ADVANCING OUR PIPELINE
Developing therapies for solid tumors and other diseases
PLN-101095: ONCOLOGY
Our oncology program focuses on increasing the sensitivity of “cold” tumors to checkpoint inhibition therapies by blocking avβ8-mediated TGF-β activation in the tumor microenvironment.
Over the past several years, the checkpoint inhibitor class of immuno-oncology drugs has changed the way many cancers are treated. Checkpoint inhibitors work to block signals that prevent the body’s immune system from recognizing tumor cells. By blocking checkpoint signals such as PD-1, these drugs could sensitize T cells, allowing them to recognize and kill tumor cells. While checkpoint inhibitors have led to dramatic improvements in survival rates, there are still a significant proportion of patients who do not respond to the drugs.
One of TGF-β’s core physiologic roles is an anti-inflammatory effect that it provides in the wound healing process. In the tumor microenvironment, however, certain integrins, such as avβ8, can be overexpressed on multiple different cell types, resulting in increased activation and signaling of TGF-β. This mechanism is becoming increasingly recognized as a potential cause of the resistance to checkpoint inhibitors such as anti-PD-1 therapies seen in many tumors.
EXPLORE HOW OUR LEAD CANDIDATE, PLN-101095, WORKS
Integrins activate TGF-β on cancer cells and multiple other cell types in the tumor micro-environment, leading to immune suppression and resistance to immuno-oncology therapies. PLN-101095 is designed to selectively inhibit integrin binding to the latent TGF-β complex and has the potential to safely block TGF-β activation and enhance the efficacy of multiple checkpoint inhibition pathways.
PLN-101095 ONCOLOGY PROGRAM HIGHLIGHTS
- More than 40 percent of U.S. patients with cancer are estimated to be eligible for checkpoint inhibitors, but less than 13 percent respond to the treatment
- By targeting TGF-β activating integrins such as avβ8 that are upregulated in certain tumors, our goal is to remove the anti-inflammatory effect and, ultimately, sensitize tumors to checkpoint inhibitors
- We have shown in an EMT6 anti-PD-1 resistant tumor mouse model that our small molecule inhibitors of αvβ8-mediated TGF-β activation are able to sensitize tumors to anti-PD-1 therapy and extend survival
- PLN-101095, a dual selective inhibitor of avβ8 and avβ1 integrins and our lead oncology candidate, was spotlighted as a novel immunotherapy approach at the 2026 American Association for Cancer Research (AACR) 2026 Annual Meeting Highlights Plenary Session
PLN-101095 DEVELOPMENT STATUS
- Pliant is conducting FORTIFY, a Phase 1a/1b dose escalation/indication expansion trial (NCT 06270706) in patients with solid tumors resistant to immune checkpoint inhibitors
- Pliant is currently enrolling patients in the Phase 1b portion of FORTIFY. Pliant will enroll three cohorts of patients including patients with NSCLC, clear cell renal cell carcinoma and a subset of tumors with high tumor mutational burden
- In April 2026, as part of an oral presentation at AACR, updated data from the Phase 1a portion of this trial was announced with antitumor activity observed with PLN-101095 dosed in combination with pembrolizumab. PLN-101095 was generally well tolerated across all doses tested
- In August 2026, Pliant was awarded Fast Track designation from the U.S. Food and Drug Administration for PLN-101095 in combination with pembrolizumab for the potential the treatment of solid tumors that are resistant to immune checkpoint inhibitors
