Aurora Therapeutics Bets on CRISPR Umbrella Approach

A new startup, Aurora Therapeutics, is betting that regulators will ease up on gene-editing treatments. The company proposes an "umbrella approach" to testing and commercializing these therapies. This strategy aims to win approval for gene-editing drugs that can be slightly adjusted or personalized without requiring costly new trials for every new version.

The need for such a change was recently endorsed by the head of the US Food and Drug Administration. The agency plans to open a new regulatory pathway for "bespoke, personalized therapies" that cannot be easily tested in conventional ways. Aurora's first target is phenylketonuria (PKU), a rare inherited disease. The company has $16 million in funding and counts CRISPR co-inventor Jennifer Doudna as an advisor.

The gene-editing technology CRISPR has been described as the biggest biotech breakthrough of the century. However, its real-world impact has been slower than many hoped. So far, there has been only one gene-editing drug approved for commercial use. That drug has been used on approximately 40 patients, all with sickle-cell disease.

Some observers note a "pall of discouragement" over the entire field. The challenge is finding ways to help more people with genetic conditions. Aurora Therapeutics believes its new approach could be the answer. The company is backed by Menlo Ventures and aims to change how these treatments are developed.

Aurora's first target is phenylketonuria, also known as PKU. This is a case in point for why a new approach is needed. People with PKU lack a working version of an enzyme needed to process the amino acid phenylalanine. If this amino acid builds up, it causes brain damage. Patients must follow a strict diet for life.

Gene editing could theoretically fix PKU. However, the problem is that many different mutations can affect the critical gene. Researchers know about 1,600 different DNA mutations that cause PKU. It is not commercially viable to develop 1,600 different gene-editing drugs.

Aurora's goal is to eventually win approval for a single gene editor. With minor adjustments, this single drug could be used to correct several of the most common mutations. One specific mutation is responsible for about 10% of the estimated 20,000 PKU cases in the US.

The company's approach relies on making small changes to a base treatment. A gene editor is a special protein that can locate a specific place in the genome and change it. To prepare one, Aurora will put genetic code for the editor into a nanoparticle along with a targeting molecule.

In total, the treatment involves about 5,000 gene letters. However, only 20 of those letters need to change to redirect the treatment to repair a different mutation. According to a partner at Menlo Ventures, "Over 99% of the drug stays the same."

The startup formed after a meeting between an investor and Fyodor Urnov, a gene-editing scientist at the University of California, Berkeley. Urnov is a co-founder of Aurora. He has previously written about the "chasm" between what editing technology can do and the realities preventing researchers from curing people.

The push for new regulations has support from the highest levels. In November, the head of the US Food and Drug Administration endorsed the need to change regulations. He stated the agency would open a "new" regulatory pathway for "bespoke, personalized therapies."

Aurora's CEO, Edward Kaye, believes the FDA has been understanding of the need for change. He stated, "We can’t have a separate [clinical trial] for each mutation. The way the FDA approves gene editing has to change."

Other scientists are also exploring similar concepts. Kiran Musunuru, a researcher at the University of Pennsylvania, co-led a team that corrected the DNA of a baby with a unique mutation. While he does not think Aurora's plans for PKU count as fully personalized editors, he acknowledges that assembling a group of frequent mutations makes a therapy commercially viable. This approach would still leave out patients with extra-rare gene errors, but it represents a significant improvement.