How have you seen the treatment of cancer evolve in the past 20-30 years?
In the timeframe that you mentioned there has been enormous research progress regarding how cancer cells can bypass normal control mechanisms and grow more rapidly, subverting signals from the outside to the inside of the cell. During the three decades I have been in cancer R&D, I have seen how basic lab research has directly led to breakthrough therapies. One example is cancer immunotherapy – it took a century for the field to evolve from Coley's toxins and arrive at the conclusion that the bacterial toxins were activating the immune system to attack the tumor. Fast forward to 2011 and we saw the approval of the first cancer immunotherapy (Yervoy) for which Jim Allison received the Nobel prize in 2018. He discovered that by blocking a protein called CTLA-4, the immune system can be re-awakened to see the cancer and attack it, an amazing advance that transformed oncology research and subsequently helped many thousands of patients around the world.
In which way did the 2011 breakthrough translate in the therapies you are doing now with Probody therapeutics?
Back in 2008, when CytomX was created, the founders had the idea to engineer antibody therapeutics and make them more targeted to cancer cells. The process of tumor cell migration and metastasis involves molecular scissors (proteases) that allow cancers to cut their way into tissues and then colonize other organs. By putting a protein mask on the antibody to avoid normal tissue and then having it cut off by these molecular scissors in the tumor microenvironment we were able to develop a whole new system for localizing the antibody in cancer and not normal tissue and therefore broaden the therapeutic window.
A great example of how we are applying our technology is our collaboration with Bristol Myers Squibb on improving Yervoy. Yervoy is a great therapeutic option, but it can cause severe inflammatory side effects in patients because the immune system can be activated throughout the body and not just in cancer. In early 2014 we started working on a safer version of this drug with BMS. By localizing the drug to the tumor microenvironment, we thought we could make it safer and more effective. Eight years later, we are excited to be in phase 2 clinical trials where the unmasked drug is being compared to our masked, Probody version in patients with melanoma.
How are you thinking about CytomX in the long term?
Our ultimate ambition is to improve the lives of thousands of cancer patients by becoming a multi-product commercial stage company.
In order to achieve this goal, we must run registrational trials and scale our manufacturing capacities. The path to market approval for biologic drugs like ours is well defined and the ability to scale biologic drug manufacturing in the U.S., Europe and China has been increased by global infrastructure developed during the pandemic.
What role does collaboration play in the development of new drugs, and specifically for CytomX?
Partnering with industry leading major pharmaceutical companies has been and continues to be a great way to broaden the reach and impact of our innovation as well as gain access to funding - more than half of the $ 1 billion we have raised over the past decade came from partnerships. At the moment, the biotech capital equity market is really tough, especially for small companies, so our partnerships are all the more important as a way to finance our important work.
Regeneron is the newest of our five major collaborators. The Regeneron alliance is focused on bispecific immunotherapies which traditionally have shown a narrow therapeutic window, meaning that the balance between toxicity and activity is frail. By getting the combination of the tumor target and the immune cell target right, and using our Probody masking technology, we believe we can bring immune cells into the tumor where they will recognize the cancer and ultimately kill it in a safer and more effective way.
To what extent can cancer be treated as one disease in the context where there is a myriad of subtypes with specific behaviors?
Cancer continues to be treated mostly based upon the tissue of origin but in the last few years we started to see approaches that go across different cancers. One of the barriers that stands in the way of the vision of standardized treatments is that traditionally new therapies are approved for use one cancer type at a time. However, there are examples of laboratory markers that are common across cancers. In 2017 Merck secured approval of an immunotherapy (KEYTRUDA) in a certain subtype of genetically altered cancers called MSI-high, regardless of the organ of origin. Early detection is another important area of intense innovation, but earlier diagnosis will need to be coupled with the right treatments. This will again require regulatory innovation since today we mostly develop cancer drugs for the patients with very advanced disease. We at CytomX, and others, are working to bring cancer therapies earlier in the treatment paradigm to have a greater impact on patients’ lives.
What do you believe is the current perception of the life sciences industry and to what extent does this impact its success?
During the pandemic life sciences emerged as a savior after a long time of living under a negative perception of the pharmaceutical industry. With recent legislative moves in the US on drug pricing I fear we are back tracking, and it remains of utmost importance to make our work understood and valued by the community as a whole. In order to shine light on the lifesaving innovations that we are trying to bring to life, we need the support of the society and the government. This will drive healthy equity capital markets to enable us to raise the funds we need to build our companies, innovate and develop new options that patients desperately need.
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