On August 7, 2023 Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported financial results for the second quarter and provided a business update (Press release, Merus, AUG 7, 2023, View Source [SID1234633888]).
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"Receiving Fast Track Designation is an important milestone for petosemtamab, which we believe further validates its potential to address the unmet need of patients with previously treated recurrent or metastatic head and neck cancer," said Bill Lundberg, M.D., President, Chief Executive Officer of Merus. "We also believe the robust clinical data observed in previously treated HNSCC support a phase 3 trial of petosemtamab monotherapy in this setting, which could potentially start in mid-2024. Additionally, we are encouraged by our progress to date with the combination of petosemtamab and Keytruda as potential front-line therapy in advanced HNSCC, and are evaluating a phase 3 trial in this setting as well."
Petosemtamab (MCLA-158: EGFR x LGR5 Biclonics): Solid Tumors
Granted Fast Track Designation (FTD) for the treatment of patients with recurrent or metastatic head & neck squamous cell carcinoma (HNSCC), enrollment continues in dose expansion in the phase 1/2 trial with petosemtamab monotherapy in previously treated HNSCC, as well as in combination with Keytruda (pembrolizumab) as front-line therapy.
Petosemtamab is in clinical development in the expansion part of a phase 1/2 open-label, multicenter trial evaluating petosemtamab monotherapy in patients with advanced solid tumors, including previously treated (recurrent or metastatic) HNSCC. Enrollment is also ongoing in a cohort investigating petosemtamab in combination with Keytruda in patients with untreated HNSCC to evaluate the safety and clinical activity in this population. Merus plans to report initial interim clinical data from this cohort in the first half of 2024.
Initiation of potential registration-enabling trial
Merus is enrolling up to a total of approximately 40 patients in previously treated (2L/3L) HNSCC with petosemtamab monotherapy at the 1100 or 1500 mg dose levels to confirm a suitable dose for future randomized trials. Based on these data and additional information and analyses, Merus anticipates potentially initiating a randomized phase 3 trial of petosemtamab monotherapy, or investigators’ choice of single agent chemotherapy or cetuximab in 2L/3L HNSCC. Merus anticipates such a trial could potentially start in mid-2024. Merus believes a randomized registration trial in HNSCC with an overall response rate (ORR) endpoint could potentially support accelerated approval and the overall survival (OS) results from the same study could potentially verify its clinical benefit to support regular approval.
Merus is also evaluating a phase 3 trial investigating petosemtamab with Keytruda as a potential front-line therapy for advanced HNSCC expressing PD-L1 (CPS > 1), pending analysis of additional data on the tolerability and safety of the drug combination.
Fast Track Designation
The U.S. Food & Drug Administration (FDA) has granted FTD for petosemtamab for the treatment of patients with recurrent or metastatic HNSCC whose disease has progressed following treatment with platinum-based chemotherapy and an anti-programmed cell death protein 1 (anti-PD-1) antibody.
FTD is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill unmet medical needs.
Interim data from AACR (Free AACR Whitepaper)
In April, Merus provided an interim clinical update at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023. As of a February 1, 2023 data cutoff date, 49 previously treated HNSCC patients were treated with petosemtamab at the initial recommended phase 2 dose of 1500 mg intravenously every two weeks. The ORR, in 43 evaluable patients, was 37.2% by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. per investigator assessment. Median duration of response was 6.0 months and median progression free survival was 5.3 months. 63% of responders had an ongoing response at the data cutoff date. Median OS was 11.5 months. Petosemtamab continued to demonstrate a manageable safety profile.
Zenocutuzumab (Zeno or MCLA-128: HER2 x HER3 Biclonics): NRG1 fusion (NRG1+) cancer and other solid tumors
Granted Breakthrough Therapy Designation (BTD) for both NRG1+ non-small cell lung cancer (NSCLC) and NRG1+ pancreatic cancer; enrollment continues in the eNRGy trial of Zeno monotherapy in NRG1+ cancer and a phase 2 trial of Zeno in combination with androgen deprivation therapy (ADT) in castration resistant prostate cancer (CRPC); as well as in combination with afatinib in NRG1+ non-small cell lung cancer (NSCLC)
The FDA has granted BTD to Zeno for the treatment of patients with advanced unresectable or metastatic NRG1+ pancreatic cancer following progression with prior systemic therapy or who have no satisfactory alternative treatment options. Additionally, the FDA has granted BTD to Zeno for the treatment of patients with advanced unresectable or metastatic NRG1+ NSCLC, following progression with prior systemic therapy. Zeno is being investigated in the phase 1/2 eNRGy trial and Early Access Program (EAP) which are assessing the safety and anti-tumor activity of Zeno monotherapy in NRG1+ cancer (Phase 1/2: NCT02912949, EAP: NCT04100694).
As of June 2023, more than 175 patients with NRG1+ cancer have been treated with Zeno monotherapy. The company continues to work with the FDA and is focused on accumulating data to support a potential Biologics License Application.
Merus believes that obtaining a commercialization partnership agreement will be an essential step in bringing Zeno to patients with NRG1+ cancer, if approved.
Merus plans to present a clinical update on Zeno in NRG1+ cancer at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2023 taking place in Madrid, Spain October 20-24, 2023. The presentations will consist of a mini-oral lecture titled: Durable efficacy of zenocutuzumab, a HER2 x HER3 bispecific antibody, in advanced NRG1 fusion-positive (NRG1+) non-small cell lung cancer (NSCLC) and a poster presentation titled: Durable efficacy of zenocutuzumab, a HER2 x HER3 bispecific antibody, in advanced NRG1 fusion-positive (NRG1+) pancreatic ductal adenocarcinoma (PDAC).
Further, Merus is evaluating Zeno in combination with an ADT (enzalutamide or abiraterone) in men with CRPC, irrespective of NRG1+ status. Merus plans to provide initial clinical data on Zeno in CRPC in the second half of 2023.
Merus is also evaluating Zeno in combination with afatinib in patients with NRG1+ NSCLC.
MCLA-129 (EGFR x c-MET Biclonics): Solid Tumors
Enrollment continues in the expansion cohorts in the phase 1/2 trial; clinical update planned for 2H23
MCLA-129 is in clinical development in a phase 1/2, open-label clinical trial evaluating MCLA-129 monotherapy in patients with EGFR ex20 NSCLC, MET ex14 NSCLC, and in HNSCC, as well as MCLA-129 in combination with Tagrisso, a third generation EGFR TKI, in patients with treatment-naïve EGFR mutant (m) NSCLC and in patients with EGFRm NSCLC that have progressed on Tagrisso.
In April, Merus provided a pre-clinical presentation of MCLA-129 in comparison with amivantamab at the AACR (Free AACR Whitepaper) Annual Meeting 2023. The Company plans to provide an initial clinical data update from the expansion cohorts, and a further clinical development strategy update in the second half of 2023.
MCLA-129 is subject to a collaboration and license agreement with Betta Pharmaceuticals Co. Ltd. (Betta), which permits Betta to develop MCLA-129 and potentially commercialize exclusively in China, while Merus retains global rights outside of China.
In July, the National Medical Products Administration in China approved the investigational new drug application permitting Betta to investigate the combination of MCLA-129 and befotertinib, a third generation EGFR tyrosine kinase inhibitor, in adult patients in China that have locally advanced or metastatic NSCLC, with an EGFR Exon 19 deletion mutation or Exon 21 (L858R) substitution mutation.
MCLA-145 (CD137 x PD-L1 Biclonics): Solid Tumors
Enrollment continues in the phase 1 trial, including in combination with Keytruda (pembrolizumab), a PD-1 inhibitor
MCLA-145 is in clinical development in a global, phase 1, open-label, clinical trial evaluating MCLA-145 in patients with solid tumors. The trial is in the dose expansion phase evaluating the combination of MCLA-145 with Keytruda, with enrollment ongoing.
Collaborations
Incyte Corporation
Since 2017, Merus has been working with Incyte Corporation (Incyte) under a global collaboration and license agreement focused on the research, discovery and development of bispecific antibodies utilizing Merus’ proprietary Biclonics technology platform. The agreement grants Incyte certain exclusive rights for up to ten bispecific and monospecific antibody programs. The collaboration is progressing, with multiple programs in various stages of preclinical and clinical development. For each program under the collaboration, Merus receives reimbursement for research activities and is eligible to receive potential development, regulatory and commercial milestones and sales royalties for any products, if approved. Further, Incyte announced, in 2023, that INCA33890, a novel TGFBr2xPD1 bispecific antibody developed through the collaboration is currently being evaluated in clinical studies. In July 2023, Merus achieved a milestone and expects a payment of $2.5 million related to the advancement of this program in the third quarter of 2023.
Loxo Oncology at Lilly
In January 2021, Merus and Loxo Oncology at Lilly, a research and development group of Eli Lilly and Company (Lilly), announced a research collaboration and exclusive license agreement to develop up to three CD3-engaging T-cell re-directing bispecific antibody therapies utilizing Merus’ Biclonics platform and proprietary CD3 panel along with the scientific and rational drug design expertise of Loxo Oncology at Lilly. The collaboration is progressing with multiple active research programs underway.
Cash Runway, existing cash, cash equivalents and marketable securities expected to fund Merus’ operations into 2026
As of June 30, 2023, Merus had $311.5 million cash, cash equivalents and marketable securities. Based on the Company’s current operating plan, the existing cash, cash equivalents and marketable securities are expected to fund Merus’ operations into 2026.
Second Quarter 2023 Financial Results
We ended the second quarter with cash, cash equivalents and marketable securities of $311.5 million compared to $326.7 million at December 31, 2022.
Collaboration revenue for the three months ended June 30, 2023 decreased by $2.2 million as compared to the three months ended June 30, 2022, primarily as a result of decreases in reimbursement revenue of $0.5 million, milestone revenue of $1.0 million and amortization of deferred revenue of $0.7 million.
Research and development expense for the three months ended June 30, 2023 decreased by $2.8 million as compared to the three months ended June 30, 2022, primarily as a result of decreases in external clinical services and drug manufacturing costs, including costs to fulfill our obligations under our collaboration agreements, related to our programs of $3.8 million and a decrease in facilities costs of $0.5 million, partially offset by an increase in personnel related expenses including stock-based compensation of $1.5 million due to an increase in employee headcount.
General and administrative expense for the three months ended June 30, 2023 increased by $3.4 million as compared to the three months ended June 30, 2022, primarily as a result of increases in facilities costs including depreciation of $1.6 million, consulting costs of $1.2 million, IP and license costs of $0.4 million, and travel expenses of $0.4 million, partially offset by a decrease in finance and human resources costs of $0.2 million.
Collaboration revenue for the six months ended June 30, 2023 decreased by $0.3 million as compared to the six months ended June 30, 2022, primarily as a result of a decrease in reimbursement revenue of $0.9 million, decrease of amortization of deferred revenue of $0.9 million partially offset by an increase in milestone revenue of $1.5 million.
Research and development expense for the six months ended June 30, 2023 increased by $5.1 million as compared to the six months ended June 30, 2022, primarily as a result of increases in personnel related expenses including stock-based compensation of $3.7 million, external clinical services and drug manufacturing costs, including costs to fulfill our obligations under our collaboration agreements, related to our programs of $1.6 million, consulting expenses of $0.6 million, and consumables expenses of $0.3 million and travel costs of $0.2 million, partially offset by decreases in facilities costs of $0.8 million and partner expenses of $0.5 million. General and administrative expense for the six months ended June 30, 2023 increased by $7.0 million as compared to the six months ended June 30, 2022, primarily as a result of increases in consulting costs of $3.6 million, facilities costs including depreciation of $2.8 million, travel costs of $0.6 million, personnel related expenses including stock-based compensation of $0.5 million due to an increase in employee headcount, and IP and license costs of $0.3 million, partially offset by decreases in finance and human resources costs of $0.8 million.
Other income (loss), net consists of interest earned and fees paid on our cash and cash equivalents held on account, accretion of investment earnings and net foreign exchange (losses) gains on our foreign denominated cash, cash equivalents and marketable securities. Other gains or losses relate to the issuance and settlement of financial instruments.