Pharmareview Corporation — Department of Health and Human Services STTR Phase II: 101

Description

DESCRIPTION provided by applicant Intracerebral hemorrhage ICH is a major public health problem with the highest mortality rate of all stroke subtypes ICH is one of the leading causes of long term disability Since there are no available FDA approved therapies for ICH it is of vast importance to search for new approaches in treatment for this devastating medical condition Lactoferrin LTF is a well known endogenous glycoprotein with anti microbial and immunoregulatory functions in part through its effective sequestration of free iron In our ongoing research using different in vitro cell culture systems to model ICH pathogenesis and clinically relevant rodent models of ICH we discovered that lactoferrin LTF has unique pleiotropic activities This makes this endogenous protein highly attractive as a therapeutic candidate for the treatment of ICH Because LTF is rapidly removed from the circulation T min we developed a novel fusion protein based on recombinant human lactoferrin rhLTF and Fc domain of IgG for neonatal Fc receptor PRC This novel molecule has indeed a significantly extended half life fold over native LTF We successfully accomplished the objectives of Phase I by defining the optimal therapeutic dose of PRC and showing extraordinary therapeutic window h in a mouse model of ICH The primary objective of this Phase II is i to validate the safety of PRC as a potential therapeutic expressed in stable CHO DG cells according to GMP standards Aim and ii to further characterize the therapeutic utility of PRC in treatment for ICH using animal models that simulate clinical risk factors and known determinants of poor outcome after ICH Aim Further commercialization of PRC will require a robust scalable procedure where the final material retains activity and meets compliance requirements for pre clinical safety and toxicology in animals We will accomplish this goal with PRC being produced in stable CHO cells under GMP protocols and tested according to GLP protocols for i pharmacokinetics ii single dose safety studies toxicity and iii repeat dose day safety studies toxicity in rats The PRC obtained from scale up production g will be used to assess early edema and long term neurological deficit i in aged female and male mice ii in spontaneously hypertensive rats SHR and iii in a pig model allowing for larger hematoma size This design should provide the strong foundation for future clinical studies PUBLIC HEALTH RELEVANCE Intracerebral hemorrhage ICH is the second most common and deadliest form of stroke Currently no effective treatment strategies exist for this devastating disease The overall goal of this project is to develop a clinical prototype for therap of ICH using a fusion molecule comprised of human lactoferrin LF with the Fc domain of IgG for the Fc neonatal receptor PRC Based on successful accomplishment of the objectives of Phase I establishing optimal dose and therapeutic window in mice we propose to assess the efficacy of PRC in aged and hypertensive rodents as well as test in a larger animal model pig We will investigate the key clinical determinates of risk and poor outcome after ICH induction This will provide the strong foundation for future clinical studies