Core Insights - Molecular Partners AG is presenting updated data from a Phase 1/2a trial of MP0533, a novel T cell engager for acute myeloid leukemia (AML) patients, at the upcoming ASH Annual Meeting [1][2] Group 1: Clinical Trial Details - The trial is a first-in-human, multicenter, open-label study evaluating MP0533 in relapsed/refractory AML and myelodysplastic syndrome (MDS)/AML patients [2] - MP0533 demonstrates an acceptable safety profile across dosing regimens DR 1–9, with preliminary signs of antitumor activity being encouraging [2] - The study is currently administering doses to patients in DR 10 [2] Group 2: Mechanism of Action - MP0533 is a tetra-specific T cell-engaging DARPin that targets three tumor-associated antigens (CD33, CD123, CD70) on AML cells and the immune activator CD3 on T cells [3] - The design allows MP0533 to preferentially bind to AML cells over healthy cells, enhancing T cell-mediated killing while minimizing damage to healthy cells [3] Group 3: Presentation Details - The presentation will occur on December 7, 2025, during the session focused on investigational drugs and cellular therapies for acute myeloid leukemias [4] - The full abstracts will be available on the ASH website starting November 3, 2025 [4] Group 4: About DARPin Therapeutics - DARPin therapeutics represent a new class of custom-built protein drugs that offer multi-functionality and multi-target specificity [5] - The platform is designed for rapid and cost-effective drug discovery, producing candidates with optimized properties and high production yields [5] Group 5: About Molecular Partners AG - Molecular Partners AG is a clinical-stage biotech company focused on developing DARPin therapeutics, primarily in oncology [6] - The company has various programs in different stages of development and collaborates with leading pharmaceutical companies [6]

Core Insights - Molecular Partners AG is advancing its logic-gated CD3 Switch-DARPin T cell engager (TCE) designed for targeted immune activation in solid tumors, particularly ovarian cancer, by presenting new preclinical data at the SITC 2025 meeting [1][4] Group 1: Product Development - The Switch-DARPin TCE utilizes an AND-gate mechanism to activate T cells only when both mesothelin (MSLN) and epithelial cell adhesion molecule (EpCAM) are present, addressing limitations of systemic toxicity and efficacy in TCEs for solid tumors [2][4] - Preclinical data indicate that the Switch-DARPin shows selective T cell cytotoxicity against cells co-expressing MSLN and EpCAM, while exhibiting reduced activity against healthy tissues [3][6] - The T cells exposed to the CD2/CD3 Switch-DARPin demonstrated improved activation and proliferation compared to CD3 engagement alone, suggesting potential to mitigate T cell exhaustion [3][4] Group 2: Safety and Efficacy - Significant tumor regression was observed in a xenograft mouse model expressing MSLN and EpCAM, without systemic cytokine release, indicating a favorable safety profile for the Switch-DARPin [3][6] - The logic-gated approach allows for conditional immune activation, enhancing both efficacy and safety compared to traditional therapies targeting a single tumor antigen [4][6] Group 3: Company Overview - Molecular Partners AG is a clinical-stage biotech company focused on developing DARPin therapeutics, which offer advantages in multi-target specificity and high stability over existing protein-based drugs [5][8] - The company has a diverse pipeline with programs in various stages of development, primarily targeting oncology [8]

Financial Performance - Total revenues for the nine months ended September 30, 2025, were CHF 0, a decrease from CHF 4.97 million in the same period of 2024[11] - Operating expenses for the nine months ended September 30, 2025, were CHF 45.5 million, down 11.5% from CHF 51.4 million in 2024[11] - The net result attributable to shareholders for the nine months ended September 30, 2025, was a loss of CHF 49.0 million, compared to a loss of CHF 42.8 million in 2024[12] - The company reported a basic and diluted net result per share of CHF (1.32) for the nine months ended September 30, 2025, compared to CHF (1.29) in 2024[12] - The Group reported a net foreign exchange loss of TCHF 4,767 for the nine months ended September 30, 2025, compared to no loss in the previous year[35] Cash and Assets - Cash and cash equivalents increased to CHF 82.4 million as of September 30, 2025, from CHF 63.9 million at the beginning of the year[14] - Total assets decreased to CHF 112.2 million as of September 30, 2025, from CHF 158.5 million at the end of 2024[10] - Shareholders' equity as of September 30, 2025, was CHF 95.5 million, down from CHF 141.6 million at the end of 2024[10] Research and Development - Research and development expenses for the nine months ended September 30, 2025, were CHF 30.9 million, a decrease of 18.5% from CHF 38.1 million in 2024[11] - The company has not reported any revenues from research and development collaborations for the third quarter of 2025, compared to CHF 681,000 in the same quarter of 2024[13] - The Group recognized no revenue from the License and Collaboration Agreement with Novartis during the three and nine months ended September 30, 2025, compared to TCHF 681 and TCHF 4,970 for the same periods in 2024, respectively[25] Shareholder Information - As of September 30, 2025, the outstanding issued share capital increased to CHF 4,037,464, divided into 40,374,641 fully paid registered shares, including 2,975,489 treasury shares[29] - The weighted average number of shares used in computing earnings per share for the nine months ended September 30, 2025, was 37,223,971, compared to 33,082,140 for the same period in 2024[37] Expenses and Restructuring - The company incurred restructuring expenses of CHF 2.7 million during the nine months ended September 30, 2025[11] - The Group recognized TCHF 2,733 as a restructuring expense for the nine months ended September 30, 2025, primarily related to personnel costs[41] - The share-based compensation costs for the nine months ended September 30, 2025, amounted to TCHF 3,446, an increase from TCHF 3,045 for the same period in 2024[34] Tax and Related Party Transactions - The Group has a tax loss carry-forward in Switzerland of TCHF 195,126 as of December 31, 2024, with no deferred tax assets recognized due to the improbability of utilizing these losses[36] - No related party transactions occurred during the interim periods presented[39] - No significant events occurred between the balance sheet date and the approval date of the financial statements that would require adjustments[42]

Pipeline Highlights - MP0712 (212Pb x DLL3) IND-enabling studies completed, IND filed[15] - Strategic collaboration with Orano Med expanded to ten 212Pb programs[15] - Lead candidate MP0726 targeting mesothelin (MSLN) nominated based on pre-clinical data[15] - Improved response rate and antitumor activity in low disease burden patients of ongoing Phase 1/2a reported for MP0533 at EHA 2025[15] - Study protocol approved for combo IIT with standard-of-care in cholangiocarcinoma for Switch-DARPin MP0317[15] Financial Position - The company has CHF ~105 million in cash as of September 30, 2025[8, 15] - The company is financed until 2028 through key value inflection points[8] MP0712 Radio-DARPin Therapy - MP0712 induces complete and durable tumor regression in NCI-H82 tumor model at 10 µCi injected every week[27] - Phase 1 study is expected to start in H2 2025, with initial safety and efficacy data in 2026[32] MP0533 Tetra-specific T-cell Engager for AML - In DR 8, 3 of 8 evaluable patients responded after cycle 1: 1 CR and 2 CRh as best overall response[62] - In DR 1-7, 12% (4) patients had response rate, while in DR 8, 37.5% (3) patients had response rate[69]

Core Insights - Molecular Partners AG is advancing its clinical-stage pipeline, focusing on DARPin therapeutics, with significant developments in its Radio-DARPin programs and T-cell engagers [1][2][3] Research & Development Highlights - The IND application for MP0712, a Radio-DARPin targeting DLL3 for small cell lung cancer, has been filed, with a Phase 1 trial expected to start by the end of 2025 [3][7] - Initial clinical imaging data for MP0712 will be presented in November, showcasing its application in compassionate care in South Africa [2][5] - MP0533, a multispecific T-cell engager for acute myeloid leukemia (AML), has shown promising results, with over 30% of evaluable patients achieving a clinical response [10][12] - The company is exploring further dosing strategies for MP0533 to enhance patient outcomes and is planning to present updated data at the ASH Annual Meeting in December [11][12] - MP0317, a tumor-localized agonist, is undergoing an investigator-initiated trial for advanced cholangiocarcinoma, with a focus on progression-free survival [13][14] Corporate Governance Highlights - Martin Steegmaier, Ph.D., has been appointed as Chief Scientific Officer, bringing extensive oncology drug development experience [17] Financial and Business Outlook - For 2025, the company anticipates total operating expenses of CHF 55-60 million, with sufficient cash reserves of CHF 105 million to fund operations until 2028 [18][19]

Financial Performance - Total revenues for H1 2025 were CHF 4.3 million, unchanged from H1 2024[28] - Operating loss for H1 2025 was CHF 33.5 million, compared to CHF 31.8 million in H1 2024, an increase of 1.6 million[28] - Net loss for H1 2025 was CHF 37.2 million, up from CHF 26.4 million in H1 2024, an increase of 10.8 million[28] - Total operating expenses decreased by CHF 2.7 million (7%) to CHF 33.5 million in H1 2025, compared to CHF 36.1 million in H1 2024[40] - The net result attributable to shareholders for the six months ended June 30, 2025, was a loss of CHF 37,167,000, compared to a loss of CHF 26,407,000 in 2024, reflecting a 40% increase in losses[61] - The total comprehensive result attributable to shareholders for the six months ended June 30, 2025, was a loss of CHF 37,089,000, compared to a loss of CHF 22,879,000 in 2024, reflecting a worsening financial position[61] Expenses - R&D expenses decreased to CHF 22.6 million in H1 2025 from CHF 27.2 million in H1 2024, a reduction of 4.6 million[28] - SG&A expenses were CHF 8.2 million in H1 2025, down from CHF 8.9 million in H1 2024, a decrease of 0.7 million[28] - Total operating expenses for the six months ended June 30, 2025, were CHF 33,458,000, down from CHF 36,123,000 in 2024, a decrease of approximately 7%[61] - The Group recognized TCHF 2,617 in restructuring expenses for the six months ended June 30, 2025, primarily related to personnel costs[93] Cash and Equity - Cash balance as of June 30, 2025, was CHF 114.5 million, down from CHF 159.1 million year-on-year, a decrease of 44.6 million[28] - Total shareholders' equity as of June 30, 2025, was CHF 106.7 million, down from CHF 155.6 million, a decrease of 48.9 million[28] - Cash and cash equivalents plus short-term time deposits decreased by CHF 35.0 million to CHF 114.5 million as of June 30, 2025[48] - The Group's total shareholders' equity decreased by CHF 35.0 million to CHF 106.7 million as of June 30, 2025[48] Future Outlook - The company expects total expenses for 2025 to be between CHF 55 million and CHF 65 million, excluding potential receipts from R&D partnerships[30] - The company anticipates being funded into 2028, extending its cash runway beyond previous guidance of 2027[24] - The workforce is expected to reduce by up to 40 positions, representing approximately 24% of total positions, to increase operational efficiency[24] Revenue Sources - In H1 2025, the Group recognized no revenue, a decrease from CHF 4.3 million in H1 2024, attributed to the completion of a collaboration with Novartis[37] - The company had no revenues from the collaboration with Novartis in the first half of 2025, while it recognized CHF 4,289,000 in revenues during the same period in 2024, marking a complete cessation of income from this source[76] - The company recorded a reimbursement of expenses from Orano Med of CHF 1,397,000 for the six months ended June 30, 2025, compared to a reimbursement of CHF 429,000 in 2024, indicating a significant increase in collaboration[75] Employee and Shareholder Information - As of June 30, 2025, the Group had 153 full-time employees, with 82% in R&D and 18% in SG&A[42] - The outstanding issued share capital increased to CHF 4,037,464 as of June 30, 2025, due to the vesting of Performance Share Units, compared to CHF 4,036,310 at the end of 2024[80] - As of June 30, 2025, the total number of outstanding PSUs and RSUs was 3,365,845, an increase from 2,593,065 at the beginning of the year[84] - The weighted average number of shares used in computing basic and diluted earnings per share for the six months ended June 30, 2025, was 37,134,928, up from 33,025,576 in 2024[89] Share-Based Compensation - The share-based compensation costs for the six months ended June 30, 2025, amounted to TCHF 2,370, compared to TCHF 1,983 for the same period in 2024[85] - The share-based compensation costs for the three months ended June 30, 2025, were TCHF 1,228, compared to TCHF 1,129 for the same period in 2024[85] Financial Risks - The Group's financial risk management focuses on minimizing exposure to foreign exchange, liquidity, and interest rate risks[55] - The Group reported a net foreign exchange loss of TCHF 4,617 for the six months ended June 30, 2025, compared to no losses in the previous year[86] - Financial income for the six months ended June 30, 2025, was TCHF 922, a decrease from TCHF 5,447 in 2024, primarily due to a net foreign exchange gain of TCHF 3,432 in 2024[86] Taxation - The Group has a tax loss carry-forward of TCHF 195,126 as of December 31, 2024, with no deferred tax assets recognized due to the improbability of utilizing these losses in the foreseeable future[88] Dividends - No dividends have been paid since the Group's inception and none are anticipated in the foreseeable future[83]

Core Insights - Molecular Partners AG is making significant progress in its clinical programs, particularly with MP0712 and MP0533, with key milestones expected in the near future [2][6] - The company has appointed Martin Steegmaier, Ph.D., as Chief Scientific Officer, enhancing its leadership team [2][15] - Financially, the company is in a strong position with cash reserves projected to last until 2028 [2][19] Research & Development Highlights - MP0533 is in a Phase 1/2a trial for acute myeloid leukemia, showing promising results with over 30% of evaluable patients achieving a clinical response [3][4] - The dosing regimen for MP0533 has been optimized to enhance patient responses, with initial data from cohort 9 expected in Q4 2025 [5][6] - MP0712, a Radio-DARPin therapy for small cell lung cancer, is preparing for an IND filing, with initial clinical data anticipated in H1 2026 [8][9] Corporate Governance Highlights - The appointment of Martin Steegmaier, Ph.D., as CSO is aimed at strengthening the company's focus on oncology drug development [15] - A strategic review led to a planned reduction of up to 40 positions, which is expected to improve operational efficiency and extend the cash runway into 2028 [16] Financial and Business Outlook - For 2025, the company expects total operating expenses between CHF 55-65 million, with a significant portion being non-cash costs [18] - As of June 30, 2025, cash and cash equivalents totaled CHF 114 million, sufficient to fund operations into 2028 [19]

Core Viewpoint - Molecular Partners AG has appointed Martin Steegmaier, Ph.D., as Chief Scientific Officer (CSO), effective October 1, 2025, to enhance its oncology drug development efforts, particularly in DARPin therapeutics [1][2]. Company Overview - Molecular Partners AG is a clinical-stage biotech company focused on developing DARPin therapeutics, which are custom-built protein drugs aimed at addressing medical challenges that other drug modalities cannot effectively tackle [6]. - The company has a pipeline that includes various programs in pre-clinical and clinical development, with a primary focus on oncology [6]. Leadership Appointment - Martin Steegmaier brings extensive experience in oncology drug development from previous roles at Roche, MorphoSys, Boehringer Ingelheim, and SOTIO Biotech, where he led the development of a broad pipeline of oncology programs [1][3][2]. - The CEO of Molecular Partners, Patrick Amstutz, expressed confidence that Steegmaier's expertise will significantly contribute to the company's research organization and the advancement of its targeted DARPin therapeutics [2]. Educational Background - Martin Steegmaier holds a Ph.D. in biochemistry from the University of Basel and an MBA from the Edinburgh Business School, which complements his extensive experience in the biotech and pharmaceutical sectors [4]. Future Directions - The company aims to innovate and advance its pipeline of targeted DARPin therapeutics, including Radio-DARPins and Switch-DARPins, which are designed for logic-gated immune cell activation [2][5].

Radio-DARPin Therapy & MP0712 - Molecular Partners is focused on oncology with differentiated assets like MP0533 and MP0712, addressing unmet medical needs[8] - The company has CHF ~149 million, ensuring funding into 2027[8, 110] - MP0712, a 212Pb-DLL3 targeted radiotherapeutic, addresses the critical unmet need in SCLC, where >85% of patients express DLL3[36, 39] - Preclinical data shows MP0712 induces complete tumor regression in ~70% of mice at 4x 10µCi and ~20% of mice at 8x 5µCi in the NCI-H82 tumor model at day 63[45] - MP0712 clinical development strategy includes Phase 0 imaging studies and Phase 1 dose escalation studies starting in H2 2025, with initial clinical data expected by YE[54] Next-Gen Immune Cell Engagers & MP0533 - MP0533 is a tetra-specific T-cell engager designed to kill AML cells by targeting CD33, CD123, and CD70[69, 77] - Preliminary data from the MP0533 Phase 1/2a study shows 4 responders reported in DR 1-7 with manageable safety[80] - An improved MP0533 exposure was achieved at DR 8 with a steeper and denser step-up dosing regimen[82, 86] Switch-DARPin Platform - The Switch-DARPin platform aims to overcome limitations of current T cell engagers by enabling targeted and conditional activation of immune cells[94, 101] - Preclinical data shows the EpCAM-MSLN-CD2/CD3 Switch induces tumor regression more efficiently than a MSLN-CD3 engager (Tritac)[107]

Company Overview - Molecular Partners is a clinical-stage biotech company pioneering DARPin therapeutics for patients, with operations in Switzerland and the US[8] - The company is well financed into 2027 with approximately CHF 149 million[8] (Note: The outlook section mentions CHF ~131 million[95], so there might be a slight discrepancy) - Molecular Partners has proprietary DARPin platforms, including Radio-DARPins and Switch / T cell engagers[8] Pipeline Highlights - MP0712 (Radio-DARPin Therapy targeting DLL3) is in co-development for SCLC & NECs[9] - The co-development agreement with Orano Med includes up to 10 RDT programs, including MP0712[9] - MP0533 (Next-Gen Immune Cell Engager) is being developed for r/r AML and AML/MDS[9] MP0712 (Radio-DARPin Therapy) - MP0712 is the first 212Pb-DLL3 targeted radiotherapeutic for SCLC, where >85% of SCLC patients express DLL3[25] - Preclinical studies show MP0712 induces complete and durable tumor regression in the NCI-H82 tumor model at 10µCi injected every week[28] - Phase 1 study is expected to start in H2 2025, with initial safety and efficacy data in 2026[33] MP0533 (Tetra-specific T-cell Engager for AML) - MP0533 is designed to induce T cell-mediated killing preferentially when 2 or 3 AML-associated antigens are co-expressed[66] - Preliminary data from the Phase 1/2a study shows encouraging blast reduction, particularly in patients with lower disease burden at baseline[75] - Improved MP0533 exposure was observed at DR 8 with a steeper and denser step-up dosing regimen[78]