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Achillion Pharmaceuticals Annual Report 2014

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Achillion Pharmaceuticals Annual Report 2014 ACHILLION PHARMACEUTICALS ANNUAL REPORT 2014 RESEARCH REALIZED 91218_Cover.indd 1 4/9/15 5:12 PM FROM THE BENCH TO THE PATIENT TRANSFORMING INNOVATION INTO NOVEL THERAPIES TO ADDRESS PATIENT NEEDS 91218_Cover.indd 1 4/9/15 5:12 PM Achillion’s wholly-owned HCV portfolio aims to achieve short duration treatments across the broadest patient populations leveraging dual- and triple-therapies in a single fi xed dose tablet. ACH-3102 NS5A Inhibitor ACH-3102 NS5A Inhibitor ACH-3422 Nucleotide NS5B Polymerase Inhibitor ACH-3422 Nucleotide NS5B Polymerase Sovaprevir Inhibitor NS3 Protease Inhibitor Dual Regimen: Triple Regimen: Achieving high Potentially shorten SVR rates across treatment duration HCV genotypes to 6 weeks or less in a well-tolerated while remaining combination used well-tolerated with for 8 weeks or less. high SVR rates across genotypes. ACHILLION COMBINES MEDICINAL CHEMISTRY AND THE STRUCTURE-GUIDED DESIGN OF NOVEL THERAPEUTICS WITH EXCELLENCE IN CLINICAL DEVELOPMENT, REGULATORY AFFAIRS, AND COMMERCIAL STRATEGIES. Orally bioavailable, potent and specifi c complement factor D inhibitor, shown bound to factor D, represents one of multiple compounds being evaluated for advancement toward clinical development. 91218_Cover_cx.indd 2 4/14/15 1:50 PM TO OUR SHAREHOLDERS, APRIL 2015 at doses of 50 mg – 700 mg once daily, achieving a 4.6 log10 reduction in viral load with the 700 mg dose after 14 days. These data, combined with the Phase 2 Proxy Study results, lead us to believe that the dual regimen of ACH-3102 and ACH-3422 can be a highly competitive regimen to cure HCV. Furthermore, we continue to develop our third HCV asset, sovaprevir, which allows us to explore a triplet regimen contain- Milind Deshpande, Ph.D. ing this NS3 protease inhibitor. Triple combinations such as this President and offer the potential for shorter treatment duration, especially in Chief Executive Offi cer harder-to-treat patient populations. As our HCV compounds continue to progress through At Achillion, we are focused on transforming innovation into clinical development, we have been focused on identifying novel therapies to address patient needs, and the past year was and advancing exciting new candidates into our pipeline. After transformational for our company. obtaining high resolution 3D structures of factor D-inhibitor Our portfolio is materializing in real time. Drug candidates complexes, we have worked to create a portfolio of novel that were once promising early molecules, generated by our small-molecule inhibitors of complement factor D which are internal discovery engine, are now in clinical development. We potent, specifi c, and orally bioavailable. are creating treatments that could prove to be life changing for The complement pathway represents the body’s fi rst line patients with chronic Hepatitis C (HCV) – dual- or triple-regimens of defense against “threats” such as trauma, infection, and that could be widely accessible and provide high SVR rates after hemorrhage. Relevant diseases within this pathway that could just 8 weeks of treatment or less. Our team has made extraordi- be targeted systemically with oral compounds include nary progress over the past year putting those pieces in place, paroxysmal nocturnal hemoglobinuria (PNH), acute hema- including generating best-in-class data for ACH-3102, a second- tologic uremic syndrome (aHUS), and myasthenia gravis (MG). generation NS5A inhibitor, establishing clinical proof of concept Achillion is also developing compounds for age-related for ACH-3422, our nucleotide NS5B polymerase inhibitor, and macular degeneration (AMD). resuming the clinical development program for sovaprevir, our Our compounds bind factor D with high affi nity, and NS3 protease inhibitor. effectively block C3 fragment deposition on cells, in contrast The integrated capabilities that have enabled us to advance to C5-targeted therapies. Our in vitro data indicated low our HCV candidates along the continuum from bench to patient off-target activity and our in vivo data demonstrated complete are also being applied to our novel platform of oral complement suppression of complement activity after oral dosing. We plan factor D inhibitors for the treatment of immune-related rare to initiate our fi rst-in-human proof of concept study by the diseases. This new program was introduced last December and end of 2015 in which we will evaluate safety, pharmacokinetics, the fi rst compound from this platform is expected to enter and pharmacodynamics in healthy volunteers. clinical development by year-end 2015. Our activities during the fi rst quarter of 2015 have begun Unsurprisingly, the HCV market has continued to evolve over preparing us for a very active year ahead. After reporting the the past 12 months. The number of approved products has 100% SVR12 data from the 6-week treatment cohort in our grown while the price points for these treatments have retracted Phase 2 Proxy Study, we successfully completed an equity as a result of discounted contracts with payors. However, two offering with net proceeds of approximately $132.6 million. important considerations remain unchanged. First, a robust and We hope to use this momentum and the exceptional profi le sustainable market persists for HCV therapeutics, with nearly $15 of ACH-3102 to our advantage as we begin evaluating 4-week billion in worldwide sales during 2014. Second, Achillion contin- and 6-week treatment regimens that leverage all of our HCV ues to be well positioned to deliver oral, once-daily, commercially assets. During the second quarter, we expect to report Phase competitive short-treatment duration regimens that could be 1b data for ACH-3422 monotherapy in genotype 2/3 patients made widely accessible to HCV patients. In fact, Achillion is one and to initiate two new studies: the Sparta Doublet Phase 2 of only three companies with a portfolio containing nucleotide, study of ACH-3422 plus ACH-3102, and the Ithaca Triplet proxy NS5A and protease inhibitor assets that can be combined to study evaluating 4-weeks of ACH-3102 with sovaprevir and achieve high SVR rates with a short duration of treatment. sofosbuvir. By the end of 2015, we anticipate beginning the Turning fi rst to ACH-3102, we were pleased to present last Sparta Triplet Phase 2 study combining all three of our HCV year results from our Phase 2 “Proxy Study” evaluating an candidates and also expect to reach an important infl ection 8-week ribavirin-free regimen with sofosbuvir. Results included point for our complement factor D inhibitor program as we 100% SVR12 in genotype 1 HCV patients, including 9 of 12 advance our fi rst clinical candidate into a Phase 1 study. patients whose viral loads were higher than 6 million IU/ml at I believe Achillion has an outstanding portfolio of assets, and baseline, the level above which patients are ineligible for 8 week because of the dedication of our talented staff and the support treatment with Gilead’s Harvoni.® Three months later, we were of shareholders like you, we also have the necessary resources able to report 100% SVR12 for the same combination but with a in place to achieve our planned milestones. I thank you for your treatment duration of just 6 weeks. This represents the shortest continued commitment to Achillion and its vision. duration and highest response achieved to date with any two- Sincerely, drug regimens for HCV, and enables us to evaluate shortening treatment duration further to potentially 4 weeks. We also announced in 2014 proof-of-concept data for ACH-3422, which was well-tolerated and demonstrated potent antiviral activity and a high barrier to resistance. The results of this fi rst-in-human study showed ACH-3422 to be well-tolerated Milind Deshpande, Ph.D. 91218_Cover_cx.indd 2 4/14/15 1:50 PM 2014 FORM 10-K UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K È ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2014 OR ‘ TRANSITION REPORT PURSUANT TO SECTIONS 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number 001-33095 ACHILLION PHARMACEUTICALS, INC. (Exact name of registrant as specified in its charter) Delaware 52-2113479 (State or other jurisdiction of (I.R.S. Employer incorporation or organization) Identification No.) 300 George Street, New Haven, CT 06511 (Address of principal executive offices) (Zip Code) Registrant’s telephone number, including area code: (203) 724-6000 Securities registered pursuant to Section 12(b) of the Act: Title of Class Name of Exchange on Which Registered Common Stock, $0.001 par value per share NASDAQ Global Select Market Securities registered pursuant to Section 12(g) of the Act: None Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes È No ‘ Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ‘ No È Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes È No ‘ Indicate by check mark whether the registrant has submitted electronically and posted on its corporate Web site, if any, every Interactive Data File required to be submitted and posted pursuant to Rule 405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit and post such files).
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