ESMO: Responses to Merus' NRG1+ drug edge up as biotech plans 'high-quality dossier' for FDA next year

Responses to Merus’ bispecific antibody in pancreatic and lung cancer are creeping higher with every data cut, giving CEO Bill Lundberg, M.D., confidence that the dual American and Dutch biotech may someday be able to give a much-needed lifeline for one of the most difficult cancers out there.

When people think of pancreatic cancer, their minds immediately go to Alex Trebek or Ruth Bader Ginsburg, who both died from the disease in 2020.

“This is just a really difficult disease. We really wish back then we had a much better therapy for pancreatic cancer,” Lundberg said in an interview with Fierce Biotech on the sidelines of the European Society for Medical Oncology Congress in Madrid. “For these NRG-1 fusion tumors, we think we really have something that's a meaningful step change above what the patients could otherwise receive.”

Ipsen’s Onivyde is currently the standard of care, which Lundberg said has about a 7% chance of response in second- to third-line patients with metastatic pancreatic ductal adenocarcinoma (PDAC) that progresses after prior treatment. Patients typically only go a couple of months before their disease progresses, he added.

“Once a patient's cancer has progressed on standard therapy … it's a very difficult diagnosis,” Lundberg said.

This is where Merus is hoping the bispecific antibody zenocutuzumab (Zeno) can make an impact. The therapy is being developed for neuregulin 1 fusion (NRG1+) cancers, including PDAC and non-small cell lung cancer (NSCLC). At the ESMO Congress, the biotech showed a 37% overall response rate and a 61% clinical benefit rate for NSCLC from 105 evaluable patients as of the July 31 cutoff.

In PDAC, where 44 patients were evaluable, the therapy led to a 42% ORR, with one patient achieving a complete response and 13 notching a partial response. Merus also reported a 72% clinical benefit rate and 82% of the patients saw tumor reduction.

The response rate compares to Merus’ earlier presentation at the American Society of Clinical Oncology annual conference in June 2022. The ORR was 34% for the entire population, 42% for pancreatic cancer and 35% for lung cancer.

On safety, Merus called the profile “extremely well tolerated” but detailed information was not provided. Of the 189 total NRG1+ patients, 6% reported grade 3 to 4 toxicities. Speaking about the higher grade of the toxicities, Lundberg said the only other option in the NRG1+ setting is chemotherapy, which can be even more difficult for patients to tolerate. Chemo comes with known side effects such as mucositis (sore/inflamed mouth), gastrointestinal upset, skin or nail changes and lowered blood counts, among others.

“There are some adverse events that are noted but the vast majority of them are only grade 1, grade 2, mild or moderate, and really self-limiting in duration,” Lundberg explained. “It appears to be a much easier drug to take than the chemotherapy that we think doesn't work as well and is harder for patients to take.”

After discussions with regulators, Merus is planning to seek approval for Zeno in the first half of next year. The therapy was granted a breakthrough tag from the FDA this summer.

On whether the regulatory and, if approved, commercial activity, will be done in-house, Lundberg said Merus can only do so much, meaning that partnering talks are welcome.

“We recognize that [we] as a small company can gain maximum effectiveness if we have really productive partnerships,” the CEO said.

Merus has a discovery partnership with Eli Lilly’s Loxo oncology unit for up to three CD3-engaging T-cell re-directing bispecific antibody therapies. That deal included an upfront payment of $40 million plus a $20 million equity investment by Lilly. The total deal value could rise to $1.6 billion in milestones. Other partners include Betta and Incyte.

The next few months for Merus will be “head down, focused on delivering a high-quality dossier to the FDA,” Lundberg said. But, thanks to a $150 million public offering done earlier this year, the CEO said his company is well funded and ready to go with its next asset, petosemtamab, a bispecific antibody for EGFR x LGR5 cancers.

“It's a little bit of an embarrassment of riches and we have to make sure that we fully resource this one,” Lundberg said of petosemtamab. “That's really how we think about prioritization, capital allocation—we really want to make sure we're successful with this.”

To read more of Fierce Biotech's coverage of the ESMO Congress, click here. Fierce Pharma's coverage is available here.