Molecular Partners Presents Clinical Data Supporting its Ongoing MP0533 Study and Preclinical Data on Next-Gen Conditioning Agent MP0621 at ASH 2024

ZURICH-SCHLIEREN, Switzerland and CONCORD, Mass., Dec. 08, 2024 (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 (“Molecular Partners” or the “Company”), today announced the presentation of additional data pertaining to two programs, including preclinical data on MP0621, a potential next-generation conditioning regimen for patients undergoing hematopoietic stem cell transplantation, and comprehensive data from the first seven cohorts of the ongoing phase 1/2a dose-escalation study of MP0533. The data are presented in two posters at the American Society of Hematology (ASH) annual meeting, being held December 7-10, 2024 in San Diego, CA.

“We are at a unique crossroads with the MP0533 program. Data from our Ph1/2a study indicate antitumor and pharmacodynamic activity despite currently sub-optimal exposure levels, mostly driven by target-mediated drug disposition,” said Patrick Amstutz, Ph.D., CEO of Molecular Partners. “The sum of these data, reviewed in close collaboration with our KOLs, allowed us to define a clear hypothesis that introducing a loading-dose-phase will improve MP0533 exposure, thereby testing the full therapeutic potential of MP0533 in AML patients. We are happy to report that these amendments are submitted, while patient treatment is still ongoing. We look forward to providing updates to the program in 2025.”

MP0533: Acceptable safety profile, exposure being optimized via protocol amendment

MP0533 is a novel tetraspecific T cell engaging DARPin which simultaneously targets the three tumor-associated antigens (TAAs) CD33, CD123 and CD70, as well as CD3 on T cells. The mechanism of action of MP0533 is designed to preferentially kill AML cells that express any combination of these three TAAs while sparing healthy cells, which express only one or none of these targets. The immune activation against the malignant cells is achieved through CD3-mediated T cell-engagement.

The data presented at ASH 2024 are from the ongoing first-in-human dose-escalation phase 1/2a study of MP0533 in patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)/AML. MP0533 continues to show an acceptable safety profile in 37 patients up to dose cohort 7, with the majority of adverse events reported being infusion-related reactions and cytokine release syndrome. Initial pharmacodynamic data provide evidence of MP0533 target engagement and resulting immune activation. Despite lower than anticipated drug exposure, four responders in total were reported in cohorts 1-7 and encouraging blast reductions were observed in patients bone marrow, particularly in patients with lower disease burden.

Based on these observations Molecular Partners is amending the protocol of this study to further optimize the dosing schedule and improve the exposure profile of MP0533 in subsequent dosing cohorts. The goal is to achieve higher response rates, as well as an improved quality and duration of response in this heterogeneous patient population.

MP0621: Intended mechanism of HSC depletion confirmed preclinically

MP0621 is a Switch-DARPin candidate designed to induce killing of hematopoietic stem cells (HSCs) as a next-generation conditioning regimen for HSC transplantation (HSCT). The Switch-DARPin platform provides a logic-gated “on/off” function (the “Switch”) to multispecific DARPin candidates leading to target activation only in the presence of defined antigens. In MP0621, the Switch-DARPin binds to either cellular cKit or to the anti-CD47 DARPin binder. Upon MP0621 binding to cKit on HSCs, the Switch-DARPin will unmask the anti-CD47 DARPin, which in turn will bind CD47 and block the “don’t-eat-me” signal, leveraging the power of CD47 inhibition without its associated toxicity to healthy cells

The preclinical results presented support the intended MP0621 mechanism of action and provide further evidence for its potential as a viable approach for HSC depletion in patients. The blockade of CD47 exclusively on target cells allows MP0621 to enhance efficacy of cKit-targeting, while reducing off-target effects seen with systemic anti-CD47 blockade. The currently available non-human primate data however do not allow Molecular Partners to conclude that MP0621 would serve as a treatment for AML patients, as previously hypothesized. As Molecular Partners’ portfolio strategy prioritizes therapeutic candidates for oncology, MP0621 is being evaluated for partnering.