Apellis Pharmaceuticals Stock

Apellis Pharmaceuticals, Inc. operates as a commercial-stage biopharmaceutical company. The company focuses on the discovery, development and commercialization of novel therapeutic compounds to treat diseases with high unmet needs through the inhibition of the complement system, which is an integral component of the immune system, at the level of C3, the central protein in the complement cascade.

In February 2023, the U.S. Food and Drug Administration, or the FDA, approved SYFOVRE (pegcetacoplan injection), the first approved treatment for geographic atrophy secondary to age-related macular degeneration, or GA. SYFOVRE has the potential to be a best-in-class treatment for patients with GA, a disease that affects more than one million people in the United States and five million people worldwide. The company launched SYFOVRE in the United States in March 2023.

In December 2022, the company also submitted a marketing authorization application, or MAA, to the European Medicines Agency, or EMA, for intravitreal pegcetacoplan for the treatment of GA. The EMA subsequently provided MAA validation and the application is under review. In January 2024, the Committee for Medicinal Products for Human Use, or CHMP, adopted a negative opinion on the marketing authorization application, or MAA, for intravitreal pegcetacoplan. The company is initiating the re-examination of the application. Marketing applications submitted to regulatory authorities in Canada, Australia, the United Kingdom, and Switzerland for the treatment of GA are under review. The company has exclusive, worldwide commercialization rights for intravitreal pegcetacoplan.

In November 2023, the company disclosed data from GALE, its long-term extension trial of SYFOVRE, which demonstrated increasing treatment effects over 36 months in patients with GA. The safety profile of SYFOVRE in the GALE trial at 36 months was consistent with previously reported Phase 3 data.

In July 2023, the company disclosed that it had received reports of a small number of events of retinal vasculitis following SYFOVRE treatment. As of mid-February 2024, and following the distribution of more than 200,000 doses (commercial and sample) of SYFOVRE, the company estimates that the rate of incidence of retinal vasculitis remains rare at approximately 0.01% per injection. In November 2023, the company updated the U.S. Prescribing Information, or USPI, for SYFOVRE in collaboration with the FDA to include the events of retinal vasculitis with or without occlusion as part of the Warnings and Precautions and Adverse Reactions - Postmarketing Experience sections of the USPI.

The U.S. Centers for Medicare & Medicaid Services assigned a permanent and product-specific J-code for SYFOVRE, which became effective on October 1, 2023. J-codes are permanent reimbursement codes used by government payers and commercial insurers to facilitate billing of Medicare Part B treatments, which must be administered by a healthcare professional.

In May 2021, the FDA approved EMPAVELI (pegcetacoplan), the first targeted C3 therapy, for the treatment of paroxysmal nocturnal hemoglobinuria, or PNH. EMPAVELI is approved for use in adults with PNH and can be used by patients who are either treatment-naïve or who are switching from C5 inhibitors eculizumab or ravulizumab. EMPAVELI has the potential to elevate the standard of care in PNH and is seeking to establish EMPAVELI as the preferred first-line treatment for patients. In October 2023, the company announced the FDA approval of the EMPAVELI Injector, a compact, single-use, on-body device designed to enhance self-administration of EMPAVELI.

In December 2021, the European Commission, or the EC, approved Aspaveli (pegcetacoplan) for the treatment of adults with PNH who are anemic after treatment with a C5 inhibitor for at least three months. In January 2024, following the submission of the Phase 3 PRINCE data in treatment-naïve PNH patients, the EC updated the Aspaveli indication statement to include all PNH patients with hemolytic anemia. As of December 31, 2023, systemic pegcetacoplan has also been approved for the treatment of PNH in Japan, Saudi Arabia, Australia, the United Kingdom and other jurisdictions. Systemic pegcetacoplan is marketed under the trade name EMPAVELI in the United States, Saudi Arabia and Australia and Aspaveli in the European Union, Japan and United Kingdom. Under its collaboration and license agreement, or the Sobi collaboration agreement, with Swedish Orphan Biovitrum AB (Publ), or Sobi, Sobi has global co-development and exclusive ex-U.S. commercialization rights for systemic pegcetacoplan and initiated the commercial launch of EMPAVELI/Aspaveli in jurisdictions outside of the United States during the first quarter of 2022. The company has commercialization rights for systemic pegcetacoplan in the United States.

The company is leading the development of systemic pegcetacoplan in C3 glomerulopathy, or C3G, and immune complex membranoproliferative glomerulonephritis, or IC-MPGN, in nephrology under its collaboration with Sobi. In October 2023, the company announced positive results from ten patients treated in the Phase 2 NOBLE trial investigating pegcetacoplan for the treatment of post-transplant recurrence of primary IC-MPGN and C3G. The results showed the potential for a treatment effect in both IC-MPGN and C3G patients treated with pegcetacoplan. Specifically, at 12 weeks, 80% of patients showed a reduction in C3c staining by one or more orders of magnitude of intensity from baseline and 40% of patients showed zero staining intensity, indicating that C3c deposits were cleared. Patients also showed improvements across key clinical measures, including a mean reduction in proteinuria, and stabilized kidney function. There were no discontinuations due to treatment-emergent adverse events. The company plans to report top-line data from the ongoing Phase 3 VALIANT trial investigating pegcetacoplan in adolescent and adult patients with native and post-transplant recurrence IC-MPGN and C3G in mid-2024. The company is also evaluating the administration of systemic pegcetacoplan as a novel approach to enabling adeno associated virus, or AAV, vector administration for gene therapies.

Under its collaboration with Sobi, Sobi is leading the development of systemic pegcetacoplan for hematopoietic stem cell transplantation-associated thrombotic microangiopathy, or HSCT-TMA, in hematology. In January 2024, together with Sobi, the company discontinued the CASCADE Phase 3 trial evaluating systemic pegcetacoplan in patients with cold agglutinin disease, or CAD, due to the decreased medical need in CAD and the limited number of patients eligible for the CASCADE trial. In May 2023, the company and Sobi announced that the Phase 2 MERIDIAN study evaluating systemic pegcetacoplan for amyotrophic lateral sclerosis, or ALS, did not meet its primary or key secondary endpoints. Based on this lack of efficacy, the company and Sobi discontinued development of systemic pegcetacoplan for ALS.

Lastly, the company is developing additional product candidates with other routes of administration. These candidates include APL-3007, a small interfering RNA, or siRNA, which is in a Phase 1 clinical trial in healthy volunteers with topline data expected in 2024, as well as an oral complement inhibitor in preclinical development. Furthermore, the company is collaborating with Beam Therapeutics, Inc., or Beam, on up to six research programs focused on C3 and other complement targets in the eye, liver and brain, using Beam's proprietary base editing technology to discover new treatments for complement-driven diseases.

Strategy

The company holds commercialization rights for systemic pegcetacoplan, which includes EMPAVELI, in the United States and worldwide commercialization rights to intravitreal pegcetacoplan, which includes SYFOVRE, in addition to worldwide commercialization rights for its other novel compounds targeting complement. The key elements of the company's strategy include bringing SYFOVRE to patients with GA globally; maximizing EMPAVELI as a first-line treatment in PNH; developing systemic pegcetacoplan for the potential treatment of C3G and IC-MPGN; and advancing early pipeline and Beam collaboration.

Programs

Pegcetacoplan targets C3, the central protein of the complement cascade. Pegcetacoplan is a conjugate of a compstatin analogue, formulated both for intravitreal administration by injections directly into the eye, and systemic administration by subcutaneous injection, which is an injection into the tissue under the skin. The company has developed and are developing pegcetacoplan and other product candidates through various routes of administration.

Ophthalmology

The company is commercializing SYFOVRE as a monotherapy for patients with GA.

Regulatory Matters

In February 2023, intravitreal pegcetacoplan was approved by the FDA with the brand name SYFOVRE for the treatment of adult patients with GA secondary to AMD. In December 2022, the company also submitted an MAA to the EMA for intravitreal pegcetacoplan for the treatment of GA. The EMA subsequently provided MAA validation and the application is under review. In January 2024, the company announced that the CHMP adopted a negative opinion on the MAA. The company is seeking immediate re-examination of the opinion. The company's marketing applications for the treatment of GA are under review by regulatory authorities in Canada, Australia, the United Kingdom, and Switzerland.

Commercial and Medical Activities for GA Launch

The company launched SYFOVRE, the first approved treatment for GA, in the United States in March 2023. SYFOVRE is the market-leading treatment for GA, a disease that affects more than one million people in the United States and five million people worldwide.

The company's U.S. field sales team has been engaging with eyecare professionals, or ECPs, focusing specifically on retina specialists and treating ophthalmologists in person, at conferences and virtually. Field teams are focused on SYFOVRE brand messaging and clinical overview, highlighting key advantages, such as increasing effects over time, its strong clinical profile, and dosing flexibility. The company's marketing efforts also reach ECPs through digital and print media. The company reaches patients through direct-to-consumer (TV, print and digital media) disease state education and branded SYFOVRE messaging encouraging them to see their eye doctor if they have symptoms or a previous diagnosis.

The company's medical affairs team is engaging with ECPs, either in-person or virtually, and through its presence at medical meetings and other in-person engagements when appropriate. Throughout 2023, the company participated in key scientific meetings, including the American Academy of Ophthalmology, Retina Society, FLORETINA, and Macula Society.

Clinical Development

The company initiated the Phase 3 DERBY and OAKS trials evaluating the efficacy and safety of SYFOVRE in patients with GA secondary to AMD in September 2018. The company presented reported 24-month results from its DERBY and OAKS trials in August 2022, following 18-month results presented in March 2022 and 12-month results presented in September 2021. In July 2018, the company received fast track designation from the FDA for pegcetacoplan in GA. In August 2017, the company completed the primary endpoint analysis for the 12-month treatment period for the Phase 2 FILLY trial and in February 2018, the company completed the analysis of data from the six-month post-treatment monitoring period from that trial. Prior to the FILLY trial, the company completed a Phase 1 trial of pegcetacoplan in patients with wet AMD in 2016.

Phase 3 Clinical Trials

The company's Phase 3 clinical program in GA consisted of two prospective, multicenter, randomized, double-masked, sham-injection controlled trials (DERBY and OAKS) conducted at more than 200 sites worldwide to assess the efficacy and safety of multiple intravitreal injections of pegcetacoplan in patients with GA.

The company completed the primary analysis for the 24-month treatment period in August 2022. The company used a liquid formulation of pegcetacoplan in its Phase 3 trials instead of the freeze-dried formulation that it used in the Phase 2 FILLY trial.

Long-term Extension Study

The company is conducting a 36-month, open-label extension study (GALE) to evaluate the long-term safety and efficacy of intravitreal pegcetacoplan in patients with GA secondary to AMD.

Phase 2 Clinical Trial

In the third quarter of 2015, the company initiated FILLY, its Phase 2 multicenter, randomized, single-masked, sham-controlled clinical trial of SYFOVRE in patients with GA.

Rare Disease

Together with Sobi, the company is developing systemic pegcetacoplan in multiple late-stage programs in rare disease indications in hematology and nephrology. The company is leading the clinical development for the treatment of C3G/IC-MPGN, and Sobi is leading the clinical development for the treatment of HSCT-TMA. In PNH, the company and Sobi has obtained approval of systemic pegcetacoplan for the treatment of PNH in multiple jurisdictions, including the United States and the European Union.

Regulatory Matters

In May 2021, systemic pegcetacoplan was approved by the FDA with the brand name EMPAVELI for the treatment of adult patients with PNH. In December 2021, the European Commission approved systemic pegcetacoplan with the brand name Aspaveli for the treatment of adults with PNH who are anemic after treatment with a C5 inhibitor for at least three months. Aspaveli was approved in the United Kingdom in March 2022 and in Japan in March 2023. In January 2024, following the submission of the Phase 3 PRINCE data in treatment-naïve PNH patients, the EC updated the Aspaveli indication statement to include all PNH patients with hemolytic anemia. In January 2022, pegcetacoplan was also approved as EMPAVELI in Saudi Arabia and Australia.

In 2022, the company submitted two sNDAs to the FDA intended to strengthen the EMPAVELI label and improve the patient experience. The first sNDA was approved in February 2023 and includes the treatment-naïve data from the PRINCE study and the longer-term, 48-week PEGASUS results. The second sNDA for the EMPAVELI injector was approved in October 2023.

Commercial and Medical Activities for EMPAVELI

The company launched EMPAVELI in the United States for patients with PNH following its approval by the FDA in May 2021.

Phase 3 Clinical Trial - PEGASUS

The company initiated the Phase 3 PEGASUS trial in patients in June 2018. The PEGASUS trial was an 80-patient randomized head-to-head trial comparing systemic pegcetacoplan monotherapy to eculizumab monotherapy in patients with PNH on treatment with eculizumab who have a hemoglobin level of less than 10.5 g/dL, regarding of eculizumab dose or transfusion history.

Phase 3 Clinical Trial - PRINCE

The company initiated the Phase 3 PRINCE trial in 2019. The PRINCE trial was a 54-patient randomized, multicenter, open-label trial to evaluate the efficacy of systemic pegcetacoplan in treatment-naïve PNH patients. The primary endpoints were avoidance of a greater than 1 g/dL decrease in hemoglobin level from baseline in the absence of transfusion through week 26 and reduction in LDH level from baseline to week 26, in patients with PNH who are not being treated with complement inhibitors.

Long-Term Extension Study

The company is conducting a long-term extension study of systemic pegcetacoplan in patients with PNH who participated in previous clinical trials with pegcetacoplan. This study is an open label, non-randomized, multi-center study to evaluate the long-term safety and efficacy of pegcetacoplan in the treatment of PNH with dosing for a longer period and at doses of 1,080 mg given either twice a week or every three days.

Safety

In all trials of pegcetacoplan administered systemically by subcutaneous injection, the company has monitored the safety of its targeting of C3 closely. Individuals who lack functional levels of C3 or C5 have been shown to be susceptible to infection by certain bacterial species, including Neisseria meningitidis in C5-deficient individuals and Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae in C3-deficient individuals.

C3 Glomerulopathy (C3G) and Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN)

In February 2018, the company initiated DISCOVERY, a Phase 2 clinical trial of systemic pegcetacoplan in biopsy-proven C3G and other glomerular diseases in which complement has been implicated, including IgA nephropathy, primary membranous nephropathy and lupus nephritis, to evaluate the safety and biologic activity of pegcetacoplan in patients with these glomerular diseases.

In October 2020, the company reported data from the DISCOVERY trial in five C3G patients treated with systemic pegcetacoplan for 48 weeks. In those patients, mean (SE) proteinuria decreased from 3.48 (0.82) mg/mg at baseline to 0.93 (0.27) mg/mg at week 48, a decrease of 73.3%, as measured by 24-hour uPCR. Importantly, this reduction in proteinuria was accompanied by a corresponding increase in mean serum albumin.

In September 2021, the company initiated a Phase 2 trial in C3G and IC-MPGN with its NOBLE trial, a randomized, controlled trial in 12 patients with post-transplant disease recurrence that focused on the histopathology of the kidneys. Trial participants were randomized in a 3:1 ratio to receive pegcetacoplan or maintain standard of care for 12 weeks and then all patients in the study received pegcetacoplan from week 13 to week 52. The primary endpoint of the study was the proportion of patients with reduction in C3c staining on renal biopsy after 12 weeks of treatment with pegcetacoplan. Secondary endpoints included 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.

In October 2023, the company announced positive results from NOBLE showing the potential for a treatment effect in both IC-MPGN and C3G patients treated with pegcetacoplan. Specifically, at 12 weeks, 80% of patients showed a reduction in C3c staining by one or more orders of magnitude of intensity from baseline and 40% of patients showed zero staining intensity, indicating that C3c deposits were cleared. Patients also showed improvements across key clinical measures, including a mean reduction in proteinuria, and stabilized kidney function. There were no discontinuations due to treatment-emergent adverse events.

In October 2023, the company announced positive results from NOBLE showing the potential for a treatment effect in both IC-MPGN and C3G patients treated with pegcetacoplan. Specifically, at 12 weeks, 80% of patients showed a reduction in C3c staining by one or more orders of magnitude of intensity from baseline and 40% of patients showed zero staining intensity, indicating that C3c deposits were cleared. Patients also showed improvements across key clinical measures, including a mean reduction in proteinuria, and stabilized kidney function. There were no discontinuations due to treatment-emergent adverse events.

Hematopoietic Stem Cell Transplantation Thrombotic Microangiopathy

Hematopoietic stem cell transplantation thrombotic microangiopathy, or 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 approximately 9,000 allogeneic transplants in the United States. 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.

In early 2022, Sobi dosed the first patient in the Phase 2 clinical trial of systemic pegcetacoplan in patients with HSCT-TMA. The Phase 2 trial is an open label, single arm, multicenter trial evaluating the pharmacokinetics, efficacy and safety and tolerability of pegcetacoplan in approximately 12 patients with HSCT-TMA.

Adeno-Associated Virus, or AAV, Vector Administration for Gene Therapies

The company is also evaluating the administration of systemic pegcetacoplan as an approach to enabling AAV vector administration for gene therapies.

Other Programs

In June 2021, the company entered into an exclusive five-year research collaboration with Beam focused on the use of Beam's proprietary base editing technology to discover new treatments for complement-driven diseases. Under the collaboration agreement, the company is collaborating on up to six research programs focused on C3 and other complement targets in the eye, liver and brain.

The company began a Phase 1 dose escalation clinical trial for APL-3007, a siRNA therapy, in healthy volunteers in June 2023 and expects topline data from this study in 2024. The company is also advancing an oral complement inhibitor which is in preclinical development.

Collaboration and License Agreement with Sobi

In 2020, the company and its subsidiaries, Apellis International GmbH and APL DEL Holdings, LLC, entered into a Collaboration and License Agreement (the Sobi collaboration agreement) with Sobi, concerning the development and commercialization of pegcetacoplan and specified other structurally and functionally similar compstatin analogues or derivatives for use systemically or for local non-ophthalmological administration (collectively referred to as the Licensed Products).

Under the Sobi collaboration agreement, the company granted Sobi an exclusive (subject to certain retained rights of it), sublicensable license of certain patent rights and know-how to develop and commercialize Licensed Products in all countries outside of the United States.

The company retains the right to commercialize Licensed Products in the United States, and, subject to specified limitations, to develop Licensed Products worldwide for commercialization in the United States.

Under the Sobi collaboration agreement, the company and Sobi originally agreed to collaborate to develop Licensed Products for the treatment of PNH, CAD, HSCT-TMA, C3G, and IC-MPGN, and any other indications subsequently agreed upon by the parties, for commercialization by or on behalf of it in the United States and by or on behalf of Sobi outside of the United States.

Research Collaboration with Beam

In June 2021, the company entered into an exclusive five-year research collaboration (the Beam collaboration agreement) with Beam focused on the use of Beam's proprietary base editing technology to discover new treatments for complement-driven diseases. The company and Beam agreed to collaborate on up to six research programs focused on C3 and other complement targets in the eye, liver and brain. Under the terms of the Beam collaboration agreement, the company is responsible for selecting specific genes within the complement system in various organs including the eye, liver and brain (the Target List) and providing analytical support while Beam will apply its base editing technology and conduct preclinical research on up to six base editing programs for the Target List.

Intellectual Property

As of December 31, 2023, the company owned a total of 24 U.S. patents, 25 pending U.S. patent applications, including original filings, continuations, and divisional applications, as well as numerous foreign counterparts of many of these patents and patent applications.

Pegcetacoplan is an analog of the cyclic peptide compstatin, based on technologies that the company has developed internally or have exclusively licensed from Penn.

The company's patents and patent applications include families of United States and foreign patent and patent applications relating, for example, to the composition of matter of certain compstatin analogs with a prolonged in vivo half-life, including pegcetacoplan, and/or to methods of treatment and dosing regimens for treating particular complement-dependent diseases. Patents in these families would expire in 2032 or 2033. The company has submitted applications for patent term extension for certain of these patents. The company's patent applications also include families relating in part to particular doses and dosing regimens for intravitreally or subcutaneously administered pegcetacoplan that are granted or pending in the United States and a number of other jurisdictions. Patents in these families would expire between 2036 and 2038. Six of the company's U.S. patents are listed for EMPAVELI in the FDA's Orange Book. The company's filings also include certain U.S. and foreign patents and patent applications relating to methods of treating eye disorders associated with complement activation, which it acquired in the acquisition of the assets of Potentia Pharmaceuticals, Inc., or Potentia. These patent rights include issued U.S. patents with claims to methods of treating AMD by administration of compstatin analogs and a granted European patent with claims to a class of compstatin analogs for use in treatment of macular degeneration. These patents have terms that extend into 2026. The company also owns a patent family relating in part to use of C3 inhibitors, including pegcetacoplan, to facilitate gene therapy with AAV vectors. Patents in this family would have terms extending into 2040. In addition, the company owns patent families relating to use of pegcetacoplan for the treatment of PNH or for the treatment of GA that have terms extending into 2041 through 2043.

In addition to the technology that the company developed internally relating to compstatin analogs, it holds exclusive licenses from Penn, including a license agreement with Penn that was assigned to it in connection with its acquisition of the Potentia's assets in September 2015. The intellectual property in-licensed under the company's two license agreements with Penn includes four U.S. patents and numerous foreign counterparts, with claims granted in Europe, Japan and elsewhere. These licensed patent rights include issued patents with claims that recite a class of compounds generically covering pegcetacoplan, and that specifically recite the active component. These patents have terms that extend to 2026.

The company also owns or has exclusive rights to a number of patent applications relating to additional modalities and molecules for inhibiting complement, including nucleic acid, small molecule, and protein-based approaches. The filings cover, for example, the composition of matter of certain of the company's product candidates and methods of use for treating particular complement-mediated disorders. Patents issuing based on these applications would have terms extending into 2041 through 2043.

The company has a non-exclusive license to intellectual property covering aspects of base editing technology, including CRISPR proteins and base editors, for use in the context of its collaboration with Beam, and have an exclusive license from Beam to this intellectual property to the extent it specifically covers therapeutic candidates developed under the collaboration.

The company granted worldwide rights to use and license the intellectual property that it holds with respect to pegcetacoplan to its wholly owned subsidiaries, APL DEL Holdings, LLC and Apellis International GmbH. Certain of the company's wholly owned subsidiaries hold rights to use its intellectual property to manage its clinical trials in certain jurisdictions or territories and exclusive rights to distribute its product with respect to specific indications within certain jurisdictions or territories. The company granted Sobi an exclusive (subject to certain retained rights), sublicensable license of certain patent rights and know-how to develop and commercialize pegcetacoplan for non-ophthalmological indications in all countries outside of the United States.

Patent License Agreement with The Trustees of the University of Pennsylvania (Non-ophthalmic Fields of Use)

In March 2008, Apellis AG entered into an agreement with Penn for an exclusive worldwide license, under specified patent rights controlled by Penn, to develop and commercialize products covered by the licensed patent rights for all fields except the treatment of ophthalmic indications. This license was assigned to the company in 2010 in connection with its acquisition of Apellis AG, and it has the right to grant sublicenses under this license.

The patent rights licensed to the company by Penn include patents with claims that recite a class of compounds generically covering pegcetacoplan, and specifically recite the active component. The company has the right to grant sublicenses under the license.

The company also obligated to use commercially reasonable efforts to develop licensed products in accordance with a development plan, which it will update annually, and a development milestone timetable specified in the agreement and to use commercially reasonable efforts to commercialize licensed products.

Amended and Restated Patent License Agreement with The Trustees of the University of Pennsylvania (Ophthalmic Field of Use)

At the same time that it entered into the agreement with Apellis AG, Penn licensed rights to the same portfolio of cases to Potentia, to develop and commercialize products covered by the licensed patent rights for the treatment of ophthalmic indications. In September 2015, Potentia assigned the license agreement between Potentia and Penn to the company in connection with its acquisition of the assets of Potentia pursuant to an asset purchase agreement with Potentia. Three of the licensed patents are listed for SYFOVRE in the FDA's orange book.

The company has the right to grant sublicenses under the license.

Competition

The company is aware of other companies that are actively developing product candidates for the treatment of GA, including the following product candidates that are in clinical development: ANX007, a C1q inhibitor being developed by Annexon Biosciences, Inc. and preparing to enter into Phase 3 clinical trials; pozelimab, an anti-C5 antibody developed by Regeneron Pharmaceuticals Inc. in combination with cemdisiran, an RNAi therapeutic targeting C5 developed by Alnylam Pharmaceuticals, Inc., is preparing to enter into Phase 3 clinical trials; IONIS-FB-LRX (RG6299), a complement factor B inhibitor being developed by Ionis (in collaboration with Roche/Genentech) in Phase 2 clinical trials; danicopan (ALXN2040), an orally administered factor D inhibitor being developed by AstraZeneca in Phase 2 clinical trials; JNJ1887, an intravitreal gene therapy targeting CD59 being developed by The Janssen Pharmaceutical Companies of Johnson & Johnson (after acquisition from Hemera Biosciences) in Phase 2 clinical trials; and other product candidates that do not target the complement system that are either in a single Phase 3 or in Phase 2 clinical trials, including but not limited to therapies being developed by Alkeus Pharmaceuticals, Inc., Stealth BioTherapeutics, Inc., Belite Bio, Inc., Lineage Cell Therapeutics, Inc. (in collaboration with Roche/Genentech), Aviceda Therapeutics, Inc., and Ocugen Inc. Novartis has initiated a Phase 2 trial of orally administered iptacopan (marketed as Fabhalta),, a factor B inhibitor, in patients with early or intermediate AMD.

The principal competitors for EMPAVELI, and possibly other indications in the company's hematology and nephrology programs are eculizumab (marketed as Soliris) and ravulizumab (marketed as Ultomiris), which are C5 inhibitors marketed by AstraZeneca.

The company is aware of several other companies that are actively developing product candidates using complement inhibition for the treatment of PNH in late-stage clinical development, including crovalimab, an anti-C5 antibody developed by Roche and Chugai Pharmaceutical Co., under regulatory review in the United States; pozelimab + cemdisiran is in Phase 3 clinical trials; and danicopan, a Factor D inhibitor being developed by AstraZeneca as an add-on treatment to eculizumab and ravulizumab, in Phase 3 clinical trials, as well as other products in early stages of development.

Sales and Marketing

The company retains the U.S. commercialization rights for systemic pegcetacoplan and worldwide commercialization rights for intravitreal pegcetacoplan. The company is conducting commercialization efforts for EMPAVELI and SYFOVRE in the United States and plans to conduct commercial development for systemic pegcetacoplan in the United States if it is approved in other indications. Sobi has global co-development and exclusive ex-U.S. commercialization rights for systemic pegcetacoplan. The company plans to conduct commercial development for intravitreal pegcetacoplan worldwide for GA.

For EMPAVELI and SYFOVRE the company has defined its marketing, disease education, patient support and distribution strategies, identified primary and secondary payers representing a significant percentage of patients with PNH and GA, have built its field market access team and its sales team. Sobi is responsible for commercialization of systemic pegcetacoplan outside of the United States.

For programs involving compounds other than pegcetacoplan, the company plans to develop its own capabilities to commercialize its products worldwide.

Manufacturing

The company has entered into a commercial supply agreement with Bachem Americas, Inc., or Bachem, agreeing to purchase a significant portion of its requirements for the pegcetacoplan drug substance, and a commercial supply agreement with NOF Corporation, or NOF, to purchase activated polyethylene glycol derivative, or PEG, which is a component of pegcetacoplan.

Commercial Supply Agreement with Bachem

On December 30, 2020, the company entered into a commercial supply agreement, or the Bachem Agreement, with Bachem to supply the drug substance for the finished dosage form of systemic pegcetacoplan and intravitreal pegcetacoplan.

Under the Bachem Agreement, the company agreed to purchase from Bachem a significant portion of its requirements for the drug substance during the term of the agreement, and to purchase all of its requirements for drug substance for commercial sale, subject to certain exceptions, for a period after the effective date of the agreement. Unless earlier terminated, the initial term of the Bachem Agreement continues until December 31, 2025, or the Initial Term.

Amended and Restated Commercial Supply Agreement with NOF

On March 10, 2021, the company entered into an amended and restated commercial supply agreement, or the NOF Agreement, with NOF to purchase PEG, which is a component of each of systemic pegcetacoplan and intravitreal pegcetacoplan. Under the NOF Agreement, NOF's affiliate, NOF America Corporation, supplies PEG to the company on a non-exclusive basis.

Research and Development

The company's research and development expenses included $354.4 million for the year ended December 31, 2023.

History

Apellis Pharmaceuticals, Inc. was founded in 2009. The company was incorporated under the laws of the state of Delaware in 2009.