ESSA NonConfidential Slide Deck 052219 Final · 1. Surveillance Research, American Cancer Society....
Transcript of ESSA NonConfidential Slide Deck 052219 Final · 1. Surveillance Research, American Cancer Society....
ESSA PharmaNASDAQ: EPIX; TSX-V: EPI
Non-Confidential Presentation, May 22nd 2019
Forward Looking StatementThis presentation may contain forward-looking statements. Forward-looking statements and information are subject tovarious known and unknown risks and uncertainties, many of which are beyond the ability of ESSA to control or predict,and which may cause ESSA’s actual results, performance or achievements to be materially different from those expressedor implied thereby. Such statements reflect ESSA’s current views with respect to future events, are subject to risks anduncertainties and are necessarily based upon a number of estimates and assumptions that, while considered reasonableby ESSA as of the date of such statements, are inherently subject to significant medical, scientific, business, economic,competitive, political and social uncertainties and contingencies. In making forward-looking statements, ESSA may makevarious material assumptions, including but not limited to the market and demand for the securities of ESSA, generalbusiness, market and economic conditions, obtaining positive results of clinical trials, and obtaining regulatory approvals.
Forward-looking information is developed based on assumptions about such risks, uncertainties and other factors set outherein and in ESSA’s Annual Report on Form 20-F dated December 13, 2018 under the heading “Risk Factors”, a copy ofwhich is available on ESSA’s profile on the SEDAR website at www.sedar.com, ESSA’s profile on EDGAR at www.sec.gov,and as otherwise disclosed from time to time on ESSA’s SEDAR profile. Forward-looking statements are made based onmanagement's beliefs, estimates and opinions on the date that statements are made and ESSA undertakes no obligationto update forward-looking statements if these beliefs, estimates and opinions or other circumstances should change,except as may be required by applicable Canadian and United States securities laws. Readers are cautioned againstattributing undue certainty to forward-looking statements.
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ESSA Corporate OverviewFocused on the development of novel therapies for the treatment of prostate and other hormone-driven cancers
Founded with technology licensed from The University of British Columbia and the BC Cancer Agency
Sites in Houston, South San Francisco and Vancouver
First-in-class N-terminal domain (NTD) inhibitors of the androgen receptor (“Anitens”)
EPI-7386 nominated as IND candidate
Initial clinical development focused on resistant mCRPC as a single agent with future development in combination with antiandrogens in CRPC and HSPC
Breast cancer in TNBC AR+
Listed on NASDAQ (EPIX) & TSX-V (EPI)
Cash balance of $8.6M(March 31, 2019)
Company Technology & Products Financial Details
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David R. Parkinson, MDPresident & Chief Executive Officer, Director
Peter Virsik, MS, MBAEVP & Chief Operating Officer
David S. Wood, MBA, CPA, CMAChief Financial Officer
Experienced Management Team
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Acquisition of Realm Therapeutics
Key Transaction Terms
Strategic Rationale
• On May 15, 2019, ESSA announced it will acquire 100% of Realm Therapeutics (“Realm”) with newly issued shares:
─ Realm’s issued and outstanding shares valued at approximately $21.5 million, which represents a 5% premium over Realm’s estimated net cash amount of $20.5 million at the closing of the acquisition
─ Realm Shareholders will be entitled to receive approximately 0.058 ESSA ordinary shares for each Realm share, valued at $3.19 per share 1
─ ESSA’s shareholders will have pro forma equity interest of approximately 54% 1
• The acquisition of Realm’s cash, combined with the the proposed additional financing, will deliver sufficient financial resources to achieve multiple value-inflection points and key near-term objectives in the coming two years including:
─ Completion of a Phase 1 clinical trial for EPI-7386 in patients with advanced prostate cancer;
─ Proof-of-concept clinical data from a Phase 1 trial for EPI-7386 in combination with anti-androgens in prostate cancer patients; and
─ Continued development of our early preclinical pipeline of novel anitens for the potential treatment of breast cancer
• We believe the Realm acquisition will bring in cash at a lower cost of capital and higher ESSA shareholder value than other financing options
51. Based upon a 60-day volume-weighted average price of $3.19 per share of ESSA as of the close of trading on May 14th, 2019, subject to a final adjustment based on Realm’s final net cash amount prior to closing of the acquisition
PUBLIC HEALTH PROBLEM
LARGE MARKET
VALIDATED THERAPEUTIC TARGET
NEED FOR NEW THERAPEUTIC STRATEGIES
Prostate Cancer Disease Landscape
61. Surveillance Research, American Cancer Society. 2018.2. Robinson D, et al. Cell. 2015.3. Katsogiannou M, et al. Cancer Treat Rev. 2015.
• Prostate cancer is the 2nd
most common cause of male cancer deaths1
• Each year in the US, ~165,000 men are diagnosed and ~29,000 die due to prostate cancer
• Over $5B in global sales generated in 2017 by leading anti-androgens, Zytiga® (abiraterone acetate) and Xtandi®(enzalutamide)
• Prostate cancer disease progression is associated with androgen receptor (AR) signaling. 2,3,4
• An estimated ~60% of mCRPC tumors post-Xtandi or Zytiga failure may still be AR-driven 5
• Despite new therapies, mCRPC anti-androgen resistance is inevitable 6,7
4. Azad AA, et al. Clin Cancer Res. 2015.5. Wyatt. JAMA. 2016. 6. Watson PA, et al. Nat Rev Cancer. 2015.
7. Attard G, et al. ASCO Annual Meeting. 2017.
Current Anti-androgen Therapies Target the Androgen Receptor Ligand Binding Domain
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• All current anti-androgens function through the ligand-binding domain of the androgen receptor
• Known anti-androgen resistance mechanisms develop at the ligand binding domain
ANDROGEN
Zytiga® (abiraterone acetate)Eligardä, Lupron® (leuprolide)Zoladex® (goserelin)Firmagon® (degarelix)
N-terminal domain DNA-binding domain Ligand-binding domain
Erleada® (apalutamide)Xtandi® (enzalutamide)Nilandron® (nilutamide)Casodex® (bicalutamide)Eulexin® (flutamide)
Inhibit androgen synthesis
Block androgen binding
AR Amplification1
Splice variants3,4,5
Promiscuous activation (i.e., glucocorticoids, progesterone) 6,7
Gain-of-function mutations1,2
Anti-androgen Resistance Mechanisms
6. Chen EJ, et al. Clin Cancer Res, 20157. Culig Z, et al. Cancer Res, 1994
4. Mostaghel EA, et. Al. Clin Cancer Res, 20115. Sun S, et al. J Clin Invest, 2010
1. Azad AA, et al. Clin Cancer Res, 20152. Joseph JD, et al. Cancer Discov, 20133. Antonarakis ES, et al. NEJM, 2014
Targeting the AR NTD: Novel Transcription Factor Inhibition of Androgen-driven Prostate Cancer Biology
• Novel method of inhibiting the AR
• Proposed binding of Anitens to Tau-5 region of AF1 1
• Anitens active against multiple forms of AR:
o Wild-type AR, LBD mutant AR, and splice-variant AR2,3,4
81. De Mol E, et al. ACS Chem Biol. 2016.2. Andersen RJ, et al. Cancer Cell. 2010.
N-terminal domain DNA-binding domain Ligand-binding domain
Granted unique USAN drug stem of “Aniten” as an N-terminal inhibitor of AR
3.De Mol E, et al. ACS Chem Biol. 2016.4.Yang YC, et al. Clin Cancer Res. 2016.
EPI362
C404
438
Tau-5
Aniten
DESIGN An adaptive Phase 1 first-in-man dose escalation / dose expansion study
DOSE EPI-506 (EPI-002 active) oral once-daily or twice-daily dosed as a soft-gel capsule
POPULATIONmCRPC patients progressing after abiraterone, enzalutamide, or both; allowed to have also failed one regimen of docetaxel chemotherapy
STUDY SIZE 28 patients
ENDPOINTS Safety, PK, maximum tolerated dose, recommended Phase 2 dose
STUDY STATUS Completed at 5 sites in US and Canada
First-Generation EPI-506 Phase 1 Study in Patients w/mCRPC
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EPI-002 (active drug)
EPI-506 (tri-acetate prodrug)
OO
(S)(S)
O(S)(S)
O
Cl
O
EPI-506O
O O
EPI-002
First-Generation EPI-506 Phase 1 Data Demonstrates Signs of Anti-Tumor Activity Despite Suboptimal PK Profile
• Significant first-pass metabolism seen: minimal exposure time above target IC50• PSA declines in resistant tumors, but too little and not sustained
0 6 12 18 241
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EPI-002 PK - day 8
Time (hr)
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1280 mg
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1800 mg bid simulatedEPI-002 cell IC50
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g36
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mg
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640
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Patients receiving < 1280 mgPatients receiving > 1280 mg
320
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Maximal PSA Change at Any Time from Start of Multi-dose Period (N=27)
EPI-506: Safe and Well-tolerated Until Very High Doses
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Most Commonly Reported Adverse Event > 10% All Grades, N (%)Diarrhea, nausea 13 (46%)
Fatigue 7 (25%)
Decreased appetite, pain in extremity 6 (21%), each
Vomiting 5 (18%)
Back Pain 4 (14%)
Abdominal distension, anemia, arthralgia, musculoskeletal pain, UTI 3 (11%), each
Adverse Events ≥ Grade 3 N (%) Relationship to Study DrugAnemia 3 (11%) Not related.
AST elevated 2 (7%) Probably related, Possibly related.
Neutropenia 2 (7%) Not related.
Abdominal pain, diarrhea 1 (4%), each Possibly related.
ALT elevated, amylase elevated, angina, hypertension, dizziness postural 1 (4%), each Probably related.
Arthralgia, gastrointestinal hemorrhage, pain in extremity, syncope, thrombocytopenia, urinary retention
1 (4%), each Not related.
Lessons Learned: A Blueprint for Next Generation Anitens
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Experience informed the specifications for a next-generation Aniten compound:• Higher potency• Less metabolism with a longer half-life• Maintain on-target specificity• Ease of manufacturing / shelf-life stability• Commercial formulation
Process to discover next-generation Aniten:• Strengthened ESSA’s chemistry and preclinical team in early 2018• Augmented external chemistry efforts to expand the synthesis of new molecules
o >400 new compounds designed; >250 compounds screened in vitro for potency and ADME profile• Selected EPI-7386 as the IND candidate
In Vitro Potency and Stability of Next-Generation Anitens
13CONFIDENTIAL
Stability threshold
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itro
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oten
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Potency threshold
Target compounds
• Significant gains made in in vitro potency and stability compared to EPI-002• Preclinical characterization limited to only the most potent and stable compounds
Enzalutamide
EPI-002 potency is >> 4500nM
TPP CRITERIA STATUS SPECIFICS
Increased potency In vitro potency goal achieved (>20X more potent than EPI-506 / 002)
ENZ-resistant activity In vitro cellular activity in numerous ENZ-resistant cell lines and models
Xenograft in vivo activity Equal anti-tumor activity to ENZ in ENZ-sensitive LNCaP xenograft model; improved anti-tumor activity in ENZ-resistant VCaP model
Clean off-target profile Nuclear receptor & CEREP screening indicates minimal off-target binding
Reduced metabolism Much less metabolized in vitro than EPI-506 / 002
In vivo PK profile Mouse/rat/dog metabolism & PK studies support once-daily dosing and predict significant human exposures with >24hr half-life
Simple to manufacture Manufacturing process straightforward
Combination potential Solid dosage; minimal drug-drug interaction predicted
Strong IP coverage IP broadly filed on new Anitens; patent expirations anticipated 2037+
Next-Generation Aniten EPI-7386 Product Characteristics
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EPI-7386 Cellular Potency Increased > 20X Compared to EPI-002
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• Next-generation anitens exhibit cellular potency’s in a similar magnitude to the leading anti-androgens in a full-length androgen receptor cellular model
0.01 0.1 1 10 1000
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Concentration (uM)
LNCa
P AR
E-Lu
c %
inhi
bitio
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SD
EnzalutamideBicalutamideApalutamideDarolutamideEPI-002EPI-7386
Compound IC50 (nM)* nEPI-002 9,580 2
EPI-7386 421 5Enzalutamide 154 5Bicalutamide 242 7Darolutamide 616 3Apalutamide 4,540 3
* Assay is conducted in LNCaP cells containing the T878A LBD AR mutation utilizing the PSA(6.1kB) luciferase reporter plasmid
EPI-7386- Significantly Improved In Vitro Metabolic Stability & Mouse & Dog PK
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• EPI-7386 in vitro hepatocyte stability significantly improved over EPI-002
• EPI-7386 displays favorable mouse & dog pharmacokinetic profile
0 4 8 12 16 20 241
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Mean Plasma conc after PO dosing in male CD-1 mice
Time (hr)[p
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a] in
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mL
EPI-7386 - PO5 mg/kg
ENZA - PO5 mg/kg
EPI-002 -PO5 mg/kg
Hepatocyte T1/2 (min)Compound HumanEPI-002 38
EPI-7386 >360Enzalutamide >360
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• EPI-7386 shows activity in AR-V7-driven cellular models whereas ENZ does not
LNCaP95 Cell Proliferation Androgen Receptor PSA Luciferase
Similar reduction of PSA-luciferase when driven by AR-V7 only (green) or a combination of AR-V7 and full-length AR (red)
AR-V7-Driven Prostate Cancer Model
Full-Length AR-Driven Prostate Cancer Model
Non AR-Driven Prostate Cancer Model
EPI-7386 Active in ENZ-Resistant AR-V7-Driven Cellular Models
EPI-7386 Exhibits Similar Anti-tumor Activity to ENZ in ENZ-Sensitive LNCaP Xenograft Model
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• LNCaP is driven by full-length androgen receptor and ENZ shows excellent activity
• ENZ was dosed at a supratherapeutic doseo ENZ dose was 2X the human
exposure while EPI-7386 was ½ the exposure of ENZ
• Despite differences in exposure, EPI-7386 displays similar efficacy to ENZ
• VCaP (castrate) growth is initially driven by AR-overexpression followed by AR-V7-driven growth
• Significant & sustained antitumor activity observed with EPI-7386 & Combo groupo Enzalutamide tumors escape after
day 24 and become resistant
• Compared to ENZ, EPI-7386 exhibits no signs of resistance or loss of activity through day 52
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EPI-7386 Exhibits Better Anti-Tumor Response vs. ENZ in an ENZ-Partial Resistant VCaP Xenograft Model
-100
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om b
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Enzalutamide - 15 mg/kg- PO qd
Combo Enza - 15 mg/kg / EPI-7386 - 60/30 mg/kgEPI-7386 - 30 mg/kg- PO qd
EPI-7386 Exhibited Improved Individual Anti-Tumor Responses vs. ENZ in a VCaP Xenograft Study on Day 41
The Combo demonstrates a homogeneous tumor response èAdvantage of targeting the AR through two mechanisms
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Arm Progressive Disease (PD)
Stable Disease (SD)
Partial Response (PR)
Complete Response (CR)
ENZ (15 mpk) 4 (57%) 3 (43%) 0 (0%) 0 (0%)
EPI-7386 (30 mpk) 1 (14%) 5 (71%) 0 (0%) 1 (14%)
COMBO (ENZ+EPI-7386) 0 (0%) 1 (20%) 4 (80%) 0 (0%)
Clinical Development Strategy
• Phase I dose escalation trial in patients progressing on current anti-androgens
• Detailed biological characterization of individual patient tumors
• Dose escalation with real-time dose/PK/tumor biological effect correlations with clinical efficacy/tolerability
• Opportunity for seamless Phase I/extension/Phase II clinical trialso Possibility exists for accelerated registration/approval strategies
• IND filing and clinical trial initiation anticipated Q1 2020
• Opportunity for early Phase I combination trial with anti-androgens
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Initial mCRPC Market Opportunity for EPI-7386
Initial Indication: For the treatment of patients with mCRPC progressing on second generation antiandrogens.
221. Eligible patients are estimated as the yearly mortality incidence due to prostate cancer.2. American Cancer Society Cancer Statistics, 2019; Ferlay, J. et al. Cancer Statistics, European Journal of Cancer, 2018.
Territory mCRPC Eligible Patients per Year 1,2
Monthly Price3
Months / Patient4
Total Market Opportunity
US 31,620 $7800 6 months $1.5B
EU28 81,540 $3700 6 months $1.8B
US+EU28 113,160 $3.3B
3. Evaluate Pharma, 2018; 4. Estimate from Medivation 1Q2016 Quarterly Conference Call, 2016.
EPI-7386 Market Share25% 50% 75%
Net Sales (US + EU28) $800M $1.6B $2.4B
• Market opportunity for EPI-7386 in combination with second generation antiandrogens in earlier CRPC or hormone-sensitive prostate cancer patients is several fold larger than this initial mCRPC market
Financial Position & Capitalization (March 31, 2019)
Nasdaq: EPIX ; TSXV: EPI-VCash $8.6M
Debt Principal $4.6M
Shares ~8.0M- I/O shares and prefunded warrants
Warrants ~500k @ $35.36
Stock Options ~1.1M @ $4.59
Top Shareholders Blackstone Group LP., Omega Fund Management LLC., BVF Inc., Eventide Asset Management LLC.
Covering Analysts David Martin, Bloom Burton; Joe Pantginis, HCW
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STATUS SPECIFICS
Select final Aniten molecules for selectivity and xenograft preclinical studies
Medical conference presentation(s) of the initial preclinical findings of Aniten molecules
IND candidate selection and initiation of IND-enabling studies
Medical conference presentation of the preclinical findings of Aniten molecules in antiandrogen-resistant prostate models and in combination with antiandrogens
Q1 IND filing of the next-generation Aniten
Q1 First patient dosed in phase 1 mCRPC study with next-generation Aniten
ESSA Upcoming Milestones
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