Eloxx Pharmaceuticals has acquired Zikani Therapeutics and will expand its research program in ribosomal RNA-targeted therapies, with the goal of treating diseases such as cystic fibrosis (CF) caused by a specific type of genetic mutation.
Eloxx is currently evaluating the investigational therapy ELX-02 in Phase 2 clinical trials in CF patients who carry nonsense mutations in the CFTR gene — the cause of almost 13% of CF cases.
Nonsense mutations create an early stop signal in the gene, resulting in the production of a shorter, non-functional CFTR protein. As this protein is involved in the balance of water and salts in cells of the lungs and other organs, a CFTR deficiency results in thick mucus production that affects lung function and promotes infections.
ELX-02 is designed to help the ribosome — the molecular machinery that builds proteins in cells — ignore the early stop signal (called read-through) to generate a fully functional CFTR protein.
“With the strength of our ELX-02 program for cystic fibrosis, this acquisition provides us with the opportunity to amplify the potential of our innovative science by developing a new class of therapies to treat diseases with limited to no treatment options under the stewardship of leaders with a proven ability to translate technology into treatments for patients,” Tomer Kariv, Eloxx’s chairman, said in a press release.
The acquisition includes Zikani’s research program, which has focused on preclinical studies across several disease states using its TURBO-ZM platform. According to the company, this technology enables the rapid production of ribosome modulating agents (RMAs) that target ribosomes in a disease-specific manner.
TURBO-ZM’s platform and library of small molecule compounds, along with ELX-02, is set to expand Eloxx’s research programs in CF and many other diseases and certain cancers.
“We are excited about the potential of ELX-02 and combining the companies opens the door to build a leadership position in genetic therapy by rapidly developing treatments that can restore functional proteins in patients with nonsense mutations in their RNA,” said Sumit Aggarwal, Zikani’s president and CEO, who will lead the new company.
“The combined capabilities of Eloxx and Zikani in chemistry, biology, regulatory and drug development … will further accelerate our ability to impact the lives of those who have rare diseases with the type of urgency and novel thinking that they deserve,” added Aggarwal, now president and CEO at Eloxx.
After positive results in preclinical studies, Phase 1 testing in healthy volunteers showed the therapy was well-tolerated. It also demonstrated a high level of absorption into the body (bioavailability) as well as consistent pharmacokinetics — its movement into, through, and out of the body — in both single and multiple-dose studies.
Now, the ongoing Phase 2 clinical trials — EL-012 (NCT04135495) and EL-004 (NCT04126473) — are testing the safety, tolerability, and pharmacological profile of ELX-02 in CF patients with at least one G542X mutation, the most common CF-causing nonsense mutation.
EL-012 is an Eloxx-sponsored proof-of-concept study seeking to enroll up to eight adults at sites across the U.S.; more information and contacts can be found here. EL-004 is an international study currently enrolling up to 16 patients in Israel, Germany, and Australia. More information on that Eloxx-sponsored study, which is enrolling participants ages 16 and older, can be found here.
“The Phase 2 trials are designed to validate the safety of ELX-02 and assess its biological activity,” said Vijay Modur, MD, PhD, who served as Zikani’s chief scientific and medical officer, and has now been appointed as Eloxx’s head of research and development. “We look forward to completing enrollment in the first four treatment arms [groups] by mid-year and reporting data from these treatment arms in the second half of this year.”
Eloxx also develops RMA oral therapies for nonsense mutations causing the blistering skin conditions known as junctional epidermolysis bullosa and recessive dystrophic epidermolysis bullosa. In 2022, the company will submit an application to the U.S. Food and Drug Administration to begin clinical trials, researchers said.
In addition, the technology is being applied to read-through nonsense mutations in genes that suppress tumors, with a specific focus on an inherited pre-cancerous colorectal disease called familial adenomatous polyposis, Eloxx said.
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