Table 1.

Translational trajectory for MLP probes.

Targets	MLP probes	Post-MLP trajectory
Serine hydrolases	ML081, ML174, ML211, ML225, ML226, ML256, ML257, ML294, ML295, ML296	Screening and assay platforms, serine hydrolase-directed small-molecule libraries and serine hydrolase inhibitors, resulting in part from MLP projects, have been licensed to Abide Therapeutics, which is pursuing the further identification, preclinical, and clinical development of serine hydrolase inhibitors for a variety of indications, in particular neurological, immunological and metabolic diseases.
P. falciparum, T. cruzi	ML238, ML341	The identification of the MLP malaria probe led to a Gates Foundation-funded Chemical Diversity Initiative that has explored the use of the DOS collections more broadly in infectious disease and has yielded promising compounds that target the etiological agents of malaria tuberculosis via novel mechanisms. In work supported by the Global Health Innovation Technology (GHIT) fund and in collaboration with Eisai, the MLP anti-trypanosomal probe is being optimized to enable in vivo proof of concept studies and a DOS-based antimalarial agent is being optimized towards IND-enabling studies.
S1P1 agonists	ML007	Receptos licensed intellectual property surrounding S1P1 agonists including the racemate of its clinical candidate RPC1063, which is currently in two Phase- III studies in relapsing multiple sclerosis and about to enter Phase-III testing in ulcerative colitis and Phase-II testing in Crohn’s disease.
M4 mAChR	ML108, ML253	AstraZeneca has licensed intellectual property associated with the M4 PAMs and the company is pursuing preclinical development of the compounds as a potential treatment for the neuropsychiatric symptoms associated with AD and schizophrenia.
GCase	ML198	This probe and related analogs have been licensed to Lysosomal Therapeutics Inc., which is pursuing preclinical development of these non-inhibitory GCase chaperones.
Integrin αIIbβ3 receptor antagonist	ML165	Rockefeller Medical School and NCATS are pursuing an IND based on a derivative of ML165 indicated for pre-hospital therapy of patients with ST segment elevated myocardial infarction (STEMI).
P97 AAA ATPase inhibitor	ML240	Cleave BioSciences licensed intellectual property surrounding ML240. A derivative of this probe, CB-5083, is currently in two Phase-I studies, one in relapsed and refractory multiple myeloma and the other in solid tumors refractory to the standard-of-care.