Covant Therapeutics Debuts with Boehringer Partnership Targeting ADAR1

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Boston-based Covant Therapeutics gained $10 million upfront in a deal with Boehringer Ingelheim to chase after a cancer immunotherapy target, ADAR1 (adenosine deaminase acting on RNA). The goal is to turn cold tumors hot.  

The research collaboration and worldwide licensing agreement, announced Tuesday, centers on developing a novel small molecule immunotherapy targeting ADAR1.

To do this, the companies will combine Boehringer’s oncology and immuno-oncology pipeline with Covant’s platform, coupling high-throughput chemoproteomics-based screening in the innate immune setting with structural proteomics.

Covant has been incubating inside Roivant Sciences for the last 10 months, CEO Matt Maisak, Ph.D., told BioSpace in an interview. Maisak said he views the transaction as enabling and validating for Covant on both the scientific and business side.   

The partnership comes just weeks after Covant revealed its Scientific Advisory Board.

Maisak said Covant engaged Boehringer in late 2022 around a potential ADAR1 collaboration.

“We had been working on that in the background," he said. 

In addition to the $10 million upfront, Covant is eligible to receive $471 million if milestones are met, plus tiered royalties on global sales should the product reach the market.

ADAR1 is a relatively new immuno-oncology target.

Maisak said direct inhibition of ADAR1 is a first in the industry.  

“There is a multitude of genetic and [small] RNA studies showing its importance across various tumor types,” he said. “But its real potential lies in combination therapy with some of the classic BO1 inhibitor antibodies that exist at big pharmas similar to [Boehringer Ingelheim]. We were really looking for a partner that could help us maximize the potential of this.”

A resulting ADAR1 inhibitor would be intended for use in combination with other immunotherapies to improve efficacy, the companies stated in Tuesday’s press release.

Boehringer’s scale will enable the pair to run global trials for combination therapies and allow expansion in different indications, Maisak said.

Iván Cornella, Ph.D., CSO at Covant, told BioSpace ADAR1 is known as a target for cancer because of the pivotal role it plays in controlling innate immune response and how tumors evade that response. The innate immune response is one of the body’s surveillance mechanisms for detecting aberrant behaviors, such as infections, he added.

“[Cold] tumors develop ways to hide themselves in the innate immune response in a way in which they can continue to proliferate without being stopped by the immune cells,” Cornella said. By turning these tumors hot, it is possible to reveal their disguise or activate T cells and other cell types to recognize those tumors as something to be attacked.

Covant’s technique essentially puts a label on the cold tumor microenvironment. Cornella likened it to a laser pointer that points to the bad cells.

“ADAR1 is an exciting immuno-oncology target with significant therapeutic potential,” Lamine Mbow, global head of cancer immunology and immune modulation at Boehringer Ingelheim, said in Tuesday’s press release.

Boehringer did not immediately respond to BioSpace’s request for comment.

A Two-Pronged Strategy

Maisak said Covant has been working to establish all the auspices of a biotech company, from its SAB to its assets, which include proteomics and intractable targets. He said creative deal structuring is within the DNA of Roivant, adding that the company expects more partnerships and collaborations in the near future.

“I think this is really just the beginning," Maisak said. 

Covant’s strategy is two-pronged. In the first prong, Maisak said the company will continue to execute partnerships around targets like ADAR. The second prong is an antibody-on-a-pill strategy.

“We’re going after clinically and commercially validated targets for which there are existing therapies but with different modalities. Those modalities, while widespread, come with systemic disadvantages,” he said, citing their limited treatment time and their cost for payers.

“We're looking to ultimately develop early bioavailable surveillance covalent small molecules to attack those targets, and I think we're very well-suited to do that,” Maisak said. “I look forward to portfolio growth and the advancement of those programs through the stages of discovery.”