Exaluren

A nonsense mutation puts an early stop signal in a gene, so the cell stops building the protein partway through. In Alport syndrome that gene is COL4A5, COL4A3 or COL4A4, which carry the instructions for type IV collagen in the kidney's filters. Exaluren is designed to help the ribosome, the cell's protein builder, read past that early stop signal so full-length protein can be made ^[2].

It is related in structure to aminoglycoside antibiotics ^[9], and Eloxx says it is taken up and concentrated in kidney cells ^[6]. It can only help people whose Alport syndrome comes from a nonsense mutation, so genetic test results decide who can take part.

EXACT (NCT07523581) is a randomized, double-blind, placebo-controlled, delayed-start Phase 2 trial, which Eloxx calls Phase 2b, in about 24 people aged 12 and older. It enrolls men with a nonsense mutation in COL4A5, or men or women with one in COL4A3 or COL4A4, who have an eGFR, a measure of how well the kidneys filter, above 40, a urine protein to creatinine ratio of at least 300mg/g, and a stable dose for at least 12 weeks of an ACE inhibitor or ARB, blood pressure medicines used to protect the kidneys.

People with an organ transplant, on dialysis, with cirrhosis, with liver enzymes or bilirubin above 1.5 times normal, with a sudden kidney injury in the past 4 weeks or with active dizziness are excluded. It is delayed-start, meaning the placebo group starts exaluren after 16 weeks. Its main measure is the change in podocyte foot process effacement, a sign of damage to the kidney's filtering cells, seen in kidney biopsies at weeks 16 and 32 ^[10]; Eloxx says the biopsy measure applies to adults and to children outside the US ^[1].

ClinicalTrials.gov lists a Denver site and 2 London sites as recruiting, and UCLA, Stanford, the University of Minnesota, Hackensack, Penn, a San Antonio site, Alder Hey in Liverpool and Royal Manchester Children's as not yet recruiting ^[10]. Eloxx announced on September 11, 2026 that the first 2 patients had been dosed, and it expects results from the 16-week placebo part in mid-2027 and final 32-week results by the end of 2027 ^[1].

Eloxx's earlier open-label Alport pilot (NCT05448755) treated 3 people with a drug it then called ELX-02. By the registry's numbers, filtration slit density, a biopsy measure of the filtering cells, improved in all 3, foot process width improved in 2 and rose 6.8% in 1, and urine protein fell in 1 and rose in 2 ^[11]. Eloxx said effacement was lower in all 3 and described the proteinuria results as stabilized or improved ^[4]. Eloxx has not published a statement linking the ELX-02 code to the name exaluren.

In Eloxx's earlier 3-person Alport pilot, there were no deaths or serious side effects; reported side effects included sore throat, headache and injection site redness in 2 people each, and dizziness on standing, tiredness, migraine, itching and chills in 1 person each ^[11]. In a study of repeat doses in 62 healthy volunteers, injection site reactions were most common.

At the highest dose, 5.0mg/kg, 3 of 6 people had hearing test changes, and in 2 of them the changes were consistent with possible damage to hearing; 2 of 3 people on placebo in that group also had changes. All changes resolved or were resolving after dosing stopped. The study authors were Eloxx employees or consultants, and EXACT uses 0.75mg/kg ^{[9] [10]}.

Eloxx says the drug is designed to avoid the hearing and kidney damage aminoglycoside antibiotics can cause ^[6]; hearing is a fair question to raise with the trial team, since many people with Alport syndrome already have hearing loss. People with active dizziness are excluded from EXACT ^[10]. No clinical hold has been reported.