Pituitary suppression in ART cycles

SEEKING PARTNERS FOR AN APPROVED PATENT

Parthenogen holds full rights on a PCT patent for an innovative drug product intended for the treatment of human infertility. The patent is already approved in Europe (PCT/EP2012/060122 – 15/15 claims approved) whereas the procedures for the USA approval are still ongoing.

The project was so far entirely managed in-house. Although it is a low demanding project, any further development largely exceeds the current investment and operative capability of the company, accordingly we are seeking partners willing to invest.

Parthenogen is open to any proposal allowing the project to reach the market for the benefit of the patients: we are definitely convinced that this new treatment strategy has the potential to significantly improve the clinical gain from Controlled Ovarian Hyperstimulation intended for Assisted Reproduction Technologies. Thus, we would be happy for any funds conferred to the company to develop the project with the support of our internal expertise in the field in exchange for a very generous participation to the revenues. In alternative, we are ready to fully release the project, also in front of a very limited compensation, to anybody ensuring a serious interest to progress with the development.

The project carries a series of unique features that may make the investment appealing. The promise for a far better efficacy vouches for a fast growth of sales and for a high market share. The drug product is predicted to be simple and cheap to manufacture on one side and to candidate for an innovation premium price on the other, it may be very profitable.

On the other side the time and cost to reach the market may be as well very small. The new product, being based on a well-known molecule by a new route of administration, is suitable for the centralised EU registration, which is a quite convenient path. The molecule is already well known and clinically investigated in the same target group (ladies in child bearing age) at far higher doses (200 mg x 3 per os compared to 0.5 mg by nasal route) and will not require an extensive pre-clinical phase. Phase 1 studies will be very limited (just to show no drug in circulation) and phase 3 may be accomplished with a surprisingly small size clinical study.

HOW DOES IT WORK

The small amount of progesterone (P) released by human follicles at their very final stage of maturation plays as the main trigger of the mid-cycle gonadotrophin surge. Indeed, under raising estradiol concentration, hypothalamic cells expose P receptors (PR) that are extremely sensitive and may react to the very small amounts of hormone released from the end stage follicle. The activation of hypothalamic PR triggers the release of a peak of GnRH, which in turn triggers the midcycle gonadotrophin surge.This mechanism opens the opportunity to modulate the release of the midcycle surge within controlled ovarian hyperstimulation (COH) cycles by administering a receptorial progesterone inhibitor, namely mifepristone.

Mifepristone, 1 mg by oral route, had been already shown to suppress the midcycle surge in 100% of the patients but it was toxic to follicles at slightly higher doses (5 mg). This problem has been addressed by administering M by the nasal route so to achieve a direct nose-to brain delivery ensuring full efficacy at very low doses (< 1 mg) without any systemic interference.

In clinical practice the new product will be assumed by nasal puff once daily starting from the day of FSH stimulation in which the follicles reach the size of 18 mm and will be withdrawn as soon the criteria for final maturation have been reached (similar to a GnRH antagonist schedule). On that day, the injection of a small amount of Progesterone (e.g. 5mg) will trigger the midcycle surge for a oocyte pick-up about 72 hours later as usual.

This new COH strategy carries several advantages. First, the pituitary will be active during the cycle and thus regulating the endocrine backgroung, which means i) timed release of the proper LH pulses and, ii) better coordination with the endometrium. Second, at time of triggering, differently from  LH surrogacy with hCG as done in current COH based on agonist or antagonist pituitary suppression, a pituitary-generated physiologic gonadotropin surge will occur. Therefore: A FSH peak will parallel the LH peak as in physiologic cycles and; The occurrence of a natural LH peak is anticipated to avoid the issues of hyperstimulation syndrome complicating the current hCG triggering. Last but not least, the new schedule is definitely more physiology friendly, patient friendly (no injections) and very likely to be cost-effective.

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