
Repair Biotechnologies



Stage: Preclinical development
Area: Cell therapy
Status: Ongoing
Patent: Main patent secured and licenced, more patents filed and in progress
Background
Atherosclerosis is the main cause of cardiovascular disease (CVD), an age-related disease ranking as the number 1 killer in the world, responsible for a quarter of all deaths according to recent World Health Organization data. In atherosclerosis, plaques that are mainly made up of cholesterol build up over time in the walls of arteries, restricting or even blocking the flow of oxygen-rich blood to organs and other parts of the body. In arteries, cholesterol is carried by low-density lipoproteins or LDLs. In young individuals, macrophages help clear excess LDL cholesterol from artery walls but with aging, they become overwhelmed and ineffective.
To date, no therapy can reduce plaque size. Current medical treatments for atherosclerosis, like statins, which are inhibitors of cholesterol production, can only slow its accumulation in plaques. Statins do reduce cardiovascular events by about 25%, which is already a huge achievement, but do not cure atherosclerosis.
Aims, Hypothesis & Results
Repair Bio aims to solve macrophage dysfunction with their “Cholesterol-Degrading Platform” (CDP), a novel allogeneic cell therapy. Concretely, the idea is to produce macrophage cells engineered to have better LDL disposal capabilities and deliver them to patients.
Repair manufactures these enhanced macrophages in a series of steps (see figure below):
- First they obtain induced pluripotent stem cells (iPSC, a cell that can be converted into any other type of cell) from healthy donors
- Then they modify these cells so that they are not recognized and attacked as foreign by patients’ immune systems, in other words, they make them universal
- At this point they add proprietary genetic instructions for the cells to produce an LDL-degrading protein in a tightly controlled way, to avoid tampering with the cholesterol normally required by cell membranes
- Finally they convert the cells into macrophages
In-vitro tests of these enhanced macrophages have shown that they can break down excess ingested cholesterol into safe catabolites. Encouraging results were also obtained in vivo in a strain of mice used for studying cardiovascular disease: in this proof of concept (POC) study, mice on a high-fat diet were treated with a gene therapy implementation of Repair’s approach. The treated mice exhibited a rapid halving of atherosclerotic plaque lipids, an outcome needing only a one-month period following a single treatment, with no identified side effects.
Timeline
- End 2023: Out of preclinical studies
- Mid 2024: Clinical studies start (IND enabling)
- Beginning 2024: GMP manufacturing
- End 2024: Phase 1/2a
Required Funding: $50,000 (more required but that’s what we’re providing)
Status: Ongoing
VitaDAO Board Evaluation Writeup
Repair Bio is targeting the deadliest aging-related diseases and a multi-billion dollar market. They have encouraging results of human in-vitro and mice in-vivo proofs of concept as well as comprehensive and recent intellectual property protection. The effort is lead by a solid team with drug development and clinical trial knowledge. There were some risks considered such as early stage approval of iPSC-based therapy, potential side effects of allogeneic cell therapy, and complex manufacturing process.

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