Tyra Biosciences Reports Interim Clinical Proof-of-Concept Data for TYRA-300, an Investigational Oral FGFR3-Selective Inhibitor, in Phase 1/2 SURF301 Study in Patients with Metastatic Urothelial Cancer (mUC)
Tyra Biosciences announced promising interim clinical data for TYRA-300, their investigational oral FGFR3-selective inhibitor, in treating metastatic urothelial cancer (mUC). In patients receiving ≥90mg daily doses, 6 out of 11 (54.5%) achieved confirmed partial response, with 100% disease control rate. The study included 41 heavily pre-treated patients, with 44% receiving ≥3 prior therapies. TYRA-300 demonstrated favorable safety results across all doses, showing infrequent FGFR2/FGFR1-associated toxicities. Only 4 serious adverse events (10%) were reported, with one dose-limiting toxicity of grade 3 diarrhea at 90mg daily.
Tyra Biosciences ha annunciato dati clinici interim promettenti per TYRA-300, il loro inibitore orale selettivo per FGFR3 in fase di sperimentazione, per il trattamento del cancro uroteliale metastatico (mUC). Nei pazienti che ricevevano dosi giornaliere di ≥90mg, 6 su 11 (54,5%) hanno raggiunto una risposta parziale confermata, con un tasso di controllo della malattia del 100%. Lo studio ha incluso 41 pazienti con precedenti trattamenti intensivi, di cui il 44% aveva ricevuto ≥3 terapie precedenti. TYRA-300 ha dimostrato risultati di sicurezza favorevoli in tutte le dosi, mostrando tossicità associate a FGFR2/FGFR1 rare. Sono stati riportati solo 4 eventi avversi gravi (10%), con una tossicità da dose limitante di diarrea di grado 3 a 90mg al giorno.
Tyra Biosciences anunció datos clínicos interinos prometedores para TYRA-300, su inhibidor oral selectivo de FGFR3 en investigación, en el tratamiento del cáncer urotelial metastásico (mUC). En pacientes que recibieron dosis diarias de ≥90mg, 6 de 11 (54.5%) lograron una respuesta parcial confirmada, con una tasa de control de la enfermedad del 100%. El estudio incluyó a 41 pacientes con un tratamiento previo intensivo, de los cuales el 44% había recibido ≥3 terapias anteriores. TYRA-300 demostró resultados de seguridad favorables en todas las dosis, mostrando toxicidades asociadas a FGFR2/FGFR1 poco frecuentes. Solo se reportaron 4 eventos adversos graves (10%), con una toxicidad limitante por dosis de diarrea de grado 3 a 90mg diarios.
Tyra Biosciences는 전이성 요로상피암(mUC) 치료를 위한 실험적인 경구 FGFR3 선택적 억제제인 TYRA-300의 유망한 중간 임상 데이터를 발표했습니다. 하루에 ≥90mg의 복용량을 받은 환자 중 11명 중 6명(54.5%)이 확인된 부분적인 반응을 보였으며, 질병 통제율은 100%에 달했습니다. 이 연구에는 41명의 심각한 이전 치료를 받은 환자가 포함되었으며, 그 중 44%가 ≥3개의 이전 치료를 받은 적이 있었습니다. TYRA-300은 모든 용량에서 우호적인 안전성 결과를 보여주었으며, FGFR2/FGFR1과 관련된 독성은 드물게 나타났습니다. 심각한 이상 반응은 4건(10%)이 보고되었으며, 90mg의 복용량에서 3도 설사로 인한 용량 제한 독성이 있었습니다.
Tyra Biosciences a annoncé des données cliniques intermédiaires prometteuses pour TYRA-300, leur inhibiteur oral sélectif FGFR3 en investigation, dans le traitement du cancer urotélial métastatique (mUC). Chez les patients recevant des doses quotidiennes de ≥90mg, 6 sur 11 (54,5%) ont obtenu une réponse partielle confirmée, avec un taux de contrôle de la maladie de 100%. L'étude a inclus 41 patients ayant reçu de nombreux traitements antérieurs, dont 44% avaient reçu ≥3 thérapies antérieures. TYRA-300 a montré des résultats de sécurité favorables à toutes les doses, présentant des toxicités associées à FGFR2/FGFR1 peu fréquentes. Seuls 4 événements indésirables graves (10%) ont été rapportés, avec une toxicité limitante de dose de diarrhée de grade 3 à 90mg par jour.
Tyra Biosciences hat vielversprechende interim Daten für TYRA-300, ihren experimentellen oralen FGFR3-selektiven Inhibitor zur Behandlung von metastasiertem urothelialem Karzinom (mUC), angekündigt. Bei Patienten, die tägliche Dosen von ≥90mg erhielten, erreichten 6 von 11 (54,5%) eine bestätigte partielle Remission, mit einer Krankheitskontrollrate von 100%. Die Studie umfasste 41 stark vorbehandelte Patienten, von denen 44% ≥3 vorherige Therapien erhalten hatten. TYRA-300 zeigte günstige Sicherheitsdaten über alle Dosen hinweg, wobei selten FGFR2/FGFR1-assoziierte Toxizitäten auftraten. Es wurden nur 4 schwerwiegende unerwünschte Ereignisse (10%) berichtet, darunter eine dosislimitierende Toxizität in Form von Durchfall der Grad 3 bei 90mg täglich.
- 54.5% partial response rate in patients receiving ≥90mg daily doses
- 100% disease control rate achieved at ≥90mg daily doses
- Favorable safety profile with infrequent toxicities
- Only 4 (10%) serious adverse events reported
- No grade 4 or higher treatment-related adverse events
- One dose-limiting toxicity of grade 3 diarrhea at 90mg daily dose
- One treatment-related adverse event leading to discontinuation
Insights
The interim clinical data for TYRA-300 shows significant promise in treating metastatic urothelial cancer (mUC). The key highlights include a
The drug's selective FGFR3 inhibition mechanism appears to deliver on its design goals, showing fewer FGFR1/FGFR2-associated toxicities compared to existing pan-FGFR inhibitors. The safety profile is notably strong, with only
The positive early efficacy signals, combined with the favorable tolerability profile, suggest strong potential for expanded applications in bladder cancer and achondroplasia, significantly broadening the drug's market opportunity.
These clinical results represent a significant milestone for TYRA, potentially establishing them as a leader in the targeted FGFR3 inhibitor space. The market opportunity is substantial - bladder cancer therapeutics market alone is projected to grow significantly and TYRA-300's improved safety profile could help capture meaningful market share from existing treatments.
The drug's potential expansion into non-muscle invasive bladder cancer and achondroplasia represents additional revenue streams. With a market cap of
- Encouraging preliminary anti-tumor activity observed in heavily pre-treated population -
- At ≥ 90 mg QD, 6 out of 11 (
- Positive safety results across all QD doses, with infrequent FGFR2/FGFR1-associated toxicities -
- Conference call scheduled for October 25th, 2024, at 8AM EDT -
"FGFR3 alterations are known to drive tumor biology in a subset of urothelial cancer. While pan-FGFR inhibitors have demonstrated benefit and are approved for use in FGFR3 altered urothelial cancer, they are associated with multiple intolerable on-target toxicities that limit their clinical utility. There remains an unmet need to deliver improved precision medicine for urothelial cancer patients, that allow patients to not only live longer, but live better," said Ben Tran, M.D., Associate Professor, Peter McCallum Cancer Centre,
Summary of Interim Clinical Results
As of August 15, 2024, the data cutoff date, 41 patients were enrolled in the Phase 1 portion of the SURF301 Phase 1/2 study. Eligible participants were adults with advanced malignancies with or without FGFR3 alterations, including those with prior treatment with erdafitinib. The enrolled patient population was heavily pre-treated, with
- Preliminary PK/PD analysis in 41 patients as of the data cutoff date: TYRA-300 plasma concentrations indicate adequate target coverage at ≥ 90 mg QD, with further pharmacokinetic characterization ongoing.
- In patients with FGFR3+ mUC who received doses ≥ 90 mg QD, anti-tumor activity was observed in all patients:
- 6 out of 11 (
54.5% ) patients at ≥ 90 mg QD achieved a PR, 3 of which are still ongoing. - 5 out of 10 (
50% ) patients at 90 mg QD achieved a PR. - 1 out of 1 (
100% ) patient at 120 mg QD achieved a PR. - A
100% disease control rate (DCR) was achieved for all patients at ≥ 90 mg QD (PR + stable disease).
- 6 out of 11 (
- TYRA-300 has demonstrated favorable interim safety results as of the data cutoff date:
- Preliminary data from SURF301 suggest TYRA-300 to be generally well-tolerated, with infrequent FGFR2- and FGFR1-associated toxicities.
- In doses from 10 mg up to 120 mg QD, there were 4 (
10% ) serious adverse events related to TYRA-300, 1 dose-limiting toxicity (DLT) of grade (Gr) 3 diarrhea at 90 mg QD, and 1 treatment-related adverse event (TRAE) leading to discontinuation of treatment (Gr3 ALT, 90 mg QD). - There were no ≥ Gr4 TRAEs.
- The 120 mg QD dose was the highest dose evaluated with no DLTs reported.
"The preliminary data are what we were expecting to see with TYRA-300, being generally well-tolerated with fewer toxicities, and anti-tumor activity in FGRF3+ mUC patients," said Doug Warner, M.D., Chief Medical Officer of TYRA. "The emerging profile of TYRA-300 supports further development in metastatic urothelial cancer, where an attractive opportunity exists for a more tolerable option in second line."
Dr. Warner continued, "We are grateful for the support of our study participants, their families and our global collaborators on SURF301. We remain focused on progressing TYRA-300 through dose optimization in SURF301 and toward patients in need."
"Our team set out to solve an ambitious chemistry problem that had stumped the field of precision oncology - to create an efficacious FGFR3-selective inhibitor with a favorable tolerability profile to address the limitations of pan-FGFR inhibitors. We believe that today's interim results provide clinical support for addressing this difficult problem, and the data are in line with our expectations," said Todd Harris, CEO of TYRA. "These data give us confidence to advance TYRA-300 through Part B in SURF301 and explore larger opportunities with Phase 2 studies in metastatic urothelial cancer, non-muscle invasive bladder cancer and achondroplasia."
ENA 2024 presentation details:
Title: "Preliminary safety and anti-tumor activity of TYRA-300, a highly selective FGFR3 inhibitor, in participants with advanced solid tumors with activating FGFR3 mutations/fusions (SURF301)"
Session: Late Breaking Abstracts and Proffered Papers: Novel discoveries in drug development
Date: Friday, October 25, 2024
Time: 15:36 - 15:48 hrs CEST
Abstract #: 500LBA
Conference Call Information
TYRA is hosting a conference call and webcast on October 25, 2024, at 8am ET to review the interim clinical proof-of-concept results demonstrated with TYRA-300 in mUC. Participants may access a live webcast of the call and the associated slide presentation on the "For Investors" page of the TYRA website at https://ir.tyra.bio. To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the Company's website for at least 30 days.
About TYRA-300 and the SURF301 Study
TYRA-300 is TYRA's lead precision medicine program stemming from its in-house SNÅP platform. TYRA-300 is an investigational, oral, FGFR3-selective inhibitor currently in development for the treatment of cancer and skeletal dysplasias, including achondroplasia and hypochondroplasia. In oncology, TYRA-300 is being evaluated in a multi-center, open label Phase 1/2 clinical study, SURF301 (Study in Untreated and Resistant FGFR3+ Advanced Solid Tumors) (NCT05544552). The study is designed to determine the optimal and the recommended Phase 2 dose (RP2D) of TYRA-300, as well as to evaluate the preliminary anti-tumor activity of TYRA-300. Part A of the study included patients with all solid tumors who are FGFR3 +/-, and explored doses of TYRA-300 ranging from 10mg -120mg once-daily (QD). Part A of SURF301 is complete. The Company continues to advance TYRA-300 through dose expansion in Part B, which includes patients with solid tumors who are FGFR3+, to evaluate potentially therapeutic doses in preparation for potential future Phase 2 studies in metastatic urothelial carcinoma (mUC) and non-muscle invasive bladder cancer (NMIBC).
In skeletal dysplasias, TYRA-300 has demonstrated positive preclinical results in achondroplasia and hypochondroplasia. In July 2023 and January 2024, the FDA granted Orphan Drug Designation (ODD) and Rare Pediatric Designation (RPD) to TYRA-300, respectively, for the treatment of achondroplasia.
About Tyra Biosciences
Tyra Biosciences, Inc. (Nasdaq: TYRA) is a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in FGFR biology. The Company's in-house precision medicine platform, SNÅP, enables rapid and precise drug design through iterative molecular SNÅPshots that help predict genetic alterations most likely to cause acquired resistance to existing therapies. TYRA's expertise in FGFR biology has created a differentiated pipeline with three clinical-stage programs in targeted oncology and genetically defined conditions. The Company's lead precision medicine stemming from SNÅP, TYRA-300, is a potential first-in-class selective FGFR3 inhibitor that is designed to avoid the toxicities associated with inhibition of FGFR1, FGFR2 and FGFR4, while being agnostic for the FGFR3 gatekeeper mutations. TYRA-300 is in development for the treatment of cancer in the SURF301 Phase 1/2 study and for skeletal dysplasias, including achondroplasia and hypochondroplasia. TYRA is also developing TYRA-200, an investigational, FGFR1/2/3 inhibitor, in the SURF201 study for metastatic intrahepatic cholangiocarcinoma, and TYRA-430, an investigational FGFR4/3-biased inhibitor for FGF19+/FGFR4-driven cancers. TYRA is based in
For more information about our science, pipeline and people, please visit www.tyra.bio and engage with us on LinkedIn.
Forward-Looking Statements
TYRA cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to: the potential to develop next-generation precision medicines and for TYRA-300 to be first-in-class, and the potential safety and therapeutic benefits of TYRA-300; the continued evaluation of TYRA-300 through Part B dose escalation in SURF301; the expected timing and phase of clinical development of TYRA-300; and the potential for SNÅP to develop therapies in targeted oncology and genetically defined conditions. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: interim results of a clinical trial are not necessarily indicative of final results and one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data, as follow-up on the outcome of any particular patient continues and as more patient or final data becomes available, including the risk that unconfirmed responses may not ultimately result in confirmed responses to treatment after follow-up evaluations; the potential for proof-of-concept results to fail to result in successful subsequent development of TYRA-300; we are early in our development efforts, have only recently begun testing TYRA-300 and TYRA-200 for oncology in clinical trials and the approach we are taking to discover and develop drugs based on our SNÅP platform is novel and unproven and it may never lead to product candidates that are successful in clinical development or approved products of commercial value; potential delays in the commencement, enrollment, data readouts and completion of preclinical studies and clinical trials; results from preclinical studies or early clinical trials not necessarily being predictive of future results; our dependence on third parties in connection with manufacturing, research and preclinical testing; acceptance by the FDA of INDs or of similar regulatory submissions by comparable foreign regulatory authorities for the conduct of clinical trials of TYRA-300 in pediatric achondroplasia and hypochondroplasia; an accelerated development or approval pathway may not be available for TYRA-300 or other product candidates and any such pathway may not lead to a faster development process; later developments with the FDA may be inconsistent with the minutes from our prior meetings, including with respect to the proposed design of our planned Phase 2 study of TYRA-300 in ACH; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval, and/or commercialization; the potential for our programs and prospects to be negatively impacted by developments relating to our competitors, including the results of studies or regulatory determinations relating to our competitors; unfavorable results from preclinical studies; we may not realize the benefits associated with ODD, including that orphan drug exclusivity may not effectively protect a product from competition and that such exclusivity may not be maintained, or from the RPD Designation, including receipt of a Priority Review Voucher or any value therefrom; regulatory developments in the United States and foreign countries; our ability to obtain and maintain intellectual property protection for our product candidates and proprietary technologies; and other risks described in our prior filings with the Securities and Exchange Commission (SEC), including under the heading "Risk Factors" in our annual report on Form 10-K and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.
Contact:
Amy Conrad
aconrad@tyra.bio
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