Therapeutic treatment with Auxora shown to
hasten the recovery of kidney function and improve survival in a
rat model of acute kidney injury (AKI)
Preclinical results are consistent with
clinical observations made with Auxora, supporting the KOURAGE
trial in patients with severe AKI that will start enrolling in 2Q
2024
LA
JOLLA, Calif., March 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, last evening presented data
from preclinical studies of Auxora™ in acute kidney injury (AKI) at
the 29th International Acute Kidney Injury and
Continuous Renal Replacement Therapy Conference (AKI & CRRT) in
San Diego, CA. David Basile, Ph.D., Professor of Anatomy, Cell
Biology and Physiology at Indiana
University, gave an oral and poster presentation entitled
"The Store-Operated Calcium Channel Inhibitor Auxora Improves Renal
Function Following Ischemia-Induced Acute Kidney Injury in
Rats."
"At AKI & CRRT, Prof. Basile discussed the most recent
preclinical study of Auxora in an acute kidney injury model that
used a treatment regimen of three daily doses of drug started six
hours after ischemic injury, which resembles the dosing in our
clinical protocol. The positive results from this study build on
prior preclinical data and indicate that inhibiting Orai1 activity
in an AKI model improves kidney function," said Kenneth Stauderman, Ph.D., Founder and Chief
Scientific Officer of CalciMedica. "In rats with ischemic kidney
injury akin to Stage 2 AKI, Auxora was shown to provide nearly
complete recovery of kidney function, as evidenced by improved
glomerular filtration rate (GFR) at 72 hours after injury, while
placebo-treated animals showed little improvement in GFR. In rats
with kidney injury akin to Stage 3 AKI, the rats treated with
placebo died while those on Auxora survived and showed modest
recovery of GFR. We are excited as these studies support clinical
observations of Auxora that suggest the drug may be beneficial for
AKI patients."
AKI is a serious acute critical illness and denotes a sudden
reduction in kidney function, or the organ's ability to clean and
filter the blood, that results from a complication of critical
illness. These animal model studies support observations from
CalciMedica's clinical trials, particularly CARDEA, the Company's
Phase 2 trial in patients with severe and critical COVID-19
pneumonia, where AKI was a relatively common co-morbidity or a
common sequela of the disease. Compared to placebo-treated
patients, Auxora-treated patients in CARDEA had lower levels of key
biomarkers associated with kidney injury, lower incidence of
treatment-emergent AKI and reduced mortality in those patients with
decreased kidney function at the time of treatment. Additionally,
previous preclinical studies conducted by CalciMedica and others
suggest that Orai1 activity contributes to the activation and
infiltration of pro-inflammatory Th17 cells in the kidney, which is
associated with the development of AKI. CalciMedica has also shown
that the active ingredient in Auxora, zegocractin, inhibits release
of IL-17, which is a key pro-inflammatory cytokine from Th17
cells.
"As we initiate KOURAGE, our Phase 2 trial of Auxora in severe
AKI patients with associated acute hypoxemic respiratory failure,
we are encouraged to have additional supporting data showing that
Auxora has beneficial activity in animal models of AKI," said
Sudarshan Hebbar, M.D., Chief
Medical Officer of CalciMedica. "Patients randomized in KOURAGE
will have Stage 2 and Stage 3 AKI, so the results from Prof.
Basile's recent preclinical study, most notably the survival
benefit, are particularly meaningful. Severe AKI in the presence of
respiratory failure has a mortality of approximately 50% and we are
heartened to see that Auxora has the potential for a positive
impact on patients with this devastating disease."
Data Presented at the AKI & CRRT Conference
The data presented at AKI & CRRT was from a series of
studies referred to as Study 1 and Study 2. In Study 1, AKI was
induced in a rat model through ischemia reperfusion injury (I/R), a
transient ligation of the renal artery, while control animals
underwent sham-surgery. Within 30 minutes of injury, the animals
were treated with a single intravenous infusion of either 16 mg/kg
of Auxora or placebo over a period of 4 hours. GFR, an important
indicator of kidney function, was evaluated at 24 hours
post-injury. Study 2 evaluated recovery of kidney function
following I/R similar to Study 1 but varying in intensity to mimic
different severity of disease. In Study 2, GFR was measured 2-4
hours after injury but before treatment, and treatment with 16
mg/kg of Auxora or placebo was administered at 6, 24 and 48 hours
post-injury, with GFR again evaluated at 72 hours.
Results from Study 1 showed that at 24 hours post-injury, GFR
was significantly higher in rats treated with Auxora 30 minutes
after injury versus placebo (61%, p<0.05). Additionally, animals
treated with Auxora showed a reduction in Th17 cells in the kidney
of approximately 50% as compared to those treated with placebo. In
Study 2, in a group of animals with initial GFR reductions of
approximately 50%, similar to Stage 2 AKI, GFR at 72 hours was
significantly greater in Auxora-treated animals as compared to
placebo-treated animals (0.81±0.03 vs. 0.47±0.04 ml/min/100g
respectively; p<0.001). In a group of animals with GFR
reductions ≥66%, similar to Stage 3 AKI, placebo-treated rats
experienced 100% mortality by 72 hours while Auxora-treated rats
had no mortality at 72 hours and were stable, showing modest
recovery of kidney function. These results indicate that Auxora has
the ability to hasten the recovery of kidney function and improve
survival in rat models of AKI.
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 critical illness such as sepsis, pneumonia and
acute pancreatitis, and other causes such as trauma, surgery and
burns. There are approximately 3.7 million patients 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 acute hypoxemic respiratory failure (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 KOURAGE
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).
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 immune system
cells, endothelium cells and pancreatic acinar 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,
(iii) a Phase 2 dose-ranging pharmacodynamic study in critical
COVID-19 patients and (iv) a Phase 2 trial in AKI with associated
AHRF, 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 its Phase 2
KOURAGE 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.
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, expected patient enrollment thereof
and the expected timing for the release of data from those trials,
including its planned Phase 2 KOURAGE 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, and its Phase
2 dose-ranging pharmacodynamic study in critical COVID-19 patients;
the potential benefits of Auxora for the treatment of AKI, AP and
AIPT; the potential of Auxora for the treatment of other acute
indications including acute respiratory distress syndrome; the
potential of CalciMedica's proprietary technology to provide
therapeutic benefits in life-threatening inflammatory and
immunologic diseases; pre-clinical and clinical studies of
Auxora supporting the rationale for and design for the KOURAGE
trial and the estimated patient population in the United States for AKI. 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
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SOURCE CalciMedica, Inc.