Leading Development of Radiopharmaceuticals to Detect and Treat Cancer

Transcription

1 Leading Development of Radiopharmaceuticals to Detect and Treat Cancer October 2018 All trademarks, registered or otherwise, are the property of their respective owner Progenics Pharmaceuticals, Inc.

2 DISCLOSURE NOTICE This presentation may contain projections and other forward-looking statements regarding future events. Such statements are predictions only, and are subject to risks and uncertainties that could cause actual events or results to differ materially. These risks and uncertainties include, among others, the cost, timing and results of clinical trials and other development activities; the unpredictability of the duration and results of regulatory review of New Drug Applications and Investigational NDAs; the performance of our partners; market acceptance for approved products; generic and other competition; the possible impairment of, inability to obtain and costs of obtaining intellectual property rights; and possible safety or efficacy concerns, general business, financial and accounting matters, litigation and other risks. More information concerning Progenics and such risks and uncertainties is available on its website, and in its press releases and reports it files with the U.S. Securities and Exchange Commission. Progenics is providing the information in this presentation as of its date and does not undertake any obligation to update or revise it, whether as a result of new information, future events or circumstances or otherwise. Additional information concerning Progenics and its business may be available in press releases or other public announcements and public filings made after the date of this presentation. This presentation may not be copied, reproduced, altered or disseminated in any manner or medium without written consent of Progenics. 2

3 OUR MISSION Leading Development of Radiopharmaceuticals to Detect and Treat Cancer AZEDRA (iobenguane I 131) for Ultra Orphan neuroendocrine tumors (NET) Prostate-specific membrane antigen (PSMA) - Portfolio for Prostate Cancer First FDA Approved treatment for adults and pediatric patients 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy Imaging agents and therapeutics designed to improve diagnosis, treatment and monitoring of prostate cancer 3

4 PIPELINE ULTRA-ORPHAN THERANOSTIC AZEDRA Malignant Pheochromocytoma & Paraganglioma PROSTATE CANCER THERANOSTICS 1404 PSMA-targeted SPECT Imaging Agent PyL PSMA-targeted PET Imaging Agent 1095 PSMA-targeted Small Molecule Therapeutic PSMA-TTC Thorium Conjugate Therapeutic DIGITAL TECHNOLOGY Preclinical Phase 1 Phase 2 Phase 3 NDA Approved PSMA CADx Automated reading of PSMA PET/SPECT/CT images based on AI and deep learning OIC TREATMENT Based on data from 1404 Studies 4 RELISTOR SC Opioid-induced Constipation RELISTOR Tablets Opioid-induced Constipation

5 FDA Approved July 30, 2018 AZEDRA (iobenguane I 131) First FDA Approved treatment for adults and pediatric patients 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy

6 Pheochromocytoma and paraganglioma (pheo and para) Extremely rare neuroendocrine tumors that can dramatically impact survival in people of all ages 1 Pheo and para tumors produce fight or flight hormones, which can overwhelm the nervous system and cause the spontaneous onset of multiple symptoms 2 Final diagnosis is delayed an average of 3 years after the initial onset of symptoms 3 If the tumors are not diagnosed or appropriately treated, the disease is almost always fatal 4 with a survival rate as low as 12% 5 Symptoms related to catecholamine secretion cause up to 30% of metastatic/malignant Pheo/Para deaths 6 PARA 6 1 Martucci VL, Pacak K. Curr Probl Cancer. 2014;38(1):7-41, 2 Gunawardane PTK, Grossman A. Adv Exp Med Biol. 2017;956: , 3 Lefebvre M, Foulkes WD. Curr Oncol. 2014;21(1):e8-e17, 4 Kantorovich V, Eisenhofer G, Pacak K. Ann N Y Acad Sci. 2009;1148: , 5 Park J, et al. Korean J Urol. 2011;52: , 6 Baudin et al European Journal of Endocrinology (2014) 171, R111-R122.

7 AZEDRA (iobenguane I 131) Treats pheochromocytoma and paraganglioma via the norepinephrine transporter 1 In the clinical trial, provided clinically meaningful and persistent anti-tumor effect Contains over 99% active, therapeutic I-131 MIBG 1 Orphan Drug Designation, Fast Track Status, Breakthrough Therapy Designation, Priority Review Approved - July 30, 2018 AZEDRA is the first FDA approved therapy for pheo and para 1 Barrett JA, et al. Cancer Biother Radiopharm. 2010;25(3):

8 Clinical trial achieved primary endpoint and favorable tumor response rates Responders (%) Primary Endpoint Lower bound of Confidence Interval Upper bound of Confidence Interval Best Confirmed Overall Tumor Response Assessment per RECIST Criteria Responders (%) Overall (n=68) 17 (25%) 16.15% 36.52% 15 (22%) Two Doses (n=50) 16 (32%) 20.70% 45.87% 15 (30%) One Dose (n=18) 1 (6%) 0.0% 27.65% 0 (0%) Met the primary endpoint evaluating the proportion of patients who achieved a 50% reduction of all antihypertensive medication for at least six months The primary endpoint is achieved if the lower limit of the two-sided 95% confidence interval is >10%; 12 patients required to achieve endpoint Key secondary endpoint: the proportion of patients with overall tumor response as measured by RECIST Of the 15 tumor responders, 53% experienced durable tumor responses lasting 6 months Reduction was sustained 8

9 Safety Most Common Severe Adverse Events (Grade 3-4) Adverse Event (%) Lymphopenia 78% Neutropenia 59% Thrombocytopenia 50% Fatigue 26% Anemia 24% Increased International Normalized Ratio 18% Nausea 16% Dizziness 13% Hypertension 11% Vomiting 10% 9

10 Pheochromocytoma and paraganglioma Annual incidence: 2 to 8 per million in the U.S. 15% 35% 16% of cases are metastatic/malignant and not eligible for surgery 1,2 of resectable cases who receive surgery experience disease recurrence 3 Tumor progression is the leading cause of death in advanced cases Recurrence usually presents 5 15 years after initial surgery, with a 3.2-fold higher risk in patients with familial disease AZEDRA indication: Adults and children 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy 1 Lefebvre et al Curr Oncol (2014) 21: e8 e17; Ayala-Ramirez et al J Clin Endocrinol Metab (2011) 96: Ayala-Ramirez et al J Clin Endocrinol Metab (2011) 96: Amar et al Metab Res (2012) 44:

11 U.S. market engaged with small dedicated salesforce Majority of patients are treated at centers, many of which are sites that participated in our registrational trial Guidelines recommend referral to multidisciplinary centers with specialized resources Small sales, technical and medical affairs teams NCCN Guidelines now include AZEDRA 11

12 Executing Launch Strategy Commercial Launch Key Activities Establish differentiated and compelling product profile Build team Sales, Access, Medical Identify and profile centers of excellence Establish meaningful value proposition and engage payers NCCN Guidelines acknowledge AZEDRA as only FDA-approved option Experienced Nuclear Medicine and Oncology Sales Team has existing relationships in more than half of key accounts All key geographic regions have centers working to make AZEDRA available Tier 1 & 2 account numbers growing 40+ payer presentations have taken place 12

13 13 The AZEDRA Service Connection TM Hub is now active

14 PSMA TARGETED PIPELINE

15 ADDRESSING PROSTATE CANCER WITH A NOVEL PORTFOLIO OF PSMA TARGETED DIAGNOSTICS AND THERAPEUTICS Diagnose Treat Monitor 1404 PyL TM 1095 Technetium-99m labeled small molecule PSMA-targeted SPECT/CT imaging agent to diagnose and detect localized prostate cancer as well as soft tissue and bone metastases Fluorinated PSMA-targeted Positron Emission Topography (PET) imaging agent for prostate cancer Targeted small molecule radiotherapeutic that selectively binds to PSMA Phase 3 Phase 2/3 Phase 1 PSMA TTC Licensed to Bayer Preclinical development in process PSMA CADx Automated reading of PSMA PET/SPECT/CT images based on AI and deep learning Development in progress based on 1404 Phase 1 and Phase 2 studies 15

16 PSMA TARGETED DIAGNOSTICS Current imaging procedures used for detection or staging of prostate cancer depend on morphology of lymph nodes or bone metabolism that do not always meet diagnostic needs. Maurer T et al, Nrurol 2016 Why the Oligometastatic Space has Increased in Prostate Cancer: The Advent of PET Imaging PSMA PSMA imaging significantly better in identifying aggressive tumor in prostate. Zamboglou, C. et al, EJNMMI 2016 Presented by: Felix Feng, MD 2018 ASCO GU Symposium PSMA imaging study found a high impact on management intent, with a planned management change in 51% of patients. Roach, PJ. et al, JNM

17 1404 PSMA-TARGETED IMAGING AGENT SPECT/CT radiopharmaceutical product candidate targeting PSMA Potential to transform clinical practice with improved detection & monitoring Initial application: enabling Active Surveillance 17

18 1404 PHASE 3 STUDY Topline Results 471 Biopsy Confirmed Low Grade PC (Gleason Score 3+4) patients who are candidates for Active Surveillance 1404 Dosing SPECT/ CT Imaging Prostatectomy or biopsy Histopathology Co-Primary Endpoints Met endpoint for specificity; did not meet endpoint for sensitivity The lower limits of the two-sided 95% CIs for specificity and sensitivity of 1404 imaging to detect clinically significant prostate cancer must be at least 60% Specificity Sensitivity 71-75% (95% CI of 64% to 80%) 47-51% (95% CI of 41% to 56%) Safety and tolerability The most frequent treatment related events included headache (2.3%), dizziness (1.1%) and fatigue (0.8%). Next Steps: Conduct a thorough analysis of the full data and determine the appropriate development path for this novel agent in patients with low-grade prostate cancer by year end 18

19 PyL TM : PSMA-TARGETED PET/CT IMAGING AGENT Enables visualization of both bone and soft tissue metastases Highly specific to prostate cancer cells, not confounded by degenerative or inflammatory conditions Very high standardized uptake values (SUV) even in small lesions Identified more lesions than conventional imaging PyL Research Access Program underway 19 Image from JHU Study J1418

20 PyL CLINICAL DEVELOPMENT PROGRAM TO SUPPORT NDA Indication: PET/CT imaging agent to determine the presence or absence of recurrent and/or metastatic prostate cancer High Risk and/or metastatic prostate cancer Biochemical Recurrence (BCR) of prostate cancer N 383 patients (266 with localized high risk prostate cancer, 117 with recurrent or metastatic disease) ~200 Primary Objective To assess the diagnostic accuracy of PyL PET/CT imaging in patients with high risk and/or metastatic prostate cancer To assess the detection rate of PyL PET/CT imaging in patients with recurrent prostate cancer Reference standard to be used Histopathology of pelvic lymph nodes Histopathology of pelvic lymph nodes and FDA approved imaging modalities Study Status Enrollment completed 2Q18; topline data expected 4Q18 Planned trial; Expect to initiate by year-end 20

21 PSMA AI A patient centric approach that applies artificial intelligence to image analysis for information driven healthcare practice in prostate cancer. Using expertise from absi, a validated imaging biomarker, to develop PSMA computer-aided diagnosis (CADx) Automated reading of PSMA-targeted SPECT/PET images based on deep learning Using 1404/PyL Phase 2 and Phase 3 data to develop and validate PSMA CADx Objective and reproducible assessment to standardize PSMAtargeted imaging in patients with prostate cancer Sold only in Japan and investigational in the U.S. 21

22 % CHANGE IN PSA 1095: PSMA TARGETED SMALL MOLECULE THERANOSTIC FOR PROSTATE CANCER 100 * Best PSA Response in 25 patients Targeted small molecule radiotherapeutic that selectively binds to PSMA Markedly reduced prostate-specific antigen levels in a heavily pretreated group of 25 evaluable patients, and reduced bone pain in German compassionate use setting in advanced prostate cancer PATIENT NUMBER Zechmann et al. Eur J Nucl Med Mol Imaging,

23 1095 PHASE 1 STUDY DESIGN: Open Label, Dose Escalating, Safety & Efficacy Study 1095 Study Overview: mcrpc Patients Screening Phase Eligibility Dosimetry Treatment Phase Part 1 Dose Escalation Safety Treatment Phase Part 2 Safety Efficacy Follow up Patient Population Subjects with metastatic castration-resistant prostate cancer (mcrpc) who have demonstrated tumor avidity to 1095 N Clinical Endpoints ~40 patients Safety & tolerability, preliminary efficacy Determine the maximum tolerated dose of 1095 Determine biodistribution of 1095 Define an optimal dose for Phase 2 23

24 PSMA-TARGETED THORIUM CONJUGATE (PSMA-TTC) Partnered with Bayer In a prostate cancer mouse model, PSMA-TTC proved efficacious to suppress tumor growth and bone degradation 1 Phase 1 in patients with mcrpc planned to commence in 2018 Potential added effect on bone metastases due to decay product Ra-223 homing to bone Financial terms Received $4M upfront payment and $3M in regulatory and development milestones as of 2Q18 Additional potential clinical and regulatory development milestones up to an aggregate total of $46M Potential net sales milestone payments up to an aggregate total of $130M PSMA-TTC Single digit royalties on net sales 1 Hammer S., et al., AACR; Cancer Res 2017;77(13 Suppl):5200. doi: / am

25 CORPORATE OVERVIEW

26 FINANCIAL OVERVIEW 2Q18 Financial Snapshot $87.5M cash as of 6/30/18 Quarterly Revenue: $3.9M Net loss: $0.20 per share 75.4M shares outstanding Strong financial position to advance portfolio and launch AZEDRA RELISTOR franchise provides financial foundation: Marketed by Bausch Health Royalty scale based on U.S. net sales, ranging from 15%-19% Entitled to receive 60% of revenues received by Bausch Health from ex-u.s. sub-licensees Royalty-backed agreement with Healthcare Royalty Partners $50M of non-recourse loan proceeds received November 2016 Progenics retains long-term upside potential, including rights to the sales milestones totaling up to $200M, including $10M on first $100M in sales 26

27 LEADING DEVELOPMENT OF TARGETED RADIOPHARMACEUTICALS TO DETECT AND TREAT CANCER 2018 Program Goals 1Q18 2Q18 3Q18 4Q18 AZEDRA FDA Approved July 30, P3 Data PyL Complete First P2/3 P2/3 Data & Initiate 2 nd P3 PSMA-TTC Initiate P1 by Year-End (Bayer) PSMA CADx Using 1404 data to develop and validate PSMA CADx 27 FIND FIGHT AND FOLLOW

28 Leading Development of Radiopharmaceuticals to Detect and Treat Cancer October 2018