TD-6450 / Innoviva, Trek Therapeutics - LARVOL DELTA

INHIBITORS OF THE NON-STRUCTURAL PROTEIN 5A: FROM THE CONTROL OF HEPATITIS C TO THAT OF MALARIA? (EHA 2024) - "We have shownthat TD-6450, an NS5A inhibitor of hepatitis C virus (iNS5AHCV) kills the asexual stages, responsible forsymptoms and stiffens mature gametocytes of Plasmodium falciparum, responsible for transmission...The 3 NS5Ai (velpatasvir, elbasir, ravidasvir) are as effective on either P. falciparum artemisinin-sensitive (F-32TEM) and artemisinin-resistant (F32-ART) strains with IC50s lower than 2µM... All iNS5AHCV tested are active against P. falciparum (class effect). Ravidasvir, recently approved for thetreatment of hepatitis C in Indonesia (at a very low cost), is effective against the different stages of P. falciparum. If this multi-stage antimalarial activity is clinically confirmed, the addition of ravidasvir to combinedantimalarial treatments would generate multi-therapies that are resilient to resistance and effective intransmission blocking."

Hepatitis C • Hepatology • Infectious Disease • Inflammation • Malaria

Safe drugs with high potential to block malaria transmission revealed by a spleen-mimetic screening. (PubMed, Nat Commun) - P1 | "NITD609, an orally administered PfATPase inhibitor with known effects on P. falciparum, killed and stiffened transmission stages in vitro at nanomolar concentrations. Pharmacokinetic modelling showed that these concentrations can be reached in the plasma of subjects receiving short courses of TD-6450. This physiologically relevant screen identified multiple mechanisms of action, and safe drugs with strong potential as malaria transmission-blocking agents which could be rapidly tested in clinical trials."

Journal • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Malaria

Two safe and orally administered drugs to block the transmission of malaria inducing splenic retention of mature gametocytes (ASTMH 2022) - "Concentration-time simulation ofTD-6450 in healthy volunteers showed that these concentrations can be reached in almost allsubjects with a single-dose oral administration. NITD609 and TD-6450 are strong candidatesfor clinical trials in human volunteers."

Infectious Disease • Malaria

A Study of Faldaprevir, TD-6450 and Other Antivirals in Participants With Genotype 1b Hepatitis C Virus Infection (clinicaltrials.gov) - P2; N=25; Recruiting; Sponsor: Trek Therapeutics, PBC; N=15 ➔ 25

Enrollment change • Biosimilar • Hepatitis C Virus • Immunology