Arbor Raises $73.9M Series C to Support Clinical Trials of ABO-101, a Novel Treatment for Primary Hyperoxaluria Type 1

Arbor Biotechnologies, a pioneering gene editing company established nine years ago by CRISPR luminary Feng Zhang, has successfully closed a $73.9 million Series C financing round, spearheaded by ARCH Venture Partners and TCGX. This infusion of capital represents a crucial lifeline in the currently turbulent gene editing sector, where numerous companies have faced retrenchment and even closure amidst waning investor confidence in the long-term viability of one-and-done genetic cures. Arbor’s secured funding will enable the company to advance its lead therapy into clinical trials, a significant milestone in its mission to combat inherited diseases.

The company’s primary focus is on developing a transformative treatment for primary hyperoxaluria type 1 (PH1), a rare but devastating genetic disorder that afflicts young children. PH1 is characterized by a genetic mutation that disrupts the liver’s metabolic pathways, resulting in the overproduction of oxalate. This excess oxalate forms sharp, excruciating kidney stones, leading to severe pain, renal failure, and, in some cases, the necessity for dual liver and kidney transplants. Arbor’s innovative therapeutic approach diverges from traditional gene correction strategies. Instead of attempting to repair the primary disease-causing mutation, Arbor’s therapy leverages CRISPR Cas12i2 to introduce a secondary, compensatory mutation. This mutation effectively reroutes the metabolic pathway, shunting oxalate production towards glycolate, a water-soluble molecule that is readily excreted by the kidneys. This ingenious strategy, which has received clearance from the U.S. Food and Drug Administration (FDA) through an investigational new drug (IND) application, is poised to enter clinical trials in the first half of the current year.
Arbor’s selection of Cas12i2, a CRISPR enzyme distinct from the widely utilized Cas9, is rooted in its unique mechanism of action. Unlike Cas9, which creates a clean double-stranded DNA break, Cas12i2 cleaves a larger segment of DNA, excising a chunk of 10 to 20 nucleotides. Arbor believes this distinctive cleavage pattern offers significant advantages in terms of both efficacy and safety. The upcoming clinical trial will mark a watershed moment, representing the first instance of an in vivo infusion of a non-Cas9 CRISPR therapy, delivered via lipid nanoparticles, within the United States.

While navigating the competitive landscape, which includes Alnylam Pharmaceuticals’ Oxlumo, an siRNA-based therapy for PH1, Arbor is simultaneously advancing a diversified portfolio of gene editing programs. The company is actively developing its proprietary “RT editing” technology, a refined iteration of prime editing, which combines a DNA-targeting enzyme with a reverse transcriptase to enable precise genetic modifications. This technology is being explored for the treatment of rare pediatric liver diseases. Furthermore, Arbor is in the preliminary stages of developing multiple gene editing therapies for amyotrophic lateral sclerosis (ALS), a debilitating neurodegenerative disorder. However, the company has made a strategic decision to discontinue its program targeting transthyretin amyloidosis (ATTR), citing a lack of differentiation from existing experimental CRISPR and siRNA therapies. This strategic realignment underscores Arbor’s unwavering commitment to developing truly groundbreaking and clinically impactful gene editing treatments.

Source:
https://endpts.com/crispr-startup-arbor-raises-73-9m-as-it-nears-first-trial/#:~:text=Arbor%20Biotechnologies%2C%20a%20startup%20founded,children%20with%20an%20inherited%20disease