LONDON – Vivet Therapeutics has raised $41 million in a series A round to fund development of liver-targeted gene therapies for treating inherited metabolic disorders.

The company has three preclinical programs, with the lead product for treating Wilson disease expected to enter clinical trials next year.

Each will use the next-generation Anc80 adeno-associated synthetic viral vector developed by Massachusetts Ear and Eye (MEE) Infirmary, which in addition to the ability to deliver therapeutic genes to hepatocytes is designed to avoid the pre-existing immunity that about 20 percent of patients have to naturally occurring adenoviruses.

That offers two significant advantages, “increasing the level of translation in the liver,” while at the same time ensuring “more patients can be treated,” Jean-Philippe Combal, co-founder and CEO of Vivet, told BioWorld Today.

Complementing the MEE vectors, Vivet has rights to gene constructs developed at the Center for Applied Medical Research at the University of Navarra, Spain, where Vivet co-founder and Chief Scientific Officer Gloria Gonzalez Aseguinolaza directs a program in gene therapy of liver diseases.

Vivet’s lead program, VTX-801, aims to deliver a correct copy of ATP7B, the gene that encodes for the copper-transporting enzyme ATPase2. In Wilson disease, defects in ATP7B interfere with copper metabolism, leading free, toxic metal to accumulate in the liver and the brain, rather than being excreted in bile.

Symptoms include the occurrence of a brown ring in the cornea, slurred speech, swallowing difficulties and psychiatric problems, leading to hepatitis or liver failure by late childhood or early adolescence.

There are several treatments for the disorder, which affects approximately 10,000 patients in the U.S. and 15,000 in Europe. Those include the copper chelators penicillamine and trientine, which promote copper excretion in the urine, and zinc salts that reduce copper absorption by inducing the production of metallothionein, a protein that binds metal.

In addition, Wilson Therapeutics AB, of Stockholm, has WTX-101, which acts as a copper buffer, in phase II development.

But while alleviating symptoms, those drugs do not address the underlying pathology. Late diagnosis, poor adherence and the fact that drugs can become ineffective means the disease frequently causes neurological damage and liver disease.

“There is a significant impact, including the need for liver transplants. There is need for a different approach to [copper] homeostasis,” said Combal.

In February 2016, Aseguinolaza’s research group published a paper reporting sustained expression of ATP7B in a mouse model of Wilson disease, following a single parenteral administration of a truncated form of the gene, using an AAV8 vector. The researchers demonstrated that normal copper metabolism was restored, reducing liver damage and improving liver function.

Vivet has now performed animal studies using the Anc80 vector. “This showed higher potency,” Combal said.

Combal, who previously was chief operating officer of Gensight Biologics SA, of Paris, a specialist in gene therapy for retinal diseases, is to present the Anc80 data at the American Society for Gene and Cell Therapy meeting next week.

The company now plans to have discussions with regulators before the end of October, with the aim of starting clinical studies in the U.S and Europe in the second half of 2018.

Paris-based Vivet has two further programs, in progressive familial intrahepatic cholestasis type 2 and 3, and citrullinemia, a urea cycle disorder.

“The series A provides enough funding to go into initial trials and up to proof of concept in Wilson disease and to get to [the] point of filing INDs for the other two,” said Combal. The company will then look to find partners before raising more funds, he said.

Although Vivet’s technology was sourced in the U.S. and Spain, it was decided to base the company in Paris to take advantage of the country’s R&D tax credits and to be close to manufacturing partners, Combal said.

The round was led by Novartis Venture Fund (NVF) and the Spanish fund Columbus Venture Partners, of Madrid, with Roche Venture Fund, Kurma Partners and Ysios Capital. “We have pulled together significant partners [who have] an interest in metabolic disease,” said Combal.

Florent Gros, managing director of NVF, said the firm has “searched extensively” for next-generation AAV technologies and clinical applications. “[Vivet] has outstanding management, assets and capabilities,” he said.

While the Anc80 vector has been licensed by other companies, Vivet has exclusive rights in liver disorders. In combination with gene constructs developed at the University of Navarro, that will enable the company to develop a broad gene therapy technology platform, Combal said.

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