Step 1: Find a novel target

Happy New Year and thanks for joining me on this Drug Discovery journey,

My intention is to take a DIY approach towards creating new medical drugs… and include you all in the educational process. We can learn together.

First of all, I’ve combined my previous Rising Tide Biology email list from MailChimp over to this Substack account. We’re all in it together now. If anyone wants to un-subscribe, I won’t be offended.

Okay…. so where to begin.

Here are the key steps in the process of developing a new drug.

  1. Target discovery

  2. Target-to-hit

  3. Hit-to-lead

  4. Lead optimization

  5. Preclinical

  6. Phase I

  7. Phase II

  8. Phase III

  9. Regulatory submission

  10. FDA approval

Our current drug development process in the US requires about 10-12 years and costs about 1-2B in US dollars. Meanwhile, the efficiency of R&D investment has been dropping for decades. Can we do better? I think so.

How?

We have entered into an era of big biological datasets and advanced computational methods (generative AI, predictive models, machine learning, multi-omic analysis). The application of these new technologies should produce a better class of targets, more informative biomarkers and new drug entities with a higher chance of Phase 2 and Phase 3 success.

Let’s start at the beginning. How do we discover a new target?

Here are three tools to start searching for biological mechanisms that are correlated with diseases. Bookmark these links.

  1. GWAS Catalog

  2. Proteome exchange

  3. Gene expression omnibus

These are all free and publicly available tools. The intention here is to find genetic variants or gene expression profiles that are correlated or causative for a disease. AI drug discovery platforms exist that will integrate these searches for you. But, before we start doing that, we need to familiarize ourselves with each of these tools.

I recommend starting with a gene or protein that is already implicated with a genetic disorder (e.g. hemoglobin beta gene HBB for sickle cell disease). This allows you to become familiar with these platforms while using a validated target.

Okay… let’s start tinkering around. I’ll be back in two weeks to report any progress.

Kevin

Rising Tide Biology

Please follow along and learn from my mistakes or chime in and share some hot tips and insights. I’ll pass them on to the group.

Who am I?

I’m a molecular biologist with 20 years of lab experience (a lot of pipetting).

Most recently, I’ve been advising, consulting and teaching seminars for biotech and pharma companies (a focus on cell and gene therapies).