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Progressing the first Radio-DARPin Therapeutic MP0712 (212Pb x DLL3) for SCLC into the clinic Patrick Amstutz, CEO Webcast call following TWC 2026 presentation February 2, 2026 ➢ New patient imaging and dosimetry data ➢ Update on Phase 1/2a study
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Disclaimer This presentation contains forward looking statements. Any statements contained in this presentation that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995, as amended, including without limitation: implied and express statements regarding the clinical development of Molecular Partners’ current or future product candidates; expectations regarding timing for reporting data from ongoing clinical trials or the initiation of future clinical trials; the potential therapeutic and clinical benefits of Molecular Partners’ product candidates and its RDT and Switch-DARPin platforms; the selection and development of future programs; Molecular Partners’ collaboration with Orano Med including the benefits and results that may be achieved through the collaboration; and Molecular Partners’ expected business and financial outlook, including anticipated expenses and cash utilization for 2026. These statements may be identified by words such as “aim”, "anticipate", “expect”, “guidance”, “intend”, “outlook”, “plan”, “potential”, “will” and similar expressions, and are based on Molecular Partners’ current beliefs and expectations. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Some of the key factors that could cause actual results to differ from Molecular Partners’ expectations include its plans to develop and potentially commercialize its product candidates; Molecular Partners’ reliance on third party partners and collaborators over which it may not always have full control; Molecular Partners’ ongoing and planned clinical trials and preclinical studies for its product candidates, including the timing of such trials and studies; the risk that the results of preclinical studies and clinical trials may not be predictive of future results in connection with future clinical trials; the timing of and Molecular Partners’ ability to obtain and maintain regulatory approvals for its product candidates; the extent of clinical trials potentially required for Molecular Partners’ product candidates; the clinical utility and ability to achieve market acceptance of Molecular Partners’ product candidates; the potential that Molecular Partners’ product candidates may exhibit serious adverse, undesirable or unacceptable side effects; the impact of any health pandemic, macroeconomic factors and other global events on Molecular Partners’ preclinical studies, clinical trials or operations, or the operations of third parties on which it relies; Molecular Partners’ plans and development of any new indications for its product candidates; Molecular Partners’ commercialization, marketing and manufacturing capabilities and strategy; Molecular Partners’ intellectual property position; Molecular Partners’ ability to identify and in-license additional product candidates; unanticipated factors in addition to the foregoing that may cause Molecular Partners’ actual results to differ from its financial and business projections and guidance; and other risks and uncertainties set forth in Molecular Partners’ Annual Report on Form 20-F for the year ended December 31, 2024 and other filings Molecular Partners makes with the SEC from time to time. These documents are available on the Investors page of Molecular Partners’ website at www.molecularpartners.com. In addition, this presentation contains information relating to interim data as of the relevant data cutoff date, results of which may differ from topline results that may be obtained in the future. Any forward-looking statements speak only as of the date of this presentation and are based on information available to Molecular Partners as of the date of this release, and Molecular Partners assumes no obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise. 2
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Speakers 3 Patrick Amstutz CEO Philippe Legenne CMO Michael T Stumpp EVP Projects Ken Herrmann Chair, Scientific Advisory Board
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Making Alpha Therapies a Reality with DARPins and 212Pb MOLECULAR PARTNERS PIONEERS of DARPIN THERAPEUTICS ORANO MED PIONEERS of TARGETED ALPHA THERAPY FULL VALUE CHAIN PARTNERSHIP: ✓ World class technologies & capabilities combined ✓ DARPins as ideal vectors for radiopharmaceuticals ✓ 212Pb as potent therapeutic payload, proven clinical efficacy 4 Radio-DARPin HLE
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MP0712 - Why DLL3 Targeted Radio Therapy for SCLC T-Cell engagers - Tarlatamab approved - 40% RR - DoR: 9.7 months - Substantial side effects Antibody-Drug Conjugates - Phase I/II - 70% RR - Risk of chemo-resistance - Manageable side effects Radio Therapy (MP0712) - Phase 0/I - SCLC highly radio sensitive - Manageable side effects - Combinable with other MoAs 5MoA, mode of action; RR, response rate. DLL3
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MP0712: high tumor uptake via DLL3 replenishment 6 DARPin binding properties and extended systemic half-life exploit the rapid internalization & replenishment of DLL3 for high radioisotope accumulation in SCLC cells Very low DLL3 copy number on tumor cells (DLL3: <1000; PSMA: >100’000 receptors/cell) PSMA: Lückerath et al., JNM 2018; Kwon et al, Journal of Biomedical Optics 2023. DLL3 quantification carried out in-house, on NCI-H82 tumors, n=6. 100x
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MP0712 Development Pathway 1. Imaging 2. Treatment MP0712 203Pb 212Pb MP0712 SCLC patient SCLC patient MP0712 binding to tumor cells MP0712-induced tumor cell death tumor tumor Solid tumor cells Dying tumor cells 7 SPECT Re-imaging Phase 1/2a Study: Named Patient Access Program: ➢ Imaging and dosimetry with 203Pb ➢ Option for treatment with 212Pb Request from NuMeRI, Pretoria, South Africa* ➢ Safety of 212Pb ➢ Efficacy signals ➢ Includes an imaging and dosimetry step with 203Pb NuMeRI, Nuclear Medicine Research Infrastructure; SCLC, small cell lung cancer; SPECT, single-photon emission computed tomography.
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SPECT/CT Imaging with 203Pb-MP0712 in a Patient with Metastatic Small Cell Lung Cancer (mSCLC) Patient characteristics • 69-year-old male (smoker) • Small cell neuroendocrine carcinoma of the lung • Stage III at referral (mediastinal lesion) Treatment history • Radio- & chemotherapy Dosing • 185 MBq of 203Pb-MP0712 Result • Stage IV by MP0712 - SPECT with 4 liver mets Primary lesion Liver mets Initial high blood pool, followed by specific uptake in primary & metastatic lesions over time in line with MP0712 MoA 116 h post injection4 h post injection 24 h post injection 8 Patient imaged as part of a Named Patient Access Program at NuMeRI, Pretoria, South Africa. Example of patient case series presented with courtesy of Prof. Dr. M. Sathekge. Complete SPECT/CT imaging data set presented by Dr. Joseph Kabunda (Abstract-ID 207).
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212Pb timeframe (<48h) • Continued tumor uptake during imaging period (up to 116 h) • Higher uptake in liver metastases as compared to primary lesion • Washout from healthy organs visible from 24 h onwards • Healthy organ profile consistent with profile observed in other patients Biodistribution Profile of 203Pb-MP0712 in mSCLC Patient Quantitative image analysis performed by RAPID, LLC. 9 Tumor Lesions Healthy Organs 0.000 0.004 0.008 0.012 0.016 0.020 0 24 48 72 96 120 % IA/g Time [hours] Kidneys Liver Lungs Spleen Red Marrow Tumor Liver Met1 Liver Met2 Liver Met3 Liver Met4 mSCLC, metastatic small cell lung cancer.
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203Pb-MP0712 Uptake in Tumor Lesions • Progressive uptake of MP0712 across different tumor types o ~80% of uptake reached at 24h o Strong tumor retention with continued uptake during imaging period (up to 7 days) • Preferential uptake in metastatic lesions ➢ Ph1 study in US expected to enroll metastatic SCLC patients 10 mSCLC SCLC 0 2 4 6 8 10 0 48 96 144 SUVmean Time [hours] mSCLC mUC0 2 4 6 8 10 0 48 96 144 SUVmean Time [hours] mSCLC SCLC SUVmean SUVmax* mSCLC 10.6 (Day 5) 67 SCLC 4.5 (Day 5) 88 mUC 10.3 (Day 7) 402 Complete SPECT/CT imaging data set presented by Dr. Joseph Kabunda (Abstract-ID 207). Quantitative image analysis performed by RAPID, LLC. * SPECT imaging with 203Pb does not allow reliable SUVmax determination. Mediastinal Lesion Metastatic Lesion Mediastinal lesions Metastatic lesions mUC, metastatic urothelial bladder cancer; SUV, standard uptake volume. Day 5 Day 5 mUC Day 5
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MP0712 Organ Dosimetry and Projection to Phase 1 11 Dosimetry extrapolations suggest kidneys & red marrow as potential dose-limiting organs for 212Pb-MP0712 • At Phase 1 starting dose (75 MBq) and at max. anticipated single dose (200 MBq) all healthy organs are within EBRT limits ➢ Monitor hematologic recovery to guide repeated dosing strategies Kidneys Red Marrow 203Pb Time-Activity Curves 0 0.004 0.008 0.012 0 50 100 150 %IA/g Patients Mean 0 0.002 0.004 0.006 0 50 100 150 %IA/g Time [hours] Patients Mean 1x 75 MBq 212Pb 1x 200 MBq 212Pb 2.1 0.8 0 2 4 6 Kidneys Red Marrow Absorbed Dose 212Pb (Gy) 5.7 2.2 0 2 4 6 Kidneys Red Marrow Absorbed Dose 212Pb (Gy) Dosimetry calculations for 212Pb performed by RAPID, LLC on 5 evaluable patients; RBE = 5. Complete dosimetry dataset presented by Dr. Kamo Ramonaheng (Abstract-ID 260). EBRT, external beam radiation therapy; RBE, relative biologic effectiveness.
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Phase 2 studies MP0712 Phase 1/2a Study for SCLC and other NECs • First-in-Human, US multicenter, Phase 1/2a study of MP0712 monotherapy (NCT07278479) • Patients with small cell lung cancer (SCLC) and other neuro-endocrine cancers (NECs) – Every patient will be imaged (203Pb) before treatment (212Pb) – Patient pre-selection on DLL3 expression: not planned for SCLC and LC NEC of lung, foreseen for epNEC Registration study 2L+ SCLC patients IO, immuno-oncology; LC NEC, large cell neuroendocrine cancer; PoC, proof-of-concept; RP2D, recommended phase 2 dose. 12 Phase 1: Dose Escalation Main objectives: safety, RP2D N=15–39 patients SCLC and lung LC NEC; N=9-39 patients epNEC 203Pb- MP0712 Imaging / dosimetry (SPECT) 75 MBq n=3* 105 MBq n=3-12* 150 MBq n=3-12* RP2D 200 MBq n=6-12* Phase 2a: Dose Expansion and PoC Main objectives: efficacy signals, confirm safety and RP2D N=30 patients SCLC and NEC 212Pb-MP0712 (treatment): * Evaluable patients (Bayesian Logistic Regression Model guided dose escalation) **epNEC to start at a dose level previously tested in SCLC or LC NEC of lung at which a first signal of pharmacological activity is detected. RP2D for epNEC is anticipated to be same as RP2D for SCLC/LC NEC of lung. Dose Y** n=6-12* Dose X** n=3-12* … Registration in patients with other NECs 1–2L combination with IO SCLC
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Clinical Perspective on Data Presented ➢All boxes checked: • First favorable in human biodistribution represents an important milestone • 203Pb-MP0712 SPECT images indicate strong tumor uptake visible until 120-168h • Majority of tumor lesions show increased uptake over time, whereas normal organ uptake seems to wash out • Visual and dosimetric results clear the bar of first in human therapy trial with highest intended starting dose within EBRT limits ➢Next: see how the therapeutic (212Pb-MP0712) performs in patients – now clinical parameters are key Prof. Ken Herrmann, M.D. Chair, Department of Nuclear Medicine, University Hospital Essen, Germany
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2 MP0712 Conclusions Conclusion • Optimized tumor uptake and retention, by leveraging DLL3 replenishment/internalization • Favorable biodistribution and dosimetry on healthy organs, focus on blood recovery • Support MP0712 Phase 1 study design starting at meaningful dose for DLL3+ indications Outlook • MP0712 Phase 1/2a study open in the US, first patient dosing imminent • Initial safety data anticipated in H1 2026, initial activity in H2 2026 14
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Long tumor retention make DARPins alpha-agnostic 15 212Pb window (<48h) Tumor Kidney Blood Time Concentration 225Ac window (>30d) Radio-DARPins • DARPin profile can work for both 212Pb and/or 225Ac • Opportunity to evaluate both isotopes in parallel and decide on the best isotope with data 212Pb 225Ac 225Ac 212Pb
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Radio - F Radio - C Ovarian Cancer 212Pb x MSLN SCLC & NECs 212Pb x DLL3 Radio DARPin Pipeline – News Flow in 2026 RESEARCH PRE-CLINICAL PHASE 1 PHASE 2 Radio - D Radio - E CANDIDATEPLATFORM MP0712 MP0726 Undisclosed Programs (Solid Tumors) alpha-isotope agnostic Co-development* *The co-development agreement with Orano Med includes up to 10 targeted radiotherapy programs, including MP0712 and MP0726. AML, acute myeloid leukemia; DLL3, Delta-like ligand 3; HSCT, hematopoietic stem cell transplant; MDS, myelodysplastic syndrome; MSLN, mesothelin; NEC, neuroendocrine cancer; r/r, relapsed/refractory; SCLC, small cell lung cancer. Co-development* Radio- DARPin Therapy (RDT) 212Pb 225Ac 225Ac 212Pb Evaluate Radio-DARPin candidates in an alpha-agnostic approach Evaluate Radio-DARPin candidates in an alpha-agnostic approach Progress MP0726 into FIHProgress MP0726 into FIH Nominate new RDT programsNominate new RDT programs Aim: 1 cohort per Q Safety in H1, activity H2
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Acknowledgments 17 Team at Molecular Partners AG Julien Torgue Amal Saidi Aaron Schatzmann Tania Stallons Amy Wong Federico Rojas Amanda Reyes Jessica Johnson Rob Chastain Haley Sprague Volker Wagner & clinical team Orano Med Team Patients and their Families NuMeRI Team Mike Sathekge Joseph Kabunda Honest Ndlovu
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Twenty Years of Pioneering DARPin Therapeutics for Patients Thank you!