Achondroplasia (ACH), the most common form of disproportionate short stature, is caused by gain–of–function point mutations in fibroblast growth factor receptor 3 (FGFR3). Abnormally elevated activation of FGFR3 modulates chondrocyte proliferation and differentiation via multiple signaling pathways, such as the MAPK pathway. Using a mouse model mimicking ACH (Fgfr3Y367C/+), we have previously shown that daily treatment with infigratinib (BGJ398), a selective and orally bioavailable FGFR1-3 inhibitor, at a dose of 2 mg/kg, significantly increased bone growth. In this study, we investigated the activity of infigratinib administered at substantially lower doses (0.2 and 0.5 mg/kg, given once daily) and using an intermittent dosing regimen (1 mg/kg every 3 days). Following a 15–day treatment period, these low dosages were sufficient to observe significant improvement of clinical hallmarks of ACH such as growth of the axial and appendicular skeleton and skull development. Immunohistological labeling demonstrated the positive impact of infigratinib on chondrocyte differentiation in the cartilage growth plate and the cartilage end plate of the vertebrae. Macroscopic and microcomputed analyses showed enlargement of the foramen magnum area at the skull base, thus improving foramen magnum stenosis, a well–recognized complication in ACH. No changes in FGF23 or phosphorus levels were observed, indicating that the treatment did not modify phosphate homeostasis. This proof–of–concept study demonstrates that infigratinib administered at low doses has the potential to be a safe and effective therapeutic option for children with ACH.

2024-04-30·JNCI cancer spectrum

Derazantinib alone and with atezolizumab in metastatic urothelial carcinoma with activating FGFR aberrations

Article

作者: Yoon, Shinkyo ; Powles, Thomas ; Necchi, Andrea ; McKernan, Phil ; Loriot, Yohann ; Engelhardt, Marc ; Bernat, Mathieu ; Scaleia, Federica ; Ramlau, Rodryg ; Tahbaz, Rana ; De Santis, Maria ; Deville, Jean-Laurent ; Pouessel, Damien ; Marszewska, Michalina ; Giannatempo, Patrizia ; Fontana, Elisa ; Chaudhry, Arvind ; Saulay, Mikael ; Todenhöfer, Tilman ; Siefker-Radtke, Arlene ; Häckl, Manuel ; Falcón González, Alejandro

Abstract:

Background:

This Phase 1b/2 study assessed the efficacy in terms of objective response rate (ORR) of the FGFR1/2/3 kinase inhibitor derazantinib as monotherapy or in combination with atezolizumab in patients with metastatic urothelial cancer (mUC) and FGFR1-3 genetic aberrations (FGFR1-3GA).

Methods:

This multicenter, open-label study comprised 5 substudies. In Substudies 1 and 5, patients with mUC with FGFR1–3GA received derazantinib monotherapy (300 mg QD in Substudy 1, 200 mg BID in Substudy 5). In Substudy 2, patients with any solid tumor received atezolizumab 1200 mg every 3 weeks plus derazantinib 200 or 300 mg QD. In Substudy 3, patients with mUC harboring FGFR1–3GA received derazantinib 200 mg BID plus atezolizumab 1200 mg every 3 weeks. In Substudy 4, patients with FGFR inhibitor-resistant mUC harboring FGFR1–3GA received derazantinib 300 mg QD monotherapy or derazantinib 300 mg QD plus atezolizumab 1200 mg every 3 weeks.

Results:

The ORR for Substudies 1 and 5 combined was 4/49 (8.2%, 95% confidence interval = 2.3% to 19.6%), which was based on 4 partial responses. The ORR in Substudy 4 was 1/7 (14.3%, 95% confidence interval = 0.4% to 57.9%; 1 partial response for derazantinib 300 mg monotherapy, zero for derazantinib 300 mg plus atezolizumab 1200 mg). In Substudy 2, derazantinib 300 mg plus atezolizumab 1200 mg was identified as a recommended dose for Phase 2. Only 2 patients entered Substudy 3.

Conclusions:

Derazantinib as monotherapy or in combination with atezolizumab was well-tolerated but did not show sufficient efficacy to warrant further development in mUC.Clinicaltrials.gov NCT04045613, EudraCT 2019-000359-15

2024-04-01·Nature reviews. Clinical oncology

FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions

Review

作者: Wainberg, Zev A ; Brandi, Giovanni ; Loriot, Yohann ; Katoh, Masaru ; Tavolari, Simona ; Katoh, Masuko

Fibroblast growth factor (FGF) signalling via FGF receptors (FGFR1-4) orchestrates fetal development and contributes to tissue and whole-body homeostasis, but can also promote tumorigenesis. Various agents, including pan-FGFR inhibitors (erdafitinib and futibatinib), FGFR1/2/3 inhibitors (infigratinib and pemigatinib), as well as a range of more-specific agents, have been developed and several have entered clinical use. Erdafitinib is approved for patients with urothelial carcinoma harbouring FGFR2/3 alterations, and futibatinib and pemigatinib are approved for patients with cholangiocarcinoma harbouring FGFR2 fusions and/or rearrangements. Clinical benefit from these agents is in part limited by hyperphosphataemia owing to off-target inhibition of FGFR1 as well as the emergence of resistance mutations in FGFR genes, activation of bypass signalling pathways, concurrent TP53 alterations and possibly epithelial-mesenchymal transition-related isoform switching. The next generation of small-molecule inhibitors, such as lirafugratinib and LOXO-435, and the FGFR2-specific antibody bemarituzumab are expected to have a reduced risk of hyperphosphataemia and the ability to overcome certain resistance mutations. In this Review, we describe the development and current clinical role of FGFR inhibitors and provide perspective on future research directions including expansion of the therapeutic indications for use of FGFR inhibitors, combination of these agents with immune-checkpoint inhibitors and the application of novel technologies, such as artificial intelligence.

项与 FGFR 2/3 Inhibitor(BioArdis) 相关的新闻（医药）

2024-10-24

·PRNewswire

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)

- 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

临床结果孤儿药临床1期临床2期AACR会议

2024-08-07

·PRNewswire

Tyra Biosciences Reports Second Quarter 2024 Financial Results and Highlights

- SURF301 Ph1 initial results and ACH IND submission expected in 2H24 - - Reported preclinical proof-of-concept with TYRA-300 in HCH, demonstrating increases in long bone length and binding against the HCH altered protein - - IND cleared for TYRA-430, an FGFR4/3 biased inhibitor for HCC - - Announced Chief Medical Officer transition plan; search for an external candidate underway with guidance from Science & Technology (S&T) Committee of the Board, including recent additions Dr. Susan Moran and Dr. S. Michael Rothenberg - - Cash, cash equivalents, and marketable securities of $373.8 million at Q2 2024 - CARLSBAD, Calif., Aug. 7, 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, today reported financial results for the quarter ended June 30, 2024, and highlighted recent corporate progress. "This is an exciting time at TYRA. With the recent clearance of our IND for TYRA-430, our FGFR4/3 biased inhibitor, we are well positioned with three potentially best-in-class precision molecules in the clinic for oncology. In skeletal dysplasias, we made great progress with preclinical proof-of-concept data in hypochondroplasia and continued execution towards the filing of our IND anticipated in the second half of 2024 to support our planned Phase 2 study in achondroplasia," said Todd Harris, CEO of TYRA. Mr. Harris continued, "We also announce today the transition of our Chief Medical Officer position by the end of the year. We thank Hiroomi for his many contributions to TYRA over the past four years. He was instrumental in the translation of our SNÅP drug discovery platform into a robust pipeline of product candidates. As we move forward, I am delighted to have the support of our S&T Committee, including recent additions to our Board Susan Moran and Michael Rothenberg, whose collective expertise in solid tumors and achondroplasia will be invaluable." Dr. Moran added, "I am pleased to have the opportunity to support the TYRA team as we prepare to advance multiple early-stage clinical programs into later-stage clinical development and evaluate the broad potential of our precision molecules in oncology and rare diseases." Second Quarter 2024 and Recent Corporate Highlights TYRA-300 SURF301 Phase 1/2 Study for Oncology Continued to Advance. The SURF301 study for oncology ( Study in Untreated and Resistant FGFR3+ Advanced Solid Tumors) (NCT05544552) continued to advance. The study is a multi-center, open label study designed to determine the optimal and the recommended Phase 2 dose (RP2D) of TYRA-300, as well as to evaluate the preliminary antitumor activity of TYRA-300. TYRA expects that the Phase 1 portion of SURF301 will provide data to inform the dosing schedule of TYRA-300 we intend to evaluate in potential future studies in metastatic urothelial carcinoma (mUC) and non-muscle invasive bladder cancer (NMIBC). Part A of SURF301 is complete and the expansion cohorts in Part B are evaluating potentially therapeutic once daily and twice daily doses, in preparation for potential future Phase 2 studies in NMIBC and mUC. TYRA remains on track to report initial results from the SURF301 Phase 1 portion at a scientific congress in the second half of 2024. Phase 2 Achondroplasia (ACH) Study Planning Continued to Advance. TYRA remains on track to submit an Investigational New Drug application (IND) to the FDA in the second half of 2024 for the initiation of a Phase 2 clinical trial testing multiple doses of TYRA-300 to support children with achondroplasia. TYRA expects that the primary objective of this study will be to assess safety and tolerability in children with achondroplasia and determine the dose(s) for further development. TYRA also expects that secondary objectives will include evaluating change in growth velocity, growth proportionality and pharmacokinetics (PK). TYRA is also planning exploratory assessments of clinical outcomes and quality of life measures, and an evaluation of biomarkers to determine dose-response relationships to TYRA-300. Expanded Development into Hypochondroplasia (HCH). In July 2024, TYRA announced the expansion of development of TYRA-300 into HCH based on positive preclinical results. In a preclinical HCH model, TYRA-300 demonstrated increases in long bone length and binding against the HCH altered protein. HCH is a skeletal dysplasia closely related to achondroplasia (ACH), the most common form of dwarfism. HCH is most commonly caused by the N540K mutation (~70-80%) in the FGFR3 gene. The design of TYRA-300 may inhibit the alteration driving FGFR3-related skeletal dysplasias including ACH, HCH and others. TYRA-200 Phase 1 SURF201 Study Continued to Advance. The SURF201 ( Study in Previo Usly treated and Resistant FGFR2+ Cholangiocarcinoma and Other Advanced Solid Tumors) (NCT06160752) continued to advance. The study is a multi-center, open label study designed to evaluate the safety, tolerability, and PK of TYRA-200 and determine the optimal and maximum tolerated dose (MTD) and RP2D, as well as evaluate the preliminary antitumor activity of TYRA-200. TYRA-200 is an investigational, FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations. The SURF201 study is currently enrolling and dosing adults with unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating FGFR2 gene alterations. TYRA-430 IND Cleared by the FDA. TYRA announced today that the FDA cleared its IND to proceed with a Phase 1 clinical study of TYRA-430, an investigational, FGFR4/3-biased inhibitor for FGF19+/FGFR4-driven cancers. The Phase 1 study will be a multicenter, open-label, first-in-human study of TYRA-430 in advanced hepatocellular carcinoma (HCC) and other solid tumors with activating FGF/FGFR pathway aberrations (SURF431). We believe TYRA-430 has the potential to address a significant unmet need in HCC, where there are no approved biomarker-driven, targeted therapies. Corporate Strengthened Board with New Appointments. TYRA announced changes to its Board of Directors with the appointments of Susan Moran, M.D., M.S.C.E. and S. Michael Rothenberg, M.D., Ph.D. as independent directors, and the resignation of Isan Chen, M.D. Announced Chief Medical Officer Transition. TYRA announced today that Hiroomi Tada, M.D., Ph.D., the Company's Chief Medical Officer (CMO), will be departing from his position by the end of year to transition to an advisor role. TYRA is conducting a search for an external candidate to replace Dr. Tada, who will stay on as CMO to assist in the transition process until a successor has been named. TYRA's Science and Technology Committee of the Board of Directors, which includes, among others, Board members Susan Moran, M.D., M.S.C.E. and S. Michael Rothenberg, M.D., Ph.D., will be involved in the CMO search and transition period. The Company does not expect any disruption to ongoing clinical work during this time. Dr. Tada joined TYRA in 2020 as CMO prior to the Company's initial public offering. He was integral in the development of the Company's clinical strategy and building the in-house clinical operations group who have advanced multiple product candidates into clinical development. SNÅP Platform and Pipeline TYRA continued to advance its in-house precision medicine discovery engine, SNÅP, to develop therapies in targeted oncology and genetically defined conditions. Second Quarter 2024 Financial Results Second quarter 2024 net loss was $18.7 million compared to $13.3 million for the same period in 2023. Second quarter 2024 research and development expenses were $18.0 million compared to $12.2 million for the same period in 2023. Second quarter 2024 general and administrative expenses were $5.5 million compared to $3.9 million for the same period in 2023. As of June 30, 2024, TYRA had cash, cash equivalents, and marketable securities of $373.8 million. The Company's current cash, cash equivalents and marketable securities are expected to allow TYRA to execute on its plans through at least 2026. About TYRA-300 TYRA-300 is the Company'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), which was designed to determine the recommended Phase 2 dose (RP2D) of TYRA-300, as well as to evaluate preliminary antitumor activity. In skeletal dysplasias, TYRA-300 has demonstrated positive preclinical results in achondroplasia and hypochondroplasia, and the Company expects to submit an IND in the second half of 2024 for the initiation of a Phase 2 clinical study in pediatric achondroplasia. 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-200 TYRA-200 is an investigational, oral, FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations currently in development for the treatment of cancer. TYRA-200 is being evaluated in a multi-center, open label Phase 1 clinical study, SURF201 ( Study in Previo Usly treated and Resistant FGFR2+ Cholangiocarcinoma and Other Advanced Solid Tumors). SURF201 (NCT06160752) was designed to determine the optimal and MTD and the RP2D of TYRA-200, as well as to evaluate the preliminary antitumor activity of TYRA-200. SURF201 is currently enrolling adults with advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating alterations in FGFR2. 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 initial focus is on applying its accelerated small molecule drug discovery engine to develop therapies in targeted oncology and genetically defined conditions. 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 and potentially best-in-class precision medicines and the potential safety and therapeutic benefits of TYRA-300, TYRA-200, TYRA-430 and other product candidates; the ability to advance multiple early-stage clinical programs into later-stage clinical development; the sufficiency of our cash position to support our clinical and operational plans; expected cash runway; the expected timing and phase of clinical development of TYRA-300, TYRA-200, and TYRA-430, including timing of a submission of an IND for TYRA-300 in pediatric achondroplasia, design of our planned Phase 2 study in achondroplasia and the presentation of SURF301 clinical data at a scientific congress; 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: 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; potential difficulty or delay in transitioning the CMO position and any resulting adverse impacts on our development programs or otherwise; our dependence on third parties in connection with manufacturing, research and preclinical testing; we may expend our limited resources to pursue a particular product candidate and/or indication and fail to capitalize on product candidates or indications with greater development or commercial potential; 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; we may use our capital resources sooner than we expect; unstable market and economic conditions and military conflict may adversely affect our business and financial condition and the broader economy and biotechnology industry; 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

临床1期临床2期高管变更临床申请财报

2024-08-01

·GlobeNewswire-Health Care

BridgeBio Pharma Reports Second Quarter 2024 Financial Results and Business Update

Acoramidis demonstrated a significant impact on mortality, hospitalizations, and quality of life Starting at Month 3, patients taking acoramidis showed meaningful and sustained improvement in time to first event (CVH or ACM)Acoramidis demonstrated a 42% reduction in composite CVH and ACM events relative to placebo by Month 30Increased serum TTR levels by Day 28 were correlated with a reduced risk of events (ACM, CVM, and CVH) through Month 30Acoramidis resulted in a statistically significant reduction in ACM in the intention-to-treat (ITT) population at Month 30 Shared +2.50 cm/yr annualized height velocity (AHV) at Month 18 in Cohort 5 of PROPEL 2, the Phase 2 study of infigratinib in achondroplasia, as well as the first ever reported statistically significant improvement in body proportionalityThe first child consented in ACCEL, the observational run-in study for infigratinib in children living with hypochondroplasia, a skeletal dysplasia closely related to achondroplasiaThe Company surpassed its interim analysis enrollment target for its Phase 3 FORTIFY study of BBP-418 in individuals living with limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9)The Company ended the quarter with $587 million in cash, cash equivalents, marketable securities and short-term restricted cash PALO ALTO, Calif., Aug. 01, 2024 (GLOBE NEWSWIRE) -- BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio or the Company), a commercial-stage biopharmaceutical company focused on genetic diseases, today reported its financial results for the second quarter ended June 30, 2024, and provided an update on the Company’s operations. “Our team has continued its preparation for the commercial launch of acoramidis while also executing against our goal of fully enrolling our three Phase 3 clinical programs by the end of 2024. We are well positioned to launch acoramidis and achieve three readouts in 2025. Our differentiated capability to develop multiple candidates for genetic-based diseases provides a unique opportunity to create significant value for patients and shareholders,” said Dr. Neil Kumar, CEO and Founder of BridgeBio. Pipeline overview: ProgramStatusNext expected milestoneAcoramidis for ATTR-CMNDA filed with FDANovember 29, 2024 PDUFA dateEncaleret for ADH1Enrolling CALIBRATE, Phase 3 studyEnrollment completion in 2024BBP-418 for LGMD2I/R9Enrolling FORTIFY, Phase 3 studyEnrollment completion in 2024Low-dose infigratinib for achondroplasiaEnrolling PROPEL 3, Phase 3 studyEnrollment completion in 2024Low-dose infigratinib for hypochondroplasiaEnrolling observational run-in for ACCEL 2, Phase 2 studyEnrollment completion date to be announcedBBP-631 for congenital adrenal hyperplasia (CAH)Dose finding / analysis in Phase 2 studyProgram update in August 2024BBP-812 for Canavan diseaseEnrolling at high dose in Phase 1/2 studyKey regulatory interactions Program updates: Acoramidis (AG10) – Transthyretin (TTR) stabilizer for transthyretin amyloid cardiomyopathy (ATTR-CM): During the 2024 International Symposium of Amyloidosis (ISA), five new analyses were disclosed through oral presentations and posters, discussing the following: Acoramidis treatment resulted in increased serum transthyretin (TTR) levels by Day 28 that were sustained and were correlated with a reduced risk of all-cause mortality (ACM), cardiovascular mortality (CVM), and cardiovascular hospitalization (CVH) in ATTR-CM participants through Month 30.Acoramidis treatment resulted in a significant improvement in the composite endpoint of ACM and CVH in ATTR-CM participants, with benefit evident as early as Month 3.In ATTRibute-CM, participants with at least one CVH had a significantly higher risk of mortality, highlighting the need for ATTR-CM treatments that reduce the risk of CVH.BridgeBio also shared the rationale and design of ACT-EARLY, the acoramidis ATTR amyloidosis prevention trial, which it expects to initiate later this year. At this year’s European Society of Cardiology Heart Failure (ESC-HF) Congress 2024, BridgeBio shared four positive analyses, which included the following data: In a pre-specified Cochran-Mantel-Haenszel sensitivity analysis applied to the entire ITT population of the study (N=632), acoramidis significantly reduced ACM (p=0.04), with no safety signals of potential clinical concern.Among ATTRibute-CM participants enrolled with Stage 4 chronic kidney disease (CKD) (N=21), acoramidis treatment was associated with proportionally fewer deaths compared with placebo, with no safety signals of potential clinical concern.At Month 30 of the ATTRibute-CM study, acoramidis treatment resulted in a statistically significant and clinically important reduction in the progressive decline in health-related quality of life as assessed by the EuroQoL Health Outcomes Assessment tool, EQ-5D-5L.Acoramidis treatment also reduced the decline in health status and quality of life as shown by statistically significant and clinically meaningful benefits in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score and supported by numerical and consistent benefits in individual KCCQ domains.In ATTRibute-CM, acoramidis significantly improved NT-proBNP indices that can be a signal of ATTR-CM disease progression and be predictive of subsequent mortality risk. During the 2024 American College of Cardiology (ACC), BridgeBio presented cardiac magnetic resonance (CMR) imaging evidence consistent with clinical improvement observed in the ATTRibute-CM. The data demonstrate that targeting near-complete TTR stabilization with acoramidis may enable cardiac remodeling and functional recovery in patients with ATTR-CM. Encaleret – Calcium-sensing receptor (CaSR) inhibitor for autosomal dominant hypocalcemia type 1 (ADH1): CALIBRATE, the Phase 3 clinical trial of encaleret in ADH1, continues to enroll; the Company anticipates sharing topline data from CALIBRATE in 2025. BBP-418 – Glycosylation substrate for limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9): BridgeBio has surpassed its interim analysis enrollment target for its Phase 3 FORTIFY study of BBP-418 in individuals living with LGMD2I/R9, with top-line results from the interim analysis expected in 2025.Recent Type C interactions with U.S. FDA focused on the validated glycosylated alpha-dystroglycan (αDG) bioassay and our interim analysis plans reinforce BridgeBio’s belief that there is potential to pursue Accelerated Approval for BBP-418.Rare Pediatric Disease Designation for BBP-418 highlights that LGMD2I/R9 is a rare disease with serious manifestations, which primarily impacts children. If BBP-418 is approved, BridgeBio may qualify for a Priority Review Voucher, which can be applied to another therapy in the Company’s pipeline for a shorter timeline during the review process of a NDA or can be sold to another company looking to receive priority review for one of its applications. Low-dose infigratinib – FGFR1-3 inhibitor for achondroplasia and hypochondroplasia: BridgeBio shared data from Month 12 and 18 for Cohort 5 of PROPEL 2 (0.25 mg/kg/day), its Phase 2 trial in achondroplasia with the oral treatment, infigratinib, with results including: 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).At Month 18, there was a statistically significant improvement in body proportionality (p-value of 0.001). The mean upper to lower body segment ratio was 1.88 at Month 18, as compared to 2.02 at baseline.Infigratinib continues to be well-tolerated as a single daily oral therapy with no adverse events (AEs) assessed as treatment-related in any participant in Cohort 5. Infigratinib for achondroplasia was granted Fast Track Designation and Rare Pediatric Drug Designation by the U.S. FDA. If infigratinib is approved, BridgeBio may qualify for a Priority Review Voucher.In May 2024, the first participant consented to be part of ACCEL, the observational run-in study for infigratinib in children living with hypochondroplasia. Second Quarter 2024 Financial Results: Cash, Cash Equivalents, Marketable Securities and Short-term Restricted Cash Cash, cash equivalents, marketable securities and short-term restricted cash, totaled $587.2 million as of June 30, 2024, compared to $392.6 million of cash, cash equivalents and short-term restricted cash as of December 31, 2023. The $194.6 million net increase in cash, cash equivalents, marketable securities and short-term restricted cash was primarily attributable to net proceeds received from the term loan under the credit facility with Blue Owl of $434.0 million, net proceeds received from various equity financings of $314.8 million, proceeds from the sale of investments in equity securities of $63.2 million, and special cash dividends received from investments in equity securities of $25.7 million. These were primarily offset by refinancing of the Company’s previous senior secured credit term loan, inclusive of prepayment fees and exit-related costs in aggregate of $473.4 million, net cash used in operating activities of $144.8 million, purchases of equity securities of $20.3 million, and repurchase of shares to satisfy tax withholdings of $4.7 million during the six months ended June 30, 2024. Revenue Revenue for the three and six months ended June 30, 2024 were $2.2 million and $213.3 million, respectively, as compared to $1.6 million and $3.5 million for the same periods in the prior year. The increase of $0.6 million in revenue for the three months ended June 30, 2024, compared to the same period in the prior year, was primarily due to the recognition of services revenue under the exclusive license and collaboration agreements with Bayer and Kyowa Kirin. Revenue for the three months ended June 30, 2023 primarily consists of the recognition of services revenue under the Navire-BMS License Agreement, which terminated effective June 2024. The increase of $209.8 million in revenue for the six months ended June 30, 2024, compared to the same period in the prior year, was primarily due to $202.9 million from recognition of non-refundable upfront payments and service revenue under the Bayer and the Kyowa Kirin exclusive license and collaboration agreements. Operating Costs and Expenses Operating costs and expenses for the three and six months ended June 30, 2024 were $177.7 million and $388.5 million, respectively, compared to $147.7 million and $275.7 million for the same periods in the prior year. The overall increase of $30.0 million in operating costs and expenses for the three months ended June 30, 2024, compared to the same period in the prior year, was primarily due to an increase of $23.4 million in selling, general and administrative (SG&A) expenses mainly to support commercialization readiness efforts, an increase of $7.2 million in research and development and other expenses (R&D) to advance the Company’s pipeline of research and development programs, offset by a decrease of $0.6 million in restructuring, impairment and related charges. The overall increase of $112.8 million in operating costs and expenses for the six months ended June 30, 2024, compared to the same period in the prior year, was primarily due to an increase of $58.1 million in SG&A expenses mainly to support commercialization readiness efforts, and an increase of $55.3 million in R&D expenses to advance the Company’s pipeline of research and development programs, offset by a decrease of $0.6 million in restructuring, impairment and related charges. Operating costs and expenses for the six months ended June 30, 2024, include $22.5 million of nonrecurring deal-related costs for transactions that were closed during the three months ended March 31, 2024. Restructuring, impairment and related charges for the three and six months ended June 30, 2024 amounted to $2.9 million and $6.3 million, respectively. These charges primarily consisted of impairments and write-offs of long-lived assets, severance and employee-related costs, and exit and other related costs. Restructuring, impairment and related charges for the same periods in the prior year was $3.5 million and $6.9 million, respectively. These charges primarily consisted of winding down, exit costs, and severance and employee-related costs. Stock-based compensation expenses included in operating costs and expenses for the three months ended June 30, 2024 were $21.5 million, of which $4.9 million is included in R&D expenses, $16.5 million is included in SG&A expenses, and $0.1 million is included in Restructuring expenses. Stock-based compensation expenses included in operating costs and expenses for the same period in the prior year were $27.2 million, of which $13.2 million is included in R&D expenses, and $14.0 million is included in SG&A expenses. Stock-based compensation expenses included in operating costs and expenses for the six months ended June 30, 2024 were $50.3 million, of which $17.7 million is included in R&D expenses, $32.5 million is included in SG&A expenses, and $0.1 million is included in Restructuring expenses. Stock-based compensation expenses included in operating costs and expenses for the same period in the prior year were $50.7 million, of which $25.0 million is included in R&D expenses, and $25.7 million is included in SG&A expenses. Total Other Income (Expense), netTotal other income (expense), net for the three and six months ended June 30, 2024 were $100.0 million and $63.5 million, respectively, compared to ($14.6) million and ($31.2) million for the same periods in the prior year. The increase in total other income (expense), net of $114.6 million for the three months ended June 30, 2024, compared to the same period in the prior year, was primarily due to the Company’s gain on deconsolidation of a subsidiary of $126.3 million. This was partially offset by a net loss from an equity method investment of $7.9 million and an increase in interest expense of $2.3 million. The increase in total other income (expense), net of $94.7 million for the six months ended June 30, 2024, compared to the same period in the prior year, was primarily due to the Company’s gain on deconsolidation of a subsidiary of $126.3 million and an increase in other income (expense), net of $8.1 million mainly from income or mark to market fair value adjustments from the Company’s investments in equity securities. These were partially offset by a loss on extinguishment of debt of $26.6 million, a net loss from an equity method investment of $7.9 million and an increase in interest expense of $5.7 million. Net Loss Attributable to Common Stockholders of BridgeBio and Net Loss per Share For the three months and six months ended June 30, 2024, the Company recorded a net loss attributable to common stockholders of BridgeBio of $73.5 million and $108.7 million, respectively, compared to $157.9 million and $298.1 million, respectively for the three months and six months ended June 30, 2023. For the three months and six months ended June 30, 2024, the Company reported a net loss per share of $0.39 and $0.59, respectively compared to $0.98 and $1.90, respectively for the three months and six months ended June 30, 2023. BRIDGEBIO PHARMA, INC.Condensed Consolidated Statements of Operations(in thousands, except shares and per share amounts) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 (Unaudited) (Unaudited) Revenue $2,168 $1,641 $213,288 $3,467 Operating costs and expenses: Research, development and other expenses 115,293 108,087 256,863 201,599 Selling, general and administrative 59,523 36,122 125,330 67,230 Restructuring, impairment and related charges 2,891 3,531 6,291 6,900 Total operating costs and expenses 177,707 147,740 388,484 275,729 Loss from operations (175,539) (146,099) (175,196) (272,262)Other income (expense), net: Interest income 5,195 4,514 9,270 8,667 Interest expense (22,937) (20,594) (46,408) (40,715)Gain on deconsolidation of a subsidiary 126,294 — 126,294 — Loss on extinguishment of debt — — (26,590) — Net loss from equity method investment (7,925) — (7,925) — Other income (expense), net (632) 1,476 8,851 875 Total other income (expense), net 99,995 (14,604) 63,492 (31,173)Net loss (75,544) (160,703) (111,704) (303,435)Net loss attributable to redeemable convertible noncontrolling interests and noncontrolling interests 2,088 2,804 3,032 5,380 Net loss attributable to common stockholders of BridgeBio $(73,456) $(157,899) $(108,672) $(298,055)Net loss per share, basic and diluted $(0.39) $(0.98) $(0.59) $(1.90)Weighted-average shares used in computing net loss per share, basic and diluted 187,586,680 160,535,435 183,145,995 156,645,838 Three Months Ended June 30, Six Months Ended June 30, Stock-based Compensation 2024 2023 2024 2023 (Unaudited) (Unaudited) Research, development and other expenses $4,937 $13,229 $17,716 $25,008 Selling, general and administrative 16,471 13,947 32,542 25,645 Restructuring, impairment and related charges 43 — 43 — Total stock-based compensation $21,451 $27,176 $50,301 $50,653 BRIDGEBIO PHARMA, INC.Condensed Consolidated Balance Sheets(In thousands) June 30, December 31, 2024 2023 Assets (Unaudited) (1) Cash, cash equivalents and marketable securities $447,771 $375,935 Investments in equity securities — 58,949 Receivables from licensing and collaboration agreements 660 1,751 Short-term restricted cash 139,409 16,653 Prepaid expenses and other current assets 28,396 24,305 Investment in nonconsolidated entity 117,006 - Property and equipment, net 9,840 11,816 Operating lease right-of-use assets 7,267 8,027 Intangible assets, net 25,123 26,319 Other assets 18,903 22,625 Total assets $794,375 $546,380 Liabilities, Redeemable Convertible Noncontrolling Interests and Stockholders’ Deficit Accounts payable $18,126 $10,655 Accrued and other liabilities 96,517 122,965 Operating lease liabilities 11,682 13,109 Deferred revenue 32,059 9,823 2029 Notes, net 737,882 736,905 2027 Notes, net 544,270 543,379 Term loan, net 435,447 446,445 Other long-term liabilities 485 5,634 Redeemable convertible noncontrolling interests (223) 478 Total BridgeBio stockholders' deficit (1,092,925) (1,354,257)Noncontrolling interests 11,055 11,244 Total liabilities, redeemable convertible noncontrolling interests and stockholders’ deficit $794,375 $546,380 (1)The condensed consolidated financial statements as of and for the year ended December 31, 2023 are derived from the audited consolidated financial statements as of that date. BRIDGEBIO PHARMA, INC.Condensed Consolidated Statements of Cash Flows(Unaudited)(In thousands) Six Months Ended June 30, 2024 2023 Operating activities: Net loss $(111,704) $(303,435)Adjustments to reconcile net loss to net cash used in operating activities: Stock-based compensation 38,511 49,085 Loss on extinguishment of debt 26,590 — Accretion of debt 3,683 4,580 Depreciation and amortization 3,170 3,270 Noncash lease expense 2,093 2,024 Accrual of payment-in-kind interest on term loan — 6,742 Net loss from equity method investment 7,925 — Loss (gain) on deconsolidation of subsidiaries (126,294) 1,241 Gain from investment in equity securities, net (8,136) (2,399)Fair value adjustment of warrants — (222)Other noncash adjustments (1,911) (328)Changes in operating assets and liabilities: Receivables from licensing and collaboration agreements 1,091 8,466 Prepaid expenses and other current assets (6,506) 1,057 Other assets 942 32 Accounts payable 8,858 (4,098)Accrued compensation and benefits (8,378) (11,071)Accrued research and development liabilities 7,067 (11,322)Operating lease liabilities (2,981) (2,443)Deferred revenue 22,236 (3,184)Accrued professional and other liabilities (1,090) 4,330 Net cash used in operating activities (144,834) (257,675)Investing activities: Purchases of marketable securities (93,811) (19,754)Maturities of marketable securities 55,000 41,550 Purchases of investments in equity securities (20,271) (71,504)Proceeds from sales of investments in equity securities 63,229 67,068 Proceeds from special cash dividends received from investments in equity securities 25,682 — Payment for an intangible asset (3,190) — Purchases of property and equipment (749) (440)Decrease in cash and cash equivalents resulting from deconsolidation of subsidiaries (98) (503)Net cash provided by investing activities 25,792 16,417 Financing activities: Proceeds from term loan under Financing Agreement 450,000 — Issuance costs and discounts associated with term loan under Financing Agreement (15,986) — Repayment of term loan under Loan and Security Agreement (473,417) — Proceeds from issuance of common stock through public offerings, net 314,759 144,049 Proceeds from BridgeBio common stock issuances under ESPP 2,364 1,809 Proceeds from stock option exercises, net of repurchases 778 312 Repurchase of RSU shares to satisfy tax withholding (4,679) (1,715)Other financing activities — 4,563 Net cash provided by financing activities 273,819 149,018 Net increase (decrease) in cash, cash equivalents and restricted cash 154,777 (92,240)Cash, cash equivalents and restricted cash at beginning of period 394,732 416,884 Cash, cash equivalents and restricted cash at end of period $549,509 $324,644 Six Months Ended June 30, 2024 2023 Supplemental Disclosure of Cash Flow Information: Cash paid for interest $49,046 $28,738 Supplemental Disclosures of Noncash Investing and Financing Information: Unpaid public offering issuance costs $18 $— Deferred and unpaid issuance costs recorded to "Accrued and other liabilities" $74 $— Unpaid property and equipment $70 $131 Transfers to noncontrolling interests $(1,929) $(5,940)Reconciliation of Cash, Cash Equivalents and Restricted Cash: Cash and cash equivalents $407,958 $302,438 Restricted cash 139,409 19,930 Restricted cash — Included in “Other assets” 2,142 2,276 Total cash, cash equivalents and restricted cash at end of period shown in the condensed consolidated statements of cash flows $549,509 $324,644 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 suffer from 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 and Twitter. BridgeBio Pharma, Inc. Forward-Looking Statements This 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 and therapeutic, market potential of the Company’s programs and product candidates, including the statements in Dr. Kumar’s quote regarding the potential commercial launch of acoramidis (if approved) and the Company’s goal of fully enrolling its three Phase 3 clinical programs, continued advancement in the Company’s pipeline, including enrollments in clinical trials and anticipated readouts, and other benefits resulting from recent financing activities; the statements related to the FDA’s planned actions regarding the Company’s NDA for acoramidis for the treatment of ATTR-CM; the potential outcomes of regulatory interactions with and reviews by the FDA and the European Medicines Agency; the timing and success of the Company’s clinical development programs, including the progress of the Company’s clinical development program for acoramidis for patients with ATTR-CM, and the Company’s plan for, and the expected timing of, initiation of ACT-EARLY, the Company’s planned acoramidis ATTR amyloidosis prevention trial; the potential payments we may receive under the recent license agreement with Bayer and Kyowa Kirin; the continuation of PROPEL 3, the Company’s Phase 3 study of infigratinib for achondroplasia and the expected timing for completion of the study; the Company’s commitment to exploring the potential of infigratinib and expectation regarding the Company’s clinical program for hypochondroplasia; the continuation and progress of FORTIFY, the Phase 3 trial of BBP-418 for LGMD2I/R9, including the expected receipt of top-line results from the interim analysis population, and the potential to pursue Accelerated Approval for BBP-418 based on recent interactions with the FDA; the Company’s ability to qualify for Priority Review Vouchers with respect to BBP-418 and infigratinib; the continued enrollment in CALIBRATE, the Phase 3 clinical trial of encaleret, and the timing for sharing topline data from CALIBRATE; and the Company’s financial performance, capitalization status, strategy, business plans and goals reflect the Company’s current views about the Company’s plans, intentions, expectations and strategies, which are based on the information currently available to us and on assumptions we have made. Although the Company believes that its 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 the Company’s preclinical studies and clinical trials not being indicative of final data, the potential size of the target patient populations the Company’s product candidates are designed to treat not being as large as anticipated, the design and success of ongoing and planned clinical trials, future regulatory filings, approvals and/or sales, despite having ongoing and future interactions with the FDA or other regulatory agencies to discuss potential paths to registration for the Company’s product candidates, the FDA or such other regulatory agencies not agreeing with the Company’s regulatory approval strategies, components of the Company’s filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted, the continuing success of the Company’s collaborations, the Company’s ability to obtain additional funding, including through less dilutive sources of capital than equity financings, potential volatility in the Company’s share price, 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 business operations and expectations, as well as those risks set forth in the Risk Factors section of the Company’s most recent Annual Report on Form 10-K and the Company’s 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 the Company’s 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

临床结果临床3期临床2期财报快速通道

100 项与 FGFR 2/3 Inhibitor(BioArdis) 相关的药物交易

登录后查看更多信息