On November 3, 2023 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, reported that it 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) (Free SITC Whitepaper), being held November 1–5 in San Diego, California (Press release, Molecular Partners, NOV 3, 2023, View Source [SID1234636916]). MP0317 is a CD40 agonist designed to activate immune cells specifically within the tumor microenvironment (TME) by anchoring to fibroblast activation protein (FAP).

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"MP0317 continues to demonstrate its potential to overcome the limitations of existing CD40 agonists through its unique DARPin design that allows to activate immune cells directly within the TME, while avoiding eliciting systemic toxicities," said Philippe Legenne M.D, acting CMO of Molecular Partners. "The encouraging results presented at SITC (Free SITC Whitepaper) provide clinical evidence of MP0317-induced, tumor-targeted CD40 activation. The observed remodeling of the TME and MP0317’s favorable safety profile across all dosing cohorts, including the highest planned doses, support further investigation of MP0317 in later-stage clinical studies including combination trials."

Details of the poster presenting updated results from the ongoing MP0317 Phase 1 study at the SITC (Free SITC Whitepaper) 2023 Annual Meeting can be found below. The poster will be made available on Molecular Partners’ website after the presentation.

Title: 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
Poster number: 721
Location & Timing: Exhibit Hall B, Friday November 3, 2023, 9am – 7pm ET

This update, based on data from 46 patients, corroborates earlier reported findings of MP0317-induced CD40 activation and related remodeling of the TME. 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.

MP0317 continues to display a favorable safety profile across all dosing cohorts (0.03–10 mg/kg, Q3W & Q1W), with limited systemic inflammation-related adverse reactions compared to other CD40 agonists. Dose-limiting toxicity was reported in only one patient to date (transient asymptomatic Grade 3 elevation of liver enzymes), at the highest planned MP0317 dose of 10 mg/kg administered Q3W.

The positive results of this fully enrolled Phase 1 study in patients with refractory/relapsed tumors support continued clinical evaluation of MP0317 and potential investigation in combination studies. The Company expects to share final results of this study in 2024. For further information please see clinicaltrials.gov (NCT05098405).

This ongoing first-in-human Phase 1, open-label, dose-escalation study assesses the safety and tolerability as well as pharmacokinetics/pharmacodynamics and preliminary antitumor activity of MP0317 monotherapy in patients with advanced solid tumors known to express FAP and CD40 (NCT05098405). Recruitment for the dose-escalation portion of the study is complete, with 46 patients enrolled in the Netherlands and France across nine dosing cohorts. Patients received MP0317 at doses of 0.03–10 mg/kg in every-3-weeks (Q3W) or weekly (Q1W) schedules (data cut-off 10 October 2023).

About MP0317
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.