Prothena Corporation plc Overview

Transcription

1 November 11, 2014 Prothena Corporation plc Overview 2014 Credit Suisse HC Conference The Arizona Biltmore Phoenix, AZ

2 Forward-Looking Statements This presentation contains forward-looking statements. These statements relate to, among other things, our ability to advance and meet the expected timelines for our three lead programs, NEOD001, PRX002 and PRX003, and our ability to meet our projected cash burn, net loss and year-end cash position. These forward-looking statements are based on estimates, projections and assumptions that may prove not to be accurate, and actual results could differ materially from those anticipated due to known and unknown risks, uncertainties and other factors, including but not limited to the risks and uncertainties described in the Risk Factors sections of our Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on March 7, 2014, and our subsequent Quarterly Reports on Form 10-Q filed with the SEC. Prothena undertakes no obligation to update publicly any forward-looking statements contained in this presentation as a result of new information, future events or changes in Prothena's expectations. 2

3 Prothena Vision We target proteins in novel ways to resolve unmet clinical need in patients 3

4 Prothena Overview Advancing and developing novel antibodies for diseases caused by amyloid or cell adhesion Team has track record of discovering and developing immunotherapy products including abeta immunotherapy and Tysabri Lead programs in the pipeline (all mabs): NEOD001, for AL amyloidosis, expected to enter P2/3 in 4Q14 PRX002, α-synuclein immunotherapy for Parkinson s disease, in Phase 1 SAD and MAD (worldwide collaboration with Roche) PRX003, anti-mcam antibody for psoriasis, expected to enter P1 SAD in 1H15 Robust cash position of $306M at end of 3Q14 4

5 R&D Pipeline for Lead Programs LEAD PROGRAM Preclinical Phase 1 Phase 2 Phase 3 COMMERCIALIZATION RIGHTS NEOD001 AL Amyloidosis Phase 1 MAD Phase 2/3 PRX002 Parkinson s Disease Phase 1 SAD Phase 1 MAD PRX003 Psoriasis Phase 1 SAD Preclinical Ongoing Planning 5

6 Upcoming Milestones NEOD001 for AL Amyloidosis New data from ongoing Phase 1 MAD study expected later in 2014 Expect to initiate Phase 2/3 trial later in 2014 PRX002 for Parkinson s disease and other related synucleinopathies (worldwide collaboration with Roche) Phase 1 SAD data in healthy subjects expected in 1H15 Phase 1 MAD data in patients expected in 2016 PRX003 for psoriasis and other inflammatory diseases Announced initial indication as a potentially rapid clinical path to proof-of-biology Expect to initiate Phase 1 SAD trial in first half 2015 Expect to initiate Phase 1 MAD trial in

7 NEOD001 for AL Amyloidosis

8 Systemic Amyloidoses are Orphan Diseases with Unmet Need and No Approved Therapies Immunotherapy mabs to treat amyloid AL amyloidosis represents majority of systemic amyloidoses (including AA and ATTR) 1 ~15,000 patients in US and Europe Does not include ~12,000 patients with multiple myeloma who also have AL amyloidosis 2 Clinical characteristics Median onset age of 60 years Affects multiple organs including heart, kidney and peripheral nerves Median cardiac survival ~1 year 3 Reducing disease progression remains significant unmet need Existing off-label therapies reduce production, but do not address resident amyloid, and have significant associated adverse events Substantial need for safe and well tolerated disease modifying therapies that improve organ function 8 1. van Gameren, I., et al. (2010) Arthritis Care Res, 62: Gertz, 2013 and Mahmood, Based on a survey of ~23 publications

9 Amyloid Deposits Buildup in Multiple Organs and Cause Organ Failure 1 HEART (50-65%) Fatigue (inability to be active) Shortness of breath (dyspnea) Irregular heart beat Fainting (syncope) Leads to congestive heart failure All patients show cardiac involvement at autopsy KIDNEYS (60-80%) Large amounts of protein in urine (proteinuria) Swelling of feet and legs End stage kidney disease Transplant can be required PERIPHERAL NERVES (20-45%) Neuropathy Impotence No temperature sensation in hands and feet OTHER ORGANS Liver (15-30%) GI Tract (5-16%) Eyes (10-25%) Tongue (~10%) Soft Tissue (20-35%) 9 1. Based on a survey of ~23 publications

10 Potential NEOD001 MOAs: Neutralizes Soluble Amyloid and Clears Insoluble Amyloid Plasma cells overproduce light chains that misfold, aggregate and become toxic amyloid NEOD001 neutralizes and disaggregates circulating soluble amyloid NEOD001 clears deposited insoluble amyloid by inducing macrophages to phagocytose amyloid NEOD001 recycled to continue neutralizing soluble amyloid and clearing deposited insoluble amyloid 10

11 Summary NEOD001 Results from Ongoing Phase 1 Trial in Patients with AL Amyloidosis Chronic monthly infusions of NEOD001 are safe and well-tolerated in AL Amyloidosis patients 18 patients enrolled in 6 dosing cohorts; 14 of 18 patients continue to receive NEOD001 (4 patients discontinued) 106 infusions administered and mean treatment duration of 6 months per patient 1 No hypersensitivity reactions No drug-related SAEs PK consistent with infusions every 28 days No anti-drug antibodies 56% cardiac response (n=5) and 33% stabilization (n=3) 2 rates Cardiac response rate compares favorably to rates in prior AL Amyloidosis study of 26% 3 Phase 1 MAD Data Supports and Informs Planned Phase 2/3 Study Equivalent to 6 infusions per patient (IV q28 days) 2. Based on Any Response criteria 3. Comenzo, et al., Leukemia. 2012;26: Unaudited interim data as of 3/11/14

12 Ongoing NEOD001 Phase 1 Trial Design Primary Objectives Secondary Objectives Evaluate the safety and tolerability of NEOD001 Determine maximum tolerated dose or Phase 2/3 recommended dose of NEOD001 Evaluate the serum pharmacokinetics (PK) of NEOD001 Assess immunogenicity of NEOD Exploratory Objectives Evaluate organ response (e.g., NT-proBNP, proteinuria and alkaline phosphatase) and hematologic response (dflc) Trial Design Multiple Ascending Dose (3+3) Up to 30 patients with AL amyloidosis 7 cohorts; IV q28 days; determine MTD/P2RD 1 mg/kg 2 mg/kg 4 mg/kg 8 mg/kg 16 mg/kg 30 mg/kg* Expansion Phase Additional patients with selected organ dysfunction 0.5 mg/kg 12 * Maximum of 2500 mg per dose permitted 24 mg/kg selected based on patient body weights Clinicaltrials.gov identifier: NCT

13 High Rate of Cardiac Biomarker Response and Stabilization in NEOD001-Treated Patients Progression 29% Stable 21% Single-Agent NEOD001 Stable 44.4% Response Response 55.6% 50% Best Response (N=9) Progression 11.1% Stable 33.3% Response 55.6% Any Response (N=9) Patients Continuing to have Cardiac Dysfunction Post-Standard of Care % of Cardiac AL Amyloidosis Patients 13 NOTE: Cardiac response defined as >30% and 300 pg/ml decrease in NT-proBNP and cardiac progression defined as >30% and 300 pg/ml increase in NT-proBNP in patients without progressive renal dysfunction with baseline NT-proBNP of 650 pg/ml. Stable is defined as being neither a responder or progressor. Interim unaudited data as of 3/11/14

14 Beneficial Changes in NT-proBNP Correlates to Mortality in Patients Heart Failure 1 AL Amyloidosis High-High 0.8 Cumulative mortality (%) Log rank test p< Low-High Low-Low Proportion surviving p<0.001 p<0.001 Response Stable 0.2 High-Low 0.1 Progression Days from randomization Time (Months) NT-proBNP progression (at least 300 ng/l and 30% increase), 169 patients NT-proBNP stable, 108 patients NT-proBNP response (at least 300 ng/l and 30% decrease), 100 people Masson, et al., Journal of the American College of Cardiology. 2008;52: Comenzo, et al., Leukemia. 2012;26:

15 PRX002 for Parkinson s Disease and Other Related Synucleinopathies (worldwide collaboration with Roche)

16 Parkinson s is a Neurodegenerative Disease with No Approved Disease-Modifying Therapies Parkinson s disease (PD) is the 2nd most common neurodegenerative disorder Current treatments manage early symptoms, not disease There are an estimated 7-10 million Parkinson s patients worldwide Genetic mutations cause early and aggressive disease Synuclein pathology strongly implicated in PD Also associated with other CNS and peripheral diseases, including some orphan indications Synuclein is the predominant component of Lewy bodies found in Parkinson s disease and other synucleinopathies 16

17 Synuclein Immunotherapy may Reduce Neuronal Toxicity and Prevent Cell-to-Cell Transfer Synaptic Loss and Pathogenic Spread Antibodies Reduce Pathogenic Spread and Decrease Synuclein Pathology 17

18 Prothena mab Reduces CNS Synuclein Pathology in Transgenic Mouse Model of Parkinson s Disease α-synuclein Pathology in the CNS 25 % area of the neuropil Control mab 0 Control mab Anti-synuclein mab Treated with Anti-Synuclein 18 Masliah (2013) First International Novartis Parkinson s Disease Symposium. Organized by Osaka University. Osaka, JAPAN

19 Lowering Synuclein with Prothena mab Protects Synapses and Improves Behavior in Transgenic Mice Synapse Protection Improved behavior in Morris Water Maze 35 % Area Synaptophysin-IR Distance (m) * Control mab * * * Wild Type P<0.05 Anti- Synuclein Training Session (day) Transgenic mice 19 Masliah (2013) First International Novartis Parkinson s Disease Symposium. Organized by Osaka University. Osaka, JAPAN

20 Worldwide PRX002 Collaboration with Roche Total Milestones $600M Upfront and near-term Clinical, regulatory and first sale Ex-U.S. sales milestones U.S. Profit & Loss Split U.S. Co-Develop U.S. Co-Promote Ex-U.S. 45M 380M 175M 30% Ability to opt-out 1 Ability to opt-in Up to double digit royalties % Will lead the clinical development Will lead the commercialization Sole responsibility to develop and commercialize Total milestones expected to more than fully fund U.S. clinical development of PRX002 Continue to participate through Joint Steering Committee $45M already received in 2014 Retain significant financial upside Ability to build U.S. specialty sales force Upon opting out of the co-development and cost and profit sharing on any co-developed Licensed Products, Prothena instead would receive U.S. commercial sales milestones totaling up to $155.0 million and tiered, single-digit to high double-digit royalties in the teens based on U.S. annual net sales, subject to certain adjustments

21 PRX002 Phase 1 SAD and MAD Studies Underway Worldwide collaboration with Roche Phase 1 SAD study in healthy subjects underway; data expected in first half 2015 Phase 1 MAD placebo-controlled double blind study in PD patients underway (n=60 patients); data expected in 2016 Biomarkers from CNS and periphery anticipated to guide Phase 2 dose selection Potential development of follow-on antibodies for other related synucleinopathies 21

22 PRX003 for Psoriasis and Other Inflammatory Diseases

23 MCAM Blockade Potentially More Effective Approach for Treating Inflammation Compared to anti-il17 Therapies IL-12 T H 1 cell Peptide-MHC molecule IL-4 T H 2 cell DC Naïve T cell TCR TGFß T Reg cell TGFß and IL-6 (IL-1 and IL-23) T H 17 cell IL17 IL22 CCL20 IL26 (IFNg) (IL6) (TNF) RORgt 23 Figure modified from: Zou & Restifo, Nature Reviews Immunology10: (2010)

24 PRX003 Clinical Trial Expected to Initiate in 2015 Selected psoriasis as a potentially rapid clinical path to proof-of-biology Expect to initiate Phase 1 SAD trial in first half 2015 Expect to initiate Phase 1 MAD trial in

25 Corporate Information

26 Financial Overview SUMMARY INFORMATION Cash and cash equivalents (September 30, 2014) $306M Shares outstanding (October 24, 2014) M 2014 GUIDANCE Net cash burn from operating activities $7 to $12M Net loss $13 to $18M Projected year-end cash position (mid-point) ~$285M Does not include 2.6mm ordinary shares underlying options with a weighted average strike price of $13.10

27 Q&A Session