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Platform Evolution

Establishing new scientific frontiers by challenging the perceived limits of drug discovery

Arvinas’ founder, Professor Craig Crews of Yale University, was an early pioneer in targeted protein degradation, and published many “firsts” in the field.

Since its founding, Arvinas has led the way to the most significant breakthroughs in targeted protein degradation:

  • Extending medicinal chemistry “beyond the rule of 5” to create orally bioavailable degraders
  • Generating PROTAC® protein degraders that cross the blood-brain barrier

We aren't stopping there. At Arvinas, we believe that every problem has a solution, and we are investing in our platform to solve the critical challenges facing the field of targeted protein degradation.

Targeting “difficult to drug” proteins

Up to 80% of proteins have traditionally been considered “undruggable,” as scientists have been unable to design small molecule drugs to inhibit them. But because PROTAC protein degraders do not require strong binding to be effective, they represent a promising new approach to rendering these targets “druggable.” However, creating PROTAC degraders for these targets will often require identifying new target ligands (binders). To identify these ligands, Arvinas is investing strongly in technologies to rapidly screen new chemical entities for binding to traditionally “undruggable” targets.

Expanding our portfolio of E3 ligases

Arvinas has historically used binders to five different E3 ligases to create PROTAC protein degraders. However, the human body has more than 600 E3 ligases. Arvinas is focused on generating the next wave of targeted therapies using novel PROTAC protein degraders that harness tissue-restricted E3 ligases. We are interested in creating PROTAC® degraders that utilize E3 ligases with targeted expression patterns, such as tumor or central nervous system-localized E3 ligases for the development of targeted cancer and neurologic therapies.

Increasing our rate of success

Since 2013, Arvinas has had a ~95% success rate at degrading the proteins we’ve attempted to degrade. But as in many fields, we believe we can learn as much from our mistakes as from our successes. We want to understand why we haven’t degraded 5% of the proteins we’ve targeted in order to better understand human biology and increase our success in the future.

Increasing potency and specificity with privileged linkers

A PROTAC degrader can be exquisitely specific; Arvinas has multiple examples of degraders that can destroy mutant proteins (with single-amino-acid changes) while sparing healthy, normal protein. Improving our ability to rapidly design this specificity into PROTAC degraders, especially by using privileged linkers that increase potency and selectivity, will result in therapies that are more targeted and applicable to a greater number of diseases.