Signs that interest in antisense oligonucleotide therapies is on the up?
Earlier this month, listed Californian AAV gene therapy company, Audentes Therapeutics, announced it would advance AAV-antisense treatments for the treatment of Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1).
Audentes paid $7 million to the Research Institute at Nationwide Children's Hospital for an exclusive licence to its AAV-antisense product candidate, AT702. AT702 reportedly demonstrated >75% RNA transcript correction and 40-100% protein expression in preclinical animal studies. Audentes expects to commence a Phase 1/2 study in Q4 2019 in DMD patients with duplications in exon 2 and mutations in exons 1 – 5 of the dystrophin gene (~2% of DMD patients) .
Following last week, Avidity Biosciences, a privately-held biotech also based in California, announced that it had signed a global licensing and research collaboration with Lilly to develop antibody-oligonucleotide conjugates (AOCs). The partnership will focus on generating therapeutic targets in undisclosed disease areas that to date have challenged oligonucleotide-based approaches.
Avidity's AOCs leverage the specificity of antibodies to deliver the nucleic acids to tissue-specific cell markers outside the liver, and then rely on endocytosis to internalize the active agent.
Avidity will receive $20 million upfront, a $15 million investment from Lilly and is eligible to receive up to $405 million in milestones per target, plus mid-single to low-double digit tiered royalties.
Avidity is also pursuing DMD therapies. Late last year, it received an equity investment from CureDuchenne to advance pre-clinical development of potential AOC therapies to treat patients with DMD. The AOC approach is said to address a key challenge for use of oligonucleotide therapeutics in DMD; delivery to muscle, diaphragm and heart. AOCs are reported to have demonstrated a 100-fold increase in potency in an MDX mouse model and Avidity is hoping that its approach will allow for reduced dose levels and reduced dosing frequency.
The increased interest in antisense oligonucleotide therapies is a positive but also highlights the potential competition from other delivery approaches for ASOs. When Phylogica releases in vivo results for its second generation CPP-ASOs in coming months, I hope that it can clearly explain the competitive advantages of its CPP-ASO conjugates over alternative AAV-ASO and AOC approaches.
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