THPO

Medikine’s first therapeutic candidate, MDK-703, an Interleukin-7 (IL-7) mimetic with an extended half-life, will be studied in healthy volunteers, with top-line results expected in the fourth quarter of 2022 Company plans to investigate MDK-703 in solid tumors following completion of the Phase 1 clinical trial MDK-703 is an immunoglobulin Fc fragment-peptide fusion protein incorporating an IL-7 PEPTIKINE™ discovered using Medikine’s innovative platform technology to improve drug properties MENLO PARK, Calif.--(BUSINESS WIRE)-- Medikine, Inc., a biopharmaceutical company developing transformative therapeutics for cancer, autoimmune disorders, and infectious diseases using its novel PEPTIKINE™ technology, today announced it has initiated dosing of MDK-703, an extended half-life IL-7 mimetic. The Phase 1 clinical trial, in healthy volunteers, will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single, ascending intramuscular doses of MDK-703 compared to placebo. Top-line results from the clinical trial are expected in the fourth quarter of 2022. MDK-703 is the First IL-7 Mimetic to be Studied in Humans MDK-703 is an investigational biologic drug incorporating an IL-7 PEPTIKINE discovered using Medikine’s platform technology. Medikine’s PEPTIKINES are substantially smaller molecules than the cytokines they emulate, structurally unrelated to natural cytokines, engineered for low immunogenicity, and readily amenable to incorporating targeting and other pharmacological features. IL-7 is a cytokine critical for the development and maintenance of T cells, including enhancing generation, function, and survival of memory T cells. In oncology, treatments with these biological attributes, alone or in combination with other immune-based therapies, may enhance the rate, depth, and durability of clinical response. In addition to these anti-tumor properties, MDK-703 has the beneficial property that it will not generate anti-drug antibodies (ADAs) that neutralize native IL-7, an issue previously observed with IL-7 agents that have been studied in humans. The company plans to investigate MDK-703 in solid tumors following the completion of the Phase 1 clinical trial in healthy volunteers. Medikine has shown that MDK-703 behaves similarly to IL-7 in human immune cell in vitro studies and in humanized mice and non-human primates in vivo studies. In addition to increasing the total number of CD8 T cells and CD4 T cells, MDK-703 increased the number of memory T cells, particularly T memory stem (TSCM) cells. TSCM cells are a subset of memory T cells that have the potential to self-renew and differentiate, thereby reconstituting the entire spectrum of memory and effector cell types.1 In addition, MDK-703 had negligible-to-no impact on the expansion of CD4 T regulatory and natural killer (NK) cell populations. “Based on preclinical data, we believe that MDK-703 has best-in-class potential, with biology consistent with facilitating the differentiation, maintenance, and survival of the T cell subsets that are critical for durable anti-tumor activity in humans. The initial study of MDK-703 in healthy subjects is designed to provide important proof-of-pharmacology that is relevant to cancer treatment, including the impact on specific T-cell populations and the lack of neutralizing IL-7 ADAs,” commented Dr. Joseph Leveque, president and chief medical officer of Medikine. Medikine Applies Expertise in PEPTIKINE Technology to Next-Generation Cytokine Drug Development Medikine’s founding team of Ronald W. Barrett, Ph.D. (chief executive officer and chairman of the Board), William J. Dower, Ph.D. (scientific advisor), and Michael C. Needels, Ph.D. (chief technology officer), have worked together since the 1990s. They are experts in peptide library technology and its application to the discovery of cytokine receptor agonists and antagonists. Their groundbreaking work at the Affymax Research Institute resulted in the discovery of peptide mimetics of erythropoietin and thrombopoietin. At Medikine, they have been taking this concept to a new level of sophistication and utility by engineering novel PEPTIKINES for multi-subunit cytokine receptors. As Medikine moves from PEPTIKINE discovery research into clinical development, the company’s leadership team is well prepared with the recent addition of Joseph Leveque, M.D., as president and chief medical officer, and Marcos Milla, Ph.D., as interim chief scientific officer. Dr. Leveque previously has held senior executive and therapeutic area leadership roles at Mirati Therapeutics, Synthorx, ARMO BioSciences, Bristol Meyers Squibb, and Amgen. Dr. Milla is currently a venture partner at Samsara BioCapital and was previously chief scientific officer at Synthorx, head of Therapeutics Discovery at Adaptive Biotechnologies, and head of Emerging Science and Innovation of Janssen Discovery Sciences. Research by Drs. Leveque and Milla at Synthorx to discover and develop a “non-alpha” IL-2 derivative led to Synthorx’s acquisition by Sanofi for $2.5 billion in late 2019. Dr. Milla commented, “With its versatile drug discovery platform, Medikine is well-positioned to develop transformative therapies for cancer and other serious diseases. I am particularly intrigued by the pharmacology of MDK-703, with its unique action on key T cell memory populations of great importance to find and destroy cancer cells―one that I believe could offer advantages over other cytokine-based therapies in development. I am thrilled to help realize the possibilities of this lead program and the rest of Medikine’s pipeline.” Medikine’s Pipeline of PEPTIKINE Therapeutics In addition to its lead product candidate, MDK-703, Medikine also has identified novel PEPTIKINES that activate the IL-2/15βγ receptor complex. The company is exploring their use for engineering bispecific cytokine mimetics with differentiated pro including an IL-7 and IL-2/15βγ dual receptor agonist, and a cell-targeted IL-2/15βγ attenuated receptor agonist. Medikine also has identified multiple high-affinity peptide ligands for both subunits of the IL-18 receptor that do not bind to the IL-18 decoy soluble receptor. Medikine is exploring the use of these peptide ligands as part of IL-18 PEPTIKINES. ABOUT MEDIKINE Medikine is a biopharmaceutical company with a mission to transform the discovery of oncology, autoimmune disorder, and infectious disease therapeutics by employing a versatile drug discovery platform that generates modular “PEPTIKINES”- peptide mimetics of cytokines that are smaller in molecular size than, and structurally unrelated to, the natural cytokines they emulate. These PEPTIKINES are engineered for low immunogenicity and are readily amenable to the incorporation of targeting and other pharmacological features. Medikine’s lead candidate, MDK-703, currently in a Phase 1 clinical trial in healthy volunteers, is an IL-7 PEPTIKINE fused to an immunoglobulin Fc-domain. MDK-703 emulates the beneficial properties of IL-7, a cytokine critical for maintenance of T cell responses. For more information, please visit . REFERENCES Gattinoni L, Speiser D, Lichterfeld M, et al. T memory stem cells in health and disease. Nat Med. 2017;23:18–27. doi:10.1038/nm.4241