ACHN 2017 Annual Report

pathway factor D inhibitor to be tested in humans. We have completed both single-ascending dose and multiple-ascending dose phase I clinical trials designed to understand the safety, pharmacokinetics and pharmacodynamics of the drug candidate after oral administration. We have advanced or plan to advance ACH-4471 in three phase II clinical trials for patients with C3G: • A 14-day duration trial for which we have announced data from the first two sentinel patients and are continuing to enroll up to eight additional patients. We anticipate reporting data from this trial in the third quarter of 2018. • A 6-month duration trial which will be double-blind and placebo-controlled and enroll up to 20 patients randomized 1:1 to receive either ACH-4471 or placebo. We anticipate initiating dosing in this trial in the first half of 2018 and reporting data in 2019. • A 12-month duration trial which will consist of a single open-label arm and in which we expect to enroll up to 20 patients. We anticipate initial dosing in this trial in the first half of 2018 and expect that interim data would be released in the fourth quarter 2018. • Advance ACH-4471 in clinical development for PNH. We have advanced or plan to advance ACH-4471 in the following phase II clinical trials in patients with PNH: • A monotherapy trial assessing ACH-4471 in patients with PNH from which we announced interim data for the first four patients in August 2017. We continue to enroll PNH patients in this trial, planning to treat a total of eight to twelve PNH patients and report data by the fourth quarter of 2018. • An add-on trial assessing ACH-4471 dosed with eculizumab, a therapy for PNH that is marketed by a third party, in patients that are deemed to have a sub-optimal response and continue to experience disease symptoms such as anemia and fatigue despite treatment with eculizumab monotherapy. We anticipate initial dosing in this trial in the first half of 2018, planning to treat a total of eight PNH patients, and releasing interim data in the fourth quarter 2018. • Advance ACH-5228 and ACH-5548, next-generation compounds for oral systemic administration, to treat other complement mediated diseases. In addition to advancing ACH-4471, we have advanced ACH-5228 into a phase I, single-ascending dose clinical study in healthy volunteers and have another compound, ACH-5548, in late stage preclinical development. We anticipate that ACH-5548 will enter a phase I, single-ascending dose clinical study in the second quarter of 2018. We expect to report data from the phase I clinical studies of ACH-5228 and ACH-5548 in the fourth quarter 2018. Our objective for these next-generation compounds is to have them advanced either by us for PNH, C3G or other complement diseases, or by potential collaborators for diseases that are not our strategic focus. Our Complement Factor D Program The first clinical compound from our complement inhibitor platform is ACH-4471. ACH-4471 is designed to target and inhibit complement factor D. The next clinical compounds from our complement inhibitor platform that we are focusing on are ACH-5228 and ACH-5548, both of which are next-generation factor D inhibitors that we are seeking to advance for oral administration. ACH-4471. ACH-4471 is a potent and specific inhibitor of factor D which has demonstrated preliminary proof-of-concept in a phase II clinical trial in patients with PNH and another phase II clinical trial in patients with C3G. We are currently continuing to conduct these phase II clinical trials of ACH-4471, and plan to conduct additional trials in patients with PNH and in patients with C3G or IC-MPGN. ACH-4471 has exhibited the following characteristics in preclinical studies and clinical trials: • Pharmacokinetics and Metabolism . Pharmacokinetic results and activity in preclinical studies and clinical trials suggest that ACH-4471 should be explored in clinical development for potential oral dosing twice or three times daily. Controlled release formulation systems are also being developed for 3