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Vividion Inks $135 Million Deal with Roche for Targeted Protein Degraders
By Ruchi Jhonsa, Ph.D.
Three years back, when the San Diego-based biotech spun out of Scripps Research Institute in La Jolla, California, it decided to expand its cutting edge discovery platform to identify small molecules for targeting proteins that nobody has been able to touch before. Now, it has made a substantial push towards commercializing its expertise.
Although Vividion Therapeutics is pursuing multiple targets, their current favorite is a targeted protein degrader that could bind to a target and an E3 ligase (blue), to drive ubiquitylation and degradation by the proteasome. E3 ligases have therefore been a subject of therapeutic interest for quite a while. Several targeted protein degraders have been synthesized around E3 ligases that kill the problematic protein in the cell by engaging defective proteins with the ligase. However, these degraders can kill only some proteins, but not all, making it necessary to target novel E3 ligases with different catalytic activities.
What Vividion is doing is screening small molecules to target novel E3 ligases. The small molecules are combined with the target to make a targeted protein degrader. The degrader brings the target and the ligase closer, resulting in target degradation. By discovering ligands for new E3 ligases, Vividion will be able to generate a new class of drugs with different pharmacology compared to existing E3 ligases based degraders.
Partnership with Roche
Centered on E3 ligases, Vividion entered a partnership with Roche on 19th May in which it will use its proteomic screening platform and proprietary small molecule library to target novel E3 ligases as well as various cancer and immunology therapeutic targets identified by Roche. The exclusive worldwide license agreement will grant Vividion an upfront payment of $135 million in cash and several billion dollars in payment based on the achievement of preclinical, development, and commercial milestones.
Additionally, the company will receive royalties on the sales of commercialized products resulting from the collaboration. According to the terms, Vividion will be responsible for the early drug discovery as well as preclinical work pertaining to the drugs, and Roche will have the exclusive rights to license compounds that will come out of the deal at different stages of development.
This is not Vividion’s first big deal. It is already in a four-year partnership with Celgene- now part of Bristol Myers Squibb, in which the company will identify ligands and discover new candidates against difficult targets.
“We are thrilled to partner with Roche, marking the second major collaboration for Vividion focused on developing small molecule drugs against promising, untapped therapeutic targets,” stated Dr. Diego Miralles, CEO of Vividion. “This collaboration with Roche will further expand a new pillar of our pipeline focused on leveraging distinct E3 ligases to bring cutting-edge treatments to patients in need.”
Adding to this, Dr. Fred Aslan, President and Chief Business Officer, said,” “Our proprietary platform has demonstrated the ability to identify molecules that can drug challenging protein classes, such as transcription factors, adaptor proteins, and E3 ligases. We look forward to discovering new therapies with Roche while simultaneously advancing our wholly owned pipeline.”
Novel E3 Ligases
VIvidion has identified a small molecule targeting novel E3 ligase that is highly potent. They demonstrated the activity of this ligand by incorporating it into a bifunctional degrader using three different target recruiting ligands against FKBP12, BRD4, and multiple kinases. These bifunctional degraders were able to degrade all the test target proteins within 4 hours and were highly potent when compared to conventional degraders designed for the same targets. Vividion will give more updates about the novel E3 ligase engager at the upcoming AACR virtual meeting in June.
Why Invest in Targeted Protein Degraders?
Targeted protein degraders have become of the hottest areas in small molecule drug discovery. Instead of inhibiting the mutated proteins, they probe them for destruction by cell’s protein disposal system. The hope with the protein degraders is that they will be able to target previously undruggable proteins.
Several companies have adopted this method to target a diverse range of proteins. In late 2018, Kymera Therapeutics raised $30 million in series A funding to develop protein degraders. Earlier that year, US-based biotechnology firm Arvinas signed a research pact with Pfizer, amounting to $830 million. Arvinas entered its targeted therapy against androgen receptor and estrogen receptor into clinical trials the very next year.
Cullgen, a protein degrader startup, also received seed funding of up to $15 million to develop ubiquitin-mediated small molecule protein degraders for various oncology targets. Several researchers are now repurposing inactive cancer cell binders into an active degrader. In 2019, a group of researchers from Novartis Institutes for Biomedical Research showed that a new degrader developed by integrating an inactive drug in a protein degrader could bring down leukemia cells in the lab. Looking at the positive results, it is safe to say that this technology is here to stay.
Editor: Rajaneesh K. Gopinath, Ph.D.
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