MONDAY, NOVEMBER 17

12:00pm Main Conference Registration

Challenges in Process Development of API Synthetic Routes

1:30 Chairperson’s Welcoming Remarks
Robert Hughes, Ph.D., Scientist II, Chemical Development, Vertex Pharmaceuticals, Inc.

1:40 Process Development of Eribulin Mesylate (E7389), a Halichondrin B Inspired Breast Cancer Therapy
Bryan Lewis, Ph.D., Associate Director, Process Research, Eisai Research Institute
Eribulin mesylate, an analog of halichondrin B, is currently in Phase III clinical trials for the treatment of breast cancer. Process development activities from the point of candidate selection will be described, emphasizing the final assembly and illustrating that molecular complexity of a natural product is not an impediment to drug development.

2:10 Large-Scale Synthesis of Discodermolide, a Marine Natural Product for the Treatment of Advanced Solid Tumors
Frederick Kinder, Ph.D., Executive Director, Oncology Research, Novartis Institutes for BioMedical Research
(+)-Discodermolide (DCD), a novel polyketide isolated from the sponge Discodermia dissoluta,is a potent microtubule stabilizing agent that was evaluated in an advanced solid tumor Phase I trial. The total synthesis of DCD utilized a "hybrid" route derived from the published syntheses of Paterson and Smith and from chemistry developed by Novartis Medicinal and Process Chemists. The 60 g Phase I synthesis batch involved 39 steps (26 linear) and several chromatographic purifications.  Efficiencies gained from medicinal chemists working with process chemists during scale-up synthesis will also be highlighted.

2:40 Route Selection and Process Development for the Synthesis of Flt-3 Kinase Inhibitors for Cancer Therapeutics
Wen-Chung Shieh, Ph.D., Novartis Leading Scientist, Chemical & Analytical Development, Novartis Pharmaceuticals Corporation
Powered by combinatorial synthesis, drug discovery efforts often lead to the selection of a package of several drug candidates, containing similar chemical scaffolds and biological profiles, for further clinical evaluations.  As a result, developing chemical processes that can be utilized to manufacture these drug candidates with minimal time and resources has become a challenge for process chemists during the early stage of drug development. This lecture will discuss route selection and process development strategies utilized by a Novartis team for the manufacturing of a triad of Flt-3 (FMS-like tyrosine 3) kinase inhibitors, to be evaluated for treatment of leukemia patients with specific somatic Flt-3 mutations. The ultimate synthesis is convergent, ecologically and environmentally friendly, practical, safe and required no chromatographic purification.

3:10 APIs: Simplicity by Design. A Low-Tech Approach for Quality and Profitability
Girish Malhotra, PE, President, Epcot International
This presentation will review various API patents to illustrate how simple chemistry modifications can create a win-win for all by reducing costs to the manufacturer and environment and ultimately to the consumer. Process optimization that achieves the following through practical, up-front, strategically planned chemistry will be highlighted:

3:40 Networking Refreshment Break, Poster and Exhibit Viewing

Roundtable/Break-Out Session Topics

4:15
Roundtables will run concurrently; attendees select one to participate in. The bullets listed below are only suggested topics; the moderators will shape the discussion around the major interests of the participants.

Table 1: Biocatalysis in Practice
Moderator: Jim LaLonde, Ph.D., Vice President, Research and Development, Codexis, Inc.

Table 2: Challenges in Route Design 
Moderator: Neal G. Anderson, Ph.D., Anderson’s Process Solutions

Table 3: PAT and Continuous Processing
Moderator: Klavs Jensen, Ph.D., Department of Chemical Engineering, Massachusetts Institute of Technology

Table 4: Genotoxicity Discussion
Moderator: Ambarish K. Singh, Ph.D., Associate Director, Chemistry Manufacturing and Control, Bristol-Myers Squibb Co.

5:15 Networking Reception (sponsorship available), Poster and Exhibit Viewing

6:00 End of Day