I hope that you all have had a chance to enjoy some sunshine and warm days in July. Cyxone, in collaboration with our partners, has been working even during the month of July to ensure that the studies with T20K will go as planned, and to prepare financing for the Phase IIB studies with our new pipeline substance Rabeximod for rheumatoid arthritis.
Some of you readers with good memory may recall that we will investigate whether we are able to inhibit the MS-like symptoms which can be provoked in mice with a protein which is believed to irritate the human immune system in MS. In previous studies using a murine EAE model, T20K has shown to be very effective when the experiments have been carried out using standard scientific research methods, that is, mice divided in different groups were given T20K in pre-determined intervals (for example one dose per day). With the new study, we want to demonstrate that if a mouse is treated only once it starts getting sick, which would be the case with human patients, then we would be more successful in offsetting the symptoms or even preventing them from evolving altogether. However, we should remember that even though the murine EAE model is the only truly accepted animal model for MS, it is different from the human disease in many details: for example, the disease cycle in mice takes only about 2 weeks while in humans it can be as long as 30 to 40 years. At the moment, we are studying the experimental conditions we will be using because this type of treatment has not been used previously.
A central part in our application to secure the approval to study T20K in humans is to show that the substance is not toxic in animals. Because free concentration of T20K cannot be measured in plasma after oral administration of the substance we begin with administering the substance as an infusion. Once we have established the relation between the amount of T20K in plasma and tissues including its toxicity we will be ready to calculate the oral dosage of T20K. There are many details we must check using the Good Laboratory Practice (GLP) study which will build the foundation in our application to the regulatory authorities. Among other studies, we have investigated how much T20K gets caught in the tubes which are used to administer the substance to animals. This is done to exclude the existence of any “false factors” which may affect our determination for low toxicity. The study to compare toxicity after a so-called bolus dose (all substance is administered at once) to toxicity after infusion (substance is slowly administered intravenously) will begin shortly, and we are very interested in the outcome which will allow us to determine how to administer T20K orally. The toxicity program will continue with for example studies on how the substance affects various organs.
We are currently following up the results we obtained during the spring from our in vitro pharmacology studies which indicated that T20K might only affect a few biomolecules. Once we get the results from the follow-up study we will know more about the effects of T20K in the body.
We are preparing a reference substance for T20K in which we have replaced certain atoms with heavier counterparts in order to quantify T20K with mass spectrometry in the different organs and in plasma with certainty (a so-called” internal standard”).
Synthesis of T20K
The synthesis of T20K for animal tests and for studies conducted in humans is progressing according to the plans at Bachem in Switzerland. It is crucial that we receive well-manufactured and well-documented T20K for our studies, which is why this work is time-consuming. However, we keep on schedule and count on receiving all the substance, including the portion for the clinical studies, right after new year.
I have spent some time at OxyPharma to check the documentation the company has worked on and completed during the entire development program up to and including the Phase II studies. I am very impressed of how organized the company is with their documents, including approvals, plans, protocols and associated signatures. In addition, OxyPharma has several kilograms of Rabeximod in stock. The manufacturer of Rabeximod is currently analyzing the batch which OxyPharma has used in its Phase II studies. If the analysis has a successful outcome Cyxone will not need to have more substance prepared for its animal tests and for its phase IIB study.
Malmö August 8, 2017
Kjell G Stenberg