Protein-Losing Enteropathies

This article will introduce the new GPCR-related drugs approved by the FDA in 2023. Filspari (Sparsentan)On February 17th, 2023, Travere Therapeutics' Filspari (Sparsentan) is a dual antagonist of the endothelin A receptor (ETAR) and the angiotensin II (Ang II) type 1 receptor (AT1R), exhibiting high-affinity binding to both receptors (with an affinity of 9.3 nM for ETAR and 0.8 nM for AT1R). This drug is indicated for adults with primary IgA nephropathy (IgAN) who may experience rapid progression of the disease, and it can reduce proteinuria. Endothelin-1 and angiotensin II are part of the pathogenesis of IgA nephropathy (IgAN), a disease characterized by an increase in antibodies against galactose-deficient IgA1 (Gd-IgA1). Antibodies to Gd-IgA1 can lead to mesangial cell activation and proliferation, thus stimulating the production of ET-1 and Ang II. As a dual antagonist of AT1R and ETAR, Sparsentan can reduce proteinuria in patients with IgAN. The selectivity of Sparsentan for ETAR and AT1R is more than 500-fold higher than for the type B endothelin receptor and the subtype 2 of the angiotensin II receptor. On May 13th, 2023, the renowned medical journal The Lancet online published the results of Travere's clinical study on Sparsentan in patients with IgA nephropathy. The findings showed that, compared to the monotherapy with AT1R antagonist irbesartan, daily treatment with the dual-acting agent Sparsentan significantly reduced proteinuria in adult patients with IgA nephropathy. Zavzpret(zavegepant)On March 10, 2023, the U.S. Food and Drug Administration (FDA) approved Pfizer's new medication, Zavegepant (Zavzpret), for the treatment of acute migraine. Zavzpret is the world's first and only calcitonin gene-related peptide (CGRP) receptor antagonist nasal spray, indicated for the acute treatment of migraine in adults. According to the pivotal Phase 3 study data released by the company, Zavzpret demonstrated statistically superior results compared to placebo on the twin primary endpoints of pain freedom and freedom from the most bothersome symptom at two hours post-dosing. Additionally, in the predefined secondary endpoints, Zavzpret provided the earliest pain relief, starting at 15 minutes, compared to the placebo. Veozah (fezolinetant)On May 12, 2023, the FDA approved the New Drug Application (NDA) submitted by Astellas Pharma US, Inc. for the commercialization of Veozah (fezolinetant). Veozah is an orally administered medication designed to treat moderate to severe vasomotor symptoms associated with menopause, such as hot flashes. This marks the first FDA-approved Neurokinin 3 (NK3) receptor antagonist for the treatment of moderate to severe hot flashes due to menopause. It functions by binding to NK3 receptors and blocking their activity. On April 1, 2023, the internationally renowned medical journal "The Lancet" published a clinical research paper titled "Fezolinetant for treatment of moderate to severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomized controlled study," which demonstrated the therapeutic effectiveness of Fezolinetant on moderate to severe hot flashes. Fezolinetant is among the first batch of non-hormonal NK3 receptor antagonists developed for the treatment of vasomotor symptoms during menopause. NK3 receptor antagonists are potential non-hormonal therapies for treating vasomotor symptoms in menopausal women. For those women who cannot or do not wish to undergo hormone therapy, this type of therapy represents a scarce option. IZERVAY(avacincaptad pegol)On August 4, 2023, the FDA approved IZERVAY™ (avacincaptad pegol) for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). IZERVAY is a novel complement C5 inhibitor and is the only approved treatment for GA. In the 12-month primary endpoints of two Phase III clinical trials, IZERVAY demonstrated a significant reduction in the progression rate of geographic atrophy. Avacincaptad pegol is an RNA aptamer covalently linked to branched polyethylene glycol (PEG) molecules, which binds to the complement protein C5 and inhibits its activity. By inhibiting C5, avacincaptad pegol prevents its cleavage into C5a and C5b, thereby reducing the formation of the membrane attack complex (MAC). According to the patent description related to Avacincaptag pegol, Avacincaptag pegol (research code ARC1905) is an aptamer molecule composed of a 39-nucleotide long RNA molecule and a 43 kD branched PEG. The amine group at the 5' end of the RNA molecule provides a chemical reactive group for pegylation. TALVEY™ (talquetamab-tgvs)On August 9th, Johnson & Johnson announced that the U.S. FDA approved TALVEY™ (talquetamab-tgvs) for the treatment of adult patients with relapsed or refractory multiple myeloma. Talquetamab is a bispecific T-cell engager antibody targeting both the CD3 receptor on T cells and GPRC5D. GPRC5D is a novel therapeutic target belonging to the Class C group of G protein-coupled receptors, which is expressed on some normal cells but overexpressed in myeloma cells. In December 2022, the Johnson & Johnson team published their first article in The New England Journal of Medicine, presenting the phase 1 clinical study results of the GPRC5D bispecific antibody Talquetamab, used for the treatment of multiple myeloma. The results showed that 232 patients received talquetamab treatment (102 intravenously, 130 subcutaneously). The median follow-up time was 11.7 months for patients receiving a 405 microgram dose and 4.2 months for those receiving an 800 microgram dose, with response rates of 70% and 64%, respectively. The median durations of response were 10.2 and 7.8 months, respectively. Common adverse reactions for the two subcutaneous dosing regimens (weekly 405 mcg/kg and biweekly 800 mcg/kg) included cytokine release syndrome (CRS) in 77% and 80% of patients, respectively, skin-related events in 67% and 70%, and oral ulcers in 63% and 57%. Except for one case of CRS, all other adverse reactions were Grade 1 or 2. According to information from Johnson & Johnson's official website, the FDA submission included the latest clinical study data. The phase 2 MonumenTAL-1 study of Talquetamab included patients (187 individuals) who had at least four prior lines of therapy and had not received prior T cell redirecting therapy, showing a meaningful Overall Response Rate (ORR). At a subcutaneous (SC) dosing of 0.8 mg/kg biweekly, 73.6% of patients achieved ORR. During a median follow-up of nearly 6 months (range 0 to 9.5 months) after the first response, 58% of patients achieved a Very Good Partial Response (VGPR) or better, with 33% achieving a Complete Response (CR) or better. At a weekly SC dose of 0.4 mg/kg, 73.0% of patients achieved ORR. During a median follow-up of nearly 14 months (range 0.8 to 15.4 months) after the initial response, 57% of patients achieved VGPR or better, of which 35% achieved CR or better. Notably, the safety profile of TALVEY™ includes a "Boxed Warning" for cytokine release syndrome and neurotoxicity. The "Warnings and Precautions" include oral toxicity and weight loss, infections, cytopenias, skin toxicity, hepatotoxicity, and embryo-fetal toxicity. The most common adverse reactions (≥20%) were pyrexia, CRS, dyspepsia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight loss, dry mouth, skin dryness, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache. The most common Grade 3 or 4 laboratory abnormalities (≥30%) were lymphocyte count decrease, neutrophil count decrease, white blood cell decrease, and hemoglobin decrease. Veopoz (pozelimab)On August 18, 2023, Regeneron Pharmaceuticals, Inc. announced that the U.S. FDA has approved pozelimab (Veopoz™) for the treatment of CHAPLE disease, also known as CD55 deficiency with protein-losing enteropathy, in adults and children aged one year and older. Pozelimab is currently the first and only treatment specifically developed for CHAPLE disease. CHAPLE disease is an ultra-rare, life-threatening genetic immune disorder caused by an overactivation of the complement system. For healthy individuals, the complement system is a mechanism that helps eliminate microbes. However, patients with CHAPLE disease have mutations in the CD55 gene which render them unable to regulate complement activity. Without proper regulation by CD55, the complement system may attack normal cells, damaging blood and lymphatic vessels in the upper gastrointestinal tract, leading to the loss of circulating proteins. Less than 10 cases of CHAPLE disease have been identified in the United States. Pozelimab (REGN3918) is a fully humanized IgG4 monoclonal antibody developed by Regeneron Pharmaceuticals that binds with high affinity to C5 and its variants. In May 2020, the Regeneron team published preclinical study results for the first time in the journal PLOS One, reporting findings from studies on humanized C5 mice and the discovery using fully human anti-C5 antibodies. A series of full-length antibodies were identified, which bind with high affinity to human and monkey-derived C5 without interacting with mouse C5. Pozelimab (REGN3918) binds with high affinity to C5 and its variants and effectively blocks complement-mediated hemolysis in vitro. APHEXDA™(motixafortide)On September 11, 2023, BioLineRx announced that the U.S. FDA has approved APHEXDA™ (motixafortide) for use in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to peripheral blood for collection in patients with multiple myeloma, facilitating autologous stem cell transplantation. Motixafortide is a high-affinity, long-acting synthetic peptide antagonist of CXCR4 (BKT-140), originally developed by Biokine Therapeutics, which later licensed it to BioLineRx for joint clinical development (BL-8040). Motixafortide takes advantage of the expression of CXCR4 receptors on different immune cells to enhance the immune system's anticancer capabilities. Among immune cells that express CXCR4, some have anticancer activity, such as effector T cells, while others promote tumor growth and support its survival. By blocking the infiltration of immune suppressive cells mediated by CXCR4, motixafortide alleviates immune suppression. Filgrastim (G-CSF) is a short-acting recombinant non-glycosylated human granulocyte colony-stimulating factor (G-CSF) analog produced via DNA recombinant technology, which has been approved for inducing granulocyte production and reducing the risk of infection following myelosuppressive therapy. Filgrastim's various therapeutic uses include treatment and prevention of infections as well as febrile neutropenia in patients undergoing myelosuppressive chemotherapy or radiotherapy. It is also used to control severe chronic neutropenia and to mobilize hematopoietic stem cells in peripheral blood for leukapheresis in patients undergoing peripheral blood stem cell collection and therapy. Exxua (Gepirone)On September 28th, 2023, Fabre-Kramer Pharmaceuticals announced on its official website that the U.S. Food and Drug Administration (FDA) had approved Gepirone Hydrochloride Extended-Release Tablets (brand name Exxua). Exxua is the first and only FDA-approved oral antidepressant that selectively agonizes the 5HT1a receptor. It works by modulating the activity of serotonin in the central nervous system and is indicated for the treatment of major depressive disorder (MDD) in adults. The company first submitted a New Drug Application (NDA) for Gepirone Hydrochloride in September 1999, but it was initially rejected by the FDA in 2002. After three subsequent rejections, Exxua was finally approved after 24 years of rigorous review. Below is an excerpt from the letter the FDA sent to Fabre-Kramer following the approval of Exxua: Gepirone (BMY-13805), a selective small molecule partial agonist targeting the 5-HT1A receptor, was developed by Bristol-Myers Squibb and licensed to Fabre-Kramer Pharmaceuticals in 1993. Fabre-Kramer submitted its marketing application in 1999. The U.S. FDA rejected the marketing applications for Gepirone in 2002 and again in 2004. In May 2007, after providing extra information from clinical trials, Fabre-Kramer submitted the NDA once more. However, in 2012, Fabre-Kramer was unsuccessful in convincing the FDA of Gepirone's efficacy for anxiety and depression. In December 2015, the FDA gave a negative evaluation of Gepirone's efficacy in treating depression due to concerns over its effectiveness. Nevertheless, in March 2016, the FDA reversed its decision, providing a positive evaluation for Gepirone Extended-Release Tablets. According to two key updated 8-week randomized, double-blind, placebo-controlled clinical studies, studies 134001 and FKGBE007, utilizing the improvement in the total scores on the Hamilton Depression Rating Scale (HDRS-17 or HAMD-17), Exxua was shown to be superior to placebo, confirming its efficacy in treating MDD. Based on the primary efficacy endpoint of improved HAMD-17 scores, Exxua's effects were generally observed starting from the second week, with its antidepressant effects increasing over the subsequent weeks. The full manifestation of Exxua’s effects generally occurs by the third week or later. VELSIPITY (etrasimod)On October 12th, 2023, the U.S. Food and Drug Administration (FDA) approved Pfizer's new drug VELSIPITY™ (etrasimod) for the treatment of moderate to severe ulcerative colitis. Etrasimod is an orally administered, once-daily selective sphingosine 1-phosphate (S1P) receptor modulator with a recommended dose of 2 mg. Etrasimod was originally developed by Arena Pharmaceuticals. In 2022, Pfizer announced a $6.7 billion acquisition of Arena Pharmaceuticals, with the aim of adding their clinical candidate for the treatment of moderate to severe ulcerative colitis to their portfolio. Zilbrysq (zilucoplan)On October 17th, 2023, the U.S. FDA approved UCB's Zilbrysq (zilucoplan) for the treatment of adult patients with generalized Myasthenia Gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive. Generalized Myasthenia Gravis is an autoimmune disease characterized by the presence of pathogenic autoantibodies that bind to AChRs. Zilucoplan is a synthetic macrocyclic peptide consisting of 15 amino acids and acts as a complement inhibitor, preventing the activation of the complement protein C5, which plays a role in initiating inflammatory responses within the innate immune system. The precise mechanism of action of Zilucoplan in generalized Myasthenia Gravis has not been fully elucidated.

This year we’re taking the branded drug names that were officially approved by the FDA in 2022 and 2023 - now it's your turn to vote for your winner. LAUNCHED: Wednesday, March 20, 7:00 a.m. ET It’s March, so it’s time for some #FierceMadness. Last year, we channeled the NCAA tournament for the best pharma ad campaigns, but, this year, we’re looking for the best of the best in drug names. Here’s how it works. We’ve chosen 64 of the most distinctive drug names to come out of the FDA’s 2022 and 2023 crop of new approvals. Whittling down to 64 from the 92 drug names available was our staff challenge, but now it’s up to you, readers, to deliberate and vote down to the final winner. Remember, this isn’t about the drugs themselves—neither how well they may work (or not) nor any controversies in how they may have been approved. Our goal is to assess their marketing suitability, considering how well they perform in their respective field and against competitors. Ready to play? Check out the bracket here (PDF) and see the full Madness 64 list below. Then vote is via our poll here. You can vote from now until Friday, March 22, at 6 p.m. ET. Check back here Monday, March 25, for your results, and the chance to vote in the next round.   After that, we’ll be back with a new round each Wednesday and Monday through Monday, April 8, when you can vote for your championship winner. Any remote robo-voting will be noted, and those votes will be discarded. Please play fair. Don’t forget to tell us why you picked what you picked in the voting poll comments section—and what you think each drug name really sounds like. We’ll include the funniest and most out-of-the-box comments in our recaps every round, so make 'em good! New this year: Our sister publication Fierce Biotech is also running its own Madness tournament for the best of the best in biotech company names. Check out and vote in its championship here.  Good luck, and happy Madness! #FierceMadness 2024: The full bracket of 64   Jesduvroq vs. Lamzede Jesduvroq Maker: GSK Indication: Anemia due to chronic kidney disease Sounds like: When you hit your finger with a hammer, but it’s in front of your children so you’re trying not to swear   Lamzede Maker: Chiesi Indication: Non-central nervous system manifestations of alpha-mannosidosis Sounds like: A vegan meal   Pluvicto vs. Lunsumio Pluvicto Maker: Novartis Indication: Prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer following other therapies Sounds like: A new planet   Lunsumio Maker: Roche Indication: Relapsed or refractory follicular lymphoma, a type of non-Hodgkin lymphoma Sounds like: A Japanese wrestler   Briumvi vs. Camzyos Briumvi Maker: TG Therapeutics Indication: Relapsing forms of multiple sclerosis Sounds like: A sixth-generation cheese    Camzyos Maker: Bristol Myers Squibb Indication: Obstructive hypertrophic cardiomyopathy Sounds like: A Spanish holiday resort   Voquezna vs. Mounjaro Voquezna Maker: Phathom Pharmaceuticals Indication: Helicobacter pylori infection Sounds like: A sports drink with a kick   Mounjaro Maker: Eli Lilly Indication: Lowering blood sugar levels in Type 2 diabetes Sounds like: A legendary medieval sword fighter    Vtama vs. Amvuttra Vtama Maker: Dermavant Indication: Plaque psoriasis Sounds like: A mouthful   Amvuttra Maker: Alnylam Indication: Polyneuropathy of hereditary transthyretin-mediated amyloidosis Sounds like: A pope’s gift    Xenpozyme vs. Daxxify Xenpozyme Maker: Sanofi Indication: Acid sphingomyelinase deficiency Sounds like: An alien protein   Daxxify  Maker: Revance Indication: The treatment of cervical dystonia and for the temporary improvement of frown lines  Sounds like: A ray gun to make you sassy    Fruzaqla vs. Sotyktu Fruzaqla Maker: Takeda Pharmaceuticals Indication: Refractory, metastatic colorectal cancer Sounds like: A European swear word   Sotyktu Maker: Bristol Myers Squibb Indication: Moderate to severe plaque psoriasis Sounds like: Gesundheit!   Terlivaz vs. Imjudo Terlivaz Maker: Mallinckrodt Pharmaceuticals Indication: Improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function Sounds like: A Hungarian dance   Imjudo Maker: AstraZeneca Indication: Unresectable hepatocellular carcinoma Sounds like: A self-confident martial artist   Elahere vs. Vabysmo Elahere Maker: ImmunoGen Indication: Recurrent ovarian cancer that is resistant to platinum therapy Sounds like: An inebriated attempt at Hawaiian   Vabysmo Maker: Roche Indication: Neovascular (wet) aged-related macular degeneration and diabetic macular edema Sounds like: A new way of saying fantastic   Pyrukynd vs. Rystiggo Pyrukynd Maker: Agios Indication: Hemolytic anemia in pyruvate kinase deficiency Sounds like: A drunk Scrabble game   Rystiggo Maker: UCB Indication: Generalized myasthenia gravis in adults who are anti-acetylcholine receptor- or anti-muscle-specific tyrosine kinase antibody-positive Sounds like: An Italian village     Beyfortus vs. Xdemvy Beyfortus Maker: AstraZeneca Indication: To prevent respiratory syncytial virus lower respiratory tract disease Sounds like: A medieval stronghold   Xdemvy Maker: Tarsus Pharmaceuticals Indication: Demodex blepharitis Sounds like: Elon Musk’s drunk attempt at renaming his business   Tzield vs. Rezlidhia Tzield Maker: Provention Bio Indication: Delay the onset of stage 3 Type 1 diabetes Sounds like: An electronic barrier   Rezlidhia Maker: Rigel Pharmaceuticals  Indication: Relapsed or refractory acute myeloid leukemia with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation Sounds like: A new Disney princess     Krazati vs. Leqembi Krazati Maker: Mirati Therapeutics Indication: KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer in adults who have received at least one prior systemic therapy Sounds like: A crazy party   Leqembi Maker: Eisai Indication: Alzheimer’s disease Sounds like: An inspirational French aphorism   Cibinqo vs. Brenzavvy Cibinqo Maker: Pfizer Indication: Refractory, moderate to severe atopic dermatitis Sounds like: A game of cheeky bingo   Brenzavvy Maker: TheracosBio Indication: Glycemic control in adults with Type 2 diabetes mellitus as an adjunct to diet and exercise Sounds like: Heard in a copy of "Pirates of the Caribbean"   Jaypirca vs. Skyclarys Jaypirca Maker: Eli Lilly Indication: Relapsed or refractory mantle cell lymphoma in adults who have had at least two lines of systemic therapy, including a BTK inhibitor Sounds like: A strong coffee   Skyclarys Maker: Biogen Indication: Friedreich’s ataxia Sounds like: A high-rise building   Zavzpret vs. Paxlovid Zavzpret Maker: Pfizer Indication: Migraine treatment Sounds like: A Turkish fast-food restaurant   Paxlovid Maker: Pfizer Indication: Mild to moderate COVID-19 in adults at high risk for progression to severe COVID-19 Sounds like: A bizarre Pac-Man sequel   Inpefa vs. Columvi Inpefa Maker: Lexicon Pharmaceuticals Indication: Heart failure Sounds like: An anti-fascist offshoot group   Columvi Maker: Roche Indication: Diffuse large B-cell lymphoma, not otherwise specified, or large B-cell lymphoma arising from follicular lymphoma after two or more lines of systemic therapy Sounds like: An ancient Roman detective   Daybue vs. Zynyz Daybue Maker: Acadia Indication: Rett syndrome Sounds like: How my five-year-old insists debut is spelled    Zynyz Maker: Incyte Indication: Metastatic or recurrent locally advanced Merkel cell carcinoma Sounds like: Drug naming companies may be running out of ideas   Rezzayo vs. Qalsody Rezzayo Maker: Melinta Therapeutics Indication: Candidemia and invasive candidiasis Sounds like: A phrase used when you’ve had a great nap in the day   Qalsody Maker: Biogen Indication: Amyotrophic lateral sclerosis in adults who have a SOD1 gene mutation Sounds like: From the makers of “Better Call Saul” comes “better Qalsody”   Elfabrio vs. Veozah Elfabrio Maker: Chiesi Indication: Fabry disease Sounds like: The lost Spanish Mario brother   Veozah Maker: Astellas Indication: Moderate to severe hot flashes caused by menopause Sounds like: A Broadway play     Epkinly vs. Zurzuvae Epkinly Makers: AbbVie/Genmab Indication: Relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma after two or more lines of systemic therapy Sounds like: Someone who watches too many streaming episodes   Zurzuvae Makers: Sage/Biogen Indication: Postpartum depression Sounds like: A mouthful   Izervay vs. Talvey Izervay Maker: Iveric Bio Indication: Geographic atrophy secondary to age-related macular degeneration Sounds like: A new app for scanning the land   Talvey Maker: Johnson & Johnson Indication: Relapsed or refractory multiple myeloma who have received at least four prior therapies Sounds like: A little too close to talc…   Elrexfio vs. Veopoz Elrexfio Maker: Pfizer Indication: Relapsed or refractory multiple myeloma who have received at least four prior lines of therapy Sounds like: A new dinosaur found in Mexico   Veopoz Maker: Regeneron Pharmaceuticals Indication: Patients 1 year old and older with CD55-deficient protein-losing enteropathy Sounds like: Double-plus good!   Zilbrysq vs. Ojjaara Zilbrysq Maker: UCB Indication: Generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive Sounds like: Absolute zero   Ojjaara Maker: GSK Indication: Intermediate or high-risk myelofibrosis in adults with anemia Sounds like: “What’s my name?”     Exxua vs. Pombiliti Exxua Maker: Fabre-Kramer Pharmaceuticals Indication: Major depressive disorder Sounds like: Someone who’s always leaving   Pombiliti Maker: Amicus Indication: Late-onset Pompe disease Sounds like: The ability to treat Pompe disease (this feels a little on the nose)    Rivfloza vs. Velsipity Rivfloza Maker: Novo Nordisk Indication: Urinary oxalate levels in patients 9 years and older with primary hyperoxaluria type 1 and relatively preserved kidney function Sounds like: An exuberant DJ   Velsipity Maker: Pfizer Indication: Moderately to severely active ulcerative colitis in adults Sounds like: A deodorant brand you wouldn’t want to buy   Bimzelx vs. Omvoh Bimzelx Maker: UCB Indication: Moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy Sounds like: Throwing away unwanted antacids   Omvoh Maker: Eli Lilly Indication: Ulcerative colitis Sounds like: A new age prayer   Loqtorzi vs. Defencath Loqtorzi Maker: Coherus Biosciences Indication: Recurrent or metastatic nasopharyngeal carcinoma when used together with or following other therapies Sounds like: How you close the door in a magical kingdom   Defencath Maker: CorMedix Indication: Reduce the incidence of catheter-related bloodstream infections in adults with kidney failure receiving chronic hemodialysis Sounds like: A Dungeons and Dragons character   Augtyro vs. Ryzneuta Augtyro Maker: Bristol Myers Squibb Indication: ROS1-positive non-small cell lung cancer Sounds like: A virtual reality game where you’re the bad guy   Ryzneuta Maker: Acrotech Biopharma Indication: Neutropenia Sounds like: Getting rid of someone’s charisma   Truqap vs. Ogsiveo Truqap Maker: AstraZeneca Indication: Breast cancer that meets certain disease criteria Sounds like: A limit on truth   Ogsiveo Maker: SpringWorks Indication: Progressing desmoid tumors who require systemic treatment Sounds like: Oh, give us a go!     Quviviq vs. Ztalmy Quviviq Maker: Idorsia Indication: Insomnia Sounds like: A producer asking a biotech founder turned politician to get ready for his TV appearance   Ztalmy Maker: Marinus Indication: Seizures in cyclin-dependent kinase-like 5 deficiency disorder Sounds like: A nefarious Yevgeny Zamyatin character   Opdualag vs. Wainua Opdualag Maker: Bristol Myers Squibb Indication: Unresectable or metastatic melanoma Sounds like: A Russian prison   Wainua Maker: AstraZeneca Indication: Polyneuropathy of hereditary transthyretin-mediated amyloidosis Sounds like: A Premier League footballer

Third quarter 2023 revenues increased 15% to $3.36 billion versus third quarter 2022 Third quarter 2023 Dupixent® global net sales(recorded by Sanofi) increased 33% to $3.10 billion versus third quarter 2022 Third quarter 2023 U.S. net sales for EYLEA® and EYLEA HD were $1.49 billion, including $43 million from EYLEA HD Third quarter 2023 Libtayo® global net sales increased 62% to $232 million versus third quarter 2022 Third quarter 2023 GAAP diluted EPS of $8.89 and non-GAAP diluted EPS(a) of $11.59; includes unfavorable $0.77 impact from acquired IPR&D charge FDA approved EYLEA HD for wet age-related macular degeneration (wAMD), diabetic macular edema (DME), and diabetic retinopathy (DR) and Veopoz™ for CHAPLE disease Two-year results reported for EYLEA HD from pivotal PULSAR trial demonstrated durable vision gains at extended dosing intervals in wAMD FDA accepted for priority review BLA for odronextamab for follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) and sBLA for Dupixent in eosinophilic esophagitis (EoE) in children aged 1 to 11 years of age Acquisition of Decibel Therapeutics completed, strengthening genetic medicines portfolio TARRYTOWN, N.Y., Nov. 02, 2023 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced financial results for the third quarter of 2023 and provided a business update. "We have continued our momentum in the third quarter of 2023 with double-digit year-over-year revenue growth, driven by strong Dupixent and Libtayo performance, as well as strong initial uptake of EYLEA HD following its late August launch," said Leonard S. Schleifer, M.D., Ph.D., Board Co-Chair, President and Chief Executive Officer of Regeneron. "We are also making significant progress across our diversified pipeline, with FDA priority review designations for odronextamab in relapsed/refractory (R/R) follicular lymphoma and R/R diffuse large B-cell lymphoma as well as for Dupixent in pediatric eosinophilic esophagitis, while also adding a promising gene therapy platform to our portfolio through the recent acquisition of Decibel Therapeutics." Financial Highlights ($ in millions, except per share data) Q3 2023 Q3 2022 % Change Total revenues $ 3,363 $ 2,936 15 % GAAP net income $ 1,008 $ 1,316 (23 %) GAAP net income per share - diluted $ 8.89 $ 11.66 (24 %) Non-GAAP net income(a) $ 1,329 $ 1,270 5 % Non-GAAP net income per share - diluted(a) $ 11.59 $ 11.14 4 % "Our third quarter financial results reflect robust execution across the enterprise, including notable pipeline advances and strong commercial performance," said Robert E. Landry, Executive Vice President, Finance and Chief Financial Officer of Regeneron. "We also continued to deliver on our capital allocation priorities, primarily investing in internal and external innovation coupled with opportunistic share repurchases." Business Highlights Key Pipeline Progress Regeneron has approximately 35 product candidates in clinical development, including a number of marketed products for which it is investigating additional indications. Updates from the clinical pipeline include: EYLEA HD (aflibercept) 8 mg In August 2023, the U.S. Food and Drug Administration (FDA) approved EYLEA HD for the treatment of patients with wAMD, DME, and DR. The Company announced top-line, two-year (96 weeks) data from the pivotal PULSAR trial in patients with wAMD. The longer-term data follow the positive two-year results from the PHOTON trial in DME, with PULSAR similarly demonstrating that the vast majority of patients with wAMD were able to maintain or further extend the dosing intervals. In addition, visual gains for EYLEA HD remained largely consistent with those observed in the first year of the trial. In PULSAR, the safety of EYLEA HD continued to be similar to EYLEA through two years and remained consistent with the known safety pro EYLEA from previous clinical trials for wAMD. These results were also presented at the 23rd EURETINA Congress in October 2023. Dupixent (dupilumab) In September 2023, the Ministry of Health, Labour and Welfare (MHLW) in Japan approved Dupixent for the treatment of pediatric and adolescent patients with atopic dermatitis. The FDA accepted for priority review the supplemental Biologics License Application (sBLA) for the treatment of children aged 1 to 11 years with EoE, with a target action date of January 31, 2024. The Company and Sanofi also presented, at the American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting, positive results from a Phase 3 trial that showed consistent efficacy and safety for up to one year (52 weeks) in children aged 1 to 11 years with EoE. In October 2023, the FDA issued a Complete Response Letter (CRL) for the sBLA for Dupixent in chronic spontaneous urticaria (CSU). The CRL states that additional efficacy data are required to support an approval; it did not identify any issues with safety or manufacturing. An ongoing Phase 3 clinical trial (in biologic-naïve patients) continues to enroll patients, with results expected in late 2024. Based on recent feedback from the FDA, in addition to the positive results of the Phase 3 BOREAS study, a positive interim analysis of the replicate Phase 3 NOTUS study in chronic obstructive pulmonary disease (COPD) would enable an sBLA submission. The independent data monitoring committee will conduct an interim analysis of the NOTUS study later this year. Oncology Programs In September 2023, the FDA accepted for priority review the BLA for odronextamab, a bispecific antibody targeting CD20 and CD3, to treat adult patients with relapsed/refractory FL and relapsed/refractory DLBCL who have progressed after at least two prior systemic therapies, with a target action date of March 31, 2024. A regulatory application for odronextamab has also been submitted in the European Union (EU). Phase 3 studies were initiated for odronextamab in earlier lines of FL and DLBCL. The FDA granted Fast Track designation to fianlimab, an antibody to LAG-3, in combination with Libtayo (cemiplimab) for the first-line treatment of patients with metastatic melanoma (for which a Phase 3 study is ongoing). A Phase 3 study was initiated for linvoseltamab, a bispecific antibody targeting BCMA and CD3, in multiple myeloma. The Company presented key secondary endpoints, demonstrating encouraging event-free survival, from a Phase 2 trial with Libtayo as a neoadjuvant monotherapy in cutaneous squamous cell carcinoma (CSCC) at the European Society for Medical Oncology (ESMO) Congress 2023. These results were also concurrently published in The Lancet Oncology. Other Programs The FDA approved Veopoz (pozelimab-bbfg), an antibody to C5, for the treatment of adult and pediatric patients 1 year of age and older with CHAPLE disease, also known as CD55-deficient protein-losing enteropathy. CHAPLE is an ultra-rare hereditary disease that can cause potentially life-threatening gastrointestinal and cardiovascular symptoms. The Company announced preliminary, positive safety and efficacy results from the first patient (<2 years of age) dosed in the Phase 1/2 trial of DB-OTO, an AAV-based gene therapy, in children with profound genetic hearing loss due to mutations of the otoferlin gene. Business Development Updates In September 2023, the Company completed its acquisition of Decibel Therapeutics, Inc. and paid $101 million in cash, and may also pay up to a maximum of approximately $97 million to Decibel shareholders upon achievement of certain clinical development and regulatory milestones for DB-OTO within specified time periods. The acquisition builds upon a prior collaboration between the companies and includes several ongoing gene therapy programs targeting different forms of congenital, monogenic hearing loss, including DB-OTO. In August 2023, the Company expanded its agreement with the Biomedical Advanced Research and Development Authority (BARDA) of the U.S. Department of Health and Human Services (HHS) to support clinical development, clinical manufacturing, and the regulatory licensure process of a next-generation COVID-19 monoclonal antibody therapy for the prevention of SARS-CoV-2 infection. The new contract has an estimated value of up to approximately $326 million of government funding for certain development activities. In September 2023, the Company and Intellia Therapeutics, Inc. expanded their existing collaboration to develop additional in vivo CRISPR-based gene editing therapies focused on neurological and muscular diseases. The collaboration will leverage the Company's proprietary antibody-targeted adeno-associated virus (AAV) vectors and delivery systems and Intellia's proprietary Nme2 CRISPR/Cas9 (Nme2Cas9) systems adapted for viral vector delivery and designed to precisely modify a target gene. Corporate Updates The Company is participating in Together for CHANGE™, a national health and education equity initiative established by Nashville, Tennessee-based Meharry Medical College. The Together for CHANGE initiative seeks to address inequities in science, technology, engineering, and mathematics (STEM) careers and research. In addition, the Company announced a five-year, $5 million strategic investment to bolster Nashville's STEM ecosystem through high-quality, equitable engagement programs for students and science teachers. The Company announced that Robert E. Landry, Executive Vice President, Finance and Chief Financial Officer of Regeneron, will retire in February 2024. Christopher Fenimore, current Senior Vice President, Head of Accounting and Controller at Regeneron, will succeed Mr. Landry as Chief Financial Officer upon his retirement. The Company announced that Kathryn Guarini, Ph.D., and David P. Schenkein, M.D., joined the Company's Board of Directors effective September 8, 2023. Dr. Guarini recently retired as Chief Information Officer of IBM. Dr. Schenkein is a General Partner and Co-lead of the Life Sciences team at GV (Google Ventures). Third Quarter 2023 Financial Results Revenues ($ in millions) Q3 2023 Q3 2022 % Change Net product sales: EYLEA - U.S. $ 1,448 $ 1,629 (11 %) EYLEA HD - U.S. 43 — * Libtayo - Global** 232 126 84 % Praluent® - U.S. 40 30 33 % Evkeeza® - U.S. 19 13 46 % Inmazeb® - U.S. 4 3 33 % Total net product sales 1,786 1,801 (1 %) Collaboration revenue: Sanofi 1,065 711 50 % Bayer 377 333 13 % Other (3 ) 6 * Other revenue 138 85 62 % Total revenues $ 3,363 $ 2,936 15 % * Percentage not meaningful ** Effective July 1, 2022, the Company began recording net product sales of Libtayo outside the United States. Excluded from the third quarter of 2022 is approximately $17 million of net product sales recorded by Sanofi in connection with sales in certain markets (Sanofi recorded net product sales in such markets during a transition period). The percentage change shown would be 62% if such sales were included (see Table 5). Net product sales of EYLEA in the U.S. decreased in the third quarter of 2023, compared to the third quarter of 2022, primarily due to a lower net selling price driven by changing market dynamics, including increased competition. In August 2023, the FDA approved EYLEA HD and the Company commenced recording sales in the United States in the third quarter of 2023. Sanofi collaboration revenue increased in the third quarter of 2023, compared to the third quarter of 2022, primarily due to the Company's share of profits from commercialization of antibodies, which were $863 million in the third quarter of 2023, compared to $551 million in the third quarter of 2022. The change in the Company's share of profits from commercialization of antibodies was driven by higher profits associated with an increase in Dupixent sales. In addition, during the third quarter of 2023, the Company earned the final $50 million sales-based milestone from Sanofi upon aggregate annual sales of antibodies outside the U.S. exceeding $3.0 billion on a rolling twelve-month basis. Refer to Table 4 for a summary of collaboration revenue. Other revenue during the third quarter of 2023 included the recognition of $34 million of revenue in connection with the Company's agreement with BARDA to fund certain costs for a next-generation COVID-19 monoclonal antibody therapy for the prevention of SARS-CoV-2 infection. Operating Expenses GAAP % Change Non-GAAP(a) % Change ($ in millions) Q3 2023 Q3 2022 Q3 2023 Q3 2022 Research and development (R&D) $ 1,075 $ 911 18 % $ 954 $ 817 17 % Acquired in-process research and development (IPR&D) $ 100 $ — ** * * n/a Selling, general, and administrative (SG&A) $ 641 $ 529 21 % $ 534 $ 467 14 % Cost of goods sold (COGS) $ 225 $ 141 60 % $ 181 $ 109 66 % Cost of collaboration and contract manufacturing (COCM) $ 212 $ 177 20 % * * n/a Other operating (income) expense, net $ (1 ) $ (46 ) (98 %) * * n/a * GAAP and non-GAAP amounts are equivalent as no non-GAAP adjustments have been recorded. ** Percentage not meaningful GAAP and non-GAAP R&D expenses increased in the third quarter of 2023, compared to the third quarter of 2022, driven by additional costs incurred in connection with higher headcount and headcount-related costs, the advancement of the Company's late-stage pipeline, and increased manufacturing activity associated with the Company's product candidates. Acquired IPR&D expense in the third quarter of 2023 related to a $100 million development milestone in connection with the Phase 1 ALN-APP program, which is in collaboration with Alnylam Pharmaceuticals, Inc. GAAP and non-GAAP SG&A expenses increased in the third quarter of 2023, compared to the third quarter of 2022, primarily due to higher headcount and headcount-related costs and higher contributions to an independent not-for-profit patient assistance organization. Other operating (income) expense, net, decreased in the third quarter of 2023, compared to the third quarter of 2022, due to the recognition of $44 million of income in 2022 that did not recur during 2023 as a result of discontinuing further clinical development of fasinumab related to the Company's Teva and Mitsubishi Tanabe Pharma collaborative arrangements. Other Financial Information GAAP other income (expense) included the recognition of net unrealized losses on equity securities of $100 million in the third quarter of 2023, compared to $254 million of net unrealized gains in the third quarter of 2022. GAAP and Non-GAAP other income (expense) also included interest income of $134 million in the third quarter of 2023, compared to $43 million in the third quarter of 2022. In the third quarter of 2023, the Company's GAAP effective tax rate (ETR) was 9.3%, compared to 12.9% in the third quarter of 2022. In the third quarter of 2023, the non-GAAP ETR was 11.9%, compared to 12.1% in the third quarter of 2022. GAAP net income per diluted share was $8.89 in the third quarter of 2023, compared to $11.66 in the third quarter of 2022. Non-GAAP net income per diluted share was $11.59 in the third quarter of 2023, compared to $11.14 in the third quarter of 2022. A reconciliation of the Company's GAAP to non-GAAP results is included in Table 3 of this press release. During the third quarter of 2023, the Company repurchased shares of its common stock and recorded the cost of the shares, or $507 million, as Treasury Stock. As of September 30, 2023, $1.8 billion remained available for share repurchases under the Company's share repurchase program. 2023 Financial Guidance(c) The Company's full year 2023 financial guidance consists of the following components: 2023 Guidance Prior Updated GAAP R&D $4.315–$4.455 billion $4.370–$4.455 billion Non-GAAP R&D(a) $3.825–$3.925 billion $3.875–$3.925 billion GAAP SG&A $2.540–$2.680 billion $2.585–$2.685 billion Non-GAAP SG&A(a) $2.180–$2.280 billion $2.210–$2.270 billion GAAP gross margin on net product sales(d) 87%–89% 87%–88% Non-GAAP gross margin on net product sales(a)(d) 89%–91% 89%–90% COCM(e)* $820–$880 million $840–$880 million Capital expenditures* $760–$830 million $660–$700 million GAAP effective tax rate 8%–9% Unchanged Non-GAAP effective tax rate(a) 10%–11% Unchanged * GAAP and non-GAAP amounts are equivalent as no non-GAAP adjustments have been or are expected to be recorded. A reconciliation of full year 2023 GAAP to non-GAAP financial guidance is included below: Projected Range ($ in millions) Low High GAAP R&D $ 4,370 $ 4,455 Stock-based compensation expense 475 500 Acquisition and integration costs 20 30 Non-GAAP R&D $ 3,875 $ 3,925 GAAP SG&A $ 2,585 $ 2,685 Stock-based compensation expense 300 320 Acquisition and integration costs 75 95 Non-GAAP SG&A $ 2,210 $ 2,270 GAAP gross margin on net product sales 87 % 88 % Stock-based compensation expense 1 % 1 % Intangible asset amortization expense 1 % 1 % Acquisition and integration costs <1 % <1 % Charges related to REGEN-COV <(1 %) <(1 %) Non-GAAP gross margin on net product sales 89 % 90 % GAAP ETR 8 % 9 % Income tax effect of GAAP to non-GAAP reconciling items 2 % 2 % Non-GAAP ETR 10 % 11 % (a) This press release uses non-GAAP R&D, non-GAAP SG&A, non-GAAP COGS, non-GAAP gross margin on net product sales, non-GAAP other income (expense), net, non-GAAP ETR, non-GAAP net income, non-GAAP net income per share, total revenues excluding Ronapreve(b), and free cash flow, which are financial measures that are not calculated in accordance with U.S. Generally Accepted Accounting Principles (GAAP). These non-GAAP financial measures are computed by excluding certain non-cash and/or other items from the related GAAP financial measure. The Company also includes a non-GAAP adjustment for the estimated income tax effect of reconciling items. A reconciliation of the Company's GAAP to non-GAAP results is included in Table 3 of this press release. The Company makes such adjustments for items the Company does not view as useful in evaluating its operating performance. For example, adjustments may be made for items that fluctuate from period to period based on factors that are not within the Company's control (such as the Company's stock price on the dates share-based grants are issued or changes in the fair value of the Company's investments in equity securities) or items that are not associated with normal, recurring operations (such as acquisition and integration costs). Management uses these non-GAAP measures for planning, budgeting, forecasting, assessing historical performance, and making financial and operational decisions, and also provides forecasts to investors on this basis. With respect to free cash flows, the Company believes that this non-GAAP measure provides a further measure of the Company's operations' ability to generate cash flows. Additionally, such non-GAAP measures provide investors with an enhanced understanding of the financial performance of the Company's core business operations. However, there are limitations in the use of these and other non-GAAP financial measures as they exclude certain expenses that are recurring in nature. Furthermore, the Company's non-GAAP financial measures may not be comparable with non-GAAP information provided by other companies. Any non-GAAP financial measure presented by the Company should be considered supplemental to, and not a substitute for, measures of financial performance prepared in accordance with GAAP. (b) The casirivimab and imdevimab antibody cocktail for COVID-19 is known as REGEN-COV® in the United States and Ronapreve™ in other countries. The Company records net product sales of REGEN-COV in the United States and Roche records net product sales of Ronapreve outside the United States. (c) The Company's 2023 financial guidance does not assume the completion of any business development transactions not completed as of the date of this press release. (d) Gross margin on net product sales represents gross profit expressed as a percentage of total net product sales recorded by the Company. Gross profit is calculated as net product sales less cost of goods sold. (e) Corresponding reimbursements from collaborators and others for manufacturing of commercial supplies is recorded within revenues. Conference Call Information Regeneron will host a conference call and simultaneous webcast to discuss its third quarter 2023 financial and operating results on Thursday, November 2, 2023, at 8:30 AM Eastern Time. Participants may access the conference call live via webcast, or register in advance and participate via telephone, on the "Investors and Media" page of Regeneron's website at Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the Company's website for at least 30 days. About Regeneron Pharmaceuticals, Inc. Regeneron is a leading biotechnology company that invents, develops, and commercializes life-transforming medicines for people with serious diseases. Founded and led for 35 years by physician-scientists, Regeneron's unique ability to repeatedly and consistently translate science into medicine has led to numerous FDA-approved treatments and product candidates in development, almost all of which were homegrown in Regeneron's laboratories. Regeneron's medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, hematologic conditions, infectious diseases, and rare diseases. Regeneron is accelerating and improving the traditional drug development process through its proprietary VelociSuite® technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center®, which is conducting one of the largest genetics sequencing efforts in the world. For additional information about Regeneron, please visit or follow Regeneron on LinkedIn. Forward-Looking Statements and Use of Digital Media This press release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. ("Regeneron" or the "Company"), and actual events or results may differ materially from these forward-looking statements. Words such as "anticipate," "expect," "intend," "plan," "believe," "seek," "estimate," variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of products marketed or otherwise commercialized by Regeneron and/or its collaborators or licensees (collectively, "Regeneron's Products") and product candidates being developed by Regeneron and/or its collaborators or licensees (collectively, "Regeneron's Product Candidates") and research and clinical programs now underway or planned, including without limitation EYLEA® (aflibercept) Injection, EYLEA® HD (aflibercept) Injection 8 mg, Dupixent® (dupilumab), Libtayo® (cemiplimab), Praluent® (alirocumab), Kevzara® (sarilumab), Evkeeza® (evinacumab), Veopoz™ (pozelimab), odronextamab, itepekimab, fianlimab, garetosmab, linvoseltamab, REGN5713-5714-5715, Regeneron's other oncology programs (including its costimulatory bispecific portfolio), Regeneron's and its collaborators' earlier-stage programs, and the use of human genetics in Regeneron's research programs; the likelihood and timing of achieving any of the anticipated milestones described in this press release; safety issues resulting from the administration of Regeneron's Products and Regeneron's Product Candidates in patients, including serious complications or side effects in connection with the use of Regeneron's Products and Regeneron's Product Candidates in clinical trials; the likelihood, timing, and scope of possible regulatory approval and commercial launch of Regeneron's Product Candidates and new indications for Regeneron's Products, including those listed above and/or otherwise discussed in this press release (such as any potential regulatory approval of Dupixent in chronic obstructive pulmonary disease); the extent to which the results from the research and development programs conducted by Regeneron and/or its collaborators may be replicated in other studies and/or lead to advancement of product candidates to clinical trials, therapeutic applications, or regulatory approval; ongoing regulatory obligations and oversight impacting Regeneron's Products, research and clinical programs, and business, including those relating to patient privacy; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize Regeneron's Products and Regeneron's Product Candidates; competing drugs and product candidates that may be superior to, or more cost effective than, Regeneron's Products and Regeneron's Product Candidates; uncertainty of the utilization, market acceptance, and commercial success of Regeneron's Products and Regeneron's Product Candidates and the impact of studies (whether conducted by Regeneron or others and whether mandated or voluntary) or recommendations and guidelines from governmental authorities and other third parties on the commercial success of Regeneron's Products and Regeneron's Product Candidates; the ability of Regeneron to manufacture and manage supply chains for multiple products and product candidates; the ability of Regeneron's collaborators, suppliers, or other third parties (as applicable) to perform manufacturing, filling, finishing, packaging, labeling, distribution, and other steps related to Regeneron's Products and Regeneron's Product Candidates; the availability and extent of reimbursement of Regeneron's Products from third-party payers, including private payer healthcare and insurance programs, health maintenance organizations, pharmacy benefit management companies, and government programs such as Medicare and Medicaid; coverage and reimbursement determinations by such payers and new policies and procedures adopted by such payers; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its financial projections or guidance and changes to the assumptions underlying those projections or guidance, including GAAP and non-GAAP R&D, GAAP and non-GAAP SG&A, GAAP and non-GAAP gross margin on net product sales, COCM, capital expenditures, and GAAP and non-GAAP ETR; the potential for any license or collaboration agreement, including Regeneron's agreements with Sanofi and Bayer (or their respective affiliated companies, as applicable), to be cancelled or terminated; the impact of public health outbreaks, epidemics, or pandemics (such as the COVID-19 pandemic) on Regeneron's business; and risks associated with intellectual property of other parties and pending or future litigation relating thereto (including without limitation the patent litigation and other related proceedings relating to EYLEA and REGEN-COV® (casirivimab and imdevimab)), other litigation and other proceedings and government investigations relating to the Company and/or its operations (including the pending civil litigation initiated by the U.S. Attorney's Office for the District of Massachusetts), the ultimate outcome of any such proceedings and investigations, and the impact any of the foregoing may have on Regeneron's business, prospects, operating results, and financial condition. A more complete description of these and other material risks can be found in Regeneron's filings with the U.S. Securities and Exchange Commission, including its Form 10-K for the fiscal year ended December 31, 2022 and its Form 10-Q for the quarterly period ended September 30, 2023. Any forward-looking statements are made based on management's current beliefs and judgment, and the reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not undertake any obligation to update (publicly or otherwise) any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise. Regeneron uses its media and investor relations website and social media outlets to publish important information about the Company, including information that may be deemed material to investors. Financial and other information about Regeneron is routinely posted and is accessible on Regeneron's media and investor relations website ( ) and its LinkedIn page ( ). Non-GAAP Financial Measures This press release and/or the financial results attached to this press release include amounts that are considered "non-GAAP financial measures" under SEC rules. As required, Regeneron has provided reconciliations of such non-GAAP financial measures. Contact Information: Ryan Crowe Christina Chan Investor Relations Corporate Affairs 914-847-8790 914-847-8827 ryan.crowe@regeneron.com christina.chan@regeneron.com TABLE 1 REGENERON PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED BALANCE SHEETS (Unaudited) (In millions) September 30, December 31, 2023 2022 Assets: Cash and marketable securities $ 15,692.1 $ 14,334.1 Accounts receivable, net 5,584.5 5,328.7 Inventories 2,562.0 2,401.9 Property, plant, and equipment, net 4,006.1 3,763.0 Intangible assets, net 1,017.2 915.5 Deferred tax assets 2,316.8 1,723.7 Other assets 984.6 747.6 Total assets $ 32,163.3 $ 29,214.5 Liabilities and stockholders' equity: Accounts payable, accrued expenses, and other liabilities $ 4,013.7 $ 3,301.4 Finance lease liabilities 720.0 720.0 Deferred revenue 542.6 547.7 Long-term debt 1,982.6 1,981.4 Stockholders' equity 24,904.4 22,664.0 Total liabilities and stockholders' equity $ 32,163.3 $ 29,214.5 TABLE 2 REGENERON PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (Unaudited) (In millions, except per share data) Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Revenues: Net product sales $ 1,786.1 $ 1,801.4 $ 5,226.2 $ 5,194.4 Collaboration revenue 1,438.3 1,050.6 4,133.1 3,326.7 Other revenue 138.3 84.2 323.6 237.4 3,362.7 2,936.2 9,682.9 8,758.5 Expenses: Research and development 1,075.3 911.3 3,261.8 2,549.4 Acquired in-process research and development 100.0 — 156.1 225.1 Selling, general, and administrative 640.5 529.1 1,893.6 1,455.4 Cost of goods sold 224.5 141.3 625.3 497.8 Cost of collaboration and contract manufacturing 211.9 176.5 673.5 522.0 Other operating (income) expense, net (0.5 ) (45.7 ) (1.6 ) (83.3 ) 2,251.7 1,712.5 6,608.7 5,166.4 Income from operations 1,111.0 1,223.7 3,074.2 3,592.1 Other income (expense): Other income (expense), net 17.6 301.4 32.2 (16.0 ) Interest expense (17.8 ) (15.3 ) (54.7 ) (42.0 ) (0.2 ) 286.1 (22.5 ) (58.0 ) Income before income taxes 1,110.8 1,509.8 3,051.7 3,534.1 Income tax expense 103.0 194.1 257.7 392.8 Net income $ 1,007.8 $ 1,315.7 $ 2,794.0 $ 3,141.3 Net income per share - basic $ 9.48 $ 12.31 $ 26.16 $ 29.30 Net income per share - diluted $ 8.89 $ 11.66 $ 24.57 $ 27.73 Weighted average shares outstanding - basic 106.3 106.9 106.8 107.2 Weighted average shares outstanding - diluted 113.4 112.8 113.7 113.3 TABLE 3 REGENERON PHARMACEUTICALS, INC. RECONCILIATION OF GAAP TO NON-GAAP FINANCIAL INFORMATION (Unaudited) (In millions, except per share data) Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 GAAP R&D $ 1,075.3 $ 911.3 $ 3,261.8 $ 2,549.4 Stock-based compensation expense 107.4 93.7 356.0 275.8 Acquisition and integration costs 13.5 1.0 17.7 15.6 Non-GAAP R&D $ 954.4 $ 816.6 $ 2,888.1 $ 2,258.0 GAAP SG&A $ 640.5 $ 529.1 $ 1,893.6 $ 1,455.4 Stock-based compensation expense 74.4 59.8 224.5 178.0 Acquisition and integration costs 32.4 2.0 58.5 3.1 Non-GAAP SG&A $ 533.7 $ 467.3 $ 1,610.6 $ 1,274.3 GAAP COGS $ 224.5 $ 141.3 $ 625.3 $ 497.8 Stock-based compensation expense 22.1 12.8 64.1 39.2 Acquisition and integration costs 0.9 — 1.4 — Intangible asset amortization expense 20.7 15.1 59.0 15.1 Charges related to REGEN-COV — 4.9 (10.0 ) 62.9 Non-GAAP COGS $ 180.8 $ 108.5 $ 510.8 $ 380.6 GAAP other income (expense), net $ (0.2 ) $ 286.1 $ (22.5 ) $ (58.0 ) Losses (gains) on investments, net 127.0 (253.5 ) 324.5 117.3 Non-GAAP other income (expense), net $ 126.8 $ 32.6 $ 302.0 $ 59.3 GAAP net income $ 1,007.8 $ 1,315.7 $ 2,794.0 $ 3,141.3 Total of GAAP to non-GAAP reconciling items above 398.4 (64.2 ) 1,095.7 707.0 Income tax effect of GAAP to non-GAAP reconciling items (77.1 ) 18.9 (211.5 ) (133.4 ) Non-GAAP net income $ 1,329.1 $ 1,270.4 $ 3,678.2 $ 3,714.9 Non-GAAP net income per share - basic $ 12.50 $ 11.88 $ 34.44 $ 34.65 Non-GAAP net income per share - diluted $ 11.59 $ 11.14 $ 31.90 $ 32.39 Shares used in calculating: Non-GAAP net income per share - basic 106.3 106.9 106.8 107.2 Non-GAAP net income per share - diluted 114.7 114.0 115.3 114.7 RECONCILIATION OF GAAP TO NON-GAAP FINANCIAL INFORMATION (Unaudited) (continued) Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Revenue reconciliation: Total revenues $ 3,362.7 $ 2,936.2 $ 9,682.9 $ 8,758.5 Global gross profit payment from Roche in connection with sales of Ronapreve — 6.4 222.2 230.9 Other (5.7 ) — (9.5 ) — Total revenues excluding Ronapreve $ 3,368.4 $ 2,929.8 $ 9,470.2 $ 8,527.6 Effective tax rate reconciliation: GAAP ETR 9.3 % 12.9 % 8.4 % 11.1 % Income tax effect of GAAP to non-GAAP reconciling items 2.6 % (0.8 %) 2.9 % 1.3 % Non-GAAP ETR 11.9 % 12.1 % 11.3 % 12.4 % Nine Months Ended September 30, 2023 2022 Free cash flow reconciliation: Net cash provided by operating activities $ 3,504.3 $ 3,295.0 Capital expenditures (467.2 ) (437.9 ) Free cash flow $ 3,037.1 $ 2,857.1 TABLE 4 REGENERON PHARMACEUTICALS, INC. COLLABORATION REVENUE (Unaudited) (In millions) Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Sanofi collaboration revenue: Antibody: Regeneron's share of profits in connection with commercialization of antibodies $ 863.0 $ 551.1 $ 2,250.6 $ 1,463.0 Sales-based milestones earned 50.0 — 50.0 50.0 Reimbursement for manufacturing of commercial supplies 151.5 160.5 506.0 466.8 Other — (0.2 ) — 28.7 Immuno-oncology — — — 11.3 Total Sanofi collaboration revenue 1,064.5 711.4 2,806.6 2,019.8 Bayer collaboration revenue: Regeneron's share of profits in connection with commercialization of EYLEA outside the United States 349.9 315.3 1,031.0 993.4 Reimbursement for manufacturing of ex-U.S. commercial supplies 27.2 17.5 79.7 60.3 One-time payment in connection with change in Japan arrangement — — — 21.9 Total Bayer collaboration revenue 377.1 332.8 1,110.7 1,075.6 Other collaboration revenue: Global gross profit payment from Roche in connection with sales of Ronapreve — 6.4 222.2 230.9 Other (3.3 ) — (6.4 ) 0.4 Total collaboration revenue $ 1,438.3 $ 1,050.6 $ 4,133.1 $ 3,326.7 TABLE 5 REGENERON PHARMACEUTICALS, INC. NET PRODUCT SALES OF REGENERON-DISCOVERED PRODUCTS (Unaudited) (In millions) Three Months Ended September 30, 2023 2022 % Change U.S. ROW(g) Total U.S. ROW Total (Total Sales) EYLEA(a) $ 1,448.2 $ 872.2 $ 2,320.4 $ 1,629.4 $ 816.9 $ 2,446.3 (5 %) EYLEA HD(a) $ 42.7 $ — $ 42.7 $ — $ — $ — (h) Dupixent(b) $ 2,366.3 $ 731.3 $ 3,097.6 $ 1,824.0 $ 506.1 $ 2,330.1 33 % Libtayo(c) $ 144.1 $ 88.3 $ 232.4 $ 94.7 $ 48.5 $ 143.2 62 % Praluent(d) $ 40.4 $ 125.1 $ 165.5 $ 29.7 $ 84.0 $ 113.7 46 % REGEN-COV(e) $ — $ — $ — $ — $ 22.8 $ 22.8 (100 %) Kevzara(b) $ 52.4 $ 43.3 $ 95.7 $ 53.1 $ 35.0 $ 88.1 9 % Other products(f) $ 23.4 $ 15.5 $ 38.9 $ 17.5 $ 14.7 $ 32.2 21 % Nine Months Ended September 30, 2023 2022 % Change U.S. ROW Total U.S. ROW Total (Total Sales) EYLEA(a) $ 4,382.1 $ 2,605.6 $ 6,987.7 $ 4,768.2 $ 2,544.2 $ 7,312.4 (4 %) EYLEA HD(a) $ 42.7 $ — $ 42.7 $ — $ — $ — (h) Dupixent(b) $ 6,369.6 $ 2,002.4 $ 8,372.0 $ 4,731.7 $ 1,500.6 $ 6,232.3 34 % Libtayo(c) $ 384.0 $ 241.0 $ 625.0 $ 264.5 $ 144.7 $ 409.2 53 % Praluent(d) $ 121.1 $ 330.6 $ 451.7 $ 94.5 $ 239.5 $ 334.0 35 % REGEN-COV(e) $ — $ 613.2 $ 613.2 $ — $ 681.2 $ 681.2 (10 %) Kevzara(b) $ 148.5 $ 125.2 $ 273.7 $ 153.1 $ 123.7 $ 276.8 (1 %) Other products(f) $ 64.0 $ 48.9 $ 112.9 $ 39.5 $ 54.1 $ 93.6 21 % (a) Regeneron records net product sales of EYLEA and EYLEA HD in the United States. Bayer records net product sales of EYLEA outside the United States. The Company records its share of profits/losses in connection with sales of EYLEA outside the United States. (b) Sanofi records global net product sales of Dupixent and Kevzara. The Company records its share of profits/losses in connection with global sales of Dupixent and Kevzara. (c) Prior to July 1, 2022, Regeneron recorded net product sales of Libtayo in the United States and Sanofi recorded net product sales of Libtayo outside the United States. The parties equally shared profits/losses in connection with global sales of Libtayo. Effective July 1, 2022, the Company began recording net product sales of Libtayo outside the United States and pays Sanofi a royalty on global sales. Included in this line item for the nine months ended September 30, 2023 is $6 million of first quarter 2023 net product sales recorded by Sanofi in connection with sales in certain markets outside the United States (Sanofi recorded net product sales in such markets during a transition period until inventory on hand as of July 1, 2022 had been sold through to the end customers). (d) Regeneron records net product sales of Praluent in the United States. Sanofi records net product sales of Praluent outside the United States and pays the Company a royalty on such sales. (e) Regeneron records net product sales of REGEN-COV in the United States and Roche records net product sales of Ronapreve outside the United States. The parties share gross profits from global sales of REGEN-COV and Ronapreve based on a pre-specified formula. (f) Included in this line item are products which are sold by the Company and others. Refer to "Third Quarter 2023 Financial Results" section above for a complete listing of net product sales recorded by the Company. Not included in this line item are net product sales of ARCALYST®, which are recorded by Kiniksa; net product sales of ARCALYST were $54 million for the second quarter of 2023. (g) Rest of world (ROW) (h) Percentage not meaningful