Phacilitate: PsiOxus is developing a proprietary platform technology for next generation oncolytic viruses (T-SIGn). For our investment readers, why is immuno-oncology such as an exciting area for biotech research?

Dr John Beadle: For many decades new forms of chemotherapy and even targeted cancer therapeutics have offered only incremental and often marginal gains in cancer patient survival. Immuno-oncology is now exciting because for the first time new oncology therapies are offering the potential of real long term benefit for a significant number of patients. The “cure” word is of course overused and it is too early to talk of that, but we do see a significant percentage of patient’s treated with these new immuno-oncology products who have very real long term disease control. That is very exciting, it means that the human immune system is able to hold cancer in check and perhaps even to eliminate it if turned on in the right way. However, despite these great successes, we still see that somewhere around 80% of cancer patients do not respond anywhere near as well to these treatments. Now, finding ways to treat the 80% of patients with unmet needs, that is what excites us here at PsiOxus as we develop our T-SIGn cancer gene therapy platform. It should certainly also excite investors that there is still a significant unmet market need in about 80% of the cancer market. Immuno-oncology is already revolutionising cancer therapy and I believe that we will also ultimately find ways to treat that 80%, the question now is how quickly can we discover and develop those new treatments.

Phacilitate: What are the advantages of a company developing a platform technology rather than focus on a specific therapeutic target? How does this reduce portfolio risk and present opportunities?

Dr John Beadle: We are learning, not surprisingly, that cancer-immunology is exceptionally complex. The roughly 80% of cancer patients who do not respond well to current immune-therapies do so for many different reasons and the solution for addressing that 80% will vary from patient to patient. For PsiOxus, having our T-SIGn cancer gene therapy platform gives us the ability to address this problem from multiple different angles with a pipeline of products. For example, delivering one set of genes to cancers may help one sub-group of patients but not others. It is currently hard to say whether those responders will represent 5% or 50% or more of the patients with unmet need but we are learning more and more each day about what those responders and non-responders may look like. The old classifications of cancer, based on the anatomical origin such as ovarian, prostate or lung and histological cell types such as small cell or non-small cell, are increasingly going to be less important than the biomarkers that those cancers display. Significant change of course always creates investment opportunities and risks. Our platform approach with multiple different products each addressing different aspects of this problem gives us multiple shots on goal by addressing different subsets of the current non-responders. That not only reduces portfolio risk through the classic “shots on goal” mantra, it also really increases the potential market size of our overall offering, since each product in our T-SIGn portfolio has the ability to address a different patient sub-set.

Phacilitate: With an exponential number of emerging biotechs now exploring different immuno-oncology targets, as the field has been somewhat ‘validated’, what questions investors should be asking to judge the robustness/strength of data coming from early research studies?

Dr John Beadle: Cancer immuno-oncology is complex and early data can often be difficult to interpret. Over interpretation of results in small, uncontrolled early clinical trials should certainly be avoided. Small trials should be designed for a specific scientific purpose and getting clear actionable data readouts from those small early trials is the key challenge of early clinical research. At early stages, I think that investors should seek clear data readouts from well-designed studies, but they should not expect to see clear efficacy signals, because only larger studies are realistically going to demonstrate efficacy. By the time efficacy is demonstrated the value will be baked into the price. For example, a key to our T-SIGn cancer gene therapy platform is that we need to deliver our viruses systemically and they should then get to the tumor and replicate efficiently but only in the cancer cells. We designed a clinical study specifically to investigate that question. The results from that early study demonstrated that our viruses not only reach the tumor and replicate within cancer cells but that tumors infected with our virus become inflamed. This was exciting and valuable data to validate our platform as a gene vector system for cancer therapy. That study was not designed to show anti-tumor efficacy and indeed it would have been impossible to draw any efficacy conclusions from that study design, but the results of that small proof of concept study later led directly to the commercial deals that we completed with BMS last year and represent the fundamental underpinnings of our internal development programs and current value. I think that finding that sort of clear early clinical proof of concept data can create significant value for investors.

Phacilitate: Being the founding CEO of PsiOxus Therapeutics, can you give us a perspective on how you are aligning investor expectations with the realities of clinical development timelines?

Dr John Beadle: As CEO, I have always felt that it is important for investors to understand the significant risks, costs and timelines of investing in innovative cutting edge cancer therapeutics. To hide the fact that failure rates are high would be incredibly disingenuous and to pretend that results will be delivered in unrealistic timelines is equally unhelpful. In a company like PsiOxus, we do cutting edge science every day and at the best of times cancer science is difficult. Certainly when we started out as PsiOxus it was not the best of times, we were in a deep recession and the world was not yet enamoured with the field of immune-oncology, that is a relatively recent event and in those days cancer-immunotherapy was a graveyard of commercial failure. Since then things have changed and immune-oncology has become a “hot area” as our own commercial deal with BMS on our T-SIGn cancer gene therapy platform has shown. Along the way we needed to demonstrate success to investors with every step. The key to managing risks is to predict where the key risks lie and how you can eliminate them. It is a truism in drug development that anything can go wrong at any time, but an experienced drug development team can identify key risks and look to remove them. At PsiOxus we have a very experienced drug development team. Every risk removed is a upward value inflection point, making ultimate commercial success more likely. Is the drug safe to administer? Does it get to the tumor? Does it do to the tumor what we want it to do? Can we manufacture the drug in a cost effective way? Sophisticated investors ask these questions all the time and answering them is our bread and butter. I believe that our recent deals with BMS validate not only our science but also the drug development expertise and approach at PsiOxus.

Phacilitate: What messages from advanced therapeutics research would you like to share with our investment audience at Phacilitate’s Summit in May?

Dr John Beadle: I think that the term advanced therapeutics can on occasions be off-putting for some investors. It has often become associated with niche indications, orphan diseases, high cost of manufacture and complex supply chains. This is certainly not always the case. At PsiOxus we are developing our T-SIGn immuno-oncology gene therapy products for the largest solid tumor indications including lung cancer and colorectal cancer. Those products will all be “off the shelf”, mass manufactured products that are distributed within the current standard pharmaceutical supply chain. Our products are defined as advanced therapeutics according to regulatory guidance but they do not fit within the same commercialisation or even development paradigm as many other cell or gene based therapeutics. The message is that the field is broader than often perceived and is also highly varied both from the basis of the science but also the potential risks and returns on offer to investors.