Summary authored by Kunal Desai, MD, MBA, MS 

Cancer Drug Development: Views from Industry

Kunal Desai, MD, MBA, MS

Dr. Engelman’s talk on drug development was of particular interest to me given my background in pharma and future career plans that will focus on drug development. He provided a good intellectual framework by identifying key attributes of a “good drug”. These include 1) target validation; 2) defining a clear unmet need; 3) defining appropriate therapeutic index; and 4) druggability of the target.

Starting with target validation – he identified the value of understanding the genomics of a tumor to select patients (e.g. EGFR mutations), then making the connection between the genotype and phenotype (i.e. tumorigenesis). His point then about ensuring that you can define a high unmet clinical need was key – this is especially true in oncology where survival is measured in months and thus there is a need for novel therapies in the salvage setting. His third point about defining the therapeutic index early on is valid – this can be challenging as most drugs have side effects thus knowing how much “room” you have between inducing toxicity and driving efficacy is critical. Dosing becomes an important factor. Finally, he gave excellent examples of druggable vs undruggable targets; knowing how amenable your target is to binding to a drug is important. This means understanding its structure and activity. He gave the example of kinase inhibitors which bind to the ATP-binding pocket; however, a target like K-RAS is more difficult as it lacks binding pockets. Finally, the part of his presentation that looked at the business aspects of biotech was fascinating. He gave us a vivid example of a biotech startup and its founder who became increasingly diluted (vis-a-vis equity held in the company) as venture capitalists investedin successive venture rounds. This brought forth the balance between holding a smaller piece of a big pie vs a big piece of a small pie.