Radically different
Chris Moxham, PhD, has been a “drug hunter” for three decades, building data-driven platforms as vice president of quantitative biology at Eli Lilly, and CSO of Folcrum Therapeutics, in recent years.
“Technology is now advancing to allow us to interrogate the transcriptome, which is a phenomenal blueprint for cell state and fate,” he told GEN Edge.
Moxham currently leads Transcripta Bio as founder and CEO. The AI-driven drug discovery start-up is developing small molecule therapeutics to modulate gene expression disease signatures.
Transcripta has now announced a $24 million funding raise to advance IND-enabling studies and clinical preparation of its neurological disease portfolio, including autism spectrum disorder (ASD) and facioscapulohumeral muscular dystrophy (FSHD). Mayo Clinic and Omnimed will join JAZZ Venture Partners, BlueYard Capital, and a group of life sciences family offices, as investors.
Phase II clinical trials are “where the rubber meets the road,” says Moxham. He emphasizes that de-risking therapies early is key to improving drug discovery success rates, which often fall below 10%.
Founded in 2023, the Palo Alto-based company currently houses fifteen employees. “This isn’t a company you could have built five years ago,” highlighted Moxham. He cites the intersection of scalable sequencing technology, compute power, and lab automation among the factors enabling the rise of AI-driven biology.
While much of the field has defined transcriptome AI models as the “virtual cell,” Moxham emphasizes Transcripta’s translational focus.
The company’s proprietary platform takes a three-pronged approach. First, disease signatures are identified using patient-derived single cell RNA-seq (scRNA-seq) data. An in-house generated “drug atlas” then measures the effects of small molecule perturbations across 80% of the transcriptome, capturing full dose-response profiles in diverse cellular contexts, including glutamatergic and motor neurons, fibroblasts, and keratinocytes. These data power AI models that identify promising compounds that can therapeutically modulate gene expression.
Transcripta’s neurological disease pipeline is structured as a tiered portfolio of novel molecules and repurposed clinical-stage assets, with the latter benefiting from existing human safety data that can shorten development timelines and lower costs.
In 19q12 syndrome, a form of ASD, the team demonstrated that entrectinib, an FDA-approved oncology drug, could reverse disease when given at low concentrations. One patient case demonstrated clinical benefit within nine months after taking the drug.
In Huntington’s disease, Transcripta’s platform identified novel molecules that could downregulate DNA mismatch repair protein and validated therapeutic target, MSH3. The company plans to file an IND next year. Transcripta is also pursuing pre-IND research in FSHD and myonic dystrophy.
Moxham emphasizes the generalizability of the platform. “We are now looking at hundreds of diseases with this type of approach,” he says.
Transcripta plans to introduce another cohort of therapeutic programs by Q2 of 2027.
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Dozens of researchers funded by the federal Agency for Healthcare Research and Quality received notices last week that they would not receive future installments of funding for their ongoing research grants. While frustrating, the development was largely not a surprise to these researchers, many of whom had been waiting months for renewed funding or been unable to get explanations as to why the funding spigots had run dry from staffers at the agency.
The notices punctuated nearly a year of uncertainty for health services researchers funded by AHRQ and left those who lost funding concerned about the future of their field. AcademyHealth, a professional organization representing health services researchers, has confirmed at least 78 grants worth $200 million have been affected. In all, those grants had $109.2 million in funding remaining, it estimated.
Grant recipients were told in a letter of “non-award” that “AHRQ is adjusting its discretionary health services research award portfolio in order to better prioritize agency resources towards the above-mentioned priorities to best serve the interests of the Federal Government,” according to one such letter reviewed by STAT. The letter states the agency is prioritizing research on patient safety, antibiotic resistance, AI, long Covid, nutrition, and understanding autism, among others.
Two children with an ultra-rare epilepsy linked syndrome called SCN2A-developmental and epileptic encephalopathy (DEE) have been treated with personalized antisense oligonucleotide (ASO) therapies for their specific genetic mutations.
Both children, 9 and 14-year old boys, experienced significant improvements from the therapy. They both had less seizures and could cut back or stop some of the anti-seizure medications. They also achieved improvements in language and motor skills, with the older patient walking independently for the first time after being treated.
SCN2A‑DEE is a severe early‑onset epilepsy syndrome caused by pathogenic variants in the SCN2A gene, which encodes a voltage‑gated sodium channel in excitatory neurons. These variants typically lead to DEE with difficult‑to‑control seizures and profound neurodevelopmental impairment and impact around 16,000 people in the U.S.
Like many rare diseases, children with SCN2A‑DEE often have different mutations, albeit in the same gene. “The therapy is deliberately designed to target the individual’s genetic diagnosis,” said principal investigator Olivia Kim‑McManus, MD, associate professor of neurosciences at UC San Diego School of Medicine and director of the Rady Precision Therapeutics Neuro-Interventional Program at Rady Children’s Hospital San Diego, in a press statement. “The ASO modifies genetic expression and what proteins are expressed.”
This study, which is published in Nature Medicine, involved investigation, design, and treatment of the two boys in parallel. To begin with, the researchers designed allele‑selective ASOs targeting heterozygous intronic SNPs in SCN2A to suppress the mutant transcript while sparing the wild-type copy.
They then ran two parallel first‑in‑human N-of-1 trials for the two boys with individualized dosing. The primary endpoints were seizure frequency and neurodevelopment, plus phenotype‑tailored measures like impact on autism-like symptoms, movement problems, and gastrointestinal function.
Notably, the team scanned 19 infants with related SCN2A disorders and found that three of them could be eligible for treatment with the same ASO as the one given to the 14 year old boy in the future, as it is designed to treat a number of different mutations on the SCN2A gene.
Both boys had fewer seizures on the customized drug. The younger child had an estimated 26% reduction and could come off phenytoin treatment without losing overall control, while the older child’s seizures fell by about 90%, with longer seizure‑free stretches and less need for rescue medication.
Families and clinicians also saw improvements in motor function, abnormal movements, communication and gastrointestinal symptoms, and no serious safety signals emerged from the study.
“We’ve seen changes across the board, showing that targeting the root genetic cause can produce measurable improvement,” said Kim‑McManus.
One key improvement was that the older child began to walk on his own for the first time. “Since then, he’s been walking independently,” said Kim-McManus. “When we really think about precision therapy in a personalized way, you can’t get more personalized than that.”
The researchers are now hoping to use a similar approach to treat more children with SCN2A-related disorders as well as other monogenic conditions.
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