RCDP Plasmalogen Therapy Program Updates

Hello RCDP community! It's been a while since we provided everyone with a few key updates regarding the the RCDP therapeutics program. As many of you know, the Natural History Study officially launched this past June. Enrolment is going exceptionally well, and we continue to encourage participation! Data generated will be used to describe clinical aspects of RCDP in a consistent manner that ultimately will act as the comparison to the future PPI-1040 treatment group. We realize that participating in this study is a huge commitment on the part of parents and caregivers, and for that we thank you! Any questions or feedback regarding logistical or other issues you might have experienced on your first visit are welcome and can be sent to Candace at Nemours. 

 With respect to the quality of life survey that many parents have been involved in, we have completed preliminary analysis of the test data and are in the process of further refining the questions. This involves evaluating the answers to determine which questions best describe the impact of the RCDP and whether any improvements can be made. There will likely further testing required before the questionnaire is officially added to the Natural History Protocol, so stay tuned for further updates. The diagram below highlights some of the preliminary findings.

Results of preliminary quality of life questionnaire testing. The left graph shows the percent of subjects answering the number of times per week to each of the questions, while the right hand plot shows whether their response were less than, equal to, or greater than that of an average or typical week. For example, we can see that the burden on caregivers is high with more than half of the participants answering that they spend more than 5 days a week worrying about hospitalization, getting inadequate sleep, and spending more than 3 hours per day caring for their child. On the other hand, few to none reported that their child aspirated or stopped breathing in the past week. These are preliminary findings of which the results will be used to refine future versions of the survey.

The last topic that we have not provided an update on for some time is the status of the drug synthesis and safety studies. Last year we had initiated the program to begin process optimization with the goal of being able to manufacture large quantities in an industrial setting. In fact, over half of our time is probably spent on this aspect of the program, which include multiple weekly conference calls with our manufacturing site, chemistry and regulatory consultants, formulation team, and preclinical vendor. We have now completed all of the process development and confirmed the synthetic route is compatible with large scale industrial processes. Getting to this point from the initial synthetic chemistry developed prior to MLD was a massive undertaking, but we're finally there. As of this week, the first large-scale industrially produced batch of PPI-1040 will be sent from the manufacturing site to the company that will formulate the drug into the final finished product in preparation for the first animal safety and pharmacology studies! The formulation company has also been working hard testing various drug containment packaging options on smaller batches to ensure there are no stability issues and that the product will have an acceptable shelf life. We are really excited about this progress on the formulation, as we have achieved what we believe to be the first and only highly concentrated stable vinyl-ether plasmalogen formulation in the world. The two main goals of the up and coming animal studies are to first to determine optimum dosing levels, and confirm that there are no safety concerns. These studies will begin shortly in the new year at an FDA-compliant facility and set us on the path to an official Investigational New Drug (IND) application with the FDA later in 2020.

Lastly, but definitely not least importantly, MLD has secured a minimum of $5 million from its shareholders to continue the development of this therapeutics program specifically for RCDP. This investment will be used to continue funding all aspects of the program, with a concerted effort to move forward as quickly, but also as safely, as possible.