MCLA-145 / Merus - LARVOL DELTA

MCLA-145-CL01: A Study of Bispecific Antibody MCLA-145 in Patients With Advanced or Metastatic Malignancies (clinicaltrials.gov) - P1 | N=72 | Completed | Sponsor: Merus N.V. | Active, not recruiting ➔ Completed | N=238 ➔ 72 | Trial completion date: Dec 2025 ➔ Nov 2024 | Trial primary completion date: Dec 2025 ➔ Nov 2024

Enrollment change • Metastases • Trial completion • Trial completion date • Trial primary completion date • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

MCLA-145-CL01: A Study of Bispecific Antibody MCLA-145 in Patients with Advanced or Metastatic Malignancies (clinicaltrials.gov) - P1 | N=238 | Active, not recruiting | Sponsor: Merus N.V. | Recruiting ➔ Active, not recruiting | N=118 ➔ 238 | Trial completion date: Dec 2022 ➔ Dec 2025 | Trial primary completion date: Dec 2022 ➔ Dec 2025

Enrollment change • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Phase I study of MCLA-145, a bispecific antibody targeting CD137 and PD-L1, in solid tumors, as monotherapy or in combination with pembrolizumab. (ASCO 2024) - P1 | "MCLA-145 given alone or in combination with pembrolizumab had a well-tolerated and manageable safety profile with encouraging clinical activity, including in pts who relapsed after PD-(L)1 therapies."

Combination therapy • Monotherapy • P1 data • Anemia • Brain Cancer • CNS Tumor • Constipation • Cough • Fatigue • Febrile Neutropenia • Gastric Cancer • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Glioblastoma • Hematological Disorders • Immunology • Lung Cancer • Merkel Cell Carcinoma • Myositis • Neutropenia • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Sarcoma • Skin Cancer • Solid Tumor • CD8 • TNFRSF9

Merus Presents Interim Data on MCLA-145 Monotherapy and in Combination with Pembrolizumab at the 2024 ASCO Annual Meeting (GlobeNewswire) - P1 | N=118 | NCT03922204 | Sponsor: Merus N.V. | "Merus...announced updated interim clinical data on MCLA-145 monotherapy and in combination with pembrolizumab were presented at the 2024...ASCO Annual Meeting....As of a January 3, 2024 data cutoff date, 72 pts with multiple cancer types were treated; 25% of pts had non-small cell lung cancer (NSCLC)....In monotherapy, 52 pts with a variety of tumor types and treated at different dose levels were evaluable for response: 5 partial responses (PRs) were observed at different dose levels in glioblastoma (ongoing as of the cutoff date for >3 years), sarcoma (pretreated with pazopanib and gemcitabine/docetaxel), cervical, anal, and gastric cancer by Response Evaluation Criteria in Solid Tumors v1.1. per investigator assessment....In combination with pembrolizumab, 19 pts with a variety of tumor types and treated at different dose levels were evaluable for response: 1 PR in Merkel cell carcinoma was observed at 25 mg Q3W."

P1 data • Anal Carcinoma • Cervical Cancer • Gastric Cancer • Glioblastoma • Non Small Cell Lung Cancer • Sarcoma

Merus Announces Publication of Abstracts for Presentation at the 2024 ASCO Annual Meeting (GlobeNewswire) - P1 | N=118 | NCT03922204 | Sponsor: Merus N.V. | "Merus N.V...announced the publication of an abstract regarding MCLA-145 and an abstract regarding MCLA-129 at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting taking place in Chicago May 31-June 4, 2024....5 partial responses (PRs) were observed in a variety of tumor types including: glioblastoma (ongoing>3 years), sarcoma, cervical, anal, and gastric cancer (treated for 2-11 month (mo)) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. per investigator assessment. Combination: 19 pts were treated with MCLA-145 10, 25 or 40 mg plus pembrolizumab Q3W: The RDE was established at 40 mg Q3W."

P1 data • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Merus Announces Abstracts Accepted for Presentation at the 2024 ASCO Annual Meeting (GlobeNewswire) - "Merus...announced the acceptance of three abstracts for presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting....Petosemtamab in combination with pembrolizumab in 1L HNSCC initial interim clinical data selected for rapid oral session presentation. MCLA-145 as monotherapy or in combination with pembrolizumab in solid tumors initial interim clinical data selected for rapid oral session presentation. MCLA-129 in NSCLC with c-MET exon 14 skipping mutations initial interim clinical data selected for poster presentation."

Clinical data • Non Small Cell Lung Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A Human CD137×PD-L1 Bispecific Antibody Promotes Anti-Tumor Immunity via Context-Dependent T Cell Costimulation and Checkpoint Blockade (IO-SUMMIT EUROPE 2023) - "MCLA-145 shows enhanced T cell priming and can promote long-term T cell immunity. In vivo, MCLA-145 demonstrates anti-tumor activity superior to the current standard immune checkpoint inhibitor comparators."

Checkpoint block • Checkpoint inhibition • Immune Modulation • Oncology • PD-L1 • TNFRSF9

[VIRTUAL] MCLA-145 (CD137xPD-L1): a potent CD137 agonist and immune checkpoint inhibitor that that does not show signs of peripheral toxicity. (SITC 2020) - P1 | "Conclusions Conditional activation of CD137 signaling by MCLA-145, triggered by a neighboring target cell expressing of PD-L1, may provide both improved efficacy and safety. MCLA-145 is currently undergoing clinical investigation (NCT03922204)."

Checkpoint inhibition • Late-breaking abstract • Oncology • CD8 • IFNG

[VIRTUAL] MCLA-145 is a bispecific IgG1 antibody that inhibits PD-1/PD-L1 signaling while simultaneously activating CD137 signaling on T cells (SITC 2020) - P1 | "Conclusions These experiments demonstrate the dual anti-cancer activity of MCLA-145 in preclinical models: release of T-cell checkpoint inhibition through PD-L1; and activation and expansion of T cells through CD137, therefore overcoming T-cell exhaustion and increasing T-cell presence/activity (infiltration) in tumors. MCLA-145 is currently undergoing clinical development in an ongoing trial (NCT03922204)."

IO Biomarker • Late-breaking abstract • Oncology • TNFA

[VIRTUAL] MCLA-145 is a bispecific IgG1 antibody that inhibits PD-1/PD-L1 signaling while simultaneously activating CD137 signaling on T cells (SITC 2020) - P1 | "Conclusions These experiments demonstrate the dual anti-cancer activity of MCLA-145 in preclinical models: release of T-cell checkpoint inhibition through PD-L1; and activation and expansion of T cells through CD137, therefore overcoming T-cell exhaustion and increasing T-cell presence/activity (infiltration) in tumors. MCLA-145 is currently undergoing clinical development in an ongoing trial (NCT03922204)."

IO Biomarker • Late-breaking abstract • Oncology • TNFA

[VIRTUAL] MCLA-145 (CD137xPD-L1): a potent CD137 agonist and immune checkpoint inhibitor that that does not show signs of peripheral toxicity. (SITC 2020) - P1 | "Conclusions Conditional activation of CD137 signaling by MCLA-145, triggered by a neighboring target cell expressing of PD-L1, may provide both improved efficacy and safety. MCLA-145 is currently undergoing clinical investigation (NCT03922204)."

Checkpoint inhibition • Late-breaking abstract • Oncology • CD8 • IFNG

Identification and characterization of MCLA-145 (CD137 x PD-L1): A bispecific antibody that requires PD-L1 binding to activate CD137. (SITC 2019) - P1; "MCLA-145 is currently undergoing clinical development (NCT03922204)."

IO Biomarker • PD(L)-1 Biomarker

MCLA-145, an anti CD137×PD-L1 Bispecific antibody, induces T cell activation and proliferation in ex vivo models of hepatocellular carcinoma (SITC 2022) - "Additionally, TIL proliferation upon either anti-CD3/CD28 stimulation or autologous B cell blasts electroporated with tumor-associated antigens (TAA) glypican-3 (GPC3) and/or melanoma-associated antigen (MAGE)-C2 stimulation was assessed ex vivo in presence of MCLA-145, its bivalent monospecific parental mAbs, the bivalent mAbs urelumab (anti-CD137) or atezolizumab (anti-PD-L1) or isotype control. Conclusions Biclonics ® antibody MCLA-145 has the capacity to enhance activation and proliferation of tumor-derived CD8+ T cells in the PD-L1 expressing tumor microenvironment of HCC ex vivo , warranting further evaluation in HCC. Ethics Approval Ethical approval (METC) for this study has been obtained."

IO biomarker • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Melanoma • Oncology • Solid Tumor • CD8 • FCGR2A • GPC3 • PD-1

Phase I Dose Escalation Study of MCLA-145, a Bispecific Antibody Targeting CD137 and PD-L1 in Solid Tumors (ESMO-IO 2021) - P1 | "Legal entity responsible for the study The authors, Incyte Corporation, and Merus NV. Funding This study was funded by Incyte Corporation, Wilmington, DE, USA, and Merus NV, Utrecht, Netherlands."

P1 data • Oncology • Solid Tumor • TNFRSF9

"$INCY Incyte Provides Update on Parsaclisib and MCLA-145 https://t.co/F9mtMMtKV8" (@stock_titan)

Merus Appoints Shannon Campbell as Chief Commercial Officer and Regains Worldwide Rights to MCLA-145 (GlobeNewswire) - "Merus also announced today that Incyte (Nasdaq: INCY) has elected to opt-out of its ex-U.S. development of MCLA-145, restoring full global rights to Merus....Incyte’s opt-out of ex-U.S. rights to MCLA-145 provides Merus the exclusive right to develop and commercialize potential MCLA-145 products globally....Additionally, per the Agreement, the parties will continue to collaborate on the development and commercialization of up to ten bispecific or monospecific antibody programs."

Licensing / partnership • Oncology • Solid Tumor

"$UCB: bimekizumab Ph3 data in PSA and axial spondyloarthritis $UCB: zilucoplan Ph3 data in MG - Q4'21 Conferences #AES2021 - 3-7 Dec #ESMOImmuno21 - 8-12 Dec - $MRUS will present first Ph1/2 data for MCLA-145 in solid tumors - $ACHL will present manufacturing updates 2/3" (@KempenLS)

Ankylosing Spondylitis • Immunology • Oncology • Seronegative Spondyloarthropathies • Solid Tumor • Spondylarthritis

Merus Presents Clinical Data on MCLA-145 at the ESMO Immuno-Oncology Congress 2021 (GlobeNewswire) - P1, N=118; NCT03922204; Sponsor: Merus N.V; "Observations in the presentation include: As of the data cutoff date of July 14, 2021, 34 patients with advanced or metastatic solid tumors with median age of 60.5 (range 27-81) years have been treated at 8 dose levels ranging from 0.4-75mg Q2W; Median (range) duration of treatment with MCLA 145 was approximately 6 (1–74) weeks. Reported adverse events (AEs) have been managed with drug interruption and/or administration of steroids in some patients. Treatment-emergent AEs (TEAEs) occurred in 33 patients (97.1%); treatment-related TEAEs occurred in 23 patients (67.6%), most commonly fatigue (n=6, 17.6%) and decreased neutrophil count (n=6, 17.6%)...Peripheral blood shows robust T-cell activation, including activation of cytotoxic CD8+ cells and cytokines, across the 10 to 75 mg biweekly dosing range. Further evaluation of optimal dose and efficacy in PD-L1+ tumors is planned."

P1 data • Oncology • Solid Tumor

Merus Announces Poster Presentation on Clinical Data on MCLA-145 at the ESMO Immuno-Oncology Congress 2021 (GlobeNewswire) - "Merus N.V...announced the publication of the abstract highlighting interim data, as of a July 14, 2021 cutoff, from the phase 1/2 trial of bispecific antibody MCLA-145 in patients with solid tumors. The e-poster will be presented at the ESMO Immuno-Oncology (ESMO IO) Congress 2021 being held December 8-11, 2021 in Geneva, Switzerland."

P1 data • Oncology • Solid Tumor

Merus Announces Regulatory Update on Zenocutuzumab, Financial Results for the Third Quarter and Provides Business Update (GlobeNewswire) - "MCLA-158 (petosemtamab: Lgr5 x EGFR Biclonics®): Solid Tumors; Dose expansion continues in the phase 1 trial: update planned for 2022...MCLA-145 (CD137 x PD-L1 Biclonics®): Solid Tumors: Phase 1 trial continues: update planned for ESMO Immuno-Oncology Congress 2021."

P1 data • Oncology • Solid Tumor

Merus Announces Financial Results for the Second Quarter and Provides Business Update (GlobeNewswire) - "MCLA-145 (CD137 x PD-L1 Biclonics®): Solid Tumors; Phase 1 trial continues: update planned for Q4’21....MCLA-129 (EGFR x c-MET Biclonics®): Solid Tumors; The phase 1/2, open-label, single-agent clinical trial of MCLA-129 is ongoing and consists of a dose escalation phase, to be followed by planned expansion cohorts evaluating MCLA-129 for the treatment of patients with advanced non-small cell lung cancer (NSCLC) and other solid tumors."

New P1 trial • Trial status • Oncology • Solid Tumor

A human CD137×PD-L1 bispecific antibody promotes anti-tumor immunity via context-dependent T cell costimulation and checkpoint blockade. (PubMed, Nat Commun) - "Non-human primates treated with 100 mg/kg/week of MCLA-145 show no adverse effects. The conditional activation of CD137 signaling by MCLA-145, triggered by neighboring cells expressing >5000 copies of PD-L1, may provide both safety and potency advantages."

Checkpoint inhibition • Journal • Graft versus Host Disease • Immune Modulation • Immunology • Inflammation • Oncology • CD8 • TNFRSF9

Merus Announces Publication in Nature Communications on MCLA-145’s Novel Mechanism of Action Promoting Tumor Immunity and Context Dependent T-Cell Costimulation (GlobeNewswire) - “Merus N.V…announced the novel mechanism of action (MOA) of MCLA-145, the Company’s clinical stage Biclonics® T-cell agonist…MCLA-145 was identified by screening hundreds of bispecific IgG antibodies for immune activation via PD-L1 engagement among other characteristics. MCLA-145 was shown to potently activate T cells even in the presence of suppressive conditions. Furthermore, MCLA-145 was shown to enhance T cell priming and to promote long-term T cell immunity.”

Clinical • Oncology • Solid Tumor

Merus Announces Financial Results for the Fourth Quarter and Full Year 2020 and Provides Business Update (GlobeNewswire) - "Clinical Programs and Business Update: (i) Zenocutuzumab, or 'Zeno' (MCLA-128: HER3 x HER2 Biclonics®): NRG1 gene fusion (NRG1+) Cancers - Phase 1/2 eNRGy trial clinical data and program update planned for Q2 2021; (2) MCLA-145 (CD137 x PD-L1 Biclonics®): Solid Tumors - Phase 1 trial advancing with clinical update planned for 2H 2021; (3) MCLA-129 (EGFR x c-MET Biclonics®): Solid Tumors - First patient planned to be dosed in 2021."

P1 data • P1/2 data • Trial status • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Data from Incyte’s Oncology Portfolio Accepted for Presentation at the Society for Immunotherapy of Cancer 2020 Annual Meeting (Businesswire) - “Incyte…announced that abstracts highlighting data from its oncology portfolio will be presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting, held virtually from November 11-14, 2020…‘In particular, initial translational data from the ongoing clinical trial support further development of our orally administered PD-L1 inhibitor INCB86550 — a novel small-molecule discovered at Incyte.’”

Clinical data • Endometrial Cancer • Microsatellite Instability • Oncology • Solid Tumor