By the time the FDA approved Luxturna the pioneering gene therapy for an inherited retinal disease Henry Klassen had been researching and treating the group of diseases known as retinitis pigmentosa for more than 20 years.

Spark Therapeutics success there had not just inspired a $4.3 billion takeover by Roche, it had also emboldened other biotechs pursuing a therapy that would deliver one of the genes tied to different variations of the disorder. Nightstar Therapeutics subsequently scored its own buyout with Biogen, and MeiraGTx recently posted early but exciting data on its J&J-partnered program.

But Klassen went a different way.

Catching on the stem cell craze right at the turn of the millennium, he took inspiration from scientists who transplanted neural progenitor cells into the retina and developed a method to grow retinal progenitor cells instead as a therapy. Starting out as the director of stem cell research at the Childrens Hospital of Orange County, he continued the work at the University of California, Irvine, eventually spinning out a biotech dubbed jCyte in 2012.

Over the weekend jCyte reported positive Phase IIb results from what they call one of the largest studies ever conducted in RP, suggesting that patients on the treatment saw improved functional vision compared to the placebo group.

The credit to the gene therapies is that theyre actively trying to fix the gene underlying the problem. Thats very commendable, and were not doing that, Klassen told Endpoints News. But our treatment as it stands should have impact across a variety of different genotypes.

The study enrolled a total of 84 patients, of whom 74 were included for the final analysis. For each patient on the primary endpoint of best corrected visual acuity (measured with glasses on), the mean change from baseline to month 12 for the sham, low dose and high dose arms were +2.81, +2.96, and +7.43 letters, respectively.

In a post hoc analysis for a target subgroup, the difference was even more prominent: +1.85, -0.15, and +16.27 letters, respectively.

There was one serious adverse event in the low dose arm, but jCyte said the grade 3 ocular hypertension resolved with treatment and other side effects were generally minor.

CEO Paul Bresge noted that the target subgroup analysis was intended to hammer out the criteria they might use to recruit patients into Phase III which would likely have a similar design and use the same primary endpoint of BCVA, the gold standard in the context of FDA. The late-stage trial is slated for 2021.

We did enroll a very wide patient population into our Phase IIb, including patients that had vision anywhere from 20/80 to 20/800, just to learn which patients would potentially be the best responders, he said.

The target subgroup is characterized by having reliable fixation on the study eye, and a study eye that does not have significantly worse BCVA (15 letters) than the fellow eye.

He added that investigators also observed encouraging results with the secondary endpoints such as low light mobility, contrast sensitivity kinetic visual fields and a vision function questionnaire, although the data werent disclosed.

Typically people think about the disease as a narrowing of this peripheral vision in a very nice granular way, but thats actually not what happens, he said about the visual fields finding. What happens in the disease is that patients lose like islands of vision. So what were doing in our tests is actually measuring [] islands that the patients have at baseline, and then what were seeing after treatment is that the islands are expanding. Its similar to the way that one would track, lets say a tumor, in oncology of course were looking for the opposite effect. Were looking for the islands of vision to expand.

The therapy works primarily by preserving photoreceptors, Klassen posits, not by generating new ones. But what he thinks is happening is that photoreceptors are regenerating the outer segment if photoreceptors are radios, these would be the antenna thereby regaining some function.

That could position it as a treatment for a different stage of the disease than Sparks or Nightstars. Klassen, whos also researching retinal reconstruction using stem cells, is happy to not view it through the competitive lens.

If you look into the future, one could imagine that gene therapies will be most effective very early in the course of a disease before photoreceptors are lost, he said. Then as photoreceptors begin to be lost anyway, if that happens, then a therapy like ours would become extremely valuable. And if ours starts to lose power late in the course of a disease, maybe cell transplantation under the retina could have a role.

Read more:

Can progenitor cells go further than gene therapy in retinal disorders? A biotech's answer shines in PhIIb - Endpoints News