Microsoft powerpoint - flamel.7-9-13

Forward Looking Statements
The following presentation regarding Flamel Technologies SA includes a number of matters, particularly as related to the status of various research projects and technology platforms, that constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.
presentation reflects the current views of Flamel's management with respect to future events and is subject to risks and uncertainties that could cause actual results to differ materially from those contemplated in such forward-looking statements. These risks include risks that products in the development stage may not achieve scientific objectives or milestones or meet stringent regulatory requirements, uncertainties regarding market acceptance of products in development, the impact of competitive products and pricing, and the risks associated with Flamel's reliance on outside parties and key strategic alliances. These and other risks are described more fully in Flamel's public filings. Except as required by law, Flamel does not intend, and disclaims any duty or obligation, to update or revise any forward-looking statements contained in this presentation to reflect new information, future events or otherwise.
Flamel’s Comparative Advantage
„ Flamel was founded in 1990 to develop technologies based on its
expertise in polymer chemistry.
„ Two Best in Class Drug Delivery Platforms:
• Micropump for Small Molecules:
– Chosen by GSK to defend Coreg® franchise.
• Medusa for Proteins and Peptides:
– Allows controlled release without loss of bioactivity. „ Flamel’s proprietary technologies may be applied in partnership to improve: • New chemical entities.
• New proteins or currently approved drugs.
„ Flamel also develops projects through proof of concept using its Flamel’s Business Model
„ Flamel selects and licenses its products to partners capable of
developing them and maximizing their market value:
• We benefit from large companies’ depth of experience in managing clinical trials, the registration process, and its sales force.
• Partners benefit from our focus on drug delivery technology and our ability to develop and, if necessary, manufacture on tight timetables.
„ Flamel receives upfront payments, milestones and royalties based
on the partner’s sales.
„ Flamel retains a right to recover the project if the partner decides
not to develop or to market it.
„ Goal is for partnership development revenues and milestones to be
used for internal projects, allowing royalty revenues to flow
directly to earnings.
Micropump®: Controlled Release
of Small Molecule Drugs
for Better Efficacy and Compliance
Micropump® - Oral Delivery System
for Small Molecules
Core: active ingredient
Coating:
200-500 µm
Size Matters
Advantages of the Micropump® System
„ Transit time in the small intestine is extended (up to 12 hours), allowing
greater flexibility in treatment, such as chronotherapy.
„ Bioavailability improvements are possible for drugs with poor bioabsorption.
„ Intersubject and intrasubject variability is minimized.
„ Versatile presentation to serve all markets from pediatric to geriatric with
• Suspensions• Capsules• Tablets• Sachets „ High Drug Loading Ratio.
„ Enables the delivery of low-solubility or high-solubility drugs.
„ Combination therapy is facilitated, as each microparticle is its own delivery
The majority of small molecule drugs are candidates for Micropump®
COREG-CR™: Partnered Product with
COREG CR™ Therapeutic Indications &
Advantages
Indicated for:
„ Mild to Severe Congestive Heart Failure.
„ Left Ventricular Dysfunction Following Myocardial Infarction.
Partnership
„ Coreg 2006 sales were over $1.4 billion and grew at 38%:
• 1H 2007 annualized sales for the Coreg franchise were $1.65 billion.
„ Growth has been driven by Coreg’s success in treating congestive
heart failure (CHF):
• Only beta-blocking agent FDA approved to improve survival in mild to • Only beta-blocker approved for reducing cardiovascular mortality in Post MI patients with left ventricular dysfunction.
„ We are the exclusive supplier for Coreg-CR microparticles using our
Micropump® platform:
• Plant capacity in Pessac was expanded at GSK’s cost.
• Second supply agreement announced August, 2006 to increase capacity by 50%.
• Potential further capacity expansion.
Four Catalysts for Success of COREG CR
COREG CR’s unique release profile creates
therapeutic benefits
PK Equivalence: Mean Steady-State Plasma Concentration-
Time Profiles for COREG and COREG CR in LVD Patients
edilol (ng/mL)
rv
COREG CR 80 mg QD (n= 42)
COREG 25 mg Q12h (n= 42)
Time (hours)
Packer M et al. Am J Cardiol. 2006;98:39L–45L.
In a 122 patient crossover study, patients initially
receiving COREG CR reported 24% fewer adverse events
than patients receiving regular Coreg.
Articles from American Journal of Cardiology 2006, 98 1. Pharmacokinetic Properties of a New Controlled-Release Formulation of Carvedilol: David Tenero et al.
2. Pharmacokinetic Profile of Controlled-Release Carvedilol in Patients with Left Ventricular Dysfunction Associated with Chronic Heart Failure of After Myocardial Infarction: Milton Packer et al.
3. Pharmacokinetic and Pharmacodynamic Comparison of Controlled-Relesae Carvedilol and Immediate Release Carvedilol at Steady State in Patients with Hypertension: Linda Henderson et al.
4. Controlled-Release Carvedilol in the Treatment of Essential Hypertension: Michael Weber et al.
5. Cardiovascular Risk Factors in Hypertension: Rationale and Design of Studies to Investigate the Effects of Controlled-Release Carvedilol on Regression of Left Ventricular Hypertrophy and Lipid Profile: George 6. Rationale and Design of CASPER: Compliance and Quality of Life Study Comparing Once-Daily Carvedilol CR and Twice-Daily Carvedilol IR in Patients with Heart Failure: Paul Hauptman et al.
7. COMPARE: Comparison of the Effects of Carvedilol CR and Carvedilol IR on Left Ventricular Ejection Fraction in Patients with Heart Failure: Barry Greenberg et al.
8. Effect of Beta Blockers, Particularly Carvedilol, on Reducing the Risk of Events After Acute Myocardial 9. Controlled-Release Carvedilol: A Concluding Perspective: Milton Packer.
COREG CR versus Coreg®: the COMPARE Trial
„ A study to compare the Effects of Coreg CR and Coreg IR on Heart Function in Subjects with Stable Chronic Heart Failure: - 700 patients with stable heart failure.
- Compares left ventricular ejection fraction to baseline six months post- - Change in left ventricular remodelling;- Change in Brain Natriuretic Peptide (BNP) level;- Hospitilizations fro heart failure;- Drug dose tolerability; and- Compliance Diabetes and Hypertension
„ Over 13 million Americans have both diabetes and hypertension:
• It is estimated that over 65% of these patients require treatment with two or more different anti-hypertensive medications at recommended levels to reach suggested blood pressure levels.
„ The American Diabetes Association recommends diabetic patients
should be treated to a systolic/diastolic level of <130/80:
• Hypertension is typically defined as blood pressure greater than 140/85.
Coreg is the only approved beta blocker shown not to
raise glycemia levels and to increase insulin
sensitivity in diabetic patients.
COREG CR Hypertension Trials
COREG CR + Lisinopril Combination Trials:
• The CLEVER study – COREG CR and left ventricular mass regression: - 200 patients with Stage 1 or 2 hypertension and left ventricular hypertrophy.
• COREG and Lisinopril Combination Therapy in Hypertensive Subjects (COSMOS) Trial: - 643 patients with Stage 1 or 2 hypertension.
• The Vascular Effects of Carvedilol CR + Lisinopril Versus Lisinopril + Hydrochlorothiazide in Abdominally Obese Hypertensive Patients.
• Vascular Benefits of Adding Carvedilol CR to Type 2 Diabetic Patients on ACEI.
• COREG CR Monotherapy Trial:
ƒ COREG CR vs TOPROL-XL on the lipid profile of normolipidemic or mildly dyslipidemic RING FENCES PROTECT COREG CR IP
„ Notice of Allowance issued by United States Patent and Trademark
Office March 23, 2007:
• To cover carvedilol dihydrogen phosphate hemihydrate through
• At least eight other claims reserved.
„ Micropump I Formulation Patents extend to 2016.
„ Micropump II Formulation Patent in Prosecution to extend to 2023.
„ Hatch Waxman Exclusivity on Coreg CR to extend at least three
„ New possible combination products to receive further potential
Hatch Waxman exclusivity as well.
Abuse of Opioid analgesics:
the Trigger Lock™ Solution
First Do No Harm
„ All opioid analgesics face considerable abuse:
• Leads to potential under-treatment of severe pain.
• Legal and regulatory ovesight of this market is increasing.
„ Trigger Lock is designed to deliver sustained release of drugs
susceptible to abuse:
• Microparticles effectively cannot be crushed• Dissolution in alcohol and other domestic solvents reduced• Injection is effectively impossible• Possible application for Oxycontin® ($2.0 billion in US sales in 2004) „ Trigger Lock allows us to formulate these drugs without affecting
bioavailability:
• Potentially greater efficacy than existing platforms• Ability to introduce bioequivalent formulations of existing products due to pharmacokinetic advantage versus other abuse resistant technologies „ Two Phase I trials are planned:
• To demonstrate bio-equivalence versus a commonly prescribed controlled release opioid analgesic.
• To demonstrate resistance to alcohol-related dose dumping.
Medusa®
Third Generation Technology for Delivery of
Unmodified Human Proteins
Description of Medusa® II nanocarrier
Evolution of Therapeutic Protein Formulations
„ Generation I - Immediate release proteins:
• efficacy of human proteins,• strong side-effects,• numerous injections per week.
„ Generation II - PEGylation:
• reduces the number of injections per week,• decreases the bioactivity of the protein,• strong-side effects.
„ MEDUSA allows the creation Third Generation Therapeutic Proteins and
• maintains efficacy of human proteins with full bioactivity,• reduces the number of injections per week, and• reduces-side effects.
The Ubiquitous Polymer
„ The latest Medusa polymer is applicable to a wide variety of proteins, peptides, and other large molecules „ All pre-clinical toxicology and carcinogenicity tests have „ Use of a single polymer speeds development time and saves „ Four new projects using the new Medusa polymer: –Oncology;–Therapeutic Vaccine;–Ophthalmology;–Therapeutic Protein License Agreement with Wyeth
Pharmaceuticals
„ To develop an improved formulation of an already marketed •Upfront payment;•Development costs to be paid by Wyeth;•Milestones; and•Royalties IFN-Alpha XL
Viral Load Result (non-responder patients)
og
L
(
n
tio
Time (Hours)
Viral load decrease in non-responding genotype 1 patients: IFN XL: Safety
viraferon
(3*3MIU)
Hematological
Influenza like Illness
IFN-XL is well tolerated:
adverse events were transient and slight to moderate in severity
FT-105 Next Generation Basal Insulin
„ Phase I glucose clamp study versus Lantus® ongoing.
„ Preclinical results indicate 48 hour controlled release.
„ Promises true 24 hour coverage for 100% of patients with better glucose control than the best in class.
Financial Summary
Six months ended
Six months ended
June 30, 2006
June 30, 2007
Board of Directors
Elie Vannier
Chairman
Cornelis (Cor) Boonstra
Director
(Former Chairman and Chief Executive Officer of Frédéric Lemoine Director
Lodewijk J.R. de Vink
Director
(Former Chairman and Chief Executive Officer of Warner Lambert and Former President of Schering Plough International) John L. Vogelstein
Director
Stephen H. Willard
Director and CEO

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