Phase 2 trial, expected to begin in 1H 2024,
aims to address the unmet medical need of patients suffering from
stage 2 or 3 acute kidney injury with associated acute hypoxemic
respiratory failure, a condition associated with a high mortality
rate
Development of Auxora in AKI is supported by
both clinical and pre-clinical evidence, including results
from recently completed studies in a rat model of AKI to be
presented at the 29th International Acute Kidney
Injury and Continuous Renal Replacement Therapy Conference in
March
LA
JOLLA, Calif., Feb. 13,
2024 /PRNewswire/ -- CalciMedica, Inc. (CalciMedica
or the Company) (Nasdaq: CALC), a clinical-stage biopharmaceutical
company focused on developing novel calcium release-activated
calcium (CRAC) channel inhibition therapies for acute and chronic
inflammatory and immunologic diseases, today announced the
clearance of its Investigational New Drug (IND) application by the
U.S. Food and Drug Administration (FDA) for the Company's lead
product candidate, Auxora™, a potent and selective small molecule
inhibitor of Orai1-containing CRAC channels, to be evaluated in a
Phase 2 trial in acute kidney injury (AKI) with associated acute
hypoxemic respiratory failure (AHRF). CalciMedica expects to
initiate the trial, named KOURAGE, in the first half of 2024 and
data expected in 2025.
"The IND clearance for the Phase 2 trial of Auxora in severe AKI
is a significant milestone for CalciMedica as we work towards
addressing the serious unmet medical need faced by patients
suffering from this condition," said Rachel
Leheny, Ph.D., Chief Executive Officer of CalciMedica.
"Through KOURAGE, we aim to determine how Auxora can benefit
patients with severe AKI and potentially reduce the high mortality
rate associated with this disease."
AKI is classified as stages 1, 2 and 3 depending on the degree
of kidney injury. In the presence of AHRF, stage 2 and stage 3 AKI,
both classified as severe, put patients at a 50% or greater risk
for death while hospitalized and in the 90 days after
discharge.1 Survivors of severe AKI may develop or
progress to chronic kidney disease, leading to an eventual need for
dialysis. There are approximately 1.1 million patients in
the United States suffering from
stage 2 and 3 AKI over half of whom have associated AHRF. There are
currently no approved therapies for AKI.
KOURAGE is a randomized, double-blind, placebo-controlled study
that will evaluate 150 patients with stage 2 and 3 AKI who have
AHRF and are receiving oxygen by non-invasive mechanical
ventilation, high flow nasal cannula or intermittent mandatory
ventilation (IMV). Patients will be stratified by classification of
stage of AKI as well as the use of IMV. Patients will receive
either a four-hour infusion of Auxora or placebo at 1.25 mL/kg as a
first dose, after which they will receive Auxora or placebo at 1.0
mL/kg at hours 24, 48, 72 and 96. The primary endpoint of the trial
will be evaluation of patients through day 30 to determine days
alive, ventilator-free and dialysis-free. Secondary endpoints will
include a composite of all-cause mortality, decrease in
estimated glomerular filtration rate (eGFR), and the incidence
of dialysis over a period of 90 days, also known as MAKE-90 (Major
Adverse Kidney Events at 90 days).
"The rationale for and design of our Phase 2 KOURAGE study is
supported by our prior clinical trials and pre-clinical studies
that have indicated the potential benefits of Auxora for the
treatment of AKI," said Sudarshan
Hebbar, M.D., Chief Medical Officer of CalciMedica. "After
the learnings from our CARDEA trial revealed that treatment of
severe and critical COVID-19 pneumonia patients with Auxora reduced
the reported incidence of AKI and improved the survival of patients
with kidney disease, we confirmed this potential benefit of Auxora
in specific animal models of AKI. Currently, there are no drugs
that treat AKI, and through KOURAGE, we hope to demonstrate that
treatment with Auxora translates into a treatment option for this
critical acute disease."
AKI is a common consequence of severe COVID-19 pneumonia and in
CalciMedica's CARDEA trial, which studied Auxora in patients with
severe and critical COVID-19 pneumonia, results showed a nearly 40%
reduction in reported AKI in Auxora-treated patients as compared to
placebo-treated patients. In a post-hoc analysis of CARDEA patients
with compromised kidney function (eGFR< 60 mL/min/1.73 m2) at enrollment, the drug was
well tolerated and there was a survival benefit for patients
treated with Auxora compared to those on placebo. Biomarker
analysis from blood samples taken from over 190 CARDEA patients
showed that Auxora increased Angiopoietin-1 while decreasing
Angiopoietin-2, suggesting stabilization of the endothelium and the
potential to treat AKI. Finally, published work from others showed
that elevated serum IL–17 levels, a CRAC channel-mediated cytokine,
were differentially elevated in critically ill patients with stage
2 and 3 AKI when compared to those without AKI, and the elevation
was independently associated with both hospital mortality and
long-term adverse outcomes.2
CalciMedica's initial pre-clinical studies in an
ischemia/reperfusion injury (IRI) model of AKI were encouraging. A
single dose of Auxora after IRI increased GFR by 61% and decreased
mononuclear (inflammatory) cell infiltration by 30%. Further
details from this study and results from CalciMedica's more recent
pre-clinical study of multiple doses of Auxora given over several
days and initiated after a greater time interval following IRI were
also strong and will be presented at the 29th
International AKI & Continuous Renal Replacement
Therapy Conference taking place March
12-15, 2024 in San Diego,
CA.
About AKI
Acute kidney injury (AKI) denotes a sudden
reduction in kidney function, or the organ's ability to clean and
filter the blood, as measured by increased serum creatinine (a
cellular waste product) or decreased urine volume. AKI can result
as a complication of other serious illnesses such as sepsis,
respiratory infections and failure, acute pancreatitis, trauma,
surgery and burns. There are approximately 3.7 million hospitalized
with AKI in the United States each
year. The majority have Stage 1 AKI and recover with
supportive care alone. However, approximately 1.1 million of these
patients advance to stage 2 and stage 3 AKI, over half of whom have
associated AHRF. The risk of serious morbidities and mortality is
significant for advanced stage 2 and stage 3 AKI patients.
There are currently no approved therapies for AKI.
About Auxora™
CalciMedica's lead clinical compound,
Auxora™, is a potent and selective small molecule inhibitor of
Orai1-containing CRAC channels that is being developed for use in
patients with acute inflammatory and immunologic illnesses. CRAC
channels are found on many cell types, including pancreatic acinar
cells, lung endothelium cells and immune system cells, where
aberrant activation of these channels may play a key role in the
pathobiology of acute and chronic inflammatory syndromes. Auxora is
currently being evaluated in: (i) a Phase 2b trial for acute pancreatitis (AP) with
accompanying systemic inflammatory response syndrome (SIRS), called
CARPO, (ii) an investigator-sponsored Phase 1/2 trial called CRSPA
being conducted in pediatric patients with asparaginase-induced
pancreatic toxicity (AIPT) as a side effect of pediatric acute
lymphoblastic leukemia treatment with asparaginase, and (iii) a
Phase 2 dose-ranging pharmacodynamic study in critical COVID-19
patients, with a Phase 2 trial in AKI, called KOURAGE expected to
initiate in the first half of 2024. There are currently no approved
therapies to treat either AP, AIPT or AKI. In previous trials,
patients responded well to Auxora regardless of severity or cause
of disease. CalciMedica is also exploring the potential of Auxora
treatment for other acute indications including acute respiratory
distress syndrome.
About CalciMedica
CalciMedica is a clinical-stage
biopharmaceutical company focused on developing novel CRAC channel
inhibition therapies for inflammatory and immunologic diseases.
CalciMedica's proprietary technology targets the inhibition of CRAC
channels to modulate the immune response and protect against tissue
cell injury, with the potential to provide therapeutic benefits in
life-threatening inflammatory and immunologic diseases for which
there are currently no approved therapies. CalciMedica's lead
product candidate Auxora™, a proprietary, intravenous-formulated
CRAC channel inhibitor, has demonstrated positive and consistent
clinical results in multiple completed efficacy clinical trials.
CalciMedica is currently conducting a Phase 2b trial for a planned 216 patients (called CARPO
– NCT04681066) for AP with SIRS, with topline data expected in the
first half of 2024, as well as supporting the ongoing Phase 1/2
CRSPA AIPT study (called CRSPA – NCT04195347), with
additional data expected by 2H 2024. CalciMedica plans to initiate
a Phase 2 study in AKI in 1H 2024. CalciMedica was founded by
scientists from Torrey Pines Therapeutics and the Harvard CBR
Institute for Biomedical Research, and is headquartered in
La Jolla, CA. For more
information, please visit www.calcimedica.com.
Sources
1 Faubel, Sarah, and Charles L. Edelstein. "Mechanisms and mediators
of lung injury after acute kidney injury." Nature Reviews
Nephrology 12.1 (2016): 48-60.
2 Collett, Jason A., et al. "Serum IL-17 levels are
higher in critically ill patients with AKI and associated with
worse outcomes." Critical Care 26.1 (2022):
107.
Forward-Looking Statements
This communication contains forward-looking statements which
include, but are not limited to, statements regarding CalciMedica's
planned and ongoing clinical trials and the timing, design and
expected patient enrollment thereof, including its planned Phase 2
clinical trial of Auxora in AKI with associated AHRF, its ongoing
Phase 2b trial of Auxora for AP with
accompanying SIRS, its ongoing Phase 1/2 trial of Auxora in
pediatric patients with AIPT; the potential benefits of Auxora for
the treatment of AKI, AP and AIPT; the estimated patient population
in the United States for AKI;
pre-clinical and clinical studies of Auxora in animal models and
critical COVID-19 pneumonia patients, respectively, supporting the
rationale for and the design of CalciMedica's planned Phase 2
KOURAGE trial and the potential benefits of Auxora in AKI; plans to
present results from CalciMedica's pre-clinical studies in an IRI
model of AKI at the 29th International AKI &
Continuous Renal Replacement Therapy Conference; CalciMedica's
development plans for Auxora; the expected timing for release of
data in CalciMedica's ongoing clinical trials. These
forward-looking statements are subject to the safe harbor
provisions under the Private Securities Litigation Reform Act of
1995. CalciMedica's expectations and beliefs regarding these
matters may not materialize. Actual outcomes and results may differ
materially from those contemplated by these forward-looking
statements as a result of uncertainties, risks, and changes in
circumstances, including but not limited to risks and uncertainties
related to: the impact of fluctuations in global financial markets
on CalciMedica's business and the actions it may take in response
thereto; CalciMedica's ability to execute its plans and strategies;
the ability to obtain and maintain regulatory approval for Auxora;
results from clinical trials or preclinical studies may not be
indicative of results that may be observed in the future; potential
safety and other complications from Auxora; the scope progress and
expansion of developing and commercializing Auxora; the size and
growth of the market therefor and the rate and degree of market
acceptance thereof; economic, business, competitive, and/or
regulatory factors affecting the business of CalciMedica generally;
CalciMedica's ability to protect its intellectual property
position; and the impact of government laws and regulations.
Additional risks and uncertainties that could cause actual outcomes
and results to differ materially from those contemplated by the
forward-looking statements are included under the caption "Risk
Factors" in CalciMedica's Quarterly Report on Form 10-Q for the
quarter ended September 30, 2023 and
elsewhere in CalciMedica's subsequent reports on Form 10-K, Form
10-Q or Form 8-K filed with the SEC from time to time and available
at www.sec.gov. These documents can be accessed on CalciMedica's
web page at ir.calcimedica.com/financials-filings/sec-filings.
CalciMedica Contact:
Investors and Media
Argot Partners
Sarah Sutton/Kevin Murphy
calcimedica@argotpartners.com
(212) 600-1902
View original content to download
multimedia:https://www.prnewswire.com/news-releases/calcimedica-announces-fda-clearance-of-ind-application-for-phase-2-trial-of-auxora-for-the-treatment-of-severe-acute-kidney-injury-302060180.html
SOURCE CalciMedica, Inc.
