Petosemtamab

Merus on Friday released new data for its drug petosemtamab in multiple lines of colorectal cancer, potentially giving it additional utility beyond its primary focus of head and neck tumors. In first-line colorectal cancer, petosemtamab plus chemotherapy achieved eight responses out of 10 evaluable patients as of July 29, including one complete response. And among 13 patients in the second-line setting, petosemtamab plus chemo induced eight partial responses for a 62% objective response rate. The median follow-up time for the first- and second-line settings was 2.8 months and 4.8 months, respectively. Merus also tested petosemtamab as a monotherapy in third-line-plus colorectal cancer, which is a more difficult setting. The response rate was much lower in these patients, with only two of 20 responding to the drug. Median follow-up time was 4.2 months. Friday’s data, released at the annual “Triple Meeting” of three oncology associations, represent the first meaningful readout for petosemtamab in colorectal cancer. Merus did report some initial results at ESMO earlier this month, but the number of evaluable patients was tiny. As of April 28, petosemtamab saw three of three responses in first-line and four of eight in second-line. In the third-line setting, petosemtamab saw only one of 14 patients respond. Last month, Genmab announced its intent to acquire Merus for $8 billion, so it will reap the benefits of Friday’s data when the deal closes. The companies have been familiar with each other for years, largely due to their proximity in Europe. The buyout marked the culmination of a several-month search for Merus after petosemtamab got to late-stage testing. Much of the focus for petosemtamab is in head and neck cancer, where the drug reached what analysts called a “ home run scenario ” at ASCO earlier this year. After one year of treatment with petosemtamab and Merck’s Keytruda, 30 of 43 patients were still alive, good for a 79% overall survival rate. Currently, Merus is enrolling two Phase 3 studies in head and neck cancer: one in combination with Keytruda for the first-line setting, and another as a monotherapy in the second- and third-line settings. Petosemtamab is an antibody designed to inhibit both EGFR and LGR5.

– 100% response rate in 1L left-sided mCRC (n=8, confirmed and unconfirmed) – 62% response rate in 2L left- and right-sided mCRC (n=13, confirmed and unconfirmed) UTRECHT, The Netherlands and CAMBRIDGE, Mass., Oct. 24, 2025 (GLOBE NEWSWIRE) -- Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), an oncology company developing innovative, full-length multispecific antibodies and antibody drug conjugates (Biclonics®, Triclonics® and ADClonics®), today announced interim clinical data as of a July 29, 2025 data cutoff from the ongoing phase 2 trial of the bispecific antibody petosemtamab in combination with standard of care FOLFOX/FOLFIRI in 1L and 2L metastatic colorectal cancer (mCRC), and petosemtamab monotherapy in 3L+ mCRC. These data will be presented in a plenary session oral presentation by Dr. Moh’d Khushman M.D., Washington University School of Medicine, St. Louis, MO, at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics on Friday, October 24 at 10:20 a.m. ET. “Petosemtamab’s unique mechanism of action, including targeting both EGFR and LGR5, and potential to safely combine with FOLFOX/FOLFIRI, represents an important finding for patients with EGFR inhibitor-naïve metastatic colorectal cancer,” said Fabian Zohren, M.D., Ph.D., Chief Medical Officer of Merus. “These data demonstrate petosemtamab’s clinical activity beyond head and neck squamous cell carcinoma. We are encouraged that petosemtamab has the potential to become a transformational treatment and new standard of care for patients across a range of solid tumors.” “Metastatic colorectal cancer remains a formidable challenge with limited effective therapies. The promising early results with petosemtamab offer hope for advancing care and bringing new treatment possibilities to patients facing this difficult disease,” added Dr. Khushman. Petosemtamab (MCLA-158: EGFR x LGR5 Biclonics®) Presentation title: Petosemtamab (MCLA-158) monotherapy or with chemotherapy in metastatic colorectal cancer: Preliminary antitumor activity and safety data from a phase 2 trial Observations in the presentation include: As of a July 29, 2025 data cutoff date: 54 patients (pts) with left- and/or right-sided, KRAS, NRAS, and BRAF wildtype microsatellite stable mCRC received petosemtamab 1500 mg every two weeks, in combination with FOLFOX/FOLFIRI or as monotherapy Pts treated in 1L or 2L had no prior anti-EGFR therapy Pts treated in 2L received 1 prior chemotherapy regimen in the metastatic setting Pts treated in 3L+ received at least 2 prior regimens in the metastatic setting, including a prior anti-EGFR therapy Efficacy evaluable population consisted of patients with ≥1 dose of petosemtamab who had opportunity for ≥8 weeks follow up and ≥1 post baseline tumor assessment or discontinued petosemtamab early due to disease progression, symptomatic deterioration and/or death 1L petosemtamab with FOLFOX/FOLFIRI 14 pts were treated in 1L (10 FOLFOX and 4 FOLFIRI) 10 pts were efficacy evaluable, 8 left-sided; 10 (100%) remained on treatment 80% (8 of 10) response rate: 1 confirmed complete response, 7 partial responses (PRs) (4 unconfirmed of which 1 confirmed post data cutoff); 2 stable diseases (SDs) 88% (7 of 8) response rate in left-sided: 1 confirmed complete response, 6 PRs (3 unconfirmed, 1 unconfirmed response confirmed post data cutoff); 1 SD One SD observed to be an unconfirmed PR post data cutoff leading to 100% (8/8) response rate left-sided and 90% (9/10) response rate overall in 1L All unconfirmed PRs remained on treatment without disease progression 2L petosemtamab with FOLFOX/FOLFIRI 14 pts were treated in 2L (2 FOLFOX and 12 FOLFIRI) 13 were efficacy evaluable; 10 (77%) remained on treatment 62% response rate: 8 PRs (3 unconfirmed of which 1 confirmed post data cutoff); 4 SDs and 1 clinical deterioration prior to first scan All unconfirmed PRs and SDs remained on treatment without disease progression 3L+ petosemtamab monotherapy: 26 pts were treated 20 were efficacy evaluable, 6 (30%) remained on treatment 10% confirmed response rate: 2 PRs; 9 SDs (5 remained on treatment) Safety: Petosemtamab safety profile in mCRC observed thus far, appears consistent with its established safety profile in recurrent/metastatic head and neck squamous cell carcinoma No significant overlapping toxicities identified in combination with FOLFOX/FOLFIRI No new safety signals identified Infusion related reactions (IRRs) were managed with premedication and prolonged infusion on cycle 1 day 1; no discontinuations due to IRRs Pts treated in 1L or 2L had no prior anti-EGFR therapy Pts treated in 2L received 1 prior chemotherapy regimen in the metastatic setting Pts treated in 3L+ received at least 2 prior regimens in the metastatic setting, including a prior anti-EGFR therapy 14 pts were treated in 1L (10 FOLFOX and 4 FOLFIRI) 10 pts were efficacy evaluable, 8 left-sided; 10 (100%) remained on treatment 80% (8 of 10) response rate: 1 confirmed complete response, 7 partial responses (PRs) (4 unconfirmed of which 1 confirmed post data cutoff); 2 stable diseases (SDs) 88% (7 of 8) response rate in left-sided: 1 confirmed complete response, 6 PRs (3 unconfirmed, 1 unconfirmed response confirmed post data cutoff); 1 SD One SD observed to be an unconfirmed PR post data cutoff leading to 100% (8/8) response rate left-sided and 90% (9/10) response rate overall in 1L All unconfirmed PRs remained on treatment without disease progression 14 pts were treated in 2L (2 FOLFOX and 12 FOLFIRI) 13 were efficacy evaluable; 10 (77%) remained on treatment 62% response rate: 8 PRs (3 unconfirmed of which 1 confirmed post data cutoff); 4 SDs and 1 clinical deterioration prior to first scan All unconfirmed PRs and SDs remained on treatment without disease progression 26 pts were treated 20 were efficacy evaluable, 6 (30%) remained on treatment 10% confirmed response rate: 2 PRs; 9 SDs (5 remained on treatment) Petosemtamab safety profile in mCRC observed thus far, appears consistent with its established safety profile in recurrent/metastatic head and neck squamous cell carcinoma No significant overlapping toxicities identified in combination with FOLFOX/FOLFIRI No new safety signals identified Infusion related reactions (IRRs) were managed with premedication and prolonged infusion on cycle 1 day 1; no discontinuations due to IRRs Presentation: Title: Petosemtamab (MCLA-158) monotherapy or with chemotherapy in metastatic colorectal cancer: Preliminary antitumor activity and safety data from a phase 2 trial Session Title: Plenary Session 4: Clinical Trials Plenary Session Date and Time: Friday, October 24, 10:20 a.m. ET The same data will also be available in a poster: Session Title: Poster Session B Session Date and Time: Friday, October 24, 12:30-4:00 p.m. ET As full presentations become available at the conference, they will contemporaneously be available on the Merus website. About Merus N.V.  Merus is an 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. 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, statements regarding our belief that petosemtamab’s unique mechanism of action including targeting both EGFR and LGR5, and its potential ability to safely combine with FOLFOX/FOLFIRI represents an important finding for patients with EGFR inhibitor-naïve metastatic colorectal cancer; our belief that these data demonstrate petosemtamab’s clinical activity beyond head and neck squamous cell carcinoma; the potential for petosemtamab to become a transformational treatment and new standard of care for patients across a range of solid tumors; the promise of early results with petosemtamab to offer hope for advancing care and bringing new treatment possibilities to patients having mCRC; the potential further investigation of petosemtamab in patients with mCRC; the clinical development of our clinical candidates, including petosemtamab, future clinical trial results or interim data, clinical activity and safety profile, and development plans in the on-going trials and described in forthcoming posters or presentations. 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 June 30, 2025, filed with the Securities and Exchange Commission, or SEC, on August 5, 2025, 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. Multiclonics®, Biclonics®, Triclonics®, and ADClonics® are registered trademarks of Merus N.V. Source: Merus N.V.