FGFR3 x FGFR2 x FGFR1 x FGFR4

iStock, wildpixel Bank of America analysts said prior to Thursday’s readout that Tyra Biosciences’ TYRA-300 could rival Johnson & Johnson’s kinase inhibitor Balversa, which has suffered from safety concerns and poor tolerability. Tyra Biosciences on Thursday unveiled early proof-of-concept data for its investigational and potential first-in-class FGFR3 inhibitor TYRA-300, touting “encouraging” anti-tumor action in heavily pretreated patients with metastatic urothelial carcinoma. The findings come from the Phase I/II SURF301 trial, which is designed to conduct an initial assessment of the anti-cancer efficacy of TYRA-300 and determine its recommended Phase II dose. Interim results showed that all FGFR3-positive patients who received at least 90 mg of TYRA-300 experienced anti-tumor activity. According to Tyra, 50% of patients on 90-mg TYRA-300 once-daily reached partial response, as did the sole patient treated with a once-daily 120-mg dose. Disease control rate, defined as partial response with stable disease, was documented in 100% of patients who were given at least a 90-mg dose of TYRA-300 once-a-day. In terms of safety, SURF301 found TYRA-300 to be well-tolerated overall and resulted in “infrequent” adverse events associated with FGFR2 and FGFR1. In all TYRA-300-treated patients, there were four treatment-related serious adverse events, one dose-limiting toxicity and one study dropout due to a side effect associated with the study drug. There were no adverse events of grade 4 severity or higher. Tyra CEO Todd Harris in a statement said that these interim data “are in line with our expectations” and “provide clinical support” for TYRA-300 to address the “difficult problem” of creating an effective FGFR3 blocker that matches the efficacy, but bests the safety, of pan-FGFR inhibitors. “These data give us confidence to advance TYRA-300 through Part B in SURF301,” Harris said. Tyra will also “explore larger opportunities with Phase II studies in metastatic urothelial cancer, non-muscle invasive bladder cancer and achondroplasia.” Tyra presented these at an oral late-breaking session at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, held this week in Barcelona, Spain. Designed to be taken orally, TYRA-300 is a next-generation investigational precision therapy that selectively targets FGFR3. This mechanism of action allows TYRA-300 to sidestep current limitations of the FGFR inhibitor drug class, namely growing treatment-emergent resistance mutations and off-target side effects, according to the biotech’s website . With Thursday’s readout, Tyra begins its long trek to challenge J&J in the FGFR3 arena. The pharma owns Balversa, which like TYRA-300, is an orally available kinase inhibitor that the FDA granted accelerated approval for locally advanced or metastatic urothelial carcinoma in 2019. In January 2024, the regulator upgraded Balversa to full approval , allowing its use in patients with susceptible genetic alterations to the FGFR3 gene. However, unlike TYRA-300, Balversa‘s mechanism of action also involves targeting FGFR1, FGFR2 and FGFR4, which has resulted in substantial off-target effects. Jefferies analysts in a Friday note to investors said TYRA-300’s preliminary proof-of-concept data “exceeded” their expectations on both the safety and efficacy fronts, with safety looking “much cleaner” compared to J&J’s Balversa “with the caveat that the safety is grouped together across 10-120mg doses.” Last week, ahead of Tyra’s SURF301 readout, Bank of America analysts flagged these safety concerns for Balversa, saying that its “poor tolerability has made it largely a non-starter,” according to Seeking Alpha . Tyra, the analysts contend, could take advantage of this market gap and make safety its key differentiating factor versus other FGFR inhibitors for urothelial carcinoma.

- Encouraging preliminary anti-tumor activity observed in heavily pre-treated population - - At ≥ 90 mg QD, 6 out of 11 (54.5%) patients with FGFR3+ mUC achieved a confirmed partial response (PR), with 100% disease control rate and sustained duration of activity - - Positive safety results across all QD doses, with infrequent FGFR2/FGFR1-associated toxicities - - Conference call scheduled for October 25th, 2024, at 8AM EDT - CARLSBAD, Calif., Oct. 24, 2024 /PRNewswire/ -- Tyra Biosciences, Inc. (Nasdaq: TYRA), a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in Fibroblast Growth Factor Receptor (FGFR) biology, announced today clinical proof-of-concept data for TYRA-300 in patients with metastatic urothelial (mUC) cancer from its ongoing SURF301 Phase 1/2 study. These data will be presented in a late-breaking oral presentation at the 36th EORTC-NCI-AACR (ENA) Symposium on Molecular Targets and Cancer Therapeutics, being held October 23-25, 2024 in Barcelona, Spain. TYRA-300 is a potential first-in-class, investigational, oral, FGFR3-selective inhibitor designed to avoid the toxicities associated with inhibition of FGFR1, FGFR2 and FGFR4, while being agnostic for the FGFR3 gatekeeper mutations. "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, Melbourne, Australia. "The initial results from TYRA-300 are very encouraging. I believe TYRA-300 has the potential to be a next generation targeted therapy, with high selectivity for FGFR3. These early data provide support that TYRA-300 can deliver improved anti-tumor activity and tolerability for our FGFR3 altered urothelial cancer patients. TYRA-300 has real potential to improve outcomes, and I look forward to its continued development in all FGFR3 altered cancers." 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 44% of patients receiving ≥ 3 lines of therapy prior to receiving TYRA-300, and 76% of FGFR3+ mUC patients receiving ≥ 3 lines of therapy. Treatment with TYRA-300 was evaluated across six dose levels, ranging from 10 mg-120 mg once daily (QD). 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). 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 . 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 Carlsbad, CA. For more information about our science, pipeline and people, please visit 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 [email protected] SOURCE Tyra Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

- Breakthrough Therapy Designation was granted based on preliminary clinical evidence from the PROPEL 2 clinical trial, meeting the FDA’s requirement of potentially demonstrating substantial improvement in efficacy over available therapies on clinically significant endpoint(s) - BridgeBio will leverage the benefits of Breakthrough Therapy Designation to expedite the development and regulatory review of infigratinib in the United States and if approved, infigratinib could be the first-in-class oral therapeutic option for children living with achondroplasia - In Cohort 5 of PROPEL 2 (0.25 mg/kg/day), oral treatment with infigratinib resulted in a statistically significant and sustained increase in annualized height velocity (AHV), with a mean change from baseline of +2.51cm/yr at Month 12, and +2.50 cm/yr at Month 18 (p=0.0015) and statistically significant improvement in body proportionality at Month 18 (p-value of 0.001) PALO ALTO, Calif., Sept. 17, 2024 (GLOBE NEWSWIRE) -- BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio), a commercial-stage biopharmaceutical company focused on genetic diseases, today announced that the FDA has granted Breakthrough Therapy Designation to oral infigratinib under development for children with achondroplasia. Breakthrough Therapy Designation is designed to expedite the development and regulatory review of drugs in the U.S. that meet stringent criteria. Drugs qualifying for this Designation must show preliminary clinical evidence that the drug may demonstrate a substantial improvement on clinically significant endpoints over available therapies. “The receipt of Breakthrough Therapy Designation, the first ever for a treatment being developed for children with achondroplasia, marks another important milestone for our skeletal dysplasia program. This recognition by the FDA further confirms the strength of our Phase 2 data, and the substantial improvement on clinically significant endpoints over available therapies. We are excited by what this means for the community, and we look forward to working closely with FDA to expedite the development of infigratinib and access for families to an oral option,” said Adora Ndu, Pharm.D., J.D., Chief Regulatory Affairs Officer of BridgeBio. The Designation was received based on PROPEL 2 data, which showed that in Cohort 5, infigratinib resulted in a statistically significant and sustained increase in AHV, with a mean change from baseline of +2.51cm/yr at Month 12, and +2.50 cm/yr at Month 18 (p=0.0015). There was also statistically significant improvement in body proportionality at Month 18 (p-value of 0.001). “From the outside perspective, achondroplasia may appear to affect only the height of an individual. The reality is that achondroplasia is a skeletal dysplasia which could impact aspects of health-related quality of life and functionality. As a parent of a teenager with achondroplasia and an advocate for the community, I am pleased to learn that the FDA has granted infigratinib with its Breakthrough Therapy Designation,” said Munira Shamim, Founder of Growing Stronger, a U.S. advocacy group that supports research and develops resources for the care of individuals with achondroplasia. “This action represents a significant step towards offering the first oral treatment option more readily for families living with achondroplasia. Having a wider range of therapies empowers families with greater control and choice over their healthcare decisions. We are grateful to the medical, research, and regulatory communities for recognizing and addressing the needs of families with achondroplasia, allowing them to potentially lead lives with increased confidence and improved functionality.” PROPEL 3, the global Phase 3 registrational study of infigratinib in achondroplasia, continues to enroll on schedule, with completion of enrollment anticipated by the end of the year. Information about PROPEL 3 (NCT06164951) can be found on clinicaltrials.gov. BridgeBio is committed to exploring the potential of infigratinib on wider medical and functional impacts of achondroplasia, hypochondroplasia and other skeletal dysplasias, which hold significant unmet needs for families. In addition to receipt of Breakthrough Therapy Designation, infigratinib has also received Orphan Drug Designation, Fast Track Designation, and Rare Pediatric Disease Designation for achondroplasia from the FDA. If infigratinib is approved, BridgeBio may qualify for a Priority Review Voucher. About BridgeBio Pharma, Inc.BridgeBio Pharma, Inc. (BridgeBio) is a commercial-stage biopharmaceutical company founded to discover, create, test and deliver transformative medicines to treat patients who live with genetic diseases. BridgeBio’s pipeline of development programs ranges from early science to advanced clinical trials. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com and follow us on LinkedIn, Twitter and Facebook. BridgeBio Pharma, Inc. Forward-Looking StatementsThis press release contains forward-looking statements. Statements in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended (the Securities Act), and Section 21E of the Securities Exchange Act of 1934, as amended (the Exchange Act), which are usually identified by the use of words such as “anticipates,” “believes,” “continues,” “estimates,” “expects,” “hopes,” “intends,” “may,” “plans,” “projects,” “remains,” “seeks,” “should,” “will,” and variations of such words or similar expressions. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act. These forward-looking statements, including statements relating to the clinical, therapeutic and market potential of our programs and product candidates, including our clinical development program for infigratinib in achondroplasia, the timing and success of our clinical development programs, the progress of our ongoing and planned clinical trials of infigratinib in achondroplasia, hypochondroplasia and other skeletal dysplasias, infigratinib’s potential for obtaining a Priority Review Voucher, our planned interactions with regulatory authorities, the statements regarding the potential clinical benefits of infigratinib for patients with achondroplasia in the quotes of Munira Shamim and the timing of these events, reflect our current views about our plans, intentions, expectations and strategies, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations and strategies as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a number of risks, uncertainties and assumptions, including, but not limited to, initial and ongoing data from our clinical trials not being indicative of final data, the design and success of ongoing and planned clinical trials, difficulties with enrollment in our clinical trials, adverse events that may be encountered in our clinical trials, the FDA or other regulatory agencies not agreeing with our regulatory approval strategies, components of our filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted, the ability of infigratinib to retain Breakthrough Therapy Designation, Fast Track Designation, Rare Pediatric Disease Designation, and Orphan Drug Designation from the U.S. Food and Drug Administration, and potential adverse impacts due to global health emergencies, including delays in regulatory review, manufacturing and supply chain interruptions, adverse effects on healthcare systems and disruption of the global economy, the impacts of current macroeconomic and geopolitical events, including changing conditions from hostilities in Ukraine and in Israel and the Gaza Strip, increasing rates of inflation and rising interest rates, on our business operations and expectations, as well as those risks set forth in the Risk Factors section of our most recent Annual Report on Form 10-K and our other filings with the U.S. Securities and Exchange Commission. Moreover, we operate in a very competitive and rapidly changing environment in which new risks emerge from time to time. These forward-looking statements are based upon the current expectations and beliefs of our management as of the date of this press release, and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Except as required by applicable law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. BridgeBio Contact:Vikram Balicontact@bridgebio.com(650)-789-8220