OSM

--In a preclinical model of psoriasis, the efficacy of oral small molecule REX-7117 was comparable to an anti-IL-17A biologic SAN DIEGO, May 17, 2024 (GLOBE NEWSWIRE) -- Recludix Pharma, Inc., a leader in discovery of inhibitors of challenging targets for inflammatory disease and cancer, presented new data today in an oral plenary presentation at the Society for Investigative Dermatology (SID) Annual Meeting titled “Oral selective STAT3 inhibitors demonstrate differentiated efficacy and safety potential in preclinical models of Th17 mediated skin inflammation” (abstract #738). Recludix’s senior vice president of biology, Paul Smith, Ph.D., reviewed preclinical data on the company’s potent, selective, and orally bioavailable small molecule STAT3 inhibitors, including REX-7117. Data demonstrated that REX-7117 achieves deep, durable, and selective STAT3 inhibition and exhibits similar efficacy to biologics targeting IL-17 in in vivo models of plaque psoriasis. Data was also presented that, unlike JAK1/2 and TYK2 inhibitors, REX-7117 does not impair broader immune responses, such as interferon-dependent anti-viral immunity or growth factor signaling critical for hematologic homeostasis. “These exciting data on our oral STAT3 inhibitors demonstrate that deep STAT3 inhibition has the potential to drive potent efficacy -- such as that seen with clinically validated biologics but with improved convenience as an orally-administered medication, while high selectivity for the downstream STAT3 target may avoid some of the safety concerns observed with JAK and TYK2 inhibitors,” said Ajay Nirula, M.D., Ph.D., executive vice president and head of research and development. “Inhibiting STAT3 could be a favorable and effective approach to treating Th17- and Th1-mediated diseases, such as psoriasis, psoriatic arthritis, rheumatoid arthritis, and inflammatory bowel disease.” Both REX-7117 and REX-5376 are highly potent and selective orally-available STAT3 inhibitors, as demonstrated across biochemical and cellular assays, which have the potential to: Impair inflammatory Th17 cell function, while sparing activation of other cytokine pathways which play critical roles in the defense against viruses, bacteria, extra cellular pathogens, and parasites Spare STAT1 mediated-signaling, in contrast to the impact on STAT1 signaling seen with baricitinib (JAK1/2) and deucravacitinib (TYK2) Not impair either type I or type II interferon (IFN)-mediated antiviral activity, as shown in in vitro models Not impair STAT5-mediated signaling by hematopoietic growth factors, unlike some JAK inhibitors which have the risk of inducing anemia, thrombocytopenia, and neutropenia In a murine IL-23 induced psoriasis model, REX-7117 achieved efficacy responses similar to an anti-IL-17A antibody surrogate treatment and was more efficacious than an estimated clinically relevant dose of deucravacitinib. About STAT3 The 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. STAT3 inhibitors may also have significant opportunity in cancer settings, as STAT3 is activated in greater than 70% of human cancers. About Recludix Recludix 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, as well as numerous cancer types, such as multiple leukemias and lymphomas. 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 and oncology indications, as well as additional programs. For more information, please visit the company’s website at . Recludix Contacts: Alexandra Santos asantos@wheelhouselsa.com Aljanae Reynolds areynolds@wheelhouselsa.com

- Pioneering compounds believed to be the first orally administered reversible inhibitors to bind to and inhibit the SH2 domain potently and selectively - Proprietary STAT3 inhibitors are differentiated in several ways from alternative approaches, including potency, selectivity, reversibility and oral bioavailability Recludix Pharma, a leader in platform approaches to discover inhibitors of challenging targets for inflammatory disease and cancer, announced that in a presentation given today titled “Drugging the Undruggable,” Recludix’s senior vice president of biology, Paul Smith, Ph.D., discussed the first application of the company’s platform capabilities to target the Src Homology 2 (SH2) domain, as well as reviewed preclinical data on an early STAT3 inhibitor that was internally discovered through the platform. The presentation is available on the company’s website under the section titled “Events.” “We have had tremendous success in developing oral STAT inhibitors by targeting the SH2 domain, which has been previously considered undruggable,” said Nancy Whiting, PharmD, CEO of Recludix. “In this presentation, we highlight data from one of our earlier STAT3 discovery compounds showing its highly selective STAT3 inhibition with demonstrated potency in biochemical and cellular assays. We have continued to refine our lead STAT3 inhibitors and are in the final stages of confirming a STAT3 development candidate to move into clinical testing. We believe this could be a first- and best-in-class approach to selectively inhibit Th17-driven inflammatory diseases, such as psoriasis, rheumatoid arthritis, ulcerative colitis and Crohn's disease.” Recludix has generated potent and selective small molecule STAT3 inhibitors for Th17-driven inflammation. In T cell functional assays, Recludix’s STAT3 inhibitor potently and selectively impaired the Th17 phenotype, while still enabling the T cell to continue to perform robustly against viruses, bacteria, extracellular pathogens, and parasites. This is in contrast to the family of JAK or TYK2 inhibitors, which can be associated with changes in immune surveillance and hematopoiesis, leading to dose limiting safety concerns. Data demonstrate that targeting STAT3 spares interferon-driven anti-viral gene transcription and avoids STAT5 signaling, which is important for hematologic homeostasis and is differentiated from JAK/TYK2 inhibition. In a preclinical model of multiple sclerosis, proof-of-concept was established that STAT3 inhibition modulates in vivo Th17 diseases as measured by mean clinical score compared to vehicle control, exhibiting greater preclinical disease control than the JAK inhibitor baricitinib. Activity for STAT3 was found to be dose-dependent in both prophylactic and therapeutic preclinical models. Selective STAT3 inhibition was also evaluated in an imiquimod-induced (Th17-dependent) model of psoriasis which demonstrated that STAT3 inhibition modulates disease as measured by the PASI score and skin thickness, and it does so comparably to a supra-maximal efficacious dose of the JAK inhibitor tofacitinib (30 mg/kg). About STAT3 The 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 replace JAK/TYK2 inhibitors and biologics for multiple inflammatory diseases. STAT3 inhibitors may also have significant opportunity in cancer settings, as STAT3 is activated in greater than 70% of human cancers. About Recludix Recludix 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 and founding scientific team members of Seagen and Blueprint Medicines. 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, as well as numerous cancer types, such as multiple leukemias and lymphomas. 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 and oncology indications, as well as additional programs. For more information, please visit the company’s website at https://recludixpharma.com. The content above comes from the network. if any infringement, please contact us to modify.

HAMILTON, Bermuda, Sept. 12, 2022 (GLOBE NEWSWIRE) -- Kiniksa Pharmaceuticals, Ltd. (Nasdaq: KNSA) (Kiniksa), a biopharmaceutical company with a portfolio of assets designed to modulate immunological pathways across a spectrum of diseases, today announced the closing of the global license agreement with Roche and Genentech, a member of the Roche Group (Genentech), for the rights to develop and commercialize vixarelimab, a fully human monoclonal antibody targeting oncostatin M receptor beta (OSMRβ). Closing of the transaction was subject to customary closing conditions and expiration of the waiting period under the Hart-Scott-Rodino (HSR) Antitrust Improvements Act of 1976. Under the terms of the license agreement, Kiniksa will receive $100 million in upfront and near-term payments, which include $80 million within 30 days of the closing of the transaction and $20 million within 30 days after Kiniksa’s delivery of certain drug supplies to Genentech. In addition, Kiniksa is eligible to receive up to approximately $600 million in certain clinical, regulatory, and sales-based milestones, before fulfilling upstream financial obligations. Kiniksa is also eligible to receive royalties on annual net sales. Genentech obtains rights for the global development and commercialization of vixarelimab. Kiniksa expects that its cash and cash equivalents, including the proceeds received from the vixarelimab global license agreement with Genentech, will fund its current operating plan into at least 2025. About Kiniksa Kiniksa is a biopharmaceutical company focused on discovering, acquiring, developing, and commercializing therapeutic medicines for patients suffering from debilitating diseases with significant unmet medical need. Kiniksa’s portfolio assets, ARCALYST, KPL-404, and mavrilimumab, are based on strong biologic rationale or validated mechanisms, target underserved conditions, and offer the potential for differentiation. These assets are designed to modulate immunological pathways across a spectrum of diseases. For more information, please visit . About Vixarelimab Vixarelimab is an investigational fully human monoclonal antibody that targets oncostatin M receptor beta (OSMRβ), which mediates signaling of interleukin-31 (IL-31) and oncostatin M (OSM), two key cytokines implicated in pruritus, inflammation, and fibrosis. Kiniksa Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these identifying words. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation, statements regarding anticipated milestone and royalty payments under the license agreement and our expectation about our cash reserves funding our current operating plan into at least 2025. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including without limitation, the following: Genentech’s ability to demonstrate safety and efficacy of vixarelimab in their chosen indications to the satisfaction of applicable regulatory authorities; our ability to realize anticipated milestone and royalty payments under the agreement; the impact of the COVID-19 pandemic and measures taken in response to the pandemic; and changes in our operating plan. These and other important factors discussed in our filings with the U.S. Securities and Exchange Commission (the SEC), including under the caption “Risk Factors” contained therein, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. Except as required by law, we disclaim any intention or obligation to update or revise any forward-looking statements. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. ARCALYST® is a registered trademark of Regeneron Pharmaceuticals, Inc. All other trademarks are the property of their respective owners. Every Second Counts!® Kiniksa Investor and Media Contact Rachel Frank (339) 970-9437 rfrank@kiniksa.com