Molecular Partners Reports Highlights from Q4 2024 and Key Financials for Full Year 2024

   -- DLL3 targeting Radio-DARPin MP0712 to enter first-in-human study in 2025, 
      pending regulatory clearance 
 
   -- Strategic partnership with Orano Med on Radio-DARPins now expanded to ten 
      programs 
 
   -- MP0533 Phase 1/2a clinical data show improved response rate and depth in 
      ongoing cohort, additional dosing optimization planned; data expected 
      throughout 2025 
 
   -- Strong financial position with CHF 149 million in cash, cash equivalents 
      and short-term deposits at end of 2024, expected to support operations 
      well into 2027 
 
   -- Conference call to be held on Friday March 7, 2025 at 2.00 pm CET (8.00 
      am EST) 

ZURICH-SCHLIEREN, Switzerland and CONCORD, Mass., March 06, 2025 (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 its corporate highlights and audited financial results for the full year 2024, as well as the publication of its 2024 Annual Report.

"Molecular Partners has made significant progress through 2024, setting us up for a number of key value inflection points. The potential of our Radio-DARPins is now well recognized in the field. In addition, we are advancing our next-generation immuno-oncology programs, including multispecific and Switch-DARPin T cell engagers", said Patrick Amstutz, Ph.D., Chief Executive Officer of Molecular Partners.

"Our strategic Radio-DARPin partnership with Orano Med, expanded in January, is progressing well, and we named MSLN as our second RDT program for development. We anticipate submitting an IND application for MP0712 targeting DLL3 in H1 2025, with the start of first-in-human study and initial clinical data expected by year end. In our Phase 1/2a AML trial with MP0533, we expect data on the amended dosing scheme in 2025, and we plan to present further pre-clinical data on the CD3 Switch-DARPin at AACR in Q2 2025. We have a solid financial foundation, which provides funding through these value inflection points in 2025 and beyond."

Research & Development Highlights

MP0712 & Radio-DARPin Pipeline

The Investigational New Drug $(IND.AU)$ application for MP0712, a (212) Pb Radio-DARPin therapy $(RDT.UK)$ candidate targeting the tumor-associated protein delta-like ligand 3 (DLL3) and co-developed with Orano Med, is in preparation. Dialogue with the U.S. Food and Drug Administration (FDA) is ongoing, and Molecular Partners and Orano Med anticipate submitting the IND application for MP0712 in H1 2025, with the first-in-human study to start following regulatory clearance.

The IND submission is being built, in part, on strong MP0712 preclinical results, including new in vivo data presented at the European Association of Nuclear Medicine (EANM) Congress in October 2024 and the European Targeted Radiopharmaceuticals $(TRP)$ Summit in December 2024. MP0712 demonstrated high affinity and specificity for DLL3, a highly relevant target for radiopharmaceutical therapy. DLL3 has been shown to have homogeneous expression in tumors of patients with small cell lung cancer (present in >85% of patients), and expression in healthy tissues is low.

The second RDT program co-developed with Orano Med targets mesothelin (MSLN), which is overexpressed across several cancers with high unmet need, such as ovarian cancer, and largely absent from healthy tissues. The development of therapeutics against MSLN has been hampered by high shedding of MSLN, leading to high levels of soluble MSLN. Leveraging the unique DARPin properties, Molecular Partners has developed Radio-DARPins able to selectively bind to the membrane-bound form of MSLN while not recognizing shed MSLN. Initial preclinical data for the MSLN program will be presented at the Annual Meeting of the American Association of Cancer Research (AACR) in Q2 2025.

Molecular Partners has leveraged the intrinsic properties of DARPins, such as small size, high affinity and specificity, to develop Radio-DARPins as ideal vector candidates for radiopharmaceutical therapeutics and to create a Radio-DARPin platform amenable to a broad range of tumor targets. Historically, small protein-based vectors faced challenges with kidney accumulation and toxicity, as well as suboptimal tumor uptake. Molecular Partners' RDT platform addresses these limitations with the company's half-life extension technologies and surface engineering approaches, while preserving the advantages of the small protein format.

Global Partnership with Orano Med to Develop (212) Pb-labeled Targeted Radiotherapeutics

In January 2024, Molecular Partners entered into a strategic collaboration with Orano Med to co-develop (212) Pb-based RDTs. The partnership combines Molecular Partners' leadership in DARPins with Orano Med's leading expertise and unique capabilities in (212) Pb-based Targeted Alpha Therapy $(TAT)$ preclinical and clinical development. In January 2025, the two companies further expanded their agreement to co-develop up to ten radiotherapy programs. Molecular Partners holds commercialization rights to MP0712, which is the most advanced program, and to the MSLN RDT program. In addition to its world class expertise and capabilities in the development of TAT with (212) Pb, Orano Med will also ensure the production of the (212) Pb-based Radio-DARPins for clinical trials and commercialization. Orano Med possesses virtually unlimited raw starting material for (212) Pb production and has established robust and independent supply and manufacturing capabilities required for the seamless delivery of TAT to clinical sites internationally.

In addition to the above updates, Molecular Partners continued to progress its RDT portfolio of projects in partnership with Novartis in 2024. As per contract terms, the research collaboration comes to a close in March 2025.

"We would like to thank Novartis for this groundbreaking research collaboration which enabled us to launch our activities in the field of targeted radiopharmaceuticals. We developed know-how, attracted a strong team of experts and evolved our Radio-DARPin platform. As it stands today, we are not planning to integrate these programs into our pipeline, while we are moving our first Radio-DARPin candidate MP0712, targeting DLL3, to the clinic this year", said Patrick Amstutz.

MP0533 (multispecific T cell engager)

MP0533 is currently being evaluated in a Phase 1/2a clinical trial for relapsed/refractory acute myeloid leukemia $(AML.UK)$ and myelodysplastic syndrome/AML (ClinicalTrials.gov: NCT05673057). Dose escalation in cohorts 1--7 showed an acceptable safety profile and initial activity, yet with unsustained responses (four responders reported and encouraging blast reductions across additional patients), as presented in December 2024 at the American Society of Hematology $(ASH)$ meeting.

In the ongoing cohort 8, an additional dosing timepoint was introduced to allow steeper step-up and more frequent dosing to reach the MP0533 target dose faster. Initial data of this cohort indicate increased rates and depth of responses, with three out of eight evaluable patients demonstrating responses to-date (data cutoff 16 December 2024).

The study protocol is being amended to improve the exposure profile of MP0533 based on the learnings from the dose escalation. The amended protocol foresees, pending regulatory approval, further dose densification and premedication to mitigate loss of exposure for cohorts 9--10, with the objective to further increase the rate, depth and duration of responses observed in cohort 8. Data on the amended dosing scheme are expected in 2025.

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 at least two of the three TAAs, while sparing healthy cells, which express only one or none of these TAAs. The immune activation against the malignant cells is achieved through CD3-mediated T cell engagement.

Switch-DARPin Platform (next-generation immune cell engagers)

By employing a multi-specific Switch-DARPin, Molecular Partners aims to increase the safety and potency of T cell engagers (TCEs). Preclinical proof-of-concept in a solid tumor model for a novel CD3 Switch-DARPin TCE was presented at the Annual Meeting of the Society for Immunotherapy of Cancer $(SITC)$ in November 2024. The presented data provide further validation of Switch-DARPins and show that conditional T-cell activation with potent co-stimulation in solid tumors, but not in healthy tissues, is feasible. Molecular Partners will present further pre-clinical data on the CD3 Switch-DARPin at the AACR Annual Meeting in Q2 2025.

Molecular Partners' first Switch-DARPin program, MP0621, is designed to induce killing of hematopoietic stem cells (HSCs) as a next-generation conditioning regimen for HSC transplantation. Pre-clinical proof-of-mechanism data were presented at the Annual Meetings of the European Hematology Association (EHA) and ASH in June and December 2024, respectively. As Molecular Partners' portfolio strategy prioritizes therapeutic candidates for oncology, MP0621 is being evaluated for partnering.

Molecular Partners' Switch-DARPin platform provides a logic-gated "on/off" function (the "Switch") to multispecific DARPin candidates which leads to immune activation only in the presence of defined antigens and thereby enables conditional, tumor-localized next-generation immune cell engagers.

MP0317 (localized agonist)

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