Early data on NextCure immuno-oncology lung cancer med delights investors

Shares of freshly public biotech NextCure skyrocketed on Tuesday after the company published an abstract highlighting initial data from an early-stage study of its sole experimental immuno-oncology drug.

The therapy, NC318, is engineered to inhibit Siglec-15 (S15), a key immune suppressor in certain cancer patients whose tumors are resistant to the existing raft of checkpoint inhibitors. S15 is found on certain myeloid cells in the tumor microenvironment and on certain tumor types including lung, ovarian and head, and neck cancers.

Many patients are refractory to checkpoint inhibitors due to the presence of certain immunosuppressive factors in their tumor microenvironment. Researchers have been trying to harness different molecules to stimulate the immune system, including toll-like receptor (TLR) agonists — specialized proteins that initiate an immune response to foreign pathogens or, in this case, cancer cells. NextCure is working on “normalizing” the immune system by snuffing out a factor that thwarts it from performing its defensive duties.
“Different from immune checkpoint blockade, cancer immunotherapy based on normalization aims to restore an impaired immune system to a healthy state, so it detects and destroys cancerous cells and avoids harming healthy cells,” said Lieping Chen, Yale professor and scientific founder of NextCure, in a statement in March. “(W)e identified S15 as a major immune suppressor in B7-H1 (PD-L1) negative tumors, which are resistant to currently approved anti-PD cancer therapies.”

In an abstract for the Society for Immunotherapy of Cancer (SITC) conference — the company disclosed data from a first-in-human trial of NC318, in doses ranging from 8 mg to 800 mg.

As of August, 43 patients including those with non-small cell lung, ovarian, melanoma, breast, and colorectal cancer have been enrolled. Tumor responses were evaluable in 32 patients, although 11 patients have not reached their first assessment, and their efficacy data will be reported on Saturday at SITC.

However, in patients with NSCLC — the biggest (and most lucrative) form of lung cancer, NC318 monotherapy elicited activity in 5 of 7 subjects refractory to PD-1 therapies.

Data showed 1 complete response (ongoing at 41 weeks), 1 partial response (ongoing at 14 weeks), 1 stable disease with tumor reduction (ongoing for 26 weeks), and 2 with stable disease. Overall, the therapy was also well-tolerated, NextCure said.

The Beltsville, Maryland drug developer’s shares $NXTC catapulted on Tuesday, closing up nearly 250% at $92.22. The stock began to correct itself on Wednesday, slipping more than 7% to $85.50 in premarket trading.

“Clearly, there is thirst for clear signals of activity in immuno-oncology (IO) after years of disappointing data from next-generation checkpoints and difficult-to-interpret combination data. While very interesting, two out of seven responders (NSCLC, “refractory” to anti-PD(L)1) is a very early signal, and the abstract did not make note of any single-agent activity in other solid tumors; assuming no responses outside of NSCLC, the overall response rate in the 21 evaluable patients that had reached final assessment would be 9.5%,” SVB Leerink analysts wrote in a note.

“(W)e will be looking for positive signals from the 11 additional patients (three in NSCLC), as well as patient history and biomarker data that is supportive of the biologic mechanism and hypothesis that Siglec-15 immune inhibition is not redundant with PD-1 inhibition.”

Early data on NextCure’s immuno-oncology drug in lung cancer patients delights investors