IL-22

-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

The Phase 2 study will evaluate the efficacy, safety and tolerability of the company’s lead lipidated IL-22 analogue, CK-0045, in patients with obesity and type 2 diabetes COPENHAGEN, Denmark I November 4, 2024 I Cytoki Pharma, ApS (Cytoki), a clinical-stage biotechnology company pioneering a new class of medicines that harness IL-22 biology to drive improved outcomes for metabolic disease, today announced the first patient has received CK-0045 in a Phase 2 proof-of-concept trial evaluating efficacy, safety and tolerability in individuals with obesity and type 2 diabetes. “A leading public health priority, obesity and diabetes cumulatively impact more than one billion individuals worldwide. While the emergence of incretin-based medicines has provided new treatment options, there remains a demand for novel approaches that offer additional cardiometabolic benefits beyond body weight reduction alone,” said Anne Louise Kjølbye, Ph.D., MBA, CDO at Cytoki. “CK-0045 offers a novel approach to metabolic disease treatment with the potential to prolong healthy lifespan through muscle-sparing weight loss accompanied by broader health benefits.” CK-0045 is an IL-22 analogue that leverages commercially proven lipidation technology to extend circulation time in the body, enabling subcutaneous delivery and offering first-in-class potential to address obesity and type 2 diabetes. Results from the Phase 1 clinical study of CK-0045 in healthy volunteers confirmed target engagement and exposure-dependent reductions in body mass, alongside improvements in low-density lipoprotein (LDL) cholesterol, blood insulin levels, and insulin resistance. These results, combined with a favorable safety profile, support further clinical advancement of CK-0045. “Encouraging results from the Phase 1 study of CK-0045 demonstrate the potential of its unique IL-22 based mechanism of action as a powerful new therapeutic approach to address obesity and type 2 diabetes,” said Dr Carel le Roux, Professor of Experimental Pathology, University College Dublin. “We eagerly anticipate Cytoki’s progress as it continues clinical evaluation of CK-0045 and develops its broader IL-22-derived pipeline to deliver novel treatments for metabolic disease.” The 16-week randomized, double-blind, placebo-controlled Phase 2 study ( NCT06611930 ) will evaluate the efficacy, safety and tolerability of two doses of CK-0045, administered subcutaneously once a week, in 90 patients with obesity and type 2 diabetes. The outcomes investigated in the study reflect the wide range of metabolic benefits of IL-22 modulation and include amongst others weight loss, change in HbA1c, insulin sensitivity measurements, and lipid levels. Results of the study are anticipated in the first half of 2026. Additionally, Cytoki continues to advance a robust portfolio of IL-22-based assets targeting high unmet need in metabolic disease as well as inflammatory bowel disease. About CK-0045 CK-0045 is a long-acting analogue of interleukin-22 (IL-22), an atypical, non-immunomodulatory cytokine that selectively targets epithelial cells. In-licensed from Novo Nordisk A/S, CK-0045 incorporates validated technology to optimize the pharmacologic properties of the endogenous IL-22 protein to create a differentiated, first-in-class therapy with potential to address a broad range of metabolic diseases, including obesity and type 2 diabetes, and conditions characterized by epithelial injury, such as inflammatory bowel disease. CK-0045 has been evaluated in a randomized, double-blind, placebo-controlled Phase 1 study designed to investigate its safety, tolerability, and pharmacokinetics in healthy individuals with and without obesity ( NCT05712876 ). CK-0045 is currently being investigated in a Phase 2 clinical trial for patients with type 2 diabetes and overweight / obesity ( NCT06611930 ). About Cytoki Pharma Cytoki Pharma is a clinical-stage biotechnology company pioneering a new class of medicines that harness IL-22 biology to drive improved outcomes for cardiometabolic disease. Cytoki’s lead program, CK-0045, is a lipidated IL-22 analogue that is currently being evaluated in a Phase 2 clinical study. The company is also advancing a broader portfolio of preclinical IL-22-based assets for the treatment of metabolic disease and inflammatory bowel disease. Cytoki was founded in 2019 and is led by a team of pharma industry veterans with deep expertise in the discovery and clinical development of novel drugs. Please visit www.cytokipharma.com or follow us on LinkedIn for additional details. SOURCE: Cytoki Pharma

The Phase 2 study will evaluate the efficacy, safety and tolerability of the company's lead lipidated IL-22 analogue, CK-0045, in patients with obesity and type 2 diabetes COPENHAGEN, Denmark, Nov. 4, 2024 /PRNewswire/ -- Cytoki Pharma, ApS (Cytoki), a clinical-stage biotechnology company pioneering a new class of medicines that harness IL-22 biology to drive improved outcomes for metabolic disease, today announced the first patient has received CK-0045 in a Phase 2 proof-of-concept trial evaluating efficacy, safety and tolerability in individuals with obesity and type 2 diabetes. "A leading public health priority, obesity and diabetes cumulatively impact more than one billion individuals worldwide. While the emergence of incretin-based medicines has provided new treatment options, there remains a demand for novel approaches that offer additional cardiometabolic benefits beyond body weight reduction alone," said Anne Louise Kjølbye, Ph.D., MBA, CDO at Cytoki. "CK-0045 offers a novel approach to metabolic disease treatment with the potential to prolong healthy lifespan through muscle-sparing weight loss accompanied by broader health benefits." CK-0045 is an IL-22 analogue that leverages commercially proven lipidation technology to extend circulation time in the body, enabling subcutaneous delivery and offering first-in-class potential to address obesity and type 2 diabetes. Results from the Phase 1 clinical study of CK-0045 in healthy volunteers confirmed target engagement and exposure-dependent reductions in body mass, alongside improvements in low-density lipoprotein (LDL) cholesterol, blood insulin levels, and insulin resistance. These results, combined with a favorable safety profile, support further clinical advancement of CK-0045. "Encouraging results from the Phase 1 study of CK-0045 demonstrate the potential of its unique IL-22 based mechanism of action as a powerful new therapeutic approach to address obesity and type 2 diabetes," said Dr Carel le Roux, Professor of Experimental Pathology, University College Dublin. "We eagerly anticipate Cytoki's progress as it continues clinical evaluation of CK-0045 and develops its broader IL-22-derived pipeline to deliver novel treatments for metabolic disease." The 16-week randomized, double-blind, placebo-controlled Phase 2 study (NCT06611930) will evaluate the efficacy, safety and tolerability of two doses of CK-0045, administered subcutaneously once a week, in 90 patients with obesity and type 2 diabetes. The outcomes investigated in the study reflect the wide range of metabolic benefits of IL-22 modulation and include amongst others weight loss, change in HbA1c, insulin sensitivity measurements, and lipid levels. Results of the study are anticipated in the first half of 2026. Additionally, Cytoki continues to advance a robust portfolio of IL-22-based assets targeting high unmet need in metabolic disease as well as inflammatory bowel disease. About CK-0045 CK-0045 is a long-acting analogue of interleukin-22 (IL-22), an atypical, non-immunomodulatory cytokine that selectively targets epithelial cells. In-licensed from Novo Nordisk A/S, CK-0045 incorporates validated technology to optimize the pharmacologic properties of the endogenous IL-22 protein to create a differentiated, first-in-class therapy with potential to address a broad range of metabolic diseases, including obesity and type 2 diabetes, and conditions characterized by epithelial injury, such as inflammatory bowel disease. CK-0045 has been evaluated in a randomized, double-blind, placebo-controlled Phase 1 study designed to investigate its safety, tolerability, and pharmacokinetics in healthy individuals with and without obesity (NCT05712876). CK-0045 is currently being investigated in a Phase 2 clinical trial for patients with type 2 diabetes and overweight / obesity (NCT06611930). About Cytoki Pharma Cytoki Pharma is a clinical-stage biotechnology company pioneering a new class of medicines that harness IL-22 biology to drive improved outcomes for cardiometabolic disease. Cytoki's lead program, CK-0045, is a lipidated IL-22 analogue that is currently being evaluated in a Phase 2 clinical study. The company is also advancing a broader portfolio of preclinical IL-22-based assets for the treatment of metabolic disease and inflammatory bowel disease. Cytoki was founded in 2019 and is led by a team of pharma industry veterans with deep expertise in the discovery and clinical development of novel drugs. Please visit or follow us on LinkedIn for additional details. Media Contact Lia Dangelico [email protected] +1 540-303-0180 SOURCE Cytoki Pharma WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED