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]

Financial Performance - Net loss for the three months ended March 31, 2025, was $56,166 thousand, compared to a net loss of $46,955 thousand for the same period in 2024, representing an increase of 19.3%[22] - The company reported a comprehensive loss of $56,328 thousand for the three months ended March 31, 2025, compared to a comprehensive loss of $47,789 thousand for the same period in 2024, an increase of 18.5%[22] - Net loss for the three months ended March 31, 2025, was $56.2 million, compared to a net loss of $47.0 million for the same period in 2024, with an accumulated deficit of $766.2 million[101] - The net loss for the three months ended March 31, 2025, was $56.2 million, an increase of $9.2 million from a net loss of $47.0 million in the same period of 2024[112] - The company expects to continue incurring significant losses for the foreseeable future, emphasizing the need to develop and commercialize products with substantial market potential[144] Assets and Liabilities - Total current assets decreased from $362,264 thousand as of December 31, 2024, to $311,191 thousand as of March 31, 2025, a decline of approximately 14.1%[20] - Total stockholders' equity decreased from $304,081 thousand as of December 31, 2024, to $257,164 thousand as of March 31, 2025, a decline of approximately 15.4%[20] - As of March 31, 2025, total financial assets amounted to $278.260 million, a decrease from $339.361 million as of December 31, 2024[45] - Accrued liabilities totaled $7.429 million as of March 31, 2025, down from $12.353 million as of December 31, 2024[50] - The company had cash, cash equivalents, and short-term investments of $307.1 million as of March 31, 2025[101] Cash Flow - Cash and cash equivalents increased from $71,188 thousand as of December 31, 2024, to $91,936 thousand as of March 31, 2025, an increase of approximately 29.2%[20] - Net cash used in operating activities for the three months ended March 31, 2025, was $48,864 thousand, compared to $30,271 thousand for the same period in 2024, an increase of 61.1%[31] - Cash flows from investing activities provided $69,114 thousand for the three months ended March 31, 2025, compared to $59,546 thousand for the same period in 2024, an increase of 15.8%[31] - Net cash provided by investing activities increased to $69.1 million, driven by maturities of marketable securities exceeding related purchases[125] Research and Development - Research and development expenses increased to $43,436 thousand for the three months ended March 31, 2025, from $37,146 thousand in the same period of 2024, an increase of 17.5%[22] - The company’s research and development expenses for the three months ended March 31, 2025, were $3.702 million, compared to $3.070 million in 2024, indicating a 20.5% increase[77] - Research and development expenses rose by $6.3 million to $43.4 million, primarily due to acceleration of close-out activities for the BEACON-IPF study and increased employee-related expenses[113] Debt and Financing - The company drew an additional Term Loan of $20.0 million under the Amended Loan Agreement, which upsized the existing Term Loan facility to $150.0 million[51] - Future maturities of debt as of March 31, 2025, total $30.284 million, with $20.0 million due in 2028 and $10.0 million in 2029[56] - The Amended Loan Agreement provides a total of $150.0 million in available non-dilutive capital, with an additional Term Loan of $20.0 million drawn[118] - The company acknowledges the uncertainty in estimating future losses and the potential need for additional capital to support ongoing operations and development efforts[145] Clinical Trials and Product Development - The BEACON-IPF trial was discontinued due to an imbalance in adverse events, but early evidence of efficacy was observed, with topline data expected in Q2 2025[94][99] - PLN-101095, a dual selective inhibitor, is currently in a Phase 1 trial, showing confirmed partial responses in three of six patients treated[98][100] - The company plans to analyze data from the BEACON-IPF trial and re-prioritize development of less capital-intensive product candidates[106] - The company is conducting a Phase 1 clinical trial of PLN-101095 in solid tumors and is Phase-1 ready for PLN-101325 for muscular dystrophies, with no products currently approved for commercial sale[160] Market and Regulatory Challenges - The company faces significant financial challenges, as substantial investments are required for clinical development, regulatory review, and marketing efforts for any approved product candidates[161] - The regulatory approval process varies by country, and approval by the FDA does not guarantee approval by foreign regulatory authorities[170] - The company must comply with numerous foreign regulatory requirements, which can complicate the clinical trial and marketing authorization processes[170] - The FDA has substantial discretion in the approval process, and product candidates may not be approved even if they meet primary endpoints[183] Competition and Market Acceptance - The company faces substantial competition from major biopharmaceutical companies and research organizations, which may hinder its ability to develop and commercialize products successfully[203] - Competitors include well-resourced companies such as AbbVie, AstraZeneca, and Merck, which are also targeting fibrosis treatments[204] - Market acceptance of any approved product candidates will depend on factors such as efficacy, pricing, and third-party payor coverage[210][212] Future Outlook - The company may need additional funds for operational needs and capital requirements for product development and commercialization sooner than planned[120] - Future funding requirements will depend on various factors, including the success of clinical trials and the ability to secure collaboration agreements[149] - The company expects general and administrative expenses to remain relatively consistent for the foreseeable future[114]

Corporate Update and First Quarter 2025 Financial Results Overview [Recent Developments and Program Highlights](index=1&type=section&id=Recent%20Developments%20and%20Program%20Highlights) Pliant Therapeutics updated on clinical programs, including BEACON-IPF trial close-out and promising Phase 1 PLN-101095 oncology data [Bexotegrast Program Updates](index=1&type=section&id=Bexotegrast%20Program%20Updates) BEACON-IPF Phase 2b/3 trial close-out continues, with topline data expected in Q2 2025; Phase 2a PET imaging trial results published - BEACON-IPF Phase 2b/3 trial close-out activities are ongoing, with **topline data anticipated in the second quarter of 2025**[1](index=1&type=chunk)[2](index=2&type=chunk)[7](index=7&type=chunk) - Results from a Phase 2a positron emission tomography (PET) imaging trial, reporting positive findings on collagen deposition in IPF patients, were published in the American Journal of Respiratory and Critical Care Medicine (AJRCCM)[7](index=7&type=chunk) [Oncology Program (PLN-101095) Updates](index=1&type=section&id=Oncology%20Program%20(PLN-101095)%20Updates) Interim Phase 1 data for PLN-101095 with pembrolizumab demonstrated antitumor activity and confirmed partial responses in solid tumors, with good tolerability - Interim Phase 1 data for PLN-101095 in combination with pembrolizumab showed antitumor activity with confirmed partial responses in solid tumors resistant to immune checkpoint inhibitors[2](index=2&type=chunk)[4](index=4&type=chunk) - **Three of six patients** treated at the **1000 mg BID dose** (non-small cell lung cancer, cholangiocarcinoma, and melanoma) experienced confirmed partial responses with tumor size reductions of **74%, 48%, and 42%**, respectively[4](index=4&type=chunk) - PLN-101095 was generally well tolerated across all doses tested, and the trial is currently enrolling the fourth of five potential cohorts[4](index=4&type=chunk) [Corporate Strategic Realignment](index=1&type=section&id=Corporate%20Strategic%20Realignment) Pliant Therapeutics announced a strategic realignment, including a 45% workforce reduction, to extend its cash runway and support clinical trials - A strategic realignment of workforce and operations was announced on May 1, 2025, including an approximately **45% reduction in workforce** and other cost-saving actions[5](index=5&type=chunk) - The realignment is expected to extend the cash runway to support the execution of clinical trials, including late-stage trials, and is anticipated to be substantially completed by the second quarter of 2025[1](index=1&type=chunk)[5](index=5&type=chunk) [First Quarter 2025 Financial Highlights](index=1&type=section&id=First%20Quarter%202025%20Financial%20Highlights) Pliant Therapeutics reported a net loss of $56.2 million for Q1 2025, driven by higher operating expenses, while maintaining a strong cash position of $307.1 million Key Financial Highlights (Q1 2025 vs. Q1 2024) | Metric | Q1 2025 (in millions) | Q1 2024 (in millions) | Change (YoY) | | :----------------------------- | :-------------------- | :-------------------- | :----------- | | Research and development expenses | $43.4 | $37.1 | +$6.3 | | General and administrative expenses | $15.5 | $15.2 | +$0.3 | | Net loss | $56.2 | $47.0 | +$9.2 | | Cash, cash equivalents and short-term investments (as of March 31) | $307.1 | N/A | N/A | - The increase in research and development expenses was primarily due to the acceleration of close-out activities for the BEACON-IPF study and increased employee-related expenses[11](index=11&type=chunk) [About Pliant Therapeutics, Inc.](index=3&type=section&id=About%20Pliant%20Therapeutics%2C%20Inc.) [Company Overview and Product Pipeline](index=3&type=section&id=Company%20Overview%20and%20Product%20Pipeline) Pliant Therapeutics is a clinical-stage biopharmaceutical company focused on fibrotic diseases, with lead candidate bexotegrast for IPF and other programs in oncology and muscular dystrophies - Pliant Therapeutics is a clinical-stage biopharmaceutical company focused on fibrotic diseases[8](index=8&type=chunk) - Bexotegrast (PLN-74809), the lead product candidate, is an oral, small molecule, dual selective inhibitor of αvß6 and αvß1 integrins in development for idiopathic pulmonary fibrosis (IPF)[8](index=8&type=chunk) - Bexotegrast has received **Fast Track Designation** and **Orphan Drug Designation** from the U.S. FDA and Orphan Drug Designation from the European Medicines Agency in IPF[8](index=8&type=chunk) - The pipeline includes PLN-101095 (Phase 1 for solid tumors resistant to immune checkpoint inhibitors) and PLN-101325 (Phase 1 for muscular dystrophies)[8](index=8&type=chunk) [Condensed Financial Statements](index=4&type=section&id=Condensed%20Financial%20Statements) [Condensed Statements of Operations](index=4&type=section&id=Condensed%20Statements%20of%20Operations) For Q1 2025, Pliant Therapeutics reported a net loss of $56.2 million, an increase from the prior year, primarily due to higher R&D expenses Condensed Statements of Operations (Unaudited, in thousands) | Metric | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :---------------------------------------- | :-------------------------------- | :-------------------------------- | | Research and development | $(43,436) | $(37,146) | | General and administrative | $(15,499) | $(15,246) | | Total operating expenses | $(58,935) | $(52,392) | | Loss from operations | $(58,935) | $(52,392) | | Interest and other income (expense), net | $3,568 | $5,882 | | Interest expense | $(799) | $(445) | | Net loss | $(56,166) | $(46,955) | | Net loss per share - basic and diluted | $(0.92) | $(0.78) | | Shares used in computing net loss per share | 61,222,676 | 60,180,921 | [Condensed Balance Sheets](index=5&type=section&id=Condensed%20Balance%20Sheets) As of March 31, 2025, total assets decreased to $344.8 million from $396.9 million, mainly due to reduced short-term investments, while total liabilities also decreased Condensed Balance Sheets (Unaudited, in thousands) | Metric | March 31, 2025 | December 31, 2024 | | :-------------------------------- | :------------- | :---------------- | | Cash and cash equivalents | $91,936 | $71,188 | | Short-term investments | $213,709 | $284,536 | | Total current assets | $311,191 | $362,264 | | Total assets | $344,770 | $396,949 | | Total current liabilities | $28,203 | $33,218 | | Total liabilities | $87,606 | $92,868 | | Total stockholders' equity | $257,164 | $304,081 | [Forward-Looking Statements](index=3&type=section&id=Forward-Looking%20Statements) [Disclaimer and Risk Factors](index=3&type=section&id=Disclaimer%20and%20Risk%20Factors) This section disclaims forward-looking statements, highlighting various risks and uncertainties that could cause actual results to differ materially - Statements regarding future events, conditions, or circumstances are identified as forward-looking statements, subject to risks and uncertainties[10](index=10&type=chunk) - Risks include those related to the development and commercialization of product candidates, delays in trials, macroeconomic conditions, reliance on single-source third parties, and capital requirements[10](index=10&type=chunk) - These and additional risks are discussed in the 'Risk Factors' and 'Management's Discussion and Analysis of Financial Condition and Results of Operations' sections of the company's Quarterly Report on Form 10-Q for the period ended March 31, 2025[10](index=10&type=chunk) - Pliant Therapeutics does not undertake any obligation to update forward-looking statements[10](index=10&type=chunk) [Investor and Media Contact](index=3&type=section&id=Investor%20and%20Media%20Contact) [Contact Information](index=3&type=section&id=Contact%20Information) This section provides the contact details for investor relations and corporate communications at Pliant Therapeutics - Contact for Investor and Media: Christopher Keenan, Vice President, Investor Relations and Corporate Communications[11](index=11&type=chunk) - Email: ir@pliantrx.com[11](index=11&type=chunk)

Core Insights - Pliant Therapeutics is focused on closing out the BEACON-IPF trial, with topline data expected in the second quarter of 2025, while also making progress in its oncology program with PLN-101095 showing antitumor activity [1][2][7] First Quarter and Recent Developments - The company reported a net loss of $56.2 million for the first quarter of 2025, compared to a net loss of $47.0 million in the same quarter of the previous year, primarily due to increased operating expenses related to BEACON-IPF close-out activities [12] - Research and development expenses rose to $43.4 million from $37.1 million year-over-year, driven by the acceleration of close-out activities for BEACON-IPF [6][12] Oncology Program - Interim Phase 1 data from the PLN-101095 trial in combination with pembrolizumab demonstrated confirmed partial responses in three out of six patients treated at the highest dose, with tumor size reductions of 74%, 48%, and 42% in patients with non-small cell lung cancer, cholangiocarcinoma, and melanoma, respectively [4] - The trial is currently enrolling the fourth of five potential cohorts, evaluating PLN-101095 at a dose of 1000 mg administered three times daily [4] Corporate Highlights - A strategic realignment of workforce and operations was announced, including a 45% reduction in workforce, aimed at extending the cash runway to support clinical trials [5] - The realignment process is expected to be substantially completed by the second quarter of 2025 [5] Financial Position - As of March 31, 2025, the company had cash, cash equivalents, and short-term investments totaling $307.1 million [12] - Total current assets decreased from $362.3 million at the end of 2024 to $311.2 million [16]

Core Insights - Pliant Therapeutics is undergoing a strategic restructuring, reducing its workforce by approximately 45% to extend its cash runway for late-stage clinical trials [1][3][4] - The company is awaiting topline data from the BEACON-IPF Phase 2b/3 trial of bexotegrast, expected in the second quarter of 2025, which will inform the next steps for the drug's development [2][3] Workforce Restructuring - The restructuring will impact all departments, but the company aims to maintain its late-stage clinical trial execution capabilities [3] - The process is expected to be substantially completed by the end of the second quarter of 2025 [3] Clinical Development - Bexotegrast is being developed for idiopathic pulmonary fibrosis (IPF) and has received Fast Track and Orphan Drug Designations from the FDA [4] - Pliant is also conducting a Phase 1 study for PLN-101095, targeting solid tumors, and has received clearance for a Phase 1 study of PLN-101325 for muscular dystrophies [4]

Core Viewpoint - Pomerantz LLP is investigating potential securities fraud or unlawful business practices involving Pliant Therapeutics, Inc and its officers or directors [1] Company Developments - On February 7, 2025, Pliant announced a voluntary pause in enrollment and dosing for the BEACON-IPF Phase 2b trial of bexotegrast due to recommendations from the independent Data Safety Monitoring Board [3] - Following this announcement, analysts from Wells Fargo and Citi downgraded Pliant, expressing uncertainty regarding the future of bexotegrast [3] Stock Performance - Pliant's stock price experienced a significant decline, falling by $4.72 per share, or 60.59%, closing at $3.07 per share on February 10, 2025 [4]