Actinium Pharmaceuticals, Inc. (delaware) · AMEX:ATNM
Actinium Pharmaceuticals, Inc. (delaware) — Actinium Pharmaceuticals — Corporate Update (September 2018)
35 slides from Actinium Pharmaceuticals, Inc. (delaware)'s corporate update, Sep 26, 2018
Slide 1: Company Update: Next Generation Lymphodepletion for CAR-T
Actinium Pharmaceuticals, Inc. Company Update Next Generation Lymphodepletion for CAR-T September 26th 2018 1
Slide 2: Disclaimer and Safe Harbor
Disclaimer and Safe Harbor Some of the information presented herein may contain projections or other forward-looking statements regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management’s
Slide 3: Today's Speakers
Today’s Speakers Dr. Nirav Shah Assistant Professor of Medicine, Division of Hematology and Oncology Sandesh Seth Chairman & CEO Dr. Dale Ludwig Chief Scientific Officer Actinium 3 Pharmaceuticals
Slide 4: Actinium's Next Generation Lymphodepletion for CAR-T
Actinium’s Next Generation Lymphodepletion for CAR-T Latest pipeline initiative is a universal tool addressing the unmet needs of the CAR-T space not addressed by current lymphodepletion regimens Ideation 4Q17 Value Creating Activities YTD 2018 Initiative Launched 3Q18 ♦ Identified new technology op
Slide 5: Nirav Shah, MD, MSHP
Nirav Shah, MD, MSHP ♦ Assistant Professor of Medicine, Division of Hematology and Oncology ♦ Specializes in lymphoma and stem cell transplant at Froedtert Hospital ♦ MD, University of Illinois College of Medicine at Chicago – Alpha Omega Alpha ♦ Internal medicine residency, Massachusetts General Ho
Slide 6: II. CAR-T and the Importance of Lymphodepletion
II. CAR-T and the Importance of Lymphodepletion Actinium 6 Pharmaceuticals
Slide 7: Introduction to the CAR-T Treatment Process
Introduction to the CAR-T Treatment Process ♦ Patient’s own T-cells (autologous) are extracted through leukapheresis ♦ These T-cells are engineered outside of the body to express chimeric antigen receptor (CAR) ♦ Before CAR-T cells are infused, the patient receives chemotherapy referred to as condit
Slide 8: Snapshot of the CAR-T Landscape
Snapshot of the CAR-T Landscape 2 approved CAR-T Products Crowded Field Significant Unmet Needs ♦ 200+ CAR-T trials ♦ Durability of Responses ♦ 60+ CAR-T developers ♦ Cytokine Release Syndrome ♦ 2nd & 3rd generation ♦ Neurotoxicity CAR-T’s in development ♦ Patient Access Actinium 8 Pharmaceuticals S
Slide 9: Introduction to Lymphodepletion for CAR-T
Introduction to Lymphodepletion for CAR-T ♦ Lymphodepletion is being increasingly recognized by CAR-T developers as integral to the CAR-T process and critical to successful patient outcomes ♦ Lymphodepletion is clinically necessary as it: − Depletes lymphocytes to create suitable environment for CAR
Slide 10: Lymphodepletion is a Critical Component of CAR-T Regimens
Lymphodepletion is a Critical Component of CAR-T Regimens ♦ Lymphodepletion is required for robust CAR-T cell expansion and persistance1 ♦ Lymphodepletion typically consists of cyclophosphamide (Cy) and Fludarabine (Flu) ♦ More intense lymphodepletion with Fludarabine increased the peak of expansion
Slide 11: Implications of Intense Lymphodepletion with CAR-T
Implications of Intense Lymphodepletion with CAR-T • The addition of Fludarabine to Cyclophosphamide led to significant increase in CAR-T expansion kinetics, which can result in a less optimal safety profile JCAR014: demonstrates importance of conditioning regimen Actinium Source: Juno Corporate Pre
Slide 12: Standard Flu/Cy Lymphodepletion Chemotherapy is Not Ideal
Standard Flu/Cy Lymphodepletion Chemotherapy is Not Ideal Effectiveness Flu/Cy is toxic, and not fully optimized for CAR-T programs Flu/Cy chemotherapy regimen contributes to Cytokine Release Syndrome (CRS) which remains a serious issue with CAR-T therapies Safety Concerns Multi-variable analysis id
Slide 13: Significant Advantages of Actinium's Lymphodepletion Technology
Significant Advantages of Actinium’s Lymphodepletion Technology Actinium’s next generation lymphodepletion technology offers the potential for improved outcomes, patient convenience and pharmacoeconomic benefit Multiple Doses Single Dose CAR-T Lymphodepletion Flu/Cy Lymphodepletion administration Ac
Slide 14: III. Introducing Actinium's Next Generation Lymphodepletion Technology
III. Introducing Actinium’s Next Generation Lymphodepletion Technology Actinium 14 Pharmaceuticals
Slide 15: Dale Ludwig, PhD – Actinium's CSO
Dale Ludwig, PhD – Actinium’s CSO ♦ Over 20 years of oncology biologics research and development experience at Eli Lilly and Company and ImClone Systems, Inc. ♦ Most recently, CSO, VP of Oncology Discovery Research – Biologics Technology at Eli Lilly and Company ♦ Supported development and launch of
Slide 16: Tumor Microenvironment has Significant Impact on CAR-T Efficacy
Tumor Microenvironment has Significant Impact on CAR-T Efficacy Immune Suppressive Cells in the Tumor The Hostile Tumor Microenvironment2 Microenvironment (TME): A reduction in immune (solid or liquid tumors) suppressor cells can improve the response to adoptive cell therapy (ACT)1 ♦ Both solid and
Slide 17: Actinium's Multi-Modal Targeted Lymphodepletion
Actinium’s Multi-Modal Targeted Lymphodepletion Actinium’s next generation lymphodepletion technology has the potential to create the ideal microenvironment enabling better CAR-T outcomes (1) T cells/B cells Lymphocytes are a sink within the tumor (2) immune microenvironment competing for immune cyt
Slide 18: Strong Rationale for Targeted Lymphodepletion Supported by NCI Research
Strong Rationale for Targeted Lymphodepletion Supported by NCI Research Research from the Rosenberg Lab at the NCI supports the use of radiation as an modality for achieving effective lymphodepletion ♦ 5 Gy of total body radiation delivered by external beam showed similar lymphodepletion to chemothe
Slide 19: Introduction to the Iomab-ACT Program
Introduction to the Iomab-ACT Program Targeted lymphodepletion for CAR-T ♦ Iomab-ACT program uses a low dose of apamistamab-I-131, as a single dose outpatient lymphodepleting regimen prior to CAR-T administration ♦ CD45 is expressed on leukemia and lymphoma cells and normal immune cells but not expr
Slide 20: Effective Lymphodepletion Demonstrated in Pre-clinical Studies
Effective Lymphodepletion Demonstrated in Pre-clinical Studies Targeted lymphodepletion directed at CD45 depletes immune cells with the potency of Flu/Cy and is sparing of red blood cells and platelets Peripheral Blood1 RBC WBC 10 12 Saline RBC Number (x1012/L) Saline 8 FLU/CY WBC Number (x109/L) FL
Slide 21: Macrophages are Implicated in CAR-T Toxicities
Macrophages are Implicated in CAR-T Toxicities CAR-T macrophage recruitment Activated macrophages release proinflammatory cytokines Giavidris, et al., Norelli, et al., CRS and neurotoxicity are associated with release of proinflammatory cytokines following macrophage activation Actinium 21 Pharmaceu
Slide 22: Depletion of T-reg Cells Can Improve Clinical Response
Depletion of T-reg Cells Can Improve Clinical Response Radiation based mechanism of action has been shown to enhance the depletion of immune suppressive T-reg cells, which has a statistically significant improvement in outcomes T-regs T-regs Non Responders Responders TBI Conditioning Regimen Actiniu
Slide 23: Single Dose Lymphodepletion and Clearance for CAR-T
Actinium confidential materials. Do not distribute. Single Dose Lymphodepletion and Clearance for CAR-T Favorable pharmacokinetics and effective lymphodepletion observed with Actinium’s targeted lymphodepleting technology which can be optimized for use with CAR-T ♦ Actinium’s technology fits seamles
Slide 24: Iomab-ACT Program Strong IP Portfolio and Know How
Iomab-ACT Program Strong IP Portfolio and Know How Bolstered R&D efforts have allowed us to architect an intellectual property portfolio related to the Iomab-ACT Program 6 core patent filings Composition Method of matter Formulation of use Optimization or use Flu/Cy potentially limited by CAR-T US98
Slide 25: Iomab-ACT's Value Proposition to the CAR-T Paradigm
Iomab-ACT’s Value Proposition to the CAR-T Paradigm Using a proven modality in a novel targeted manner to achieve optimized lymphodepletion to increase efficacy, reduce toxicities and expand access of CAR-T Depletes lymphocytes and reduces tumor burden – Potentially lowers risk for CRS/NT – CAR-T ce
Slide 26: III. Iomab-ACT Clinical Trial and Development
III. Iomab-ACT Clinical Trial and Development Actinium 26 Pharmaceuticals
Slide 27: Iomab-ACT Program at MCW
Iomab-ACT Program at MCW ♦ MCW intends to initiate a trial that will study Iomab-ACT as a targeted lymphodepletion in conjunction with CAR-T ♦ Together with Actinium, MCW physicians are working to finalize an Investigational New Drug (IND) application for this trial ♦ Teams are finalizing protocols
Slide 28: Proposed Iomab-ACT Clinical Study Design
Proposed Iomab-ACT Clinical Study Design CAR-T Engineering Iomab-ACT CAR-T Apheresis Lymphodepletion Infusion SINGLE Outpatient DOSE Dose 1a (if DLT) Starting dose Lymphodepletion Dose Level 1 Lymphodepletion Dose Level 2 Follow-up post-CAR-T Lymphodepletion Dose Level 3 Phase I, 3+3 dose-escalation
Slide 29: Iomab-ACT Lymphodepletion Optimized for CAR-T
Iomab-ACT Lymphodepletion Optimized for CAR-T CAR-T Engineering Apheresis* Iomab-ACT CAR-T Lymphodepletion Infusion Outpatient; single dose Day -22 to -17 Day 0 CAR-T Engineering Apheresis* Flu/Cy CAR-T Lymphodepletion Infusion Between Day -7 to -2 Day -22 to -17 Day 0 Multi-dose administration Acti
Slide 30: Iomab-ACT Program's Potential Clinical Benefits
Iomab-ACT Program’s Potential Clinical Benefits Iomab-ACT is a targeted and predictable lymphodepletion alternative to nonspecific chemotherapy regimens that can offer enhanced CAR-T expansion and persistence. Simultaneous lymphodepletion/ Improved tumor targeting/ outcomes microenvironment Iomab-AC
Slide 31: III. Iomab-ACT Program – Opportunity for Actinium and the CAR-T Industry
III. Iomab-ACT Program – Opportunity for Actinium and the CAR-T Industry Actinium 31 Pharmaceuticals
Slide 32: Latest Pipeline Initiative in CAR-T
Latest Pipeline Initiative in CAR-T Only multi-disease, multi-target pipeline for targeted conditioning and lymphodepletion Only company with a clinical stage CD45 drug candidate Actinium 32 AML = Acute Myeloid Leukemia, MDS = Myelodysplastic Syndrome, MM = Multiple Myeloma Pharmaceuticals * Investi
Slide 33: Iomab-ACT Program - Universal Potential in CAR-T
Iomab-ACT Program - Universal Potential in CAR-T Iomab-ACT Program presents significant value potential along the CAR-T paradigm Landscape Targets Indications 2 approved therapies CD19 B-Cell cancers Rapidly Growing 4 pivotal stage programs CD20 Multiple Myeloma CAR-T Opportunity 200+ development pr
Slide 34: Expected Value Creating Events
Expected Value Creating Events Iomab-ACT program planned progression and expected milestones Additional clinical and strategic initiatives focused on applying Iomab-ACT to improve CAR-T access and outcomes Present clinical and strategic updates Generate additional data further supporting Iomab-ACT’s
Slide 35: Thank You / Questions & Answer Session
Thank You Actinium Pharmaceuticals, Inc. Questions & Answer Session 35
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