Pliant Therapeutics (NASDAQ:PLRX) used its presentation at Oppenheimer’s 36th Annual Healthcare Conference to outline its strategic transition toward oncology following the discontinuation of its fibrosis efforts. Chief Executive Officer Bernard Coulie and Chief Financial Officer Keith Cummings highlighted the company’s continued focus on an integrin-targeting small molecule platform and described near-term priorities centered on advancing its lead oncology candidate and expanding a preclinical targeted drug delivery platform.
Company repositioning around integrins
Coulie described Pliant as an “integrin small molecule platform company” that has built a library of selective compounds and supporting biology capabilities over roughly a decade. After stopping its fibrosis program last year, management said it “had to rethink” how to proceed and concluded that the best course was to refocus on its core integrin platform to build a new pipeline.
Lead oncology program: PLN-101095 and the TGF-β pathway
Pliant’s most advanced program is PLN-101095, an orally administered small molecule designed to block both αvβ8 and αvβ1 integrins. Coulie said the compound is dosed twice daily and is being developed in oncology rather than fibrosis.
Management framed the program’s rationale around TGF-β biology in the tumor microenvironment. Coulie said tumors can express αvβ8 and αvβ1 in response to sustained immune activity and use those integrins to activate TGF-β, contributing to immune suppression and resistance to immune checkpoint inhibitors. He described αvβ1 expression on cancer-associated fibroblasts and αvβ8 expression on tumor cells and regulatory T cells, and said blocking these integrins can reduce activation of TGF-β locally within the tumor microenvironment. Coulie emphasized Pliant’s goal of tumor-specific modulation rather than systemic TGF-β suppression, which he said has been associated with tolerability challenges for other approaches.
Phase I experience: early response signal and biomarker changes
Coulie reviewed results from an initial Phase I study in patients with solid tumors refractory to immune checkpoint inhibitors. The trial included a 14-day monotherapy “lead-in” period with PLN-101095, followed by introduction of pembrolizumab.
According to Coulie, 16 patients were treated across five dose cohorts ranging from 250 mg twice daily to 2,000 mg twice daily. He said responses began to appear at doses of 1,000 mg twice daily and above. In that higher-dose range, he reported four clinical responders—three partial responses and one complete response—across four tumor types:
- Cholangiocarcinoma (complete response)
- Melanoma
- Non-small cell lung cancer
- Head and neck cancer
At the time of analysis (late November/early December), Coulie said the average duration among responders was 15 months, and that at least three of the four patients remained responders. He also reported an average tumor size reduction of 71% among responders and described an overall response rate of 40% in the secondary refractory population at doses of 1,000 mg twice daily or higher.
On safety, Coulie said the drug was well-tolerated and that the most common reported side effect was mild-to-moderate rash in about half of patients, which he suggested may be related to the combination of pembrolizumab and PLN-101095. He said the company did not observe safety or tolerability issues typically associated with systemic TGF-β inhibition.
The company also highlighted biomarker data from the 14-day monotherapy lead-in period. Coulie said responders showed a 3- to 12-fold increase in interferon gamma from baseline to day 14, with the elevation lasting about 28 days before beginning to decline. He said Pliant intends to explore whether interferon gamma changes could serve as an early predictor of response, though the upcoming Phase Ib expansion will not select patients based on interferon gamma increases. When asked, Coulie said the company did not see a correlation between rash and interferon gamma response.
Coulie added that Pliant plans to present the full dataset at a scientific conference in the near term.
Next steps: Phase Ib expansion and cohort strategy
Pliant plans to initiate a Phase Ib dose-expansion study in combination with pembrolizumab, with first patient in expected in the second quarter of this year. Coulie said the study will narrow the number of indications while aiming not to miss potential responsive tumor types. He outlined planned cohorts including non-small cell lung cancer, a cohort focused on patients with high tumor mutational burden (spanning multiple tumor types), and a renal cell carcinoma cohort. He said the renal cohort choice is supported by αvβ8 expression profiles and prior data from other anti–TGF-β approaches.
Cummings added that Pliant expects data from the oncology program “at some point next year,” and noted that even with aggressive development the company anticipates roughly a year of cash beyond the initial Phase Ib data readout.
Targeted siRNA delivery platform and financial runway
Beyond oncology, Coulie described a targeted drug delivery platform in which siRNA molecules are linked to integrin-binding small molecules to enable selective delivery to specific cell types. He said early work in mice has shown selective delivery to muscle cells or adipocytes without affecting other tissues, and that the company is now evaluating targeted delivery and gene knockdown in non-human primates. Coulie said Pliant expects data later this year, likely toward the end of the second quarter, as dosing is underway.
On partnering, Coulie said the platform is currently envisioned as an internal pipeline-building engine rather than an immediate partnering asset. He characterized siRNA sourcing as accessible through contract manufacturing, with delivery and target selection as the key differentiators.
On liquidity, Cummings said Pliant finished the third quarter with approximately $211 million in cash on a pro forma basis reflecting the payoff of its loan facility. He said fourth-quarter burn declined dramatically following a company restructuring and that current cash is expected to last into at least the second half of 2028. Cummings said the runway assumptions include “full, aggressive development” of the oncology program as well as continued investment in the platform. Coulie added that the restructuring reduced the company’s footprint while retaining development operations capabilities and core medicinal chemistry and integrin biology expertise.
About Pliant Therapeutics (NASDAQ:PLRX)
Pliant Therapeutics, Inc (NASDAQ: PLRX) is a clinical-stage biopharmaceutical company focused on discovering and developing novel therapies for fibrotic diseases. Headquartered in Redwood City, California, Pliant applies a precision medicine approach to target integrin-mediated signaling pathways implicated in the development and progression of fibrosis across organ systems.
The company’s lead product candidate, PLN-74809, is an oral small molecule designed to inhibit both αvβ1 and αvβ6 integrins in patients with idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC).
