Forward Looking Statements

Transcription

1 January

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 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 forwardlooking 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. January

3 Flamel Technologies Transformed Fully integrated global specialty pharmaceutical company with FDA approved products and a broad pipeline using Flamel s proprietary drug delivery platforms Two FDA approved products marketed by Flamel in the United States on track to drive significant cash flow in 2016 Incremental clinical data expected from several of Flamel s pipeline products over the next months Anticipated positive cash flow in 2015 and 2016 Net cash position of over $128 million on September 30, 2015 Strategy: Flamel controls 100% of its drug development and its future January

4 Key Milestones Achieved Launch of Bloxiverz and Vazculep in the United States Completed an equity raise of $113 million (net proceeds) Divested contract manufacturing facility Implemented corporate reorganization Shifted all intellectual property from France to Ireland Presented positive clinical and preclinical data Micropump sodium oxybate: eliminated middle of the night dose LiquiTime ibuprofen: twice-daily dosing confirmed Medusa exenatide: PK* profile compatible with release over one week in humans Generated over $170M of revenues Profitable, and cash flow positive for first time in company's history Presented positive clinical and preclinical data LiquiTime guaifenesin: twice-daily dosing confirmed Trigger Lock hydromorphone: bioequivalence criteria met (under fasted conditions) Medusa exenatide: positive interim results from a Phase 1a clinical trial Licensed exclusive U.S. rights to the LiquiTime drug delivery platform to Perrigo for the Over-The-Counter (OTC) drug market *PK = pharmacokinetics January

5 2016 Expectations Achieve total product sales of $ million Launch UMD#3 Start patient registration for pivotal study of Micropump sodium oxybate Begin licensing discussions for Trigger Lock platform Complete and report data from Phase 1b study with Medusa exenatide in patients Commence development of additional projects, including UMD#4 *UMD is Flamel s Unapproved Marketed Drugs Strategy January

6 Flamel s Goals Upcoming Milestones Evolution of Pipeline January

7 Upcoming Milestones Technology 1H H 2016 UMD Product #3* Launch in the USA Micropump Submit SPA/IND/CTA; Initiate sodium oxybate pivotal trial Pivotal trial ongoing LiquiTime Trigger Lock Medusa Confirmatory PK study for guaifenesin Pre-IND meeting with FDA Complete Phase 1b study IND/CTA filing for Phase 3 efficacy studies for ibuprofen Supplemental alcohol interaction study / partnership discussions Assess future development plans / partnership *UMD is Flamel s Unapproved Marketed Drugs Strategy January

8 Flamel s Pipeline (1H 2016) Drug/ Technology Indication Pre- Clinical Proof of Concept Dose Ranging Pivotal Under Review Approved Marketed Sales Force Bloxiverz /UMD 1 Anesthesia Flamel Vazculep /UMD 1 Anesthesia Flamel UD/UMD 1 #3 Undisclosed Flamel UD/UMD 1 #4 Undisclosed Flamel Sodium oxybate/ Micropump Narcolepsy Ibuprofen/LiquiTime Pain, fever Perrigo Guaifenesin/LiquiTime Respiratory Hydromorphone/ Trigger Lock Pain Exenatide/Medusa Diabetes TBD 2 TBD Perrigo TBD 1 UMD is Flamel s Unapproved Marketed Drugs Strategy that does not involve patented technology 2 Dose ranging not required by the FDA UD = undisclosed TBD= To Be Determined January

9 Flamel s Pipeline Looking Ahead (2H 2016) Drug/ Technology Indication Pre- Clinical Proof of Concept Dose Ranging Pivotal Under Review Approved Marketed Sales Force Bloxiverz /UMD 1 Anesthesia Flamel Vazculep /UMD 1 Anesthesia Flamel Disclosed/UMD 1 #3 Disclosed Flamel Disclosed/UMD 1 #4 Disclosed Flamel Sodium oxybate/ Micropump Narcolepsy Ibuprofen/LiquiTime Pain, fever Perrigo Guaifenesin/LiquiTime Respiratory Hydromorphone/ Trigger Lock Pain Exenatide/Medusa Diabetes TBD 2 TBD Perrigo TBD 1 UMD is Flamel s Unapproved Marketed Drugs Strategy that does not involve patented technology 2 Dose ranging not required by the FDA UD = undisclosed TBD= To Be Determined January

10 Flamel s Marketed Products Bloxiverz Vazculep January

11 Marketed Product BLOXIVERZ FDA approval on May 31, 2013; currently 1 of 3 approved versions of neostigmine methylsulfate injection Owns 50% of the market at end 2015 Approximately 4 million vials sold annually in the United States* More details can be found at * IMS January

12 Marketed Product 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) (strength: 10 mg/ml) Indication: Treatment of clinically important hypotension resulting primarily from vasodilation in the setting of anesthesia Market potential at end 2015* (estimates based on January to November data) 1mL vial 5.7 million 5mL vial 1.2 million 10mL vial 0.2 million More details can be found at * IMS January

13 Flamel s R&D Pipeline Micropump sodium oxybate LiquiTime ibuprofen LiquiTime guaifenesin Trigger Lock hydromorphone Medusa exenatide January

14 Micropump Sodium Oxybate for Narcolepsy FT218 is an extended release oral solid formulation of sodium oxybate using Micropump technology Studied in 40 healthy volunteers across 2 studies, up to 7.5g dose No safety or tolerability issues PK results at 4.5g dose in comparison to Xyrem : Onset of action similar to Xyrem Cmax lower than Xyrem Total drug exposure similar to Xyrem Sodium oxybate mean blood concentration at 7 and 8 hours after administration similar to Xyrem PK results at 6g and 7.5g doses in line with expectation relative to lower dose of FT218 Profile is consistent with the target of only one single dose before bedtime Current dosing regimen for Xyrem : two equal divided doses, first at bedtime and second 2,5 to 4 hours later Flamel met with FDA mid 2015 Next step: regulatory submission of Phase III clinical trial application and initiation of pivotal study; submission of IND / SPA during 1Q 2016 January

15 Micropump Sodium Oxybate Market Opportunity First nine months of 2015 sales for Jazz s Xyrem were $703 million; FY2015 sales could exceed $900 million >45% CAGR for Xyrem from ~178,000 narcoleptic patients in the U.S.* Jazz reports less than 13,000 patients currently on treatment May benefit from the significant number of untreated patients Limited competition to date Xyrem expected to maintain dominant position in the narcolepsy market Micropump sodium oxybate anticipated to benefit from improved profile * GlobalData January

16 LiquiTime Ibuprofen Extended release liquid oral suspension for treatment of pain and fever 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 immediaterelease 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 Exclusive U.S. rights licensed to Perrigo for the OTC drug market Next steps: IND/CTA filing 2H 2016; pivotal trial initiation January

17 LiquiTime Guaifenesin Extended release liquid oral suspension for treatment of cough and cold Guaifenesin oral suspension twice-daily dosing confirmed 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 Exclusive U.S. rights licensed to Perrigo for the OTC drug market Next steps: Confirmatory PK study in 1H 2016 January

18 LiquiTime OTC Market Opportunity Cough and cold U.S. market is estimated at $6.5b annually 1 OTC ibuprofen-containing products recorded over $490 million 2 of sales OTC guaifenesin-containing products recorded over $440 million 2 of sales Cough/cold market dominated by OTC drugs, many of which are combinations: Ibuprofen or Acetaminophen/paracetamol (analgesic and antipyretic) Chlorpheniramine or Diphenhydramine (antihistamine) Pseudoephedrine or Phenylephrine (decongestant) Dextromethorphan (antitussive) Guaifenesin (expectorant) LiquiTime allows for combination of active ingredients with potential to tailor release profile for each Exclusive U.S. rights to LiquiTime licensed to Perrigo for OTC market in October Deutsche Bank 2 IMS U.S. sales January

19 Trigger Lock Hydromorphone FT227, an abuse-deterrent, extended-release, oral hydromorphone product for treatment of pain Positive results from two pilot PK studies in healthy volunteers announced in June 2015 Bioequivalence criteria for area under the curve (AUC) and the peak plasma concentration (Cmax) met under fasted conditions No notable difference in either AUC or Cmax in fed and fasted conditions (comparing the effect of food on the PK parameters) Independent research by CRO further validates in-house data on abuse deterrent properties and robust technology FT227 demonstrated better resistance in extraction/recovery studies in different media and under several different conditions than both Exalgo and Oxycontin Shown to resist both chemical and physical manipulation Next steps: Flamel will meet with the FDA in 1H 2016; partnering discussions begun January

20 Trigger Lock Market Opportunity Trigger Lock technology is applicable to all opioids Abuse of painkillers is a major public health concern in the USA ~2.1 million in US in 2012 suffered from substance use disorders related to prescription opioid pain relievers U.S. market for prescription painkillers (all forms) in 2015 (Jan.-Nov.):$6.5b 1 OxyContin (extended-release oxycodone, Purdue): $2.1b 1 ER hydromorphone (Exalgo & generics) $138m 1 Number of prescriptions for opioids (like hydrocodone and oxycodone products) escalated from ~76 million in 1991 to ~207 million in IMS 2 America s Addiction to Opioids: Heroin and Prescription Drug Abuse (National Institute on Drug Abuse, May 14, 2014) January

21 Medusa Exenatide FT228 is a subcutaneous injection formulation of exenatide, a GLP-1 (glucagon-like peptide 1) for treatment of Type 2 diabetes Interim phase I human clinical data reported on December 22, 2015 All safety and pharmacokinetic (PK) assessment objectives throughout ascending single dose administrations of FT228 Safety profile of FT228 was favorable in healthy volunteers up to a dose of 140 mcg Extremely low incidence of the gastrointestinal side effects commonly related to twice daily subcutaneous administration of exenatide (nausea, vomiting, abdominal discomfort, loss of appetite) Low incidence of mild injection site reactions PK profile compatible with a release over one week in humans Market opportunity: GLP-1 products recorded over $3.2 billion*: $2.1b for Victoza (once a day liraglutide, Novo Nordisk) $600m for Bydureon (once-a-week exenatide, AstraZeneca) $266m for Byetta (twice-a-day exenatide, AstraZeneca) Next steps: completion of Phase 1b study in 1H 2016; seek partnership * IMS U.S. sales in 2015 (Jan. Nov.) January

22 Flamel s Strengths Diversified and proven drug delivery platforms Strong intellectual property Seasoned senior management Healthy financial situation January

23 Diversified and Proven Drug Delivery Platforms Outstanding drug delivery platforms 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 (already-marketed, off-patent or novel) Modified/Controlled Release of Solid Oral Drugs Modified/Controlled Release of Liquid Oral Drugs Modified/Controlled Release of Injectable Drugs Abuse-Resistant Modified/Controlled Release Narcotics/Opioid Analgesics Micropump, LiquiTime, Trigger Lock and Medusa are trademarks of Flamel Ireland Ltd. January

24 Strong Intellectual Property Broad portfolio of patents* 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) New patents may be issued targeting each individual product in development where a Flamel drug delivery platform is applied to a specific molecule * 2014 Annual Report on form 20-F published on April 31st, 2015 January

25 Seasoned Senior Management Name Title Appointed Experience Michael S. Anderson Chief Executive Officer years Pharma Sandy Hatten Senior Vice President, Quality and Regulatory Affairs years Pharma Phillandas T. Thompson, J.D., M.B.A. Senior Vice President, General Counsel years Legal Mike Kanan Senior Vice President and Chief Financial Officer years Financial Gregory J. Davis Vice President, Corporate and Business Development years Pharma David Monteith, Ph.D. Vice President, Research and Development years Pharma Dhiren D Silva Vice President of Irish and European Operations years Business January

26 Condensed Consolidated Statement of Operations (Unaudited) In USD million, except EPS (USD) and shares data (million) Nine months ended September30, 2014 September 30, 2015 Total Revenue $ 11.8 $129.8 Total Costs and Expenses (72.2) (135.3) Profit (loss) from continuing operations Net income (loss) from continuing operations (60.4) (5.4) (57.0) (35.4) Net income (loss) (57.8) (35.4) Diluted EPS from continuing operations (1.62) (0.88) Adjusted Diluted EPS (non-gaap) (0.44) 0.72 Diluted Shares Outstanding January

27 Condensed Balance Sheet (Unaudited) In USD million Cash & marketable securities As of Dec. 31, 2014 As of March 31, 2015 As of June 30, 2015 $92.8 $113.2 $116.1 LT debt Other LT liabilities Includes government loans for R&D projects, acquisition liability contingent consideration, warrant consideration, and royalty agreements concluded in February 2013 and December Includes provision for retirement indemnity January

28 Flamel Technologies Transformed Fully integrated global specialty pharmaceutical company with FDA approved products and a broad pipeline using Flamel s proprietary drug delivery platforms Two FDA approved products marketed by Flamel in the United States on track to drive significant cash flow in 2016 Incremental clinical data expected from several of Flamel s pipeline products over the next months Anticipated positive cash flow in 2015 and 2016 Net cash position of over $128 million on September 30, 2015 Strategy: Flamel controls 100% of its drug development and its future January

29 Drug Delivery Platforms at a Glance January

30 Micropump Platform at a Glance Extended/delayed-release of drugs in the GI tract Precise pharmacokinetics of single or combination of drugs in various formats Numerous Micropump -based products successfully tested in human clinical trials Commercial stage platform approved in the USA and EU Various dosage forms (tablet, capsule, sachet, liquid) Widely used and accepted excipients Combination of multiple release profiles and/or multiple active ingredients Rapid development time Taste-masking properties Strong IP position Easy to scale-up January

31 Micropump Microparticles for Controlled/Modified Release Granules drug granulate or layered neutral core Microparticles are dispersed in the stomach and pass into the small intestine, after which 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 January

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 This graph illustrates the different near zero-order release profiles which can be tailored for the same drug LiquiTime s versatility allows once- or twice-daily liquid formulations of a wide variety of drugs January

33 LiquiTime for Extended-Release Liquid Suspension 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 Coating controls diffusion keeps its integrity offers good resistance to stress µm Each microparticle is individually coated and behaves as an independent micro reservoir January

34 Trigger Lock Platform at a Glance 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) January

35 Trigger Lock SR Microparticles for Abuse Resistance 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 Each microparticle retains its polymer coating which is virtually impervious to further crushing January

36 Medusa Platform at a Glance Applicable to a wide range of small molecules, peptide and protein drugs Solubilization and stabilization of drugs Safe, non-immunogenic and fully biodegradable Combination of several different drugs in the same formulation Medusa Depot Sustained delivery from 1 to 7 days in human Bio-friendly, water-based, solvent-free formulation process Strong IP position January

37 Medusa Depot for Injection Made of polyglutamic acid and Vitamin E Amphiphilic and spontaneously forms stable nanoparticles in water Complexes are stable over a wide range of ph COO - Na + COO - Na + COO - Na + COO - Na + COO - Na + COO - Na + COO - Na + Polyglutamate chain Vitamin E Water clear liquid Solution Or Freeze-dried * * Injection * Drug solution or powder Formulation by simple mixing in water Non-covalent association (reversible hydrophobic and/or electrostatic interaction) of the drug with Medusa nanoparticles In Vitro In vivo depot formation In Vivo Sustained release of the unmodified drug over 1 to 7 days January

38 Specialty Pharmaceutical Company with Proprietary Drug Delivery Platforms Focused on Improved or Cost-Effective Products Headquarters 33 avenue du Dr. Georges Levy Vénissieux (Lyon) France Corporate Contact Phone: Fax: January