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MP0317 demonstrates tumor-localized CD40 activation in tumor biopsies through target occupancy and immune cell activation MP0317 demonstrates a favorable safety profile across Q3W and Q1W regimens, including the highest dose tested, 10mg/kg (Q3W) Present data support planning of future combination studies with potential partners ZURICH-SCHLIEREN, Switzerland and CONCORD, MA, USA I May 25, 2023 I 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, 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, held June 2–6 in Chicago, Illinois. The data demonstrate that 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. “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, MD, Ph.D., Chief Medical Officer of Molecular Partners. “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.” “Clinical data from 36 patients with advanced solid tumors, dosed across 8 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 Dr Carlos Gomez-Roca, Head of the Early Phase & Clinical Research Unit at IUCT-Oncopole Claudius Regaud at Toulouse, France, and investigator on the study. “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 localised CD40 activation. The current data enables further evaluation of MP0317 in combination.” This 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 (NCT05098405 ) . To date, the 36 patients enrolled in the Netherlands and France across eight dosing cohorts received MP0317 at doses of 0.03–10 mg/kg in every-3-weeks [q3w] and weekly [q1w] schedules (data cut-off 02 May 2023). 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 5 additional patients. The 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. The 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). For further information please see clinicaltrials.gov (NCT05098405). The details of the poster presenting these results from the ongoing Phase 1 study at the ASCO 2023 Annual Meeting can be found below. The poster will be made available on Molecular Partners' website after the presentation. Title: Phase I study of MP0317, a FAP-dependent DARPin, for tumor-localized CD40 activation in patients with advanced solid tumors Poster Session: Developmental Therapeutics—Immunotherapy Abstract number: 2584 Poster number: 426 Location & Timing: Hall A; June 3, 2023; 8:00–11:00am CDT Authors & Affiliations: C Gomez-Roca 1 , N Steeghs 2 , E Gort 3 , H De Winter 4 , E Fernandez 4 , V Stavropoulou 4 , N Stojcheva 4 , P Baverel 4 , J Krieg 4 , K Ioannou 4 , A Florescu 4 , P Mossi 4 , L Hoenig 4 , B Baud-Berthier 4 , V Kirkin 4 , A Goubier 4 , P Legenne 4 , P Cassier 5 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. About Molecular Partners AG Molecular Partners AG is a clinical-stage biotech company developing DARPin (designed ankyrin repeat protein) therapeutics, a new class of custom-built protein drugs designed to address challenges current modalities cannot. The Company has formed partnerships with leading pharmaceutical companies to advance DARPin therapeutics in the areas of oncology and virology and has compounds in various stages of clinical and preclinical development across multiple therapeutic areas. www.molecularpartners.com ; Find us on Twitter - @MolecularPrtnrs 1 Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France 2 The Netherlands Cancer Institute, Amsterdam, the Netherlands 3 UMC Utrecht, Utrecht, the Netherlands 4 Molecular Partners AG, Schlieren-Zurich, Switzerland; 5 Centre Léon Bérard, Lyon, France SOURCE: Molecular Partners

ZURICH-SCHLIEREN, Switzerland and CONCORD, MA, USA I January 16, 2023 I 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, announced today that the first patient has been treated in a Phase 1 first-in-human study evaluating the safety, tolerability, and efficacy of MP0533, the company’s candidate for acute myeloid leukemia (AML). MP0533 is designed to focus an immune attack against AML in a new way that preferentially spares healthy cells, which has been a historic challenge for CD3-targeting therapeutics. “AML is a notoriously difficult cancer to treat, in large part due to the overlapping targets which are expressed on both healthy, and leukemic cells. Our team has worked relentlessly over the past 3 years to develop a molecule intended to target these cancerous cells, while avoiding healthy cells. MP0533’s mechanism represents a new level of precision targeting in complex cancers that may permit greater use of the immunostimulatory power of CD3,” said Nicolas Leupin, M.D., Ph.D., Chief Medical Officer of Molecular Partners. “We are grateful to our team and our collaborators for reaching this milestone and look forward to learning more about the potential of MP0533 to help these patients.” MP0533 simultaneously targets three surface proteins, CD33, CD123, and CD70, that are vastly more likely to appear together on AML blast cells and leukemic stem cells over healthy cells. It also targets an immunostimulatory protein, CD3, on cytotoxic T cells, which will only activate when at least two of the surface proteins are bound. This novel mechanism is intended to greatly favor CD3 activation in proximity to leukemic stem cells rather than the systemic activation seen in previous CD3-based T cell engagers. The Phase 1 open-label dose escalation study will enroll patients with relapsed/refractory AML and higher-risk myelodysplastic syndromes (MDS). It is designed to assess the safety, tolerability, and efficacy of MP0533 in addition to a range of secondary endpoints, such as the effect on LSCs, pharmacodynamics, T-cell activation, and cytokine release. Between 20-45 patients are expected to be enrolled across five sites in Switzerland and the Netherlands in collaboration with certain sites within the HOVON cooperative group. Additional clinical sites are planned as well. MP0533 preclinical data demonstrates its greatly increased avidity for cells expressing two or three of the tumor associated antigens (TAAs) compared to cells expressing a single TAA. MP0533 also demonstrated an ability to induce T cell activation and killing of AML cells in samples from newly diagnosed and previously treated patients. The research also showed that MP0533 was able to directly target and kill LSCs while sparing a variety of healthy cells including hematopoietic stem cells, endothelial cells, and T cells. About Molecular Partners’ Oncology Product Candidates Molecular Partners is developing several candidates designed to activate the immune system to fight cancer while reducing damage to healthy cells. These candidates use multiple novel DARPin technologies potentially applicable against a wide range of tumor types, including DARPin candidates with the ability to restrict immune activation to the tumor microenvironment, the ability to target intracellular disease-associated proteins, and multiple novel control mechanisms for immune activation designed to direct immune attack to the right cells, at the right place, and at the right time. These capabilities can be combined during candidate design through the inherent modularity of the DARPin platform, to provide precise control over immune activation and potentially enable more effective cancer therapies. About Molecular Partners AG Molecular Partners AG is a clinical-stage biotech company developing DARPin therapeutics, a new class of custom-built protein drugs designed to address challenges current modalities cannot. The Company has formed partnerships with leading pharmaceutical companies to advance DARPin therapeutics in the areas of ophthalmology, oncology, and infectious disease, and has compounds in various stages of clinical and preclinical development across multiple therapeutic areas. www.molecularpartners.com ; Find us on Twitter - @MolecularPrtnrs SOURCE: Molecular Partners