IL-36R

Generalized pustular psoriasis (GPP) is a rare, chronic, heterogenous neutrophilic inflammatory disease associated with skin and systemic symptoms, such as fever, pain, and fatigue1,2,3,4 In China, SPEVIGO®’s expanded approval adds the reduction of occurrences of GPP in pediatric patients aged 12 and above weighing ≥40 kg, and adults5 The US FDA’s approval expands the use of SPEVIGO® to include the treatment of GPP in adults and pediatric patients aged 12 and above weighing ≥40 kg, making it the first targeted therapy that addresses the need for acute and chronic treatment for GPP patients6 SPEVIGO® is currently approved in 48 countries7 Boehringer Ingelheim today announced that the US Food and Drug Administration (FDA) has approved SPEVIGO® (spesolimab-sbzo) injection for the treatment of generalized pustular psoriasis (GPP) in adults and pediatric patients aged 12 and above weighing ≥40 kg.5 This approval follows the Chinese National Medical Products Administration’s (NMPA) recent approval of SPEVIGO® for the reduction of occurrence of generalized pustular psoriasis (GPP) in adolescents from 12 years of age with a body weight ≥40 kg and adults. SPEVIGO® is a novel, humanized selective IgG1 antibody that binds to interleukin-36 receptor (IL-36R), a key part of a signaling pathway within the immune system shown to be involved in the cause of GPP.8,9,10,11,12 The regulatory authorities’ decisions are majorly based on the positive results of the EFFISAYIL® 2 clinical trial, a 48-week clinical trial that showed that SPEVIGO® significantly reduced the risk of GPP flares by 84%, compared with placebo. In the trial with 123 patients, no flares were observed after week 4 of SPEVIGO® subcutaneous treatment in the high-dose group (n=30).13,14,15,16 In the Effisayil® 2 trial, SPEVIGO® was associated with an increased incidence (≥9 cases per 100 patient-years) of injection site reaction, urinary tract infection, arthralgia, and pruritus compared to placebo. “Until now, people living with GPP have not had any approved options to treat their disease,” said Bruce Strober, MD, PhD, Clinical Professor, Dermatology, Yale University and Central Connecticut Dermatology. “SPEVIGO® has the potential to redefine the treatment options for the patients we serve.” Distinct from plaque psoriasis, GPP is a rare, chronic, heterogenous, inflammatory neutrophilic disease associated with painful skin manifestations and systemic symptoms, such as fever, pain, and fatigue.1-4 GPP varies widely between individuals living with the condition, with symptoms presenting on a continuum, which means that it can present in either a persistent or a relapsing course.2-4 GPP often requires emergency care and can lead to life-threatening complications, such as multi-organ failure and sepsis.17 GPP’s unpredictable nature can potentially have significant long-term impacts on quality of life for people living with it, and may cause fear and anxiety over the disease course.3,18 “SPEVIGO®’s new approvals constitute a fundamental change for people living with GPP, addressing their huge need for acute and chronic treatment,” said Carinne Brouillon, Member of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim. “Experiencing GPP can be mentally and physically devastating, leaving those affected with uncertainty and fear of the next episode. Therefore, expanding the treatment of GPP is a critical step towards addressing patients’ needs.” About SPEVIGO® SPEVIGO® is a novel, humanized, selective antibody that specifically blocks the activation of the IL-36R, a signaling pathway within the immune system shown to be involved in the pathogenesis of several autoinflammatory diseases, including GPP.7-11 It is the first targeted therapy for the treatment of GPP and has been evaluated in the largest clinical program specifically for the treatment of patients with GPP.10,19 What is SPEVIGO®? SPEVIGO® is a prescription medicine used to treat generalized pustular psoriasis (GPP) in adults and children 12 years of age and older who weigh at least 88 pounds (40 kg). It is not known if SPEVIGO® is safe and effective in children under 12 years of age or who weigh less than 88 pounds. Important Safety Information Do not receive SPEVIGO® if you or your child have had a severe or life-threatening allergic reaction to spesolimab-sbzo or any of the ingredients in SPEVIGO®. What is the most important information I should know about SPEVIGO®? SPEVIGO® may cause serious side effects, including: Infections. SPEVIGO® may lower the ability of your or your child’s immune system to fight infections and may increase your or your child’s risk of infections. Your healthcare provider should check you or your child for infections and tuberculosis (TB) before starting treatment with SPEVIGO® and may treat you or your child for TB before you begin treatment with SPEVIGO® if you have a history of TB or have active TB. Your healthcare provider should watch you or your child closely for signs and symptoms of TB during or after treatment with SPEVIGO®. Tell your healthcare provider right away if you or your child have an infection or have symptoms of an infection during or after treatment with SPEVIGO®, including: fevers, chills, or sweats muscle aches cough shortness of breath blood in your phlegm (mucus) burning when you urinate urinating more often than normal Allergic reactions and infusion-related reactions. Serious allergic reactions may happen during or after your or your child’s SPEVIGO® injection. If you or your child have a serious allergic reaction, your healthcare provider will stop treatment with SPEVIGO®. If you or your child are given SPEVIGO® in a vein (intravenously) and have an infusion- related reaction, your healthcare provider will stop your or your child’s SPEVIGO® infusion and treat your or your child’s symptoms and may restart SPEVIGO® at a slower infusion rate. Tell your healthcare provider or get emergency medical help right away if you or your child get any of the following symptoms during or after your or your child’s SPEVIGO® injection: feeling faint, dizzy, or lightheaded swelling of your face, eyelids, lips, mouth, tongue, or throat trouble breathing or throat tightness fever mouth sores chest tightness hives or skin rash that is different than the rash from generalized pustular psoriasis (GPP) itching swollen lymph nodes Before you or your child receive SPEVIGO®, tell your healthcare provider about all of your medical conditions, including if you or your child: have an infection that does not go away or that keeps coming back. have TB or have been in close contact with someone with TB. have recently received or are scheduled to receive an immunization (vaccine). You or your child should not receive live vaccines during and for at least 16 weeks after treatment with SPEVIGO®. You or your child should be brought up to date with all vaccines before starting SPEVIGO®. are pregnant or plan to become pregnant. It is not known if SPEVIGO® can harm your or your child’s unborn baby. are breastfeeding or plan to breastfeed. It is not known if SPEVIGO® passes into your breast milk. Talk to your healthcare provider about the best way to feed your or your child’s baby during treatment with SPEVIGO®. Tell your healthcare provider about all the medicines you or your child take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. What are the possible side effects of SPEVIGO®? The most common side effects of SPEVIGO® given in a vein (intravenously) for GPP flare treatment include: feeling tired or weak nausea and vomiting headache itching or itchy bumps a collection of blood under the skin at the infusion site or bruising urinary tract infection The most common side effects of SPEVIGO® when given under the skin (subcutaneously) for treatment of GPP when not experiencing a flare include: redness, pain, swelling, hardening, hives, or warmth at the injection site joint pain urinary tract infection itching These are not all of the possible side effects of SPEVIGO®. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1‐800‐FDA‐1088. Please see full Prescribing Information, Medication Guide, and Instructions for Use. CL-SPG-100004 03.18.2024 About the EFFISAYIL® clinical trial program The EFFISAYIL® clinical trial program evaluated the largest and broadest population of GPP patients in trials of a therapy specifically targeting the IL-36 pathway for GPP:10,18 EFFISAYIL® 1: A Phase II study that demonstrated treatment with a single intravenous dose of spesolimab significantly improved signs and symptoms of GPP in patients experiencing a flare, including rapid pustular and skin clearance. These results supported the approval of spesolimab as the first specific treatment for GPP flares in adults in major markets10,20 EFFISAYIL® 2: A Phase IIb study that showed spesolimab significantly reduced the risk of GPP flares by 84% over 48 weeks compared to placebo. In the trial with 123 patients, no flares were observed after week 4 of spesolimab SC treatment in the high-dose group (n=30)12–15 EFFISAYIL® ON: An open-label extension study to evaluate the long-term safety and efficacy of spesolimab in patients with GPP who have completed previous spesolimab trials21 About generalized pustular psoriasis (GPP) GPP is a chronic, heterogenous, neutrophilic inflammatory disease associated with skin and systemic symptoms that is distinct from plaque psoriasis. GPP is recognized as a separate clinical entity from other forms of psoriasis, with the IL-36 pathway being a key driver of GPP and triggering response to treatment.1 Prevalence of GPP is low and varies considerably across geographical regions, ranging from 1.76 to 124 patients per million persons in reports from key countries, including France, Japan, Sweden, and South Korea.2 GPP can become life-threatening (mortality rates ranging from 2% to 16%) due to severe complications, such as multisystem organ failure and sepsis requiring urgent hospital care; many GPP patients also suffer from various comorbidities, which contribute to the ongoing burden for the patient and healthcare systems.2,16,17 GPP symptoms appear unpredictable and present on a continuum, which greatly impacts a patient’s quality of life, and may cause fear and anxiety over the disease course, as well as long-term impacts on quality of life related to work/school, emotional health, social activities, and finances.2,3,4 About Boehringer Ingelheim Boehringer Ingelheim is working on breakthrough therapies that transform lives today and for generations to come. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term, sustainable perspective. More than 53,000 employees serve over 130 markets in the two business units, Human Pharma and Animal Health. Learn more at . March 2024 MPR-CRP-100327, MPR-US-102903 References: 1Marrakchi S, Puig L. Pathophysiology of generalized pustular psoriasis. Am J Clin Dermatol. 2022;23:13–19. 2Prinz JC, Choon SE, Griffiths CEM, et al. Prevalence, comorbidities and mortality of generalized pustular psoriasis: A literature review. J Eur Acad Dermatol Venereol. 2023;37:256–273. 3Reisner DV, Johnsson FD, Kotowsky N, et al. Impact of generalized pustular psoriasis from the perspective of people living with the condition: Results of an online survey. Am J Clin Dermatol. 2022;23:65–71. 4Gooderham MJ, Van Voorhees AS, Lebwohl MG. An update on generalized pustular psoriasis. Expert Rev Clin Immunol. 2019;15:907–919. 5National Medical Products Administration. Drug approval document release, March 11 2024. 2024年03月11日药品批准证明文件送达信息发布 (nmpa.gov.cn) (Accessed 14 March 2024) 6Record on file. 7Record on file. 8Bassoy EY, Towne JE, Gabay C. Regulation and function of interleukin-36 cytokines. Immunol Rev. 2018;281:169–178. 9Marrakchi S, Guigue P, Renshaw BR, et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med. 2011;365:620–628. 10Ganesan R, Raymond EL, Mennerich D, et al. Generation and functional characterization of anti-human and anti-mouse IL-36R antagonist monoclonal antibodies. MAbs. 2017;9:1143–1154. 11Bachelez H, Choon SE, Marrakchi S, et al. Trial of spesolimab for generalized pustular psoriasis. N Engl J Med. 2021;385:2431–2440. 12Bachelez H, Choon SE, Marrakchi S, et al. Inhibition of the interleukin-36 pathway for the treatment of generalized pustular psoriasis. N Engl J Med. 2019;380:981–983. 13Boehringer Ingelheim. Spesolimab prevented generalized pustular psoriasis flares in Effisayil™ 2 trial. 2023. . (Accessed 14 March 2024). 14Morita A, Strober B, Burden AD, et al. Efficacy and safety of subcutaneous spesolimab for the prevention of generalised pustular psoriasis flares (Effisayil 2): an international, multicentre, randomised, placebo-controlled trial. Lancet. 2023;402:1541–1551. 15Gordon KB, Lebwohl M, Barker J, et al. Effect of spesolimab on achieving sustained disease remission in patients with generalized pustular psoriasis: Results from the Effisayil 2 study. European Academy of Dermatology & Venereology Congress; 2023; Berlin, Germany. Abstract P0731. 16Strober B, Augustin M, Tada Y, et al. Effect of high-dose subcutaneous spesolimab on skin manifestations: Results from the pivotal Effisayil 2 trial of flare prevention in generalized pustular psoriasis. European Academy of Dermatology & Venereology Congress; 2023; Berlin, Germany. Abstract 1732. 17Choon SE, Navarini AA, Pinter A. Clinical course and characteristics of generalized pustular psoriasis. Am J Clin Dermatol. 2022;23:21–29. 18Burden D, Mrowietz U, Skalicky AM, et al. Symptom experience and content validity of the Psoriasis Symptom Scale (PSS) in patients with generalized pustular psoriasis (GPP). Dermatol Ther (Heidelb). 2022;12:1367–1381. 19Choon SE, Lebwohl MG, Marrakchi S, et al. Study protocol of the global Effisayil 1 Phase II, multicentre, randomised, double-blind, placebo-controlled trial of spesolimab in patients with generalized pustular psoriasis presenting with an acute flare. BMJ Open. 2021;11:e043666. 20Navarini A, Prinz JC, Morita A, et al. Spesolimab improves patient- reported outcomes in patients with generalized pustular psoriasis: Results from the Effisayil 1 study. J Eur Acad Dermatol Venereol. 2022; 37:730–736. 21Effisayil™ ON: A study to test long-term treatment with spesolimab in people with generalized pustular psoriasis who took part in a previous study. . (Accessed 14 March 2024).

LUND, SE / ACCESSWIRE / March 14, 2024 / Cantargia (STO:CANTA) Cantargia (Cantargia AB; Nasdaq Stockholm:CANTA) today reported new data highlighting the potential of the CAN10 antibody, currently in phase I clinical development, as therapy in systemic sclerosis. All signaling systems targeted by CAN10 (IL-1, IL-33 and IL-36) were found to be highly upregulated in patient skin biopsies. These cytokines induce fibrosis in skin fibroblasts isolated from patients, and this manifestation of disease was blocked by CAN10. In mouse models, CAN10 reversed the aberrant expression of several genes involved in the systemic sclerosis pathogenesis in humans. The data is presented at the Systemic Sclerosis World Congress in Prague 14-16 March 2024. "We are very excited about the progress in the CAN10 program which is quickly advancing from the ongoing healthy volunteer investigations towards studies in patients. The new data provides important information further increasing our confidence in CAN10 as a future therapy of inflammatory diseases" said Göran Forsberg, CEO of Cantargia. CAN10 is currently in phase I clinical development with transition from healthy volunteers to patients planned for Q3, 2024. One of the lead indications, systemic sclerosis, is a life-threatening autoimmune disease resulting in fibrosis in the skin, lung, and other internal organs. Current treatments focus on symptomatic treatment rather than addressing underlying disease mechanisms. It is estimated that in the US, approximately 100,000 patients suffer from the disease. CAN10 has orphan drug status in the US for treatment of systemic sclerosis. The new results demonstrate that both the target for CAN10, IL1RAP, and the IL1RAP-dependent signaling molecules IL-1, IL-33 and IL-36, are upregulated in skin from systemic sclerosis patients. This disease develops as fibroblasts promote the formation of an excessive buildup of connective tissue in skin and internal organs, so-called fibrosis. The results show that IL-1, IL-33 and IL-36 collagen production on skin fibroblasts from systemic sclerosis patients, leading to fibrosis. These disease-associated mechanisms can be reduced by CAN10. These new data strengthen previously reported beneficial effects of IL1RAP-blockade in three mouse models of systemic sclerosis, where treatment with a mouse surrogate of CAN10 reduced both skin and lung fibrosis. Additional gene expression analysis of mouse systemic sclerosis skin showed decreased expression of several key disease-related profibrotic factors in the skin by CAN10. In summary, the data show that CAN10 targets central processes important for systemic sclerosis and that CAN10 provides an opportunity to treat underserved systemic sclerosis patients. These data were generated in collaboration with a world-leading research group headed by Prof. Dr. Jörg Distler at the Heinrich-Heine University, Düsseldorf, Germany and will be presented as a poster at the 8th Systemic Sclerosis World Congress March 14-16, 2024 in Prague, Czech Republic. The poster is now also available at Cantargia's web page . Title: Combined blockade of IL-1, IL-33 and IL-36 signaling by targeting IL1RAP ameliorates skin and lung fibrosis in preclinical models of systemic sclerosis Session Title: Innovative therapies Session Date and Time: Friday March 15th 1.30-2.30 pm and Saturday March 16th 1-2 pm Poster Number: 317 This information is information that Cantargia is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact persons set out above, at 2024-03-14 17:31 CET. About Cantargia Cantargia AB (publ), reg. no. 556791-6019, is a biotechnology company that develops antibody-based treatments for life-threatening diseases and has established a platform based on the protein IL1RAP, involved in a number of cancer forms and inflammatory diseases. The main program, the antibody nadunolimab (CAN04), is being studied clinically primarily in combination with chemotherapy with a focus on pancreatic cancer, non-small cell lung cancer and triple-negative breast cancer. Positive interim data for the combinations indicate stronger efficacy than would be expected from chemotherapy alone. Cantargia's second development program, the antibody CAN10, blocks signaling via IL1RAP in a different manner than nadunolimab and addresses treatment of serious autoimmune/inflammatory diseases, with initial focus on systemic sclerosis and myocarditis. Cantargia is listed on Nasdaq Stockholm (ticker: CANTA). More information about Cantargia is available at . About CAN10 The CAN10 antibody binds strongly to its target IL1RAP and has a unique capability to simultaneously inhibit signaling via IL-1, IL-33 and IL-36. Inhibition of these signals can be of significant value in the treatment of several inflammatory or autoimmune diseases. The initial focus of CAN10 will be on two severe diseases: myocarditis and systemic sclerosis. In preclinical in vivo models of myocarditis, a CAN10 surrogate antibody significantly reduced the development of inflammation and fibrosis, and significantly counteracted the deterioration of the cardiac function. The CAN10 surrogate also inhibited disease development in models of systemic sclerosis, psoriasis, psoriatic arthritis, atherosclerosis and peritonitis. A clinical phase I study, investigating CAN10 in healthy volunteers and psoriasis patients, is ongoing. Up to 80 subjects may be included in the trial, the first clinical data set shows good safety. Additional data from the trial are expected continuously during 2024. Attachments Cantargia presents new human data further supporting CAN10 in the treatment of systemic sclerosis SOURCE: Cantargia View the original press release on accesswire.com

Anaptys licenses exclusive global development and commercialization rights to a potential best-in-class BDCA2 modulator portfolio IND filing to support clinical development of ANB101 in autoimmune and inflammatory diseases expected in H2 2024 Reiterating year-end 2023 cash and investments of $400 to $410 million and cash runway through year-end 2026 AnaptysBio, Inc. (Nasdaq: ANAB), a clinical-stage biotechnology company focused on delivering innovative immunology therapeutics, today announced an exclusive license agreement for Centessa Pharmaceuticals’ (NASDAQ: CNTA) blood dendritic cell antigen 2 (BDCA2) modulator antibody portfolio, including lead asset CBS004 and related family of backup antibodies, for the treatment of autoimmune and inflammatory diseases. Anaptys anticipates filing an IND application for CBS004, which will be renamed ANB101, in H2 2024. “Acquiring the rights to this BDCA2 modulator portfolio, which specifically targets plasmacytoid dendritic cells, known to be key drivers of interferon secretion and antigen presentation, complements our portfolio of best-in-class immune cell modulators to drive differentiated clinical outcomes in systemic, heterogeneous autoimmune and inflammatory diseases,” said Daniel Faga, president and chief executive officer of Anaptys. “We now plan to file two INDs in 2024: ANB101 in H2 2024 and ANB033, our CD122 antagonist, in H1 2024.” “We are pleased to enter into this agreement with Anaptys, which enables the continued advancement of Centessa’s BDCA2 modulators,” said Saurabh Saha, M.D., Ph.D., chief executive officer of Centessa. “With their focus on developing immune cell modulators, Anaptys is well positioned to further the research and development of this program in autoimmune and inflammatory diseases.” Plasmacytoid dendritic cells (pDCs) are a key upstream node in the inflammatory cascade that serve as a bridge between innate and adaptive immunity. They have been shown to be prolific secretors of type I interferons, which drive activation of a variety of downstream cell types including T cells and monocytes. Together with their ability to present antigens to the adaptive immune system, this creates a pro-inflammatory environment for the establishment and perpetuation of autoimmune pathology. BDCA2 is a molecule specifically expressed on pDCs, a class of immune cells which, while found in relatively small numbers in healthy patients, are enriched in patients with a variety of inflammatory diseases, that is critical to the regulation of toll-like receptor signaling and interferon secretion. BDCA2 has been implicated in the pathophysiology of systemic lupus erythematosus (SLE), where there exists mechanistic clinical proof of concept for pDC modulation. ANB101 is a potentially best-in-class BDCA2 modulator antibody that targets pDCs and potently inhibits interferon secretion and modulates antigen presentation for the treatment of autoimmune and inflammatory diseases. Under the terms of the agreement, Anaptys will receive from Centessa Pharmaceuticals an exclusive, global license for ANB101. Anaptys will also receive the same rights to ANB102, an extended half-life BDCA2 modulator with the potential to enable quarterly or less frequent dosing. ANB101 has successfully completed IND-enabling studies and manufacturing scale-up. Anaptys will assume responsibility for all future clinical development. In exchange, Anaptys will pay Centessa a one-time upfront cash payment of $7 million, inclusive of a one-time cash payment of $3 million for manufactured and released GMP supply of ANB101. Centessa is eligible to receive an additional development milestone payment and low single-digit royalties on global net sales. Anaptys is a clinical-stage biotechnology company focused on delivering innovative immunology therapeutics. It is developing immune cell modulators, including two checkpoint agonists for autoimmune and inflammatory disease: rosnilimab, its PD-1 agonist, in a Phase 2b trial for the treatment of rheumatoid arthritis and in a Phase 2 trial for the treatment of ulcerative colitis; and ANB032, its BTLA agonist, in a Phase 2b trial for the treatment of atopic dermatitis. Its preclinical immune cell modulator portfolio includes ANB033, an anti-CD122 antagonist antibody, and ANB101, a BDCA2 modulator antibody, for the treatment of autoimmune and inflammatory diseases. In addition, Anaptys has developed two cytokine antagonists available for out-licensing: imsidolimab, an anti-IL-36R antagonist, in Phase 3 for the treatment of generalized pustular psoriasis, or GPP, and etokimab, an anti-IL-33 antagonist for the treatment of respiratory disorders that is Phase 2/3 ready. Anaptys has also discovered multiple therapeutic antibodies licensed to GSK in a financial collaboration for immuno-oncology, including an anti-PD-1 antagonist antibody (Jemperli (dostarlimab-gxly)) and an anti-TIM-3 antagonist antibody (cobolimab, GSK4069889). To learn more, visit www.AnaptysBio.com or follow us on LinkedIn and X. The content above comes from the network. if any infringement, please contact us to modify.