A Phase I/Ib Study of JNJ-75276617 in Combination With Conventional Chemotherapy for Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias Harboring KMT2A, NPM1, or Nucleoporin Gene Alterations

The purpose of this study is to determine the recommended Phase 2 dose(s) (RP2Ds) of JNJ-75276617 in combination with a conventional chemotherapy backbone in pediatric and young adult participants with relapsed/refractory acute leukemia harboring histone-lysine N-methyltransferase 2A1 ([KMT2A1], nucleophosmin 1 gene (NPM1), or nucleoporin alterations in Part 1 (Dose Escalation) and to further evaluate safety at the RP2D(s) of JNJ-75276617 in combination with chemotherapy in pediatric and young adult participants with relapsed/refractory acute leukemia harboring KMT2A1, NPM1, or nucleoporin alterations and safety at the RP2D(s) of JNJ-75276617 as monotherapy in a select low burden of disease cohort in Part 2 (Dose Expansion).

Start Date26 Dec 2025

Sponsor / Collaborator

Janssen Research & Development LLC

NCT06124157 / Not yet recruitingPhase 3IIT

A Randomized International Phase 3 Trial of Imatinib and Chemotherapy With or Without Blinatumomab in Patients With Newly-Diagnosed Philadelphia Chromosome-Positive or Philadelphia Chromosome-Like ABL-Class B-Cell Acute Lymphoblastic Leukemia

This phase III trial compares the effect of the combination of blinatumomab with dasatinib and standard chemotherapy versus dasatinib and standard chemotherapy for treating patients with Philadelphia chromosome positive (PH+) or Philadelphia chromosome-like (Ph-Like) ABL-class B-Cell acute lymphoblastic leukemia (B-ALL). Blinatumomab is a bispecific antibody that binds to two different proteins-one on the surface of cancer cells and one on the surface of cells in the immune system. An antibody is a protein made by the immune system to help fight infections and other harmful processes/cells/molecules. Blinatumomab may bind to the cancer cell and a T cell (which plays a key role in the immune system's fighting response) at the same time. Blinatumomab may strengthen the immune system's ability to fight cancer cells by activating the body's own immune cells to destroy the tumor. Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Giving blinatumomab and dasatinib in combination with standard chemotherapy may work better in treating patients with PH+ or Ph-Like ABL-class B-ALL compared to dasatinib and chemotherapy alone.

Start Date28 Feb 2025

Sponsor / Collaborator

National Cancer Institute

NCT06317662 / Not yet recruitingPhase 2IIT

A Phase 2 Study of Blinatumomab in Combination With Chemotherapy for Infants With Newly Diagnosed Acute Lymphoblastic Leukemia With Randomization of KMT2A-Rearranged Patients to Addition of Venetoclax

This phase II trial tests the addition of venetoclax and/or blinatumomab to usual chemotherapy for treating infants with newly diagnosed acute lymphoblastic leukemia (ALL) with a KMT2A gene rearrangement (KMT2A-rearranged [R]) or without a KMT2A gene rearrangement (KMT2A-germline [G]). Venetoclax is in a class of medications called B-cell lymphoma-2 (Bcl-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding venetoclax and/or blinatumomab to standard chemotherapy may be more effective at treating patients with ALL than standard chemotherapy alone, but it may also cause more side effects. This clinical trial evaluates the safety and effectiveness of adding venetoclax and/or blinatumomab to chemotherapy for the treatment of infants with KMT2A-R or KMT2A-G ALL.

Start Date26 Jan 2025

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Pegaspargase

100 Translational Medicine associated with Pegaspargase

100 Patents (Medical) associated with Pegaspargase

513

Literatures (Medical) associated with Pegaspargase

31 Dec 2024·Hematology

Phase II study of pegaspargase, etoposide, gemcitabine (PEG) followed by involved-field radiation therapy in early-stage extranodal natural killer/T-cell lymphoma

Article

Author: Yan, Zhimin ; Wang, Hua ; Bai, Shenrui ; Fu, Bibo ; Zhu, Lewei ; Feng, Demei ; Liang, Yang ; Xia, Zhongjun ; Gale, Robert Peter

OBJECTIVEThe prognosis of extra-nodal NK/T cell lymphoma (ENKTL) is poor, and the optimal therapy remains controversial. This study aims to evaluate the safety and efficacy of a new combined modality therapy.METHODSPhase-2 study of pegaspargase, etoposide and gemcitabine (PEG) combined with involved field radiation therapy (IFRT) in newly-diagnosed patients with early-stage ENKTL. Patients received 4 course of PEG followed by IFRT. The primary endpoints were complete response (CR), partial response (PR), and objective response rate (ORR) after IFRT. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and adverse events.RESULTS34 consecutive patients with Ann Arbor stage I/II were enrolled. 3 patients progressed on PEG, while the remaining 31 received IFRT. The ORR was 88.2% (30/34), included 28 (82.4%) complete and 2 (5.8%) partial responses. With a median follow-up of 56.0 months (Interquartile Range [IQR], 36.0-66.9 months), the estimated 5-year PFS and OS were 87.4% (95% Confidence Interval [CI],69.5%-94.8%) and 97.1% (95%CI, 80.1%-99.6%), respectively. Most adverse events were hematological and easily managed.CONCLUSIONSPEG followed by IFRT is a safe and effective initial therapy for early-stage ENKTL, demonstrating impressive PFS and OS rates. This promising approach warrants further validation in a randomized controlled trial (Registered at Clinicaltrials.gov NCT02705508).Trial registration: ClinicalTrials.gov identifier: NCT02705508.

25 Nov 2024·Future Oncology

CASPER: A Phase I trial combining calaspargase pegol-mnkl and cobimetinib in pancreatic cancer

Article

Author: Nelson, Katherine ; Roy, Preeyam ; Lessenich, Christopher ; Brody, Jonathan R ; Pegna, Guillaume ; Chen, Emerson Y ; Sheppard, Brett ; Kardosh, Adel ; Fahlman, Anne ; Vo, Johnson ; Ventura, Diane ; Rajagopalan, Brindha ; Foster, Bryan ; Sears, Rosalie C ; Fennell, Francesca ; Goodyear, Shaun M ; Taber, Erin ; Mills, Gordon B ; Edmerson, Exodus ; Guimaraes, Alexander ; Keith, Dove ; Jackson, Anna ; Brinkerhoff, Brian ; Lim, Jeong-Youn ; Ronai, Ze'ev A ; Lopez, Charles D ; Gingerich, Tasha

Asparagine synthetase (ASNS) catalyzes the biosynthesis of asparagine from aspartate and glutamine. Cells lacking ASNS, however, are auxotrophic for asparagine. Use of L-asparaginase to promote asparagine starvation in solid tumors with low ASNS levels, such as pancreatic ductal adenocarcinoma (PDAC), is a rationale treatment strategy. However, tumor cell resistance to L-asparaginase has limited its clinical utility. Our preclinical studies show that RAS/MAPK signaling circumvents L-asparaginase-induced tumor killing, but L-asparaginase and MEK inhibition potentiated tumor killing; suggesting that this combination may provide meaningful clinical benefit to patients with PDAC. This Phase I trial (NCT05034627) will evaluate the safety and tolerability of the MEK inhibitor, cobimetinib, in combination with pegylated L-asparaginase, L calaspargase pegol-mknl, in patients with locally-advanced or metastatic PDAC.

02 Oct 2024·Pediatric Hematology and Oncology

Hepatic veno-occlusive disease with asparaginase products: a review of cases reported to the FDA adverse event reporting system and published in the literature

Review

Author: Jones, S. Christopher ; Rabik, Cara A. ; Cheng, Connie ; Nayernama, Afrouz ; Dores, Graça M.

Multiple asparaginase products have been approved by the United States (US) Food and Drug Administration (FDA) for the treatment of acute lymphoblastic leukemia in pediatric and adult patients. Hepatic veno-occlusive disease (VOD) is a potentially life-threatening disorder resulting from damage to the liver sinusoidal endothelial cells. To evaluate this safety concern with asparaginase (i.e. Asparlas, Oncaspar, Rylaze, and Erwinaze) use, we performed a postmarketing review of hepatic VOD reports retrieved from the FDA Adverse Event Reporting System database and literature with these four products. We identified 55 cases of hepatic VOD following exposure to asparaginase products. The median time to onset of hepatic VOD from the first dose of asparaginase was 18 days (interquartile range 13-24 days). Notably, 80% (44/55) of cases reported grades 3-5 VOD per the Common Terminology Criteria for Adverse Events. Although patients received asparaginase with standard chemotherapeutic agents known to induce VOD, case-level data indicates that asparaginase products may have contributed to hepatic VOD. Asparaginase products are associated with hepatotoxicity and thrombosis, suggesting a plausible mechanism for asparaginase-induced hepatic VOD. Based on the totality of data, including temporality and biologic plausibility, we determined hepatic VOD to be a class effect with asparaginase products. These data contributed to the addition of hepatic VOD to the hepatoxicity warning in the US Prescribing Information for asparaginase class products.

News (Medical) associated with Pegaspargase

28 Mar 2024

·www.biospace.com

CalciMedica Reports 2023 Financial Results and Provides Clinical & Corporate Updates

Enrollment in CARPO, Phase 2b trial of Auxora™ in acute pancreatitis (AP), on track with topline data expected in 2Q 2024 Auxora granted Investigational New Drug clearance by the FDA for Phase 2 trial in severe acute kidney injury (AKI); KOURAGE initiating in 2Q 2024 CRSPA Phase 1/2 trial of Auxora in asparaginase-induced pancreatic toxicity (AIPT) expanded and progressing to Phase 2 following initial patient cohort results presented at ASH 2023 Following a private placement financing in January, Company's cash position is expected to fund operations into 2H 2025 LA JOLLA, Calif., March 28, 2024 /PRNewswire/ -- CalciMedica Inc. ("CalciMedica") (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 illnesses, today reported financial results for the year ended December 31, 2023. "Over the course of 2023 and into this year, we have continued to build upon CalciMedica's clinical and financial strength, which has culminated in several recent achievements and has positioned us to execute on key milestones in 2024 including presenting topline data from our ongoing CARPO trial in acute pancreatitis in the second quarter," said Rachel Leheny, Ph.D., Chief Executive Officer of CalciMedica. "Importantly, the support from leading life science investors in our recent private placement financing allows us to initiate KOURAGE, our Phase 2 trial of Auxora in severe AKI patients, and to continue to progress other key programs in our pipeline." Recent Clinical and Preclinical Updates and Anticipated Milestones: Phase 2b CARPO enrollment on track and topline data expected in 2Q: Enrollment in CARPO, CalciMedica's randomized, double-blind, placebo-controlled Phase 2b trial of Auxora™ in AP patients, is expected to be complete and topline data from the trial to be announced in the second quarter of 2024. IND application for Auxora in AKI approved and Phase 2 KOURAGE trial initiation underway: In February 2024, CalciMedica received clearance of its Investigational New Drug (IND) application by the U.S. Food and Drug Administration (FDA) for Auxora to be evaluated in a Phase 2 trial in AKI with associated acute hypoxemic respiratory failure (AHRF) which has been named KOURAGE. CalciMedica expects to enroll the first patient in KOURAGE in the second quarter of 2024, with data expected in 2025. Data from initial cohort of Phase 1/2 CRSPA study with St. Jude presented at ASH: In December 2023, CalciMedica's collaborators at St. Jude Children's Research Hospital presented data from the initial cohort of the Phase 1/2 CRSPA study of Auxora in AIPT at the 65th Annual American Society of Hematology Meeting & Exposition (ASH) in San Diego, CA. The data from the initial cohort compared to a historical matched control group showed fewer hospital and ICU days for treated patients. No patients in the CRSPA study required total parenteral nutrition, compared to 68.8% in the historical matched control group, who required 27 days of nutritional support on average. 27% of patients in the matched control group had greater than 30% pancreatic necrosis at 30 days compared to none of the Auxora-treated patients. CRSPA study expanded and continuing to enroll in Phase 2 portion of trial: The CRSPA study has been expanded to additional sites, the dose used in the initial cohort has been established as the recommended Phase 2 dose and a target total trial enrollment has been set at 24. Data is expected in 2025. Preclinical data presented at AKI & CRRT: In March 2024, CalciMedica presented data from preclinical studies of Auxora in AKI at the 29th International Acute Kidney Injury and Continuous Renal Replacement Therapy Conference (AKI & CRRT) in San Diego, CA. The results of the studies indicate that Auxora has the ability to hasten the recovery of kidney function and improve survival in rat models of AKI through inhibiting the Orai1 channels on Th17 and endothelial cells. 2023 Financial Results and Corporate Updates: As of December 31, 2023, CalciMedica had $11.2 million in cash, cash equivalents and short-term investments. In January 2024, CalciMedica completed a private placement of securities to new and existing investors for up to approximately $54 million in gross proceeds that includes initial upfront funding of $20.4 million and up to an additional approximately $33.1 million upon exercise of accompanying warrants. CalciMedica intends to use the upfront net proceeds from the private placement to fund the Company's ongoing Phase 2 clinical trials for Auxora in AP and AKI. As of the end of the first quarter of 2024, the Company expects its cash, cash equivalents and short-term investments to be approximately $25.5 million, which, based on its current operating plan, it expects to be sufficient to fund its operations into the second half of 2025. Total operating expenses were $38.1 million for the year ended December 31, 2023, which included $16.2 million of one-time charges of which $10.5 million was non-cash, related to accelerated vesting of stock options and severance for employees of Graybug Vision, Inc. at the time of the reverse merger with Graybug. Net loss was $34.4 million, or $7.66 per share (basic and diluted) for the year ended December 31, 2023. 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) a Phase 2 trial in acute kidney injury (AKI) with associated acute hypoxemic respiratory failure (AHRF), called KOURAGE, expected to initiate in the second quarter of 2024 and (iii) 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. There are currently no approved therapies to treat either AP, AKI or AIPT. 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 CARPO and AP CARPO is an international, randomized, double-blind, placebo-controlled, dose-ranging trial intended to establish Auxora's dose-response and efficacy in AP with accompanying SIRS. It is expected to enroll 216 patients. AP can be a life-threatening condition where the pancreas becomes inflamed, sometimes leading to pancreatic cell death or necrosis, systemic inflammation, organ failure and death. There are an estimated 275,000 hospitalizations for AP annually in the United States, of which approximately 40% present with SIRS, which can compromise the function of other tissues or organs, especially the lungs. Organ failure is responsible for much of the mortality seen in AP. There is currently no approved therapy for AP. Details of the CARPO trial are available on clinicaltrials.gov (NCT04681066). About KOURAGE and 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). AKI denotes a sudden reduction in kidney function, or the organ's ability to clean and filter the blood. 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 with approximately 1.1 million of these patients advancing 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 CRSPA and AIPT CRSPA is an investigator-sponsored Phase 1/2 trial being conducted in pediatric acute lymphoblastic leukemia (ALL) patients with AIPT, which is acute pancreatitis toxicity caused by the administration of asparaginase (such as Oncaspar and Rylaze). CalciMedica believes that the CRSPA trial has defined an optimal pediatric dose for Auxora in this setting and the trial is currently being expanded to additional sites and is expected to enroll 24 patients. Approximately 3,000 pediatric patients are treated for ALL in the United States each year and treatment with asparaginase triggers the development of AIPT in 7-10% of these patients, with approximately half developing pancreatic necrosis and/or pseudocysts. There are currently no approved therapies for AIPT. Details of the CRSPA trial are available on clinicaltrials.gov (NCT04195347). 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 (called CARPO – NCT04681066) for AP with SIRS, with topline data expected in the second quarter of 2024, as well as supporting the ongoing Phase 1/2 AIPT study (called CRSPA – NCT04195347), with data expected in 2025. CalciMedica plans to initiate its Phase 2 study (called KOURAGE) in AKI with associated AHRF in the second quarter of 2024 with data expected in 2025. 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 . Forward-Looking Statements This communication contains forward-looking statements which include, but are not limited to, statements regarding CalciMedica's expected cash, cash equivalents and short-term investments as of the end of the first quarter of 2024; CalciMedica's expected use of proceeds from the private placement; CalciMedica's expected cash runway; CalciMedica's business strategy; 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 CARPO trial of Auxora for AP with accompanying SIRS and its ongoing Phase 1/2 CRSPA trial of Auxora in pediatric patients with AIPT; the potential benefits of Auxora for the treatment of AKI, AP and AIPT; the estimated patient populations in the United States for AKI, AIPT and AP; the potential of Auxora for the treatment of other acute indications including acute respiratory distress syndrome; and the potential of CalciMedica's proprietary technology to provide therapeutic benefits in life-threatening inflammatory and immunologic diseases. 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 Annual Report on Form 10-K for the year ended December 31, 2023 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 . 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. CalciMedica Contact: Investors and Media Argot Partners Sarah Sutton/Kevin Murphy calcimedica@argotpartners.com (212) 600-1902 Company Codes: NASDAQ-NMS:CALC

Phase 2Clinical Result

11 Dec 2023

·www.prnewswire.com

CalciMedica Collaborator St. Jude Children's Research Hospital Presents Data from Initial Cohort of CRSPA Study at 65th Annual ASH Meeting & Exposition

Treatment with Auxora™ shown to potentially reduce the severity of asparaginase-associated pancreatitis, also called asparaginase-induced pancreatic toxicity, in pediatric patients with acute lymphoblastic leukemia Auxora eliminated the need for total parenteral nutrition and resulted in a 53% reduction in days in hospital and a 40% reduction in intensive care unit days as compared to historical matched control group None of the Auxora-treated patients had significant necrosis compared to 27% of historical control patients at 30 days LA JOLLA, Calif., Dec. 11, 2023 /PRNewswire/ -- CalciMedica Inc. (CalciMedica) (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 that its collaborator, St. Jude Children's Research Hospital (SJCRH), presented data from the initial cohort of the Phase 1/2 CRSPA study of Auxora™ (zegocractin injectable emulsion) in asparaginase-induced pancreatic toxicity (AIPT) at the 65th Annual American Society of Hematology (ASH) Meeting & Exposition on Sunday, December 10, 2023, in San Diego, CA. "It is extremely encouraging to see the results of our CRSPA study in this first cohort of patients as we continue to enroll new patients and expand to additional sites," said Sudarshan Hebbar, M.D., Chief Medical Officer of CalciMedica. "Notably, treatment with Auxora delivered positive results across multiple clinical endpoints. The elimination of the need for total parenteral nutrition, or TPN, for CRSPA patients who were able to eat on their own is particularly encouraging given that over half of the patients in the historical control group required TPN for several weeks on average. The ability to tolerate solid food correlates with pancreatic health and recovery from pancreatitis. Importantly, we saw an improvement in solid food tolerance in our Phase 2a acute pancreatitis trial, and time to solid food tolerance is the primary endpoint of our CARPO trial in adult patients with acute pancreatitis, which we expect to read out in the first half of 2024. With no approved therapies for asparaginase-induced pancreatic toxicity or acute pancreatitis on the market, we are excited about the potential benefits that Auxora could provide patients." Investigators at SJCRH presented results from the first cohort of the CRSPA study, consisting of nine children (average age 8.2 years) with acute lymphoblastic leukemia (ALL) experiencing asparaginase-associated pancreatitis, also known as AIPT and referred to as AAP in the abstract. AIPT is a severe complication that can arise during the treatment of ALL patients, the majority of which are children, characterized by intense abdominal pain, nausea, vomiting and systemic inflammatory response syndrome (SIRS). AIPT can lead to further chronic problems such as insulin dependence, exocrine pancreatic insufficiency and chronic pain. Many of these children can no longer be treated with current asparaginase therapy (e.g., ONCASPAR™ and RYLAYZE™) which can have a negative impact on their recovery from ALL. Eight of nine patients in the CRSPA study received a full regimen of 4 daily doses of Auxora at dose level 1 (30mg/m2 on day 1 and 42mg/m2 on days 2-4) administered as a four-hour infusion. Results from these patients were compared to a historical matched control group of 16 patients with imaging results out of a total of 51 patients who developed AIPT within 30 days of receiving asparaginase in the Total Therapy XVI study (T16). Treatment with Auxora, as compared to the historical matched control group, was shown to have the potential to reduce the severity of AIPT in pediatric patients with ALL. Study results showed that Auxora reduced the average number of days patients spent in the hospital from 13.4 to 6.3 days. The need for intensive care unit (ICU) care was also reduced, with three control patients (18.8%) requiring ICU care compared to one treated patient (12.5%), and the average number of days in the ICU was reduced from 5 to 3 days. Additionally, no patients in the CRSPA study required TPN, compared to 68.8% in the historical matched control group, who required 27 days of nutritional support on average. Finally, blinded central reading of pancreatic imaging showed a reduction in the development of significant pancreatic necrosis (≥30%) and the severity of acute pancreatitis by CT severity index (CTSI) scoring in patients treated with Auxora compared to the historical matched cohort. Based on these results, investigators have established dose level 1 as the recommended Phase 2 dose (RP2D) of Auxora for children with ALL experiencing AIPT. CTSI score definitions: 0-3 mild acute pancreatitis 4-6 moderately severe acute pancreatitis ≥7 severe acute pancreatitis About AIPT and CRSPA AIPT is an ultra-orphan indication affecting 300-400 pediatric patients in the US each year. Asparaginase (e.g. ONCASPAR™ and RYLAYZE™), an enzyme that degrades the amino acid asparagine, which is essential for the leukemic cells to survive, is one of the mainstays of therapy in pediatric ALL patients. However, the administration of asparaginase triggers the development of AAP or AIPT in 7-10% of patients, including the over 4,000 pediatric ALL patients treated per year in the United States, with similar numbers in Europe. The first cohort in the dose-finding part of the CRSPA study consisting of 9 patients has been completed at SJCRH and investigators believe that an optimal pediatric dose for Auxora™ in this setting has been defined. The study has continued to enroll patients beyond the initial 9 patient cohort and is being expanded to additional sites. The full study plans for 24 patients at the optimal dose. Details of the CRSPA study are available on clinicaltrials.gov (NCT04195347). About CARPO CARPO is an international, randomized, double-blind, placebo-controlled, dose-ranging trial intended to establish efficacy in AP with accompanying SIRS. It is expected to enroll 216 patients. AP can be a life-threatening condition where the pancreas becomes inflamed, sometimes leading to pancreatic cell death or necrosis, systemic inflammation, organ failure and death. There are an estimated 275,000 hospitalizations for AP annually in the United States, of which approximately 40% present with SIRS, which can compromise the function of other tissues or organs, especially the lungs. Organ failure is responsible for much of the mortality seen in AP. There is currently no approved therapy for AP. Details of the CARPO trial are available on clinicaltrials.gov (NCT04681066). 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 continuing the Phase 1/2 CRSPA AIPT study, with additional data expected by the second half of 2024. A Phase 2 study in acute kidney injury (AKI) is planned for early 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 . Forward-Looking Statements This communication contains forward-looking statements which include, but are not limited to, statements regarding CalciMedica's preliminary analysis, assessment and conclusions of the results of the first cohort of the Phase 1/2 CRSPA study; the design and potential benefits of Auxora, including its potential to reduce the severity of AIPT in pediatric patients with ALL; CalciMedica's plans and expected timing for developing its product candidates and potential benefits of its product candidates; CalciMedica's ongoing and planned clinical trials; the timing of the planned initiation of a Phase 2 study in AKI; the development and outcomes of CARPO and CRSPA trial programs, including the milestones, data announcements, expected enrollment, site expansion, potential benefits of and any other potential results related thereto; and the belief that an optimal pediatric dose for Auxora for children with ALL experiencing AIPT has been defined. 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 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 . 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 [email protected] (212) 600-1902 SOURCE CalciMedica, Inc.

Clinical ResultPhase 2ASH

09 Nov 2023

·www.prnewswire.com

CalciMedica Reports Third Quarter 2023 Financial Results and Provides Clinical & Corporate Updates

Continued expansion of Phase 1/2 CRSPA study of Auxora™ in asparaginase-induced pancreatic toxicity (AIPT); data from initial cohort to be presented at 65th Annual American Society of Hematology (ASH) Meeting & Exposition International expansion of Phase 2b CARPO trial in acute pancreatitis (AP) patients with accompanying systemic inflammatory response syndrome (SIRS) continues; topline data expected in the first half of 2024 LA JOLLA, Calif., Nov. 9, 2023 /PRNewswire/ -- CalciMedica Inc. ("CalciMedica") (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 illnesses, today reported financial results for the third quarter ended September 30, 2023. "As we work towards exciting milestones in the development of Auxora, we have continued to make progress across our pipeline indications throughout the third quarter, which was punctuated by our virtual Acute Pancreatitis Clinical Experts Event with doctors Joseph Miller and Georgios Papachristou," said Rachel Leheny, Ph.D., Chief Executive Officer of CalciMedica. "We look forward to reporting topline data from our international Phase 2b CARPO study in acute pancreatitis in the first half of 2024. Further, we are greatly encouraged by the promising data from the initial cohort of our Phase 1/2 CRSPA study in AIPT, which will be presented by our collaborators from St. Jude Children's Research Hospital at this year's ASH Meeting and Exposition." Clinical and Pre-Clinical Updates and Anticipated Milestones: Collaborators at St. Jude Children's Research Hospital (SJCRH) have continued expansion of the Phase 1/2 CRSPA trial of Auxora™ in pediatric patients with asparaginase-induced pancreatic toxicity (AIPT). Data from the initial cohort of the CRSPA study, including comparisons of data from CRSPA with matched historical control patients at SJCRH, will be presented by SJCRH investigators at the 65th Annual ASH Meeting & Exposition, being held December 9-12, 2023 in San Diego, CA. Data from the initial cohort of the CRSPA study compared with matched historical controls indicate that Auxora™ showed a 53% reduction in days in hospital, a 40% reduction in intensive care unit days and eliminated the need for total parenteral nutrition (in contrast to an average 27 days of total parenteral nutrition for the matched historical control group). CalciMedica's clinical investigators are continuing to enroll patients in CARPO, CalciMedica's Phase 2b clinical trial of Auxora™ in acute pancreatitis (AP) patients with accompanying systemic inflammatory response syndrome (SIRS), including in India, following the international expansion of the study there. CalciMedica anticipates that topline data from the CARPO trial will be available in the first half of 2024. CalciMedica is preparing to file an IND application for Auxora™ in acute kidney injury (AKI). If allowed, CalciMedica expects it will be in a position to initiate a Phase 2 clinical trial in AKI in the first half of 2024, subject to receipt of additional funding. Financial Results for the Three and Nine Months Ended September 30, 2023: As of September 30, 2023, CalciMedica had $14.6 million in cash, cash equivalents and short-term investments, which, based on its current operating plan, CalciMedica expects to be sufficient to fund its operations through the third quarter of 2024. Total operating expenses were $4.8 million for the three months ended September 30, 2023. Total operating expenses were $33.8 million for the nine months ended September 30, 2023, which included $16.2 million of one-time charges of which $10.5 million was non-cash, related to accelerated vesting of stock options and severance for employees of Graybug Vision, Inc. at the time of the reverse merger with Graybug. The majority of costs stemming from the reverse merger have been expensed. Net loss was $4.6 million, or $0.82 per share (basic and diluted), and $30.2 million, or $7.43 per share (basic and diluted), for the three and nine months ended September 30, 2023, respectively. Corporate Updates In September 2023, CalciMedica hosted a virtual Acute Pancreatitis Clinical Experts Event featuring Joseph Miller, M.D., Clinical Associate Professor of Emergency Medicine at Henry Ford Health and Michigan State University and Associate Director of Emergency Care Research at Henry Ford Health, and Georgios Papachristou, M.D., Ph.D., Professor of Medicine, Floyd Beman Endowed Chair in Gastroenterology and division director for Gastroenterology, Hepatology and Nutrition at The Ohio State University College of Medicine. Management and the clinical experts discussed current treatment paradigms for AP and the potential implications of CalciMedica's lead clinical compound, Auxora™. 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 AP with accompanying SIRS, called CARPO, (ii) an investigator-sponsored Phase 1/2 trial called CRSPA being conducted in pediatric patients with 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. There are currently no approved therapies to treat either AP or AIPT. 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 kidney injury and acute respiratory distress syndrome. About CRSPA CRSPA is an investigator-sponsored Phase 1/2 trial being conducted in pediatric acute lymphoblastic leukemia (ALL) patients with AIPT, which is acute pancreatitis toxicity caused by the administration of asparaginase (such as Oncaspar and Rylaze) and for which there is no approved therapy. Treatment with asparaginase triggers the development of AIPT in 7-10% of these patients, with approximately half developing pancreatic necrosis and/or pseudocysts. CalciMedica believes that the CRSPA trial has defined an optimal pediatric dose for Auxora in this setting and the trial is currently being expanded to additional sites. Details of the CRSPA trial are available on clinicaltrials.gov (NCT04195347). About CARPO CARPO is an international, randomized, double-blind, placebo-controlled, dose-ranging trial intended to establish efficacy in AP with accompanying SIRS. It is expected to enroll 216 patients. AP can be a life-threatening condition where the pancreas becomes inflamed, sometimes leading to pancreatic cell death or necrosis, systemic inflammation, organ failure and death. There are an estimated 275,000 hospitalizations for AP annually in the United States, of which approximately 40% present with SIRS, which can compromise the function of other tissues or organs, especially the lungs. Organ failure is responsible for much of the mortality seen in AP. There is currently no approved therapy for AP. Details of the CARPO trial are available on clinicaltrials.gov (NCT04681066). 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 in 216 patients called CARPO for acute pancreatitis (AP) with systemic inflammatory response syndrome (SIRS), with topline data expected in the first half of 2024, as well as continuing the Phase 1/2 CRSPA AIPT study, with data from the first cohort expected to be presented in the fourth quarter of 2023. A Phase 2 study in acute kidney injury (AKI) is planned for the first half 2024, subject to receipt of additional funding. 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 . Forward-Looking Statements This communication contains forward-looking statements which include, but are not limited to, statements regarding CalciMedica's expected cash runway; CalciMedica's business strategy; the design and potential benefits of Auxora; CalciMedica's plans and expected timing for developing its product candidates and potential benefits of its product candidates; CalciMedica's ongoing and planned clinical trials; CalciMedica's plans and expected timing for filing an IND application for Auxora in AKI; the development and outcomes of CARPO and CRSPA trial programs, including the milestones, data announcements, expected enrollment and any other potential results related thereto. 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: CalciMedica's need to obtain substantial additional funding to complete the development and any commercialization of its product candidates; CalciMedica's ability to continue as a going concern; 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 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 . 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 [email protected] (212) 600-1902 SOURCE CalciMedica

Phase 2Clinical ResultASH

100 Deals associated with Pegaspargase

External Link

KEGG	Wiki	ATC	Drug Bank
D05387	Pegaspargase	L01XX24	DB00059

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Lymphoma	JP	Nihon Servier Co., Ltd.	26 Jun 2023
Hypersensitivity	US	Servier Pharmaceuticals LLCStartup	03 Jan 2019
Acute Lymphoblastic Leukemia	US	Servier Pharmaceuticals LLCStartup	01 Feb 1994

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Hematologic Neoplasms	Phase 2	FR	Servier Group	30 Jan 2022
Adult Lymphoblastic Lymphoma	Phase 2	US	Shire Plc	01 Jun 2012
Adult Lymphoblastic Lymphoma	Phase 2	CA	Shire Plc	01 Jun 2012
Lymphoma	Phase 2	US	Enzon Pharmaceuticals, Inc.	31 Aug 2006
Solid tumor	Phase 2	US	Enzon Pharmaceuticals, Inc.	31 Aug 2006
Acute Lymphoblastic Leukemia	Phase 2	CA	Aventis Pharmaceuticals, Inc.	13 Oct 1998
Acute Lymphoblastic Leukemia	Preclinical	CA	Aventis Pharmaceuticals, Inc.	13 Oct 1998

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


LAL1913CAMPUS ALL MULTICENTER STUDY (EHA2024) Manual	Phase 4	Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia	421	Pegaspargase	(yprqbasqol) = zvxakckqng ilwrmkbkfx (rpystlfwpz ) View more	Positive	14 May 2024
				Pegaspargase (LAL1913 clinicaltrial)	(yprqbasqol) = zpeeufqfxp ilwrmkbkfx (rpystlfwpz ) View more
EHA2024	Not Applicable	Ph-Like Acute Lymphoblastic Leukemia	43	PEG-ASP	(telrfqhsgi) = anouqrjbrb mxvmkocnhf (sgemueelxs )	-	14 May 2024
EHA2024	Not Applicable	Leukemia	13	PEG-ASP + Vincristine-Daunorubicin-Steroid based induction	dokwwfospp(uczsbrkope) = zggcjnplpt yajqyzzgxq (hyqnvmidca )	Positive	14 May 2024
				PEG-ASPARAGINASE	(yaowiwvine) = slresambrk wyrdwozibn (lmsunyhkuc )
NCT04956666 (ALL, CTgov)	Phase 2	Acute Lymphoblastic Leukemia	75	Lyophilized S95014	umsixdgocf(aszzulbkxo) = xeaqlbehsb uqzuublelh (egvoxaewfv, mhknneqpxn - rbkvfyorsq) View more	-	29 Dec 2023
NCT04954326 (ALL, CTgov)	Phase 2	Acute Lymphoblastic Leukemia	89	Lyophilized S95014 (S95014 Lyophilizate)	qwddsokqwi(axivdohode) = ccmgamfqmq zgrzqeeyud (bjdnohcdjj, yupzfokoyg - hnldhrisgc) View more	-	05 Jul 2023
				Liquid S95014 (S95014 Liquid)	qwddsokqwi(axivdohode) = bscbjusokx zgrzqeeyud (bjdnohcdjj, rmkvgcyrkb - rufcybgfwj) View more
ICML2023	Not Applicable	Extranodal NK-T-Cell Lymphoma NRI score	20	Gemcitabine	(wvbrbjsuaj) = grade 3 or severer leukopenia in 65% of patients qbsacmzcih (xosguqwghy ) View more	Positive	09 Jun 2023
				Pegaspargase
ICML2023	Phase 2	Extranodal NK-T-Cell Lymphoma EBV DNA levels	22	Pegarspargase	(ttdxnlhqvi) = iidkrmfanz lhutjtniaw (cfsvdmyuzz, 42.7 - 78.8) View more	Positive	09 Jun 2023
EHA2023	Phase 2	T-Cell Lymphoma	22	Pegarspargase and Sintilimab	(yduldqumwk) = eymajazfea wshfgeidns (vjpqbbfpul, 42.7 - 78.8) View more	-	08 Jun 2023
EHA2023	Not Applicable	T-Cell Lymphoma	62	Camrelizumab + Low-dose Apatinib + Pegaspargase	(kjtmnhvsue) = llavefsmoc mdrjzijoca (wjhgkfxctl, 54.4% - 81.9%) View more	-	08 Jun 2023
NCT02101853 (AALL1331, CTgov)	Phase 3	Recurrent B Acute Lymphoblastic Leukemia \| Pre B-cell acute lymphoblastic leukemia	669	Asparaginase+Etoposide+CYCLOPHOSPHAMIDE+Leucovorin Calcium+pegaspargase+Therapeutic Hydrocortisone+Mitoxantrone+Dexamethasone+Vincristine Sulfate+Methotrexate+Cytarabine (Arm A (HR and IR Control))	mwddjpkdcn(sxwwgakxbb) = bbuaiycakx vpbmthuymh (ihqzinlwon, rrazcxyfdk - enilqobnif) View more	-	06 Dec 2022
				Pharmacological Study+Therapeutic Hydrocortisone+blinatumomab+Dexamethasone+Methotrexate+Cytarabine (Arm B (HR and IR Blinatumomab))	mwddjpkdcn(sxwwgakxbb) = blrrvfxefn vpbmthuymh (ihqzinlwon, ejvnzcowfo - ewcdqqkctr) View more

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis