Aurora Therapeutics, Inc.

Menlo named the FDA’s “plausible mechanism pathway\" as one of the changes that support Aurora’s approach.\n Menlo Ventures has made a $16 million bet that the “baby KJ” custom CRISPR therapy success story is repeatable. The funding has enabled CRISPR co-inventor Jennifer Doudna, Ph.D., and baby KJ scientist Fyodor Urnov, Ph.D., to launch Aurora Therapeutics with a vision of treating the long tail of rare diseases.California-based VC shop Menlo has backed Aurora in the belief that the conditions needed to develop treatments for the rarest of rare diseases, down to conditions that affect a single patient, are now in place. As Menlo sees things, the genetic causes of many of the more than 7,000 rare diseases that affect 350 million people globally are known and correctable. The challenge has been acting on that knowledge.Menlo named the FDA’s “plausible mechanism pathway,” which offers a route to market for personalized therapies, as one of the changes that mean action is now possible. The VC fund also flagged technologies that could accelerate drug design and testing and support personalized manufacturing as key advances. Encouraged by the developments, Menlo incubated Aurora, provided seed funding and installed Edward Kaye as CEO. Kaye, the former CEO of Sarepta and Stoke Therapeutics, will lead a team that is pushing a phenylketonuria (PKU) program toward the clinic. PKU is caused by PAH gene mutations that lead to toxic elevations of phenylalanine. Researchers have found hundreds of gene variants in people with PKU, making the indication a proving ground for Aurora’s ambition to go beyond the relatively common mutations that are typically the focus of rare disease R&D. The biotech plans to address multiple PKU-causing mutations from the outset and add more over time.    Aurora’s approach reflects emerging regulatory support for grouping multiple mutations within a disease into unified development paths. The biotech is betting that grouping variants will make personalized therapies economically and operationally viable. Aurora said its PKU work is supported by preclinical proof-of-concept data and “encouraging” regulatory feedback. 

CRISPR-based gene editing has enormous therapeutic potential, but historically, the drug development pathway for such treatments has been lengthy, expensive and inefficient. But now, the technological and regulatory stars are aligning. To capitalise on the moment, Menlo Ventures has brought together an all-star team of experts to make genetic medicines at scale. The VC firm on Friday unveiled Aurora Therapeutics, which it incubated and seeded with $16 million to achieve a "vision of CRISPR-based cures for everyone with a rare disease."According to Menlo's Johnny Hu and Greg Yap, there are more than 350 million people around the world living with over 7000 rare diseases. But, they noted, most rare diseases are caused by hundreds or thousands of genetic variants, not one. "The most common mutation in a disease may justify the cost and complexity of a clinical trial, but less common mutations (which often collectively make up a majority of patients with that disease) rarely do," they wrote in a blog post. "Aurora is building a platform to efficiently treat every patient with rare disease, from the most common mutations to unique mutations that may affect only a single patient."Edward Kaye, the former CEO of Stoke Therapeutics and Sarepta Therapeutics, is helming Aurora as chief executive. The newco was founded by CRISPR co-inventor and Nobel Laureate Jennifer Doudna alongside Fyodor Urnov, a leader in genome editing. A professor at UC Berkeley, Urnov also worked on the first-ever bespoke CRISPR therapy, which was used to treat Baby KJ, an infant with CPS1 deficiency.The successful development and administration of that treatment, paired with a new regulatory framework and advances in AI and manufacturing technologies, convinced the team that creating personalised genetic treatments with a "a repeatable, systematic approach" was possible. 'Uniquely positioned'According to Aurora, a "key component" of its business model is the FDA's "plausible mechanism" pathway, introduced in November. The framework, also inspired by Baby KJ, was created to make it possible for certain cell and gene therapies to receive marketing approval based on data from studies involving just a few patients, such as an umbrella approach that groups individuals with multiple mutations within a disease setting into one unified clinical strategy (see – ViewPoints: How plausible is the FDA's plausible mechanism pathway?).A benefit of the pathway, Aurora said, is that it can "make personalised therapies economically and operationally viable," adding that it is "uniquely positioned to execute this model by pairing deep gene-editing expertise and hands-on clinical experience with purpose-built clinical, manufacturing, and quality systems designed for rapid, parallel development of mutation-specific therapies."The company also noted that advancements with high throughput assay have enabled data generation and collection at-scale, which in turn informs next-generation AI tools. On the manufacturing front, the pair said advanced modalities have allowed the flexible development of multi-component, personalised treatments. "We can now design, test, and iterate with unprecedented speed and precision," Hu and Yap wrote.Aurora's first programme is geared towards treating phenylketonuria (PKU). Based on preclinical data and regulatory feedback, the company is designing treatments that address multiple disease-causing mutations.

A biotechnology firm hatched by two prominent researchers publicly debuted on Friday, aiming to use a new regulatory framework to quickly develop many gene editing treatments for rare diseases.Called Aurora Therapeutics, the startup was co-founded by Nobel laureate Jennifer Doudna and genetic medicine expert Fyodor Urnov and seeded by Menlo Ventures. It intends to simultaneously work on multiple therapies for the same condition, each of which target different genetic mutations, and quickly advance them with the help of the Food and Drug Administrations recently unveiled plausible mechanism pathway.Aurora is led by Ed Kaye, a veteran biotech executive and former leader of Sarepta Therapeutics and Stoke Therapeutics. Menlo provided $16 million in seed funding to the startup, which will first test its approach on phenylketonuria, a genetic disease that disrupts the bodys ability to metabolize an important amino acid.Auroras emergence represents the latest attempt to solve a business problem thats slowing the progress of genetic medicine.Advances in sequencing technologies and powerful tools like CRISPR have made it possible to rapidly pinpoint and correct genetic errors known to drive thousands of rare diseases. But the small number of patients with those conditions and the exorbitant costs of developing gene-based treatments for them make for a daunting investment proposition, leaving many would-be therapies out of reach.Notable headway has been made in recent years, though. Academic researchers have, in multiple cases, designed custom therapies for specific individuals. The most prominent example came last year, when researchers at the Childrens Hospital of Philadelphia and elsewhere designed and developed within months a CRISPR-based treatment for a critically ill baby named KJ Muldoon. That treatment has helped stabilize KJs condition.KJs story caught the eye of Food and Drug Administration leaders. Last November, Commissioner Marty Makary and top deputy Vinay Prasad featured it while explaining the plausible mechanism pathway, a regulatory tool meant to speed along treatments for rare and serious conditions. Crucially for gene editing companies, they described how developers could use data from an initial approval say, for a person whose disease is tied to a specific genetic mutation to make minor modifications that could support additional clearances for people with other mutations.Aurora will test that blueprint. Leaning on technical advances enabling the faster design and production of gene editing components, the company is working on what it claimed in a statement would be the first platform to treat the types of mutations historically impossible to address at scale.According to Kaye, Aurora will start out by focusing on a diseases more frequent mutations. Doing so would enable it to get a commercial foothold that generates revenue while building a way to efficiently develop subsequent therapies for rarer mutations.Eventually, we could get to a point where we could very quickly respond to individual patient needs, as was the case with baby KJ, Kaye said. But we first really need to have a well-developed system that is sustainable before we go after very, very rare indications.Aurora believes it can build that system by starting with phenylketonuria, or PKU. The disease is caused by a wide range of mutations to a gene called PAH. While its currently managed with lifelong therapy, dietary restrictions and monitoring, those approaches arent curative and can still leave patients with cognitive deficiencies.PKU is also well-understood biologically and, as a result, long been a target of genetic medicine. But unlike previous efforts, Aurora is designing multiple therapies. The first will simultaneously address the three most common PKU-causing mutations. Aurora will then broaden its approach and add more.Kaye believes that, as a result, the disease fits in the plausible mechanism pathway perfectly.We understand the proximate cause of the disease, and we know how to address it, he said. '