MP0250 / Molecular Partners - LARVOL DELTA

A phase 1b/2 study evaluating efficacy and safety of MP0250, a designed ankyrin repeat protein (DARPin) simultaneously targeting vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), in combination with bortezomib and dexamethasone, in patients with relapsed or refractory multiple myeloma. (PubMed, EJHaem) - P1/2 | "These findings are in line with the results of recent trials testing new agents on comparable patient cohorts and provide initial evidence of clinical benefit for patients with refractory/relapsed MM treated with MP0250 in combination with bortezomib/dexamethasone. Further clinical evaluation in the emerging MM treatment landscape would be required to confirm the clinical potential of MP0250."

Combination therapy • Journal • P1/2 data • Cardiovascular • Hematological Disorders • Hematological Malignancies • Hypertension • Multiple Myeloma • Oncology • Pulmonary Arterial Hypertension • Renal Disease • Solid Tumor • Thrombocytopenia • HGF • VEGFA

First-in-class phase I study evaluating MP0250, a VEGFand HGFneutralizing DARPIN molecule, in patients with advanced solid tumors. (ASCO 2018) - P1/2; "In this FIH study, MP0250 was well tolerated with most AEs being consistent with profound inhibition of the VEGF pathway. Signs of single agent antitumour activity were observed and MP0250 is being further developed in lung cancer and multiple myeloma."

Clinical • P1 data • Lung Cancer • Multiple Myeloma

First-in-class phase I study evaluating MP0250, a VEGFand HGFneutralizing DARPIN molecule, in patients with advanced solid tumors. (ASCO 2018) - P1/2; "In this FIH study, MP0250 was well tolerated with most AEs being consistent with profound inhibition of the VEGF pathway. Signs of single agent antitumour activity were observed and MP0250 is being further developed in lung cancer and multiple myeloma."

Clinical • P1 data • Lung Cancer • Multiple Myeloma

MP0250 IN COMBINATION WITH BORTEZOMIB AND DEXAMETHASONE IN PATIENTS WITH RELAPSED-AND-REFRACTORY MULTIPLE MYELOMA: FIRST SAFETY AND EARLY EFFICACY ANALYSIS OF MP0250-CP201 (EHA 2018) - P1/2; "Early data from patients treated in cohort 1 with MP0250 plus bortezomib + dex show an acceptable safety profile and promising activity in RRMM patients. Enrollment is ongoing and updated data from cohorts 1 (8 mg/kg) and 2 (12 mg/kg) will be presented."

Clinical • Combination therapy • Multiple Myeloma

MP0250 Combined with Bortezomib and Dexamethasone in Multiple Myeloma Patients Previoulsy Exposed to Proteasome Inhibitors and Immunomodulatory Drugs (ASH 2018) - P1/2; "Patients were enrolled to receive iv MP0250 on day 1 + subcutaneous bortezomib 1.3 mg/m² on days 1, 4, 8, 11, oral dexamethasone (dex) 20 mg on days 1-2, 4-5, 8-9, 11-12 of each 21-day cycle. SummaryData from cohort 1 (8 mg/Kg q3w) suggest that MP0250 can be safely combined with bortezomib and dex in patients with relapsed and refractory MM. Durable responses were seen in patients who came from PI based pretreatment suggesting that MP0250 might be capable to reverse PI resistance."

Clinical • Biosimilar • Hematological Disorders • Hematological Malignancies • Hypertension • Immune Modulation • Inflammation • Multiple Myeloma • Oncology • Renal Disease

First-in-class phase I study evaluating MP0250, a VEGF and HGF neutralizing DARPIN molecule, in patients with advanced solid tumors. (ASCO 2018) - P1/2; "In this FIH study, MP0250 was well tolerated with most AEs being consistent with profound inhibition of the VEGF pathway. Signs of single agent antitumour activity were observed and MP0250 is being further developed in lung cancer and multiple myeloma."

Clinical • P1 data • Lung Cancer • Multiple Myeloma

The MP0250-CP201 Mirror Study: A Phase 2 Study Update of MP0250 Plus Bortezomib and Dexamethasone in Relapse/Refractory Multiple Myeloma (RRMM) Patients Previously Exposed to Proteasome Inhibitors and Immunomodulatory Drugs (ASH 2019) - P1/2; "Analysis of the preliminary efficacy results showed an encouraging ORR of 40%. Recruitment to this Phase 2 study is ongoing."

Clinical • P2 data • Hematological Disorders • Hematological Malignancies • Hypertension • Immune Modulation • Inflammation • Multiple Myeloma • Oncology • Renal Disease • Thrombocytopenia • HGF

A Phase 2 Trial of MP0250 Plus Bortezomib + Dexamethasone in Patients With Multiple Myeloma (clinicaltrials.gov) - P1/2; N=33; Completed; Sponsor: Molecular Partners AG; Active, not recruiting ➔ Completed

Clinical • Trial completion • Hematological Malignancies • Multiple Myeloma • Oncology

First-in-Human Phase I Study of MP0250, a First-in-Class DARPin Drug Candidate Targeting VEGF and HGF, in Patients With Advanced Solid Tumors. (PubMed, J Clin Oncol) - "MP0250 is a first-in-class DARPin drug candidate with suitable tolerability and appropriate pharmacokinetic properties for further development in combination with other anticancer therapies."

Clinical • Journal • P1 data • Hypertension • Oncology • Renal Disease • Solid Tumor

A Phase 2 Trial of MP0250 Plus Bortezomib + Dexamethasone in Patients With Multiple Myeloma (clinicaltrials.gov) - P1/2; N=33; Active, not recruiting; Sponsor: Molecular Partners AG; Trial completion date: Jul 2023 ➔ Jan 2021; Trial primary completion date: Oct 2021 ➔ Nov 2020

Clinical • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

A Phase 2 Trial of MP0250 Plus Bortezomib + Dexamethasone in Patients With Multiple Myeloma (clinicaltrials.gov) - P1/2; N=33; Active, not recruiting; Sponsor: Molecular Partners AG; Recruiting ➔ Active, not recruiting; N=54 ➔ 33

Clinical • Enrollment change • Enrollment closed • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

MP0250 DARPin® Protein Plus Osimertinib in Patients With EGFR-mutated NSCLC (clinicaltrials.gov) - P1b/2; N=8; Terminated; Sponsor: Molecular Partners AG; N=40 ➔ 8; Trial completion date: Jul 2021 ➔ Apr 2020; Active, not recruiting ➔ Terminated; Trial primary completion date: Apr 2021 ➔ Aug 2019; Sponsor's decision

Clinical • Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • EGFR • MRI

A Phase 2 Trial of MP0250 Plus Bortezomib + Dexamethasone in Patients With Multiple Myeloma (clinicaltrials.gov) - P1/2; N=54; Recruiting; Sponsor: Molecular Partners AG; N=40 ➔ 54; Trial completion date: Dec 2019 ➔ Jul 2023; Trial primary completion date: Oct 2019 ➔ Oct 2021

Clinical • Enrollment change • Trial completion date • Trial primary completion date

"#MolecularPartners Receives #OrphanDrugDesignation for #MP0250 for #MultipleMyeloma $MOLN https://t.co/GONB11tD0V" (@1stOncology)

Orphan drug

"#pharmaschlagzeile @cashch Der Produktkandidat MP0250 des Biotechunternehmens Molecular Partners, zur Behandlung des #MultiplesMyelom, hat von der @US_FDA den "Orphan Drug"-Status erhalten #seltenekrankheiten #medikamente #krebstherapie https://t.co/mwnqB0rmZw" (@infonlinemed)

Orphan drug

MP0250 DARPin® Protein Plus Osimertinib in Patients With EGFR-mutated NSCLC (clinicaltrials.gov) - P1b/2; N=40; Active, not recruiting; Sponsor: Molecular Partners AG; Recruiting ➔ Active, not recruiting

Clinical • Combination therapy • Enrollment closed

Immune modulatory activity of MP0250, a tri-specific VEGF and HGF neutralizing DARPin drug candidate (AACR 2019) - "This concept is currently being tested in phase II clinical trials in multiple myeloma in combination with bortezomib and in NSCLC in combination with osimertinib. Taken together we have shown that MP0250 has immune modulatory activity and potentiates the activity of anti-PD1 therapy in mice. This paves the way for a clinical combination of MP0250 with anti-PD1 or other immune activating therapies in patients."