Slides
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1 (NASDAQ:DRTS) R&D Update Day
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2 This presentation (together with oral statements made in connection herewith, the "Presentation") is for informational purposes only to assist interested parties in making their own evaluation with respect to Alpha Tau Medical Ltd. (“Alpha Tau” or the “Company”). The information contained herein does not purport to be all-inclusive and neither the Company nor any of its respective subsidiaries, stockholders, shareholders, affiliates, representatives, control persons, partners, directors, officers, employees, advisers or agents make any representation or warranty, express or implied, as to the accuracy, completeness or reliability of the information contained in this Presentation. You should consult your own counsel and tax and financial advisors as to legal and related matters concerning the matters described herein, and, by accepting this Presentation, you confirm that you are not relying upon the information contained herein to make any decision. You shall not rely upon any statement, representation or warranty made by any other person, firm or corporation in making its investment ordecision to invest in the Company. To the fullest extent permitted by law, in no circumstances will the Company or any of its subsidiaries, stockholders, shareholders, affiliates, representatives, control persons, partners, directors, officers, employees, advisers or agents be responsible or liable for any direct, indirect or consequential loss or loss of profit arising from the use of this Presentation, its contents, its omissions, reliance on the information contained within it, or on opinions communicated in relation thereto or otherwise arising in connection therewith. As previously stated, this Presentation does not purport to be all-inclusive or to contain all of the information that may be required to make a full analysis of the Company. The general explanations included in this Presentation cannot address, and are not intended to address, your specific investment objectives, financial situations or financial needs. Use of Data Certain information contained in this Presentation relates to or is based on studies, publications, surveys and the Company'sown internal estimates and research. In addition, all of the market data included in this Presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while the Company believes its internal research is reliable, such research has not been verified by any independent source and none of the Company nor any of its affiliates nor any of its control persons, officers, directors, employees or representatives make any representation or warranty with respect to the accuracy of such information. Forward-Looking Statements This presentation contains forward-looking statements, including without limitation, statements related to: Alpha Tau becoming the leader in delivering innovative devices in medical technology, our ability to expand our development pipeline, opportunities to expand our portfolio through partnerships and collaborations, the progress, timing and results of our clinical trials, the safety and efficacy of our development programs, the timing of the potential approval of our products, the timing and commercial success of our products, strategies for completion and likelihood of success for our business and activities, size and growth of markets in which we may compete and potential market opportunity, and potential growth opportunities. Forward-looking statements can be identified by the words “believe,” “anticipate,” “continue,” “estimate “project,” “expect,” “plan,” “potential,” “intends,” “will,” “would,” “could,” “should” or the negative or plural of these words or other similar expressions that are predictions or indicate future events, trends or prospects but the absence of these words does not necessarily mean that a statement is not forward-looking. In addition, any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially and reported results should not be considered as an indication of future performance. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, among others, those inherent in the preclinical and clinical development process and the regulatory approval process, the risks and uncertainties in commercialization and gaining market acceptance, the risks associated with protecting and defending our patents or other proprietary rights, the risk that our proprietary rights may be insufficient to protect our development programs, the risk that we will be unable to obtain necessary capital when needed on acceptable terms or at all, competition from other products or procedures, our reliance on third-parties to conduct our clinical and non-clinical trials, our reliance on any third-party suppliers to manufacture clinical, non-clinical and any future commercial supplies of our products, and increased regulatory requirements. These statements are subject to the risk that clinical trial data are subject to differing interpretations, and regulatory agencies, medical and scientific experts and others may not share Alpha Tau’s views of the clinical study data. There can be no assurance that the clinical studies for our development programs will be successful in demonstrating safety and/or efficacy, that we will not encounter problems or delays in clinical development, or that any of our products will ever receive regulatory approval or be successfully commercialized. These forward-looking statements are based on information available to Alpha Tau as of the date of this Presentation and speak only as of the date of this Presentation. Alpha Tau disclaims any obligation to update these forward-looking statements, except as may be required by law. This Presentation is for informational purposes only and does not constitute an offer to sell or a solicitation of an offer to purchase any securities of any nature whatsoever, and it may not be relied upon in connection with the purchase of securities. Trademarks This Presentation may contain trademarks, service marks, trade names and copyrights of other companies, which are the property of their respective owners. Solely for convenience, some of the trademarks, service marks, trade names and copyrights referred to in this Presentation may be listed without the TM, SM © or ® symbols, but Alpha Tau will assert, to the fullest extent under applicable law, the rights of the applicable owners, if any, to these trademarks, service marks, trade names and copyrights. Disclaimer
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Today’s Presenters 3 Raphi Levy CFO Alpha Tau Robert Den, MD CMO Alpha Tau Corey Miller, MD, MSc Endoscopist McGill University Prof. Aron Popovtzer, MD Head of Oncology Hadassah Medical Center Philip Blumenfeld, MD, MPH Radiation Oncologist Hadassah Medical Center
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4 Agenda Updated Interim Pancreatic Cancer Data as of Jan 8, 2025 Robert Den, MD, CMO | Alpha Tau Introduction Raphi Levy, CFO | Alpha Tau1 Treatment Experience – Endoscopic Delivery to the Pancreas Corey Miller, MD, MSc | McGill University Clinical Challenges in Reirradiation: Lung & Rectal Case Studies Philip Blumenfeld, MD, MPH | Hadassah Medical Center 5 6 7 First Treatment of Liver Metastases Robert Den, MD, CMO | Alpha Tau Combination Treatment of Alpha DaRT and Checkpoint Inhibitor Prof. Aron Popovtzer, MD | Hadassah Medical Center 8 Pancreatic Cancer Case Study Philip Blumenfeld, MD, MPH | Hadassah Medical Center 3 2 4 Next Steps, Milestones and Q&A Raphi Levy, CFO | Alpha Tau
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The Alpha Tau Mission 5 Broad potential applicability for local tumor control, together with signs of compelling immuno-stimulatory activity Platform technology has the potential to be utilized alone or synergistically with other cancer treatment modalities Milestones and data from multiple clinical trials in various phases in different indications expected in 2025 and 2026 1st potential U.S. marketing authorization in 2026, with blockbuster market opportunity across multiple tumor types A novel approach using localized alpha particle radiotherapy designed to precisely destroy solid tumors while sparing surrounding healthy tissue
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Healthy Tissue Healthy Tissue Alpha Radiation is Focal - Short Range Limits Clinical Use 6 Alpha Radiation Short range in tissue limits damage to surrounding organs but also limits coverage Beta/Gamma Radiation Long therapeutic range with risk to surrounding organs Whereas beta and gamma radiation can penetrate tissue with sufficient range to facilitate tumor coverage (while risking damage to healthy tissue), alpha radiation has short range in tissue (<100 μm), which limits its clinical usefulness in local delivery
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7 Mechanism of Action of the Alpha DaRT Technology 224Ra Decay Chain Alpha DaRT leverages the innate decay chain of Radium-224 The decay chain of Radium-224 includes four alpha particles Radium-224 has a half-life of ~3.7 days, while the remaining decay chain has a total half -life of approximately 12 hours, before eventually stabilizing in inert form Alpha DaRT The Alpha DaRT utilizes stainless steel or titanium sources that are impregnated with Radium -224 When the Alpha DaRT source is injected into the tumor, the radium remains attached to the source while its daughter atoms detach, emitting cytotoxic alpha particle payloads as they move deeper into the tumor until eventually stabilizing Alpha DaRT is designed to overcome the range limitations of alpha particles through precise release of alpha emitters into the tumor, generating a potent and tight distribution of alpha radiation α 224Ra 3.7d 220Rn 216Po 212Pb 212Bi 56s 0.15s 10.64h α α 212Po 208Pb 208Tl α α - - -
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Alpha DaRT - Diffusing Alpha-emitters Radiation Therapy 8 https://www.youtube.com/watch?v=nwfzJHm0fTQ
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Therapeutic Focus We are focused on delivering solutions to three markets that we believe would be best served by the unique characteristics of the Alpha DaRT 9 Localized & Unresectable • Localized tumors that are not surgical candidates and tumors that recur after surgery and are resistant to other therapies, specifically radiotherapy • Alpha DaRT to be evaluated as a later line therapy • Tumor types we are targeting include SCC, H&N SCC and prostate High Unmet Need • Solid tumors that have limited treatment optionswith limited standard of care offering • Alpha DaRT could potentially target broad patient populations • Tumor types we are targeting include GBM and pancreatic cancer Metastatic • Alpha DaRT being evaluated for its potential to induce an immune response in metastatictumors • Alpha DaRT being evaluated in combination with checkpoint inhibitorsas an adjuvant therapy • Tumor types we are targeting include liver, breast and H&N (which includes lip, oral cavity, salivary glands, oropharynx & pharynx) cancers
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Initial Foray into Superficial Tumors 10 Alpha DaRT first tested in superficial tumors – tumors of the skin or head & neck, due to: • Ease of access • Straightforward control • Ongoing monitoring • Strong initial preclinical data in Squamous Cell Carcinoma (SCC) Treatment of hundreds of tumors to date : • Indicated a mild safety profile • Generated marketing authorization in Israel to treat SCC of the skin or oral cavity • Allowed us to submit to PMDA in Japan for marketing authorization to treat recurrent head & neck cancer Pivotal trial (“ReSTART”) underway in the U.S. for recurrent cutaneous SCC
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Key Eligibility Criteria Recurrent non-metastatic cutaneous SCC Patient with no curative standard-of- care options No previously untreatedSCC Treatment and Procedure Treatment planbased on CT- simulation Sources 1cm length, 0.7mm diam. Activity per source3 µCi Local anesthesia Shifting focus to Mohs surgeons Timeline and Follow-Up Alpha DaRT sources insertion Removal after 14 to 21 days Weekly follow-up during the treatment period Primary / safety objectives: Outline of The Multicenter Pivotal Recurrent SCC study Sample size N = 86 patients Secondary objectives: Evaluate O-DOR, local control, PFS and OS (all up to 12 months), and QoL Metrics 11 • ORR based on Best Overall Response • DOR 6 months after initial response • Assess the safety based on statistics of device -related AEs (per CTCAE v5) Targeted Date of Completion: Q3 2025 Targeted Submission to FDA: H1 2026
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Therapeutic Focus We are focused on delivering solutions to three markets that we believe would be best served by the unique characteristics of the Alpha DaRT 12 Localized & Unresectable • Localized tumors that are not surgical candidates and tumors that recur after surgery and are resistant to other therapies, specifically radiotherapy • Alpha DaRT to be evaluated as a later line therapy • Tumor types we are targeting include SCC, H&N SCC and prostate High Unmet Need • Solid tumors that have limited treatment optionswith limited standard of care offering • Alpha DaRT could potentially target broad patient populations • Tumor types we are targeting include GBM and pancreatic cancer Metastatic • Alpha DaRT being evaluated for its potential to induce an immune response in metastatictumors • Alpha DaRT being evaluated in combination with checkpoint inhibitorsas an adjuvant therapy • Tumor types we are targeting include liver, breast and H&N (which includes lip, oral cavity, salivary glands, oropharynx & pharynx) cancers
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13 Agenda Updated Interim Pancreatic Cancer Data as of Jan 8, 2025 Robert Den, MD, CMO | Alpha Tau Introduction Raphi Levy, CFO | Alpha Tau1 Treatment Experience – Endoscopic Delivery to the Pancreas Corey Miller, MD, MSc | McGill University Clinical Challenges in Reirradiation: Lung & Rectal Case Studies Philip Blumenfeld, MD, MPH | Hadassah Medical Center 5 6 7 First Treatment of Liver Metastases Robert Den, MD, CMO | Alpha Tau Combination Treatment of Alpha DaRT and Checkpoint Inhibitor Prof. Aron Popovtzer, MD | Hadassah Medical Center 8 Pancreatic Cancer Case Study Philip Blumenfeld, MD, MPH | Hadassah Medical Center 3 2 4 Next Steps, Milestones and Q&A Raphi Levy, CFO | Alpha Tau
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Overview of Trial Design 14 Three single-arm safety and feasibility trials treating pancreatic cancer patients in parallel: • CTP-PANC-101 monotherapy treatment at 2 sites in Montreal, Canada – up to 37 patients total • CTP-PANC-02 monotherapy treatment at 1 site in Jerusalem, Israel – up to 15 patients total • CTP-ALL-00 flexible basket trial at 1 site in Jerusalem, Israel – no specified limit on number of patients Following initial results, there are some situations where chemotherapy has been used in the first two trials • CTP-PANC-101 allows chemotherapy 30 days after Alpha DaRT treatment • CTP-PANC-02 was modified to allow concomitant chemotherapy Therefore, after initially embarking on monotherapy exploration, a small number of patients from all three trials have received chemotherapy treatment alongside or following Alpha DaRT treatment Due to the exploratory nature of the trials, they do not focus on a specific patient sub -population but rather a broad mix of patients with non-resectable pancreatic cancer
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Patient Characteristics 15 Including the first five patients from the interim data released in late 2023, a total of n = 41 patients have been treated thus far with pancreatic cancer across the three trials Canada (n=24) Israel (n=17) Characteristic (n) PANC-101 PANC-02 ALL-00 Total Gender Male 10 7 6 23 Female 14 2 2 18 Median Age 70 75 72 71 Cancer Stage 2 4 1 0 5 3 4 3 2 9 4 16 5 6 27 Previous/concurrent lines of chemotherapy 0 7 1 1 9 1 9 3 3 15 2 8 5 4 17
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Highlights of Feasibility and Safety 16 100% success in delivering Alpha DaRT sources (feasibility) Strong safety results • Total of 151 adverse events (AEs) reported • 38 were associated with Alpha DaRT (possibly, probably or definitely related), of which 29 were mild (Grade 1), five were moderate (Grade 2) and four were severe (Grade 3), of which three were SAEs • Three related SAEs included: o Two cases of elevated liver functions: ▪ One patient hospitalized and discharge ▪ One patient declined to hospitalize and recovered at home o One case of sepsis – stabilized, hospitalized and discharge
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Possibly-, Probably- or Definitely-Related Adverse Events (by CTCAE) 17 CTCAE Coded Term 1 – Mild 2 – Moderate 3 – Severe 4 – Life- Threatening 5 – Death Total Abdominal pain 6 1 7 Fatigue 5 2 7 Anorexia 3 1 4 Not yet coded 2 1 1 4 Nausea 3 3 Blood bilirubin increased 1 1 2 Gallbladder obstruction 1 1 2 Alkaline phosphatase increased 1 1 Back pain 1 1 Bloating 1 1 Chills 1 1 Gastroesophageal reflux disease 1 1 Sepsis 1 1 Stomach pain 1 1 Vomiting 1 1 Weight loss 1 1 Total 29 5 4 0 0 38
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High Disease Control Rate Observed 18 Among the 41 patients treated, 33 had a measured objective response, with 5 patients awaiting response evaluation and 3 who discontinued prior to evaluation. Results are presented below using Best Overall Response (BOR) for those with a measured response. 18% Objective Response Rate (CR + PR) 91% Disease Control Rate (CR + PR + SD) Including first two patients (heavily underdosed / feasibility only) 19% Objective Response Rate (CR + PR) 97% Disease Control Rate (CR + PR + SD) Excluding first two patients (heavily underdosed / feasibility only)
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Key Caveats: • The data are still relatively immature, but ongoing • Trial designs were focused on feasibility and safety, without the frequent monitoring visits common in studies focused on precise measurement of survival • Five patients treated since Nov 25, 2024, and three patients who exited the study very shortly after treatment, in all cases with insufficient time to reach objective response measurement, were excluded from OS analysis for lack of data maturity • Therefore, a total of n = 33 patients are evaluated for OS using Kaplan-Meier analysis In light of the heterogeneity of the population, we conducted ad-hoc analyses of key sub-groups to offer context vs. expected OS for each group Highlights of Overall Survival (OS) Data 19 Of n=33 patients analyzed, 13 have died The remaining 20 (and the five newer patients) remain alive Population OS Since Diagnosis / Initiation of Last Chemotherapy (mo) OS Since Alpha DaRT Treatment (mo) Overall Population (n=33) 18.6 10.9
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3.0 3.5 7.5 Zjilstra et al Cancer Patients Alliance Alpha DaRT Median OS Since Diagnosis Without Chemo (months) Analysis of Overall Survival in Key Sub-Populations (1/3) Newly Diagnosed / Not Eligible for Chemotherapy (n=8) 20 Note: Median follow-up in Alpha DaRT group of 6.3 months For Illustrative Purposes Only - no head-to-head clinical study has been conducted comparing Alpha DaRT to other products or candidates. Differences exist between trial designs, subject characteristics and other factors, and caution should be exercised when comparing data across unrelated studies Sources: Zijlstra, M. et al (2018). Patient characteristics and treatment considerations in pancreatic cancer: a population based study in the Netherlands. https://doi.org/10.1080/0284186X.2018.1470330 https://pancreatica.org/pancreatic-cancer/pancreatic-cancer-prognosis/ 4/8 Patients Still Alive 8 8 5 4 2 1 1 0 0 2 2.5 4 5 6 7.5 8 10 12 12.5 14 Time from Diagnosis/last chemo. tx. to Death/LFU (months) 0.0 0.2 0.4 0.6 0.8 1.0 Survival Probability At Risk Product-Limit Survival Estimate With Number of Subjects at Risk 8 8 5 4 2 1 1 0 0 2 2.5 4 5 6 7.5 8 10 12 12.5 14 Time from Diagnosis/last chemo. tx. to Death/LFU (months) 0.0 0.2 0.4 0.6 0.8 1.0 Survival Probability At Risk Censored Product-Limit Survival Estimate With Number of Subjects at Risk
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11.1 10.8 10.1 NR* Conroy 2011 Singhal 2014 Dahan 2021 Alpha DaRT Median OS Since Initiation of 1L FOLFIRINOX (months) Analysis of Overall Survival in Key Sub-Populations (2/3) Metastatic (Stage IV) Patients After 1L FOLFIRINOX (n=10) 21 * Median Kaplan-Meier estimate was not reached (NR); median follow-up time was 15.1 months For Illustrative Purposes Only - no head-to-head clinical study has been conducted comparing Alpha DaRT to other products or candidates. Differences exist between trial designs, subject characteristics and other factors, and caution should be exercised when comparing data across unrelated studies Sources: Thierry Conroy et al., FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer. New England Journal of Medicine (2011). DOI: 10.1056/NEJMoa1011923 Singhal MK, et al. A phase III trial comparing FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. Ann Oncol. 2014;25(suppl 4):iv210–53. Laetitia Dahan et al., Randomized Phase II Trial Evaluating Two Sequential Treatments in First Line of Metastatic Pancreatic Cancer: Results of the PANOPTIMOX-PRODIGE 35 Trial. JCO 39, 3242-3250(2021). DOI:10.1200/JCO.20.03329 8 / 10 Patients Still Alive 10 10 10 10 9 7 6 5 5 3 2 1 1 1 1 1 1 1 1 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 Time from Diagnosis/last chemo. tx. to Death/LFU (months) 0.0 0.2 0.4 0.6 0.8 1.0 Survival Probability At Risk Product-Limit Survival Estimate With Number of Subjects at Risk 10 10 10 10 9 7 6 5 5 3 2 1 1 1 1 1 1 1 1 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 Time from Diagnosis/last chemo. tx. to Death/LFU (months) 0.0 0.2 0.4 0.6 0.8 1.0 Survival Probability At Risk Censored Product-Limit Survival Estimate With Number of Subjects at Risk
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Analysis of Overall Survival in Key Sub-Populations (3/3) Progressed After 2L Gemcitabine-Abraxane (n=7) 22 Note: Median follow-up in Alpha DaRT group of 18.9 months For Illustrative Purposes Only - no head-to-head clinical study has been conducted comparing Alpha DaRT to other products or candidates. Differences exist between trial designs, subject characteristics and other factors, and caution should be exercised when comparing data across unrelated studies Source: Mita N, Iwashita T, Uemura S, Yoshida K, Iwasa Y, Ando N, Iwata K, Okuno M, Mukai T, Shimizu M. Second-Line Gemcitabine Plus Nab-Paclitaxel for Patients with Unresectable Advanced Pancreatic Cancer after First-Line FOLFIRINOX Failure. J Clin Med. 2019 May 29;8(6):761. doi: 10.3390/jcm8060761. PMID: 31146420; PMCID: PMC6616879 Huh G, Lee HS, Choi JH, Lee SH, Paik WH, Ryu JK, Kim YT, Bang S, Lee ES. Gemcitabine plus Nab-paclitaxel as a second-line treatment following FOLFIRINOX failure in advanced pancreatic cancer: a multicenter, single-arm, open-label, phase 2 trial. Ther Adv Med Oncol. 2021 Nov 10;13:17588359211056179. doi: 10.1177/17588359211056179. PMID: 34790261; PMCID: PMC8591648. Portal A et al. Nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma after Folfirinox failure: an AGEO prospective multicentre cohort. Br J Cancer. 2015 Sep 29;113(7):989-95. doi: 10.1038/bjc.2015.328. Epub 2015 Sep 15. PMID: 26372701; PMCID: PMC4651133. 3 / 7 Patients Still Alive 7.6 9.9 8.8 23.0 Mita 2019 Huh 2021 Portal 2015 Alpha DaRT Median OS Since Initiation of 2L Gemcitabine + Abraxane (months) 9.0 Months Median OS Since Alpha DaRT 7 7 7 7 6 6 5 4 4 4 3 2 2 2 1 0 0 2 4 5 6 8 10 12 14 15 16 18 20 22 24 25 26 28 30 Time from Diagnosis/last chemo. tx. to Death/LFU (months) 0.0 0.2 0.4 0.6 0.8 1.0 Survival Probability At Risk Product-Limit Survival Estimate With Number of Subjects at Risk 7 7 7 7 6 6 5 4 4 4 3 2 2 2 1 0 0 2 4 5 6 8 10 12 14 15 16 18 20 22 24 25 26 28 30 Time from Diagnosis/last chemo. tx. to Death/LFU (months) 0.0 0.2 0.4 0.6 0.8 1.0 Survival Probability At Risk Censored Product-Limit Survival Estimate With Number of Subjects at Risk
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Pancreatic Cancer Clinical Trial: USA Pilot Newly Diagnosed MetastaticPancreatic Cancer N=12 8-12 cycles of mFOLFIRINOX Insertion (During Cycles 1-4) Primary Endpoint: Incidence of Treatment- Emergent Adverse Events Secondary Endpoints: Overall Survival Progression-Free Survival Pain Improvement 1 2
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Pancreatic Cancer Clinical Trial: French Multicenter LAPC Treated with mFOLFIRINOX N=40 Screening 850mg/m2 BID (28 days) FOLLOW-UP up to 12 months until EOT or tumor progression* Capecitabine Primary Endpoint Safety Secondary Endpoints • Objective Response Rate based on Best Overall Response • Overall Survival • Progression Free Survival • Resectability rate 1 2 CT-scan (RECIST 1.1) every 8 weeks Only patients with stable disease or tumor response according to RECIST 1.1 after mFOLFIRINOX are eligible for the trial Blood samples for PBMC and ctDNA analysis before Alpha DaRT, and every 2 months EOT *Therapeuticoptions (investigator’schoice): Tumor response/stability: • Surgery if resectable disease • Therapeutic pause Tumor progression: 2nd line chemotherapy or Best Supportive Care
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25 Agenda Updated Interim Pancreatic Cancer Data as of Jan 8, 2025 Robert Den, MD, CMO | Alpha Tau Introduction Raphi Levy, CFO | Alpha Tau1 Treatment Experience – Endoscopic Delivery to the Pancreas Corey Miller, MD, MSc | McGill University Clinical Challenges in Reirradiation: Lung & Rectal Case Studies Philip Blumenfeld, MD, MPH | Hadassah Medical Center 5 6 7 First Treatment of Liver Metastases Robert Den, MD, CMO | Alpha Tau Combination Treatment of Alpha DaRT and Checkpoint Inhibitor Prof. Aron Popovtzer, MD | Hadassah Medical Center 8 Pancreatic Cancer Case Study Philip Blumenfeld, MD, MPH | Hadassah Medical Center 3 2 4 Next Steps, Milestones and Q&A Raphi Levy, CFO | Alpha Tau Disclosures: Consultant for Alpha Tau Medical
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First Pancreatic Cancer Patient with CR – ALL-00-HA-006 26 • Patient Background: o 70yo male with pancreatic adenocarcinoma metastatic to the liver o Treated by FOLFIRINOX May-Nov 2023 but demonstrated progressive disease o Treated by Gemcibatine + Abraxane from Dec 2023, demonstrated progression at primary tumor but otherwise stable disease o Treated with Alpha DaRT in Jan 2024, together with continued chemotherapy • Observed Response: o Interim 30-day PET scan demonstrated positive response in radiated tumor but seeming continued liver metastasis o 90-day PET showed complete response in primary tumor and resolution of liver metastasis
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First Pancreatic Cancer Patient with CR – Pancreatic Tumor Response 27 >30 Days Post Treatment 10-Mar-2024 >90 Days Post Treatment 12-May-2024 Before 23-Nov-2023 PET of the pancreatic tumor after 30 days demonstrates minimal SUV uptake at lesion, potential post-treatment inflammation distal to treated lesion. PET after 90 days demonstrates no PET activity and no further inflammation
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First Pancreatic Cancer Patient with CR – Liver Metastasis Response 28 >30 Days Post Tx 10-Mar- 2024 After 90 days post treatment, the lesion no longer remains evident on PET despite no change in systemic therapy, and cancer markers have dropped significantly >90 Days Post Tx 12-May- 2024
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29 Agenda Updated Interim Pancreatic Cancer Data as of Jan 8, 2025 Robert Den, MD, CMO | Alpha Tau Introduction Raphi Levy, CFO | Alpha Tau1 Treatment Experience – Endoscopic Delivery to the Pancreas Corey Miller, MD, MSc | McGill University Clinical Challenges in Reirradiation: Lung & Rectal Case Studies Philip Blumenfeld, MD, MPH | Hadassah Medical Center 5 6 7 First Treatment of Liver Metastases Robert Den, MD, CMO | Alpha Tau Combination Treatment of Alpha DaRT and Checkpoint Inhibitor Prof. Aron Popovtzer, MD | Hadassah Medical Center 8 Pancreatic Cancer Case Study Philip Blumenfeld, MD, MPH | Hadassah Medical Center 3 2 4 Next Steps, Milestones and Q&A Raphi Levy, CFO | Alpha Tau
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30 EUS-Guided Alpha DaRT Insertion: A Novel Treatment for Pancreatic Cancer Disclosures: Consultant for Alpha Tau Medical Consultant for Boston Scientific
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Background PANCREATIC CANCER • Endoscopic ultrasound provides best access to pancreas and provide pathologic diagnosis • Currently, surgical resection is the only potentially curative treatment, but only 15- 20% of patients are candidates • In non-resectablepatients there is NO STANDARD LOCAL TREATMENT • Morbidity from local symptoms (blockages, pain) 31
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Alpha Tau LoadingDevice 32 https://www.youtube.com/watch?v=Ws6ey-lvo38 https://www.youtube.com/watch?v=Ws6ey-lvo38
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Procedure Setup
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Insertion 34 Image: Flaticon.com
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Adjustable Stopper 35 Same “feel” as standard FNA User-friendly “Standard” technique
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Retraction Handle 36 Especially when more challenging to reach Time efficiency Allows 4 Alpha DaRT sources to be delivered with one pass
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Endoscopist Experience 37 Natural extension of the skillset of a trained EUS specialist Procedure length not prohibitive ➔ Room setup only modestly longer after brief learning curve Confidence in safety outcomes ~45 minutes Barrier to adoption is low EUS-guided biopsy, celiac plexus neurolysis Technique is intuitive
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A Word on Radiation Safety For the endoscopist and technologist directly handling the scope, for the first 5 patients: • The max doses on skinwas between 0.8-1.6 µSv • The max dose at 10 mm from skin was between 0.2-0.7 µSv 38 We could perform over 25,000 cases like these before reaching the annual limit for members of the public CNSC limits: Equivalent dose to the skin annual limit 500 mSv (i.e., 500,000 µSv) for nuclear energy workers and 50 mSv (i.e., 50,000 µSv) for the public
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Patient Experience 39 Outpatient procedure Minimally invasive Discharged Same Day 100% discharged after standard endoscopy recovery Good Safety Profile • Few important related adverse events • Mostly minor discomfort • Vast majority with no related symptoms Pain relief within a few days Lack of tumor growth in vast majority
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Grant: Moving Forward • Development of an augmented reality-based navigation model that allows the operator to visualize the anatomy of interest, thus enhancing Alpha DaRT delivery. • In collaboration with Concordia University computer science, bioimaging, engineeringand Alpha Tau’s Technology team Indication Pancreatic cancer Procedure Endoscopic Ultrasound
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Team WorkMakes the Dream Work!
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42 Final Thoughts The Alpha DaRT insertion is straightforward to integrate into our clinical workflow Endoscopists engage pancreatic cancer patients early on the patient journey Patient benefit through pain relief, stabilization of disease Need to consider incorporation of Alpha DaRT in management of metastatic lesions as primary tumor is under better local control Given the safety profile, the incorporation of Alpha DaRT insertion into non-resectablecases is quite promising to become standard of care
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43 Agenda Updated Interim Pancreatic Cancer Data as of Jan 8, 2025 Robert Den, MD, CMO | Alpha Tau Introduction Raphi Levy, CFO | Alpha Tau1 Treatment Experience – Endoscopic Delivery to the Pancreas Corey Miller, MD, MSc | McGill University Clinical Challenges in Reirradiation: Lung & Rectal Case Studies Philip Blumenfeld, MD, MPH | Hadassah Medical Center 5 6 7 First Treatment of Liver Metastases Robert Den, MD, CMO | Alpha Tau Combination Treatment of Alpha DaRT and Checkpoint Inhibitor Prof. Aron Popovtzer, MD | Hadassah Medical Center 8 Pancreatic Cancer Case Study Philip Blumenfeld, MD, MPH | Hadassah Medical Center 3 2 4 Next Steps, Milestones and Q&A Raphi Levy, CFO | Alpha Tau
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Clinical Challenges in Reirradiation 44 • The treatment of recurrent or new primary cancers within or in close proximity topreviously irradiated tissue is a clinically challenging problem due to tissue tolerance concerns: o Reirradiation with SBRT for ultracentral lung tumors (such as the mediastinum) carries a high risk of severe toxicity, including pneumonitis, esophagitis, and fatal hemoptysis. o Reirradiation in the pelvis, such as rectum, carries high risk of rectal dysfunction, nerve damage, fibrosis • Balancing the need to optimize tumor control while minimizing adverse effectsis much more difficult when dealing with prior radiation therapy. • In such scenarios, options include non-curative systemic therapy or reirradiation with conventional or advanced techniques (SBRT or Proton Beam Radiotherapy)
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Current treatment options for recurrent thoracic cancers after previous radiation: SBRT 45 • Sood et al. reported 35% of patients experienced grade 2+ pneumonitis, and 10% had fatal hemorrhage, though likely unrelated to treatment. • Rock et al. found 20% of patients had grade 2+ pneumonitis, and 12% experienced grade 3+ toxicity, including three cases of fatal hemoptysis. • Peulen et al. linked SBRT reirradiation for central tumors to severe toxicity, including grade 5 massive bleeding. • Despite good local control, reirradiation for ultracentral tumors requires cautious patient selection and meticulous dose planning. • Ultra-Central Thoracic Re-Irradiation Using 10-Fraction Stereotactic Body Radiotherapy for Recurrent Non-Small-Cell Lung Cancer Tumors: Preliminary Toxicity and Efficacy Outcomes.Sood S, Ganju R, Shen X, Napel MT, Wang F. Clinical Lung Cancer. 2021;22(3):e301-e312. • Ten Fraction Hypofractionated Stereotactic Body Radiotherapy for the Management of Ultracentral Lung Tumors: A Retrospective Analysis of Dosimetry, Outcomes, and Toxicity.Rock C, Sood S, Cao Y, et al. Radiation Oncology (London, England). 2023;18(1):128. • Toxicity After Reirradiation of Pulmonary Tumours With Stereotactic Body Radiotherapy.Peulen H, Karlsson K, Lindberg K, et al. Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology. 2011;101(2):260-6.
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Current treatment options for recurrent cancers after previous radiation: Proton Therapy 46 • Despite the advantages, proton therapy is not without risks. Chao et al. reported that 42% of patients experienced grade 3 or higher acute and/or late toxicity, with six grade 5 toxicities observed. • Increased overlap with the central airway region and concurrent chemotherapy were associated with higher toxicity rates. • Local failure following radiation remains a problem (close to 25-40%) • Multi-Institutional Prospective Study of Reirradiation With Proton Beam Radiotherapy for Locoregionally Recurrent Non-Small Cell Lung Cancer.Chao HH, Berman AT, Simone CB, et al. Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer. 2017;12(2):281-292. • Feasibility of Proton Beam Therapy for Reirradiation of Locoregionally Recurrent Non-Small Cell Lung Cancer. McAvoy SA, Ciura KT, Rineer JM, et al. Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology. 2013;109(1):38-44. • Definitive Reirradiation for Locoregionally Recurrent Non-Small Cell Lung Cancer With Proton Beam Therapy or Intensity Modulated Radiation Therapy: Predictors of High-Grade Toxicity and Survival Outcomes. McAvoy S, Ciura K, Wei C, et al. International Journal of Radiation Oncology, Biology, Physics.
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Lung Cancer Case Study 47
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48 70-year old male with limited stage small cell lung cancer received external radiation to the lung primary and mediastinum completing August 2023 with concurrent chemotherapy Locally Recurrent Lung Cancer Case Study (1/5)
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49 • Metastatic progression 6 months post treatment s/p chemotherapy and palliative external radiation to several locations with good response • PET-CT in August 2024 demonstrated enlarged and uptake of paratracheal node (mediastinum), SUV 9 which was in region of high dose radiation • Patient referred for Alpha DaRT trial (NCT05632913) Locally Recurrent Lung Cancer Case Study (2/5)
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50 • 10 Alpha DaRT sources were implanted into the paratracheal lymph node (4R station, arrow) • The lymph node’s initial volume was 3.6 cm³, which reduced to 2.1 cm³ at 30 days and 1.7 cm³ at 60 days post-procedure • The Alpha DaRT sources are visible within the treated lesion as white region in panels B and C A. Baseline B. 30-day follow-up C. 60-day follow-up Scans of the first patient treated with Diffusing Alpha-emitters Radiation Therapy (Alpha DaRT) for recurrent lung cancer Change in volume of irradiated lymph node metastasis Baseline 30-day follow-up 60-day follow-up 3.6 cm3 2.1 cm3 1.7 cm3 Percent Change (41.6)% (52.7)% 52.7% Decrease in Tumor Volume at two months Locally Recurrent Lung Cancer Case Study (3/5)
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51 Initial reduction in PET SUV to 7 Post-treatment PET-CT (60 days) Locally Recurrent Lung Cancer Case Study (4/5)
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52 No treatment-related adverse events following the radiation treatment Dose to Normal Organs Locally Recurrent Lung Cancer Case Study (5/5)
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Rectal Cancer Case Study 53
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54 70-year old male presented to our institution after undergoing chemoradiotherapy followed by chemotherapy for a low-lying rectal adenocarcinoma • PET and exam demonstrated residual tumor at the rectum, involving sphincter approximately 3 cm • APR recommended,patient declined Locally Recurrent Rectal Cancer Case Study (1/2)
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55 • In September 2022, patient underwent Alpha DaRT insertion • Exam was normal in March 2023 • PET-CT SUV uptake: 4 • Exam was normal in March 2024 • PET-CT SUV uptake: none • Patient denies any bowel or bladder issues No treatment-related adverse events Locally Recurrent Rectal Cancer Case Study (2/2)
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Conclusion 56 Despite the high risk associated with reirradiation, initial cases of reirradiation of internal organs (lung, rectum) using Alpha DaRT demonstrate high efficacy potential and minimal toxicity
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57 Agenda Updated Interim Pancreatic Cancer Data as of Jan 8, 2025 Robert Den, MD, CMO | Alpha Tau Introduction Raphi Levy, CFO | Alpha Tau1 Treatment Experience – Endoscopic Delivery to the Pancreas Corey Miller, MD, MSc | McGill University Clinical Challenges in Reirradiation: Lung & Rectal Case Studies Philip Blumenfeld, MD, MPH | Hadassah Medical Center 5 6 7 First Treatment of Liver Metastases Robert Den, MD, CMO | Alpha Tau Combination Treatment of Alpha DaRT and Checkpoint Inhibitor Prof. Aron Popovtzer, MD | Hadassah Medical Center 8 Pancreatic Cancer Case Study Philip Blumenfeld, MD, MPH | Hadassah Medical Center 3 2 4 Next Steps, Milestones and Q&A Raphi Levy, CFO | Alpha Tau
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Key Eligibility Criteria Referred for a two-staged hepatectomy to resect liver metastases of colorectal cancer No prior use of systemic investigational agents for primary cancer Sample size N = 10 patients Treatment and Procedure Treatment planbased on CT scan or MRI Sources 0.7 mm in diameter and 1 cm in length Activity per source3 µCi General anesthesia Timeline • 1st operation: one side of the liver is cleared from its metastases & Alpha DaRT sources are implanted in the other side of the liver • 3 - 4 cycles of chemotherapy (6 - 8 weeks) • 2nd operation: The liver lobe containing the metastasis with the sources is resected, to leave the patient with a disease-free liver Primary objectives: Evaluate feasibility & safety of Alpha DaRT implanted in liver metastases Outline of Liver Metastases Study - CTP-LIV-00 Secondary / exploratory objectives: Evaluate pathological and radiological response, determine immunological impact, stratify differences in response by histopath. growth patterns (vascular / immuno.) 58
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Primary Objective Study Schema Alpha DaRT insertion Imaging Pathology Analysis Liver study 59
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First Patient Treated for Liver Cancer 60 • Patient Background: o 48yo male with bilateral liver colorectal metastases o The patient was off chemotherapy for 8 weeks prior to surgery o First stage of two-stage hepatectomy performed on May 9, 2024, with resection of primary colorectal tumor (sigmoidectomy), colorectal liver metastases resected from liver segments 2 and 4, and 25 Alpha DaRTs implanted into a lesion in liver segment 8 (~6% coverage of GTV) • Observations at Day 7 scan and follow-up: o Patient doing well, no signs of distress or dyspnea, no clear jaundice o Treated lesion in segment 8 reduced in dimension from 6.0 cm length to 4.9 cm length o Largest untreated lesion also regressed – the largest hepatic metastatic lesion in segment 7 reduced in dimension from 4.0 cm to 2.9 cm o No newly developed hepatic lesions, portal and hepatic veins remain patent
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First Patient Treated for Liver Cancer – CT Scans 61 Before Tx 24-Apr- 2024 Post Tx 23-May- 2024 Treated Lesion Untreated Lesion
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Post-Treatment Clinical Course 62 • Second surgery conducted on 17-Jun-2024, 5 weeks after initial operation): right liver was resected, including the Alpha DaRT-treated lesion • No significant complications or unexpected events during the post -operative period • The patient was discharged as planned • Recovery post-discharge was uneventful, without any complications • Histopathological observations: o Treated tumor was non-desmoplastic o Adjacent (non-treated but responding) tumor was desmoplastic o Minimal to no damage observed in the surrounding liver parenchyma Adjacent liver parenchyma appears viable and normal
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Adaptive Immune Response 63 • Increased infiltration of CD8+ T cells in the right liver lesions (both treated and untreated), particularly at the tumor margin of the Alpha DaRT-treated lesion o Despite the temporal distance from chemotherapy • This observation may support our hypothesis that enhanced antigen exposure induced by the Alpha DaRT sources can activate cytotoxic T cells • This heightened response was reflected in the increased abundance of cytotoxic T cells (CD8) at the Alpha DaRT- treated tumor margin, as well as higher levels of helper T cells (CD4) and B cells (CD20) • This is not typical for non-desmoplastic tumors, which tend to have a more innate immune microenvironment, and may be explained by the presence of Alpha DaRT in this tumor Right sided liver tumor (Alpha DaRT-treated) CD8 cells cluster at the liver- tumor margin in a right-sided liver tumor Right sided liver tumor, not treated with Alpha DaRT (liver/tumor margin) Significant tumor necrosis can be visualized
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Innate Immune Response 64 • The innate immune response displayed a mixed pattern in the Alpha DaRT-treated tumor, with a notable increase in dendritic cells and neutrophils but a lower abundance of macrophages compared to the untreated tumor • This finding is significant, particularly in light of research in mouse models showing that macrophages can contribute to CD 8 T cell apoptosis and increased resistance to immunotherapy Alpha DaRT-treated tumor Low levels of CD68 stain are seen in the tumor
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Case Summary 65 • The implantation of (Alpha DaRT) was performed without significant technical difficulties • No adverse events related to Alpha DaRT treatment were observed throughout the clinical course of the patient • There was no evidence of source migration, and complete removal of all Alpha DaRT sources from the liver was confirmed during the second hepatectomy • No safety concerns were observed regarding the insertion of Alpha DaRT source for either the medical staff, nursing staff, or the patient • No instances of excessive hemorrhage • The patient’s recovery followed a normal trajectory, and the postoperative course was consistent with expectations for liver resection • The adaptive immune response appeared more pronounced in the Alpha DaRT-treated tumor • Reduced macrophages may indicate reduced immune suppressionand corresponds to the preclinical findings • Decrease in the tumor size was observed in the untreated adjacent lesiondespite long period without chemotherapy
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66 Agenda Updated Interim Pancreatic Cancer Data as of Jan 8, 2025 Robert Den, MD, CMO | Alpha Tau Introduction Raphi Levy, CFO | Alpha Tau1 Treatment Experience – Endoscopic Delivery to the Pancreas Corey Miller, MD, MSc | McGill University Clinical Challenges in Reirradiation: Lung & Rectal Case Studies Philip Blumenfeld, MD, MPH | Hadassah Medical Center 5 6 7 First Treatment of Liver Metastases Robert Den, MD, CMO | Alpha Tau Combination Treatment of Alpha DaRT and Checkpoint Inhibitor Prof. Aron Popovtzer, MD | Hadassah Medical Center 8 Pancreatic Cancer Case Study Philip Blumenfeld, MD, MPH | Hadassah Medical Center 3 2 4 Next Steps, Milestones and Q&A Raphi Levy, CFO | Alpha Tau Disclosures: Consultant for Alpha Tau Medical
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Key Eligibility Criteria Recurrent unresectableor metastatic head and neck squamous cell carcinoma (like KEYNOTE-048) No previous treatment for metastatic disease Primary objective: Evaluate confirmed Best Overall Response (BOR) per RECIST version 1.1 Outline of Checkpoint Inhibitor Combination Trial – CTP-HNCPI-00 Secondary objectives: Evaluate Safety, Progression Free Survival (PFS), Overall Survival (OS) and Duration of Response (DOR) 67 Trial Objectives • Using the H1 optimal EF design, in the first stage 18 patients are evaluated: if no more than 2 patients respond, then terminate the trial for futility, if more than 6 patients respond then stop the trial for success • Otherwise, accrual continues to a total of 43 patients • Allowing for a 10% loss to follow-up, we may recruit up to 48 patients to the study • We would conclude that the treatment is effective if more than 12 of the 43 patients have a BOR of CR, PR, or SD Two-Stage Adaptive Design Note: Sample size calculated for this trial design assuming p1 = 35% and p0 = 20% for power (1 -β) of 80%, and α of 10%
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Treatment Regimen and KEYNOTE-048 Benchmark 68 Source: Burtness, B. et al (2019). Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. The Lancet. doi:10.1016/s0140-6736(19)32591-7 Note: Benchmark data provided for illustrative purposes only. Not a head-to trial. KEYNOTE-048: Benchmark comparator data for 1L Pembrolizumab in patients with recurrent or metastatic HNSCC Population Benchmark Regimen Systemic ORR Systemic CR % PD-L1 CPS ≥ 20 Pembrolizumab Alone 23% 8% PD-L1 CPS ≥ 1 Pembrolizumab Alone 19% 5% Total population Pembrolizumab Alone 17% 5% (-35) – (-17) -16 0 5 15 26 Alpha DaRT Insertion ICF Signature Alpha DaRT Removal Pembrolizumab cycle Pembrolizumab cycle Follow up period Continuous Tumor Response Every 6 weeks Continue Pembrolizumab cycles Q3W Days Screening period 24 Months
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Subject Disposition 69 Screened Screen Failure N = 10 Enrolled & Treated N = 8 • ECOG of 3 • Tumor not amenable to DaRT insertion N = 2 Terminated N = 5 • 3 deaths • 1 withdrew consent • 1 adverse event Ongoing Follow-up N = 3
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Demographics and Tumor Characteristics 70 Subject ID Age Sex Stage Alpha DaRT Target Tumor Location Tumor Volume (cm3) HNCPI-00-01-001 74 Male Stage IV Neck 2.6 HNCPI-00-01-002 90 Male Stage IV Tongue 4.7 HNCPI-00-01-003 96 Female Stage IV Mandibular alveolus 7.6 HNCPI-00-01-004 63 Female Stage II Neck 79.8 HNCPI-00-01-007 69 Female Stage IV Jaw 6.1 HNCPI-00-01-008 92 Male Stage IV Left mandible 13.0 HNCPI-00-01-009 71 Male Stage III Neck 210.2 HNCPI-00-01-010 61 Male Stage IV Neck 13.0
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Adverse Events 71 Subject ID AE # Adverse Event Description SAE Relationship to Device Severity HNCPI-00-01-002 1 Cardiac arrest Yes Not related 5 - Death 2 Weight loss No Not related 1 - Mild 3 Fall No Not related 2 - Moderate HNCPI-00-01-003 1 Skin infection No Not related 2 - Moderate HNCPI-00-01-004 1 General deterioration Yes Not related 5 - Death 2 Hypothyroidism No Not related 1 - Mild 3 Tracheostomy No Not related HNCPI-00-01-007 1 Lymphadenopathy No Not related 1 - Mild 2 Hyperthyroidism No Not related 2 - Moderate 3 Inflamation No Not related 2 - Moderate 4 Tachycardia No Not related 1 - Mild HNCPI-00-01-009 1 Pulmonary embolism No Not related 3 - Severe 2 Thyroiditis autoimmune No Possibly related 1 - Mild 3 Intestinal perforation Yes Not related 3 - Severe HNCPI-00-01-010 1 Fever No Not related 1 - Mild 2 Rash No Probably related 1 - Mild
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Early Interim Data as of Jan 9, 2025 Show Strong Systemic Responses 72 • Patients received an average of 4 cycles of pembrolizumab (range 2 -9) • Systemic responses observed: o Three complete responses o Three partial responses o Two patients died prior to evaluation • Only two Alpha DaRT-related adverse events, both were Grade 1 (mild) 37.5% Systemic Complete Responses 75% Systemic Objective Response Rate (CR + PR) No Related SAEs
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HNCPI-00-01-003 Pembrolizumab Combination Case Study 73
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Case Background – HNCPI-00-01-003 74 Age 96 Sex Female Tumor Type SCC Date of First Diagnosis Jul-2022 Location Alveolar ridge & lip plus dermal involvement Prior Treatments None Medical Background • Cardio • Dementia • ECOG3 Cancer Stage • Stage IV • T2N1M1
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Alpha DaRT Treatment 75 After Alpha DaRT Removal Oct-2022 Follow-Up Jan-2023 Alpha DaRT Insertion Sept-2022
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Clinical Follow-Up 76 Nine Weeks Post TreatmentPre-Treatment
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Post-Treatment Mar-2024 Pre-Treatment Aug-2022 PET Follow-Up 77
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Patient Status 78 Patient stopped Pembrolizumab after 12 months Patient still alive with no evidence of disease at October 2024 followup
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79 Agenda Updated Interim Pancreatic Cancer Data as of Jan 8, 2025 Robert Den, MD, CMO | Alpha Tau Introduction Raphi Levy, CFO | Alpha Tau1 Treatment Experience – Endoscopic Delivery to the Pancreas Corey Miller, MD, MSc | McGill University Clinical Challenges in Reirradiation: Lung & Rectal Case Studies Philip Blumenfeld, MD, MPH | Hadassah Medical Center 5 6 7 First Treatment of Liver Metastases Robert Den, MD, CMO | Alpha Tau Combination Treatment of Alpha DaRT and Checkpoint Inhibitor Prof. Aron Popovtzer, MD | Hadassah Medical Center 8 Pancreatic Cancer Case Study Philip Blumenfeld, MD, MPH | Hadassah Medical Center 3 2 4 Next Steps, Milestones and Q&A Raphi Levy, CFO | Alpha Tau
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Therapeutic Focus We are focused on delivering solutions to three markets that we believe would be best served by the unique characteristics of the Alpha DaRT 80 Localized & Unresectable • Localized tumors that are not surgical candidates and tumors that recur after surgery and are resistant to other therapies, specifically radiotherapy • Alpha DaRT to be evaluated as a later line therapy • Tumor types we are targeting include SCC, H&N SCC and prostate High Unmet Need • Solid tumors that have limited treatment optionswith limited standard of care offering • Alpha DaRT could potentially target broad patient populations • Tumor types we are targeting include GBM and pancreatic cancer Metastatic • Alpha DaRT being evaluated for its potential to induce an immune response in metastatictumors • Alpha DaRT being evaluated in combination with checkpoint inhibitorsas an adjuvant therapy • Tumor types we are targeting include liver, breast and H&N (which includes lip, oral cavity, salivary glands, oropharynx & pharynx) cancers
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81 USA - Proposed Trials For Initiation In 2025 Pancreas – Pilot – Approved Head & Neck – Combination with Pembrolizumab Recurrent GBM – Early Feasibility Study • Under Breakthrough Device Designation + TAP Program
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Geography Target Indication H1 2025 H2 2025 H1 2026 United States Recurrent Cutaneous SCC Pancreatic Cancer Recurrent GBM Israel Brain Cancer (GBM or Metastases) Europe Pancreatic Cancer (French Multicenter) Japan Head & Neck Cancer Anticipated Milestones Clinical Regulatory Completion of multi-center pivotal trial recruitment 82 Targeted first patient treated First Patient in Pilot Study Data Readout + Potential FDA submission Complete Recruitment in Pilot Study Readout from Pilot Study Early Feasibility Study IDE Targeted first patient treated PMDA Response Readout from Early Feasibility Study
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Geography Target Indication Pre-Clinical Research Feasibility Trial Pivotal Trial Marketing Authorization Anticipated Milestones North America Rec. Cutaneous SCC • Complete patient recruitment in Q3 2025 Pancreatic Cancer • IDE received, targeting first patient Q2 2025 Recurrent GBM • Targeting IDE for early feasibility study in Q2 2025 Pancreatic Cancer Liver Metastases Israel Skin & Oral SCC All Skin & Oral Cancers la/mHNSCC (combo with pembrolizumab) • Exploring U.S. IDE submission for similar study Pancreatic Cancer Lung Cancer Brain (GBM + mets) • Targeting first patient in H1 2025 Prostate Cancer Europe Skin Cancers Vulvar SCC Pancreatic Cancer • Targeting first patient in H2 2025 in French trial Japan Head & Neck Cancer • Targeting PMDA response in Q2 2025 Development Pipeline U.S. U.S. • FDA Breakthrough Device Designation received for certain uses in skin cancer and GBM 83 Canada Canada U.S.
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Questions? 84