Taking On Big Competitors with an Oral Therapy to Treat Achondroplasia

·23 min·2 clips

One in five children with achondroplasia may need major brainstem surgery by age two due to bone growth complications.

The episode begins with host Daniel Levine introducing the topic of achondroplasia and Tyra Biosciences' experimental once-daily oral medicine. Guest Todd Harris, CEO of Tyra, defines achondroplasia as the most common form of dwarfism, caused by a genetic alteration on the FGFR3 gene where glycine swaps to arginine at site 388. He describes the condition's effects beyond short stature, including a higher frequency of sudden infant death syndrome and complications requiring surgery in one in five children by age two. Harris notes social challenges but also community pride. When asked about community ambivalence toward pharmacological intervention, he emphasizes Tyra's focus on the science of targeting FGFR3. Levine lists competitors like Biomarin, Ascendis, and BridgeBio, prompting Harris to explain Tyra's competitive edge: their drug is a selective FGFR3 inhibitor taken orally, unlike others that hit multiple FGFR isoforms and cause side effects. Harris details Tyra 300's development, starting with preclinical validation of selectivity and safety, then treating over 100 people in cancer trials. He highlights reduced side effects like hyperphosphatemia and nail disorders compared to non-selective inhibitors. The discussion shifts to development paths: Tyra just dosed its first child in a phase two study for achondroplasia and is also in phase two for intermediate-risk non-muscle invasive bladder cancer. Harris explains bladder cancer management challenges, including high recurrence rates despite surgery, making an oral agent appealing. He mentions Tyra's SNAP discovery engine, which uses in-house protein crystallography for rapid iterations to design selective inhibitors. Harris notes the company chose FGFR3 due to unmet need and toxicity issues with existing drugs. On financing, he says Tyra has raised over $350 million, has cash through 2027, and focuses on two key programs. The episode concludes with thanks and promotional information.

As heard by us

A focused RareCast discussion on FGFR3 selectivity and Tyra's experimental oral achondroplasia therapy.

Achondroplasia gets a tightly focused RareCast discussion through Todd Harris, CEO of Tyra Biosciences, who frames the condition around genetic diagnosis, bone growth, and drug development.

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Why you'd press play

You want achondroplasia explained through Tyra Biosciences' experimental once-daily oral medicine and the FGFR3 biology shaping its design.

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