Relif ®

Dr. Denis C. Bauer CEOProf. Dr. Chol Hee Jung CSODr. Andrew Ringsmuth Business Development ManagerDr. Kimberly Wadsworth IP Manager

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fIntroduction

• Currently,1.3 Million people suffer from acute depression.

• Estimated to increase exponentially within 10 years.

• Don Monger : “Depression will be the major impact on modern society”

On the Threshold of Eternity by Vincent Van Gogh

What if depression can be reduced to a

small inconvenience - like headache?

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fOverview

• Drug development Prof. Dr. Chol Hee Jung– Scientific Overview

– Science behind the reliF® approach

• Motivation and Progress – Market analysis

– Financial overview

• IP portfolio

• Pitch

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fSerotonin messaging

• Pre-synaptic neuron : releases serotonin• Post-synaptic neuron : recognizes serotonin with 5-HRR and

relays the signal.• In healthy individuals, about 90% of serotonin released into the

synaptic cleft is re-absorbed into pre-synaptic neurons with only 10% bound to post-synaptic neurons.

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fDepression, treatment, side-effect

• Failure of serotonin messaging is currently regarded as the most likely cause of Depression.

• Traditional treatment blocks serotonin re-absorption (SSRI) increasing the amount of post-synaptic serotonin binding.

• Results in loss of serotonin.

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fSerotonin Messaging by transporting

Jung, C.H., Serotonin messaging mediated by 5-HR-channels not 5-HR-receptor, Nature, 2006, 20, 1159-1165Jung, C.H., Total serotonin concentration unaffected in Depression type I, Nature, 2005, 20, 1159-1165

• No serotonin loss in serotonin messaging• No serotonin loss in serotonin messaging– 10% of serotonin released from pre-synaptic neurons is absorbed into post-

synaptic neurons.

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fAbnormal serotonin-concentration in Depression

Jakobs, D.R., et al., Serotonin concentration involved in depression type I, Science, 2006, 21, 501-509

• Low serotonin concentration in post-synaptic neurons.

Fig3. Measured serotonin concentration in pre- and post-synaptic neurons for time point 5 and 20 in control group and depression (Drc-). The Figure shows that there is no lack of serotonin in the pre- synaptic neurons, yet absorbed serotonin levels in post-synaptic are too low.

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fNormal number of HRCs

Jung, C.H. et al., SSRI induced 5-HR increase only a hack , Nature, 2006, 21, 180-185

Fig2. Flourescence images of pre- and post-synaptic neurons for the control group and depression (Drc-). The images show that the amount of 5-HR channels (red fluorescence) is not reduced in Drc-, yet the absorbed serotonin (green fluorescence) in the post-synaptic neurons is significantly reduced.

Control Drc-

• No observable difference in concentration of HRCs in post-synaptic neurons.

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fCorrelation of Fsr9 with low serotonin

absorption

Fig2. Correlation between over expression of Fsr9 and reduced serotonin intake of post-synaptic neurons in depression (Drc-). Panel A : Fsr9 in Drc- is present in high concentrations very early in the time course. Panel B : The early onset of Fsr9 stops the absorption of serotonin into the post-synaptic neurons, resulting in an overall lower serotonin concentration.

Chen, L.L. et al. ,The role of Fsr9 in Depression Type I , Int J Dev Neurosci, 2007, 22, 180-185

• Fsr9, responsible for the serotonin concentration in post-synaptic neurons.

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fFsr9 blocks 5-HR channels

Fig2. Flourescence images of pre- and post-synaptic neurons in depression (Drc-) for 5-HRC and Fsr9. The images show the co-localization of Fsr9 (green fluorescence) and 5-HRC (blue fluorescence) as yellow fluorescence.

Chen, L.L. et al. , Co-localization of 5-HRC and Fsr9 suggest a new drug target for depression, Neurophysiology, 2007, 20

• Fsr9, adjust the serotonin concentration.• Not in regulatory manner, but in physical manner

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fSerotonin messaging

- The full picture

Jung, C.H. et al. , RNA interference of fsr9 - a new generation antidepressant, Nature, 2007, 23Vesicle-mediated release licensed by Capsulution®

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fEfficiency

time

20

Jung, C.H. et al. , RNA interference of fsr9 - a new generation antidepressant, Nature, 2007, 23

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fComparison

reliF ® SSRI

Onset hours weeks

Biological resources

neutral intensive

Solution long-term short-term

Side effects no known actual serotonin loss

Jung, C.H. et al. , The breakthrough in antidepressants, Nature, 2008, in submission

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fThe reliF®

Approach

• Fsr9-specific RNAi molecules are transported to serotonin absorbing synapses.

• Transport is mediated by glycosylation-pattern recognizing vesicles produced by Capsulution®

• The constant delivery of RNAi molecules prevents the premature onset of Fsr9 expression.

• The normal absorption period of HRCs is restored.• Leading to a healthy concentration of serotonin in the

post-synaptic neurons, with no known side effects.

Jung, C.H. et al. , RNA interference of fsr9 - a new generation antidepressant, Nature, 2007, 23

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fOverview

• Goal - Develop an effective, side-effect free drug to provide fast relief from depression.

• Motivation and Progress Dr. Andrew Ringsmuth

– Market analysis– Financial overview

• IP Portfolio

• Pitch

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fMarket for reliF®

• Depression affects 7-18% of the population (In USA, 14 million adults/yr diagnosed)

• Clinical depression is the leading cause of disability in North America

• Expected to become the second leading cause worldwide by 2020 (World Health Organization)

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fThe existing world market (2006)*

• Antidepressant drugs (SSRIs, NRIs, MAOIs)– US$17 billion

• Psychotherapy– US$5.2 billion

• Electroconvulsive therapy– US$120 million

• Other methods (e.g. acupuncture, hypnotherapy, meditation)– Est. US$3.5 billion

Total annual market value US$25.82 billion

Projected market growth**: >5.2% by 2010 (>US$27.16 billion)

*World Health Organisation annual report 2006**GlaxoSmithKline, 2006

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fThe reliF® advantage

• Problems with SSRIs (7 FDA approved, 87% of existing antidepressant market):

– Slow acting (upto 6-8wks. 55% of prescriptions accompany psychotherapeutic treatments)

– Unpredictable efficacy and side effects (Average sufferer trials 1 drug unsuccessfully+)

• reliF– Fast acting (same day)– Shown to be effective in >97% cases where an SSRI is effective++

– No known side effects

• Predicted cost to consumer– 5-15% above most popular SSRI (Cymbalta)– Analysts predict price to be competitive

+ Davis, K. & James, P. (2006). ‘The efficacy of drug-based depression treatments’. J. Neur. Psych. 131(3): 496-507.

++ Jung, C.H. et al. , RNA interference of fsr9 - a new generation antidepressant, Nature, 2007, 23.

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fExpanding market potential

• Evidence1 to suggest that reliF technology is adaptable to other depression-associated neurotransmitters (targeted by other existing antidepressants)

• R&D costs for adaptation << potential market value

1Jung, C.H. et al. , RNA interference of fsr9 - a new generation antidepressant, Nature, 2007, 23

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fInvestment opportunity

• Investment to complete Phase II (3-5 years):– AUD $3.8 million (>$2.0 million startup + milestone payments)

• Benefits to investor during Phase II:– 40% share in permON– Position on board of directors

• permON exit strategy:– Option 1: Licensing

• Initial licensing fee: ~AUD $25 million • Worldwide royalties: 7-10% (subj. to neg.)

– Option 2: Sale• Complete sale: >AUD $100 million• Partial sale: Retain a part share in permON when reliF goes to market

• Investor return:– Option 1:

• Initial licensing: ~AUD: $10 million• 40% share in permON royalties (> USD $700 million in first year, assuming 5-10% share of SSRI market)

– Option 2:• Complete sale: >AUD $40 million• Partial sale: Return determined by share retained

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fOverview

• Goal - Develop an effective, side-effect free drug to provide fast relief from depression.

• Motivation and Progress - Large demand and even growing market in the future.

• IP Portfolio Dr. Kimberly Wadsworth

• Pitch

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fIP Portfolio

Scientific discovery: Fsr9 discovered: March 2005 reliF® works on Fsr9: December 2005

Provisional patent application filed in the USA: Fsr9: 13 June 2005 reliF®: 7 January 2006

Publications:Jung, C.H., Total serotonin concentration unaffected in Depression type I, Nature, 2005, 20, 1159-1165Jung, C.H., Serotonin messaging mediated by 5-HR-channels not 5-HR-receptor, Nature, 2006, 20,

1159-1165Jakobs, D.R., et al., Serotonin concentration involved in depression type I, Science, 2006, 21, 501-509

Jung, C.H. et al., SSRI induced 5-HR increase only a hack , Nature, 2006, 21, 180-185 Chen, L.L. et al. ,The role of Fsr9 in Depression Type I , Int J Dev Neurosci, 2007, 22, 180-185 Chen, L.L. et al. , Co-localization of 5-HRC and Fsr9 suggest a new drug target for depression,

Neurophysiology, 2007, 20 Jung, C.H. et al. , RNA interference of fsr9 - a new generation antidepressant, Nature, 2007, 23 Jung, C.H. et al. , The breakthrough in antidepressants, Nature, 2008, in submission

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fIP Portfolio

Formation of permON® : 3 April 2006

PCT (Patent Cooperation Treaty) application filed: Fsr9: 12 June 2006 reliF® : 6 January 2007

National phase entry: Fsr9 (13 December 2007 - 13 January 2008): Australia United States of America Europe Japan CanadaPlans to enter national phase for reliF® in same jurisdictions

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fTrademarks and licensing

Trademarks:

reliF®

permON®

Licensing:

Capsulution®

Obtained commercial license

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fPitch

• reliF® is an effective, side-effect free drug to provide fast relief from depression.

• Large demand in an ever growing market.

• We have taken reliF® to pre-clinical trials (proof of concept)

• For your $3.8 million, you will see a return of at least $10 million plus royalties.

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fOutside opinions of leading clinicians

“When depression becomes a small inconvenience, rather than the major impact on human society, we can look forward to a bright future and reliF® is better suited than vicodin.”

Dr. Gregory House

“reliF® will be a major breakthrough in depression treatment.”

Dr. Meredith Grey

“reliF® and Aspirin, two man made miracles”

Dr. Frank Campion