Tyra Biosciences is weeks away from the first clinical test of an unusual three-pronged strategy: use one oral drug to turn down the same molecular switch across two cancers and a rare bone-growth condition.
But a decade ago, co-founders Todd Harris and Daniel Bensen were merely neighbors in San Diego whose kids were friends.
“If I walk out my front door, I see Dan's house,” said Harris, Tyra’s CEO.
At first, neither realized the other worked in biotech until they ran into each other at the Johnson & Johnson biotech incubator, JLABS, in San Diego. That meeting led to shop talk and, eventually, a desire to work together.
“Both of us just quit our jobs and jumped off the deep end and started this company together back in 2018,” Harris said.
Now, their lead candidate, the oral FGFR3 inhibitor dabogratinib, is in development for three seemingly unrelated indications: two types of urothelial cancer and achondroplasia, the most common type of dwarfism.
“Whenever I tell people we have the same drug and it works for bladder cancer and achondroplasia, they sort of look at me with a very confused look,” Harris said. “There’s nothing that would suggest that those should be linked.”
Yet all three indications are driven by mutations in the FGFR3 gene.
In urothelial cancer, activating FGFR3 alterations can keep the receptor signaling “always on,” driving abnormal cell growth. Those alterations are common in low-grade bladder cancer and upper tract urothelial carcinoma, Harris said.
In patients with achondroplasia, a different gain-of-function FGFR3 mutation makes the receptor overly active, slowing cartilage and bone growth at the growth plates.
“It’s very disparate biology, but all linked by the same gene,” Harris said.
Dabogratinib turns FGFR3 activity down by different degrees, depending on the dose.
“You can turn it all the way off, you can turn it mostly off, you can turn it midway off,” Harris said.
Tyra’s current phase 2 studies will determine optimal dosages for each indication, with: dose response data in non-muscle invasive bladder cancer expected in September; initial achondroplasia data by the end of the first quarter of 2027; and initial low-grade upper tract urothelial carcinoma data in 2027, according to the company’s Aug. 4 clinical update.
Tyra is developing other FGFR-targeting drugs for cancer, too, including an FGFR1/2/3 inhibitor and an FGFR4/3-biased inhibitor.
A trifecta of unmet needs
When they founded Tyra, Harris and Bensen were driven by a desire to develop a small molecule for unmet needs in oncology.
“That led us pretty quickly to the target of FGFR3,” Harris said.
In the case of non-muscle invasive bladder cancer, the standard of care can be burdensome, involving invasive treatments directly in the bladder — and the chance of recurrence is high. An oral therapy could change that, Harris said.
Their pursuit of FGFR3 also led the company to an unmet need in achondroplasia, which currently has just two approved therapies, BioMarin Pharmaceutical’s Voxzogo and Ascendis Pharma’s newly approved Yuviwel, which both target FGFR3 via a different pathway. BridgeBio submitted an NDA in August for a third drug, the oral FGFR3 inhibitor infigratinib.
However, each of these three have limitations, according to Harris. Voxzogo and Yuviwel are both injectables and the growth they provide patients is “modest” in his view. While infigratinib is oral, its dose limitations also limit height benefit, he said.
Tyra hopes its approach can deliver greater height gains while also addressing clinical complications associated with achondroplasia, including disproportionality, spinal stenosis and limitations in reach and gait, Harris said.
“We want to be able to hit a dose that gets to a level of benefit that hasn't been achieved with the three products that have come before,” he said.
The third indication presents a different opportunity.
Harris believes dabogratinib’s first approved indication could be in low-grade upper tract urothelial carcinoma because it's a relatively rare disease with poor treatment options. Treatment can involve removing the affected kidney and ureter, and Harris said the smaller patient population could allow Tyra to pursue approval with a smaller clinical data set.
“A kidney-sparing pill could really change the lives of these patients,” he said.
Ultimately, Harris said that is what he and Bensen set out to do with Tyra: develop drugs that deliver more than “incremental” changes.
“What we’re setting out to do, if we can do it, will just truly change the standard of care and change the game,” he said.
