Aphasia

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

What did an ancient Chinese emperor from 1,500 years ago look like? A team of researchers reconstructed the face of Chinese Emperor Wu of Northern Zhou using DNA extracted from his remains. The study suggests the emperor's death at the age of 36 might be linked to a stroke. It also sheds light on the origin and migration patterns of a nomadic empire that once ruled parts of northeastern Asia. What did an ancient Chinese emperor from 1,500 years ago look like? A team of researchers reconstructed the face of Chinese Emperor Wu of Northern Zhou using DNA extracted from his remains. The study, published March 28 in the journal Current Biology, suggests the emperor's death at the age of 36 might be linked to a stroke. It also sheds light on the origin and migration patterns of a nomadic empire that once ruled parts of northeastern Asia. Emperor Wu was a ruler of the Northern Zhou dynasty in ancient China. Under his reign from AD 560 to AD 578, Emperor Wu built a strong military and unified the northern part of ancient China after defeating the Northern Qi dynasty. Emperor Wu was ethnically Xianbei, an ancient nomadic group that lived in what is today Mongolia and northern and northeastern China. "Some scholars said the Xianbei had 'exotic' looks, such as thick beard, high nose bridge, and yellow hair," says Shaoqing Wen, one of the paper's corresponding authors at Fudan University in Shanghai. "Our analysis shows Emperor Wu had typical East or Northeast Asian facial characteristics," he adds. In 1996, archaeologists discovered Emperor Wu's tomb in northwestern China, where they found his bones, including a nearly complete skull. With the development of ancient DNA research in recent years, Wen and his team managed to recover over 1 million single-nucleotide polymorphisms (SNPs) on his DNA, some of which contained information about the color of Emperor Wu's skin and hair. Combined with Emperor Wu's skull, the team reconstructed his face in 3D. The result shows Emperor Wu had brown eyes, black hair, and dark to intermediate skin, and his facial features were similar to those of present-day Northern and Eastern Asians. "Our work brought historical figures to life," says Pianpian Wei, the paper's co-corresponding author at Fudan University. "Previously, people had to rely on historical records or murals to picture what ancient people looked like. We are able to reveal the appearance of the Xianbei people directly." Emperor Wu died at the age of 36, and his son also died at a young age with no clear reason. Some archaeologists say Emperor Wu died of illness, while others argue the emperor was poisoned by his rivals. By analyzing Emperor Wu's DNA, researchers found that the emperor was at an increased risk for stroke, which might have contributed to his death. The finding aligns with historical records that described the emperor as having aphasia, drooping eyelids, and an abnormal gait -- potential symptoms of a stroke. The genetic analysis shows the Xianbei people intermarried with ethnically Han Chinese when they migrated southward into northern China. "This is an important piece of information for understanding how ancient people spread in Eurasia and how they integrated with local people," Wen says. Next, the team plans to study the people who lived in ancient Chang'an city in northwestern China by studying their ancient DNA. Chang'an was the capital city of many Chinese empires over thousands of years and the eastern terminus of the Silk Road, an important Eurasian trade network from the second century BC until the 15th century. The researchers hope that the DNA analysis can reveal more information about how people migrated and exchanged cultures in ancient China.

Abecma demonstrated superiority over standard regimens in the Phase 3 KarMMa-3 trial, with a 51% reduction in risk of disease progression or death and a well-established safety pro mostly low-grade and transient occurrences of cytokine release syndrome and neurotoxicity Approval reinforces Bristol Myers Squibb’s commitment to bring the transformative potential of cell therapy into earlier lines of treatment PRINCETON N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced that the European Commission (EC) has granted approval to Abecma® (idecabtagene vicleucel; ide-cel) for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies, including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 antibody and have demonstrated disease progression on the last therapy. Abecma is the first chimeric antigen receptor (CAR) T cell immunotherapy approved in the European Union (EU) for use in earlier lines of therapy for relapsed and refractory multiple myeloma. This expanded approval of Abecma covers all EU member states.* In the EU, Abecma has maintained its Orphan Designation for the treatment of multiple myeloma. “Today’s approval in the European Union marks an exciting milestone in our efforts to bring the transformative potential of cell therapies into earlier lines of treatment,” said Monica Shaw, M.D., senior vice president and head of European Markets, Bristol Myers Squibb. “Abecma is an important treatment option for patients with triple-class exposed relapsed and refractory multiple myeloma who have received at least two prior therapies and is leading the way toward a promising shift in the treatment paradigm.” The current treatment paradigm for multiple myeloma includes IMiDs, PIs, and anti-CD38 monoclonal antibodies; however, many patients go on to relapse and/or become refractory to these classes of therapy. With increased use of the three main classes of therapy as combination regimens, more patients are becoming triple-class exposed earlier in their treatment journey. There have historically been limited options for patients with triple-class exposed relapsed and/or refractory multiple myeloma, and patients tend to have poor outcomes with a median progression-free survival of three to five months. “As patients with multiple myeloma become exposed to the three main classes of therapy earlier in treatment and still experience relapsed and/or refractory disease, it is critical that we continue to add innovative treatment options to our arsenal that can potentially provide long-term disease control,” said Paula Rodriguez-Otero, M.D., Ph.D., Department of Hematology, Clinica Universidad de Navarra, Pamplona, Spain. “This expanded approval of ide-cel represents key progress in bringing a personalized therapy that delivers significantly improved, durable outcomes to patients with triple-class exposed relapsed and refractory multiple myeloma after two prior therapies.” With a significant increase in manufacturing capacity and over 90% manufacturing success rate globally, Bristol Myers Squibb is prepared to meet increased demand for Abecma. The company is focused on making Abecma available in the EU for this indication, including completion of reimbursement procedures. Based on the KarMMa-3 study, Abecma is also the first cell therapy approved in Switzerland for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior lines of therapies and the first cell therapy approved in Japan for adult patients with triple-class exposed relapsed or refractory multiple myeloma after two prior lines of therapy. Abecma is also approved in the U.S. for adult patients with triple-class exposed relapsed or refractory multiple myeloma after four or more prior lines of therapy and approved in Great Britain and Israel for adult patients with triple-class exposed relapsed and refractory multiple myeloma after three or more prior lines of therapy. A supplemental Biologics License Application for Abecma for triple-class exposed relapsed and refractory multiple myeloma is currently under review with the U.S. Food and Drug Administration (FDA). The FDA’s Oncologic Drugs Advisory Committee (ODAC) recently voted positively that Abecma demonstrated a favorable benefit/risk pro patients with triple-class exposed relapsed or refractory multiple myeloma based on results from the pivotal Phase 3 KarMMa-3 study. *Centralized Marketing Authorization does not include approval in Great Britain (England, Scotland and Wales). Abecma KarMMa-3 Clinical Trial Results The EC approval of Abecma is based on results from KarMMa-3, a pivotal Phase 3, open-label, global, randomized controlled study evaluating Abecma compared to standard combination regimens in patients with relapsed and refractory multiple myeloma who received two to four prior lines of treatment, including an IMiD, a PI, and an anti-CD38 monoclonal antibody (triple-class exposed), and who were refractory to the last treatment regimen. At a pre-specified interim analysis with a median follow-up of 18.6 months, treatment with Abecma (n=254) significantly improved progression-free survival (PFS), the study’s primary endpoint, compared to standard regimens (n=132), with a median PFS of 13.8 months (95% CI: 11.8-16.1) versus 4.4 months (95% CI: 3.4-5.8) (HR: 0.49 [95% CI: 0.38-0.63]; p<0.0001), representing a 51% reduction in the risk of disease progression or death. Results from the primary analysis, with a median follow-up of 30.9 months, were consistent with the interim analysis and represent the longest follow-up for a randomized Phase 3 CAR T cell therapy in this patient population. Treatment with Abecma also showed a significant improvement in overall response rate (ORR) with the majority (71.3% [95% CI: 65.7-76.8]) of patients treated with Abecma achieving a response, and 43.7% achieving a complete or stringent complete response. In comparison, less than half of patients (42.4% [95% CI: 34-50.9]) who received standard regimens achieved a response, with 5.3% experiencing a complete response or stringent complete response. The KarMMa-3 trial had a patient-centric design that allowed for crossover from standard regimens to Abecma upon confirmed disease progression, with more than half (56%) of patients in the standard regimens arm crossing over to receive Abecma as a subsequent therapy, due to disease progression while receiving standard regimens. Median overall survival (OS), a secondary endpoint of the study, was 41.4 months with Abecma (95% CI: 30.9-NR) and 37.9 months with standard regimens (95% CI: 23.4-NR) (95% CI: 0.73-1.40; HR: 1.01). Based on real-world evidence, median OS for patients with triple-class exposed relapsed and refractory multiple myeloma is approximately 13 months, underscoring the confounding impact that crossover had on the median OS observed with standard regimens in the KarMMa-3 trial. Based on a pooled analysis of the KarMMa, CRB-401 and KarMMa-3 studies (n=409), Abecma has exhibited a well-established and consistent safety pro mostly low-grade and transient occurrences of cytokine release syndrome (CRS) and neurotoxicity. In patients treated with Abecma, any grade CRS has occurred in 84.6% of patients, with Grade ≥3 CRS occurring in 5.1% of patients and fatal (Grade 5) CRS reported in 0.7% of patients. The median time to onset of CRS was one day (range: 1 to 17) and the median duration of CRS was four days (range: 1 to 63). In the KarMMa and KarMMa-3 studies (n=353), any-grade neurotoxicity occurred in 16.1% of patients, with Grade 3/4 neurotoxicity occurring in 3.1% of patients, and no Grade 5 events reported. Median time to onset of neurotoxicity was three days (range: 1-317 days) and median duration of neurotoxicity was three days (range: 1-252 days). No cases of Parkinsonism were reported. About Abecma Abecma is a CAR T cell therapy that recognizes and binds to the B-cell maturation antigen (BCMA) on the surface of multiple myeloma cells leading to CAR T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells. Abecma is the first-in-class BCMA-directed CAR T cell immunotherapy approved by the U.S. FDA for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Please see the Important Safety Information section below, including Boxed WARNINGS for Abecma regarding CRS, neurologic toxicities, Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome and Prolonged Cytopenia. Abecma is being jointly developed and commercialized in the U.S. as part of a Co-Development, Co-Promotion, and Profit Share Agreement between Bristol Myers Squibb and 2seventy bio. Bristol Myers Squibb assumes sole responsibility for Abecma drug product manufacturing and commercialization outside of the U.S. The companies’ broad clinical development program for Abecma includes ongoing and planned clinical studies (KarMMa-2, KarMMa-9) for patients with multiple myeloma. For more information visit clinicaltrials.gov. Full European Summary of Product Characteristics for Abecma is available from the EMA website at . Abecma U.S. FDA-Approved Indication ABECMA® (idecabtagene vicleucel) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. U.S. Important Safety Information BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, AND PROLONGED CYTOPENIA Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with ABECMA. Do not administer ABECMA to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids. Neurologic Toxicities, which may be severe or life-threatening, occurred following treatment with ABECMA, including concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with ABECMA. Provide supportive care and/or corticosteroids as needed. Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS) including fatal and life-threatening reactions, occurred in patients following treatment with ABECMA. HLH/MAS can occur with CRS or neurologic toxicities. Prolonged Cytopenia with bleeding and infection, including fatal outcomes following stem cell transplantation for hematopoietic recovery, occurred following treatment with ABECMA. ABECMA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA REMS. WARNINGS AND PRECAUTIONS: Cytokine Release Syndrome (CRS): CRS, including fatal or life-threatening reactions, occurred following treatment with ABECMA in 85% (108/127) of patients. Grade 3 or higher CRS occurred in 9% (12/127) of patients, with Grade 5 CRS reported in one (0.8%) patient. The median time to onset of CRS, any grade, was 1 day (range: 1 - 23 days) and the median duration of CRS was 7 days (range: 1 - 63 days). The most common manifestations included pyrexia, hypotension, tachycardia, chills, hypoxia, fatigue, and headache. Grade 3 or higher events that may be associated with CRS include hypotension, hypoxia, hyperbilirubinemia, hypofibrinogenemia, acute respiratory distress syndrome (ARDS), atrial fibrillation, hepatocellular injury, metabolic acidosis, pulmonary edema, multiple organ dysfunction syndrome, and HLH/MAS. Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS. Fifty four percent (68/127) of patients received tocilizumab (single dose: 35%; more than 1 dose: 18%). Overall, 15% (19/127) of patients received at least 1 dose of corticosteroids for treatment of CRS. All patients that received corticosteroids for CRS received tocilizumab. Ensure that a minimum of 2 doses of tocilizumab are available prior to infusion of ABECMA. Monitor patients at least daily for 7 days following ABECMA infusion at the REMS-certified healthcare facility for signs or symptoms of CRS and monitor patients for signs or symptoms of CRS for at least 4 weeks after ABECMA infusion. At the first sign of CRS, institute treatment with supportive care, tocilizumab and/or corticosteroids as indicated. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. Neurologic Toxicities: Neurologic toxicities, including immune effector cell-associated neurotoxicity syndrome (ICANS), which may be severe or life- threatening, occurred concurrently with CRS, after CRS resolution, or in the absence of CRS following treatment with ABECMA. Neurologic toxicities occurred in 28% (36/127) of patients receiving ABECMA, including Grade 3 in 4% (5/127) of patients. One patient had ongoing Grade 2 neurotoxicity at the time of death. Two patients had ongoing Grade 1 tremor at the time of data cutoff. The median time to onset of neurotoxicity was 2 days (range: 1 - 42 days). CAR T cell-associated neurotoxicity resolved in 92% (33/36) of patients with a median time to resolution of 5 days (range: 1 - 61 days). The median duration of neurotoxicity was 6 days (range: 1 - 578) in all patients including 3 patients with ongoing neurotoxicity. Thirty-four patients with neurotoxicity had CRS with onset in 3 patients before, 29 patients during, and 2 patients after CRS. The most frequently reported manifestations of CAR T cell-associated neurotoxicity include encephalopathy, tremor, aphasia, and delirium. Grade 4 neurotoxicity and cerebral edema in 1 patient, Grade 3 myelitis, and Grade 3 parkinsonism have been reported with ABECMA in another study in multiple myeloma. Monitor patients at least daily for 7 days following ABECMA infusion at the REMS-certified healthcare facility for signs or symptoms of neurologic toxicities and monitor patients for signs or symptoms of neurologic toxicities for at least 4 weeks after ABECMA infusion and treat promptly. Rule out other causes of neurologic symptoms. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed. Counsel patients to seek immediate medical attention should signs or symptoms occur at any time. Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS): HLH/MAS occurred in 4% (5/127) of patients receiving ABECMA. One patient developed fatal multi-organ HLH/MAS with CRS and another patient developed fatal bronchopulmonary aspergillosis with contributory HLH/MAS. Three cases of Grade 2 HLH/MAS resolved. All events of HLH/MAS had onset within 10 days of receiving ABECMA with a median onset of 7 days (range: 4 - 9 days) and occurred in the setting of ongoing or worsening CRS. Two patients with HLH/MAS had overlapping neurotoxicity. The manifestations of HLH/MAS include hypotension, hypoxia, multiple organ dysfunction, renal dysfunction, and cytopenia. HLH/MAS is a potentially life-threatening condition with a high mortality rate if not recognized early and treated. Treatment of HLH/MAS should be administered per institutional guidelines. ABECMA REMS: Due to the risk of CRS and neurologic toxicities, ABECMA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA REMS. Further information is available at or 1-888-423-5436. Hypersensitivity Reactions: Allergic reactions may occur with the infusion of ABECMA. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO) in ABECMA. Infections: ABECMA should not be administered to patients with active infections or inflammatory disorders. Severe, life-threatening, or fatal infections occurred in patients after ABECMA infusion. Infections (all grades) occurred in 70% of patients. Grade 3 or 4 infections occurred in 23% of patients. Overall, 4 patients had Grade 5 infections (3%); 2 patients (1.6%) had Grade 5 events of pneumonia, 1 patient (0.8%) had Grade 5 bronchopulmonary aspergillosis, and 1 patient (0.8%) had cytomegalovirus (CMV) pneumonia associated with Pneumocystis jirovecii. Monitor patients for signs and symptoms of infection before and after ABECMA infusion and treat appropriately. Administer prophylactic, pre-emptive, and/or therapeutic antimicrobials according to standard institutional guidelines. Febrile neutropenia was observed in 16% (20/127) of patients after ABECMA infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care. Viral Reactivation: CMV infection resulting in pneumonia and death has occurred following ABECMA administration. Monitor and treat for CMV reactivation in accordance with clinical guidelines. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against plasma cells. Perform screening for CMV, HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) in accordance with clinical guidelines before collection of cells for manufacturing. Prolonged Cytopenias: In the clinical study, 41% of patients (52/127) experienced prolonged Grade 3 or 4 neutropenia and 49% (62/127) experienced prolonged Grade 3 or 4 thrombocytopenia that had not resolved by Month 1 following ABECMA infusion. In 83% (43/52) of patients who recovered from Grade 3 or 4 neutropenia after Month 1, the median time to recovery from ABECMA infusion was 1.9 months. In 65% (40/62) of patients who recovered from Grade 3 or 4 thrombocytopenia, the median time to recovery was 2.1 months. Three patients underwent stem cell therapy for hematopoietic reconstitution due to prolonged cytopenia. Two of the three patients died from complications of prolonged cytopenia. Monitor blood counts prior to and after ABECMA infusion. Manage cytopenia with myeloid growth factor and blood product transfusion support. Hypogammaglobulinemia: Hypogammaglobulinemia was reported as an adverse event in 21% (27/127) of patients; laboratory IgG levels fell below 500 mg/dl after infusion in 25% (32/127) of patients treated with ABECMA. Monitor immunoglobulin levels after treatment with ABECMA and administer IVIG for IgG <400 mg/dl. Manage appropriately per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis. The safety of immunization with live viral vaccines during or after ABECMA treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during ABECMA treatment, and until immune recovery following treatment with ABECMA. Secondary Malignancies: Patients treated with ABECMA may develop secondary malignancies. Monitor life-long for secondary malignancies. If a secondary malignancy occurs, contact Bristol-Myers Squibb at 1-888-805-4555 to obtain instructions on patient samples to collect for testing of secondary malignancy of T cell origin. Effects on Ability to Drive and Operate Machinery: Due to the potential for neurologic events, patients receiving ABECMA are at risk for altered or decreased consciousness or coordination in the 8 weeks following ABECMA infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period. Adverse Reactions: The most common nonlaboratory adverse reactions include CRS, infections – pathogen unspecified, fatigue, musculoskeletal pain, hypogammaglobulinemia, diarrhea, upper respiratory tract infection, nausea, viral infections, encephalopathy, edema, pyrexia, cough, headache, and decreased appetite. Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide. Bristol Myers Squibb: Creating a Better Future for People with Cancer Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future. About Bristol Myers Squibb Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram. Forward-Looking Statement of Bristol Myers Squibb This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that the outcome of pricing and reimbursement negotiations in individual countries in Europe may delay or limit the commercial potential of Abecma® (idecabtagene vicleucel) for the additional indication described in this release, any marketing approvals, if granted, may have significant limitations on their use, and that continued approval of Abecma for such additional indication described in this release may be contingent upon verification and description of clinical benefit in confirmatory trials, and whether Abecma for such additional indication described in this release will be commercially successful. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2023, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise. corporatefinancial-news