IRF3

- Transaction Includes JNT-517, a Potential First-In-Class Oral Treatment for Phenylketonuria (PKU) - - Expands Specialty and Autoimmune Portfolios and Drug Discovery Technologies - TOKYO and BOSTON, Aug. 01, 2024 (GLOBE NEWSWIRE) -- Otsuka Pharmaceutical Co., Ltd. (Otsuka) and Jnana Therapeutics Inc. (Jnana) today announced that they have entered into a definitive merger agreement pursuant to which Otsuka will acquire Jnana, making it a wholly owned subsidiary through Otsuka’s 100-percent owned subsidiary, Otsuka America, Inc. (OAI). The acquisition is expected to be completed in the third quarter of fiscal 2024, subject to customary closing conditions. Based on the terms of the agreement, Otsuka will pay USD $800 million to the shareholders of Jnana upon completion of the acquisition, as well as up to an additional USD $325 million in development and regulatory milestones. 1．Reasons for the acquisition Jnana’s novel approach to drug discovery is enabled by RAPID – the company’s next-generation chemoproteomics platform designed to discover medicines for highly validated but challenging-to-drug targets. The platform leverages a high-throughput, binding-based screening approach that is inherently flexible, enabling the discovery of binding sites across the surface of a target protein and the identification of small molecules that elicit diverse pharmacologies. Jnana has used RAPID to successfully identify first-in-class compounds and address a range of historically challenging-to-drug target classes, including solute carriers, transcription factors, and signaling scaffold proteins. Jnana pursues drug discovery based on concepts that are complementary to those of Astex Pharmaceuticals, a subsidiary of Otsuka based in Cambridge, UK. While Jnana's RAPID platform is not limited to any specific therapeutic area, the company has built a unique competitive position by concentrating on PKU, a rare inherited metabolic disorder in which phenylalanine accumulates to abnormally high levels in the blood, and autoimmune diseases, where small molecule drug discovery has been challenging. Jnana’s technology successfully generated JNT-517, an allosteric small molecule inhibitor of SLC6A19, an SLC (solute carrier) that regulates amino acid reabsorption in the kidney. JNT-517 has the potential to become a first-in-class oral treatment for PKU, as it has been shown to be effective, well-tolerated, and safe in a Phase 1b/2 study. A majority of the PKU population is not effectively treated with existing therapies, and JNT-517 is an approach that could address individuals of all ages across the spectrum of mild to severe disease. In the autoimmune disease field, the company is pursuing small molecule drug discovery for highly validated, but challenging-to-drug, targets such as interferon regulatory factor 3 (IRF3), a master transcription factor for the production of interferon. Otsuka has advanced contributions to patients with a wide range of rare diseases, not only in the renal area with JINARC (approved for autosomal dominant polycystic kidney disease), sibeprenlimab (IgA nephropathy), and voclosporin (lupus nephritis), but also by adding new specialty drugs such as donidalorsen (hereditary angioedema). Additionally, through Visterra, a Boston-based company that Otsuka acquired in 2018, Otsuka is advancing research and development in the autoimmune field using antibody drug technology, while also expanding its drug discovery platform. Makoto Inoue, president and representative director of Otsuka Pharmaceutical commented, "I am gratified that Otsuka has entered into an agreement with Jnana. The addition of Jnana's drug discovery technology and small molecule pipeline in PKU and autoimmune diseases will strengthen our R&D in the Boston area of the U.S., one of the most important bioclusters in the world, and in a combined form will have a synergistic effect on Otsuka Pharmaceutical's global expansion.” Joanne Kotz, Ph.D., CEO and co-founder of Jnana, commented, "This transaction recognizes the Jnana team’s accomplishments since the founding of the company, which include creating RAPID – a world-class small molecule drug discovery platform. Leveraging our platform, the team discovered JNT-517, a potential first-in-class oral medicine for the treatment of PKU, and has demonstrated positive clinical proof of concept for JNT-517 in individuals with PKU. We are excited to join Otsuka with our shared goal of developing transformative therapies for patients and look forward to advancing JNT-517 into a registrational study in 2025 and continuing to progress our pipeline of innovative oral medicines for autoimmune diseases." 2．Outline of the acquisition Upon completion of the acquisition, Jnana will operate as a wholly owned subsidiary of Otsuka in Boston and will continue its research and development. The acquisition will be implemented by merging a special purpose company, established under OAI for this acquisition, into Jnana Therapeutics, with Jnana remaining as the surviving company. Existing shareholders of Jnana will be paid cash as consideration for this merger. Although the Boards of Directors of both Otsuka and Jnana have approved this acquisition, the execution of this acquisition may require the approval of Jnana's shareholders and the fulfillment of conditions under U.S. antitrust laws. After completion of necessary procedures, we aim to complete the acquisition during the third quarter of 2024. 3．Additional information about Otsuka (https://www.otsuka.co.jp/en/) Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: Otsuka–people creating new products for better health worldwide. Otsuka researches, develops, manufactures, and markets innovative products, with a focus on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health.In pharmaceuticals, Otsuka is a leader in the challenging areas of mental, renal, and cardiovascular health and has additional research programs in oncology and on several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does. 4．Additional information about Jnana (https://www.jnanatx.com/) Jnana Therapeutics is a clinical-stage biotechnology company leveraging its next-generation RAPID chemoproteomics platform to discover medicines for highly validated, challenging-to-drug targets to treat diseases with high unmet needs. Jnana is focused on developing first- and best-in-class therapies to treat a wide range of diseases, including rare diseases and immune-mediated diseases. Jnana’s lead program, JNT-517, which targets an allosteric site on the phenylalanine transporter SLC6A19, is a potential first-in-class oral approach for the treatment of PKU, a rare genetic metabolic disease. Located in Boston, Jnana brings together scientific leaders in small molecule drug discovery and development, a highly experienced management team, and the backing of leading life science investors Bain Capital Life Sciences, RA Capital Management, Polaris Partners, Versant Ventures, Avalon Ventures, Pfizer Ventures, and AbbVie Ventures. 5．Advisors Centerview Partners LLC acted as financial advisor to Jnana and Latham & Watkins LLP acted as its legal advisor.

Otsuka Pharmaceutical agreed to acquire Jnana Therapeutics under a deal potentially worth over $1.1 billion, gaining the latter’s lead pipeline asset JNT-517 for phenylketonuria (PKU). The transaction, which has been approved by the boards of both companies, is expected to close in the third quarter.As part of the merger agreement announced Thursday, Otsuka will pay $800 million upon closing of the acquisition, with Jnana shareholders eligible for up to $325 million in development and regulatory milestones. “The addition of Jnana's drug discovery technology and small-molecule pipeline in PKU and autoimmune diseases will strengthen our R&D in…the US…and in a combined form will have a synergistic effect on…global expansion,” remarked Makoto Inoue, president of Otsuka.Jnana — founded in 2017 with $50 million in financing — employs its RAPID chemoproteomics platform to discover candidates against validated but difficult-to-drug targets. The approach has led to the identification of JNT-517 to treat PKU, and other small molecules for autoimmune disease targets, such as interferon regulatory factor 3 (IRF3). The firm partnered with Roche in 2020 to develop small-molecule drugs targeting metabolite transporters, with the alliance expanded in 2022.JNT-517, an allosteric small-molecule inhibitor of SLC6A19, has been proven effective, well tolerated and safe in a Phase Ib/II study, with the potential to address patients across all age groups and disease severity. Joanne Kotz, chief executive and co-founder of Jnana, said they are confident of “advancing JNT-517 into a registrational study in 2025.”

Scientists have found that statins -- commonly used cholesterol-lowering drugs -- may block a pathway that leads to the development of cancer in the context of chronic inflammation. A new study led by investigators from Mass General Cancer Center, a founding member of the Mass General Brigham healthcare system, reveals that statins -- commonly used cholesterol-lowering drugs -- may block a particular pathway involved in the development of cancer that results from chronic inflammation. The findings are published in Nature Communications. "Chronic inflammation is a major cause of cancer worldwide," said senior author Shawn Demehri, MD, PhD, a principal investigator at the Center for Cancer Immunology and Cutaneous Biology Research Center of Massachusetts General Hospital and an associate professor of Dermatology at Harvard Medical School. "We investigated the mechanism by which environmental toxins drive the initiation of cancer-prone chronic inflammation in the skin and pancreas," says Demehri, who is also theBob and Rita Davis Family MGH Research Scholar 2023-2028. "Furthermore, we examined safe and effective therapies to block this pathway in order to suppress chronic inflammation and its cancer aftermath." Demehri and his colleagues' study relied on cell lines, animal models, human tissue samples and epidemiological data. The group's cell-based experiments demonstrated that environmental toxins (such as exposure to allergens and chemical irritants) activate two connected signaling pathways called the TLR3/4 and TBK1-IRF3 pathways. This activation leads to the production of the interleukin-33 (IL-33) protein, which stimulates inflammation in the skin and pancreas that can contribute to the development of cancer. When they screened a library of U.S. Food and Drug Administration-approved drugs, the researchers found that a statin, pitavastatin, effectively suppresses IL-33 expression by blocking the activation of the TBK1-IRF3 signaling pathway. In mice, pitavastatin suppressed environmentally-induced inflammation in the skin and the pancreas and prevented the development of inflammation-related pancreatic cancers. In human pancreas tissue samples, IL-33 was over-expressed in samples from patients with chronic pancreatitis (inflammation) and pancreatic cancer compared with normal pancreatic tissue. Also, in analyses of electronic health records data on more than 200 million people across North America and Europe, use of pitavastatin was linked to a significantly reduced risk of chronic pancreatitis and pancreatic cancer. The findings demonstrate that blocking IL-33 production with pitavastatin may be a safe and effective preventive strategy to suppress chronic inflammation and the subsequent development of certain cancers. "Next, we aim to further examine the impact of statins in preventing cancer development in chronic inflammation in liver and gastrointestinal tract and to identify other novel, therapeutic approaches to suppress cancer-prone chronic inflammation" said Demehri.