Mayo Clinic, Rochester, Minnesota; 2 Tufts Medical Center, Boston, Massachusetts; 3

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1 NEOD001 Demonstrates Organ Biomarker Responses in Patients With Light Chain Amyloidosis and Persistent Organ Dysfunction: Final Results From a Phase 1/2 Study Morie A. Gertz, 1 Raymond L. Comenzo, 2 Heather Landau, 3 Vaishali Sanchorawala, 4 Brendan Weiss, 5 Jeffrey Zonder, 6 Jackie Walling, 7 Gene G. Kinney, 8 Martin Koller, 8 Dale B. Schenk, 8 Spencer D. Guthrie, 8 Enchi Liu, 8 Michaela Liedtke 9 1 Mayo Clinic, Rochester, Minnesota; 2 Tufts Medical Center, Boston, Massachusetts; 3 Memorial Sloan Kettering Cancer Center, New York, New York; 4 Boston University School of Medicine, Boston, Massachusetts; 5 University of Pennsylvania, Philadelphia, Pennsylvania; 6 Karmanos Cancer Institute, Detroit, Michigan; 7 JW Consulting, Hillsborough, California; 8 Prothena Biosciences Inc, South San Francisco, California; 9 Stanford University School of Medicine, Stanford, California

2 Disclosures: Dr Gertz Honoraria Celgene Millennium Novartis Ionis Med Learning group Research to Practice Prothena 2

3 Background AL amyloidosis is caused by an accumulation of misfolded proteins (amyloid), resulting in the dysfunction of vital organs (eg, heart and kidney) Existing therapies reduce LC production But they DO NOT address resident amyloid ~75% of patients do not achieve organ response and have persistent organ dysfunction 1-6 a major unmet need Safe and well-tolerated therapies are needed to improve organ function NEOD001 is an investigational antibody that specifically targets AL amyloid We report final data from the dose-escalation phase and the expansion cohorts of the phase 1/2 study of NEOD001 in previously treated patients with AL amyloidosis and persistent organ dysfunction (NCT ) 3 AL, amyloid light chain; LC, light chain. 1. Palladini G et al. Blood. 2015;126. Abstract Palladini G et al. Blood. 2015;126: Comenzo RL et al. Leukemia. 2012; Palladini G et al. Haematologica. 2013;98: Dispenzieri A et al. Blood. 2012;119: Reece DE et al. Blood. 2011;118:

4 NEOD001 Phase 1/2 Trial (N = 69) Design All patients previously received PCD treatment and had persistent organ dysfunction Dose-escalation phase (3+3) 27 patients with AL amyloidosis 7 cohorts; IV every 28 days; determine MTD/RP3D All patients escalated to 24 mg/kg 0.5 mg/kg 1 mg/kg 2 mg/kg 4 mg/kg 8 mg/kg 16 mg/kg 24 mg/kg Expansion Cohorts 42 additional previously treated patients with cardiac, renal, and/or peripheral neuropathy involvement Primary objectives Evaluate the safety and tolerability of NEOD001 Determine MTD or recommended dose for future clinical study of NEOD001 Secondary objectives Evaluate the serum PK of NEOD001 Assess the immunogenicity of NEOD001 Evaluate organ response (cardiac, renal, peripheral neuropathy) 4 Maximum of 2500 mg per dose permitted 24 mg/kg selected based on patient body weight. IV, intravenous; MTD, maximum tolerated dose; PC, plasma-cell directed; PK, pharmacokinetics; RP3D, recommended phase 3 dose.

5 Ongoing NEOD001 Phase 1/2 Study Design: Expansion Cohorts Enrolled 42 additional previously treated patients with AL amyloidosis and prospectively defined organ involvement 24 mg/kg; IV every 28 days Cardiac Cohort n = 15 Key inclusion: Cardiac involvement as defined by elevated NT-proBNP of 650 pg/ml in the absence of renal failure Clinical outcome: NT-proBNP best response Key exclusion NT-proBNP level >7000 pg/ml Renal Cohort n = 16 Key inclusion: Renal involvement as defined by proteinuria >0.5 g/day in a 24-hour urine collection Clinical outcome: Proteinuria best response Peripheral Neuropathy Cohort n = 11 Key inclusion: Positive findings on sural nerve biopsy or evidence of typical sensorimotor peripheral neuropathy due to amyloidosis and not chemotherapy; 2 baseline NIS-LL Clinical outcome: NIS-LL (change, baseline to month 10) 5 IV, intravenous; NIS-LL, Neuropathy Impairment Score Lower Limb; NT-proBNP, N-terminal probrain natriuretic peptide.

6 Patient Characteristics All Patients (N = 69) Median age, years (range) 61 (38-82) Sex, n (% male) 42 (61) Median time since initial diagnosis, years (range) 2.9 ( ) Median previous regimens, n (range) 2 (1-8) No. previous PCD regimens per patient, n (%) 1 22 (32) 2 16 (23) 3 31 (45) No. organ systems involved, n (%) 1 22 (32) 2 29 (42) 3 18 (26) Median months since last PCD treatment, months (range) 5.8 ( ) Median NT-proBNP (pg/ml) at baseline, median (range) Total cardiac evaluable [n = 36 patients] 1507 ( ) 6 PCD, plasma-cell directed.

7 Safety and Dosing Summary NEOD001 was safe and well tolerated No dose-limiting toxicities No treatment-related discontinuations or SAEs No anti-drug antibodies detected 1 treatment-emergent patient death (not related) Treatment duration (every 28 days): mean, 12.8 months (range, 2-35) Total number of infusions: 994 (N = 69 patients) 7 SAEs, serious adverse events.

8 Treatment-Emergent Adverse Events ( 10%) Regardless of Relationship to NEOD001 8 Most Common TEAEs (preferred terms) Total Patients (N = 69) Total AEs, N (%) Grade 3, n (%) Fatigue 24 (34.8) 1 (1.4) Nausea 22 (31.9) 0 Upper respiratory tract infection 21 (30.4) 0 Peripheral edema 19 (27.5) 0 Diarrhea 18 (26.1) 0 Anemia 15 (21.7) 1 (1.4) Increased blood creatinine 13 (18.8) 0 Dizziness 12 (17.4) 0 Cough 11 (15.9) 0 Constipation 10 (14.5) 0 Headache 10 (14.5) 0 Vomiting 10 (14.5) 0 Dyspnea 9 (13.0) 0 Pain in extremity 9 (13.0) 0 Back pain 8 (11.6) 0 Muscle spasms 8 (11.6) 0 Rash 7 (10.1) 0 Urinary tract infection 7 (10.1) 0 AEs, adverse events; TEAEs, treatmentemergent adverse events.

9 Cardiac Functional Biomarker Responses 9

10 NEOD001: Cardiac Biomarker Response Best Response Analysis NT-proBNP % Change From Baseline Total cardiac evaluable (n = 36) 19 responders (53%) 17 stable (47%) * Median time to initial response: 2 months 10 Evaluable patients had baseline NT-proBNP 650 pg/ml without progressive renal dysfunction 1,2 Response: >30% and >300 pg/ml decrease in NT-proBNP Progression: >30% and >300 pg/ml increase in NT-proBNP Stable disease: Neither response nor progression *30% decline, 453 pg/ml reduction from baseline. 42% decline, 271 pg/ml reduction from baseline. 1. Comenzo R et al. Leukemia. 2012;26: Palladini G et al. J Clin Oncol. 2012;30:

11 NEOD001 Cardiac Responses Continue to Deepen After 38 Doses NT-proBNP % Change From Baseline 11 0% 0% 0% 0% 0% 0% NEOD001 start: 10 months after hematologic CR with no change 4 mg/kg 24 mg/kg progression threshold response threshold OLE 24 mg/kg 38 doses of NEOD001 0% OLE NEOD001 Treatment, n CR, complete response; CyBorD, cyclophosphamide, bortezomib, dexamethasone; OLE, open-label extension. 47-Year-Old Man Previous treatment: CyBorD Baseline NT-proBNP: 3312 pg/ml Best NT-proBNP: 513 pg/ml ( 85%) Safety: 1 grade 3 SAE (chest pain), not related; no dose interruptions Clinical outcome: Progressive functional improvement; edema significantly improved with reduction in diuretic needs; NYHA improved from II to I Includes 3 time points from OLE

12 Renal Functional Biomarker Responses 12

13 NEOD001: Renal Biomarker Response Best Response Analysis Proteinuria % Change From Baseline Total renal evaluable (n = 36) 23 responders (64%) 13 stable (36%) Median time to initial response: 4 months 13 egfr, estimated glomerular filtration rate. Evaluable patients had baseline proteinuria >0.5 g/24 hours Palladini G et al. Blood. 2014;124: Response: >30% decrease in proteinuria or a decrease to <0.5 g/24 hours in the absence of renal progression Progression: >25% worsening in egfr Stable disease: Neither response nor progression

14 NEOD001 Renal Responses Continues to Deepen After 32 Doses 61-Year-Old Man 24-Hour Proteinuria NEOD001 start: 40 months after hematologic CR with no change 32 doses of NEOD001 Previous treatment: LDex then Bor-LDex then HDM/ ASCT Baseline proteinuria (24 hours): 5129 mg/d Best proteinuria (24 hours): 294 mg/d ( 94%) Safety: No SAEs; no grade 3 AEs; no dose interruptions NEOD001 Treatment, n Clinical outcome: Progressive functional improvement; edema completely resolved; patient no longer has fatigue 14 ASCT, autologous stem cell transplantation; Bor-LDex, bortezomib, lenalidomide, dexamethasone; HDM, high-dose melphalan; LDex, lenalidomide, dexamethasone.

15 15 Peripheral Neuropathy Responses

16 NEOD001: Neuropathy Response at Month 10 (NIS-LL) Peripheral Neuropathy Expansion Cohort (N = 11) 9 responders (82%) 2 progressors (18%) Point Change in NIS-LL % Change in NIS-LL NIS-LL Difference From Baseline * NIS-LL % Change From Baseline * 16 Response: <2-point increase in NIS-LL from baseline; response criteria established in patients with diabetic nephropathy and in use in clinical trials for diabetic neuropathy and transthyretin polyneuropathy. * Patient discontinued at month 4; last observation carried forward for 2 patients without NIS-LL at month 10. Complete resolution

17 NEOD001 Peripheral Neuropathy Response Remains Durable After 19 Doses NIS-LL % Change From Baseline NEOD001 start: 31 months after hematologic VGPR 24 mg/kg 19 doses of NEOD Year-Old Man Previous treatment: HDM/ ASCT then CyBorD Achieved VGPR 31 months before NEOD001 Baseline NIS-LL: 32 (wheelchair bound) NIS-LL at dose 19: 22 ( 31%) Safety: No SAEs; no grade 3 AEs; no dose interruptions Clinical outcome: Muscle strength increased; improvement in mobility; improvement in edema 17 VGPR, very good partial response. NEOD001 Treatment, n Includes 1 OLE dose

18 NEOD001 Organ Responses Not Related to Previous Plasma Cell Directed Therapy Not related to depth of best or last hematologic response Not related to time since best or last hematologic response Not related to time since last plasma cell directed therapy Not related to type of previous plasma cell directed therapy These data will be presented during session 647 (ASH2016, Dr. Michaela Liedtke, 8 AM) 18

19 Conclusions NEOD001 was safe and well tolerated Encouraging results have now been observed across 3 organ systems Cardiac (n = 36; 53%) and renal (n = 36; 64%) best response rates are better than those reported for patients treated with plasma cell directed therapies 50% of NEOD001 cardiac responders show improved NYHA status that was correlated with duration of NEOD001 treatment (presented at HFSA 2016) Improvement in peripheral neuropathy (median NIS-LL decrease of 23%; n = 11) was seen for the first time in patients with AL amyloidosis, leading to a response rate of 82% Ongoing studies Global phase 2b PRONTO study: previously treated patients with persistent cardiac dysfunction (NCT ) Global phase 3 VITAL study: patients with newly diagnosed AL amyloidosis with cardiac involvement (NCT ) 19 HFSA, Heart Failure Society of America; NYHA, New York Heart Association.

20 Phase 2b: Phase 3: Patients must have previously received 1 therapy ( 6 months before study start) with partial hematologic response or better, confirmed AL amyloidosis diagnosis, and persistent cardiac dysfunction Patients must be treatment naive and have a confirmed diagnosis of AL amyloidosis with cardiac involvement 20