Biotech veterans, chasing Merck and Novartis, tap Frazier, Alpine for cash to move STING modulators into the clinic

Mavu’s focus on orally bioavailable, non-nucleotide drugs sets it apart from the more advanced, intratumoral cyclic dinucleotides.

A team of biotech veterans has pulled in $20 million to advance modulators of the STING pathway into human testing. The series A positions the startup, Mavupharma, to further its preclinical work on the use of oral STING modulators to treat cancer and infectious diseases. 

Frazier Healthcare Partners led the round with the support of Alpine BioVentures. The investment follows the Frazier playbook of building teams with a track record of hustling drugs forward and putting them in charge of high-potential science.

In the case of Mavu, the founding team features Calistoga Pharmaceuticals and Stromedix cofounder Michael Gallatin, Ph.D., and ex-VentiRx and ICOS VP Greg Dietsch, Ph.D. Clayton Knox, M.D., formerly of Acerta Pharma and Merck, has more recently come on board as COO. Bob Baltera, CEO of Cirius Therapeutics, another Frazier play, will serve as executive chairman. 

The team has come together to work on orally bioavailable, non-nucleotide modulators of the STING pathway. STING, an abbreviation of stimulator of interferon genes, is a protein essential to immune signalling around the identification of cytosolic DNA, making it a potential target for cancer and infectious diseases. 

“Mavu’s novel approach uses non-nucleotide small molecules to indirectly and conditionally modulate the pathway,” Gallatin said in a statement.

In the case of cancer, the argument for pursuing STING is underpinned by studies tying its absence  to weak adaptive anticancer immunity.

The role STING plays in anticancer immune responses has attracted other research teams, although Mavu’s focus on orally bioavailable, non-nucleotide drugs sets it apart from the more advanced, intratumoral cyclic dinucleotides (CDNs) in development at its rivals. 

Novartis inadvertently entered the field in 2007, the year before STING was discovered, when it acquired the rights to vascular disrupting agent ASA404 from Antisoma. The drug hit a wall after failing to improve survival in patients with non-small cell lung cancer and was dumped before researchers fully understood its mechanism of action, or lack thereof. 

Those details emerged several years later when researchers showed ASA404 activated the mouse, but not human, form of STING. That explained the disconnect between preclinical and clinical results.

RELATED: Novartis tackles immuno-oncology with a $750M Aduro deal for new R&D group

Novartis made a more deliberate move into immunotherapies targeting the STING pathway in 2015 when it paid $200 million upfront and committed $500 million more in milestones to team up with Aduro Biotech.

The partners moved synthetic STING pathway activator ADU-S100 into a phase 1 dose-escalation trial the following year. And followed up with a phase 1b study that recently began testing the drug in combination with Novartis’ PD-1 checkpoint inhibitor PDR001. Both trials are treating patients with accessible solid tumors and lymphomas. 

Merck followed Aduro and Novartis into the clinic at the start of this year. Its phase 1 is assessing the dosing of the STING agonist MK-1454 as a monotherapy and in combination with Keytruda in patients with advanced solid tumors and lymphomas.

Mavu’s approach differs in key respects from that being pursued by Aduro and Novartis. ADU-S100 and MK-1454 are both synthetic versions of the CDNs bacteria and immune cells express. Mavu is working on non-nucleotide STING modulators. More importantly, Mavu thinks its candidates will be orally bioavailable. ADU-S100 and MK-1454 are delivered by intratumoral injection. 

Bristol-Myers Squibb cemented STING’s status as a hot niche in August when it struck a backloaded $2.3 billion deal to acquire IFM Therapeutics and its preclinical STING program. Two months later, Celgene picked up an option to acquire certain rights to Nimbus Therapeutics’ preclinical STING program.