PLIANT THERAPEUTICS INC

Previous wording

We are a late-stage biopharmaceutical company focused on discovering and developing novel therapies for the treatment of fibrosis and related diseases. Our initial focus is on treating fibrosis by inhibiting integrin-mediated activation of TGF-β. We have applied our deep understanding of fibrosis biology, along with our medicinal chemistry and translational medicine expertise to develop a set of proprietary tools designed to discover and de-risk product candidates quickly and efficiently. Our wholly owned lead product candidate, bexotegrast (PLN-74809), is an oral, small molecule, dual selective inhibitor of αvß6 and αvß1 integrins that we are developing for the treatment of idiopathic pulmonary fibrosis, or IPF, and primary sclerosing cholangitis, or PSC. We announced positive data from our Phase 2a INTEGRIS-IPF trial in May 2023 and positive long-term data from our Phase 2a INTEGRIS-PSC trial in July 2024. We are currently conducting BEACON-IPF, a 52-week, randomized, double-blind, placebo-controlled adaptive Phase 2b/3 trial in patients with IPF.

Current wording

We are a late-stage biopharmaceutical company focused on discovering and developing novel therapies for the treatment of fibrosis and related diseases. Our initial focus is on treating fibrosis by inhibiting integrin-mediated activation of TGF-β. We have applied our deep understanding of fibrosis biology, along with our medicinal chemistry and translational medicine expertise to develop a set of proprietary tools designed to discover and de-risk product candidates quickly and efficiently. Our wholly owned lead product candidate, bexotegrast (PLN-74809), is an oral, small molecule, dual selective inhibitor of αvβ6 and αvβ1 integrins that we are developing for the treatment of idiopathic pulmonary fibrosis, or IPF, and primary sclerosing cholangitis, or PSC. We announced positive data from our Phase 2a INTEGRIS-IPF trial in May 2023 and positive long-term data from our Phase 2a INTEGRIS-PSC trial in July 2024. We are currently conducting BEACON-IPF, a 52-week, randomized, double-blind, placebo-controlled adaptive Phase 2b/3 trial in patients with IPF.

Previous wording

In January 2023, we received FDA clearance of investigational new drug application, or IND, for our third clinical program to date, PLN-101095, a small molecule, dual selective inhibitor of integrins αvß8 and αvß1 for the treatment of solid tumors that are resistant to immune checkpoint inhibitors. We are currently dosing the third of five dose cohorts in a Phase 1 open label dose-escalation trial of PLN-101095 as monotherapy and in combination with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors. Preliminary data is expected in late 2024 or early 2025.

Current wording

In January 2023, we received FDA clearance of investigational new drug application, or IND, for our third clinical program to date, PLN-101095, a small molecule, dual selective inhibitor of integrins αvβ8 and αvβ1 for the treatment of solid tumors that are resistant to immune checkpoint inhibitors. We are currently dosing the third of five dose cohorts in a Phase 1 open label dose-escalation trial of PLN-101095 as monotherapy and in combination with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors. Preliminary data is expected in early 2025.

Previous wording

Our fourth program, PLN-101325, is in development for treatment of muscular dystrophies, including Duchenne muscular dystrophy. PLN-101325 is a monoclonal antibody designed to act as an allosteric agonist of integrin α7ß1. In the first quarter of 2024, we received regulatory clearance for the conduct of a first-in-human Phase 1 clinical study of PLN-101325.

Current wording

Our fourth program, PLN-101325, is in development for treatment of muscular dystrophies, including Duchenne muscular dystrophy. PLN-101325 is a monoclonal antibody designed to act as an allosteric agonist of integrin α7β1. In the first quarter of 2024, we received regulatory clearance for the conduct of a first-in-human Phase 1 clinical study of PLN-101325.

Previous wording

•Enrollment remains on track in BEACON-IPF, a pivotal adaptive Phase 2b/3 trial of bexotegrast in patients with idiopathic pulmonary fibrosis (IPF). The BEACON-IPF Phase 2b trial is a 52-week, multinational, randomized, dose-ranging, double-blind, placebo-controlled trial evaluating bexotegrast at once-daily doses of 160 mg or 320 mg in 360 patients with IPF. Enrollment is expected to be complete in the first quarter of 2025 with data anticipated in mid-2026.

Current wording

•Enrollment remains on track in BEACON-IPF, a pivotal adaptive Phase 2b/3 trial of bexotegrast in patients with idiopathic pulmonary fibrosis (IPF). The BEACON-IPF Phase 2b/3 trial is a 52-week, multinational, randomized, dose-ranging, double-blind, placebo-controlled trial evaluating bexotegrast at once-daily doses of 160 mg or 320 mg. The Phase 2b portion of BEACON-IPF will enroll 360 patients with IPF. Enrollment in this portion of this trial is expected to be complete in the first quarter of 2025 with data anticipated in mid-2026.

Previous wording

•INTEGRIS-IPF Phase 2a trial results published in the American Journal of Respiratory and Critical Care Medicine (AJRCCM). Also known as the “Blue Journal”, AJRCCM is a leading peer-reviewed journal published by the American Thoracic Society. The publication Bexotegrast in Patients with Idiopathic Pulmonary Fibrosis: The INTEGRIS-IPF Study reviews the previously reported positive results from the multinational, randomized, double-blind, placebo-controlled INTEGRIS-IPF Phase 2a trial that enrolled 119 patients with IPF.

Current wording

•Results from Phase 2a PET imaging target engagement trial published in the American Journal of Respiratory and Critical Care Medicine (AJRCCM). Also known as the “Blue Journal,” AJRCCM is a leading peer-reviewed journal published by the American Thoracic Society. The publication reviews the previously reported positive results from an open-label trial in which bexotegrast showed dose-dependent αvβ6 integrin receptor occupancy in lungs of patients with IPF.

Previous wording

•Phase 1 trial of PLN-101095 in solid tumors is progressing with dosing of the third of five cohorts. PLN-101095 is an oral, small molecule, dual selective inhibitor of αvβ8 and αvβ1 integrins designed to block TGF-β activation in the tumor microenvironment. The Company is currently enrolling the third of five cohorts in the Phase 1 open label, dose-escalation trial of PLN-101095 as monotherapy and in combination with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors. Preliminary data is expected in late 2024 or early 2025.

Current wording

•Phase 1 trial of PLN-101095 in solid tumors is progressing with dosing of the third of five cohorts. PLN-101095 is an oral, small molecule, dual selective inhibitor of αvβ8 and αvβ1 integrins designed to block TGF-β activation in the tumor microenvironment. The Company has completed enrollment in the third of five cohorts in the Phase 1 open-label, dose-escalation trial. In this trial, PLN-101095 is being tested as monotherapy and in combination with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors. Preliminary data is expected in early 2025.

Previous wording

•PLN-101325 applications beyond muscular dystrophies. PLN-101325 is a monoclonal antibody that acts as an allosteric agonist of integrin α7β1, currently in development for treatment of muscular dystrophies. Based on preclinical data, PLN-101325 may have the potential to treat additional indications in organ systems outside of muscle. The Company is currently generating additional evidence in support of potential expansion of the scope of PLN-101325 prior to initiating a Phase 1 trial.

Current wording

•PLN-101325 applications beyond muscular dystrophies. PLN-101325 is a monoclonal antibody that acts as an allosteric agonist of integrin α7β1, currently in development for treatment of muscular dystrophies. The Company is currently generating additional evidence in support of potential expansion of the scope of PLN-101325 prior to initiating a Phase 1 trial.

Previous wording

Since inception, we have had significant operating losses. Our net loss was $55.9 million and $41.2 million for the three months ended June 30, 2024 and 2023, respectively. Our net loss for the six months ended June 30, 2024 and 2023 was $102.8 million and $78.7 million, respectively. As of June 30, 2024, we had an accumulated deficit of $602.6 million and cash, cash equivalents, and short-term investments of $438.1 million. We expect to continue to incur net losses for the foreseeable future, and we expect our research and development expenses, general and administrative expenses, and capital expenditures will increase in connection with our ongoing activities, as we:

Current wording

Since inception, we have had significant operating losses. Our net loss was $57.8 million and $41.5 million for the three months ended September 30, 2024 and 2023, respectively. Our net loss for the nine months ended September 30, 2024 and 2023 was $160.6 million and $120.2 million, respectively. As of September 30, 2024, we had an accumulated deficit of $660.3 million and cash, cash equivalents, and short-term investments of $406.0 million. We expect to continue to incur net losses for the foreseeable future, and we expect our research and development expenses, general and administrative expenses, and capital expenditures will increase in connection with our ongoing activities, as we:

Previous wording

Under the terms of the Novartis Agreement, we received an upfront license fee payment of $50.0 million for the worldwide, exclusive license to PLN-1474, an αvß1 inhibitor developed by Pliant to target metabolic dysfunction-associated steatohepatitis, or MASH, and an additional $29.0 million upon the achievement of specified research and development milestones. As part of a broad strategic realignment, Novartis has discontinued clinical development in MASH and, as a result, discontinued development of PLN-1474. In February 2023, Novartis issued a termination notice for the collaboration and license agreement, and returned global rights to Pliant for PLN-1474.

Current wording

Under the terms of the Novartis Agreement, we received an upfront license fee payment of $50.0 million for the worldwide, exclusive license to PLN-1474, an αvβ 1 inhibitor developed by Pliant to target metabolic dysfunction-associated steatohepatitis, or MASH, and an additional $29.0 million upon the achievement of specified research and development milestones. As part of a broad strategic realignment, Novartis has discontinued clinical development in MASH and, as a result, discontinued development of PLN-1474. In February 2023, Novartis issued a termination notice for the collaboration and license agreement, and returned global rights to Pliant for PLN-1474.

Previous wording

Following termination of the Novartis Agreement, we are no longer eligible to receive additional milestone or royalty payments under the arrangement; however, we continued to earn research and development services revenues through the effective termination date of April 18, 2023. We recognized nil and $0.2 million in revenues for performing research and development activities associated with PLN-1474 and integrin research targets in the three months ended June 30, 2024 and 2023, respectively.

Current wording

Following termination of the Novartis Agreement, we are no longer eligible to receive additional milestone or royalty payments under the arrangement; however, we continued to earn research and development services revenues through the effective termination date of April 18, 2023. There were no revenues for performing research and development activities associated with PLN-1474 and integrin research targets in the three months ended September 30, 2024 and 2023, respectively.

Previous wording

Research and development expenses for the three months ended June 30, 2024 increased $12.6 million, primarily due to BEACON-IPF, a Phase 2b study of bexotegrast in patients with IPF, and related manufacturing activities.

Current wording

Research and development expenses for the three months ended September 30, 2024 increased $15.4 million, primarily due to BEACON-IPF, a Phase 2b/3 study of bexotegrast in patients with IPF, and related manufacturing activities.

Previous wording

General and administrative expenses for the three months ended June 30, 2024 increased $0.4 million, primarily due to a marginal increase in professional service expenses.

Current wording

General and administrative expenses for the three months ended September 30, 2024 decreased $1.1 million, primarily due to a decrease in professional service expenses.

Previous wording

Interest expense for the three months ended June 30, 2024 increased $0.5 million due to additional borrowings under the Amended Loan Agreement executed March 11, 2024.

Current wording

Interest expense for the three months ended September 30, 2024 increased $0.6 million due to additional borrowings under the Amended Loan Agreement executed March 11, 2024.

Previous wording

The following table summarizes our research and development expenses for the six months ended June 30, 2024 and 2023 (in thousands):

Current wording

The following table summarizes our research and development expenses for the nine months ended September 30, 2024 and 2023 (in thousands):

Previous wording

General and administrative expenses for the six months ended June 30, 2024 increased $1.5 million, primarily attributable to employee-related costs, driven by increased headcount.

Current wording

General and administrative expenses for the nine months ended September 30, 2024 increased $0.5 million, primarily attributable to employee-related costs, driven by increased headcount.

Previous wording

Interest expense for the six months ended June 30, 2024 increased $0.7 million due to additional borrowings under the Amended Loan Agreement executed March 11, 2024.

Current wording

Interest expense for the nine months ended September 30, 2024 increased $1.2 million due to additional borrowings under the Amended Loan Agreement executed March 11, 2024.

Previous wording

As of June 30, 2024, we had $438.1 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.

Current wording

As of September 30, 2024, we had $406.0 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.

Previous wording

In March 2024 we entered into the Oxford Loan Agreement with Oxford Finance LLC the (or the “Lender” or “Oxford”) which upsized our existing term loan facility to a total size of $150.0 million of available non-dilutive capital. Pursuant to the Oxford Loan Agreement, we drew an additional Term Loan of $20.0 million and may borrow up to $70.0 million at our option upon the satisfaction of certain conditions related to the development of bexotegrast. A further $50.0 million may be made available to us at the sole discretion of Lender. See Note 7 to the Notes to our condensed financial statements of this Report for more information.

Current wording

In March 2024 we entered into an Amended Loan Agreement with Oxford Finance LLC (or the “Lender” or “Oxford”) which upsized our existing Term Loan facility to a total size of $150.0 million of available non-dilutive capital. Pursuant to the Amended Loan Agreement, we drew an additional Term Loan of $20.0 million and may borrow up to $70.0 million at our option upon the satisfaction of certain conditions related to the development of bexotegrast. A further $50.0 million may be made available to us at the sole discretion of Lender. See Note 7 to the Notes to our condensed financial statements of this Report for more information.

Previous wording

We believe that our existing capital resources, together with the funds available to us under the Amended Loan Agreement, 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 change, and we may need additional funds to meet operational needs and capital requirements for product development and commercialization sooner than planned.

Current wording

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 change, and we may need additional funds to meet operational needs and capital requirements for product development and commercialization sooner than planned.

Previous wording

Net cash used in operating activities increased $20.5 million compared to the six months ended June 30, 2023, driven by an increase in net loss of $24.1 million, which was partially offset by the receipt of accreted value associated with maturities on our short-term investment portfolio during the six months ended June 30, 2024.

Current wording

Net cash used in operating activities increased $16.6 million compared to the nine months ended September 30, 2023, driven by an increase in net loss of $40.3 million, which was partially offset by the receipt of accreted value upon maturities of short-term investment portfolio during the nine months ended September 30, 2024.

Previous wording

Net cash provided by investing activities increased over the same period of prior year as maturities of marketable securities exceeded related purchases during the six months ended June 30, 2024, while purchases exceeded maturities during the six months ended June 30, 2023 as a result of the public offering of common stock in January 2023.

Current wording

Net cash provided by investing activities increased over the same period of prior year as maturities of marketable securities exceeded related purchases during the nine months ended September 30, 2024, while purchases exceeded maturities during the nine months ended September 30, 2023 as a result of the public offering of common stock in January 2023.

Previous wording

Net cash provided by financing activities decreased $251.0 million primarily due to net proceeds of $270.3 million from the Company's January 2023 underwritten public offering, which was partially offset by additional Term Loans entered into during the current six months ended June 30, 2024 associated with the Amended Loan agreement.

Current wording

Net cash provided by financing activities decreased $251.2 million primarily due to net proceeds of $270.3 million from the Company's January 2023 underwritten public offering, which was partially offset by additional Term Loans entered into during the current nine months ended September 30, 2024 associated with the Amended Loan Agreement.