San Diego Business Journal Lineage Cell Therapeutics is rapidly expanding its cell therapy pipeline. In late March, the company announced a new investigational product candidate – an auditory neuronal cell transplant for the treatment of hearing loss, with an initial focus on the treatment of auditory neuropathy spectrum disorders.  
 
And in the last week of April, Lineage announced a cell therapy development program to transplant photoreceptor neural cells (PNC) for the treatment of vision loss due to photoreceptor dysfunction or damage.  


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Brian Culley CEO Lineage Cell Therapeutics

The two new programs come on the heels of Lineage’s successful OpRegen program, which has demonstrated to be able to replace and restore retinal pigment epithelial cells in patients with geographic atrophy secondary to age-related macular degeneration. Because of that program’s success in human testing, in December of last year, pharmaceutical giants Roche and Genentech signed the industry’s first regenerative medicine deal with Lineage.  


“Lineage was able to show Roche and Genentech that we were able to not just halt the disease in its tracks for multiple years, but in some cases even reverse the disease - and that’s really special because human beings do not have the ability to regrow retinal tissue,” said Lineage CEO Brian Culley.  


The deal for the OpRegen program gave Lineage $670 million “biobucks,” with $50 million up front and double-digit royalties that increase with certain sales thresholds – “for just one asset,” Culley said.  


“The deal was transformative, not just because of the dollar amount, but because of the validation of our approach to cell therapy,” he said. “What we have done is use this first pharma deal as a springboard to show that this approach can be applied in other areas.”  


A Cure for Hearing Loss?  


Because of the deal with Roche and Genentech, Lineage was able to free up resources and pursue other cell therapies.  


Culley said pursuing hearing loss was born when his next-door neighbor “planted a seed” with him after she asked about cell therapy to treat the condition.  

 
According to the World Health Organization, hearing loss currently afflicts over 5% of the world’s population, or more than 430 million people, and by 2050 it is estimated that one in every 10 people, or more than 700 million people, will have disabling hearing loss.  


“We believe auditory neuronal transplants represent a unique opportunity to leverage our knowhow and capabilities in cellular differentiation into an indication with a large unmet need,” Culley said. “In addition to the speed with which the team created this new program from our internal technology, we have done so with a modest investment of capital so far, because we were able to take advantage of our established manufacturing infrastructure and broad knowhow in the expansion and differentiation of pluripotent stem cells.”  


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Stefan Heller Ph.D. Professor Stanford University School of Medicine

To support this new therapeutic effort, Lineage has filed for intellectual property covering the composition and methods for generating auditory neuronal progenitors which may be capable of functioning as sensory neurons and the connecting neuronal ganglion cells of the ear, and to methods of treatment that employ these cells for the potential treatment of auditory neuropathy.  

 
“Hearing loss is a major sensory deficit which affects an enormous number of individuals worldwide, yet current approaches leave much room for improvement,” said Stefan Heller, Ph.D., Edward C. and Amy H. Sewall professor at Stanford University School of Medicine, Department of Otolaryngology – Head & Neck Surgery and Institute for Stem Cell Biology and Regenerative Medicine (ISCBRM).

 
Heller will be advising Lineage and helping develop the cell therapy program.  


A Second Vision Program  


In April, Lineage filed for intellectual property protection covering the composition and methods for generating photoreceptor neural cells (PNCs). With the success of the OpRegen program, Lineage demonstrated the feasibility of retinal regeneration, which the company believes can now be applied to a large-scale method for producing both types of photoreceptors, known as rods and cones.


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Dr. Rami Skaliter CEO Cell Cure Neurosciences

“We believe this accomplishment will provide new opportunities for clinical, and ultimately commercial, production of photoreceptors in areas of large unmet need such as retinitis pigmentosa, Stargardt’s Macular Dystrophy and retinal detachments, either independently or through strategic alliances,” said Dr. Rami Skaliter, who leads the manufacturing function for Lineage and is CEO of Cell Cure Neurosciences.  


Other Indications  


Lineage’s new initiatives in hearing loss and photoreceptors are just the first two programs out of many that are possible.

 
“We have the ability to make different types of cells and deliver them to show that we can treat certain conditions,” Culley said.  “If there’s a cell type that’s dysfunctional in the body, it’s conceivable that we can invest in that area and generate replacement cells and maybe further build our business around that new indication.”  


And Lineage’s platform can go from concept to IND in about two years, depending on each indication.  

 
“We can go very quickly to produce new programs,” Culley said, adding that because of the newness of cell therapy it is “always possible FDA could want to look at these more closely. But broadly, the agency appears to be favorable to cell therapy programs.”  

 
The existing platform with one proven asset has allowed Lineage to establish its business as “a flywheel that can throw off new programs which can quickly and inexpensively get into clinical testing. If they show some efficacy in clinical testing, we can either own them for longer or partner them as we did with Roche and Genentech,” Culley said.  


In addition to the new hearing and PNC programs, Lineage also is continuing to advance its cell regeneration program for spinal cord injury. “Our spinal cord cells have been administered to 30 people so far with promising results and Lineage plans to continue clinical testing this year,” Culley said.


Lineage Cell Therapeutics
Founded: 1990
CEO: Brian Culley
Headquarters: Carlsbad
Business: Cell therapies
Employees: 55
Stock: LCTX (NYSE American)
Revenue: $3.89 million (2021)
Website: 
lineagecell.com
Notable: Lineage is the only company that has shown retinal restoration using stem cells.