Scientific Contributions in Drug Development as Principal of Wetzel Chemistry Consulting, LLC:

Background: Dr. Wetzel’s consulting services are provided under confidentiality.  His contributions to some representative projects are described below in general terms. Central Findings: Project 1: The original, laboratory-scale synthetic process for a drug candidate was modified to improve safety and efficiency, and scaled up to produce >1 kg under cGMP. Multiple topical formulations were developed, manufactured under cGMP, and used in Phase 1 and 2 clinical trials. The API process and supporting analytical methods were further optimized in preparation for pending Phase 3 clinical trials. Project 2: A parenteral drug product was manufactured under cGMP and used in Phase 1 and 2 trials. The API process is currently undergoing optimization in preparation for a Phase 3 clinical trial.  Project 3: The structure of the API (MW > 1000, several chiral centers) was proven by 2D NMR.  A deuterium-labeled reference standard was synthesized and used in the development and validation of bioanalytical methods.  Three batches of a parenteral drug product were manufactured under cGMP.  An improved formulation for reconstitution of the lyophilized drug product was developed, and its in-use stability was demonstrated. A Phase 1 clinical trial was completed.  Project 4: A complex polymorph landscape was elucidated and stable form identified; the API process was optimized and 9 kg of cGMP API manufactured.  Project 5:  A sixteen-step convergent synthesis was optimized, analytical methods developed and qualified, and 10 kg of cGMP API manufactured. An IND was filed and Phase II trial completed.  Project 6:  Route scouting, process development and a salt/polymorph screen were conducted, resulting in >1kg of cGMP API and three US patent applications. An IND was filed and Phase I trial completed.  Project 7:  An API process was optimized, a polymorph screen conducted; analytical methods developed and qualified; and 10 kg of cGMP API manufactured. A novel oral formulation was developed and manufactured, resulting in good bioavailability for a poorly water soluble API and a patent application. Bioanalytical methods were developed, validated and used to support nonclinical and clinical studies. An IND was filed and Phase 1 clinical trial completed.  Project 8:  A synthetic route was developed on laboratory scale. Scale-up is in progress.  Project 9: A parental drug product was manufactured under cGMP. Project 10:  Several antibacterial and antiviral drug development programs were evaluated and ranked on behalf of a US government contractor.

Dr. Wetzel’s Role: All laboratory and manufacturing activities described for Projects 1-10 were outsourced under his management or co-management. For most of these projects, and several others, he authored CMC sections, which were submitted in regulatory filings. he participated in several pre-IND meetings with FDA and addressed any CMC-related regulatory concerns, resulting in Study May Proceed letters from FDA.