A Phase 2A/B, Multi-center, Open-Label Study Evaluating the Efficacy and Safety of Dabogratinib (TYRA-300) in Participants With Low Grade Upper Tract Urothelial Carcinoma (SURF303)

A Phase 2A/B study of Dabogratinib (TYRA-300) in Low Grade Upper Tract Urothelial Carcinoma

开始日期2025-12-22

申办/合作机构

Tyra Biosciences, Inc.

NCT06995677

/ Recruiting临床2期

A Phase 2 Multicenter, Open-Label Study Evaluating the Efficacy and Safety of TYRA-300 in Participants With FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer (SURF302)

Phase 2 Study of TYRA-300 in FGFR3 Altered Low Grade, Intermediate Risk NMIBC

开始日期2025-06-27

申办/合作机构

Tyra Biosciences, Inc.

NCT06842355

/ Recruiting临床2期

A Multicenter, Phase 2, Dose-Escalation/Dose-Expansion Study of TYRA-300 in Children With Achondroplasia With Open Growth Plates: BEACH301

The purpose of this study is to evaluate the safety, tolerability, and identify potentially effective dose(s) of TYRA-300 in children with achondroplasia with open growth plates.

开始日期2025-03-04

申办/合作机构

Tyra Biosciences, Inc.

100 项与 Dabogratinib 相关的临床结果

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100 项与 Dabogratinib 相关的转化医学

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100 项与 Dabogratinib 相关的专利（医药）

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项与 Dabogratinib 相关的文献（医药）

2026-03-02·MOLECULAR CANCER THERAPEUTICS

Dabogratinib (TYRA-300), an FGFR3 Isoform-Selective Inhibitor: Preclinical and Initial Clinical Evidence of Antitumor Activity

Article

作者: Lihou, Christine ; Hudkins, Robert L. ; Loriot, Yohann ; Fuentes-Antrás, Jesús ; Allen, Eric L. ; Iyer, Samhita ; Pobel, Cedric ; Goluboff, Erik ; Neal, Melissa ; Boni, Valentina ; Ye, Qing ; Starrett, Jacqueline H. ; Swanson, Ronald V. ; Zalutskaya, Alena ; Degaonkar, Viraj

Abstract:

Despite recent advances in the treatment of fibroblast growth factor receptor 3 (FGFR3)–altered metastatic urothelial carcinoma, there is no approved precision therapy that selectively targets FGFR3 while sparing other FGFR isoforms. Dabogratinib (TYRA-300)—a rationally designed selective FGFR3 inhibitor—was evaluated in vitro and in vivo. We also report three patient cases from the ongoing first-in-human, phase I/II SURF301 study (NCT05544552). Dabogratinib elicited a dose-dependent reduction in downstream signaling across three bladder cancer cell lines harboring an FGFR3 fusion, mutation, or gatekeeper resistance mutation. In a xenograft model driven by an FGFR3S249C-activating mutation, dabogratinib treatment resulted in dose-dependent tumor growth inhibition with tumor regression observed at the highest doses. These preclinical findings are supported by the three case reports from the SURF301 study, which demonstrate early clinical activity in patients with advanced metastatic urothelial carcinoma with an FGFR3 fusion or activating mutation.

2025-11-01·TRENDS IN PHARMACOLOGICAL SCIENCES

Next-generation isoform-selective fibroblast growth factor receptor inhibitors

Review

作者: Chen, Lingfeng

Dysregulated fibroblast growth factor receptor (FGFR) signaling - driven by amplifications, mutations, or fusions - represents a clinically validated oncogenic driver across diverse malignancies. Pan-FGFR-selective inhibitors (erdafitinib, pemigatinib, and futibatinib) have been developed in clinical practice. However, their therapeutic efficacy is substantially limited by inevitable on-target resistance mutations and toxicities via FGFR1/4 inhibition. Next-generation FGFR isoform-selective small-molecule inhibitors are emerging and represent active research frontiers. FGFR2-selective inhibitor lirafugratinib, FGFR3-selective inhibitors LOXO-435 and TYRA-300, FGFR2/3-selective inhibitor ABSK061, and FGFR4-selective inhibitors are in clinical development. Additionally, novel isoform-selective FGFR-targeting degraders, FGFR2b/FGFR3-selective antibodies, and de novo-designed 'c' isoform-selective proteins provide novel treatment strategies. This review provides an overview of the current FGFR-targeted therapeutics and limitations and evaluates next-generation inhibitor development to guide future research.

2025-07-10·ACS Medicinal Chemistry Letters

Discovery of Potent FGFR2/3 Inhibitors to Overcome Mutation Resistance and Treat Achondroplasia

Article

作者: Hu, Zhilong ; Yang, Fanglong ; Han, Tian ; Yang, Zimo ; Xia, Yuanfeng ; Jin, Lei ; Fu, Donglin ; Wang, Siqi

Achondroplasia (ACH), the most prevalent form of human dwarfism, is caused by the G380R mutation in FGFR3 in approximately 99% of cases. Through structural hybridization of Tyra-300 and LY2874455, we developed compound 23, a new dual-target FGFR2/3 inhibitor demonstrating potent activity against both wild-type and mutant FGFR3. In preclinical ACH mouse models, compound 23 showed a dose-dependent improvement in growth rate, with significantly enhanced efficacy versus infigratinib at equivalent doses. This work presents a new structural scaffold for developing FGFR3 kinase inhibitors to target pathogenic FGFR3 mutations and treat ACH.

项与 Dabogratinib 相关的新闻（医药）

2026-06-10

·药学观澜

JMC｜上海有机所丁克/王震&科恩泰：新型三环骨架共价FGFR2/3抑制剂KNT-0919实现亚纳摩尔级抑制与肿瘤消退

点击蓝字 ↑ 关注药学观澜近日，上海有机所丁克/王震与中南大学陈永恒、广州科恩泰生物医药科技常少华、密歇根大学Arul M. Chinnaiyan等团队在药物化学权威期刊 Journal of Medicinal Chemistry 上发表了一篇题为 "基于三环骨架的新型强效选择性共价FGFR2/3抑制剂的结构导向设计与优化" 的研究论文。该研究基于结构生物学策略，设计并优化了一系列含三环骨架的共价FGFR2/3抑制剂，其中代表性化合物 KNT-0919 对FGFR2和FGFR3表现出亚纳摩尔级抑制活性（IC₅₀分别为1.1 nM和0.20 nM），对FGFR1的选择性达16倍以上，且在416种激酶筛选中展现出高度选择性。该化合物通过丙烯酰胺弹头与FGFR2/3 P-loop中的半胱氨酸残基形成共价键，经质谱与X射线晶体学确证；在SNU-16胃癌异种移植模型中，口服给药可实现肿瘤消退，口服生物利用度达56%，为FGFR2/3驱动型肿瘤（包括耐药突变型）的精准治疗提供了具有全新化学骨架的候选药物。 Introduction 成纤维细胞生长因子受体（FGFRs）是调控细胞增殖、分化、存活和血管生成的受体酪氨酸激酶家族（FGFR1−4），其信号失调由基因扩增、激活突变和染色体易位等遗传改变驱动，是多种癌症发病的关键因素：FGFR2改变常见于胆管癌、胃癌和子宫内膜癌，FGFR3改变主要与膀胱癌和多发性骨髓瘤相关。FDA已批准futibatinib、erdafitinib和pemigatinib等泛FGFR抑制剂用于FGFR2/3改变的癌症，但临床应用受限于FGFR1抑制导致的高磷血症、FGFR4抑制引起的腹泻等剂量限制性毒性，以及激酶域看门人突变（如FGFR2V564F/I）引发的获得性耐药。因此，选择性靶向FGFR2/3成为治疗策略新方向，目前已有lirafugratinib（首个高选择性共价FGFR2抑制剂）、LOXO-435（高选择性FGFR3抑制剂，保留看门人突变活性）和TYRA-300（可逆选择性FGFR3抑制剂）等进入临床阶段。本研究基于结构生物学设计，发现了一类三环四氢吡嗪-吡咯-嘧啶氨基衍生物作为新型共价FGFR2/3抑制剂，代表性化合物KNT-0919对FGFR2/3表现出亚纳摩尔级抑制活性，对临床相关突变保持效力，口服生物利用度达56%，并在SNU-16胃癌异种移植模型中实现显著抗肿瘤效果。 Results ①分子设计药物化学研究以已获批的不可逆泛FGFR抑制剂futibatinib（TAS-120）为起点，该化合物对FGFR1−4的酶抑制IC₅₀为1.3−8.3 nM，对常见看门人突变FGFR2V564F的IC₅₀为83 nM。利用公开的TAS-120与FGFR2共晶结构（PDB: 8W2X），分析发现其吡唑并[3,4-d]嘧啶骨架与铰链区Glu565和Ala567形成氢键，丙烯酰胺弹头与P-loop中的Cys491形成共价键，二甲氧基苯基延伸至疏水性后口袋，其中一个甲氧基与Asp644形成氢键。受Relay Therapeutics前期工作启发——即利用FGFR1与FGFR2 P-loop柔性差异可增强FGFR2选择性——研究者将TAS-120的吡唑基和哌啶基环化以引入结构刚性；同时，TAS-120与FGFR2V564F的预测结合模式显示Val564替换为Phe564后，一个甲氧基产生空间位阻，因此去除一个甲氧基并采用环合并策略，使新形成的环与邻近Phe645形成π−π相互作用，且在新环中引入氮原子以维持与Asp644的关键氢键。由此得到化合物8a，对接研究显示其在野生型FGFR2和FGFR2V564F中均保留了与Cys491的共价键、铰链区氢键及与Asp644的氢键等关键相互作用，且苯并[d]噻唑部分避免了与Phe564的空间位阻并与Phe645形成π−π相互作用；与FGFR3的对接则揭示了与FGFR2相似的结合模式，这些计算结果为后续合成与生物学评价提供了支持。 ②结构优化 Ba/F3细胞增殖抑制活性作为主要评价指标。TAS-120验证显示其对各亚型及看门人突变均具低纳摩尔级活性，与文献一致。化合物8a保留对Ba/F3-FGFR2（IC₅₀=7.8 nM）和Ba/F3-FGFR3（21.2 nM）的强效抑制，对Ba/F3-FGFR1活性降低（337 nM），对亲本Ba/F3细胞大于1000 nM，且对V564F突变效力略优于TAS-120。R¹位置考察中，含氢键接受氮原子的8b−e活性均低于8a。受KIN-3248启发，在8a和8c中引入炔键相邻二氟 motif得到8f和8g，8f对FGFR3和V564F的IC₅₀分别提升至6.8 nM和29.1 nM，较8a增强约3倍。基于8f与FGFR2的对接模型，后口袋可容纳小型疏水基团，据此设计8h−m；甲基取代8h对FGFR3活性增强，乙基（8i）和环丙基（8k）因位阻增加活性降低，异丙基（8j）、环丁基（8l）和环戊基（8m）活性最弱。进一步分析发现哌啶环对侧存在未占据空间，遂引入手性甲基得到8n、8o、8r及KNT-0919（8s），并设计8p和8q以提高代谢稳定性。手性甲基显著增强各细胞系活性，8n对FGFR2/3/V564F的IC₅₀分别为0.78、0.63和0.89 nM。KNT-0919表现最均衡：对FGFR2、FGFR3和V564F的IC₅₀分别为1.1、0.20和5.6 nM，亚型选择性最高（FGFR2/FGFR1为16倍，FGFR3/FGFR1为85倍），酶抑制与细胞水平活性趋势一致。 ③KNT-0919选择性抑制FGFR2/3激酶活性采用ADP-Glo激酶活性检测法评价KNT-0919对FGFR1−4的抑制活性，结果显示其对FGFR2和FGFR3的IC₅₀分别为0.8 nM和0.3 nM，而对FGFR1（IC₅₀=2.2 nM）和FGFR4（IC₅₀=20.3 nM）活性较低。为表征共价抑制动力学，测定了对FGFR1和FGFR2的稳态动力学参数：KNT-0919对FGFR2的Kᵢ为0.4 nM、kᵢₙₐcₜ为0.00405 s⁻¹，kᵢₙₐcₜ/Kᵢ效率常数为0.01053 nM⁻¹·s⁻¹；对FGFR1的相应参数分别为5.3 nM（Kᵢ）、0.00599 s⁻¹（kᵢₙₐcₜ）和0.00113 nM⁻¹·s⁻¹（kᵢₙₐcₜ/Kᵢ），表明其对FGFR2优于FGFR1的选择性主要由可逆结合亲和力而非共价键形成速率决定。在100 nM浓度下对416种蛋白激酶进行筛选，除FGFR家族外，仅RET野生型激酶（RET改变型癌症的已验证靶点）抑制率大于90%；KNT-0919同时对多种临床相关FGFR2和FGFR3突变变体表现出强效抑制活性。这些结果表明KNT-0919选择性抑制FGFR2/3激酶活性。 ④KNT-0919与FGFR2和FGFR3的共价结合为验证共价结合机制，进行了完整蛋白质质谱分析：重组FGFR2与过量KNT-0919孵育后出现明确的完整质量偏移，与KNT-0919-FGFR2共价复合物的形成一致；高能碰撞诱导解离（HCD）MS/MS进一步确认Cys491发生共价修饰，在修饰样品中鉴定出对应KNT-0919加合物的独特肽段。X射线共晶结构解析显示，在KNT-0919-FGFR2复合物（PDB: 22ZR）中，三环四氢吡嗪-吡咯-嘧啶氨基核心通过Glu565和Ala567的氢键锚定于铰链区，苯并[d]噻唑部分延伸至疏水性后口袋，丙烯酰胺弹头与P-loop中的Cys491形成不可逆共价键，且丙烯酰胺羰基与Arg630形成两个额外氢键，可能稳定共价结合构象；由于FGFR2结构中激活环定义不清，噻唑氮与Asp644之间的预测氢键未能清晰解析。相反，在KNT-0919-FGFR3复合物（PDB: 22ZS）中，该相互作用在噻唑氮与Asp635之间被明确观察到。总体而言，KNT-0919在FGFR3中的结合模式与FGFR2一致：核心与铰链区Glu556和Ala558形成氢键，丙烯酰胺弹头共价修饰Cys482，其羰基与Arg621形成氢键。这些结果确认KNT-0919与FGFR2和FGFR3均形成共价结合。 ⑤KNT-0919选择性抑制FGFR2依赖性癌细胞增殖及下游信号并诱导凋亡在四种携带不同FGFR改变的癌细胞系中评价KNT-0919的抗增殖活性：A204（FGFR1扩增）、SNU16（FGFR2扩增）、KATO III（FGFR2扩增）、KMS-11（FGFR3 Y373C及融合）、MDA-MB-453（FGFR4-Y367C突变）和HEK-293T（人胚肾细胞）。KNT-0919对FGFR2依赖的SNU16和KATO III细胞表现出强效活性（IC₅₀分别为6.2 nM和6.3 nM），对FGFR3依赖的KMS-11细胞IC₅₀为13.5 nM，而对A204（IC₅₀=75.3 nM）、MDA-MB-453（1310 nM）和HEK-293T（>1000 nM）活性显著降低。此外，KNT-0919对表达FGFR2突变体的Ba/F3细胞保持强效抑制，对FGFR2V564I和FGFR2N549K的IC₅₀分别为9.6 nM和20.4 nM。Western blot检测显示，在SNU-16细胞中KNT-0919剂量依赖性抑制FGFR2磷酸化及其下游效应分子FRS2α、Akt和ERK1/2的磷酸化；同时以剂量依赖性方式诱导SNU-16细胞凋亡，100 nM处理48 h后约28%细胞发生凋亡，而相同条件下A204细胞几乎无凋亡发生。这些结果表明KNT-0919选择性抑制FGFR2依赖性癌细胞增殖和下游信号，并促进细胞凋亡。 ⑥KNT-0919在大鼠中表现出良好的口服生物利用度及体内强效抗肿瘤活性 KNT-0919的药代动力学特征在Sprague-Dawley大鼠中经静脉（1 mg/kg）和口服（10 mg/kg）给药后评估，口服生物利用度为55.6%，最大血浆浓度（Cₘₐₓ）为500 ng/mL，暴露量（AUC₀₋∞）为1708 ng·h/mL。体内疗效在SNU-16异种移植小鼠模型中评价，KNT-0919以3、10和30 mg/kg剂量每日两次口服给药，连续35天，结果显示剂量依赖性抑制肿瘤生长，肿瘤生长抑制率（TGI）分别为78.6%、97.4%和115.6%，最高剂量下观察到肿瘤消退；所有治疗均耐受良好，研究期间未出现显著体重下降。体内药效学评估证实KNT-0919治疗导致FGFR2及其下游信号磷酸化的剂量依赖性抑制；治疗结束时肿瘤样本分析显示治疗组凋亡增加，H&E和TUNEL染色证实这一点。进一步疗效研究中，TAS-120作为阳性对照每日一次口服10 mg/kg，KNT-0919以10 mg/kg每日一次或两次口服给药，连续22天，结果显示KNT-0919每日两次给药的抗肿瘤活性与TAS-120相当，且未出现显著体重下降。 Conclusions 选择性靶向FGFR2和/或FGFR3已成为治疗这些特定亚型驱动癌症的有前景治疗策略，但目前尚无此类抑制剂获批临床使用，因此需要具有不同化学骨架的新型选择性FGFR2/3抑制剂。本研究报道了一类三环四氢吡嗪-吡咯-嘧啶氨基衍生物作为不可逆FGFR2/3抑制剂的设计与合成，其中代表性化合物KNT-0919对FGFR2和FGFR3驱动的Ba/F3细胞表现出强效抗增殖活性，IC₅₀分别为1.1 nM和0.20 nM，对表达FGFR2看门人突变的Ba/F3细胞保留活性，而对Ba/F3-FGFR1细胞（IC₅₀=17.1 nM）和亲本Ba/F3细胞（IC₅₀>1000 nM）活性降低。在416种激酶筛选中，KNT-0919选择性抑制FGFR2和FGFR3，包括临床相关突变变体；为更好缓解FGFR1相关全身毒性，该化合物的选择性仍可进一步优化。值得注意的是，研究者采用了更刚性的三环骨架，成功增强了对FGFR2/3的亚型选择性，进一步证明构象限制是提高激酶抑制剂选择性的有效策略。KNT-0919与FGFR2和FGFR3的共价结合经完整蛋白质质谱和X射线共晶结构确证。此外，KNT-0919表现出良好的药代动力学性质，包括56%的口服生物利用度。重要的是，口服给药KNT-0919在SNU-16异种移植小鼠模型中导致显著肿瘤消退，且未观察到毒性。尽管仍需更多表征以研究其疗效和安全性特征，但这些发现确立了KNT-0919作为有前景的共价FGFR2/3抑制剂，支持其进一步开发用于FGFR2/3驱动恶性肿瘤的治疗，包括与获得性耐药突变相关的肿瘤。文献详细全面信息请跳转原文阅读： https://doi.org/10.1021/acs.jmedchem.6c00585 说明欢迎合理转载，请写明来源于【药学观澜】，公众号内容为阅读文献提炼总结的内容，学识有限，恳请批评指正。标记【原创】指原创编译，是出于便于传播目的，著作权归出版社与作者所有。合作，投稿，商务等请联系后台分享让更多人看看

2026-05-21

·PRNewswire

TYRA BIOSCIENCES AND BCAN ESTABLISH MAY 21 AS UPPER TRACT UROTHELIAL CANCER (UTUC) AWARENESS DAY

-Collaboration aims to raise awareness of UTUC and the need for continued innovation for patients living with this rare and difficult-to-treat cancer- CARLSBAD, Calif., May 21, 2026 /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 announced the establishment of Upper Tract Urothelial Cancer (UTUC) Awareness Day, in collaboration with the Bladder Cancer Advocacy Network (BCAN). Continue Reading BCAN UTUC is a rare cancer affecting the lining of the kidneys and ureters, with a high prevalence of activating FGFR3 alterations. Standard treatment approaches frequently involve endoscopic tumor ablation or, in more advanced cases, surgical removal of the kidney and ureter (nephroureterectomy), which can lead to long-term health complications. There remains a significant unmet need for an effective, kidney-sparing treatment option. Currently, there is no well-established systemic standard of care for patients with UTUC. Through this collaboration, TYRA and BCAN aim to increase awareness of the disease, amplify the patient experience, and highlight the importance of continued research and innovation for people living with UTUC. "Patients diagnosed with UTUC often describe feeling isolated, overwhelmed, and uncertain about where to turn for information and support," said Meri-Margaret Deoudes, Chief Executive Officer of BCAN. "As a rare form of urothelial cancer, UTUC has historically received limited attention despite the profound impact it can have on patients' lives. Establishing UTUC Awareness Day is an important step toward building greater recognition, creating a patient community, and encouraging more education, advocacy, and research focused on this disease." TYRA is currently dosing patients with dabogratinib, an investigational oral FGFR3-selective inhibitor, in a Phase 2 study called SURF303 (NCT07265947) for low-grade UTUC (LG-UTUC). "At TYRA, we are committed to advancing new treatment approaches for patients living with urothelial cancers, particularly those facing limited therapeutic options and significant treatment burden," said Todd Harris, Ph.D., Chief Executive Officer of TYRA Biosciences. "Dabogratinib is the only oral therapeutic candidate currently in clinical development for patients with low-grade UTUC, and we believe our approach may offer the potential for meaningful clinical benefit with a differentiated tolerability profile. Importantly, we believe oral dabogratinib has the potential to provide a kidney-sparing treatment approach for many patients who today may ultimately face loss of their kidney as part of the standard treatment journey for UTUC. We are proud to establish UTUC Awareness Day with BCAN and support efforts that drive progress for this patient community." More information about TYRA's ongoing clinical studies with oral dabogratinib can be found on the Patients page of the Company's website. About BCAN The Bladder Cancer Advocacy Network (BCAN) was founded in 2005 and provides patients with the critical information and community support they need to thrive today – and champions innovative research and responsive national policy to inspire hope for tomorrow. 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. TYRA's in-house precision medicine platform, SNÅP, enables rapid and precise drug design through iterative molecular SNÅPshots that help TYRA design and predict which candidates may demonstrate the highest potency, selectivity and tolerability in the clinic. TYRA's expertise in FGFR biology has created a differentiated pipeline with clinical-stage programs in targeted oncology and genetically defined conditions. TYRA's lead precision medicine stemming from SNÅP, oral dabogratinib, is a potential first-in-class selective FGFR3 inhibitor in development for LG-UTUC, IR NMIBC and ACH. TYRA is also developing TYRA-430, an oral, investigational FGFR4/3-biased inhibitor for FGF19+/FGFR4-driven cancers, in the SURF431 study for advanced hepatocellular carcinoma, and TYRA-200, an oral, investigational, FGFR1/2/3 inhibitor, in the SURF201 study for metastatic intrahepatic cholangiocarcinoma. 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 their potential to be first-in-class and the potential safety and therapeutic benefits of, and market opportunities for, our product candidates. 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, 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, recruitment, 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; 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; 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 21% more press release views with Request a Demo

临床2期

2026-05-17

·网易号

一年涨280%的医药股，为何有基金仍在加仓？

5月15日，HighVista Strategies向美国证券交易委员会（SEC）提交了一份持仓变动文件。这家资产管理机构在过去一个季度增持了Tyra Biosciences（NASDAQ:TYRA）96,218股，按季度平均收盘价估算，这笔交易价值约311万美元。增持完成后，Tyra Biosciences占其13F报告资产管理规模的1.39%。这笔交易本身规模不算惊人。真正引人注意的是时机——截至5月14日，Tyra Biosciences的股价在过去一年已经飙升280%，跑赢标普500指数250个百分点。一只已经涨了近三倍的股票，为何还能吸引机构投资者继续买入？HighVista的持仓清单或许能提供一些线索。根据最新披露，其前五大重仓分别为：DBC（3061万美元，8.5%）、ABVX（1261万美元，3.5%）、PRAX（848万美元，2.3%）、COGT（758万美元，2.1%）、SYRE（738万美元，2.0%）。Tyra Biosciences以311万美元的新增持仓位列于其后。从配置结构来看，HighVista对生物科技板块有明显偏好，前五重仓中有四只为纳斯达克上市的生物医药公司。Tyra Biosciences的核心故事围绕一款名为TYRA-300的候选药物展开。这是一款FGFR3抑制剂，针对肌层浸润性膀胱癌。公司的管线还包括FGFR2驱动的胆管癌、FGFR3相关的软骨发育不全、RET激酶以及FGFR4相关癌症等项目。所有项目均处于临床前或早期临床阶段，公司目前尚无产品销售收入。支撑估值的关键在于其SNAP平台——一套用于加速分子设计的专有技术体系。Tyra试图通过这套平台解决肿瘤治疗中的耐药性问题，这在靶向肿瘤学领域是一个普遍痛点。公司将自己定位为"精准疗法"开发商，瞄准的是成纤维细胞生长因子受体（FGFR）相关的癌症和遗传疾病。过去一年股价的暴涨，与管理层推进的"dabogratinib 3x3"战略密切相关。该战略旨在针对FGFR3生物学的三大适应症开展关键性研究。公司最近宣布，SURF303研究——针对低级别上尿路尿路上皮癌——已完成首例患者给药。此外，膀胱癌和软骨发育不全项目的二期临床数据也在陆续释放。HighVista选择在这个时点加仓，暗示部分投资者认为即将到来的临床催化剂可能支撑更高的估值预期。但这也带来一个典型的生物科技投资困境：当股价已经反映大量乐观预期后，后续的临床数据是否还能带来超额回报？从交易结构看，HighVista的增持使该笔持仓的季末价值增加了411万美元，这一数字包含新增股份和股价增值两部分。考虑到Tyra过去一年280%的涨幅，早期布局的投资者已经获得丰厚回报，而新进入者则面临更高的成本基础和更窄的安全边际。对于关注该领域的投资者而言，需要区分两个层面的问题。一是SNAP平台的技术价值是否被充分验证——这关系到管线的整体成功率；二是TYRA-300在特定适应症中的临床数据质量——这决定短期股价催化剂的方向。HighVista的加仓行为表明，至少有一家机构对这两个问题的答案持积极态度。不过， preclinical-stage（临床前阶段）生物科技公司的投资风险结构特殊：没有产品收入意味着完全依赖资本市场融资，股价波动与临床进展高度绑定。过去一年280%的涨幅既反映了市场对FGFR3靶点的热情，也可能透支了部分未来空间。HighVista此时加码，是在押注"3x3"战略即将进入数据密集期，还是单纯基于组合配置的再平衡，文件本身并未给出更多线索。值得跟踪的后续信号包括：SURF303研究的入组进度、二期数据的读出时间表，以及公司现金跑道（cash runway）的持续时间。这些变量将决定HighVista这笔增持最终是锦上添花，还是高位接盘。

100 项与 Dabogratinib 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
肾盂和输尿管尿路上皮癌	临床2期	美国	Tyra Biosciences, Inc.	2025-12-22
肾盂和输尿管尿路上皮癌	临床2期	西班牙	Tyra Biosciences, Inc.	2025-12-22
软骨发育不全	临床2期	美国	Tyra Biosciences, Inc.	2025-03-04
软骨发育不全	临床2期	澳大利亚	Tyra Biosciences, Inc.	2025-03-04
软骨发育不全	临床2期	加拿大	Tyra Biosciences, Inc.	2025-03-04
软骨发育不全	临床2期	法国	Tyra Biosciences, Inc.	2025-03-04
软骨发育不全	临床2期	荷兰	Tyra Biosciences, Inc.	2025-03-04
软骨发育不全	临床2期	西班牙	Tyra Biosciences, Inc.	2025-03-04
软骨发育不全	临床2期	瑞典	Tyra Biosciences, Inc.	2025-03-04
软骨发育不全	临床2期	英国	Tyra Biosciences, Inc.	2025-03-04

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT06995677 (SURF302, ASCO_GU2026)	临床2期	FGFR3-altered	60	Dabogratinib 50 mg QD (Randomized)	鹽選淵餘遞顧鏇製襯艱(衊壓繭觸艱網夢淵襯築) = 蓋範網衊廠網憲廠構壓鹹夢鹹鹽觸糧顧膚鑰夢 (鏇齋願簾夢遞憲繭製餘 )	积极	2026-02-26
				Dabogratinib 60 mg QD (Randomized)	鹽選淵餘遞顧鏇製襯艱(衊壓繭觸艱網夢淵襯築) = 齋繭廠願膚製繭鹽選淵鹹夢鹹鹽觸糧顧膚鑰夢 (鏇齋願簾夢遞憲繭製餘 ) 更多
NCT05544552 (SURF301, ASCO_GU2026)	临床1/2期	转移性尿路上皮癌 FGFR3-altered	21	Dabogratinib	簾鹹糧廠鹽醖窪觸鑰蓋(齋衊蓋蓋夢鏇糧鏇糧繭) = 構憲壓鹽衊醖願憲餘憲鏇窪簾願觸鹹築夢獵膚 (積蓋築獵鹹醖廠構鬱願 )	积极	2026-02-26
NCT05544552 (SURF301, PRNewswire) 人工标引	临床1/2期	转移性尿路上皮癌	41	TYRA-300	範範衊範選簾壓憲築壓(願憲膚鏇窪遞夢觸構餘) = 壓製廠製鬱襯鏇製淵衊簾鏇積網觸築齋鏇壓艱 (構構夢鑰鬱鹽鬱構餘範 ) 更多	积极	2024-10-24
				TYRA-300 (≥90 mg)	築醖網蓋築壓範壓顧願(製繭願範鑰觸齋齋鑰醖) = 積願簾糧鹽製願醖獵築鬱壓築衊壓積膚憲選艱 (顧積餘鏇憲憲遞築鬱願 ) 更多