RNA startup ADARx raises $200M from Bain, TCG to bring RNAi ‘to the next level’

The RNA startup ADARx Pharmaceuticals has raised a $200 million Series C, aiming to advance multiple clinical programs that directly challenge the leaders of the RNA interference space.

Zhen Li

The San Diego biotech announced the round, led by Bain Capital Life Sciences and The Column Group Crossover (or TCGX for short), on Wednesday and plans to grow from 50 to 80 employees over the next year. ADARx emerged from stealth in the fall of 2021 alongside a $75 million Series B round.

All three of ADARx’s most advanced therapies trail behind more clinically advanced RNAi drugs. But the startup’s leaders say they’re confident they can ultimately be best-in-class, if not first. With the new cash, ADARx plans to advance its lead program to Phase II next year while also bringing a third RNAi drug into the clinic in 2024.

“This funding will really allow us to take multiple candidates into the clinic in parallel,” CEO Zhen Li told Endpoints News in an interview.

Li, an industry veteran of over 20 years at drugmakers like Merck and Arrowhead Pharmaceuticals, co-founded ADARx in February 2020. While the biotech started out focused on RNA editing, which aims to correct single mutations on messenger RNA molecules, Li said the company shifted focus to RNAi after gaining insights that “RNAi veterans did not know.”

Ricky Sun

“That gave us the confidence that we can take RNAi to the next level,” she said.

Ricky Sun, a partner at Bain Capital Life Sciences, said when he first heard of ADARx, he thought it was another gene editing startup. ADAR stands for adenosine deaminase acting on RNA, which are types of enzymes used in RNA editing. But early results with its RNAi approach excited Sun’s team, which has been studying the RNAi field for years.

“The large round speaks to the level of enthusiasm, but also how broad the platform could be in terms of really exciting clinical drug candidates,” said Sun, who joined ADARx’s board as part of this recent raise.

Going up against Alnylam, Ionis, Arrowhead 

ADARx’s pipeline competes with some of the more established leaders in the RNA field, like Alnylam, Ionis, and Li’s former employer Arrowhead Pharmaceuticals. It also shows how, despite all the excitement around RNA-based therapies, delivery limits the field: All three of ADARx’s programs target the liver, where it’s been easiest to deliver genetic medicines.

ADARx’s lead program, ADX-324, targets a rare genetic swelling disorder called hereditary angioedema, or HAE. There are multiple approved HAE drugs and RNAi therapies further along in the clinic, but Li said ADARx’s program could compete on potency, durability and safety.

“The attack reduction rate is high, but the key is a patient being attack-free,” Li said. “That rate is not high at all.” She added ADARx aims to have over 90% of patients attack-free.

ADX-324 could be dosed every six months or longer, Li said, with a Phase II trial planned to start in the first half of 2024. Takeda’s approved drug, Takhzyro, is given every other week, while Ionis has a once-a-month HAE drug candidate with a Phase III readout expected in the first half of next year. Ionis’ drug showed a 97% mean reduction in attack rates after two doses in a mid-stage study.

ADARx’s other clinical-stage candidate is called ADX-038, targeting complement Factor B. ADARx will initially focus on the rare genetic disease paroxysmal nocturnal hemoglobinuria “to compare and benchmark our candidate,” Li said. PNH is also competitive, as Alexion’s Soliris and Ultomiris have long been mainstay therapies and Novartis’ iptacopan succeeded in a Phase III study earlier this year.

“We have multiple indications lined up now, and the funding will give us the opportunity to pursue multiple indications in complement-mediated diseases,” Li said.

A third program targets angiotensinogen, a liver-mediated target to treat hypertension. Here too, ADARx will follow in competitor footsteps: Alnylam recently struck a deal with Roche to push ahead its Phase II angiotensinogen targeter, zilebesiran. ADARx plans to enter the clinic in the first half of 2024.

Li said ADARx has earlier research looking beyond the liver, particularly in targeting the central nervous system. But the privately held company is holding its approach close to the chest for the time being, declining to share details about that work.

“I can’t tell you how we target CNS yet, but we have a different way,” Li said. “And we have the data to show that delivery or tissue penetration is much deeper than others.”

Looking ahead, Bain’s Sun said the $200 million infusion could give the company the option, but not the need, to consider an IPO.

“Whether this is next year or the year after that, hopefully, that’s a choice we’ll have the luxury to have versus saying we’re going tomorrow,” Sun said.

gene editing
pharmaceuticals
biotech
life sciences