TOKYO: Takeda Pharmaceutical and a subsidiary have decided to invest in two San Diego biotech companies — one seeking to make a better therapy for celiac disease and the other to develop more applications for RNA-based drugs. PvP Biologics will get $35 million from Osaka-based Takeda to develop the celiac therapy, which breaks down gluten in the stomach before it reaches the intestine. Avidity Biosciences has raised $16 million in a venture-financing round led by the subsidiary, Takeda Ventures. Avidity has invented a technology that delivers a class of RNA medications more widely throughout the body. PvP Biologics’ therapy is called KumaMax, an enzyme that degrades the parts of gluten that cause autoimmune reactions. It was developed at the University of Washington. In return for funding KumaMax, Takeda has an exclusive option to acquire PvP.
Celiac disease is a genetic disorder. Patients can’t tolerate gluten, which is found in wheat and related grains. More precisely, certain parts of gluten aren’t digested efficiently in the stomach and pass through into the small intestine. It’s these fragments that can trigger an immune reaction. The response damages the small intestine, so nutrients can’t be properly absorbed. Up to 3 million Americans are estimated to have celiac disease; that’s roughly 1 percent of the population. Even supposedly gluten-free foods may contain traces that can trigger the autoimmune response in some patients, said Ingrid Swanson Pultz, a University of Washington researcher who developed KumaMax. “This enzyme is highly active in the stomach,” Pultz said. “What we’re trying to prevent is the immune response to gluten before it even happens.” Meanwhile, Avidity is focused on expanding uses for the RNA drugs, which are called small interfering RNAs, or siRNAs. These RNA molecules interfere with gene expression by destroying messenger RNA made from genes.
Avidity’s technology delivers siRNAs by conjugating them to certain antibodies, producing what are called antibody-siRNA conjugates, or ASCs. These can be targeted to various cell types. Once the conjugate molecules reach the targeted cells, they release the siRNAa, which are then transported across the cell membrane into the interior, said Troy Wilson, president and chief executive for Avidity. Existing siRNA compounds are most easily taken up by the liver, which has the job of identifying ingested substances and detoxifying the poisonous ones. Most other cells don’t have this affinity for the substances. Other investors for Avidity include Alethea Capital, Alexandria Real Estate Equities, Brace Pharma, EcoR1 Capital, F-Prime Capital, Moore Venture Partners and Tavistock Life Sciences.
The funding will help the company further develop its technology and find more commercial opportunities, Wilson said. Avidity was founded in early 2014. Since then, it has shown in preclinical studies that antibody-siRNA conjugates efficiently reach tumor, muscle, heart, lung, liver and certain immune cells, he said. “What that allows one to do is build on the foundation that (RNA drug companies) Alnylam, Ionis (Pharmaceuticals in Carlsbad) and others have laid in the liver, and now begin to think about how we can extend these approaches,” he added. Avidity can either work with an already-developed RNA drug supplied by a partner or help it customize new medications. “We haven’t ruled out the idea that we’ll do our own products,” Wilson said. But the opportunities are so vast, it may make sense to help other companies adapt their drugs to this platform. “You talk about this and everybody goes, ‘Wow, this is an elegant, simple idea. Why hasn’t this been done before? It’s so obvious,’” Wilson said. “Well, it turns out it’s not so obvious how to make it work.”