Molecular Partners AG will present additional positive data from the ongoing phase 1 study of MP0317, a CD40 agonist designed to activate immune cells specifically within the tumor microenvironment by anchoring to fibroblast activation protein (FAP), at the 2023 ASCO (American Society of Clinical Oncology) annual meeting, June 2 to 6 in Chicago, U.S.\n\n\n\nThe data demonstrate that Molecular Partners' MP0317 shows evidence of tumor-localized CD40 activation (analyses in paired tumor biopsies). The detection of MP0317 in tumors positively correlated with immune activation when comparing high vs. low doses of MP0317. This detection was associated with a statistically significant CD40-mediated increase of antigen-presenting cells and interferon γ signature. Furthermore, MP0317 has demonstrated a favorable safety profile. The current data support planning of future combination studies.\n\n\n\n“These positive data continue to demonstrate that MP0317’s unique mechanism of action has the potential to overcome the limitations of existing therapies that target CD40 by activating only in the tumor microenvironment and therefore, avoid systemic toxicities seen by other treatments,” said Nicolas Leupin, chief medical officer of Molecular Partners. \n\n\n\n“MP0317 encapsulates the advantages we believe we can achieve through our DARPin platform: to design candidates to overcome biological challenges that other drug classes like antibodies cannot address. These data of the ongoing study will further support the advancement of MP0317 into later-stage clinical research with partners and highlight the potential of MP0317 for evaluation in combination settings.”\n\n\n\nAnti-tumor activity\n\n\n\n“Clinical data from 36 patients with advanced solid tumors, dosed across eight dose levels, confirms that the tumor-FAP-targeted CD40 agonist MP0317 is safe and well tolerated with limited systemic inflammation compared to other CD40 agonists,” said Carlos Gomez-Roca, head of the early phase & clinical research unit at IUCT-Oncopole Claudius Regaud at Toulouse, France, and investigator on the study. \n\n\n\n“The analysis of paired pre- and on treatment tumor biopsies as well as peripheral biomarkers provides evidence of target occupancy and pharmacodynamic modulation in the tumor microenvironment, consistent with tumor localized CD40 activation. The current data enables further evaluation of MP0317 in combination.”\n\n\n\nThis ongoing first-in-human phase 1, open-label, dose-escalation study assesses the safety and tolerability as well as pharmacokinetics/pharmacodynamics and antitumor activity of MP0317 monotherapy in patients with refractory/relapsed solid tumors known to express FAP and CD40. To date, the 36 patients enrolled in the Netherlands and France across eight dosing cohorts received MP0317 at doses of 0.03 to 10 mg/kg in every-3-weeks [q3w] and weekly [q1w] schedules.\n\n\n\nMolecular Partners' MP0317 monotherapy was seen to result in tumor-localized CD40 activation: biomarker data confirmed presence of MP0317 in the tumors of patients with evaluable pre- and on-treatment biopsies as of the cutoff date. This detection of MP0317 in tumors positively correlates when comparing high vs. low doses of MP0317 and was associated with a statistically significant CD40-mediated increase of antigen-presenting cells as well as interferon γ production within the tumor microenvironment. To date, one patient achieved an unconfirmed partial response, and stable disease was observed in five additional patients.\n\n\n\nThe observed safety profile of MP0317 monotherapy to date is favorable. A dose-limiting toxicity was reported in one patient (transient asymptomatic Grade 3 elevation of liver enzymes), at the highest planned MP0317 dose of 10 mg/kg administered q3w.\n\n\n\nThe positive results of this ongoing phase 1 study in patients with refractory/relapsed tumors support continued clinical evaluation of MP0317 and potential investigation in combination studies. The study continues to enroll one more cohort (q1w). \n\n\n\nIt is a new significant development in research against solid tumors.\n\n\n\nAbout Molecular Partners' MP0317\n\n\n\nMolecular Partners' MP0317 targets both the FAP and the immunostimulatory protein CD40 to enable tumor-localized immune activation. Through this proposed mechanism of action, MP0317 is designed to activate immune cells specifically within the tumor microenvironment, potentially delivering greater efficacy with fewer side effects compared to systemic CD40-targeting therapies.