While many drugs work by blocking disease-driving proteins, RNA medicines can stop production of these proteins in the first place. ADARx Pharmaceuticals’ research could help shape the next generation of RNA-targeting drugs, and with a lead program in pivotal testing for a rare inherited disease, the biotech has joined the public markets.
Thursday evening, ADARx priced its IPO of more than 26 million shares at $17 each, raising $446.3 million. That tops the 21.9 million shares the San Diego-based company initially planned to offer in the range of $15 to $17 per share. Concurrent with the IPO, ADARx partner AbbVie purchased additional shares in a private placement that raised $89 million, bringing the biotech’s total haul to $535.3 million. Shares of ADARx began trading on the Nasdaq Friday under the stock symbol “ADRX.”
ADARx is working in a class of genetic medicines that employ small-interfering RNA (siRNA) to target and degrade the messenger RNA for a protein that causes disease. This knockdown of a gene’s expression of a protein is also known as RNA interference or gene silencing. Some disease-driving proteins are already drugged by large and small molecule medicines. But these modalities still leave many other proteins unaddressed, an unmet that could be filled by siRNA therapies.
“Many proteins are undruggable by small molecules or [monoclonal antibodies] due to the lack of accessible binding sites, intracellular localization or structural complexity,” ADARx said in the IPO filing. “siRNA directly addresses these challenges through the sequence-based rational design and the selective silencing of target mRNA, inhibiting the target at its source, making it a powerful technology with the potential to overcome the limitations of traditional therapeutic modalities.”
FDA-approved drugs from companies such as Alnylam Pharmaceuticals and Arrowhead Pharmaceuticals validated siRNA medicines, but they still have limitations. The available siRNA drugs only go after liver targets. The frequent dosing of these medicines can also be a burden to patients.
ADARx’s drugs come from two technology platforms, one that designs siRNAs for better potency, precision, and durability, and the other that enables delivery to organs and tissues beyond the liver. The most advanced program is onvuzosiran, an experimental treatment for hereditary angioedema (HAE), a rare inherited disorder that leads to swelling attacks throughout the body. These attacks come without warning and can become fatal when they close off the airway. Onvuzosiran is designed to interfere with mRNA for pre-kallikrein, a protein in the pathway that leads to HAE swelling attacks.
The available HAE drugs span oral small molecules and biologics that are injected or infused. The only RNA-targeted therapy is Ionis Pharmaceuticals’ Dawnzera, which the FDA approved last year for preventing HAE attacks. This antisense oligonucleotide, designed to target pre-kallikrein mRNA, is dosed by subcutaneous injection every four or eight weeks.
In addition to better efficacy, ADARx aims to ease the dosing burden. In Phase 1/2 testing, onvuzosiran led to “robust reduction” in blood levels of pre-kallikrein and kallikrein, along with durability that supports dosing every three or six months, according to the filing. A 90-patient placebo-controlled Phase 3 study is ongoing with preliminary data expected by the end of 2027. If those data are positive, ADARx expects to file an FDA submission in 2028.
ADARx is also enrolling patients in mid-stage tests of agazisiran, a siRNA designed to block factor B, a protein in the complement system. Three Phase 2 studies are underway spanning rare kidney diseases, the rare blood disorder paroxysmal nocturnal hemoglobinuria, and the eye disease geography atrophy secondary to age-related macular degeneration. ADARx expects preliminary data will start coming out in the second half of next year.
The third clinical-stage program is ADX-626, a siRNA designed to target a protein called Factor XI for secondary stroke prevention. A Phase 1 test in healthy volunteers is ongoing. ADARx plans to start a Phase 2a/b clinical trial in 2027 with preliminary data expected by the end of that year. ADARx’s preclinical programs aim to demonstrate siRNA delivery beyond the liver. ADX-077 is designed to target adipose tissue for potential applications in obesity. ADX-199 target neurons for the potential treatment of Alzheimer’s disease.
In its history as a private company, ADARx raised $352.5 million, according to the filing. Its last financing was a $200 million Series C round in 2023 led by Bain Capital Life Sciences and TCGX. The filing shows OrbiMed is ADARx’s largest shareholder with a 22.7% post-IPO stake. The company also has money from AbbVie, which last year paid ADARx $335 million up front to begin a partnership on siRNA drugs in neuroscience, immunology, and oncology. When the private placement closes, AbbVie will own about 4.9% of ADARx’s outstanding shares, the biotech said.
As of the end of June, ADARx reported its cash position was $427.3 million. That capital and the IPO proceeds will support the pipeline. About $65 million is planned for completion of onvuzosiran’s pivotal trial in HAE as well as pre-commercialization activities. Another $180 million is budgeted for completing the Phase 2 test of agazisiran and advancing that program to Phase 3.
ADARx has budgeted $80 million for ADC-626’s Phase 1 test in healthy volunteers and the start of Phase 2 testing in secondary stroke prevention. The company also plans an exploratory trial of this siRNA for stroke prevention in atrial fibrillation. Another $25 million will go toward ADX-077’s Phase 1 trial. ADARx estimates its capital will last into 2030.
Illustration: Getty Images
