In this podcast and accompanying article, we talked with Dr. Paul Wotton, Chief Executive Officer, Obsidian Therapeutics about the evolution of cancer therapy and new advancements in the space including precision medicine. Our discussion included Obsidian’s cytoDRiVE™ platform that provides a technology, in which the level and timing of protein activity are fully controlled in a dose-dependent manner by an FDA-approved small molecule.
I began the interview by asking Dr. Wotton, about why the company chose the name Obsidian. He explained that the volcanic rock obsidian was used to make the most precise scalpels and that bringing precision to cell and gene therapies is Obsidian Therapeutics’ goal. In addition, there are over 50 people working for Obsidian Therapeutics from all over the world, just like the obsidian rock is found all over the world, so it is also a good representation of the company’s diversity.
I then asked Paul why after many years in the cell therapy industry, he was drawn to cancer therapeutics. He said that he has been involved in a number of cell therapy companies prior to joining Obsidian Therapeutics and sees cell and gene therapy as the future of medicine. He was working at one of these companies when his wife was diagnosed with cancer and he stepped down to be with her through the chemotherapy treatment. At the beginning of this year, Obsidian approached him and they had oncology targets, which were now of heightened interest. He also was very impressed with their technology platform that he felt was extremely relevant to where cell and gene therapy is moving in the future. The platform addresses a problem in the industry that Paul sees as the missing link – the ability to control cytokine activation and to be able to modulate cell and gene therapies similar to dosing strategies seen with small molecule drugs. With the Obsidian platform, it is possible to modulate and regulate cell and gene therapies in the body.
Next I asked him how cancer therapy has evolved in the last decades and what he sees as some of the recent advancements in the space. He said that immune-oncology approaches, using the body’s own immune system to fight tumors through the use of checkpoint inhibitors, has been a huge success and has revolutionized the way that some cancers are being treated. More recently the success of CAR-T therapies is a big advancement.
We then discussed some of the current limitations in cell and gene therapy. He talked about how most of the cell therapies used to treat cancer today are autologous, where a patient’s own cells are removed, engineered and then administered back to the patient. The challenge with this approach is that processing these cells takes time, often a few weeks, and it is expensive to make. He believes that we will start to see a shift toward “off the shelf therapies”, which will likely be more accurate and affordable. This is a focus of Obsidian Therapeutics, to make cell and gene therapies more controllable and to improve their performance by giving the cells a more robust appearance allowing them to persist longer and/or be able to survive longer within the tumor environment.
We then expanded on this topic and Paul described Obsidian’s cytoDRiVE™ technology platform. He explained the very interesting details of the science behind the technology and how it was originally developed by Professor Tom Wandless at Stanford University. In summary, the technology provides a way to control protein degradation using FDA-approved small molecules, permitting precise control of the timing and level of protein expression. The cytoDRiVE™ platform can be applied to design controllable intracellular, membrane and secreted proteins for cell and gene therapies as well as other applications. Paul explained that it is the first time anyone has utilized this type of control over cell and protein activity by administering a small molecule drug, particularly commonly available small molecule drugs that have been widely used in therapies for decades.
Next I asked about what differentiates Obsidian’s platform from other comparable companies in the space. Paul explained that other companies have tried to turn on and off protein activity, but it is generally an all or nothing situation. Either the protein is on or off. Obsidian has created a dimmer switch for the protein in which it can be modulated and the protein or cytokine activity can be turned up or down based on the dose response to the small molecule.
I asked Paul if there were any other applications for the platform. He gave me some examples, modulating cytokine activity within a cell by tagging it with drug responsive domains. You could also use tag transcription factors, which would permit control of secretion protein output from a cell. This use of the technology would allow modulation of gene therapies by providing a more precise dose control. He also shared that there are numerous applications with auto immune disorders, eye disorders, enzyme replacement therapy, just to name a few.
Next, I asked if he could share a specific example of a current therapy that could benefit from this approach and he shared some breaking news with me. Obsidian has identified their first clinical programs will be in tumor infiltrating lymphocytes. Currently there are therapies where patients’ own lymphocytes are harvested from within their tumor. These cells are already trained to go after the tumor. Harvested cells are expanded to a larger number and returned to the patient. There has already been great clinical success with this approach. Obsidian would now make cells more robust by giving them their own cytokine that would be produced on demand via administration of a small molecule.
He went on to explain why this would improve on the current therapy. The current therapy can take weeks to produce and patients are required to take a high dose of Interleukin 2. This is challenging because there are significant side effects with Interleukin 2. Furthermore, there are only a handful of clinics that can administer this therapy because of the need for support rooms in case there is a problem. The Obsidian approach would eliminate or reduce the need for IL-2 by giving the cells their own store of the cytokine, thus producing no side effects. Thereby, permitting more clinics to be able to administer the therapy without the need for IL-2 support.
I asked Paul if he could describe the role for precision medicine in cancer care. He said we can look to the success of CAR-T therapies currently and in the future we could expand this success to other cell types, for example natural killer cells. Overall, we can expand the number of cell types that can be used to treat patients.
I wanted to find out what was next for Obsidian in the near term and which indications the company would be focusing on. Paul said that the platform knows no bounds, so they will select areas where regulating cell and gene therapies can make a difference. There are a broad number of disease states to which this would apply.
Then I asked where Obsidian would be in 5 years and the strategy for moving forward. Paul told me that their goal is to be in the clinic by 2022 and that takes strategic planning. They are planning to have a commercial product on the market within 5 years time and to broaden their current pipeline. They will put multiple strategic partnerships in place to achieve these goals and timelines.
I closed the interview by asking Paul if he had anything else to add for our listeners. He said that a business is all about its people and they have built a very strong team at Obsidian. Everyone is working really hard and moving quickly to achieve the company goals. He also wanted to thank the Venture Capital companies who have bet on their platform and the support of the Obsidian Board of Directors.
To learn more about Obsidian Therapeutics, please visit their website at https://obsidiantx.com/