Brian Culley is chief executive officer of Lineage Cell Therapeutics.

Brian Culley

At the 2021 Association for Research in Vision and Ophthalmology (ARVO) Virtual Meeting, 

 presented the latest data from their ongoing clinical trial (NCT02286089) of OpRegen in patients with dry 

The updated data included a minimum of 4.5 months of follow-up on all 24 treated patients, as well as new results from the 12 patients in Cohort 4. Notably, 83% of those patients' treated eyes were at or above baseline visual acuity at last assessment post-transplant with Lineage's proprietary cell replacement therapy that utilizes allogeneic human retinal pigment epithelium cells injected directly into the subretinal space.

, Lineage chief executive officer Brian Culley spoke about the OpRegen program, including the importance of working closely with the FDA on therapy and trial development, as well as other areas of interest where Lineage's cell therapy technology has shown promise. 

Interview transcript: (edited for clarity)

: This is the first time that OpRegen has been tested in humans. We have completed 24 patients; the first 12 patients were all legally blind. That's a safety component, as you're not going to do any harm if you've got patients who already have negligible vision, but we had some encouraging early signs and the procedure was well tolerated. We were able to then move into the next 12 patients who had higher levels of baseline vision. In fact, they would be high enough that they could even drive a car, and that's where we saw better efficacy. We think that makes sense because patients that have less advanced disease are more likely to respond to our transplant approach. So, we've completed enrollment in the study, all 24 patients are now in the follow-up period, and every few months we've been putting out interim updates on how the patients are doing. Soon this year, we'll go and talk to the FDA about the next clinical study that will be used with OpRegen.

The FDA has been very responsive to the growing wave of new cell and gene therapies, so sponsors like Lineage and others are really rushing to the clinic because this is a brand new technology which holds tremendous promise. The number of clinical trials for cell and gene therapies has really been growing, so the agency has been really responsive. I think what we're going to see is an increased level of expectation from sponsors. What I mean by that, specifically, is that at one time, you didn't have to do as much analysis of the cells. But I think that the threshold, the requirements to be able to show that you have control over your cell production, to ensure that you're putting the same material in patients every time, which is really the foundational aspect of doing an experiment—to reduce variability—[are going to be greater]. Having control over your process, being able to scale your process, these are all important areas, but I think that the FDA is well aware of them and experienced in them and is communicating not only with Lineage but also others to ensure that these new technologies can reach patients without delay.

I think this is going to be an incredible year; I thought last year was great, and we're going to really try to outdo it. What I mean by that is that we will continue to have very important data updates from the dry AMD program. I'm working to get our spinal cord program back into the clinic; we had achieved a lot of manufacturing improvements to make that commercially viable, so that was a breakthrough achievement. And then we hope to finish enrollment and report data from our oncology program with our dendritic cell vaccines, so that's a lot of clinical data. And then of course, there are always opportunities for partnerships big and small. When you've got, you know, many hundreds of patents out there, we have more technology than we could ever possibly develop on our own, so I think there are a lot of areas for news and growth from Lineage this year.

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.

Videos

Lineage Cell Therapeutics CEO Brian Culley shares a clinical trial update on their leading cell therapy candidate and discusses the important role of the FDA as more players enter the cell and gene therapy space. 

Cell Therapy for Dry AMD and Beyond: Next Steps

, 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 

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. 

: 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.

The CEO of Lineage Cell Therapeutics discusses their unique approach to addressing degenerative vision loss in dry age-related macular degeneration. 

Brian Culley

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Cell Therapy for Dry AMD and Beyond: Next Steps

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