The gene therapy world is in turmoil, but Arbor, armed with more than a billion dollars in partnerships and raises, is going forward.
Despite rough seas for gene editing, one company has generated some excitement and cash. Cambridge-based Arbor Biotechnologies has picked up a $73.5 million series C to advance a pipeline of CRISPR-based genetic therapies targeting the liver and central nervous system.
“Gene editing has undergone your typical Gartner hype cycle,” Arbor’s CEO Devyn Smith told BioSpace in an interview. “A few years ago, there was a lot of excitement to change the world. Now we’re in a show-me state, and investors are waiting to see.”
Arbor came out of stealth in March 2018 after closing a $15.6 series A financing round in June 2017. A huge Series B followed in 2021, with Arbor scoring $215 million. The company was co-founded by Feng Zhang, a professor at the Broad Institute and MIT and founder of the gene editing company Editas Medicine.
Editas is emblematic of some of the recent troubles dogging the gene therapy space. Once one of the most hyped gene editing biotechs, it let go of 60% of its staff was in a cost-cutting measure this past December after the company failed to find a developmental partner for its sickle cell disease therapy. Editas was beat to the markets by CRISPR Therapeutics and Vertex Pharmaceuticals with a sickle cell gene editing treatment called Casgevy. But even CRIPSR has not been immune, despite achieving the first-ever approval for a CRISPR-based gene editor. In early March the company announced layoffs of an undisclosed number of employees, despite a strong balance sheet totaling nearly $2 billion.
In the broader gene therapy space, the former billion-dollar darling of gene therapy, bluebird bio, was ignominiously sold to private investment firms for $30 million this February.
Collectively these events have given investors plenty of fodder to think twice about gene therapy and gene editing. Nevertheless, Smith remains optimistic, buoyed by the finalized raise.
“I’m very bullish that gene editing is a modality that can be applied to many diseases successfully. We’ve dosed 200 patients in the whole entire space worldwide. It’s early days but it’s going to be a game changer.”
The series C will give Arbor a cash runway into 2027. The round was led by previous investors ARCH Venture Partners and TCGX, with several new participants, notably Vertex.
Vertex previously partnered with CRISPR, taking Casgevy to approval. But the pharma has also supported Arbor for years. In 2018, Vertex paid $30 million to Arbor to target cystic fibrosis, then in 2021 promised up to $1.2 billion in milestone payments targeting diabetes and blood disorders. The pact was extended in 2023 to three further unannounced diseases.
Battling Sea Urchins in The Kidneys
Most of the money will go toward clinical development of Arbor’s lead molecule, ABO-101, for the rare liver-and-kidney condition primary hyperoxaluria type 1 (PH1). ABO-101 has already been granted orphan drug and rare pediatric disease designations, as well as an investigational new drug (IND) clearance in December 2024.
Arbor is advancing ABO-101 in a Phase I/II trial called RedePHine for the treatment of PH1. That trial has an estimated primary completion date of 2029.
PH1 arises from a gene mutation specific to the liver that results in a build-up of oxalate in multiple organs, but most crucially in the kidneys. That oxalate forms “sea urchin-like” kidney stones, as Smith described them. Patients are often diagnosed in childhood as having simpler kidney stones without accounting for their genetic source, and these cases often end in kidney failure and kidney transplants.
ABO-101 doesn’t correct the underlying mutation; according to Arbor, it instead knocks down the expression of another protein that produces an oxalate precursor molecule, lowering oxalate levels throughout the body.
Just like its gene editing peers, Arbor is tapping CRISPR, but the platform uses a different version of the genetic scissors. Smith pointed to a few technical differences he hopes will set the company apart. Instead of using Cas9—the canonical CRISPR gene editor—Arbor uses Cas12, a related but smaller protein, to do its editing. That smaller protein means smaller guide RNAs, which together hopefully mean cheaper production costs overall. Smith also said that the company has used AlphaFold to engineer changes in Cas12 to reduce off-target cuts.
Outside of the liver, Arbor is also working in the neurobiology space, taking aim at amyotrophic lateral sclerosis (ALS), hoping to develop viral vectors to deliver gene therapies to the brain.
“Our view is that there are two types of indications we like. There are those that affect younger kids, where parents just want the disease to just go away,” said Smith. “The other kind is in ALS, where you’re at the end of the spectrum, where there’s nothing that’s effectively treated patients. The need is huge, and the biology is getting better, so there’s opportunity to affect ALS with gene editing.”
