Exelixis shells out $100M cash in a pair of deals, shooting for different takes on CD47, ADCs

Now that its cabozantinib franchise — branded Cabometyx in the US and Cometriq in the EU — has nestled its way into blockbuster status, Exelixis is replenishing the pipeline with some early-stage bets.

The biotech revealed a pair of deals right as it reported Q3 results, shelling out a total of $100 million in cash to grab a preclinical antibody targeting SIRPα and a Phase I peptide-drug conjugate. There are also plenty of biobucks attached should the compounds make it down the treacherous development journey.

Exelixis’ deals shed light on two private startups that have kept a relatively low profile. Sairopa, which is supplying the anti-SIRPα drug, is the reincarnation of troubled Aduro Biotech after kidney-focused Chinook Therapeutics reverse merged with Aduro and spun out the remaining oncology assets. Cybrexa, on the other hand, is partnered with the National Cancer Institute on its tech for selectively delivering a toxic payload to tumor cells.

First, the Sairopa deal: Exelixis has its eyes on ADU-1805, which blocks SIRPα. Expressed on macrophages and other myeloid cells, the protein is thought to play a key role in the CD47 “don’t eat me” signal put out by cancer cells to evade an immune attack — making it a promising checkpoint target.

Peter Lamb

Peter Lamb, EVP, scientific strategy and CSO at Exelixis, noted that the drug has been “carefully optimized” to maximize benefit and minimize potential toxicities. In addition to monotherapy, his team is looking at combining the drug with an in-house tyrosine kinase inhibitor and other approved checkpoint inhibitors. Sairopa has also lined up a suite of follow-on antibodies hitting the same target.

An IND is expected in early 2023. After Sairopa completes certain Phase I studies, Exelixis will have an option to license the program. On top of $40 million in upfront and $70 million in milestones to grab the option, it promises Sairopa an option exercise fee of $225 million.

As for Cybrexa, its CBX-12 is a peptide-drug conjugate composed of what it calls a pH-low insertion peptide, a linker and the cancer-killing agent exatecan. The peptide is designed to insert itself into tumor cells when and only when it encounters an acidic tumor microenvironment. While the concept is similar to antibody-drug conjugates in that it aims to hit cancer cells while sparing healthy cells, it’s a target-independent approach, according to the company.

The upfront of $60 million gives Exelixis the right to acquire CBX-12 pending results from an ongoing Phase I. The bigger biotech will also take up some development and manufacturing expenses. All told, the acquisition fee and milestones add up to $642.5 million.

“Today’s announcement further highlights our ongoing strategy to leverage our balance sheet to gain access to new assets with compelling potential upside in a risk-sharing model, where we can work with partners to further establish proof of concept before investing more heavily,” CEO Michael Morrissey said in a statement.

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antibodies
antibody-drug conjugates
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