Entrepreneurs Thomas Collet and Bruce Markham founded Phrixus to validate the potential of Carmeseal-MD (P-188 NF) to treat heart failure in boys with Duchenne muscular dystrophy. The Phrixus team selected P-188 NF not only for the seminal work of Professor Joseph Metzger at the University of Michigan, but also for the investment Burroughs Wellcome and other companies had made in P-188 NF in unrelated development efforts that were ultimately unsuccessful, but established the P-188 NF is safe for use in humans.
Professor Metzger, now chair of Integrative Biology and Physiology at the University of Minnesota, has shown that P-188 NF could boost the blood pumping capacity of damaged hearts by binding to the damaged regions of cell membranes. When P-188 NF, which Dr. Metzger and his colleagues call a “molecular band-aid” is infused into the bloodstream, it finds and attached to microscopic tears in the heart muscle. This can prevent the damaging pathological leakage of calcium into the heart cells that prevents the heart from delivering sufficient oxygen to the vital organs.
Subsequently, Phrixus conducted a development program that lowered the therapeutically effective dose by two orders of magnitude; established that P-188 NF can seal tears not only in the membranes of heart cells, but also of diaphragm cells; and demonstrated that both cardiac and respiratory benefits can be achieved after once-a-day subcutaneous dosing, a novel route of administration that had not previously tried before.
To fully appreciate the benefits of P-188 NF as a therapeutic, it is important to remember that dose must be low and delivered using the subcutaneous route of administration.