IL-3

Venture capitalists have been scouring the globe in search of better immunology drugs. Biotech startup creator Versant Ventures is among them, having formed and funded several companies in recent years looking to change the way certain inflammatory diseases are treated.Versant isnt done with that effort. On Thursday, the firm revealed its latest foray into immunology research a startup called Granite Bio thats already secured $100 million in funding and has two drugs either in, or nearing, clinical testing.Granite is a product of Ridgeline Therapeutics, part of an initiative Versant hatched more than a decade ago to help turn scientific discoveries into new companies. Operating in stealth mode, the company raised a $30 million Series A led by Versant and Novartis venture arm in 2021 and a $70 million Series B from Forbion and Sanofis venture fund two years later.The startup is working on two antibody drugs for inflammatory conditions. One, dubbed GRT-001, is being developed for inflammatory bowel disease and is currently in Phase 1 testing in healthy volunteers, with a trial in ulcerative colitis patients expected later this year. Another, GRT-002, is seen as a new way to potentially treat itch and allergies and should start its first trial in 2026.GRT-001 homes in on white blood cells called pro-inflammatory monocytes, which are part of the immune systems response to infections and inflammation. According to Granite CEO Patrick Loustau, this approach targets the “cellular source“ of IBD and has the potential to “reset“ patients' immune systems, which could lead to better and longer-lasting results than existing therapies.Monocyte depleters could have a similar impact on the innate immune system as B-cell targeting drugs appear to have on the adaptive part of the bodys defenses, giving them the potential to treat a range of inflammatory conditions,Loustau wrote in an email to BioPharma Dive.Granites other drug, GRT-002, homes on IL-3, a different inflammatory cytokine than the ones targeted by drugs like Dupixent and Cosentyx. Granite, in a statement announcing its launch, noted how IL-3 is a key player in autoimmunity as well as a kind of immune response called type 2 inflammation.Versant has started up several immune disease-focused biotechsof late. In 2024 alone, the firm formed Santa Ana Therapeutics, a developer of targeted immune therapies, as well as Borealis Biosciences, which is focused on medicines for inflammatory kidney diseases.Immunology investments more than doubled last year, surging to about $3.1 billion among the private rounds involving the prominent venture firms tracked by BioPharma Dive. Theyre on a similar trajectory in 2025, with about $1 billion raised so far. '

LEXINGTON, Mass., Jan. 9, 2025 /PRNewswire/ -- Partner Therapeutics, Inc. (PTx) today announced a collaboration with the Biomedical Advanced Research and Development Authority (BARDA), part of the Administration for Strategic Preparedness and Response (ASPR) at the U.S. Department of Health and Human Services to fund a phase 2 study in patients with sepsis to assess the safety and enable dose selection of LEUKINE (sargramostim, rhu GM-CSF). The partners also will evaluate monocyte human leukocyte antigen-DR (mHLA-DR) and other biomarkers of immune status that could enable more precise identification of patients with sepsis who could benefit from LEUKINE treatment in addition to standard of care. Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, characterized by altered immune homeostasis.1 It represents a critical unmet public health need urgently requiring safe and effective therapeutics guided by biomarkers to enable precise treatment approaches to reduce morbidity and mortality.2,3 In 2017, 1.7 million sepsis cases were reported in the US and 48.9 million cases were reported globally resulting in 11 million deaths.21 Since much of the morbidity and mortality from chemical, biological, radiological and nuclear (CBRN) threats is due to sepsis, the availability of a host-directed therapy to treat sepsis utilizing validated biomarkers to inform treatment would greatly enhance health security. Leukine is currently held for use by ASPR-Strategic National Stockpile (SNS) for the treatment of hematopoietic acute radiation syndrome (H-ARS) as a host-directed therapy. The PTx-BARDA partnership seeks to enhance patient care through restoration of immune homeostasis in patients with sepsis exhibiting a persistent immune suppressed state. Research shows that patients with sepsis with persistent immune suppression are unable to mount a sufficient immune response and experience significant mortality.2,4,5 The clinical study will further evaluate the safety of LEUKINE in these critically ill patients and seeks to confirm the utility of mHLA-DR as a marker to identify sepsis-associated immune dysregulation.2,6-10 Additional promising biomarkers of immune status in patients with sepsis also will be evaluated. Under a prior collaboration, BARDA and PTx supported the establishment of a Laboratory Developed Test (LDT) for mHLA-DR, which will be utilized in this collaboration. "We are grateful to BARDA for their support of this program, which has the potential to advance medical care for patients with sepsis by evaluating potential tools for measuring immune status to inform targeted immunomodulatory therapy," stated John L. McManus, President, Health Security and Critical Care of Partner Therapeutics, Inc. In small randomized clinical trials in critically ill patients with severe sepsis or septic shock, LEUKINE has been shown to promote immune homeostasis, as measured by a rapid and sustained improvement in mHLA-DR expression, as well as other markers of innate and adaptive immune function.7,11-16 The observed changes in immune status were accompanied by improved clinical outcomes including 28-day survival and resolution of infection. GM-CSF helps maintain immune homeostasis via innate and adaptive responses, and promotes tissue repair mechanisms.2,7,17 While classically known for promoting differentiation of bone marrow (BM) precursor cells, and stimulating proliferation, differentiation, and maturation of myeloid cells, GM-CSF also induces mHLA-DR and plays important roles in antigen presentation, T-cell activation, and myeloid cell survival and function.7,17-19 HLA-DR is part of the heterodimeric major histocompatibility complex class II (MHC II) on monocytes and is a measure of the cells' capacity for antigen-presentation. MHC II regulates monocytes' crosstalk with T helper cells, enabling the activation of the adaptive immune system.4,20 This project has been supported in whole or in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under contract number 75A50124C00061. REFERENCES Singer M et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801-810. doi: 10.1001/jama.2016.0287 Cajander S et al. Profiling the dysregulated immune response in sepsis: overcoming challenges to achieve the goal of precision medicine. Lancet Resp Med. 2023;12(4):305-322. doi: 10.1016/S2213-2600(23)00330-2 Shankar-Hari M et al. Reframing sepsis immunobiology for translation: towards informative subtyping and targeted immunomodulatory therapies. Lancet Resp Med. 2024;12(4):323 – 336. doi: 10.1016/S2213-2600(23)00468-X Venet F, Monneret G. Advances in the understanding and treatment of sepsis-induced immunosuppression. Nat Rev Nephrol. 2018 Feb;14(2):121-137. doi: 10.1038/NRNEPH.2017.165 Lindell RB, Meyer NJ. Charting a course for precision therapy trials in sepsis. Lancet Respir Med. 2024 Apr;12(4):265-267. doi: 10.1016/S2213-2600(24)00070-5 Monneret G, Lepape A, Voirin N, Bohé J, Venet F, Debard A-L, Thizy H, Bienvenu J, Gueyffier F, Vanhems P. 2006. "Persisting Low Monocyte Human Leukocyte Antigen-DR Expression Predicts Mortality in Septic Shock." Intensive Care Medicine 32 (8): 1175–83. doi: 10.1007/S00134-006-0204-8 Meisel C, Schefold JC, Pschowski R, Baumann T, Hetzger K, Gregor J, Weber-Carstens S, et al. 2009. "Granulocyte–Macrophage Colony-Stimulating Factor to Reverse Sepsis-Associated Immunosuppression." American Journal of Respiratory and Critical Care Medicine 180 (7): 640–48. doi: 10.1164/RCCM.200903-0363OC Venet F, Lukaszewicz AC, Payen D, Hotchkiss R, Monneret G. Monitoring the immune response in sepsis: a rational approach to administration of immunoadjuvant therapies. Curr Opin Immunol. 2013 Aug;25(4):477-83. doi: 10.1016/J.COI.2013.05.006 Morris AC, Datta D, Shankar-Hari M, Stephen J, Weir CJ, Rennie J, Antonelli J, et al. 2018. "Cell-Surface Signatures of Immune Dysfunction Risk-Stratify Critically Ill Patients: INFECT Study." Intensive Care Medicine 44 (5): 627–35. doi: 10.1007/S00134-018-5247-0 Tremblay JA, Peron F, Kreitmann L, Textoris J, Brengel-Pesce K, Lukaszewicz AC, Quemeneur L, Vedrine C, Tan LK, Venet F, Rimmele T, Monneret G, et al. A stratification strategy to predict secondary infection in critical illness-induced immune dysfunction: the REALIST score. Annals of Intensive Care 2022 12:76. doi: 10.1186/S13613-022-01051-3 Rosenbloom AJ, Linden PK, Dorrance A, Penkosky N, Cohen-Melamed MH, Pinsky MR. 2005. "Effect of Granulocyte-Monocyte Colony-Stimulating Factor Therapy on Leukocyte Function and Clearance of Serious Infection in Nonneutropenic Patients." CHEST 127 (6): 2139–50. doi: 10.1378/CHEST.127.6.2139. Hall, MW., Knatz NL, Vetterly C, Tomarello S, Wewers MD, Volk HD, Carcillo JA. 2011. "Immunoparalysis and Nosocomial Infection in Children with Multiple Organ Dysfunction Syndrome." Intensive Care Medicine 37 (3): 525–32. doi: 10.1007/S00134-010-2088-X Spies C, Luetz A, Lachmann G, Renius M, von Haefen C, Wernecke K-D, Bahra M, Schiemann A, Paupers P, Meisel C. 2015. "Influence of Granulocyte-Macrophage Colony-Stimulating Factor or Influenza Vaccination on HLA-DR, Infection and Delirium Days in Immunosuppressed Surgical Patients: Double Blind, Randomised Controlled Trial." Edited by Sachin Yende. PLOS ONE 10 (12): e0144003. doi: 10.1371/JOURNAL.PONE.0144003 Pinder EM, Rostron Aj, Hellyer TP, Ruchaud-Sparagano M-H, Scott J, Macfarlane JG, Wiscombe S, et al. 2018. "Randomised Controlled Trial of GM-CSF in Critically Ill Patients with Impaired Neutrophil Phagocytosis." Thorax 73 (10): 918–25. doi: 10.1136/THORAXJNL-2017-211323 Hassan SA, Alamed Z, Syed U, Nadeem MT, Khushdil A. The Effect of Granulocyte-Macrophage Colony-Stimulating Factor on Neutropenia and Mortality in Neonatal Sepsis. Pak Armed Forces Med J 2023; 73(6): 1644-1647. doi: 10.51253/PAFMJ.V73I6.7456 Vacheron CH, Lepape A, Venet F, Monneret G, Gueyffier F, Boutitie F, Vallin H, Schwebel C, Maucort-Boulch D, Friggeri A; GRID Study Group. Granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients presenting sepsis-induced immunosuppression: The GRID randomized controlled trial. J Crit Care. 2023 Dec;78:154330. doi: 10.1016/J.JCRC.2023.154330 Dougan M, Dranoff G, Dougan SK. GM-CSF, IL-3, and IL-5 Family of Cytokines: Regulators of Inflammation. Immunity. 2019 Apr 16;50(4):796-811. doi: 10.1016/j.immuni.2019.03.022 Mathias B, Szpila BE, Moore FA, Efron PA, Moldawer LL. 2015. "A Review of GM-CSF Therapy in Sepsis." Medicine 94 (50): e2044. doi: 10.1097/MD.0000000000002044 Joshi I et al. Utility of monocyte HLA-DR and rationale for therapeutic GM-CSF in sepsis immunoparalysis. Front Immunol. 2023;14:1130214. doi: 10.3389/fimmu.2023.1130214 Shi Y, et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and T-cell responses: what we do and don't know. Cell Res. 2006;16(2):126-133. doi: 10.1038/sj.cr.7310017 Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet. 2020 Jan 18;395(10219):200-211. doi: 10.1016/S0140-6736(19)32989-7 ABOUT LEUKINE LEUKINE (sargramostim) is a glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) produced by recombinant DNA technology in yeast. The product is commercially available in the United States and accessible through a named patient program operated by Tanner Pharma Group outside of the United States. LEUKINE is indicated: To shorten time to neutrophil recovery and to reduce the incidence of severe and life-threatening infections and infections resulting in death following induction chemotherapy in adult patients 55 years and older with acute myeloid leukemia (AML). For the mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis and autologous transplantation in adult patients. For the acceleration of myeloid reconstitution following autologous bone marrow or peripheral blood progenitor cell transplantation in adult and pediatric patients 2 years of age and older. For the acceleration of myeloid reconstitution following allogeneic bone marrow transplantation in adult and pediatric patients 2 years of age and older. For treatment of delayed neutrophil recovery or graft failure after autologous or allogeneic bone marrow transplantation in adult and pediatric patients 2 years of age and older. To increase survival in adult and pediatric patients from birth to 17 years of age acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome [H-ARS]). Important Safety Information for LEUKINE (sargramostim) Contraindications Do not administer LEUKINE to patients with a history of serious allergic reaction, including anaphylaxis, to human granulocyte-macrophage colony-stimulating factor, sargramostim, yeast-derived products, or any other component of LEUKINE. Warnings and Precautions Serious hypersensitivity reactions, including anaphylactic reactions, have been reported with LEUKINE. If a serious allergic or anaphylactic reaction occurs, immediately discontinue LEUKINE therapy, and institute medical management. Discontinue LEUKINE permanently for patients with serious allergic reactions. LEUKINE can cause infusion-related reactions that may be characterized by respiratory distress, hypoxia, flushing, hypotension, syncope, and/or tachycardia. Observe closely during infusion, particularly in patients with preexisting lung disease; dose adjustment or discontinuation may be needed. LEUKINE should not be administered simultaneously with or within 24 hours preceding cytotoxic chemotherapy or radiotherapy or within 24 hours following chemotherapy. Edema, capillary leak syndrome, and pleural or pericardial effusions have been reported in patients after LEUKINE administration. LEUKINE should be used with caution in patients with preexisting fluid retention, pulmonary infiltrates, or congestive heart failure. Such patients should be monitored. Supraventricular arrhythmia has been reported in uncontrolled studies during LEUKINE administration, particularly in patients with a history of cardiac arrhythmia. Use LEUKINE with caution in patients with preexisting cardiac disease. If absolute neutrophil count (ANC) > 20,000 cells/mm3 or if white blood cell (WBC) counts > 50,000/mm3, LEUKINE administration should be interrupted, or the dose reduced by half. Monitor complete blood counts (CBC) with differential twice per week. Discontinue LEUKINE therapy if tumor progression, particularly in myeloid malignancies, is detected during LEUKINE treatment. Treatment with LEUKINE may induce neutralizing anti-drug antibodies. Use LEUKINE for the shortest duration needed. Avoid administration of solutions containing benzyl alcohol (including LEUKINE for injection reconstituted with Bacteriostatic Water for Injection, USP [0.9 % benzyl alcohol]) to neonates and low birth weight infants. Drug Interactions Avoid the concomitant use of LEUKINE and products that induce myeloproliferation. Monitor for clinical and laboratory signs of excess myeloproliferative effects. Adverse Reactions Adverse events occurring in >10% of patients receiving LEUKINE in controlled clinical trials and reported at a higher frequency than in placebo patients are: In recipients of autologous bone marrow transplantation (BMT)–asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder In recipients of allogeneic BMT–abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, GI hemorrhage, pruritus, bone pain, arthralgia, eye hemorrhage, hypertension, tachycardia, bilirubinemia, hyperglycemia, increased creatinine, hypomagnesemia, edema, pharyngitis, epistaxis, dyspnea, insomnia, anxiety, high glucose, low albumin In patients with AML–fever, weight loss, nausea, vomiting, anorexia, skin reactions, metabolic laboratory abnormalities, edema ABOUT PARTNER THERAPEUTICS Partner Therapeutics, Inc. (PTx), an integrated biotechnology company, focuses on development and commercialization of late-stage therapeutics to improve health outcomes in treatment of cancer and other serious diseases. The company believes in delivering products and supporting medical teams with the purpose of achieving superior outcomes for patients and their families. Visit MEDIA CONTACT [email protected] SOURCE Partner Therapeutics, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

-REX-7117 is an oral, potent and selective STAT3 SH2 domain inhibitor, which demonstrated strong efficacy in an in vivo model of inflammatory arthritis -STAT3 inhibition does not impair the interferon-mediated antiviral defense or hematopoietic growth factor signaling, as seen with JAK/TYK2 inhibitors SAN DIEGO, Nov. 14, 2024 (GLOBE NEWSWIRE) -- Recludix Pharma, a leader in discovery of inhibitors of challenging targets for inflammatory disease, today announced pre-clinical inflammatory arthritis data for REX-7117, an oral, reversible, SH2 domain-targeting STAT3 inhibitor, will be presented at the American College of Rheumatology (ACR) Convergence meeting being held November 14–19, 2024 in Washington, D.C. In multiple in vivo models of inflammatory arthritis, REX-7117 achieved deep, durable, and selective STAT3 inhibition, decreased inflammatory biomarkers such as c-reactive protein (CRP), and achieved statistically significant efficacy compared to vehicle and comparable efficacy to a high-dose of the JAK inhibitor, baricitinib. Unlike both JAK1/2 and pan-JAK inhibitors, REX-7117 did not impair innate interferon-dependent viral replication or growth factor signaling critical for hematologic homeostasis. “We have multiple preclinical datasets in inflammatory diseases confirming the differentiated therapeutic potential of selectively targeting STAT3,” said Ajay Nirula, M.D., Ph.D., executive vice president and head of research and development. “In these most recent studies for arthritis, we have demonstrated that by inhibiting STAT3, we can potently dampen inflammatory cytokines that drive rheumatologic diseases. Importantly, we are able to do so while avoiding the pathways that trigger the safety concerns seen with JAK/TYK2 inhibitors. A selective STAT3 inhibitor could be a promising therapy for diseases such as rheumatoid arthritis, psoriasis, psoriatic arthritis, and inflammatory bowel disease.” REX-7177 was found to: Be highly selective to STAT3, including across the SH2 domain family and other STAT proteins;Achieve deep and durable STAT3 inhibition;Dose-dependently reduce arthritis disease clinical scores, similar to the highest dose of baricitinib tested;Significantly reduce serum CRP, an IL-6 dependent biomarker of inflammatory activity;Effectively reduce histopathological changes, including inflammation, cartilage damage, pannus formation, periosteal proliferation and bone resorption;And, not impair either type I or type II interferon-mediated antiviral activity. In contrast, the JAK inhibitors tofacitinib and baricitinib broadly inhibited multiple phosphoSTAT pathways. JAK/TYK2 inhibitors are associated with on-target safety signals, including opportunistic infections and dysregulated hematologic homeostasis (anemia, thrombocytopenia). Poster Presentation Details: Title:REX-7117 Is a Highly Potent and Selective Oral STAT3 Inhibitor That Demonstrated Potential Efficacy and Safety Differentiation versus JAK/TYK2 Targeting in Preclinical Models of Inflammatory ArthritisPoster Number:0947Session:Poster Session B, RA – Animal Models PosterDate and Time:Sunday, November 17, 2024; 10:30 a.m. - 12:30 p.m. ET About STAT3The interleukin cytokines IL-23 and IL-6 signal through STAT3 and promote the generation and function of pathogenic T helper type-17 (Th17) cells, a type of immune cell that is pro-inflammatory. Th17 cells are considered pivotal players in certain inflammatory diseases, including rheumatoid arthritis, psoriasis, inflammatory bowel disease and others. Inhibiting STAT3 can also offer potential efficacy beyond Th17 / IL-17 driven diseases in clinical indications where blocking the IL-6 pathway is clinically validated. Furthermore, clinical trials inhibiting oncostatin M (OSM) and IL-22, both STAT3 dependent cytokines, have been reported as efficacious in inflammatory disease. A selective, oral STAT3 inhibitor has potential to provide an attractive alternative to JAK/TYK2 inhibitors and biologics for multiple inflammatory diseases. About RecludixRecludix is a leader in developing platform approaches to discover potent and selective inhibitors of challenging protein targets. The company’s management team includes industry veterans with a track record of success, including former leaders of Seagen, Blueprint Medicines, and Lilly. Recludix has developed a unique drug discovery platform that integrates custom generated DNA-encoded libraries, massively parallel determination of structure activity relationships, and a proprietary screening tool to ensure selectivity. The company is employing this approach first in the development of SH2 domain inhibitors. Recludix’s most advanced programs are focused on STAT (signal transducer and activator of transcription) proteins where abnormal activation is found in inflammatory diseases, such as rheumatoid arthritis, asthma, atopic dermatitis, and inflammatory bowel disease. The company has a strategic partnership with Sanofi for the development and commercialization of a STAT6 inhibitor. Recludix is also advancing STAT3 inhibitors for Th17-mediated I&I diseases, as well as additional programs. Recludix was named a 2024 Fierce 15 biotech company. For more information, please visit the company’s website at https://recludixpharma.com. Recludix ContactsMatt Caldemeyer Chief Business Officermcaldemeyer@recludix.com Alexandra Santos asantos@wheelhouselsa.com Aljanae Reynoldsareynolds@wheelhouselsa.com