Request-RegeneRx Non-confidential Info March 2011
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8/3/2019 Request-RegeneRx Non-confidential Info March 2011
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Version 42
March 2011
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Forward looking statements
This presentation contains certain forward-looking statements that involve risks and uncertainties that could
cause actual results to be materially different from historical results or from any future results expressed orimplied by such forward-looking statements. Examples of such forward-looking statements include statementsconcerning the target dates for completing the companys ongoing preclinical studies and clinical trials fordermal, ophthalmic, cardiovascular, neurovascular and orphan indications, the potential size of addressablemarkets, including the market for topical gels, sterile eye drops and parenteral delivery products, the companysability to enter into any collaborations with respect to the development or commercialization of its productcandidates, and the therapeutic potential of T4 for dermal, ophthalmic, cardiovascular and neurovascularwounds. Factors that may cause actual results to differ materially from any future results expressed or impliedby any forward-looking statements include the risk that although T4 has demonstrated potential therapeutic
benefit for dermal, ophthalmic, cardiovascular and neurovascular wounds, the companys product candidatesmay not demonstrate safety and/or efficacy in clinical trials, the risk that encouraging results from earlyresearch, preclinical studies, compassionate useor clinical trials may not be confirmed upon further analysis ofthe detailed results of such research, preclinical study, compassionate use or clinical trial, the risk thatadditional information relating to the safety, efficacy or tolerability of our product candidates may be discoveredupon further analysis of preclinical or clinical trial data, the risk that the companys or its collaborators will notobtain approval to market the companys product candidates in the U.S. or abroad, the risks associated withreliance on outside financing to meet capital requirements, the risks associated with reliance on collaborators
for the funding or conduct of further development and commercialization activities relating to the companysproduct candidates, and such other risks described in the companys Quarterly Report on Form 10-Q for thequarter ended September 30, 2010, and other filings the company makes with the SEC. Any forward-lookingstatements are made pursuant to Section 27A of the Securities Act of 1933, as amended, and Section 21E ofthe Securities Exchange Act of 1934, as amended, and, as such, speak only as of the date made. TheCompany undertakes no obligation to publicly update any forward-looking statements, whether as a result ofnew information, future events or otherwise.
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The RegeneRx value proposition
Thymosin beta 4 (T4) is a critical component of tissue protection, repair and
regeneration Numerous published studies validate its broad biological activities
Various T4 formulations developed to optimize clinical potential
Conducting and supporting multiple clinical trials in 2011 Phase 2 trial in patients after acute myocardial infarction (RGN-352 injectable solution)*
Phase 2 trial in patients with dry eye associated with GvHD (RGN-259 eye drops)
Phase 2 epidermolysis bullosa (EB) trial scheduled for completion in 2011 (RGN-137 topical gel)
2012 - Phase 1/2 trial in patients with multiple sclerosis (RGN-352 injectablesolution)
Several T4 fragments being developed for cosmeceutical products
Over 20 active research collaborations worldwide, most of which support currentclinical programs
Broad worldwide IP portfolio with patents/applications expiring from 2019 - 2030
Commitment to optimizing commercial value and investor return via strategiclicensing and partnerships
* In March 2011 the FDA placed a clinical hold on our Phase 2 AMI trial due to cGMP issues at a contract manufacturerssite formulating RGN-352. The timing for the resumption of this trial is unclear. The reader is referred to our press releasedated March 16, 2011.
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Cardiovascular &
Central Nervous SystemRGN-352
(injectable for acute myocardialinfarction, multiple sclerosis, stroke,
traumatic brain injury)About the cover July 2, 2009
The cover image, by Paul R. Riley,
illustrating a heart wrapped in a layer ofregenerating cells, is from a study showingthat thymosin 4 guides progenitor cellsfrom the outer layer of the heart to tissuerepair sites.
OphthalmicRGN-259
(eye drop for cornealindications)
Dermal
RGN-137(topical gel for dermal
wound healing)
Validation of RGN product candidates
Cosmeceuticals
(T4 peptidefragments)
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RegeneRx Product/Patients U.S.
Product DiseaseUS treatablepopulation/yr
RGN-137 Epidermolysis Bullosa* 12K
RGN-259 Neurotrophic Keratitis 4K
Physician-Sponsored Dry Eye*
Sjgrens Dry Eye** 3,000 K
RGN-352 Acute Myocardial Infarction* 650K
Multiple Sclerosis 300K
Ischemic Stroke 700K
Traumatic Brain Injury 500K
* Currently the subject of Phase 2 clinical trials ** Larger Phase 2 dry eye trial planned for H2 2011.
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Clinical targets
Initiation of Phase 2 Dry Eye trial Begun
First patient screened Q4 2010
Initiation of Phase 2 AMI trial Begun
First patient in TBD
Completion of Phase 2 EB trial targeted 2011 Initiation of Phase 1/2 MS trial TBD
Physician-sponsored
To be funded by institution and grants
Data from dry eye and EB trials 2011
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Product candidates time-lines
2010 H1 2011 H2 2011 H1 2012 H2 2012RegeneRx Drug Candidates
Acute Myocardial Infarction(Phase 2)
Multiple Sclerosis(Phase 1/2)
Neurotrophic Keratitis(Compassionate Use)
Dry Eye(Proof-of-Concept)
Dry Eye2nd Phase 2)
Epidermolysis Bullosa
(Phase 2)
RGN-352Injectable
RGN-259Eye drops
RGN-137
Topical
Note, the first patient enrolled in our Phase 2 AMI trial along with the trials duration
is not determinable, given the clinical hold currently in force by the FDA.
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RGN-352 (inject.) development
Phase 1 completed RGN-352 safe and well-tolerated at 4 dose levels
Study supports systemic use of RGN-352
Phase 2 in patients post-acute myocardial infarction underway
First patient targeted in TBD
Interim data targeted in TBD
Final enrolled patient targeted in TBD
Phase 1/2 trial in patients with multiple sclerosis
Collaboration with major U.S. medical institution applying for funding to conducttrial in 2012
Other supporting activities
Conducting non-clinical studies funded by $3 million NIH grant to supportcardiovascular program and pursuing other sources of Federally-funded research.
Continue collaborating with academic researchers on myocardial infarction andcentral nervous system indications
Continue strategic partnership discussions with large pharma
Developing RGN-352 in cardiovascular and CNS indications
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RGN-259 (ophthal.) first signs of human efficacy
First compassionate use of topicaleye drop
Patient Middle-age female
Severe diabetic
Serious cardiac and liver disease
Underwent vitrectomy surgery
Non-healing cornea after 23 dayspost-surgery
Wound healed after topicaladministration of T4 by Day 11
Immediate reduction of irritation andinflammation
Dr. Gabriel Sosne, Associate Professor of Ophthalmology, Wayne StateUniversity, Detroit Michigan
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RGN-259 administered to 10 patients
Compassionate use report from 10 patients
1 patient with non-healing surgical wound treated with RGN-259 healed in 11
days
6 patients with non-healing corneal ulcers that had not healed for 6 weeks to
several years either completely healed (4) or demonstrated significantimprovement (2) by end of treatment
3 additional patients enrolled with diffuse punctate erosions did not demonstrate
significant improvement, although did report reduced ocular irritation
RGN-259 shows signs of efficacy
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Patients Wound Closure (first 4 patients with discrete geographical
lesions)
Treatment period
Endoftreatment
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RGN-259 (Ophthalmic) development
Phase 1 not required due to safety profile
Phase 2 physician-sponsored study in patients with dry eye underway
20 patients in a Phase 2, double-blind, placebo-controlled study
Data expected in latter part of 2011
Other supporting activities Completed 1st non-clinical dry eye study with statistically significant benefit
Continue collaborating with U.S. military for prevention/reduction of eye damagecaused by chemical warfare agents
Continue discussions with potential ophthalmic partners
Pursuing other sources of Federal funding for expanded research.
Ophthalmic clinical program expands
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RGN-137 (topical) clinical development
Phase 1 completed RGN-137 safe and well-tolerated at 3 dose levels
Phase 2 two studies in venous stasis and pressure ulcers indicate thatRGN-137 can accelerate healing in mid-dose group
Phase 2 epidermolysis bullosa study completion targeted for 2011
Intend to meet with FDA to discuss converting current Phase 2 trial to apivotal study when data is unblinded Precedent due to small patient population
Will require robust data in current trial
FDA could require small supplemental trial and/or Phase 4 studies
Other supporting activities
Evaluating RGN-137 for reduction of scarring
Continue collaborations with academic researchers
Continue discussions with potential strategic partners
Orphan drug candidate offers potentially faster market approval
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RGN-137 Orphan Indications Rationale
Orphan drug candidate offers potentially faster market approval
Seven additional years of marketing exclusivity in the U.S. (10 in the EU)
Opportunities for additional indications
Attractive pricing and margins compensate for low patient numbers
Healthcare legislation favorable to orphan and rare indications
Precedent for Orphan Drug Strategy
Drug Company WW $ Sales
Myozyme Genzyme ~1B
Sabril Ovation ~60M
Naglazyme BioMarin ~$60M
Remicade Centocor ~$200M
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Research and development
Over 20 active research collaborations under MTAs or CRADAs
16 U.S. universities, medical schools, hospitals, government
4 European universities, research centers, and hospital
Include U.S. military, NIH, pharmaceutical company, cosmetic company, andCanadian university
Multiple areas of clinical focus Neurologic & stroke
Cardiovascular & cardiac repair
Ophthalmology
Dermatology
Pulmonary Tropical disease
Thrombosis
Cosmeceuticals
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Recent Non-dilutive funding
Awarded $733,000 from U.S. Government under Patient and Affordable Care Act
Received $3 million NIH award for supporting studies required for RGN-352
development for AMI and other intravenous uses such as multiple sclerosis,
stroke and traumatic brain injury ($1 million/year for three year
Applied for additional grants ranging from $200,000 to $3 million
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Selected financial data
OTC symbol: RGRX
Cash (01/31/11) est. $5.0 M
Shares outstanding 79.9 M
Fully diluted shares 101.3 M
Share price (03/11/11) $0.23
52-week price range $0.20 - $0.79
Market capitalization (03/11/11) ~$19 M
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Summary
Major studies show T4s significant effects in cardiac, multiple sclerosis,stroke, and traumatic brain injury models
RGN clinical trial targets in 2011
Phase 2 trial in patients after acute myocardial infarction*
Phase 2 trial in patients with dry eye
Phase 2 trial in patients with epidermolysis bullosa (EB)
2012 - Phase 1/2 trial in patients with multiple sclerosis (RGN-352 injectablesolution)
Continue productive research collaborations world-wide
Continue to build and maintain broad patent portfolio
Have received nearly $4.5 million in grants from NIH, FDA and US Treasury
and actively soliciting similar funding in 2011-2012
Continuing to pursue licensing and partnership deals in each clinical area
* In March 2011 the FDA placed a clinical hold on our Phase 2 AMI trial due to cGMP issues at a contract manufacturerssite formulating RGN-352. The timing for the resumption of this trial is unclear. The reader is referred to our press releasedated March 16, 2011.
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Appendix
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RGN Management
Dr. Allan Goldstein Chairman & Chief Scientific Advisor
Founder of RegeneRx, Discoverer of T1 and T4
Professor and Former Chair, Dept of Biochemistry and Molecular Biochemistry, GWU MedSchool, Washington, DC
Author of over 400 scientific articles; inventor of more than 25 U.S. Patents
J.J. Finkelstein President & CEO Former President and CEO, Cryomedical Sciences, Inc., Member of Board, TCM & MdBio
28 years senior management experience in biotechnology industry
Brought several medical products through FDA and to the market
C. Neil Lyons, C.P.A. Chief Financial Officer Practiced public accounting with Deloitte for over 10 years
Senior financial executive with HFS, Inc. (major defense contractor), Bell Atlantic, andSkyBridge, LP, (an international satellite broadband startup that raised $400 million in equity)
Accomplished in financial management, SEC regulations and corporate strategy
David Crockford Vice President, Clinical & Regulatory Affairs 28 years global regulatory and clinical affairs experience in pharmaceutical industry
Responsible for obtaining marketing approval for numerous drugs and in vitrodiagnostics
Negotiated corporate partnerships and licensing agreements with major pharmaceutical firms
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RGN Employee Experience
10-30 years of experience per employee
Participated in clinical development and/or launch of over 60 drug productsand medical devices
Expertise in:
Drug, Device & Diagnostic Development
Formulation, Manufacturing (Biologics & Small Molecule)
QA, QC
Clinical Development, Trial Conduct, Trial Monitoring, Investigator Support
Regulatory and Safety Management
Strategic Planning, Product P&Ls
Licensing and Alliance Management
Sales & Marketing, Market Research and Product Launch
Marketing Approvals and Product Registrations
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Scientific Advisory Board
Allan Goldstein, PhD Chairman & Chief Scientific Advisor Professor and Former Chair, Dept of Biochemistry and Molecular Biochemistry, GWU Med School,
Washington, DC
Herve Byron, MD, MSc Ophthalmologist, editorial board of several ophthalmic journals, New York, NY
Jo-David Fine, MD, MPH Professor of Medicine, Div of Dermatology, Vanderbilt Univ Med Ctr; specialist in EB, Nashville, TN
Ewald Hannappel, PhD Professor of Biochemistry, University of Erlangen, Nuremberg, Germany
Barrett Katz, MD, MBA Clinical Professor, Dept of Ophthalmology, Cornell University Medical School, New York, NY
Hynda Kleinman, PhD Former Chief of the Cell Biology Section at the NIDCR, Bethesda, Maryland
Brian Schreiber, MD Assistant Professor, Dept of Medicine, Division of Nephrology, Medical College of Wisconsin, Vice President,
Medical Affairs, Sigma Tau Pharmaceuticals, Gaithersburg, Maryland
Gabriel Sosne, MD Associate Professor, Dept of Ophthalmology, Wayne State Univ. School of Med and Kresge Eye Institute,
Detroit, MI
Deepak Srivastava, MD Director, Gladstone Inst of Cardiovascular Disease, Prof, Pediatrics and Biochemistry & Biophysics, Pirag
Distinguished Professor in Pediatric Dev Cardiology, Univ of California, San Francisco, CA
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RGN-259 Ophthalmic PreclinicalStudies
Mechanisms of Cellular Processes of Corneal Wound Healing
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7 days PBS 7 days Tb4
Mechanisms of Cellular Processes of Corneal Wound Healingpromoted by T4
Representative day 7 Slit lamp photographs of mouse eyes following alkali injury.(A) PBS-treated eye demonstrating dense corneal opacification and inflammation.(B) T4-treated eye with evident red reflex, indicating increase corneal clarity andhealing.
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T4 Promotes Human Corneal Epithelial Cell Migration
Day 0 Day 4
Media
Tb4
Human Corneal Epithelial Cells
Sosne et al., 2001
Rat Cornea Scrape Wound
24 hours
T4 Promotes Superior Corneal Epithelial Healing After Scrape
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T4 Promotes Superior Corneal Epithelial Healing After ScrapeInjury
Rat Corneas 36 Hours after wounding
20x MAG
control T4
T4 Promotes Corneal Epithelial Cell Adhesion to Basal Lamina
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T4 Promotes Corneal Epithelial Cell Adhesion to Basal Laminaand Intercellular Contacts in vivo
Mouse cornea heptanol debridement 42hrs
Control T4
T4 Promotes Improved Corneal Epithelial Intercellular Adhesions
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T4 Promotes Improved Corneal Epithelial Intercellular AdhesionsFollowing Injury
Mouse cornea heptanol debridement 42hrs
Control T4
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RGN-352 MS Preclinical Studies
Th i 4 Bi l i A ti iti
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Preclinical studies have shown several key activities for T4 in MS
Thymosin 4 Biologic Activities
Biological Activities Mechanisms of Action
Increases oligodendrocyte progenitor cells
(OPCs) and mature oligodendrocytes inbrain7
Stimulates
oligodendrogenesis/OPCdifferentiation7
Reduces inflammatory infiltrates7 Unknown
Induction of remyelination*Alignment of newly differentiatedOPCs along axons*
* Unpublished results
P li i l O i
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Preclinical Overview
Results OPCs increased by >200 % in brain SVZ and >80% in white matter (p
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T4 Increases Progenitor Cells in Brain after Stroke
b
T4 increases progenitor cells after stroke. NG-2 staining isincreased in the ipsilateral SVZ, striatum and corpus callosum
(CC) adjacent to the ischemic core of the T4 treated rats whencompared to saline control (see arrows). Quantitative datashow significantly increased density in these areas in the T4treated rats compared to the saline control.
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RGN-352 Cardiac Preclinical Studies
About the cover July 2, 2009
The cover image, by Paul R. Riley,illustrating a heart wrapped in a layer ofregenerating cells, is from a study showing thatthymosin 4 guides progenitor cells from theouter layer of the heart to tissue repair sites.
Th mosin 4 Biologic Acti ities
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Preclinical Studies Have Shown Several Key Activities for T4 to Support
Cardiac Tissue Protection & Repair
Biological Activities Mechanisms of Action
Promotes cell migration 1,2,4,6 Regulates G- and F-actin
Promotes angiogenesis and stem celldifferentiation 2,5,7,11
Unknown
Prevents apoptosis and promotes cellsurvival 7,9,13
Activates the PI 3K/Akt signaling pathwayUpregulates the survival kinase, Akt
Reduces inflammation 1,10,12,13
Down-regulates inflammatory cytokinesand chemokines
Inhibits leukocyte invasion and adhesionSuppresses activation of NFB
Thymosin 4 Biologic Activities
Preclinical Pharmacology
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Preclinical Pharmacology
T4 Significantly Improves Ventricular Function
Bock-Marquette, et. al, Thymosin B4 activates integrin-linked kinase and promotes cardiac cell migration,
survival and repair, NATURE, 2004
~65% Improvement of Fractional
Shortening at 4 Weeks
~100% Improvement of Ejection
Fraction at 4 Weeks
45 mice evaluated I.P., I.C., I.P. + I.C. Evaluated at 2 & 4 wks
Preclinical Pharmacology
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Preclinical Pharmacology
Bock-Marquette, et. al, Thymosin B4 activates integrin-linked kinase and promotes cardiac cell migration, survival and repair,
NATURE, 2004
T4 Reduces Heart Muscle Damage After Heart Injury
Blue staining indicates scar tissue, red indicates viable
myocardium
p < 0.02
~53% Reduction in Scar Volume
Biologic Activities
1. Prevents apoptosis
2. Enhanced myocardial salvage
20 mice
I.P., I.C. Evaluated at 14 days post-ligation
Preclinical Pharmacology
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Preclinical Pharmacology
T4 Affects Cardiomyocyte and Endothelial Cell Survival and Inflammation
T4 Enhances PosthypoxicCardiomyocyte Survival
T4 Reduces LeukocyteAdhesion In Vitro
# p
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Animal T4 Dose Regimen ROA Pub
Permanently ligatedmouse (25-30 g)
150 gOnce every 3rd dayfor 28 days
Intraperitoneal Nature 2004
Permanently ligated
mouse (25-30 g)
15 g150 g1500 g
QD for 14 days Intravenous (tail vein)Ann NY Acad Sci
2007
Mouse embryos with heart-specific T4 deficiency andepicardial explants
NA NANA - in vitroexposure ofepicardial explants to T4
Nature 2007
Ischemia-reperfusion(LAD) pig model (24-26 kg)
15 mg Single dosePressure-regulated 10-minuteretroinfusion into the anteriorinterventricular vein
Circulation 2008
Permanently ligatedmouse (25-30 g)
150 g Single dose IntraperitonealJ Mol CellCardiology 2009
Preclinical Dosing and Regimen Overview
Preclinical Cardiac
Preclinical Cardiac
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RGN-352/T4 Preclinical Cardiac Data Highlights
T4-treated neonatal cardiomyocytes migrate further, beat more rhythmically, more rapidly and morevigorously and survive for up to 28 days vs 7-14 days compared to controls (p
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