Tiziana Life Sciences Plc plc (Nasdaq: TLSA) (“Tiziana” or the “Company”), a biotechnology company focused on innovative therapeutics for inflammatory, autoimmune and infectious diseases, announced today that it pursuant to an asset purchase agreement it has acquired all of the intellectual property relating to a nanoparticle-based formulation of Actinomycin D (Act D; a.k.a. Dactinomycin), from Rasna Therapeutics, Inc. (“Rasna”) to expand its pipeline for a consideration of an initial $120,000 upfront payment and milestone payments of up to an additional aggregate $630,000.
This formulation technology was invented by Dr. Kunwar Shailubhai when he was previously an executive officer at Rasna, which he remains a director.
Act D, an antibiotic drug, was approved initially for infectious diseases in the United States in 1964. Subsequently, this antibiotic was shown to exhibit anti-cancer activity in 1974 (1). Since then the drug has been used to treat various types of cancer, including Wilms tumor, rhabdomyosarcoma, Ewing’s sarcoma, trophoblastic neoplasm, and testicular cancer. The drug is on the World Health Organization’s List of Essential Medicines as the most effective medicines needed in a health system (2). Falini et al., reported in New England Journal of Medicine that intravenous administration of Act D could be used for treatment of patients with Acute Myeloid Leukemia (AML) carrying NPM1 gene mutation (3). Recent studies have also suggested that Act D, being a potent inhibitor of RNA synthesis, may have potential for treatment of COVID-19 patients (4). Currently, the drug is intravenously (IV) administered, which produces severe toxicities possibly due to excessive Cmax in blood during the first couple of hours after administration.
The nanoparticle-based Act D (NP-ACT D) is formulated such that the release of Act D is slow and Cmax in blood may be pre-adjusted to a desired level. In pharmacokinetics (PK) and safety studies in rats, free Act D or an equivalent dose of NP-Act D were intravenously administered side-by-side to compare PK, tolerability, and toxicity. Results from these animal studies indicated that the PK of NP-Act D was slow, and sustained for over 32 hours, whereas the PK in blood within an equivalent dose of free Act D activity was rapid. Importantly, another study comparing side-by-side free Act D with an equivalent dose of NP-Act D, showed 0% mortality in rats dosed with NP-Act D for up to 13 days. By contrast, mortality in rats dosed with free Act D began on 6th day, reaching >90% mortality on 13th day of the study. These results demonstrate that PK of IV administered NP-Act D is slow and sustained for extended period and it is relatively well-tolerated with minimal toxicities. However, safety and tolerability of NP-Act D needs to be evaluated in healthy volunteers prior to clinical studies.
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It is important to note that the Company has not, at the current time, conducted any clinical or pre-clinical research into the use of NP-ACT D as a treatment for COVID-19 but is basing its assessment for potential on research involving NP-ACT D with other strains of coronavirus.