Transcripta Bio & Synfini Collaborate to Identify a Lead Candidate Against a Key Driver of Huntington’s Disease Progression in a Matter of Weeks

Transcriptome-scale target biology and AI-driven automated chemistry produced a validated lead candidate in weeks, against an industry standard of 12-18 months

PALO ALTO, Calif. & MENLO PARK, Calif.--(BUSINESS WIRE)--Transcripta Bio, an AI-powered drug discovery company focused on neurological and neuromuscular disease, and Synfini, Inc., an agile AI foundry for small-molecule drug discovery, today announced results from a research collaboration that has produced a validated-quality lead candidate directed at MSH3, a gene increasingly understood to drive the somatic repeat expansion that paces the progression of Huntington’s disease. The companies reached the milestone in a matter of weeks.

Industry benchmarks place the path from hit identification to candidate nomination at approximately 12-18 months. Working together, Transcripta Bio and Synfini compressed the discovery and chemistry cycle into a small fraction of the time, in one of the most difficult areas of drug development and against a disease that has no approved therapy capable of altering its course.

Huntington’s disease affects an estimated 41,000 symptomatic Americans, with more than 200,000 additional individuals at risk of inheriting it. The disease is autosomal dominant: every child of an affected parent has a 50 percent chance of carrying the gene. Symptoms typically begin between the ages of 30 and 50 and worsen over 10 to 25 years. The causative gene was identified in 1993. Thirty-three years later, there is still no approved treatment that halts, slows or reverses the disease, only therapies that manage its symptoms.

“In Huntington’s disease, the biology has been studied for decades, and chemistry has been the limiting step,” said Chris Moxham, Ph.D., founder and CEO of Transcripta Bio. “Our platform identified compounds that moved the target in the right direction. Synfini turned that signal into molecules we could test, and it did so in weeks rather than years.”

What each company contributed

Transcripta Bio supplied the target biology and the compound signal. Its discovery engine converts every measurement, both what a disease does to cells and what a drug does to cells, into transcriptomic data so that the two can be compared directly. A Drug-Gene Atlas profiles how compounds shift gene expression in disease-relevant cell types. Conductor AI, a machine learning system trained on more than one billion gene responses, searches that space for molecules that reverse the disease signature. Measuring the full transcriptome rather than a single readout is what surfaced compounds that suppress MSH3 expression via a novel mechanism, a signal a narrower assay would not have detected.

Synfini supplied the chemistry. Its agile AI chemistry foundry closes the design-make-test-analyze loop within a single integrated system: SynDesign for AI-driven molecular design, SynRoute for synthesis route planning, SynJet for high-throughput chemistry and SynBuild for robotic automation. Most discovery platforms are design-only or biology-first and transfer their outputs to a contract laboratory. Synfini designs, makes and tests in-house, reducing the synthesis step that typically extends each iteration cycle from days to months. Transcripta Bio’s starting compounds entered that loop and returned as a lead series with the potency and property profile the collaboration was targeting.

“Transcripta Bio identified and validated the disease biology and the starting compounds,” said Doug Donzelli, CEO of Synfini. “From those starting points, we generated and evaluated more than five million synthetically accessible designs using our predictive AI and molecular modeling tools and sent the strongest candidates directly to our AI-driven robotic synthesis. Linking two complementary AI platforms took us from validated biology to a validated-quality lead candidate in a matter of weeks.”

MSH3 is among the most closely followed targets in Huntington’s disease research. Human genetics studies have repeatedly identified it as a modifier of somatic instability and disease severity in both Huntington’s disease and myotonic dystrophy type 1, and it acts upstream of the CAG repeat expansion that accumulates in vulnerable neurons over a patient’s lifetime. Slowing that expansion is one of the field’s leading hypotheses for altering the course of the disease rather than treating its symptoms.

About Transcripta Bio

Transcripta Bio is an AI-powered drug discovery company developing treatments for neurological and neuromuscular diseases. The company's closed-loop discovery engine uses transcriptomic signature matching to identify drug candidates whose molecular signatures are the inverse of patient-derived disease signatures, enabling a faster, more capital-efficient path to the clinic. Transcripta Bio's pipeline spans four programs including Myotonic Dystrophy, Facioscapulohumeral Muscular Dystrophy (FSHD), Autism Spectrum Disorder (ASD), and Huntington's Disease (HD). The company is based in Palo Alto, California. For more information, visit transcriptabio.com.

About Synfini

Synfini, Inc. is revolutionizing small molecule drug discovery with its AI Cloud Foundry, a platform that integrates artificial intelligence, chemistry automation, and cloud-native workflows to generate better molecules, faster. Founded by domain experts in synthetic chemistry, machine learning, and drug development, Synfini partners with biotech and pharmaceutical companies to bring forward breakthrough therapies with greater speed and precision.