shareholder update q3 2016 - hexima€¦ · certain statements in this presentation relate to the...
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Shareholder Update Q3 2016
Forward looking statements
Certain statements in this presentation relate to the future, including forward looking statements relatingto Hexima’s future expectations, beliefs, goals, plans, prospects, financial position and strategy. Theseforward looking statements involve known and unknown risks, uncertainties, assumptions and otherimportant factors that could cause the actual results, performance or achievements of Hexima to bematerially different from future results, performance or achievements expressed or implied by suchstatements. Neither Hexima nor any other person gives any representation, assurance or guarantee thatthe occurrence expressed or implied in any forward looking statements in this document will actuallyoccur and you are cautioned not to place undue reliance on such forward looking statements.
Subject to any continuing obligations under applicable law, Hexima disclaims any obligation orundertaking to disseminate any updates or revisions to any forward looking statements in this documentto reflect any change in expectations in relation thereto or any change in events, conditions orcircumstances on which any such statement is based.
Hexima Limited
Research labs located in the La Trobe Institute for Molecular Science (LIMS)• 28 research scientists• 5 administration staff• 2 PhD students
Greenhouse facilities located at the La Trobe R&D Park• PC2 accredited facility• Nine individual compartments
—several compartments leased to third parties• Suitable for transgenic and non-transgenic plants
Hexima’s technology platforms
Antifungal• Human applications – fungal nail infections (onychomycosis)• Plant applications – transgenic crops, fungicides for seed coatings and crop sprays
Income generating programs• Insecticidal gene discovery program – crop protection• Leasing of greenhouse facilities
Other applications of Hexima technology• MGEV – production of multiple proteins in plants• Cyclic peptides – ability to manufacture pharmaceuticals in plants
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Plant antifungal
Hexima has identified several antifungal peptide combinations that provide protection against fungal disease in cotton or corn.
Hexima is looking for a suitable partner to continue development of this technology.
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Control lines Transgenic linesEffect of AFP constructs on disease reduction in corn. Transgenic lines (right) have fungal lesions that are ~70% smaller than those in the control lines (left).
Insecticidal gene discovery program
Collaboration funded by DuPont-Pioneer since 2014 to identify novel insect-active genes.Royalties to Hexima for any commercial outcomes.Timeline for a return from this project is long (>5 years) but project is
cash positive for Hexima in the short term.
In June 2016, Hexima and DuPont-Pioneer announced the discovery of a novel insect-control gene that is active against certain crop-destroying insect pests.
6Image taken from: https://www.pioneer.com/home/site/us/agronomy/crop-management/corn-insect-disease/corn-earworm/
Multi Gene Expression Vehicle (MGEV)
Allows the DNA code for several proteins to be transferred into plants in a single unit.• Reduces the need for additional regulatory
elements• Allows for co-ordinated expression of two
proteins—Same time/same location
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Without MGEV
With MGEV
Promoter PromoterTerminator TerminatorProtein 1 Protein 2
Promoter TerminatorProtein 1 Protein 2
MGEV linker
IP valid until 2027Non-exclusive commercial licence granted to DuPont-Pioneer.
Financial PositionBalance Sheet (as at 30 September 2016)Please note: these are unaudited figures.CURRENT ASSETSCash and cash equivalents $3,875,306Receivables $214,184TOTAL CURRENT ASSETS $4,089,491
NON-CURRENT ASSETSInvestments $22Plant and equipment $1,957,361TOTAL NON-CURRENT ASSETS $1,957,383
TOTAL ASSETS $6,046,873
CURRENT LIABILITIESTrade and other payables $2,477,317TOTAL CURRENT LIABILITIES $2,477,317
NON-CURRENT LIABILITIESEmployee benefits $79,036TOTAL CURRENT LIABILITIES $79,036
TOTAL LIABILITIES $2,556,353
NET ASSETS $3,490,520
EQUITYShare capital $57,659,831Reserves $1,168,094Accumulated losses $-55,337,405TOTAL EQUITY $3,490,520 8
Cash and receivables as at 30 September 2016 of $4.09 million
81,180,469 shares on issue.
HXP124: an onychomycosis therapeutic opportunity
Global onychomycosis market
US$3.06 billion in 2015 and projected to reach US$4.7 billion by 2021. Major 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 infections are not receiving treatment.
Large potential for rapid growth in the market with an effective product.
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Approved Topical Therapies for Onychomycosis
Loceryl®(5% Amorolfine)
48 week treatment~US$160
1-2% complete cure rate
Penlac®/Rejuvenail®(8% Ciclopirox)
48 week treatment~US$830
5-9% complete cure rate
KERYDIN®(5% Tavaborole)
48 week treatment~US$8,400
6-9% complete cure rate
Jublia®(10% Efinaconazole)48 week treatment
~US$8,400 15-18% complete cure rate
Global onychomycosis products
Jublia® is the number 1 selling topical product (by revenue) in the USA• Launched in 2014 by Valeant Pharmaceuticals• US$330 million sales in 2015 • Japanese version of product sold US$190 million in FY 2015 (Clenafin, Kaken Pharmaceuticals)
HXP124
Hexima is developing a novel therapeutic (HXP124) for the treatment of fungal nail infections (onychomycosis).
HXP124 has the potential to be superior to current therapies.• Potent, broad-spectrum antifungal molecule
—Member of the Plant Defensin class of molecules
• Readily penetrates nails (>20% within 72 h)• Rapidly kills the fungus
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Plant defensins
Potent, broad spectrum antifungal agents.• Small peptides• Naturally produced by plants for protection
against fungal diseases• Water soluble• Very stable in formulation• Manufacturable using yeast fermentation• Rapidly purified to achieve quality required
for clinical trials
Hexima has built the world’s leading competency in plant defensins and a broad IP portfolio.• 6 patent families relating to the use of plant defensins to treat human and plant fungal disease.• Patent coverage for plant defensins as a treatment for onychomycosis valid to 2033 (if granted).
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HXP124: a broad-spectrum antifungal defensin
Kills several human fungal pathogens including the yeast Candida and the agents responsible for fungal nail infections.
Very specific for fungal cells. • Not active against mammalian cells• Not active against bacteria
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No treatment Low dose (10 µg/mL)
High dose(50 µg/mL)
Growth of Trichophyton rubrum (causative agent of ~90% of fungal nail infections) in the presence and absence of HXP124.
HXP124 kills fungi more readily than current treatments for nail infections
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Kills fungal cells within 30 min.• Inefficient killing by drugs currently
on the market means the fungus is likely to become resistant during long treatment times and will regrow when treatment is stopped.
Fluorescence Associated Cell Sorting (FACS) of Propidium Iodide stained cells was used to identify living and dead Candida albicans cells after 30 min treatment with antifungal molecules.
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
HXP124 Efinaconazole(Jublia®)
Tavaborole(Kerydin®)
Terbinafine Ciclopirox(Penlac®)
Perc
ent l
ivin
g ce
lls
Fungi do not readily develop resistance to HXP124We cultured C. albicans in the presence of
HXP124 and efinaconazole to examine how quickly resistance could develop.
C. albicans does not become resistant to HXP124 after 15 rounds of selection.• HXP124 has very high kappa (steepness of
killing curve) and rapid cell killing kinetics, both of which are important to prevent the development of resistance.
• C. albicans becomes highly resistant to efinaconazole (Jublia® active ingredient) after <10 rounds of selection.
16*MIC = Minimal Inhibitory Concentration (lowest concentration that inhibits >90% of growth)
0
100
200
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0 5 10 15
Fold
orig
inal
MIC
whe
re g
row
th is
obs
erve
d
Rounds of selection
HXP124 Efinaconazole (Jublia®)
0%
5%
10%
15%
20%
25%
0 5 10 15
Perc
ent t
hrou
gh n
ail
Day
Cumulative nail penetration
HXP124 Tavaborole Ciclopirox Efinaconazole
HXP124 penetrates nails faster and more efficiently than current marketed products
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Topical treatments for fungal nail disease must penetrate human nails to reach the site of infection. An in vitro nail adapter assay can be used
to assess nail penetration. 15%*
3%*
0.06%*
24%
nail adaptercadaver nail or nail clipping
saline-soaked cotton wool
Permeation model based on method developed by Dr Howard Maibach. (UCSF Medial Centre, Hui et al., 2007)
13%
2%0.7%
* Data for competitor actives obtained from literature
HXP124 accumulates in the nail plate
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0
5
10
15
Dose Site Peripheral edgeAmou
nt o
f HXP
124
in d
rill s
ite
(µg)
HXP124 within the nail plate
Dose site
HXP124 accumulates in the nail under the site of application and diffuses sideways to areas that were not dosed.
Nails dosed with HXP124 in nail penetration assays were drilled to collect nail material from the dose site (yellow arrow) and the edge of the nail (white arrow) and the amount of HXP124 present at each site was analysed.
HXP124 is as effective as Jublia®
in an infected nail model
MedPharm (UK) have tested HXP124 in an “infected nail model” to provide additional confidence that HXP124 passes through nails and kills fungal cells.• Industry standard assay.• Nail and fungal growth conditions more
representative of clinical condition.
Jublia® and Penlac® were used as comparator products in this study.• Jublia® is the current industry ‘gold
standard’.
nail adapterhuman nail
1. fungal infection developed on underside of nail
2. HXP124 applied topically
3. Viability of fungal cells measured
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HXP124 is as effective as Jublia®
in an infected nail model
20*ATP levels are used as a measure of cell survival
0%
10%
20%
30%
40%
HXP124 Jublia® Penlac® HXP124 Jublia® Penlac® HXP124 Jublia®
7 days 14 days 21 days
ATP
leve
ls*
(% re
lativ
e to
infe
cted
con
trol
)
Produced in off-patent yeast system.Two-step purification process.
• Highly pure protein (>99.99%)
GMP* manufacture completed by LuinaBiounder contract.
HXP124 is stable in formulation for >4 weeks at 40 degrees Celsius.• No loss of activity• No degradation/modification or aggregation
—mass spec, RP-HPLC, spectroscopy
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500 L fermentor in Pharmasynth’sGMP facility (Brisbane, AUS).
HXP124 can be produced rapidly and economically in Australia
*GMP = Good Manufacturing Practice
HXP124 has a good safety profile in initial preclinical toxicology studies
Bovine corneal opacity and permeability study (assess potential eye irritation in case of accidental exposure)• No increase in opacity or permeability of isolated corneas• HXP124 classified as ‘No Category’ (poses minimal risk to ocular structures)
Human ether-a-go-go related gene (hERG) assay (assess effect on cardiac channels in case of systemic exposure)• No effect on hERG channels at >5000 fold the intended clinical dose
Buehler sensitization assay (guinea pig model to assess potential allergenicity)• No signs of irritation at dose site• No signs of an allergic response
Mouse local lymph node assay (mouse model to assess potential allergenicity)• HXP124 produced a positive result in this assay making it a potential sensitiser
— concentrations that produced a positive result were higher than the intended clinical dose 22
HXP124 development plan
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Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar
ManufactureScale up of manufacture under GMP conditions
Production of material for clinical trials
PreclinicalFormulation
Infected nail modelStability testing
Toxicology/animal safety studiesPreliminary toxicology studies
Minipig dermal toxicity dose range-finding studyMinipig dermal toxicity GLP study
Additional systemic toxicity studies (if required)
Clinical studiesPhase I/IIa multiple-dose safety/efficacy study
Sufficient animal toxicology data to gain ethics approval for PhI/IIa clinical
trials.
2018
Proof that HXP124 can be applied topically and kill fungus growing on the underside of
nails.
Evidence that HXP124 does not irritate pig skin when applied
repeatedly.
First in-human safety data obtained (single dose).
2015
Initial efficacy data and multiple-dose safety
data obtained.
20172016
*activities marked in grey have been completed.
HXP124 commercialisation plan
Proof-of-concept efficacy data is a significant value creation step during drug development.
If positive clinical efficacy data is obtained, Hexima intends to licence HXP124 to a pharmaceutical companie(s) to generate upfront and future milestone payments and licensing revenue.
Proof-of-concept efficacy data is expected to be obtained in early 2018.
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Hexima’s defensin platform is applicable to other fungal diseases
Vulvovaginal 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
Fungal infections of traumatic injuries/wounds• HXP124 and other lead candidates kill non-dermatophyte moulds, the most common
pathogens in fungal infected wounds.
Fungal skin infections and dandruff
Fungal sinusitis
Veterinary applications
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Summary
Hexima has developed a defensin platform applicable to a range of applications.
Hexima is developing HXP124 as a superior therapeutic for onychomycosis.• Better nail penetration.• Rapidly kills fungal cells.• Anticipating shorter treatment regimen.
—4 weeks vs 48 weeks.
Hexima expects to begin clinical trials in H1, 2017.26
