shareholder update q1 2017 - hexima...• launched in 2014 by valeant pharmaceuticals • us$330...
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Shareholder Update Q1 2017
Forward looking statements
Certain statements in this presentation relate to the future, including forward looking statements relating toHexima’s future expectations, beliefs, goals, plans, prospects, financial position and strategy. These forwardlooking statements involve known and unknown risks, uncertainties, assumptions and other importantfactors that could cause the actual results, performance or achievements of Hexima to be materiallydifferent from future results, performance or achievements expressed or implied by such statements.Neither Hexima nor any other person gives any representation, assurance or guarantee that the occurrenceexpressed or implied in any forward looking statements in this document will actually occur and you arecautioned not to place undue reliance on such forward looking statements.
Subject to any continuing obligations under applicable law, Hexima disclaims any obligation or undertakingto disseminate any updates or revisions to any forward looking statements in this document to reflect anychange in expectations in relation thereto or any change in events, conditions or circumstances on whichany such statement is based.
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
• Rapidly kills the fungus
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Recent progress
CY 2017 CY 2018
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
Pre-clinical animal toxicology studies
Phase I/IIa human clinical safety and efficacy studies
United States Food and Drug Administration Investigational New Drug (IND) application
Business Development
Proof of concept studies for new fungal disease indications
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Complete
Pre-clinical animal toxicology studies are complete and preparation is underway for clinical trials.
Recent progress - HXP124 was not toxic in a dermal irritation minipig study
42-day GLP repeat-dose dermal toxicity study in minipigs• No Observable Adverse Effect Level (NOAEL) of 50 mg/kg (highest dose)
• Very low absorption through the skin
• No systemic toxicity effects at the highest dose (50 mg/kg)
• Very slight dermal irritation at dose site – also present in the placebo group
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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 treatment1-2% complete cure rate
Penlac®/Rejuvenail®(8% Ciclopirox)
48 week treatment5-9% complete cure rate
KERYDIN®(5% Tavaborole)
48 week treatment>$8,000
6-9% complete cure rate
Jublia®(10% Efinaconazole)48 week treatment
>$8,00015-18% 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: 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 mayregrow 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 HXP124
We cultured C. albicans in the presence of HXP124 and efinaconazole to examine how quickly resistance could develop.
C. albicans did 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.
10*MIC = Minimal Inhibitory Concentration (lowest concentration that inhibits >90% of growth)
HXP124 is likely to penetrate nails faster and more efficiently than current 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.
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)
* Data for competitor actives obtained from literature
HXP124 accumulates in the nail plate
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0
5
10
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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 at 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
14*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
)
HXP124 killed over 95% of fungal cells within 7 days and was as efficient as Jublia®
in this model.
nail adapterhuman nail
1. fungal infection developed on underside of nail
2. HXP124 applied topically
3. Viability of fungal cells measured
Produced in off-patent yeast system.Two-step purification process.
• Highly pure protein (>99.99%)
GMP* manufacture completed by LuinaBio under contract.
HXP124 is stable in formulation for >4 weeks at 40 degrees Celsius.• No loss of activity• No degradation/modification or aggregation
—measured by 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)• There were no local signs of irritation at the dose site. However, the proliferation response of lymph node cells
indicates that HXP124 may be a sensitiser. This is inconsistent with the results of the Buehler sensitization assay and may require follow-up toxicology studies.
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HXP124 was not toxic in a dermal irritation minipig study
42-day GLP repeat-dose dermal toxicity study in minipigs• No Observable Adverse Effect Level (NOAEL) of 50 mg/kg (highest dose)
• Very low absorption through the skin
• No systemic toxicity effects at the highest dose (50 mg/kg)
• Very slight dermal irritation at dose site – also present in the placebo group
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HXP124 development timetable
CY 2017 CY 2018
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
Pre-clinical animal toxicology studies
Phase I/IIa human clinical safety and efficacy studies
United States Food and Drug Administration Investigational New Drug (IND) application
Business Development
Proof of concept studies for new fungal disease indications
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Complete
Pre-clinical animal toxicology studies are complete and preparation is underway for clinical trials.
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 mid 2018.
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Licencing HXP124 in Japan
Hexima intends to seek to licence HXP124 for the Japan market in 2017, prior to obtaining results from phase I/IIa clinical trials. • Hexima believes that the large, proven Japanese market for onychomycosis
makes it a key target market for HXP124. • Hexima believes that a co-development process with a Japanese partner is the
most effective way to obtain approval for HXP124 in the Japanese market.
Hexima has spoken with several Japanese pharmaceutical companies and is currently in mature discussions with a prospective partner. • there is no assurance that these discussions will result in any legally binding
arrangement between the parties.
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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• Pursuant with our strategy to provide proof-of-concept data for additional indications, HXP124 will be
tested in a mouse model of vulvovaginal candidiasis
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 clinical trials to be initiated in H2, 2017.
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Financial position
Rights issue to raise ~$4 million completed in March.
Cash and receivables of ~$6 million as at 31 May 2017.
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Balance Sheet (as at 31 May 2017)Please note: these are unaudited figures.CURRENT ASSETSCash and cash equivalents $4,622,927Receivables $1,364,879TOTAL CURRENT ASSETS $5,987,806
NON-CURRENT ASSETSInvestments $22Plant and equipment $1,800,265TOTAL NON-CURRENT ASSETS $1,800,287
TOTAL ASSETS $7,788,093
CURRENT LIABILITIESTrade and other payables $1,784,784TOTAL CURRENT LIABILITIES $1,784,784
NON-CURRENT LIABILITIESEmployee benefits $81,910TOTAL CURRENT LIABILITIES $81,910
TOTAL LIABILITIES $1,866,694
NET ASSETS $5,921,400
EQUITYShare capital $61,556,496Reserves $1,234,828Accumulated losses $-56,295,327TOTAL EQUITY $5,921,400
Share trading
Some shareholders have indicated that they wish to buy or sell Hexima Shares. Hexima has been contacted by two shareholders, including an entity
controlled by G.F. Dan O’Brien, willing to purchase Hexima shares at a price of $0.08.Hexima has appointed Bell Potter to co-ordinate a secondary sale
process of Hexima Shares.Any parties wishing to buy or sell shares should contact Bell Potter.
• Athol White (Ph. 03 9235 1781; email [email protected] )• Nicole Gregory (Ph. 03 9235 1727; email [email protected] )
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