Tell us about you, your career, how you founded SIWA Therapeutics.
Lewis Gruber: I was a patent attorney specializing in biotech-related inventions for several years before becoming an entrepreneur. I was enticed to move from Chicago to San Francisco and become CEO of my first company, Hyseq, Inc., because of the exciting genomics technology that I had helped the inventors patent. While I was Hyseq’s CEO, we completed the largest biotechnology company IPO in 1997 (led by Salomon Smith Barney, Lehman Bros. and Fahnestock) as well as collaborations totaling over $100 million. When I moved back home to Chicago, I became CEO and Co-Founder of Arryx, Inc. – we licensed laser technology for manipulating material in the micro and nano length scales from the University of Chicago for which we then found commercial applications. We won numerous awards including ones for World Economic Forum Technology Pioneer (2005) and Red Herring Top 100 Innovator before the company was sold. I then served as interim CEO of ZelleRX Corporation, a biotechnology company that was developing a natural killer cell cancer therapy when I decided to found SIWA Therapeutics.
We initially looked for technology to acquire and develop, but, after spending a few years without finding anything we liked, I decided to build on work I had begun in graduate school and turned to finding a treatment for the underlying causes of aging-related diseases. We now have a proprietary monoclonal antibody, 318H, that selectively targets cells with an abnormally high level of glycolysis and oxidative stress, which is a causal factor in aging. Cells with our targeted marker include specifically cancer cells, senescent cells, and most if not all, virally-, bacterially- and parasite-infected cells. I hope to take our antibody myself when it is available to keep me healthy well beyond what is normally considered old age.
How does SIWA Therapeutics innovate?
Lewis Gruber: For us, the first element is to focus on what we have developed to ensure that 318H gets into the market and is available for those who need it – and aggressive cancers are where we are focused. With that said, we believe that because of the versatility of 318H, we can plan for future products – we are pleased that for 318H shows promise to be developed into a broad-spectrum antimicrobial drug as well as a comprehensive cancer therapy.
How has the coronavirus pandemic affected your business? Did you have to make difficult choices, and what are the lessons learned?
Lewis Gruber: Although having to work remotely has made some of our work more difficult, we have been able to adapt perhaps more easily than some as we were already having much of our work done by major contract research organizations. For example, we are collaborating with a major institution in pancreatic cancer with all work being done at the institute while we provide the requisite amount of 318H. Charles River Laboratories, Inc. recently completed in vivo 318H tolerability and pharmacokinetic studies in non-human primates in preparation for filing an IND application with the FDA. As we work with the data generated as opposed to generating the data, everything has remained more or less on schedule.
An unplanned positive impact is that although we knew that the target for 318H appears not only on cancer cells, and senescent cells but also on cells that are virally or bacterially infected, we had not deemed infectious disease to be a priority area. However, the severity of the COVID-19 pandemic presented us with an opportunity to explore how 318H could be used to treat infectious diseases including COVID-19 disease, Influenza A and other viral diseases and thus become a broad-spectrum antiviral. In studies done for us at a Biosafety Level 3 facility authorized to do COVID-19 testing, 318H has been shown to bind to SARS-CoV-2 and Influenza A; testing of bacterially-infected cells is in progress. As our focus remains on aggressive cancers, we are seeking a licensee for infectious disease applications of 318H.
We demonstrated that 318H binds to three types of cells: cancer cells, senescent cells, and virally-infected cells. By removing these dysfunctional cells, the body can repair itself and recover from disease faster. We believe 318H has the potential to treat a wide variety of infectious diseases and to provide a powerful therapeutic to support patients who recover from COVID-19 but then suffer from long term complications.
Although the pandemic brought the opportunity to fast-track our infectious disease research, like many businesses, we experienced considerable supply chain disruptions during the pandemic. The pace of our testing was slowed by new restrictions on lab capacity and delayed shipments of testing materials. Despite these difficulties, we were able to push forward into a new area of research on infectious diseases, which we feel is more important now than ever.
Overall, despite the obstacles we have dealt with in recent months, we are coping pretty well with the situation and using this time to explore more possibilities. One last comment is that attending conferences virtually is much more efficient timewise, especially when considering the time saved in not having to travel.
Who are your competitors, and how do you plan to stay in the game?
Lewis Gruber: We founded SIWA to develop therapies for slowing/reversing aging by removing dysfunctional cells including cancer cells (people over 65 account for 70% of cancer deaths) and senescent cells (“SCs”). Both cell types are causally involved in aging-related and degenerative diseases; more importantly, they also produce substantial amounts of our marker. There are a handful of companies working in aging-related disease. In February 2020, SIWA was named a “key player” in Anti-Aging Drugs by the MIT Technology Review in its prestigious list of the 10 Breakthrough Technologies of 2020; I would generally say that our closest competitors would be in that list as they are focused on removing senescent cells. Although our specific focus is one aggressive cancer, including metastasizing cancers, we also deplete senescent cells – this is important for cancer treatment as 318H uniquely attacks not only the cancer cells but also the SCs surrounding the cancer cells in the tumour micro-environment that stimulate, feed, and protect them.
With respect to senescent cell depletion and our competitors, we believe we are the only company using a biologic, i.e. a monoclonal antibody. The others use chemical or gene therapy techniques to interfere with intracellular processes which promote formation or survival of senescent cells. While each of these techniques may have value for certain applications, their intracellular site of action leads to issues with off-target effects or interference with other therapies, particularly those which also act intracellularly.
SIWA has focused on depleting senescent cells by attacking them from outside the cell. Specifically, 318H, a humanized antibody recognized as ”self” by the body binds to our marker on the surface of targeted cells to identify them for destruction by the natural process of immune surveillance which ordinarily removes cells like cancer cells producing an abnormal surface protein or an abnormal amount of a normal surface protein. In this way, 318H merely supplements a natural process which is a young, healthy individual would be sufficient to remove dysfunctional cells, but in an elderly or diseased individual is overwhelmed with many years of accumulation or overly rapid accumulation, respectively. Thus, with SIWA’s proposed therapy, the body is conducting a process it would normally pursue if it had the capability to do so.
How do you project SIWA Therapeutics in the future?
Lewis Gruber: Our vision of the future is one where everyone on Earth will be vaccinated against diseases of aging, using our vaccine approach, just as they are vaccinated against childhood diseases today. Vaccination would be supplemented by treatment with our monoclonal antibody drug in extreme situations of injury or disease where additional protection could be helpful.
Your final thoughts?
Lewis Gruber: As a final thought, we need to take the COVID-19 disease seriously as SARS-CoV-2 and Influenza A viral infections have been observed to occur together.
The CDC has indicated that they may provide a combined threat of infection in the next flu season.