#JPM21: Avidity CSO Art Levin runs full speed to the clinic with 'dream' antibody oligonucleotide conjugate therapy
Art Levin is living his “scientist’s dream come true.”
The Avidity Biosciences CSO set out years ago to build a new class of oligonucleotide-based therapies for severe muscle diseases, like Duchenne muscular dystrophy (DMD) and myotonic dystrophy (DM1) — rare, genetic disorders that causes progressive muscle weakness.
“As you might imagine, in the 15 or 16 years I’ve been working on this, I’ve seen boys go from being toddlers, to being wheelchair-bound, or even ventilator-bound,” he said, referring to DMD. “It would be really … a scientific dream of mine to actually make a difference for this patient population.”
At JP Morgan, Avidity is updating investors that their DM1 candidate is officially off to the races — headed for a Phase I/II trial in the second half of this year. The team is also diving into a partnership with Bristol Myers Squibb subsidiary MyoKardia to explore their approach in cardiac tissue.
“It’s really gratifying that this technology that we built and engineered in-house ourselves is coming to fruition,” Levin said.
DM1 is caused by hundreds of thousands of nucleotide repeats at the end of a gene called DMPK. When the DMPK gene is transcribed into RNA, the RNA also carries the nucleotide repeats, which form a hairpin loop structure, making the RNA toxic to the cell.
“Using the technology that we’re talking about, you can reverse that and replace these misplaced proteins or misspliced RNA with properly spliced RNA,” Levin told Endpoints back in 2019. “In the actual treatment of patients, we should actually be able to reverse some of the nature of this disease.”
The idea that you can use oligonucleotides to modify human RNA isn’t new. The problem has always been delivery, Levin said.
“Cells have evolved over eons to try and keep out RNA and keep out foreign DNA,” he said. “So you really have to trick the cell into wanting to take up our oligonucleotide therapeutic.”
The team is working on Antibody Oligonucleotide Conjugates (AOCs) — oligonucleotides combined with monoclonal antibodies into a single conjugate that can be more easily directed to precise tissues.
Avidity also has AOC programs for facioscapulohumeral muscular dystrophy (FSHD), Duchenne muscular dystrophy (DMD), and muscle atrophy (MA). The FSHD program is headed for IND enabling studies this year, and the biotech expects to file for a clinical trial in 2022. There are three programs within DMD, the leader of which targets Exon 44. The company plans on submitting for permission to enter the clinic in 2022.
In June, the biotech landed a nearly $300 million IPO to make it all happen. They tagged $65 million for their DM1 candidate, $35 million for DMD, and $25 million for MA, according to an S-1/A.
“We also intend to pursue the development of AOCs in cell types in addition to muscle. In preclinical models, we observed the ability of AOCs not only to deliver to the liver, skeletal and cardiac muscle, but also to other tissue and cell types, including immune cells,” the document states.
Eli Lilly holds 6.6% of Avidity’s stock, according to the S-1/A. Back in 2019, Avidity inked a licensing and research deal with Lilly, snagging $20 million upfront and an investment of $15 million. Lilly is offering up to $405 million more in milestones, plus royalties.
Levin kept mum about what the company is working on with MyoKardia, only revealing that they’re developing a “single therapeutic entity.” The companies are keeping the financial terms of the deal under wraps for now.
“We’re now really now seeing the fruits of all those labors come true,” Levin said. “We can build on people’s new appreciation for what is a fundamental building block of life: RNA. People are finally beginning to realize that this is a real way to create therapeutic entities.”
A correction has been made to clarify that Levin was referring to DMD, not DM1, in his quote in the third paragraph.