CalciMedica Announces Publication in JCI Insight of Preclinical Data Supporting CRAC Channel Inhibitor as a Potential Therapy for Pulmonary Arterial Hypertension
CalciMedica (Nasdaq: CALC) announced publication in JCI Insight of preclinical data for its CRAC channel inhibitor CM5480, showing benefit in a monocrotaline (MCT) rat model of pulmonary arterial hypertension (PAH).
Key findings: daily CM5480 at 20 mg/kg reduced pulmonary neomuscularization, right ventricular systolic pressure (RVSP), pulmonary vascular resistance (PVR) and RV hypertrophy; CM5480 restored heart contraction, cardiac output and several disease‑linked gene and metabolic pathways. Combination therapy with ambrisentan or sildenafil produced greater improvements than either SOC agent alone. Authors include CalciMedica leaders and PAH researchers from Inserm and Université Paris‑Saclay.
The release links these results to CalciMedica's lead program Auxora and the ongoing Phase 2 KOURAGE trial in AKI, with data expected in 1H 2026.
CalciMedica (Nasdaq: CALC) ha pubblicato su JCI Insight dati preclinici sul suo inibitore del canale CRAC CM5480, che mostrano benefici in un modello di ipertensione arteriosa polmonare (PAH) indotto da monocrotalina (MCT) nel ratto.
Scoperte chiave: CM5480 somministrato quotidianamente a 20 mg/kg ha ridotto la neomuscolarizzazione polmonare, la pressione sistolica del ventricolo destro (RVSP), la resistenza vascolare polmonare (PVR) e l'ipertrofia del ventricolo destro; CM5480 ha ripristinato la contrazione cardiaca, la gittata cardiaca e diverse vie geniche e metaboliche legate alla malattia. La terapia combinata con ambrisentan o sildenafil ha prodotto miglioramenti più grandi rispetto a ciascun agente SOC da solo. Gli autori includono leader di CalciMedica e ricercatori PAH di Inserm e Université Paris‑Saclay.
Il comunicato collega questi risultati al programma principale Auxora di CalciMedica e al trial di fase 2 KOURAGE per l'AKI, con i dati previsti nella 1H 2026.
CalciMedica (Nasdaq: CALC) anunció la publicación en JCI Insight de datos preclínicos sobre su inhibidor del canal CRAC CM5480, que muestran beneficios en un modelo de hipertensión arterial pulmonar (PAH) en ratas inducido por monocrotalina (MCT).
Hallazgos clave: CM5480 administrado diariamente a 20 mg/kg redujo la neomuscularización pulmonar, la presión sistólica del ventrículo derecho (RVSP), la resistencia vascular pulmonar (PVR) y la hipertrofia del ventrículo derecho; CM5480 restauró la contracción cardíaca, el gasto cardíaco y varias vías génicas y metabólicas asociadas a la enfermedad. La terapia de combinación con ambrisentan o sildenafil produjo mejoras mayores que cualquiera de los agentes SOC por sí solo. Los autores incluyen a líderes de CalciMedica y a investigadores de PAH de Inserm y la Université Paris‑Saclay.
El comunicado relaciona estos resultados con el programa principal Auxora de CalciMedica y el ensayo de Fase 2 KOURAGE en AKI, con datos esperados en la 1H 2026.
CalciMedica (Nasdaq: CALC)는 JCI Insight에 CRAC 채널 억제제 CM5480의 전임상 데이터를 발표했으며, 단당비소(MCT)에 의해 유도된 흉부동맥 고혈압(PAH) 쥐 모델에서 이점이 있음이 확인되었다.
주요 발견: 매일 CM5480을 20 mg/kg로 투여하면 폐 혈관 신생화가 감소하고 우심실 수축기 압력(RVSP), 폐혈관 저항(PVR), 우심실 비대가 감소했다; CM5480은 심장의 수축력과 심박출량 및 질병 관련 여러 유전자 및 대사 경로를 회복시켰다. ambrisentan 또는 sildenafil과의 병용 요법은 단독 SOC 제제보다 더 큰 개선을 보였다. 저자들은 CalciMedica의 리더들과 Inserm 및 Université Paris‑Saclay의 PAH 연구자들을 포함한다.
발표는 이 결과를 CalciMedica의 주요 프로그램 Auxora와 진행 중인 AKI의 2상 KOURAGE 임상시험으로 연결시키며, 데이터는 1H 2026에 예상된다.
CalciMedica (Nasdaq : CALC) a publié dans JCI Insight des données précliniques sur son inhibiteur du canal CRAC, CM5480, montrant des bénéfices dans un modèle de hipertension artérielle pulmonaire (PAH) chez le rat induit par la monocrotaline (MCT).
Principales conclusions : l'administration quotidienne de CM5480 à 20 mg/kg a réduit la néomuscularisation pulmonaire, la pression systolique du ventricule droit (RVSP), la résistance vasculaire pulmonaire (PVR) et l'hypertrophie du ventricule droit ; CM5480 a restauré la contraction cardiaque, le débit cardiaque et plusieurs voies génétiques et métaboliques liées à la maladie. Une thérapie de combinaison avec ambrisentan ou sildenafil a produit des améliorations supérieures à celles de n'importe quel agent SOC pris seul. Les auteurs incluent des responsables de CalciMedica et des chercheurs PAH de l'Inserm et de l'Université Paris-Saclay.
Le communiqué relie ces résultats au programme principal Auxora de CalciMedica et au essai de phase 2 KOURAGE dans l'AKI, avec des données attendues dans le 1er semestre 2026.
CalciMedica (Nasdaq: CALC) kündigte die Veröffentlichung in JCI Insight von präklinischen Daten zu ihrem CRAC-Kanal-Inhibitor CM5480 an, die einen Nutzen in einem Monocrotalin (MCT)-Rattenmodell der pulmonal-arteriellen Hypertension (PAH) zeigen.
Zentrale Ergebnisse: Tägliche Gabe von CM5480 mit 20 mg/kg reduzierte die pulmonale Neomuskularisierung, RVSP, den pulmonalen Gefäßwiderstand (PVR) und die Rechtsherzhypertrophie; CM5480 stellte die Kontraktion des Herzens, das Herzzeitvolumen und mehrere krankheitsbezogene Gen- und Stoffwechselwege wieder her. Die Kombinationstherapie mit Ambrisentan oder Sildenafil führte zu größeren Verbesserungen als jeder SOC-Einzelwirkstoff. Die Autoren umfassen CalciMedica-Führungskräfte und PAH-Forscher von Inserm und der Université Paris‑Saclay.
Die Pressemitteilung verbindet diese Ergebnisse mit CalciMedicas Lead-Programm Auxora und der laufenden Phase-2-Studie KOURAGE bei AKI, mit Daten, die in der 1H 2026 erwartet werden.
CalciMedica (بورصة ناسداك: CALC) أعلنت نشر في JCI Insight لبيانات ما قبل السريرية عن مثبّت قناة CRAC CM5480، التي تُظهر فائدة في نموذج فئران ارتفاع ضغط الدم الرئوي PAH الناتج عن monocrotaline (MCT).
النتائج الرئيسية: أعطِ CM5480 يومياً بجرعة 20 mg/kg خفض التصنيع الشرياني الرئوي، ضغط البطين الأيمن الانقباضي (RVSP)، المقاومة الوعائية الرئوية (PVR) وتضخم RV؛ استعاد CM5480 انقباض القلب، الناتج القلبي وخ pathways جينية وميتابولية مرتبطة بالمرض. العلاج بالتركيبة مع ambrisentan أو sildenafil أحدث تحسنات أكبر من أي دواء SOC بمفرده. المؤلفون يشملون قيادات CalciMedica وباحثين PAH من Inserm وجامعة Paris‑Saclay.
يُربط البيان هذه النتائج ببرنامج CalciMedica الرائد Auxora وب trial المرحلة الثانية KOURAGE في AKI، مع توقع بيانات 1H 2026.
- Daily CM5480 dosing at 20 mg/kg reduced RVSP in MCT rats
- CM5480 decreased pulmonary vascular resistance and neomuscularization
- Combination with ambrisentan or sildenafil produced greater benefit
- Results are limited to preclinical MCT rat models; human translation is unproven
- No clinical PAH efficacy or safety data reported for CM5480 yet
Insights
Preclinical JCI Insight data show CM5480 reduces pulmonary hypertension and improves right‑heart remodeling; clinical relevance remains unproven.
CM5480, a selective Orai1/CRAC channel inhibitor, produced statistically significant improvements in pulmonary neomuscularization, RV systolic pressure, pulmonary vascular resistance, RV hypertrophy, and measures of cardiac function in an MCT rat model when given at 20 mg/kg. Combination dosing with ambrisentan or sildenafil delivered larger improvements than either SOC agent alone, supporting a complementary mechanism to existing PAH therapies.
Key dependencies and risks include translation to humans and regulatory proof: these results are preclinical only and do not establish safety or efficacy in patients. The company links these findings to its clinical-stage program (Auxora) and notes Phase 2 KOURAGE data expected in
Preclinical data support CRAC channel inhibitor, CM5480, as a potential first-in-class, differentiated therapy for pulmonary arterial hypertension (PAH), both as monotherapy and in combination with existing treatments
Cardiac benefit supports the mechanistic rationale for CRAC channel inhibition in acute kidney injury (AKI), being evaluated in the Phase 2 KOURAGE trial with data expected in 1H 2026
The study, entitled, " Combination of Orai1 Inhibitor CM5480 with Specific Therapy Mitigates Pulmonary Hypertension and Its Cardiac Dysfunction ," was co-authored by Sudarshan Hebbar, M.D., CMO of CalciMedica, and Kenneth A. Stauderman, Ph.D., co-Founder and CSO of CalciMedica. Experiments were conducted by Fabrice Antigny, Ph.D., Director of Research at the French National Institute of Health and Medical Research (Inserm), within the department of Marc Humbert, M.D., Ph.D., Professor of Respiratory Medicine at Université Paris-Saclay and Head of the Pneumology Department at Bicêtre Hospital, both also co-authors of the paper and leading PAH researchers.
PAH is a rare pulmonary vascular disease characterized by progressive narrowing and thickening of pulmonary arteries, resulting in chronic elevation in pulmonary artery pressure and pulmonary vascular resistance (PVR), leading to right ventricular (RV) hypertrophy, RV dysfunction (RVD), RV failure (RVF), and eventually death. Current standard of care (SOC) therapies for patients with PAH target several key disease-related signaling pathways but do not address the Orai1 pathway. These SOC therapies are not curative and do not directly target RV function, which is the primary determinant of prognosis in PAH. It is important, therefore, to develop new treatment strategies targeting both RV function and pulmonary vascular disease. Previous preclinical studies have demonstrated that dysregulation of calcium entering pulmonary smooth muscle and endothelial cells through CRAC channels is a critical contributor to the pathogenesis of PAH and RVD. Furthermore, translational studies have found that Orai1 expression is increased in pulmonary arterial smooth muscle cells and pulmonary venous smooth muscle cells in patients with pulmonary veno-occlusive disease (PVOD), a rare form of PAH.
"Despite recent improvements in the treatment of PAH, it remains a severe disease for which there is no cure, and patients often progress to RVF," said Dr. Humbert. "We continue to search for new potential drugs with novel mechanisms that can enhance current treatment strategies. Our translational work has suggested that CRAC channel inhibition could offer such a mechanism, and the results from these in vitro and in vivo models further support this hypothesis."
In the study, investigators evaluated CM5480 as both a monotherapy and combination therapy with two SOC PAH therapies in an animal model of PAH. Pulmonary hypertension was induced in rats by monocrotaline (MCT) exposure and then CM5480 was administered daily at 20 mg/kg. Between day 14 and day 21 in the study, the rats were treated with CM5480, either alone or in combination with ambrisentan, an endothelin-1 receptor antagonist, or with sildenafil, a phosphodiesterase type 5 inhibitor.
The study found significant reductions in pulmonary neomuscularization, RV systolic pressure (RVSP), PVR, and RV hypertrophy in MCT rats treated with CM5480 as a monotherapy. RV remodeling was also reduced in CM5480-treated rats, and several pathways and functions that become dysregulated in animals with PAH were restored or improved. These included heart contraction and cardiac output, gene expression profiles impacted by the disease, DNA repair, and metabolic pathways. Dual therapies combining CM5480 with either ambrisentan or sildenafil yielded significantly greater benefits than the respective therapies administered independently, including more pronounced reductions of RVSP and RV hypertrophy, as well as more prominent improvements in PVR and pulmonary vessel and RV remodeling.
"Given PAH is a complex disease involving several dysregulated signaling pathways, the most effective treatment will likely involve a combination of drugs," said Dr. Antigny. "These preclinical results show that targeting Orai1 delivered several key benefits: it improved pulmonary vascular remodeling by reducing pulmonary arterial smooth muscle cell and pulmonary endothelial cell dysfunctions; it improved RVD; and combination therapy with CM5480 provided significantly greater benefits in reducing pulmonary arterial remodeling and improving cardiac function compared to monotherapies. This suggests Orai1 inhibition as a potential new therapeutic approach for PAH."
"Beyond PAH, these results have implications for our clinical programs, suggesting CRAC channel inhibition may directly improve the RVD seen in roughly half of patients with sepsis, the leading cause of AKI," said Dr. Hebbar of CalciMedica. "RVD in septic patients is associated with a three-fold increase in 28-day mortality. If CRAC channel inhibitors such as Auxora improve RVD, this may translate into clinical benefit for patients in our ongoing Phase 2 KOURAGE trial evaluating Auxora in severe AKI with acute hypoxemic respiratory failure."
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™ has demonstrated positive and consistent clinical results in multiple completed efficacy clinical trials and been well-tolerated in over 350 critically ill patients dosed. CalciMedica has announced data for a Phase 2b trial (called CARPO –
NCT04681066
) in patients with acute pancreatitis (AP) and accompanying systemic inflammatory response syndrome (SIRS) and for a Phase 2 trial (called CARDEA –
NCT04345614
) in patients with COVID pneumonia. The Company is currently conducting a Phase 2 trial (called KOURAGE –
NCT06374797
) in patients with acute kidney injury (AKI) with associated respiratory failure, with data expected in the first half of 2026. For more information, please visit
www.calcimedica.com
.
Forward-Looking Statements
This communication contains forward-looking statements which include, but are not limited to CalciMedica's planned and ongoing clinical trials and the timing, design, expected patient enrollment thereof and the expected timing for updates and the release of data from its Phase 2 KOURAGE trial of Auxora in AKI with associated respiratory failure in the first half of 2026; and the potential of CalciMedica's proprietary technology to provide therapeutic benefits in PAH and other acute and chronic inflammatory and immunologic diseases such as AKI and AP. 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; the impact of government laws and regulations; and CalciMedica's financial position and need for additional capital. 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, 2025, being filed with the Securities and Exchange Commission (SEC) later today, 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
. The forward-looking statements contained herein are made as of the date hereof, and CalciMedica undertakes no obligation to update them after this date, except as required by law.
Contact Information
Kevin Murphy
calcimedica@argotpartners.com
(212) 600-1902
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SOURCE CalciMedica, Inc.
FAQ
What did CalciMedica (CALC) announce on November 12, 2025 about CM5480?
What dose of CM5480 was used in the preclinical PAH study reported by CALC?
How did CM5480 perform in combination with standard PAH therapies in the study?
Does the CM5480 publication mean CalciMedica has clinical PAH data for CALC?
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