Apellis & Sobi Enter Collaboration for Global Co-Development & Ex-US Commercialization of Systemic Pegcetacoplan
Apellis Pharmaceuticals, Inc. and Swedish Orphan Biovitrum AB recently announced a strategic collaboration to accelerate the advancement of systemic pegcetacoplan, a targeted C3 therapy, for the treatment of multiple rare diseases with high unmet need that impact more than 275,000 patients globally.
Sobi will receive global co-development and exclusive ex-US commercialization rights for systemic pegcetacoplan. Apellis retains US commercialization rights for systemic pegcetacoplan and worldwide commercial rights for ophthalmological pegcetacoplan, which is being evaluated by Apellis in two fully enrolled Phase 3 studies in geographic atrophy (GA). Pegcetacoplan targets excessive activation of C3 in the complement cascade, part of the body’s immune system, which can lead to the onset and progression of many serious diseases.
Apellis and Sobi plan to jointly advance the clinical development of systemic pegcetacoplan in five parallel registrational programs across hematology, nephrology, and neurology. These include new registrational programs in cold agglutinin disease (CAD) and hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA), both of which are expected to start in 2021. By controlling complement activation centrally, pegcetacoplan offers the potential to become a transformative new therapy in several rare diseases where patients have few or no treatment options today.
“This collaboration enables us to further expand on the broad platform potential of targeting C3 for serious rare diseases that impact hundreds of thousands of patients around the world,” said Cedric Francois, MD, PhD, Co-founder and Chief Executive Officer of Apellis. “We evaluated numerous companies, medium and large, and chose Sobi because of their global leadership in hematology and rare diseases, track record of successful product launches, and deep commitment to patients. Together, we will quickly advance systemic pegcetacoplan in multiple registrational programs across hematology, nephrology, and neurology while also preparing for our first potential U.S. launch in PNH. Financially, this transaction also strengthens our position, with our cash runway expected to extend into the second half of 2022.”
“We are excited to collaborate with Apellis, a leader in targeted C3 therapies. The collaboration will significantly strengthen and broaden our late-stage R&D portfolio and be a catalyst for further internationalization. The products have an excellent fit with our strategic focus on hematology and immunology,” said Guido Oelkers, Chief Executive Officer and President of Sobi. “Given the central role of C3 in the complement cascade, pegcetacoplan has the potential to become the foundation for a broader platform in rare diseases. With positive Phase 3 data in PNH, pegcetacoplan can elevate the standard of care for this debilitating blood disorder.”
As part of the collaboration, Apellis and Sobi will co-develop systemic pegcetacoplan in the following rare diseases:
PNH represents the first potential indication to market for systemic pegcetacoplan. Marketing applications for pegcetacoplan for the treatment of PNH were submitted to the US FDA and the European Medicines Agency (EMA) based on positive results from the Phase 3 PEGASUS study. Top-line results from the Phase 3 PRINCE study, which is evaluating pegcetacoplan in treatment-naïve patients with PNH, are expected in the first half of 2021.
Sobi will lead development activities for the Phase 3 study in CAD and a potentially registrational Phase 2 study in HSCT-TMA, both planned to start in 2021.
Apellis has initiated and will continue to lead a registrational program in IC-MPGN and C3G, which includes Phase 2 and Phase 3 studies.
Apellis has initiated and will continue to lead a potentially registrational Phase 2 study in ALS. Multiple other neurological conditions are under consideration for future clinical development.
Sobi will make an upfront payment of $250 million to Apellis and up to $915 million in other regulatory and commercial milestone payments, and will contribute $80 million in reimbursement payments over a four-year period for research and development to support the initial development plan, which includes ongoing studies in PNH, IC-MPGN/C3G, and ALS and new studies in CAD and HSCT-TMA. Apellis will also be eligible for tiered double-digit royalties on sales ranging from high teens to high twenties. Sobi intends to finance these payments with available funds. Sobi will receive reimbursement payments for the costs incurred by Sobi in connection with the CAD and HSCT-TMA trials that Sobi will conduct. The parties have agreed to split costs 50/50 for any future global studies beyond the initial development plan.
Per the terms of the agreement, Apellis will be responsible for all regulatory and commercial activities in the United States and the ongoing Marketing Authorization Application (MAA) review for PNH in the European Union, which will be subsequently transferred to Sobi. Sobi will be responsible for regulatory and commercial activities for systemic pegcetacoplan in ex-US markets. The co-development of systemic pegcetacoplan will be overseen by a joint development committee, and the commercial strategy will be overseen by a joint commercial committee.
Pegcetacoplan is an investigational, targeted C3 therapy designed to regulate excessive 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 across hematology, ophthalmology, nephrology, and neurology. Pegcetacoplan was granted Fast Track designation by the US FDA for the treatment of PNH and the treatment of geographic atrophy and received orphan drug designation for the treatment of C3G by the FDA and European Medicines Agency.
In October, the European Medicines Agency validated the Marketing Authorization Application (MAA) for pegcetacoplan in PNH, and an opinion from the Committee for Medicinal Products for Human Use is expected in 2021. A decision by the US FDA regarding the acceptance of the New Drug Application (NDA) and a Prescription Drug User Fee Act (PDUFA) target action date is expected in the fourth quarter of 2020. Top-line results from the Phase 3 PRINCE study, which is evaluating pegcetacoplan in treatment-naïve patients with PNH, are expected in the first half of 2021.
The NDA and MAA submissions for pegcetacoplan for the treatment of PNH are based on positive results from the Phase 3 PEGASUS study (APL2-302; NCT03500549), a multi-center, randomized, active-comparator controlled Phase 3 study in 80 adults with PNH. The primary objective of PEGASUS was to establish the efficacy and safety of pegcetacoplan compared to eculizumab. Pegcetacoplan is also being evaluated in the Phase 3 PRINCE study (APL2-308; NCT04085601), a randomized, multi-center, controlled study evaluating pegcetacoplan in 53 patients with PNH who had not received a complement inhibitor within three months before entering the study.
PNH is a rare, chronic, life-threatening blood disorder characterized by the destruction of oxygen-carrying red blood cells through extravascular and intravascular hemolysis. Persistently low hemoglobin can result in frequent transfusions and debilitating symptoms such as severe fatigue, hemoglobinuria, and difficulty breathing (dyspnea). A retrospective analysis shows that, even on eculizumab, approximately 72% of people with PNH have anemia, a key indicator of ongoing hemolysis. The analysis also finds that 36% of patients require one or more transfusions a year and 16% require three or more.
CAD is a severe, chronic, rare blood disorder that currently has no approved therapies and impacts ~10,500 people across the United States and Europe. People living with CAD may suffer from chronic anemia, transfusion requirements, and an increased risk of life-threatening thrombotic events such as stroke. In people with CAD, immunoglobin M (IgM) autoantibodies cause red blood cells to agglutinate, or clump together, at temperatures below 30oC or as a result of a compromised immune system or infection. This activates the complement cascade to destroy healthy red blood cells through extravascular and intravascular hemolysis.
HSCT-TMA is rare blood disease that can be a fatal complication of a bone marrow transplant or HSCT. In HSCT-TMA, microscopic blood clots form in small blood vessels, leading to organ damage. The kidneys are commonly affected, although any organ may be involved. HSCT-TMA occurs in up to 40% of HSCT recipients; every year, there are ~9,000 allogeneic transplants in the United States and ~18,000 in the EU+. Excessive complement activation is a high-risk feature in patients with HSCT-TMA, and C3 is believed to play a critical role in TMA based on proinflammatory and procoagulant properties of C3a and C3b.
IC-MPGN and C3G are rare, debilitating kidney diseases that affect ~18,000 people in the US and Europe. 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. Approximately 50% of people living with IC-MPGN and C3G ultimately suffer kidney failure within five to 10 years of diagnosis. 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.
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. The death of motor neurons leads to the progressive loss of voluntary muscle movement required for speaking, walking, swallowing and breathing. In individuals with ALS, high levels of C3 are present at the neuromuscular junction 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. There are no treatments that stop or reverse the progression of ALS, which impacts ~225,000 patients worldwide.
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 transformative therapies for a broad range of debilitating diseases that are driven by excessive activation of the complement cascade, including those within hematology, ophthalmology, nephrology, and neurology. For more information, please visit http://apellis.com.
Sobi is a specialized international biopharmaceutical company transforming the lives of people with rare diseases. Sobi is providing sustainable access to innovative therapies in the areas of hematology, immunology and specialty indications. Today, Sobi employs approximately 1,500 people across Europe, North America, the Middle East, Russia and North Africa. In 2019, Sobi’s revenue amounted to SEK 14.2 billion. Sobi’s share (STO:SOBI) is listed on Nasdaq Stockholm. You can find more information about Sobi at www.sobi.com.
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