Actinium Pharmaceuticals, Inc. ATNM: NYSE AMERICAN Investor Presentation February 2018

Transcription

1 , Inc. ATNM: NYSE AMERICAN Investor Presentation February

2 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 current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of s products and services, performance of clinical research organizations and other risks detailed from time to time in 's filings with the Securities and Exchange Commission (the SEC ), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time. This presentation does not constitute an offer to sell securities including but not limited to within any jurisdiction in which the sale of such securities would be unlawful. This presentation does not constitute a solicitation or offer to sell securities. Such offer and the information set forth herein have not been reviewed, approved or disapproved, nor has the accuracy or adequacy of the information set forth herein been passed upon, by the SEC or any state securities administrator. Any representation to the contrary is a criminal offense. An investment in the securities offered by the company is speculative and involves a high degree of risk. Investment in the securities offered hereby is suitable only for persons of substantial financial means who can afford a total loss of their investment. 2

3 Executive Overview Only company with a multi-product, multi-disease pipeline focused on improving bone marrow transplant access and outcomes through improved myeloablation: Iomab-B: Pivotal Phase 3 in Relapsed/Refractory AML age 55+ targeting CD45 Actimab-MDS: Phase 2* in Myelodysplastic syndromes patients with P53 mutations targeting CD33 Only company with a CD33 program with best-in-class potential in multiple diseases: Actimab-A: Phase 2 in Newly diagnosed AML age 60 and above Actimab-MDS: Phase 2* in Myelodysplastic syndromes patients with P53 mutations Actimab-M: Phase 1 in Relapsed or Refractory Multiple Myeloma AWE Technology Platform focused on creating Radio-Conjugates or ARC s and biobetters Highly accomplished, execution oriented team focused on building the leading myeloablation franchise to serve a growing unmet need in transplants and cell therapies Company poised to enter a period rich in clinical milestones with additional value accretion potential via collaborations and partnerships * Expected to enter Phase 2 in

4 Leadership Team Sandesh Seth Chairman & Chief Executive Officer Mark Berger, MD Chief Medical Officer Dale Ludwig, Ph.D. Chief Scientific Officer Anil Kapur Chief Commercial Officer Nitya Ray, Ph.D. EVP, Head of Product Development, Manufacturing & Supply Chain Steve O Loughlin Principal Financial Officer 25+ years of pharmaceutical, biotechnology and financial services industry experience Includes product development, business development and corporate strategy (Pfizer, Warner-Lambert, SmithKline), equity research (Bear Stearns, Commonwealth Associations), healthcare investment banking (Cowen & Co., Laidlaw & Co.) MBA, Finance, NYU ; M.S., Pharmaceutical Science, University of Oklahoma 25+ years of drug development experience and 10 years in patient care and lab-based cancer research Executed clinical development leading to approval of Mylotarg for AML and Tykerb for breast cancer Pharma experience at Wyeth (Pfizer) and GlaxoSmithKline and biotechnology experience at Kadmon, Deciphera and Gemin (Acquired by Cephalon in 2011 for $525 mm) M.D. University of Virginia, Board Certified: Internal Medicine, Hematology and Medical Oncology 20 years of oncology antibody drug discovery and development experience Chief Scientific Officer/VP, Oncology Discovery Research - Biologics Technology at Eli Lilly & Co. Head of Molecular & Cellular Engineering at ImClone Systems, Inc. (acquired by Eli Lilly) Supported development and successful launch of 4 biologic oncology therapies and clinical advancement of 10 additional therapeutic antibodies Ph.D., Microbiology, East Carolina University, B.S., Biology, James Madison University 20+ years of US and international oncology commercialization, sales, and product strategy experience VP, Head of Early Assets, Biomarkers & External Innovation, Worldwide Oncology Commercialization at BMS Advanced early I-O (Symphogen) & CAR-T (Precision Bio-Sciences) partnerships, as VP, Oncology at Baxalta Led launch of multiple Oncology blockbusters at Johnson & Johnson including Imbruvica, and Darzalex MBA, Duke University; M.S., Industrial Engineering, Louisiana Tech University 30 years of radiopharmaceutical and biologics product development and manufacturing experience Sr. VP, Manufacturing and CMC Leader at CytoDyn, Inc., a Phase 3 biologic HIV therapeutic company Sr. VP, Manufacturing at Progenics, Inc., a radiopharmaceutical and oncology company Manufacturing roles at Hoffman-La Roche and Verax Corporation focused on biologics Ph.D., Biochemical Engineering, Rutgers University Nearly a decade of corporate finance, investment banking and business development experience Vice President and Corporate Officer, Protea Biosciences Group, Inc. Business development at Lucid, Inc. (now Caliber I.D.) Investment banking Jesup & Lamont and Forge Financial B.S. Business Administration, finance concentration, Ramapo College of New Jersey 4

5 A Progressing and Expanding Pipeline Multiple value drivers from clinical assets and platform in 2018 and beyond Indications Indications Development Stage Pre Iomab-B Bone Marrow Transplant (BMT) Conditioning ** Relapsed or Refractory Acute Myeloid Leukemia (AML) in Patients Age 55 and Above Other Blood Cancers * Pivotal Phase 3 Phase 1/2* Myeloablation Myeloablation Actimab-A Actimab-M Blood Cancers Newly Diagnosed Acute Myeloid Leukemia in Patients Age 60 and Above Relapsed or Refractory Multiple Myeloma (MM) age 18 and above * Bone Marrow Myelodysplastic Syndromes Transplant (MDS) in patients with P53 Phase 2 (BMT) MDS mutations Conditioning ** Expected to enter Phase 2 in 2018 Actimab- Phase 1* Phase 2 Therapeutic Therapeutic /Myeloablation Myeloablation AWE Platform Liquid & Solid Tumors Antibody Radio-Conjugate (ARC) CD38 daratumumab Pre * Investigator initiated trials using technology ** Conditioning is also known as myeloablation 5

6 Bone Marrow Transplant and Myeloablation Bone Marrow produces stem cells and red and white blood cells that form our blood and immune systems Certain cancers and diseases occur when this process goes awry A Bone Marrow Transplant or BMT involves exchanging diseased for healthy bone marrow is a potential cure for numerous diseases 1 : stem cells red and white blood cells T-cells B-cells Current Standard of Care Currently most patients receive highly toxic high dose chemotherapy to wipe out the diseased bone marrow before a Bone Marrow Transplant. This process is known as conditioning or Myeloablation. Limitations of Chemotherapy Myeloablation Prohibits many patients from receiving BMT - Highly toxic older, generic chemicals - Not well tolerated, especially elderly patients High treatment failure and mortality - Not targeted, requires high doses - Systemic side effects, death - BMT failure and relapse 1) Diseases potentially cured by BMT. Leukemias & Lymphomas such as AML, ALL, CLL, CML, Hodgkins, Non-Hodgkins, Myelodysplastic Syndromes, Multiple Myeloma. Other bone marrow diseases including inherited immune disorders like beta thalassemia major and Sickle cell disease. 6

7 Transforming Myeloablation is focused on improving access and outcomes for transplant via improved myeloablation s drug candidates Targeted to bone marrow Effectively ablates bone marrow Improves access and outcomes Iomab-B 10,000+ Addressable Patients 1 Actimab-MDS 8,500+ Addressable Patients 1 Improved Access Improved Outcomes Patients unable to withstand high toxicity of chemotherapy are eligible for s drug candidates Targeted, non-chemotherapy approach spares healthy organs and is well tolerated by patients enabling greater access to the procedure Reduces time to transplant by at least one third Nearly all patients receiving Iomab-B are able to proceed to a BMT Nearly universal engraftment or initial success of the BMT 2 Improved outcomes as measured by overall survival and cures 1) Company Estimates 2) Iomab-B BMT: Blood 114: (2009) and additional data on file Pagel et. al. (n=36) 7

8 Iomab-B Opportunity to Democratize Myeloablation Iomab-B was developed at the Fred Hutchinson Cancer Research Center ( the Hutch ) and utilized by generations of doctors at the Hutch over two decades and presently Iomab-B boasts a uniquely de-risked profile approximately 500 patients treated in several phase 1 and phase 2 clinical trials for various blood cancers with improved outcomes including transplant success and cures is democratizing access to Iomab-B by conducting the SIERRA trial and forging ahead with a commercial plan Iomab-B first in class targeting CD45 and only clinical program in industry Iomab-B CD45 mab & Iodine-131 DNA Cancer Cell CD45 is the ideal target for myeloablation as it is expressed on proliferating blood cancer cells, normal bone marrow cells and cancer stem cells 1. CD45 NOT found on nonhematopoietic tissues 1 Iodine 131 Beta Emitter Range: 0.8 mm Energy: 0.2 MeV 2 1) Matthews DC, Appelbaum FR, Eary JF, et al. Phase I study of 131I-anti-CD45 antibody plus cyclophosphamide and total body irradiation for advanced acute leukemia and myelodysplastic syndrome. Blood. 1999;94(4): ) Silberstein, Edward B., et al. Journal of Nuclear Medicine (2012):

9 Iomab-B Potential Enhanced Access, Improved Outcomes Regimen Time to BMT Rate of BMT BMT Engraftment Overall Survival Salvage Chemo 2 No BMT 42 days ~15% ~12% 100 elderly patients with relapsed or refractory AML Salvage Chemo + BMT 1 12 days Nearly Universal Nearly Universal Iomab-B + BMT 2 1) Biol Blood Marrow Transplant 15 : (2009), MD Anderson outcomes analysis. (Chemo + BMT n=19) (Salvage Chemo n = 95) 2) Iomab-B BMT: Blood 114: (2009) and additional data on file Pagel et. al. (n=36) 9

10 Pivotal Phase 3 SIERRA Trial Overview 150 Patients relapsed/refractory AML age 55 and above Randomized 1:1 Study Arm: Iomab-B + BMT crossover Control Arm: Salvage Chemo Primary Endpoint durable Complete Response (dcr) at 180 days. SIERRA trial sites 25-30% of BMT market by volume 1 Crossover: Patients without a Complete Response in the control arm are considered failures for that arm and may crossover to the Iomab-B arm. Secondary Endpoint is 1-year Overall Survival. Phase 3 Timeline and Milestones Ad hoc DMC #1 Ad hoc DMC #2 % enrolled: 25% 50% 75% 100% Top Line Results 1) CIBMTR Volumes Dataset National Marrow Donor Program (NMDP)/Be The Match and the Medical College of Wisconsin 10

11 Iomab-B Compelling Commercial Market Opportunity Concentrated and Growing Market with No Competition BMT is Concentrated at a Few Key Centers 1 Allogeneic BMT Growing at a Rapid Pace % growth since % CAGR 1, PPS Exempt Centers Centers of Advisors Top 30 Center Highly concentrated BMT landscape enables to independently commercialize Iomab-B in US with small investment Prospective Payment System (PPS) exempt cancer centers perform over 20% of the AML BMT procedures offering immediate revenue ramp post approval Acute Myeloid Leukemia (AML) sponsored pivotal Phase 3 trial Total 1) CIBMTR Volumes Dataset National Marrow Donor Program (NMDP)/Be The Match and the Medical College of Wisconsin 2) Pasquini MC, Zhu. Current uses and outcomes of hematopoietic stem cell transplantation: CIBMTR Summary Slides, ) Company estimates $2.0B Indications studied at Fred Hutch representing potential label expansion Myelodysplastic Syndrome (MDS) $1.6B Acute Lymphoblastic Leukemia (ALL) $250M Non-Hodgkin s Lymphoma (NHL)/Hodgkin s Lymphoma (HL) Multiple Myeloma (MM) Worldwide Market Potential 3 $1.4B $1.3B $6.6B 11

12 s Industry Leading CD33 Program Industry focused on AML is focused on multiple indications targeting CD33 Actimab-A AML Ongoing Phase 2 Actimab-M Multiple Myeloma Ongoing Phase 1 Actimab-MDS MDS Planned Phase 2 Drug has the only unpartnered CD33 program CD33 Program Disease Prevalence is Meaningful To Even Large Companies Disease Addressable US, EU Market 4 Actimab-A AML 69,800 Actimab-M CD33 Positive Multiple Myeloma 47,400 Actimab-MDS MDS SCT Prep 14,250 Addressable Patient Population: 131, Clinicaltrials.gov 2. Company Materials 3. Conference Abstracts (ASH, AACR, ASCO) 4. Company estimates 12

13 s CD33 Targeting Antibody Radio-Conjugate Developed at the Memorial Sloan Kettering Cancer Center ARC technology has distinct advantages over other modalities targeting CD CD33 Target Antigen DNA Range:.06 mm 1 Energy: 6 MeV 1 CD33 mab CD33 is expressed in approximately 90% of AML patients 2, 25%-35% of Multiple Myeloma patients 3 and 75% of MDS patients 4 Advantages of the ARC approach in CD33 ARC Radio-Conjugate Very high potency - actinium-225 can kill a cell with a single alpha hit 1 No internalization required unlike antibodies or ADCs No known resistance mechanism High potency allows for monotherapy Easy administration, short infusion of one or two doses Short path length minimizes damage to normal cells Enhanced safety/tolerability allows focus on unfit patients 1) Sgouros et al. Radiobiology and Dosimetry of a-particle Emitters for Targeted Radionuclide Therapy. The Journal of Nuclear Medicine 2010; 51: ) Blood Cancer J Jun; 4(6): e218. Distribution and levels of surface expression of CD33 and CD123 in acute myeloid leukemia 3) H Avet-Loiseau, CD33 is expressed on plasma cells of a significant number of myeloma patients, and may represent a therapeutic target, Leukemia (2005) 19, ) 4) Leuk Lymphoma August ; 57(8): CD33 is frequently expressed in cases of myelodysplastic syndrome and chronic myelomonocytic leukemia with elevated blast count. 13

14 Change in Bone Marrow Blasts Actimab-A Promising AML Program Demonstrated ability to generate a response in difficult to treat patients First Generation Bismab-A Results Second Generation Actimab-A Results 100% 223 % Median survival 4x greater than historical data 1 Phase 1 Results 2 Phase 2 ASH % 50% 25% 0.5 mci/kg 0.75 mci/kg 1.0 mci/kg 1.25 mci/kg Dose Level (µci/kg/ fraction) Low PB patient Response Rate (CRc) Dose Level (µci/kg/ fraction) Response Rate (CRc) All low PB 0% 2 x 0.5 0% 2 x 1.5 Enrolling -25% -50% 2 x % 2 x % (9/13) -75% 2 x % -100% 2 x % Single agent activity evidenced by most recent 69% response rate in Phase 2 trial Median age of 75, 6 (67%) patients had prior hematologic disease - 5 (MDS) & 1 (tcml) Limited non-hematologic toxicities > grade 3 Moved to 2 x 1.5 µci/kg/fraction to reduce myelosuppression with data in 2H:2018 Differentiated ARC mechanism of action has good potential in combination trials 1) Median survival 7.6 mo. vs 1.7 mo. historically for untreated. Each bar equals an individual patient response. 2) Jurcic et al ASH Abstract. Phase 1 Trial of Targeted Alpha-Particle Therapy with -225-Lintuzumab and LDAC in patients Age 60 or Older with Untreated AML. 3) 2017 ASH Abstract #2638. A Phase 2 Study of -225-Lintuzumab in Older Patients with Previously Untreated AML Unfit for Intensive Chemotherapy. Program: Oral and Poster Abstracts. Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster II 14

15 Actimab-M First CD33 Agent in Multiple Myeloma Multiple myeloma remains incurable, limited treatment options for refractory patients Poorer outcomes associated with CD33 expression 1 Sizeable addressable market underserved by existing treatment options Multiple Myeloma Prevalence Total # of Patients 3 CD33 Positive 2 US 89,600 22,400 Europe 100,000 25,000 Total 189,600 47,400 CD33 is a risk factor with 3-year mortality 60% greater in CD33+ patients 3 Significant numbers ~25% - 35% of all myeloma patients have CD33 expression 1 Actimab-M Proof of Concept trial data expected in ) Levy, Moshe et al "CD33 Is Expressed in a Significant Subset of Multiple Myeloma Patients in the US and May Represent a Viable Therapeutic Target." Blood 130.Suppl 1 (2017): Web. 05 Jan ) H Avet-Loiseau, CD33 is expressed on plasma cells of a significant number of myeloma patients, and may represent a therapeutic target, Leukemia (2005) 19, ) 3) Onyx, SEER, NCI, ACS, Celgene, Myeloma Euronet, GLOBOCAN, CIBMTR, Kyprolis insert, W Matsui JHI estimate, Ferlay et al Eur J Cancer

16 Strictly Private Actimab-MDS: Myeloablation Agent in High-Risk MDS & Confidential Provide improved treatment for the most difficult-to-treat MDS patients by rapidly and safely bridging them to transplant Gail J. Roboz, M.D Principal Investigator MDS Clinical Research Consortium Despite treatments for higher-risk MDS (Vidaza, Dacogen, Revlimid), p53+ patients have median survival under 2 years CD33 expressed in ~75% of MDS patients 1 and is a good target Trial being done in collaboration with the MDS Clinical Research Consortium Meeting with FDA to discuss regulatory pathway in 1H:2018, initiate Phase 2 trial in mid- 2018, complete enrollment in 2H:2019 1) Leuk Lymphoma August ; 57(8): CD33 is frequently expressed in cases of myelodysplastic syndrome and chronic myelomonocytic leukemia with elevated blast count. 16

17 The Myeloablation Opportunity Outlook is the only company with a multi-product, multi-disease pipeline focused on improved transplant access and outcomes via improved myeloablation Potential for 2 Drug Approvals in the timeframe Compelling revenue opportunity with focus on the top transplant centers 1) SEER Database, Company Estimates 2) CIBMTR Volumes Dataset National Marrow Donor Program (NMDP)/Be The Match and the Medical College of Wisconsin 17

18 Expected Value Addition Milestones Multiple value drivers from clinical assets and platform in 2018 and beyond Program & Milestones 1H:2018 2H:2018 1H:2019 2H: Improved Myeloablation Iomab-B 50%, 75% & 100% enrollment DMC Safety Analyses Ad Hoc Interim Analyses Top line data readout BLA filing submission Commercialization preparation Commercial launch Actimab-MDS Pre-IND meeting with FDA Phase 2 clinical trial CD33 Program Actimab-A Complete patient enrollment Top line analysis FDA End of Phase 2 meeting Pivotal trial initiated Continue Phase 2/Pivotal trial Actimab-M Complete Phase 1 trial enrollment Top line data readout Initiate Phase 2/Pivotal trial Continue Phase 2/Pivotal trial Collaborations & Pipeline Partnering and Pipeline AWE collaborations Product/program partnerships New clinical programs 18

19 Thank-You, Inc. 19