Apellis Pharmaceuticals Will Commence APL-9 Program to Control the Complement System in Host Responses to AAV Vector Administration for Gene TherapiesBy Matthew Miessau In All, Portfolio
CRESTWOOD, Ky. and WALTHAM, Mass., – Apellis Pharmaceuticals Inc., (Nasdaq:APLS) a clinical-stage biopharmaceutical company focused on the development of novel therapeutic compounds to treat disease through the control of the complement system, today announced its plans to develop APL-9 for the prevention of complement immune system activation coincident with adeno-associated virus (AAV) vector administration for gene therapies. APL-9, an investigational drug, is a pegylated synthetic cyclic peptide designed to modulate the complement cascade centrally at C3.
“Gene therapies are among the most exciting medical advancements of our time. However, they also pose a great technical challenge, since the AAV particles designed to deliver genes to tissues are subject to immediate and overwhelming immune attack, specifically by complement C3, which may result in significant safety and efficacy constraints,” said Cedric Francois, CEO and co-founder of Apellis. “We believe that the targeted control of C3 may prevent the C3-mediated attack on AAV particles, yielding three important potential advantages. First, controlling C3 may significantly increase the efficiency of gene therapy delivery by protecting the AAV particles on their journey from the site of administration to the target tissue. Second, control of C3 may minimize the formation of anti-AAV neutralizing antibodies that can complicate subsequent retreatment with the same AAV. Finally, by countering the rapid activation of C3 upon administration of AAV particles, control of C3 may prevent inflammatory reactions that can lead to significant organ damage, for example in the kidneys. Apellis is committed to the development of APL-9 to target host responses to AAV vector administration and thus potentially improve patients’ well-being while undergoing AAV administered gene therapies.”
In Phase I testing, Apellis treated 20 healthy volunteers with single doses of APL-9 ranging from 30 mg to 600 mg, administered as an intravenous infusion. APL-9 demonstrated control of complement through modulation of C3 within 1 hour of administration, that lasted up to 12 hours after the end of the infusion. Multiple doses tested achieved complete suppression of the AH50 hemolytic activity. In this Phase I study, APL-9 was well tolerated with no serious adverse events reported.
APL-9, an investigational drug, is designed to modulate the complement cascade centrally at C3 and may have the potential to treat a range of complement-mediated conditions more effectively than is possible with partial inhibitors of complement. APL-9, is a second-generation C3 modulator that leverages the same mechanism of action as Apellis’ lead compound, APL-2 (pegcetacoplan), but has a lower molecular weight and shorter half-life. APL-9 is designed to be intravenously administered for acute use whereas APL-2 is designed for chronic subcutaneous or intravitreal administration.
About Apellis’ lead candidate APL-2 (pegcetacoplan)
APL-2, an investigational drug, is designed to modulate the complement cascade centrally at C3 and may have the potential to treat a wide range of complement-mediated diseases more effectively than is possible with partial inhibitors of complement. APL-2 is a synthetic cyclic peptide conjugated to a polyethylene glycol (PEG) polymer that binds specifically to C3 and C3b, effectively blocking all three pathways of complement activation (classical, lectin, and alternative). Apellis is currently evaluating APL-2 in clinical studies in patients with geographic atrophy (GA), in patients with paroxysmal nocturnal hemoglobinuria (PNH) who are being treated with eculizumab or who are naïve to complement inhibitor treatment, in patients with cold agglutinin disease (CAD) and warm autoimmune hemolytic anemia (wAIHA), and in patients with C3 glomerulopathy (C3G) and other glomerular diseases. For additional information regarding these clinical trials, visit www.apellis.com/clinical-trials.html.
Apellis Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on the development of novel therapeutic compounds for the treatment of a broad range of life-threatening or debilitating autoimmune diseases based upon complement immunotherapy through the inhibition of the complement system at the level of C3. Apellis is the first company to advance chronic therapy with a C3 inhibitor into clinical trials. For additional information about Apellis and APL-2, please visit http://www.apellis.com.
Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to the implications of preliminary clinical data. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: whether the Company’s clinical trials will be initiated, fully enrolled and completed when anticipated; whether preliminary or interim results from a clinical trial will be predictive of the final results of the trial; whether results obtained in preclinical studies and clinical trials will be indicative of results that will be generated in future clinical trials; whether APL-2 or APL-9 will successfully advance through the clinical trial process on a timely basis, or at all; whether the results of such clinical trials will warrant regulatory submissions and whether APL-2 or APL-9 will receive approval from the FDA or equivalent foreign regulatory agencies for GA, PNH, CAD, wAIHA, C3G or any other indication; whether, if Apellis’ products receive approval, they will be successfully distributed and marketed; and other factors discussed in the “Risk Factors” section of Apellis’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 7, 2019 and the risks described in other filings that Apellis may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Apellis specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.