This Startup Just Raised $50 Million To Deliver Gene Therapies For Rare Diseases

In early 2019, Tom Woiwode, managing director at Versant Ventures, took a meeting with gene therapy pioneer James Wilson at the University of Pennsylvania. The duo had worked together earlier founding biotech startup Passage Bio, which is focused on providing gene therapy to patients with disorders of the central nervous system. During their meeting, Woiwode learnt that Wilson’s research interests had shifted to gene editing. Without much delay, the two decided to start another company together called iECURE, with the aim of using gene editing tools to treat paediatric genetic liver disorders. 

The Philadelphia based-startup has raised $50 million in Series A round led by Versant Ventures and OrbiMed Advisors, the company announced Thursday.

“What sets us apart from many other companies is that what we do is mutation agnostic,” says Joseph Truitt, the company’s CEO. In this instance “mutation agnostic” means it doesn't matter where a targeted mutation is located in a patient’s DNA. That’s because iECURE’s technology inserts copies of healthy pairs of genes into the genome, irrespective of where or what the mutation is on the defective gene. 

The company’s technology does this by delivering a pair of molecular “scissors” called nucleases, which make nicks in the patient’s liver genome, and a pair of healthy genes. The nucleases and healthy genes are delivered into the patient’s cells using an adenovirus (a type of virus that causes a common cold) that’s had its disease-causing parts removed. Experiments performed by Wilson’s laboratory where healthy genes have been inserted in newborn primates have shown promising results, says Truitt. “They were able to show that the expression of the healthy genes was durable, the effect was durable  and the safety was adequate to continue.”

iECURE’s focus is on liver disorders in newborns, because much of the work done in Wilson’s laboratory was using liver tissues. Moreover, the liver rapidly divides in newborns, which leads to greater expression of the newly inserted healthy genes compared to adult livers, Truitt adds.

Among liver disorders, iECure’s will work on conditions called Ornithine Transcarbamylasedeficiency and phenylketonuria. The former is a rare genetic condition that causes inadequate production of an enzyme which removes nitrogen from the body. The latter, also a rare inherited genetic disorder, leads to abnormal buildup of amino acid called phenylalanine in the body. If left untreated, both conditions can lead to severe side effects such as neurological disorders. 

In addition to those genetic disorders, iECURE has also partnered with a biotech company called Precision BioSciences to work on a treatment for Familial hypercholesterolemia, a genetic disorder caused by a defect on chromosome 19 that prevents sufferers from removing ‘bad’ cholesterol from their blood. Precision BioSciences will provide the DNA snipping nucleases to iECURE, in return. “These disorders have a nearly 20% mortality rate,” Truitt says.

 The new funding will be used for filing Investigational New Drug applications with the FDA for the clinical trials for all the three conditions, which will enable the company to move into clinical trials. The capital will also go into developing the company’s manufacturing infrastructure, Truitt says. 

This isn’t Versant’s first investment in the gene editing field. It’s already invested in Crispr Therapeutic and Graphite Bio. “iECURE is addressing the holy grail of gene editing in pursuing in vivo mutation-agnostic gene insertion,” says Tom Woiwode, who is collaborating with James Wilson for the second time. “The management team is also highly knowledgeable with deep expertise in running a company and in liver disorders and rare diseases,” he adds. 

There may not necessarily be smooth sailing ahead, however.  Many gene therapy startups haven’t lived up to their initial promise. One common issue is that a patient’s immune system reacts to the virus used to ferry healthy genes into cells. This is why, for example, gene startup Ally Therapeutics, which spun  out of Harvard geneticist’s George Church’s laboratory in 2018, shut down this year, according to a report in Endpoints News. 

However, Truitt says that their initial results are encouraging. Truitt believes that someday they would be able to give children with fatal liver conditions, a normal life. He also hopes to bring the therapy to adults some day.  “It is almost like science fiction. It is going to be awesome,” Truitt adds.