59 Elm St. Suite 200, New Haven, CT 06510(203) 404-1131

Our science

Two mechanisms, delivered where the tumor is.

Getting past the blood-brain barrier

The blood-brain barrier protects the brain from toxins, but it also keeps out most medicines. Drugs given by mouth or by injection travel through the bloodstream, and only a small fraction reaches brain tissue. Raising the dose to compensate often brings side effects elsewhere in the body.

The upper nasal cavity offers another way in. Nerve pathways that connect the nose to the brain, the olfactory and trigeminal routes, can carry suitable molecules directly into brain tissue and the fluid around it. LMP01 is an intranasal formulation designed to use this route.

Conceptual model of intranasal delivery of LMP01: the formulation is deposited in the nasal cavity and absorbed through the epithelium, then reaches the brain along the olfactory and trigeminal nerve pathways, with further distribution through cerebrospinal fluid, perivascular spaces and the glymphatic system. Material cleared from the nose to the gut is expected to have low bioavailability.
Conceptual model of intranasal CNS delivery of LMP01. Intranasal administration is proposed to bypass the blood-brain barrier through the olfactory and trigeminal nerve pathways, followed by distribution through perineural, perivascular and glymphatic routes. This receptor-independent strategy is designed to increase brain exposure while limiting systemic exposure.

From the nose to the tumor

Reaching the brain is the first step. The components then need to reach the tumor and the infiltrating cells around it at concentrations high enough to act. Our current studies measure how much of each component reaches the brain. They also measure how much ends up in the lungs and gut, where a small share of any intranasal dose is expected to go. These data will tell us how closely the model above matches what happens in practice.

Two pathways, one combination

Glioblastoma cells rewire their metabolism to rely on aerobic glycolysis, a fast but inefficient way of producing energy that also supplies the building blocks for new cells. At the same time, RAS and cell-cycle signaling push the cells to keep dividing.

LMP01 combines two small molecules, each acting on one of these pathways. Tumors are adaptable, and a cell that finds a way around one pressure point can still be held back by the other. Our cell-based studies show synergy between the two components, and our in vivo and proteomic work is helping us understand how the combination acts.

Two pathways, one combination Inside a glioblastoma cell, aerobic glycolysis supplies energy and building blocks while RAS and cell-cycle signaling drive proliferation. Each LMP01 component acts on one of these pathways. Glioblastoma cell Aerobic glycolysis Energy and building blocks RAS and cell-cycle signaling Proliferation LMP01 component 1 LMP01 component 2
Simplified illustration of the two pathways LMP01 is designed to act on.

Built on existing molecules

Both LMP01 components are existing compounds with a substantial body of published preclinical and clinical research. Building on that knowledge lets us focus our work on what is new: the combination, the dose and the route of delivery.

Our current studies are designed to test efficacy in glioblastoma models and to measure where each component goes in the body. Read about LMP01’s development status.