Tyra Crystallizing The First Oral FGFR3 Therapy For Achondroplasia

By Ray Dogum, Chief Editor, Drug Discovery Online

Achondroplasia is the most common form of short-limbed dwarfism and is caused by a genetic mutation in the FGFR3 gene. It affects about 1 in 25,000 births worldwide. There are very few treatments for this rare genetic condition.

Although rare, I have a family member who was diagnosed with achondroplasia when he was born and seeing how challenging their day-to-day can be made this story personal.

Treating Achondroplasia

If you’ve followed this indication closely, you know the biology: a single gain‑of‑function mutation in FGFR3 chronically over‑brakes endochondral bone growth. That mechanistic clarity drove the development of Voxzogo (vosoritide), a daily injection that increases annualized bone growth and, in 2021, became the first FDA‑approved treatment for children with achondroplasia who have open growth plates. Still, daily injections are a heavy lift for families, not to mention the cost to treat patients. Thankfully, for many families with good health insurance in the US, much of the $30,000 per month treatment is covered. Unfortunately, for some families, the treatment is simply unaffordable or inaccessible. 

Discovering Tyra’s Dabogratinib

Enter Tyra Biosciences with dabogratinib (formerly TYRA‑300), a once‑daily oral drug and FGFR3‑selective inhibitor that has advanced into Phase 2 (BEACH301) in children ages 3–10 with open growth plates. The company announced the first child dosed in August 2025; the program holds FDA Orphan Drug Designation (2023) and Rare Pediatric Disease Designation (2024) and received IND clearance to proceed with BEACH301 in late 2024.

What’s distinctive here isn’t just the molecule; it’s the process behind its discovery. Tyra’s proprietary discovery platform, SNÅP, turns structural biology data into a high‑throughput discovery engine, where crystal structures, focused cellular assays, and iterative medicinal chemistry are stitched into a tight design‑test‑learn loop. Tyra describes the output as sequential structural “SNÅPshots,” real‑world interactions that guide design down to a tenth of an angstrom (Å).

When I asked Daniel Bensen, Tyra’s cofounder and COO, what makes SNÅP tick, he talked about their own empirical data sets and how they’ve “taken what can be a PhD thesis and turned it into to a 2–3 day turnaround time on designing crystal structures.”  

Bensen acknowledged, “companies like Schrodinger and Relay Tx have built their whole lives on molecular modeling platforms. Those platforms are great, but they're really hamstrung by the inputs that you feed into the top of it, and those inputs are crystal structures. Often, they’ll take a couple of crystal structures, feed them to their machine learning model and you're working with a limited data set.” He continued, “But if you can feed 100 crystal structures into that model you can make a much better prediction.”

That empirical data matters. In kinase drug discovery, modeling is only as good as the structures you feed it. Tyra does use molecular modeling and machine learning, but the inputs are the differentiator. Dozens of fresh crystal structures that are generated each week inform every design tweak’s consequences.

Tyra’s Unique Approach

Bensen’s background in structural biology and protein chemistry significantly influences Tyra’s approach to drug discovery. "Iterative structural biology is kind of the cornerstone of the SNÅP platform that we employ here for discovery," Bensen highlights. The SNÅP platform is a testament to Tyra's commitment to cutting-edge science, enabling the rapid production of crystal structures, which are integral to their drug discovery process.

Bensen recalls that the company’s founding vision wasn’t just a scientific hypothesis; it was a conviction he had to sell. “Our single biggest thesis when spinning up Tyra and raising our first big financing was that we could engineer true FGFR3 selectivity,” he said. “I literally pounded the table telling investors we were going to get that done.” That passion mattered. Selectivity had eluded big pharma for years, and the skepticism was real. But Bensen’s insistence, backed by a clear plan and his deep structural biology expertise convinced investors. It wasn’t just about promising a drug; it was about proving Tyra could rewrite the rules of kinase design with speed, precision, and empirical rigor.

The SNÅP platform was born from a shared vision and tight collaboration. As Bensen explains, it started with finding “the chemist I had been kind of searching for my whole life” in Bob Hudkins, Ph.D., now Tyra’s Chief Technology Officer, and partnering with CEO Todd Harris, Ph.D., currently still his (across-the-street) neighbor. Bensen recalls promising Hudkins, “We’re going to make it rain crystal structures on the programs we go after,” a bold commitment that captures the ambition driving Tyra’s discovery engine.

Why Selectivity Isn’t Optional in Peds

The early generation of FGFR therapies tilted pan‑FGFR (FGFR1/2/3/4). That brought efficacy, but also dose‑limiting effects—hyperphosphatemia (FGFR1), ocular toxicity and stomatitis (FGFR2), and GI issues (FGFR4)—that can be showstoppers in pediatrics. Tyra’s oncology program, SURF301, has been a proving ground for FGFR3 selectivity in adults with metastatic urothelial carcinoma harboring FGFR3 alterations.

For achondroplasia, the translational logic is straightforward: hit FGFR3, spare FGFR1/2/4, and you expand the therapeutic window to sustain dosing in growing children.

Bensen’s view on selectivity was clear when he said, “It’s very important to engineer in the selectivity for the isoform that you want, and that was our absolute single biggest thesis.”

From Cancer Treatment to Kids

One smart part of Tyra’s strategy was to start in oncology. By doing first‑in‑human work in FGFR3‑altered bladder cancer, Tyra built a safety and PK foundation that informed pediatric dose selection, supplemented by the required nonclinical pediatric studies, of course.

“We really understand our safety profile for this molecule, so we were able to choose doses where we feel like we’re going to have a really great shot at efficacy and also be very safe and tolerable at the same time,” Bensen said.

If dabogratinib gets FDA approval, it’ll be thanks not just to the drug itself, but to Tyra’s data-driven approach using SNÅP.

Learn more about Tyra Biosciences and its Chief Operating Officer, Daniel C Bensen.