Development of Novel and Affordable Neoglycosylated, Long Acting Superactive Analog of Human FSH for Infertility

PROJECT SUMMARY ABSTRACT It is estimated that overof all American couples suffer from infertilitya topic of great importance to NICHD and cited frequently by this InstituteProfessional American women andampthose from all developed nations increasingly delay childbearing for several years compared to the past because of career advancement and increasing social acceptabilityThis problem is not solely a woman s health issue but equally affects men as onlyof infertility is attributable solely to womenwhile an estimated equalis attributable to the male partner who also contributes to anotherof combined female andampmale causesCurrentlyrecombinantrhumanhfollicle stimulating hormoneFSHis the single largest therapeutic component of the infertility market with sales considerably in excess of $billion per yearof whichof that total over $Million per year in the much higher priced and growing US market and anotherin the European marketSeveral infertility consultants to the Trophogen PIs have confirmed that rhFSH therapy for infertility is much too expensive for most American women as the cost is not covered by insurance in many states andeven if coveredthere are often prohibitive out of pocket costsIn additionthe results with current rhFSH treatments are far from optimal with only an average response rate ofper cycleand much worse for women overespecially for greatly under reportedpoor respondersThe latter include both to conventional first line in vivo FSH stimulation performed with intrauterine inseminationIUIas well as to more effective but costly and invasive in vitro fertilizationIVFPoor responders often produce fewer thanoocytes per superovulation cycle of variable quality and may require repeated cycles up toor more to achieve a full term pregnancyif they are successful at allwith devastating emotional and financial cost to infertile couplesMoreoverrhFSH stimulation is an important component of many rapidly growing additional markets limited only by costelective and medical egg bankingethical preferred sexing of IVF babies andampespecially important to the PIsfuture disease prevention using cutting edge entire genome screening of IVF embryos for even more than currently screened chromosomic aberrationsall known monogenic diseases and even proclivity to complex genetic and epigenetic diseases the latter using newest metabolomics techniquesTo be most effective in disease preventionall such methods also require an improved rhFSH analog to produce the largest possible number of high quality IVF embryos of which onlyand in the future onlywill be transferred to the uterusTrophogen has recently designed ard generation neoglycosylatedlong acting bovine FSH analog already licensed to Zoetisformerly Pfizer Animal Health and the world s largest animal pharmawhich has performed extensive due diligence on the safety and all aspects of the superiority of this analog compared to all currently used wild type animal FSH productsThis new bovine FSH analog has recently inspired the homologous design of the hFSH analog on an hFSH templateamino acids different from the bovineUsing the expedited FDAbNDA regulatory track for Biosuperiors and with all these attributespotencymaximal efficacylong actionmuch lower production costs than big pharma using only inexpensive internet marketing with no need for a sales forceTrophogen is confident it will still be highly profitablepricing its vastly superior new FSH analog in the US well below that of both currently branded FSH as well as coming biosimilars to quickly assume a dominant position within the infertility treatment market in the US andampgloballyIn the current studiesthe PIs propose in Phasetoestablish unequivocally the superiority of the lead TRmolecule based on extended in vivo testing andampstimulation of ovarian weightsize andampnumber of antral folliclesto establish a master Chinese Hamster OvaryCHOcell bank for future good manufacturing practicesGMPproduction providing high level expression of the lead FSH analogproduce andamppurify additional larger of the final FSH analog candidate in roller bottles or bioreactors sufficient to submit an IND using methods of production and purification optimized in preliminary data research studiesPhasetransfer Trophogen s previously developed smaller scale GLP production methods and purification methods developed in Phaseto the GMP facility of its about to be selected foreign pharma partner or alternatively to an outstanding commercial GMP facility tentatively selected with previous methods now adapted to major up scaling for large commercial disposable bioreactors plus addition of required new viral clearance stepsobtain larger amounts of GMP material sufficient for an FDA agreed upon Phasecombined clinical trial as well as only one more final PhaseB clinical pathway for Biosuperiorsperform all FDA required efficacyspecificitystabilitymetabolicpharmacokineticpharmacodynamic and analytic studiesPerform FDA IND required toxicology studies without repro tox studies with supplemental support from NCATS BrIDGspreparation andampsubmission of INDAdvanced development of this vastly superior FSH analog on a low costFast track NDA for Biosuperiors using internet marketing will make rhFSH treatment for infertility andampmany other growing marketsfor the first timemuch more effective andampaffordable for US andampwomen throughout the world!It is estimated that overof all American couples suffer from infertilitya topic of greatimportance to NICHD and cited frequently by this InstituteProfessional American women andampthosefrom all developed nations increasingly delay childbearing for several years compared to the pastbecause of career advancement and increasing social acceptabilityThis problem is not solely awoman s health issue but equally affects men as onlyof infertility is attributable solely towomenwhile an estimated equalis attributable to the male partner who also contributes toanotherof combined female andampmale causesCurrentlyrecombinantrhumanhfollicle stimulating hormonerhFSHis the single largesttherapeutic component of the infertility market with sales considerably in excess of $billion peryearof whichof that total or over $Million per year in the much higher priced andgrowing US marketTrophogen has recently designed a new long acting and more effective FSH analog for cattle andother livestock reproduction which is already licensed to Zoetisformerly Pfizer Animal Health andthe world s largest animal pharmawhich has performed extensivedue diligenceconfirming thesafety andampall aspects of the superiority of this analogThis new bovine FSH analog has recently inspired the analogous design by the principalinvestigators inventors at Trophogen of a similar long actingrequiring many fewer injectionsmuch more potent and effectivehFSH for infertility showing similar great superiority to allcurrent FSH productsWith its very low production costs for this much more potent drugand its vastly smaller overheadcosts than big pharmaTrophogen is confident it will still be highly profitablepricing itsvastly superior new FSH analog in the US well below that of both currently branded FSH as well ascoming generics calledbiosimilarswhich will quickly assume a dominant FSH market position inthe US and globallyThe advanced development of this vastly superior FSH analog for infertility on a low costfasttrack FDA pathway for superior biotech drugs using novel internet marketing will make rhFSHtreatment for infertility and many other growing marketsfor the first timemuch more effectiveand affordable for U Sand women throughout the world!