Slide 1: Final Results for the year ended 31 March 2018
EVGEN PHARMA PLC Final Results for the year ended 31 March 2018 Investor Presentation Dr Stephen Franklin (CEO) Richard Moulson (CFO) June 2018
Slide 2: Disclaimer
Disclaimer This document has been prepared by, and is the sole responsibility of Evgen Pharma plc (the "Company” or “Evgen”) which trades on the AIM market of the London Stock Exchange under ticker EVG. By attending this presentation and/or reviewing the slides, you agree to be bound by the followin
Slide 3: Full year highlights
Full year highlights § Interim data released from ongoing STEM Phase IIa clinical study in breast cancer § Eleven new sites opened for STEM trial and 44 patients recruited to date § Two new sites opened for SAS trial and 65 patients recruited to date § Launch of Scientific and Medical Advisory Board
Slide 4: Company summary
Company summary § Clinical stage drug development company with a new class of pharmaceuticals § Based in Cheshire (UK) and listed on AIM (LSE: EVG) § Focused on the development of well-tolerated, stable, sulforaphane-based compounds that: Ø inhibit the STAT3 pathway – a target for reducing cancer pr
Slide 5: Sulforaphane modulates STAT3 and Nrf2 presenting opportunities in oncology and neurology
Sulforaphane modulates STAT3 and Nrf2 presenting opportunities in both oncology and neurology Improving outcomes for Improving outcomes for patients with patients becoming resistant neurodegenerative conditions to cancer therapies References: Sulforaphane as a potential protective phytochemical agai
Slide 6: Pipeline
Pipeline Drug Indication Preclinical Phase I Phase IIa Phase IIb Phase III (MoA) SFX-01 Subarachnoid Haemorrhage (Nrf2) SFX-01 Metastatic Breast Cancer (ER+) (STAT3) SFX-01 Investigator-Initiated Clinical Studies† e.g. Triple Negative Breast Cancer, Ischaemic stroke § Potential for different formula
Slide 7: Growth in sulforaphane publications and strong academic collaborations
Growth in sulforaphane publications and strong academic collaborations support the scientific fundamentals Scientific publications on "sulforaphane" (Source: Pubmed) 200 180 New sulforaphane analogues Acute Lymphoblastic 160 Leukemia 140 Osteoporosis 120 100 80 60 Chemical proteomics / MoA 40 Ischae
Slide 8: SFX-01 in ER+ Metastatic Breast Cancer
SFX-01 in ER+ (Estrogen-Receptor Positive) Metastatic Breast Cancer 6
Slide 9: ER+ metastatic breast cancer
ER+ metastatic breast cancer § ER+ breast cancer is the most prevalent breast cancer sub-type § Metastatic breast cancer (also known as “Advanced” or “Stage 4”) means that the cancer has spread to other parts of the body § 5-year survival rates are 22%1 § First-line hormone therapy can provide c.15
Slide 10: Market landscape in ER+ metastatic breast cancer
Market landscape in ER+ metastatic breast cancer § Incidence of ER+ metastatic breast cancer is approximately 130,0001 in US and Europe § CDK4/6 inhibitors are now first line treatment, in combination with hormone therapy § Pfizer (Ibrance®/palbociclib), Novartis (Kisqali®/ribociclib) and Eli Lilly
Slide 11: SFX-01 presents a unique mechanism of action in the metastatic breast cancer landscape
SFX-01 presents a unique mechanism of action in the metastatic breast cancer therapy landscape Estradiol PI3K Aromatase inhibitors mTOR inhibitors AKT Anastrazole, Letrozole, Everolimus Exemestane ER modulators mTOR SFX-01 Tamoxifen, Fulvestrant ER CDK4/6 inhibitors STAT3 Palbociclib, Ribociclib Cyc
Slide 12: Entry point: the potential to change the standard of care in second-line therapy
Entry point: the potential to change the standard of care in second-line therapy First-line therapy Second-line therapy Aromatase Inhibitors (AI)1 Fulvestrant/Exemestane Chemotherapy CDK4/6i2 Everolimus Median PFS c.15 months for AI, Median PFS 3.7-6.5 months for Fulvestrant extended to c.25 months
Slide 13: SFX-01 targets cancer stem cells, deactivates STAT3 and reduces metastases
SFX-01 targets cancer stem cells, deactivates STAT3 and reduces metastases A C B Li et al (2010) were the first to observe that sulforaphane reduces the size and number of primary mammospheres in human breast cancer cells (A); a property of cancer stem cells (CSCs) In ER+ PDX tumours, SFX-01 reduces
Slide 14: Current clinical progress
Current clinical progress § STEM: SFX-01 Treatment and Evaluation in patients with Metastatic breast cancer § A European, multi-centre, Phase II trial on 60 patients evaluating SFX-01 as an adjunct to failing hormone therapy (i.e. the “salvage” setting) § Hormone resistant patients: tamoxifen, aroma
Slide 15: STEM Interim Update (June 2018)
STEM Interim Update (June 2018) § SFX-01 is proving to be well tolerated with no safety concerns arising § SFX-01 shows encouraging early signs of anti-tumour activity: - Four patients had their disease stabilised (that is, having joined the trial with progressive disease their tumours stopped progr
Slide 16: A clinical pathway for SFX-01 as a potential second line therapy post CDK4/6i
A clinical pathway for SFX-01 as a potential second line therapy post CDK4/6i Phase II Phase IIb/III SFX-01 (300mg BID) + Fulv/Exem (20 patients) SFX-01 + Fulv/Exem (100+ patients) 2nd line ER+ mBC post CDK4/6i 2nd Line ER+ mBC post CDK4/6i Final Analysis Final analysis SFX-01 (300mg QD) + Fulv/Exem
Slide 17: Commercial opportunity and monetisation
Commercial opportunity and monetisation § Substantial market opportunity – CDK4/6i sales projected to reach c.$9bn by 2021e1 § Potential to partner and/or co-develop SFX-01 as second-line therapy to CDK4/6i § Up-front payment potential of c.$50m2 (although some deals e.g. AstraZeneca/Innate up-front
Slide 18: SFX-01 in Subarachnoid Haemorrhage
SFX-01 in Subarachnoid Haemorrhage 16
Slide 19: Subarachnoid haemorrhage (SAH)
Subarachnoid haemorrhage (SAH) § Defined by bleeding in the outer layers of the brain due to a ruptured brain aneurysm § 40% of patients die within 30 days and for the survivors c.50% will have long-term cognitive impairment § A Delayed Cerebral Ischaemia (DCI) occurs days after the SAH and, at that
Slide 20: SAH market landscape
SAH market landscape § Annual incidence of 9 per 100,0001 equating to c.45,000 in the EU1 and c.30,000 in US2 § Current standard of care, nimodipine, reduces calcium-dependent smooth muscle contraction § Nimodipine side-effects include unusually fast or slow heart beats and systemic hypotension is a
Slide 21: In experimental SAH, sulforaphane upregulates Nrf2, reduces apoptosis
In experimental SAH, sulforaphane upregulates Nrf2, reduces apoptosis and ameliorates motor deficits A B “In the SUL [sulforaphane]- treated group, early brain damage such as brain edema, blood–brain barrier (BBB) impairment, cortical apoptosis, and motor deficits was significantly ameliorated compa
Slide 22: Sulforaphane reduces delayed cerebral ischaemia and improves behavioural scores
Furthermore, sulforaphane reduces the delayed cerebral ischaemia and improves behavioural scores A B “SFN [sulforaphane] has a therapeutic benefit in post- SAH, and this may be due to elevated Nrf2-ARE pathway activity and inhibition of SFN SAH SAH+SFN cerebral vascular Basilar arteries proinflammat
Slide 23: Current clinical progress
Current clinical progress § SAS: SFX-01 After Subarachnoid Haemorrhage – a Phase II, double-blind, placebo-controlled trial on 90 patients (45 in test and placebo arm respectively) § Administered alongside the calcium channel antagonist, nimodipine § Primary Endpoints: improved blood flow (ultrasoun
Slide 24: The next clinical trial is a pivotal Phase III
The next clinical trial is a pivotal Phase III potentially leading to registration in the US and EU Phase III SFX-01 + nimodipine 175+ patients Primary Futility analysis Final Analysis Analysis Placebo + nimodipine 175+ patients 30 month trial Futility analysis at mid-point New sachet SFX-01 formula
Slide 25: Commercial opportunity and monetisation
Commercial opportunity and monetisation § Estimated peak sales of $500m+ (c.f. $1.7bn for EG19621) as SAH orphan drug § Partner and/or co-develop post-Phase IIb (2019) to fund pivotal Phase III Ø Up-front payment potential post-Phase IIb of >$70m2 and post-Phase III of >$150m2 Ø Royalty rates estima
Slide 26: Financial Results
FINANCIAL RESULTS for the year ended 31 March 2018 24
Slide 27: Financial Highlights
Financial Highlights § Total comprehensive loss of £2.6m (2017: £3.1m) § Net cash outflow (before equity raise) of £2.3m (2017: £3.3m) § Net outflow after fundraise £0.2m (2017: 3.3m) § Cash and short term investments and cash on deposit at 31 March 2018 of £3.6m (31 March 2017: £3.9m) § Operating e
Slide 28: Financial Summary
Financial Summary (£’000) Y/ended 31 March Y/ended 31 March 2018 2017 Operating expenses (2,915) (3,449) Share based compensation (111) (209) Total operating expenses (3,026) (3,658) Finance income/(expense) (net) - 14 Tax credit 443 576 Loss for the period (2,583) (3,068) Cash used in operations (2
Slide 29: Summary
Summary § Evgen is building a stabilised sulforaphane platform (Sulforadex®) with multiple commercialisation routes § Lead product, SFX-01, is in two Phase II trials (ER+ metastatic breast cancer and subarachnoid haemorrhage), with read-outs around the end of 2018 § To date, SFX-01 is well tolerated
Slide 30: Evgen Pharma plc
Evgen Pharma plc Correspondence address: The Colony Altrincham Road Wilmslow Cheshire SK9 4LY Registered office: Liverpool Science Park IC2 146 Brownlow Hill Liverpool L3 5RF www.evgen.com 28
Slide 31: Appendices
APPENDICES 29
Slide 32: Board of Directors
Board of Directors Barry Clare, Chairman Dr Stephen Franklin, Richard Moulson, CFO Dr Marc d’Abbadie, NED Dr Sue Foden, NED Dr Alan Barge, NED Former main Board CEO Founder of Evgen Qualified chartered Investor Director at NED and Chair of the Former CMO of ASLAN member of Boots Pharma and former CE
Slide 33: Sulforaphane inhibits breast cancer stem cells (publication)
NIH Public Access Published in final edited form as: NIH-PA Author Clin Cancer Res. 2010 May 1; 16(9): 2580–2590. doi:10.1158/1078-0432.CCR-09-2937. Author Manuscript Clin Cancer Res. Author manuscript; available in PMC 2011 May 1. Published in final edited form as: Sulforaphane, a Dietary Component
Slide 34: Metastatic Breast Cancer
mões1, Denis Alferez1, Rachel Eyre1, Kath Spence1, Angelica Santiago-Gomez1, Iris Tanaka1, Francesca Chemi1, Bertram Kohler1, Andy Sims2, Elisabetta Marangoni3, Julia Gee4, east Cancer David Howat5, Sacha Howell1,6, Robert Clarke1 AXIN2 Figure 4: AXIN2, LEF1 and DKK1 genes in 164 primary tumours ACT
Slide 35: Subarachnoid Heamorrhage
Subarachnoid Heamorrhage 33
Slide 36: Role of the Nrf2-ARE Pathway in Early Brain Injury
The nuclear factor erythroid 2-related factor 2 and anti- subarachnoid hemorrhage (SAH; oxidant-response element (Nrf2-ARE) pathway is a key Treatment of EBI is considered regulator for modulating inflammation and oxidative management of patients surviving Journalwhich damage, of Neuroscience are in
Slide 37: IP Schedule (April 2018): SFX-01 Composition and Process
IP Schedule (April 2018): SFX-01 Composition and Process Country Applicant Client Ref. Application No Application Date Grant No Grant Date Status Australia PharmAgra Stabilized Sulforaphane AU2008209543 23/Jan/2008 AU2008209543 26/Jun/2014 Granted Canada PharmAgra Stabilized Sulforaphane CA2,672,971
Slide 38: IP Schedule (April 2018): Novel sulforaphane analogues
IP Schedule (April 2018): Novel sulforaphane analogues Country Applicant Client Ref. Application No Application Date Grant No Grant Date Status Sulforaphane Australia CSIC and University of Seville AU2013229355 06/Mar/2013 AU2013229355 08/Jun/2017 Granted Derivatives Sulforaphane Canada CSIC and Uni
Slide 39: Development pipeline – Metastatic ER+ Breast Cancer
Development pipeline – Metastatic ER+ Breast Cancer Company Drug/Combination Drug Target Phase I Phase II Phase III GDC9545 +/- Palbo SERD GDC-0077 +/- Let/Fulv/Palbo PIK3CA H3B6545 SERCA Balixafortide + Eribulin CXCR4 Seribantumab + Fulv HER3 mAB Abiraterone + Exe Antiandrogen MLN0128 + Fulv TORC1/
Slide 40: Development pipeline – NRF2
Development pipeline – NRF2 Company Drug Indication Phase I Phase II Phase III CXA-10 Focal Segmental Glomerulosclerosis CXA-10 Pulmonary Arterial Hypertension Omaveloxolone Friedrich’s Ataxia SFX-01 Subarachnoid haemorrhage Bardoxolone Pulmonary Arterial methyl Hypertension Bardoxolone Alport Syndr
Slide 41: Development pipeline – STAT-3
Development pipeline – STAT-3 Company Drug Indication(s) Phase I Phase II Phase III AZD9150 DLBCL C188-9 Multiple solid tumours IMX-110 Multiple solid tumours SFX-01 Breast cancer 39