Bexotegrast

FORTIFY, a Phase 1b indication expansion trial of PLN-101095, experiencing strong enrollment Appointed seasoned oncology drug development leaders Flavia Borellini, Ph.D. and Robert Iannone, M.D., M.S.C.E. to Board of Directors SOUTH SAN FRANCISCO, Calif., Aug. 11, 2026 (GLOBE NEWSWIRE) -- Pliant Therapeutics, Inc. (Nasdaq: PLRX), a clinical-stage biotechnology company focused on the discovery and development of integrin-based therapeutics, today provided a corporate update and reported second quarter 2026 financial results. “In the second quarter, we continued to execute across the portfolio, led by strong enrollment in FORTIFY,” said Bernard Coulie, M.D., Ph.D., President and Chief Executive Officer of Pliant. “With the appointments of Flavia and Robert to the board, Pliant now has deep global oncology drug development and commercialization expertise at this important time for our oncology program. We continue to make progress on our proprietary integrin-targeted drug-delivery platform and look forward to sharing more information on the platform soon.” ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); Oncology Program PLN-101095 is an oral, small molecule, dual selective inhibitor of αvβ8 and αvβ1 integrins designed to overcome checkpoint resistance by blocking TGF-β activation in the tumor microenvironment. Pliant is currently conducting FORTIFY, a Phase 1a/1b open-label, dose-escalation and indication expansion trial ( NCT0670706 ), to evaluate the safety, tolerability, pharmacokinetics, and preliminary evidence of antitumor activity of PLN-101095, in combination with pembrolizumab, in patients with immune checkpoint inhibitor (ICI)-refractory advanced or metastatic solid tumors. Enrollment continues in FORTIFY, a Phase 1b indication expansion trial. FORTIFY will enroll up to 102 patients across three cohorts including non-small cell lung cancer (NSCLC), clear cell renal cell carcinoma (ccRCC) and tumors with high tumor mutational burden. Patients are treated for 14 days with PLN-101095 dosed at 1,000 mg twice daily as monotherapy, after which pembrolizumab is added as combination therapy. Enrollment remains strong, progressing ahead of schedule. Interim data is expected in 2027. Oral presentation at AACR of updated PLN-101095 Phase 1 data highlights monotherapy biomarker data showing a coordinated T-cell reactivation cascade in responders. In July, at the American Association for Cancer Research’s (AACR) Drug Discovery and Development conference, the Company reviewed encouraging PLN-101095 Phase 1 monotherapy biomarker data. As previously reported, all responding patients showed large increases in plasma interferon gamma (IFN-γ), a modulator of anti-tumor immunity, after 14 days of monotherapy with PLN-101095. Updated data show that blocking of αvβ8 by PLN-101095 also resulted in increases in CXCL9, a recruiter of T cells, and granzyme-B, a marker for cytotoxic arming in responding patients. Increased IFN-γ, CXCL9 and granzyme-B after PLN-101095 monotherapy signals a shift in the tumor microenvironment that could potentially resensitize tumors to pembrolizumab. Importantly, no non-responders experienced increases in these biomarkers. Integrin-Targeted Delivery Platform Utilizing cell-specific integrin receptors, Pliant has developed a platform to deliver drug payloads, including siRNAs, to selective tissue types. Current programs are focused on delivering siRNAs to skeletal muscle cells and other tissues. Preclinical proof-of-concept studies are currently ongoing. The Company believes this integrin-targeting drug-delivery platform has the potential for broad applicability across multiple disease areas utilizing a variety of drug payloads. Pliant plans to provide additional detail on the platform and path forward, including initial treatment indications, in the second half of 2026. Corporate Highlights Appointed Flavia Borellini, Ph.D. and Robert Iannone, M.D., M.S.C.E. to the Company’s Board of Directors. Dr. Borellini brings more than 25 years of executive management experience in the biopharmaceutical industry with a focus on the global development of targeted oncology drugs from preclinical to commercial stage. Dr. Iannone, who currently serves as Executive Vice President, Research and Development and Chief Medical Officer at Jazz Pharmaceuticals, brings more than two decades of executive drug development and regulatory leadership, including the approval of several targeted and immuno-oncology medicines. Second Quarter 2026 Financial Results Research and development expenses were $16.7 million, as compared to $32.2 million for the prior-year quarter. The decrease was primarily due to completing close-out activities for BEACON-IPF, a Phase 2b/3 study of bexotegrast, in 2025 and reduced personnel-related expenses, including stock based compensation, driven by decreased headcount compared to prior year. General and administrative expenses were $7.1 million, as compared to $13.4 million for the prior-year quarter. The decrease was primarily due to personnel-related expenses, including stock-based compensation, driven by decreased headcount compared to prior year. Net loss was $22.4 million as compared to $43.3 million for the prior-year quarter. The decrease was primarily due to significantly lower operating expenses following the termination of bexotegrast development in IPF in 2025 and decreased personnel-related expenses, including stock-based compensation, driven by reduced headcount compared to prior year. As of June 30, 2026, the Company had cash, cash equivalents and short-term investments of $159.6 million which the Company expects to be sufficient to fund operations into the second half of 2028. About Pliant Therapeutics, Inc. Pliant Therapeutics is a clinical-stage biopharmaceutical company focused on the discovery and development of integrin-based therapeutics. Pliant’s lead program is PLN-101095, a small molecule, dual-selective inhibitor of αvß8 and αvß1 integrins, that is being developed for the treatment of ICI-refractory advanced or metastatic solid tumors. PLN-101095 is being investigated in FORTIFY, a Phase 1b indication expansion trial, enrolling patients with NSCLC, tumors with high tumor mutational burden or clear cell renal cell carcinoma. Pliant’s preclinical research is focused on tissue-specific delivery and internalization of drug payloads utilizing integrin receptor-binding molecules with programs focused on delivering siRNAs to skeletal muscle cells, adipocytes, and renal cells. For additional information, please visit: . Follow Pliant on social media at X , LinkedIn and Facebook . Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "anticipate," "estimate," "intend," and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. These statements include express or implied statements regarding ongoing clinical trial development of PLN-101095, including timing of enrollment and data; the potential benefits of PLN-101095; and Pliant’s plans for the continued development of PLN-101095; and plans for its integrin-based drug delivery platform, including timing of additional details, including initial treatment indications; among others. Because such statements deal with future events and are based on Pliant’s current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Pliant could differ materially from those described in or implied by the statements in this press release. These risks and uncertainties, including those related to the development and commercialization of Pliant’s product candidates, including any delays in Pliant’s ongoing or planned preclinical studies or clinical trials, the impact of current macroeconomic, geopolitical and marketplace conditions on Pliant’s business, operations, clinical supply and plans, Pliant’s reliance on single-source third parties located in foreign jurisdictions, including China, for critical aspects of Pliant development operations, the risks inherent in the drug development process, the risks regarding the accuracy of Pliant’s estimates of expenses and timing of development, its capital requirements and the sufficiency of its cash to support Pliant’s planned operations, and Pliant’s ability to obtain and maintain intellectual property protection for Pliant’s product candidates. These and additional risks are discussed in the sections titled "Management's Discussion and Analysis of Financial Condition and Results of Operations" and "Risk Factors" in Pliant’s Quarterly Report on Form 10-Q for the period ended June 30, 2026, which Pliant is filing with the Securities and Exchange Commission (SEC) today, and which will be available on the SEC's website at as well as other risks or uncertainties set forth in Pliant’s future SEC filings. Unless otherwise noted, Pliant is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. Investor and Media Contact: Christopher Keenan Vice President, Investor Relations and Corporate Communications Pliant Therapeutics, Inc. ir@pliantrx.com Pliant Therapeutics, Inc. Condensed Statements of Operations (Unaudited) (In thousands, except number of shares and per share amounts) Three Months Ended June 30, 2026 Six Months Ended June 30, 2026 2026 2025 2026 2025 Operating expenses: Research and development $ (16,727 ) $ (32,198 ) $ (30,311 ) $ (75,634 ) General and administrative (7,135 ) (13,394 ) (15,323 ) (28,893 ) Total operating expenses (23,862 ) (45,592 ) (45,634 ) (104,527 ) Loss from operations (23,862 ) (45,592 ) (45,634 ) (104,527 ) Interest and other income (expense), net 1,491 3,101 3,223 6,669 Interest expense — (809 ) — (1,608 ) Net loss $ (22,371 ) $ (43,300 ) $ (42,411 ) $ (99,466 ) Net loss per share - basic and diluted $ (0.36 ) $ (0.71 ) $ (0.69 ) $ (1.62 ) Shares used in computing net loss per share - basic and diluted 61,919,233 61,386,183 61,861,670 61,304,881 Pliant Therapeutics, Inc. Condensed Balance Sheets (Unaudited) (In thousands) June 30, 2026 December 31, 2025 Assets Current assets Cash and cash equivalents $ 24,883 $ 45,445 Short-term investments 133,218 145,499 Prepaid expenses and other current assets 4,135 4,464 Property and equipment held for sale 906 1,040 Total current assets 163,142 196,448 Property and equipment, net 2,414 2,940 Operating lease right-of-use assets 22,289 23,966 Restricted cash 1,482 1,482 Other non-current assets 554 392 Total assets $ 189,881 $ 225,228 Liabilities and stockholders’ equity Current liabilities Accounts payable $ 1,531 $ 480 Accrued research and development 9,028 4,804 Accrued liabilities 3,653 9,634 Lease liabilities, current 2,272 1,447 Total current liabilities 16,484 16,365 Lease liabilities, non-current 26,471 27,658 Total liabilities 42,955 44,023 Commitments and Contingencies Stockholders’ equity Preferred stock — — Common stock 6 6 Additional paid-in capital 1,049,124 1,040,610 Accumulated deficit (901,807 ) (859,396 ) Accumulated other comprehensive loss (397 ) (15 ) Total stockholders’ equity 146,926 181,205 Total liabilities and stockholders’ equity $ 189,881 $ 225,228

你的器官正在悄悄"变硬" 解密器官纤维化——从"疤痕"到"逆转"还有多远 科学认知 · 前沿治疗 · 逆转可能 你有没有想过——我们身体里的器官，也会像皮肤一样"结痂"？ 皮肤破了，会结一个痂。痂掉了，底下是新的好皮肤。 但如果伤口一直反复破、反复愈合，疤痕就会越来越厚，最后变成一块硬邦邦的"老茧"，失去弹性，再也回不到原来的样子。 器官纤维化，就是这个过程——发生在你的肝脏、肺脏、肾脏、心脏里面。 全球约 25% 的人口受到各种器官纤维化的影响，每年新增病例比例接近 5%。更可怕的是，目前几乎没有任何药物能真正逆转已形成的纤维化。器官移植，往往是唯一的"终极大招"。 但好消息是——科学界正在以空前的速度攻破这个难题。2024年，首个MASH相关肝纤维化新药在美国获批；2025年，AI设计的抗纤维化药物进入临床二期；2026年，mRNA靶向递送系统实现了纤维化组织的精准治疗…… 今天，我们就来把"器官纤维化"这件事，从原理到治疗，彻底说清楚。 （全文约4500字，阅读约需12分钟） 一、纤维化到底是怎么回事？"水管生锈"三步曲 在深入之前，我们先建立两个关键认知： 第一，纤维化本身不是坏事。当细胞受伤时，身体会派"修复队"（成纤维细胞）去堵伤口，产生胶原蛋白来加固组织——这是我们身体最基础的自我修复机制。 第二，纤维化的坏，坏在"过犹不及"。如果损伤反复发生（比如持续的病毒感染、酒精刺激、高血糖、高血压），修复信号就会紊乱，"修复队"收到"永远在干活"的错误指令，胶原蛋白越堆越多，正常组织被硬疤痕取代。 你可以把它想象成一根水管： 正常水管内壁光滑，水流顺畅。但当水质不好（持续损伤），内壁开始生锈（炎症），锈层越积越厚（胶原蛋白堆积），水管内径越来越窄，水流越来越小，最后——水管彻底堵死（器官衰竭）。 这个过程，大致分三步： 第一步：损伤。病毒感染（乙肝、丙肝）、高脂高糖饮食（脂肪肝）、酒精、吸烟、空气污染（PM2.5）、高血压、自身免疫疾病……各种原因让器官细胞反复受伤。 第二步：炎症。身体启动"应急响应"，免疫细胞涌向伤口，释放大量炎症信号分子（如TGF-β——纤维化的总指挥）。这个信号本该是"临时加班通知"，结果变成了"永久上班命令"。 第三步：疤痕堆积。在TGF-β的持续指挥下，成纤维细胞大量活化，变成"肌成纤维细胞"——一种疯狂生产胶原蛋白的"织布机"细胞。它们日夜不停地织啊织，最终用"胶原毯"把正常的器官组织活活闷死。说人话： 纤维化就是你的器官在反复受伤后，长了一层又一层的"厚痂"。这层痂如果只长一次，问题不大；但如果它一直长、不停长，就会把原本柔软有弹性的器官变成一块硬邦邦的"老茧"。  二、哪些器官会"变硬"？每一处都是致命危机 纤维化可以发生在几乎任何器官，但以下五个是最常见的"重灾区"：肝脏纤维化 肝脏是纤维化的"头号靶器官"。乙肝、丙肝、脂肪肝、酒精肝都可能发展为肝纤维化→肝硬化→肝癌。全球约 7.3% 的人存在显著肝纤维化，每年约 5800万 新增慢性肝病病例、140万 死亡。一旦进入肝硬化期，5年生存率低于50%。肺纤维化 特发性肺纤维化（IPF）是一种原因不明的致命疾病。患者的中位生存期仅 2.5-3.5年，比很多癌症还要凶险。肺组织逐渐被疤痕取代，就像两块玻璃之间的气泡被胶水填满——气体交换越来越困难，患者最终因缺氧而窒息。我国IPF发病率约0.57-4.51/10万人，且呈逐年上升趋势。肾纤维化 几乎所有慢性肾病（CKD）的终末期都表现为肾纤维化。全球约 8.5亿 人受慢性肾病影响，其中大量患者最终走向肾衰竭，需要终身透析或肾移植。肾纤维化的早期几乎无症状，当发现时往往已无法逆转。心脏纤维化 心梗后、高血压长期控制不佳，都会导致心肌纤维化。正常的心肌像有弹性的橡皮筋，纤维化后变成"硬塑料"——心脏收缩舒张功能严重受限，最终走向心力衰竭。胰腺纤维化 反复发作的胰腺炎可导致胰腺纤维化，破坏胰岛β细胞，引发继发性糖尿病。 受累器官 主要病因 进展结局 打个比方 肝脏 乙肝/丙肝、脂肪肝、酒精 肝硬化→肝癌 水管内壁生锈堵死 肺脏 吸烟、PM2.5、不明原因 呼吸衰竭 海绵变成石头 肾脏 糖尿病、高血压 肾衰竭→透析 净水器的滤芯堵了 心脏 心梗、高血压 心力衰竭 橡皮筋变成铁丝 三、目前的治疗：能做什么？局限性在哪？ 这是本文读者最关心的问题。我们必须坦诚地说：目前，晚期纤维化的治疗效果非常有限。但不同阶段、不同器官，策略完全不同。第一层：病因治疗——治标防本 这是最关键的一步。如果导致纤维化的"火源"不灭，任何药物都像"一边救火一边加油"。 • 抗病毒治疗：乙肝/丙肝患者用抗病毒药清除病毒后，部分早期肝纤维化可以自行逆转• 戒酒：酒精性肝病在戒酒6-12个月后，部分纤维化可以减轻• 控制代谢：减重、控制血糖、降血脂——代谢相关脂肪性肝炎（MASH）患者减重≥10%后，相当比例肝纤维化可改善• 降压药（ACEI/ARB类）和SGLT2抑制剂（如达格列净）可延缓肾纤维化进展局限性 ：病因治疗只能阻止纤维化继续恶化，对于已经形成的纤维化疤痕，效果微乎其微。就像一个水管已经锈了5毫米——即使水质变好了，这5毫米锈也不会自己消失。 第二层：目前仅有的抗纤维化药物 目前全球经过大型临床试验证实有效、获批上市的抗纤维化药物，仅寥寥几种： 药物 适用器官 机制 获批年份 吡非尼酮 肺（IPF） 抑制TGF-β、抗炎 2011/2014 尼达尼布 肺（IPF/PPF） 多靶点激酶抑制剂 2014 Resmetirom 肝（MASH） THR-β激动剂 2024 司美格鲁肽 肝（MASH） GLP-1激动剂（间接作用） 2024 ⚠️ 局限性： • 只能延缓，不能逆转：吡非尼酮和尼达尼布仅能将肺功能年下降量减少约50%，但不能阻止疾病进展，不能逆转已形成的纤维化，也未能显著改善生存率• 副作用明显：尼达尼布常见腹泻（发生率高达62%），吡非尼酮常见光敏皮疹和胃肠道不适，很多患者因为副作用无法长期用药• 适用范围极窄：这些药物只对特定器官的特定类型纤维化有效，肝纤维化药物不能用于肺，反之亦然• 费用高昂：尼达尼布年治疗费用约10-15万美元，对大多数患者难以承受 那米司特（Namilumab） 是2025年IPF领域唯一在III期试验中取得阳性的新药，可延缓FVC下降约67ml/年。但近10年来，抗纤维化新药从II期进入III期的成功率仅约15%，研发难度极高。第三层：终末手段——器官移植 当器官功能彻底衰竭，目前唯一的"治愈"手段就是器官移植。肝移植、肾移植、肺移植、心脏移植——把"锈死的旧水管"换成"崭新的新水管"。 局限性：供体极度稀缺（中国每年仅约1万例器官移植，而需要的人数超过30万），终身服用免疫抑制剂，排异反应风险，手术本身的高风险和巨额费用（30-80万元）。 四、前沿战局：正在攻克的六条技术路线 虽然目前的治疗方案有限，但全球科学家正在从多个方向同时进攻纤维化这个难题。以下是最有希望的六大技术路径：1. 新一代抗纤维化小分子药物 中国自主研发的羟尼酮（Hydronidone）是一种TGF-β1抑制剂，已完成慢性乙肝肝纤维化的II期临床，并已在国内申请上市。这是全球少数针对肝纤维化的创新药之一。 Rentosertib 是全球首个由AI设计的抗纤维化药物，靶向多种激酶，2025年公布的II期数据显示：60mg剂量组FVC平均增加98.4ml（安慰剂组下降20.3ml），同时DLCO和6分钟步行距离也有改善趋势。这是AI制药在纤维化领域的重要里程碑。2. 靶向TGF-β通路——但更聪明 TGF-β是纤维化的"总指挥"，但直接抑制它就像"把所有人的手机信号全屏蔽"——好消息是纤维化的指挥没了，坏消息是免疫系统也瘫痪了。因此，科学家转向更精准的策略： • αvβ6/αvβ1整合素抑制剂（如Bexotegrast）：只抑制在纤维化组织中激活TGF-β的一种特殊"开关"，不干扰全身的TGF-β功能• YAP/TAZ通路抑制剂：靶向纤维化细胞"感受到机械压力"的信号传导通路• MERTK抑制剂：在多个器官的纤维化模型中均显示疗效3. CAR-T细胞疗法：免疫细胞的精准打击 2022年，宾夕法尼亚大学的研究团队在《Science》上发表了一个令人震惊的发现：用CAR-T细胞靶向攻击活化的成纤维细胞，可以逆转心脏纤维化——让已经硬化的心脏重新变软。 这打破了"纤维化不可逆"的传统认知。现在，多家公司正在开发针对纤维化的"通用型"CAR-T和CAR-NK疗法。2026年的多项研究表明，这种策略在肝纤维化和肺纤维化动物模型中同样有效。打个比方： 传统的抗纤维化药物像是"给织布机减少原材料"，让疤痕织得慢一点；而CAR-T疗法像是"直接派杀手去拆织布机"——更加彻底，但也需要更精准的控制，防止误伤正常组织。 4. mRNA-LNP精准递送：给药物装上"导航" 2026年2月，北京大学苗蕾团队在JACS上发表研究，开发了一种名为"FOCUS"的mRNA递送系统。这个系统利用纤维化组织中特异性高表达的FAP（成纤维细胞活化蛋白）作为靶点，将编码抗纤维化蛋白（如HGF、BMP-7）的mRNA精准递送到纤维化病灶。 就像给药物装上了"GPS导航"——只在病变组织里释放药效，不伤及健康器官。5. 干细胞与再生医学 间充质干细胞（MSCs）具有强大的免疫调节和抗炎能力。多项临床试验正在探索MSC治疗肝纤维化、肺纤维化的安全性和有效性。2026年的最新数据显示，MSC外泌体疗法在抗纤维化方面展现出了特别的潜力——不需要活的干细胞，只需要它们分泌的"修复因子"，就能减轻纤维化。6. AI驱动的药物发现 纤维化药物研发的II期临床成功率仅15%，远低于其他领域。AI正在改变这个局面。从靶点发现到分子设计，AI可以将药物发现周期缩短30%以上。Rentosertib的成功就是最好的例证——它完全由AI平台设计，从化合物筛选到进入临床仅用了不到3年。 五、未来：纤维化从"不治之症"到"可控慢病"？ 2026年的今天，我们正处在一个关键的转折点。 十年前，纤维化被认为是像水泥一样一旦凝固就永远不可逆的。今天，我们已经知道： • 早期纤维化在去除病因后可以自行逆转• 靶向活化成纤维细胞的CAR-T疗法在动物模型中实现了"逆转"• AI设计的抗纤维化药物已在人体中显示疗效信号• mRNA/LNP精准递送系统正在将抗纤维化药物靶向到病变组织 未来5-10年，我们很可能看到： • 早期筛查：通过无创的液体活检（血液纤维化标志物）+AI影像分析，在纤维化还处于早期可逆阶段时就发现它• 精准治疗：根据患者的基因组学、蛋白质组学特征，选择最适合的抗纤维化药物组合• 逆转策略：新一代疗法（CAR-T、mRNA、基因编辑）可能有能力真正"溶解"已经形成的纤维疤痕• 多器官协同治疗：认识到纤维化在不同器官存在共同的分子机制，开发"泛器官"抗纤维化药物 但也要清醒地认识到，这条路的挑战依然巨大： • 疾病异质性——不同患者、不同器官的纤维化机制显著不同• 缺乏可靠的早期生物标志物• 临床试验周期长（纤维化进展通常以年为单位）• 安全性——特别是CAR-T和基因编辑疗法的长期安全性数据还远远不够 写在最后 器官纤维化是医学界最顽固的挑战之一，它造成的死亡人数超过了大多数癌症。 但它正在从"绝症"慢慢变成"可以管理"的慢性病。而且，我们每个人手里都有最有效的"预防药"—— 控制体重、少喝酒、不抽烟、管理血压血糖、接种乙肝疫苗。 这些事做对了，你的器官大概率不会走到纤维化的那一步。 参考来源：Nature Signal Transduction and Targeted Therapy (2026)、MDPI Molecules (2025)、Dovepress DDDT (2026)、中华结核和呼吸杂志年度进展 (2026)、北京大学JACS (2026)、ClinicalTrials.gov