OTCQX: RESX Investor Presentation July 2015 This presentation
OTCQX: RESX Investor Presentation July 2015 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. 2 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 3 Experienced Management Team 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 4 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 5 Summary Product Portfolio & Timelines Program / Therapeutic Area 2014 2015 2016 OPHTHALMOLOGY RES-529
ONCOLOGY Glioblastoma Multiforme (GBM) ERMATOLOGY Acne Formulation / Nonclinical Phase I/II 6 RES-529 First-in-class PI3K/Akt/mTOR pathway inhibitor 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-529s 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 8 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 9 Ophthalmology RES-529 First-in-class PI3K/Akt/mTOR pathway inhibitor Ophthalmology Market 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 20 million cases of Wet AMD in the US/EU Age-Related Macular Degeneration 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 Competitor Lucentis (Genentech/Novartis) Eylea (Regeneron/Bayer/Sanofi) Cost Cost of single injection approximately $2,000.00 Cost of single injection approximately $2,000.00 Treatment Treatments every four to six weeks
Treatments every eight to twelve weeks Approximately $4 billion for all indications Approximately $2.8 billion for all indications Sales 11 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 12 RES-529 Inhibits VEGF Induced Angiogenesis and Permeability 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
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):95517. RES-529 = P529 = Palomid 529 13 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 AgeRelated 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) 251:27052709. RES-529 = P529 = Palomid 529 14 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) Temporary haze attributed to drug particles at highest dose studied (0.5 mg ) 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 15 RES-529: Upcoming Studies in AMD 2015 Finalize CMC work for subconjunctival administration Complete pre-clinical studies necessary to allow for next clinical studies to be initiated in 2016 2016 Phase I/II clinical trial in AMD Safety and tolerability, as well as clinical efficacy
Determine MTD for subconjunctival administration 16 Oncology RES-529 First-in-class PI3K/Akt/mTOR pathway inhibitor RES-529 in Glioblastoma A True Unmet Medical Need 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 Penetrates the blood brain barrier PI3K/Akt/mTOR pathway significantly up-regulated in glioblastoma First-in-class mechanism of action exerting PI3K/Akt/mTOR pathway control above other drugs targeting this pathway Specifically targets TORC1/TORC2 implicated in GBM Orally available: allows for improved administration and reduction in health care costs FDA Orphan Drug Designation granted January 2015 Market size expected to grow dramatically: 2013 World Wide market ~ $1 billion
2020 Expected WW market ~ $4.5 billion (Growth Rate of ~28%.* Growth will be driven primarily by new agents.) ** Treatment options and outcomes for glioblastoma in the elderly patient, N.D. Arvold and D. A. Reardon, lin Interv Aging. 2014; 9: 357367 EvaluatePharma, Adis R&D Insight 18 RES-529 Inhibits C6V10 Glioma Tumor Growth C6V10 model (fast growing tumor, constitutive VEGF secreting tumor)* Control C6V10 RES-529 C6V10 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 Control C6V10 *Data from Xue Q. et al Cancer Res 2008;68(22):95517. RES-529 = P529 = Palomid 529 RES-529 C6V10 19 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) Control 25mg *Data from Xue Q. et al Cancer Res 2008;68(22):95517. RES-529 = P529 = Palomid 529 50mg 20 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
Efficacy in multiple tumor types In NCI60 cell line panel3 Breast cancer: efficacy in orthotopic xenografts4 Prostate cancer: synergy with radiotherapy and chemotherapy in xenografts5,6 Lung cancer: efficacy in appropriate model 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):95517 and Xue Q. unpublished data. 2 Lin F. et al. Dual mTORC1 and mTORC2 inhibitor Palomid 529 penetrates the BloodBrain Barrier without restriction by ABCB1 and ABCG2. Int J Cancer 2013Sep1;133(5):1222-33. 3 Diaz 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. 4 Xiang T. et al. Targeting the Akt/mTOR pathway in Brca1-deficient cancers. Oncogene 20011May26;30(21):2443-50. 5 Gravinia 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. 6 Gravinia 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 1 RES-529 = P529 = Palomid 529 21 RES-529: Planned Studies in Glioblastoma/Oncology 2015 2016 Finalize CMC work for oral administration Conduct pre-clinical studies necessary to allow for IND clinical studies to be initiated in 2016
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 22 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 23 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% 24
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 2H 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 25 Appendix
Oncology RES-529 First-in-class PI3K/Akt/mTOR pathway inhibitor RES-529: Penetration of the Blood Brain Barrier Both IV and oral administration of RES-529 demonstrated penetration of the blood brain barrier * Plasma, brain, and tumor concentrations were evaluated in a U87 orthotopic xenograft model. Results demonstrated penetration of the blood brain barrier, similar concentrations in plasma, brain and tumor, no effect of the Abcb1 or Abcg2 transporters, and a statistically significant inhibition of tumor growth *Data from Lin F. et al.. Int J Cancer 2013Sep1;133(5):1222-33. RES-529 = P529 = Palomid 529
29 RES-529 Enhances Effect of XRT in U251 Glioblastoma Orthotopic Xenograft Treatment groups: vehicle irradiation RES-529 RES-529 plus irradiation Kaplan-Meier curve showing survival of mice control (Black), irradiation (4 Gy, Blue),
Palomid 529 (50 mg/kg, Red), or Palomid 529 (50 mg/kg) plus irradiation (4 Gy) (Purple).Log-rank test p=0.021 (IR vs. Palomid 529 plus IR) and p=0.016 (Palomid 529 vs. Palomid 529 plus IR) U251 cells were injected and treatment begun on day 3. Mice received four doses of RES-529 (QDx4, 50 mg/kg) by oral gavage and whole brain irradiation (4 Gy) was done after the 3rd dose of RES-529 (Day 5). Each group contained five mice. *Data from Cerna et al. AACR2010, abst 2506. RES-529 = P529 = Palomid 529 30 RES-529 Suppressed the Tumor Growth of Several Breast Cancer Orthotopic Xenografts
RES-529 was tested in orthotopic xenografts of both Brca1tr/tr MEFs or MCF7 cells expressing GFP or Akt1 shRNA. Nine weeks after tumor implantation mice were treated with RES-529 at 40mg/kg or vehicle for 18 days. Suppression of tumor growth was observed in all experiments. *Data from Xiang T. et al. Oncogene 20011May26;30(21):2443-50. RES-529 = P529 = Palomid 529 31 RES-529 Enhanced the Effect of Radiation Therapy in Prostate Cancer Xenografts RES-529 was evaluated in PC-3 and 22rv1 xenografts alone and in combination with either radiation therapy (XRT). Tumors were injected subcutaneously and
grew to 0.5-0.8cm3 (~10 days) and treatment was initiated. RES-529 (100mg/kg po 5d/wk), XRT (4Gy single fraction), or RES-529 + XRT were tested. *Data from Gravinia GL. et al. Prostate 2014JanJun74(8);852-68. RES-529 = P529 = Palomid 529 32 RES-529 Enhanced the Effect of Chemotherapy in Prostate Cancer Xenografts RES-529 was evaluated in PC-3 and 22rv1 xenografts alone and in combination with chemotherapy (docetaxel [DTX]
or cisplatin [Cis]). Tumors were injected subcutaneously and grew to 0.5-0.8cm3 (~10 days) and treatment was initiated. RES-529 (100mg/kg po 5d/wk) vs. DTX (7.5 mg/kg/wk IP), Cis (30mg/kg q21d), RES-529 + DTX, and RES-529 + Cis were tested *Data from Gravinia GL. et al. Endocrine Related Cancer (2011);18:385-400 RES-529 = P529 = Palomid 529 33 RES-529 Inhibits Growth in Doxycycline Induced EGFR (T790M) Lung Cancer Model RES-529 was tested in a doxycycline (dox) induced lung cancer model (EGFR
[L858R/T790M]). Mice began IP injections of RES-529 concurrent with dox in a prevention modality study. 34
File Management Practice. Click the start button at the bottom left hand corner of your desktop. Click on "All Programs." Use your mouse to scroll or the arrow keys to choose "Microsoft Office." Then click "Microsoft Word." File management practice...
"Surely God is good to Israel, to those who are pure in heart!But as for me, my feet came close to stumbling; My steps had almost slipped.For I was envious of the arrogant, as I saw the prosperity of the...
Use the industrial organization (I/O) model to explain how firms can earn above-average returns. ... GE - headquartered in the U.S., yet up to 60% of its revenue growth through 2015 will be generated from rapidly developing economies such as...
AGVISE Laboratories summarized Soybean Cyst Nematode (SCN) levels on a regional basis, based upon the zip code region or county of the sample. These SCN data are summarized based upon the zip code of the submitter and may not reflect...
Goals of Presentation. Bring Eel River stakeholders up-to-speed on objectives, scope, methods, and status of this ongoing project. Help foster potential collaboration and coordination between pikeminnow research, monitoring, and control efforts in the Eel River basin.
Star Video. In the Star folder, use the drop down to select video for royalty-free video clips. Drag your star video selection to the timeline. Star images. Select images for royalty-free picture. Drag your star image selection to the timeline....
Responders must be mindful to ensure the power is cut-off to the vehicle and should not assume that the power source has been secured based on lack of noise from the vehicle Extrication Considerations Stabilizing the Vehicle For Tesla EVs,...
Ready to download the document? Go ahead and hit continue!