Despite the PDUFA date being extended by three months for Merus’ zenocutuzumab, Truist Securities analyst Asthika Goonewardene in a Tuesday note to investors said the delay is not a cause for concern with an approval expected.
Merus on Tuesday announced that the FDA has extended its review of the investigational bispecific antibody zenocutuzumab, which the biotech is proposing as a treatment for non-small cell lung cancer and pancreatic ductal adenocarcinoma patients carrying certain genetic mutations.
The delay will give the regulator “sufficient time” to review additional Chemistry, Manufacturing and Controls (CMC) information that the company submitted in response to a previous request. Merus emphasized that the FDA did not request additional clinical efficacy or safety data, nor did the agency point out problems with zenocutuzumab’ data package.
The new target action date is Feb. 4, 2025. The previous PDUFA date was Nov. 4, 2024.
Zenocutuzumab is a bispecific antibody that works by binding to the HER2 protein and disrupting the binding between the HER3 receptor and neuregulin or its associated fusion. Preclinical studies have helped establish that this mechanism of action prevents the proliferation and survival of cancer cells.
Merus is developing zenocutuzumab for non-small cell lung cancer and pancreatic ductal adenocarcinoma positive for fusions of the NRG1 gene. While these genetic anomalies are rare, they are often associated with oncogenic events in various cancers. The FDA accepted Merus’ Biologics License Application on May 6, 2024, and gave it Priority Review.
In a note to investors, Truist Securities analyst Asthika Goonewardene said that a third-party manufacturer is handling the manufacturing of zenocutuzumab and “our read is that the FDA questions were something that the third-party should have anticipated and addressed earlier,” adding that his firm does not think there is a serious underlying issue.
Leerink Partners analyst Andrew Berens said that the delay “may pressure” Merus’ stock, though his firm does not expect it to be of significant consequence to Merus since “zeno is not core to most investor’s theses.”
“We do not see readthrough to [petosemtamab] and the rest of the pipeline as this is limited to a manufacturing issue,” Berens wrote.
BMO Capital Markets analyst Etzer Darout largely agreed, calling zenocutuzumab a “modest commercial opportunity” for Merus, with estimated peak sales of $462 million globally. The biotech “has expressed interest in partnering the program,” suggesting that Merus would rather invest its capital into the more promising petosemtamab, Darout said. The delay “does not impact our MRUS thesis,” he added.
Petosemtamab is a human, full-length IgG1 monoclonal antibody designed to bind to EGFR and LGR5, both of which are known cancer targets. According to Merus’ website, petosemtamab has three independent mechanisms of action—it blocks EGFR signaling, prevents the LGR-5-dependent internalization and degradation of EGFR in cancer cells and boosts the body’s anti-cancer response.
Merus is developing petosemtamab for the first-line treatment of head and neck squamous cell carcinoma, with a Phase III trial initiated in the third quarter of 2024. In May, the biotech reported Phase I/II data for the antibody, touting a 67% overall response rate in patients regardless of PD-L1 expression levels.
Petosemtamab is also being assessed as a second-line treatment for metastatic colorectal cancer, with a Phase II study initiated in the third quarter.
