Gates Package — page 58

From: Olinger, Gene (NIH/NIAID) [C] [mailto J@nih.gov] Sent: Thursday, July 24, 2014 9:55 AM To: Hu-Primmer, Jean; Hensley, Lisa E (NIH); Honko, Anna N (NIH) Subject: RE: today's Ebola MCM working group Here are a few comments to consider: With unlimited funds, we would take as many "shots on goal" as possible, however, my experience is that there is limited funding and we will have prioritize. Anna made a wonderful comment the other day about rushing to use something that has potential too soon and killing it because of the rush! It is something we should all consider. Dr. Kobinger has demonstrated neutralization with two of the mabs in the cocktail and binding with all three mabs to the current isolate (unpublished, personal communication). The biggest issue past funding and time, will be scale up of the process to produce large lots of the drug (estimate 1-3 months). They are planning dose sparing studies in Sept. which could alter production and offer 2X, 5X or 10X production/doses numbers. That study could be expedited. BCX4430 has published data against Marburg and Ebola for guinea pigs but only Marburg virus for NHPs. Maybe there is unpublished data, but I expect (given my experience) there was less efficacy observed for EBOV versus MARV. It is also encouraging to see that the noted issues with toxicity, immune suppression, and high risk potential in phase I is listed for this product. I did see where NIH NIAID provided additional support for this product a few weeks ago. The recommendation for UV4 makes no sense as written. If UV4 is going to be listed, there really should be many other compounds listed that have demonstrated efficacy against Ebola in vitro, rodents, and in some cases NHPs. The work Lisa and Peter did with various drugs with efficacy should be considered. In addition, while at RIID we screened all of the approved drugs and there are many drugs that could be repurposed/given off-label with efficacy in mice (they are working on NHP studies; short list attached but many others). Most of the drugs I mention here are approved and could be given off label. We are also still missing vaccination. Both Dr. Sullivan's and the VSV platform should be considered as there are preclinical and clinical data available. The WHO has plans with the University of Geneva to use VSV (a cGMP lot) for those exposed and mabs for those that develop symptoms. Anna and I were on the telcon for Lisa the last few days with WHO. Would love to share some of the discussions. There was a lot of discussion on convalescent serum and how quickly a process could be developed to pursue that approach. Gene From: Hu-Primmer, Jean (FDA/OC) Sent: Thursday, July 24, 2014 9:09 AM To: Hensley, Lisa (NIH/NIAID) [E]; Honko, Anna (NIH/NIAID) [E]; Olinger, Gene (NIH/NIAID) [C] Subject: Fw: today's Ebola MCM working group FYI - Please take a look at the document Jules put together. I also asked them to include Tekmira after receiving this document. Please let me know if you know of anywhere we can get more information on the gaps Jules discussed - as well as if you