8-K: Tyra Biosciences Announces Promising Interim Results for TYRA-300 in Metastatic Urothelial Cancer

Tyra Biosciences reported positive interim clinical data for TYRA-300, showing significant anti-tumor activity and a favorable safety profile in patients with metastatic urothelial cancer.

Summary

• Tyra Biosciences shared interim clinical results from the SURF301 Phase 1/2 study of TYRA-300 in metastatic urothelial cancer (mUC).
• The data cutoff was August 15, 2024, with 41 patients enrolled in the Phase 1 portion of the study.
• The study included patients with advanced malignancies, including those previously treated with erdafitinib.
• 44% of patients had received three or more prior lines of therapy, and 76% of FGFR3+ mUC patients had received three or more prior lines of therapy.
• TYRA-300 was evaluated at doses ranging from 10 mg to 120 mg once daily.
• Pharmacokinetic analysis showed adequate target coverage at 90 mg QD.
• In FGFR3+ mUC patients receiving doses of 90 mg QD or higher, anti-tumor activity was observed in all patients.
• 6 out of 11 patients (54.5%) at 90 mg QD achieved a confirmed partial response (PR), with 3 ongoing.
• 5 out of 10 patients (50%) at 90 mg QD achieved a PR.
• 1 out of 1 patient (100%) at 120 mg QD achieved a PR.
• A 100% disease control rate (DCR) was achieved for all patients at 90 mg QD.
• TYRA-300 was generally well-tolerated, with infrequent FGFR2and FGFR1-associated toxicities.
• There were 4 (10%) serious adverse events related to TYRA-300, 1 dose-limiting toxicity (DLT) of grade 3 diarrhea at 90 mg QD, and 1 treatment-related adverse event (TRAE) leading to discontinuation of treatment (Gr3 ALT, 90 mg QD).
• The 120 mg QD dose was the highest dose evaluated with no DLTs reported.

Sentiment

Score: 8

Explanation: The document presents very positive interim clinical results for TYRA-300, with a high response rate and a favorable safety profile. While there are some risks and uncertainties, the overall tone is optimistic and suggests a promising future for the drug.

Positives

• TYRA-300 shows promising anti-tumor activity in heavily pre-treated mUC patients.
• The drug appears to be well-tolerated with a manageable safety profile.
• The 54.5% confirmed partial response rate at 90 mg QD is encouraging.
• The 100% disease control rate at 90 mg QD suggests a strong therapeutic effect.
• TYRA-300 is a selective FGFR3 inhibitor, potentially reducing off-target toxicities.

Negatives

• There were 4 serious adverse events related to TYRA-300.
• One dose-limiting toxicity of grade 3 diarrhea was observed at 90 mg QD.
• One treatment-related adverse event led to discontinuation of treatment at 90 mg QD.
• The study is still in Phase 1, and the optimal dose is yet to be determined.

Risks

• Interim results may not be indicative of final results, and clinical outcomes may change as patient enrollment continues.
• Proof-of-concept results may not lead to successful subsequent development of TYRA-300.
• There are potential delays in the commencement, enrollment, data readouts, and completion of clinical trials.
• Results from early clinical trials may not be predictive of future results.
• The company is dependent on third parties for manufacturing, research, and preclinical testing.
• Unexpected adverse side effects or inadequate efficacy of product candidates may limit their development.
• The company's programs and prospects could be negatively impacted by competitors.
• The company may not realize the benefits associated with orphan drug designation or rare pediatric disease designation.

Future Outlook

Tyra plans to continue development of TYRA-300 in mUC, prioritizing once-daily dosing, and is also exploring its potential in non-muscle invasive bladder cancer (NMIBC) and achondroplasia (ACH).

Management Comments

• The company is encouraged by the preliminary anti-tumor activity of TYRA-300 in heavily pre-treated patients, especially at doses of 90 mg QD.
• The company believes the data warrants continued development in mUC, prioritizing QD dosing.

Industry Context

The results are significant in the context of the treatment landscape for mUC, where FGFR3 alterations are common and targeted therapies are needed. The company is comparing the results to the existing treatment erdafitinib.

Comparison to Industry Standards

• The 54.5% confirmed partial response rate for TYRA-300 at 90 mg QD compares favorably to the 35.3% overall response rate (ORR) reported in the erdafitinib label for FGFR3+ mUC.
• Erdafitinib, marketed as Balversa, has shown efficacy in mUC but is associated with significant toxicities, including nail disorders, stomatitis, and hyperphosphatemia.
• TYRA-300 appears to have an improved tolerability profile compared to pan-FGFR inhibitors like erdafitinib, with infrequent FGFR2and FGFR1-associated toxicities.
• The company is also comparing the results to other FGFR inhibitors such as pemigatinib and infigratinib, which have shown ORRs of 23% and 24% respectively in mUC.

Management Changes

Stakeholder Impact

• Shareholders may react positively to the promising clinical data.
• Patients with mUC may benefit from a new treatment option with improved tolerability.
• Employees may be motivated by the positive progress of the drug development program.
• The company's reputation may be enhanced by the successful clinical trial results.

Next Steps

• Further dose optimization of TYRA-300.
• Submission of a Phase 2 IND.
• Initiation of a Phase 2 study.

Key Dates

Keywords

TYRA-300, FGFR3, metastatic urothelial cancer, mUC, clinical trial, partial response, disease control rate, targeted therapy, oncology, SURF301