Roots Analysis: We are aware that Tosk is focused on the development of discovery stage drug candidates targeting KRAS mutations. Can you provide some insights on the plan for IND-enabling studies and the likely clinical development timeline for the products?
Tosk: We have a proprietary drug discovery platform which allows us to discover candidate drugs for a number of previously considered “undruggable” targetsusing genetically modified Drosophila melanogaster models. Our KRAS program recently received a USD 2 million grant from the US National Cancer Institute to support this effort. Currently, the program is in the lead selection and optimization stage. Although it is difficult to predict IND filing for a research-stage project, our plan calls for filing within 18-24 months.
It is worth mentioning that, in addition to the KRAS program, we are currently using a different fruit fly technology platform to identify drugs for other biological targets. Three drugs have emerged from this program, including one which is already in clinical studies, and one is in late stage preclinical testing. This gives us confidence that fruit fly screening is an effective drug discovery tool.
Roots Analysis: As difficult-to-modulate targets are known to lack specific lig and binding sites, what is your opinion on the current challenges and how do you expect to tackle them?
Tosk: There have been numerous attempts by scientists in industry, academia, and research institutes around the world to address these targets. So far, the results have been disappointing. Although no one can minimize the challenges, we think that we have an advantage due to our proprietary drug discovery platform. As indicated earlier, we use a whole animal model, a genetically modified fruit fly, instead of the traditional approaches to drug screening. This helps us to predict whether a drug candidate is likely to work, and we believe that our technology provides a relatively better platform to discover drugs for difficult-to-modulate targets.
Roots Analysis: What are your views on the current status and likely future evolution of this segment of the industry?
Tosk: This domain has captured the interest of many companies and R&D institutions, and there are a myriad of drug discovery efforts and platforms being deployed. For instance, the US National Cancer Institute has a major internal program in this area, in addition to funding extramural efforts, such as those at Tosk. On the other hand, there are a number of targets, and we expect that there will be more than one success story in the foreseeable future, hopefully including one or more from Tosk.
Roots Analysis: Considering the commercial opportunity, we are led to believe that the market size for drugs targeting difficult-to-modulate targets, such as KRAS, is likely to be around USD 2 billion. What is your opinion on this estimate?
Tosk: I believe that the market opportunity for difficult-to-modulate targets is much higher than that.It is hard to provide accurate projections at this point, as there are many variables that need to be considered. However, we are working on a target for which the commercial opportunity can be more easily estimated. A KRAS mutation is estimated to be present in 90% of pancreatic cancers, 45% of colon cancers, 35% of lung cancers, and a smaller percentage in most other tumor types as well. Therefore, the opportunity for the drug / therapy class targeting KRAS is very large and could represent a significant fraction of all new cancer cases, which number some 1.7 million per year in the US alone.
KRAS targeting drugs also have the potential to be used in combination with existing therapies. Consider EGFR-inhibiting drugs, such as Erbitux®. These treatments are ineffective in about 40% of the patient population due to the presence of an autogenic KRAS gene. Using our approach, it may be possible to block the activity of this gene. Therefore, a KRAS therapy in combination with an EGFR inhibitor could prove effective in the aforementioned, unserved, 40% of the target patient population. Industry reports suggest EGFR-inhibiting drugs have current annual sales of about USD 2 billion. So, if we were to extrapolate this opportunity to include the previously untreatable patients, sales of EGFR-inhibitors could increase by USD 1 billion or more. Much of the value of this increase could be captured by the KRAS drug needed to effectively treat these patients.
Similarly, there are other drug classes which may benefit from combination therapies using anti-KRAS drugs. Adding these to the potential monotherapytreatment options for KRAS positive cancers yields an overall sales potential for therapies targeting difficult-to-modulate targets well into the billions of USD.
Roots Analysis:What is your opinion on the likely pricing of such targeted therapeutics?
Tosk: Our mission at Tosk is to develop drugs that are both effective and affordable, drugs that are not extremely expensive to manufacture or administer. There are many companies that are developing expensive, end-of-life cancer therapies, which cost hundreds of thousands of US dollars and require a sophisticated research hospital environment to administer. We are on the opposite end of that spectrum.
If Tosk is successful, the cost of our therapeutics should be closer to that of typical small molecule drugs. Also, the overall cost of administration of these drugs should very low as compared to the immunotherapies and other biologics that are currently under development. If we are successful, our drugs will be administrable in a much less sophisticated clinical setting, making them available to many more patients around the world. Tosk’s goal is to discover and develop very high value products that have the potential to reduce the overall cost of therapy while improving outcomes for cancer patients worldwide.
Erbitux® is a registered trademark of Eli Lilly and Company