Relif ® Dr. Denis C. Bauer CEO Prof. Dr. Chol Hee Jung CSO Dr. Andrew Ringsmuth Business Development Manager Dr. Kimberly Wadsworth IP Manager Feel the relief
Jun 21, 2015
Relif ®
Dr. Denis C. Bauer CEOProf. Dr. Chol Hee Jung CSODr. Andrew Ringsmuth Business Development ManagerDr. Kimberly Wadsworth IP Manager
Feel the relief
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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