Opioids and Immunotherapy: A Hidden Connection?

Welcome back to the podcast blog! In our latest episode, available here, we spoke with Justin Chickles, CEO and Co-Founder of Glycyx Therapeutics, about a fascinating and potentially critical issue in cancer treatment: the negative impact of opioids on the effectiveness of immunotherapy. Many patients undergoing cancer treatment rely on opioids for pain management, but emerging evidence suggests these medications may inadvertently hinder the very therapies designed to save their lives. This blog post will delve deeper into this unseen threat, explore the science behind it, and highlight the innovative work Glycyx Therapeutics is doing to address this problem with their axelopran therapy, currently in Phase 2 trials. We’ll also examine Justin Chickles' journey from big pharma to biotech pioneer, providing a glimpse into the dedication and ingenuity driving advancements in oncology.

The Promise of Immunotherapy and a Potential Roadblock

Immunotherapy has revolutionized cancer treatment, offering hope to patients who previously had limited options. Unlike traditional chemotherapy, which directly targets and kills cancer cells (often with significant side effects), immunotherapy harnesses the power of the patient's own immune system to recognize and destroy cancer. This approach can lead to more durable responses and fewer debilitating side effects for some patients.

The key to immunotherapy lies in activating specific immune cells, particularly T cells, to identify and attack cancer cells. This activation often involves "checkpoint inhibitors," drugs that block signals that would otherwise prevent T cells from attacking cancer. By releasing these brakes on the immune system, checkpoint inhibitors allow T cells to recognize and eliminate cancer cells more effectively. This approach has shown remarkable success in treating various cancers, including melanoma, lung cancer, and kidney cancer.

However, the success of immunotherapy is not universal. Many patients do not respond to immunotherapy, and researchers are working tirelessly to understand why. One potential reason, often overlooked, is the widespread use of opioids for pain management in cancer patients. Opioids, while effective at relieving pain, have been shown to have immunosuppressive effects. This means they can weaken the immune system, potentially hindering the ability of immunotherapy to work effectively.

This is where the "roadblock" comes in. If opioids are suppressing the immune system, they could be directly interfering with the mechanisms by which immunotherapy is supposed to work. The very drugs intended to provide comfort and improve quality of life may be inadvertently undermining the chances of successful cancer treatment. This realization has spurred a significant interest in finding ways to mitigate the immunosuppressive effects of opioids without sacrificing pain relief for cancer patients.

Glycyx Therapeutics and Axelopran: A Novel Approach

Glycyx Therapeutics is a biopharmaceutical company focused on developing novel therapies to address unmet needs in cancer treatment. Recognizing the potential negative impact of opioids on immunotherapy, they have developed axelopran, a peripherally acting mu opioid receptor antagonist (PAMORA). Axelopran is designed to block the opioid receptors in the gut, reducing opioid-induced constipation, a common side effect of opioid use. Importantly, axelopran does not cross the blood-brain barrier, meaning it does not interfere with the pain-relieving effects of opioids in the brain.

The rationale behind axelopran's potential benefit in immunotherapy lies in its ability to counteract the immunosuppressive effects of opioids. While the exact mechanisms are still being investigated, it is believed that opioids can suppress the immune system through several pathways. By blocking opioid receptors in the gut, axelopran may help to restore normal immune function and enhance the effectiveness of immunotherapy.

The development of axelopran represents a significant advancement in the field of oncology. It offers a potential solution to a growing problem: the unintentional undermining of immunotherapy by opioid use. By specifically targeting the peripheral effects of opioids, axelopran aims to minimize the negative impact on the immune system without compromising pain management. This approach has the potential to significantly improve outcomes for cancer patients undergoing immunotherapy.

Glycyx's innovative approach has garnered significant attention in the oncology community. Their dedication to addressing this complex issue underscores the importance of considering all factors that may influence the success of cancer treatment. The development of axelopran is a testament to the power of translational science, taking research findings from the laboratory and translating them into potential therapies for patients.

Justin Chickles' Journey: From Pharma to Biotech Pioneer

The story of Glycyx Therapeutics is intertwined with the career of its CEO and Co-Founder, Justin Chickles. Justin's journey from a large pharmaceutical company to leading a cutting-edge biotech startup is an inspiring example of innovation and entrepreneurial spirit. His experience at Johnson & Johnson provided him with a solid foundation in drug development and commercialization. However, he felt a strong desire to be more involved in the early stages of drug discovery and development, leading him to transition to the world of biotech.

Justin's move to biotech allowed him to take on more responsibilities and have a direct impact on the development of novel therapies. He gained experience in leading multiple startups, navigating the challenges of fundraising, building teams, and advancing drug candidates through preclinical and clinical development. His passion for oncology and his commitment to improving patient outcomes drove him to co-found Glycyx Therapeutics.

Justin's leadership has been instrumental in guiding Glycyx through the complexities of drug development. His deep understanding of the pharmaceutical industry, coupled with his entrepreneurial drive, has enabled him to build a strong team, secure funding, and advance axelopran into Phase 2 clinical trials. His story is a testament to the power of vision, perseverance, and a relentless focus on improving the lives of cancer patients.

The success of Glycyx Therapeutics is a reflection of Justin's commitment to innovation and his ability to identify and address unmet needs in cancer treatment. His journey from pharma to biotech pioneer is an inspiring example of how individual initiative and a passion for science can drive meaningful change in the healthcare industry. He emphasizes the importance of collaboration, scientific rigor, and a patient-centric approach to drug development.

The Science Behind the Connection: Opioids and the Immune System

Understanding the connection between opioids and the immune system is crucial to appreciating the potential impact of axelopran. Opioids exert their analgesic effects by binding to opioid receptors in the brain and spinal cord, reducing the perception of pain. However, opioid receptors are also found on immune cells, including T cells, B cells, and natural killer (NK) cells. This widespread expression of opioid receptors suggests that opioids can directly influence immune function.

Studies have shown that opioids can suppress various aspects of the immune system. They can inhibit the proliferation and activation of T cells, reduce the production of cytokines (signaling molecules that regulate immune responses), and impair the function of NK cells, which are critical for killing cancer cells. These immunosuppressive effects can weaken the body's ability to fight off infections and potentially hinder the effectiveness of immunotherapy.

The mechanisms by which opioids suppress the immune system are complex and not fully understood. However, it is believed that opioids can modulate immune cell signaling pathways, alter gene expression, and disrupt the delicate balance of immune regulation. Furthermore, opioids can affect the gut microbiome, which plays a critical role in shaping the immune system. Changes in the gut microbiome can lead to inflammation and immune dysfunction, further contributing to the immunosuppressive effects of opioids.

The impact of opioids on the immune system can vary depending on several factors, including the type of opioid, the dose, the duration of use, and the individual's genetic background. Some studies have shown that certain opioids, such as morphine, are more immunosuppressive than others. Additionally, chronic opioid use can lead to tolerance, requiring higher doses to achieve the same pain relief, which can further exacerbate the immunosuppressive effects.

Phase 2 Trials: What's Next for Axelopran?

Axelopran is currently in Phase 2 clinical trials, a crucial stage in the drug development process. Phase 2 trials are designed to evaluate the safety and efficacy of a drug in a larger group of patients. The primary objectives of the Phase 2 trials for axelopran are to assess its ability to mitigate the immunosuppressive effects of opioids in cancer patients undergoing immunotherapy and to determine whether it can improve the overall response rate to immunotherapy.

The Phase 2 trials are enrolling patients with various types of cancer who are receiving both opioid pain management and immunotherapy. Patients are being randomized to receive either axelopran or a placebo, in addition to their standard cancer treatment. The researchers are closely monitoring the patients' immune function, including T cell activity, cytokine levels, and NK cell function. They are also tracking the patients' response to immunotherapy, including tumor shrinkage, progression-free survival, and overall survival.

The results of the Phase 2 trials will provide valuable information about the potential benefits of axelopran in optimizing immunotherapy outcomes. If the trials are successful, they could pave the way for Phase 3 trials, which are larger, randomized, controlled trials designed to confirm the drug's efficacy and safety in a broad patient population. Positive results from Phase 3 trials could lead to regulatory approval and the widespread use of axelopran in cancer treatment.

The Phase 2 trials for axelopran represent a significant step forward in addressing the unmet need for strategies to mitigate the immunosuppressive effects of opioids in cancer patients. The results of these trials will have a profound impact on the future of cancer treatment and could potentially improve outcomes for countless patients undergoing immunotherapy.

Why This Matters: The Future of Cancer Treatment

The potential negative impact of opioids on immunotherapy effectiveness is a critical issue that demands attention. As immunotherapy becomes an increasingly important component of cancer treatment, it is essential to identify and address factors that may limit its success. The widespread use of opioids for pain management in cancer patients makes this a particularly relevant concern.

By recognizing and addressing the potential interaction between opioids and the immune system, we can optimize immunotherapy outcomes and improve the lives of cancer patients. The development of axelopran represents a significant step in this direction, offering a potential solution to mitigate the immunosuppressive effects of opioids without compromising pain relief. The ongoing Phase 2 trials will provide valuable data on the safety and efficacy of axelopran and could pave the way for its widespread use in cancer treatment.

Looking to the future, it is clear that personalized medicine will play an increasingly important role in cancer treatment. This approach involves tailoring treatment strategies to the individual patient, taking into account their genetic makeup, disease characteristics, and other relevant factors. Understanding the individual patient's immune status and their opioid use is crucial for optimizing immunotherapy outcomes. By integrating this information into treatment planning, we can ensure that patients receive the most effective and appropriate therapies.

Continued research is needed to further elucidate the complex interplay between opioids, the immune system, and cancer. This research will help us to develop more targeted and effective strategies to mitigate the immunosuppressive effects of opioids and improve outcomes for cancer patients undergoing immunotherapy. The future of cancer treatment lies in a holistic approach that considers all factors that may influence the success of therapy, including pain management, immune function, and personalized medicine.

Conclusion: Hope for Optimizing Immunotherapy Outcomes

In conclusion, the potential negative impact of opioids on cancer immunotherapy effectiveness is a serious concern that warrants further investigation. Glycyx Therapeutics' axelopran represents a promising approach to addressing this issue by mitigating the immunosuppressive effects of opioids without compromising pain relief. Justin Chickles' journey from pharma to biotech pioneer highlights the importance of innovation and entrepreneurial spirit in driving advancements in oncology.

The ongoing Phase 2 trials for axelopran will provide valuable data on its safety and efficacy, potentially paving the way for its widespread use in cancer treatment. By optimizing immunotherapy outcomes, we can improve the lives of countless cancer patients and offer them renewed hope for a brighter future. As we learned in our episode with Justin Chickles, available here, the fight against cancer requires a multi-faceted approach, and addressing the opioid-immunotherapy interaction is a crucial piece of the puzzle. We are excited to follow the progress of Glycyx Therapeutics and their groundbreaking work in this important area.