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OneMedForum New York Company Presentation: Soligenix, Inc., a late-stage biopharmaceutical company, focuses on the development of products to treat life-threatening side effects of cancer treatments. Learn More at: http://www.onemedplace.com/database/list/cid/14016
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OTC BB: SNGX
Forward-Looking Statements
This presentation contains forward-looking statements that reflect Soligenix, Inc.'s current expectations about its future results, performance, prospects and opportunities. Statements that are not historical facts, such as "anticipates," "believes," "intends," or similar expressions, are forward-looking statements. These statements are subject to a number of risks, uncertainties and other factors that could cause actual events or results in future periods to differ materially from what is expressed in, or implied by, these statements. Soligenix cannot assure you that it will be able to successfully develop or commercialize products based on its technology, including orBec®, SGX201, RiVax™, and LPMTM, particularly in light of the significant uncertainty inherent in developing vaccines against bioterror threats, manufacturing and conducting preclinical and clinical trials of vaccines, and obtaining regulatory approvals, that its cash expenditures will not exceed projected levels, that product development and commercialization efforts will not be reduced or discontinued due to difficulties or delays in clinical trials or due to lack of progress or positive results from research and development efforts, that it will be able to successfully obtain any further grants and awards, maintain its existing grants which are subject to performance, enter into any biodefense procurement contracts with the US Government or other countries, that the US Congress may not pass any legislation that would provide additional funding for the Project BioShield program, that it will be able to patent, register or protect its technology from challenge and products from competition or maintain or expand its license agreements with its current licensors, or that its business strategy will be successful. Important factors which may affect the future use of orBec® for gastrointestinal GVHD include the risks that: the FDA's requirement that Soligenix conduct additional clinical trials to demonstrate the safety and efficacy of orBec® will take a significant amount of time and money to complete and positive results leading to regulatory approval cannot be assumed; Soligenix is dependent on the expertise, effort, priorities and contractual obligations of third parties in the clinical trials, manufacturing, marketing, sales and distribution of its products; orBec® may not gain market acceptance if it is eventually approved by the FDA; and others may develop technologies or products superior to orBec®. Factors affecting the development and use of SGX201, RiVax™, and LPMTM are similar to those affecting orBec®. These and other factors are described from time to time in filings with the Securities and Exchange Commission, including, but not limited to, Soligenix's reports on Forms 10-Q and 10-K. Unless required by law, Soligenix assumes no obligation to update or revise any forward-looking statements as a result of new information or future events.
2
Soligenix, Inc. is a late-stage, biopharmaceutical
company developing products to treat life-threatening
side effects of cancer treatments and serious
gastrointestinal diseases, and vaccines for certain
bioterrorism agents
Soligenix
3
Value Proposition
1. Low current valuation of approximately $60 million • Potential for exponential growth with the achievement of a single milestone – A positive
confirmatory Phase 3 clinical trial of orBec®
• Relatively low risk and late stage drug development proposition due to existing orBec® Phase 3 data
2. Four active clinical trials
3. Clean capital structure with no debt or preferred stock outstanding
4. FDA SPA and EMEA agreement on Phase 3 protocol supports regulatory path to approval in US and EU
5. 35% royalty generating North American partnership with Sigma-Tau on orBec®
6. orBec® addresses a potential $400 million global GVHD market, where there is an unmet medical need with poor therapeutic options
7. Oral BDP application in other GI areas - Radiation Enteritis and Crohn’s Disease; markets in excess of $500 million worldwide
8. LPM™ - novel oral delivery system for drugs such as leuprolide
9. Diversified portfolio: BioTherapeutics and BioDefense• BioDefense - Grant funded and revenue generating – New $9.4 million NIH grant
− Soligenix is world leader in ricin toxin vaccine research
4
Pipeline
Biotherapeutics Preclinical Phase 1 Phase 2 Phase 3orBec® Treatment of GVHD orBec®Prevention of GVHD orBec®Treatment of Chronic GVHD SGX201 Radiation Enteritis SGX203Crohn’s Disease LPM™ LeuprolideProstate Cancer/Endometriosis Biodefense Proof of Concept Animal Phase 1 Phase 2/3
RiVax™ - VaccineRicin Toxin Exposure SGX202 - Therapeutic Radiation Injury
FAST TRACK and ORPHAN DESIGNATION
ORPHAN DESIGNATION
ORPHAN DESIGNATION
FAST TRACK DESIGNATION
ORPHAN DESIGNATION
Programs highlighted in green are supported in whole or in part by NIH funding .
FDA ANIMAL RULE
FDA ANIMAL RULE
5
Management Team
Executive Yrs. Exp Industry Experience
Christopher J. Schaber, PhD 21 Discovery Laboratories, Inc. (COO)
President and CEO Acute Therapeutics, Inc. (Co-Founder)Ohmeda PPD, Inc.The Liposome Company, Inc.Wyeth Ayerst
Evan Myrianthopoulos 15 CVL Advisors Group, Inc., - Life science Chief Financial Officer financial consulting firm
Discovery Laboratories (CFO, VP Finance)Paramount Capital Investments, LLC
Brian Hamilton, MD, PhD 30 Astra, USA Chief Medical Officer Wyeth Research
Alkermes, Inc.University of Washington
Robert Brey, PhD 27 Lederle-Praxis, division of American Chief Scientific Officer Cyanamid
Vaxcel, Inc.
6
orBec®
Gastrointestinal Graft-versus-Host Disease (GI GVHD)
An Unmet Medical Need
BioTherapeutics – Lead Program
7
Gastrointestinal GVHD
Normal Upper GI Mucosa Acute GvHD
• Unmet medical need – orphan disease• Occurs in leukemia and other blood cancer patients who undergo bone
marrow or stem cell transplantation• Patients’ tissue attacked by lymphocytes of donor marrow/stem cells• Most debilitating symptoms occur in stomach and small intestine• Symptoms include anorexia, nausea, vomiting, bloody stool, necrosis and
exfoliation of endothelial cells• Treated with high dose systemic prednisone – for lack of better treatment
Normal Upper GI Mucosa Acute GvHD
8
orBec® (oral beclomethasone dipropionate or BDP)
• Beclomethasone – Potent, topically active, anti-inflammatory steroid− Designed to treat inflammation within lining of GI tract
• orBec® strategy is to decrease need for prolonged use of high dose systemic prednisone
• Treatment with prednisone: effective, but highly toxic− Increases susceptibility to opportunistic infection− Inhibits positive Graft-versus-Leukemia (GvL) effect
• orBec® clinical advantage gained by:− Fewer opportunistic infections− Enhanced GvL effect - fewer relapses, improved survival− Shortening of prednisone course− Sustained remission of GI GVHD
• Fast Track and Orphan Drug Designations for treatment of acute GI GVHD
orBec®
9
orBec® - A Targeted Approach to GI GVHD
A Two-Pill System• Each tablet contains 1 mg BDP
• 1 Immediate Release (IR) tablet designed to release in the upper GI tract and 1 Enteric Coated (EC) tablet designed to release in the lower GI tract
• Total of only 8 mgs BDP per day
Diagram showing dispersion of IR tablet in the stomach
Diagram showing dispersion of IR and EC tablets in small intestine
10
orBec® - Risk/Benefit Analysis
Clinical Significance:• Statistically significant reductions in GVHD treatment failures
• Statistically significant increase in daily caloric intake ability
• Statistically significant reductions in mortality
Safety:• Well established – beclomethasone known to FDA
• No major side effects seen in orBec® trials
• Superior safety profile compared to high dose prednisone
• Beclomethasone use previously approved by FDA:
− Becloforte® – inhalant marketed by Glaxo and used to treat asthma
− Beconase® – nasal spray marketed by Glaxo for rhinitis
− Propaderm® – topical cream for psoriasis
Positive Phase 2 and 3 clinical trial data provide strong support for Confirmatory, Pivotal Phase 3 Study
11
McDonald et al. 1998. Gastroenterology
Primary endpoint achieved – Positive response to orBec® therapy at Day 30• Positive response defined as the ability to consume > 70% of expected daily caloric
requirements• Rapid control of GI GVHD not requiring additional prednisone
Secondary endpoint achieved• Positive treatment response through Study Day 40
orBec® - Phase 2 Study Results
60-patient randomized, double-blind, placebo-controlled, single center trial
Endpoints orBec®
n=31Placebo
n=29p-value
Treatment Responders at Day 30 (Primary endpoint)
22 (71%) 12 (41%) 0.021
Treatment Responders at Day 40 16 (52%) 5 (17%) 0.005
12
orBec® - Previous Phase 3 Study Results
Endpoints orBec®
n=62Placebo
n=67p-value
Time to Treatment Failure through Day 50 (primary endpoint)
0.118
Treatment Failure Rate at Day 50
18 (31%)
30 (48%)
0.051
Time to Treatment Failure through Day 80
0.023
Treatment Failure Rate at Day 80
22 (39%)
39 (65%)
0.005
Mortality Rate at 200 Days Post-Transplant
5 (8%)
16 (24%)
0.014
Placebo
BDP
0.00
0.25
0.50
0.75
1.00
Days since randomization
0 10 20 30 40 50 60 70 80 90
Time to Treatment Failure through Day 80
p = 0.0226
129-patient randomized, double-blind, placebo-controlled, multicenter trial
Hockenbery et al. 2007. Blood
13
orBec® - Comprehensive Mortality Data
Long-Term SurvivalOutcomes orBec® Placebo
p-value orBec® vs.
placebo
Percentagereduction
in mortality
Mortality Rate at 200 days posttransplant - Pivotal Phase 3 study
5 (8%) 16 (24%) .013 66%
Mortality Rate at 200 days posttransplant - Prior Phase 2 study
3 (10%) 6 (21%) 0.18 55%
Mortality Rate among mismatcheddonors at 200 days post transplant Pivotal Phase 3 study
1 (4%) 10 (42%) 0.02 94%
Mortality Rate at 1 year postrandomization - Pivotal Phase 3 study
18 (29%) 28 (42%) 0.04 46%
Mortality Rate at 1 year postrandomization - Prior Phase 2 study
6 (19%) 9 (31%) 0.26 45%
Mortality Rate at median time periods at 3.5 years – Both studies combined
37 (40%) 49 (51%) 0.03 37%
Hockenbery et al. 2007. Blood
14
orBec® Clinical Development Path Forward
• Special Protocol Assessment (SPA) for confirmatory, pivotal Phase 3 clinical trial cleared by FDA− Highly powered clinical trial of similar design to previous Phase 3
study is acceptable to support a regulatory submission seeking new drug approval
− Enrollment sample size – approximately166 patients
− New Primary Endpoint – Treatment failure rate at Study Day 80 – highly statistically significant in previous Phase 3 trial with p-value of 0.005
• EMEA Agreement on Phase 3 protocol for potential EU approval
• With 2 positive trials completed – strong basis for confidence in efficacy of confirmatory trial
• Trial initiated; completion targeted for 1H 2011
15
Prior Phase 3 Confirmatory Phase 3
Number of sites Multicenter Multicenter
Number of patients
129 166
Patient population
Allogeneic transplant patients with
Grade 2 GI GVHDSame
Powering80% at a two-sided significance level of
0.0590% at a two-sided significance level of
0.05
Primary endpointTime to Treatment Failure Through Day
50Treatment Failure Rate at Day 80
(p-value of 0.005 in prior Phase 3)
Dosing regimen8 mg BDP per day / 1 mg BDP per
tablet
/ dosing duration 50 daysSame
Design
2 Randomized groups: High dose prednisone for 10 days followed by
rapid taper with 50 days on placebo or drug
Same
Confirmatory Phase 3 Replicates Prior Study
Improvements in design including change of primary endpoint increase likelihood of success The key factors - drug, dose, patient population and expected control group outcomes - have
remained constant since the prior Phase 3
16
Sigma-Tau Partnership and Commercialization
• Marketing partnership with Sigma-Tau aimed at launching orBec® in North America− 35% royalty on net sales back to Soligenix− $10 million in milestones with $1 million milestone received upon enrollment of first patient in
confirmatory trial− Soligenix to lead all R&D and regulatory
• Certain inherent market factors suggest quick launch and significant penetration− No competition – Nothing approved by FDA for GI GVHD − Rapid dissemination of information− Focused market – 15 transplant centers do 60% of all transplants
• Soligenix seeking marketing partners in Europe and ROW
17
Lifecycle Management – New BDP Trials
Program Purpose# of Available
PatientsStatus
Prevention of GVHD Decrease incidence or severity of acute GVHD 10,000+ US
Phase 2 – 140 patientsenrollment completed 1H 2010
Radiation Enteritis
Block inflammatory component of acute radiation enteritis in GI tract in rectal cancer patients receiving radiation therapy
50,000+ US
Initiated. Supported by $500,000 NIH grantFast Track granted Completion targeted 1H 2011
Chronic GI GVHDDecrease need for systemic immunosuppressive therapy in chronic GI GVHD
6,000+ USPhase 2 protocol Initiation targeted for 2H 2010
Crohn’s Disease Minimize inflammation in chronic GI conditions
500,000 US100,000 Pediatric US
TBD
18
Worldwide Potential Oral BDP Market
$300
$100
0
50
100
150
200$ M
illi
on
s
250
300
$200
orBec®
GVHDTreatment
$120
400
450
350
orBec®
GVHDPrevention
orBec®
GVHD Chronic
Oral BDPRadiationEnteritis
Assumptions~ 20,000 allogeneic transplants annually
~ 7% annual market growth
Acute GI GVHD Treatment 5,000 Patients US 5,000 Patients Europe
Acute GVHD Prevention10,000 Patients US
10,000 Patients Europe
Chronic GI GVHD Treatment6,000 Patients US
6,000 Patients Europe
Radiation Enteritis50,000 Patients US
50,000 Patients Europe
Crohn’s Disease500,000 Patients US
500,000 Patients EuropeOral BDPCrohn’sDisease
>$500500
19
Lipid Polymer Micelle (LPMTM)
Delivery System
for Improving Oral Drug/Peptide Absorption
BioTherapeutics – Pipeline Expansion
20
Lipid Polymer Micelles (LPM)
• Drug delivery system potentially applicable to a wide variety of poorly absorbable water-soluble drugs/peptides (500 - 5,000 daltons)
• Stable reverse micelle composed of GRAS lipids and polymers
• Transiently opens tight junctions in intestinal mucosa
• High relative bioavailability
• First candidate selected: − GnRH analog: Leuprolide (1200 daltons)
• Pre-clinical proof-of-concept: Reproducible and consistent absorption in rats and dogs− LPM achieved 20-40% bioavailability with leuprolide versus <5% with
straight oral delivery
• Next steps: Complete preclinical work and conduct Phase 1 human PK study to confirm preclinical findings
21
Paracellular Transport
Peptides and small proteins do not normally penetrate intestinal epithelial barriers
Tight junctions (TJ) are inter-cellular contact points that regulate intestinal absorption of solutes and nutrients
TJ consist of a belt of protein strands and lipids that surround the lateral membrane of epithelial cells and seals the outermost end of the intercellular space.
In the presence of LPM (polymer stabilized reverse micelles) tight junctions transiently open and allow the penetration of small proteins and peptides with a hydrodynamic radius in the range of small molecules, proteins and cells across these barriers in the range of 8–20 degrees.
Apical surface
Intestinal epithelial cells
Basal surface
surface
Paracellular transport of peptides
Tight Junction
Reverse Micelles and Paracellular Transport
22
Leuprolide Market
• Annual US sales of Leuprolide approx. $1.7 billion
• Other approved/marketed LHRH agonists:
− Lupron (Lupron Depot, TAP)
− Goserelin (Zoladex, Astra/Zeneca), 1-3 month s.c. implant
− Nafarelin (Synarel, Pharmacia), intranasal solution
− Histrelin (Supprelin, Roberts), s.c. daily injection
• Indications:
− Prostate cancer
− Endometriosis and puberty in children
• Other depot formulations available (1,3,4 & 6 months)
• No oral product on the market
23
RiVaxTM
Ricin Toxin Vaccine (Phase 1)
BioDefense – Lead Program
Castor Bean
24
Ricin - Evolution Of A Threat
from “Ricin: Technical Background and potential Role in Terrorism,” Dana Shea and Frank Gottron, CRS Report for Congress; February 4, 2004
1940s – weaponized by UK military“Compound W”
1978 – Umbrella Assassination in London of Bulgarian dissident Georgi Markov
1991 – Minnesota Patriots Council found with 0.7 g ricin; arrested and convicted
1995 – Thomas Lewis Lavy arrested for possession of 130 g ricin while crossing into Canada from Alaska
2002 – Kenneth Olson arrested and sentenced 13 years for producing ricin
2003 – Secret Service intercepted a letter contaminated with ricin addressed to the White House
2004 – US Senate closed - Ricin detected in mail sent to Senate Majority Leader Bill Frist
2004 - Reports of ricin in Afghanistan/Al Qaeda
2005 - Reports of ricin possession in Florida and Arizona
2007- Ricin highlighted in FBI terrorism report as top bioterror threat along with Anthrax
2008 - Roger Bergendorff put himself in coma after ricin exposure in Las Vegas Motel
25
2007 FBI Terrorism Report
“Ricin and the bacterial
agent anthrax are
emerging as the most
prevalent agents involved
in WMD investigations”
FBI Terrorism Report,
November 2007
26
RiVax™
Profile:• Soligenix is world leader in ricin toxin vaccine research• Vaccine is derived from a non toxic recombinant ricin A chain• Retains immunogenic properties: induces production of serum antibodies capable of neutralizing native ricin toxin
Funding:• Recent $9.4 million NIH grant to develop heat stable vaccines• Received >$20 million NIAID grant funding to date• Partner UT Southwestern received $3.6 million grant funding
Status:• Phase 1 clinical trial complete: Demonstrated safety and immunogenicity in humans• Non-human primate study initiated• Phase 1b clinical trial underway at UTSW: adjuvant formulation• Scale-up GMP process optimization and development completed
Next Milestones:• Complete Phase 1B clinical trial• Manufacture large scale commercial grade batches for future clinical
trials and potential procurement contracts• Continue development under new $9.4 million heat stabilization grant
Castor beans
27
Milestone Events - Past & Future
Event 22009 1H 2010
2H 2010
1H 2011
SPA cleared by FDA and EMEA for orBec® confirmatory Phase 3 trial √
Fast Track granted for SGX201 for Radiation Enteritis √ Completed $30 million partnership with Sigma-Tau for orBec® in NA √ Received $9.4 million NIH grant award for heat stable vaccine development
√
Initiated confirmatory orBec® Phase 3 study in acute GI GVHD √ Initiated Phase 1/2 Radiation Enteritis study with SGX201 √ Patents granted in US for treatment of IBS and in EU for treatment of inflammatory GI disorders
√
Complete enrollment of orBec® Phase 2 study in prevention of acute GVHD
√
Announce results of orBec® Phase 2 study in prevention of acute GVHD
+
Complete Phase 1B clinical trial for RiVax™ + Initiate Phase 2 study of orBec® in chronic GI GVHD + Complete European partnership for orBec® + Initiate Phase 1 PK study of LPMTM leuprolide + Complete confirmatory Phase 3 clinical trial of orBec® in GI GVHD + Complete Phase 1/2 study with SGX201 in radiation enteritis +
28
Investment Highlights
29
1. Low current valuation of approximately $60 million • Potential for exponential growth with the achievement of a single milestone – A positive
confirmatory Phase 3 clinical trial of orBec®
• Relatively low risk and late stage drug development proposition due to existing orBec® Phase 3 data
2. Four active clinical trials
3. Clean capital structure with no debt or preferred stock outstanding
4. FDA SPA and EMEA agreement on Phase 3 protocol supports regulatory path to approval in US and EU
5. 35% royalty generating North American partnership with Sigma-Tau on orBec®
6. orBec® addresses a potential $400 million global GVHD market, where there is an unmet medical need with poor therapeutic options
7. Oral BDP application in other GI areas - Radiation Enteritis and Crohn’s Disease; markets in excess of $500 million worldwide
8. LPM™ - novel oral delivery system for drugs such as leuprolide
9. Diversified portfolio: BioTherapeutics and BioDefense• BioDefense - Grant funded and revenue generating – New $9.4 million NIH grant
− Soligenix is world leader in ricin toxin vaccine research
THANK YOU www.soligenix.com
BioTherapeutics | BioDefense