Targeting and Treating Cancer Mark R. Baker, Chief Executive Officer Jefferies 2016
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PROGENICS: TARGETING AND TREATING CANCER Building an oncology company with a portfolio of therapeutics/diagnostics Near-term commercial opportunity with late-stage program in ultra-orphan indication RELISTOR Oral PDUFA Date: July 19, 2016; triggers $50M milestone payment PSMA-targeted pipeline: potential to transform clinical practice in prostate cancer Strong financial position: $65.7M as of 3/31/2016 AZEDRA 1404 PyL TM PSMA ADC 1095 RELISTOR Pivotal trial More sensitive in Potential to Demonstrated Potent activity in SC Formulation under SPA for detecting cancer detect minimal activity, tolerability advanced cancer, Marketed by Valeant Pheochromocytoma vs. MRI in Phase 2 levels of cancer, in Phase 2 MSKCC to start in US for OIC and Paraganglioma sites of relapse Phase 1 3
PIPELINE Preclinical Phase 1 Phase 2 Pivotal/ Phase 3 Approved ULTRA-ORPHAN THERANOSTIC AZEDRA Theranostic Pheochromocytoma REGISTRATIONAL PHASE 2 UNDER SPA PROSTATE CANCER THERANOSTICS EXINI Bone BSI Bone Scan Index Software APPROVED FOR USE IN EU, JAPAN AND US (not currently available in US) 1404 PSMA-targeted SPECT Imaging Agent PSMA ADC Therapeutic Prostate Cancer PyL PSMA-targeted PET Imaging Agent 1095 Small Molecule Therapeutic PSMA Antibody Radiolabeled with Alpha Emitter Licensed to Bayer OIC Treatment RELISTOR SC Opioid-induced constipation : 4 RELISTOR ORAL Opioid-induced Constipation PDUFA DATE: July 19, 2016
AZEDRA: ULTRA-ORPHAN THERANOSTIC Adrenal Glands Novel, targeted radiotherapy candidate Phase 2b pivotal trial under SPA for malignant pheochromocytomas and paragangliomas Enrollment completed Top-line data expected late 2016/early 2017 FDA Breakthrough Therapy Designation and Fast Track Status Pheochromocytoma and paraganglioma are rare tumors found primarily in the adrenal glands Results in the release of excess hormones that control heart rate, metabolism and blood pressure Left untreated, tumors most often lead to death due to high blood pressure, heart failure, stroke or metastatic disease No currently approved therapies in the U.S. Potential utility in treating neuroblastoma and other neuroendocrine diseases 5 Plan to commercialize independently
PIVOTAL PHASE 2 TRIAL UNDER SPA Study Design Data* Number of patients 58 planned; 68 enrolled 41 received therapeutic dose(s) Dosing regimen Patients receive 2 therapy doses, 3 months apart 7 patients have received 1 dose 34 have received 2 doses Primary endpoint under SPA Secondary objectives 25% of study patients respond (>50% reduction in anti-hypertensive medication) Proportion of subjects with PR by RECIST criteria 32% responded n=13 14/34 (41%) Next Steps Top-line data late 2016 / early 2017 6 *Data from patients dosed 2009-2010 by MIP prior to acquisition by Progenics
AZEDRA Phase 2 Tumor Response Rates 85% had measurable decrease in tumor size * Response Rates Measured by RECIST Best change in sum of target lesion diameters from baseline at any time point Best change (%) in sum of target lesion diameters from baseline at any time point Yes = achieve reduction of antihypertensive medication by at least 50% for 6 months. No = did not achieve reduction of antihypertensive medication by at least 50% for 6months. 7 *Data from patients dosed 2009-2010 by MIP prior to acquisition by Progenics
AZEDRA Advancing Toward Market Upcoming Milestones Targeted Market Late 2016/Early 2017 Topline results from pivotal Phase 2b trial 1H 2017 Anticipated submission of NDA to FDA Ultra-Orphan - Less than 1,000 cases of pheochromocytoma and paraganglioma diagnosed in the U.S. each year 25-30% of cases are genetic U.S. market reachable with a small specialty salesforce targeting major centers where these rare tumors are treated 8
PROSTATE CANCER THERANOSTICS EXINI Bone BSI Bone Scan Index Software 1404 SPECT/CT PSMA-targeted Imaging Agent PyL PET/CT PSMA-targeted Imaging Agent 1095 PSMA-targeted Small Molecule Therapeutic PSMA Antibody Radiolabeled with Alpha Emitter Licensed to Bayer 9
MULTIPLE OPPORTUNITIES TO USE PSMA TARGETED IMAGING AGENTS POINT IN TREATMENT PATH PRODUCT CLINICAL NEED Initial Diagnosis (after elevated PSA) 1404 (SPECT/CT) Localize lesions for targeting biopsy; avoid over/under diagnosis associated with biopsy Active Surveillance (initial diagnosis low risk cancer) 1404 (SPECT/CT) Lower morbidity than biopsy and higher specificity than PSA Primary Staging 1404 (SPECT/CT) PyL (PET/CT) PSMA identifies lymph node and visceral lesions in addition to bone mets Treatment Planning and Monitoring 1404 (SPECT/CT) PyL (PET/CT) Improve accuracy of surgery and radical radiotherapy; open curative window for treatment of metastases Detecting Recurrent Disease PyL (PET/CT) Images lesions that are not detected by current technologies 10
40-50% of men are now choosing Active Surveillance 1404 has the potential to enable Active Surveillance 11
1404 PSMA-TARGETED IMAGING AGENT SPECT radiopharmaceutical product candidate targeting PSMA In Phase 3 with interim results expected 2H 2016 Positive Phase 2 data: higher detection rate vs. MRI SPECT/CT 1404 scan showing primary prostate cancer Potential to transform clinical practice with improved detection and monitoring 12
DETECTING PROSTATE CANCER IN THE GLAND - MRI Gleason 4+5 Lesion Prostate 13
DETECTING PROSTATE CANCER IN THE GLAND 1404 SPECT/CT Histopathology 14
1404: PHASE 2 RESULTS Detected prostate cancer in the prostate gland with a high degree of sensitivity (94%) 1404 readers detected more prostate cancer in the prostate gland (94%) than MRI (86%) T:B quantitative and semiquantitative methods of assessing gland/lobe uptake show highly significant correlation with Gleason score (p<0.0001) Uptake of 1404 in the prostate gland is significantly lower in treated patients (p<0.0001) 15
1404 PHASE 3 STUDY DESIGN Patient Population Biopsy confirmed low-grade prostate cancer who are eligible for active surveillance but decided to have a radical prostatectomy N Primary Endpoint ~450 evaluable patients; interim analysis for futility or need for sample size re-estimation performed after approximately one-third of the patients have been treated (expected 2H16) Specificity of 1404 to identify patients without clinically significant prostate cancer Sensitivity of 1404 to identify patients with clinically significant prostate cancer Secondary Endpoint Safety and tolerability; Location of disease 1404 Study Overview: Biopsy Confirmed Gleason Score 3+4 99m Tc-MIP- 1404 Dosing SPECT/ CT Imaging Prostatectomy Histopathology of prostate 16
PyL: PET/CT IMAGING AGENT PET Radiopharmaceutical product candidate targeting PSMA In-licensed from Johns Hopkins University PSMA Targeting Enables visualization of both bone and soft tissue metastases Highly specific to prostate cancer cells, not confounded by degenerative or inflammatory conditions Scanned in >100 patients to date 17
PYL: PET/CT IMAGING AGENT Pilot Study Data: Investigator Sponsored Studies Men with Elevated PSA Following Radical Prostatectomy 1 N=30 Very high standardized uptake values (SUV) even in small lesions Men with Metastatic N=8 Identified more lesions than conventional imaging Prostate Cancer 2 Proof of Concept N=9 Can detect lesions as small as 3mm Study 3 Well tolerated with no SAEs to date; few mild AEs Next Steps Several clinical trials, including two phase 2 studies 1 Gorin, M., et al., AUA 2016 2 Rowe, S. et al, Mol Imaging Biol April 2016 3 Szabo Z, et al. Mol Imaging Biol. April 2015 18
1095: PSMA TARGETED SMALL MOLECULE THERANOSTIC FOR PROSTATE Targeted small molecule radiotherapeutic that selectively binds to PSMA 100 * Best PSA Response in 25 patients Delivers lethal dose of radiation directly to prostate cancer cells with minimal impact on surrounding healthy tissue Markedly reduced PSA levels in a heavily pretreated group of 25 evaluable patients, and reduced bone pain in German compassionate use study in advanced prostate cancer % CHANGE IN PSA 0 Primary study site for Phase 1: Memorial Sloan Kettering, the Coordinating Center for the Prostate Cancer Clinical Trials Consortium (PCCTC) -100 0 5 10 15 20 25 PATIENT NUMBER Zechmann CM, et al. Eur J Nucl Med Mol Imaging. 2014 19
EXINI Located in Lund, Sweden Capabilities Sophisticated software that assists physicians and patients in visualizing, understanding, targeting and treating cancer Successful development and commercialization of software products based on medical image analysis and machine learning Relationships with key European partners, clinicians, and researchers to support late-stage pipeline EXINI Bone BSI Quantifies tumor burden of the skeleton and calculates the Bone Scan Index BSI outcome not affected by human reader variability Reduced turnaround time Observer-independent FDA 510(k) clearance and CE-marked 20
LEVERAGING OUR PSMA ANTIBODY TECHNOLOGY April 2016 Granted Bayer worldwide rights to develop and commercialize products combining our PSMA Antibody Technology exclusively with Bayer s alpha-emitting radionuclides Upfront payment of $4M million Up to an additional $49M in potential clinical and regulatory development milestones Potential net sales milestone payments up to an aggregate total of $130M Single digit royalties on net sales 21
RELISTOR ORAL (July 19, 2016 PDUFA) An estimated 3% of the adults in the US are receiving long- term opioid therapy 41% of those patients, or approximately 3.7 million patients, develop Opioid Induced Constipation (OIC) The prescription market for OIC is growing rapidly now that there is an oral option In our phase III program, Relistor oral significantly increased the percentage of patients with a rescue-free bowel movement (RFBM) within 4 hours 22 Spencer Dorn, et al. American Journal of GASTROENTEROLOGY 2014
RELISTOR Economics of Valeant Collaboration Marketed by Valeant Valeant creating pain-specific sales force to detail RELISTOR Subcutaneous formulation approved for patients with insufficient response to laxatives with: OIC in advanced illness who are receiving palliative care OIC in chronic, non-cancer pain All patients with OIC (Europe) NDA for RELISTOR Oral submitted June 2015, PDUFA July 19, 2016 $50M licensing milestone upon U.S. approval of RELISTOR Oral Royalty scale based on WW net sales, ranging from 15%-19% Commercial licensing milestones totaling up to $200M, including $10M on first $100M in sales Entitled to receive 60% of revenues received by Valeant from ex-u.s. sub-licensees (SOBI) 23
2016 PRIORITIES Top -Line Data for Pivotal Phase 2 AZEDRA Trial Late 2016/Early 2017 Interim Analysis for Pivotal Phase 3 1404 Trial Initiate Phase 2 Trial for PyL Initiate Phase 1 Trial for 1095 Commercialize EXINI Bone BSI in the US RELISTOR Oral July19, 2016 PDUFA AZEDRA 1404 PyL PSMA ADC 1095 RELISTOR Pivotal trial More sensitive in Potential to Demonstrated Potent activity in SC Formulation under SPA for detecting cancer detect minimal activity, tolerability advanced cancer, Marketed by Valeant Pheochromocytoma vs. MRI in Phase 2 levels of cancer, in Phase 2 MSKCC to start in US for OIC and Paraganglioma sites of relapse Phase 1 24
Targeting and Treating Cancer Mark R. Baker, Chief Executive Officer Jefferies 2016