-reaching impact on human health by providing a powerful and non-invasive means to clear the body of toxins.”
Laurence Blumberg, M.D., Founder and COO of Syntimmune, commented, “Syntimmune continues to advance its clinical-stage lead program, SYNT001, a biologic that precisely blocks FcRn-IgG interactions and is being developed for the treatment of IgG-mediated autoimmune diseases. Based on the activity and safety profile demonstrated by SYNT001 in Phase 1, we have initiated a broad Phase 1b/2a development campaign that includes multiple independent Phase 1b/2a studies of SYNT001 across a range of prioritized indications that provide compelling clinical and commercial opportunities.”
Founded in 2013, Syntimmune is advancing novel therapies based on its leading position in the biology of the neonatal Fc receptor (FcRn). As a core part of a central common pathway that enables abnormal IgG responses, FcRn is a well-validated target for the treatment of IgG-mediated autoimmune diseases. Syntimmune’s lead candidate, SYNT001, is a biologic that specifically blocks FcRn-IgG interactions and is being studied in multiple 1b/2a trials for the treatment of IgG-mediated autoimmune diseases. In addition to SYNT001, Syntimmune is developing two earlier-stage therapeutic programs, including SYNT002, which target other unique aspects of FcRn biology. The Syntimmune team has world-class experience in the field of FcRn biology and has successfully pioneered and advanced biologics targeting FcRn, including approved therapies currently on the market. Since its founding, the Company has received a total of $28 million in funding commitments from leading life sciences investors, led by Apple Tree Partners. For more information on Syntimmune, please visit the Company’s website at www.syntimmune.com.
Media: Burns McClellan
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