Clear Scientific, LLC

Clinical Development of a Therapeutic Agent for Rapid Reversal of Methamphetamine Intoxication - 1 Project Summary 2 There Is an Urgent Need for a Rapidly Acting Antidote for Methamphetamine. Methamphetamine 3 (METH) Is the Fastest Growing Drug of Abuse in the U.s., Representing Over 798,000 Annual Emergency Department 4 (ED) Visits, With Deaths Increasing 14-FOLD Since 2015 (32,856 Deaths in 2021 Alone), Yet No Current Therapeutics 5 Are Available to Treat Meth Intoxication. Our Objective Is to Obtain Federal Drug Administration (FDA) Approval 6 for Sale and Marketing of CS-1103, a Small-molecule Sequestrant, to Treat Acute Meth Intoxication. CS-1103 7 Selectively Binds Meth in Blood and Dramatically Accelerates Its Removal From the Body by Clearance Into the 8 Urine, Representing a New Approach to the Reversal of Drug Effect: Remove the Cause and Remove the Effect. 9 the Indication for CS-1103 Is to Lower the Level of Methamphetamine in the Human Body. CS-1103 Is 10 Well-tolerated in Rodent and Canine and Is Highly Effective in Lowering the Level of Meth and Rapidly Reversing 11 Its Toxic Effects in Non-human Primates. in Our Current U01 Program (5U01DA053054-03), We Have Achieved 12 Key Milestones in Current Good Manufacturing Practice (CGMP) Manufacturing, Good Laboratory Practice (GLP) 13 Toxicology and Pharmacology Studies, and Held a Pre-investigational New Drug Application (IND) Meeting With 14 the Fda. the Current U01 Will Conclude With Completion of the Phase 1A First-in-human Clinical Trial. 15 We Propose Here to Further Develop CS-1103 by Completing Phase 1B and Phase 2A Clinical Trials. These Significant 16 Milestones on the Path to Fda Approval Will Be Achieved via Completion of the Following Aims: Aim 1 Will 17 Optimize Manufacturing Process and Produce Drug Substance and Drug Product Under CGMP. We 18 Will Produce Drug Substance and Drug Product That Meet Fda Requirements and Generate a CMC Document. 19 Expected Outcome Is 100 KG of CS-1103 and 5000 Vials of Drug Product. Aim 2 Will Demonstrate the Safety 20 and Tolerability of CS-1103 in the Presence of Methamphetamine in a Phase 1B Clinical Trial. the 21 Phase 1B Trial Is a Randomized, Double-blinded, Placebo-controlled 2-PERIOD Crossover Clinical Study to Evaluate 22 Safety, Tolerability, and PK of CS-1103 Following a Single Iv Dose After an Iv Dose of Meth in 10 Individuals With 23 Meth Use Disorder Not Seeking Treatment. Expected Outcome Is That CS-1103 Is Safe, and We Can Obtain Fda 24 Approval to Proceed to Phase 2A. Aim 3 Will Determine Dosing Requirements for CS-1103 in a Phase 25 2A Clinical Trial. the Phase 2A Trial Is an Open-label, Placebo-controlled, Dose Range-finding Clinical Study to 26 Evaluate Efficacy and Dose-response of CS-1103. Single Iv Dose of CS-1103 Will Be Administered After an Iv Dose 27 of Meth in 64 Individuals With Meth Use Disorder Not Seeking Treatment. Objectives Are to: 1) Establish Dose 28 Response of CS-1103 to Remove Meth From the Body by Quantification of Meth in Plasma and Urine, 2) Evaluate 29 Efficacy of CS-1103 VS. Time After Administration of Meth, and 3) Select CS-1103 Dose for Phase 2B/PHASE 3 Trials. 30 Expected Outcome Is Fda Approval to Proceed to the Pivotal Phase 2B/PHASE 3 Trials.