Eloxx Pharmaceuticals 3rd Annual Guggenheim Healthcare Innovation Conference

Thanks for having us. Happy to.

what is going forward. We have been public now for almost eight years, when we went through a bit of a cathartic time three years ago.

But last, in June, we raised money to prosecute both our programs. We are focused on rare kidney diseases, and we have two programs, one in Alport syndrome and the other in autosomal dominant polycystic kidney disease, ADPKD. We are targeting nonsense mutations, which are a subset of these diseases, with our lead asset, ELX-02. We have learned a lot about our drug. The drug has been trialed in 145 subjects. We have almost 90 patients, month subject months of exposure. So very good safety profile so far. And we have had data that showed we could reverse the structural damage that is associated with Alport syndrome, which is really a functional cure if you can see it extend over a longer period of time.

The mechanism of the drug is PTC read-through. When you have a nonsense mutation, a nonsense mutation is a mutation in the gene where instead of a regular ATCG, you have a stop, and it causes a formation of a premature termination codon. What this drug does is it reads past that premature termination codon and inserts an amino acid that results in full-length proteins getting formed again. This was a mechanism first described about 30 years ago when observed with gentamicin. It is an aminoglycoside, like gentamicin, which was specifically engineered to not have the two liabilities that gentamicin antibiotics have, which are, one, antibiotic activity, and second, mitochondrial toxicity. The drug has almost no antibiotic activity and has almost a two log, two orders of magnitude lower mitochondrial toxicity.

What that means is you do not see the kidney tox or the hearing loss that would normally be expected to be seen with aminoglycoside antibiotics. We have taken this molecule and really applied it to the kidney space, and having learned a lot from our earlier program in cystic fibrosis, both we learned about safety, we learned about the thresholds of exposure we need for efficacy. In the kidney, like aminoglycoside antibiotics, the drug gets taken up in a much larger exposure in the kidney itself. At the doses we are treating these patients, we have a 43-fold exposure in the kidney relative to plasma. Just for contrast, the lung exposure to plasma is only one to one. We can get about 30, 35 micromolar of exposure if you look at the AUC over 24 hours in the kidney versus only one micromolar in the plasma.

That helps us achieve the PKPD that we need to have for efficacy in all our programs.

Okay. You touched on this, but you do have some biopsy data that kind of- Yes, if I double-click into the Alport data that we have, we treated three patients that had an Alport nonsense mutation, a collagen IV gene.

Alport is a disease that is caused by mutations in one of three collagen IV genes, collagen IV A3, A4, or A5, and these patients had a mutation in collagen A4. After eight weeks of treatment, all the three patients, when looked at under the microscope in the biopsies, we saw a remodeling of the kidney. The two main elements of the kidney filtration structure are the glomerulus and the proximal tubules. The glomerulus is where the bulk of the filtration occurs. In Alport syndrome, the glomerular basement membrane gets irregular and becomes leaky, and then you have foot processes that attach to the glomerular basement membrane that start to efface or flatten out.

After eight weeks, we saw the glomerular basement membrane become more normal, and the foot process effacement reached about 80% of normal, starting with about 50% of normal.