Alport syndrome with nonsense mutations is a genetic disorder that occurs in 1 in 50,000 newborns in the United States.1,2 It is caused by the loss of 1 of 3 collagen IV subtypes.1,2 This disease is signaled by blood (hematuria) and protein(proteinuria) in the patient's urine , and characterized by progressive kidney disease, hearing loss, and eye abnormalities.1,2
85% percent of cases are from x-linked COL4A51
• ~6% of patients have nonsense mutations (~9,400 to 12,750 pts)1
>200k total patients in the United States, Europe, Japan, and China1
Leads to end-stage renal disease (ESRD) by 18 years of age1*
No approved disease modifying therapies exist for nonsense mutations
ELX-02 IS PREFERENTIALLY TAKEN UP IN THE KIDNEYS
Preclinical data support development of ELX-02 for Alport Syndrome as it is preferentially transported to kidneys with significant, potentially therapeutic levels readthrough in COL4A5 nonsense mutations
• Expected >50-fold exposure in the kidneys vs plasma.
ELX-02 exposure in
kidney at 1mg/kg:
PBPK estimate in
human (ng*mL/hr)3
Dose dependent
readthrough activity
of ELX-02 in
Cystic Fybrosis patient's
organoids4
ELX-02 EXPOSURE IN KIDNEY AT 1mg/kg:
PBPK ESTIMATE IN HUMAN (ng*mL/hr)2
DOSE DEPENDENT READTHROUGH ACTIVITY
OF ELX-02 IN CYSTIC FYBROSIS PATIENT'S
ORGANOIDS3
Proof-of-concept clinical trial
ELX-02: Potential to Address Mutant COL4A5 in Patients with Alport Syndrome
Population < 8 Alport Syndrome with nonsense mutations patients >12 years of age
Outcome Measures
- Primary: Safety, tolerability, and pharmacokinetics
- Secondary: Change in proteinuria
- Trial initiation: Second half of 2022
- Initial results: June 2023
*Median age
References: 1. Kidney International website. 2020; 98, 1605–1614. 2. Alport syndrome. Medline Plus website. https://medlineplus.gov/ genetics/condition/alport-syndrome/#causes. Accessed April 5, 2022. 3. J Am Soc Nephrolv.28(6); 2017 JunPMC5461786 4. J Clin Invest 1995 Sep;96(3):1404-13
