On November 26, 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 the publication of two abstracts regarding MCLA-129 on the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia Congress website (Press release, Merus, NOV 26, 2023, View Source [SID1234637963]). The abstracts highlight updated interim clinical data from expansion cohorts in non-small cell lung cancer (NSCLC) and in previously treated head and neck squamous cell carcinoma (HNSCC) for presentation at the ESMO (Free ESMO Whitepaper) Asia Congress 2023 taking place in Singapore December 1-3, 2023.

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"MCLA-129 is now the third asset, together with our other clinical assets petosemtamab and zenocutuzumab, developed from the Merus proprietary Biclonics platform to demonstrate strong clinical activity," said Bill Lundberg, M.D., President, Chief Executive Officer of Merus. "As we continue the development of MCLA-129, we are planning to take a disciplined capital allocation approach, making focused investments in the program to identify areas of potential differentiation. We remain open to potential business development opportunities as a means to leverage added resources, infrastructure and expertise of a potential partner to more fully evaluate and develop MCLA-129."

MCLA-129 (EGFR x c-MET Biclonics): Solid Tumors
Interim data included in the abstracts describe data from three expansion cohorts in the open label trial evaluating MCLA-129 in combination with osimertinib, a third generation EGFR TKI, in treatment-naïve EGFR mutant (m) NSCLC and in EGFRm NSCLC that has progressed on osimertinib, as well as MCLA-129 monotherapy in previously treated HNSCC.

Updated clinical data, with additional patients and a later data cutoff date, will be included in the mini-oral presentation on NSCLC and the poster on HNSCC at ESMO (Free ESMO Whitepaper) Asia next week.

Mini-oral presentation title: Efficacy and safety of MCLA-129, an EGFR x c-MET bispecific antibody, combined with osimertinib, as first-line therapy or after progression on osimertinib in non-small cell lung cancer (NSCLC)
Observations in the abstract include:

As of a May 10, 2023 data cutoff date, 48 patients (pts) with advanced/metastatic EGFRm NSCLC were treated (14/1L, 34/2L+)
In the 1L setting, 14 pts were treated, with 10 pts evaluable for response
2 confirmed partial responses (PRs) and 6 unconfirmed PRs were observed (8/10, 80%; 95% CI 44-98) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. per investigator assessment; all responses were ongoing as of the data cutoff date
90% disease control rate (DCR) (95% CI 56-100)
10 weeks (range 2-26) median duration of exposure with 93% continuing treatment
In the 2L+ setting, 34 pts were treated, with 22 pts evaluable for response
All received prior osimertinib in 1L/2L setting, 71% as the most recent therapy; 24% received prior chemotherapy
6 confirmed PRs and 5 unconfirmed PRs were observed (11/22, 50%; 95% CI 28-72) by RECIST v1.1. per investigator assessment; 9 responses were ongoing as of the data cutoff date, including 4 of the unconfirmed PRs
82% DCR (95% CI 60-95)
10 weeks (range 2-38) median duration of exposure with 68% continuing treatment
Early safety assessment in 48 NSCLC pts treated with MCLA-129 plus osimertinib included
Most common adverse events (AEs) regardless of causality were infusion related reactions (IRRs; composite term) in 85% (6% ≥ grade(G) 3)
Skin toxicity (composite term) in 75% (4% G3)
Treatment related interstitial lung disease (ILD)/pneumonitis in five patients (10%), two were G2, two were G3, and one was G5 and one progressed to G5 after the data cutoff date
Venous thromboembolic (VTE) events in 15%; 4% treatment related
Presentation Details:
Session: Thoracic Cancer
Date: Sunday, December 3, 2023
Time: 9:40 -9:45 a.m. SGT
Presentation #: 516MO

Poster presentation title: Efficacy and safety of MCLA-129, an anti-EGFR/c-MET bispecific antibody, in head and neck squamous cell cancer (HNSCC)
Observations in the abstract include:

As of a May 10, 2023 data cutoff date, 18 pts with previously treated HNSCC were treated
Pts received median of two lines prior therapy, 89% prior chemotherapy, 78% prior anti-PD-(L)1, 28% prior cetuximab
12 pts were evaluable for response
2 unconfirmed PRs were observed (2/12, 17%) by RECIST v1.1. per investigator assessment; one response was ongoing as of the data cutoff date
67% DCR (95% CI 35-90%)
8 weeks (range 2-17) median duration of exposure with 50% continuing on treatment
Early safety assessment in 18 HNSCC pts treated with MCLA-129 monotherapy included
Most common AEs regardless of causality were IRRs (composite term) in 72% (28% ≥ G3), all on cycle 1 day 1, that led to treatment discontinuation in two pts
Skin toxicity in 61% (11% G3)
No ILD or VTE events were reported
Presentation details:
Session Category: Poster session
Date: Saturday, December 2, 2023
Time: 17:50-18:45 p.m. SGT
Presentation #: 362P

MCLA-129 Development Strategy
In EGFRm NSCLC, with the strong clinical activity for MCLA-129 shown in the interim data presented today, we are encouraged by the potential for MCLA-129 in the treatment of lung cancer and beyond. We have identified focused investment opportunities. We continue to follow patients with EGFRm NSCLC treated with MCLA-129 in combination with osimertinib, to evaluate potential for biomarkers as a means to maximize efficacy, while proactively addressing safety signals seen to date.

We plan to start a cohort of MCLA-129 in combination with chemotherapy in 2L+ EGFRm NSCLC in the first quarter of next year.

Additionally, we remain interested and are continuing investigation of cohort B evaluating MCLA-129 in patients with MET exon14 skipping NSCLC. We also remain interested in exploring partnering MCLA-129 with other companies to sufficiently resource the development of MCLA-129 and potential benefit it may have for patients.

In HNSCC, based on the interim data, we observed clinical activity with MCLA-129. However, we view the clinical activity with MCLA-129 monotherapy as of the cutoff date as modest, with 2 unconfirmed partial responses or 17%. The safety profile was manageable, and there were no reported ILD or VTE events. Our assessment of this cohort is that the clinical activity of MCLA-129 in second line head and neck cancer appears substantially inferior to that of our lead asset petosemtamab, and only on par with other EGFR or cetuximab-based monoclonal or bispecific antibodies as monotherapy in a similar setting. We believe this efficacy is insufficient to warrant further development in head and neck cancer.

Zenocutuzumab (Zeno or MCLA-128: HER2 x HER3 Biclonics): NRG1 fusion (NRG1+) cancer and other solid tumors
An abstract for an encore of a recent ESMO (Free ESMO Whitepaper) Congress 2023 presentation on zenocutuzumab interim clinical data from the eNRGy trial and Early Access Program in patients with NRG1 fusion (NRG1+) NSCLC has also been accepted for presentation at ESMO (Free ESMO Whitepaper) Asia.

Presentation details:
Title: Durable efficacy of zenocutuzumab, a HER2 x HER3 bispecific antibody, in advanced NRG1 fusion-positive (NRG1+) non-small cell lung cancer (NSCLC)
Session Category: Poster session
Date: Saturday, December 2, 2023
Time: 17:50-18:45 p.m. SGT
Presentation #: 595P

As full presentations become available at the ESMO (Free ESMO Whitepaper) Asia Congress 2023, they will contemporaneously be available on the Merus website.

Company Conference Call and Webcast Information
Merus will hold a conference call and webcast for investors on November 27, 2023 at 8:00 a.m. ET. A replay will be available after the completion of the call in the Investors and Media section of our website for a limited time.

Date and Time: November 27, 2023 at 8:00 a.m. ET
Webcast link: Available on our website
Dial-in: Toll-Free: 1 (800) 715-9871 / International: 1 (646) 307-1963
Conference ID: 2833671