The following discussion and analysis should be read in conjunction with our condensed financial statements and related notes appearing elsewhere in this Report, as well as our audited financial statements and related notes included in our 2025 10-K. This discussion and analysis contains forward-looking statements based upon current beliefs, plans and expectations that involve risks, uncertainties and assumptions, such as statements regarding our plans, objectives, expectations, intention, beliefs and projections. Our actual results and the timing of events could differ materially from those anticipated in these forward-looking statements as a result of several factors, including those set forth in the section titled “Risk Factors” under Part II, Item 1A of this Report and under Part I, Item 1A of our 2025 10-K. In some cases, you can identify forward-looking statements by terminology such as “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potentially,” “predict,” “should,” “will” or the negative of these terms or other similar expressions. In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this Report, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate we have conducted exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements. Overview We are a clinical-stage biopharmaceutical company focused on discovering and developing integrin-based therapeutics. Our lead program is focused on the development of treatments for solid tumors by inhibiting integrin-mediated activation of transforming growth factor-β (TGF-β). We have applied our deep understanding of integrin biology, along with our medicinal chemistry and translational medicine expertise to develop a proprietary drug discovery platform that we believe has broad applicability across multiple areas of disease. Our wholly owned lead product candidate, PLN-101095, is an oral, small molecule, dual selective inhibitor of αvβ8 and αvβ1 integrins in development for the treatment of solid tumors. In 2025, we announced positive data from a Phase 1 open-label dose-escalation trial of PLN-101095 as monotherapy and in combination with the immunotherapy pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors. We also continue to explore the full potential of our drug discovery platform consisting of a proprietary library of over 15,000 integrin binding molecules, focusing on integrin-based target-mediated drug delivery. Since inception, we have had significant operating losses. Our net loss was $22.4 million and $43.3 million for the three months ended June 30, 2026 and 2025, respectively. As of June 30, 2026, we had an accumulated deficit of $901.8 million and cash, cash equivalents, and short-term investments of $159.6 million. We expect to continue to incur net losses for the foreseeable future as we: •perform research and development activities to identify and develop product candidates; •advance product candidates into and through clinical development; •require the manufacture of supplies to support research and development, preclinical studies and clinical trials; •seek regulatory approvals for any product candidates that successfully complete clinical trials; •maintain, expand and protect our intellectual property portfolio; and •invest in or in-license other technologies or product candidates. Second Quarter and Recent Developments Oncology Program •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 21 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. Components of Operations Operating Expenses Research and Development Our research and development expenses consist of expenses incurred in connection with the development of our product candidates. Research and development expenses include: •employee-related expenses, which include salaries, benefits and stock-based compensation for our research and development personnel; •expenses incurred under agreements with third-party contract organizations for pre-clinical studies, clinical trials and consultants that conduct research and development activities on our behalf; •costs associated with the manufacture of supplies to support research and development, preclinical studies and clinical trials; •depreciation of laboratory equipment and costs of equipment and supplies; •facilities expenses, which include expenses for rent and other facility related costs; and •other expenses and other allocations associated with research and development. The following table summarizes our research and development expenses for the three months ended June 30, 2026 and 2025 (in thousands): Three Months Ended June 30, 2026 2025 $ Change Employee related expenses $ 4,390 $ 12,279 $ (7,889) Outside and consulting services for preclinical studies and research and development activities by third-party contract organizations 595 4,087 (3,492) Clinical trials expenses 8,779 11,291 (2,512) Depreciation of lab equipment and costs of equipment and supplies 449 1,291 (842) Facilities expenses 1,415 1,742 (327) Other expenses and other allocations 1,098 1,508 (410) Total research and development expenses $ 16,727 $ 32,198 $ (15,471) We expense all research and development costs in the periods in which they are incurred. We do not allocate our internal costs by product candidates or by preclinical programs as these are in early stages of clinical trials or development, and any such allocation would involve significant estimates and judgments and, accordingly, would be imprecise. Where appropriate, we allocate our third-party research and development expense by product candidate or preclinical program. These expenses primarily relate to outside consultants, clinical research organizations and contract manufacturing organizations. When we refer to the research and development expenses associated with a specific product candidate or preclinical program, these refer exclusively to the allocated third-party expenses associated with that product candidate. 22 Following the discontinuation of bexotegrast development, our current quarter results are reflective of the re-prioritized development pipeline and research and development expenses should be relatively consistent in the near term, increasing commensurate with the progress of our phase 1b trial. The process of conducting the necessary clinical research to obtain regulatory approval is costly and time-consuming, and the successful development of our product candidates is highly uncertain. As a result, we are unable to determine the duration and completion costs of our research and development projects or when and to what extent we will generate revenue from the commercialization and sale of any of our product candidates. General and Administrative Our general and administrative expenses consist primarily of salaries, benefits and stock-based compensation for our general and administrative personnel, allocated facilities costs, insurance and other expenses for outside professional services, including legal, marketing, investor relations, human resource and accounting services. We expect general and administrative expenses to remain relatively consistent for the foreseeable future. In addition, if we obtain regulatory approval for any of our product candidates and do not enter into a third-party commercialization collaboration, we expect to incur significant expenses related to building a sales and marketing team to support product sales, marketing and distribution activities. Interest and Other Income (Expense), net Our interest and other income (expense), net consists of interest, accretion income and amortization expense on cash, cash equivalents, and short-term investments, and realized gains and losses on short-term investments. Interest Expense Our interest expense was derived from a term loan executed under the Amended Loan Agreement with Oxford Finance LLC that was terminated in October 2025. Financial Operations Overview Comparison of the three months ended June 30, 2026 and 2025 (in thousands) Three Months Ended June 30, 2026 2025 $ Change Operating expenses: Research and development $ (16,727) $ (32,198) $ 15,471 General and administrative (7,135) (13,394) 6,259 Total operating expenses (23,862) (45,592) 21,730 Loss from operations (23,862) (45,592) 21,730 Interest and other income (expense), net 1,491 3,101 (1,610) Interest expense — (809) 809 Net loss $ (22,371) $ (43,300) $ 20,929 Research and development expenses The following table summarizes our research and development expenses for the three months ended June 30, 2026 and 2025 (in thousands): 23 Three Months Ended June 30, 2026 2025 $ Change Program-specific external expenses: Program expense including clinical trial and third-party contracting costs $ 9,595 $ 1,292 $ 8,303 Bexotegrast - clinical trial and third party contracting costs (311) 13,359 (13,670) R&D non-program spend 90 727 (637) Total program-specific external expenses 9,374 15,378 (6,004) Unallocated internal expenses Employee-related expenses 4,390 12,279 (7,889) Depreciation of lab equipment and costs of equipment and supplies 450 1,291 (841) Facilities expenses 1,415 1,742 (327) Other expenses and other allocations 1,098 1,508 (410) Total unallocated internal expenses 7,353 16,820 (9,467) Total research and development expenses $ 16,727 $ 32,198 $ (15,471) Research and development expenses for the three months ended June 30, 2026 decreased $15.5 million, primarily due to discontinuing development of bexotegrast in IPF and lower employee-related expenses, driven by a reduction in headcount resulting from our 2025 restructuring activities. These decreases were partially offset by an $8.3 million increase in expense primarily associated with development of PLN-101095. General and Administrative Expenses General and administrative expenses for the three months ended June 30, 2026 decreased $6.3 million, primarily due to a decrease in employee related costs driven by reduced headcount resulting from our 2025 restructuring activities. Interest and Other Income (Expense), Net Interest and other income (expense), net decreased $1.6 million due to lower investment balances due to continued funding of operating activities. Interest Expense Interest expense for the three months ended June 30, 2026 decreased $0.8 million due to full repayment of the Amended Loan Agreement in 2025. Comparison of the six months ended June 30, 2026 and 2025 (in thousands) Six Months Ended June 30, 2026 2025 $ Change Operating expenses: Research and development $ (30,311) $ (75,634) $ 45,323 General and administrative (15,323) (28,893) 13,570 Total operating expenses (45,634) (104,527) 58,893 Loss from operations (45,634) (104,527) 58,893 Interest and other income (expense), net 3,223 6,669 (3,446) Interest expense — (1,608) 1,608 Net loss $ (42,411) $ (99,466) $ 57,055 Research and development expenses The following table summarizes our research and development expenses for the six months ended June 30, 2026 and 2025 (in thousands): 24 Six Months Ended June 30, 2026 2025 $ Change Program-specific external expenses: Program expense including clinical trial and third-party contracting costs $ 15,180 $ 2,728 $ 12,452 Bexotegrast - clinical trial and third party contracting costs (1,088) 34,948 (36,036) R&D non-program spend 902 1,675 (773) Total program-specific external expenses 14,994 39,351 (24,357) Unallocated internal expenses Employee-related expenses 9,654 26,467 (16,813) Depreciation of lab equipment and costs of equipment and supplies 1,003 2,684 (1,681) Facilities expenses 2,820 3,619 (799) Other expenses and other allocations 1,840 3,513 (1,673) Total unallocated internal expenses 15,317 36,283 (20,966) Total research and development expenses $ 30,311 $ 75,634 $ (45,323) Research and development expenses for the six months ended June 30, 2026 decreased $45.3 million, primarily due to discontinuing development of bexotegrast in IPF and lower employee-related expenses, driven by a reduction in headcount resulting from our 2025 restructuring activities. These decreases were partially offset by a $12.5 million increase in expense primarily associated with development of PLN-101095. General and Administrative Expenses General and administrative expenses for the six months ended June 30, 2026 decreased $13.6 million, primarily due to a decrease in employee related costs driven by reduced headcount resulting from our 2025 restructuring activities. Interest and Other Income (Expense), Net Interest and other income (expense), net decreased $3.4 million due to lower investment balances due to continued funding of operating activities. Interest Expense Interest expense for the six months ended June 30, 2026 decreased $1.6 million due to full repayment of the Amended Loan Agreement in 2025. Liquidity and Capital Resources Overview As of June 30, 2026, we had $159.6 million of cash, cash equivalents and short-term investments. Our short-term investments consist of U.S. Treasury securities, U.S. Government agency securities and highly rated, investment-grade corporate debt securities. On March 30, 2026 we entered into a Sales Agreement with Leerink Partners LLC (the "Leerink Sales Agreement"), as sales agent, pursuant to which we may issue and sell shares of common stock in an "at-the-market" offering. On March 30, 2026 we filed a registration statement on Form S-3 (File No. 333-294737) which included an "at the market offering" prospectus covering the offering, issuance and sale of up to $50.0 million of common stock under the Leerink Sales Agreement and a base prospectus registering the offer and sale of up to $300.0 million of debt securities, common stock, preferred stock, units and/or warrants. As of the date of this Report, we have not issued any shares pursuant to any at-the-market offerings, including pursuant to the Leerink Sales Agreement, but may do so at a future date. In October 2025, we completed a voluntary prepayment of our Amended Loan Agreement with Oxford for $32.4 million, representing all outstanding principal, accrued and unpaid interest, fees, costs and expenses. Upon prepayment, all obligations, covenants, debts and liabilities under the Amended Loan Agreement were satisfied and discharged in full. We believe that our existing capital resources will be sufficient to fund our anticipated operating expenses and capital expenditure requirements for the next 12 months and beyond. We have based these estimates on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we currently expect. Further, our operating plan may 25 change, and we may need additional funds to meet operational needs and capital requirements for product development and commercialization sooner than planned. Funding Requirements Our primary use of cash is to fund operating expenses, primarily research and development expenditures. Cash used to fund operating expenses is impacted by the timing of when we pay these expenses, as reflected in the change in our outstanding accounts payable, accrued expenses and prepaid expenses. Our future funding requirements will depend on many factors, including the following: •the initiation, progress, timing, costs and results of preclinical studies and clinical trials for our product candidates; •the clinical development plans we establish for these product candidates; •the timelines of our clinical trials and the overall costs to conduct and complete the clinical trials, which may be impacted by health epidemics and pandemics, such as COVID-19; •the number and characteristics of product candidates that we develop; •the outcome, timing and cost of meeting regulatory requirements established by the FDA, and other comparable foreign regulatory authorities including but not limited to the European Medicines Agency (EMA) and the U.K. Medicines and Healthcare products Regulatory Agency (MHRA); •whether we enter into any collaboration agreements and the terms of any such agreements; •the cost of filing, prosecuting, defending and enforcing our patent claims and other intellectual property rights; •the cost of defending intellectual property disputes, including patent infringement actions brought by third parties against us or our product candidates; •the effect of competing technological and market developments; •the cost and timing of completion of commercial-scale outsourced manufacturing activities; •the cost and timing of achieving favorable pricing and reimbursement agreements with the pricing authorities in each market of interest, including of securing a positive recommendation after undergoing a health technology assessment by health technology authorities; •the cost of establishing sales, marketing and distribution capabilities for any product candidates for which we may receive regulatory approval in regions where we choose to commercialize our products on our own; and •the cost of operating as a public company. Further, our operating plan may change, and we may need additional funds to meet operational needs and capital requirements for clinical trials and other research and development expenditures. If we need to raise additional capital to fund our operations, funding may not be available to us on acceptable terms, or at all. In addition, the discontinuation of our development of bexotegrast in IPF may intensify the risk that we will be unable to access capital on favorable terms, or at all, as and when needed. If we are unable to obtain adequate financing when needed, we may have to delay, reduce the scope of or suspend one or more of our preclinical studies, clinical trials, research and development programs or commercialization efforts. We may seek to raise any necessary additional capital through a combination of public or private equity offerings, debt financings, collaborations and other licensing arrangements. If we raise additional capital through debt financing, we may be subject to covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends. If we raise additional capital through marketing and distribution arrangements or other collaborations, strategic alliances or licensing arrangements with third parties, we may have to relinquish certain valuable rights to our product candidates, technologies, future revenue streams or research programs or grant licenses on terms that may not be favorable to us. Cash Flows Comparison of the six months ended June 30, 2026 and 2025 The following summarizes our cash flows for the periods indicated (in thousands): 26 Six Months Ended June 30, 2026 2025 Net cash used in operating activities $ (32,026) $ (89,467) Net cash provided by investing activities 11,390 104,601 Net cash provided by financing activities 74 498 Net increase in cash and cash equivalents $ (20,562) $ 15,632 Cash Used in Operating Activities Net cash used in operating activities decreased $57.4 million, primarily due to the discontinuation of the BEACON-IPF study in 2025 and the related restructuring of operations that reduced workforce and refocused development efforts toward PLN-101095, which is in an earlier, less capital-intensive phase of development. Cash Provided by Investing Activities Net cash provided by investing activities decreased $93.2 million compared to the same period of the prior year due to declining marketable securities balances resulting from continued funding of operations and thus less overall maturities coupled with a higher relative volume of marketable securities purchases compared to the prior year period. Cash Provided by Financing Activities Net cash provided by financing activities decreased $0.4 million, as lower headcount and a decreased stock price yielded smaller proceeds associated with our Employee Stock Purchase Plan during the six months ended June 30, 2026. Contractual Obligations and Other Commitments At June 30, 2026, we have a non-cancelable operating lease for office and laboratory space through March 31, 2031. Refer to Note 14 and Note 15 to our financial statements appearing elsewhere in this Report for a discussion of material obligations and commitments. Off-Balance Sheet Arrangements During the periods presented, we did not have, nor do we currently have, any off-balance sheet arrangements or holdings in any variable interest entities. Critical Accounting Polices and Estimates Our management’s discussion and analysis of our financial condition and results of operations is based on our financial statements, which have been prepared in accordance with United States generally accepted accounting principles. The preparation of these financial statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the financial statements, as well as the reported expenses incurred during the reporting periods. Our estimates are based on our historical experience and on various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions. There have been no material changes to our critical accounting policies and estimates from those described in “Part II, Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations” included in our 2025 10-K. Recent Accounting Pronouncements See Note 2 to the Notes to Condensed Unaudited Financial Statements of this Report for more information.