Amicus Therapeutics Highlights Data Featured at Lysosomal Disease Network WORLD Symposium 2014

Amicus Therapeutics Highlights Data Featured at Lysosomal Disease Network WORLD Symposium 2014    First Scientific Meeting to Present Preclinical Proof-of-Concept Data for     Next-Generation Pompe ERT and Proprietary Enzyme Targeting Technology   Encouraging Additional Post-Hoc Analyses of Interim Data from Phase 3 Fabry                             Monotherapy Study 011  CRANBURY, N.J., Feb. 12, 2014 (GLOBE NEWSWIRE) -- Amicus Therapeutics (Nasdaq:FOLD), a biopharmaceutical company at the forefront of therapies for rare and orphan diseases, today summarized the key highlights from 2 oral platform presentations featuring its Pompe and Fabry programs at the Lysosomal Disease Network WORLD Symposium (LDN WORLD) 2014. LDN WORLD is taking place in San Diego, CA from February 10-13, 2014.  John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics, Inc., stated, "At this year's WORLD Symposium we are highlighting data from several of our ongoing development programs. This is the first scientific meeting to feature our next-generation Pompe ERT and proprietary enzyme targeting technology, purchased through our acquisition of Callidus Biopharma. Together with our Chaperone-Advanced Replacement Therapy, or CHART, platform these technologies may provide a unique tool set to address some of the major challenges with currently marketed ERT products – enzyme activity and stability; targeting and uptake; and tolerability and immunogenicity. We are also pleased to present further, post-hoc analyses of 6-month data from our first of two ongoing Phase 3 Fabry monotherapy studies, which we believe demonstrate that migalastat HCl is having a positive impact in Fabry patients with amenable mutations."  Preclinical Proof-of-Concept Data for Next-Generation Pompe ERT and Proprietary Enzyme Targeting Technology  Preclinical proof-of-concept data for AT-B200, Amicus' proprietary recombinant human acid-alpha glucosidase (rhGAA) for Pompe disease, as well as an overview of the Company's proprietary peptide tagging technology (vIGF-2), will be presented to a scientific audience for the first time at LDN WORLD 2014. AT-B200 is differentiated from other Pompe ERTs by its unique carbohydrate structure. This ERT may be further optimized through co-formulation with Amicus' pharmacological chaperone AT2220 to improve enzyme stability and tolerability, and by applying the Company's peptide tagging technology for better targeting. Preclinical results have shown that AT-B200 and AT-B200 conjugated with vIGF-2 ("tagged AT-B200") were better than Lumizyme for clearing glycogen in skeletal muscles in GAA knock-out mice after 4 weekly IV bolus administrations^1.  Hung Do, PhD, Senior Vice President, Amicus Therapeutics, Inc., stated, "After spending over a decade developing enzyme replacement therapies for Pompe and other lysosomal storage diseases at Genzyme and Novazyme, AT-B200 was developed to be a next-generation Pompe ERT with a unique carbohydrate structure that may better target skeletal muscles. Our preclinical studies to date demonstrate the potential for AT-B200 in Pompe disease, as well as the differences between our peptide tagging technology and other IGF-2 tagging approaches in development. We look forward to further preclinical development to evaluate tissue uptake and glycogen clearance with longer dosing schedules of AT-B200, with and without a pharmacological chaperone."  Updated 6-Month Data from Fabry Monotherapy Phase 3 Study 011                                                                       Study 011 6-Month (Stage 1) Data        Migalastat Group Placebo Group P-Value Primary Endpoint: Responder Analysis (≥ 50% Reduction in Interstitial Capillary 41%              28%           0.300 GL-3) (ITT; n = 64; 32 per group)^1 Post-Hoc Analysis: Mean Change in       -0.22 ± 0.11     +0.06 ± 0.09  0.052 Inclusions Per Capillary* (mITT; n = 60; 30 per group)^2                                        Post-Hoc Analysis: Mean Change in Inclusions Per Capillary* in GLP HEK Amenable Patients (n = 46; 25 in        -0.31 ± 0.12     +0.10 ± 0.13  0.002 migalastat HCl group, 21 in placebo group)^3  ^1ITT = patients with evaluable baseline kidney biopsies; patients with unevaluable 6-month biopsies counted as non-responders.  ^2mITT = patients with evaluable paired biopsies (baseline and month 6)  ^3GLP HEK Amenable = patients with amenable mutations in GLP-validated HEK assay  *ANCOVA model with covariate adjustment for baseline value and treatment-by-baseline interaction  Migalastat HCl monotherapy is being investigated in two ongoing Phase 3 studies (Study 011 and Study 012) in Fabry patients with amenable mutations. Study 011 enrolled a total of 67 patients to compare migalastat HCl to placebo in reducing kidney interstitial capillary globotriaosylceramide (GL-3). Top-line data from the 6-month double-blind, placebo-controlled treatment period (Stage 1) in Study 011 was previously reported. Updated Stage 1 data, including a post-hoc analysis of the mean change from baseline in inclusions per capillary as a continuous variable ("mean change in GL-3"), are being presented at LDN WORLD^2.  Raphael Schiffmann, M.D., M.H.Sc., Medical Director of the Institute of Metabolic Disease, Baylor Research Institute, stated, "As an investigator working on the development of migalastat HCl and other new treatments for patients living with Fabry disease, I was very encouraged to see the post-hoc analysis of Stage 1 data from Study 011. These data clearly show that migalastat HCl has a biological effect in Fabry patients with amenable mutations. We look forward to seeing the 12- and 24-month data from this study later this year."  The primary endpoint in Study 011 analyzed the percent change in kidney interstitial capillary GL-3 inclusions from baseline to month 6 (responder analysis with a 50% reduction threshold). However, the variability and low levels of GL-3 at baseline contributed to a higher-than-anticipated placebo response. Following the unblinding of the Stage 1 data, and while still blinded to the Stage 2 data, Amicus identified a more appropriate way to control for the variability in GL-3 levels in Study 011. A post-hoc analysis of the mean change in GL-3 was deemed appropriate to measure the biological effect of migalastat HCl.  Amicus plans to analyze the mean change in GL-3 at 12 months (Stage 2) in the modified-intent-to treat population as well as a subgroup of patients with amenable mutations in a GLP-validated human embryonic kidney (HEK) cell-based in vitro assay ("GLP HEK assay"). The Stage 2 results and complete data from the 24-month study, including clinical outcome measures such as eGFR and proteinuria, are expected during the second quarter of 2014. Amicus remains blinded to the 12- and 24-month data at this time. Top-line data is anticipated in the second half of 2014 from the second Phase 3 study, or Study 012, which is comparing migalastat HCl to current standard of care ERTs.  About Study 011  Study 011 is a 24-month study consisting of a 6-month double-blind, placebo-controlled treatment period (Stage 1); a 6-month open-label follow-up period (Stage 2); and a 12-month open-label extension phase. All patients received migalastat HCl during Stage 2 and the open-label extension phase. Change from baseline in kidney interstitial capillary GL-3 is being assessed by histology in kidney biopsies at the end of Stage 1 and Stage 2.  Summary of Amicus Data Presentations and Posters at LDN WORLD  Amicus' development programs will be highlighted in a total of three oral presentations and five posters at LDN WORLD. The poster sessions will be held Tuesday, February 11 through Thursday, February 13, 2014 from 4:00 p.m. to 6:00 p.m. PT.  Pompe Disease:    *Chemical Conjugation of Targeting Peptide to ERTs Improve Receptor Binding     and Substrate Clearance in Mouse Models of Disease – Hung Do, PhD     (presentation) and Russell Gotschall (poster), Amicus Therapeutics, Inc.     (Oral Presentation: Wednesday, February 12 at 2:45 p.m. PT)   *Subcutaneous Administration of Recombinant Human Acid Alpha-Glucosidase     Co-formulated with the Pharmacological Chaperone AT2220 Leads to Lysosomal     Uptake of rhGAA and Glycogen Reduction in Disease-relevant Tissues of     Pompe Mice – Yi Lun, Amicus Therapeutics, Inc.   *Strategy to Assess the Effect of Duvoglustat Co-administered with     Alglucosidase Alfa Infusion on the Immune Response to Enzyme Replacement     Therapy for Pompe Disease – Xiaoyang Wu, Amicus Therapeutics, Inc.   *Liquid Chromatography-Tandem Mass Spectrometry Determination of AT2220 in     Rodent Plasma and Tissues – Leo B. Dungan, Amicus Therapeutics, Inc.  Fabry Disease:    *Phase 3 Study (FACETS) of Migalastat HCl for Fabry Disease: Post hoc GLA     Mutation-Based Identification of Subjects Likely to Show a Drug Effect –     Jeffrey P. Castelli, PhD (presentation) and Elfrida R. Benjamin (poster),     Amicus Therapeutics, Inc. (Oral Presentation: Thursday, February 13 at     11:15 a.m. PT)  Gaucher Disease:    *Glucosylceramide and Glucosylsphingosine Quantitation by Liquid     Chromatography-Tandem Mass Spectrometry to Enable Studies of Neuronopathic     Gaucher Disease – Rick Hamler, Amicus Therapeutics, Inc. (Oral     Presentation: Tuesday, February 11 at 10:30 a.m. PT)  About Amicus Therapeutics  Amicus Therapeutics (Nasdaq:FOLD) is a biopharmaceutical company at the forefront of therapies for rare and orphan diseases. The Company is developing novel, first-in-class treatments for a broad range of human genetic diseases, with a focus on delivering new benefits to individuals with lysosomal storage diseases. Amicus' lead programs include the small molecule pharmacological chaperones migalastat HCl as a monotherapy and in combination with enzyme replacement therapy (ERT) for Fabry disease; and AT2220 (duvoglustat HCl) in combination with ERT for Pompe disease.  About Chaperone-Advanced Replacement Therapy (CHART)  The Chaperone-Advanced Replacement Therapy (CHART™) platform combines unique pharmacological chaperones with enzyme replacement therapies (ERTs) for lysosomal storage diseases (LSDs). In a chaperone-advanced replacement therapy, a unique pharmacological chaperone is designed to bind to and stabilize a specific therapeutic enzyme in its properly folded and active form. This proposed CHART mechanism may allow for enhanced tissue uptake of active enzyme, greater lysosomal activity, more reduction of substrate, and lower immunogenicity compared to ERT alone. Improvements in enzyme stability may also enable more convenient delivery of next-generation therapies. Amicus is leveraging the CHART platform to develop proprietary next-generation therapies that consist of lysosomal enzymes co-formulated with pharmacological chaperones.  ^1Do et al., LDN WORLD 2014  ^2Castelli et al., LDN WORLD 2014  ^3Dr. Schiffmann is an investigator in Amicus' clinical studies of migalastat HCl, as well as a consultant and research collaborator of Amicus  Forward-Looking Statements  This press release contains, and the accompanying conference call will contain, "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 relating to preclinical and clinical development of Amicus' candidate drug products, the timing and reporting of results from preclinical studies and clinical trials evaluating Amicus' candidate drug products and the projected cash position for the Company. Words such as, but not limited to, "look forward to," "believe," "expect," "anticipate," "estimate," "intend," "potential," "plan," "targets," "likely," "may," "will," "would," "should" and "could," and similar expressions or words identify forward-looking statements. Such forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. The inclusion of forward-looking statements should not be regarded as a representation by Amicus that any of its plans will be achieved. Any or all of the forward-looking statements in this press release may turn out to be wrong. They can be affected by inaccurate assumptions Amicus might make or by known or unknown risks and uncertainties. For example, with respect to statements regarding the goals, progress, timing and outcomes of discussions with regulatory authorities and the potential goals, progress, timing and results of preclinical studies and clinical trials, actual results may differ materially from those set forth in this release due to the risks and uncertainties inherent in the business of Amicus, including, without limitation: the potential that results of clinical or pre-clinical studies indicate that the product candidates are unsafe or ineffective; the potential that it may be difficult to enroll patients in our clinical trials; the potential that regulatory authorities may not grant or may delay approval for our product candidates; the potential that preclinical and clinical studies could be delayed because we identify serious side effects or other safety issues; the potential that we will need additional funding to complete all of our studies and, our dependence on third parties in the conduct of our clinical studies. Further, the results of earlier preclinical studies and/or clinical trials may not be predictive of future results. With respect to statements regarding projections of the Company's cash position, actual results may differ based on market factors and the Company's ability to execute its operational and budget plans. In addition, all forward looking statements are subject to other risks detailed in our Annual Report on Form 10-K for the year ended December 31, 2012. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, and Amicus undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.  FOLD–G  CONTACT: Investors/Media:          Sara Pellegrino          spellegrino@amicusrx.com          (609) 662-5044                   Media:          Dan Budwick          dan@purecommunicationsinc.com          (973) 271-6085