Alpha Tau Medical Ltd · NASDAQ:DRTS
Alpha Tau Medical — Investor Presentation (July 2022)
68 slides from Alpha Tau Medical's investor presentation, Jul 18, 2022
Slide 1: Revolutionary Alpha-Emitters Radiotherapy KOL Investor Event
(NASDAQ:DRTS) Revolutionary Alpha-Emitters Radiotherapy KOL Investor Event 1
Slide 2: Disclaimer
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”). By accepting this Presentation, you
Slide 3: Today's Presenters
Today’s Presenters Raphi Levy CFO Alpha Tau Dr. Robert Den Radiation Oncologist Alpha Tau Chief Medical Officer Prof. Michael J. Zelefsky Radiation Oncologist Memorial Sloan Kettering Cancer Center Alpha Tau Scientific Advisory Board Dr. Marc D’Andrea Radiation Oncologist University Cancer Centers 3
Slide 4: Agenda
AGENDA ra) nee Albia Tau 11:00 - 11:15 Pe eles ache Systemic Effect Overview of Potential Systemic Effect Dr. Robert Den, CMO TS ec Local Effect Results from Previous Clinical Studies 11:25 - 11:40 Dr. Michael Zelefsky, Memorial Sloan Kettering Cancer Center User Experience & Selected Case Studies 1
Slide 5: Intro to Alpha Tau
Intro to Alpha Tau Raphi Levy, CFO
Slide 6: Alpha Tau – Key Investment Highlights
Alpha Tau – Key Investment Highlights Proprietary Alpha DaRT designed to safely deliver alpha radiation with localized precision in solid tumors, sparing surrounding healthy tissue 1 Broad potential and preclinical evidence supporting evaluation across various solid tumors (skin, pancreas, breast, G
Slide 7: Types of Radioactive Decay
Types of Radioactive Decay Due to the mass of the alpha particle, in comparison to beta particle, alpha has a low penetration power. This means that the outside layer of the human skin, for example, can block these particles. 7
Slide 8: Mechanism of Action of the Alpha DaRT Technology
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
Slide 9: Alpha DaRT - Diffusing Alpha-emitters Radiation Therapy
Alpha DaRT - Diffusing Alpha-emitters Radiation Therapy 9 https://www.youtube.com/watch?v=nwfzJHm0fTQ Confidential
Slide 10: Intra-tumoral Delivery Methods
Intra-tumoral Delivery Methods We Have a Total of Seven Applicators Which Have Been Developed for a Range of Potential Uses to Accommodate for: Treatment Delivery Method Duration of Implantation Tumor Location Our Applicators Allow Us Flexibility to Deliver Alpha DaRTs Into Both Superficial and Inte
Slide 11: Therapeutic Focus
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 11 Localized & Unresectable • Localized tumors that are not surgical candidates and tumors that recur after surgery and are resistant to othe
Slide 12: Applicable Market Size – Estimates of Annual Incidence Data
Applicable Market Size – Estimates of Annual Incidence Data 12 Surgery, 900,000, 90% Non-Surgery, 100,000, 10% Surgery Recurrence, 4.5%, 40,500 US Applicable Mkt. Size SCC / H&N Annual Incidence US 1,000,000 China 133,500 Japan 28,000 Europe 550,000 Canada 17,500 Breast Annual Incidence US 276,480 C
Slide 13: Local Control & Immune/Abscopal Effect
Local Control & Immune/Abscopal Effect LOCAL CONTROL Dr. Marc D’Andrea & Prof. Michael Zelefsky SYSTEMIC EFFECT Dr. Robert Den 13
Slide 14: Overview of Potential Systemic Effect
Overview of Potential Systemic Effect Dr. Robert Den, CMO
Slide 15: Observed Cancer-Specific Immune Protection (1/2)
In challenging mice 4 months after treatment, those previously treated by the Alpha DaRT displayed a meaningful retained protection against regrowth of the same tumor type, as compared to the two control groups (1) Three groups of mice were inoculated with 5 x 105 CT26 tumor cells and then treated w
Slide 16: Observed Cancer-Specific Immune Protection (2/2)
Observed Cancer-Specific Immune Protection (2/2) Tumor Re-Inoculation2 (Challenge Assay) Colon3 / Breast4 Tumor Cell Re-inoculation 0% 100% 100% 100% Colon (n=10) Breast (n=8) Colon (n=10) Breast (n=10) Tumor-bearing mice ~2 months post re-inoculation Tumor-free DaRT-treated mice Naïve mice Naïve Mi
Slide 17: Alpha DaRT Elicits Effect from anti-PD1 in SCC Mouse Model
Alpha DaRT Elicits Effect from anti-PD1 in SCC Mouse Model (SQ2) While mice with the SQ2 squamous cell carcinoma model showed little to no effect when treated with a murine anti-PD1 agent, the observed effect was larger for the combination with Alpha DaRT than for Alpha DaRT on its own 0 5 10 15 20
Slide 18: Alpha DaRT Increases Infiltration of CD3+ T-cells Into the Tumor
Alpha DaRT Increases Infiltration of CD3+ T-cells Into the Tumor anti PD-1 Alpha DaRT + anti PD-1 Inert DaRT aPD-1 DaRT+anti-PD1 0 5 10 15 TILs in SQ2 tumors % C D 3 + C e l l s / T u m o r c e l l s p=0.005 p=0.03 p=0.02 The combination of Alpha DaRT with anti-PD1 demonstrates the highest level of
Slide 19: Potential Systemic Immune Effect Observed in One Patient
Potential Systemic Immune Effect Observed in One Patient Where a Second, Untreated Lesion Manifested CR Before After 29-Dec-17 30-Nov-17 Untreated Tumors Treated Tumor Before After 29-Dec-17 30-Nov-17 Complete Response + Potential Systemic Immune Effect 19
Slide 20: Results from Previous Clinical Studies
Results from Previous Clinical Studies Michael J. Zelefsky, MD Professor of Radiation Oncology Chief, Brachytherapy Service Memorial Sloan Kettering Cancer Center
Slide 21: CTP-SCC-00: First Clinical Trial
Results from Previous Clinical Studies CTP-SCC-00: First Clinical Trial
Slide 22: Outline of Our First Clinical Study: Skin / Head & Neck SCC
Key Eligibility Criteria SCC histopathologically confirmed Lesions ≤ 5 cm* Age ≥ 18 ECOG performance scale ≤ 2 Patients W/O immunosuppression De-novo or recurrent disease *in the longest diameter (without nodal spread). Treatment and Procedure Treatment plan based on CT- simulation Sources 1cm lengt
Slide 23: CTP-SCC-00: Diagram of Study Subjects & Cases
CTP-SCC-00: Diagram of Study Subjects & Cases 32 Subjects Screened 27 Subjects Treated (31 cases treated) 5 Subjects Excluded Did not meet the eligibility criteria 3 Subjects Excluded • N=1 received treatment outside the protocol • N=1 passed away prior to day 30 FU session • N=1 had the seeds remov
Slide 24: Skin / Head & Neck SCC Study Results
Skin / Head & Neck SCC Study Results 100% overall response rate Durable responses observed Responses observed within days Well tolerated; no systemic toxicity observed Efficacy Results (Patient median age = 80.5 years) Overall Response (n=28) 21.4% 78.6% 0% 20% 40% 60% 80% 100% Partial Response Comp
Slide 25: AP-022 Complete Response
AP-022 Complete Response During 30-Aug-2018 After 30-Sep-2018 Before 27-Aug-2018 During 30-Aug-2018 Applicators used 12 Alpha DaRT sources inserted 24 Total activity [µCi] 48 Age 68 Previous treatments None Tumor initial volume [cm3] 2.8 25
Slide 26: Alpha DaRT Treatment was Well Tolerated
Targeted treatment Designed to spare neighboring healthy tissue No systemic toxicity observed Negligible and short-term radioactivity in the patient’s body Safe procedure for caregivers No special shielding required Alpha DaRT Treatment was Well Tolerated Minimal local toxicity observed Minimal loca
Slide 27: U.S. Pilot Skin / Superficial Soft Tissue Study CTP-SCC-MSK-00
Results from Previous Clinical Studies U.S. Pilot Skin / Superficial Soft Tissue Study CTP-SCC-MSK-00
Slide 28: Outline of Our U.S. Pilot Skin / Superficial Soft Tissue Study
Key Eligibility Criteria Malignant skin or superficial soft tissue Lesions ≥ 1 to 5 cm, depth ≥ 4 mm Suitable for percutaneous interstitial radiotherapy Treatment and Procedure Treatment plan based on CT- simulation Sources 1cm length, 0.7mm diam. Timeline and Follow-Up Alpha DaRT sources insertion
Slide 29: Trial Overview & Subject Disposition
Trial Overview & Subject Disposition Screened (N=11) Treated (N = 10) Screen Failure (N = 1) Eligible (N = 10) Completed (N = 10) First Patient In: July 2021 Last Patient In: Oct. 2021 Last Patient Out: March 2022 29
Slide 30: Patient / Tumor Characteristics
Demographics & Disease Characteristics Treated Subjects (N = 10) Age, years mean ± std Median (min, max) 73.9 ± 10.8 71.5 (57, 92) Sex, n (%) Female Male 4 (40%) 6 (60%) Race, n (%) White 10 (100%) Histopathology, n (%) Basal Cell Carcinoma (BCC) Squamous Cell Carcinoma (SCC) 6 (60%) 4 (40%) Stage,
Slide 31: Safety Results
Safety Results Adverse Event Severity Grade 1 2 3 Dermatitis radiation 2 1 0 Localized edema 1 0 0 Joint range of motion decreased 0 1 0 Pain 0 1 0 Pruritis 2 0 0 Wound infection 0 1 0 Note: Adverse events are presented according to CTCAE V5 coded terms. Number of Subjects with Procedure-or Device-R
Slide 32: Efficacy Results
Efficacy Results All 10 subjects achieved a complete response (CR) at the 12-week follow-up visit There were no reported relapses of disease by the final study visit at 24 weeks 32
Slide 33: User Experience & Selected Case Studies
User Experience & Selected Case Studies Dr. Mark D’Andrea, University Cancer Centers PRAUNNERSUTY
Slide 34: My Background
My Background 34 Rural Areas Southeast Texas • High prevalence of Skin Cancer • Network of 5 cancer centers in SE Texas • Patient draw of 100’s Square Miles
Slide 35: My Research Interests (1/2)
My Research Interests (1/2) • Dozens of patents for radiotherapy / brachytherapy devices and methods of treatment for use in: ➢ Head & Neck ➢ Bladder ➢ Rectum ➢ Sarcoma ➢ Gynecologic ➢ Others 35
Slide 36: My Research Interests (2/2)
My Research Interests (2/2) • Authored a chapter on the abscopal effect in radiotherapy 36
Slide 37: Case 1 - Recurrent BCC on the Nose
Case 1 - 77 Y/O with Recurrent BCC on the Nose Prior treatments: Surgery (2005) Tumor Size: Longest diameter 1.59 cm Depth 0.5 cm Volume 0.65 ml Alpha DaRT Treatment: Applicators used 15 Alpha DaRT sources inserted 20 Total activity [µCi] 40 37
Slide 38: Case 1 - Results
Removal Day 15 days Complete Response 12 weeks Simulation Day Insertion Day Results Case 1 - 77 Y/O with Recurrent BCC on the Nose 38
Slide 39: Case 2 - 92 Y/O with BCC on the Chin
Prior treatments: None Tumor Size: Longest diameter 2.38 cm Depth 0.84 cm Volume 2.3 ml Alpha DaRT Treatment: Applicators used 29 Alpha DaRT sources inserted 58 Total activity [µCi] 116 Case 2 - 92 Y/O with BCC on the Chin 39
Slide 40: Case 2 - Results
Removal Day 15 days Complete Response 12 weeks Simulation Day Insertion Day Case 2 - 92 Y/O with BCC on the Chin Results 40
Slide 41: Case 3 - 75 Y/O with BCC on the Chin / Cheek
Prior treatments: None Tumor Size: Longest diameter 1.7 cm Depth 0.9 cm Volume 1.7 ml Alpha DaRT Treatment: Applicators used 23 Alpha DaRT sources inserted 35 Total activity [µCi] 70 Case 3 - 75 Y/O with BCC on the Chin / Cheek 41
Slide 42: Case 3 - Results
Removal Day 15 days Complete Response 12 weeks Simulation Day Insertion Day Case 3 - 75 Y/O with BCC on the Chin / Cheek Results 42
Slide 43: Case 4 - 71 Y/O with BCC on the Nose
Prior treatments: Cryotherapy (1998), Resection (2005) Tumor Size: Longest diameter 2.59 cm Depth 0.6 cm Volume 1.95 ml Alpha DaRT Treatment: Applicators used 15 Alpha DaRT sources inserted 23 Total activity [µCi] 46 Case 4 - 71 Y/O with BCC on the Nose 43
Slide 44: Case 4 - Results
Removal Day 15 days Complete Response 12 weeks Simulation Day Insertion Day Case 4 - 71 Y/O with BCC on the Nose Results 44
Slide 45: Case 5 - 66 Y/O with Recurrent SCC on the Eye
Prior treatments: Cryotherapy (2000) Tumor Size: Longest diameter 1.63 cm Depth 0.6 cm Volume 0.98 ml Alpha DaRT Treatment: Applicators used 16 Alpha DaRT sources inserted 25 Total activity [µCi] 50 Case 5 - 66 Y/O with Recurrent SCC on the Eye 45
Slide 46: Case 5 - Treatment
Insertion Day Removal Before Insertion Day Case 5 - 66 Y/O with Recurrent SCC on the Eye Treatment 46
Slide 47: Case – Patient Testimonial
Case 5 – Patient Testimonial 47 https://www.youtube.com/watch?v=t2MXPoS5ql4 Confidential
Slide 48: Upcoming Clinical Studies, Including US Pivotal Study
Upcoming Clinical Studies, Including US Pivotal Study Dr. Robert Den, CMO
Slide 49: How Are We Moving Forward?
How Are We Moving Forward? Our guiding principle is to have our scientific discoveries inform our clinical trials and then have our clinical trials inform our scientific research Toward that end: Laboratory Clinic Design experiments that mirror the clinic Focused on neo-adjuvant setting Mechanism Bu
Slide 50: Clinical Trial Portfolio: Superficial to Internal Organs
Temporary Implants Japan Pivotal Trial US Multi-center Pivotal Trial Expanding to Other Histologic Types: Israel Pathologic Response Neoadjuvant Prostate: Israel Liver: Two-stage Hepatectomy: Canada Breast Cancer: Israel Unmet Need / Inoperable Pancreas: Israel/Canada Liver: Israel/Canada Breast: Is
Slide 51: Study Specifics: Pivotal Recurrent Cutaneous SCC Study
Study Specifics A Prospective International Multicenter, Pivotal, Single Arm, Open Label Clinical Study to Assess the Efficacy and Safety of Intratumoral Alpha DaRT224 for the Treatment of Patients with Recurrent Cutaneous Squamous Cell Carcinoma Protocol Number: CTP-SCC-03 51
Slide 52: Outline of Our Multicenter Pivotal Recurrent SCC Study
Key Eligibility Criteria Recurrent non-metastatic cutaneous SCC Patient with no curative standard-of- care options No previously untreated SCC Treatment and Procedure Treatment plan based on CT- simulation Sources 1cm length, 0.7mm diam. Activity per source 3 µCi Local anesthesia Timeline and Follow
Slide 53: Other Indications
Other Indications AlpheTAU
Slide 54: Alpha DaRT In Men With Prostate Cancer CTP-PRST-02
Other Indications Alpha DaRT In Men With Prostate Cancer CTP-PRST-02 54
Slide 55: Outline of our Neoadjuvant Prostate Study
Key Eligibility Criteria Resectable prostate adenocarcinoma Non-metastatic tumor Lesions ≤ 3 cm* Targetable lesion Previously untreated : No prior TURP or prostate surgery No prior pelvic radiation Sample size N = 10 patients Treatment & Procedure Treatment plan based on PSMA PET-CT or multiparametr
Slide 56: Plant Applicator Overview
Plant Applicator Overview 56 https://www.youtube.com/watch?v=hSKbj16moFQ Confidential
Slide 57: Feasibility and Safety Study on Advanced Pancreatic Cancer AT-PANC-101
Other Indications A Feasibility and Safety Study of Intratumoral Diffusing Alpha Radiation Emitters on Advanced Pancreatic Cancer AT-PANC-101 57
Slide 58: Outline of the Pancreas Study
Key Eligibility Criteria Locally advanced (Stage II or III) or metastatic (Stage IV) pancreatic adenocarcinoma Inoperable pancreatic cancer because: • Unresectable • Metastatic disease • Medically unfit for surgery No concomitant chemotherapy or immunotherapy Sample size N = 30 patients Treatment an
Slide 59: Study for Treatment of Liver Metastases CTP-LIV-00
Other Indications A Feasibility and Safety study of Intratumoral Diffusing Alpha Radiation Emitters for the Treatment of Liver Metastases CTP-LIV-00 59
Slide 60: Liver Study Schema
Primary Objective Study Schema Alpha DaRT insertion Imaging Pathology Analysis Liver study 60
Slide 61: Outline of Draft Liver Metastases Study
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 plan based on CT scan or MRI Sources 0.7 mm in diameter and
Slide 62: Early Look at Efforts in Glioblastoma Multiforme
Other Indications Early Look at Efforts in Glioblastoma Multiforme
Slide 63: Alpha DaRT + Avastin Combo Showed Attenuated Growth of GBM Xenografts
0 200 400 600 800 1,000 1,200 1,400 0 5 10 15 20 25 30 35 40 45 Tumor Volume (mm 3 ) Days Post Alpha DaRT Insertion Alpha DaRT+ Avastin Alpha DaRT + IgG Inert + IgG Inert + Avastin n=6 n=7 n=7 n=6 Avastin / IgG control injections 3 times per week for 3 weeks Alpha DaRT Insertion Alpha DaRT + Avastin
Slide 64: Radial Applicator Overview
Radial Applicator Overview 64 https://www.youtube.com/watch?v=IJY965J0xMk Confidential
Slide 65: Future Outlook
Future Outlook Raphi Levy, CFO
Slide 66: Anticipated Milestones by Geography and Indication
Geography Indication Pre-Clinical Research Feasibility Trial Pivotal Trial Marketing Authorization Anticipated Milestones North America Skin Cancers • First patient into US pivotal trial targeted for 2H 2022 Pancreatic Cancer • First patient in feasibility trial 2H 2022 Liver Cancer • Trial in plann
Slide 67: Anticipated Milestones
Geography Indication 2H 2022 1H 2023 2H 2023 North America Recurrent Cutaneous SCC (United States) Pancreatic Cancer (Canada) (Tentative) Israel Prostate Cancer Pancreatic Cancer Japan Head & Neck SCC Anticipated Milestones Clinical / Enrollment Regulatory Completion of multi-center pivotal trial re
Slide 68: Questions?
AlpheTAU Questions?
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