The overall goal of this application is the timely advancement of a new anti-tuberculosis drug candidate, SQ109, into Phase I Clinical Trials in human volunteers. Developed by Sequella in partnership with the NIH, SQ109 is a small molecule drug candidate that is being developed for the treatment of pulmonary tuberculosis (TB). It is orally bioavailable, has high potency against Mycobacterium tuberculosis, is effective against profoundly drug-resistant M. tuberculosis, and is suitable to replace the first-line drug ethambutol during the intensive phase of the WHO-recommended Directly Observed Therapy (DOT) drug regimen. At the present time, SQ109 has completed preclinical development, and we expect to file an IND shortly. Preliminary Phase 1a and Phase 1b clinical protocols have been developed to determine the safety and tolerability, and to evaluate the pharmacokinetics of SQ109 in healthy, male and female volunteers after a single-dose (Phase la) and a multiple-dose (Phase Ib) administration. The present R34 Grant Application will allow us to complete the planning and design of the trials, and to prepare the necessary documentation that accompanies Good Clinical Practice (GCP) trials of new drugs. Specifically, during the planning period we will analyze the preliminary design of both Phase 1a and 1b clinical studies and make necessary changes with our NIH colleagues. We will incorporate the animal studies data into the protocols to establish the initial dose for healthy adult subjects and to address potential toxicity issues. We will also select CRO for the clinical trials and obtain approval of the clinical protocols from the IRB, select a CRO for the studies, and obtain approval from the relevant Institutional Review Board, IRB. We will use this planning period to develop the Investigator's Brochure for new therapeutic SQ109 based on FDA regulations, and seek approval from the IRB of identified CRO. We will develop the Informed Consent that represents an agreement of human volunteers to the planned studies. The informed consent will also be approved before the trials begin. ? ? ?
