PARIS and TARRYTOWN, N.Y., May 21, 2013 /PRNewswire/ -- Sanofi (EURONEXT: SAN and NYSE: SNY) and Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that the New England Journal of Medicine published online the positive Phase 2a study results of dupilumab (SAR231893/REGN668) in patients with moderate-to-severe allergic asthma. Dupilumab is an investigational monoclonal antibody targeting the alpha subunit of the interleukin 4 receptor (IL-4R alpha), which modulates signaling of both IL-4 and IL-13, drivers of Th2 (Type 2 helper T cell) immune response. The study results will also be presented today at a late-breaking clinical trials session at the American Thoracic Society 2013 International Conference.

The proof-of-concept study enrolled 104 patients with moderate-to-severe, persistent asthma that was not well controlled with inhaled glucocorticosteroids (ICS) and long-acting beta agonist (LABA) therapy, and who had elevated blood or sputum eosinophils (immune cells used as a marker of Th2 asthma in this study).

The primary objective of the trial was to assess the effect of dupilumab, dosed subcutaneously, weekly at 300 milligrams (mg) for twelve weeks. Patients were treated with dupilumab (N=52) or placebo (N=52) on top of ICS and LABA therapy for the first four weeks of the study. The LABA was withdrawn at week four and the ICS was tapered to withdrawal between weeks six and nine. Patients were treated for 12 weeks or until they experienced a protocol-defined asthma exacerbation, the primary endpoint of the study. 23 patients (44.2%) receiving placebo experienced an asthma exacerbation compared to three patients (5.8%) receiving dupilumab, resulting in an 87% reduction in the incidence of asthma exacerbations for the dupilumab arm compared to placebo (p<0.0001).

Clinically meaningful and statistically significant improvements were observed for lung function and other asthma control parameters, such as forced expiratory volume over one second (FEV₁) (difference from baseline to week 12 between dupilumab and placebo of 0.27 L, p<0.001).

Treatment-emergent adverse events (AEs) were reported by a similar proportion of patients in both groups (76.9% placebo; 80.8% dupilumab). AEs were generally non-specific and of mild-to-moderate intensity. The most common AEs for placebo and dupilumab were injection-site reaction (9.6% and 28.8%), nasopharyngitis (3.8% and 13.5%), upper respiratory tract infection (17.3% and 13.5%), headache (5.8% and 11.5%) and nausea (1.9% and 7.7%).

"Despite existing therapies, a significant number of patients with moderate-to-severe, persistent allergic asthma are not optimally controlled, which puts them at risk of poor clinical outcomes. These patients contribute to the significant economic burden of asthma," said Sally Wenzel, M.D., Professor of Medicine and Director of the Asthma Institute at the University of Pittsburgh and lead investigator of this trial. "These encouraging data support the potential role of IL-4/IL-13 blockade in an important subset of asthma patients and warrant continued clinical investigation."

"Through blockade of IL-4R alpha, dupilumab modulates signaling of both the IL-4 and IL-13 pathways, which have been implicated in the pathophysiology of Th2 mediated, or allergic, diseases such as asthma," said George D. Yancopoulos, M.D., Ph. D., Chief Scientific Officer of Regeneron and President of Regeneron Laboratories. "These data, combined with our previously-reported positive proof-of-concept clinical results of dupilumab in atopic dermatitis, support the idea that blocking the IL-4/IL-13 pathway may be an effective mechanism to treat multiple allergic conditions. We look forward to initiating Phase 2b studies in both asthma and atopic dermatitis shortly."

These data will be presented by Dr. Sally Wenzel this morning at the American Thoracic Society 2013 International Conference in a presentation entitled, "Efficacy and safety of SAR231893/REGN668 in patients with moderate-to-severe, persistent asthma and elevated eosinophil levels."

About IL-4R and the IL-4/IL-13 Pathway

Atopic dermatitis and some types of asthma are characterized by the induction of a specific type of an immune response that is driven by a subset of immune cells called Type 2 helper T cells, or Th2 cells. IL-4 and IL-13 are key cytokines that are required for the initiation and maintenance of this Th2 immune response. IL-4 and IL-13 signaling occurs through Type I and II IL-4 receptors (IL-4 through both receptors and IL-13 through Type II receptors), which both contain a common IL-4R alpha subunit.

About Dupilumab (SAR231893/REGN668)

Dupilumab is a fully human monoclonal antibody directed against IL-4R alpha and is administered via subcutaneous injection. By blocking IL-4R alpha dupilumab modulates signaling of both IL-4 and IL-13, drivers of a Th2 immune response. Dupilumab was created using Regeneron's pioneering VelocImmune^® technology and is being co-developed with Sanofi. Dupilumab is currently being studied in both atopic dermatitis and asthma.

About Asthma

Asthma is a chronic inflammatory disease of the airways characterized by airway sensitivity to environmental and biologic factors such as dust, chemicals, smoke, allergens, and viral infections leading to an acute and chronic narrowing of the airway and increased mucus production. Patients with asthma can experience wheezing, shortness of breath, cough and chest tightness, and in severe cases, these symptoms can be life-threatening. For most asthma patients, currently available treatments can control the disease. However, an estimated 10% to 20% of asthmatic patients are less than optimally controlled despite existing therapies. Moderate-to-severe asthma can negatively impact the lives of patients and is associated with a high burden to society both in terms of direct costs of medical care and prescription drugs, as well as loss of productivity. Moderate-to-severe asthma is recognized as a heterogeneous disease; the Th2 inflammation pathway is believed to play a role in disease pathogenesis in approximately 50% of these patients. It is estimated that approximately 25 million people in the United States are known to have asthma. The worldwide estimates are between 235-300 million people, with 180,000 deaths annually.

About Sanofi

Sanofi, an integrated global healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients' needs. Sanofi has core strengths in the field of healthcare with seven growth platforms: diabetes solutions, human vaccines, innovative drugs, consumer healthcare, emerging markets, animal health and the new Genzyme. Sanofi is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).

About Regeneron Pharmaceuticals, Inc.

Regeneron is a leading science-based biopharmaceutical company based in Tarrytown, New York that discovers, invents, develops, manufactures, and commercializes medicines for the treatment of serious medical conditions. Regeneron markets medicines for eye diseases, colorectal cancer, and a rare inflammatory condition and has product candidates in development in other areas of high unmet medical need, including hypercholesterolemia, oncology, rheumatoid arthritis, allergic asthma, and atopic dermatitis. For additional information about the company, please visit www.regeneron.com.

Sanofi Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future financial results, events, operations, services, product development and potential, and statements regarding future performance. Forward-looking statements are generally identified by the words "expects", "anticipates", "believes", "intends", "estimates", "plans" and similar expressions. Although Sanofi's management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such product candidates, the absence of guarantee that the product candidates if approved will be commercially successful, the future approval and commercial success of therapeutic alternatives, the Group's ability to benefit from external growth opportunities, trends in exchange rates and prevailing interest rates, the impact of cost containment policies and subsequent changes thereto, the average number of shares outstanding as well as those discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in Sanofi's annual report on Form 20-F for the year ended December 31, 2012. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements.

Regeneron Forward-Looking Statements

This news release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron, and actual events or results may differ materially from these forward-looking statements. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of Regeneron's products, product candidates, and research and clinical programs now underway or planned; including without limitation dupilumab; unforeseen safety issues resulting from the administration of products and product candidates in patients; the likelihood and timing of possible regulatory approval and commercial launch of Regeneron's late-stage product candidates; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize Regeneron's products and product candidates; competing drugs and product candidates that may be superior to Regeneron's products and product candidates; uncertainty of market acceptance of Regeneron's products and product candidates; the ability of Regeneron to manufacture and manage supply chains for multiple products and product candidates; coverage and reimbursement determinations by third-party payers, including Medicare and Medicaid; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its sales or other financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license or collaboration agreement, including Regeneron's agreements with Sanofi and Bayer HealthCare, to be cancelled or terminated without any further product success; and risks associated with third party intellectual property and pending or future litigation relating thereto. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2012 and our From 10-Q for the quarter ended March 31, 2013. Regeneron does not undertake any obligation to update publicly any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise, unless required by law.

SOURCE Regeneron Pharmaceuticals, Inc.

QUEBEC CITY, May 20, 2013 /PRNewswire/ -- Asmacure Ltee, a clinical-stage biopharmaceutical company focused on the development of novel, proprietary compounds that target cholinergic receptors for the treatment of pulmonary diseases, today announced presentations of four studies of ASM-024, Asmacure's lead compound in development for asthma and chronic obstructive pulmonary disease (COPD). The data were presented at the 2013 American Thoracic Society (ATS) International Conference in Philadelphia.

"We believe the combined data presented confirm the significant potential for our lead compound, ASM-024, to positively impact the treatment of asthma and other respiratory disorders," said Yvon Cormier, M.D., Asmacure's founder and chief medical officer. "ASM-024's novel dual mechanism of action, which has been shown to induce smooth muscle relaxation as well as anti-inflammatory and bronchodilating effects, may address a significant need as an adjunctive treatment with current standard of care in patients with moderate to severe asthma or chronic obstructive pulmonary disease. We anticipate moving ASM-024 into a phase 2 trial in COPD later this year."

Highlights of the studies presented follow below:
(Poster #B25)

• The first study positively evaluated the safety, tolerability and clinical activity of ASM-024 delivered as a solution for nebulization formulation in people with mild allergic asthma in a phase 2 allergen challenge clinical trial, representing the first clinical proof-of-concept data for ASM-024 in an asthma patient population. ASM-024 was shown to reduce methacholine airway responsiveness and improve baseline lung function. No serious adverse events were reported in the study with poor taste and cough observed as the most common side effects. ASM-024, significantly inhibited IgE-mediated activation of basophils in vitro and decreased allergen-induced CD203c expression on circulating basophils of mild asthmatic subjects after 9 days treatment.

(Poster #507)

• A second study evaluated ASM-024's ability to activate potassium channels and the sodium/potassium (NA+/K+) ATPase pump, which pumps sodium out of and potassium into cells to regulate resting potential, in guinea pig tracheal rings. Previous studies have shown that ASM-024 reduces airway resistance in mice and has smooth muscle relaxant properties in vitro by acting directly on airway smooth muscle cells by a mechanism independent of cGMP or cAMP pathways; however, ASM-024's action on potassium channels and Na+/K+ ATPase is unknown. Researchers measured changes in tension with cumulative doses of ASM-024 (0.1-1000 microns). To investigate the potential mechanisms involved in the relaxant activity of ASM-024, the tracheal rings were pretreated with channel and pump inhibitors. Results showed that ASM-024's relaxant properties are independent of ATP-sensitive potassium channels, calcium-sensitive potassium channels or Na+/K+-ATPase activation, and further confirmed that ASM-024's mechanism of action is linked to its interaction with the nicotinic receptor.

(Poster #F76)

• A third study explored and differentiated between ASM-024, which has dual nicotinic and muscarinic action, and commonly used short- and long-acting muscarinic acetylcholine receptor antagonists. These antagonists are used in COPD and severe asthma to reduce enhanced cholinergic activity, but may be less effective on bronchoconstriction induced by histamine. Researchers measured relaxant responses to methacholine or histamine contraction via isometric tension measurement of guinea pig tracheal rings, and found that ASM-024 not only induces in vitro smooth muscle relaxation of histamine-contracted tracheas, but also has an additive relaxant effect to muscarinic acetylcholine receptor agonists after methacholine-induced contraction, suggesting that ASM-024 has different functional activity from these drugs. The precise mechanisms of action of ASM-024 continue to be studied; data develop to date indicate that ASM-024 has effects at the nicotinic and muscarinic levels. The results further suggest that ASM-024 could be considered as an add-on agent to current standard of care in patients with poorly controlled asthma, and in COPD patients who present insufficient bronchodilator response to current medication.

(Poster #B41)

• A final study evaluated the relaxant effects of ASM-024 on Beta2-agonist desensitized guinea-pig tracheas. Inhaled Beta2-agonists are widely used in asthma and COPD; however, prolonged use of these agonists induces functional desensitization of the Beta2-adrenoreceptors, which may lead to reduced efficacy when used chronically. The study assessed ASM-024's efficacy in promoting the relaxation of guinea pig tracheas that were rendered unresponsive to Beta2-agonists. Findings showed that ASM-024 elicits relaxation of Beta2-desensitized tracheal preparations, suggesting that ASM-024 mediates smooth muscle relaxation through a different target and signaling pathway than conventional Beta2-adrenergic receptor agonists; ASM-024 could thus potentially be used as an add-on therapy in patients with insufficient bronchodilator response to currently available Beta2-agonists.

About Asthma
Asthma is a reversible obstructive lung disease, caused by increased reaction of the airways to various stimuli. It is a chronic inflammatory condition with acute exacerbations. Asthma can be a life-threatening disease if not properly managed. According to the American Lung Association in 2011 it was estimated that 25.9 million Americans currently have asthma, including 7.1 million children under 18. Of these, 13.2 million Americans (4.1 million children) had an asthma attack. Close to 2.1 million emergency room visits were attributed to asthma in 2009.

About ASM-024
The company's lead development compound, ASM-024, with its novel mechanism of action, has demonstrated the capabilities of inhibitory effects on inflammation, bronchoprotection and smooth muscle relaxation in pre-clinical asthma models. ASM-024 delivered as a solution for nebulization achieved proof of concept in the treatment of patients with asthma in a phase 2 clinical trial program. The company is now focused on bridging from the ASM-024 solution formulation to the development of the compound in a dry powder for inhalation (DPI) dosage form. Typically, DPI's are a preferred dosage form for pulmonary products by allowing for delivery of lower, more optimal dosing with greater lung deposition.

ASM-024 demonstrated a highly-significant effect on FEV₁and methacholine PC₂₀ pre-allergen challenge in a phase 2 study utilizing the solution for nebulization formulation. In pre-clinical asthma models, ASM-024 has demonstrated an adjunctive benefit when combined with long- and short-acting Beta-agonists and long- and short-acting muscarinic antagonists.

Based on recent findings about the novel mechanism of action for ASM-024 with nicotinic and muscarinic effects, Asmacure will initiate a phase 2 study in COPD patients in the third quarter of this year.

About Asmacure
Asmacure Ltee is a clinical-stage biopharmaceutical company focused on the development of novel, proprietary compounds that target cholinergic receptors for the treatment of inflammation, notably pulmonary airway diseases. The company's lead compound, ASM-024, has a novel mechanism with multi-functional properties at the nicotinic and muscarinic levels. Asmacure was founded by Dr. Yvon Cormier, a noted pulmonologist, and Evelyne Israel-Assayag in 2002 and is based in Quebec City, Quebec, Canada. Asmacure is a privately-held company with the major investors including Domain Associates, Fonds de solidarite des travailleurs du Quebec (F.T.Q.) and Desjardins-Innovatech s.e.c. For more information visit www.asmacure.com.

Contact Information
E. Blair Schoeb
Tel: 917-432-9275
blair@biotechcomm.com

SOURCE Asmacure