Exploring the Benefits of Cell Transplant Therapy for Dry AMD

In an interview with GeneTherapyLive, Brian Culley, chief executive officer of Lineage Cell Therapeutics, sat down to discuss the clinical-stage biotechnology company's pipeline, specifically their development of a novel cell therapy for the treatment of dry age-related macular degeneration (AMD).

Culley has high hopes that their proprietary cell replacement therapy, OpRegen, will be successful in addressing the large unmet need in dry AMD, which currently has no approved treatments.

Using an established pluripotent cell line, Lineage creates and injects allogeneic human retinal pigment epithelium cells directly into the subretinal space. The company completed enrollment in their phase 1/2a trial (NCT02286089) in November 2020, treating a total of 24 patients. The latest interim results presented in March 2021 showed that 75% of treated eyes in patients in cohort 4, which included 12 patients with less advanced disease, were at or above baseline visual acuity at the most recent assessment. In contrast, 75% of patients' untreated eyes were below baseline acuity values at the same assessment.

The company plans to present additional OpRegen data at the upcoming Association for Research in Vision and Ophthalmology (ARVO) annual meeting, taking place virtually May 1-7, 2021.

Interview transcript: (edited for clarity)

Brian Culley: At Lineage Cell Therapeutics, we're aware that there are more than 200 different types of cells that make up the human body, and from time to time, there are conditions or diseases that the hallmark is the loss or the inactivity or the death of those cell types. We manufacture those cells and replace them, and we're doing that in 3 clinical settings. Today, we can manufacture retina cells to treat dry AMD [age-related macular degeneration], we can manufacture spinal cord cells to treat paralysis after spinal cord injury, and we can manufacture dendritic cells to help present antigens to the immune system to treat cancer.

We're really more like transplant science or transplant medicine than we are cell therapy, and the reason for that is that our cells are differentiated. If you want to treat a disease like dry AMD, for which the loss of specialized retina cells called RPE [retinal pigment epithelium] lead to the loss of activity, ie vision, we can manufacture brand new RPE cells by the billions, and we transplant about 100,000 of them right into the eye. And in doing so we are trying to reverse the course of the disease or stop it from progressing any further. This is an approach that is unique because traditional approaches such as small molecules and antibodies have never been successful; there is in fact nothing approved to treat dry AMD. So we think that by using an entire cell replacement strategy we may be able to get benefits that other approaches have failed to reach.

There are a bunch of places where this approach really does seem to have key advantages over other approaches. One thing to be clear about is that these are allogeneic cells; we are not taking cells from a patient, manipulating them or repairing them and putting them back in. That's a personalized approach, which can become very expensive. We actually have cell lines that were characterized decades ago, and we just treat those cells in a way in order to make them all become retina cells and then those cells can be administered to any patient. There, we have never seen any cases of acute or delayed rejection of our cells. In part, that's because the eyes enjoy some immuno-privilege, as there's not a lot of white blood cells floating around there to reject cells. We have patients that are now more than 5 years out and still having a transplant. We place the cells specifically into the subretinal space as that's where the old cells that have died off are supposed to be located. We don't just put them into the vitreous and hope that they secrete positive factors--that's really a different kind of cell therapy and that's not our approach; we are doing more of a transplant. We use specialized tools in order to deposit or deliver the cells right to the subretinal space, and in doing so we're trying to stop the progression of the disease. We also lastly recently developed a new thaw and inject formulation, so you don't even have to plate these cells and wash them the day before. They are literally taken out of the freezer, put into a warm bath, put into the injection needle, and placed into the subretinal space of the patient in about a half-hour procedure.

Certainly safety is paramount; we always treat the worse eye, as people sometimes have the disease in both eyes and we don't want to cause any harm. Because this is a Phase 1/2a clinical trial, we're always treating the worse eye, and what we have seen is that the cells have been very well-tolerated. There are adverse events that occur in any clinical trial. Most of those have to do with background medications and so forth, as this is typically an elderly population. But overall, despite this being a new technology, we've been very pleased that we've got a very high rate of success with respect to the pausing of cells, and in fact, when we've moved into patients that have better vision, so not legally blind where we started, but we've moved into patients that have better vision, we've seen some really exciting results: about 75% or 9 out of 12 patients so far actually have had a stabilization or improvement of their vision. Again, this is a disease that only gets worse, so we're really excited that we've been able to have a very nice safety and efficacy profile to date. But it is still early, we've only treated a total of 24 patients so far.

Forward Looking Statements for Lineage:

This interview is for informational purposes only and is not an offer to sell or a solicitation of an offer to buy any securities of Lineage Cell Therapeutics, Inc. (“Lineage”). This interview includes certain information obtained from trade and statistical services, third-party publications, and other sources. Lineage has not independently verified such information and there can be no assurance as to its accuracy. All statements in this interview, other than statements of historical fact, are forward-looking statements within the meaning of federal securities laws. In some cases, you can identify forward-looking statements by terms such as “may,” ”will,” “expect,” “plan,” “anticipate,” “strategy,” “designed,” “could,” “intend,” “believe,” “estimate,” “target,” or “potential” and other similar expressions, or the negative of these terms. Forward-looking statements involve risks, uncertainties and assumptions that may cause Lineage’s actual results, performance, or achievements to be materially different from those expressed or implied by the forward-looking statements in this interview, including risks and uncertainties inherent in Lineage’s business and other risks described in Lineage’s filings with the Securities and Exchange Commission (SEC). Lineage’s forward-looking statements are based upon its current expectations and involve assumptions that may never materialize or may prove to be incorrect. All forward-looking statements are expressly qualified in their entirety by these cautionary statements. Further information regarding these and other risks is included under the heading “Risk Factors” in Lineage’s periodic reports filed with the SEC, including Lineage’s most recent Annual Report on Form 10-K and its other reports, which are available from the SEC’s website. You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date on which they were made. Lineage undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.