Since much of the work performed at Avanti Polar Lipids is either confidential or contracted, most of the intellectual input on projects is unpublished or unrecognized in the form of authorship on scientific papers. The following are examples of work that are in the public domain.
 
Improved delivery of fenretinide
 
Historically, fenretinide was delivered as a corn oil suspension in a gel capsule. In this form, the dosing level for the drug was quite high due to the poor absorption and variable bioavailability. Also, the size and number of capsules needed made it unacceptable for use in a pediatric study. Avanti formulated the drug in an organized lipid matrix (Lym-X-Sorb™) which improved the bioavailability, however, the formulation suffered from several drawbacks that limited its use in a pediatric study. The physical form was still a paste at room temperature or oil at elevated temperature so it required use of a capsule for delivery, and the viscosity increased dramatically in the presence of water to yield a hard wax which limited uptake. I developed a powder formulation using flour and sugar that increased the surface area of the lipid/drug matrix improving bioavailability, and provided a form that could be mixed with a variety of food or beverage choices (orange juice, oatmeal, applesauce, etc.) for delivery to a pediatric patient population. This product is currently in clinical trials and has demonstrated high bioavailability at lower doses than the corn oil capsules.
 
Maurer BJ, Frgala T, Sun BC, Vlckova J, Reynolds CP, Yesair DW, Burgess SW, McKee RT, Shaw WA: Improved oral fenretinide delivery with novel Lym-X-Sorb™ organized lipid complex. Proc Amer Assoc Cancer Res 2004; 45: 148.
 
Maurer BJ, Kalous O, Yesair DW, Wu X, Janeba J, Maldonado V, Khankaldyyan V, Frgala T, Sun BC, McKee RT, Burgess SW, Shaw WA, Reynolds CP. Improved oral delivery of N-(4-hydroxyphenyl) retinamide with a novel LYM-X-SORB organized lipid complex. Clin Cancer Res. 2007 May 15; 13(10):3079-86.
 
Maurer BJ, Kang MH, Villablanca JG, Janeba J, Groshen S, Matthay KK, Sondel PM, Maris JM, Jackson HA, Goodarzian F, Shimada H, Czarnecki S, Hasenauer B, Reynolds CP, Marachelian A. Phase I trial of fenretinide delivered orally in a novel organized lipid complex in patients with relapsed/refractory neuroblastoma: a report from the New Approaches to Neuroblastoma Therapy (NANT) consortium. Pediatr Blood Cancer. 2013 Nov; 60(11):1801-8.
 
Improved lipid adjuvants for vaccine development
 
In the late 1990’s, Avanti developed a bacterial-derived monophosphoryl Lipid A (MPL) similar to the MPL produced by Ribi/Corixa/GSK for commercial vaccine development. Unlike Corixa, Avanti did not operate a cGMP fermentation facility to control the production of lipopolysaccharide (LPS). The cost to outsource the cGMP production of LPS was prohibitively expensive, therefore Avanti shifted its resources to developing a synthetic pathway to the production of MPL. Development began in 2004, with the initial product, PHAD®, being released in 2005. We have continued to modify the structure to produce analogs with differing activities for fine tuning vaccine function during development. Avanti currently has three commercially available lipid adjuvants, with an additional compound currently in development. My role in the development of these products was both in identifying the analogs to develop, as well as assisting our synthetic team in solving synthesis and purification problems encountered during development. The lipid adjuvants developed by Avanti are currently in multiple clinical trials.
 
Shaw, Walter A; Burgess, Stephen W; Li, Shengrong; Hickman, David T; Lopez-Deber, Maria Pilar. 2016. Disaccharide Synthetic Lipid Compounds and Uses Thereof. U.S. Patent No. 9241988.
 
Shaw, Walter A; Burgess, Stephen W; Li, Shengrong; Hickman, David T; Lopez-Deber, Maria Pilar. 2016. Disaccharide Synthetic Lipid Compounds and Uses Thereof. U.S. Patent No. 9518078.
 
Shaw, Walter A; Burgess, Stephen W; Li, Shengrong; Hickman, David T; Lopez-Deber, Maria Pilar. 2018. Disaccharide Synthetic Lipid Compounds and Uses Thereof. U.S. Patent No. 10143744.