RX-10001

Scientists are testing a novel technology to treat endodontic diseases more effectively through tissue regeneration instead of root canal therapy. Because the technology promotes formation of the type of stem cells that can differentiate into dentin (tooth), bone, cartilage or fat, it has huge potential for the field of regenerative medicine beyond the tissues in the teeth. It could be used to grow bones in other parts of the body. Want to avoid a root canal? In the future, you might be able to opt for tissue regeneration instead. ADA Forsyth scientists are testing a novel technology to treat endodontic diseases (diseases of the soft tissue or pulp in your teeth) more effectively. The study, "RvE1 Promotes Axin2+Cell Regeneration and Reduces Bacterial Invasion," which appeared in The Journal of Dental Research, demonstrates regenerative properties of resolvins, specifically Resolvin E1 (RvE1), when applied to dental pulp. Resolvins are part of a greater class of Specialized Proresolving Mediators (SPMs). This class of molecule is naturally produced by the body and is exquisitely effective in the control of excess inflammation associated with disease. "Pulpitis (inflammation of dental pulp) is a very common oral health disease that can become a serious health condition if not treated properly," said Dr. Thomas Van Dyke, Vice President at the Center for Clinical and Translational Research at ADA Forsyth, and a senior scientist leading the study. "Root canal therapy (RCT) is effective, but it does have some problems since you are removing significant portions of dentin, and the tooth dries out leading to a greater risk of fracture down the road. Our goal is to come up with a method for regenerating the pulp, instead of filling the root canal with inert material." Inflammation of this tissue is usually caused by damage to the tooth through injury, cavities or cracking, and the resulting infection can quickly kill the pulp and cause secondary problems if not treated. The study applied RvE1 to different levels of infected and damaged pulp to explore its regenerative and anti-inflammatory capacities. There were two major findings. First, they showed RvE1 is very effective at promoting pulp regeneration when used in direct pulp-capping of vital or living pulp (replicating conditions of reversible pulpitis). They were also able to identify the specific mechanism supporting tissue regeneration. Second, the scientists found that placing RvE1 on exposed and severely infected and necrotic pulp did not facilitate regeneration. However, this treatment did effectively slow down the rate of infection and treat the inflammation, preventing the periapical lesions (abscesses) that typically occur with this type of infection. Previous publications have shown that if the infected root canal is cleaned before RvE1 treatment, regeneration of the pulp does occur. While this study focused on this technology in treating endodontic disease, the potential therapeutic impact is far reaching. Dr. Van Dyke explained, "because application of RvE1 to dental pulp promotes formation of the type of stem cells that can differentiate into dentin (tooth), bone, cartilage or fat, this technology has huge potential for the field of regenerative medicine beyond the tissues in the teeth. It could be used to grow bones in other parts of the body, for instance." The study was funded by Alvin Krakow Harvard/Forsyth Research Fund (Y. Wu), and USPHS grant DE025020 from the National Institute of Dental and Craniofacial Research (NIDCR) (T.E. Van Dyke). Study authors include Yu-Chiao Wu, Ning Yu, Carla Alvarez Rivas, Nika Mehrnia, and Alpdogan Kantarci.

Dr. Sznol to guide clinical investigation of Resolvin-based therapies in metastatic melanoma ESSEX, CT., November 7, 2023. Thetis Pharmaceuticals LLC (“Thetis”), a biopharmaceutical company developing a first-in-class small molecule ChemR23 agonist to treat cancer and autoimmune diseases small molecule (TP-317) to treat cancer and autoimmune diseases, announced today that Dr. Mario Sznol has joined its Scientific Advisory Board (SAB). Dr. Sznol is Professor of Medicine, Clinical Research Team Leader (Melanoma-Renal Cancer Program), and Co-Leader of Cancer Immunology Program at the Yale Cancer Center. Gary Mathias, Chief Executive Officer of Thetis, commented, “Dr. Sznol has an international reputation with unique expertise and experience in cancer immunotherapy, drug development for cancer, and treatment of patients with melanoma and renal cell carcinoma, which makes him a perfect choice to help Thetis in the development of TP-317 to treat metastatic melanoma. Dr. Sznol is an expert in clinical application of immune checkpoint inhibitors and brings an important perspective to our clinical strategy for TP-317, which in preclinical studies has shown single agent efficacy comparable to standard-of-care immunotherapy and chemotherapy and enhanced efficacy when combined with these other agents.” Dr. Sznol noted that “TP-317 offers a highly differentiated strategy to address resistance to immunotherapy in the tumor microenvironment (TME), which is an important target in cancer drug development. I am delighted to join the Thetis SAB to help develop this promising small molecule drug for metastatic melanoma.” Dr. Sznol joins the Thetis SAB with 35 years of experience in cancer research and development. He graduated from Baylor College of Medicine where he subsequently trained in internal medicine, and then completed a medical oncology fellowship in the Department of Neoplastic Diseases at Mount Sinai Hospital. He spent the next twelve years in the Cancer Therapy Evaluation Program of the National Cancer Institute. From 1999-2004, he served as Vice President of Clinical Development and Executive Officer of Vion Pharmaceuticals in New Haven, Connecticut. In 2004, he joined the medical oncology faculty of the Yale University School of Medicine as co-leader of the Melanoma Program and is currently Professor of Internal Medicine, Leader of the Melanoma-Renal Cancer Clinical Research Team, and Co-Director of Cancer Immunology Program. About TP-317 and Disease Programs TP-317 is a patent-protected small molecule drug that delivers Resolvin E1 (RvE1), an endogenous lipid mediator that restores immune homeostasis. Unlike anti-inflammatory drugs and anti-cancer agents that are immuno-suppressive, TP-317 activates innate and adaptive immune pathways to treat disease without compromising host-protective immunity. Cancer Program: In cancer, TP-317 is being developed as an adjunct to immune checkpoint inhibitors in refractory metastatic melanoma and advanced non-small cell lung cancer (NSCLC), and as adjunct to chemotherapy in pancreatic cancer. TP-317 has demonstrated potent single agent activity in melanoma, lung cancer and pancreatic cancer tumor models, and enhanced efficacy when combined with immune checkpoint inhibitors or chemotherapy in “immune cold” and immune-responsive tumors. In the same studies, TP-317 has been shown to promote myeloid directed antigen presentation and increased IFN-y response in the tumor microenvironment, which may contribute to TP-317’s robust anti-tumoral effects. IBD Program: In inflammatory bowel disease, TP-317 is being developed as a first-line oral therapy for mild-to-moderate Crohn’s disease and as second-line oral therapy for mild-to-moderate ulcerative colitis patients who are not well controlled on 5-ASA or corticosteroids. In colitis models, oral TP-317 dosed once daily has shown efficacy in DSS, TNBS, TNFΔARE and T-cell transfer colitis models. In DSS-induced colitis, TP-317 has shown comparable efficacy to 5-ASA and the JAK inhibitor filgotinib and enhanced efficacy when combined with 5-ASA. Mechanistically, RvE1 has demonstrated a unique ability to shift the inflamed mucosa towards immune homeostasis and promote intestinal barrier repair, a key driver and measure of efficacy in human IBD. About Thetis Pharmaceuticals Thetis is a biopharmaceutical company dedicated to improving the lives of patients suffering from cancer and inflammatory bowel disease. Thetis’ proprietary HEALER™ technology enables the pharmaceutical development of Resolvins, overcoming the stability, manufacturing, and formulation hurdles that have limited their commercial development. Thetis is supported by venture capital investors, NIH, and leading private philanthropies, including the Helmsley Charitable Trust, the Crohn’s & Colitis Foundation, and the Kenneth Rainin Foundation. Disclaimer TP-317 is an investigational drug product that has not been approved by the U.S. Food and Drug Administration. For more information, please visit Thetis Pharmaceuticals’ website ( ). Contact Information Gary Mathias, CEO gmathias@thetispharma.com