Hexima Ltd · ASX:HXL
Hexima — Shareholder Meeting (November 2018)
37 slides from Hexima's shareholder meeting presentation, Nov 20, 2018
Slide 1: Annual General Meeting 2018
Annual General Meeting 2018 KPMG Level 36, 727 Collins St Melbourne Tuesday 20 November 2018 11.00am
Slide 2: Forward looking statements
Forward looking statements Certain statements in this presentation relate to the future, including forward looking statements relating to Hexima’s future expectations, beliefs, goals, plans, prospects, financial position and strategy. These forward looking statements involve known and unknown risks,
Slide 3: AGM 2018 – CEO
AGM 2018 Dr Nicole van der Weerden – Chief Executive Officer
Slide 4: Key achievements for 2018
Key achievements for 2018 ØFully enroled a 48-patient phase I/IIa clinical trial for HXP124 as a treatment for onychomycosis • Part 1 completed – results announced October 2018 — No treatment-related adverse events, HXP124 substantially reduced the area of infected nail • Part 2 data available Janua
Slide 5: Key achievements for 2018
Key achievements for 2018 ØDemonstrated that HXP124 and other proprietary defensins are active against the new superbug, Candida auris. ØPartner in the $5 million Industry Transformation Research Hub for Medicinal Agriculture grant to La Trobe University • Provides funding for screening Hexima’s nat
Slide 6: HXP124
HXP124 ØHexima is developing a novel therapeutic (HXP124) for the treatment of fungal nail infections (onychomycosis). ØHXP124 has the potential to be superior to current therapies. • Potent, broad-spectrum antifungal molecule —Member of the Plant Defensin class of molecules • Readily penetrates nai
Slide 7: Global onychomycosis market
Global onychomycosis market ØUS$3.06 billion in 2015 and projected to reach US$4.7 billion by 2021. ØMajor deficiencies in current therapies. • Poor efficacy rates • Long treatment times • Oral therapies can be toxic • Expensive —Estimated that between 50 and 90% of individuals with fungal nail infe
Slide 8: Global onychomycosis products
Global onychomycosis products Approved Topical Therapies for Onychomycosis Loceryl® Penlac®/Rejuvenail® KERYDIN® Jublia® HXP124 (5% Amorolfine) (8% Ciclopirox) (5% Tavaborole) (10% Efinaconazole) 48 week treatment 48 week treatment 48 week treatment 48 week treatment 6 week treatment* 1-2% complete
Slide 9: HXP124 kills fungi better than current treatments for nail infections
HXP124 kills fungi better than current treatments for nail infections 100% 90% 80% ØKills fungal cells within 30 min. 70% Percent living cells • Inefficient killing by the drugs 60% currently on the market means the 50% fungus is likely to become 40% resistant during long treatment 30% times and may
Slide 10: HXP124 is as effective as efinaconazole in an infected nail model
HXP124 is as effective as efinaconazole in an infected nail model ØMedPharm (UK) tested HXP124 in 2. HXP124 applied topically an “infected nail model” to provide additional confidence that HXP124 passes through nails and kills fungal nail adapter cells. human nail • Industry standard assay. 1. funga
Slide 11: HXP124 is as effective as efinaconazole in an infected nail model
HXP124 is as effective as efinaconazole in an infected nail model ØHXP124 killed over 95% of fungal cells within 7 days and was as efficient as Jublia® in this model. 40% (% relative to infected control) 2. HXP124 a pplied topically ATP levels* 30% nail adapter human nail 20% 1. fungal infection dev
Slide 12: Phase I/IIa clinical trial fully enroled
Phase I/IIa clinical trial fully enroled ØRandomised, Double-Blind, Vehicle-Controlled Multiple Ascending Dose Study in Healthy Volunteers with Mild to Moderate Onychomycosis. • Patients treat nails daily with HXP124 (or placebo) for 42 days • Follow-up at 1, 2, 6, 9 and 12 weeks ØPart 1 data announ
Slide 13: Clinical trial design
Clinical trial design Cohort 3 Cohort 4 7 days HXP124 2% Highest safe dose N=6 patients N=30 patients (ra ndomised 2:1) (randomised 3:1) 12-week follow up 12-week follow up 52-week follow up Cohort 2 7 days HXP124 1% N=6 patients (ra ndomised 2:1) Cohort 1 HXP124 0.5% N=6 patients ra ndomised 2 (dru
Slide 14: Phase I/IIa clinical trial endpoints
Phase I/IIa clinical trial endpoints ØThe trial was designed to address 3 questions: Is HXP124: 1. safe when applied topically? 2. effective in treating onychomycosis? 3. likely to be superior to current best Day 0 Day 90 therapies for onychomycosis? Infected area ØPrimary endpoint Clear nail growth
Slide 15: Phase I/IIa - Part 1 results
Phase I/IIa - Part 1 results Ø Follow-up period for Part 1 was 12 weeks. • Due to the slow rate of toenail growth, only partial clearing of the infected nail area could be expected over this time. Ø Part 1 was not intended to include sufficient patients to provide statistically-significant results.
Slide 16: Q1. Is HXP124 safe when applied topically?
Q1. Is HXP124 safe when applied topically? ØHXP124 is safe when applied topically over the period of the study. • No drug-related adverse events. • HXP124 did not cause pain or irritation. • HXP124 was not detected in the bloodstream.
Slide 17: Q2. Is HXP124 an effective treatment for onychomycosis?
Q2. Is HXP124 an effective treatment for onychomycosis? ØThe data indicate that HXP124 is an Increase in healthy nail area (%) over time as a percentage of initial infected area effective therapy for onychomycosis. 50% Ø12 of 13 treated nails showed a clear 45% Increase in healthy nail area (%) y =
Slide 18: Q3. Is HXP124 likely to be superior to current therapies?
Q3. Is HXP124 likely to be superior to current therapies? Ø31% of HXP124-treated patients Clinical efficacy (<10% infected nail area) 35% achieved clinical efficacy Pa ti ents with <10% i nfected a rea (%) 30% (defined as <10% of the nail 25% 20% area infected) within 12 weeks. 15% • It takes 48-wee
Slide 19: Q3. Is HXP124 likely to be superior to current therapies?
Q3. Is HXP124 likely to be superior to current therapies? ØRate of clear nail growth suggests Clear nail growth (mm) over time a path of superior efficacy to 2.50 y = 0.0277x efinaconazole (Jublia®). 2.00 Cl ea r nail growth (mm) • HXP124-treated patients averaged 1.50 2.4 mm of clear nail growth in
Slide 20: Selected images of HXP124-treated patients
Selected images of HXP124-treated patients Baseline Week 12 Baseline Week 12 Baseline Week 12 Baseline Week 12
Slide 21: Recruitment strategy
Recruitment strategy ØFacebook recruitment very effective. • 1.7 million impressions • 20,000 link clicks • 3,000 leads passed pre-screen ØHexima achieved recruitment rate of 10 patients/month. • Typical recruitment rates for onychomycosis trials are 3.5 patients/month ØSignificant learnings for pha
Slide 22: Decrease in cost of production
Decrease in cost of production ØHXP124 is produced in an off-patent yeast expression system. ØConstruct optimisation during 2018 achieved a >4.5-fold increase in yield of HXP124. • Substantial reduction in cost of production • Strain ready for transfer to Good Manufacture Practice (GMP)-accredited m
Slide 23: Patent portfolio
Patent portfolio ØUnited States patent for use of HXP124 to treat fungal nail infections has been allowed. • Expiry 2035 (17 years patent life remaining) • Patent pending in several other jurisdictions including —Australia, Brazil, Canada, China, Europe, India, Japan, Malaysia, Mexico, New Zealand,
Slide 24: HXP124 commercialisation plan
HXP124 commercialisation plan ØProof-of-concept clinical efficacy data is a major value creation step during drug development. ØHexima is engaged in discussions with several pharmaceutical companies regarding licencing of HXP124. • USA and Japan are highest priority • Europe, China and Australia add
Slide 25: Business development expertise
Business development expertise Mr Scott Robertson Dr John Bedbrook Dr Michael Rabson Dr Kevin Judice • Former Business • Experienced biotechnology • Lawyer with >20 years of • Experienced drug Development Director for founder and chief executive experience providing advice development entrepreneur.
Slide 26: Development timeline for HXP124
Development timeline for HXP124 Launch Pre-clinical Phase I Phase II Phase III BLA 2019 2020 2021 2022 2023 2024 2023 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 pre-IND meeting with FDA IND submission phase II/III clinical trial Manufacturing scale-up BLA submission Mark
Slide 27: Capital raising 2019
Capital raising 2019 ØSeeking $25 million to fund clinical and non-clinical development through to a BLA. ØKey dates • Dec 2018 – Appoint US investment bank • Jan 2019 –12-week clinical data from Part 2 available • Apr 2019 – pre-IND meeting with FDA • May-Jun 2019 – close funding round 27
Slide 28: Focus for 2019
Focus for 2019 Ø Business development activities for HXP124 • Licencing discussions with preferred partners Ø Raise additional capital ($25 million) to progress development of HXP124 Ø Pre-Investigational New Drug (IND) meeting with FDA to discuss key requirements for marketing approval • Design of
Slide 29: AGM 2018 – Chief Science Officer
AGM 2018 Prof Marilyn Anderson – Chief Science Officer
Slide 30: Hexima's defensin platform is applicable to other fungal diseases
Hexima’s defensin platform is applicable to other fungal diseases ØVulvovaginal candidiasis (thrush) • HXP124 and other Hexima lead candidates rapidly kill Candida spp • HXP124 is stabile in a topical formulation which is a significant advantage for this application ØSystemic candidiasis • SIEF STEM
Slide 31: Defensins are active in a rat model of vaginal thrush
Defensins are active in a rat model of vaginal thrush ØTopical treatment with defensin reduced the number of C. albicans cells in vaginal fluid by 70-87% within 3 days • Less effective than miconazole after 5 days —BUT - Miconazole is fungistatic and yeast cells re-emerge after 9-12 days • Need to a
Slide 32: Candida auris is an emerging pathogen
Candida auris is an emerging pathogen ØCauses serious infections • 30% mortality rate ØOften resistant to current drugs • 90% of strains resistant to fluconazole • 50% of strains resisant to multiple classes of antifungals • ~5% resistant to all current antifungal drugs ØSpreads through hospitals an
Slide 33: HXP124 has excellent activity against the emerging pathogen Candida auris
HXP124 has excellent activity against the emerging pathogen Candida auris Ø8-fold lower MIC against C. auris relative to C. albicans 0.3 0.25 Abs595nm (fungal growth) 0.2 0.15 Candida auris 1 Candida auris 2 0.1 Candida auris 3 0.05 Candida albicans 0 0 10 20 30 40 50 C. auris #1 has increased HXP12
Slide 34: C. albicans biofilm development
C. albicans biofilm development ØCandida biofilms on medical device implants are a major cause of systemic infections • Help protect the fungus from antifungal drugs ØHexima’s defensins kill established Candida biofilms SEM of C. albicans in a biofilm. Growth a nd development of a C. albicans ba s e
Slide 35: Defensins enhance the activity of 'gold standard' antifungal drugs
Defensins enhance the activity of ‘gold standard’ antifungal drugs 120% ØCaspofungin is a best-in-class therapy for systemic fungal infections 100% Relative living biomass 80% ØDefensins enhance the activity of 60% caspofungin against C. albicans biofilms 40% 20% 0% 35
Slide 36: Plant defensins and plant extracts are active against Malessezia
Plant defensins and plant extracts are active against Malessezia ØMalessezia is a yeast (fungus) that Inhibition of the yeast Malessezia by plant causes dandruff defensins 0.04 • Hexima proprietary plant defensins OD595nm (fungal growth) 0.035 and plant extracts kill Malessezia 0.03 Extract 1 spp. 0
Slide 37: Pioneer project and natural products library
Pioneer project and natural products library ØA natural products library of >10,000 diverse plant samples and 57,500 bacteria has been collected. ØHexima is screening this library for novel antimicrobial molecules • Funding received through La Trobe ARC ITRH for Medicinal Plants. ØNovel insect-activ