Financial Performance - Net loss for the nine months ended September 30, 2025, was $125,767,000, a reduction of 21.7% compared to a net loss of $160,572,000 for the same period in 2024[24]. - Comprehensive loss for the three months ended September 30, 2025, was $26,266,000, compared to $56,298,000 for the same period in 2024, indicating a 53.3% improvement[24]. - The company reported a net loss of $26.3 million for the three months ended September 30, 2025, compared to a net loss of $57.8 million for the same period in 2024, representing a decrease of $31.5 million[106]. - Net loss for the nine months ended September 30, 2025, was $125,767, a 21.7% improvement from a net loss of $160,572 in the same period of 2024[32]. - The company had an accumulated deficit of $835.8 million as of September 30, 2025[106]. Assets and Liabilities - Total current assets decreased from $362,264,000 as of December 31, 2024, to $245,588,000 as of September 30, 2025, a decline of approximately 32.3%[21]. - Total liabilities decreased from $92,868,000 as of December 31, 2024, to $76,294,000 as of September 30, 2025, a reduction of approximately 17.9%[21]. - Total stockholders' equity decreased from $304,081,000 as of December 31, 2024, to $200,306,000 as of September 30, 2025, a decline of approximately 34.2%[21]. - The company’s total financial assets amounted to $226,913 as of September 30, 2025, down from $339,361 as of December 31, 2024, a decrease of 33.1%[46]. - As of September 30, 2025, total accrued liabilities amounted to $8,173,000, a decrease of 33.4% from $12,353,000 as of December 31, 2024[51]. Cash Flow - Cash and cash equivalents increased from $71,188,000 as of December 31, 2024, to $93,732,000 as of September 30, 2025, representing a growth of 31.7%[21]. - Cash flows from operating activities resulted in a net cash used of $110,548 for the nine months ended September 30, 2025, compared to $107,841 in 2024, indicating a slight increase in cash outflow[32]. - Net cash provided by investing activities was $132,522 for the nine months ended September 30, 2025, compared to $101,208 in 2024, reflecting a 30.8% increase[32]. - Cash and cash equivalents at the end of the period increased to $95,214 as of September 30, 2025, up from $81,098 at the end of 2024, representing a 17.4% increase[32]. - As of September 30, 2025, the company had approximately $243.3 million in cash, cash equivalents, restricted cash, and short-term investments, which is expected to fund operations for the next 12 months[161]. Research and Development - Research and development expenses for the three months ended September 30, 2025, were $17,938,000, down 62.5% from $47,754,000 in the same period of 2024[24]. - Research and development expenses decreased by $29.8 million to $17.9 million for the three months ended September 30, 2025, primarily due to the discontinuation of the bexotegrast development in IPF[118]. - Research and development expenses for the nine months ended September 30, 2025 decreased by $36.9 million to $93.6 million, primarily due to the discontinuation of the bexotegrast development in IPF[124]. - The company discontinued the BEACON-IPF Phase 2b trial and the development of bexotegrast in idiopathic pulmonary fibrosis due to an unfavorable risk-benefit profile[36]. - The company completed enrollment in the Phase 1 trial of PLN-101095, which showed an objective response rate of 50% in the third ascending dose cohort[100]. Stock and Compensation - The number of shares used in computing net loss per share increased from 60,730,935 in Q3 2024 to 61,406,475 in Q3 2025[24]. - The company had $28.4 million of unrecognized compensation costs related to stock options expected to be recognized over a weighted-average period of 2.4 years[71]. - As of September 30, 2025, the company had $9.5 million of unrecognized stock-based compensation expense related to outstanding RSUs, expected to be recognized over a weighted-average period of 1.7 years[73]. - The company issued 61,231 shares of common stock under the 2020 ESPP during the three months ended September 30, 2025[77]. - For the three months ended September 30, 2025, total stock-based compensation expense was $6.418 million, a decrease from $8.899 million in the same period of 2024[79]. Debt and Interest - The company drew an additional Term Loan of $20 million in March 2024, increasing the total Term Loan facility to $150 million[52]. - The effective interest rate for the Term Loan was 10.61% for the three months ended September 30, 2025, compared to 11.57% for the same period in 2024[57]. - Interest expense for the three months ended September 30, 2025, was $0.8 million, a slight decrease from $0.9 million in the same period of 2024[57]. - Cash paid for interest increased to $2,192 for the nine months ended September 30, 2025, compared to $1,850 in 2024, reflecting an increase of 18.5%[32]. - Interest expense increased by $0.2 million due to additional borrowings under the Amended Loan Agreement[128]. Operational Challenges - The company expects to continue incurring net losses for the foreseeable future as it advances its product candidates[106]. - The company requires substantial additional capital to fund operations and may be forced to delay or eliminate research and drug development programs if unable to raise capital on acceptable terms[160]. - Clinical development is a lengthy and expensive process, with the potential for significant setbacks, as demonstrated by the discontinuation of the BEACON-IPF trial and the development of bexotegrast in IPF[173]. - The company may experience fluctuations in quarterly operating results due to competing technological developments and the costs associated with establishing sales and marketing capabilities[163]. - The company faces significant risks in clinical trials, with most product candidates that commence trials never receiving approval[174]. Market and Regulatory Environment - The company has no products approved for commercial sale and has not generated any revenue from product sales to date, indicating a high dependency on the success of product candidates[166]. - Market acceptance of product candidates is crucial for commercial success, and lack of acceptance may hinder revenue generation and profitability[215]. - Coverage and reimbursement from third-party payors, including government programs like Medicare and Medicaid, are critical for new product acceptance and sales[217]. - There is significant uncertainty regarding the coverage and reimbursement status of products, which may affect their marketability[217]. - The FDA's evolving regulatory standards can complicate the approval process, making it difficult to predict outcomes[176].

Financial Performance - Research and development expenses for Q3 2025 were $17.9 million, down from $47.8 million in Q3 2024, primarily due to the discontinuation of the BEACON-IPF trial[6] - General and administrative expenses decreased to $10.3 million in Q3 2025 from $14.3 million in Q3 2024, attributed to lower personnel-related costs from workforce restructuring[6] - The net loss for Q3 2025 was $26.3 million, a reduction from $57.8 million in the same quarter last year, mainly due to the discontinuation of BEACON-IPF and reduced personnel costs[6] - Total operating expenses for Q3 2025 were $28.3 million, significantly lower than $62.0 million in Q3 2024[11] Cash and Assets - As of September 30, 2025, the company had cash, cash equivalents, and short-term investments totaling $243.3 million[6] - The total assets as of September 30, 2025, were $276.6 million, down from $396.9 million at the end of 2024[13] Clinical Trials - The Phase 1 trial of PLN-101095 in solid tumors has completed enrollment, with interim data showing a 50% objective response rate in one of the dose cohorts[3] - Close out activities for the BEACON-IPF Phase 2b/3 clinical trial are expected to be completed in Q4 2025, with full results to be submitted for future publication[4] Strategic Initiatives - The company is evaluating a range of opportunities to create shareholder value moving forward[3] - The company completed a voluntary prepayment of all outstanding principal and interest under the March 11, 2024 Loan Agreement with Oxford Finance LLC in October 2025[5]

Core Insights - Pliant Therapeutics is advancing its oncology program with data from the Phase 1 trial of PLN-101095 expected by the end of 2025, which has shown a 50% objective response rate in one of the dose cohorts [2][3] - The company is winding down activities related to the BEACON-IPF trial, with close-out activities expected to be completed in the fourth quarter of 2025 [3] - Financial results for the third quarter of 2025 show a significant reduction in net loss to $26.3 million from $57.8 million in the prior-year quarter, primarily due to the discontinuation of BEACON-IPF and reduced personnel costs [6][10] Oncology Program - The Phase 1 open-label trial of PLN-101095 has completed enrollment, targeting solid tumors resistant to immune checkpoint inhibitors [2] - Interim data from the trial indicated that PLN-101095 was well tolerated, with a 50% objective response rate in one of the ascending dose cohorts [2] - Full data from the trial, including results from the two highest dose cohorts, is anticipated by the end of 2025 [2] BEACON-IPF Trial - Close-out activities for the BEACON-IPF Phase 2b/3 clinical trial are expected to be finalized in the fourth quarter of 2025 [3] - Full results from the BEACON-IPF trial will be submitted for future publication [3] Financial Performance - Research and development expenses decreased to $17.9 million from $47.8 million year-over-year, attributed to the discontinuation of BEACON-IPF [6][10] - General and administrative expenses also fell to $10.3 million from $14.3 million, mainly due to lower personnel-related costs from workforce restructuring [6][10] - As of September 30, 2025, the company reported cash, cash equivalents, and short-term investments totaling $243.3 million [6] Corporate Developments - In October 2025, the company completed a voluntary prepayment of all outstanding principal and interest under a loan agreement with Oxford Finance LLC [4] - Pliant has received regulatory clearance for a Phase 1 study of PLN-101325, a monoclonal antibody targeting muscular dystrophies [7]

Core Insights - Biotech stocks experienced significant gains in after-hours trading on September 9, 2025, driven by clinical updates, insider buying, and investor conference appearances across several small- and mid-cap companies [1] Company Summaries - **Immutep Ltd. (IMMP)**: Shares rose by 4.37% to $1.67 after-hours, following a decline of 6.98% during regular trading. The stock's rebound was fueled by the acceptance of data from its EFTISARC-NEO Phase II trial for oral presentation at CTOS 2025, focusing on a rare cancer with high unmet need [2][3] - **Nautilus Biotechnology Inc. (NAUT)**: Shares surged by 12.25% to $0.7521 after-hours, recovering from a 4.42% decline in regular trading. The increase was attributed to insider buying by CEO Sujal M. Patel, who purchased 83,500 shares, signaling confidence in the company [4][5] - **Pliant Therapeutics Inc. (PLRX)**: The stock ended regular trading at $1.75, up 1.16%, and jumped 16.00% to $2.03 after-hours. The upcoming third-quarter earnings report on November 6, 2025, is expected to provide updates on its lead candidate targeting idiopathic pulmonary fibrosis [6][7] - **Jin Medical International Ltd. (ZJYL)**: Shares closed at $0.6532, gaining 3.65% during regular trading and rising 7.15% to $0.6999 after-hours. The catalyst for this movement was the announcement of expanded production capabilities in China, aimed at enhancing global delivery of medical equipment [7][8] - **Phio Pharmaceuticals Corp. (PHIO)**: The stock rose 8.20% to $2.64 after-hours, building on a 13.49% increase during regular trading. The momentum was driven by participation in the H.C. Wainwright 27th Annual Global Investment Conference, where updates on its Phase 1b clinical trial for PH-762 will be presented [8][9] - **Kura Oncology Inc. (KURA)**: Shares increased by 6.12% to $8.50 after-hours, following a 1.60% decline in regular trading. The rally was linked to the company's presentation at the H.C. Wainwright conference, highlighting key developments and upcoming regulatory milestones for Ziftomenib [10][11][12]

PART I. FINANCIAL INFORMATION [Item 1. Condensed Financial Statements (Unaudited)](index=6&type=section&id=Item%201.%20Condensed%20Financial%20Statements%20(Unaudited)) Unaudited condensed financial statements for June 30, 2025, show total assets decreased to $299.8 million and a net loss of $99.5 million for the six-month period, reflecting operational cash usage and reduced R&D [Condensed Balance Sheets](index=6&type=section&id=Condensed%20Balance%20Sheets) As of June 30, 2025, total assets decreased to $299.8 million from $396.9 million, primarily due to reduced cash and investments, reflecting net losses Condensed Balance Sheet Highlights (In thousands) | Balance Sheet Highlights | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $86,820 | $71,188 | | Short-term investments | $176,053 | $284,536 | | **Total Assets** | **$299,824** | **$396,949** | | **Liabilities & Equity** | | | | Total Liabilities | $79,742 | $92,868 | | Total Stockholders' Equity | $220,082 | $304,081 | | **Total Liabilities and Stockholders' Equity** | **$299,824** | **$396,949** | [Condensed Statements of Operations and Comprehensive Loss](index=7&type=section&id=Condensed%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) Net loss for Q2 2025 improved to $43.3 million from $55.9 million in Q2 2024, primarily due to decreased R&D expenses, with a six-month net loss of $99.5 million Condensed Statements of Operations (In thousands) | Statement of Operations | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | :--- | :--- | | Research and development | $(32,198) | $(45,617) | $(75,634) | $(82,763) | | General and administrative | $(13,394) | $(15,022) | $(28,893) | $(30,268) | | **Loss from operations** | **$(45,592)** | **$(60,639)** | **$(104,527)** | **$(113,031)** | | **Net loss** | **$(43,300)** | **$(55,854)** | **$(99,466)** | **$(102,809)** | | Net loss per share | $(0.71) | $(0.92) | $(1.62) | $(1.71) | [Condensed Statements of Stockholders' Equity](index=8&type=section&id=Condensed%20Statements%20of%20Stockholders'%20Equity) Total stockholders' equity decreased to $220.1 million from $304.1 million, primarily due to a $99.5 million net loss, partially offset by stock-based compensation Stockholders' Equity Movement (In thousands) | Stockholders' Equity Movement | Amount | | :--- | :--- | | Balance at December 31, 2024 | $304,081 | | Net loss (Six months ended June 30, 2025) | $(99,466) | | Stock-based compensation expense | $15,291 | | Issuance of common stock under benefit plans | $498 | | Net unrealized loss on short term investments | $(322) | | **Balance at June 30, 2025** | **$220,082** | [Condensed Statements of Cash Flows](index=10&type=section&id=Condensed%20Statements%20of%20Cash%20Flows) Net cash used in operating activities increased to $89.5 million for the six months ended June 30, 2025, with investing activities providing $104.6 million, leading to a $15.6 million net cash increase Cash Flow Summary (In thousands) | Cash Flow Summary | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(89,467) | $(75,568) | | Net cash provided by investing activities | $104,601 | $70,248 | | Net cash provided by financing activities | $498 | $22,472 | | **Net increase in cash and cash equivalents** | **$15,632** | **$17,152** | [Notes to Condensed Financial Statements](index=11&type=section&id=Notes%20to%20Condensed%20Financial%20Statements) Key notes highlight the discontinuation of the bexotegrast program, a 45% workforce reduction incurring $3.8 million in restructuring costs, and the adoption of a stockholder rights agreement - In June 2025, the company announced the discontinuation of the development of bexotegrast in Idiopathic Pulmonary Fibrosis (IPF) after the Phase 2b BEACON-IPF trial demonstrated an unfavorable risk-benefit profile[35](index=35&type=chunk) - On May 1, 2025, the company announced a workforce reduction impacting approximately **45% of its employees**, with an expected total cost of about **$3.8 million**[91](index=91&type=chunk) - In March 2025, the company's board adopted a stockholder rights agreement (a "poison pill") intended to reduce the likelihood of a hostile takeover, expiring on March 11, 2026[64](index=64&type=chunk)[65](index=65&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=21&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the discontinuation of bexotegrast, strategic restructuring to extend cash runway, and focus on oncology and muscular dystrophy programs, with **$264.4 million** in cash as of Q2 2025 [Overview and Recent Developments](index=21&type=section&id=Overview%20and%20Recent%20Developments) The company discontinued bexotegrast development in IPF due to an unfavorable risk-benefit profile and initiated strategic restructuring, while advancing its oncology program PLN-101095 - Bexotegrast development in IPF was discontinued following an analysis of the full safety and efficacy data from the BEACON-IPF Phase 2b/3 trial, which showed an unfavorable risk-benefit profile[100](index=100&type=chunk) - The Phase 1 trial of PLN-101095 in solid tumors is ongoing, with initial data from the two highest dose cohorts expected by the end of **2025**[101](index=101&type=chunk) - A strategic restructuring of the workforce and other cost-saving actions were largely completed by the end of Q2 **2025** to extend the company's cash runway[102](index=102&type=chunk) [Results of Operations](index=23&type=section&id=Results%20of%20Operations) R&D expenses decreased by **$13.4 million** for Q2 2025 due to the discontinuation of the BEACON-IPF trial, with general and administrative expenses also decreasing by **$1.6 million** R&D Expense Breakdown (In thousands) | R&D Expense Breakdown | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | $ Change | | :--- | :--- | :--- | :--- | | Bexotegrast - clinical trial costs | $13,359 | $26,360 | $(13,001) | | Other pipeline programs | $2,019 | $1,673 | $346 | | Unallocated internal expenses | $16,820 | $17,584 | $(764) | | **Total R&D Expenses** | **$32,198** | **$45,617** | **$(13,419)** | - General and administrative expenses decreased by **$1.6 million** for the three months ended June 30, 2025, primarily due to reduced employee-related costs following the workforce reduction[113](index=113&type=chunk) [Liquidity and Capital Resources](index=25&type=section&id=Liquidity%20and%20Capital%20Resources) As of June 30, 2025, the company held **$264.4 million** in cash and investments, deemed sufficient for over 12 months, despite increased cash used in operating activities to **$89.5 million** - The company had **$264.4 million** in cash, cash equivalents, and short-term investments as of June 30, 2025[121](index=121&type=chunk) - Management believes existing capital resources are sufficient to fund anticipated operating expenses and capital requirements for the next **12 months and beyond**[123](index=123&type=chunk) - Net cash used in operating activities increased by **$13.9 million** for the six months ended June 30, 2025, primarily due to settling payables related to the bexotegrast program close-out[127](index=127&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=27&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company's primary market risk is interest rate fluctuations on its investment portfolio and variable-rate term loan, though a 100 basis point change is not expected to be material - The company's main market risk is interest rate sensitivity on its **$264.4 million** of cash, cash equivalents, and short-term investments, and its **$30.0 million** term loan[137](index=137&type=chunk) - Due to the short-term nature of its investments, the company believes a hypothetical **10% change** in interest rates would not have had a material impact on its financial statements[138](index=138&type=chunk) [Item 4. Controls and Procedures](index=27&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of June 30, 2025, with no material changes to internal control over financial reporting during the quarter - As of June 30, 2025, the CEO and CFO concluded that the company's disclosure controls and procedures were effective at a reasonable assurance level[140](index=140&type=chunk) - No changes to internal control over financial reporting occurred during the quarter ended June 30, 2025, that would be reasonably likely to have a material effect[141](index=141&type=chunk) PART II. OTHER INFORMATION [Item 1. Legal Proceedings](index=27&type=section&id=Item%201.%20Legal%20Proceedings) As of the filing date, the company is not a party to any material legal matters or claims, though future involvement in ordinary course legal matters is acknowledged - The company is not currently party to any material legal matters or claims[144](index=144&type=chunk) [Item 1A. Risk Factors](index=28&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant financial, R&D, commercialization, intellectual property, third-party reliance, operational, and stock-related risks, including a history of losses and high dependence on early-stage candidates - **Financial Risk:** The company has incurred significant net losses since inception (**$809.5 million** accumulated deficit as of June 30, 2025) and expects to continue incurring losses, requiring substantial additional capital[147](index=147&type=chunk)[151](index=151&type=chunk) - **R&D Risk:** The business is highly dependent on the success of its remaining clinical-stage product candidates after discontinuing bexotegrast in IPF, with drug discovery being an unproven, lengthy, expensive, and uncertain process[165](index=165&type=chunk)[169](index=169&type=chunk)[170](index=170&type=chunk) - **Third-Party Reliance Risk:** The company relies on single-source third-party suppliers, including some located in China, to manufacture its drug candidates, posing disruption risks from business or geopolitical events[17](index=17&type=chunk)[317](index=317&type=chunk)[318](index=318&type=chunk) - **Operational Risk:** The recent restructuring and **45% workforce reduction** may increase dependence on remaining key personnel and could lead to loss of institutional knowledge, decreased morale, or attrition[333](index=333&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=73&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) There were no unregistered sales of equity securities during the reporting period - No unregistered sales of equity securities occurred during the period[400](index=400&type=chunk) [Item 5. Other Information](index=73&type=section&id=Item%205.%20Other%20Information) No directors or officers adopted, modified, or terminated a Rule 10b5-1 trading arrangement during the three months ended June 30, 2025 - No directors or officers adopted, modified, or terminated a Rule 10b5-1 trading plan during the quarter[403](index=403&type=chunk) [Item 6. Exhibits](index=74&type=section&id=Item%206.%20Exhibits) This section lists all exhibits filed with the Quarterly Report on Form 10-Q, including CEO and CFO certifications and interactive data files (XBRL) - The report includes certifications from the CEO and CFO pursuant to Sections 302 and 906 of the Sarbanes-Oxley Act of 2002, along with other corporate documents and XBRL data[405](index=405&type=chunk)

Core Insights - Pliant Therapeutics has largely completed its workforce and operational realignment while focusing on closing out the BEACON-IPF activities and maintaining core capabilities for future developments [2][5] - The company is on track to deliver additional data from its Phase 1 oncology trial by the end of 2025 [1][4] Second Quarter and Recent Developments - Development of bexotegrast for idiopathic pulmonary fibrosis (IPF) has been discontinued due to an unfavorable risk-benefit profile despite early signs of efficacy [3] - The Phase 1 trial of PLN-101095, targeting solid tumors, continues to enroll patients, with initial data expected by the end of 2025 [4] Financial Results - Research and development expenses decreased to $32.2 million from $45.6 million year-over-year, primarily due to the discontinuation of BEACON-IPF [8] - General and administrative expenses also decreased to $13.4 million from $15.0 million, attributed to personnel-related costs from the workforce restructuring [8] - The net loss for the second quarter was $43.3 million, down from $55.9 million in the prior year [8][13] - As of June 30, 2025, the company had cash, cash equivalents, and short-term investments totaling $264.4 million [8]

Clinical Trial Results of PLN-74809 - PLN-74809 demonstrated dose-dependent target engagement and TGF-β suppression in prior studies[24] - PLN-74809 was well-tolerated over 12 weeks of treatment in the INTEGRIS-IPF trial[32] - PLN-74809-treated patients experienced an 80% reduction in FVC decline over 12 weeks (-15.1 mL, Pooled Active Groups) compared to Placebo (-74.1 mL)[33] - An improvement in FVC (+24.6 mL) was observed in PLN-74809 80 mg dose cohort[34] - A dose-dependent antifibrotic effect was seen on QLF Imaging, with no progression in the 160 mg group at Week 12[34] - PLN-74809 decreased serum biomarkers of collagen synthesis (PRO-C3 and PRO-C6) relative to placebo[34] Safety and Tolerability - Most Treatment Emergent Adverse Events (TEAEs) were mild or moderate in severity, and there were no discontinuations due to adverse events, deaths, or drug-related Serious Adverse Events (SAEs)[34] - The most frequent TEAE seen was diarrhea, but it was only observed in patients on standard of care[54] FVC Analysis - PLN-74809-treated participants experienced a benefit in FVC change from Baseline to Week 12 (-15.1 mL for pooled PLN-74809 group) compared to those on placebo (-74.1 mL)[77] - A dose-dependent reduction was observed in the proportion of participants with FVCpp decline of ≥10%[34] - Quantitative Lung Fibrosis (QLF) imaging showed a dose-dependent antifibrotic effect, with no progression in the 160 mg group at Week 12 based on mean change from baseline[84]

Company Highlights and Financial Position - Pliant Therapeutics has raised over $625 million to date, including a 2020 IPO and a follow-on offering in July 2022 [8] - The company's cash balance was $360 million as of September 30, 2022, funding operations to mid-2025 [8] Bexotegrast (PLN-74809) in IPF and PSC - Bexotegrast is in Phase 2a development for Idiopathic Pulmonary Fibrosis (IPF) and Primary Sclerosing Cholangitis (PSC) [8] - In the INTEGRIS-IPF study, bexotegrast treatment resulted in an 80% reduction in FVC decline over 12 weeks compared to placebo (-15.1 mL vs -74.1 mL) [47, 48] - In the INTEGRIS-IPF study, an actual improvement in FVC (+24.6 mL) was observed in the 80 mg dose cohort [48] - In the INTEGRIS-IPF study, the proportion of participants with FVCpp decline ≥ 10% was 4.5% in the 160 mg group compared to 17.4% in the placebo group [55] PLN-101095 for Solid Tumors - An IND has been submitted for PLN-101095, a potential first-in-class small molecule dual αVβ8/αVβ1 inhibitor addressing ICI resistance in solid tumors, with Phase 1 initiation expected in 2Q 2023 [8, 9] - PLN-101095, combined with αPD-1, demonstrated high tumor growth inhibition in the EMT6 syngeneic mouse model [91] Market Opportunity in IPF - The two marketed agents for IPF, Esbriet® and Ofev®, had >$3 billion in total global revenues in 2021 [17]

Core Viewpoint - Pliant Therapeutics has discontinued the development of bexotegrast for idiopathic pulmonary fibrosis (IPF) following an unfavorable risk-benefit profile identified in the BEACON-IPF Phase 2b/3 clinical trial [1][3][5] Group 1: Clinical Trial Results - The BEACON-IPF trial was a randomized, double-blind, placebo-controlled study that revealed an imbalance in IPF-related adverse events, leading to its voluntary discontinuation [2] - Analysis of safety and efficacy data indicated that bexotegrast at doses of 160 mg and 320 mg increased the risk of adverse events related to IPF progression, with an average time to disease progression of 33 weeks for treated participants [3] - At Week 12, the 160 mg and 320 mg treatment groups showed improvements in forced vital capacity (FVC) decline of 72 mL (p<0.05) and 46 mL (p>0.05) respectively, while at Week 24, improvements were 58 mL (p>0.05) and 8 mL (p>0.05) respectively compared to placebo [4] Group 2: Future Development Plans - The company continues to enroll patients in a Phase 1 trial for PLN-101095, a dual-selective inhibitor targeting solid tumors resistant to immune checkpoint inhibitors, with interim results showing 50% confirmed partial responses at the highest dose tested [6] - Pliant's drug discovery platform includes over 15,000 integrin binding molecules and aims to support early-stage programs across multiple disease areas, focusing on tissue-specific delivery mechanisms [7][9]

Core Insights - Pliant Therapeutics presented clinical and preclinical data at the ATS 2025 International Conference, highlighting the antifibrotic activity of bexotegrast and its potential in treating fibrotic diseases [1] Group 1: Antifibrotic Activity of Bexotegrast - Bexotegrast, a dual inhibitor of αVβ6/αVβ1 integrins, demonstrated reduced expression of genes related to TGF-β signaling and fibrogenesis in alveolar type 1 cells and various fibroblast subpopulations [2] - Single-nuclei RNAseq analysis showed that bexotegrast significantly reduced the expression of type I collagen and other profibrotic genes in aberrant basaloid cells and fibroblasts, indicating its distinct pharmacodynamic profile compared to nintedanib [4] Group 2: Biomarker Analysis - A comparative analysis of circulating plasma biomarkers identified dysregulated biomarkers across multiple ILD subtypes, which could aid in clinical decision-making for ILD [3] Group 3: Company Overview - Pliant Therapeutics is a clinical-stage biopharmaceutical company focused on developing novel therapeutics for fibrotic diseases, with bexotegrast as its lead product candidate undergoing evaluation for idiopathic pulmonary fibrosis [6] - The company has received Fast Track and Orphan Drug Designations from the FDA for bexotegrast, and is also conducting Phase 1 studies for other drug candidates targeting solid tumors and muscular dystrophies [6]