When Chinook Therapeutics looks at 2021, it foresees a host of clinical trials that will bring precision medicine to the kidney disease space.
When Chinook Therapeutics looks at 2021, it foresees a host of clinical trials that will bring precision medicine to the kidney disease space.
That’s a major change. “Precision medicine – using biomarkers, precise targeting, and patient segmentation – is common in oncology and some rare diseases, but is unusual for kidney diseases,” Eric Dobmeier, president and CEO, Chinook Therapeutics, told BioSpace.
Its application has the potential to enable smaller and faster trials, and thus deliver innovative therapies to a broad population years faster than otherwise would be possible.
Chinook’s nearest milestone is the initiation of a 300-patient Phase 3 ALIGN trial of atrasentan for IgA nephropathy (Berger’s disease) that is expected to begin early this year.
A Phase II basket trial to expand applications of that drug for a variety of glomerular diseases also is planned for the first half of 2021. FSGS, Alport syndrome, and diabetic kidney disease – all driven by proteinuria (protein in the urine) – are potential applications. “We’re planning a combination arm with sodium/glucose cotransporter 2 (SGLT2) inhibitors and have a small data set showing atrasentan pairs well with them,” Dobmeier said.
“Atrasentan addresses the damage caused by IgA nephropathy, but BION-1301 has the potential to address the underlying cause of it,” he added. “We’re excited to see the combination of the two.
“BION-1301 is a monoclonal antibody that targets a proliferation inducing ligand (APRIL), which is a key element of the immune complexes causing IgA nephropathy,” he elaborated. The company has reported healthy volunteer data and expects to report Phase I interim patient data this year.
Chinook acquired BION-1301 as part of the merger with Aduro Biotech, Inc. last October. It is currently in a Phase Ib trial.
Chinook also is advancing the first drug it developed in-house towards an IND, with a Phase I trial initiation anticipated in the second half of 2021. Called CHK-336, it is designed for primary hyperoxaluria, a liver enzyme deficiency.
“We’ve made a very potent liver-targeted oral small molecule drug,” Dobmeier said. It has the potential to fill the therapeutic gaps left by siRNA therapeutics. For example, although some siRNA therapeutics have been approved for primary hyperoxaluria and others are in development, they are administered intravenously and would be used mainly for the most severe cases.
CHK-336, in contrast, is a convenient oral dosage that can be used to address less severe forms of the disease, such as PH 2, and 3, and for patients who develop the condition after gastric bypass surgery.
Overall, only a handful of innovative kidney therapeutics have been approved during the past 20 years, and many patients are treated with steroids or immunosuppressants. The field has largely missed the advancements that have informed other fields of medicine.
“Now that dynamic is changing,” Dobmeier said. “Kidney disease is an exciting area that is just coming into its own.”
To reach this point, companies faced many challenges. Currently, “Kidney disease often is considered a symptom of other diseases…as a side effect of diabetes, for example.”
Also, he admitted, “It’s harder to get the tissue biopsies that would allow an ‘omics approach and thus identify biomarkers that could be used as surrogate endpoints.” Therefore, only hard endpoints were accepted. That has changed in the past few years.
The FDA acceptance of surrogate endpoints in kidney disease is a key factor that will enable clinical trials to be completed faster and that involve smaller, more targeted patient populations. Rather than waiting for a decade or longer for disease progression, the FDA now is open to such surrogate endpoints as proteinuria reduction and estimated glomerular filtration rate (eGFR), potentially reducing the duration time until reaching the primary endpoint to about six months. “That’s a huge difference,” Dobmeier said.
“Ultimately, we want kidney disease to become a chronic – rather than fatal – disease,” he said.
2020 may live in infamy in terms of public health but, for Chinook, it was a productive, prolific year highlighted by a reverse merger that took it public, $290 million in capital to see it through the first half of 2023, the quadrupling of staff (largely independent of the merger), and pipeline advances.
“It accelerated our maturation as a company,” Dobmeier summarized. “Coming off 2020, there’s a lot to execute on. Our goal is to build a leading company in kidney disease. We’re laser-focused, and we have the capital and the people.”
In other words, Chinook is poised to continue its momentum.
