Replicor announces post-mortem analysis of ALG-10133 failure
MONTREAL, March 30th, 2022 – Replicor Inc., a privately held biopharmaceutical company targeting functional cure for patients with chronic hepatitis B and D infection, announced the publication of its post-mortem analysis of the LNA-modified NAPs following the termination of their development by Aligos Therapeutics in the journal Molecular Therapy Nucleic Acids (see here). At dosing which yields 4-7 log10 reduction of HBsAg with Replicor’s NAPs REP 2055, REP 2139 and REP 2165, the LNA-modified analog of REP 2165 (ALG-10133) failed to show any meaningful HBsAg response in human patients (see here).
This published analysis describes the many artifacts inherent in the transfection-based tissue culture systems used by Aligos in their assessment of the antiviral activity of NAPs. These artifacts underly the disconnect between in vitro observations of apparent efficacy of LNA-modified NAPs and their inactivity in humans. The unsuitability of transfection for in vitro NAP analysis in HBV was previously established by Replicor in several independent collaborations with NAP compounds having validated in vivo activity.
Dr. Andrew Vaillant, CSO, Replicor commented, “We first described LNA-modified NAPs such as ALG-10133 twenty years ago – the termination of ALG-10133 for lack of antiviral effect demonstrates why this modification of NAPs was discarded by Replicor very early on in the NAP development process. The inhibition of NAP function by the LNA-modification is caused by its inhibition of oligonucleotide flexibility well known in the field for more than a decade. Oligonucleotide flexibility is a key feature of NAP activity well documented in more than 20 publications by Replicor since 2006. Early signals of the failure of ALG-10133 were present in the in vitro and pre-clinical data publicly presented by Aligos.”
Dr. Vaillant went on to emphasize that all of Replicor’s in vitro and in vivo studies on NAPs were conducted with multiple independent expert academic labs. The activity of NAPs observed in all its clinical trials has also been validated with independent expert test laboratories.
Replicor is a privately held biopharmaceutical company with the most advanced animal and human clinical data in the development of the cure for HBV and HDV. The company is dedicated to accelerating the development of an effective treatment for patients with HBV and HBV/HDV co-infection. For further information about Replicor please visit our website at www.replicor.com.