Chinook Therapeutics, Inc. (Nasdaq: KDNY), a biopharmaceutical
company focused on the discovery, development and commercialization
of precision medicines for kidney diseases, announced a free
communication presentation on CHK-336 presented today at the 60th
ERA Congress being held virtually and live in Milan, Italy.
“The data presented from the phase 1 study of CHK-336 at this
year’s ERA Congress successfully demonstrates hepatic LDH target
engagement in healthy volunteers and establishes proof-of-mechanism
for CHK-336 to decrease hepatic oxalate production,” said Andrew
King, chief scientific officer of Chinook Therapeutics. “As we
continue to investigate the SAE observed in the 125 mg MAD cohort
and consider next steps, the CHK-336 program will remain
paused.”
CHK-336, A First-in-Class Orally Administered LDH
Inhibitor: Safety, PK and Target Engagement in a First-in-Human
Phase 1 Healthy Volunteer Study
CHK-336 is an oral small molecule LDHA inhibitor with
liver-targeted tissue distribution in development for the treatment
of patients with primary hyperoxaluria (PH) and other kidney stone
disorders driven by endogenous overproduction of oxalate.
The phase 1 single-center trial (see www.clinicaltrials.gov,
identifier NCT05367661) was designed to evaluate the safety,
tolerability, pharmacokinetic profile of CHK-336 in 104 healthy
volunteers in randomized, placebo-controlled, double-blinded,
single-ascending dose (SAD) and multiple-ascending dose (MAD)
settings. Healthy volunteers in the SAD portion of the study
received placebo or a single dose of CHK-336 ranging from 15 mg to
500 mg on day 1. Healthy volunteers in the MAD portion of the study
were to receive placebo or multiple doses of CHK-336 ranging from
30 mg to 500 mg given daily for 14 days.
Key highlights from the presentation include the
following:
- CHK-336 was generally well tolerated in HVs who received single
doses up to 500 mg and multiple doses (14 days) up to 60 mg.
- There were no dose-related trends in adverse events, vital
signs or EKG findings.
- The most common treatment emergent adverse event was headache
in six subjects receiving CHK-336 (8.8%) and no placebo subjects,
with no dose-related trend.
- There was one serious adverse event (SAE) of anaphylaxis that
occurred in a single HV following the first dose in the 125 mg MAD
group. The SAE had a rapid onset within one hour following the
first dose and rapidly resolved after treatment with an
antihistamine, without requiring epinephrine administration. The HV
had clinically significant elevations in serum tryptase levels
during the event, confirming anaphylaxis. This SAE resulted in
voluntary pausing of the trial to enable further
investigation.
- PK was well characterized with dose proportional exposures, a
plasma half-life consistent with once daily oral dosing and no
exposure accumulation following repeat dosing.
- The successful utilization of a novel 13C2-glycolate tracer in
the trial establishes proof-of-mechanism for CHK-336 as an orally
administered small molecule inhibitor of hepatic LDH. CHK-336
effectively blocked conversion of the 13C2-glycolate tracer to
13C2-oxalate with maximal inhibition observed following a single
dose of CHK-336 at 60-125 mg.
Accumulation of Maladaptive Tubular Epithelial Cells
(TECs) is Ubiquitous in Chronic Kidney Diseases and Represents a
Common Initiating Mechanism of Disease Progression
Disease-associated maladaptive TECs have been described in
rodent models and are characterized by a failed repair phenotype
that contributes to tubulointerstitial inflammation and fibrosis.
This study explores the significance of maladaptive TECs in the
NURTuRE chronic kidney disease (CKD) cohort by integrating
clinical, histological, transcriptomic and proteomic data from
blood and urine to gain insights into mechanisms of CKD
progression. The NURTuRE consortium biobank comprises patient
samples from a broad range of CKD diagnoses and kidney functional
states with rich clinical data from over 3,500 subjects.
Human gene signatures for two maladaptive tubule subtypes were
identified in human CKD scRNA-Seq datasets. Based on unbiased
analysis, maladaptive tubule signatures were found to be among the
most highly associated with CKD progression in the NURTuRE cohort
and a high maladaptive tubule gene signature score at time of
biopsy was significantly associated with shorter renal event-free
survival in the NURTuRE cohort (304 patients across 12 disease
etiologies). The emergence of maladaptive tubules is associated
with disease progression across multiple CKDs and targeting these
cells may potentially be an effective strategy to preserve kidney
function broadly in CKD.
About Chinook Therapeutics, Inc.Chinook
Therapeutics, Inc. is a clinical-stage biopharmaceutical 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, a phase 3
endothelin receptor antagonist for the treatment of IgA nephropathy
and proteinuric glomerular diseases. Zigakibart (BION-1301), an
anti-APRIL monoclonal antibody, is being evaluated in a phase 1/2
trial for IgA nephropathy. CHK-336, an oral small molecule LDHA
inhibitor for the treatment of hyperoxalurias, is in phase 1
development. In addition, Chinook’s research and discovery efforts
are focused on building a pipeline of precision medicines for rare,
severe chronic kidney diseases with defined genetic and molecular
drivers. Chinook is leveraging insights from kidney single cell RNA
sequencing and large CKD patient cohorts that have been
comprehensively panomically phenotyped, with retained biosamples
and prospective clinical follow-up, to discover and develop
therapeutic candidates with mechanisms of action targeted against
key kidney disease pathways. To learn more, visit
www.chinooktx.com.
Forward-Looking Statements In addition to
historical information, this communication contains forward-looking
statements within the meaning of applicable securities law,
including statements regarding the advancement of its product
candidates and product pipeline, and the clinical development of
its product candidates, including expectations regarding the
results of clinical trials. In addition, when used in this
communication, the words “will,” “expects,” “could,” “would,”
“may,” “anticipates,” “intends,” “plans,” “believes,” “seeks,”
“targets,” “estimates,” “looks for,” “looks to,” “continues” and
similar expressions, as well as statements regarding our focus for
the future, are generally intended to identify forward-looking
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communication involves risks and uncertainties that could cause
actual results to differ materially from these forward-looking
statements. Factors that might cause or contribute to such
differences include, but are not limited to: expected revenues,
cost savings, synergies and other benefits from the proposed merger
might not be realized within the expected time frames or at all and
costs or difficulties relating to integration matters, including
but not limited to employee retention, might be greater than
expected; the requisite regulatory approvals and clearances for the
proposed transaction may be delayed or may not be obtained (or may
result in the imposition of conditions that could adversely affect
the combined company or the expected benefits of the proposed
merger); the requisite approval of Company stockholders may be
delayed or may not be obtained, the other closing conditions to the
proposed merger may be delayed or may not be obtained, or the
merger agreement may be terminated; business disruption may occur
following or in connection with the proposed merger; Novartis or
Chinook’s businesses may experience disruptions due to
transaction-related uncertainty or other factors making it more
difficult to maintain relationships with employees, other business
partners or governmental entities; the milestones for the proposed
CVRs may not be achieved; the possibility that the proposed merger
is more expensive to complete than anticipated, including as a
result of unexpected factors or events; and diversion of
management’s attention from ongoing business operations and
opportunities as a result of the proposed merger or otherwise.
Additional factors that may affect the future results of Novartis
and Chinook are set forth in their respective filings with the U.S.
Securities and Exchange Commission (the “SEC”), including in the
most recently filed annual report of Novartis on Form 20-F,
subsequently filed Current Reports on Form 6-K and other filings
with the SEC, which are available on the SEC’s website at
www.sec.gov, and Chinook’s most recently filed Annual Report on
Form 10-K, subsequent Quarterly Reports on Form 10-Q, Current
Reports on Form 8-K and other filings with the SEC, which are
available on the SEC’s website at www.sec.gov. The risks described
in this communication and in Novartis and Chinook’s filings with
the SEC should be carefully reviewed. Undue reliance should not be
placed on these forward-looking statements, which speak only as of
the date they are made. Novartis and Chinook undertake no
obligation to publicly release any revisions to the forward-looking
statements or reflect events or circumstances after the date of
this communication, except as required by law.
Additional Information and Where to Find It In
connection with the proposed merger between Novartis and Chinook,
Novartis and Chinook intend to file relevant materials with the
SEC, including a preliminary and definitive proxy statement to be
filed by Chinook. The definitive proxy statement and proxy card
will be delivered to the stockholders of Chinook in advance of the
special meeting relating to the proposed merger. CHINOOK’S
STOCKHOLDERS ARE URGED TO READ THE DEFINITIVE PROXY STATEMENT IN
ITS ENTIRETY WHEN IT BECOMES AVAILABLE AND ANY OTHER DOCUMENTS
FILED BY EACH OF NOVARTIS AND CHINOOK WITH THE SEC IN CONNECTION
WITH THE PROPOSED MERGER OR INCORPORATED BY REFERENCE THEREIN
BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION ABOUT THE PROPOSED
TRANSACTION AND THE PARTIES TO THE PROPOSED TRANSACTION. Investors
and security holders will be able to obtain a free copy of the
proxy statement and such other documents containing important
information about Novartis and Chinook, once such documents are
filed with the SEC, through the website maintained by the SEC at
www.sec.gov. Novartis and Chinook make available free of charge at
the Novartis website and Chinook’s website, respectively (in the
“Investors” section), copies of materials they file with, or
furnish to, the SEC. The contents of the websites referenced above
are not deemed to be incorporated by reference into the proxy
statement.
Participants in the Solicitation This document
does not constitute a solicitation of proxy, an offer to purchase
or a solicitation of an offer to sell any securities. Novartis,
Chinook and their respective directors, executive officers and
certain employees may be deemed to be participants in the
solicitation of proxies from the stockholders of Chinook in
connection with the proposed merger. Information regarding the
special interests of these directors and executive officers in the
proposed merger will be included in the definitive proxy statement
referred to above. Security holders may also obtain information
regarding the names, affiliations and interests of the Novartis
directors and executive officers in the Novartis Annual Report on
Form 20-F and Form 20-F/A for the fiscal year ended December 31,
2022, which were filed with the SEC on February 1, 2023, and May
15, 2023, respectively. Security holders may obtain information
regarding the names, affiliations and interests of Chinook’s
directors and executive officers in Chinook’s Annual Report on Form
10-K for the fiscal year ended December 31, 2022, which was filed
with the SEC on February 27, 2023, and its definitive proxy
statement for the 2023 annual meeting of stockholders, which was
filed with the SEC on April 28, 2023. To the extent the holdings of
Chinook’s securities by Chinook’s directors and executive officers
have changed since the amounts set forth in Chinook’s definitive
proxy statement for its 2023 annual meeting of stockholders, such
changes have been or will be reflected on Statements of Change in
Ownership on Form 4 filed with the SEC. Additional information
regarding the interests of such individuals in the proposed merger
will be included in the definitive proxy statement relating to the
proposed merger when it is filed with the SEC. These documents
(when available) may be obtained free of charge from the SEC’s
website at www.sec.gov, the Novartis website at
https://www.novartis.com and Chinook’s website at
https://www.chinooktx.com. The contents of the websites referenced
above are not deemed to be incorporated by reference into the proxy
statement.
Investor Contact:
Noopur Liffick, MPH
Senior Vice President, Investor Relations & Corporate Communications
investors@chinooktx.com
Media Contact:
Kelly North
Senior Manager, Investor Relations & Corporate Communications
media@chinooktx.com
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