Mapping first steps toward scaling genetic medicines: C-Path’s Romero on the BioCentury Show

One to Millions will begin with shared ASO safety data, but its ambitions extend far beyond rare disease

The Critical Path Institute’s One to Millions Initiative is using individualized rare disease therapies as the starting point for a development framework that could ultimately extend across all genetically defined diseases.

The initiative seeks to bring form to FDA’s Plausible Mechanism Framework by standardizing how evidence and methods can be reused across therapies and patients.

On The BioCentury Show, C-Path CEO and CSO Klaus Romero said the principal bottleneck is no longer the ability to design therapies for individual patients. It is the absence of a standardized regulatory and development system that can translate one success into many.

“We’re not reinventing the wheel. We are trying to maximize what has been done into a joint movement that can meet the vision of what FDA laid out in the guidance,” Romero said.

With experience building public-private consortia and regulatory science tools, C-Path plans to bring companies, academics, patient groups, and regulators together to share data and address recurring development bottlenecks.

The initiative will begin with antisense oligonucleotides, a relatively mature genetic modality with enough experience across programs to support cross-program learning. One of its first planned deliverables is a shared safety database.

The goal is to use aggregated safety data and analytical tools to reduce the need to repeat the same preclinical studies for every individualized therapy, shortening development timelines and lowering costs.

“Do you really need to repeat the same primate studies all the time, or can you use novel advanced methods to confirm the signals in the first pass to make the efficient and scientifically sound evidence that you need to demonstrate that early efficacy?” said Romero.

By standardizing drug development for genetic diseases, One to Millions could make individualized medicines economically viable.

Although rare diseases stand to benefit most immediately, Romero said C-Path eventually wants to create a framework that can be applied to all genetically defined diseases.

He pointed to Parkinson’s disease, which has been increasingly segmented by causal mutations, creating subtypes with a “similar rare disease situation.”

“It’s not so much about the frequency of a given condition, but the specificity of the potentially druggable mutation that could be the target for these technologies,” added Romero.