Bexotegrast

PLN-101095 Phase 1 data showed deep and durable ongoing responses in checkpoint inhibitor refractory solid tumors PLN-101095 accelerated development plan underway with initiation of Phase 1b indication expansion trial SOUTH SAN FRANCISCO, Calif., March 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 fourth quarter 2025 financial results. “We ended 2025 with encouraging data from our lead oncology program in ICI-refractory patients, an area of unmet medical need, that informed the initiation of our accelerated development plan for PLN-101095,” said Bernard Coulie, M.D., Ph.D., President and Chief Executive Officer of Pliant. “In addition to oncology and the early-stage pipeline programs emerging from Pliant's proprietary integrin platform, we continue to assess opportunities to expand our clinical-stage pipeline that leverage our areas of expertise and align with creating shareholder value.” Fourth Quarter and Recent Developments 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 a Phase 1a/1b open-label, dose-escalation and indication expansion trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary evidence of antitumor activity of PLN-101095, as monotherapy and in combination with pembrolizumab , in patients with immune checkpoint inhibitor (ICI)-refractory advanced or metastatic solid tumors. Data from the Phase 1 trial of PLN-101095 showed deep and durable ongoing responses. In December, the Company announced positive data showing that, in a heavily pretreated patient population, PLN-101095 demonstrated anti-tumor activity in combination with pembrolizumab , an FDA-approved ICI. Four responders were observed consisting of one confirmed complete response and three partial responses (two confirmed, one unconfirmed) out of the 10 secondary ICI refractory patients. These clinical responses were observed in patients with cholangiocarcinoma, melanoma, head and neck squamous cell carcinoma and non-small cell lung cancer (NSCLC). Notably, all responding patients showed large increases in plasma interferon gamma (IFN-γ) after 14 days of monotherapy with PLN-101095 prior to the addition of pembrolizumab . No non-responders showed meaningful increases in plasma IFN- γ. PLN-101095 was generally well tolerated across all doses tested. IFN-γ is known to play a multifaceted role in modulating anti-tumor immunity, with increased tumor expression levels having previously been linked with better outcomes from immune checkpoint blockade. Accelerated development plan of PLN-101095 underway with initiation of Phase 1b indication expansion trial. Based on the encouraging response data and supportive IFN- γ biomarker data from the Phase 1 trial, the Company is advancing an accelerated clinical development plan of PLN-101095 and has initiated a Phase 1b indication expansion trial. The Phase 1b open-label, single dose trial will enroll three cohorts of patients including NSCLC, clear cell renal cell carcinoma and tumors with high tumor mutational burden. Tumor selection was based on data from the Phase 1 trial, as well as strong mechanistic rationale for integrin inhibition. Patients will be treated for 14 days with PLN-101095 dosed at 1,000 mg twice daily as monotherapy, after which pembrolizumab will be added as combination therapy. Study start activities for this trial are underway with first patient enrollment anticipated in second quarter. Interim data is expected in 2027. PLN-101095 Phase 1 data accepted for presentation at AACR Annual Meeting 2026. Data from the Phase 1 trial of PLN-101095 will be the subject of a poster presentation and an oral presentation as part of the Clinical Trials Minisymposium at the upcoming American Association of Cancer Research (AACR) conference to be held April 17-22, 2026, in San Diego, California. 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. The Company believes this integrin-targeting delivery platform has the potential for broad applicability across multiple disease areas utilizing a variety of drug payloads. Corporate Highlights Appointment of Minnie Kuo as Chief Operating Officer. Ms. Kuo joined Pliant in September 2023 as Chief Development Officer, bringing more than 20 years of multinational clinical development experience across various therapeutic areas. In this expanded role, Ms. Kuo bridges Pliant’s science and operations with oversight of clinical operations, early development, program management, regulatory affairs and compliance. INTEGRIS-PSC results published in the Journal of Hepatology . The manuscript, “ Phase II INTEGRIS-PSC trial of bexotegrast, an αvβ6 and αvβ1 integrin inhibitor, in primary sclerosing cholangitis ”, appears in the January 2026 issue of the Journal of Hepatology . Fourth Quarter 2025 Financial Results Research and development expenses were $15.6 million as compared to $38.8 million for the prior-year quarter. The decrease was primarily driven by the discontinuation of BEACON-IPF. General and administrative expenses were $8.0 million as compared to $14.5 million for the prior-year quarter. The decrease was primarily due to lower personnel-related costs resulting from the strategic restructuring of our workforce. Net loss was $23.6 million as compared to $49.7 million for the prior-year quarter. The decrease was primarily attributable to the discontinuation of BEACON-IPF coupled with the decrease in personnel-related costs resulting from the strategic restructuring of our workforce. As of December 31, 2025, the Company had cash, cash equivalents and short-term investments of $192.4 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. The Company’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 solid tumors. Pliant’s early-stage platform includes preclinical research focused on tissue-specific delivery and internalization of drug payloads utilizing integrin receptor-binding molecules. For additional information, please visit: . Follow us on social media 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 express or implied statements include those regarding PLN-101095's development plan, including anticipated timing of data from our ongoing Phase 1 trial and our Phase 1b indication expansion trial, expansion of our clinical-stage pipeline and creation of shareholder value, and the potential of our integrin-targeted delivery platform, among others. Because such statements deal with future events and are based on our current expectations, they are subject to various risks and uncertainties and our actual results, performance or achievements could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including those related to the clinical development of our product candidates, including any delays in our ongoing or planned preclinical or clinical trials, or interactions with regulators, as well as the impact of current macroeconomic, geopolitical and marketplace conditions on our business, operations, clinical supply and plans, our reliance on single-source third parties located in foreign jurisdictions, including China, for critical aspects of our development operations, the risks inherent in the drug development process, the risks regarding the accuracy of our estimates of expenses and timing of development, our capital requirements and the need for additional financing, and our ability to obtain and maintain intellectual property protection for our product candidates. These and additional risks are discussed in the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" in our Annual Report on Form 10-K for the period ended December 31, 2025 which we are filing with the SEC today, available on the SEC's website at 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 December 31, Twelve Months Ended December 31, 2025 2024 2025 2024 Operating expenses: Research and development $ (15,585 ) $ (38,793 ) $ (109,157 ) $ (169,310 ) General and administrative (7,992 ) (14,527 ) (47,216 ) (59,055 ) Total operating expenses (23,577 ) (53,320 ) (156,373 ) (228,365 ) Loss from operations (23,577 ) (53,320 ) (156,373 ) (228,365 ) Interest and other income (expense), net 1,964 4,422 11,416 21,085 Interest expense (136 ) (834 ) (2,559 ) (3,024 ) Loss on extinguishment of debt (1,828 ) — (1,828 ) — Net loss $ (23,577 ) $ (49,732 ) $ (149,344 ) $ (210,304 ) Net loss per share - basic and diluted $ (0.38 ) $ (0.82 ) $ (2.43 ) $ (3.47 ) Shares used in computing net loss per share - basic and diluted 61,449,290 60,854,322 61,366,887 60,538,639 Pliant Therapeutics, Inc. Condensed Balance Sheets (Unaudited) (In thousands) December 31, 2025 December 31, 2024 Assets Current assets Cash and cash equivalents $ 45,445 $ 71,188 Short-term investments 145,499 284,536 Prepaid expenses and other current assets 4,464 6,540 Property and equipment held for sale 1,040 — Total current assets 196,448 362,264 Property and equipment, net 2,940 5,525 Operating lease right-of-use assets 23,966 27,243 Restricted cash 1,482 1,482 Other non-current assets 392 435 Total assets $ 225,228 $ 396,949 Liabilities and stockholders’ equity Current liabilities Accounts payable $ 480 $ 5,960 Accrued research and development 4,804 14,363 Accrued liabilities 9,634 12,353 Lease liabilities, current 1,447 542 Total current liabilities 16,365 33,218 Lease liabilities, non-current 27,658 29,439 Long-term debt — 30,211 Total liabilities 44,023 92,868 Commitments and Contingencies Stockholders’ equity Preferred stock — — Common stock 6 6 Additional paid-in capital 1,040,610 1,013,806 Accumulated deficit (859,396 ) (710,052 ) Accumulated other comprehensive (loss) gain (15 ) 321 Total stockholders’ equity 181,205 304,081 Total liabilities and stockholders’ equity $ 225,228 $ 396,949

自身免疫性肝病 因发病机制不明，治疗难度大，若控制不佳易进展为肝硬化、肝衰竭，让患者陷入长期焦虑。 2025 年，自身免疫性肝病领域的研究取得一系列进展，从治疗理念、发病机制到治疗方案均实现革新，精准化、个体化治疗成为主流，为患者带来新希望。以下从核心进展、临床价值、实操建议三方面，为你清晰解读。 治疗新理念 从 “控制指标”  到 “追求再代偿” 长期以来，自身免疫性肝病的治疗目标仅聚焦于稳定肝功能指标，但 2025 年的研究提出了更积极的方向 ——“再代偿”，即让已出现肝硬化失代偿（如腹水、肝性脑病）的患者，通过治疗恢复稳定状态，重新摆脱失代偿症状。 原发性胆汁性胆管炎（PBC）： 首次明确了 “再代偿” 的临床判定标准，让这一概念从模糊共识变得可评估、可操作；淋巴细胞 - 单核细胞比值可作为预测患者能否实现 “再代偿” 的关键指标，帮助医生提前判断治疗效果。 自身免疫性肝炎（AIH）： 研究证实，实现 “再代偿” 的患者能获得明确临床获益，肝性脑病分级和终末期肝病模型联合钠（MELD-Na）评分的下降幅度，是影响 “再代偿” 能否成功的重要因素。 强化治疗理念： 针对 PBC 患者中对熊去氧胆酸应答不佳或无法耐受的人群，提出 “强化治疗” 方案，包括早期识别、以碱性磷酸酶复常为目标的联合用药、结合生物标志物和肝脏硬度的风险分层，让治疗更精准。 发病新机制 聚焦肝脏免疫微环境 找到精准干预靶点 对发病机制的深入研究，为开发靶向药物提供了基础，2025 年的研究聚焦肝脏局部的免疫失衡。 固有免疫与适应性免疫的 “对话” 异常： PBC 患者肝脏中的库普弗细胞（肝脏巨噬细胞）自噬活性异常，会激活 CD8+T 细胞，进而损伤胆管，这一发现为通过调节巨噬细胞功能干预疾病提供了新思路。 免疫细胞的异常招募与功能转换： 特定 B 细胞会招募组织驻留 T 细胞，加重肝脏炎症；原本负责抑制炎症的调节性 T 细胞，会转化为促炎细胞，形成 “自我强化” 的炎症环路，持续损伤肝脏。 肝细胞铁死亡失控： 肝细胞的铁死亡机制异常激活，会进一步加重肝脏炎症，成为疾病进展的重要推手。 治疗新选择 个体化方案更贴合患者需求 基于新的理念和机制，2025 年的治疗方案更具针对性，覆盖不同疾病类型和症状。 原发性胆汁性胆管炎（PBC）： 二线治疗明确：奥贝胆酸撤市后，苯扎贝特成为核心二线选择，长期真实世界数据证实，它在改善肝功能指标、缓解症状、保护肝脏组织甚至延长生存期方面均有优势。 新型药物登场：PPARδ 选择性激动剂 Seladelpar 治疗 2 年，能稳定改善肝功能和瘙痒症状，安全性良好。 新药研发-症状靶向治疗：回肠胆汁酸转运体抑制剂 Linerixibat 在 Ⅲ 期临床试验中证实有效，针对性解决困扰患者的瘙痒问题，让治疗从 “只护肝” 转向 “兼顾患者整体生活质量”。 自身免疫性肝炎（AIH）： 风险因素明确：肝硬化和生化应答不充分是影响患者生存期的主要因素； 激素方案优化：急性 AIH 患者采用激素缓慢减量方案，能延长生存期并减少不良反应； IgG4 相关疾病：伊奈利珠单抗可降低复发风险，提高 1 年内无复发完全缓解的概率，为靶向治疗提供新选择。 原发性硬化性胆管炎（PSC）： 多款靶向药进入临床试验：Nebokitug（靶向炎症招募）、Bexotegrast（抑制纤维化激活）、Elafibranor（调节胆汁酸代谢）等，均显示出改善肝功能或纤维化的潜力； 精准治疗时代 规范应对是关键 2025 年自身免疫性肝病领域的进展，标志着诊疗已迈入 “精准化、个体化” 时代。从 “控制指标” 到 “追求再代偿”，从 “广谱用药” 到 “靶向干预”，这些突破让患者不再被动承受疾病，而是有了更主动的治疗方向。 对患者而言，核心是做好 “规范治疗、定期复查、精准匹配” ： 不放弃现有治疗基础，主动关注新进展，与医生充分沟通自身病情（如是否有肝硬化、药物应答情况、症状困扰），制定适合自己的方案。 相信随着研究的深入，未来会有更多精准疗法落地，帮助患者更好地控制病情，拥有更高质量的生活。 文章改编自：尚玉龙, 韩英 . 2025 年自身免疫性肝病研究进展：迈向精准调控与个体化治疗[J]. 中华肝脏病杂志, 2026, 34(1):10-12. DOI: 10.3760/cma.j.cn501113-20251219-00541. ⬆ 点击上方名片 ⬆ 关注护肝百科 获取更多权威肝病诊疗内容 声明：本文仅作健康科普，不能替代医院的检查和治疗。如有相关疾病，请及时前往正规医疗机构就诊，并谨遵医嘱。