Note: This is NOT an IPO. This a NASDAQ Uplisting – a public offering. Eloxx Pharmaceuticals’ common stock is quoted the OTC Pink Limited Market under the symbol “ELOX” – according to the prospectus.

(Incorporated in Delaware) 

We are a clinical-stage biopharmaceutical company developing novel, small molecule product candidates designed to modulate the ribosome and promote readthrough of premature stop codons induced by nonsense mutations (“NMs”) to enable the production of full-length proteins. Targeting ribosome subunits provides a therapeutic approach to addressing a number of genetic diseases. According to the Human Gene Mutation Database, NMs account for approximately 10% to 12% of patients with a given genetic disease. There are over 7,000 inherited genetic diseases that collectively affect 350 million people worldwide. Our immediate focus is to advance the clinical development of our product candidate, exaluren, for the treatment of rare kidney diseases. We have also exclusively licensed our product candidate, ZKN-013, to Almirall, S.A. (“Almirall”), who is developing it for the treatment of rare skin diseases.

Exaluren is a novel eukaryotic ribosome-selective glycoside product candidate that is designed to induce premature termination codon (“PTC”) readthrough in the presence of NMs and promote the restoration of full-length proteins. We believe this mechanism has the potential to apply to all genetic diseases caused by NMs. We are initially developing exaluren to induce full-length Collagen IV protein for the treatment of Alport syndrome (“AS”) with NMs (“NMAS”). NMAS, a subset of AS, is a genetic kidney disorder that is caused by the loss of one of three Collagen IV subtypes, Collagen IV alpha 3 (“COL4A3”), alpha 4 (“COL4A4”), or alpha 5 (“COL4A5”), and the resulting loss of the Collagen IV alpha 3,4,5 trimer. This trimer is made in podocyte cells and required for the functioning of the filtration structure of the kidney comprising the glomerular basement membrane (“GBM”), foot processes and slit diaphragms.

We estimate that NMAS affects roughly 7% of AS patients or approximately 4,200 patients in the United States and approximately 11,000 patients worldwide. NMAS is characterized by hematuria and proteinuria, or blood and protein, respectively, in the patient’s urine and results in progressive kidney disease, hearing loss and eye abnormalities. The median age to kidney failure in patients with NMAS is 20 years and 30 years for patients with NMs in the COL4A3/4 genes and the COL4A5 gene, respectively. Although angiotensin converting enzyme inhibitor and angiotensin receptor blocker therapies can slow progression to end-stage kidney disease, they do not prevent kidney failure, and there are no therapies approved by the U.S. Food and Drug Administration (“FDA”) specifically indicated to address the underlying genetic cause of AS. Exaluren has received Orphan Drug Designation for the treatment of AS from the FDA.

We have evaluated exaluren in eight clinical trials, including four Phase 1 studies in healthy volunteers, one Phase 2a study in NMAS, two Phase 2 studies in cystic fibrosis (“CF”) patients with NMs, and one Phase 2 study in nephropathic cystinosis patients with NMs. In total, 145 subjects have received at least one dose of exaluren during these clinical trials with 89.4 subject-months exposure. In these studies, no dose-limiting toxicities were reported and no serious adverse events were attributed to exaluren.

Between January 2023 and April 2024, we conducted a proof-of-concept Phase 2a open-label trial in the United Kingdom in three patients with autosomal recessive AS and a NM in the COL4A4 gene. The primary endpoint of this study was to assess the number of participants with adverse events associated with administration of exaluren. The secondary endpoints were change from baseline in proteinuria, measured by the urine protein-to-creatinine ratio (“UPCR”) in a patient’s urine samples, and hematuria, and change in baseline in Collagen IV expression. All three patients showed a reduction in podocyte foot process effacement (“FPE”), which is the flattening and loss of specialized kidney cell structures that form the filtration barrier and attach to the podocytes and GBM, in transmission electron microscopy (“TEM”) images. FPE is a hallmark of kidney diseases, including AS, and the severity of FPE has historically been associated with time to kidney failure. TEM images of biopsy samples also showed an improvement in the GBM width in all treated patients. FPE was also measured as a 50% increase in the filtration slit density (“FSD”). These results were consistent with exaluren’s proposed mechanism of functional full-length protein restoration as reflected by improvements in GBM architecture and FPE observed in kidney biopsies. At the end of treatment, UPCR had decreased for one patient and increased for two patients. We received clearance to proceed with a Phase 2b clinical trial for exaluren in NMAS patients (without kidney biopsies in U.S. pediatric patients) under an Investigational New Drug application (“IND”) from the FDA and we plan to initiate this trial in the third quarter of 2026. We anticipate topline data from the initial 16-week placebo-controlled part of the study by mid-2027 with the final readout by the end of 2027.

(Note: Eloxx Pharmaceuticals