Boehringer Ingelheim signed a deal to buy out a small, private immuno-oncology player this morning, and AbbVie’s been at it, too, inking a deal to snap up Mavupharma.
The company is a little-known, Seattle-based outfit working on STING, a relatively new and typically trendy target for some biopharmas aimed at beating back cancer. We don’t know how much they paid for the company, but we know a little more about its focus.
STING—or STimulator of INterferon Genes—in a nutshell works to activate the pathway and, it is hoped, kick-start an innate immune response against cancer cells in the tumor microenvironment.
The innate immune system is the body’s first line of defense against pathogens, and interest in the STING pathway stems from experiments showing injecting killed bacteria into tumors can cause them to get smaller.
It had a lot of promise wedded to it, but some of the promise eroded last year when Merck suffered a nasty reaction to STING.
At the 2018 annual meeting of the American Society of Clinical Oncology, the U.S. Big Pharma posted lackluster results as a monotherapy when a phase 1 trial showed that its attempt, MK-1454, was unable to achieve any partial or complete responses when used on its own in patients with advanced solid tumors or lymphomas.
A glimmer of hope appeared when partial responses were seen when it was given alongside Merck’s PD-1 checkpoint inhibitor Keytruda (pembrolizumab), but this beat back expectations a notch.
Mavupharma is hoping for better, and joins the likes of Novartis, IFM Therapeutics, Aduro and Celgene/BMS in getting the target to work. The young biotech came into the public’s eye back in 2017, when a team of biotech veterans pulled in $20 million to advance modulators of the STING pathway into human testing.
The team came together to work on orally bioavailable, non-nucleotide modulators of the STING pathway.
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.
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.
Mavu’s approach differs, however, in key respects from that being pursued by Aduro and Novartis. Aduro’s ADU-S100 and Merck’s MK-1454 are both synthetic versions of the CDNs bacteria and immune cells express. Mavu, meanwhile, 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.
“AbbVie's vision in oncology is to advance breakthrough areas of science leading to a strong pipeline of innovative cancer therapies,” said Steve Davidsen, Ph.D., vice president of oncology discovery at AbbVie, of today’s deal.
“AbbVie has built a leadership position in oncology and their world-class capabilities will enable the accelerated development of our pipeline of STING modulators,” said Michael Gallatin, Ph.D., former president and a co-founder of Mavupharma.
“We made tremendous strides in developing our novel STING modulators and advancing MAVU-104 towards the clinic. We are confident in AbbVie's ability to continue to advance this exciting science for patients,” added former chief scientific officer and co-founder Gregory Dietsch, Ph.D.