Common use of Clinical Development Plan Clause in Contracts

Clinical Development Plan. Licensee has developed a technique to quantify reverse cholesterol transport (RCT) in both animals and humans through the use of stable isotopes and isotope-ratio mass spectrometry. Quantification of peripheral cholesterol mobilization from tissues into plasma, referred to as efflux, and elimination of plasma-derived cholesterol as fecal sterols, referred to as excretion, is made in a single procedure. Although the cardioprotective effects of HDL on RCT in both humans and experimental animals are well documented in the literature, the functional significance of RCT in atherosclerosis remains controversial. This uncertainty can be attributed, in large part, to the previous inability to measure RCT fluxes in vivo, particularly in humans, and thereby test hypotheses experimentally. It is clear that the concentration of HDL particles in blood does not accurately reflect efflux rate of cholesterol or global flux through the RCT pathway. This was most recently illustrated in the outcome of the Torcetrapib trial where, despite dramatically increased HDL concentration, no benefit on atherosclerosis was observed. Accordingly, it is critical to evaluate in humans the effect of HDL targeted therapies on cholesterol flux prior to commencing large and costly clinical outcome trials. Licensee intends to use its proprietary ability to directly measure RCT to direct and expedite the clinical development of 5A. Licensee has already assessed 5A with this proprietary technology in animals and has shown (see above) 5A's ability to increase RCT in a relevant animal model. As the only company with access to this patented method, Licensee intends to symmetrically apply its technology to demonstrate human Proof-of-concept in early Phase I studies of 5A. Licensee then intends to maximize the chances of successful development of SA by using its technology to optimize the dose-response of SA against RCT activity in phase Ib and Phase II studies. The most important element of the development plan is to establish clinical proof-of-principle in patients as quickly and efficiently as possible. Early assessment of clinical efficacy in healthy volunteers will be performed in Phase Ia and Ib through the use of Licensee's stable-isotope based kinetic measurement of RCT. This method, in contrast to either IMT or IVUS imaging metrics or traditional clinical outcomes, provides for rapid evaluation of drug efficacy on one of the primary targets of mimetic therapies, modulation of cholesterol flux through the RCT pathway. In its initial Phase II study, Licensee will evaluate the 5A mimetic therapy to subjects with diagnosed intermittent claudication. The primary outcome in all subjects will be standard diagnostic criteria for intermittent claudication changes in ankle-brachial indices and doppler ultrasound of the peripheral arteries, with secondary endpoints being treadmill tests, forearm vascular reactivity and Licensee's measurement of RCT. By using standard outcomes for intermittent claudication in phase II and III studies, Licensee will have a clear path to approval for 5A that does not require the classic large and long cardiovascular outcome studies. At the same time, Licensee's added measurement of RCT in phase II will allow for subject identification/stratification, accurate dose finding through rapid dose-response and pK/pD evaluation to optimize the design of phase III clinical trials. The phase III registration study will be designed to show non-inferiority to the current standard of care for intermittent claudication. The phase III study guided by the Licensee enabled measurement of RCT to determine the optimal' dose regimen for 5A will have a much higher likelihood of success than with standard metrics alone. Additionally, Licensee will pursue a parallel phase II study in subjects with known coronary artery disease (CAD). Licensee will measure changes in carotid IMT, or other imaging modality as a primary outcome. Licensee hopes to show that increased RCT flux with 5A in subjects with known CAD can be a therapeutic for reversing atherosclerosis. Licensee expects to partner the phase III development and further commercialization in the CAD indication with a partner with established late-stage and commercialization experience to gain market approval of Licensed Products in the CAD indication. The initial Licensed Product shall be positioned for regulatory market approval and launch in peripheral artery disease (PAD). After successful Phase II study in intermittent claudication, Licensee shall work with its commercial partner to develop the optimal commercialization plan for the drug based upon the demonstrated drug activity. Licensee may build or acquire a specialty commercialization group that can effectively penetrate the relatively centralized markets such as interventional cardiologists that diagnose and treat intermittent claudication. Licensee may also or alternatively enter into a commercial partnership with a drug or drug/device company that already has a commercial presence in these markets to facilitate rapid market penetration in these specialty market segments. Licensee expects to partner with a leading pharmaceutical company to facilitate the timely completion of the larger, longer-term clinical development studies for the large and expensive registrational outcome studies leading to the launch of a Licensed Product to prevent and treat CAD in the U.S. followed by subsequent commercial launches in other Licensed Territories. · O▇▇ license reference number (L-XXX-200X10) · Reporting period · Catalog number and units sold of each Licensed Product (domestic and foreign) · Gross Sales per catalog number per country · Total Gross Sales · Itemized deductions from Gross Sales · Total Net Sales · Earned Royalty Rate and associated calculations · Gross Earned Royalty · Adjustments for Minimum Annual Royalty (MAR) and other creditable payments made · Net Earned Royalty due