In this post I will build on previous blogs (here, here, here) about genetics for target ID and validation (TIDVAL). Here, I argue that new targets with unambiguous promotable advantage will emerge from studies that focus on genetic pathways rather than single genes.
This is not meant to contradict my previous post about the importance of genetic studies of single genes to identify new targets. However, there are important assumptions about the single gene “allelic series” approach that remain unknown, which ultimately may limit its application. In particular, how many genes exist in the human genome have a series of disease-associated alleles? There are enough examples today to keep biopharma busy. Moreover, I am quite confident that with deep sequencing in extremely large sample sizes (>100,000 patients) such genes will be discovered (see PNAS article by Eric Lander here). Given the explosion of efforts such as Genomics England, Sequencing Initiative Suomi (SISu) in Finland, Geisinger Health Systems, and Accelerating Medicines Partnership, I am sure that more detailed genotype-phenotype maps will be generated in the near future.
[Note: Sisu is a Finnish word meaning determination, bravery, and resilience; it is about taking action against the odds and displaying courage and resoluteness in the face of adversity. …
A key learning from my time in academia was the value of collaborations. Much of my most enjoyable and productive research was conducted in collaboration with fellow scientists across the globe.
I am pleased to report that industry is no different. After one year working for Merck, I have found that in addition to collaborations across the company ties with external scientific experts focused on advancing programs of interest are actively encouraged.
It is heartening to see how some recent progress in several notable drug development programs is leading to increased excitement around the application of human genetics in identifying human drug targets. As I have previously noted, human genetics can also provide insights to identifying pathways enriched for approved drugs (see Nature article here), which indicates that novel pathways may provide an important foundation for novel drug discovery programs. Indeed, the use of pathway-based approaches, including phenotypic screens, can provide a powerful way to make complex genetic pathways actionable for drug discovery.
Today, I am excited to note that Merck has launched a Merck Innovation Network (MINt) Request for Proposals to identify collaborations with academic scientists to evaluate genetic targets or genetic pathways for their potential to become drug discovery programs. …