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Seattle-based Chinook Therapeutics, Inc. (NASDAQ: KDNY) ($15.96, +1.33%) (52-wk range $2.10- $21.68), a biopharmaceutical company focused on the discovery, development and commercialization of precision medicines for kidney diseases, announced this week that the U.S. Food and Drug Administration (FDA) has granted rare pediatric disease designation for CHK-336, an investigational oral small molecule inhibitor of lactate dehydrogenase A (LDHA) for primary hyperoxaluria (PH). PH is a group (PH1, PH2 and PH3) of ultra-rare genetic diseases caused by enzyme mutations that result in excess oxalate production in the liver, and in its most severe forms, can lead to end-stage kidney disease at a young age. Inhibition of LDHA with CHK-336 allows for the potential to treat all forms of PH and other disorders arising from excess oxalate, while its liver-targeted tissue distribution profile enables maximal inhibition of liver oxalate production with minimal systemic exposure.
The FDA defines a rare pediatric disease as a serious or life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years and the disease affects fewer than 200,000 people in the United States. Through the FDA’s Rare Pediatric Disease Designation and Voucher Programs, the FDA may grant a priority review voucher at the time of product approval for a “rare pediatric disease.” The priority review voucher may be redeemed to receive priority review for a subsequent marketing application for a different product candidate or may be sold or transferred.
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Alan Glicklich, M.D., Chief Medical Officer at Chinook Therapeutics (NASDAQ: KDNY)
About CHK-336
CHK-336, is a first-in-class, liver-targeted oral small molecule LDHA inhibitor for the treatment of PH. LDHA catalyzes the final step in the production of oxalate from glyoxalate in the liver, therefore LDHA inhibition has the potential to treat all forms of PH as well as other disorders arising from excess oxalate. CHK-336 has the potential for robust efficacy by rapidly distributing to the site of oxalate production, while minimizing systemic exposures and potential for off-target activity, to facilitate a favorable tolerability profile required in this chronic disease. In PH1 mouse models, CHK-336 demonstrated significant and dose-dependent reductions in urinary oxalate, with the majority of CHK-336-treated mice reaching the normal range seen in wild-type mice. CHK-336 is currently progressing through IND-enabling studies with phase 1 initiation planned for the second half of 2021.
About Chinook Therapeutics, Inc. (NASDAQ: KDNY)
Chinook Therapeutics, Inc. is a clinical-stage biotechnology company developing precision medicines for kidney diseases. Chinook’s product candidates are being investigated in rare, severe chronic kidney disorders with opportunities for well-defined clinical pathways. Chinook’s lead program is atrasentan, an investigational phase 3 endothelin receptor antagonist for the treatment of IgA nephropathy and other primary glomerular diseases. BION-1301, an investigational anti-APRIL monoclonal antibody is being evaluated in a phase 1b trial for IgA nephropathy. In addition, Chinook is advancing CHK-336, an investigational oral small molecule LDHA inhibitor for the treatment of primary hyperoxaluria, as well as research programs for other rare, severe chronic kidney diseases, including polycystic kidney disease. Chinook is building its pipeline by leveraging insights in kidney single cell RNA sequencing, human-derived organoids and new translational models, to discover and develop therapeutics with differentiating mechanisms of action against key kidney disease pathways. To learn more, visit www.chinooktx.com.
INTERESTING KIDNEY DISEASE BACKGROUND
Chronic kidney diseases are a severe and growing worldwide problem with a lack of effective treatments often leading to dialysis, transplantation, and high costs to health care systems. In the U.S. alone, kidney diseases affect an estimated 37 million people and account for over $120 billion in annual costs.
Drug development in kidney diseases is experiencing a resurgence due to greater understanding of disease biology, utilization of novel translational platforms and patient stratification tools, and emergence of accelerated regulatory pathways based on surrogate endpoints. These dynamics have converged to create attractive opportunities for the development of precision therapies.
One of the key challenges in studying and treating kidney disease has been the complexity of the organ, with nearly 30 distinct cell types, each with its own function and purpose. This cellular diversity and structure has made understanding the mechanisms associated with kidney function loss challenging. However, the recent development of single-cell RNA sequencing of different kidney cell populations presents a new opportunity to clearly understand the molecular mechanisms of kidney function and disease. Chinook utilizes single-cell RNA sequencing techniques and proprietary datasets developed by their academic founder, Ben Humphreys (Washington University, St. Louis, MO), to gain unprecedented insights into kidney disease mechanisms.
The cellular complexity of the kidney also presents barriers to developing translationally-relevant models of human kidney diseases. Recently, kidney organoids and patient-derived 3D kidney cellular systems have emerged as advanced preclinical models to study kidney disease. Chinook partners with leading academic collaborators to apply these novel human organoids as translational model systems for target validation in indications such as polycystic kidney disease. In addition, we’ve established patient-derived 3D cellular models of polycystic kidney disease in-house. We believe our approach using these and other validation tools provides significant insights into human disease mechanisms and allows us to select and validate key targets that are central drivers of human kidney diseases.
CHINOOK’s LATEST PUBLICATIONS
Single Cell Transcriptomic Analysis to Define Cellular Heterogeneity in Human ADPKD
American Society of Nephrology Kidney Week 2020 Reimagined | October 2020
Discovery of CHK-336: A First-in-Class, Liver-Targeted, Small Molecule Inhibitor of Lactate Dehydrogenase for the Treatment of Primary Hyperoxaluria
American Society of Nephrology Kidney Week 2020 Reimagined | October 2020
A Phase 3, Randomized, Double‐Blind, Placebo‐Controlled Study of Atrasentan in Patients with IgA Nephropathy (The ALIGN Study)
American Society of Nephrology Kidney Week 2020 Reimagined | October 2020
Results of a Phase 1 Trial to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BION-1301 in Healthy Volunteers (Encore)
American Society of Nephrology Kidney Week 2020 Reimagined | October 2020
Results of a Phase 1 Trial to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BION-1301 in Healthy Volunteers (Encore)
Asian Pacific Congress of Nephrology | October 2020
TRIBE PUBLIC INTERVIEW OF CHINOOK’ S CEO
Recently, I hosted Chinook’s President & CEO Eric Dobmeier at our sister organization, Tribe Public’s Presentation and Q&A event, Tuesday, Jan. 26th. Please view this presentation now at the Tribe Public YouTube Channel.
You can also learn more and track Chinook’s progress at Vista’s Chinook Therapeutics’ Dedicated Page within our VPWatchlist section of our website.