LIFNano Therapeutics Technology

LIFNano Therapeutics was founded in 2013 as a spin-out from the University of Cambridge, progressing to a clinical stage Nano-Bio-Med company specifically focused on targeted delivery of the biologic, Leukaemia Inhibitory Factor (LIF).

Why LIF?

"Multiple Sclerosis: One Protein, Two Healing Properties" Metcalfe: Nature 2011

LIF is a small stem cell signaling protein that has unique biological properties and our LIFNano medicinal is able to harness these for therapeutic benefit, not only to promote tissue repair but also to suppress disease-linked inflammation. Accordingly - by exploiting nature's own reparative mechanisms - LIFNano represents a new era in Nano-Med, working with the body's natural repair pathways. Therapy is achieved by targeted delivery of the LIF protein using biodegradable, biocompatible polymeric nanoparticles.

Myelin repair in vivo, with LIFNano therapy (left) and without (right) Ref: Rittchen et al Biomaterials 2015 vol 56, p.78-85

LIF restores reparative immunity

"Stem cell therapy versus T lymphocytes: friend or foe?" Metcalfe: Stem Cells 2015

The focus of the company is to treat chronic inflammatory diseases, initially for Multiple Sclerosis, where pathogenesis and progression is driven by inflammation. Inflammation in turn is driven by cytokines including interleukin-6 (IL-6). LIFNano was invented following the discovery of a simple binary switch in T lymphocytes operated by LIF (quiescence) versus IL-6 (inflammation). Crucially, LIF directly opposes IL-6 activity. Thus LIF is able to break the vicious cycle of the inflammatory disease process and reset the body's own self-tolerance mechanisms. Since the underpinning binary switch for tolerance also underpins regenerative and reparative pathways, the value of LIFNano is amplified by promoting tissue repair.

Mode of Action: A Binary Switch for Tolerance plus Repair

In the immune response evidence suggests that LIFNano's underlying mode of action lies at the heart of a biological switch that allows inflammation to occur when necessary. The switch is counter-controlled by LIF, versus IL-6, providing reciprocity in signaling - achieving a dynamic balance in the immune response. If the switch becomes chronically unbalanced, such as in chronic inflammatory conditions, IL-6 becomes dominant and levels of LIF become too low to regain normal counter-control.

It is thought that LIFNano, by targeted delivery of LIF to T lymphocytes, restores the natural balance of the cell's binary switch with recovery of normal responsiveness to both LIF and IL-6. Importantly, in the absence of inflammatory stimuli, tolerant T lymphocytes release LIF and - since LIF promotes tissue repair - tolerance and repair are directly linked.

When a T lymphocyte is activated by its antigen, it matures into either a tolerant T cell "Treg" or an effector cell, eg the inflammatory "Th17" cell. This is a critical fate-decision fork permitting self-tolerance to co-exist with immune attack against pathogens. If it goes wrong, auto-immune disease could result should naturally self-tolerant T cells become improperly switched towards self-attack - as occurs in MS where rogue TH17 cells start to attack myelin. A simple binary switch between LIF (for tolerance) and IL-6 (for inflammation) plays a critical role in regulating this fate decision fork - each exerting mutually opposing effects on the other. In auto-immune disease, LIFNano guides the switch for tolerance so protecting against autoimmunity.

Nano-Bio-Medical technology

The nano-engineering platform employed in manufacture of LIF-Nano has flexible design to deliver LIF to specific sites of disease with tunable release rate of cargo and tunable target selection. The platform technology is safe and efficacious in vivo, is approved by the FDA, and is fully biodegradable and biocompatible. Moreover, our LIFNano approach - beneficial as a monotherapy - also has added value in providing synergistic potential to current treatment regimens.

RegMed Solutions without RegMed Problems

LIFNano overcomes the two key barriers to regenerative medicine using cell or tissue grafts: (i) immune rejection of the graft and (ii) risk of biologic contamination. As a cell-free, viral-free, regenerative medicinal LIFNano restores the body's own reparative immunity, reducing or limiting the need for prescription drugs. Unlike cell-based approaches, LIFNano's products are free from graft rejection or contaminating biological agents.

Affordable, Simple, Safe

Bulk manufacture of LIFNano provides Global access to cell-free regenerative medicine where economy of scale reduces costs of treatment.

•   Cell-free, viral-free, safe, non-immunogenic
•   Free from contaminating biologics
•   Long shelf-life
•   Standard manufacturing methods and bulk production
•   Clear regulatory pathway
•   Clear reimbursement mechanisms