Leapfrog Bio is employing a novel approach to cancer drug development by screening clinical-stage drugs to identify targeted therapies for specific cancer genotypes. The company's Precision PGx platform focuses on drugs that have already passed Phase II clinical trials, aiming to reduce the time and risk associated with traditional drug development.
Addressing Translational Development Challenges
Tomas Babak, PhD, founder of Leapfrog Bio, experienced firsthand the challenges of translational development while at Celgene. "I got a chance to work on drugs that were going straight into phase one clinical trials... Long story short, it all failed," Babak said, highlighting the high failure rate of drugs entering clinical trials. Approximately 90% of drug candidates fail, and those that succeed typically take 10-15 years and cost around $1 billion.
To improve these odds, Leapfrog Bio developed a drug-screening platform using genetically engineered cells carrying known oncogenic mutations. This platform screens drugs that have already reached Phase II, focusing on identifying safe drugs for patient populations with specific genotypes likely to respond.
Precision PGx Platform
The Precision PGx platform screens clinically actionable molecules to target major solid tumor markets. Leapfrog CEO Greg Vontz stated, "We have now conducted internally over 20 or more cancer cell-derived xenograft (CDX) experiments in-house, and every one of these that the platform has predicted has read out extremely well in line with or better than current targeted therapy."
Targeting Loss-of-Function Mutations
A key aspect of Leapfrog's platform is its ability to discover therapeutic options for cancers caused by loss-of-function mutations. Approximately two-thirds of cancers result from such mutations, yet only about 2% of these cancers are treatable with approved drugs.
Vontz contextualizes Leapfrog’s approach with PARP inhibitors, noting that while they exploit synthetic lethality in tumors with BRCA1 or BRCA2 mutations, Leapfrog aims to expand this concept to other loss-of-function mutations. "We don’t really understand cells very well at all, or cancer cells for that matter, so we have to ask the cells," Vontz explained.
CODA-PGx Platform
Babak’s innovation lies in the clinically optimized driver-associated pharmacogenomic (CODA-PGx) platform. This platform replicates known synthetic lethal interactions, such as PARP with BRCA, and has made new discoveries. "This took a lot of work to figure out—doing [the screen] in a context where that perturbation that we put in replicates a loss of tumor suppressor biology," Babak said.
By limiting the screening to Phase II candidates, Leapfrog aims to accelerate the development of targeted therapies. Vontz added, "This allows us to potentially bring a drug to the market in half the time and, we believe, with considerably less risk than starting with a target ID and building a molecule from scratch."
Clinical Plans
Leapfrog has selected a lead drug and plans to initiate clinical trials in lung, colon, and bladder cancers. Vontz believes the frequency of loss-of-function mutations in the targeted tumor suppressor genes indicates significant potential. Babak has filed for five methods of treatment patents unrelated to PARP inhibitors.
The next step for Leapfrog is to complete Series A financing to support future clinical trials. With only 2% of the catalog of Phase II drugs screened, Leapfrog Bio anticipates identifying numerous potential cancer drugs.
