CLIP

MNI's scheme for imaging biomarker development enables focused, rapid, efficient development and application of radioligands for drug development.

Clinical Ligand Innovation Program (CLIP)

MNI has developed an efficient, rapid and focused ligand development process. This strategy is driven by the premise that specific imaging biomarkers are essential drug development decision-making. Furthermore, it is optimal for radioligand development to be initiated at an early stage in drug development to best ensure that imaging biomarkers will be available to assist in critical decisions early in drug development such as assessment of brain penetrance, target receptor occupancy, selectivity and kinetics, and in phase 2/3 to evaluate drug efficacy in a disease process.

The key features of CLIP are:

1. Compound identification - Novel compounds for a specific target may be synthesized in MNI's laboratory or MNI chemists may modify or utilize compounds from Pharma sponsors or academic collaborators for customized radioligand development. Physical chemistry properties of candidate compounds are assessed for optimal brain penetrance and minimal non-specific binding, using criteria developed from our radioligand development experience.
2. In vitro assessment - Assessment of the in vitro binding affinity of the compound to the target receptor then enables selection of candidate   ligands for further in vivo assessments. MNI chemists will then develop a radiolabeling strategy for SPECT or PET ligands.
3. In vivo assessment in nonhuman primates- Candidate radioligands are administered to ovarectomized female nonhuman primates to assess in vivo brain penetrance, regional specific binding, tracer selectivity, and ligand metabolite profile.  Nonhuman primate studies also allow evaluation of dose dependence and are extremely valuable for initial assessment of quantitative outcome testing for eventual human use.
4. In vivo assessment in Humans - MNI's primary goal is to develop and apply radioligands for human use. MNI will rapidly test those ligands that demonstrate good performance in nonhuman primates, in humans, under an investigational IND.

The CLIP process is customized to meet the needs of a specific research program. MNI will work closely with sponsors at each stage of ligand development to flexibly create solutions that will meet the needs of the specific ligand development program. For radioligands that are now in human use-in general, the time-line from compound identification to completion of early studies in humans is approximately 6-9 months.

John Seibyl, Andrei Koren, David Russell, Rafik Omar-Amrani, George Zubal, Ken Marek, Herve DaCosta, David Alagille and Gilles Tamagnan

5-IA α4β2 nicotinic agonist

mNI 187 β-amyloid protein

INER selective norepinephrine transporter

mZINT selective serotonin transporter

IBVM selective cholinergic transporter (AD)

MNI 200 adenosine 2A receptor

MNI 201 α4β2 nicotinic antagonist