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Investor Presentation
June 2015OTC: RESX
2
This presentation includes "forward-looking statements" under the Private Securities Litigation Reform Act
of 1995. All statements other than statements of historical facts contained in this presentation, including
statements regarding our anticipated future clinical and regulatory events, future financial/position,
business strategy and plans and objectives of management for future operations, are forward-looking
statements. Forward-looking statements can be identified by words such as “potential,” "may," "will,"
"should," "forecast,“ "project," "could," "expect," "believe," "estimate," "anticipate," "intend," "plan,“
“continue”, other words of similar meaning, derivations of such words and the use of future dates.
Forward-looking statements in this presentation include, without limitation, statements regarding our
current business strategies, the potential future commercialization of our product candidates, potential
estimated market sizes for our product candidates, anticipated start dates, durations and completion
dates, as well as potential future results, of our future clinical trials, anticipated designs of our future
clinical trials, and anticipated future regulatory submissions and events. Uncertainties and risks may cause
actual results to be materially different than those expressed in or implied by our forward-looking
statements. Particular uncertainties and risks include, among others, uncertainties regarding our ability to
license out our existing and license in additional products and technologies and the terms of such licenses;
uncertainties involved in clinical testing, the difficulty of developing pharmaceutical products, obtaining
regulatory and other approvals and achieving market acceptance, and other risks and uncertainties
described in our filings with the Securities and Exchange Commission, including our most recent annual
report on Form 10-K/A, subsequent quarterly reports on Form 10-Q and final prospectus dated July 31,
2014. All forward-looking statements in this presentation speak only as of the date of this presentation
and we undertake no obligation to update or revise any forward-looking statement, whether as a result of
new information, future events or otherwise.
3
Company Highlights
• Specialty biopharmaceutical company focused on developing
products for ophthalmology, oncology and dermatology
• Two core proprietary technologies applicable in multiple
indications
– RES-529: PI3K/Akt/mTOR Pathway Inhibitor (AMD, Glioblastoma)
– RES-440: “Soft” Anti-Androgen (Acne)
– Strong preclinical in-vitro and in-vivo data
• Two Phase I clinical trials completed for RES-529 in AMD
• Three Phase I/II clinical trials to be initiated in mid-2016
– Age Related Macular Degeneration (AMD)
– Glioblastoma (Orphan Drug designation received)
– Acne
• Solid balance sheet with no debt
• Experienced management team supported by strong board of
directors
4
• Stephen M. Simes - Chief Executive Officer
– BioSante, Unimed, Bio-Technology General, Gynex, Searle
• Phillip B. Donenberg, CPA – Chief Financial Officer
• BioSante, Unimed, Gynex
• Mark Weinberg, MD, MBA – Senior VP, Clinical Development
– Astellas, Lundbeck, Ovation, Takeda, Abbott
• David Sherris, Ph.D. - Chief Scientific Officer
– Paloma/Vasculomedics, OXiGENE, Serono, Unilever, Centocor
– Ph.D. in Biochemistry and Molecular Genetics
Experienced Management Team
5
Strong Board of Directors
• Sol Barer, PhD - Chairman
– Former CEO & Executive Chairman, and Chairman, Celgene Corporation
– Board member Teva Pharmaceuticals, Aegerion Pharmaceuticals, Amicus Therapeutics
– Chairman of Medgenics, InspireMD and Contrafect Corporation
• Isaac Blech - Vice-Chairman
– Leading biotechnology entrepreneur and investor
– Genetic Systems, Nova, Celgene, ICOS, Texas BioTechnology, Pathogenesis
• Stephen M. Simes – CEO
– BioSante, Unimed, Bio-Technology General, Gynex, Searle
• Rex Bright
– SkinMedica, J&J, GlaxoSmithKline, Allergan
• Nelson Stacks
– Waveguide Corporation
• David Sherris, PhD – Chief Scientific Officer
– Paloma/Vasculomedics, OXiGENE, Serono, Unilever, Centocor
6
Program / Therapeutic Area 2014 2015 2016
RES-529
OPHTHALMOLOGY
Age-Related Macular Degeneration
(AMD)
ONCOLOGY
Glioblastoma Multiforme (GBM)
RES-440
DERMATOLOGY
Acne
Phase I IVR
Formulation / Nonclinical
Phase I/II
SubConj
Formulation / Nonclinical Phase I/II
Formulation / Nonclinical Phase I/II
Phase I
SubConj (NEI)
Summary Product Portfolio & Timelines
Data expected from three clinical trials in 2017
RES-529
First-in-class PI3K/Akt/mTOR pathway inhibitor
8
RES-529 & the PI3K Pathway
• The PI3K/Akt/mTOR pathway is an important signaling pathway for
many cellular regulation functions such as cell proliferation,
angiogenesis and vascular permeability
– Significant therapeutic opportunities for pathway signaling
– Agents in development affect different targets
• PI3K inhibitors
• Akt inhibitors
• mTOR inhibitors
• RES-529 is a novel approach to inhibition of the PI3K pathway
– Rather than interfering with the pathway directly via specific signaling proteins
(e.g. PI3K, Akt, mTOR), RES-529’s action results in the loss of the TORC1 and
TORC2 protein complexes thus preventing these complexes from generating
and potentiating signaling within the pathway.
RES-529 is a first-in-class PI3K/Akt/mTOR pathway inhibitor
9
RES-529 Mechanism of Action
RES-529 interferes with the molecular components that form TORC1 and TORC2 preventing these complexes
from generating and potentiating signaling and thereby interferes with the activities of the PI3K/Akt/mTOR
pathway: translation, cell growth, ribosome biogenesis, metabolism, proliferation, and authophagy
Ophthalmology
RES-529
First-in-class PI3K/Akt/mTOR pathway inhibitor
11
20 million cases of Wet AMD in the US/EU
10% of patients 66 to 74 years of age will have findings of macular
degeneration
Prevalence increases to 30% in patients 75 to 85 years of age
Age-Related
Macular
Degeneration
Competitor
Cost
Treatment
Sales
Lucentis (Genentech/Novartis)
Cost of single injection approximately
$2,000.00
Treatments every four to six weeks
Approximately $4 billion for all indications
Eylea (Regeneron/Bayer/Sanofi)
Cost of single injection approximately
$2,000.00
Treatments every eight to twelve weeks
Approximately $2.8 billion for all indications
• RES-529 initial ophthalmologic indication is for Wet AMD
• Back of the eye diseases have large market size and financial potential
• Wet AMD has approximately $6 billion in WW sales
Ophthalmology Market
12
RES-529 Clinical Advantage in Wet AMD
• RES-529 is being developed as a subconjunctival injection
• Clinical trials for RES-529 will be designed to demonstrate that patients
may transition from initial therapy (Lucentis, Avastin, Eylea) to RES-529
– Enabling patients to be maintained with subconjunctival (vs. intravitreal) administration
– Once every three months therapy compared with monthly or on demand therapy requiring
frequent follow up
Intravitreal – needle
penetrates into the
globe of the eye
Subconjunctival – fluid is
injected beneath the
conjunctiva
13
VEGF Induced Angiogenesis
• Mice pretreated with RES-529 IP 24 hrs prior to intradermal injection of
adenovirus expressing mouse VEGF-A164 to mouse ear
VEGF Induced Permeability
• Mice pretreated with RES-529 IP 24 hrs prior to intradermal injection of 100 ng
VEGF to ear; 0.1 ml of 0.5% Evans Blue given IV 30 minutes after VEGF treatment
RES-529 Inhibits VEGF Induced Angiogenesis and
Permeability
VEGF VEGF + RES-529
Xue Q. et al. Palomid 529, a Novel Small-Molecule Drug, Is a TORC1/TORC2 Inhibitor That Reduces Tumor Growth, Tumor Angiogenesis, and Vascular Permeability. Cancer Res 2008;68(22):9551–7.
RES-529 = P529 = Palomid 529
14
RES-529: Completed Phase I Trials in AMD
• Protocol P52901 Company sponsored and conducted by Dr. Jeffrey Heier
(Ophthalmic Consultants of Boston) and Dr. David Brown (Retinal
Consultants Houston)
– A Phase I Open-Label Study to Investigate the Safety, Tolerability and
Pharmacokinetic Profile of Single Intravitreal and Subconjunctival Doses of
RES-529 in Patients with Advanced Neovascular Age-Related Macular
Degeneration (AMD)
• 15 patients treated via intravitreal injection
• Doses between 0.004mg and 0.5mg
• Protocol 11-EI-0066 sponsored by National Eye Institute (NEI) and
conducted by Dr. Catherine Meyerle
– A Phase I Unmasked Study to Investigate the Safety and Tolerability of
Subconjunctival Injections of RES-529 in Patients with Neovascular Age-
Related Macular Degeneration*
• 5 patients treated with subconjunctival injections of 2mg qmo x 3
*Dalal M. et al. Subconjunctival Palomid 529 in the treatment of neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol (2013) 251:2705–2709.
RES-529 = P529 = Palomid 529
15
RES-529: Clinical Data in AMD
• Patients Enrolled:
– End stage patients who were refractory or not appropriate for VEGF
therapy
– Most had significant visual deficits and retinal fluid on OCT
• Safety/Tolerability:
– Intravitreal administration (Company sponsored study)
• 0.5 mg (highest dose studied) associated with temporary visual
disturbance from haze in vitreous attributed to drug particles in the
vitreous. This effect resolved.
– Subconjunctival administration (NEI study)
• 2mg monthly x 3 administered; generally well tolerated
• Depot formed at injection site
• Efficacy:
– Preliminary evidence of biologic activity based on:
• Fluid pocket reduction
• Retinal thinning
• Cyst reduction
16
RES-529: Upcoming Studies in AMD
• Finalize CMC work for subconjunctival
administration
• Complete pre-clinical studies necessary
to allow for next clinical studies to be
initiated in 2016
2015
• Phase I/II clinical trial in AMD
• Safety and tolerability, as well as
clinical efficacy
• Determine MTD for subconjunctival
administration
2016
Oncology
RES-529
First-in-class PI3K/Akt/mTOR pathway inhibitor
18
RES-529 in Glioblastoma
• A True Unmet Medical Need – Glioblastoma
– PI3K/Akt/mTOR pathway significantly up-regulated in glioblastoma
– Orally available: allows for improved administration and reduction in
health care costs
– FDA Orphan Drug Designation granted January 2015
– Significant financial upside due to limited and modestly effective
therapies currently available
– Phase 2a studies expected to commence in other tumors once MTD is
determined
• Market size expected to grow dramatically:
– 2013 World Wide market ~ $1 billion
– 2020 Expected WW market ~ $4.5 billion (Growth Rate of approximately 28%.* Growth
will be driven primarily by new agents.)
• EvaluatePharma, Adis R&D Insight
19
RES-529 in Glioblastoma
• Current Standards of Care:
– Temodar, Avastin, Gliadel Wafer
– Median survival with only supportive care, less than 6 months**
– Median survival with aggressive chemotherapy in combination with
radiotherapy, 12 to 15 months**
• RES-529 potential advantages:
– Activity shown in multiple in vitro and in vivo animal models for GBM
with evidence that it can pass the blood brain barrier
– First-in-class mechanism of action exerting PI3K/Akt/mTOR pathway
control above other drugs targeting this pathway (PI3K pathway
significantly up-regulated in GBM)
– Specifically targets TORC1/TORC2 implicated in GBM
** Treatment options and outcomes for glioblastoma in the elderly patient, N.D. Arvold and D. A. Reardon, lin Interv Aging. 2014; 9: 357–367
20
RES-529 Inhibits C6V10 Glioma Tumor Growth
• Tumor growth inhibited in subcutaneous
xenograft models
• Mice pretreated with RES-529 at 200
mg/kg/2 day, intraperitoneal for one week
• At second week, rat glioma cells were
injected subcutaneous
• Treatment continued while tumors were
allowed to grow for 21 days
• At termination, tumor volume reduced by
70% percent
*Data from Xue Q. et al Cancer Res 2008;68(22):9551–7.
RES-529 = P529 = Palomid 529
C6V10 model (fast growing tumor, constitutive VEGF secreting tumor)*
RES-529 C6V10
RES-529 C6V10
Control C6V10
Control C6V10
21
RES-529 Inhibits U87 Glioma Tumor Growth
• Tumor growth inhibited in subcutaneous xenograft models
– U87 model (slow growing tumor)*
• Mice were injected subcutaneous with U87 glioma cells
• At day 3, mice began treatment with RES-529 at doses of 25 and 50 mg/kg/2 day
intraperitoneal
• U87 tumors were allowed to grow for 24 days
• At termination, tumor volume reduced by 29% (25mg) and 76% (50 mg)
*Data from Xue Q. et al Cancer Res 2008;68(22):9551–7.
RES-529 = P529 = Palomid 529
Control 25mg 50mg
22
RES-529: Extensively Studied in Preclinical Oncology Models
• Efficacy in glioma subcutaneous xenograft model
– Similar efficacy regardless of route of administration (iv, po, or ip)1
• Penetration of the blood brain barrier with pharmacologically
active levels reached in murine brain2
• Potent effects in multiple tumor types
– In NCI60 cell line panel3
– Efficacy in breast cancer orthotopic xenografts4
– Synergy with radiotherapy and chemotherapy in prostate cancer
xenografts5,6
– Efficacy in lung cancer model
1Xue Q. et al. Palomid 529, a Novel Small-Molecule Drug, Is a TORC1/TORC2 Inhibitor That Reduces Tumor Growth, Tumor Angiogenesis, and Vascular Permeability. Cancer
Res 2008;68(22):9551–7 and Xue Q. unpublished data.
2Lin F. et al. Dual mTORC1 and mTORC2 inhibitor Palomid 529 penetrates the Blood–Brain Barrier without restriction by ABCB1 and ABCG2. Int J Cancer
2013Sep1;133(5):1222-33.
3Diaz R. et al. The novel Akt inhibitor Palomid 529 (P529) enhances the effect of radiotherapy in prostate cancer. Br J Cancer 2009Mar24;100(6):932-40.
4Xiang T. et al. Targeting the Akt/mTOR pathway in Brca1-deficient cancers. Oncogene 20011May26;30(21):2443-50.
5Gravinia GL. et al. Torc1/Torc2 Inhibitor, Palomid 529, Enhances Radiation Response Modulating CRM1-Mediated Survivin Function and Delaying DNA Repair in Prostate
Cancer Models. Prostate 2014JanJun74(8);852-68.
6Gravinia GL. et al. The TORC1/TORC2 inhibitor, Palomid 529, reduces tumor growth and sensitizes to docetaxel and cisplatin in aggressive and hormone-refractory prostate
cancer cells. Endocrine Related Cancer (2011);18:385-400
RES-529 = P529 = Palomid 529
23
RES-529: Planned Studies in Glioblastoma/Oncology
• Finalize CMC work for oral administration
• Conduct pre-clinical studies necessary to allow
for IND clinical studies to be initiated in 2016
2015
• Phase I/II clinical trial in glioblastoma
- Efficacy assessment in recurrent glioblastoma
- Determine MTD in glioblastoma
• Plan Phase 2a studies in other tumor types
using MTD dose
- non-clinical data in breast, prostate, and lung
2016
24
Summary of Clinical Timelines & Milestones
– 2015:
• Finalize CMC work for early clinical trials with RES-529 and RES-440
• Conduct pre-clinical studies necessary to enable submission of INDs and/or conduct
of next clinical studies
– 2016:
• AMD:
– Phase I/II clinical trial in AMD
» Safety and tolerability, as well as clinical efficacy
» Determine MTD for subconjunctival administration
• Glioblastoma:
– Phase I/II clinical trial in glioblastoma
» Efficacy assessment in recurrent glioblastoma
» Determine MTD in glioblastoma
– Plan Phase IIa studies in other oncology indications using MTD dose
» Current non-clinical data supports breast, prostate, and lung cancers
• Acne:
– Phase I/II clinical trial
» Assess safety and tolerability as well as efficacy
• Near-term goal: increased stockholder value through active
implementation of development programs
25
RestorGenex Summary Financial Information
as of March 31, 2015
• Cash: $19,200,000
• Debt: $0
• Planned burn rate in 2015: ~ $1.0 million/month
• Shares outstanding: 18,614,968
• Options outstanding: 3,248,430
• Warrants outstanding: 4,815,266
• Fully diluted: 26,678,664
• Insider ownership: 30%
26
Key Takeaways
• Specialty biopharmaceutical company focused on
developing products for ophthalmology, oncology and
dermatology
– Pipeline based on proprietary platforms
• Two Phase I clinical trials completed for RES-529 in AMD
• Three Phase I/II clinical trials to be initiated in 1H 2016
– Age Related Macular Degeneration (AMD)
– Glioblastoma (Orphan Drug designation received)
– Acne
• Solid balance sheet with no debt
• Experienced management team supported by strong
board of directors
Restorgenex SCSSC June 2015 Presentation

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Restorgenex SCSSC June 2015 Presentation

  • 2. 2 This presentation includes "forward-looking statements" under the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts contained in this presentation, including statements regarding our anticipated future clinical and regulatory events, future financial/position, business strategy and plans and objectives of management for future operations, are forward-looking statements. Forward-looking statements can be identified by words such as “potential,” "may," "will," "should," "forecast,“ "project," "could," "expect," "believe," "estimate," "anticipate," "intend," "plan,“ “continue”, other words of similar meaning, derivations of such words and the use of future dates. Forward-looking statements in this presentation include, without limitation, statements regarding our current business strategies, the potential future commercialization of our product candidates, potential estimated market sizes for our product candidates, anticipated start dates, durations and completion dates, as well as potential future results, of our future clinical trials, anticipated designs of our future clinical trials, and anticipated future regulatory submissions and events. Uncertainties and risks may cause actual results to be materially different than those expressed in or implied by our forward-looking statements. Particular uncertainties and risks include, among others, uncertainties regarding our ability to license out our existing and license in additional products and technologies and the terms of such licenses; uncertainties involved in clinical testing, the difficulty of developing pharmaceutical products, obtaining regulatory and other approvals and achieving market acceptance, and other risks and uncertainties described in our filings with the Securities and Exchange Commission, including our most recent annual report on Form 10-K/A, subsequent quarterly reports on Form 10-Q and final prospectus dated July 31, 2014. All forward-looking statements in this presentation speak only as of the date of this presentation and we undertake no obligation to update or revise any forward-looking statement, whether as a result of new information, future events or otherwise.
  • 3. 3 Company Highlights • Specialty biopharmaceutical company focused on developing products for ophthalmology, oncology and dermatology • Two core proprietary technologies applicable in multiple indications – RES-529: PI3K/Akt/mTOR Pathway Inhibitor (AMD, Glioblastoma) – RES-440: “Soft” Anti-Androgen (Acne) – Strong preclinical in-vitro and in-vivo data • Two Phase I clinical trials completed for RES-529 in AMD • Three Phase I/II clinical trials to be initiated in mid-2016 – Age Related Macular Degeneration (AMD) – Glioblastoma (Orphan Drug designation received) – Acne • Solid balance sheet with no debt • Experienced management team supported by strong board of directors
  • 4. 4 • Stephen M. Simes - Chief Executive Officer – BioSante, Unimed, Bio-Technology General, Gynex, Searle • Phillip B. Donenberg, CPA – Chief Financial Officer • BioSante, Unimed, Gynex • Mark Weinberg, MD, MBA – Senior VP, Clinical Development – Astellas, Lundbeck, Ovation, Takeda, Abbott • David Sherris, Ph.D. - Chief Scientific Officer – Paloma/Vasculomedics, OXiGENE, Serono, Unilever, Centocor – Ph.D. in Biochemistry and Molecular Genetics Experienced Management Team
  • 5. 5 Strong Board of Directors • Sol Barer, PhD - Chairman – Former CEO & Executive Chairman, and Chairman, Celgene Corporation – Board member Teva Pharmaceuticals, Aegerion Pharmaceuticals, Amicus Therapeutics – Chairman of Medgenics, InspireMD and Contrafect Corporation • Isaac Blech - Vice-Chairman – Leading biotechnology entrepreneur and investor – Genetic Systems, Nova, Celgene, ICOS, Texas BioTechnology, Pathogenesis • Stephen M. Simes – CEO – BioSante, Unimed, Bio-Technology General, Gynex, Searle • Rex Bright – SkinMedica, J&J, GlaxoSmithKline, Allergan • Nelson Stacks – Waveguide Corporation • David Sherris, PhD – Chief Scientific Officer – Paloma/Vasculomedics, OXiGENE, Serono, Unilever, Centocor
  • 6. 6 Program / Therapeutic Area 2014 2015 2016 RES-529 OPHTHALMOLOGY Age-Related Macular Degeneration (AMD) ONCOLOGY Glioblastoma Multiforme (GBM) RES-440 DERMATOLOGY Acne Phase I IVR Formulation / Nonclinical Phase I/II SubConj Formulation / Nonclinical Phase I/II Formulation / Nonclinical Phase I/II Phase I SubConj (NEI) Summary Product Portfolio & Timelines Data expected from three clinical trials in 2017
  • 8. 8 RES-529 & the PI3K Pathway • The PI3K/Akt/mTOR pathway is an important signaling pathway for many cellular regulation functions such as cell proliferation, angiogenesis and vascular permeability – Significant therapeutic opportunities for pathway signaling – Agents in development affect different targets • PI3K inhibitors • Akt inhibitors • mTOR inhibitors • RES-529 is a novel approach to inhibition of the PI3K pathway – Rather than interfering with the pathway directly via specific signaling proteins (e.g. PI3K, Akt, mTOR), RES-529’s action results in the loss of the TORC1 and TORC2 protein complexes thus preventing these complexes from generating and potentiating signaling within the pathway. RES-529 is a first-in-class PI3K/Akt/mTOR pathway inhibitor
  • 9. 9 RES-529 Mechanism of Action RES-529 interferes with the molecular components that form TORC1 and TORC2 preventing these complexes from generating and potentiating signaling and thereby interferes with the activities of the PI3K/Akt/mTOR pathway: translation, cell growth, ribosome biogenesis, metabolism, proliferation, and authophagy
  • 11. 11 20 million cases of Wet AMD in the US/EU 10% of patients 66 to 74 years of age will have findings of macular degeneration Prevalence increases to 30% in patients 75 to 85 years of age Age-Related Macular Degeneration Competitor Cost Treatment Sales Lucentis (Genentech/Novartis) Cost of single injection approximately $2,000.00 Treatments every four to six weeks Approximately $4 billion for all indications Eylea (Regeneron/Bayer/Sanofi) Cost of single injection approximately $2,000.00 Treatments every eight to twelve weeks Approximately $2.8 billion for all indications • RES-529 initial ophthalmologic indication is for Wet AMD • Back of the eye diseases have large market size and financial potential • Wet AMD has approximately $6 billion in WW sales Ophthalmology Market
  • 12. 12 RES-529 Clinical Advantage in Wet AMD • RES-529 is being developed as a subconjunctival injection • Clinical trials for RES-529 will be designed to demonstrate that patients may transition from initial therapy (Lucentis, Avastin, Eylea) to RES-529 – Enabling patients to be maintained with subconjunctival (vs. intravitreal) administration – Once every three months therapy compared with monthly or on demand therapy requiring frequent follow up Intravitreal – needle penetrates into the globe of the eye Subconjunctival – fluid is injected beneath the conjunctiva
  • 13. 13 VEGF Induced Angiogenesis • Mice pretreated with RES-529 IP 24 hrs prior to intradermal injection of adenovirus expressing mouse VEGF-A164 to mouse ear VEGF Induced Permeability • Mice pretreated with RES-529 IP 24 hrs prior to intradermal injection of 100 ng VEGF to ear; 0.1 ml of 0.5% Evans Blue given IV 30 minutes after VEGF treatment RES-529 Inhibits VEGF Induced Angiogenesis and Permeability VEGF VEGF + RES-529 Xue Q. et al. Palomid 529, a Novel Small-Molecule Drug, Is a TORC1/TORC2 Inhibitor That Reduces Tumor Growth, Tumor Angiogenesis, and Vascular Permeability. Cancer Res 2008;68(22):9551–7. RES-529 = P529 = Palomid 529
  • 14. 14 RES-529: Completed Phase I Trials in AMD • Protocol P52901 Company sponsored and conducted by Dr. Jeffrey Heier (Ophthalmic Consultants of Boston) and Dr. David Brown (Retinal Consultants Houston) – A Phase I Open-Label Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of Single Intravitreal and Subconjunctival Doses of RES-529 in Patients with Advanced Neovascular Age-Related Macular Degeneration (AMD) • 15 patients treated via intravitreal injection • Doses between 0.004mg and 0.5mg • Protocol 11-EI-0066 sponsored by National Eye Institute (NEI) and conducted by Dr. Catherine Meyerle – A Phase I Unmasked Study to Investigate the Safety and Tolerability of Subconjunctival Injections of RES-529 in Patients with Neovascular Age- Related Macular Degeneration* • 5 patients treated with subconjunctival injections of 2mg qmo x 3 *Dalal M. et al. Subconjunctival Palomid 529 in the treatment of neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol (2013) 251:2705–2709. RES-529 = P529 = Palomid 529
  • 15. 15 RES-529: Clinical Data in AMD • Patients Enrolled: – End stage patients who were refractory or not appropriate for VEGF therapy – Most had significant visual deficits and retinal fluid on OCT • Safety/Tolerability: – Intravitreal administration (Company sponsored study) • 0.5 mg (highest dose studied) associated with temporary visual disturbance from haze in vitreous attributed to drug particles in the vitreous. This effect resolved. – Subconjunctival administration (NEI study) • 2mg monthly x 3 administered; generally well tolerated • Depot formed at injection site • Efficacy: – Preliminary evidence of biologic activity based on: • Fluid pocket reduction • Retinal thinning • Cyst reduction
  • 16. 16 RES-529: Upcoming Studies in AMD • Finalize CMC work for subconjunctival administration • Complete pre-clinical studies necessary to allow for next clinical studies to be initiated in 2016 2015 • Phase I/II clinical trial in AMD • Safety and tolerability, as well as clinical efficacy • Determine MTD for subconjunctival administration 2016
  • 18. 18 RES-529 in Glioblastoma • A True Unmet Medical Need – Glioblastoma – PI3K/Akt/mTOR pathway significantly up-regulated in glioblastoma – Orally available: allows for improved administration and reduction in health care costs – FDA Orphan Drug Designation granted January 2015 – Significant financial upside due to limited and modestly effective therapies currently available – Phase 2a studies expected to commence in other tumors once MTD is determined • Market size expected to grow dramatically: – 2013 World Wide market ~ $1 billion – 2020 Expected WW market ~ $4.5 billion (Growth Rate of approximately 28%.* Growth will be driven primarily by new agents.) • EvaluatePharma, Adis R&D Insight
  • 19. 19 RES-529 in Glioblastoma • Current Standards of Care: – Temodar, Avastin, Gliadel Wafer – Median survival with only supportive care, less than 6 months** – Median survival with aggressive chemotherapy in combination with radiotherapy, 12 to 15 months** • RES-529 potential advantages: – Activity shown in multiple in vitro and in vivo animal models for GBM with evidence that it can pass the blood brain barrier – First-in-class mechanism of action exerting PI3K/Akt/mTOR pathway control above other drugs targeting this pathway (PI3K pathway significantly up-regulated in GBM) – Specifically targets TORC1/TORC2 implicated in GBM ** Treatment options and outcomes for glioblastoma in the elderly patient, N.D. Arvold and D. A. Reardon, lin Interv Aging. 2014; 9: 357–367
  • 20. 20 RES-529 Inhibits C6V10 Glioma Tumor Growth • Tumor growth inhibited in subcutaneous xenograft models • Mice pretreated with RES-529 at 200 mg/kg/2 day, intraperitoneal for one week • At second week, rat glioma cells were injected subcutaneous • Treatment continued while tumors were allowed to grow for 21 days • At termination, tumor volume reduced by 70% percent *Data from Xue Q. et al Cancer Res 2008;68(22):9551–7. RES-529 = P529 = Palomid 529 C6V10 model (fast growing tumor, constitutive VEGF secreting tumor)* RES-529 C6V10 RES-529 C6V10 Control C6V10 Control C6V10
  • 21. 21 RES-529 Inhibits U87 Glioma Tumor Growth • Tumor growth inhibited in subcutaneous xenograft models – U87 model (slow growing tumor)* • Mice were injected subcutaneous with U87 glioma cells • At day 3, mice began treatment with RES-529 at doses of 25 and 50 mg/kg/2 day intraperitoneal • U87 tumors were allowed to grow for 24 days • At termination, tumor volume reduced by 29% (25mg) and 76% (50 mg) *Data from Xue Q. et al Cancer Res 2008;68(22):9551–7. RES-529 = P529 = Palomid 529 Control 25mg 50mg
  • 22. 22 RES-529: Extensively Studied in Preclinical Oncology Models • Efficacy in glioma subcutaneous xenograft model – Similar efficacy regardless of route of administration (iv, po, or ip)1 • Penetration of the blood brain barrier with pharmacologically active levels reached in murine brain2 • Potent effects in multiple tumor types – In NCI60 cell line panel3 – Efficacy in breast cancer orthotopic xenografts4 – Synergy with radiotherapy and chemotherapy in prostate cancer xenografts5,6 – Efficacy in lung cancer model 1Xue Q. et al. Palomid 529, a Novel Small-Molecule Drug, Is a TORC1/TORC2 Inhibitor That Reduces Tumor Growth, Tumor Angiogenesis, and Vascular Permeability. Cancer Res 2008;68(22):9551–7 and Xue Q. unpublished data. 2Lin F. et al. Dual mTORC1 and mTORC2 inhibitor Palomid 529 penetrates the Blood–Brain Barrier without restriction by ABCB1 and ABCG2. Int J Cancer 2013Sep1;133(5):1222-33. 3Diaz R. et al. The novel Akt inhibitor Palomid 529 (P529) enhances the effect of radiotherapy in prostate cancer. Br J Cancer 2009Mar24;100(6):932-40. 4Xiang T. et al. Targeting the Akt/mTOR pathway in Brca1-deficient cancers. Oncogene 20011May26;30(21):2443-50. 5Gravinia GL. et al. Torc1/Torc2 Inhibitor, Palomid 529, Enhances Radiation Response Modulating CRM1-Mediated Survivin Function and Delaying DNA Repair in Prostate Cancer Models. Prostate 2014JanJun74(8);852-68. 6Gravinia GL. et al. The TORC1/TORC2 inhibitor, Palomid 529, reduces tumor growth and sensitizes to docetaxel and cisplatin in aggressive and hormone-refractory prostate cancer cells. Endocrine Related Cancer (2011);18:385-400 RES-529 = P529 = Palomid 529
  • 23. 23 RES-529: Planned Studies in Glioblastoma/Oncology • Finalize CMC work for oral administration • Conduct pre-clinical studies necessary to allow for IND clinical studies to be initiated in 2016 2015 • Phase I/II clinical trial in glioblastoma - Efficacy assessment in recurrent glioblastoma - Determine MTD in glioblastoma • Plan Phase 2a studies in other tumor types using MTD dose - non-clinical data in breast, prostate, and lung 2016
  • 24. 24 Summary of Clinical Timelines & Milestones – 2015: • Finalize CMC work for early clinical trials with RES-529 and RES-440 • Conduct pre-clinical studies necessary to enable submission of INDs and/or conduct of next clinical studies – 2016: • AMD: – Phase I/II clinical trial in AMD » Safety and tolerability, as well as clinical efficacy » Determine MTD for subconjunctival administration • Glioblastoma: – Phase I/II clinical trial in glioblastoma » Efficacy assessment in recurrent glioblastoma » Determine MTD in glioblastoma – Plan Phase IIa studies in other oncology indications using MTD dose » Current non-clinical data supports breast, prostate, and lung cancers • Acne: – Phase I/II clinical trial » Assess safety and tolerability as well as efficacy • Near-term goal: increased stockholder value through active implementation of development programs
  • 25. 25 RestorGenex Summary Financial Information as of March 31, 2015 • Cash: $19,200,000 • Debt: $0 • Planned burn rate in 2015: ~ $1.0 million/month • Shares outstanding: 18,614,968 • Options outstanding: 3,248,430 • Warrants outstanding: 4,815,266 • Fully diluted: 26,678,664 • Insider ownership: 30%
  • 26. 26 Key Takeaways • Specialty biopharmaceutical company focused on developing products for ophthalmology, oncology and dermatology – Pipeline based on proprietary platforms • Two Phase I clinical trials completed for RES-529 in AMD • Three Phase I/II clinical trials to be initiated in 1H 2016 – Age Related Macular Degeneration (AMD) – Glioblastoma (Orphan Drug designation received) – Acne • Solid balance sheet with no debt • Experienced management team supported by strong board of directors