some game-changing drugs that give durable treatments. We can develop drugs that weren ’ t technically possible before, and we know which nodes to target. There ’ s also more organizational alignment among philanthropic groups, the government and pharmaceutical companies.
What is unique about Sonoma Bio ’ s approach and platform? Sonoma was built on the premise that we can use genetic engineering to incorporate genes that encode CAR-Treg to enable selective targeting of immune regulatory cells to a particular protein at a certain site. In principle, the CAR-Tregs get activated at that inflamed site and focus on both increasing the specific activity of the natural Tregs and reducing the risk of systemic effects. Our goal is to create durable, safe and pathway-specific drugs. What applications are in the pipeline? The first indication for Sonoma Bio is rheumatoid arthritis, which affects 5 million people annually and is very difficult to control despite the wealth of approved drugs. The target we chose for the CAR is expressed in other inflammatory diseases, including certain lung and skin diseases. Thus, we initiated a second clinical trial in hidradenitis suppurativa ( HS ) patients. HS is a devastating and painful disease that creates abscesses and tunnels in the skin and, in turn, emotional and physical debilitation. Eighty percent of the patients are women, mostly women of color. Should we see a strong clinical response, our first product could be used in other diseases with similar causation. Finally, we have partnered with Regeneron, a great company built on novel science and technology, to expand our disease portfolio. We are working on four more indications, including Crohn ’ s disease and ulcerative colitis. It ’ s been a monolithic endeavor requiring tremendous effort and collaboration. What are the current limitations and risks of immunotherapy? If the immune system had a simple on/off switch, it would be easy to develop drugs. But it is more like a thermostat. If you move too far to one side, you get autoimmunity. If you move too far to the other side, you get immune suppression and infections. The immune system must balance right in the middle. We must refine the therapies to ensure we don ’ t go too far and induce other diseases while treating the primary ones. We are also working to engineer cells with receptors that allow for more specificity to activate at the disease site and shut down inflammation locally without systemic effects. Of course, one of the greatest challenges is accessibility. As a community of drug developers, we must find ways to make these therapies less expensive and logistically challenging to make them available to everyone in need. What ’ s next? Next, immunotherapy will target non-immune-based diseases. We ’ ll see an explosion of immunotherapy in functionally inflammatory diseases. Many diseases are affected by immune inflammation, including neurodegenerative diseases like Parkinson ’ s, Alzheimer ’ s, ALS, heart disease and stroke, for which there ’ s an initial instigating event not necessarily involving the immune system. But the immune response to that event causes much of the damage. On the treatment side, some argue that statins reduce both cholesterol and inflammation. That may also be what drugs like Ozempic do, and we ’ re seeing early evidence of their possible utility in autoimmunity with Crohn ’ s or ulcerative colitis. The future is combining multiple treatments targeting distinct pathways to induce durable cures. In Treg biology, we ’ ve learned that about half of Tregs are in circulation, and the other half sit in tissue. Fat and the intestine have more Tregs than anywhere else in the body. These Tregs control inflammation in the fat and the gut and make repair factors for damaged tissues. Excessive obesity, for instance, can cause cellular and transcriptional alterations in the Tregs, affecting their ability to modulate local and systemic inflammation and contributing to insulin resistance. The microbiome ( bacteria in the gut ) can alter Treg function to create susceptibility to inflammatory bowel syndrome. Treg and Treg-friendly cell therapies are potential treatments for these impacted tissues. Is there anything people can do to support their immune tolerance or immune balance or even rebuild their immune system? Everything I ’ ve talked about is fundamentally about inflammation. Unwanted inflammation causes immune system dysregulation. A healthy lifestyle with a reasonable diet and good exercise, combined with reduced stress, will lead to a more stable and reliable immune system. External forces constantly create imbalances in the immune system, but a more centered, balanced life will help center and balance it. What is your ultimate vision for immunotherapy and cell therapy? People say never to use the word cure because it sets the bar too high. But I expect cell therapies to become curative medicine. I would love for cell therapy to become so routine, effective and accessible that it is literally a pill in a bottle for people to rebuild and rebalance their immune systems. I hope it is transformational in how we treat diseases. This interview has been edited for length and clarity.
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