The initial program will focus on one degrader combined with multiple proprietary E3 ligase platforms and use VantAI’s geometric deep learning platform.
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Germany’s Boehringer Ingelheim is teaming up with one of Vivek Ramaswamy’s “vant” companies, VantAI. It is an early discovery research collaboration to identify potential protein degrading molecules for traditionally “undruggable” targets.
The initial program will focus on one degrader combined with multiple proprietary E3 ligase platforms. They will use VantAI’s geometric deep learning platform to “computationally streamline the design of new molecules optimized for each E3 platform.” Then, they will leverage these target E3 interface contacts to make unique routes for drug parameters like potency and selectivity.
No financial details were released, although Boehringer is paying VantAI an upfront fee with additional preclinical, clinical and commercial milestones. Boehringer will hold exclusive commercial licenses to the protein degraders for the initial target under the deal and will handle global development and commercialization.
“We’re extremely excited to partner with Boehringer Ingelheim in the induced proximity space, particularly on ‘undruggable’ disease targets, where new approaches are needed to overcome long-standing hurdles,” said Zachary Carpenter, Ph.D., founder and chief executive officer of VantAI. “BI’s deep early discovery experience and VantAI’s unique geometric deep learning technology are well poised in combination to unlock novel solutions with significant advantages for patients.”
VantAI was founded in 2019 and is based in New York. It falls under Vivek Ramaswamy’s Roivant Sciences umbrella. On April 13, VantAI announced it had entered a multi-year deal with Janssen Pharmaceutical, a Johnson & Johnson company. Under that deal, the partners will use VantAI’s geometric deep learning platform to generate molecular-glue and hetero-bifunctional, protein degrader drug candidates and collaborate on discovering and implementing novel E3 ubiquitin ligase platforms. Very similar territory to the Boehringer Ingelheim deal.
Ubiquitin is a small protein found in all eukaryotic cells. It has a few functions where it attaches to target proteins. One of those functions is to degrade proteins, acting as a kind of garbage can for the cells. Part of the technological approach for this agreement is to target specific disease-associated proteins for degradation.
VantAI and Janssen will focus on two degrader programs in addition to a novel E3 ligase platform. Janssen will hold an exclusive commercial license to all programs under the partnership and handle global development and commercialization.
VantAI’s technology uses geometric deep learning to “generate insights from millions of years of naturally occurring, evolved interfaces.” Then, they mimic those interfaces when they design a drug. This is called a “Protein-Contact-First” or PCF approach, “yielding non-obvious, more glue-like solutions with optimized parameters including potency, selectivity and molecule size.”
Carpenter said at the time, “At VantAI we believe that induced proximity systems can provide significant value across a range of debilitating diseases where traditional small molecule approaches have struggled. We are thrilled to be working with the scientists at Janssen to use machine learning to rationally engineer the protein interface component of these systems.”
E3 ubiquitin ligase is part of a cascade of enzymes involved in protein ubiquitination, a posttranslational modification that plays a key role in mediating a broad range of cellular functions. For example, in a 2018 study, 13% of mutations in E3 ligase genes were associated with neurological disorders — 83 total genes linked to 70 different neurological diseases. The same study noted that there are more than 600 E3 ligase genes.
In addition to partnerships with Janssen and Boehringer Ingelheim, VantAI has deals with Blueprint Medicines, Proteovant Therapeutics, Tara, Clexio, Homeicos Therapeutics and DermaXon.
Nor is this the first deal Boehringer has made on protein degradation. In December 2020, it inked an agreement with Vienna, Austria’s Proxygen, to collaborate on identifying molecular glue degraders against various cancer targets. Molecular glue degraders and PROTACs use the power of a cell’s recycling machinery to selectively eliminate disease-causing proteins. Molecular glue degraders do this by bridging the distance between target proteins and ubiquitin ligases, then flag the target proteins for rapid degradation.
