XtalPi Names First siRNA Preclinical Candidate for IgA Nephropathy

AI and robotics-driven drug and materials discovery company XtalPi announced the nomination of its first internally developed small interfering RNA (siRNA) preclinical candidate (PCC) for the treatment of immunoglobulin A nephropathy (IgAN). The company achieved this milestone in nine months, utilizing its Kodexia™ platform which integrates generative AI and first-principles modeling.

IgAN is one of the world's most common primary glomerular diseases, affecting an estimated 10 million people globally. The condition can lead to progressive renal decline and kidney failure. The new candidate's preclinical data demonstrated significant potency and durability.

According to XtalPi, the developed siRNA candidate exhibited "subnanomolar silencing potency" in laboratory tests, achieving an IC50 tens of times lower than corresponding values for two clinical-stage reference molecules targeting the same pathway. Furthermore, a single dose was shown to maintain robust target-protein suppression for months in non-human primates.

XtalPi utilized the Kodexia™ platform to identify a previously unexplored active target region and jointly optimize the siRNA sequence and chemical modifications. The company also stated that it was able to address "freedom-to-operate" considerations early in the design phase.

XtalPi plans to advance the candidate towards clinical development and seeks partnerships for developing next-generation RNA interference therapies.