The next frontier of gene medicine may be a one-time therapy, in vivo editing work in the patient’s body. But one challenge is that some genetic diseases have hundreds of mutations. Joseph Truitt, CEO of iCURE, said that in order to solve all of these problems, you need to develop a therapy for each mutation-this is an unscalable effort.
The number of mutations has nothing to do with iCURE. Some in vivo gene editing therapies are being developed to repair specific mutations in genes, while iCURE aims to replace the entire problem gene, making the method independent of any disease-causing mutation.
“This is about gene insertion and replacement, replacing defective genes with healthy genes,” Truitt said.
The Philadelphia-based company is based on research by University of Pennsylvania scientist James Wilson (a pioneer in gene therapy) and has proven that its methods can work in animals.ICURE now has US$50 million in Series A financing Because it is committed to introducing in vivo gene editing therapy into human testing. The Series A financing announced on Thursday was led by Versant Ventures and OrbiMed Advisors.
IECURE will use Wilson’s gene editing and in vivo methods, and the startup may choose as many as 13 programs from his laboratory. Truitt said that iCURE has so far identified three diseases: familial hypercholesterolemia, phenylketonuria and ornithine transcarbamylase deficiency. They are rare liver diseases, which is the focus of the company.
Truitt said Wilson tried various gene editing tools, including CRISPR, but had little success until he used Precision Bioscience’s technology. The clinical stage biotechnology company in Durham, North Carolina has developed a technology called ARCUS that delivers a cutting enzyme called an endonuclease to a target segment of DNA. The endonuclease is delivered by adeno-associated virus (AAV), which is an engineered virus widely used in gene medicine.
Chief Scientific Officer Derek Jantz said at the company’s virtual R&D event on Thursday that the Precision Bio enzyme derived from algae is the smallest compared to other enzymes used in gene editing research. The smaller size means that more enzymes can be loaded into AAV, enabling it to perform complex editing, such as gene insertion.
Penn started working with Precision Bio in 2018, partnership Focus on using ARCUS to develop in vivo gene editing products.That year, the partners’ preclinical studies were Published in “Nature Biotechnology” Shows that ARCUS can knock out the cholesterol regulatory gene PCSK9 in monkeys.In February of this year, Wilson published an article Molecular Therapy Papers Described three years of data, showing that PCSK9 protein has been reduced by 85%, and LDL cholesterol levels have been reduced by 56%. It is also worth noting that the one-time treatment continues to prove to be safe, with no reports of adverse reactions.
Penn/Precision Bio research shows that ARCUS can knock out genes that cause disease. This cooperation paved the way for iCURE’s new cooperation. The startup will also use ARCUS, but will knock in healthy genes or gene insertions.The startup has Licensed ARCUS from Precision Bio is used for the rights of four liver indications. In exchange, iCURE will advance Precision Bio’s PCSK9 therapy into the first phase of testing for familial hypercholesterolemia.
Precision Bio has acquired an unspecified equity interest in iCURE. If any products developed by iCURE and ARCUS enter the market, it will also receive milestone payments and sales royalties. But the North Carolina company is expected to get more revenue. Cindy Atwell, the top business development director of Precision Bio, said that the successful iCURE clinical trial results will also provide validation of the technology for therapies using ARCUS. The company is seeking verification of gene knockout through internal programs and cooperation with Eli Lilly.
Precision Bio and iCURE are expected to submit applications to start clinical testing of candidates for familial hypercholesterolemia in early 2022. In parallel with this plan, iCURE will also study plans selected from the University of Pennsylvania. Truitt said that the first two diseases that the startup aims to solve with ARCUS are phenylketonuria and ornithine transcarbamylase deficiency. The other two will be selected later. Precision Bio reserves the rights of ARCUS for all other indications.
According to Truitt, IECURE is the result of an informal meeting between Versant’s managing director Tom Woiwode and Wilson two years ago. Versant is one of Passage Bio’s initial financial backers, Passage Bio is a now-listed gene therapy developer founded by Wilson. Versant’s genetic medicine investments also include gene editing companies such as CRISPR Therapeutics and Graphite Bio. Wilson mentioned that he has been quietly conducting gene editing research for many years, paying particular attention to neonatal diseases where gene therapy does not work.
One of Wilson’s findings is that this gene insertion is most suitable as a neonatal treatment. Truitt said newborns have rapidly dividing liver cells, which is necessary for rapid gene editing therapy. Adult livers do not have rapidly dividing cells and therefore do not receive treatment. Wilson researched familial hypercholesterolemia and ornithine transcarbamylase deficiency. The animal data excited Woiwode and prompted Versant to contact OrbiMed, another Passage Bio investor. They established iCURE and hired Truitt, a veteran in the biotechnology industry, as CEO in February. Wilson’s laboratory came up with the name iCURE, which is a reference to the Latin word “iecur” for liver. “We added an “e” to indicate cure,” Truitt said.
Penn and Wilson hold shares in iCURE; Truitt said that although Wilson is a consultant, he is not an employee of the company. According to the agreement between iCURE and the university, the Wilson laboratory will conduct preclinical research and manufacturing for the procedures selected by iCURE. When the research is ready for research new drug applications, iCURE will take over and handle clinical development, and if approved, it will be commercialized.
Truitt said that this $50 million should support the company by early 2023. A large part of the cash will be used in manufacturing. But Truitt pointed out that working with Wilson Labs’ already extensively researched project puts iCURE far ahead of most start-ups in raising the first round of funding.
“Jim has three years of ARCUS data,” Truitt said. “If we start again, we won’t be able to use it. This is a brand new company, but for a gene editing company, these programs are quite mature.”
Photo: Mark Markla of The Washington Post, from Getty Images
