PD-L1 upregulation
Activates the cGAS–STING/IRF3 pathway, transcriptionally upregulating PD-L1. Validated in vitro and in two syngeneic in vivo models in combination with atezolizumab.
Immuno-oncology · Phase I · 2026
Converting cold tumors
into hot.
Isosceles is developing IPI201, a synthetic small-molecule immunotherapy adjuvant designed to expand the reach of checkpoint inhibitors like Keytruda into the patients they currently leave behind.
Cold tumors
Low PD-L1 expression. Excluded from or unresponsive to checkpoint inhibitors. The majority of solid tumors today.
Hot, treatable
Upregulated PD-L1, repolarized macrophages, restored anti-tumor immunity, sensitive to checkpoint therapy.
The opportunity
Checkpoint therapy works brilliantly, for a minority of patients.
PD-1 inhibitors like Keytruda generate objective responses in only 15–30% of patients across most solid tumors. The majority remain "cold" non-responders, representing the largest unmet need in modern oncology. IPI201 doesn't compete with checkpoint inhibitors. It expands them.
15–30%
Responder rate to checkpoint inhibitors across most solid tumors
70%
Of triple-negative breast cancer patients excluded from immunotherapy
71%
Of TME gene-expression changes in colorectal tumor mouse model attributable to IPI201 + anti-PD-1
Apr '26
Phase I trial initiated
Mechanism of action
Four convergent pathways. One immunological reset.
IPI201 activates a coordinated set of innate-immunity, anti-inflammatory, and tissue-perfusion mechanisms, simultaneously priming the tumor microenvironment to respond to checkpoint and cellular immunotherapies.
M1 → M2 repolarization
Shifts tumor-associated macrophages toward an anti-inflammatory M2 phenotype via A2A adenosine and CB2 receptor signaling, dampening the inflammatory drivers of immune exclusion.
TNF-α and ROS reduction
Reduces TNF-α, reactive oxygen species, and broader inflammatory mediators, restoring anti-tumor immune infiltration so checkpoint therapy can take hold.
Cerebral and tissue reperfusion
Regulates blood flow to enhance reperfusion following hypoxic injury via GPR18, GPR55, and 5-HT1A receptor activation, relevant to traumatic brain injury and ischemia-related indications.
Clinical validation
"A 50% objective response rate in PD-1 refractory triple-negative breast cancer. Direct evidence that checkpoint resistance is convertible in humans."
Cromolyn study, Nature Medicine, June 2025, plus a parallel 50% ORR result in Phase II trial NCT05076682 with camrelizumabThese independent results, combined with Isosceles' proprietary preclinical data, establish the rationale for the IPI201 development program. That data includes a 625% increase in cancer-cell killing when IPI201 is combined with NK cells, and the discovery that IPI201 is only the third known molecule (alongside IL-2 and IL-15) sufficient to sustain NK cell survival in vitro.
The pipeline
Two assets. One immuno-modulatory platform.
IPI201 is our lead clinical candidate, a patented synthetic resorcinyl isoprenyl benzene derivative formulated for intravenous administration and currently in Phase I clinical studies. IPI301, a dissolving microneedle patch, extends the same molecule into a rapid intradermal delivery platform for adjacent indications.
Asset
Indication
Stage
IPI201
IV synthetic small molecule · immunotherapy adjuvant
PD-1 Relapsed or Refractory
Phase I trial
Phase I trial
Preclinical
Phase I
Phase II
Phase III
Approval
IPI301
Dissolving microneedle patch · intradermal delivery
Rapid onset for inflammatory indications
Preclinical
Phase I
Phase II
Phase III
Approval
Partnerships & investment
Building the next generation of immunotherapy adjuvants.
We work with checkpoint inhibitor manufacturers, cellular immunotherapy partners, and clinical research organizations to bring IPI201 from the lab into patients.