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| 8-K - FORM 8-K - Fibrocell Science, Inc. | fcsc051816form8-k.htm |
Corporate Presentation May 18, 2016
This presentation and our accompanying remarks contain “forward-looking statements” within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. All statements that are not historical facts are hereby identified as forward-looking statements for this purpose and include, among others, statements relating to: the potential advantages of our product candidates; the initiation, design and timing of pre-clinical studies and clinical trials and activities and the reporting of the results thereof; the timing of regulatory submissions and actions; expected milestones; and all other statements relating to our future operations, future financial performance, future financial condition, prospects or other future events. Forward-looking statements are based upon our current expectations and assumptions and are subject to a number of known and unknown risks, uncertainties and other factors that could cause actual results to differ materially and adversely from those expressed or implied by such statements. Factors that could cause or contribute to such differences include, among others: our ability to obtain additional capital to fund our operations; FDA allowance to treat pediatric subjects in the Phase II portion of our Phase I/II clinical trial of FCX-007; uncertainties relating to the initiation and completion of clinical trials and whether the results will validate and support the safety and efficacy of our product candidates; the risk that results seen in pre-clinical studies may not be replicated in humans; varying interpretation of clinical and pre-clinical data; our ability to maintain our collaborations with Intrexon; and the other factors discussed under the caption “Item 1A. Risk Factors” in our most recent annual report on Form 10-K which is available through the “Investors—SEC Filings” page of our website at www.fibrocell.com. As a result, you should not place undue reliance on forward-looking statements. The forward-looking statements made in connection with this presentation represent our views only as of the date of this presentation (or any earlier date indicated in such statement). While we may update certain forward-looking statements from time to time, we specifically disclaim any obligation to do so, even if new information becomes available in the future. 2 Forward-Looking Statements
Company Highlights • Cell and gene therapy company developing a pipeline of autologous biologics for localized treatment of diseases affecting the skin, connective tissue and joints Pipeline based on proprietary fibroblast platform • Phase II azficel-T program for Vocal Cord Scarring resulting in Chronic or Severe Dysphonia Last subject visit for primary endpoint analysis completed April 2016 Phase II data expected June 2016 • FCX-007 for Recessive Dystrophic Epidermolysis Bullosa (RDEB) Expect to initiate Phase I clinical trial in adults June 2016 Granted pediatric rare disease designation by FDA Collaboration with Intrexon (NYSE: XON) • FCX-013 for Linear Scleroderma Proof-of-concept completed January 2016; IND planned 2017 Received FDA orphan drug designation for treatment of localized scleroderma Collaboration with Intrexon • New gene therapy program with Intrexon for Arthritis and related conditions Goal is to deliver a protein therapy locally to the joint providing sustained efficacy while avoiding key side effects typically associated with systemic therapy 3
Autologous Fibroblasts as a Platform for Therapy • Fibroblasts repair tissue infrastructure by producing extracellular matrix proteins including collagen and growth factors •Most common cell in skin and connective tissue •Key advantages of our autologous fibroblast platform for creating cell and gene therapies: Localized administration avoids side effects typically associated with systemic therapy Reduced rejection concerns because autologous fibroblasts are compatible with the unique biology of each patient Fibroblasts are genetically-modified ex vivo to enable testing for safety and confirmation of protein expression prior to administration Expertise in manufacturing fibroblasts •We are using our proprietary technology to create personalized biologics 4
Two Product Engines – Multiple Therapeutics in Development 5 Personalized Biologics Approach
• Leveraging existing azficel-T BLA and cell manufacturing process for all pipeline candidates (Genetically-Modified & non-GM) • Experts in cGMP manufacturing of autologous fibroblasts •Operator of cGMP cell therapy manufacturing facility routinely inspected by FDA for production of azficel-T •Process is proven, reproducible, scalable 6 Manufacturing Expertise
Development Pipeline 7 Personalized Biologics Indication Research Pre-Clinical Development Phase I Phase II Phase III azficel-T* Vocal Cord Scarring Resulting in Chronic or Severe Dysphonia FCX-007√ Orphan Product Candidate Recessive Dystrophic Epidermolysis Bullosa (RDEB) FCX-013√ Orphan Product Candidate Linear Scleroderma New Gene Therapy Program√ Arthritis *azficel-T currently approved for treatment of nasolabial fold wrinkles in adults √ Program partnered with Intrexon
Vocal Cord Scarring Resulting in Chronic or Severe Dysphonia 8 Disease Current Treatments Epidemiology Damage to the fibroblast layer causes scarring and edema, which limits air flow and results in severe and significant limitations in voice quality, often loss of voice Current treatments only address symptoms: • Voice therapy • Surgery Injection (collagen, fat, calcium, hyaluronic acid) Implant (PTFE, silastic) Approximately 64,000 patients in the U.S. suffer with vocal cord scarring resulting in chronic or severe dysphonia1 Healthy Vocal Cord Scarred Vocal Cord
Clinical Data Support Our Approach in Vocal Cord Scarring Positive Phase I clinical trial results published in peer-reviewed journal2 • Injection of azficel-T into scarred vocal cord was well-tolerated in trial (n=5) All patients completed the trial No serious adverse events reported •Positive trend of sustained improvement Sustained improvement from month 3 through 12 was noted in a majority of patients in the mucosal wave grade assessment, voice handicap index Primary endpoint data summary (n=5) 9 Scale Result (Mean + StDev) Baseline 4 Months (change from baseline) 12 Months (change from baseline) Mucosal Wave Grade* 1.3 + 0.5 3 + 1.5 (1.7) 3.2 + 1.6 (1.9) Voice Handicap Index# 83.8 + 10.9 55.8 + 9.8 (-28) 52.6 + 13.5 (-31.2) *Measured on a 1-5 scale, 1 = wave absent and 5 = wave normal. #Subject scored over 30 items from 0-4. A reduction in score is an improvement in voice quality. An 18-point change is considered significant.
Vocal Cord Scarring—Phase II Trial 10 •Double-blind, randomized, placebo-controlled (21 subjects) One dose per vocal cord per month x 3 treatments Last subject visit completed for primary endpoint analysis April 2016 • Primary endpoint: Four-month efficacy on three different scales Voice Handicap Index Mucosal Wave Grade GRBAS (grade, roughness, breathiness, asthenia & strain) • Expect to report primary endpoint results June 2016
Recessive Dystrophic Epidermolysis Bullosa 11 Disease Current Treatments Epidemiology • Cause: A mutation in the COL7A1 gene that encodes for COL7 • Devastating, progressive, painful blistering disease that often leads to death • Diagnosed at infancy • High mortality rate • Current treatments only address symptoms Bandaging & antibiotics – bandaging alone can exceed $10,000 per month3 Feeding tubes Surgery, including hand and esophageal Dystrophic EB (DEB) ~5,500 – 12,500 US4 • RDEB ~1,100 – 2,500 US5
FCX-007 Providing Hope for RDEB Patients 12 RDEB patients do not produce type VII collagen (COL7) due to mutation in COL7A1 gene Main component of anchoring fibrils that connect skin layers FCX-007 is an autologous human dermal fibroblast transduced with a lentiviral (LV) vector encoded for COL7A1 Simple, local injection to the papillary dermis
13 Detection of COL7 Expression by Immunofluorescence • In vitro COL7 expression noted from FCX-007 replicates (red) • FCX-007 expresses higher levels of COL7 than normal human dermal fibroblasts (NHDF) as depicted by a brighter signal • No expression in RDEB-positive cells NHDF RDEB+ FCX-007 Replicate 1 FCX-007 Replicate 2 Magnification 20x
COL7 Expression Confirmation 14 Culture supernatant evaluated for in vitro COL7 expression • ELISA assay indicates virus dose-dependent protein expression • Trimeric form of COL7 produced by RDEB patient fibroblasts transduced with LV-COL7 •Must be trimeric to be functional Reference: Bruckner-Tuderman, Leena. Can Type VII Collagen Injections Cure Dystrophic Epidermolysis Bullosa? Molecular Therapy (2008) 17 1, 6–7. RD EB + C o n tr o l P u ri fi e d C OL 7 FC X -0 0 7 -0 1 FC X -0 0 7 -0 2 Trimeric COL7 (900kDa) COL7 IP Immunoprecipitation (IP)/Western Blot COL7 Formation Trimeric Form (900kDa)
The persistence of COL7 expressed by FCX-007 will be evaluated in clinical trials. We believe persistence will be long-lasting due to: • Autologous cells having less rejection risk • Direct administration of FCX-007 to the upper dermis ensures COL7 is expressed in the vicinity of the basement membrane zone where anchoring fibrils are formed • The integrative nature of the lentivirus allows the COL7A1 gene to be passed to daughter cells as FCX-007 cells divide • Academic research suggests that in vivo COL7 expression persists for at least one year in RDEB skin tissue regenerated on immunodeficient mice6 • Even if COL7A1 transgene expression were silenced, COL7 anchoring fibers would persist, perhaps for years, due to slow turnover rate and long life of molecules7 15 COL7 Persistence
FCX-007 Phase I/II Clinical Trial Design 16 Title A Phase I/II Trial of FCX-007 (Genetically-Modified Autologous Human Dermal Fibroblasts) for Recessive Dystrophic Epidermolysis Bullosa (RDEB) Statement of Purpose The purpose of this study is threefold: 1) To evaluate the safety of FCX-007 2) To evaluate COL7 expression & presence of anchoring fibrils resulting from FCX-007 3) To analyze wound healing as a result of FCX-007 administration Objectives Primary 1) The primary objective of this protocol is to evaluate the safety of FCX-007 Secondary 1) To evaluate mechanism of action of FCX-007 at weeks 12, 25, 52 and unscheduled visits through the evaluation of skin biopsies for COL7 expression and the presence of anchoring fibrils 2) To evaluate the efficacy of FCX-007 through an intra-subject paired analysis of target wound area at weeks 4, 12, 25, 52 and unscheduled visits, comparing FCX-007 treated wounds to untreated wounds in Phase I and to wounds administered sterile saline in Phase II through the evaluation of digital imaging of wounds Number of Subjects Twelve subjects consisting of six adults in the Phase I portion of the trial and, subject to FDA allowance, six pediatrics in the Phase II portion of the trial. Next Step Expect to initiate Phase I portion of the trial June 2016
Linear Scleroderma 17 Disease Epidemiology • Excess production of collagen I and III characterized by skin fibrosis and linear scars • The linear areas of skin thickening may extend to underlying tissue and muscle in children which may impair growth in affected legs and arms or forehead • Lesions appearing across joints impair motion and may be permanent • Localized Scleroderma ~200,000 sufferers US8 comprised of many different sub-types Linear Scleroderma Initial target for FCX-013 is a group of ~40,000 patients who have scleroderma over a major joint and exhibit severe joint pain9 Current Treatments Current treatments only address symptoms: • Systemic or topical corticosteroids • UVA light therapy • Physical therapy Photo: Reprinted from the Journal of the American Academy of Dermatology, Volume 59, Issue 3, Stéphanie Christen-Zaech, Miriam D. Hakim, F. Sule Afsar, Amy S. Paller. Pediatric morphea (localized scleroderma): Review of 136 patients, Figure 1, pp. 385-396. Copyright Sept 2008. Used with permission from Elsevier Ltd.
FCX-013 Development Progressing 18 •Product profile Autologous fibroblasts genetically modified using lentivirus and encoded for a protein responsible for breaking down excess collagen I and III Incorporates Intrexon’s RheoSwitch Therapeutic System® (RTS®) •Proof-of-concept animal study data achieved January 2016 Demonstrated protein expression •Preparing scale-up manufacturing •Received FDA orphan drug designation for treatment of localized scleroderma •Next steps include dose-ranging and toxicology/biodistribution studies •IND submission expected 2017
FCX-013 Proof-of-Concept Study 19 • Study Design Bleomycin treated SCID mouse model N=30 mice over test and control groups Assessed histologically for reduction of dermal thickness and sub-dermal muscle in the presence of FCX-013 and oral ligand • Result Bleomycin treatment resulted in skin fibrosis, measured by a significant increase in dermal thickness Demonstrated that FCX-013 with ligand reduced the dermal thickness of fibrotic tissue to levels similar to non-bleomycin (saline) with ligand treated skin Further reduced the thickness of the sub-dermal muscle layer Blecomycin treatments Ligand Treatment D0 D28 D29 D39 Cell injection Harvest skin samples CONTROL: Saline (no Bleo) No Cells TEST: Bleomycin FCX-013 CONTROL: Bleomycin Non-Modified Cells
• FCX-013 employs Intrexon’s RheoSwitch Therapeutic System® (RTS®) The RTS® biologic switch is activated by an orally- administered activator ligand (AL) that provides the ability to control level and timing of protein expression in those diseases where such control is ideal • Enhances the safety profile of FCX-013 by providing control over the expression of the protein responsible for breaking down excess collagen • In vitro studies support RTS® control over FCX- 013 protein expression: Significant increase in expression of the target protein in the presence of the AL In the absence of the AL, the expression is reduced to normal cellular production of the target protein Cells transduced with RTS® and off-target gene construct (RTS-GFP) and non-transduced fibroblasts (mock) express normal cellular production levels 20 RheoSwitch® Control RTS-GFP Control FCX-013 1:16 Mock Control FCX-013 RTS® Control no AL + AL Ta rg et P ro tein Conce n tr ati o n
New Gene Therapy Collaboration with Intrexon 21 •Goal is to deliver a protein therapy locally to the joint providing sustained efficacy while avoiding key side effects typically associated with systemic therapy • Collaboration combines Fibrocell’s autologous fibroblast technology with Intrexon’s cellular engineering to develop localized gene therapies • Focused on addressing chronic inflammation and degenerative diseases of the joint Arthritis (characterized by joint inflammation, pain and decreased range of motion) is the leading cause of disability in the U.S. affecting >52 million adults and 300,000 children
Expected Milestones & Corporate Information 22 •Cash = $13.1 million at 31 Mar 2016 (unaudited) •43.9 million common shares of FCSC outstanding at 31 Mar 2016 5.3 million warrants; 4.0 million options Expected Milestones Timing FCX-007 Phase I/II Trial Initiation June 2016 azficel-T Phase II Data June 2016 FCX-013 IND Submission 2017
Company Highlights • Cell and gene therapy company developing a pipeline of autologous biologics for localized treatment of diseases affecting the skin, connective tissue and joints Pipeline based on proprietary fibroblast platform • Phase II azficel-T program for Vocal Cord Scarring resulting in Chronic or Severe Dysphonia Last subject visit for primary endpoint analysis completed April 2016 Phase II data expected June 2016 • FCX-007 for Recessive Dystrophic Epidermolysis Bullosa (RDEB) Expect to initiate Phase I clinical trial in adults June 2016 Granted pediatric rare disease designation by FDA Collaboration with Intrexon (NYSE: XON) • FCX-013 for Linear Scleroderma Proof-of-concept completed January 2016; IND planned 2017 Received FDA orphan drug designation for treatment of localized scleroderma Collaboration with Intrexon • New gene therapy program with Intrexon for Arthritis and related conditions Goal is to deliver a protein therapy locally to the joint providing sustained efficacy while avoiding key side effects typically associated with systemic therapy 23
References 1Data on file. Fibrocell Science, Inc. 2Chhetri D, et al. Injection of cultured autologous fibroblasts for human vocal fold scars. The Laryngoscope. 2011;121(4):785-792. 3The Dystrophic Epidermolysis Research Association of America (DebRA). DEB brochure, page 6: http://www.debra.org/pdfs/Debra-of-America-Brochure.pdf; accessed 07/20/15. 4DEBRA International. What is EB Infographic: http://www.debra-international.org/epidermolysis-bullosa.html.; accessed 10/06/2014. 5Petrof G., et al. Fibroblast cell therapy enhances initial healing in recessive dystrophic epidermolysis bullosa wounds: results of a randomised, vehicle-controlled trial. Brit J Dermatol. 2013 Nov;169(5):1025-33. 6Siprashvili Z., et al. Long-term type VII collagen restoration to human epidermolysis bullosa skin tissue. Human Gene Therapy. 2010 Oct;21(10): 1299-1310. 7Chen M., et al. Restoration of type VII collagen expression and function in dystrophic epidermolysis bullosa. Nat Genet. 2002 Dec;32(4):670-5. 8The Scleroderma Foundation. What is Scleroderma? http://www.scleroderma.org/site/PageServer?pagename=patients_whatis#.VaUwk7BFBMw, paragraph 6; accessed 10/09/2014—states, “It’s estimated that about 300,000 Americans have scleroderma. About one third of those people have the systemic form of scleroderma (i.e., 200,000 have a form of localized scleroderma).” 9The Scleroderma Foundation. “Localized Scleroderma” brochure, pages 4, 6-7: http://www.scleroderma.org/site/DocServer/Localized.pdf?docID=317; accessed 07/20/15—states, “Some patients with localized scleroderma, an estimated 10 to 20 percent (20% of 200,000 = 40,000 patients), develop joint pain (arthralgia) during the course of their disease.” 24