Announcement PDF Lantheus Strategic Investment and Capital Raising June 2024 Not for release to US wire services or distribution in the United R A DIO States P H A R M TH E R A N O STIC S L TD 20 24 1 IMPORTANT NOTICE AND DISCLAIMER The information in this presentation does not constitute personal investment advice. The presentation is not intended to be comprehensive or provide all information required by investors to make an informed decision on any investment in Radiopharm Theranostics Ltd ACN 647 877 889 (Company). In preparing this presentation, the Company did not take into account the investment objectives, financial situation and particular needs of any particular investor. Further advice should be obtained from a professional investment adviser before taking any action on any information dealt with in the presentation. Those acting upon any information without advice do so entirely at their own risk. 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R A DIO P H A R M TH E R A N O STIC S L TD 20 24 2 RAD IS AT THE CUTTING EDGE OF RADIOPHARMACEUTICALS, A TRANSFORMATIVE MODALITY WITHIN CANCER TREATMENT 1 Differentiated Within Radiopharmaceuticals • Clinical-stage company with deep pipeline of radiotherapeutic assets pursuing novel targets, leveraging insights from ADCs, using innovative targeting moieties such as nanobodies – – 2 3 4 5 Targets include PD-L1, HER2, TROP2 (nanobody platform); integrin αVβ6 (peptide) fatty acid synthase (small molecule) Preclinical technologies (mAb-based) Radiopharm Ventures, a Joint Venture with MD Anderson Cancer Center • • JV (private company) in-licensed from MDACC technologies for radiopharmaceuticals use First technology has been disclosed (B7H3-targeting molecule) Radiopharmaceuticals Expertise, In licensing Strategy & Intellectual Property • • • • All team members with previous imaging and therapeutic radiopharmaceutical experience Extensive Scientific Advisory Board of accredited multinational researchers Proprietary molecules designed to identify and target a broad range of malignancies in solid tumors Extensive patent portfolio for targets through 2040 Lantheus Strategic Investment • Lantheus Omega, LLC, a wholly owned subsidiary of Lantheus Holdings, Inc (LNTH.NASDAQ, Market Cap approximately US$5.5Bn) (Lantheus) has entered into agreement with Radiopharm to invest, subject to shareholder approval, ~A$7.5m. Shares to be acquired at A$0.05, which represents a ~47% premium to the last closing price on 19 June 2024 and a ~57% premium to the 5-day VWAP. Option to invest a further ~A$7.5m within 6 months • Under a separate agreement, Lantheus will also secure rights over two early preclinical assets in exchange for a ~A$3m upfront payment Strong Cash and Funding Position Post Capital Raising • Raising of approximately A$70.0m via a two-tranche placement at an Offer Price of A$0.04 per share, representing a 17.6% premium to the closing price of Radiopharm’s shares on 19 June 2024 • • Subject to shareholder approval, Executive Chairman, Paul Hopper, will be participating for A$3m under the Offer Post completion of the capital raise, Radiopharm will have a pro forma cash balance of A$72.9m, which it expects will fully fund its current clinical programs until the end of 2026 R A DIO P H A R M TH E R A N O STIC S L TD 20 24 3 LANTHEUS STRATEGIC INVESTMENT Lantheus Holdings Inc (LNTH.NASDAQ, market cap approximately US$5.5Bn) is a global leader in the development, manufacture and commercialisation of diagnostic and therapeutic radiopharmaceutical products with offices in Massachusetts, New Jersey, Canada and Sweden. Lantheus is investing ~A$7.5m into Radiopharm Shares to be acquired at $0.05 per share. A ~57% premium to the 5-day VWAP Lantheus will secure rights over two early preclinical assets for a A$3m upfront payment Global rights for RAD 206 Development (TROP-2) and RAD 502 (DUNP19) in exchange for a A$3 million upfront payment Option to invest a further ~A$7.5m within 6 months Additional investment to be made at $0.05 per share. A ~57% premium to the 5-day VWAP * Subject to shareholder approval. Shares subscribed for by Lantheus will be escrowed for 12 months from allotment date * Assumes an AUD/USD exchange rate of $0.6670 “We are pleased to make a strategic investment in RAD and partner with them to further expand our innovative pipeline. Radiopharmaceutical theranostics are changing the way cancer is diagnosed and treated, yet we still have more work to do and are inspired to further advance this field with these two preclinical oncology assets.” Brian Markison, Chief Executive Officer of Lantheus R A DIO P H A R M TH E R A N O STIC S L TD 20 24 4 CASE STUDY: LANTHEUS STRATEGIC INVESTMENT IN PERSPECTIVE THERAPEUTICS • • On 9th January 2024, Lantheus announced it had entered into multiple strategic agreements with Perspective Therapeutics, Inc. (NYSE:CATX)* Perspective is a clinical stage radiopharmaceutical company with advanced treatment applications for cancers throughout the body. * • Three assets currently completing a Phase 1/2a trial Option to exclusively license Perspective’s Pb212-VMT-⍺-NET and an option to co-develop certain early stage therapeutic candidates for an aggregate upfront payment of US$28 million in cash 20.0 18.0 16.0 14.0 12.0 10.0 8.0 6.0 4.0 2.0 0.0 Strategic investment of approximately US$33 million to acquire approximately 19.9% of Perspective Perspective Therapeutics Share Price – YTD 2024 Announcement of strategic partnership with Lantheus * See Lantheus announcement here: https://lantheusholdings.gcs-web.com/news-releases/news-release-details/lantheus-expands-radiopharmaceutical-oncology-pipeline-strategic * The performance of Perspective Therapeutics is not necessarily indicative of RAD’s future performance * Share price chart as at 24 June 2024. Source: Capital IQ Perspective share price ~+150% since the beginning of 2024 and the subsequent announcement of a strategic partnership with Lantheus in January 2024 R A DIO P H A R M TH E R A N O STIC S L TD 20 24 5 GROWING INTEREST IN RADIOPHARMA DEAL SPACE (2018 TO PRESENT) Selected Recent M&A Transactions Selected Recent Strategic Agreements • Lantheus/Perspective (‘24) - $61MM upfront/investment • POINT/LLY (‘23) - $1.4B acquisition • Roche/Genentech/PeptiDream (‘23) - $40MM upfront (PD) • Bayer/Bicycle (‘23) - $45MM upfront (product) • Bicycle/Novartis (‘23) - $50MM upfront (PD) • Actinium/Immedica (‘22) - $35MM upfront/commercial • Lantheus/POINT (‘22) - $260MM upfront (product) Public companies: 14, $12B combined Cap Private Companies: 25+, $5.4B combined Cap • Mariana acquired by Novartis for US$1.0B (May ‘24) • Fusion Pharmaceuticals acquired by AstraZeneca US$2.4B (March ‘24) • RayzeBio, Inc acquired by Bristol Myer Squibb for US$4.1B (December ‘23) • POINT BioPharma acquired by Eli Lilly for US$1.4B (October ‘23) 40+ public financings raised >$3.5B 100+ Acquisitions or Alliances Provided $37B in Payments PD = product development. Strategic Agreements and Financing Deals = Biomedtracker, Oct 4 2023; Public companies market cap = Fact Set Research and Brookline Capital Market estimates: Oct 4 2023; Private company info: Pitchbook and Brookline Capital Market estimates: Oct. 1 2023 R A DIO P H A R M TH E R A N O STIC S L TD 20 24 6 6 RADIOPHARMACEUTICALS DELIVER RADIATION DIRECTLY TO CANCER CELLS CANCER CELL LINKER TARGET TARGETING MOLECULE RADIOACTIVE ISOTOPE Building Blocks of Radiopharmaceuticals Considerations Targeting Molecule (high affinity small molecule, peptide or antibody) Serum half-life, immunogenicity, tumor uptake and retention, plasma clearance (especially via renal system) Radioactive Isotope (imaging / therapeutic) Target heterogeneity, tissue anatomy, desired cross-fire effect, mechanism of cytotoxicity, imaging properties Linker (joins targeting molecule and radioactive isotope) Stability, uptake in desired versus undesired organs Imaging Therapeutics SEE and measure disease with radioactive isotopes TREAT cancer with high energy particle emitters Imaging compounds precisely delivers radioactive isotopes to detect and image cancer cells Very high selectivity to cancer cells while limiting damage to healthy tissues R A DIO P H A R M TH E R A N O STIC S L TD 20 24 7 EXPANDING RADIOPHARMACEUTICAL TARGETS AND INDICATIONS Novel Radiopharmaceutical Targets With Validated Biology beyond PSMA, SSTR2, FAPI PD-L1, HER2, (nanobodies); αVβ6 Integrin (peptide), fatty acid synthase (small molecule) Tuned Isotope Selection Lu177 (beta), Ac225 (alpha), Tb161 (beta + Auger) Optimized Binding Moieties Supply Chain Enhancement Nanobodies, high affinity peptides, small molecules R A DIO P H A R M TH E R A N O STIC S L TD 20 24 8 CLINICAL PIPELINE (Nanobodies, Peptide, Small Molecule) PROGRAM RAD204 RAD202 RAD301 RAD302 TARGET & MOLECULE PD-L1 (Nanobody) HER 2 (Nanobody) Integrin αVβ6 (Peptide) INDICATION Dx/Tx ISOTOPE NON-SMALL CELL LUNG CANCER Therapy Lu177 Phase 1 enrolling in Australia, NCT06305962 BREAST / GASTRIC CANCER Therapy Lu177 Ethics approval in Q3 2024 Phase 1 trial starting in Q3-Q4 2024 Imaging Ga68 Therapy Lu177 PRECLINICAL PHASE I PHASE II NOTES FDA Orphan Drug Designation Phase 1 enrolling in the US, NCT05799274 PANCREATIC CANCER Preclinical package to be completed by 2024 Phase 1 trial planned in early 2025 Phase 2a Phase 2b RAD101 RAD102 Fatty Acid Synthase (Small Molecule) Imaging F18 IND preparation for Phase 2b in US (n=30) Therapy I123 Preclinical studies progressing BRAIN METS R A DIO P H A R M TH E R A N O STIC S L TD 20 24 9 PRECLINICAL ASSETS PROGRAM TARGET & MOLECULE INDICATION Dx/Tx ISOTOPE PROSTATE Therapy Tb161 PRECLINICAL PHASE I PHASE II NOTES KLK3 RAD402 (mAb) CMC production ongoing, BioD study ongoing (Phase 1 in 2025 depending on financials) JV with MD Anderson PROGRAM TARGET & MOLECULE B7H3 RV01 (mAb) INDICATION Dx/Tx ISOTOPE Multiple Indications Therapy Lu177 PRECLINICAL PHASE I PHASE II NOTES CMC production ongoing Phase 1 planned in 1H 2025 R A DIO P H A R M TH E R A N O STIC S L TD 20 24 10 Fully Funded To Achieve Upcoming Milestones, which is anticipated to include Four Read-Outs 1H 2024 PROGRAM TARGET & MOLECULE INDICATION Dx/Tx ISOTOPE RAD204 PD-L1 (Nanobody) NON-SMALL CELL LUNG CANCER Therapy Lu177 RAD202 HER 2 (Nanobody) BREAST / GASTRIC CANCER Therapy Lu177 Imaging Ga68 Therapy Lu177 Imaging F18 Therapy I123 RAD301 RAD302 RAD101 RAD102 Integrin αVβ6 (Peptide) Fatty Acid Synthase (Small Molecule) PANCREATIC CANCER 2H 2024 1H 2025 P1 in Aus 2H 2025 read-out P1 in Aus P1 in USA 1H 2026 read-out read-out P1 in USA P2b in USA read-out BRAIN METS P1 in USA R A DIO P H A R M TH E R A N O STIC S L TD 20 24 11 KEY MANAGEMENT TEAM Paul Hopper Riccardo Canevari Chief Executive Officer Vittorio Puppo Chief Operating Officer Dr. Sherin Al-Safadi • Founder of Radiopharm Theranostics • Radiopharm Theranostics CEO since September 2021 • 25 years experience as a life-sciences entrepreneur • Previously, Chief Commercial Officer of Novartis Company Advanced Accelerator Applications S.A. • Has served as Chief Operating Officer since June 2022 • Served in the role since Aug 2023 • Served in the role since September 2023 • Previously, VP Medical Affairs at Point Biopharma • Previously Vice President, Head of CMC and Supply Chain at Orum Therapeutics Executive Chairman • Founder, Chairman, nonexecutive director or CEO of more than fifteen companies in the US, Australia and Asia • Previous and current Boards include Imugene, Chimeric Therapeutics, Viralytics, Prescient Therapeutics, Polynoma and Arovella Therapeutics • Lead for Lutathera inmarket growth strategy & Pluvicto launch strategy • Senior Vice President & Global Head, Breast Cancer Franchise, for Novartis Oncology since 2017 • Previously, Chief Marketing Officer at Bracco Imaging, a world leader in diagnostics • Managed businesses in Europe and Asia for Accuray, Covidien, Mallinckrodt and Amersham • Board member of Life Sciences Capital Vimal Patel VP, Medical Affairs • Lead Strategic & Tactical planning radiopharmaceutical Phase III programs • Global Director, Medical Affairs at Bayer VP, CMC • Led the successful manufacture of two ADCs and contributed to filing an IND leading to a Phase-I trial • Director of Process Sciences and Manufacturing at Actinium Pharmaceuticals R A DIO P H A R M TH E R A N O STIC S L TD 20 24 12 CLINICAL PIPELINE (Nanobodies, Peptide, Small Molecule) R A DIO P H A R M TH E R A N O STIC S L TD 20 24 13 RAD 204 Therapeutic: PD-L1 NANOBODY PD-L1 NANOMAB Single domain monoclonal antibody (Sd mAb) CANCER CELL TARGET PD-L1 PD-L1 Immune Checkpoint Protein Overexpression mediates evasion of immune responses by cancer cells Blockade by antibodies leads to tumour regression LINKER TARGETING MOLECULE Sd mAb RADIOACTIVE ISOTOPE 99Tc to SEE 177Lu to TREAT BENEFITS OF NANOBODY MOIETY • Provides the specificity of a full-size antibody; can bind different epitopes than full-sized antibodies • Allows for more rapid tumor accumulation • Rapidly cleared from blood circulation THERAPY • Strong potential as a preferred combination partner with checkpoint inhibitors (overcome ICI resistance + abscopal effect) • Proven targeting of different epitope vs atezolizumab • PFE/Seagen PD-L1 ADC in development in combination with ICI • Phase I data Pluvicto + pembrolizumab shows promising results (synergistic effect in Prostate Cancer) R A DIO P H A R M TH E R A N O STIC S L TD 20 24 14 RAD 204 Therapeutic: PD-L1 NANOBODY CLINICAL DEVELOPMENT & REGULATORY STRATEGY • Human pharmacokinetic and biodistribution validated with imaging agent (positive Phase I in 16 pts) • Phase I therapeutic dose escalation trial in Australia started • Phase II combo therapy trial with checkpoint inhibitor to follow • No other PD-L1-targeted radiopharmaceuticals in preclinical or clinical development PRECLINICAL √ Imaging PHASE I Therapeutic PHASE I PHASE II 16pts 27 pts 50 pts √ Q1 2024– Q2 2025 Q4 2025 – Q3 2027 R A DIO P H A R M TH E R A N O STIC S L TD 20 24 15 RAD 204 (NM-01) Does Not Interfere With ICI Binding - Combination Potential Binding kinetics at different doses with or without the presence of atezolizumab Biodistribution of [99mTC]-NM-01 in mice 180 Human PD-L1 Kd = 0.8 nM Resp. Diff 130 80 30 200 400 600 800 Biodistribution at 30 min 1000 Time %ID/g 250 200 Resp. Diff 150 2 100 50 0 (50) Biodistribution at 90 min 250 200 150 100 50 3 2 1 1 0 0 NM-01 Atezo + NM-01 Atezo (100) (150) (200) 0 250 200 150 100 50 3 %ID/g (20) 0 100 200 300 400 500 600 700 800 Time In vitro, our nanobody exhibited sub-nanomolar affinity to human PD-L1 and atezo saturation has no impact on its binding Source: Wong et al. AJNMMI 2021; 11(3):154-156. Note: NM-01 is our anti-PD-L1 sdAb Group 1 – 37 MBq, 10ug NM-01 Group 2 – 37 MBq, 200ug NM-01 Group 3 – 37 MBq, 10ug NM-01 + 2 mg atezo In vivo, atezo pre-treatment in mice does not reduce NM-01’s tumor uptake when compared to administration with NM-01 alone R A DIO P H A R M TH E R A N O STIC S L TD 20 24 16 RAD 204 - Imaging with 99mTc Favorable Biodistribution and Diagnostic Characteristics in NSCLC Time–activity curves for organs with highest 99mTc-RAD204 uptake Presence of intra-patient heterogeneity in PD-L1 expression between primary tumor and nodal malignancies • PI FIH study: SPECT imaging of 16 NSCLC patients with 99mTc-labeled RAD 204 (NM-01) • Heterogeneity of PD-L1 expression between primary tumor and nodal sites of disease within same patient • • PD-L1 expression detection by imaging is fast and noninvasive, and may be preferred compared to invasive IHC No reported adverse reactions and acceptable radiation dosimetry Xing Y. et al, J Nucl Med 2019;60:1213–1220 R A DIO P H A R M TH E R A N O STIC S L TD 20 24 17 RAD 204 TRIAL DESIGN 177Lu-anti-PD-L1 single domain Ab in metastatic non-small cell lung cancer • Primary Objectives (Phase 1, Treatment): • To assess the safety and tolerability of 177Lu-RAD204tr • To determine the recommended dose(s) of 177Lu-RAD204tr for future exploration • Population: ≥ 18 years of age with a documented history of PD-L1 positive (>1%) metastatic NSCLC Phase 0 (Imaging Period with 177LuRAD204im) • Design Methodology: BOIN for escalation / de-escalation. N=23 • Imaging: Imaging and dosimetry with low dose 177Lu-RAD204im, consisting of 177Lu-RAD204im Safety Lead-in, with or without dose escalation. • Therapeutic Dose: 177Lu-RAD204tr dose escalation. Treatment period of up to 3 cycles every 6 weeks. Phase I (Treatment Period with 177LuRAD204tr) Dose Level1 Dose (mCi) Dose (GBq) Imaging dose 10 0.37 Dose Level2 Dose (mCi) Dose (GBq) DL1 30 1.1 DL2 40 1.5 DL3 TBD TBD DL4 TBD TBD • Estimated Time to Primary Completion: ~15 months • Dosimetry (Phase 0, Imaging): To assess the biodistribution, pharmacokinetics and radiation dosimetry of 177Lu-RAD204im in selected organs and tumor lesions. R A DIO P H A R M TH E R A N O STIC S L TD 20 24 18 RAD 202 Therapeutic: HER-2 NANOBODY HER-2 NANOMAB Single domain monoclonal antibody (Sd mAb) CANCER CELL TARGET HER2 HER-2 pathway validated in Oncology. Overexpression in Breast Cancer and Gastroesophageal cancers LINKER TARGETING MOLECULE Sd mAb RADIOACTIVE ISOTOPE 99Tc to SEE 177Lu to TREAT BREAST & GASTRIC HER2+ THERAPY FOR PATIENTS REFRACTORY TO ENHERTU Why Post-Enhertu Market Is Increasingly Attractive • Enhertu is moving up treatment lines (DESTINY-BREAST trial) • DAISY trial demonstrated Enhertu activity in HER2-low and undetectable breast cancer patients • No established post-Enhertu therapy • Increasing HER2-low identification efforts to incorporate more patients R A DIO P H A R M TH E R A N O STIC S L TD 20 24 19 RAD 202 Therapeutic: HER-2 NANOBODY CLINICAL DEVELOPMENT & REGULATORY STRATEGY • Human pharmacokinetic and biodistribution proven with imaging agent (positive Phase I in 10pts in 2021, followed by IIT in Germany in additional 6 pts. • 99mTc-labeled single-domain antibody for SPECT/CT assessment of HER2 expression demonstrated favorable safety for use in breast cancer imaging, with reasonable radiation doses, biodistribution and imaging characteristics (Zhao, et al. Molecular Pharmaceutics) • Preclinical package and CMC completed; clinical protocol finalized • Phase I therapeutic dose escalation in Breast / Gastric Cancers planned in Australia in H2 2024 PRECLINICAL √ Imaging PHASE I PHASE I PHASE II 10pts + IIT in 6pts 21 pts 50 pts √ H2 2024 – H1 2026 H1 2026 – H2 2027 R A DIO P H A R M TH E R A N O STIC S L TD 20 24 20 RAD202 - 99mTc SPECT Imaging of Breast Cancer Patients to Determine HER2 Status Favorable Biodistribution and Diagnostic Characteristics Varied uptake of 99mTc-RAD202 in primary and metastatic lesions (CT – top) and SPECT/CT (bottom), demonstrating heterogeneity of HER2 expression Time–activity curves for organs • PI FIH study: SPECT imaging with 99mTclabeled RAD 202 (NM-02) to detect HER2 status of 10 breast cancer patients • Rapid clearance of 99mTc-RAD204 from liver, spleen, and intestines 1 h after injection • No reported adverse reactions and acceptable radiation dosimetry Zhao L, et al. Mol Pharm. 2021 Sep 6;18(9):3616-3622 • Accumulation of 99mTc-RAD204 observed in metastases with varying degrees of uptake • Intra- and inter-tumoral heterogeneity in HER2 expression highlights need for noninvasive imaging to drive treatment decisions R A DIO P H A R M TH E R A N O STIC S L TD 20 24 21 RAD 202 - TRIAL DESIGN HEAT Trial (HER2 Antibody Therapy with Lutetium-177) in patients with HER2+ advanced solid tumors • Primary Objectives (Phase 1, Treatment): • To assess the safety and tolerability of 177Lu-RAD202tr • To determine the recommended dose(s) of future exploration for 177Lu-RAD202 • Population: Advanced solid tumours with HER2 amplification by local testing, including IHC,FISH and/ NGS • Design Methodology: TITE-BOIN to support the doseescalation of 177Lu-RAD202 to allow continuous accrual and real-time dose assignment for new participants. N=21 Phase 0 (Imaging Period 177 Lu-RAD202im) with Phase I (Treatment Period with 177 Lu-RAD202tr) Dose Level Imaging dose Dose Level2 Dose (mCi) 10 mCi Dose (mCi) %Change levels in DL1 ~1.1 GBq (30 mCi) +0% • Imaging: 177Lu-RAD202im, consisting of 177Lu-RAD202im Safety Lead-in, with or without dose escalation. DL2 ~2.2 GBq (60 mCi) +100% • Therapeutic Dose: 177Lu-RAD202tr dose escalation. Treatment period of up to 3 cycles every 6 weeks. DL3 ~4.4 GBq (120mCi) +100% DL4 ~6.6 GBq (180 mCi) +50% DL5 ~8.8 GBq (240 mCi) +33.33% • Estimated Time to Primary Completion: ~12-18 months • Dosimetry (Phase 0, Imaging): To assess the biodistribution, pharmacokinetics and radiation dosimetry of 177Lu-RAD202im in selected organs and tumour lesions. R A DIO P H A R M TH E R A N O STIC S L TD 20 24 dose 22 RAD 301/302 : Imaging and Therapy for Pancreatic Cancer TRIVEHEXIN RGD peptide (arginylglycylaspartic acid) Integrin αvβ6 receptor antagonist CANCER CELL TARGET integrin αvβ6 LINKER TARGETING MOLECULE trivehexin RADIOACTIVE ISOTOPE 68Ga to SEE 177Lu to TREAT INTEGRIN αvβ6 • Design features include hydrophilicity to reduce nonspecific uptake into undesired organs and increase clearance in plasma, trimerization to increase affinity, cyclicity for better selectivity, uptake and tumor retention Target often referred to as “the cancer integrin” given its role in activation of TGFβ and resultant immunosuppression; Expression correlates with decreased survival in numerous carcinomas • Pliant Phase IIa data validates the target in Lung and Liver Fibrosis • PFE/Seagen αvβ6 integrin planning Phase III in NSCLC THERAPY FOR αvβ6 INTEGRIN EXPRESSING TUMORS • Pancreatic cancer is the first targeted indication (~60% expression) • Multi-indication potential beyond PDAC (Head & Neck, NSCLC, TNBC, Colorectal) R A DIO P H A R M TH E R A N O STIC S L TD 20 24 23 RAD 301 Imaging: Ga68-Integrin αVβ6 CLINICAL DEVELOPMENT & REGULATORY STRATEGY • 66 patients already dosed under compassionate use (No drug-related adverse events reported) • 33 patients dosed under Investigator Initiated Research (presented at EANM 9/2023) • IND approved Phase I started, plans to leverage Real-World Evidence and seek a registrational trial • USD 240m peak yearly sales potential in Imaging PDAC (Bell Potter independent report) • Only 1 expected competitor: Integrin αvβ6 - αvβ1 (UC Davis) currently in Phase I COMPASSIONATE USE (Germany) Pilot study in PDAC + H&N PHASE I 66 pts 33pts 9 pts ~100 pts √ √ READ OUT in 2024 1H 2025 – 1H 2026 PHASE II PHASE III R A DIO P H A R M TH E R A N O STIC S L TD 20 24 24 RAD301 Clinical Development (Imaging) 68Ga-trivehexin PET/MRI Imaging Patients with Pancreatic Tumors • • • Selective detection of αvβ6 integrin-expressing tumour lesions in patients with PDAC 66 patients administered RAD301 (as of 2022) – 60 pancreatic cancer and GI tumours – 5 with head and neck cancer – 1 patient with tumour of unknown origin Results indicate that RAD301 can be used to detect and monitor pancreatic cancer – Rapid and specific accumulation in many target PDAC primary lesions and metastases – Low background accumulation and purely renal elimination 68Ga-trivehexin PET/CT Imaging vs F18-FDG • • • Selective detection of αvβ6 integrin-expressing tumor lesions in patients with PDAC & HNSCC 33 patients administered RAD301 Results indicate that RAD301 shows incremental value over F18-FDG in PDAC & HNSCC – Favorable tumor-to-background contrast vs F18-FDG – Sharper images and negligible uptake in the surrounding normal tissue 68Ga-trivehexin PDAC imaging shows superior resolution vs F18-FDG 68Ga-TRIVEHEXIN PDAC IMAGING Partnered with TRIMT Quigley NG Notni J. Eur J Nucl Med 2021 Partnered with TRIMT Data presented at World Theragnostic Congress 2022 (Wiesbaden, Germany) & follow up presented at EANM 9/2023 (Vienna) R A DIO P H A R M TH E R A N O STIC S L TD 20 24 25 MULTI-INDICATION POTENTIAL BEYOND PANCREATIC CANCER Expression of αvβ6-integrin in human cancers High expression case studies NSCLC (103 cases, 291 specimens) ESCC (100 cases, 306 specimens) R A DIO P H A R M TH E R A N O STIC S L TD 20 24 26 RAD 302 Therapeutic: Lu177-Integrin αVβ6 CLINICAL DEVELOPMENT & REGULATORY STRATEGY • GMP peptide production ongoing • GLP Tox and Biodistribution study planned in 2024 • IND submission in H2 2024 • Next step: Phase I dose escalation basket trial (multiple indications) planned for early 2025 R A DIO P H A R M TH E R A N O STIC S L TD 20 24 27 RAD 101: Imaging and Therapy for Brain Metastases F18-PIVALATE CANCER CELL TARGET Fatty acid oxidation Selectively targets fatty acid synthase which is overexpressed in tumours but not normal brain cells LINKER TARGETING MOLECULE pivalate RADIOACTIVE ISOTOPE 18F to SEE 131I / 123I / 211At to TREAT THERAPY FATTY ACID SYNTHASE IS A VIABLE TARGET • • Upregulation of de novo fatty acid synthesis via FASN enables cancer cells to grow in the lipidderived microenvironment of the brain • R&D stage for candidate selection at Imperial College of London • Isotope selection based on chemical stability Disruption of FASN activity can impair growth of brain metastases, representing a viable therapeutic target • Potential use beyond brain mets (e.g., gliomas) R A DIO P H A R M TH E R A N O STIC S L TD 20 24 28 RAD 101 Imaging: F18-PIVALATE CLINICAL DEVELOPMENT & REGULATORY STRATEGY • Ongoing Tech transfer from UK to USA. IND approval after Tech transfer finalized • 24 months to complete late-stage development (Phase IIb + Phase III) • Only 1 expected competitor: Axumin (Bracco) currently in Phase III PRECLINICAL √ PHASE I PHASE IIa PHASE 2b PHASE 3 24 pts 17 pts 30 pts 150 pts √ √ 2H 2024-1H 2025 2H 2025 – 2H2026 R A DIO P H A R M TH E R A N O STIC S L TD 20 24 29 RAD 101 Delivers Positive Phase II Data in Brain Metastasis Trial RAD101 Phase IIa Clinical Trial: F18-p