CFF Awards $15.9M to Eloxx for Clinical Development of ELX-02

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The Cystic Fibrosis Foundation (CFF) has awarded up to $15.9 million to Eloxx Pharmaceuticals to support the company’s clinical program for ELX-02, an investigational therapy for cystic fibrosis (CF) patients with nonsense mutations.

A total of $7 million will be provided upfront, with additional funding granted based on the achievement of clinical milestones in the testing of ELX-02.

With the funding, Eloxx plans to support an expansion of its ongoing Phase 2 studies in North America — the EL-012 trial (NCT04135495) — and other locations. Its EL-004 trial (NCT04126473) is underway in Australia, Germany, and Israel.

The expanded trials are now evaluating whether the combination of ELX-02 with the approved CF treatment Kalydeco (ivacaftor) has greater therapeutic effects than ELX-02 alone in patients who carry the G542X mutation — the most common CF-causing nonsense mutation — or another nonsense mutation with similar effects.

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While dosing is already underway, the trials are enrolling. More information can be found here for the EL-012 study in the U.S. and Canada, and here for the EL-004 trial.

Top-line data of the expansion part are expected by the end of the first half of this year, according to Eloxx.

“Despite therapeutic advances for many people with CF, therapies that target nonsense mutations are still urgently needed,” Michael Boyle, MD, president and CEO of CFF, said in a press release.

“We are aggressively funding the expansion of Eloxx’s clinical program to ensure we continue to improve our scientific understanding in this critical area of research,” Boyle added.

CF is caused by different types of mutations in the CFTR gene that lead to a faulty or absent CFTR protein. In about 90% of cases, the common F508del mutation is present, for which most CFTR modulators are targeted.

Nonsense mutations are thought to account for approximately 10% of cases. These mutations cause cells to prematurely stop production of CFTR partway through. The resulting shortened protein is not functional, and is degraded by the cell. Nonsense mutations are included in a group of mutations called Class 1.

“Class 1 CF patients with mutations do not have any available treatment options, and so our ability to work urgently is critical on behalf of patients,” Sumit Aggarwal, president and CEO of Eloxx, said in a company press release announcing the funding.

Administered as an under-the-skin injection, ELX-02 is designed to bypass the nonsense stop signals, which may allow the cell to produce a full-length, functional CFTR protein.

ELX-02 has been granted orphan drug and fast track designations in the U.S., both of which are intended to speed the therapy’s development.

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CFF Awards Up to $2M to Advance Eloxx’s Therapy ELX-02

The parallel EL-012 and EL-004 trials, both Phase 2, are testing the safety, tolerability, and pharmacological profile of the therapy in patients ages 16 and older. Secondary goals include changes in levels of sweat chloride — a biomarker of CFTR function — and in lung function.

Participants receive four increasing doses of ELX-02. Three of the doses, specifically 0.3, 0.75, and 1.5 mg/kg, were each given for one week, whereas the highest dose of up to 3 mg/kg was given for two weeks.

Top-line results showed that the treatment was generally safe and well-tolerated, with no serious adverse events reported.

One week of daily treatment with 1.5 mg/kg resulted in a significant drop in sweat chloride, with reductions similar to those previously seen in CF therapies approved for patients with other types of mutations. No significant reductions in sweat chloride were observed at the other doses.

While no improvements in lung function were observed, this likely was due to the short treatment duration, Eloxx noted.

Further, data from lab-grown organoids, or “mini-organs” — grown from CF patient cells — suggested that ELX-02 in combination with Kalydeco may be more effective than ELX-02 alone.

The trials now will evaluate whether a combination of the established ELX-02 dose (1.5 mg/kg per day) and Kalydeco, developed by Vertex Pharmaceuticals, leads to further improvements in CF patients with nonsense mutations.

Participants will receive one week of ELX-02 treatment alone, followed by four weeks of ELX-02 plus Kalydeco, which will be given as a 150 mg tablet twice daily. The trial’s goals will be the same as in the earlier single therapy part.

CFF’s funding to support these studies is part of the foundation’s Path to a Cure initiative, aimed at accelerating treatments that target CF’s underlying causes and developing cures.

The award adds to previous funding from the CFF to ELX-02’s development, with up to $2 million last year, and up to $1.6 million in 2019.

“What we learn from these studies will be critically important for informing future research and drug development of therapies for these notoriously difficult-to-treat targets for years to come,” said Tony Durmowicz, MD, vice president of clinical development at the CFF.

Eloxx said it will pay the CFF royalties tiered to the foundation’s actual funding levels if the therapy is approved.

“We are incredibly grateful for this significant level of financial and scientific support from the CF Foundation, which will enable us to build [upon our] clinical results announced in November 2021 and the potential of ELX-02 to bring forward a treatment for Class 1 CF patients with nonsense mutations,” Aggarwal said.