UTRECHT, The Netherlands and CAMBRIDGE, Mass., Feb. 05, 2025(Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics® and Triclonics®), today announced that the New England Journal of Medicine (NEJM) published results of the registrational phase 2 eNRGy trial for Bizengri® (zenocutuzumab), the first and only treatment indicated for adults with pancreatic adenocarcinoma or non-small cell lung cancer (NSCLC) that are advanced unresectable or metastatic and harbor a neuregulin 1 (NRG1) gene fusion who have disease progression on or after prior systemic therapy.
"This manuscript provides comprehensive data on the safety and efficacy of Bizengri® and demonstrates the meaningful results observed in the eNRGy trial," said Bill Lundberg, M.D., President, Chief Executive Officer of Merus. "We continue to make significant progress across our clinical pipeline of important and new cancer therapeutic candidates, all from our own Biclonics® antibody technologies."
NRG1 fusions are unique cancer drivers that create oncogenic chimeric ligands rather than the more widely described chimeric receptors (TRK, RET, ROS1, ALK, and FGFR fusions). This is the first reported prospective clinical trial targeting cancers with this rare genomic alteration, a population enriched for cancer types with limited effective treatment options.1, 2, 3
The publication reviews the results of 204 patients with 12 tumor types enrolled and treated on the eNRGy study, concluding "Zenocutuzumab demonstrated durable efficacy in patients with advanced NRG1+ cancer, notably NSCLC and pancreatic adenocarcinoma, with a favorable safety profile."
"This medicine fills an important need among patients with NRG1 fusion pancreatic adenocarcinoma and lung cancer who have not previously had targeted treatment options," said Alison Schram M.D., an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, a principal investigator for the eNRGy trial, and lead author on the NEJM manuscript.
In December, Merus announced it had entered into an agreement with Partner Therapeutics, Inc. (PTx), a private, fully-integrated biotechnology company with a focus in hematology and oncology, in which Merus has exclusively licensed to PTx the right to commercialize zenocutuzumab (Zeno, tradename Bizengri®) for the treatment of NRG1 fusion-positive (NRG1+) cancer in the United States (U.S.).
Indications:
BIZENGRI® (zenocutuzumab-zbco) is indicated for adults with pancreatic adenocarcinoma or non-small cell lung cancer (NSCLC) that are advanced unresectable or metastatic and harbor a neuregulin 1 (NRG1) gene fusion who have disease progression on or after prior systemic therapy. These indications are approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
IMPORTANT SAFETY INFORMATION
BOXED WARNING: EMBRYO-FETAL TOXICITY
Embryo-Fetal Toxicity: Exposure to BIZENGRI® during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception.
WARNINGS AND PRECAUTIONS
Infusion-Related Reactions/Hypersensitivity/Anaphylactic Reactions
BIZENGRI® can cause serious and life-threatening infusion-related reactions (IRRs), hypersensitivity and anaphylactic reactions. Signs and symptoms of IRR may include chills, nausea, fever, and cough.
In the eNRGy study, 13% of patients experienced IRRs, all were Grade 1 or 2; 91% occurred during the first infusion.
Administer BIZENGRI® in a setting with emergency resuscitation equipment and staff who are trained to monitor for IRRs and to administer emergency medications. Monitor patients closely for signs and symptoms of infusion reactions during infusion and for at least 1 hour following completion of first BIZENGRI® infusion and as clinically indicated. Interrupt BIZENGRI® infusion in patients with = Grade 3 IRRs and administer symptomatic treatment as needed. Resume infusion at a reduced rate after resolution of symptoms. Immediately stop the infusion and permanently discontinue BIZENGRI® for Grade 4 or life-threatening IRR or hypersensitivity/anaphylaxis reactions.
Interstitial Lung Disease/Pneumonitis
BIZENGRI® can cause serious and life-threatening interstitial lung disease (ILD)/pneumonitis. In the eNRGy study, ILD/pneumonitis occurred in 2 (1.1%) patients treated with BIZENGRI®. Grade 2 ILD/pneumonitis (Grade 2) resulting in permanent discontinuation of BIZENGRI® occurred in 1 (0.6%) patient. Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold BIZENGRI® in patients with suspected ILD/pneumonitis and administer corticosteroids as clinically indicated. Permanently discontinue BIZENGRI® if ILD/pneumonitis = Grade 2 is confirmed.
Left Ventricular Dysfunction
BIZENGRI® can cause left ventricular dysfunction.
Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including BIZENGRI®. Treatment with BIZENGRI® has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment.
In the eNRGy study, Grade 2 LVEF decrease (40%-50%; 10 - 19% drop from baseline) occurred in 2% of evaluable patients. Cardiac failure without LVEF decrease occurred in 1.7% of patients, including 1 (0.6%) fatal event.
Before initiating BIZENGRI®, evaluate LVEF and monitor at regular intervals during treatment as clinically indicated. For LVEF of less than 45% or less than 50% with absolute decrease from baseline of 10% or greater which is confirmed, or in patients with symptomatic congestive heart failure (CHF), permanently discontinue BIZENGRI®.
Embryo-Fetal Toxicity
Based on its mechanism of action, BIZENGRI® can cause fetal harm when administered to a pregnant woman. No animal reproduction studies were conducted with BIZENGRI®. In postmarketing reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In animal models, studies have demonstrated that inhibition of HER2 and/or HER3 results in impaired embryo-fetal development, including effects on cardiac, vascular and neuronal development, and embryolethality. Advise patients of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of BIZENGRI®. Advise females of reproductive potential to use effective contraception during treatment with BIZENGRI® and for 2 months after the last dose.
ADVERSE REACTIONS
NRG1 Gene Fusion Positive Unresectable or Metastatic Pancreatic Adenocarcinoma
Serious adverse reactions occurred in 23% of patients with NRG1 Gene Fusion Positive Pancreatic Adenocarcinoma who received BIZENGRI®.
There were 2 fatal adverse reactions, one due to COVID-19 and one due to respiratory failure.
In patients with NRG1 Gene Fusion Positive Pancreatic Adenocarcinoma who received BIZENGRI® the most common (=20%) adverse reactions, including laboratory abnormalities, were increased alanine aminotransferase (51%), diarrhea (36%), increased aspartate aminotransferase (31%), increased bilirubin (31%), decreased phosphate (31%), increased alkaline phosphatase (28%), decreased sodium (28%) musculoskeletal pain (28%), decreased albumin (26%), decreased potassium (26%), decreased platelets (26%), decreased magnesium (24%), increased gamma-glutamyl transpeptidase (23%), decreased hemoglobin (23%), vomiting (23%), nausea (23%), decreased leukocytes (21%), and fatigue (21%).
NRG1 Gene Fusion Positive Unresectable or Metastatic NSCLC
Serious adverse reactions occurred in 25% of patients with NRG1 Gene Fusion Positive NSCLC who received BIZENGRI®. Serious adverse reactions in = 2% of patients included pneumonia (n=4) dyspnea and fatigue (n=2 each). Fatal adverse reactions occurred in 3 (3%) patients and included respiratory failure (n=2), and cardiac failure (n=1). Permanent discontinuation of BIZENGRI® due to an adverse reaction occurred in 3% of patients. Adverse reactions resulting in permanent discontinuation of BIZENGRI® included dyspnea, pneumonitis and sepsis (n=1 each).
In patients with NRG1 Gene Fusion Positive NSCLC who received BIZENGRI®, the most common (>20%) Adverse Reactions, including laboratory abnormalities, were decreased hemoglobin (35%), increased alanine aminotransferase (30%), decreased magnesium (28%), increased alkaline phosphatase (27%), decreased phosphate (26%) diarrhea (25%), musculoskeletal pain (23%), increased gamma-glutamyl transpeptidase (23%), increased aspartate aminotransferase (22%), and decreased potassium (21%).
Please see full Prescribing Information, including Boxed WARNING, at BIZENGRI.com/pi.
About BIZENGRI®
BIZENGRI® is a bispecific antibody that binds to the extracellular domains of HER2 and HER3 expressed on the surface of cells, including tumor cells, inhibiting HER2:HER3 dimerization and preventing NRG1 binding to HER3. BIZENGRI® decreased cell proliferation and signaling through the phosphoinositide 3-kinase-AKT-mammalian target of rapamycin pathway. In addition, BIZENGRI® mediates antibody-dependent cellular cytotoxicity. BIZENGRI® showed antitumor activity in mouse models of NRG1+ lung and pancreatic cancers.4
About the eNRGy Trial
The eNRGy trialNCT02912949) is a multicenter, open-label clinical trial that includes patients with advanced unresectable or metastatic NRG1+ pancreatic adenocarcinoma or NRG1+ NSCLC who have disease progression on or after prior systemic therapy. There were 30 patients in the NRG1+ pancreatic adenocarcinoma group and 64 patients in the NRG1+ NSCLC group. The main outcome measures were ORR and DOR, as determined by BICR according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.4
In the NRG1+ pancreatic adenocarcinoma group, the median age was 49 years (range, 21-72 years); 43% were female; 87% were White, 7% were Asian, and 3.3% were Black or African American. All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and all patients had metastatic disease. Patients received a median of 2 prior systemic therapies (range, 0-5); 97% had prior systemic therapy with prior chemotherapy.4
In the NRG1+ NSCLC group, the median age was 64 years (range, 32-86 years); 64% were female, 33% were White, 56% were Asian, and 3.4% were Black or African American. ECOG performance status was 0 or 1 in 97% of patients or 2 in 3% of patients, and 98% of patients had metastatic disease. Patients received a median of 2 prior systemic therapies (range, 1-6).4
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation, benefits of a license between PTx and Merus; whether and when Merus will receive any future payment under the license agreement, including milestones or royalties, and the amounts of such payments; our progress across our clinical pipeline of important and new cancer therapeutic candidates, all from our own Biclonics® antibody technologies; the belief that this medicine fills an important need among patients with NRG1 fusion pancreatic adenocarcinoma and lung cancer who have not previously had targeted treatment options. These forward-looking statements are based on management's current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our need for additional funding, which may not be available and which may require us to restrict our operations or require us to relinquish rights to our technologies or antibody candidates; potential delays in regulatory approval, which would impact our ability to commercialize our product candidates and affect our ability to generate revenue; the lengthy and expensive process of clinical drug development, which has an uncertain outcome; the unpredictable nature of our early stage development efforts for marketable drugs; potential delays in enrollment of patients, which could affect the receipt of necessary regulatory approvals; our reliance on third parties to conduct our clinical trials and the potential for those third parties to not perform satisfactorily; impacts of the volatility in the global economy, including global instability, including the ongoing conflicts in Europe and the Middle East; we may not identify suitable Biclonics® or bispecific antibody candidates under our collaborations or our collaborators may fail to perform adequately under our collaborations; our reliance on third parties to manufacture our product candidates, which may delay, prevent or impair our development and commercialization efforts; protection of our proprietary technology; our patents may be found invalid, unenforceable, circumvented by competitors and our patent applications may be found not to comply with the rules and regulations of patentability; we may fail to prevail in potential lawsuits for infringement of third-party intellectual property; and our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks.
These and other important factors discussed under the caption "Risk Factors" in our Quarterly Report on Form 10-Q for the period ended September 30, 2024, filed with the Securities and Exchange Commission, or SEC, on October 31, 2024, and our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change, except as required under applicable law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.
References:
1Chang JC, Offin M, Falcon C, et al. Comprehensive molecular and clinicopathologic analysis of 200 pulmonary invasive mucinous adenocarcinomas identifies distinct characteristics of molecular subtypes. Clin Cancer Res 2021;27:4066-76.
2Drilon A, Duruisseaux M, Han JY, et al. Clinicopathologic features and response to therapy of NRG1 fusion-driven lung cancers: the eNRGy1 global multicenter registry. J Clin Oncol 2021;39:2791-802.
3Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet 2014;384:665-73.
4BIZENGRI. Prescribing information. Merus N.V.; 2024.
About Merus
Merus is a clinical stage oncology company developing innovative full-length human bispecific and trispecific antibody therapeutics, referred to as Multiclonics®. Multiclonics® are manufactured using industry standard processes and have been observed in preclinical and clinical studies to have several of the same features of conventional human monoclonal antibodies, such as long half-life and low immunogenicity. For additional information, please visit Merus' website, and LinkedIn.
Multiclonics®, Biclonics®, Triclonics®, and Bizengri® are registered trademarks of Merus N.V.
