powerpoint presentation · – 2015 clinical trial starts (tendon, dermatology and hair) ... –...
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Safe Harbor Statements
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Various assumptions or factors are typically applied in drawing conclusions or making the forecasts or projections set out in forward-looking information. Those assumptions andfactors are based on information currently available to our Company, including information obtained from third-party industry analysts and other third party sources. In some instances,material assumptions and factors are presented or discussed elsewhere in this presentation in connection with the statements or disclosure containing the forward-lookinginformation. You are cautioned that the following list of material factors and assumptions is not exhaustive. The factors and assumptions include, but are not limited to:• no unforeseen changes in the legislative and operating framework for the business of our Company;• a stable competitive environment; and• no significant event occurring outside the ordinary course of business such as a natural disaster or other calamity.
These statements are only predictions and involve known and unknown risks, uncertainties and other factors, which may cause our or our industry’s actual results, levels of activity orperformance to be materially different from any future results, levels of activity or performance expressed or implied by these forward-looking statements. These risks anduncertainties include:• negative results from any of our clinical trials;• Failure to advance research and development programs into clinical trials;• the effects of government regulation on our business;• the viability and marketability of our cell replication technologies;• our failure to successfully implement our marketing plan;• the development of superior technology by our competitors;• the failure of consumers and the medical community to accept our technology as safe and effective;• the risk that publications on which certain data in this presentation are based are withdrawn or invalidated;• risks associated with our ability to obtain and protect rights to our intellectual property;• risks and uncertainties associated with our ability to raise additional capital; and• other factors beyond our control.
Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity or performance. Further,any forward-looking statement speaks only as of the date on which such statement is made, and, except as required by applicable law, we undertake no obligation to update anyforward-looking statement to reflect events or circumstances after the date on which such statement is made or to reflect the occurrence of unanticipated events. New factors emergefrom time to time, and it is not possible for management to predict all of such factors and to assess in advance the impact of such factors on our business or the extent to which anyfactor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statement.
Readers should consult all of the information set forth herein and should also refer to the risk factor disclosure outlined in the Company’s annual report on Form 20-F for the fiscalyear ended December 31, 2013 and other periodic reports filed from time-to-time with the Securities and Exchange Commission on Edgar at www.sec.gov and with the CanadianSecurities Commissions on Sedar at www.sedar.com.
Not an Offer to Purchase or Sell Securities. This presentation is for informational purposes and is not an offer to sell or a solicitation of an offer to sell any securities in theCompany, nor shall there be any sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securitieslaws of such jurisdiction. This presentation may not be relied upon in connection with the purchase of any security. Securities of the Company, if offered, will only be available toparties who are “qualified investors”, pursuant to applicable securities laws.
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BioAsia 2015
“Japan is on the leading edge in regenerative medicine. We will make it possible to generate cells at private-sector factories.”
- Prime Minister Shinzo Abe, World Economic Forum, Davos, Jan, 22, 2014
“The international race for regenerative medicine leadership is on and Japan is leading with respect to regulations. RepliCel has already partnered with Shiseido Company and now looks towards other partnerships in Japan for its fibroblast program.”
- David Hall, CEO, RepliCel, BioJapan, Yokohama, October 15th, 2014
“The Act on Safety of Regenerative Medicine and the revised PMD Act are both bold and enlighten legislative steps. Japan has jumped years ahead of other jurisdictions on a regulatory basis. However, demonstrable activity under the reformed regulations is needed to validate the progressive vision of Japan’s leaders. Still, I am confident the regulators will embrace increased clinical activity while being vigilant in terms of patient safety.”
- David Hall, CEO, RepliCel, BioAsia, Tokyo, March 24th, 20153
RepliCel – Cells for Healing
• Product portfolio – large commercial applications– Two distinct cell therapy platforms built on hair follicle cell science– Developed a unique dermal injector device (replaces any need for an anesthetic) – Strong IP covering process/use of hair follicle cells in a variety of indications
• Strong near-term clinical pipeline
* funded by Shiseido
• Near-term milestones– 2015 clinical trial starts (tendon, dermatology and hair)– 2015 Dermal Injector device CE mark– Data read outs for tendon and skin trials 12 months post-initiation
Chronic tendinosis RCT-01 1/2 Canada
Aging and sun damaged skin RCS-01 1 2015 Germany
Pattern Baldness RCH-01 2 2015 Germany
Pattern Baldness RCH-01 TBD 2015 Japan *
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RepliCel Overview
Virtual Strategy: Minimize costs, lever R&D, commercialization partners.
Partner Strategy: Pre-commercial licensing to partners.Leverage Japan: Initial deals to be Asian-focused licenses with Japanese partners.
Technology: Cell therapies. Injector. Manufacturing, reagents, logistics.
Markets: Orthopedics. Dermatology. Baldness.
Near-term Value Creation:
• Contract manufacture (Innovacell, CCRM)• Contract research (UBC, CCRM)
• First deal (2013): $35M+ deal with Shiseido• Licensing tendon, skin & injector • Leverage partner expertise, cash & capacity• Leverage Japanese early market access• Reserve ROW market for later-stage
• Fibroblast platform (RCS, RCT)• Dermal Sheath Cup Cells (RCH)• Dermal injector (RCI)• Mfg optimization
• Significant cash-pay markets• Success not tied to reimbursement• Employer-insurance for tendinosis• 2015 trial launches• 2016 Q1 data readouts• 2015/6 geographic licenses 5
Pipeline Activities2015 2016 2017
CLINICAL
RCT-01 (Tendon), Canada
RCS-01 (Skin), Germany
RCH-01- RepliCel (Hair), Germany- Shiseido (Hair), Japan
Gen II Injector
MANUFACTURING OPTIMIZATION
Serum-free media
Bioreactor (Closed System)
Cell Isolation (Automated)
Secondary manufacturing facility
LICENSING/PARTNERSHIPS
Asian markets- RCT-01 (Japan as base)- RCS-01 (Japan as base)
Other markets- Gen II Injector
FUNDING
Strengthening cash position
Data
Data
CE submission/CE Mark
Complete
License & equity
Data
Closed manufacturing process
Closed manufacturing process
Tech transfer
1. Condition is diagnosed
2. Biopsy taken from scalp
3. Cells isolated from hair follicle
4. Cells grow (5-8 weeks)
5. Cells mixed with carrier and frozen
6. Cells injected back into patient
Platform
NBDSFibroblasts(RCT-01, RCS-01)
Dermal Sheath Cup Cells (RCH-01)
Proprietary delivery device
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(DP)
Platform Technology from Hair Follicles
• Non-bulbar dermal sheath (NBDS) fibroblast cells are prolific type I collagen production (5x dermal fibroblasts)1
• Active fibroblasts promote tendon healing and dermal matrix rejuvenation
• RCT-01 Phase 1/2 (Tendon), RCS-01 Phase 1 (Skin Aging)
Dermal Sheath Cup Cells (DSC)
Fibroblast Platform (NBDS)
• DSC cells are responsible for maintaining the dermal papillae (DP) cell populations• DP cells are responsible for the thickness and
growth of a hair fibre
• RepliCel’s RCH-01 Phase 2 (Pattern Baldness)• Shiseido’s RCH-01 Trial (Pattern Baldness) 1 Source: Jun Kyu Oh, et al, JSID, 2012
(NBDS)
(DSC)
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30
RepliCel’s Position in the Regen Med Industry
Pre-Clinical | Early-Stage Trial | Mid-Stage Trials | Late-Stage Trials | On Market
Isolated Target Cells
Adult Stem Cells
Target CellsInduced
Pluripotent Stem Cells
Adult Stem Cells
Induction Differentiation
Target Cells
Embryonic Stem Cells
Regulatory Burden
High
Low
Expanded Target Cells
Allogeneic & Autologous
Differentiated cell products
RepliCel represents a lower technical, clinical & regulatory risk than many companies in the sector 9
Chronic Tendinosis – Fibroblast Deficit
• Chronic tendinosis– Cycle of incomplete healing & re-injury– Chronic degeneration of the tendon– Problem: deficit of active fibroblasts
• Standard of Care– Physiotherapy, PRP, ultrasound,
acupuncture, dextrose injections and surgery
• Incidence (North America 21-60 yr old) – Achilles: 485,000 (0.24%)– Elbow: 6,200,000 (3.0%)– Knee: 412,000 (0.20%)
• RepliCel Treatment– Injection of fibroblasts into the injury
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Phase 1 Chronic Achilles Tendinosis - 63 Yr-old Male
• 3-years of chronic pain
• Failed eccentric loading, casting & platelet rich plasma
• Chronic tendinosis: unorganized tissue formation
• Pain reduction
• Tendon thickness reduction
• Organized tissue formation
• Healing complete: return to normal tendon structure
Ultrasound Image Before Treatment – Day 1
Ultrasound Image After Treatment – 6 Months
Source: D. Connell et al, JBJS 2012, Note: JBJS has issued an expression of concern about this publication due to proper clearances. Both Connell and RepliCel believe these allegations are without merit and working to resolve the allegations. 11
Phase 1 Chronic Achilles Tendinosis
Past Clinical: Phase 1 Achilles Tendinosis1
(D. Connell et al., Royal National Orthopaedic Hospital)
Treatment – Adipose derived dermal fibroblasts
• 24 patients (unilateral disease)– 12 treated, 12 controlled– Mean age 45.2 years (20 male, 12 female)– VISA questionnaire & VAS scores @ 6 months
• VISA median values (p<0.001)– Cell group improved 127%– Control improved 11%
• VAS median values (p<0.001)– Cell group decreased 66%– Control decreased 20%
Function
Pain Measurement
1 Source: D. Connell et al, JBJS 2012 12
Chronic Tendinosis – Fibroblast Deficit
• Phase 1/2 Trial for Achilles Tendinosis (UBC) cleared by Health Canada– 28 patients, 21 treated & 7 placebo– Estimated 3 months to complete enrollment– Primary endpoint - safety through 6 months– Secondary endpoint – efficacy at 6 months
• Function, pain, tendon appearance & biomechanics, blood flow, activity scale, quality of life measured at 1, 2, 4, & 6 months
– Treatment: fibroblast cells from hair follicle sheath• Abundant, healthy and easily accessible• Prolific producers of type I collagen
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Aging and Sun Damaged Skin – Fibroblast Deficit
• Skin damage caused by aging, UV exposure, lifestyle factors
• As we age fibroblasts in the skin produce less collagen causing skin to lose its elasticity and structure
• Injection of collagen-rich fibroblasts is designed to reverse skin damage
YOUNG SKIN OLDER SKINHistology Histology
Collagen Fibroblast FibroblastCollagen
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RCS-01 Proposed Phase 1 Trial 2014
• Treatment: Injection of RCS-01 fibroblasts– Prolific producers of type I collagen
• 30 healthy volunteers (24 treated, 6 placebo)
• Primary endpoint – local safety & tolerance
• Secondary endpoints– Efficacy at 6 and 12 months– 16 patients biopsied for gene expression of
skin aging markers– 12 patients biopsied for histopathology
analysis• Assess structural characteristics underlying
the skin • Assess molecular markers associated with
skin aging
BEFORE
AFTER
New collagen growth
RCS-01 Injection
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Dermal Sheath Cup Deficit: Pattern Baldness
• Human scalp follicles develop with a fixed amount of dermal papillae (DP) cells (approx. 500)
• Total # of DP cells determines the # and thickness of hair fibers
• Diminishing volume of active DP cells leads to pattern baldness
• Drug treatments do not increase DP cells
• Only dermal sheath cup (DSC) cells regulate the volume of DP cells and therefore hair fiber growth
• RepliCel solution: deliver missing dermal sheath cup cells (collected from back of scalp)
(DP)
(DSC)
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Platform Technology from Hair Follicles
GROWTH PHASEAnagen = up to 3 yrs
CELL REASSEMBLYTelogen = 2-3 wks
FOLLICLE QUIESCENCETelogen = 2-3 mo
DISASSEMBLY PHASECatagen= 3 wks
GROWTH PHASEAnagen = up to 3 yrs
Cellular structure of a hair follicle bulb disaggregates during the regression to resting phase
The Hair Cycle: From growth phase to resting phase
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RCH-01: Phase 1 Safety - Six Month Results
• 63% of subjects responded with increases in density greater than the 6-month 5% target1
– Mean change in total hair density at 6-months = 6.1% vs 5.0% target
• 70% of responders were above 10% - average 14.3%1
19.6%19.2%
17.2%13.6%
12.0%11.2%
10.6%9.6%
6.2%5.1%
2.1%1.9%
1.1%-3.7%
-4.6%-6.2%
Change in total hair density after 6 months
≥5% responders (n=10)Average = 11.8%
≥10% responders (n=7) (70%)Average = 14.3%
Density Increase from Drug at 12 mthsPropecia® (Finisterade) - 7-14%Rogaine® (Minoxidil) - 8-16%
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RCH-01: Phase 2 Pattern Baldness
• Planned Phase 2 Trial for Pattern Baldness 2015 (Charité, Freiburg and Münster)– 160 participants– 396 RCH-01 treatment group sites (vs. 16 in P1), with 244 placebo sites– Designed to measure dosing and treatment frequency– Primary commercial endpoint – efficacy at 52 weeks after final injection
• efficacy measured as total density, hair thickness, cumulative hair and treatment response rate
– Secondary endpoints – 52 weeks• local tolerance, systemic safety
Screening
Inclusion Criteria:• Male
pattern baldness
RCH-01 Group 2: Day 1 + day 91 injections, 4 sites, 3 doses, 1 placebo (n=66)
Placebo Group 1: Single placebo injection, 4 sites, all placebo (n=14)
Placebo Group 2: Day 1 + day 91 repeat injections, 4 sites, all placebo (n=14)
N = 160
RCH-01 Group 1: Single injection, 4 sites, 3 doses, 1 placebo (n=66)
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Injector Devices
Generation 1 Injector
• Current RCS-01, RCH-01
Generation 2 Injector (RCI-02) for Dermal Injections
• Prototype build stage
• CE mark, 510K pathway
• Focused licensing program into dermal filler market
Programmable depth & dose
Treatment specific interchangeable heads
Built-in freezing replaces anesthetic (Pelletier Element)
Generic cartridge e.g. hyaluronic acid, fat
grafting
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Shiseido – RCH-01 Partner
Kobe Biomedical Innovation Cluster
Business Support Centre for Biomedical Research Activities
• $35 Million ($4M upfront, $31M in sales milestones and royalties), July 2013
• Geographic license for Japan, China, Korea and ASEAN nations
• Shiseido opened SPEC (Shiseido cell-Processing & Expansion Centre) facility in May 2014– Located at Kobe Biomedical Innovation
Cluster (KBIC) – Japanese centre for regenerative medicine– Capable of handling all
aspects of the RCH-01 technology• Tissue-sample processing,
manufacturing and product packaging
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RepliCel’s Leadership in Japan
• RepliCel is one of only a handful of foreign cell therapy companies with a Japanese partnership already in place (Shiseido)
• RepliCel is only 1 of 2 foreign cell therapy companies with a connection to a cell manufacturing facility in Japan (Shiseido)
• RepliCel may be the only foreign cell therapy company with a clinical trial poised to commence in Japan (Shiseido)
• RepliCel has a credible profile in the Japan amongst investors, strategic partners, and government
• RepliCel is frequently in Japan to participate in industry conferences
• RepliCel is acknowledged in the West as a leader in understanding Japanese regulations
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Japanese Regenerative Medicine Policy Reform
• 2012 Shinzō Abe elected Prime Minister (2014 re-elected) on a clear vision for revitalizing the Japanese economy (Abenomics) – Policy to support the development of a robust, world-leading
regenerative medicine industry in Japan including ¥110 billion (US$1B) in funding for stem cell research over 10 years
• Intl & domestic leadership of Drs. Yaminaka and Okano– Elevated emphasis on manufacturing safety
• accreditation and licensure of cell processing facilities; training and certification of personnel
– Regulatory revision for cell therapies• revisions to the physician-sponsored & “clinical research” pathway
– risk-based analysis tiers products into categories representing different levels of safety risk – to be subjected to different levels of review
• revisions to the industry-sponsored “clinical trial” pathways – allows for conditional approval with confirmation of safety and
“predicted efficacy” 23
Foreign Cell Rx Company Partnerships in Japan
• Mesoblast & JCR Pharmaceuticals– MBTLY came to JCR through acquisition of Prochymal assets from Osiris
– Prochymal (allogeneic, bone marrow-derived MSC): approved in CDA & NZ for refractory pediatric GvHD, filed for conditional approval in December 2014 in Japan & granted priority review
– JCR has manufacturing in place in Japan
• Living Cell Technologies & Otsuka Pharmaceutical Factory– 2011 JV company established called Diatranz Otsuka Limited (DOL) to bring DIABECELL (encapsulated
porcine-derived islets in development for treatment of T1 diabetes) to market
– 2014 Otsuka Pharmaceutical Factory licensed DIABECELL from DOL for Japanese and US markets
• Cytori Therapeutics
– Tokyo-based medical subsidiary Cytori Therapeutics KK was established largely to support the sale of the Cellution System for autologous, point-of-care, adipose (fat)-derived regenerative cells into the Japanese market for treatment of various conditions
• Athersys - Licensed Mulitstem for ischemic stroke to Chugai for Japan.
• RepliCel Life Sciences– July 2013 - Licensing agreement with Shiseido Company, Limited for RCH-01 for Asian markets
– 2014 Shiseido opens cell manufacturing facility in Japan to advance RCH-01 and completes tech transfer & validation runs
– 2015 Shiseido-sponsored clinical trials to commence in Japan 24
Other Foreign Cell Rx Company Activity in Japan
• Cellectis – 2014 sold Cellectis AB (company focused on applications of human embryonic stem cell products and technologies) to Takara Bio
• Stemgent, Inc. – 2014 ReproCELL acquired the iPS Cell Business Unit of Stemgent
• PluriStem – 2014 announced they are evaluating co-development and commercialization opportunities for its Placental eXpanded cell therapies in Japan
• SanBio – 2014 announced joint development and license agreement with Sumitomo Dainippon Pharma for exclusive marketing rights for SB623 in US and Canada
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Sponsor PMDA and prefecture
Pharmaceuticals and Medical Devices Agency (PMDA)
Review
Ministry of Health, Labour & Welfare (MHLW)
Conditional/time-limited authorization pathway
Normal authorization pathway
Business licenses applications (if use new facilities)
Marketing authorization (conditional time-limited)
Marketing authorization (normal)
Advisory Committee (Pharmaceutical & Food
Sanitation Council)
Marketing authorization application
Review Report
Market Authorization Pathway in Japan
If the application meets the criteria (biological heterogeneity, etc.)
(adapted from http://www.pmda.go.jp)
Regenerative Medicine Promotion Act: Proposed in April 2013, Passed in 2014
Allowing commissioning cell processing to licensed enterprises (outside of hospital) faster & safer manufacturing
To promote research and faster translation into clinics
Regenerative Medicine Promotion Act in Japan
(adapted from http://www.pmda.go.jp)
ACT ON SAFETY OF REGENERATIVE MEDICINE
•Applies to Clinical Research & Physician-Initiated Studies•Academic purposes (development of new therapies)
ACT ON PHARMACEUTICALS & MEDICAL DEVICES (PMD ACT) REVISED
•Applies to Clinical Trials•Product marketing authorization purposes
Conditional/time-limited authorization faster & higher number of product
approval
Risk-dependent evaluation and accreditation of cell-process centres
Post-marketing safety measures (ie, data collection and revocation, if needed)
Cell Therapy Process Prior to Japanese Acts
GCTP
PMD Act. (revised PAL): Market Authorization
Manufacturer (Accreditation)
Manufacturer (Accreditation)
Obtaining Cells
Purchase of Approved Product and its Delivery
Cell processing
Cell processing
Outside hospital
Cell processing
(adapted from http://www.pmda.go.jp)
Contract
Hospital
Cell collection
Product Delivery
Overview of Two Japanese Acts
GCTP
The Act on the Safety of Regenerative Medicine PMD Act. (revised PAL): Market Authorization
Manufacturer (Accreditation)
Hospital Manufacturer (Accreditation)
Obtaining Cells
Purchase of Approved Product and its Delivery
Cell collection
Cell processing
Cell processing
Outside hospital
Cell processing
(adapted from http://www.pmda.go.jp)
Contract
Product Delivery
Clinical Study
Phased clinical trials(confirmed safety & efficacy)z
Marketing authorization
Marketing
Clinical Study
Clinical Trials (confirmed
safety & predictedefficacy)
Conditionalterm-limited authorization
Re-a
pplic
atio
n (w
ithin
max
7 y
rs)
Marketing
Final marketing
authorizationor
Revocation
Marketing (Further
confirmation of efficacy and
safety)
[New scheme]
Benefits of new Conditional Approval System: to shorten lengthy review processes normally required by the traditional system to evaluate safety and efficacy of heterogeneous cellular products. allowing for timely provision of safe regenerative medicine.
Post-marketing safety measures must be taken, including prior
informed consent of risk to patients
Japanese Expedited Approval System Under PMD Act
(adapted from http://www.pmda.go.jp)
[Traditional approval process]
RepliCel’s Advantage
TECHNOLOGY - no other cell therapy company:• using cells derived from the hair follicle• in clinical development of a treatment for pattern baldness
LOWER RISK – Not an IPS cell play • lower technical, clinical, and commercial risk than most
TIMING CATALYSTS - Near-term clinical value-creation milestones• clinical data launches, execution, data readouts• licensing• not a one-trick pony -- platform technology with deep and broad pipeline already in
clinical development
TEAM - Management is commercially-focused and strategic• aggressively pursuing building licensing value and getting deals done• non-dilutive revenue and nearer-term exit(s)• building ‘ancillary’ value (manufacturing, injector, reagents, etc.)
COMMERCIALIZATION – Leveraging Japan’s new early market access pathway• one of the few foreign companies already in place in Japan to take advantage of
the early market access program they have just launched for cell therapies31
RepliCel Life Sciences Inc.
OTCQB: REPCFTSXV: RP
David M HallCEO & [email protected]
R. Lee BucklerVP Business Development
604.248.8693 [email protected]