petosemtamab (MCLA-158) / Merus - LARVOL DELTA

Genmab Announces Completion of Tender Offer for Outstanding Common Shares of Merus N.V. and Commencement of Subsequent Offering Period (GlobeNewswire) - "Transaction adds petosemtamab, a late-stage asset with two Breakthrough Therapy Designations, to Genmab’s portfolio....Genmab expects to launch petosemtamab in 2027, subject to clinical results and receipt of regulatory approvals. Genmab also intends to broaden and accelerate petosemtamab’s development with potential expansion into other lines of therapy. Following the initial approval of petosemtamab, Genmab believes that petosemtamab will be accretive to EBITDA with at least one-billion-dollar annual sales potential by 2029, with multi-billion-dollar annual revenue potential thereafter."

Commercial • Squamous Cell Carcinoma of Head and Neck

Preclinical evaluation of petosemtamab, an epidermal growth factor receptor (EGFR) and leucine-rich repeat-containing G protein-coupled receptor (LGR5) bispecific antibody, on cancer stem cells (AACR-NCI-EORTC 2025) - P1/2 | "Petosemtamab in combination with pembrolizumab (400 mg Q6W) as 1L treatment for PD-L1+ r/m HNSCC demonstrated a 63% ORR and 79%-overall survival rate at 12 months in 43 efficacy evaluable pts [van Herpen, 2025 ASCO]...EGFR and LGR5 protein expression were analyzed by western blot in EGFR+LGR5+ colorectal cancer organoid model P18T after treatment with petosemtamab, its single-Fab arm variants, and cetuximab. EGFR internalization and degradation were studied by immunofluorescence imaging over time (24 hours), in the presence or absence of proteosome inhibitor bortezomib...Inhibition of the EGFR–RAS/RAF/MAPK signaling pathway has previously been shown to lead to increased LGR5 expression [High, 2025 AACR] supporting petosemtamab evaluation in relevant targeted therapies. These results confirm petosemtamab mediates efficient EGFR degradation in colorectal cancer cells in an organoid model expressing both EGFR and LGR5, and supports the further clinical development of..."

Cancer stem • IO biomarker • Preclinical • Colorectal Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • LGR5 • PD-L1

Merus’ Interim Data on Petosemtamab in Metastatic Colorectal Cancer Demonstrates Monotherapy Activity and Robust Response Rate in Combination with FOLFOX/FOLFIRI with Well Tolerated Safety - "'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."

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Merus’ Interim Data on Petosemtamab in Metastatic Colorectal Cancer Demonstrates Monotherapy Activity and Robust Response Rate in Combination with FOLFOX/FOLFIRI with Well Tolerated Safety (GlobeNewswire) - "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)...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...3L+ petosemtamab monotherapy...10% confirmed response rate: 2 PRs; 9 SDs (5 remained on treatment)."

P2 data • Colorectal Cancer

Petosemtamab (MCLA-158) monotherapy or with chemotherapy in metastatic colorectal cancer: Preliminary antitumor activity and safety data from a phase 2 trial (AACR-NCI-EORTC 2025) - P1/2 | "10 pts were treated in 2L (1 FOLFOX and 9 FOLFIRI), with 8 ongoing... Petosemtamab demonstrates promising efficacy and manageable safety across 1L, 2L and 3L+ mCRC. Updated data will be provided; biomarker analysis is ongoing."

Clinical • Metastases • Monotherapy • P2 data • Colorectal Cancer • Oncology • Solid Tumor • BRAF • KRAS • LGR5 • NRAS

Petosemtamab (MCLA-158) monotherapy or with chemotherapy in metastatic colorectal cancer: Preliminary antitumor activity and safety data from a phase 2 trial (AACR-NCI-EORTC 2025) - P1/2 | "10 pts were treated in 2L (1 FOLFOX and 9 FOLFIRI), with 8 ongoing... Petosemtamab demonstrates promising efficacy and manageable safety across 1L, 2L and 3L+ mCRC. Updated data will be provided; biomarker analysis is ongoing."

Clinical • Metastases • Monotherapy • P2 data • Colorectal Cancer • Oncology • Solid Tumor • BRAF • KRAS • LGR5 • NRAS

Merus Announces Publication of an Abstract on Petosemtamab in Metastatic Colorectal Cancer at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (GlobeNewswire) - "(i) 1L petosemtamab with FOLFOX/FOLFIRI: 7 pts were treated in 1L (6 FOLFOX and 1 FOLFIRI), with 6 ongoing; 3 pts were efficacy evaluable, with median follow up of 2.6 months; 1 unconfirmed complete response and 2 partial responses (PR; 1 unconfirmed) observed; (ii) 2L petosemtamab with FOLFOX/FOLFIRI: 10 pts were treated in 2L (1 FOLFOX and 9 FOLFIRI), with 8 ongoing; 8 were efficacy evaluable, with median follow up of 3.4 months; 4 PRs (2 unconfirmed), 3 stable diseases (SD; all ongoing) and 1 clinical deterioration prior to first scan."

P2 data • Colorectal Cancer

Merus Announces Petosemtamab in Metastatic Colorectal Cancer Abstract Selected for Plenary Session Oral Presentation at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (GlobeNewswire) - "Initial interim data from the phase 2 trial evaluating petosemtamab in combination with standard chemotherapy in 1L and 2L metastatic colorectal cancer (mCRC), and as monotherapy in heavily pretreated (3L+) mCRC will be presented in a plenary session....Merus will also present a poster regarding the preclinical evaluation of petosemtamab on cancer stem cells."

P2 data • Preclinical • Colorectal Cancer

Genmab A/S…and Merus N.V…announced today that they have entered into a transaction agreement pursuant to which Genmab intends to acquire all the shares of Merus, a clinical-stage biotechnology company with its late-stage breakthrough therapy asset petosemtamab...for USD 97.00 per share in an all-cash transaction value of approximately USD 8.0 billion. (GlobeNewswire) - "Following the closing of the transaction, Genmab will have four proprietary programs expected to drive multiple new drug launches by 2027."

M&A • Esophageal Squamous Cell Carcinoma • Gastroesophageal Junction Adenocarcinoma • Non Small Cell Lung Cancer • Pancreatic Adenocarcinoma • Squamous Cell Carcinoma of Head and Neck

Merus is currently running two Phase 3 trials in first- and second/third line head and neck cancer, with topline interim readout of one or both trials anticipated in 2026. (GlobeNewswire) - "...Genmab anticipates the potential for the initial launch of petosemtamab in 2027...Following its initial anticipated approval, Genmab believes that petosemtamab will be accretive to EBITDA with at least one-billion-dollar annual sales potential by 2029..."

Launch • P3 data: top line • Squamous Cell Carcinoma of Head and Neck

Merus Announces Financial Results for the Second Quarter 2025 and Provides Business Update (GlobeNewswire) - "Petosemtamab (MCLA-158: EGFR x LGR5 Biclonics):...LiGeR-HN1, a phase 3 trial evaluating the efficacy and safety of petosemtamab in combination with pembrolizumab in 1L PD-L1+ r/m HNSCC compared to pembrolizumab, and LiGeR-HN2, a phase 3 trial evaluating the efficacy and safety of petosemtamab in 2/3L HNSCC compared to standard of care, are enrolling and we expect both trials to be substantially enrolled by YE25....We expect to provide topline interim readout of one or both phase 3 registration trials in 2026....A phase 2 trial evaluating petosemtamab in combination with standard chemotherapy in 1L and 2L mCRC, and as monotherapy in heavily pretreated (3L+) mCRC, is enrolling. We expect to provide initial clinical data for petosemtamab in mCRC in 2H25."

Enrollment status • P2 data • P3 data: top line • Colorectal Cancer • Squamous Cell Carcinoma of Head and Neck

PREVENTING SKIN TOXICITIES INDUCED BY NOVEL BISPECIFIC EGFR INHIBITORS BY TOPICALLY BLOCKING DRUG-RECEPTOR INTERACTION (MASCC-ISOO 2025) - "In our previous work, we developed a compound (SDT-011) and method to prevent "on-target" skin toxicity by topically blocking the drug-receptor interactions of cetuximab and panitumumab at the site of toxicity...Additionally, in silico docking experiments provided insights into SDT-011's mechanism of action in blocking amivantamab, petosemtamab, and izalontamab...Conclusions Our innovative topical approach aims to prevent skin toxicities caused by EGFRi monoclonal and bispecific antibodies by blocking the initial trigger causing skin damage. By mitigating skin toxicities associated with bispecific EGFR inhibitors, SDT-011 could enhance treatment adherence and improve patients' quality of life, ultimately optimizing cancer therapy outcomes."

Oncology • ERBB3

LiGeR-HN phase III trials of petosemtamab + pembrolizumab and petosemtamab monotherapy in recurrent or metastatic HNSCC. (PubMed, Future Oncol) - P3 | "LiGeR-HN2 (NCT06496178) evaluates petosemtamab versus investigator's choice of monotherapy (cetuximab, methotrexate, or docetaxel) in patients with previously treated r/m HNSCC. Primary endpoints in both trials are objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review, and overall survival. Both trials are recruiting at the time of publication.Clinical Trial Registration: NCT06525220 and NCT06496178 (ClinicalTrials.gov)."

Journal • Monotherapy • P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • LGR5

Petosemtamab (MCLA-158) with pembrolizumab as first-line (1L) treatment of PD-L1+ recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC): Phase 2 trial. (ASCO 2025) - P1/2, P3 | "Petosemtamab, a first-in-class EGFR x LGR5 bispecific antibody, in combination with pembrolizumab continues to demonstrate promising clinical efficacy and a well-tolerated safety profile as 1L treatment for pts with r/m PD-L1+ HNSCC. A global phase 3 trial, LiGeR-HN1 (NCT06525220), is ongoing to evaluate petosemtamab in combination with pembrolizumab in 1L PD-L1+ r/m HNSCC."

Clinical • Metastases • P2 data • Dermatitis • Dermatology • Head and Neck Cancer • Immunology • Oncology • Otorhinolaryngology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Petosemtamab, a Bispecific Antibody Targeting Epidermal Growth Factor Receptor (EGFR) and Leucine-Rich G Repeat-Containing Protein-Coupled Receptor (LGR5) Designed for Broad Clinical Applications. (PubMed, Cancers (Basel)) - "The safety profile is generally favorable, with low rates of skin and gastrointestinal toxicity. Phase 3 trials are ongoing in both first-line programmed death-ligand 1-positive (PD-L1+) and second/third-line r/m HNSCC."

Journal • Review • Colon Cancer • Colorectal Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • LGR5 • PD-L1

Merus’ Petosemtamab with Pembrolizumab Interim Data Demonstrates Robust Efficacy and Durability in 1L PD-L1+ r/m HNSCC (Merus Press Release) - P1/2 | N=53 | NCT03526835 | Sponsor: Merus N.V. | "Observations in the presentation include as of a February 27, 2025 data cutoff date: 45 patients (pts) were treated The efficacy evaluable population consisted of 43 patients who were treated (with one or more doses) as of the data cutoff date and either ≥1 post-baseline tumor assessment, or discontinued early due to disease progression or death Median follow up of 14.3 months for the 45 patients In 43 evaluable patients: Confirmed overall response rate: 63% (27/43, 95% CI: 49-75), including 6 complete responses, 21 partial responses by Response Evaluation Criteria in Solid Tumors v1.1. per investigator assessment, including: 4 of 8 patients with HPV associated cancer responded Responses observed across PD-L1 levels (CPS 1-19: 47% [8/17]; CPS > 20: 73% [19/26]) Median progression-free survival was 9 months (95% CI: 5.2-12.9)..."

P2 data • Squamous Cell Carcinoma of Head and Neck

Merus Announces Financial Results for the First Quarter 2025 and Provides Business Update (GlobeNewswire) - "A phase 2 trial evaluating petosemtamab in combination with standard chemotherapy in 1L and 2L mCRC, and as monotherapy in heavily pretreated (3L+) mCRC, is enrolling. We expect to provide initial clinical data for petosemtamab in mCRC in 2H25."

Enrollment status • P2 data • Colorectal Cancer

Merus Announces the Journal Publication of Petosemtamab Mechanism of Action (GlobeNewswire) - "Merus N.V...announced publication on the mechanism of action of petosemtamab, a bispecific antibody targeting Epidermal Growth Factor Receptor (EGFR) and Leucine-Rich G (LGR5), in the scientific journal 'Cancers', a MDPI publication....'This publication outlining the scientific rationale for petosemtamab, a bispecific targeting EGFR and LGR5, underpins the strong previously reported phase 2 interim clinical data in both 1L PD-L1+ r/m HNSCC in combination with pembrolizumab and as a single-agent in 2L+ r/m HNSCC.'"

Clinical • Trial status • Colorectal Cancer • Squamous Cell Carcinoma of Head and Neck

Merus Announces Abstract Accepted for Presentation at the 2025 ASCO Annual Meeting (GlobeNewswire) - "Merus N.V...today announced the acceptance of an abstract for presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, being held in Chicago, Illinois on May 30- June 3, 2025. An updated analysis of the interim clinical data from the phase 2 trial of petosemtamab with pembrolizumab as 1L treatment of PD-L1+ recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC) will be presented in a poster at 2025 ASCO. The presentation will include data on the entire 45 patient dataset and follows the early clinical efficacy and encouraging safety data previously presented at 2024 ASCO."

P2 data • Squamous Cell Carcinoma of Head and Neck

Topical strategy to prevent skin toxicities from bispecific-EGFR inhibitors by blocking drug-receptor interactions in skin (ESMO-TAT 2025) - "In our previous work, we developed a compound and method to prevent "on-target" skin toxicity by topically blocking the drug-receptor interactions of cetuximab and panitumumab at the site of toxicity...To gain deeper insights into the mechanism of action, in silico docking experiments were conducted to understand how SDT-011 blocks amivantamab, petosemtamab, and izalontamab. SDT-011 demonstrated effective blocking of anti-EGFR bispecific monoclonal antibodies binding to EGFR, including amivantamab, petosemtamab, and izalontamab... SDT-011 offers a promising approach for treating on-target skin toxicity by topically blocking EGFRi monoclonal and bispecific antibodies at the site of toxicity. By potentially reducing the incidence and severity of skin toxicities associated with EGFR inhibitors, SDT-011 could improve patients' quality of life and treatment compliance, ultimately enhancing the overall effectiveness of cancer therapies."

Oncology

Merus Announces Financial Results for the Fourth Quarter and Full Year 2024 and Provides Business Update (GlobeNewswire) - "Petosemtamab (MCLA-158: EGFR x LGR5 Biclonics): Solid Tumors - (i) LiGeR-HN1 phase 3 trial in 1L PD-L1+ r/m head and neck squamous cell carcinoma (HNSCC) and LiGeR-HN2 phase 3 trial in 2/3L r/m HNSCC enrolling - we expect both trials to be substantially enrolled by YE25; (ii) clinical update on phase 2 trial in combination with pembrolizumab in 1L PD-L1+ r/m HNSCC planned for 1H25; (iii) phase 2 trial in 1L, 2L and 3L+ metastatic colorectal cancer (mCRC) enrolling; mCRC initial clinical data planned for 2H25."

Enrollment status • P2 data • Colorectal Cancer • Squamous Cell Carcinoma of Head and Neck

Petosemtamab granted Breakthrough Therapy designation by the U.S. FDA for 1L PD-L1 positive head and neck squamous cell carcinoma (GlobeNewswire) - "Merus...announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation (BTD) to petosemtamab in combination with pembrolizumab for the first-line treatment of adult patients with recurrent or metastatic programmed death-ligand 1 (PD-L1) positive head and neck squamous cell carcinoma (r/m HNSCC) with combined positive score (CPS) ≥ 1....BTD is supported by updated data from the ongoing phase 1/2 open-label, multicenter trial evaluating petosemtamab in combination with pembrolizumab in 1L HNSCC expressing PD-L1 (CPS≥1) (NCT03526835)."

Breakthrough therapy • Evidence highlight • Squamous Cell Carcinoma of Head and Neck • PD-L1

Merus announces First Patient Dosed in Phase 2 Trial of Petosemtamab in 3L+ mCRC (GlobeNewswire) - "Merus...announced that the first patient has been dosed in the Company’s phase 2 trial evaluating petosemtamab monotherapy in heavily pretreated (3L+) metastatic colorectal cancer (mCRC)....The phase 2, open-label trial will evaluate the safety and antitumor activity of petosemtamab monotherapy in 3L+ mCRC, post anti-EGFR therapy. To be eligible for enrollment, patients must lack certain mutations as detected in plasma by ctDNA NGS, including KRAS, NRAS."

Trial status • Colorectal Cancer

Petosemtamab Clinical Development (GlobeNewswire) - "r/m HNSCC:...phase 2 trial of petosemtamab in combination with pembrolizumab in PD-L1+ 1L HNSCC ongoing with a clinical data update planned for 2025; mCRC:...phase 2 trial in 1L mCRC in combination with standard chemotherapy planned to initiate in 2025, and phase 2 trial in 3L+ monotherapy planned to initiate in 2025; mCRC initial clinical data planned for 2025."

New P2 trial • P2 data • Colorectal Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Merus’ Petosemtamab Monotherapy Interim Data Continues to Demonstrate Clinically Meaningful Activity in 2L+ r/m HNSCC (GlobeNewswire) - P1/2 | N=567 | NCT03526835 | Sponsor: Merus N.V. | "As of a July 5, 2024 data cutoff date, 82 pts were treated with petosemtamab 1500 mg Q2W...Confirmed overall response rate (ORR): 36% (90% CI: 27–46; 27/75) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. per investigator assessment, including 4 complete responses (CRs), with one CR continuing on treatment for more than 3 years as of the data cutoff; and 13% (2/15) ORR in HPV associated cancer with another 5 patients achieving stable disease...Median duration of response (DOR), progression free survival (PFS) and overall survival (OS) were 6.2, 4.9 and 11.4 months...As of a July 5, 2024 data cutoff date, 28 pts were treated with petosemtamab 1100 mg Q2W...ORR: 19% (90% CI: 8–35; 5/27), including 2 CRs, by RECIST v1.1. per investigator assessment."

P1/2 data • Squamous Cell Carcinoma of Head and Neck