When Tony Johnson departed AstraZeneca last year, he was just the latest in a string of Big Pharma executives to move into, or back into, biotech. With no hands-on experience running a biotech company, he left his post, SVP of early clinical development, to helm Goldfinch Bio, which aims to use a precision medicine approach to become “the kidney company.”
He chose Goldfinch because he saw the chance to do something that Big Pharma had failed to do.
“I’ve worked in several large pharma companies—Glaxo Wellcome, GSK, BMS, AstraZeneca—and in those companies, they’d all been trying to discover and develop drugs for the kidney. But there’s been a great deal of failure. What was special about Goldfinch Bio was that we were bringing precision medicine to the kidney,” Johnson said.
While precision medicine is, or should be, applicable to any disease, it is most tangibly understood in the context of cancer. Historically, treatment for certain cancers focused on chemotherapy, but in the last decade or so, treatments have targeted specific pathways that occur in different cancers, Johnson said.
“Being very pathway-specific, it’s what I’d call precision medicine: selecting patients for particular treatments based on what’s driving their cancer. We’re doing the exact same thing at Goldfinch ... I thought this would be the way that one could make headway in diseases of the kidney,” he said.
The company’s pipeline is based on its Kidney Genome Atlas, a patient registry containing genomic, transcriptomic and proteomic data with thousands of anonymized clinical patient profiles. It has used the database to identify mutations or sequence variants that occur in patients with kidney disease. Goldfinch has found the same sequence variants causing kidney diseases different patients, suggesting that the “historical way of using histology,” or tissue analysis, to diagnose these diseases is incorrect, Johnson said.
Goldfinch’s lead candidate is a TRPC5 inhibitor for the treatment of focal segmental glomerulosclerosis (FSGS), a rare disease with no approved treatments that affects the kidney’s filtering units, called glomeruli. The drug, dubbed GFB-887, targets the TRPC5 ion channel, which is thought to be involved in FSGS by triggering the Rac1-TRPC5 pathway. The company also has candidates for polycystic kidney disease (PKD) and diabetic nephropathy in the works.
So why has large pharma tried and failed in the kidney disease space?
“Basically, not doing precision medicine has been the main reason,” Johnson said. “But [it’s also] driven by the heterogeneity of disease.”
The mechanisms that cause kidney disease, as well as the genetic drivers or risk factors behind it, were poorly understood. Testing therapies in all comers—that is, all patients with kidney disease—rather than identifying groups of patients with a particular driver for their particular kidney disease was setting them up for failure.
“Specific mechanisms were not working in enough patients to show adequate treatment effect to justify going forward with that program,” Johnson said.
A second reason is translating preclinical results to the clinic. In other disease areas, such as infectious disease, animal models predict quite well what happens in humans, Johnson said. But this isn’t the case in animal models of the kidney.
“All those companies I've worked in, we’d find success with various drug targets in animals and when we went to man, we wouldn’t see the same success. We wouldn’t see any effect, or a very minimal effect, because we had not gone after the right patient population,” he said.
In addition to targeting the right patient groups, Johnson said, Goldfinch is testing its drugs in podocytes, a type of kidney cell, and kidney organoids, both created from human stem cells. Translational science will be helped along with in vivo organoids, where researchers implant these organoids under the kidney capsule of animals.
Scientific issues aside, the regulatory environment hasn’t been particularly helpful either.
"[It] has been hostile and difficult for those interested in discovering and developing drugs for the kidney. And by that, I mean up to this point, regulators—the FDA, the EMA in Europe—they’ve wanted and needed large outcomes trials in order to approve a drug for kidney diseases,” Johnson said.
“That’s been a barrier for investors including large pharma. A lot of them have walked away from the kidney,” he added.
But that is changing: The FDA and EMA held a two-day workshop this year, in which academics and industry—including Goldfinch—also participated. They decided after “reviewing data over the past 10 years or so” that certain surrogate endpoints could be acceptable endpoints for approval. This would reduce the size and duration of clinical trials required for kidney drugs to reach approval.
When asked why Goldfinch, why the kidney, Johnson pointed to medical need, a market opportunity and a personal reason.
“Eleven percent of the U.S. population has chronic kidney disease so this is a very, very big problem,” he said. Yet, despite this number and the importance of the kidney in the body’s function, investment in the kidney has “substantially” lagged that in other therapeutic areas.
“I thought there would be low-hanging fruit and opportunities to be successful in focusing on the kidney versus oncology, where there are a very large number of companies all competing for the same space,” he said.
Finally, in 18 years of clinical practice, Johnson looked after patients who had kidney disease along with comorbidities, such as cardiovascular disease.
“And so, I felt this was an area where I had not only scientific, but clinical, expertise [and] I could bring that to bear, leverage that, and be successful.”
While Johnson had never worked in a biotech company, he spent just over a year as a venture partner at OrbiMed Advisors, where he “gained firsthand knowledge of what it was like to be in a biotech.” He met with the management teams of “a large number, probably 300” biotech companies and sat on the boards of Cardioxyl, which was eventually acquired by Bristol-Myers Squibb, and the oncology player Rgenix.
“I thought I had a good understanding of the way they operated and some of their challenges, so it wasn’t completely blind going from large pharma to Goldfinch Bio,” Johnson said.
An early challenge was adapting to the depth and breadth required of a biotech CEO. At Bristol-Myers and AstraZeneca, he had been responsible for managing hundreds of people, but only within one company function: early clinical development.
It’s not like that at Goldfinch.
“In a half-hour period, I could be worrying about discovery research [and] clinical development, but also have we got the right legal representation, or what’s happening with our lease?” he said. “I knew it was going to happen, but that was a little more challenging at first than I was expecting.”
Goldfinch will present five abstracts at the American Society of Nephrology’s Kidney Week at the end of October and is on track to file its first IND in the first half of 2019.
And beyond that?
Goldfinch is focusing on orphan indications like FSGS as a small company, but Johnson thinks there’s the potential to invest in and explore subsets of larger indications using its precision medicine approach. And it doesn’t expect to expand its focus to other disease areas.
“We’re committed to being the kidney company and we’re also committed to using appropriate genomics an multiomics, to apply precision medicine for diseases of the kidney. We believe that there’s potential for many years to come to grow this company, Goldfinch Bio, into a fully functional and fully differentiated company that has research and development, and commercializes our products for diseases of the kidney,” he said.