MAGFORCE AG FIGHTING CANCER WITH NANO MEDICINE 2014, Berlin, Germany
2 EXECUTIVE SUMMARY Company Profile Headquartered in Berlin, Germany Current Management Team: B. Lipps, H. Tawfik, C. von Volkmann Frankfurt Stock Exchange (Entry Standard: MF6) Shares outstanding: 23.9 million Achievements First and only nanotechnology device approved for the treatment of brain cancer (EU) therapeutic potential and proof-of-principle for other solid tumors Three NanoActivators installed in Germany for treatment of brain tumors / Glioblastoma USA subsidiary incorporated MagForce USA, Inc. Pre-Sub meeting with FDA
NANOTHERM THERAPY
4 TUMOR THERAPY FROM THE INSIDE OUT: NANOTHERM THERAPY Therapy component NanoTherm NanoPlan NanoActivator Brain (EU approved) Pancreas (Phase II) Prostate (Phase I) 12nm Core Coating Functional surface (Aminosilane) Mode of action Step 1 Step 2 Step 3 NanoTherm magnetic fluid injected directly into tumor tissue Nanoparticles remain in place due to their special coating After the injection the treating physician plans a therapy session based on a simulation with NanoPlan The simulation takes into account the tumor size, distribution of the Nano- Therm particles and tumor location Magnetic field causes NanoTherm particles to oscillate and produce heat Heat destroys or makes cells susceptible to concomitant radio- or chemotherapy
GLIOBLASTOMA MULTIFORME: NANOPLAN 5 MRI of glioblastoma multiforme CT after instillation of the magnetic nanoparticles Calculated temperature distribution: range from 40 C (blue line) to 50 C (red line) Jordan et al., Der Onkologe 2007; 13: 894-902
6 PREVIOUS EUROPEAN CLINICAL TREATMENT EXPERIENCE Patients Glioblastoma Multiforme 80 Prostate Cancer 29 Esophageal Cancer 10 Pancreatic Cancer 7 Other Indications ~20
POTENTIAL SOLID TUMOR CANCER TREATMENTS ENHANCED BY NANOTHERM THERAPY 7 2012 Estimated total number of cancer incidence per year in selected tumor indications 1 Prostate 70,800 323,800 +XX 899,100/year Head & Neck 15,600 95,400 634,800/year Pancreas 14,700 69,700 278,700/year Brain 6,200 37,000 214,100/year Germany EU27 World 1 Source: GLOBOCAN 2008, IARC 29. Apr. 2013; total numbers of estimated cancer incidence, all ages, both sexes; cartoon adapted to numbers of incidence in log scale
SIGNIFICANT MARKET POTENTIAL IN THE TREATMENT OF BRAIN AND PROSTATE CANCERS WITH REGIONAL EXPANSION 8 Total numbers of cancer incidence in selected tumor indications 1 Prostate 70,800 186,320 323,800 899,100 Projected Annual Medical Treatment Expense > 10 Billion Euros 580,920 (65%) 62,827 (29%) Projected Annual Medical Treatment Expense > 2 Billion Euros Brain 6,200 19,627 37,000 214,100 Germany USA EU27 World 1 Source: GLOBOCAN 2008, IARC 29. Apr. 2013; total numbers of estimated cancer incidence, all ages, both sexes; cartoon adapted to numbers of incidence in log scale
CLINICAL OVERVIEW
10 MAGFORCE CLINICAL DEVELOPMENT FOR NANOTHERM INDICATION Feasibility Efficacy STATUS Brain tumors GBM post-marketing EU approval Initiating ongoing Prostate carcinoma Pancreatic carcinoma Clinical Development Status/Targets: Brain tumors: post-marketing study to establish NanoTherm therapy in the medical community Prostate carcinoma: focus on early to intermediate stage disease to prolong active surveillance period, support organ preservation, and enhance quality of life Pancreas carcinoma: provide additional therapy to expand currently limited treatment options, increase efficacy of available chemotherapy and prolong survival SIGNIFICANT THERAPEUTIC POTENTIAL IN A VARIETY OF SOLID TUMOR INDICATIONS
11 APPROVAL STUDY DEMONSTRATES THAT NANOTHERM THERAPY IS A UNIQUE METHOD TO SUCCESSFULLY TREAT GLIOBLASTOMA Phase II study results 1 +7.2 months of patient life 6.2 13.4 After diagnosis of first tumor recurrence Historical control ² ³ +8.6 months of patient life 14.6 23.2 After diagnosis of primary tumor NanoTherm therapy¹ Clinical study highlights Results of phase II study with 59 patients published (recurrent GBM) Approval received in Europe for treatment of all (primary and recurring) brain tumors Concurrent therapy to radiotherapy Good safety profile and efficacy shown in clinical trials Viable treatment option for recurring GBM Well tolerated treatment with only low to moderate side effects Positive risk-benefit profile NanoTherm will First be Used as Additional Treatment for Recurring Glioblastoma and has Potential to Later Substitute Radiotherapy 1 Maier-Hauff et al. (2010), Journal of Neurooncology 103(2): 317-324 2 Stupp et al. (2009), Lancet Oncology 10:459-466 3 Stupp et al. (2005), N Engl J Med 352:987-996
12 NEW STUDY WITH NANOTHERM IN RECURRENT GLIOBLASTOMA COMPANY INTENTION Establish NanoTherm with the medical community as a valued therapy for brain cancer STUDY DESIGN Open label, randomized 2:2:1, 3 arms, two-step design STUDY OBJECTIVE Efficacy and safety evaluation of NanoTherm monotherapy and in combination with radiotherapy versus radiotherapy alone PATIENTS NUMBER 285 patients END POINTS 1-year survival rate from randomization; overall survival; progression free survival TIMELINE Start 2014; 2 year recruitment phase + 1 year read out SITES WITH ACTIVATOR University Hospitals (10 to 15 in total): In place: Berlin, Muenster Installation ongoing: Cologne, Kiel Next planned: Frankfurt, Nuremberg, Stuttgart
13 CHARACTERISTICS OF CURRENT NANOTHERM TECHNOLOGY Advantages 1. Thermotherapy with magnetic nanoparticles in combination with percutaneous radiotherapy is feasible and safe 2. Therapeutic temperatures can be reached in the treatment area 3. Promising therapeutic effect 4. Moderate side effect profile 5. Positive risk/benefit ratio 6. Enhances existing therapies + Impairments 1. Metallic bodies within 40 cm/15.7 from the treatment area are not allowed with current large NanoActivator 2. MRI cannot be used for further diagnosis due to artifacts in region of nanoparticle placement - no other imaging procedures are affected alternate procedures e.g. CT, PET, PET-CT
Tumor volume (cm 3 ) NANOTHERM THERAPY REDUCES PROSTATE CANCER GROWTH IN THE ORTHOTOPIC DUNNING R3327 RAT MODEL 14 14 12 10 8 6 4 2 0 Controls P<0.01 NTT 8 10 12 14 16 18 20 Days after tumor induction C2 C1 C3 T P<0.001 C1: Control growth C2: Magnetic fluid without magnetic field (no magnetic field exposure) C3: Normal saline with magnetic field T: Magnetic fluid with magnetic field (magnetic field exposure) NTT Effectiveness Activity: 50% mean tumor weight reduction 50.% mean tumor growth inhibition Mode of action: Necrosis, direct tumor tissue destruction Tumor growth curves from tumor volume measurements using ultrasound Johannsen, M et al. Magnetic Fluid Hyperthermia (MFH) reduces prostate cancer growth in the orthotopic dunning R3327 rat model. The Prostate 64:283-292 (2005)
15 PROSTATE CARCINOMA: CLINICAL STUDIES WITH NANOTHERM THERMOTHERAPY Monotherapy with NanoTherm therapy: Feasibility study in 10 patients with recurrent prostate cancer Combination therapy with NanoTherm therapy and 125 I-Brachytherapy: Feasibility and safety study in 19 patients with intermediate primary prostate cancer COMPLETED Low number of patients but data are promising High number of patients had disease-related symptoms already at baseline which improved after NanoTherm therapy
PROSTATE CARCINOMA: 5-YEAR PSA VALUE AFTER TREATMENT WITH COMBINATION THERAPY (NANOTHERM /BRACHYTHERAPY); PROMISING REDUCTION 16 Primary efficacy endpoint, 5-year PSA course (tumor control) 20 18 16 14 12 SN003 SN006 10 8 SN009 SN002 SN002 SN009 6 SN006 4 2 0 SN006 SN003 SN001 SN002 SN003 SN004 SN006 SN007 SN008 SN009 SN010 SN011 SN012 SN13 SN14 SN015 SN016 SN017 SN018 SN019
17 TREATMENT OF PROSTATE CANCER IN USA (1) 2011 An Evidence Review of Active Surveillance in Men with Localized Prostate Cancer 240,000 men projected to be diagnosed with prostate cancer 33,000 men projected to die from prostate cancer Health Care Cost > $12B Men over 65 years of age Fastest growing group MagForce USA NanoTherm Therapy: Monotherapy Focal treatment for intermediate primary prostate cancer Combination therapy (NanoTherm /External Radiation) treatment for recurrent prostate cancer (1) AHRQ Number 204
INVESTMENT OPPORTUNITY
19 LEAD INDICATION: GLIOBLASTOMA WITH SIGNIFICANT MARKET POTENTIAL MEDICAL NEED Less than 10% of patients are still alive 5 years after diagnosis Limited treatment advancements in the last 20 years CURRENT STATUS 63,000 cases of brain cancers per year in the major markets: Germany, EU 27, and USA Glioblastoma multiforme (GBM) is the most malignant brain tumor HIGH MEDICAL NEED FOR IMPROVED GBM TREATMENT OPTIONS CURRENT TREATMENT Current standard therapy for GBM includes surgery, radio- and chemotherapy NanoTherm therapy has synergistic effect with concurrent treatment
20 5-YEAR STRATEGIC PLAN Expansion of Brain Tumor Therapy 2013 2017 Conduct Post Marketing Study with Recurrent Glioblastoma in the US & Europe PMA filing to the FDA 2013 & 2014 Install 10-15 NanoActivators in Germany & Europe & USA 2014 + Provide opportunity to treat commercial patients, in Germany, who are not eligible for inclusion in the Post Marketing Study 2013 2014 2015 2016 2017 2018 Prostate Carcinoma Treatment 2013 2014 Define NanoTherm Prostate Cancer Therapy Options Registration in USA / EU to be determined
WORLDWIDE ROLL-OUT SCENARIOS FOR GBM AND PROSTATE CANCER TREATMENT 21 1. Sequential Strategy MagForce s market roll-out can be executed sequentially, at a less aggressive approach 2. Accelerated Strategy With additional financing rounds, market entry could be accelerated The overhead is kept on a minimum level and regional expansion will be supported by strong cooperation partners that would receive significant revenue shares Sequential strategy Accelerated strategy 150m 100m 2019 2019 5 Year Financial Target Annual Revenues of EUR 100-150 Million
22 SUMMARY Estimated annual healthcare expense to treat brain and prostate cancers in Germany, USA & EU 27 exceeds 12 billion Euros. NanoTherm therapy (NTT) is a unique and exciting therapy for treating solid tumors. MagForce has solid intellectual property protection and has the technical capability to establish with the medical community NTT as a valued Mono or Combined Therapy for the treatment of brain and prostate cancer.
MAGFORCE AG FIGHTING CANCER WITH NANO MEDICINE Ben J. Lipps Chief Executive Officer & Chairman of the Management Board Deutsche Bank dbaccess German, Swiss & Austrian Conference Berlin, Germany