MP0317 / Molecular Partners - LARVOL DELTA

MP0317, a tumor-targeting FAP-dependent CD40 agonist DARPin, in combination with chemoimmunotherapy in first-line treatment for patients with advanced biliary tract carcinoma: A randomized non-comparative proof- of-concept phase II study (ESMO 2026) - No abstract available

Clinical • Combination therapy • Metastases • P2 data • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • CD40

Tumor-localized CD40 agonism with MP0317, a FAP x CD40 DARPin, reprograms the tumor microenvironment in patients with advanced solid tumors: an open-label, nonrandomized, dose-escalation phase 1 study. (PubMed, Nat Cancer) - P1 | "Collectively, these data confirm a favorable safety profile for MP0317 and support further clinical evaluation in combination with complementary immunotherapies. ClinicalTrials.gov registration: NCT05098405 ."

Biomarker • IO biomarker • Journal • P1 data • Oncology • Solid Tumor • CD40 • IFNG

Molecular Partners AG…announces the dosing of first patients in an investigator-initiated Phase 2 proof-of-concept (POC) study of MP0317 in combination with chemoimmunotherapy in first line treatment for patients with advanced biliary tract carcinoma (TACTIC), also known as cholangiocarcinoma. (The Manila Times) - "Nine expert trial sites are now activated and patient treatment is ongoing. A data update from the trial is expected in 2027, and completion of the study in 2028. A trial-in-progress poster on the MP0317 Phase 2 study has been accepted for presentation at the European Society for Medical Oncology (ESMO) Congress 2026, taking place October 23-27 in Madrid, Spain."

P2 data • Trial completion date • Trial status • Cholangiocarcinoma

Molecular Partners AG…announced the publication of Phase 1 clinical data in Nature Cancer demonstrating the potential of the tumor-localized CD40 agonist, (Molecular Partners Press Release) - "The comprehensive biomarker data confirm proof-of-mechanism for MP0317, including tumor-localized activation of the CD40 pathway and evidence of TME remodeling in patients with advanced solid tumors. MP0317 displayed a favorable safety profile up to the highest tested dose and serum pharmacokinetics confirmed suitability for dosing either weekly or every three weeks. Of the 46 patients in the study, one patient achieved an unconfirmed partial response and 14 patients stable disease in this heterogeneous population with advanced diseases."

First-in-human • P1 data • Solid Tumor

MP0712, the first anti-DLL3 212Pb radio-DARPin (RDT) candidate for targeted radiotherapy of small cell lung cancer (SCLC) (AACR 2025) - "In NCI-H82 tumors, median survival duration increased up to 3-fold with MP0317 compared with the buffer control. MP0712 also showed a favorable safety profile in vivo up to 30µCi. These preclinical results support our 212Pb-based RDT against DLL3 as a promising treatment option for SCLC, with encouraging in vivo antitumor activity and a good safety profile for our first DLL3-targeting 212Pb-RDT candidate for further development into the clinic."

Lung Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • DLL3

2024/926: TACTIC : MP0317, A TUMOR TARGETING FAP DEPENDENT CD40 AGONIST DARPIN, IN COMBINATION WITH CHEMOIMMUNOTHERAPY IN FIRST LINE TREATMENT FOR PATIENTS WITH ADVANCED BILIARY TRACT CARCINOMAnA RANDOMIZED NON COMPARATIVE PROOF OF CONCEPT PHASE II STUDY (clinicaltrialsregister.eu) - P1/2 | N=75 | Recruiting | Sponsor: Centre Hospitalier Regional Universitaire

New P1/2 trial • Biliary Cancer • Biliary Tract Cancer • Gallbladder Cancer • Oncology • Solid Tumor

TACTIC: MP0317 in Combination With Chemoimmunotherapy in First Line Treatment for Patients With Advanced Biliary Tract Carcinoma (clinicaltrials.gov) - P2 | N=75 | Recruiting | Sponsor: Centre Hospitalier Universitaire de Besancon | Not yet recruiting ➔ Recruiting | Trial completion date: Jun 2029 ➔ Nov 2029 | Initiation date: Jun 2025 ➔ Dec 2025 | Trial primary completion date: Jun 2028 ➔ Nov 2028

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Oncology • Solid Tumor

Molecular Partners is supporting an investigator-initiated trial of MP0317, for which a study protocol has been approved (NCT07036380) (GlobeNewswire) - "This proof-of-concept randomized Phase 2 study, to be conducted by an expert network in France, is designed for the treatment of patients with advanced cholangiocarcinoma in combination with anti-PD-L1 therapy (durvalumab) and gemcitabine-cisplatin-based chemotherapy. The main objective of the study is to assess the 12-month progression free survival (PFS) in the experimental arm (N = 50 patients)."

Trial status • Biliary Tract Cancer • Cholangiocarcinoma

TACTIC: MP0317 in Combination With Chemoimmunotherapy in First Line Treatment for Patients With Advanced Biliary Tract Carcinoma (clinicaltrials.gov) - P2 | N=75 | Not yet recruiting | Sponsor: Centre Hospitalier Universitaire de Besancon

New P2 trial • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor

Molecular Partners Reports Financial Results and Highlights from Q1 2025 (GlobeNewswire) - "Molecular Partners is in discussion with leading academic centers regarding potential investigator-initiated trials of MP0317 in 2025, in combination with immune checkpoint inhibitors and additional standard of care for patients with solid tumors."

New trial • Solid Tumor

Comprehensive biomarker analyses from a phase 1 study reveals marked tumor microenvironment modulation in patients with advanced solid tumors treated with MP0317, a FAP-localized CD40 agonistic DARPin (SITC 2024) - P1 | "Conclusions The biomarker analyses of this Phase 1 study of MP0317 revealed localized CD40 activation within the TME post treatment with doses ≥1.5 mg/kg and demonstrated MP0317`s pharmacodynamic effects, characterized by an increase in antigen-presenting cells, IFNγ signature, plasma and Tfh cells within the TME, alongside correlations between intra-tumoral and peripheral clinical biomarkers. These findings support further clinical investigation of MP0317, in combination with complementary anticancer therapies."

Biomarker • Clinical • IO biomarker • Metastases • P1 data • Tumor microenvironment • Oncology • Solid Tumor • CD40 • CD69 • CXCL10 • CXCL9 • FAP • ICAM1 • IFNG

MP0317: Comprehensive biomarker data further support CD40 activation locally in tumor microenvironment (GlobeNewswire) - P1 | N=46 | NCT05098405 | Sponsor: Molecular Partners AG | "The poster presents the results of a comprehensive biomarker analyses from the completed Phase 1 multi-center, open label, dose-escalation trial of MP0317 monotherapy in patients with advanced solid tumors. The research further demonstrates the ability of MP0317 to induce a targeted, tumor-localized CD40 activation and its suitability for Q3W (every three weeks) and Q1W (weekly) dosing. The CD40 pathway is activated in a broad-spectrum of cancer types and various tumor locations. Evidence of TME remodeling in patients treated with pharmacologically active doses is exemplified by increases in dendritic cells, M1 macrophages, plasma cells, and T follicular helper cells, as well as IFNγ downstream activation and an increased dendritic cell maturation gene signature score."

Biomarker • P1 data • Solid Tumor

Molecular Partners Announces upcoming poster presentations at the 2024 SITC Annual Meeting (GlobeNewswire) - "Molecular Partners AG...today announced that the Company will introduce proof-of-concept data for its new CD3 Switch-DARPin designed to overcome current T cell engager challenges in solid tumors, as well as present additional analyses from its Phase 1 study of MP0317 in patients with advanced solid tumors, at the 2024 Annual Meeting of the Society for Immunotherapy of Cancer (SITC), being held November 8-10 in Houston, TX."

P1 data • Preclinical • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Transcriptomic analysis from a Phase 1 clinical trial of the effects of MP0317, a FAP localized CD40 agonist DARPin, shows profound changes in the tumor microenvironment (CRI-ENCI-AACR ICIC 2024) - P1 | "Conclusions We used single cell data analysis and ex vivo experiments to derive gene signatures to be used as pharmacodynamics biomarkers in a clinical trial of MP0317, a FAP-dependent CD40 engaging DARPin. Our transcriptomics analysis of patient biopsies pre and post treatment with MP0317 showed that this molecule remodels the tumor microenvironment by inducing infiltration of B, plasma, dendritic and T follicular helper cells."

Biomarker • Clinical • IO biomarker • Omic analysis • P1 data • Tumor microenvironment • Oncology • Solid Tumor • CD40 • CD8 • FAP • IFNG

Effect of MP0317, a FAP x CD40 DARPin, on safety profile and tumor-localized CD40 activation in a phase 1 study in patients with advanced solid tumors. (ASCO 2024) - P1 | "MP0317 had a favorable safety profile in 46 patients across all 9 dose-escalation cohorts exploring Q3W and Q1W regimens. Doses ≥1.5 mg/kg showed evidence of pharmacodynamic TME modulation, indicating tumor-localized CD40 activation. The data support further clinical evaluation of MP0317 including combination with complementary anticancer therapies."

Clinical • IO biomarker • Metastases • P1 data • Anorexia • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Oncology • Solid Tumor • CD40 • CXCL10 • FAP • IFNG

Molecular Partners Presents Positive Data From Completed Phase 1 Trial Of MP0317 (FAP X CD40 DARPin) Monotherapy In Patients With Advanced Solid Tumors At ASCO 2024 (GlobeNewswire) - P1 | N=46 | NCT05098405 | Sponsor: Molecular Partners AG | "Molecular Partners AG...today announced it had presented the final data from its Phase 1 dose-escalation study of MP0317 at the American Society of Clinical Oncology (ASCO) Annual Meeting 2024, held in Chicago, IL, USA...In terms of clinical response, one patient achieved an unconfirmed partial response and stable disease was observed in 14 additional patients...MP0317 displayed a favorable and manageable safety profile across all nine planned dosing cohorts...The most frequently observed adverse reactions were fatigue and lower grade infusion-related reactions (grade 1–2). Dose-limiting toxicity was reported in one patient...at the highest planned dose of 10 mg/kg administered Q3W."

P1 data • Oncology • Solid Tumor

MOLECULAR PARTNERS REPORTS CORPORATE HIGHLIGHTS FROM Q4 2023 AND KEY FINANCIALS FOR FULL YEAR 2023 (Molecular Partners Press Release) - "Data from the Phase 1/2a trial of MP0533, including safety and efficacy, to be presented in H1 2024; expansion of enrollment to higher dose cohorts planned in H2 2024; Initial preclinical data from first Switch-DARPin program cKIT x CD16a x CD47 expected in H1 2024; preclinical proof-of-concept studies expected in H2 2024, which should provide strong translational efficacy data; The full dataset from the MP0317 Phase 1 dose-escalation trial expected in H1 2024."

P1/2 data • Preclinical • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

MP0317-CP101: First-in-human Safety and Tolerability of MP0317 in Patients With Relapsed/Refractory Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=46 | Terminated | Sponsor: Molecular Partners AG | N=78 ➔ 46 | Recruiting ➔ Terminated; After completion of the dose-escalation part of the study, the safety profile of MP0317 in monotherapy is considered adequately characterized in the dose-escalation part of the study.

Enrollment change • Metastases • Trial termination • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • MSI

Molecular Partners to Present on DARPin Oncology Innovations at Protein & Antibody Engineering Summit Europe (PEGS) (GlobeNewswire) - "Molecular Partners AG...will present on several of its programs at the 15th Annual Protein & Antibody Engineering European Summit (PEGS Europe), which runs November 14-16 in Lisbon, Portugal....The presentation consists of a review of several differentiated mechanisms of action that leverage the DARPin platform...MP0317, a CD40 agonist, is designed to activate immune cells specifically within the tumor microenvironment by anchoring to fibroblast activation protein (FAP), which is highly expressed on tumor cells....MP0533, a novel tetra-specific DARPin for the treatment of patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (AML/MDS), engages CD3 on T cells and targets three tumor-associated antigens (TAAs) CD33, CD123, and CD70."

Clinical data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor

Ongoing phase 1 study of MP0317, a FAP-CD40 DARPin, shows a favorable safety profile and early evidence of tumor-localized CD40 activation in patients with advanced solid tumors (SITC 2023) - P1 | "Analysis of paired tumor biopsies and peripheral biomarkers provided evidence of target occupancy and pharmacodynamic modulation in the TME, consistent with tumor-localized CD40 activation. These data support continued clinical evaluation of MP0317, including combination studies."

Clinical • IO biomarker • Metastases • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD40 • CXCL10 • FAP • IFNG

Molecular Partners Presents Updated Positive Data from Ongoing Phase 1 Trial of MP0317 (FAP X CD40) Monotherapy in Patients with Advanced Solid Tumors at the 2023 SITC Annual Meeting (GlobeNewswire) - P1 | N=78 | NCT05098405 | Sponsor: Molecular Partners AG | "Molecular Partners AG...will present additional positive data from its Phase 1 study of MP0317 in patients with advanced solid tumors at the 2023 Annual Meeting of the Society for Immunotherapy of Cancer (SITC), being held November 1–5 in San Diego, California....The detection of MP0317 in tumor biopsies is associated with an increase in CD40-mediated re-programming of immune cells illustrated by IFNg production and dendritic cell (DC) maturation within the TME. Elevation of serum levels of CXCL10, an effector chemokine downstream of IFNg signaling, and changes in soluble biomarkers (sFAP & sCD40) post-MP0317 treatment support these findings. To date, one patient achieved a partial response and stable disease was observed in eight additional patients....The Company expects to share final results of this study in 2024."

P1 data • Oncology • Solid Tumor

MOLECULAR PARTNERS INTERIM MANAGEMENT STATEMENT Q3 2023: CONTINUED VALIDATION SEEN ACROSS THE DARPIN PORTFOLIO (Molecular Partners Press Release) - "Recruitment in the MP0533 Phase 1/2a trial in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome/AML (MDS/AML) is on track, with patients presently being treated at dose regimen five. Initial safety and activity data from this ongoing clinical trial will be presented at the American Society of Hematology (ASH) Annual Meeting and Exposition in December 2023. Additional data are expected to be presented in H1 2024....The Company has completed patient recruitment of the ongoing MP0317 dose escalation portion of the Phase 1 trial in patients with advanced solid tumors at the highest planned doses and will present latest results from this ongoing trial at the Society for Immunotherapy of Cancer (SITC) Annual Meetings on November 3, 2023....Final data of this Phase 1 study are anticipated in H1 2024."

Enrollment status • P1 data • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor

Potentiating Local and Abscopal Antitumor Efficacy through Radiation with FAP-CD40 DARPin and Anti-PD1 Therapy (ASTRO 2023) - "Human FAPxCD40 (MP0317) is being evaluated in Phase I trials... mFAP-CD40 DARPin with RT and a-PD1 proved efficacious to control primary and secondary tumors in a murine lung carcinoma model with no detected toxicities."

Clinical • IO biomarker • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD40 • FAP

Potentiating Local and Abscopal Antitumor Efficacy through Radiation with FAP-CD40 DARPin and Anti-PD1 Therapy. (PubMed, Int J Radiat Oncol Biol Phys) - "mFAP-CD40 DARPin with RT and α-PD1 proved efficacious to control primary and secondary tumors in a murine lung carcinoma model with no detected toxicities."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD40 • FAP

Phase I study of MP0317, a FAP-dependent DARPin, for tumor-localized CD40 activation in patients with advanced solid tumors. (ASCO 2023) - P1 | "Clinical data and the lack of pro-inflammatory circulating cytokines confirm MP0317 is safe and well-tolerated, while analysis of paired pre- and on-treatment tumor biopsies suggests early evidence of tumor-localized CD40 activation. The current data enables further evaluation in a combination setting. Clinical trial information: NCT05098405."

Clinical • IO biomarker • Metastases • P1 data • Immune Modulation • Oncology • Solid Tumor • CCL20 • CCR6 • CD40 • CXCL10 • CXCL3 • CXCL8 • CXCL9 • CXCR5 • IFNG • IL2 • IL6 • TNFA