credible science. incredible therapeutics.

Transcription

1 credible science. incredible therapeutics. Corporate Presentation NASDAQ: SPHS O c t o b e r 2018

2 2 Forward-Looking Statement Certain information contained in this presentation may constitute forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other applicable securities laws. Such forward-looking statements or information include, without limitation, statements or information about the results of our studies, anticipated financial performance, business prospects, strategies, regulatory developments and market acceptance. Forward-looking statements and information can be identified by the use of words such as anticipated, expected, estimated or similar words and phrases that state or indicate that certain actions, events or results may, could, might or will be taken, occur or be achieved. Such statements or information reflect Sophiris current views with respect to future events and are subject to certain risks, uncertainties and assumptions including, without limitation, the actual results of our studies, our actual financial performance, our ability to carry out our research and development plans, including our ability to obtain or maintain regulatory approvals, competition and market demand for any future product and our ability to obtain financing. Forward-looking statements and information are necessarily based upon estimates and assumptions that, while considered reasonable by management, are inherently subject to significant risk and uncertainty. Many factors could cause our actual results, performance or achievements to be materially different from those that may be expressed or implied by such forward-looking statements or information. Such factors and corresponding risks and uncertainties are detailed in Sophiris SEC filings. Should one or more of these risks or uncertainties materialize, or if assumptions underlying the forward-looking statements or information prove incorrect, actual results may vary materially from those described herein. Except as required by law, Sophiris expressly disclaims any intention or obligation to update or revise any forward-looking statements and information. All forward-looking statements and information are expressly qualified in their entirety by the foregoing cautionary statements.

3 3 LOCALIZED PROSTATE CANCER (Clinically Significant) 2 INDICATIONS BENIGN PROSTATIC HYPERPLASIA (BPH or Enlarged Prostate) PHASE 2b Confirm dose and delivery to ablate prostate cancer cells PROSTATE PHASE 3 1 st BPH study successfully met primary endpoint FIRST-IN-CLASS DRUG Topsalysin (PRX302) SINGLE SPECIALIST Localized, targeted, ultrasound-guided administration; in-office setting by Urologists

4 Topsalysin Activated by Enzymatically-Active PSA - Only within the Prostate 4 NATIVE PRO-AEROLYSIN (pore-forming protein) Inactive Pro-Aerolysin Active Aerolysin Inactive Topsalysin TOPSALYSIN Active Topsalysin Active Domain (Aerolysin) T H E B E N E F I T Cleavage Site + Cleavage by Furin Enzyme Modification Cleavage Site + Cleavage by Enzymatically-Active PSA Prostate-specific activation Inhibitory Sequence

5 5 Prostate-Specific MOA Targeted at the Cellular Level Binding Topsalysin binds to GPIanchored receptors and becomes concentrated on cell surface Cleavage Active PSA cleaves tail, activating aerolysin on cell surface, exposing hydrophobic domains Oligomerization and Transmembrane Pore Cell Death Cell contents leak out causing cell death, through cell lysis PRX302 Aerolysin GPI- Anchored Receptor PSA Aerolysin Heptamer Selectively Destroys Prostate Tissue

6 6 ONE Drug Topsalysin Works in TWO Indications LOCALIZED PROSTATE CANCER ENLARGED PROSTATE (BPH) PROSTATE Bladder Cancerous Prostate Enlarged Prostate Urethra High concentration of PSA in and around prostate tumors High concentration of PSA in transition zone

7 7 Single Physician Specialty: Urologists Potential Treatment Option for Two Patient Populations Potential to provide good efficacy outcomes with: Minimal side effects Preservation of Quality of Life Simple, Rapid, Minimally Invasive Procedure TRUS guided transrectal or transperineal intraprostatic injection Similar to prostate biopsy; very familiar to urologists Office-based procedure, minimal learning curve

8 8 Focal Treatment of LO C A L I Z E D P R O S TAT E C A N C E R LOCALIZED PROSTATE CANCER (Clinically Significant) PHASE 2b Confirm dose and delivery to ablate prostate cancer cells PROSTATE BENIGN PROSTATIC HYPERPLASIA (BPH or Enlarged Prostate) PHASE 3 1 st BPH study successfully met primary endpoint

9 9 Localized Prostate Cancer at a Glance 2ND MOST COMMON CANCER IN MEN New Cases Expected to be Diagnosed in 2017 (US) ~20% Spread/ Metastasized ~127K 161K Men ~80% Localized Diagnosed with Localized Disease Not Yet Spread Beyond Prostate 50% ACTIVE SURVEILLANCE (~63K Men) 50% TREATMENT (~63K Men) Source: SEER Database, Stat Fact Sheet Prostate Cancer, ICER, Cooperberg et al 2010, Ahmed 2012

10 Localized Prostate Cancer Treatment: Enabled by Advances in Imaging Technology 10 Imaging (multi-parametric MRI) Targeted biopsy Lesions more precisely identified and located for treatment Stratify patients for treatment based on identified risk: GLEASON SCORE FROM BIOPSY <6 Active Surveillance 6-7 Focal Therapy 8+ Radical Therapy mpmri images can be co-registered with live, 3D ultrasound images Focal/Targeted treatment of pre-identified lesion(s)

11 11 Today s Localized Prostate Cancer Treatment Options Non-Invasive More Invasive ACTIVE SURVEILLANCE FOCAL THERAPY RADICAL THERAPY PSA levels monitored Biopsies as indicated Selected, targeted treatment of cancer/lesions with preservation of surrounding, normal prostatic tissue T O P S A L Y S I N Cryotherapy, HiFU, RF, Photo Dynamic Treatment, Brachytherapy Radiation Prostatectomy (Surgical removal of prostate) Potential to provide: Good efficacy outcomes Low probability of side effects Preserved quality of life High cost Side effect profiles Longer procedures Special training Serious co-morbidities: Sexual dysfunction Urinary incontinence Rectal toxicities

12 12 Phase 2a Study Design: Localized Prostate Cancer STUDY DESIGN Treatment Delivery/Guidance Outcomes Single center, open label, biopsy at 6 months: University College, London 18 patients with localized clinically significant prostate cancer Gleason score 7 and 10mm Maximum Cancer Core Length (MCCL) Gleason score 6 (3+3) and > 3mm MCCL Delivered using ultra-sound guided injection One treatment Doses up to 5 µg/g of prostate Up to 1000 µg/g of tumor Previously obtained mpmri images mapped to real time, 3D ultrasound images, using fusion software to facilitate the administration of Topsalysin Primary endpoint: Safety and tolerability over 6 months Histological evidence of tumor control at 6 months (targeted biopsy)

13 13 Phase 2a Efficacy: Localized Prostate Cancer Both MCCL-Only Gleason-Only Response Post-Treatment Effect on Disease 6 Months (n=18 Patients) 9 6 MRI An Example 2 1 Complete Ablation Complete Ablation/ Improvement Partial Response No Change No Response (Increase) No Change/ Slow Progression Pre Treatment Tumor hyperintense region 2 Weeks Post Treatment Tumor no longer visible Presented at EUA and AUA, 2017

14 14 Phase 2a Key Learnings from POC Study D O S E D E L I V E R Y S A F E T Y L E A R N I N G C U R V E Future studies with dose based on size of tumor as well as prostate Slow diffusion of Topsalysin into and around the tumor Appears to be well tolerated in this patient population, no serious adverse events; sexual and urinary function preserved Minimal learning curve in order to treat a targeted tumor Could be administered in the doctor s office

15 15 Phase 2a Safety: Localized Prostate Cancer Adverse Events CONCLUSIONS Dizziness Urge Incontinence Anal Pruritis Penile Pain Hematospermia Dysuria Urgency Hematuria Perineal Pain 6% 6% 6% 6% 11% 11% 17% 22% 28% No Serious Adverse Events and No New Safety Signals Doses up to 5µg/g of prostate (up to 1,000µg/g of tumor) Safety profile consistent with that observed in the BPH program, in which a lower dose of 0.6µg/g of prostate was used 0% 5% 10% 15% 20% 25% 30% AEs attributable to Topsalysin or injection procedure All mild in severity Presented at EUA and AUA, 2017

16 16 Phase 2b Study Design: Localized Prostate Cancer STUDY DESIGN Multi-center, UK and US, open label, biopsy at 6 months 38 patients have been enrolled with localized clinically significant prostate cancer Gleason score 7 and 10mm Maximum Cancer Core Length (MCCL) Gleason score 6 (3+3) and 6mm MCCL Treatment Delivery/Guidance Transrectal ultra-sound (TRUS) guided administration Doses up to 1000 µg/g of tumor Includes the option for a 2 nd administration after 6 month biopsy No significant adverse events from the 1 st administration Response to 1 st administration but a clinically significant lesion remains Previously obtained mpmri images mapped to real time 3D ultrasound images using fusion software to facilitate the injection of Topsalysin Outcomes Safety and tolerability Primary efficacy endpoint: histological evidence of tumor control at 6 months (targeted biopsy)

17 Phase 2b Interim Safety and Biopsy Data: Single Administration: 6-Months Post-Treatment 17 Adverse Events (more than 5%) (n=38 patients) Biopsy Results (n=37 patients) Strangury Micturition Urgency 2 patients 2 patients Nocturia Urinary Retention 2 patients 3 patients Dysuria AEs considered by the Investigator attributable to Topsalysin 3 patients 0% 2% 4% 6% 8% 10% Typically considered mild in severity Clinical Responder Partial Response No Response Complete Ablation Reduction in Gleason Score and/or MCCL No Response Results Support Moving Forward into Potential Registration Studies with Single Administration

18 Phase 2b: Second Administration 18 Eligibility Includes the option for a 2 nd administration after 6 month biopsy No significant adverse events from the 1 st administration Response to 1 st administration but portion of the targeted lesion remains Status 11 patients have received a 2 nd administration 10 patients continued to be monitored One patient died subsequent to the 2 nd administration which was deemed unlikely related to the study drug or the procedure Six month biopsy data from the 2 nd administration will be available in the 4 th quarter of 2018 Potential to Move Forward with a 2 nd Administration in Future Clinical Development to be Evaluated

19 19 E N L A R G E D P R O S TAT E ( B P H ) LOCALIZED PROSTATE CANCER (Clinically Significant) PHASE 2b Confirm dose and delivery to ablate prostate cancer cells PROSTATE BENIGN PROSTATIC HYPERPLASIA (BPH or Enlarged Prostate) PHASE 3 1 st BPH study successfully met primary endpoint

20 BPH (Enlarged Prostate): Large Growing Market with Significant Unmet Need 20 AFFECTS 70% OF MEN 60+ YEARS 3 Million Non-Invasive Current Treatment Options Limited 200K More Invasive 1.8M Untreated 5M Bothered by BPH ~3.2M Treated Oral Drugs Alpha Blockers/ 5-alpha Reductase Inhibitors (5ARI) T O P S A L Y S I N MIST Minimally Invasive Surgical Techniques TURP Transurethral Resection of the Prostate Patients Actively Seeking Alternative Treatment Options LIMITATIONS Lack of sustained efficacy Poorly tolerated: side effects, e.g., sexual dysfunction, cardiovascular A New Treatment Option Which Is Designed to be Safe, Simple, Convenient and to Produce Rapid, Sustained Relief LIMITATIONS Need for catheterization Safety concerns, e.g., bleeding Complications, e.g., long-term sexual dysfunction Hospitalization/anesthesia (TURP)

21 21 Significant Clinical Expertise in BPH TRIUMPH PRX Randomized, double-blinded, vehicle-controlled study of transrectal intraprostatic injection of topsalysin 61 active (0.6µg/g) 31 vehicle Plus-1 PRX Randomized, double-blinded, vehicle-controlled, multicenter safety and efficacy study of a single intraprostatic treatment of topsalysin 239 active (0.6µg/g) 240 vehicle 2nd Phase 3 Study Required for Approval S U M M A R Y 365 BPH patients treated with Topsalysin across all BPH programs Clinically meaningful improvement of symptoms consistently across studies Appears to be safe and well tolerated PHASE 2B PHASE 3 PHASE 3

22 22 Phase 3: Plus-1 Study Design BPH STUDY DESIGN Patient/Location 479 patients randomized 1:1, in a double-blinded, international multi-center, vehiclecontrolled study Treatment Delivery Transrectal intraprostatic injection of Topsalysin Dose 0.6µg/g of prostate vs vehicle and volume 20% of total prostate volume Primary Endpoint IPSS total score change from baseline (CFB) over 52 weeks analyzed using repeated measures linear mixed model Secondary Endpoints IPSS CFB at 6, 12, 18, 26, 32, 39 & 52 weeks Self-assessment of disease specific quality of life at 6, 12, 18, 26, 32, 39 & 52 weeks Qmax (CFB in maximum urine flow rate) + Safety Mild 0 7 Outcomes International Prostate Symptom Score (IPSS) Moderate Severe Patient-reported; 7 questions Validated endpoint used to approve currently marketed BPH therapies

23 23 Phase 3 BPH Clinical Trial Results: IPSS Change in International Prostate Symptom Score (IPSS) Change in IPSS Over 52 Weeks Primary Endpoint Achieved Improvement in IPSS Score (from Baseline to 52 weeks) 7.6 vs 6.58 Overall Improvement (p=0.043) 1 Vehicle Topsalysin Weeks P value P value calculation: repeated measures linear mixed model analysis 2 P value calculation: ANCOVA using last observation carried forward. Maximal effect: 8.31 vs % of maximal effect persisted at week 52

24 24 Phase 3 BPH Clinical Trial Results: Quality of Life and Qmax Disease-Specific Quality of Life * Global Question 2 Sustained 1.6 to 1.7 patient improvement weeks Statistically significant Vehicle PRX Weeks PEAK URINE FLOW RATE (QMAX) Qmax change from baseline over 52 weeks showed an overall improvement of 1.77 ml/sec for Topsalysin, representing a statistical trend that narrowly missed statistical significance (p = 0.055) compared to the vehicle group P value *Patient questionnaire (global question): 8 th question on the IPSS questionnaire 1 P value calculation: ANCOVA using last observation carried forward

25 Phase 3 BPH Clinical Trial Results: Attractive Safety Profile 25 Adverse Events CONCLUSIONS Topsalysin Vehicle Dysuria e.g., Burning, pain or discomfort on urination Hematuria or presence of red blood cells in urine Pollakiuria or increased frequency of urination Pyrexia Fever Perineal Pain 5.8% 4.2% 5.4% 8.3% 9.6% 8.8% 8.8% 15.0% 18.8% 20.1% Adverse events were typically Mild to moderate Occurred on the day of injection Transient with a median duration of less than a day No evidence of any treatment related sexual or cardiovascular side effects 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% *Occurring in 5% of subjects treated with Topsalysin

26 Topsalysin: A Differentiated Solution for a Bothersome Condition 26 Lower EFFICACY Higher Fewer SIDE EFFECTS/ SAFETY CONCERNS More Oral Drugs PRX302 MISTS TURP A new treatment option designed to be safe, simple, convenient and to produce rapid, sustained relief Simple, short office-based procedure Used after oral meds discontinued, but before more radical treatments IPSS Improvement 3-6 Points 7-8 Points Points 16 Points

27 27 Experienced Senior Management Lars Ekman, M.D., Ph.D. Executive Chairman Randall Woods President, CEO Allison Hulme, Ph.D. COO, Head of R&D Peter Slover CFO advised by world-class urologists

28 28 Next Steps PHASE 2B Localized Prostate Cancer Confirm dose and optimize delivery of Topsalysin Complete multi-center, open label study in 38 patients with clinically significant localized prostate cancer Final biopsy data on patients who receive a 2nd dose in Q Evaluate the opportunity to utilize a 2 nd dose of topsalysin in future clinical trials PHASE 3 Plus-2 Study: BPH Funding options being evaluated 500+ patients in study similar to positive PLUS-1 study

29 29 Selected Financial Data Selected Income Statement Data Operating Expenses Research and Development General and Administrative Total Operating Expenses Interest Expense Interest Income NET LOSS Six Months Ended June 30, 2018 $6.9M $2.3M $9.2M $0.4M ($0.2M) $9.4M Cash Is Expected to Fund the Company Through June 2019 Selected Balance Sheet Data Equity Cash Balance Total Assets Working Capital Debt June 30, 2018 $18.5M $19.6M $14.1M $6.9M Issued Common Shares 30.1M June 30, 2018 Average Exercise Price Warrants 5.8M $4.05 Stock Options 2.9M $2.85

30 30 Summary First-in-class drug Topsalysin, for two conditions affecting millions of men, underserved by current therapies Clinical trials have demonstrated efficacy and an attractive safety profile Focus on Urologists enabling them to offer a less radical treatment option for both BPH and localized prostate cancer Potentially attractive to Payors by eliminating or delaying need for more expensive treatments Important near-term milestones to drive value

31 credible science. incredible therapeutics. Corporate Presentation NASDAQ: SPHS