Lowering uric acid levels

“The company is founded on the idea that you can take ideas that merit development,” Dr Davidoff says, “develop them through the early stages, all the way through the end of the first proof of concept studies in individuals with a given disease. So we really add value from an early idea through to the end of the first clinical trials.”

The company is focused on developing kidney disease treatments. Progressing kidney disease caused by Type 2 Diabetic Nephropathy or Polycystic Kidney disease starts because of the underlying cause, but as it progresses, xanthine oxidase, an enzyme that helps produce uric acid, becomes more active, accelerating the progression of the disease.

At present, therapies for progressive kidney disease focus on treating high blood pressure or glucose control, but do not address the mechanism of progressive kidney disease due to xanthine oxidase activity and high uric acid as drivers of progression injury.

“There are very good clinical trials suggesting that, if you lower uric acid in individuals with progressing kidney disease, you have the opportunity to slow or stop their progression, in some cases reverse that progression, and that means you can keep individuals off dialysis [which], while it’s lifesaving, is also life-altering, because it requires a lot of commitment.”

XORTX is developing these therapies as a first-in-class treatment to meet this unmet need. The company began to learn of these benefits in the mid-2000s, when it discovered that uric acid was driving a number of health issues, such as obesity, high blood pressure, insulin resistance, metabolic syndrome and diabetes.

“Along with those discoveries of this previously unknown role, there was an opportunity to begin to not only patent and expand that patent portfolio, but to test individual compounds, like our lead compound, oxypurinol. What we have seen over the course of pharmacology and toxicology and human studies, is that the drug is safe and effective.”

The drug is now being applied to clinical trials, and recent study meetings with the FDA have indicated that the program for oxypurinol and Polycystic Kidney Disease is ready to move into Phase III trials. The company is now producing the regulatory filings that need to be filed in advance of starting a Phase III trial, and will work towards initiating that in the future.

“We also have noted from the COVID-19 pandemic that acute kidney injury is associated with the worst outcome for individuals with a COVID-19 infection. We’re working with a number of groups from New York, Italy and Denver to develop that therapy quickly, as a way to treat and prevent acute kidney injury, and hopefully that means fewer symptoms from COVID-19 infection, a shorter path to recovery, and we hope decreasing the rate of death.”

Ongoing value creation

The company is a micro-cap with three programs in advanced stages, with a great unmet need being identified in Autosomal Dominant Polycystic Kidney Disease, type 2 diabetic nephropathy and in acute kidney injury associated with COVID-19. Despite all of that progress, the company’s market cap compared to comparable companies remains reasonably low. 

“We continue to work to add progress in terms of our regulatory and clinical filings, and we’re working towards setting up Phase III clinical trials in both of those programs. What that means is ongoing value creation should at some point see us move towards the mean of valuations. We expect that, for any investor, that’s a fairly compelling case.”

The company’s impressive executive team is comprised of a number of individuals with experience working in drug development, who like Dr Davidoff himself have worked in a variety of different areas.

“Collectively, executive members and directors have worked on every area of drug development,” Dr. Davidoff says, “from manufacturing to regulatory filings, to clinical trials, and all of the technical developments that are included in that critical path of progress. Some of those programs are now drugs marketed globally.”

Additionally, the company has a large number of individuals who are currently consulting for the company. The collective team is not only extremely experienced, but the majority of it has also worked on the xanthine oxidase inhibitor class of drugs.

“That gives us a special opportunity to not only understand the drugs and how they can be developed, but because of our experience developing these drugs in the past and reapplying them to these two areas, Polycystic Kidney Disease and COVID-19, we have a certain agility by understanding what the FDA requires [and] the critical steps needed to progress.”

The bonus to this experience is that the company has been developing oxypurinol, which the FDA has deemed reasonably safe and effective for a variety of uses. All this experience has created an extremely strong executive team. 

“With respect to our Board of Directors, we have individuals like Mr Bruce Rowlands, who has not only worked in pharma but also worked in the financial market space; Bruce Cousins, who was an executive with J&J for a number of years, and we’re fortunate to have him on our board; and then others like Paul Van Damme with a number of successful bio-pharma companies and Allan Williams who brings substantial public and retail market experience.”

The immediate goal for the company is to continue manufacturing and developing formulations for oxypurinol, which allows it to extend its patent portfolio and is also a step towards advancing the Phase III trials in these areas.

“Near-term, we see advancing regulatory filings, initiating those Phase III studies, and we have had a number of pharma companies around the globe reach out to us and we think that as we take these early immediate steps then we move quickly into the setting where there will be potential licensing discussions. That is where the value creation comes into play.”

In the long-term, the company seeks partners in both Autosomal Dominant Polycystic Kidney Disease and Type 2 Diabetic Nephropathy to develop through to late-stage clinical trials through regulatory filings and marketing. The company will however continue to progress regardless of the timing of the entry of those parties.

“We have a strong, experienced development team. We’re in advanced, late-stage clinical programs. We believe that these are highly de-risked, because we’re taking a drug that we know is eminently approvable and applying it to these new areas. That means we’ve proven out a lot of the key risk steps in the course of developing these drugs, and that should allow us very soon to change the way that kidney disease will be treated in the future.”

Dr Davidoff has been involved in life sciences and biopharmaceutical research for almost thirty years, with seventeen years in industry. His professional experience includes developing drugs in Cardiovascular, Neurological and Renal fields from concept to marketing applications and approval.

“I think the lessons [I’ve learned] are simple ones: commit 100% to any project you take on, remain rigorous about what’s needed to succeed, and to find that very early, but also look down the road for risk and understand what’s needed to risk-mitigate. A global business like drug development requires you to build and maintain a network and constantly strive to look ahead and understand that you need to prepare for what’s coming up.”

With two first-in-class programs moving into advanced stages of development, XORTX Therapeutics is helping improve the quality of life and future of patients suffering from chronic kidney disease. Find out more about XORTX Therapeutics by visiting www.xortx.com.