Kevetrin (thioureidobutyronitrile) / Innovation Pharma - LARVOL DELTA

Naoxintong capsule accelerates mitophagy in cerebral ischemia-reperfusion injury via TP53/PINK1/PRKN pathway based on network pharmacology analysis and experimental validation. (PubMed, J Ethnopharmacol) - "This study demonstrates that NXT promotes mitophagy in CIRI through restraining p53 and promoting PINK1/PRKN in vivo and in vitro."

Journal • Cardiovascular • CNS Disorders • Ischemic stroke • Reperfusion Injury • Vascular Neurology

Aquaporin 1 Facilitates Ferroptosis, M1 Polarization, Mitochondrial Dysfunction, and Autophagy Damage on Lipopolysaccharide-Induced Macrophage Through Down-Regulation of P53 Signaling Pathway. (PubMed, DNA Cell Biol) - "Interestingly, this phenomenon was markedly alleviated by Kevetrin hydrochloride (70 μM), a P53 agonist...Indeed, inhibition of P53 expression by PIF treatment dramatically reversed this effect on the basis of LPS+si-AQP1. Therefore, we concluded for the first time that AQP1 can promote ferroptosis, M1 polarization, mitochondrial dysfunction, and autophagy impairment by inhibiting the expression of P53 in LPS-stimulated RAW264.7 cells, and AQP1 or P53 may be considered as a crucial determiner that can regulate the biological behavior of RAW264.7 cells stimulated by LPS."

Journal • Metabolic Disorders • AQP1

Discovery of a novel Kevetrin analog as a potential therapeutic for ovarian cancer (AACR 2023) - P1 | "Kevetrin has shown promise in preliminary clinical studies in solid tumor patients. The new analog 900 is >100 fold more potent than Kevetrin and holds great promise to be developed further for ovarian and other mechanistically relevant cancers."

Oncology • Ovarian Cancer • Solid Tumor • ANXA5 • CASP3 • CASP7 • CCNA2 • CCNE1 • CDKN1A • HDAC6 • HSP90AA1

Inhibition of mycobacteria proliferation in macrophages by low cisplatin concentration through phosphorylated p53-related apoptosis pathway. (PubMed, PLoS One) - "DDP may be a new host-directed therapy for tuberculosis treatment, as well as the p53 promoter Kevetrin hydrochloride."

IO biomarker • Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • BAX • BCL2

Kevetrin induces apoptosis in TP53 wild‑type and mutant acute myeloid leukemia cells. (PubMed, Oncol Rep) - "Gene expression profiling revealed a common core transcriptional program altered by drug exposure and the downregulation of glycolysis, DNA repair and unfolded protein response signatures. These findings suggest that kevetrin may be a promising therapeutic option for patients with both wild‑type and TP53‑mutant AML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Innovation Pharmaceuticals Announces Publication of Independent Research on Kevetrin, the Company’s p53 Drug Candidate, in Oncology Reports (GlobeNewswire) - "In the recently published Kevetrin AML research, linked below, Kevetrin treatment was shown to arrest cell growth and cause cell death (apoptosis) in AML cells. Multiple p53 targets, several cellular processes and oncogenic pathways were also shown to be positively impacted by Kevetrin. Kevetrin was further shown to exhibit preferential cytotoxic activity against leukemia blast cells, while largely not affecting the immune microenvironment, supporting a less toxic drug profile."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

[VIRTUAL] Development of TP53 targeted treatment strategy in esophageal squamous cell carcinoma based on clinical information, TP53 mutation status and p53 RNA expression level (AACR-II 2020) - "Drugs which have different effects were used, e.g. Fluorouracil, Cisplatin, APR-246 (which reactivates mutant p53), kevetrin (which activates wild p53). The function of ESCC is thought to differ depending on TP53 mutation status, and it is suggested that prognosis may be improved by the selection of drugs according to TP53 mutation status. We integrate and analyze clinical information and TP53 DNA, RNA status from ESCC specimens, and report this theme along with the relevant literature."

Biomarker • Clinical • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Thoracic Cancer • TP53

Cellceutix prepares phase 2a ovarian cancer trial of kevetrin, a novel p53-modulating drug candidate, based upon phase 1 topline data (MarketWired) - "The Phase 1 dose-escalation study, with dosing amounts ranging from 10mg/m2 to 750mg/m2, met its primary endpoint in showing no clinically significant adverse effects of Kevetrin in patients based on clinical laboratory parameters through all dosing levels and across the duration of treatment....Our near-term focus is now on preparing for a Phase 2a trial of Kevetrin in treating late-stage ovarian cancer, which we anticipate will start in the fourth quarter this year," said Cellceutix President and Chief Medical Officer Dr. Arthur P. Bertolino."

Anticipated new P2 trial • P1 data • Oncology • Ovarian Cancer

Cellceutix requesting meeting with FDA on Kevetrin for pediatric retinoblastoma (Digital Journal) - "Cellceutix Corporation...is requesting a meeting with the U.S. Food and Drug Administration (FDA) to discuss the advancement of the Company's anti-cancer drug candidate Kevetrin for the treatment of pediatric retinoblastoma...

Anticipated FDA event • Oncology

Cellceutix clinical trial of anti-cancer drug kevetrin entering eighth cohort (The Wall Street Journal) - "Cellceutix Corporation...report[ed] that the safety committee overseeing the Phase 1 clinical trial evaluating Cellceutix's lead anti-cancer drug Kevetrin for solid tumors being conducted at Dana-Farber Cancer Institute and Beth Israel Deaconess Medical Center has approved dosing for the eighth cohort. The dosing was been increased approximately 33 percent from the seventh cohort to 215 mg/m2. Enrollment for the eighth cohort is expected to commence shortly."

Trial status • Oncology

Cellceutix and Kevetrin aligning with the Pharmacyclics growth curve (SeekingAlpha) - “The trial is evaluating Kevetrin in solid tumors in late-stage cancer patients, a perfect patient population for Cellceutix to potentially glean efficacy data while evaluating safety and maximum tolerated dose.”

Review • Oncology

Innovation Pharmaceuticals highlights preclinical data by independent cancer researchers supporting p53 drug candidate Kevetrin’s potential in treating acute myeloid leukemia (GlobeNewswire) - "Building on Kevetrin data in AML presented at the 2017 European Hematology Association (EHA) Annual Meeting, a group of independent cancer researchers recently presented additional data at the June 2019 EHA Annual Meeting, and at the October 2019 Italian Society of Hematology Annual Meeting. Results showed that Kevetrin alters cellular metabolism and several key genes, including TP53 and MYC, both of which when dysfunctional are implicated in many types of cancers, including AML."

Preclinical

Innovation Pharmaceuticals Provides Corporate Update Highlighting Clinical Pipeline Progress and Business Development Activities (GlobeNewswire, Innovation Pharmaceuticals, Inc.) - BEVERLY, Mass., July 29, 2019 (GLOBE NEWSWIRE) -- Innovation Pharmaceuticals (OTCQB:IPIX) (“the Company”), a clinical stage biopharmaceutical company, is pleased to provide a corporate update highlighting recent accomplishments, clinical pipeline progress, and ongoing business development activities across its first-in-class drug candidates, Brilacidin and Kevetrin. “A significant milestone was recently achieved with our execution of a global licensing agreement with Alfasigma—an Italy-based multinational pharmaceutical company with robust R&D and manufacturing capabilities, employing 3,000 people and generating 2018 revenues in excess of €1 billion—granting them worldwide rights to develop locally-administered Brilacidin in Ulcerative Proctitis/ Ulcerative Proctosigmoiditis (UP/UPS).

Clinical • Commercial

Innovation Pharmaceuticals provides corporate update highlighting clinical pipeline progress and business development activities (Innovation Pharma Press Release) - "'Kevetrin Dampens MYC Expression and Cellular Metabolism in Acute Myeloid Leukemia'—in collaboration with independent cancer researchers; presented at the European Hematological Association (EHA) 2019 Annual Meeting. Results showed Kevetrin alters cellular metabolism and several key genes, including MYC, which when dysfunctional is implicated in many types of cancers."

Preclinical

KEVETRIN DAMPENS MYC EXPRESSION AND CELLULAR METABOLISM IN ACUTE MYELOID LEUKEMIA (EHA 2019) - "GSEA of microarray data showed that kevetrin-treated cells shared the downregulation of glycolysis, DNA repair, unfolded protein response and MYC target gene sets (Figure).Conclusion Our results show kevetrin alters several key genes and cellular metabolism. Along with cellular data, this study could provide a rationale for an experimental trial in AML patients, especially those carrying TP53 mutation who actually have very few therapeutic options."

Innovation Pharmaceuticals to Attend 2019 BIO International Convention, June 3-6 (GlobeNewswire, Innovation Pharmaceuticals, Inc.) - Innovation Pharmaceuticals plans to leverage the conference to continue to build and strengthen business development relationships across its clinical pipeline, which includes: Brilacidin, an immunomodulatory drug candidate with anti-inflammatory and antibiotic properties granted Fast Track designation by the Food and Drug Administration (FDA); and Kevetrin, an FDA Orphan Drug-designated p53-modulating anti-cancer drug candidate. “Both Brilacidin and Kevetrin are Platform drug candidates with multiple therapeutic applications given unique mechanisms of action and properties.

Clinical • Commercial • Regulatory

Innovation Pharmaceuticals Reports p53 Drug Candidate Therapeutic Potential Further Supported by Academic Research in Leukemias and in Combination with Cancer Immunotherapies (GlobeNewswire, Innovation Pharmaceuticals, Inc.) - "Innovation Pharmaceuticals (OTCQB:IPIX) (“the Company”), a clinical stage biopharmaceutical company, is pleased to report recent academic and pre-clinical research further supports the therapeutic potential of Kevetrin, the Company’s p53 drug candidate, in leukemias and in combination with cancer immunotherapies."

Combination therapy • Preclinical