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Opioid Induced Immunotherapy Failure (OIIF) in Cancer
Opioids, essential for managing severe cancer pain, inadvertently compromise cancer treatment efficacy. The blocking of Immune Checkpoint Inhibitors (ICI) by opioids leads to a reduction in treatment efficacy across 4000 patients of 50% (Mao et al, 2022), impacting patient survival rates and quality of life. This issue, termed Opioid-Induced Immunotherapy Failure (OIIF), stems from opioids' immune exhaustive effect and pro-angiogenic properties, weakening the immune response to cancer and reducing ICI effectiveness.
For data on opioids vs. no opioids in 1012 mixed checkpoint inhibitor patients, see Figure 2-C in Cortellini et al, 2020.
PFS in 1012 mixed checkpoint inhibitor (ICI) patients
Cortellini 2020, Integrated analysis of concomitant medications and oncological outcomes from PD-1/PD-L1 checkpoint inhibitors in clinical practice, Journal for ImmunoTherapy of Cancer
Axelopran: Best in class peripherally-active mu-opioid receptor antagonist
Innovative OIIF Treatment
Axelopran, a leading peripherally-active mu-opioid receptor antagonist, mitigates opioids' negative immune effects while preserving their pain-relief benefits, enhancing cancer immunotherapy efficacy
Proven Development
Initially developed for opioid-induced constipation and advanced to clinical significance in Phase 2b trials, axelopran has had comprehensive development work completed and safety data.
High Potency and Selectivity
As the most potent and selective agent within the PAMORA class, axelopran stands out for its targeted mechanism of action.
Safety and Tolerability
Demonstrated in clinical trials with 544 patients, showing excellent tolerability with no severe adverse events, supporting its use in broader oncology applications as Glycyx enters Phase 2 trials.
Phase 2b Ready
Bioavailable, efficacious dose demonstrated in OIC Phase 2 with excellent safety and tolerability: 10-15mg. CMC validated with long-term manufacturing partnership. IND active in April 2024. Clinical drug completed production in February 2024
Understanding the Opioid System
The opioid system is not merely a pain-relief pathway but a complex network influencing various physiological processes, including immune response, angiogenesis, and gastrointestinal function. Our research redefines this system's role in the human body, particularly under the conditions of stress and trauma such as cancer.
Axelopran with checkpoint inhibitors shows a significant impact in head and neck, melanoma, colon and breast cancers
Next step:
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Basket Phase 2b study with common design across 3-4 cohorts of different tumor types:
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Recurrent/metastatic head & neck squamous cell carcinoma (HNSCC), CPS ≥1
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Recurrent/metastatic non small cell lung cancer (NSCLC)
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Recurrent/metastatic melanoma
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RCT: Standard of care ICI +/- axelopran in frontline Stage IV ICI-eligible patients receiving opioids at baseline
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Bayesian Simon 2-stage design with powered interim safety and futility analysis; final efficacy powering based on interim view results
