Brian Culley, chief executive officer of the biopharma company Lineage Cell Therapeutics, started his career in science as a “lab coat wearing molecular biologist.” But his true calling was business.
He left his PhD program in molecular, cellular, and developmental biology at the University of California, Santa Barbara early, but Culley didn’t need a PhD to become a leader in the pharmaceutical world. He has served as chief executive officer for two other pharmaceutical companies, Artemis Therapeutics and Mast Therapeutics before joining Lineage Cell Therapeutics.
One of Culley’s current goals is to help people with vision loss caused by age-related macular degeneration (AMD). Researchers at Lineage Cell Therapeutics are currently testing a regenerative cell therapy, OpRegen, where cells lost in the eye’s macula, retinal pigment epithelium (RPE) cells, are injected into the eye. Last year, they reported that four patients involved in the current Phase 1/2a clinical trial regained some vision 12 months after treatment; OpRegen received Fast Track designation by the FDA.
How is AMD currently treated?
There are two forms of AMD — wet and dry — and one is better understood than the other. We as an industry really understand what’s broken in patients with wet AMD. In wet AMD, fragile blood vessels grow around the back of the eye, and when they break, blood leaks and damages the macula. There are therapeutics that are approved by the FDA and other regulatory agencies in other regions to treat that condition because when we know what’s broken, we can fix it. If a car doesn’t start because the battery is dead, the battery can be replaced. But if a car won’t start, anything could be wrong. Is there gas in the car? Are the wires not connected? That’s how the industry is approaching dry AMD. There are known characteristics of the disease such as inflammation and broken cellular pathways, but no one really knows the origin of the disease. That’s why there are currently no FDA approved treatments for dry AMD. Our approach is to replace the broken car entirely using cells rather than trying to fix it using small molecules.
How does your cell-based therapy work?
We use pluripotent stem cells that can become any of the 200 cell types in the body. In the case of OpRegen, we make a very specific cell called an RPE, which is critical for vision; these cells die during aging. We manufacture replacement cells and transplant them into the eye. These replacement cells take over for the RPE cells that died and restore vision. We’ve treated 24 people with dry AMD so far, and we are excited to follow their progress. Human beings can’t regrow retinal tissue the way they can regrow skin. It was extraordinary that we could manufacture these replacement parts.
Are the cells you use patient-derived?
No, these are allogenic cell lines. We have cell lines that are pluripotent, and they can be cultured indefinitely. We differentiate these cells using a defined protocol to turn them into RPE cells. The eyeball doesn’t have a lot of white blood cells, so there is some level of protection from rejection compared to other tissues. We haven’t seen a single case of rejection in the 24 people we treated. We have followed some of those patients for more than five years. This therapy is truly off the shelf. Cells can go from a freezer to a warm bath, and five minutes later, they can be injected into the patient. One of the problems with some cell therapies is the manual work needed to get them ready for the patient. Ours is super easy; it’s a thirty-minute procedure.
How do you evaluate the efficacy of OpRegen?
There are many traditional tests for vision. The most obvious is visual acuity, where someone reads letters of different sizes on a distant board as is done for a driver’s license test. Among the 24 patients we treated, 12 were legally blind. Their vision was so far gone that it wasn’t likely that the therapy would help. But the other 12 had vision as high as 20/65. In most states, a person with 20/65 vision can drive a car. After treatment, those 12 patients could see eight more letters than they could see before.
We also use something called high resolution optical coherence tomography (OCT). OCT gives almost histological levels of visibility into the retina. If the retina is composed of ten layers of cells, OCT allows us to look at each of those ten layers and map out and measure their thicknesses. The diseased area of AMD eyes tapers down, collapses, and gets all mushy.
Those mushy areas were restored after treatment with our therapy. This is an anatomical, objective observation. We were happy to see that we restored tissue in that area using such high-resolution imaging techniques.
What excites you the most about developing therapies at Lineage Cell Therapeutics?
In theory, we could develop 200 different products because every cell type in the body could be generated through these protocols. We want to move beyond the spinal cord, cancer, or the eye into areas stem cells haven’t been used before. We want to explore the breadth of this technology.
This interview has been condensed and edited for clarity.