Apellis Initiates Registrational Programs of Pegcetacoplan in Patients with C3G / IC-MPGN and ALS, Rare Diseases with High Unmet Need

Advancing Phase 2 and Phase 3 studies of the company’s targeted C3 therapy in C3G / IC-MPGN, rare kidney diseases with no approved medicines. First patient in Phase 2 study expected to be dosed by the end of the year
Potentially registrational Phase 2 study in ALS to enroll ~200 adults globally. First patient expected to be dosed by the end of the yearWALTHAM, Mass., Oct. 05, 2020 (GLOBE NEWSWIRE) — Apellis Pharmaceuticals, Inc. (Nasdaq: APLS), a global biopharmaceutical company and leader in targeted C3 therapies, today announced that it has initiated registrational programs of pegcetacoplan, a targeted C3 therapy, for people living with C3 glomerulopathy (C3G) or immune complex membranoproliferative glomerulonephritis (IC-MPGN), rare diseases that can lead to kidney failure within five to 10 years, and amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease that leads to progressive muscle weakness and paralysis. Uncontrolled activation of the complement cascade, a part of the body’s immune system, is believed to play a role in the progression of these serious diseases.“People and families living with C3G, IC-MPGN, and ALS are in significant need of new medicines. We believe that controlling complement activation centrally, at the level of C3, has the potential to offer an important new therapeutic approach for each of these rare diseases,” said Cedric Francois, M.D., Ph.D., co-founder and chief executive officer of Apellis. “Our data in C3G support continued advancement of pegcetacoplan, and numerous studies suggest that elevated levels of C3 may play a role in the progression of ALS. These new trials build on the broad platform potential of targeting C3, and we are working urgently to advance these programs for patients.”Nephrology: Registrational Program for C3G / IC-MPGNC3G / IC-MPGN are rare kidney diseases that impact ~18,000 patients in the United States and Europe1 and currently have no approved therapies. C3 deposition in the kidneys is present in both C3G and IC-MPGN; however, substantial immunoglobulin deposition is also seen in IC-MPGN.2,3Apellis is advancing a registrational program in C3G / IC-MPGN beginning with the Phase 2 NOBLE study, a randomized, controlled trial in 12 patients with post-transplant disease recurrence that will focus on the histopathology of the kidneys. The first patient is expected to be dosed in this study by the end of 2020. Apellis also plans to begin a Phase 3 study in the first half of 2021 with reduction in proteinuria as its primary endpoint.With these trials, Apellis will be the only company actively studying a potential treatment for patients with IC-MPGN, a disease where both the alternative and classical pathways have been implicated, which supports targeting the complement cascade centrally at C3 as a potential therapeutic option.The company is advancing pegcetacoplan in C3G / IC-MPGN based on data in C3G from the Phase 2 DISCOVERY trial. Data at week 12 were positive; results at 48 weeks will be presented at a scientific congress later this year.Neurology: Potentially Registrational Phase 2 Study in ALSApellis is expanding the development of pegcetacoplan into neurology with a potentially registrational Phase 2 study in ALS, a disease that impacts approximately 225,000 patients worldwide.4In individuals with ALS, high levels of activated C3 are present at the neuromuscular junction5 where the neurons communicate directly to muscle cells. Multiple studies suggest that the elevated levels of C3 present in ALS may be responsible for the chronic neuroinflammation that leads to motor neuron death.5,6,7Apellis has initiated the MERIDIAN study, a randomized, placebo-controlled trial of pegcetacoplan in approximately 200 adults with sporadic ALS, and expects to dose the first patient by the end of 2020. The primary endpoint of the study is the Combined Assessment of Function and Survival (CAFS) rank scores at week 52.About the Phase 2 NOBLE study in C3G / IC-MPGN
The Phase 2 NOBLE study (APL2-C3G-204; NCT04572854) is a multicenter, open-label, randomized, controlled study designed to evaluate the efficacy and safety of pegcetacoplan in up to 12 adults who have post-transplant recurrence of C3G or IC-MPGN. Study participants will be randomized in a 3:1 ratio to receive pegcetacoplan or maintain standard of care for 12 weeks and then all patients in the study will receive pegcetacoplan from week 13 to week 52.
The primary endpoint of the study is the proportion of patients with reduction in C3c staining on renal biopsy after 12 weeks of treatment with pegcetacoplan. Secondary endpoints include an evaluation of safety, the proportion of patients with reduction in C3c staining on renal biopsy after 52 weeks of treatment, and the proportion of patients achieving at least a 50% reduction in proteinuria.About the Phase 2 MERIDIAN Study in ALS
The Phase 2 MERIDIAN study (APL2-ALS-206) is a potentially registrational, randomized, placebo-controlled, multicenter study that was designed to evaluate the efficacy and safety of pegcetacoplan in approximately 200 adults with sporadic ALS. Study participants will be randomized in a 2:1 ratio to receive pegcetacoplan or placebo while continuing to receive their existing standard of care treatment for ALS. After one year, all patients in the study will receive pegcetacoplan. To reduce the burden on people living with ALS and their caregivers, the trial has been designed to minimize the number of in-clinic visits, with approximately six clinic visits in the first year and four in the open-label second year.
The primary endpoint of the study is the Combined Assessment of Function and Survival (CAFS) rank scores at week 52. Key secondary endpoints include measures of lung function, muscle strength, and quality of life.About Pegcetacoplan (APL-2)
Pegcetacoplan is an investigational, targeted C3 therapy designed to regulate excessive or uncontrolled complement activation, which can lead to the onset and progression of many serious diseases. Pegcetacoplan is a synthetic cyclic peptide conjugated to a polyethylene glycol polymer that binds specifically to C3 and C3b. Apellis is evaluating pegcetacoplan in several clinical studies including paroxysmal nocturnal hemoglobinuria (PNH), geographic atrophy (GA), cold agglutinin disease (CAD), and C3 glomerulopathy (C3G). Pegcetacoplan was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of PNH and the treatment of GA, and received orphan drug designation for the treatment of C3G by the FDA and European Medicines Agency. For additional information regarding our clinical trials, visit https://apellis.com/our-science/clinical-trials.
About C3 Glomerulopathy (C3G) and Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN)
C3G and IC-MPGN are rare, debilitating kidney diseases that affect ~18,000 people in the United States and Europe.1 There are no approved therapies for the diseases, and symptoms include blood in the urine, dark foamy urine due to the presence of protein, swelling and high blood pressure.8 Approximately 50% of people living with C3G and IC-MPGN ultimately suffer kidney failure within five to 10 years of diagnosis.9 Although IC-MPGN is considered a distinct disease from C3G, the underlying cause and progression of the two diseases are remarkably similar and include overactivation of the complement cascade, with excessive accumulation of C3 breakdown products in the kidney causing inflammation and damage to the organ.2,3
About Amyotrophic Lateral Sclerosis (ALS)
ALS is a devastating neurodegenerative disease that results in progressive muscle weakness and paralysis due to the death of nerve cells, called motor neurons, in the brain and spinal cord.10,11 The death of motor neurons leads to the progressive loss of voluntary muscle movement required for speaking, walking, swallowing and breathing.10,11 In individuals with ALS, high levels of C3 are present at the neuromuscular junction5 where motor neurons communicate directly to muscle cells. Numerous studies suggest that elevated levels of C3 present throughout the motor system of ALS patients are likely to contribute to chronic neuroinflammation and the death of motor neurons.5,6,7 There are no treatments that stop or reverse the progression of ALS, which impacts ~225,000 patients worldwide.4
About Apellis
Apellis Pharmaceuticals, Inc. is a global biopharmaceutical company that is committed to leveraging courageous science, creativity, and compassion to deliver life-changing therapies. Leaders in targeted C3 therapies, we aim to develop best-in-class and first-in-class therapies for a broad range of debilitating diseases that are driven by uncontrolled or excessive activation of the complement cascade, including those within hematology, ophthalmology, nephrology, and neurology. For more information, please visit http://apellis.com.
Apellis Forward-Looking Statement
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 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 pegcetacoplan will successfully advance through the clinical trial process on a timely basis, or at all; whether the results of the company’s clinical trials will warrant regulatory submissions and whether pegcetacoplan will receive approval from the FDA or equivalent foreign regulatory agencies for GA, PNH, CAD, C3G, IC-MPGN, ALS or any other indication when expected or at all; 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 July 30, 2020 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.
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1 ClearView Analysis using physician and literature consensus.
2 Noris M, Donadelli R, Remuzzi G. Autoimmune abnormalities of the alternative complement pathway in membranoproliferative glomerulonephritis and C3 glomerulopathy. Pediatr Nephrol. 2019 Aug;34(8):1311-1323.
3 Cook HT. Evolving complexity of complement-related diseases: C3 glomerulopathy and atypical haemolytic uremic syndrome. Curr Opin Nephrol Hypertens. 2018 May;27(3):165-170.
4 Arthur K et al. Nat Commun, 2016, Vol 7, article 12408
5 Bahia El Idrissi N, et al. J Neuroinflammation. 2016;13(1):72.4 Sta M, et al. Neurobiol Dis. 2011;42(3):211-220.
6 Woodruff, et al., PNAS January 7, 2014 111 (1) E3-E4
7 Lee, et al Journal of Neuroinflammation volume 15: 171 (2018)
8 Complement 3 Glomerulopathy (C3G). National Kidney Foundation Website. https://www.kidney.org/atoz/content/complement-3-glomerulopathy-c3g. Accessed November 21, 2019.
9 C3 glomerulopathy. National Institute of Health, Genetics Home Reference. https://ghr.nlm.nih.gov/condition/c3-glomerulopathy#resources. Accessed November 21, 2019.
10 National Institute of Neurological Disorders and Stroke. (2020). Amyotrophic Lateral Sclerosis Fact Sheet. Retrieved from https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Amyotrophic-lateral-Sclerosis-ALS-Fact-Sheet
11 ALS Association. What is ALS? Retrieved June 2020 from https://www.als.org/understanding-als/what-is-als

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