Garetosmab

Dupixent® is now used to treat over a million patients globally, with continued growth and expansion in multiple indications for diseases in which type 2 inflammation plays a role EYLEA HD® and EYLEA® remained the U.S. anti-VEGF category leader in 2024; aggregate U.S. net product sales were $6 billion for full-year 2024, up 1% based on preliminary (unaudited) results EYLEA HD pre-filled syringe (PFS) submission completed; launch expected by mid-2025 Libtayo® exceeded $1 billion in 2024 annual net sales, and becomes the first and only immunotherapy to show a statistically significant clinical benefit as adjuvant therapy in high-risk cutaneous squamous cell carcinoma (CSCC) Linvoseltamab Biologics License Application (BLA) resubmitted following resolution of third-party manufacturing issues; launch anticipated mid-2025 Approximately 40 investigational candidates in industry-leading pipeline cover dozens of disease states with expansive market potential Regeneron collaborates with Truveta and leading American health systems to massively extend its DNA-linked healthcare database to further advance scientific innovation and healthcare delivery TARRYTOWN, N.Y., Jan. 13, 2025 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today will share corporate progress and highlights from the Company’s broad and diverse investigational pipeline while presenting at the annual J.P. Morgan Healthcare Conference. The presentation is scheduled for 2:15 p.m. Pacific Time (5:15 p.m. Eastern Time) and may be accessed from the "Investors & Media" page of Regeneron's website. “The Regeneron name is synonymous with innovation, brought to life through proprietary technologies and world-class science that produce medicines that make a meaningful impact on patients’ lives,” said Leonard S. Schleifer, M.D., Ph.D., Board co-Chair, President and Chief Executive Officer of Regeneron. “Thanks to our long-term and consistent R&D investment, we have – in addition to our four blockbuster medicines – one of the industry’s largest, most promising and most diverse clinical pipelines. Our therapeutic candidates tackle a myriad of diseases, with the most advanced programs addressing an aggregate commercial market opportunity expected to exceed $220 billion by 2030. We are well positioned for future growth and more confident than ever in the power of Regeneron’s science.” Marketed Products Dupixent Updates Dupixent® (dupilumab) is now used to treat over a million patients globally. The recent approval and launch in chronic obstructive pulmonary disease (COPD) has had a successful start, with coverage secured from the top commercial and Medicare payers and Dupixent now well positioned to address approximately 300,000 patients in the U.S. There is continued growth potential in existing and additional indications for diseases in which type 2 inflammation may play a role, including chronic spontaneous urticaria (CSU) with an expected U.S. Food and Drug Administration (FDA) decision by April 18, 2025, and bullous pemphigoid, for which a supplemental Biologics License Application (sBLA) was submitted in the fourth quarter of 2024. EYLEA HD and EYLEA Updates On a combined basis, EYLEA HD® (aflibercept) Injection 8 mg and EYLEA® (aflibercept) Injection 2 mg remained the U.S. anti-VEGF category leader in 2024. Based on preliminary (unaudited) results, the products achieved 1% year-over-year growth by reaching $6 billion in aggregate U.S. net product sales for the year and $1.5 billion in aggregate U.S. net product sales for the fourth quarter of 2024, despite increasing competition. EYLEA HD U.S. net product sales were $305 million in the fourth quarter of 2024. EYLEA U.S. net product sales were $1.19 billion in the fourth quarter of 2024. Combined EYLEA HD and EYLEA U.S. net product sales for the fourth quarter of 2024 were favorably impacted by approximately $85 million as a result of higher wholesaler inventory levels for EYLEA, partially offset by lower wholesaler inventory levels for EYLEA HD. The Company filed an application with the FDA for use of the EYLEA HD pre-filled syringe (PFS) with U.S. approval and launch expected by mid-2025. Longer term data in wet age-related macular degeneration (wAMD) and diabetic macular edema (DME) are under FDA review with a PDUFA date of April 20, 2025 to potentially extend dosing intervals for EYLEA HD up to every-24 weeks. The Company plans to submit a sBLA for EYLEA HD for every four-week dosing and for retinal vein occlusion (RVO) in the first quarter of 2025 to potentially maximize dosing flexibility and address more retinal diseases. Libtayo Updates Libtayo® (cemiplimab) exceeded $1 billion in sales for 2024 and remains foundational to Regeneron’s oncology portfolio. As announced this morning, a Phase 3 study demonstrated that Libtayo is the only immunotherapy to show a statistically significant and clinically meaningful benefit in high-risk cutaneous squamous cell carcinoma (CSCC) in the adjuvant setting; a recent Phase 3 trial with Keytruda® failed in the same setting.1 Specifically, adjuvant Libtayo demonstrated a 68% reduction in the risk of disease recurrence or death, compared to placebo (hazard ratio: 0.32; 95% confidence interval: 0.20-0.51; p<0.0001). Grade ≥3 adverse events occurred in 24% (n = 49 of 205) and 14% (n = 29 of 204) of patients in the Libtayo arm and the placebo arm, respectively. Detailed results will be presented at an upcoming medical meeting and will be shared with regulatory authorities with a plan for FDA submission in the first half of 2025. Phase 3 and Other Major Pipeline Opportunities Regeneron is progressing numerous promising drug candidates across diverse disease states, with advanced programs that together have a total addressable commercial market expected to exceed $220 billion by 2030. Some near-term highlights include: Itepekimab (IL-33) for COPD: Based on genetic data linking IL-33 with increased risk of COPD and Phase 2 results, Regeneron’s next innovation in COPD offers potential for benefit in a broader population, including former smokers, non-cystic fibrosis bronchiectasis and other indications. Results are expected from the Phase 3 AERIFY study in the second half of 2025, with a potential BLA submission to follow. Fianlimab (LAG3) for melanoma: Combining fianlimab and Libtayo, two potentially best-in-class checkpoint inhibitors, has the potential for differentiated efficacy and safety versus the current standard-of-care. Results from the first Phase 3 study in first-line metastatic melanoma are expected in the second half of 2025, with a potential BLA submission to follow. Linvoseltamab (BCMAxCD3) for multiple myeloma: Linvoseltamab has potential to be the best-in-class BCMAxCD3 bispecific with its differentiated clinical profile, dosing regimen and administration method. The linvoseltamab BLA has been resubmitted following resolution of third-party manufacturing issues, with launch anticipated in mid-2025. Phase 3 programs in earlier lines of therapy using linvoseltamab monotherapy and novel combinations are also underway. Odronextamab (CD20xCD3) for lymphoma: Ordspono™ (odronextamab) has been approved in the European Union for relapsed/refractory follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy, and enrollment is underway for a confirmatory study to support resubmission of the BLA for FL to the FDA in the first quarter of 2025. A broad and differentiated Phase 3 program is also underway to investigate odronextamab in earlier lines of FL and DLBCL. As reported at the American Society of Hematology annual meeting, odronextamab monotherapy showed complete responses in 12 out of 12 evaluable patients with first-line FL in the safety lead-in portion of the Phase 3 program. Factor XI for anticoagulation: Regeneron’s two-pronged approach to anticoagulation is being evaluated for its potential to control thombosis while minimizing bleeding risk in a variety of patient populations and clinical settings. Two Factor XI antibodies, REGN7508 (catalytic domain) and REGN9933 (A2 domain), will advance to pivotal trials in 2025 on the basis of positive proof-of-concept data announced in December 2024. Current standards of care for thrombosis disorders have challenges including elevated risk of bleeding resulting in underutilization, presenting an unmet need for more specific inhibition of the intrinsic coagulation pathway. Multiple approaches to obesity: Regeneron is studying various combinations with GLP-based therapies to potentially improve quality of weight loss by preserving lean muscle, as well as improve maintenance of weight loss following GLP-1/GIP discontinuations. A Phase 2 study of trevogrumab and semaglutide with and without garetosmab is now fully enrolled and a Phase 2 study testing combinations of tirzepatide and mibavademab is ongoing, with initial data expected from both in the second half of 2025. BCMAxCD3/Dupixent in severe allergy: Combining linvoseltamab and Dupixent has the potential to eliminate immunoglobulin E (IgE), the key driver of allergic reactions, and thus potentially reverse severe allergies. A trial in patients with severe food allergies is ongoing, with initial clinical data shared in today’s presentation showing profound reduction of IgE in the first patient treated with this two-drug approach. C5 Combo (pozelimab and cemdisiran) in complement-mediated diseases: Regeneron’s differentiated siRNA and antibody combination approach has the potential to address multiple complement-mediated diseases, such as generalized myasthenia gravis (Phase 3 results expected in the second half of 2025), paroyxsmal noctural hemoglobinuria (Phase 3 registrational data expected in 2026+) and geographic atrophy, an advanced form of dry AMD (Phase 3 pivotal program underway). DNA Sequence-Linked Healthcare Database Regeneron continues to grow its leadership in genetics-driven drug discovery and is building the world’s largest DNA sequence-linked healthcare database, designed to unlock profound insights into how genetics impact health and aid in the development new genetic-based therapies and optimized healthcare services. The Regeneron Genetics Center® has sequenced nearly three million people to date, all with deidentified linked healthcare records. A newly announced strategic collaboration with Truveta, Inc. is expected to dramatically expand the size of this database, with sequencing and linked Electronic Health Records for up to 10 million additional individuals from Truveta’s network of leading U.S. health systems. On the basis of its industry-leading capabilities, Regeneron Genetics Center was selected by UK BioBank consortium members to complete proteomic assay data generation for the recently announced UK Biobank Pharma Proteomics Project. “Regeneron continues to diversify our commercial, clinical and research portfolios by relentlessly pushing the boundaries of innovation and technology,” said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer of Regeneron. “In 2025, we will progress dozens of promising new assets and expand the reach of our important established medicines to help even more patients in need. We remain at the forefront of biotechnology’s most remarkable era of drug discovery, striving to change the practice of medicine with approaches spanning antibodies, bispecifics, gene editing, gene silencing, gene therapy and cell therapy supported by DNA sequence- and proteomics-linked healthcare database.” The unapproved uses of EYLEA, EYLEA HD, Dupixent, Libtayo and pozelimab noted here are investigational and have not been fully evaluated by any regulatory authority. Cemdisiran, itepekimab, fianlimab, linvoseltamab, REGN7508, REGN9933, trevogrumab and garetosmab are investigational and have also not been fully evaluated by any regulatory authority. Odronextamab is approved in the European Union as Ordspono™ to treat R/R FL or DLBCL after two or more lines of systemic therapy, but the safety and efficacy of odronextamab has not been fully evaluated by any other regulatory authority. About Regeneron Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases, and rare diseases. Regeneron pushes the boundaries of scientific discovery and accelerates drug development using our proprietary technologies, such as VelociSuite®, which produces optimized fully human antibodies and new classes of bispecific antibodies. We are shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center® and pioneering genetic medicine platforms, enabling us to identify innovative targets and complementary approaches to potentially treat or cure diseases. For more information, please visit www.Regeneron.com or follow Regeneron on LinkedIn, Instagram, Facebook or X. DUPIXENT IMPORTANT SAFETY INFORMATION AND U.S. INDICATIONS DUPIXENT® (dupilumab) is a prescription medicine used: to treat adults and children 6 months of age and older with moderate-to-severe eczema (atopic dermatitis or AD) that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies. DUPIXENT can be used with or without topical corticosteroids. It is not known if DUPIXENT is safe and effective in children with atopic dermatitis under 6 months of age. with other asthma medicines for the maintenance treatment of moderate-to-severe eosinophilic or oral steroid dependent asthma in adults and children 6 years of age and older whose asthma is not controlled with their current asthma medicines. DUPIXENT helps prevent severe asthma attacks (exacerbations) and can improve your breathing. DUPIXENT may also help reduce the amount of oral corticosteroids you need while preventing severe asthma attacks and improving your breathing. It is not known if DUPIXENT is safe and effective in children with asthma under 6 years of age. with other medicines for the maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in adults and children 12 years of age and older whose disease is not controlled. It is not known if DUPIXENT is safe and effective in children with chronic rhinosinusitis with nasal polyps under 12 years of age. to treat adults and children 1 year of age and older with eosinophilic esophagitis (EoE), who weigh at least 33 pounds (15 kg). It is not known if DUPIXENT is safe and effective in children with eosinophilic esophagitis under 1 year of age, or who weigh less than 33 pounds (15 kg). to treat adults with prurigo nodularis (PN). It is not known if DUPIXENT is safe and effective in children with prurigo nodularis under 18 years of age. with other medicines for the maintenance treatment of adults with inadequately controlled chronic obstructive pulmonary disease (COPD) and a high number of blood eosinophils (a type of white blood cell that may contribute to your COPD). DUPIXENT is used to reduce the number of flare-ups (the worsening of your COPD symptoms for several days) and can improve your breathing. It is not known if DUPIXENT is safe and effective in children with chronic obstructive pulmonary disease under 18 years of age. Do not use if you are allergic to dupilumab or to any of the ingredients in DUPIXENT®. Before using DUPIXENT, tell your healthcare provider about all your medical conditions, including if you: have eye problems. have a parasitic (helminth) infection. are scheduled to receive any vaccinations. You should not receive a “live vaccine” right before and during treatment with DUPIXENT. are pregnant or plan to become pregnant. It is not known whether DUPIXENT will harm your unborn baby. A pregnancy registry for women who take DUPIXENT during pregnancy collects information about the health of you and your baby. To enroll or get more information call 1-877-311-8972 or go to https://mothertobaby.org/ongoing-study/dupixent/. are breastfeeding or plan to breastfeed. It is not known whether DUPIXENT passes into your breast milk. A pregnancy registry for women who take DUPIXENT during pregnancy collects information about the health of you and your baby. To enroll or get more information call 1-877-311-8972 or go to https://mothertobaby.org/ongoing-study/dupixent/. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you are taking oral, topical, or inhaled corticosteroid medicines; have asthma and use an asthma medicine; or have atopic dermatitis, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis, or chronic obstructive pulmonary disease and also have asthma. Do not change or stop your other medicines, including corticosteroid medicine or other asthma medicine, without talking to your healthcare provider. This may cause other symptoms that were controlled by those medicines to come back. DUPIXENT can cause serious side effects, including: Allergic reactions. DUPIXENT can cause allergic reactions that can sometimes be severe. Stop using DUPIXENT and tell your healthcare provider or get emergency help right away if you get any of the following signs or symptoms: breathing problems or wheezing, swelling of the face, lips, mouth, tongue or throat, fainting, dizziness, feeling lightheaded, fast pulse, fever, hives, joint pain, general ill feeling, itching, skin rash, swollen lymph nodes, nausea or vomiting, or cramps in your stomach-area. Eye problems. Tell your healthcare provider if you have any new or worsening eye problems, including eye pain or changes in vision, such as blurred vision. Your healthcare provider may send you to an ophthalmologist for an exam if needed. Inflammation of your blood vessels. Rarely, this can happen in people with asthma who receive DUPIXENT. This may happen in people who also take a steroid medicine by mouth that is being stopped or the dose is being lowered. It is not known whether this is caused by DUPIXENT. Tell your healthcare provider right away if you have: rash, chest pain, worsening shortness of breath, a feeling of pins and needles or numbness of your arms or legs, or persistent fever. Joint aches and pain. Some people who use DUPIXENT have had trouble walking or moving due to their joint symptoms, and in some cases needed to be hospitalized. Tell your healthcare provider about any new or worsening joint symptoms. Your healthcare provider may stop DUPIXENT if you develop joint symptoms. The most common side effects include: Eczema: injection site reactions, eye and eyelid inflammation, including redness, swelling, and itching, sometimes with blurred vision, dry eye, cold sores in your mouth or on your lips, and high count of a certain white blood cell (eosinophilia). Asthma: injection site reactions, high count of a certain white blood cell (eosinophilia), pain in the throat (oropharyngeal pain), and parasitic (helminth) infections. Chronic Rhinosinusitis with Nasal Polyps: injection site reactions, eye and eyelid inflammation, including redness, swelling, and itching, sometimes with blurred vision, high count of a certain white blood cell (eosinophilia), gastritis, joint pain (arthralgia), trouble sleeping (insomnia), and toothache. Eosinophilic Esophagitis: injection site reactions, upper respiratory tract infections, cold sores in your mouth or on your lips, and joint pain (arthralgia). Prurigo Nodularis: eye and eyelid inflammation, including redness, swelling, and itching, sometimes with blurred vision, herpes virus infections, common cold symptoms (nasopharyngitis), dizziness, muscle pain, and diarrhea. Chronic Obstructive Pulmonary Disease: injection sites reactions, common cold symptoms (nasopharyngitis), high count of a certain white blood cell (eosinophilia), viral infection, back pain, inflammation inside the nose (rhinitis), diarrhea, gastritis, joint pain (arthralgia), toothache, headache, and urinary tract infection. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of DUPIXENT. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. Use DUPIXENT exactly as prescribed by your healthcare provider. It’s an injection given under the skin (subcutaneous injection). Your healthcare provider will decide if you or your caregiver can inject DUPIXENT. Do not try to prepare and inject DUPIXENT until you or your caregiver have been trained by your healthcare provider. In children 12 years of age and older, it’s recommended DUPIXENT be administered by or under supervision of an adult. In children 6 months to less than 12 years of age, DUPIXENT should be given by a caregiver. Please see accompanying full Prescribing Information including Patient Information. EYLEA AND EYLEA HD IMPORTANT SAFETY INFORMATION AND U.S. INDICATIONS INDICATIONS EYLEA HD® (aflibercept) Injection 8 mg is a prescription medicine approved for the treatment of patients with Wet Age-Related Macular Degeneration (AMD), Diabetic Macular Edema (DME), and Diabetic Retinopathy (DR). EYLEA® (aflibercept) Injection 2 mg is a prescription medicine approved for the treatment of patients with Wet Age-Related Macular Degeneration (AMD), Macular Edema following Retinal Vein Occlusion (RVO), Diabetic Macular Edema (DME), Diabetic Retinopathy (DR), and Retinopathy of Prematurity (ROP) (0.4 mg). IMPORTANT SAFETY INFORMATION EYLEA HD and EYLEA are administered by injection into the eye. You should not use EYLEA HD or EYLEA if you have an infection in or around the eye, eye pain or redness, or known allergies to any of the ingredients in EYLEA HD or EYLEA, including aflibercept. Injections into the eye with EYLEA HD or EYLEA can result in an infection in the eye, retinal detachment (separation of retina from back of the eye) and, more rarely, serious inflammation of blood vessels in the retina that may include blockage. Call your doctor right away if you or your baby (if being treated with EYLEA for Retinopathy of Prematurity) experience eye pain or redness, light sensitivity, or a change in vision after an injection. In some patients, injections with EYLEA HD or EYLEA may cause a temporary increase in eye pressure within 1 hour of the injection. Sustained increases in eye pressure have been reported with repeated injections, and your doctor may monitor this after each injection. In infants with Retinopathy of Prematurity (ROP), treatment with EYLEA will need extended periods of ROP monitoring. There is a potential but rare risk of serious and sometimes fatal side effects, related to blood clots, leading to heart attack or stroke in patients receiving EYLEA HD or EYLEA. The most common side effects reported in patients receiving EYLEA HD were cataract, increased redness in the eye, increased pressure in the eye, eye discomfort, pain, or irritation, blurred vision, vitreous (gel-like substance) floaters, vitreous detachment, injury to the outer layer of the eye, and bleeding in the back of the eye. The most common side effects reported in patients receiving EYLEA were increased redness in the eye, eye pain, cataract, vitreous detachment, vitreous floaters, moving spots in the field of vision, and increased pressure in the eye. The most common side effects reported in pre-term infants with ROP receiving EYLEA were separation of the retina from the back of the eye, increased redness in the eye, and increased pressure in the eye. Side effects that occurred in adults are considered applicable to pre-term infants with ROP, though not all were seen in clinical studies. You may experience temporary visual changes after an EYLEA HD or EYLEA injection and associated eye exams; do not drive or use machinery until your vision recovers sufficiently. For additional safety information, please talk to your doctor and see the full Prescribing Information for EYLEA HD and EYLEA. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. Please click here for full Prescribing Information for EYLEA HD and EYLEA. LIBTAYO IMPORTANT SAFETY INFORMATION AND U.S. INDICATIONS LIBTAYO® (cemiplimab-rwlc) is a prescription medicine used to treat: People with a type of skin cancer called cutaneous squamous cell carcinoma (CSCC) that has spread or cannot be cured by surgery or radiation. People with a type of skin cancer called basal cell carcinoma (BCC) when your BCC cannot be removed by surgery (locally advanced BCC) or when it has spread (metastatic BCC) and have received treatment with a hedgehog pathway inhibitor (HHI), or cannot receive treatment with a HHI. Adults with a type of lung cancer called non-small cell lung cancer (NSCLC). LIBTAYO may be used in combination with chemotherapy that contains a platinum medicine as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, or your lung cancer has spread to other areas of your body (metastatic lung cancer), and your tumor does not have an abnormal “EGFR,” “ALK,” or “ROS1” gene. LIBTAYO may be used alone as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, or your lung cancer has spread to other areas of your body (metastatic lung cancer), and your tumor tests positive for high “PD-L1,” and your tumor does not have an abnormal “EGFR,” “ALK,” or “ROS1” gene. LIBTAYO may be used in combination with chemotherapy that contains a platinum medicine as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, or your lung cancer has spread to other areas of your body (metastatic lung cancer), and your tumor does not have an abnormal “EGFR,” “ALK,” or “ROS1” gene. LIBTAYO may be used alone as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, or your lung cancer has spread to other areas of your body (metastatic lung cancer), and your tumor tests positive for high “PD-L1,” and your tumor does not have an abnormal “EGFR,” “ALK,” or “ROS1” gene. It is not known if Libtayo is safe and effective in children. IMPORTANT SAFETY INFORMATION FOR U.S. PATIENTS What is the most important information I should know about LIBTAYO? LIBTAYO is a medicine that may treat certain cancers by working with your immune system. LIBTAYO can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended. Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including: Lung problems: cough, shortness of breath, or chest pain Intestinal problems: diarrhea (loose stools) or more frequent bowel movements than usual, stools that are black, tarry, sticky or have blood or mucus, or severe stomach-area (abdomen) pain or tenderness Liver problems: yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach-area (abdomen), dark urine (tea colored), or bleeding or bruising more easily than normal Hormone gland problems: headache that will not go away or unusual headaches, eye sensitivity to light, eye problems, rapid heartbeat, increased sweating, extreme tiredness, weight gain or weight loss, feeling more hungry or thirsty than usual, urinating more often than usual, hair loss, feeling cold, constipation, your voice gets deeper, dizziness or fainting, or changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness Kidney problems: decrease in your amount of urine, blood in your urine, swelling of your ankles, or loss of appetite Skin problems: rash, itching, skin blistering or peeling, painful sores or ulcers in mouth or nose, throat, or genital area, fever or flu-like symptoms, or swollen lymph nodes Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with LIBTAYO. Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include: chest pain, irregular heartbeat, shortness of breath or swelling of ankles, confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs, double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight, persistent or severe muscle pain or weakness, muscle cramps, low red blood cells, or bruising Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include: nausea, vomiting, chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, feel like passing out, fever, back or neck pain, or facial swelling Rejection of a transplanted organ. Your healthcare provider should tell you what signs and symptoms you should report and monitor you, depending on the type of organ transplant that you have had Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with LIBTAYO. Your healthcare provider will monitor you for these complications Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with LIBTAYO. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with LIBTAYO if you have severe side effects. Before you receive LIBTAYO, tell your healthcare provider about all your medical conditions, including if you: have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus have received an organ transplant have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic) have received radiation treatment to your chest area have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome are pregnant or plan to become pregnant. LIBTAYO can harm your unborn baby Females who are able to become pregnant: Your healthcare provider will give you a pregnancy test before you start treatment You should use an effective method of birth control during your treatment and for at least 4 months after your last dose of LIBTAYO. Talk to your healthcare provider about birth control methods that you can use during this time Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with LIBTAYO are breastfeeding or plan to breastfeed. It is not known if LIBTAYO passes into your breast milk. Do not breastfeed during treatment and for at least 4 months after the last dose of LIBTAYO Your healthcare provider will give you a pregnancy test before you start treatment You should use an effective method of birth control during your treatment and for at least 4 months after your last dose of LIBTAYO. Talk to your healthcare provider about birth control methods that you can use during this time Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with LIBTAYO Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. The most common side effects of LIBTAYO when used alone include tiredness, muscle or bone pain, rash, diarrhea, and low levels of red blood cells (anemia). The most common side effects of LIBTAYO when used in combination with platinum-containing chemotherapy include hair loss, muscle or bone pain, nausea, tiredness, numbness, pain, tingling, or burning in your hands or feet, and decreased appetite. These are not all the possible side effects of LIBTAYO. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Regeneron Pharmaceuticals at 1-877-542-8296. Please see full Prescribing Information, including Medication Guide. 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 Dupixent® (dupilumab), EYLEA HD® (aflibercept) Injection 8 mg, EYLEA® (aflibercept) Injection, Libtayo® (cemiplimab), Ordspono™ (odronextamab), itepekimab, linvoseltamab, fianlimab, pozelimab in combination with cemdisiran, REGN7508, REGN9933, other of Regeneron's Product Candidates discussed or referenced in this press release, and the use of human genetics in Regeneron's research programs; the likelihood and timing of achieving any of the anticipated milestones discussed or referenced in this press release; 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; 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), including the studies discussed or referenced in this press release, on any of the foregoing or any potential regulatory approval of Regeneron’s Products and Regeneron’s Product Candidates; Regeneron’s expectations with respect to commercialization of Regeneron’s Products (including Dupixent, EYLEA HD, EYLEA, and Libtayo), competitive and other relevant developments affecting the market share of Regeneron’s Products, and other relevant factors (whether within or without Regeneron’s control) impacting the degree to which commercialization of Regeneron’s marketed products is successful, as well as the impact of any of the foregoing on Regeneron’s results of operations; the ability of Regeneron’s collaborators, licensees, 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 ability of Regeneron to manage supply chains for multiple products and product candidates; 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; 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; ongoing regulatory obligations and oversight impacting Regeneron’s Products, research and clinical programs, and business, including those relating to patient privacy; 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; competing drugs and product candidates that may be superior to, or more cost effective than, Regeneron’s Products and Regeneron’s Product Candidates (including biosimilar versions of Regeneron’s Products); the extent to which the results from the research and development programs conducted by Regeneron and/or its collaborators or licensees (such as those that may result from the strategic collaboration with Truveta, Inc. discussed in this press release) may be replicated in other studies and/or lead to advancement of product candidates to clinical trials, therapeutic applications, or regulatory approval; 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; the potential for any license, collaboration, or supply agreement, including Regeneron’s agreements with Sanofi and Bayer (or their respective affiliated companies, as applicable), as well as the collaboration with Truveta, Inc. discussed in this press release, 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), other litigation and other proceedings and government investigations relating to the Company and/or its operations (including the pending civil proceedings initiated or joined by the U.S. Department of Justice and 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 year ended December 31, 2023 and its Form 10-Q for the quarterly period ended September 30, 2024. 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 (https://investor.regeneron.com) and its LinkedIn page (https://www.linkedin.com/company/regeneron-pharmaceuticals). [1] Data not yet published. https://www-merck-com.libproxy1.nus.edu.sg/news/merck-provides-update-on-phase-3-keynote-867-and-keynote-630-trials/. All trademarks used are the property of their respective owners. The studies had differences in trial design specifics and no head-to-head comparisons have been conducted. Source: Regeneron Pharmaceuticals, Inc.

GLP-1减重药物的竞争已进入白热化。 如今，过去巨头们以卷减重幅度来做出Me better以强化竞争优势，但这一方向能带来的边际效应正在递减，11月Viking Therapeutics公布的VK-2735减重幅度数据展现出“同类最佳”的潜质，股价却创下了今年三月份以来的最大单日下跌。 当“更大幅度的减重”策略式微，GLP-1巨头们如何打出差异化？“更健康的减重”成为了巨头们当下更核心的迭代策略选择，减脂增肌无疑是这个策略中的“种子选手”。肌肉流失是目前GLP-1药物最常见的副作用之一，临床研究表明：接受GLP-1药物治疗的患者，其肌肉流失速度远快于通过饮食或运动减肥的人群，这导致潜在的骨折风险、心血管风险增加等各种健康问题。 随着巨头们调转枪头和减脂增肌路线被临床初步验证，推动了近两年来减脂增肌靶点管线的水涨船高，包括Scholar Rock在公布其MSTN抗体Apitegromab脊髓性肌萎缩症三期数据后股价暴涨361.99%、礼来以19.25亿美元收购核心管线为Bimagrumab（ActRIIA/ActRIIB抗体）的Versanis公司等。不过，这个赛道的“主升浪”远远未到来。2025年上半年之前，全球减脂增肌管线将井喷数个催化，礼来的Bimagrumab（以下简称：Bima）联用司美格鲁肽的二期临床完成，再生元的Trevogrumab（MSTN）和Garetosmab（Activin A抗体）两款药物读出二期数据，而Scholar Rock公司Apitegromab联用GLP-1治疗肥胖患者二期临床也将公布数据，一旦出现超预期数据，板块分子资产价值将出现极大攀升。 国内Biotech来凯医药，有望率先分享减脂增肌这一庞大全球市场的蛋糕。 11月20日，来凯医药与礼来签订一项临床合作协议，在来凯医药保留LAE102的全球权利背景下，LAE102在美国的一期研究将由礼来负责并承担相关费用。精明的MNC可不会有什么无缘无故的爱，礼来和来凯医药这一临床合作有望为首个国产减脂增肌药物出海夯实稳固的基础。 01 为什么LAE102能获得礼来青睐？ 礼来作为已经收购Bima入局减脂增肌赛道并取得全球领先位置的MNC，不可能坐视来凯医药这款潜在同类最佳的LAE102落入其他减肥药物巨头的手中。 目前，全球进入临床阶段靶向ActRII受体的药物仅有礼来的Bima和来凯医药的LAE102，其余在研临床管线均靶向ActRII配体。研究表明，阻断ActRII通路能抑制肌肉的萎缩，而ActRII的多个配体包括都被证明是骨骼肌负调控因子，阻断受体的策略比只阻断单类配体的策略在机理逻辑更加通顺，疗效大概率更加有效。 针对阻断ActRII受体的策略，来凯医药采取“多线出击”的策略，除了备受瞩目进入临床阶段LAE102（ActRIIB抗体）之外，针对ActRIIA/IIB双靶点抗体LAE123在近日达到PCC要求，并正式进入IND支持性研究阶段，加上此前已启动的LAE103（ActRIIB选择性抗体）的IND支持性研究，这样公司在确保了领先优势和留出试错空间的同时，能够对ActRII通路潜在适应症实现全面覆盖。 不仅因为机理上的逻辑通顺，靶向ActRII受体药物的成药性层面同样不存在太大问题。据礼来早前公布Bima的48周二期临床针对75名2型糖尿病的超重或肥胖患者数据显示：相比安慰剂，尽管Bima治疗组的体重只下降了6.5%，但可促成患者约20.5%脂肪含量的丢失（媲美礼来Mounjaro的疗效），并且增加3.6%的瘦体重。更重要的是，相比一般的GLP-1药物，Bima治疗组患者停止治疗12周内并未观察到体重的增加。 尽管拥有强大的减重和增肌效果，Bima并非没有缺点，这也给后来者指引出更多优化或迭代的机会。诺华2021年在JAMA发表的Bima临床数据显示：其核心不良事件是轻度腹泻(41% vs 11%)和肌肉痉挛(41% vs 3%)，尤其是首次给药后腹泻频率最高，后逐渐减少；另外，上述提到的2型糖尿病合并肥胖患者的二期临床试验中有5名患者因为不良反应事件导致研究中止，这也为后续Bima大样本临床增加了更多的不确定性。 为什么来凯医药LAE102是潜在同类最佳的分子？ 1）临床前和早期临床指标支持：LAE102在临床前就已经展现出增加肌肉并减少脂肪的潜力，同时其与GLP-1受体激动剂可以进一步减少脂肪并显著降低GLP-1受体激动剂带来的肌肉损失。来凯医药此前公告披露，LAE102在临床低剂量下就可以观察到靶点结合的早期迹象和预期的PD生物标志物变化，这极大增加了LAE102读出优良早期临床数据的可能性。 2）ActRIIA与ActRIIB路线之争不明确（强A或强B）：众所周知Bima虽是同时靶向ActRIIA和ActRIIB的抗体，但其与ActRIIB受体的结合活性远高于ActRIIA。尽管已有研究文献中，myostatin在年轻肌肉中高表达并被认为在肌肉生长调控中的关键作用，而myostatin对ActRIIB的亲和力高于ActRIIA，不过阻断受体A还是阻断受体B谁在减脂增肌中更有效，尚无定论。 来凯医药公布的临床前‌DIO模型（饮食诱导肥胖模型）数据显示，LAE102对瘦体重（Lean mass）增加呈现出了明显的效果，而公司另一款ActRIIB选择性抗体LAE103亦展出瘦体重增加的疗效，且LAE102疗效更强；在联用司美格鲁肽的‌DIO模型中，LAE102展现出了强劲的效果。这些数据结果都在扎实的支撑LAE102一跃成为赛道潜在同类最佳分子。 3）皮下注射的便捷性：目前畅销的GLP-1均为预充针皮下注射，皮下注射制剂的减重伴侣更便于减重患者联合GLP-1使用。LAE02在一期临床开启了皮下注册队列，在全球临床进度方面也是FIC的。 另外，LAE102的潜力也可通过其他层面进行印证和初探，一方面来凯医药创始人吕向阳博士是Bima共同发明人，在ActRII研究领域超过20年经验，有更大概率做出Bima的Better。另一方面，从来凯医药全力推进LAE102进度、临床执行迅速等动作可看出，公司团队对于LAE102有着充分的信心和把握。 02 礼来，大Deal的创造者 对于来凯医药而言，礼来是全球“唯二、最佳适配”的合作伙伴。 纵观礼来2023-2024年收购布局，以买“早”、买“新”、高溢价收购为主要特点。尤其在代谢领域，2023年7月礼来以19亿美元收购VersanisBio，当时核心管线Bima处于2a期临床完成/2b期入组的阶段；2023年6月礼来以3.096亿美元的总对价收购糖尿病细胞疗法公司Sigilon，溢价超过400%，并且收购时Sigilon的核心管线刚刚进入临床；而礼来最新与KeyBioscience达成总包14亿美元的扩大合作，其治疗肥胖和骨关节炎的核心管线双淀粉降钙素受体激动剂（DACRA）也刚刚完成临床一期。如今来凯医药的LAE102所处的临床早期阶段，正好在礼来收购战略的射程之内。 礼来与来凯医药关于LAE102的海外临床合作，很难不让投资者合理遐想：临床合作只是“引子”，为了打下基础，后续双方有着进一步的潜在合作甚至达成M&A。 这样的猜测并非没有依据，而是在全球MNC、Biopharma与Biotech合作中屡见不鲜。以礼来为例，其在早在2018年与Sigilon达成1型糖尿病治疗的封装细胞疗法SIG-002管线开发合作（6300万美元首付款+4.1亿美元里程碑付款），5年之后用约3亿美元将其收入囊中；再以Biontech与国内Biotech普米斯合作为例，2023年11月首次达成关于PD-L1/VEGF双抗PM8002的全球权益合作，一年之后普米斯被Biontech全资收购。 不排除来凯医药和礼来的合作重走上述发展路径，或许一切需要等待LAE102的临床数据兑现。 其次，不少投资者对礼来既收购Versanis又与来凯医药LAE102感到疑惑。实则两项交易对于礼来而言并不冲突，MNC们不会“将鸡蛋放在一个篮子里”，目前非常明显的趋势是礼来和诺和诺德都在围绕GLP-1进行迭代和组合布局，旨在加强自身竞争优势，而“减脂增肌”这个迭代方向及ActRII通路成药可行性得到验证，所以礼来的双布局一是“占位”思维，二是不放过这个通路主要研发路径，成药的分子或者FIC分子“一定要在我的体系内”。 同理，这种策略也在默沙东全力押注“IO+ADC”的布局中出现，其同时与第一三共、科伦博泰的ADC管线展开合作，力求网罗市面不同的靶点ADC。 从另一个角度看，对于来凯医药而言，礼来是LAE102全球最好的合作伙伴之一，主要基于三个层面：1）礼来作为拥有多款GLP-1药物上市和在研的MNC，不仅在海外减重代谢类药物临床设计、临床资源层面拥有丰富的经验和储备。更重要的是，未来LAE102可以通过联用礼来已上市GLP-1加速海外临床开发，实现加速上市；2）礼来在减重领域的商业化能力无可置疑，LAE102作为“减重伴侣”的角色，与礼来体系内GLP-1管线并非竞争而是协同关系，有望借GLP-1东风快速放量；3）礼来作为实力雄厚的MNC，后续大额引进LAE102又或是全资收购来凯，都具备可能性。 作为投资者和观察者，我们或许只需要等待LAE102即将出炉的国内临床数据，和来凯医药与礼来更进一步的后续合作。 03 主动权握在来凯手里 值得注意的是，尽管与巨头礼来展开合作，但来凯医药是把“话事权”牢牢把握在自己手里。 保留全球权益的海外临床合作紧接着2.3亿港元配售再融资，这一记组合拳，凸显来凯医药的“做大做强”这单BD的决心。 据国盛医药统计的2018年后国内创新药出海数据显示，临床前项目占比34-43%，一期临床项目占比19-26%，上市后项目占比22%-23%，2/3期临床和申请上市阶段占比均小于10%。一般临床推进到越后期阶段，交易首付款金额更大，交易总额也更大。 目前，来凯医药LAE102在国内处于临床一期（数据尚未读出），在美国亦处于刚进入临床的阶段。 而选择临床合作的方式等同于“借船加速发展”，一方面来凯医药借助礼来的资源实现LAE102在海外的临床加速，并让MNC自己做临床验证管线核心质地，另一方面来凯医药能够通过临床合作这种方式以“时间换空间”，最大限度的平衡授权价值风险的配比，力求将管线卖出一个最优的价格。 不少投资者对此次配售的时机有所质疑，实质上这是最佳再融资的时间窗口之一。尽管来凯医药在再融资之前至少有2年现金流管道，但继续增加现金储备一来能够给予公司更大的临床战略选择余地（License Out或者继续选择推进国内临床），更重要的是现金储备不足将不再成为潜在海外大买家压价公司要价的核心理由，这也为来凯医药日后成交大额交易增添了更多的谈判筹码。 同时，投资者可以发散的LAE102潜在交易对象不应局限于礼来，诺和诺德、罗氏、阿斯利康等MNC体内均有GLP-1产品管线，这些巨头对减重伴侣、减脂增肌创新分子的兴趣同样不弱。 曾有外媒消息爆料，去年最先和Versanis（Bima）谈判深入的买家并不是礼来，而是另有其人，随后被礼来高价截胡。 所以，未来LAE102将以什么样的价格BD、选择授权给哪家MNC的主动权，还牢牢把握在来凯医药的手里，这为公司未来的长远发展，增添了更多不同的可能性。 从潜在交易类型可能性分析，除了BD管线之外，来凯医药像被Versanis一样整体收购并非无可能，MNC酷爱收购平台型Biotech，来凯医药围绕ActRII受体阻断策略，布局了包括LAE102、LAE103和LAE123一系列的“管线纵队”，随着未来LAE102早期数据兑现和LAE123的临床前数据公布，来凯医药在Activin信号通路的平台属性或将被强验证，这无疑彰显公司的“平台性”和巨大的收购价值。 结语 随着GLP-1药物愈加广泛的使用，可以预见患者减脂增肌的需求长线增长趋势几乎是确定的。来凯医药与礼来的临床合作，相信只是中国Biotech分享全球减肥市场蛋糕的一个典型合作的缩影，不过其蕴含的远期可能性，亦可能变成一个未来巨额的BD交易案例，又或是首个港股18A Biotech被收购的里程碑事件。