Nectin’s Keytruda combo could fill gaps in immuno-oncology’s treatment paradigm

In focus with: Fabian Tenenbaum, CEO, Nectin Therapeutics

Nectin’s vision: While blockbuster checkpoint inhibitors like Merck & Co.’s Keytruda and Bristol Myers Squibb’s Opdivo have revolutionized cancer care for about a decade, these oncology stalwarts still have their shortcomings. In particular, their method of action — blocking signals that keep the immune system from attacking cancer cells — is effective in tumors with strong mutations of a certain kind. Tumors without those specific mutations are able to resist treatment.

That’s where Nectin Therapeutics is aiming its own checkpoint inhibitors and antibody-drug conjugates. By employing a different and complementary pathway to kickstart the immune system, the company’s treatments could help these immuno-oncology drugs fight more cancers of various types.

The strategy: Nectin has only one clinical candidate called NTX1088 in early-stage trials — but the company has teamed up with pharma giant Merck to test the treatment alongside the bestselling Keytruda, a checkpoint inhibitor that uses the PD-1 pathway and is approved in dozens of indications. This gives Nectin a shot at demonstrating that its drug can work on its own and that it can fill gaps in Keytruda’s checkpoint inhibition.

In earlier development stages, Nectin has one more checkpoint inhibitor with an investigational new drug permission expected in 2024 and three antibody-drug conjugates just out of preclinical tests.

The Israeli company extended a primary funding round in November to reach more than $25 million to support the development of NTX1088 and its pipeline activities.

Why it matters: Although the checkpoint inhibitor space has been saturated with effective drugs, up to 80% of patients don’t respond to these therapies. Leaders in the pharma industry have said that the future of cancer care is in drug combinations to connect the dots in tumor types and specific mutations, and Nectin could play a role in bringing that landscape to fruition.

This interview has been edited for brevity and style.

PHARMAVOICE: Tell me a little about how your technology addresses resistance to immuno-oncology treatments.

FABIAN TENENBAUM: Despite the fact that immuno-oncology has essentially taken center stage in the treatment of a lot of solid tumors, unfortunately still the vast majority of patients don’t see a response or a durable response to the available therapies. So there are significant challenges in trying to understand and then resolve those patient populations and tumors that do not benefit. What we do at Nectin is leverage unique insights that started at the Hebrew University in Jerusalem before the company was formed to use the nectin pathway, which is a family of proteins that are expressed in immune cells and on cancer cells and play a complex role in the relationship between the immune cells and the tumor cells. Often these relationships are intercrossed, complex and sometimes surprising. So our team has uncovered a lot of these mechanisms and relationships between the different receptors, and we’re developing therapies that intervene in a way that helps the immune system fight cancer more effectively and deal with the escape mechanisms, which are ways that the tumor cells either intrinsically or adaptively acquire the ability to evade the immune system.

Based on Keytruda’s success, is a combination with that treatment something you always imagined your own technology would be good for?

We started uncovering in the preclinical work both in vitro and then in animal models that NTX1088, an anti-PVR monoclonal antibody, has a very potent activity and is able to deal with and kill cancer cells very effectively. And there are models that we know if you use a PD-1 blocker like Keytruda, you do not see any kind of regression in the tumor — in those models, we’ve been able to demonstrate clearly that NTX1088 delivers a potent benefit.