RCDP is a disorder of plasmalogen lipid deficiency and therefore the most promising treatment options involve augmentation of plasmalogen levels. Despite their biological importance, plasmalogens are not naturally abundant and thus there aren’t any practical natural or dietary sources. Although there are supplements commercially available, they contain trace levels of plasmalogens from natural sources. The low doses and lack of control around the composition makes them ineffective and impractical for the treatment of RCDP.

Med-Life Discoveries (MLD) is committed to the development of the first highly potent, synthetic, plasmalogen precursor, known as PPI-1011. PPI-1011 is an ether-containing plasmalogen precursor that is readily converted by the body into an intact plasmalogen. PPI-1011 was specifically designed with a palmitoyl acid at the sn-1, DHA at the sn-2 position, and lipoic acid at the sn-3 position. The addition of the lipoic acid improves the long term stability of the molecule. After administration by mouth or feeding tube, the lipoic acid is removed in the gut by enzymes called lipases. The result is uptake of an alkylacylglycerol which is identical to the molecules synthesized naturally in the body, but which are deficient in RCDP. This backbone is then converted to a plasmalogen using the patient’s own internal enzymes.

Simply put, MLD’s strategy is to bypass the portion of the plasmalogen biosynthetic pathway that is impaired in RCDP by pharmacologically providing a plasmalogen backbone that patients lack the ability to make.

PPI-1011 is formulated in liquid coconut oil with a small amount (0.1%) of an antioxidant called thioglycerol. The formulated material is stored in amber glass bottles in the refrigerator until use. PPI-1011 will likely be dosed orally or through a feeding tube once daily, but the dosing schedule will first be evaluated in a clinical trial.

Phase I

The first step in the clinical development of most drugs, including PPI-1011, is an evaluation of safety and drug uptake (called pharmacokinetics) in healthy adult volunteers. A Phase I study of PPI-1011 took place at a specialized site in Canada between June 2023 and February 2024. This study had two parts, the first part evaluated a single dose of PPI-1011 at increasing doses (10, 25, 50, 75, and 100 mg/kg). Once it was determined that single doses of PPI-1011 were well tolerated, the second part evaluated 14 days of once daily oral administration of PPI-1011 at 75 and 100 mg/kg/day.

Since the completion of the study, we have evaluated the compiled safety data and serum plasmalogen concentration from study participants. MLD is happy to report that overall the study demonstrated that PPI-1011 is safe and generally well tolerated in single doses up to 100 mg/kg and in multiple doses up to 100 mg/kg once daily for 14 days. The study also confirmed that both single (25, 50, 75 and 100 mg/kg) and multiple-doses (75 and 100 mg/kg, once daily) of PPI-1011 can increase the target plasmalogen in serum.

Phase II

MLD is now working with the team at Nemours Children’s Hospital and a number of consultants to design a Phase II study that will evaluate the efficacy and safety of PPI-1011 in RCDP patients. This study will involve a number of in-clinic and at-home assessments while patients are on PPI-1011 treatment. The current plan is a one-year study which will involve four visits to Nemours Children’s Hospital, as well as regular at-home visits with a study nurse and will use the data from the Natural History Study as the control group.

Before this study can begin MLD must submit an Investigational New Drug (IND) application to the FDA. The FDA reviews the IND to assess the overall risk-benefit of the treatment in the patient population. Once they agree that the available information supports a positive risk-benefit balance, they will allow the study to start enrolling. Stay tuned to the news page for updates on the status of this process.