James Mackay, Ph.D., President & CEO, Crystalys Therapeutics

Your Story

Q1. What was the defining moment or insight that led you to take the helm of Crystalys Therapeutics?

I led the Ardea Biosciences team that developed and launched Zurampic and Duzallo in 2015 — the first new mechanism-of-action treatments for gout in over 50 years. Both drugs won approval from the FDA, the EMA, and regulators in dozens of other countries, but they carried a renal toxicity liability. To manage that risk, we chose a lower dose whose renal side-effect profile was comparable to the active comparator in our trials, a benefit-risk tradeoff regulators accepted.

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The tradeoff was that efficacy at the lower dose fell short of what we'd hoped for. And even though the FDA and EMA accepted the renal profile at that dose, both agencies still required a boxed warning for the renal effects seen at higher doses. That warning, combined with the more modest efficacy, ultimately kept the drugs from succeeding commercially.

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Novo Ventures, the lead investor in my previous company, Aristea Therapeutics, came back to me afterward. Aristea hadn't worked out as we'd hoped, but the firm had grown genuinely interested in the gout space and wanted to work together again. Around the same time, we were introduced to Catalys Pacific, a Japan-based venture firm that specializes in identifying drugs approved in Japan whose U.S. and European rights remain available. We combined forces — our management team, Novo Ventures, and Catalys Pacific — to found Crystalys Therapeutics.

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We carried every lesson from Zurampic and Duzallo into the search for our next molecule: something far more potent, without the renal liability. We believe we found that in dotinurad.

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Q2. In the simplest terms, what does Crystalys do, and why does it matter for patients?

Gout is the most common form of inflammatory arthritis, marked by sudden, severe attacks of pain, swelling, redness, and tenderness in one or more joints. Flares can be disabling and last for days or weeks. The disease develops when the body excretes too little uric acid (85% of patients) or produces too much (15% of patients), leading to a buildup of urate crystals and inflammation.

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Most first-line treatments target uric acid production, but they don't address the more common problem — the body's inability to excrete enough uric acid. And today, there's no adequate second-line option in the U.S. or EU for patients who fail first-line therapy.

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That's the gap dotinurad is designed to fill. It inhibits URAT1, the major transporter responsible for uric acid reabsorption and excretion in the kidney, with the potential for best-in-class safety and efficacy. It's already approved in several Asian markets, including Japan, China, the Philippines, Thailand, and Taiwan — and our job now is to bring that same benefit to patients in the U.S. and Europe.

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The Science & The Strategy

Q3. What sets dotinurad apart from others working in this space?

Two things. First, dotinurad is roughly a thousand times more potent than the molecule we developed at Ardea. Second, its safety profile is not only well-established but fundamentally different — it doesn't carry the renal toxicity liability that our earlier drug did.

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What drew us to dotinurad in particular was its track record. It was developed by the Japanese pharmaceutical company Fuji Yakuhin, approved in Japan in 2020, and is now approved in China as well. The clinical trial programs in both countries required no renal monitoring, and more than 2.2 million patients have received the drug in a postmarketing setting in Japan. There has been no change to its prescribing information over six years on the market — a large, stable safety database with no signal of renal toxicity.

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Q4. What has been your most important milestone to date, and what's next?

Last September, Crystalys emerged from stealth with a $205 million Series A financing to advance dotinurad through global Phase 3 trials — one of the largest private Series A rounds completed in 2025, co-led by Novo Holdings, SR One, and Catalys Pacific, with a broad syndicate of additional investors. Shortly after, we dosed the first patients in our two randomized, double-blind, multicenter Phase 3 studies — RUBY and TOPAZ — evaluating dotinurad as a next-generation, once-daily, oral URAT1 inhibitor for gout.

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Looking Ahead

Q5. Where do you see Crystalys in three years, and what has to go right to get there?

Our focus right now is squarely on the dotinurad Phase 3 program. We're anticipating a regulatory filing in the second half of 2028, approval in the second half of 2029, and launch to follow. In parallel, we're evaluating additional assets to add to the pipeline, both in gout and in chronic kidney disease. Those conversations are still early, but if we find something we believe is worth the investment, we'll move to bring it in.

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About The Big4Bio CEO Weekly Q&A

Every Monday, Big4Bio spotlights a life sciences CEO from one of our eight coverage regions — Boston, San Francisco Bay Area, San Diego, Philadelphia, New York City, the Capital Region, Los Angeles, and Seattle. Each feature is promoted across all eight Big4Bio daily newsletters, reaching 30,000+ life sciences professionals. CEO participation is complimentary and editorial — every CEO approves the final Q&A before publication.

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Are you a life sciences CEO or do you represent one? Contact Big4Bio editor Marie Daghlian at marie@big4bio.com to be considered for an upcoming feature.