Glomerulonephritis, Membranoproliferative

Submission is based on 2-year confirmatory results from the Phase 3 PROTECT Study in which FILSPARI demonstrated a significant reduction in proteinuria, preservation of kidney function and a generally well-tolerated safety pro with active control irbesartan SAN DIEGO, March 11, 2024 (GLOBE NEWSWIRE) -- Travere Therapeutics, Inc. (Nasdaq: TVTX) today announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for conversion of the existing U.S. accelerated approval of FILSPARI® (sparsentan) in IgA nephropathy (IgAN) to full approval. In February 2023, the FDA granted accelerated approval to FILSPARI as the first and only non-immunosuppressive treatment targeting glomerular injury in the kidney to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression. The sNDA is based on 2-year confirmatory results from the Phase 3 PROTECT Study, the only head-to-head study in IgAN versus an active comparator. “Since being introduced under accelerated approval, FILSPARI has positively impacted the lives of many people living with IgAN. The submission of the sNDA is an important step toward potentially gaining full approval in IgAN in support of reaching more people living with this devastating rare kidney disease,” said Eric Dube, Ph.D., president and chief executive officer of Travere Therapeutics. “FILSPARI is at the forefront of emerging new treatment options providing hope for a delay in kidney transplant or dialysis. The results from the pivotal Phase 3 PROTECT Study show that by directly targeting glomerular injury in the kidney with FILSPARI, patients can achieve sustained proteinuria reduction and long-term kidney function preservation. We look forward to working with the FDA throughout the upcoming review process.” FILSPARI is a once-daily, oral medication that directly targets glomerular injury in the kidney by blocking two critical pathways of IgAN disease progression (endothelin-1 and angiotensin II). FILSPARI is also the first and only non-immunosuppressive therapy approved for the treatment of this rare kidney disease. The sNDA submission is supported by results from the Phase 3 PROTECT Study that showed that FILSPARI demonstrated long-term kidney function preservation and achieved a significant reduction in proteinuria and a clinically meaningful difference in eGFR slope versus an active comparator. The FDA has 60 days from the receipt of the application to determine whether to accept it for review. The Company expects to receive notice regarding the acceptance for review of the sNDA submission as well as the timeline for sNDA review from the FDA in the second quarter of 2024. In addition to the sNDA submission to the FDA, the Company and its European commercial partner CSL Vifor recently announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended approval of the conditional marketing authorization (CMA) for sparsentan for the treatment of IgA nephropathy (IgAN) in Europe. A decision by the European Commission is expected in the second quarter of 2024. If approved, sparsentan would receive a CMA in all member states of the European Union, as well as in Iceland, Liechtenstein, and Norway. About IgA Nephropathy IgA nephropathy (IgAN), also called Berger's disease, is a rare progressive kidney disease characterized by the buildup of immunoglobulin A (IgA), a protein that helps the body fight infections, in the kidneys. The deposits of IgA cause a breakdown of the normal filtering mechanisms in the kidney, leading to blood in the urine (hematuria), protein in the urine (proteinuria) and a progressive loss of kidney function. Other symptoms of IgAN may include swelling (edema) and high blood pressure. IgAN is the most common type of primary glomerulonephritis worldwide and a leading cause of kidney failure due to glomerular disease. IgAN is estimated to affect up to 150,000 people in the U.S. and is one of the most common glomerular diseases in Europe and Japan. About the PROTECT Study The PROTECT Study is one of the largest interventional studies to date in IgA nephropathy (IgAN) and the only head-to-head trial in this rare kidney disease. It is a global, randomized, multicenter, double-blind, parallel-arm, active-controlled clinical trial evaluating the safety and efficacy of 400 mg of sparsentan, compared to 300 mg of irbesartan, in 404 patients ages 18 years and up with IgAN and persistent proteinuria despite receiving at least 50% of max label dose and maximally tolerated ACE or ARB therapy. In August 2021, the Company announced the PROTECT Study met its pre-specified interim primary efficacy endpoint with statistical significance. Based on the pre-specified, primary analyses set, after 36 weeks of treatment, patients receiving sparsentan achieved a mean reduction in proteinuria from baseline of 49.8%, compared to a mean reduction in proteinuria from baseline of 15.1% for irbesartan-treated patients (p<0.0001). The study’s confirmatory secondary endpoint in the U.S. is estimated glomerular filtration rate (eGFR) total slope from day 1 to week 110 of treatment. The confirmatory secondary endpoint in the EU is eGFR chronic slope from week 6 to week 110 of treatment, following the initial acute effect of randomized treatment. Following the 110-week blinded treatment period, treatment with study medication was discontinued for 4 weeks -- at this time, the investigator resumed standard of care treatment. In September 2023, the Company announced topline two-year confirmatory secondary endpoint results from the PROTECT Study of sparsentan in IgAN. Sparsentan demonstrated long-term kidney function preservation and achieved a clinically meaningful difference in eGFR total and chronic slope versus irbesartan, narrowly missing statistical significance in eGFR total slope while achieving statistical significance in eGFR chronic slope for purposes of regulatory review in the EU. Patients who completed the PROTECT double-blind portion of the study on treatment were eligible to participate in the open-label extension of the trial. About Travere Therapeutics At Travere Therapeutics, we are in rare for life. We are a biopharmaceutical company that comes together every day to help patients, families and caregivers of all backgrounds as they navigate life with a rare disease. On this path, we know the need for treatment options is urgent – that is why our global team works with the rare disease community to identify, develop and deliver life-changing therapies. In pursuit of this mission, we continuously seek to understand the diverse perspectives of rare patients and to courageously forge new paths to make a difference in their lives and provide hope – today and tomorrow. For more information, visit travere.com FILSPARI® (sparsentan) U.S. Indication FILSPARI is an endothelin and angiotensin II receptor antagonist indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a UPCR ≥1.5 g/g. This indication is granted under accelerated approval based on reduction in proteinuria. It has not been established whether FILSPARI slows kidney function decline in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial. FILSPARI® (sparsentan) Important Safety Information BOXED WARNING: HEPATOTOXICITY AND EMBRYO-FETAL TOXICITY Because of the risks of hepatotoxicity and birth defects, FILSPARI is available only through a restricted program called the FILSPARI REMS. Under the FILSPARI REMS, prescribers, patients and pharmacies must enroll in the program. Hepatotoxicity Some Endothelin Receptor Antagonists (ERAs) have caused elevations of aminotransferases, hepatotoxicity, and liver failure. In clinical studies, elevations in aminotransferases (ALT or AST) of at least 3-times the Upper Limit of Normal (ULN) have been observed in up to 2.5% of FILSPARI-treated patients, including cases confirmed with rechallenge. Measure transaminases and bilirubin before initiating treatment and monthly for the first 12 months, and then every 3 months during treatment. Interrupt treatment and closely monitor patients who develop aminotransferase elevations more than 3x ULN. FILSPARI should generally be avoided in patients with elevated aminotransferases (>3x ULN) at baseline because monitoring for hepatotoxicity may be more difficult and these patients may be at increased risk for serious hepatotoxicity. Embryo-Fetal Toxicity FILSPARI can cause major birth defects if used by pregnant patients based on animal data. Therefore, pregnancy testing is required before the initiation of treatment, during treatment and one month after discontinuation of treatment with FILSPARI. Patients who can become pregnant must use effective contraception before the initiation of treatment, during treatment, and for one month after discontinuation of treatment with FILSPARI. Contraindications: FILSPARI is contraindicated in patients who are pregnant. Do not coadminister FILSPARI with angiotensin receptor blockers (ARBs), ERAs, or aliskiren. Warnings and Precautions Hepatotoxicity: Elevations in ALT or AST of at least 3-fold ULN have been observed. To reduce the risk of potential serious hepatotoxicity, measure serum aminotransferase levels and total bilirubin prior to initiation of treatment, monthly for the first 12 months, then every 3 months during treatment. Advise patients with symptoms suggesting hepatotoxicity (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching) to immediately stop treatment with FILSPARI and seek medical attention. If aminotransferase levels are abnormal at any time during treatment, interrupt FILSPARI and monitor as recommended. Consider re-initiation of FILSPARI only when hepatic enzyme levels and bilirubin return to pretreatment values and only in patients who have not experienced clinical symptoms of hepatotoxicity. Avoid initiation of FILSPARI in patients with elevated aminotransferases (>3x ULN) prior to drug initiation. Embryo-Fetal Toxicity: FILSPARI can cause fetal harm. Advise patients who can become pregnant of the potential risk to a fetus. Obtain a pregnancy test and advise patients who can become pregnant to use effective contraception prior to, during, and one month after discontinuation of FILSPARI treatment. FILSPARI REMS: FILSPARI is available only through a restricted program under a REMS called the FILSPARI REMS. Important requirements include: — Prescribers must be certified with the FILSPARI REMS by enrolling and completing training. — All patients must enroll in the FILSPARI REMS prior to initiating treatment and comply with monitoring requirements. — Pharmacies that dispense FILSPARI must be certified with the FILSPARI REMS and must dispense only to patients who are authorized to receive FILSPARI. Further information is available at or 1-833-513-1325. Hypotension: There was a greater incidence of hypotension-associated adverse events, some serious, including dizziness, in patients treated with FILSPARI compared to irbesartan. In patients at risk for hypotension, consider eliminating or adjusting other antihypertensive medications and maintaining appropriate volume status. If hypotension develops, consider a dose reduction or dose interruption of FILSPARI. Acute Kidney Injury: Monitor kidney function periodically. Patients whose kidney function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute kidney injury on FILSPARI. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in kidney function while on FILSPARI. Hyperkalemia: Monitor serum potassium periodically and treat appropriately. Patients with advanced kidney disease, taking concomitant potassium-increasing drugs (e.g., potassium supplements, potassium-sparing diuretics), or using potassium-containing salt substitutes are at increased risk for developing hyperkalemia. Dosage reduction or discontinuation of FILSPARI may be required. Fluid Retention: Fluid retention may occur with ERAs, and has been observed with FILSPARI. If clinically significant fluid retention develops, after evaluation, consider modifying the dose of FILSPARI. Most common adverse reactions (5%) with FILSPARI are peripheral edema, hypotension (including orthostatic hypotension), dizziness, hyperkalemia, and anemia. Drug interactions Renin-Angiotensin System (RAS) Inhibitors and ERAs: Do not coadminister FILSPARI with angiotensin receptor blockers (ARBs), ERAs, or aliskiren. Strong and Moderate CYP3A Inhibitors: Avoid concomitant use of FILSPARI with strong CYP3A inhibitors. Monitor blood pressure, serum potassium, edema, and kidney function regularly when used concomitantly with moderate CYP3A inhibitors. Strong CYP3A Inducers: Avoid concomitant use with a strong CYP3A inducer. Antacids and Acid Reducing Agents: Administer FILSPARI 2 hours before or after administration of antacids. Avoid concomitant use of acid reducing agents (histamine H2 receptor antagonist and PPI proton pump inhibitor) with FILSPARI. Non-Steroidal Anti-Inflammatory Agents (NSAIDs), Including Selective Cyclooxygenase-2 (COX-2) Inhibitors: Monitor for signs of worsening renal function. CYP2B6, 2C9, and 2C19 Substrates: Monitor for efficacy of the concurrently administered CYP2B6, 2C9, and 2C19 substrates and consider dosage adjustment in accordance with the Prescribing Information. P-gp and BCRP Substrates: Avoid concomitant use of sensitive substrates of P-gp and BCRP with FILSPARI. Agents Increasing Serum Potassium: Monitor serum potassium frequently. Concomitant use of FILSPARI with potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other drugs that raise serum potassium levels may result in hyperkalemia. Use in specific populations Pregnancy / Females and Males of Reproductive Potential: FILSPARI can cause fetal harm, including birth defects and fetal death, when administered to a pregnant patient and is contraindicated during pregnancy. Pregnancy Testing / Contraception: Verify the pregnancy status and effective method of contraception prior to, during, and one month after discontinuation of FILSPARI treatment. The patient should contact their physician immediately for pregnancy testing if onset of menses is delayed or pregnancy is suspected. Lactation: Advise patients not to breastfeed during treatment with FILSPARI. Hepatic Impairment: Avoid use of FILSPARI in patients with any hepatic impairment (Child-Pugh class A-C). Please see Full Prescribing Information for FILSPARI here. Forward Looking Statements This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, these statements are often identified by the words “on-track,” “positioned,” “look forward to,” “will,” “would,” “may,” “might,” “believes,” “anticipates,” “plans,” “expects,” “intends,” “potential,” or similar expressions. In addition, expressions of our strategies, intentions or plans are also forward-looking statements. Such forward-looking statements include, but are not limited to, references to: statements and expectations regarding the FDA’s potential acceptance for filing of the sNDA submission for FILSPARI in IgAN and the anticipated timeline and outcome of the FDA’s review of the sNDA; statements regarding the potential conditional marketing authorization of sparsentan for the treatment of IgAN in the European Union, Iceland, Liechtenstein and Norway and the anticipated timing thereof, including the potential timing and outcome of the European Commission’s decision; and the potential for emerging new treatment options for IgAN that have the potential to provide hope for a delay in kidney transplant or a dialysis. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are risks and uncertainties associated with the regulatory review and approval process, as well as risks and uncertainties associated with the Company’s business and finances in general, the success of its commercial products and risks and uncertainties associated with the Company’s preclinical and clinical stage pipeline. Specifically, the Company faces risks associated with market acceptance of its commercial products including efficacy, safety, price, reimbursement, and benefit over competing therapies, as well as risks associated with the successful development and execution of commercial strategies for such products, including FILSPARI. The risks and uncertainties the Company faces with respect to its preclinical and clinical stage pipeline include risk that the Company’s clinical candidates will not be found to be safe or effective and that current or anticipated future clinical trials will not proceed as planned. Specifically, the Company faces risks related to the timing and potential outcome of the FDA’s potential acceptance for filing and review of the sNDA submission for full approval of FILSPARI in IgAN, and the timing and potential outcome of the European Commission’s decision regarding conditional marketing authorization of sparsentan for IgAN. There is no guarantee that the FDA will accept the sNDA submission for filing, that the European Commission will grant conditional marketing authorization of sparsentan for IgAN, or that regulators will grant full approval of sparsentan for IgAN. The Company also faces the risk that it will be unable to raise additional funding that may be required to complete development of any or all of its product candidates, including as a result of macroeconomic conditions; risks relating to the Company’s dependence on contractors for clinical drug supply and commercial manufacturing; uncertainties relating to patent protection and exclusivity periods and intellectual property rights of third parties; risks associated with regulatory interactions; and risks and uncertainties relating to competitive products, including current and potential future generic competition with certain of the Company’s products, and technological changes that may limit demand for the Company’s products. The Company also faces additional risks associated with global and macroeconomic conditions, including health epidemics and pandemics, including risks related to potential disruptions to clinical trials, commercialization activity, supply chain, and manufacturing operations. You are cautioned not to place undue reliance on these forward-looking statements as there are important factors that could cause actual results to differ materially from those in forward-looking statements, many of which are beyond our control. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Investors are referred to the full discussion of risks and uncertainties, including under the heading “Risk Factors”, as included in the Company’s most recent Form 10-K, Form 10-Q and other filings with the Securities and Exchange Commission. Contact Info Media: 888-969-7879 mediarelations@travere.com Investors: 888-969-7879 IR@travere.com

BURLINGTON, Mass.--( BUSINESS WIRE )-- Bone Biologics Corporation (NASDAQ: BBLG), a developer of orthobiologic products for spine fusion markets, reports progress with advancing its product candidate NB1 into human clinical testing for spinal fusion. Following Human Research Ethics Committee (HREC) approval last year in Australia for the multicenter, prospective, randomized pilot clinical trial, the Company reports that three hospital sites have been engaged to participate in the pilot clinical trial. This pilot clinical trial will evaluate the safety and effectiveness of NB1 in 30 adult subjects who undergo transforaminal lumbar interbody fusion (TLIF) to treat degenerative disc disease (DDD). Inclusion criteria include patients with DDD at one level from L2-S1 who may also have up to Grade 1 spondylolisthesis or Grade 1 retrolisthesis at the involved level. The study design was previously reviewed and agreed upon by the Division of Orthopedic Devices in a Pre-submission to support progression to a pivotal clinical trial in the United States. About NB1 rhNELL-1 is a recombinant human protein that is combined with demineralized bone matrix to form the Company’s product candidate NB1. NELL-1 has unique properties that suggest it will be ideal in treating spinal fusion, trauma, osteoporosis and other bone-related indications, and may be especially useful among so-called “hard healers.” This potential lies in its ability to provide rapid, specific and guided control over bone regeneration. For the NB1 bone graft device, the inclusion of rhNELL-1 provides an ancillary osteopromotive effect that is expected to increase the incidence. The proposed mechanism of action for rhNELL-1 to improve bone formation is based on published research and involves classic receptor binding and intracellular signaling transduction to the nucleus to promote osteogenic gene expression and bone formation. There is a large and established opportunity for NB1 with an estimated global market of $3 billion annually for bone graft substitutes in spine fusion for products such as growth factors, DBM, synthetic materials, stem cells and allografts. Additional longer-term market opportunities include the $11 billion annual market for treating osteoporosis and the $8 billion annual market for treating trauma. About Bone Biologics Bone Biologics was founded to pursue regenerative medicine for bone. The Company is working with select strategic partners to build on the foundation of preclinical research on rhNELL-1. Bone Biologics is focusing development efforts for its NB1 bone graft device in spinal fusion procedures, while additionally having rights to trauma and osteoporosis applications. For more information, please visit www.bonebiologics.com . Forward-Looking Statements Certain statements contained in this press release, including, without limitation, statements regarding the timing, implementation, and success of our pilot clinical trial of NB1 in human subjects with DDD, as well as statements containing the words “plan,” “will,” “expected” and words of similar import, constitute “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve both known and unknown risks and uncertainties. The Company’s actual results may differ materially from those anticipated in its forward-looking statements as a result of a number of factors, including, but not limited to, market and other conditions and risks generally associated with an undercapitalized developing company, as well as the risks contained under “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2023 and the Company’s other filings with the Securities and Exchange Commission. Except as required by applicable law, we undertake no obligation to revise or update any forward-looking statements to reflect any event or circumstance that may arise after the date hereof.

Generated $397 million in full year 2023 revenues, including $275 million for SYFOVRE® (pegcetacoplan injection) and $91 million for EMPAVELI® (pegcetacoplan)Strong SYFOVRE launch, with more than 160,000 total doses (commercial and samples) distributed in 2023 Topline data from Phase 3 VALIANT study of systemic pegcetacoplan in C3G and IC-MPGN expected in mid-2024Cash and cash equivalents of $351 million as of December 31, 2023 WALTHAM, Mass., Feb. 27, 2024 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals, Inc. (Nasdaq: APLS), today announced its fourth quarter and full year 2023 financial results and business highlights. “I am extremely proud of our team, their accomplishments and resilience in a year faced with many highs and some unexpected challenges. The SYFOVRE launch exceeded even our own expectations, with demand growth continuing into the first quarter of 2024, and we remain encouraged by the uptake and high compliance rates for EMPAVELI in PNH,” said Cedric Francois, M.D., Ph.D., co-founder and chief executive officer of Apellis. “We are well-positioned to continue our strong execution in 2024, with a focus on bringing SYFOVRE to even more patients in the U.S. and globally, maximizing EMPAVELI in PNH and C3G/IC-MPGN, advancing our earlier-stage pipeline, and delivering on our mission for patients now and in the future.” Fourth Quarter 2023 and Recent Business Highlights: Ophthalmology Highlights SYFOVRE for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD): Recorded $114.3 million and $275.2 million in SYFOVRE U.S. net product revenue for the fourth quarter and full year 2023, respectively.Delivered approximately 62,000 SYFOVRE doses to physician practices in the fourth quarter, including 55,000 commercial vials and 6,400 samples. More than 160,000 doses have been delivered to physician practices since launch in March through December 31, 2023.Permanent and product-specific J-code for SYFOVRE became effective on October 1, 2023, helping to simplify and streamline the billing and reimbursement of SYFOVRE.Significant presence at multiple medical meetings, including an oral presentation at the American Academy of Ophthalmology (AAO) meeting on data from the GALE extension study showing continued increasing treatment effects and consistent safety data over three years of continuous SYFOVRE use. Data also showed that SYFOVRE reduced nonsubfoveal GA lesion growth by 42% (monthly) in Year 3 compared to projected sham. Initiating a re-examination of the marketing authorization application of SYFOVRE with the European Medicines Agency (EMA) following a negative opinion from the Committee for Medicinal Products for Human Use (CHMP) received in January 2024. Expect a final opinion to be issued by the CHMP in the second quarter of 2024. Paroxysmal Nocturnal Hemoglobinuria (PNH) Highlights EMPAVELI for the treatment of PNH: Recorded $24.4 million and $91.0 million in EMPAVELI U.S. net product revenue for the fourth quarter and full year 2023, respectively.Continued high patient compliance rates of 97%.Following approval in October 2023, the EMPAVELI Injector is now used by approximately 60% of existing EMPAVELI patients and greater than 90% of new EMPAVELI patients.Presented post hoc data integrated from the Phase 3 PEGASUS and PRINCE studies and the long-term extension study reinforcing the safety and efficacy profile of EMPAVELI in PNH for up to three years at the American Society of Hematology (ASH) Annual Meeting. R&D Highlights C3 glomerulopathy (C3G) and immune complex glomerulonephritis (IC-MPGN): Completed enrollment in the Phase 3 VALIANT study of systemic pegcetacoplan, with topline data expected in mid-2024. Presented topline data from the Phase 2 NOBLE study investigating pegcetacoplan for the treatment of post-transplant recurrence of C3G and IC-MPGN at the American Society of Nephrology (ASN) Kidney Week Annual Meeting. Data demonstrated reduced disease activity as measured by C3c staining in as early as 12 weeks, as well as improvements across key clinical measures. Cold agglutinin disease (CAD): As previously reported by Sobi, the Companies discontinued the Phase 3 CASCADE study of systemic pegcetacoplan for CAD due to a realignment of Sobi and Apellis’ development activities as there is a decreased medical need in CAD and therefore a limited number of patients eligible for the study. There were no safety concerns in this study, and efficacy was not evaluated due to the blinded study design.Sobi is working with investigators on how to best support patients and their physicians in finding an appropriate treatment option going forward. Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA): Sobi continues to enroll patients in its Phase 2 study evaluating the efficacy and safety of systemic pegcetacoplan in patients with HSCT-TMA.APL-3007 (small interfering RNA silencing C3): Currently in a Phase 1 dose escalation study with topline data expected in 2024. Fourth Quarter and Full Year 2023 Financial Results: Cash. As of December 31, 2023, Apellis had $351.2 million in cash and cash equivalents, compared to $551.8 million in cash and cash equivalents as of December 31, 2022. Apellis anticipates its cash balance, combined with cash anticipated to be generated from the unwind of the capped call transactions and from the sales of EMPAVELI and SYFOVRE, will be sufficient to fund its projected operating expenses and capital expenditures for the foreseeable future. Total Revenue. Total revenue was $146.4 million for the fourth quarter of 2023, which consisted of $114.3 million in U.S. net product revenue of SYFOVRE, $24.4 million in U.S. net product revenue of EMPAVELI and $7.7 million in licensing and other revenue associated with the Sobi collaboration. Total revenue was $22.7 million for the fourth quarter of 2022, which consisted of $19.7 million in U.S. net product revenue of EMPAVELI and $3.0 million in licensing and other revenue associated with the Sobi collaboration.For the full year 2023, total revenue was $396.6 million, which consisted of $275.2 million in U.S. net product revenue of SYFOVRE, $91.0 million in U.S. net product revenue of EMPAVELI and $30.3 million in licensing and other revenue associated with the Sobi collaboration. For the full year 2022, total revenue was $75.4 million, which consisted of $65.1 million in U.S. net product revenue of EMPAVELI and $10.3 million in licensing and other revenue associated with the Sobi collaboration. Cost of Sales. Cost of sales was $19.9 million for the fourth quarter of 2023, compared to $2.9 million for the fourth quarter of 2022, respectively. For the full year 2023, cost of sales was $58.5 million as compared to $5.6 million for the full year 2022. Cost of sales consists primarily of costs associated with the manufacturing of SYFOVRE and EMPAVELI, royalties owed to our licensor for such sales, costs associated with Sobi revenue, and certain period costs.Prior to receiving FDA approval for EMPAVELI in May 2021 and SYFOVRE in February 2023, costs associated with the manufacturing of EMPAVELI and SYFOVRE inventory were expensed as research and development (R&D) expense. This resulted in inventory being sold during the 2022 and 2023 periods, for which a portion of the costs had been previously expensed prior to FDA approval. R&D Expenses. R&D expenses were $69.3 million for the fourth quarter of 2023, compared to $99.4 million for the fourth quarter of 2023. For the full year 2023, R&D expenses were $354.4 million compared to $387.2 million for the full year 2022.The decrease in R&D expenses for the full year 2023 was primarily attributable to a decrease in program specific external costs, including the discontinuation of the MERIDIAN study for ALS and the approval of SYFOVRE, and a decrease in non-program specific external costs. These decreases were partially offset by an increase in compensation and related personnel costs. General and Administrative (G&A) Expenses. G&A expenses were $141.7 million for the fourth quarter of 2023, compared to $84.4 million for the fourth quarter of 2022. For the full year 2023, G&A expenses were $500.8 million compared to $277.2 million for the full year 2022.The increase in G&A expenses for the full year 2023 was primarily attributable to an increase in employee related costs related to hiring activities to support the launch of SYFOVRE, an increase in commercialization related activity, an increase in professional and consulting fees, an increase in travel related expenses and higher office costs. Net Loss (Income). Apellis reported a net loss of $88.5 million and $528.6 million for the fourth quarter and full year 2023, respectively, compared to a net loss of $166.0 million and $652.2 million for the same periods in 2022. Convertible Notes. Apellis entered into agreements to unwind approximately 80% of the capped call transactions that it entered into in connection with the issuance of the Company’s 3.500% Senior Convertible Notes due 2026 (the Notes). The unwind agreements will apply to the portion of the capped call transactions in a notional amount corresponding to the $426.1 million of Notes that are held by Apellis in treasury as of December 31, 2023, or have been previously converted.The unwind transactions will be settled based on a 7-day averaging period beginning on and including February 27, 2024.Apellis anticipates that it will receive aggregate net cash proceeds of approximately $100 million in connection with this portion of the capped call transactions, although the final amount of net cash proceeds will be determined after the expiration of the 7-day averaging period.In connection with the unwind, the counterparties may sell shares of Apellis’ common stock in secondary market transactions, and/or unwind various derivative transactions with respect to Apellis’ common stock. As of December 31, 2023, the aggregate principal balance of the Notes due 2026, net of unamortized debt issuance costs, was $93.0 million. Conference Call and WebcastApellis will host a conference call and webcast to discuss its fourth quarter and year end 2023 financial results and business highlights today, February 27, 2024, at 8:30 a.m. ET. To access the live call by phone, please pre-register for the call here. A live audio webcast of the event and accompanying slides may also be accessed through the “Events and Presentations” page of the “Investors and Media” section of the company’s website. A replay of the webcast will be available for 30 days following the event. About SYFOVRE® (pegcetacoplan injection)SYFOVRE® (pegcetacoplan injection) is the first-ever approved therapy for geographic atrophy (GA). By targeting C3, SYFOVRE is designed to provide comprehensive control of the complement cascade, part of the body’s immune system. SYFOVRE is approved in the United States for the treatment of GA secondary to age-related macular degeneration. About EMPAVELI®/Aspaveli® (pegcetacoplan)EMPAVELI®/Aspaveli® (pegcetacoplan) is a targeted C3 therapy designed to regulate excessive activation of the complement cascade, part of the body’s immune system, which can lead to the onset and progression of many serious diseases. It is approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in the United States, European Union, and other countries globally. The therapy is also under investigation for several other rare diseases across hematology and nephrology. U.S. Important Safety Information for SYFOVRE® (pegcetacoplan injection) CONTRAINDICATIONS SYFOVRE is contraindicated in patients with ocular or periocular infections, and in patients with active intraocular inflammation WARNINGS AND PRECAUTIONS Endophthalmitis and Retinal Detachments Intravitreal injections, including those with SYFOVRE, may be associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering SYFOVRE to minimize the risk of endophthalmitis. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately. Retinal Vasculitis and/or Retinal Vascular Occlusion Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of SYFOVRE. Cases may occur with the first dose of SYFOVRE and may result in severe vision loss. Discontinue treatment with SYFOVRE in patients who develop these events. Patients should be instructed to report any change in vision without delay. Neovascular AMD In clinical trials, use of SYFOVRE was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (12% when administered monthly, 7% when administered every other month and 3% in the control group) by Month 24. Patients receiving SYFOVRE should be monitored for signs of neovascular AMD. In case anti-Vascular Endothelial Growth Factor (anti-VEGF) is required, it should be given separately from SYFOVRE administration. Intraocular Inflammation In clinical trials, use of SYFOVRE was associated with episodes of intraocular inflammation including: vitritis, vitreal cells, iridocyclitis, uveitis, anterior chamber cells, iritis, and anterior chamber flare. After inflammation resolves, patients may resume treatment with SYFOVRE. Increased Intraocular Pressure Acute increase in IOP may occur within minutes of any intravitreal injection, including with SYFOVRE. Perfusion of the optic nerve head should be monitored following the injection and managed as needed. ADVERSE REACTIONS Most common adverse reactions (incidence ≥5%) are ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, conjunctival hemorrhage. Please see accompanying full Prescribing Information for more information. U.S. Important Safety Information for EMPAVELI® (pegcetacoplan) BOXED WARNING: SERIOUS INFECTIONS CAUSED BY ENCAPSULATED BACTERIA EMPAVELI, a complement inhibitor, increases the risk of serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B. Life-threatening and fatal infections with encapsulated bacteria have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early. Complete or update vaccination for encapsulated bacteria at least 2 weeks prior to the first dose of EMPAVELI, unless the risks of delaying therapy with EMPAVELI outweigh the risks of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria in patients receiving a complement inhibitor.Patients receiving EMPAVELI are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious infections and evaluate immediately if infection is suspected. Because of the risk of serious infections caused by encapsulated bacteria, EMPAVELI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the EMPAVELI REMS. CONTRAINDICATIONS Hypersensitivity to pegcetacoplan or to any of the excipientsFor initiation in patients with unresolved serious infection caused by encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B WARNINGS AND PRECAUTIONS Serious Infections Caused by Encapsulated Bacteria EMPAVELI, a complement inhibitor, increases a patient’s susceptibility to serious, life-threatening, or fatal infections caused by encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis (caused by any serogroup, including non-groupable strains), and Haemophilus influenzae type B. Life-threatening and fatal infections with encapsulated bacteria have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors. The initiation of EMPAVELI treatment is contraindicated in patients with unresolved serious infection caused by encapsulated bacteria. Complete or update vaccination against encapsulated bacteria at least 2 weeks prior to administration of the first dose of EMPAVELI, according to the most current ACIP recommendations for patients receiving a complement inhibitor. Revaccinate patients in accordance with ACIP recommendations considering the duration of therapy with EMPAVELI. Note that, ACIP recommends an administration schedule in patients receiving complement inhibitors that differs from the administration schedule in the vaccine prescribing information. If urgent EMPAVELI therapy is indicated in a patient who is not up to date with vaccines against encapsulated bacteria according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible. The benefits and risks of treatment with EMPAVELI, as well as the benefits and risks of antibacterial drug prophylaxis in unvaccinated or vaccinated patients, must be considered against the known risks for serious infections caused by encapsulated bacteria. Vaccination does not eliminate the risk of serious encapsulated bacterial infections, despite development of antibodies following vaccination. Closely monitor patients for early signs and symptoms of serious infection and evaluate patients immediately if an infection is suspected. Inform patients of these signs and symptoms and instruct patients to seek immediate medical care if these signs and symptoms occur. Promptly treat known infections. Serious infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider interruption of EMPAVELI in patients who are undergoing treatment for serious infections. EMPAVELI is available only through a restricted program under a REMS. EMPAVELI REMS EMPAVELI is available only through a restricted program under a REMS called EMPAVELI REMS, because of the risk of serious infections caused by encapsulated bacteria. Notable requirements of the EMPAVELI REMS include the following: Under the EMPAVELI REMS, prescribers must enroll in the program. Prescribers must counsel patients about the risks, signs, and symptoms of serious infections caused by encapsulated bacteria, provide patients with the REMS educational materials, ensure patients are vaccinated against encapsulated bacteria at least 2 weeks prior to the first dose of EMPAVELI, prescribe antibacterial drug prophylaxis if patients’ vaccine status is not up to date and treatment must be started urgently, and provide instructions to always carry the Patient Safety Card both during treatment, as well as for 2 months following last dose of EMPAVELI. Pharmacies that dispense EMPAVELI must be certified in the EMPAVELI REMS and must verify prescribers are certified. Further information is available at www.empavelirems.com or 1-888-343-7073. Infusion-Related Reactions Systemic hypersensitivity reactions (e.g., facial swelling, rash, urticaria) have occurred in patients treated with EMPAVELI. One patient (less than 1% in clinical studies) experienced a serious allergic reaction which resolved after treatment with antihistamines. If a severe hypersensitivity reaction (including anaphylaxis) occurs, discontinue EMPAVELI infusion immediately, institute appropriate treatment, per standard of care, and monitor until signs and symptoms are resolved. Monitoring PNH Manifestations after Discontinuation of EMPAVELI After discontinuing treatment with EMPAVELI, closely monitor for signs and symptoms of hemolysis, identified by elevated LDH levels along with sudden decrease in PNH clone size or hemoglobin, or reappearance of symptoms such as fatigue, hemoglobinuria, abdominal pain, dyspnea, major adverse vascular events (including thrombosis), dysphagia, or erectile dysfunction. Monitor any patient who discontinues EMPAVELI for at least 8 weeks to detect hemolysis and other reactions. If hemolysis, including elevated LDH, occurs after discontinuation of EMPAVELI, consider restarting treatment with EMPAVELI. Interference with Laboratory Tests There may be interference between silica reagents in coagulation panels and EMPAVELI that results in artificially prolonged activated partial thromboplastin time (aPTT); therefore, avoid the use of silica reagents in coagulation panels. ADVERSE REACTIONS Most common adverse reactions in patients with PNH (incidence ≥10%) were injection site reactions, infections, diarrhea, abdominal pain, respiratory tract infection, pain in extremity, hypokalemia, fatigue, viral infection, cough, arthralgia, dizziness, headache, and rash. USE IN SPECIFIC POPULATIONS Females of Reproductive Potential EMPAVELI may cause embryo-fetal harm when administered to pregnant women. Pregnancy testing is recommended for females of reproductive potential prior to treatment with EMPAVELI. Advise female patients of reproductive potential to use effective contraception during treatment with EMPAVELI and for 40 days after the last dose. Please see full Prescribing Information, including Boxed WARNING regarding serious infections caused by encapsulated bacteria, and Medication Guide. About Apellis Apellis Pharmaceuticals, Inc. is a global biopharmaceutical company that combines courageous science and compassion to develop life-changing therapies for some of the most challenging diseases patients face. We ushered in the first new class of complement medicine in 15 years and now have two approved medicines targeting C3. These include the first-ever therapy for geographic atrophy, a leading cause of blindness around the world. We believe we have only begun to unlock the potential of targeting C3 across serious retinal, rare, and neurological diseases. For more information, please visit http://apellis.com or follow us on Twitter and LinkedIn. Apellis Forward-Looking StatementStatements 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 regarding the expected timing of clinical data, the re-examination of the marketing authorization application of SYFOVRE and the expected proceeds from the unwind of the capped call transactions. 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 benefit/risk profile of SYFOVRE following the events of retinal vasculitis will impact the Company’s commercialization efforts; whether SYFOVRE will receive approval from foreign regulatory agencies for GA when expected or at all, including the impact of the reported events of retinal vasculitis on the likelihood and timing of such approvals; whether the Company’s clinical trials will be completed when anticipated; whether results obtained in 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 systemic pegcetacoplan will receive approval from the FDA or equivalent foreign regulatory agencies for C3G and IC-MPGN or any other indication when expected or at all; the period for which the the Company believes that its cash resources will be sufficient to fund its operations; ; and other factors discussed in the “Risk Factors” section of Apellis’ Annual Report on Form 10-K with the Securities and Exchange Commission on February 27, 2024 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. Media Contact:Lissa Pavlukmedia@apellis.com617.977.6764 Investor Contact:Meredith Kayameredith.kaya@apellis.com617.599.8178 APELLIS PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED BALANCE SHEETS(Amounts in thousands, except per share amounts) December 31, December 31, 2023 2022 Assets Current assets: Cash and cash equivalents $351,185 $551,801 Accounts receivable 206,442 7,727 Inventory 146,362 85,714 Prepaid assets 38,820 36,350 Restricted cash 1,114 1,273 Other current assets 22,408 36,658 Total current assets 766,331 719,523 Non-current assets: Right-of-use assets 16,745 18,747 Property and equipment, net 4,345 6,148 Other assets 1,309 15,799 Total assets $788,730 $760,217 Liabilities and Stockholders' Equity Current liabilities: Accounts payable 37,516 37,342 Accrued expenses 127,806 95,139 Current portion of development liability 75,830 29,504 Current portion of right of use liabilities 6,441 5,625 Total current liabilities 247,593 167,610 Long-term liabilities: Long-term development liability 239,817 315,647 Convertible senior notes 93,033 92,736 Right-of-use liabilities 11,454 14,352 Other liabilities 2,312 — Total liabilities 594,209 590,345 Stockholders' equity: Preferred stock, $0.0001 par value; 10,000 shares authorized and zero shares issued and outstanding at December 31, 2023 and 2022 — — Common stock, $0.0001 par value; 200,000 shares authorized at December 31, 2023 and 2021; 119,556 and 110,772 shares issued and outstanding at December 31, 2023 and 2022 12 11 Additional paid-in capital 3,035,539 2,479,596 Accumulated other comprehensive loss (3,542) (875) Accumulated deficit (2,837,488) (2,308,860) Total stockholders' equity 194,521 169,872 Total liabilities and stockholders' equity $788,730 $760,217 APELLIS PHARMACEUTICALS, INC.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS(Amounts in thousands, except per share amounts) For the Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Revenue: Product revenue, net$138,655 $19,653 $366,281 $65,092 Licensing and other revenue 7,722 3,010 30,310 10,330 Total revenue: 146,377 22,663 396,591 75,422 Operating expenses: Cost of sales 19,912 2,925 58,510 5,636 Research and development 69,282 99,423 354,387 387,236 General and administrative 141,701 84,368 500,815 277,163 Operating expenses: 230,895 186,716 913,712 670,035 Net operating loss (84,518) (164,053) (517,121) (594,613) Loss on conversion of debt — — — (32,890) Interest income 4,548 4,575 20,933 8,914 Interest expense (7,402) (7,738) (29,581) (32,626) Other (expense)/income, net 219 (246) (727) (288) Net loss before taxes (87,153) (167,462) (526,496) (651,503) Income tax expense 1,423 (1,471) 2,132 669 Net income/(loss)$(88,576) $(165,991) $(528,628) $(652,172) Other comprehensive (loss)/gain: Unrealized (loss)/gain on marketable securities — 382 — (1) Unrealized (loss)/gain on pension plans (2,618) 1,646 (2,618) 1,646 Foreign currency gain/(loss) 141 124 (49) (430) Total other comprehensive income/(loss) (2,477) 2,152 (2,667) 1,215 Comprehensive loss, net of tax$(91,053) $(163,839) $(531,295) $(650,957) Net loss per common share, basic and diluted$(0.73) $(1.50) $(4.45) $(6.15) Weighted-average number of common shares used in net loss per common share, basic and diluted 121,232 110,629 118,678 106,114