Nectin Therapeutics announced dosing of the first solid tumor patient in a Phase I clinical trial while additional investors jumped in to expand the company’s Series A to just over $25 million.
From L-R: Nectin Co-founder and CSO Pini Tsukerman (Ph.D.) Senior Scientist Akram Obiedat (Ph.D) and Lab/Operations Manager Anas Atieh (MSc)
Nectin Therapeutics announced dosing of the first solid tumor patient in a Phase I clinical trial Wednesday while additional investors jumped in to expand the company’s Series A to just over $25 million.
The Israeli/New Jersey biotech’s lead asset, NTX1088, a monoclonal antibody, is a first-in-class PVR (CD155) blocker for patients with locally advanced and metastatic solid tumors. PVR is a transmembrane protein commonly expressed on a variety of tumors and PD1 and PDL1 immune checkpoint inhibitors.
“We are going to be the first ones exploring PVR blockade,” Fabian Tenenbaum, CEO, told BioSpace in an interview.
It was previously believed that blocking PVR would be disadvantageous due to its interface with DNAM-1, an adhesion molecule that controls NK cell cytotoxicity. But a research team out of the Hebrew University of Jerusalem discovered the interaction is short-lived and not ultimately needed for DNAM1 expression.
Their discovery has been solidified by two different independent immunotherapy research papers confirming the same finding.
NTX1088 packs a triple punch in preclinical studies. By blocking PVR, TIGIT and CD96 are suppressed while, most importantly, DNAM1 expression is restored. The enhanced DNAM1 expression interacts with receptors on the tumor to activate the immune cells to kill the cancer much more efficiently.
Nectin has developed biomarkers that measure DNAM1 expression in blood biopsies taken from patients in the trial to track the efficacy of this mechanism. This trial is being run at the MD Anderson Cancer Center and focuses on tumor types where PVR is overexpressed like colorectal, liver, lung, ovarian and more.
The Phase Ia trial is focused on dose escalation in 40-50 patients to establish the safety profile of NTX1088. An expansion phase will follow to test the drug as both a monotherapy and in combination with a PD-1 blocker already on the market. Since the contract isn’t yet finalized, Tenenbaum isn’t ready to put the partnership in print just yet.
“Tumors that express very high levels of PD-1 are often candidates for PD-1 therapy,” Tenenbaum said. “The problem is if there is a very high level of PVR expression in parallel, these patients tend not to see a good benefit from that therapy. Our study design is aiming at that patient population that has high PD-L1 and high PVR.”
Around 80 percent of cancer patients fail to respond or develop resistance to currently approved immunotherapies. Investors were particularly interested in the science and perhaps more uniquely attracted by the company’s country of origin.
David Sidransky, an oncologist and board member for Israel Biotech Fund, said IBF was looking for something in the immunotherapy space that was differentiating. He pointed to the recent early Phase II success for Gilead and Arcus Biosciences in combining anti-PD1 and anti-TIGIT therapies and was intrigued by Nectin’s PVR-blockers three-punch potential.
“We believe in this pathway and we think Nectin’s unique way of targeting it is one that actually has potential,” Sidransky told BioSpace.
IBF only invests in companies with a footprint in Israel. The group led the Series A expansion alongside Peregrine Ventures, with participation from aMoon fund - all three organizations hailing from Israel. Nectin tugged on some roots for Tenenbaum too; he called Israel home for many years, including his time in medical school.
At this point, Nectin is fairly small, with a 10-staff headcount. In addition to leveraging a network of full-time consultants to help with the launch of this Phase I, the company will also be expanding the clinical management team.
“It’s quite rare to find a new potential target, especially within immuno-oncology, and especially with kind of the unique attributes that we’re seeing in PVR,” Tenenbaum said. “The team continues to generate new data. That continues to build our confidence.”
