FDA meeting and other updates!
Hello RCDP community! It’s been awhile since our last post so we thought we would provide a few key updates.
Shawn, Tara, Dr. Bober and Dr. Carroll at the FDA, Jan 30, 2019 to discuss RCDP and PPI-1040 nonclinical development plan.
We had our second face-to-face PreIND meeting last week at the FDA in Washington DC. Attending were Drs. Shawn Ritchie and Tara Smith from MLD, Drs. Michael Bober and Ricki Carroll from Alfred I. duPont Hospital for Children in Wilmington, and Dr. Mark Cierpial from Impact Pharma. The meeting went exceptionally well, with discussion focused primarily on the animal safety and toxicity studies that are planned for this year in Montreal, Canada. The FDA continues to have a very positive response to the RCDP program, and is encouraging us to continue our interaction with them as we move forward.
Actual reactor currently being used to synthesize several kilograms of cGMP PPI-1040.
Our next update relates to ongoing work involved in the synthesis of the drug itself. Over the past year, we spent an enormous amount of time and energy optimizing the chemistry involved in both synthesizing PPI-1040, as well as its formulation and stability. The early research-grade synthetic scheme for PPI-1040 was not amenable to large-scale synthesis under good manufacturing conditions (GMP) for a number of technical reasons. Our chemistry team has therefore been diligently working over the year developing, optimizing, and testing processes that would allow for the manufacturing of PPI-1040 in a GMP production plant. We are now pleased (and super excited) that the first large-scale, multi-kilogram GMP production batch of PPI-1040 is currently under way. This involved the sourcing of hundreds of kilograms of starting materials and hundreds of litres of solvents, and is probably the first time in history that a multi-kilogram batch of a vinyl-ether plasmalogen is being synthetically manufactured under GMP conditions. There are still a couple of challenges left in the final few stages and room for further optimization, so although we’re not totally out of the woods, we’re miles ahead of where we were even a year ago. The material being manufactured in this campaign is going to be used for the IND-enabling nonclinical safety and pharmacology animal studies, as well as the adult human Phase I clinical trial.
We’ve also made exciting advancements on the formulation of the drug product. The initial formulation of PPI-1040 was poor, and the drug degraded at temperatures above -80 degrees Celsius. Extensive formulation prototype testing was carried out over the past year at a facility that specializes in drug product formulation development, resulting in a stable liquid formulation that will make administration orally or by G-Tube relatively simply.
Makenna Loyd, wearing the LENA audio recording device.
Lastly, the Natural History Study protocol is nearly complete and all of the questionnaires and surveys have been finalized. Also, a big thank-you to Makenna Loyd for beta testing the LENA audio recorder that will be part of the study. The travel logistics company, Scout Clinical, is in place to assist with travel and reimbursement. We still hope to begin enrolling the first patients in the next couple of months. If you haven’t signed up, please do so here. Your participation is crucial for the development of the drug!
In addition, and as many of you know, we have been working with Dr. Mousumi Bose who is creating an RCDP-specific quality-of-life questionnaire. Dr. Bose has taken all of the information gathered during the focus-groups last summer and created the first draft of a survey that will be tested and further refined over the coming months. The goal is to officially include the survey as part of the Natural History Study in the future. We plan to include Dr. Bose in one of our up-coming fireside chat sessions in early spring, so stay tuned! And be sure to follow our Facebook page for other updates.