May 2015 1
May 2015 2
Forward Looking Statements
This document includes statements concerning our operating results (including product sales), financial condition and product development milestones, which are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements herein that are not clearly historical in nature are forward-looking, and the words “anticipate,” “assume,” “believe,” “expect,” “estimate,” “plan,” “will,” “may,” and the negative of these and similar expressions generally identify forward-looking statements. All forward-looking statements involve risks, uncertainties and contingencies, many of which are beyond Flamel’s control and could cause actual results to differ materially from the results contemplated in such forward-looking statements. These risks, uncertainties and contingencies include the risks relating to: our dependence on a small number of products and customers for the majority of our revenues; the possibility that our Bloxiverz® and Vazculep™ products, which are not patent protected, could face substantial competition resulting in a loss of market share or forcing us to reduce the prices we charge for those products; the possibility that we could fail to successfully complete the research and development for the two pipeline products we are evaluating for potential application to the FDA pursuant to our “unapproved-to-approved” strategy, or that competitors could complete the development of such products and apply for FDA approval of such products before us; our dependence on the performance of third parties in partnerships or strategic alliances for the commercialization of some of our products; the possibility that our products may not reach the commercial market or gain market acceptance; our need to invest substantial sums in research and development in order to remain competitive; our dependence on certain single providers for development of several of our drug delivery platforms and products; our dependence on a limited number of suppliers to manufacture our products and to deliver certain raw materials used in our products; the possibility that our competitors may develop and market technologies or products that are more effective or safer than ours, or obtain regulatory approval and market such technologies or products before we do; the challenges in protecting the intellectual property underlying our drug delivery platforms and other products; our dependence on key personnel to execute our business plan; the possibility that we may cease to qualify as a foreign private issuer, which would increase the costs and expenses we incur to comply with U.S. securities laws; and the other risks, uncertainties and contingencies described in the Company’s filings with the U.S. Securities and Exchange Commission, including our annual report on Form 20-F for the year ended December 31, 2014, all of which filings are also available on the Company’s website. Flamel undertakes no obligation to update its forward-looking statements as a result of new information, future events or otherwise, except as required by law.
May 2015 3
FLAMEL Technologies Transformed
• Fully integrated global specialty pharmaceutical company with FDA approved products and a broad pipeline using Flamel’s four proprietary drug delivery platforms
• Two FDA approved products marketed by Flamel in the United States will drive significant revenue growth in 2015
• Incremental clinical data for several of Flamel’s pipeline products over the next 12-18 months
• Cash flow positive as of Q4 2014 and will be cash flow positive in 2015 and beyond
• Net cash position in excess of $113m on March 31, 2015 provides for a strong balance sheet
• New strategy: Flamel controls 100% of its drug development
May 2015 4
Key Milestones Achieved
Launched Bloxiverz® and Vazculep™ in the United States
Presented positive clinical and preclinical data • Micropump sodium oxybate: eliminated middle of the night dose (12/2014)
• LiquiTime ibuprofen: positive PK results (09/2014)
• LiquiTime guaifenesin: positive First-In-Man data (03/2015)
• Medusa exenatide: positive preclinical studies for 1x/week administration (06/2014)
Completed an equity raise of $121m • Eliminated virtually all debt
Divested contract manufacturing facility • Clear focus on product development and revenue generation
Implemented corporate reorganization • Established footprint in Ireland and shifted all intellectual property from France to
Ireland
May 2015 5
2015 Expectations
• Achieve total product sales of $170-185m
• Submit an application for UMD#3 to the FDA
• Start pivotal study for Micropump sodium oxybate
• Present human clinical data on at least one additional LiquiTime product achieved
Positive LiquiTime guaifenesin First-In-Man data announced in March 2015
• Enter into an agreement for one or more LiquiTime OTC products
• Present PK data and abuse deterrence data on Trigger Lock
• Present First-in-Man interim data on Medusa exenatide
May 2015 6
Flamel’s Goals
• Upcoming Milestones
• Evolution of Pipeline
May 2015 7
Upcoming Milestones
Technology H1 2015 H2 2015
UMD Product* FDA NDA filing
Micropump Pre-IND meeting with FDA for sodium oxybate
Sodium oxybate pivotal study initiation
LiquiTime Clinical data guaifenesin announced March 2015
Ibuprofen pivotal trial initiation
Trigger Lock Clinical data with in-vitro abuse deterrence data - 1 program
Medusa Exenatide Phase I clinical data
*UMD is Flamel’s Unapproved Marketed Drugs Strategy
May 2015 8
Drug/ Technology
Indication
Pre- Clinical
Proof of Concept
Dose Ranging
Pivotal
Under Review
Approved Marketed Sales Force
Bloxiverz/UMD* Anesthesia Flamel
Vazculep/UMD* Anesthesia Flamel
UD/UMD #3* Undisclosed Flamel
UD/UMD #4* Undisclosed Flamel
Sodium oxybate/ Micropump
Narcolepsy TBD
Ibuprofen/LiquiTime Pain, fever TBD
Guaifenesin/LiquiTime Respiratory TBD
Opioid/Trigger Lock Pain TBD
Exenatide XL/ Medusa Diabetes TBD
Flamel’s Pipeline (Q2 2015)
*UMD is Flamel’s Unapproved Marketed Drugs Strategy, but does not involve patented technology. UD = undisclosed TBD= To Be Determined
May 2015 9
Flamel’s Pipeline Looking Ahead (Q2 2016)
Drug/ Technology
Indication
Pre- Clinical
Proof of Concept
Dose Ranging
Pivotal
Under Review
Approved Marketed Sales Force
Bloxiverz/UMD* Anesthesia Flamel
Vazculep/UMD* Anesthesia Flamel
Disclosed/UMD #3 * Disclosed Flamel
Disclosed/UMD #4 * Disclosed Flamel
Sodium oxybate/ Micropump
Narcolepsy TBD
Ibuprofen/LiquiTime Pain, fever TBD
Guaifenesin/LiquiTime Respiratory TBD
Opioid/Trigger Lock Pain TBD
Exenatide XL/Medusa Diabetes TBD
*UMD is Flamel’s Unapproved Marketed Drugs Strategy, but does not involve patented technology. TBD= To Be Determined
May 2015 10
Flamel’s Marketed Products
• Bloxiverz®
• Vazculep™
May 2015 11
Marketed Products
• BLOXIVERZ®
• FDA approval on May 31, 2013 (first FDA-approved neostigmine methylsulfate injection)
• Strengths: 0.5 mg/mL or 1 mg/mL (10 mL MDV)
• Indication: reversal of the effects of non-depolarizing neuromuscular blocking agents after surgery
• Bloxiverz WAC price is $98.75 per vial
• There are approximately 5 million vials sold annually in the United States
• Website: www.bloxiverz.com
May 2015 12
Marketed Products
• VAZCULEP™
• FDA approval on June 30, 2014 (only FDA-approved phenylephrine injection available in three vial sizes)
• Form: 1 mL single use vials, 5 mL and 10 mL pharmacy bulk package vials for intravenous injection (bolus or infusion) (10 mg/mL)
• Indication: Treatment of clinically important hypotension resulting primarily from vasodilation in the setting of anesthesia
• Prices for all three sizes are competitive
• Recent data show the following approximate annual unit volumes:
• 1ml vial – 5.6m 5ml vial – 1.3m 10ml vial – 140K
• Website: www.vazculep.com
May 2015 13
Flamel’s R&D Pipeline
• Micropump® sodium oxybate
• LiquiTime® ibuprofen
• LiquiTime® guaifenesin
• Trigger-Lock™ opioid
• Medusa™ Exenatide
May 2015 14
• Micropump® sodium oxybate has been studied in 40 healthy volunteers to date across 2 studies
• Flamel’s results of its two studies at doses of 4.5g and 6g show the following:
Onset of action similar to 4.5g nightly dose of Xyrem® (sodium oxybate)
Cmax lower than 4.5g nightly dose of Xyrem® (6g dose similar to Xyrem 4.5g dose)
Mean blood concentration (μg/ml) at hours 7 and 8 similar to 4.5g nightly dose of Xyrem®
No adverse events or tolerability issues
• Micropump Sodium Oxybate 7.5g dose performed in line with expectations relative to the data at lower doses of Micropump Sodium Oxybate
• Profile is consistent with the need for only one single dose before bedtime
• Current dosing regimen for Xyrem®, the standard of care in the U.S., is two equal, divided doses: the first dose at bedtime and the second dose 2.5 to 4 hours later
• Flamel will meet with FDA in H1 2015 and begin a pivotal study at year end 2015
Micropump® Sodium Oxybate – Treatment of Narcolepsy Single Dose Nightly Formulation
May 2015 15
• 2014 sales for Xyrem® were $779m1
• Sales outside the US are quite low, but upside exists with a superior profile
• CAGR for Xyrem from 2009-2014 is in excess of 50%
• Industry sources estimate the number of Narcoleptics in the US at 200,000 with 50,000 diagnosed2
• Jazz reports less than 13,000 patients currently on treatment
• Limited competition to date
Micropump® Sodium Oxybate – Market Opportunity
1 Jazz’s fourth quarter 2014 financial results 2 Narcolepsy Network
May 2015 16
LiquiTime® Ibuprofen – Treatment of Pain and Fever Extended Release Liquid Ibuprofen
• Ibuprofen oral suspension twice-daily dosing confirmed
• First-in-Man (FIM) clinical study in healthy volunteers (15 subjects)
• Trial design: open-label, randomized, 3-way crossover with an immediate- release ibuprofen control and 2 formulations of LiquiTime ibuprofen
• PK results announced in September 2014 demonstrated:
Bioequivalence to immediate-release ibuprofen
Similar onset versus immediate-release ibuprofen
Similar blood levels at 12 hours versus immediate-release ibuprofen
No safety or tolerability issues
• US regulatory filing expected in H1 2016
• Market opportunity: OTC (Over-The-Counter) ibuprofen products recorded sales in the USA beyond $400m including combination products (source: IMS)
May 2015 17
LiquiTime® Guaifenesin – Treatment of Cough and Cold Extended Release Liquid Guaifenesin
• Highly likely to succeed in pivotal study
• First-In-Man (FIM) clinical study in healthy volunteers (16 subjects)
• Trial design: open label, randomized, 4 way crossover with an immediate release guaifenesin control dosed three times over 12 hours and three formulations of LiquiTime guaifenesin
• PK results announced in March 2015 demonstrated:
A profile that is highly likely to succeed in a pivotal bioequivalence study
Similar blood levels at 12 hours versus immediate-release guaifenesin
No safety or tolerability issues
• US regulatory filing expected in H2 2016
• Market opportunity: OTC guaifenesin products recorded sales in the USA beyond $400m including combination products (source: IMS)
May 2015 18
• Cough and cold US market is estimated at $6.5b annually1
• These markets are dominated by OTC drugs, many of which are combination of different active ingredients having distinctive actions:
• Ibuprofen or Acetaminophen/paracetamol (analgesic and antipyretic)
• Chlorpheniramine or Diphenhydramine (antihistamine)
• Pseudoephedrine or Phenylephrine (decongestant)
• Dextromethorphan (antitussive)
• Guaifenesin (expectorant)
• LiquiTime allows for the combination of those active ingredients with tailored release profiles for each of them
1 Deutsche Bank
LiquiTime OTC Franchise - Market Opportunity
May 2015 19
• PK and abuse-deterrence data expected in H1 2015
• Abuse of such drugs is a major public health concern in the USA • An estimated 2.1 million people in the US are suffering from substance use
disorders related to prescription opioid pain relievers in 2012
• Recent FDA policy on abuse of such products is positive for anti-abuse platforms such as Trigger Lock
• Market opportunity: U.S. market for prescription painkillers in 2013: $7.2b1
• Oxycontin (extended-release oxycodone, Purdue): $2.6b
• Over 34 million opioid prescriptions were written for extended-release and immediate-release oral products in the US in 20131
1 Source: IMS Health
Trigger Lock – Extended-Release Abuse-Resistant Opioid
May 2015 20
• Successfully tested in minipigs (June 2014)
• Significantly improved bioavailability versus Bydureon®
• Two successive injections were administered with very similar release profiles
• No adverse clinical signs
• Excellent local tolerability
• PK profile is compatible with a release over one week in humans
• Interim phase I human clinical data to be reported in late 2015
• Market opportunity: GLP-1 (glucagon-like peptide-1) products recorded global sales beyond $3b in 2014
Medusa Exenatide – Treatment of Type 2 Diabetes Positive Preclinical Results and Market Opportunity
May 2015 21
Flamel’s Strengths
• Diversified and proven drug delivery platforms
• Strong intellectual property
• Seasoned senior management
• Healthy financial situation
May 2015 22
Diversified and Proven Drug Delivery Platforms
• Flamel owns and develops outstanding drug delivery platforms that are able to tackle key challenges in the formulation, in various dosage forms (e.g. capsules, tablets, sachets or oral liquid suspensions; or injectable for subcutaneous administration) of a broad range of drugs (novel, already-marketed, or off-patent):
Micropump, LiquiTime, Trigger Lock and Medusa are trademarks of Flamel Technologies S.A.
Modified/Controlled Release of Solid Oral Drugs
Modified/Controlled Release of Liquid Oral Drugs
Abuse-Resistant Modified/Controlled Release Narcotics/Opioid Analgesics
Modified/Controlled Release of Injectable Drugs
May 2015 23
Strong Intellectual Property
Broad portfolio of patents*
*Source: 2014’ Annual Report on form 20-F published on April 31st, 2015
• New patents may be issued targeting each individual product in development where a Flamel drug delivery platform is applied to a specific molecule
Date of expiration of granted patents
Platform US Europe
Micropump® July 2027 July 2023
LiquiTime® September 2025 April 2023
Trigger Lock™ April 2027 May 2026 (pending)
Medusa™ June 2031 June 2027 (pending)
May 2015 24
Seasoned Senior Management
Name Title Appointed Experience
Michael S. Anderson Chief Executive Officer 2012 40+ years Pharma
Phillandas T. Thompson, J.D., M.B.A.
Senior Vice President, General Counsel 2013 16+ years Legal
Siân Crouzet Principal Financial Officer 2005 17+ years Financial
David Monteith, Ph.D.
Vice President, Research and Development 2014 25+ years Pharma
Scott Macke Vice President, Supply Chain and Operations 2012 22+ years Pharma
Jean Chatellier, Ph.D. Vice President, Alliance Management and Licensing 2010 15+ years Pharma
Séverine Martin, E.M.B.A.
Director, Human Resources and Corporate Projects 2014 13 + Human Resources
May 2015 25
Condensed Consolidated Statement of Operations
Unaudited Three months ended
In USD million, except EPS (USD) and shares data (million)
March 31, 2014 March 31, 2015
Total Revenue 4.6 32.7
Total Costs and Expenses (28.8) (22.5)
Profit (loss) from continuing operations (24.2) 10.2
Net income (loss) from continuing operations (26.9) 11.6
Net income (loss) (26.6) 11.6
Diluted EPS from continuing operations (0.95) 0.27
Adjusted Diluted EPS (non GAAP) (0.16) 0.10
Diluted Shares Outstanding 28.3 42.8
All figures are on a continuing operations basis reflecting the 4Q14 divestiture of Pessac’ Facility and all Coreg CR® related revenues
May 2015 26
Condensed Balance Sheet (Unaudited)
In USD million As of
Dec. 31, 2013 As of
Dec. 31, 2014 As of
March 31, 2015
Cash & marketable securities
7.0 92.8 113.2
LT debt 1 66.3 76.1 TBA
Other LT liabilities 2 15.9 2.3 TBA
1 Includes government loans for R&D projects + acquisition liability contingent consideration, note and warrant consideration, and facility and royalty agreements concluded in February 2013 and December 2013
2 Includes R&D credit tax financing, funding from former partner GSK, provision for retirement indemnity and employee service award provision
TBA = to be announced
May 2015 27
FLAMEL Technologies Transformed
• Fully integrated global specialty pharmaceutical company with FDA approved products and a broad pipeline using Flamel’s four proprietary drug delivery platforms
• Two FDA approved products marketed by Flamel in the United States will drive significant revenue growth in 2015
• Incremental clinical data for several of Flamel’s pipeline products over the next 12-18 months
• Cash flow positive as of Q4 2014 and will be cash flow positive in 2015 and beyond
• Net cash position in excess of $113m on March 31, 2015 provides for a strong balance sheet
• New strategy: Flamel controls 100% of its drug development
May 2015 28
Flamel Technologies SA (NASDAQ: FLML) is a specialty pharmaceutical company utilizing its core competencies in formulation development and drug delivery to develop safer and more efficacious pharmaceutical products, addressing unmet medical needs and/or reducing overall healthcare costs. Flamel currently has approvals for and markets two previously Unapproved Marketed Drugs (“UMDs”) in the USA, Bloxiverz® (neostigmine methylsulfate injection) and Vazculep™ (phenylephrine hydrochloride injection). The Company intends to add to this branded business by creating additional products, focusing on the development of products utilizing Flamel’s proprietary drug delivery platforms. Flamel currently has several products in development utilizing Micropump® (oral sustained release microparticles platform) along with its tangent technologies, LiquiTime® and Trigger Lock™. The lead project for Micropump is Sodium Oxybate. LiquiTime allows for the extended-release of liquid medicines (such as Ibuprofen and Guaifenesin) and Trigger Lock is an abuse-resistant iteration of Micropump, designed specifically for long-acting opioids. Additionally, the Company has developed a long acting injectable platform, Medusa™, a hydrogel depot technology currently being studied with Exenatide. Flamel’s products are targeting high-value molecules and will utilize either the 505(b)(2) approval process for NDAs or biosimilar pathways ultimately approved by FDA and other regulatory authorities. The Company is headquartered in Lyon, France and has operations in St. Louis, Missouri, USA, and Dublin, Ireland Additional information can be found at http://www.flamel.com.
Headquarters
33 avenue du Dr. Georges Levy
69200 Vénissieux (Lyon)
France
Corporate Contact
Phone: +33 472 783 434
Fax: +33 472 783 435
E-mail: [email protected]
Specialty Pharmaceutical Company with Proprietary Drug Delivery Platforms Focused on
Improved or Cost-Effective Products
May 2015 29
Drug Delivery Platforms at a Glance
May 2015 30
Micropump® Platform at a Glance
• Extended/delayed release of drugs best absorbed in the small intestine (75% of all small molecules)
• Precise pharmacokinetics of single or combination of drugs in various formats
• Numerous Micropump®-based products successfully tested in human clinical trials
Various dosage forms (pills, tablet, capsule, sachet, liquid)
Commercial Stage Platform approved in the USA
and EU
Widely used and accepted excipients
Rapid development time Combination of
multiple release profiles and/or multiple active ingredients
Taste-masking properties
Cost effective and easy to scale-up
Strong IP position
May 2015 31
• Microparticles are dispersed in the stomach and pass into the small intestine, where each microparticle releases the drug at an adjustable rate and over an extended period of time (up to 24 hours)
• Drug released at an adjustable rate controlled and/or delayed
• Micropump® microparticles can be used separately or together to provide highly specialized delivery profiles
Micropump Microparticles for Controlled/Modified Release
Granules drug granulate or layered neutral core
May 2015 32
LiquiTime® Platform at a Glance
LiquiTime® is a novel, proprietary and innovative delivery platform allowing the stable
Liquid and controlled release formulation of one or several combined drugs over Time
LiquiTime® meets challenges
faced in the treatment of
pediatric and geriatric patients
and patient populations who
have difficulty swallowing
tablets or capsules, and may
provide better patient
compliance
LiquiTime’s versatility allows once- or twice-daily liquid formulations of a wide variety of drugs
This graph illustrates the different near zero-order release profiles which can be tailored for the same drug
May 2015 33
Each microparticle is individually coated and behaves as an independent micro reservoir
Coating • controls diffusion • keeps its integrity • offers good resistance to stress
LiquiTime® for Extended Release Liquid Suspension
The liquid suspension contains small coated drug microparticles
A dose typically contains 5,000 to 50,000 particles
ER microparticles are suspended in the liquid medium
Granules drug granulate or layered neutral core
150-500 µm
May 2015 34
Trigger Lock™ is a proprietary and innovative delivery platform that enables
the controlled release of narcotic and opioid analgesics while deterring their
abuse
Trigger Lock™ successfully addresses the issues of narcotic/opioid analgesics
tampering:
The sustained release Micropump®-based microparticles are resistant to
crushing: each microparticle retains its polymer coating which is virtually
impervious to further crushing
Trigger Lock™ resists extraction attempts (even in boiling liquids) with
beverages (alcoholic or not) preventing injection
Trigger Lock™ preserves the bioavailability of the narcotic/opioid analgesics
Trigger Lock™ is compatible with different dosage forms (capsules, tablets)
Trigger Lock™ Platform at a Glance
May 2015 35
1. Drug loaded Micropump® microparticles Sustained Release (SR) microparticles which are resistant to crushing
2. Viscosifying ingredient(s) To prevent abuse by injection after extraction in a small volume of solvent
3. Quenching ingredient(s)
To prevent extraction in large volumes of liquid
• These ingredients are all in the size range of 150-350 µm
• The high number of microparticles per dose (>20,000) prevents easy separation of these components
Each microparticle retains its polymer coating which is virtually impervious to further crushing
Trigger Lock™ SR Microparticles for Abuse Resistance
May 2015 36
Medusa™ Hydrogel Depot
Solubilization and stabilization of drugs
Applicable to a wide range of small molecules, peptide
and protein drugs
Safe, non-immunogenic and fully biodegradable
Sustained delivery from 1 to 7 days in human
Combination of several different drugs in the same
formulation
Bio-friendly, water-based, solvent-free
formulation process
Cost effective and easy to scale-up
Strong IP position
Medusa™ Platform at a Glance
May 2015 37
Medusa™ Hydrogel Depot For Injection
COO- Na+
COO- Na+
COO- Na+
COO- Na+
COO- Na+ COO- Na+
COO- Na+
Vitamin E Polyglutamate chain
Drug solution
or powder
Formulation by simple mixing in water Non-covalent association (reversible hydrophobic and/or
electrostatic interaction) of the drug with Medusa™ hydrogel
Injection
In vivo depot formation
1 2 3
Sustained release of the unmodified drug over 1 to 7 days
*
*
*
Water clear liquid Solution
Or Freeze-dried
In Vitro In Vivo
• Made of polyglutamic acid and Vitamin E • Amphiphilic and spontaneously forms stable nanoparticles in water • Complexes are stable over a wide range of pH