Chinook Tackles Rare Chronic Kidney Diseases

In just two years, Chinook Therapeutics created a precision medicine platform to tackle rare chronic kidney diseases, developed its first in-house program targeting a rare disorder, licensed a clinical program from AbbVie that is poised for late-stage trials, reverse-merged into a public company and completed a concurrent $115 million financing.

“Precision medicines for kidney diseases is an area that has been under-resourced and overlooked for many years,” says Eric Dobmeier, CEO of Chinook Therapeutics. “What we are doing is taking a precision medicine approach that is similar to what’s been successful in other areas such as oncology or rare disease and bringing it into kidney disease.”

Photo: Eric Dobmeier, CEO of Chinook Therapeutics

The kidney is a complex organ that is made up of more than 30 different cell types, says Andrew King, head of renal discovery and translational medicine at Chinook. “We have a strong focus on building a precision medicine platform to provide insights into the genetic and molecular drivers of rare severe chronic kidney diseases,” he says.

The platform, built in partnership with academic founder Ben Humphreys of Washington University in St. Louis, Missouri, has multiple components including the use of single cell RNA sequencing technology, translational models of human disease, stem-cell derived organoid technologies, and bioinformatics and systems biology to leverage large clinical datasets. Biomarker strategies are used to identify and stratify patient populations most likely to benefit from its precision therapies.

Chinook’s lead experimental therapeutic, atrasentan, was licensed from AbbVie in early 2020, and the company plans to move into a phase 3 study in the first half of 2021. Atrasentan is a selective, small molecule inhibitor of the endothelin A receptor that has the potential to reduce kidney inflammation and fibrosis in IgA nephropathy patients. Although studied extensively in diabetic kidney disease where it demonstrated favorable effects to reduce urinary protein levels (proteinuria) and preserve kidney function, in 2015 AbbVie made the strategic decision to exit the nephrology area and atrasentan development was discontinued. King had worked on its development during a stint at AbbVie, and Chinook quickly approached AbbVie with a focused plan to in-license the compound and leverage the data AbbVie generated to potentially benefit IgA patients.

While considered an orphan disease in the United States and Europe, IgA nephropathy is the most common primary glomerular disease globally, with a higher prevalence in Asia.

“It’s still considered a rare disease,” Dobmeier says. “We are doing a number of trials in rare kidney diseases, including Alport syndrome, FSGS, and other nephropathies that we are researching. We have a precision medicine focus so we can look at causes and drivers that are specific to these diseases.”

In the second half of 2020, Chinook merged with Berkeley, California-based Aduro Biotech, an immune-oncology focused biotech with a strong cash position and a pipeline that included BION-1301, a phase 1 monoclonal antibody targeting APRIL that Aduro had pivoted from developing in multiple myeloma to IgA nephropathy in 2019. Dobmeier said Chinook was planning a series B financing and an eventual IPO in 2021, but they decided to go public by merging with Aduro Biotech because they were attracted to the disease-modifying potential of BION-1301 in IgA nephropathy.

“We announced the merger in June, we did a $115 million financing in August, and we closed both and became a public company in October,” said Dobmeier. “We built this company from a small research-focused group to a multi-product, clinical stage company moving into registrational trials in about one year. When I look back at what we did during a pandemic, it is kind of amazing.”

Now it’s time to execute. Chinook plans to start the ALIGN phase 3 trial of atrasentan soon, planning to enroll 300 patients in 15 to 20 countries. It will also commence a basket trial of atrasentan in other diseases, including Alport syndrome and FSGS, combining it with SGL2 inhibitors in diabetic kidney disease, and testing it to lower proteinuria in IgA nephropathy patients.

BION-1301 is in a phase 1b trial in IgA nephropathy with first readouts expected this year. Chinook’s third program, CHK-336, is an oral small molecule developed in-house for the treatment of kidney stone formation in patients with the rare enzymatic disorder hyperoxaluria (PH), and is expected to move into the clinic by the end of the year. CHK-336 was recently granted Rare Pediatric Disease designation by the U.S. Food and Drug Administration, which makes Chinook eligible for a potentially lucrative Rare Pediatric Disease Priority Review voucher upon the drug’s approval by the FDA.

Not being midstream when the COVID-19 pandemic hit has allowed Chinook to think a little differently about how to design its upcoming trials. This includes prioritizing locations where the pandemic is less prevalent in order to get started sooner, minimizing patient visits to their doctors by using home collection of blood and urine samples, and using telemedicine for doctors and patients to touch base.

“We’re hopeful that by the second half of the year we’ll be moving beyond the pandemic but for the time being we’re optimistic that we can start ALIGN and AFFINITY trial enrollment by using some of these mitigation strategies,” said Dobmeier. “Some of these changes are long overdue and we were forced into it by the pandemic but they should have been happening over the last five or ten years. This will be a sea change in how trials are run going forward.”

While considered an orphan disease in the United States and Europe, IgA nephropathy is the most common primary glomerular disease globally, with a higher prevalence in Asia.

“It’s still considered a rare disease,” Dobmeier says. “We are doing a number of trials in rare kidney diseases, including Alport syndrome, FSGS, and other nephropathies that we are researching. We have a precision medicine focus so we can look at causes and drivers that are specific to these diseases.”

In the second half of 2020, Chinook merged with Berkeley, California-based Aduro Biotech, an immune-oncology focused biotech with a strong cash position and a pipeline that included BION-1301, a phase 1 monoclonal antibody targeting APRIL that Aduro had pivoted from developing in multiple myeloma to IgA nephropathy in 2019. Dobmeier said Chinook was planning a series B financing and an eventual IPO in 2021, but they decided to go public by merging with Aduro Biotech because they were attracted to the disease-modifying potential of BION-1301 in IgA nephropathy.

“We announced the merger in June, we did a $115 million financing in August, and we closed both and became a public company in October,” said Dobmeier. “We built this company from a small research-focused group to a multi-product, clinical stage company moving into registrational trials in about one year. When I look back at what we did during a pandemic, it is kind of amazing.”

Now it’s time to execute. Chinook plans to start the ALIGN phase 3 trial of atrasentan soon, planning to enroll 300 patients in 15 to 20 countries. It will also commence a basket trial of atrasentan in other diseases, including Alport syndrome and FSGS, combining it with SGL2 inhibitors in diabetic kidney disease, and testing it to lower proteinuria in IgA nephropathy patients.

BION-1301 is in a phase 1b trial in IgA nephropathy with first readouts expected this year. Chinook’s third program, CHK-336, is an oral small molecule developed in-house for the treatment of kidney stone formation in patients with the rare enzymatic disorder hyperoxaluria (PH), and is expected to move into the clinic by the end of the year. CHK-336 was recently granted Rare Pediatric Disease designation by the U.S. Food and Drug Administration, which makes Chinook eligible for a potentially lucrative Rare Pediatric Disease Priority Review voucher upon the drug’s approval by the FDA.

Not being midstream when the COVID-19 pandemic hit has allowed Chinook to think a little differently about how to design its upcoming trials. This includes prioritizing locations where the pandemic is less prevalent in order to get started sooner, minimizing patient visits to their doctors by using home collection of blood and urine samples, and using telemedicine for doctors and patients to touch base.

“We’re hopeful that by the second half of the year we’ll be moving beyond the pandemic but for the time being we’re optimistic that we can start ALIGN and AFFINITY trial enrollment by using some of these mitigation strategies,” said Dobmeier. “Some of these changes are long overdue and we were forced into it by the pandemic but they should have been happening over the last five or ten years. This will be a sea change in how trials are run going forward.”