Molecular Partners Presents Positive Interim Safety and Mechanistic Data From Ongoing Phase 1 Trial of MP0317 for Treatment of Solid Tumors

ZURICH-SCHLIEREN, Switzerland and CONCORD, Mass., Nov. 10, 2022 (GLOBE NEWSWIRE) — Ad hoc announcement pursuant to Art. 53 LR : 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, today announced the presentation of positive interim results from the ongoing Phase 1 trial of the company’s MP0317 (FAP X CD40) program for the treatment of solid tumors at the Society for the Immunotherapy of Cancer 37th Annual meeting.

While holding promise, the development of CD40 agonists for cancer therapy has faced challenges due to systemic CD40 activation leading to dose-limiting toxicity (DLT). MP0317 is designed to resolve these limitations by activating immune cells specifically within the tumor microenvironment through the simultaneous binding of the immune stimulator CD40 as well as a protein highly expressed within tumors named fibroblast activation protein, or FAP.

“This first clinical data supports the potential of MP0317 as a candidate able to achieve the goal of restricting CD40 activity to tumors. We are now progressing into dosages well above those that produced dose-limiting toxicities with non-DARPin CD40 agents, a significant achievement we hope to translate into observed clinical effect,” said Nicolas Leupin, MD, Ph.D., CMO of Molecular Partners. “Our oncology programs continue displaying the potential of DARPin therapeutics to solve historical drug development challenges such as localizing potent immune activation to tumors in order to spare damage to healthy cells.”

This Phase 1, first-in-human, multicenter, open label, dose escalation study enrolling patients with relapsed/refractory advanced solid tumors is intended to evaluate the safety of MP0317 and investigate a range of other biomarkers to better characterize the candidate’s mechanism and activity. At the point of data cutoff, 4 cohorts had received an intravenous dose of MP0317 every 3 weeks until disease progression, unacceptable toxicity, or other discontinuation criteria were met.

Key reported data:

  • MP0317 was seen to be safe and well tolerated with no dose limiting CD40-related systemic toxicities having been observed to date, and no signs of inflammatory cytokine release.
  • The most frequent adverse events were grade 2 infusion related reactions (e.g., rapidly resolved infusion site inflammation) in 3/13 dosed patients at the time of data cutoff, with no DLT observed. This spans cohorts 1-4, with dosages ranging from 0.03 mg/kg to 1 mg/kg.
  • Tumor biopsies from the earlier cohorts (1-3) already show evidence of MP0317 co-localization with both CD40 and FAP, in 3 of the 5 tumor biopsies available for analysis.
  • In addition, early PD data show signs of CD40-mediated immune activation.
  • These data support that MP0317’s mechanism is working as intended.

These results will be presented at SITC 2022 in a poster, the details of which can be found below. The poster will be made available on Molecular Partners website, after the presentation on November 10.

Poster: “A phase 1 study to characterize the safety and tolerability of MP0317, a tumor targeting FAP dependent CD40 agonist DARPin, in patients with relapsed/refractory solid tumors”
Number: 1475
Timing: November 10, 2022
Presenter: Paul Baverel, PhD

The dose escalation of the Phase 1 remains ongoing and Molecular Partners expects the final data set to inform the therapeutic dose for evaluation in a potential Phase 2 trial. Subsequent to the data cutoff, current ongoing dosing levels include a 3 mg/kg cohort dosed every 3 weeks, as well as a 0.5 mg/kg weekly dosing cohort. A total of 19 patients have been enrolled in the Phase 1 study as of Nov. 1, 2022.