Plenge Lab
Date posted: May 1, 2018 | Author: | No Comments »

Categories: Drug Discovery Human Genetics

[Disclaimer: I am an employee of Celgene. The views reported here are my own.]

On a recent family vacation to Cumberland Island, a 9,800-acre barrier island off the coast of Georgia, I was mesmerized by the dense forest of live oak trees covered with Spanish moss. Upon first glance, the branches of these magnificent trees extend chaotically in all directions, and it is difficult to discern where the trees begin and end. But upon closer inspection, the root structure can be identified, moss disentangled, and the overall complexity unraveled.

These craggy oak trees serve as metaphor for our complex human biological ecosystem: a dense forest of molecules with gnarled branches of pathways meandering in all directions, without an obvious root structure of human disease. Extending the metaphor further, the oak trees make the point that I see as one of the most difficult aspect of drug discovery and development: understanding root cause of disease, and matching therapeutic modality and biological mechanism to prevent or cure devastating illness.

In this blog, I highlight two recent publications that underscore the importance of matching modality and mechanism. The first article, published in the New England Journal of Medicine, reported clinical data on 22 patients with beta-thalassemia treated with ex vivo gene therapy (here).…

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Date posted: March 2, 2017 | Author: | No Comments »

Categories: Drug Discovery Human Genetics Immunogenomics Precision Medicine

A new sickle cell anemia gene therapy study published in the New England Journal of Medicine (see here, here) gives hope to patients and the concept of rapidly programmable therapeutics based on causal human biology. But how close are we really?

It takes approximately 5-7 years to advance from a therapeutic hypothesis to an early stage clinical trial, and an additional 4-7 years of late stage clinical studies to advance to regulatory approval. This is simply too long, too inefficient and too expensive.

But how can timelines be shortened?

In the current regulatory environment, it is difficult to compress late stage development timelines. This leaves the time between target selection (or “discovery”) and early clinical trials (ideally clinical proof-of-concept, or “PoC”) as an important time to gain efficiencies. Further, discovery to PoC is an important juncture for minimizing failure rates in late development and delivering value to patients in the real world (see here).

Here, I argue that rapidly programmable therapeutics based a molecular understanding of the causal disease process is key to compressing the discovery to PoC timeline.

Imagine a world where the molecular basis of disease is completely understood. For common diseases, germline genetics contributes approximately two-thirds of risk; for rare diseases, germline genetics contributes nearly 100% of risk.…

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