The Israel-Hamas war is unprecedented in the history of Israel’s warfare not only because of the number of civilians murdered and abducted but also because of the record number of rockets fired on Israel since October 7 and the use of anti-tank missiles by Hamas in fighting in the Gaza Strip. Despite this, the IDF’s land maneuvers are progressing and one of the reasons for this is the introduction of the IDF’s first company of Merkava Barak battle tanks.
The tanks are the fifth generation in the Merkava series, which were only introduced into the IDF’s Armored Corps in September, when nobody expected that the tank’s first big test would begin so soon. In contrast to the way that tanks are slowly integrated into foreign forces like the US army, which take a long time and involve various trial stages, in Israel the tanks are first operated in real time with adjustments made on the battlefield.
Teams at the Ministry of Defense Merkava and Armored Vehicles Directorate are in the field physically monitoring the performance of the new tanks. Their aim is to study every threat and attempt to strike at the tank, raise its weapons capabilities and talk with the tank teams about how to improve the tank and enhance its operational capabilities.
Brig. Gen. Oren Giber, commanding general of the Israeli Merkava and Armored Vehicles Directorate, tells “Globes,” We are undergoing a learning curve over the years against an enemy that is trying to find the weak points in the IDF military, it doesn’t happen in a day, but we constantly try to be several steps ahead of them.”
“This process is deep and smart over many years and today the learning curve continues even amidst the war when it is more relevant than ever.”
What is the price for a foreign army?
According to the Ministry of Defense, the cost of the Merkava Barak is similar to the Merkava 4. In other words, according to overseas reports, $3.5 million for the IDF and $5 million for foreign armies.
How can it be that the cost of the Merkava Barak is the same as the Merkava 4. The Israeli Merkava and Armored Vehicles Directorate breaks the tank down to more than 150 systems and components and managing the process like this enables them to more easily stick to an organized budgetary framework.
Another factor that helps keeps the costs of the new tank the same as the previous model is the reliance on Israeli companies and suppliers. The companies whose products are included in the manufacturing, from low-tech to high-tech, are all from Israel and this allows a greater control over costs and achieving lower prices. One such example is the air-conditioning company Beth-El Group.
Technological progress also helps reduce costs. Today you can find computers and technological means that provide a better response than their predecessors, which were the best technology 20 years ago, when the Merkava 4 was put into service.
One of the critical factors in reducing costs is related to the large Israeli defense companies, Elbit Systems (Nasdaq: ESLT; TASE: ESLT), Israel Aerospace Industries (IAI) and Rafael Advanced Defense Systems, which provide leading technological solutions on a global scale, but at cost price.
“Globes” has learned that sometimes prices for the Barak tank are just 25% of the price at which the same systems are sold to foreign customers. Beyond patriotic considerations, in Israel the systems prove themselves with high intensity in real time warfare, and become even more sought-after products overseas.
Minister of Defense Yoav Gallant, former head of Southern Command, held a inaugural event with industry executives, in order to thank them for the success. He also spoke about the future in which dozens more Merkava Barak tanks are expected to be integrated annually into the IDF. Nevertheless, because a tank company has about 10 tanks, a battalion 30 and a brigade 100, it will still be some years until the fourth generation Merkava 4 will only be operated by reservists.
A technological leap forward
The Barak tank may be the world’s leading tank in technological terms but it is still far from being the most expensive. The world’s most expensive tank is France’s Leclerc AMX 56, which costs $9.3 million. South Korea’s Black Panther costs $8.5 million and India’s Arjun tank costs $7.8 million.
Despite costing ‘only’ $5 million for foreign armies, Israel’s Barak tank features unique technological capabilities, the most prominent of which is the use of artificial intelligence (AI). Similar to the F-35 helmets manufactured by Elbit Systems, which provide the pilot with real-time information analysis, a similar feature is used in the Barak tank.
Elbit’s Iron Vision system enables improved combat in densely built areas, and includes an integrated AI peripheral vision system and an advanced visor for the tank commander, which reflects what is happening outside the tank while integrating the relevant information on top of the image, with the ability to direct any device in the tank towards his eyes at the push of a button.
The tank systems receive information from the combat environment, from near and far, process it and translate it into relevant information for combat.
One of the interesting aspects of the Barak tank is that information processing is individually adapted to the person in command. For example, the perspective of the brigade commander is broader, and less concerned with micro-tactics. On the other hand, when an anti-tank shell is fired at a single tank, the focus of immediate attention is the anti-tank launcher. The diversity of combat situations and the various roles is a significant key. In battle, the professionals define the Barak tank as a technological leap forward when it comes to sensors, fusion and accessibility of information, while connecting to all the weapon systems.
The effectiveness of the Trophy protection system
Alongside the systems manufactured by Elbit is radar produced by Israel Aerospace Industries unit Elta Systems, which is one of the most famous brands of Israel’s land forces. The Trophy pro-active protection systems is produced by Rafael.
This system is a major reason for the low number of Israeli casualties despite the unprecedented amount of anti-tank fire from Hamas, in one of the most densely built areas in the world. The Trophy protection system has been operational for about 13 years, and provides the tank with 360-degree protection with extremely high effectiveness. For this reason 2,000 such systems have been sold for 16 platforms in the world, including four divisions of the US Abrams tank, as well as the German Leopard and the British Challenger tanks.
“When we hand over to the IDF soldiers, the tank or the Tiger or Eitan APCs that we developed for them, there is a feeling that you have put your greatest treasure in their hands,” says Brig. Gen. Giber. “We look at this armor with reverence because we are designing it for IDF soldiers. So we spare no effort and do everything possible to ensure that we have given them the best and most protected armament possible. You have to understand, the anti-tank shell threats confronting tanks and armored vehicles in the current war are enormous, I don’t think anyone has seen anything like it before. The IDF’s decision to provide its fighters with platforms that has a level of protection and durability that has no equal in the world, has proven itself.”
Published by Globes, Israel business news – en.globes.co.il – on December 11, 2023.
The content in this section is supplied by Business Wire for the purposes of distributing press releases on behalf of its clients. Postmedia has not reviewed the content.
In CARTITUDE-4, CARVYKTI® demonstrated clinically meaningful improvements in patient-reported outcomes when compared to standard of care
The as-treated population in CARTITUDE-4 demonstrated strong rates of progression-free survival and overall response
Longer-term data from CARTITUDE-2 showed deep and durable responses in earlier lines of treatment among patients in Cohort A and Cohort B
SOMERSET, N.J. — Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global biotechnology company developing, manufacturing, and commercializing novel therapies to treat life-threatening diseases, announced today patient-reported outcome (PRO) data from the Phase 3 CARTITUDE-4 study from an oral presentation at the 2023 American Society of Hematology (ASH) Annual Meeting ( Abstract #1063). These data showed clinically meaningful improvement in health-related quality of life following a single CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) infusion in adults lenalidomide-refractory multiple myeloma (MM) who received one to three prior lines of therapy (LOT), compared to patients treated with the standard of care (SOC) treatment regimens of either pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd).1 The PRO data also demonstrated meaningful reductions in disease-specific symptoms after a single infusion for patients in the CARVYKTI® arm, while patients in the SOC treatment arm trended toward worsening or lower degrees of improvement from baseline for most domains and symptoms.
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Eligible patients in the CARTITUDE-4 study had lenalidomide-refractory MM, and had one to three prior LOT, including a proteasome inhibitor (PI) and an immunomodulatory drug. Four hundred nineteen patients were randomized, with 208 patients in the CARVYKTI® arm and 211 patients in the SOC arm. At the clinical cut-off on November 1, 2022, 99 patients in the CARVYKTI® arm and 66 patients in the SOC arm had baseline and 12-month PRO assessments, representing data prior to disease progression. When compared to SOC, patients who received the CARVYKTI® infusion exceeded clinically meaningful thresholds for average improvement from baseline to 12 months in global health status (10.1 points vs. -1.5 points), pain (-10.2 points vs. -3.9 points), and the visual analogue scale (8.0 points vs. 1.4 points).1
“The CARTITUDE-4 data presented today reinforce the impact that a single infusion of CARVYKTI® may provide to patients,” said Roberto Mina, Assistant Professor, Division of Hematology, Department of Molecular Biotechnology and Health Sciences, University of Torino, Turin, Italy.
When compared to SOC, the PRO data for CARVYKTI® neared clinically meaningful thresholds when evaluating improvements in fatigue (-9.1 points vs. 2.8 points) and emotional functioning (9.5 points vs. 2.2 points), and numerically favored CARVYKTI® for all other domains established by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30; 100-point scale). The median time until MM symptom worsening in the CARVYKTI® arm was 23.7 months compared to 18.9 months in the SOC arm (hazard ratio [HR], 0.42), as measured with the Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q; 5-point scale).1
An additional analysis of the CARTITUDE-4 study data was presented as a poster ( Abstract #4866) at the ASH Annual Meeting. At the clinical cut-off, 176 of the 208 patients were randomized to the CARVYKTI® treatment arm. The median age of this patient population was 61 years and 34 percent had received 1 prior LOT. At a median follow-up of 16 months following randomization, 22 percent of patients received one bridging therapy cycle, 59 percent received two cycles and 18 percent received 3 cycles, and disease burden was effectively controlled across the as-treated patient set during bridging therapy.2
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At 12 months following infusion, the PFS rate was 85 percent, and the overall survival (OS) rate was 92 percent. Median PFS had not been reached. The overall response rate (ORR) was 99 percent and 86 percent of patients achieved complete response or better ( >CR). Of the minimum residual disease- (MRD) evaluable patients (n=144), 77 percent achieved both MRD negativity and >CR.2
The most common CAR-T cell-related toxicity was Cytokine Release Syndrome (CRS) at 76 percent (1 percent grade 3), the neurotoxicity rate was 21 percent (3 percent grade 3/4), and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) occurred in 5 percent of patients (no grade 3/4). Other neurotoxicities occurred in 17 percent of patients (2 percent grade 3/4). By the clinical cut-off, CRS and ICANS had resolved in all patients.2
Data from CARTITUDE-2 Cohorts A and B Demonstrated Deep and Durable Responses
During a second oral presentation, longer term efficacy and safety data from CARTITUDE-2 cohorts A and B were also presented at the ASH Annual Meeting ( Abstract #1021). At a median follow-up of approximately 29 months, patients with lenalidomide-refractory MM after one to three lines of therapy (Cohort A) and those with early relapse (Cohort B) that were treated with CARVYKTI® in earlier lines of therapy experienced deep and durable responses .3
In both Cohort A (n=20) and Cohort B (n=19), treatment with CARVYKTI® led to overall response rates of 95 percent (≥CR, 90 percent) and 100 percent (≥CR, 90 percent), respectively. In Cohort A, the 24-month PFS rate was 75 percent, and the 24-month OS rate was 75 percent. As for cohort B, the 24-month PFS and OS rates were 73 percent and 84 percent, respectively. There were no new CAR-T-related safety signals for Cohorts A and B, however one additional CAR-T related cell neurotoxicity (grade 2) was reported in cohort B.3
“We believe the safety and efficacy data presented from the CARTITUDE Clinical Development program at the 2023 ASH Annual Meeting support our continuous efforts to bring CARVYKTI® to myeloma patients in various stages of disease progression,” said Ying Huang, Ph.D., Chief Executive Officer of Legend Biotech. “Part of our mission is to improve the lives of patients worldwide, and we are excited that the CARTITUDE-4 PRO analyses indicate that patients may experience a higher health-related quality of life following a single CARVYKTI® infusion.”
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Disclosure: Dr. Mina has provided consulting, advisory, and speaking services to Legend Biotech
CARVYKTI®Important Safety Information
CARVYKTI® INDICATIONS AND USAGE
CARVYKTI® (ciltacabtagene autoleucel) 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 a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
CARVYKTI® IMPORTANT SAFETY INFORMATION
WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, and PROLONGED and RECURRENT CYTOPENIA
Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with CARVYKTI®. Do not administer CARVYKTI® to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), which may be fatal or life-threatening, occurred following treatment with CARVYKTI®, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with CARVYKTI®. Provide supportive care and/or corticosteroids as needed.
Parkinsonism and Guillain-Barré syndrome and their associated complications resulting in fatal or life-threatening reactions have occurred following treatment with CARVYKTI®.
Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), including fatal and life-threatening reactions, occurred in patients following treatment with CARVYKTI®. HLH/MAS can occur with CRS or neurologic toxicities.
Prolonged and/or recurrent cytopenias with bleeding and infection and requirement for stem cell transplantation for hematopoietic recovery occurred following treatment with CARVYKTI®.
CARVYKTI® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI® REMS Program.
WARNINGS AND PRECAUTIONS
CYTOKINE RELEASE SYNDROME (CRS) including fatal or life-threatening reactions, occurred following treatment with CARVYKTI® in 95% (92/97) of patients receiving ciltacabtagene autoleucel. Grade 3 or higher CRS (2019 ASTCT grade) occurred in 5% (5/97) of patients, with Grade 5 CRS reported in 1 patient. The median time to onset of CRS was 7 days (range: 112 days). The most common manifestations of CRS included pyrexia (100%), hypotension (43%), increased aspartate aminotransferase (AST) (22%), chills (15%), increased alanine aminotransferase (ALT) (14%) and sinus tachycardia (11%). Grade 3 or higher events associated with CRS included increased AST and ALT, hyperbilirubinemia, hypotension, pyrexia, hypoxia, respiratory failure, acute kidney injury, disseminated intravascular coagulation, HLH/MAS, angina pectoris, supraventricular and ventricular tachycardia, malaise, myalgias, increased C-reactive protein, ferritin, blood alkaline phosphatase and gamma-glutamyl transferase.
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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. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS.
Sixty-nine of 97 (71%) patients received tocilizumab and/or a corticosteroid for CRS after infusion of ciltacabtagene autoleucel. Forty-four (45%) patients received only tocilizumab, of whom 33 (34%) received a single dose and 11 (11%) received more than one dose; 24 patients (25%) received tocilizumab and a corticosteroid, and one patient (1%) received only corticosteroids. Ensure that a minimum of two doses of tocilizumab are available prior to infusion of CARVYKTI®.
Monitor patients at least daily for 10 days following CARVYKTI® infusion at a REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion. At the first sign of CRS, immediately institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids.
Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.
NEUROLOGIC TOXICITIES, which may be severe, life-threatening or fatal, occurred following treatment with CARVYKTI®. Neurologic toxicities included ICANS, neurologic toxicity with signs and symptoms of parkinsonism, Guillain-Barré Syndrome, peripheral neuropathies, and cranial nerve palsies. Counsel patients on the signs and symptoms of these neurologic toxicities, and on the delayed nature of onset of some of these toxicities. Instruct patients to seek immediate medical attention for further assessment and management if signs or symptoms of any of these neurologic toxicities occur at any time.
Overall, one or more subtypes of neurologic toxicity described below occurred following ciltacabtagene autoleucel in 26% (25/97) of patients, of which 11% (11/97) of patients experienced Grade 3 or higher events. These subtypes of neurologic toxicities were also observed in two ongoing studies.
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): Patients may experience fatal or life-threatening ICANS following treatment with CARVYKTI®, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. ICANS occurred in 23% (22/97) of patients receiving ciltacabtagene autoleucel including Grade 3 or 4 events in 3% (3/97) and Grade 5 (fatal) events in 2% (2/97). The median time to onset of ICANS was 8 days (range 1-28 days). All 22 patients with ICANS had CRS. The most frequent (≥5%) manifestation of ICANS included encephalopathy (23%), aphasia (8%) and headache (6%).
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Monitor patients at least daily for 10 days following CARVYKTI® infusion at the REMS-certified healthcare facility for signs and symptoms of ICANS. Rule out other causes of ICANS symptoms. Monitor patients for signs or symptoms of ICANS for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed.
Parkinsonism: Of the 25 patients in the CARTITUDE-1 study experiencing any neurotoxicity, five male patients had neurologic toxicity with several signs and symptoms of parkinsonism, distinct from immune effector cell-associated neurotoxicity syndrome (ICANS). Neurologic toxicity with parkinsonism has been reported in other ongoing trials of ciltacabtagene autoleucel. Patients had parkinsonian and non-parkinsonian symptoms that included tremor, bradykinesia, involuntary movements, stereotypy, loss of spontaneous movements, masked facies, apathy, flat affect, fatigue, rigidity, psychomotor retardation, micrographia, dysgraphia, apraxia, lethargy, confusion, somnolence, loss of consciousness, delayed reflexes, hyperreflexia, memory loss, difficulty swallowing, bowel incontinence, falls, stooped posture, shuffling gait, muscle weakness and wasting, motor dysfunction, motor and sensory loss, akinetic mutism, and frontal lobe release signs. The median onset of parkinsonism in the 5 patients in CARTITUDE-1 was 43 days (range 15-108) from infusion of ciltacabtagene autoleucel.
Monitor patients for signs and symptoms of parkinsonism that may be delayed in onset and managed with supportive care measures. There is limited efficacy information with medications used for the treatment of Parkinson’s disease, for the improvement or resolution of parkinsonism symptoms following CARVYKTI® treatment.
Guillain-Barré Syndrome: A fatal outcome following Guillain-Barré Syndrome (GBS) has occurred in another ongoing study of ciltacabtagene autoleucel despite treatment with intravenous immunoglobulins. Symptoms reported include those consistent with Miller-Fisher variant of GBS, encephalopathy, motor weakness, speech disturbances and polyradiculoneuritis.
Monitor for GBS. Evaluate patients presenting with peripheral neuropathy for GBS. Consider treatment of GBS with supportive care measures and in conjunction with immunoglobulins and plasma exchange, depending on severity of GBS.
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Peripheral Neuropathy: Six patients in CARTITUDE-1 developed peripheral neuropathy. These neuropathies presented as sensory, motor, or sensorimotor neuropathies. Median time of onset of symptoms was 62 days (range 4-136 days), median duration of peripheral neuropathies was 256 days (range 2-465 days) including those with ongoing neuropathy. Patients who experienced peripheral neuropathy also experienced cranial nerve palsies or GBS in other ongoing trials of ciltacabtagene autoleucel.
Cranial Nerve Palsies: Three patients (3.1%) experienced cranial nerve palsies in CARTITUDE1. All three patients had 7th cranial nerve palsy; one patient had 5th cranial nerve palsy as well. Median time to onset was 26 days (range 21-101 days) following infusion of ciltacabtagene autoleucel. Occurrence of 3rd and 6th cranial nerve palsy, bilateral 7th cranial nerve palsy, worsening of cranial nerve palsy after improvement, and occurrence of peripheral neuropathy in patients with cranial nerve palsy have also been reported in ongoing trials of ciltacabtagene autoleucel. Monitor patients for signs and symptoms of cranial nerve palsies. Consider management with systemic corticosteroids, depending on the severity and progression of signs and symptoms.
HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH)/MACROPHAGE ACTIVATION SYNDROME (MAS): Fatal HLH occurred in one patient (1%), 99 days after ciltacabtagene autoleucel. The HLH event was preceded by prolonged CRS lasting 97 days. The manifestations of HLH/MAS include hypotension, hypoxia with diffuse alveolar damage, coagulopathy, cytopenia, and multi-organ dysfunction, including renal dysfunction. HLH is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of HLH/MAS should be administered per institutional standards.
CARVYKTI® REMS: Because of the risk of CRS and neurologic toxicities, CARVYKTI® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI® REMS.
PROLONGED AND RECURRENT CYTOPENIAS: Patients may exhibit prolonged and recurrent cytopenias following lymphodepleting chemotherapy and CARVYKTI® infusion. One patient underwent autologous stem cell therapy for hematopoietic reconstitution due to prolonged thrombocytopenia.
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In CARTITUDE-1, 30% (29/97) of patients experienced prolonged Grade 3 or 4 neutropenia and 41% (40/97) of patients experienced prolonged Grade 3 or 4 thrombocytopenia that had not resolved by Day 30 following ciltacabtagene autoleucel infusion.
Recurrent Grade 3 or 4 neutropenia, thrombocytopenia, lymphopenia, and anemia were seen in 63% (61/97), 18% (17/97), 60% (58/97), and 37% (36/97) after recovery from initial Grade 3 or 4 cytopenia following infusion. After Day 60 following ciltacabtagene autoleucel infusion, 31%, 12% and 6% of patients had a recurrence of Grade 3 or higher lymphopenia, neutropenia and thrombocytopenia, respectively, after initial recovery of their Grade 3 or 4 cytopenia. Eighty-seven percent (84/97) of patients had one, two, or three or more recurrences of Grade 3 or 4 cytopenias after initial recovery of Grade 3 or 4 cytopenia. Six and 11 patients had Grade 3 or 4 neutropenia and thrombocytopenia, respectively, at the time of death.
Monitor blood counts prior to and after CARVYKTI® infusion. Manage cytopenias with growth factors and blood product transfusion support according to local institutional guidelines.
INFECTIONS: CARVYKTI® should not be administered to patients with active infection or inflammatory disorders. Severe, life-threatening or fatal infections occurred in patients after CARVYKTI® infusion.
Infections (all grades) occurred in 57 (59%) patients. Grade 3 or 4 infections occurred in 23% (22/97) of patients; Grade 3 or 4 infections with an unspecified pathogen occurred in 17%, viral infections in 7%, bacterial infections in 1%, and fungal infections in 1% of patients. Overall, four patients had Grade 5 infections: lung abscess (n=1), sepsis (n=2) and pneumonia (n=1).
Monitor patients for signs and symptoms of infection before and after CARVYKTI® infusion and treat patients appropriately. Administer prophylactic, pre-emptive and/or therapeutic antimicrobials according to the standard institutional guidelines. Febrile neutropenia was observed in 10% of patients after ciltacabtagene autoleucel 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, as medically indicated.
Viral Reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients with hypogammaglobulinemia. Perform screening for Cytomegalovirus (CMV), HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV), or any other infectious agents if clinically indicated in accordance with clinical guidelines before collection of cells for manufacturing. Consider antiviral therapy to prevent viral reactivation per local institutional guidelines/clinical practice.
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HYPOGAMMAGLOBULINEMIA was reported as an adverse event in 12% (12/97) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 92% (89/97) of patients. Monitor immunoglobulin levels after treatment with CARVYKTI® and administer IVIG for IgG <400 mg/dL. Manage per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis.
Use of Live Vaccines: The safety of immunization with live viral vaccines during or following CARVYKTI® 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 CARVYKTI® treatment, and until immune recovery following treatment with CARVYKTI®.
HYPERSENSITIVITY REACTIONS have occurred in 5% (5/97) of patients following ciltacabtagene autoleucel infusion. Serious hypersensitivity reactions, including anaphylaxis, may be due to the dimethyl sulfoxide (DMSO) in CARVYKTI®. Patients should be carefully monitored for 2 hours after infusion for signs and symptoms of severe reaction. Treat promptly and manage appropriately according to the severity of the hypersensitivity reaction.
SECONDARY MALIGNANCIES: Patients may develop secondary malignancies. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Janssen Biotech, Inc., at 1-800-526-7736 for reporting and to obtain instructions on collection of patient samples for testing of secondary malignancy of T cell origin.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Due to the potential for neurologic events, including altered mental status, seizures, neurocognitive decline, or neuropathy, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following CARVYKTI® 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, and in the event of new onset of any neurologic toxicities.
ADVERSE REACTIONS
The most common non-laboratory adverse reactions (incidence greater than 20%) are pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections of unspecified pathogen, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting. The most common laboratory adverse reactions (incidence greater than or equal to 50%) include thrombocytopenia, neutropenia, anemia, aminotransferase elevation, and hypoalbuminemia.
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ABOUT CARVYKTI® (CILTACABTAGENE AUTOLEUCEL; CILTA-CEL)
Ciltacabtagene autoleucel is a B-cell maturation antigen (BCMA)-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T-cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that express BCMA. BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B-cells and plasma cells. The cilta-cel CAR protein features two BCMA-targeting single domain antibodies designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.4
In December 2017, Legend Biotech entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. (Janssen) to develop and commercialize cilta-cel.
ABOUT CARTITUDE-4
CARTITUDE-4 ( NCT04181827) is an ongoing, international, randomized, open-label Phase 3 study evaluating the efficacy and safety of cilta-cel versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in adult patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy, including a PI and an IMiD. The primary endpoint of the study was progression-free survival.5
ABOUT CARTITUDE-2
CARTITUDE-2 ( NCT04133636) is an ongoing Phase 2 multicohort study evaluating the safety and efficacy of cilta-cel in various clinical settings (Cohorts A, B, C, D, E, F, G, H). The primary study objective is to measure the percentage of patients with negative minimal residual disease (MRD).6
ABOUT MULTIPLE MYELOMA
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.7 In 2023, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma, and more than 12,000 people will die from the disease in the U.S.8 While some patients with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.9
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ABOUT LEGEND BIOTECH
Legend Biotech is a global biotechnology company dedicated to treating, and one day curing, life-threatening diseases. Headquartered in Somerset, New Jersey, we are developing advanced cell therapies across a diverse array of technology platforms, including autologous and allogeneic chimeric antigen receptor T-cell, gamma-delta T cell (γδ T) and natural killer (NK) cell-based immunotherapy. From our three R&D sites around the world, we apply these innovative technologies to pursue the discovery of safe, efficacious and cutting-edge therapeutics for patients worldwide.
Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to Legend Biotech’s expectations for cilta-cel, expectations for Legend Biotech’s product candidates based on clinical trial results,
the potential effect of treatment with cilta-cel and the potential benefits of Legend Biotech’s product candidates. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors. Legend Biotech’s expectations could be affected by, among other things, uncertainties involved in the development of new pharmaceutical products; unexpected clinical trial results, including as a result of additional analysis of existing clinical data or unexpected new clinical data; unexpected regulatory actions or delays, including requests for additional safety and/or efficacy data or analysis of data, or government regulation generally; unexpected delays as a result of actions undertaken, or failures to act, by our third party partners; uncertainties arising from challenges to Legend Biotech’s patent or other proprietary intellectual property protection, including the uncertainties involved in the U.S. litigation process; competition in general; government, industry, and general product pricing and other political pressures; the duration and severity of the COVID-19 pandemic and governmental and regulatory measures implemented in response to the evolving situation; as well as the other factors discussed in the “Risk Factors” section of Legend Biotech’s Annual Report on Form 20-F filed with the Securities and Exchange Commission on March 30, 2023 and other filings and furnishings made by Legend Biotech with the U.S. Securities and Exchange Commission on EDGAR at www.sec.gov. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described in this press release as anticipated, believed, estimated or expected. Any forward-looking statements contained in this press release speak only as of the date of this press release. Legend Biotech specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.
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References
1 Mina, R. Patient-Reported Outcomes in the Phase 3 CARTITUDE-4 Study of Ciltacabtagene Autoleucel Vs Standard of Care in Patients with Lenalidomide-Refractory Multiple Myeloma after 1-3 Lines of Therapy. Abstract #1063 [Oral Presentation]. Presented at the 2023 American Society of Hematology Annual Meeting.
2 Sidiqi, M. H. Efficacy and Safety in Patients with Lenalidomide-Refractory Multiple Myeloma after 1-3 Prior Lines Who Received a Single Infusion of Ciltacabtagene Autoleucel As Study Treatment in the Phase 3 CARTITUDE-4 Trial. Abstract #4866 [Poster Presentation]. Presented at the 2023 American Society of Hematology Annual Meeting.
3 Hillengass, J. The Phase 2 CARTITUDE-2 Trial: Updated Efficacy and Safety of Ciltacabtagene Autoleucel in Patients with Multiple Myeloma and 1–3 Prior Lines of Therapy (Cohort A) and with Early Relapse after First Line Treatment (Cohort B) Abstract #1021 [Oral Presentation]. Presented at the 2023 American Society of Hematology Annual Meeting.
4 CARVYKTI Prescribing Information. Horsham, PA: Janssen Biotech, Inc.
5 ClinicalTrials.gov. A Study Comparing JNJ-68284528, a CAR-T Therapy Directed Against B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Participants With Relapsed and Lenalidomide-Refractory Multiple Myeloma (CARTITUDE-4). Available at: https://clinicaltrials.gov/study/NCT04181827. Last accessed Nov 2023.
6 ClinicalTrials.gov. A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Participants With Multiple Myeloma (CARTITUDE-2). Available at: https://clinicaltrials.gov/study/NCT04133636. Last accessed Nov 2023.
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CIARAN RYAN: Residents and visitors to Port Elizabeth [Gqeberha], now called Nelson Mandela Bay, may remember with fondness the old oceanarium [Bayworld] and the Happy Valley nature park, both of which fell into neglect. Well, that’s about to change. The Mandela Bay Development Agency [MBDA] is behind an ambitious plan called the Bayworld Programme, named after the old oceanarium, to revitalise tourism and commerce in the area.
The plan provides for 13 projects, including a revamped oceanarium, an International Convention Centre [ICC] and a nature park and reserve. It’s situated on the tourism strip and is spread over 55 hectares of prime land within about two-and-a-half kilometres of a planned new aerotropolis, and we’ll find out what that is in a minute, as well as two-and-a-half kilometres from the inner city and an anticipated new waterfront.
Pretty exciting stuff. To find out more, we are joined by Luvoyo Bangazi, corporate services executive, Mandela Bay Development Agency. Hi,Luvoyo, tell us a little bit about the Bayworld Programme, what does it entail and how far along are you in the development?
LUVOYO BANGAZI: Thank you very much. So Bayworld – most South Africans will remember it as that iconic tourism landmark that used to host jumping dolphins and animal shows for entertainment in the late 1970s into the 1980s, receiving about 100 000 to 300 000 visitors a year.
Unfortunately, it fell into hard times, and it went into ruin, and we had to lose our dolphins to Hong Kong.
But fast forward to 2016, this facility, which is owned by the provincial government of the Eastern Cape, is on municipal land, which is Nelson Mandela Bay, and the two parties decided that enough is enough. It’s time to rework this, it’s time to revitalise this and to reboot the economy of the city.
So when the MBDA was tasked with this job, we actually took a step back to say, look, it’s actually part of a much wider precinct. It’s not just the oceanarium. When you look at the parcels of land that are surrounding Bayworld, which includes the Happy Valley nature park that you’ve mentioned, as well as Telkom Park, which is a site that used to host the old rugby stadium, we have now circled that precinct and called it Bayworld.
Just this week, we started demolishing dilapidated structures. We’ve done the feasibility work; we’ve done the economic modelling. We are moving ahead, and we believe this is a great opportunity for investors to have a look at.
CIARAN RYAN: Okay, so this is obviously going to cost money. Where’s that going to come from? Who’s going to pay?
LUVOYO BANGAZI: The good thing is we’ve done the hard yards. We’ve done the feasibility stuff. We’ve done the economic modelling and looked at the yields from this project and we know that there is value for PPPs, which is your public-private partnerships. Some of the projects are purely developmental in nature, which means a lot more government resources will go towards them.
But what we’re planning to do on Tuesday is to really unpack these and say to potential investors and [the] community out there, have a look at this and we need to understand from you how best we can package it so that it makes sense, and it makes economic sense for you to have a look at.
So we are looking at a mix of government funds as well as PPPs.
CIARAN RYAN: Right, so the question is, how far along in the development are you? You mentioned that you started demolishing buildings. I presume that there are other facilities you’re going to have to do, set the groundwork. Are you advanced at all in terms of that?
LUVOYO BANGAZI: We’re advanced in the sense that we’ve done the costings. We have done the base work in terms of dealing with structures that we need to get rid of.
What we are not going to be doing at this point is to not interfere with the market.
We believe that those who look at this will look at the opportunity and will indicate to us what it is that they can take on, and what it is that government needs to do.
For example, we know that bulk services are a key issue, and we need to make sure that there is some provision, or at least there are offsets in terms of when we engage with whoever is keen to develop. The old stadium land parcel has intact services because it functioned with top structures. So there’s minimal work to be done there; at Bayworld, similar.
So we are not going to be investing heavy upfront and interfere with the market. I think we are listening because at this point, we need to understand how the market wishes to engage with this project.
We have done its cost. It’s going to take about R7 billion to completely do all these projects and we don’t expect that from a single investor or a single developer. We’ll probably look at different ways of packaging it.
CIARAN RYAN: Now, you mentioned there are 13 projects in the pipeline, and that’s according to the promotion that you put out. Tell us about a few of them. We talked about the oceanarium that’s being revitalised, and what is an aerotropolis?
LUVOYO BANGAZI: So the aerotropolis sits right outside the Bayworld precinct, and we’ve made reference to it because it’s a gateway to the city.
Our international airport, which needs a revamp, is a gateway to the city and the province.
So the aerotropolis is really an airport city, the likes of DBX in Dubai. An aerotropolis is typically where they have back-end logistics.
But that project is privately pursued, it’s not one of ours. We’re facilitating and supporting it. In terms of Bayworld though, and the Bayworld precinct, that’s where our effort is and that’s where the R7 billion that we’re referring to is identified to be looked at for.
CIARAN RYAN: Now, what impact do you expect this will have on the local economy?
LUVOYO BANGAZI: Huge, huge in two aspects. One, on job creation, but also in terms of the return on investment for those involved.
We know that it’s going to yield increased bed nights activity into the economy, the tourism economy. We also know that it’s going to inject much-needed indirect GDP growth into the economy of the city, which has struggled a bit.
But the three projects that are key for us in this is the oceanarium, which we know is a game changer.
We are looking at a new modern oceanarium that is not a circus, that is not an animal show, but more offering an immersive experience using the latest digital technologies.
We’ve seen these at play such as holograms and so on in other places.
The second one is the ICC. We believe that the city is ripe now for an ICC and to take advantage of the growth that we anticipate. If you think about the fact that we are the automotive hub of South Africa – every major manufacturer is in the Eastern Cape or nearby – there’s been constant demand for international motor shows, but also international conferences for the automotive sector and the downstream supplies.
And we’ve lost out on opportunities to other countries because of this.
So we believe that the ICC, the oceanarium are key, and third, maximising the natural beauty that is there with the Happy Valley nature park.
We believe that our partnership with entities such as the Eastern Cape Parks and Tourism Agency [ECPTA] will unleash potential to bring in small wildlife and add to the mix that is available so that we bring this green lung all the way down to the coast.
So those three projects, amongst the 13, are top priority for us.
CIARAN RYAN: ICC means International Convention Centre, so you’re going to be emulating what Cape Town and, I guess, the Sandton Convention Centre in Joburg has done as well. The Garden Route has obviously become world famous and a high percentage of tourists who visit South Africa, they rate it amongst the most beautiful in the world. Do you expect this development to capture a bit more of this traffic that’s moving through the city and its surroundings?
LUVOYO BANGAZI: Oh, most definitely. So the numbers we’ve done in terms of tourism projections point to the fact that we may be able to increase visitor stays between one and two days just because of this project.
That’s very key for us because we don’t want to be a thoroughfare destination.
We want value to stay in Nelson Mandela Bay; that means the more creative activity that’s engaging and attractive to a diverse set of markets, whether they’re local or international.
In fact, we’re quite focused on the domestic market because we know we are a very cheap destination for the rand value that it is. It’s easy for anyone to come to Nelson Mandela Bay from anywhere in South Africa.
It’s even more of an advantage with internationals. but our first priority is the domestic market, and we know that if we can increase from one day to two more days that’s almost a 100% increase in stay, and that’s a huge benefit for the city.
CIARAN RYAN: Very exciting stuff. Luvoyo Bangazi, corporate services executive, Mandela Bay Development Agency, thanks for joining us.
UK recruiters have warned the Bank of England of a dip in permanent hiring across UK businesses as organisations grapple with ongoing economic turbulence, according to a new report.
KPMG and the Recruitment and Employment Confederation (REC) collected data on the state of the UK jobs market for their latest UK Report on Jobs, observing a decline in the hiring landscape during November.
The REC attributed the dip to economic uncertainty and hesitancy to commit.
The report highlighted a growing disparity between the availability of new job candidates, increasing at the fastest rate since December 2020, and the number of permanent staff hires, which has fallen at the second fastest rate post-pandemic.
It was also found that London saw the sharpest decline in permanent hires across the UK.
Derek Mackenzie, CEO of Investigo, part of The IN Group, commented: “As we approach the new year, bimodal planning has become a popular trend for businesses to navigate economic uncertainty, balancing short-term plans with longer-term business strategies. Pressing business challenges such as generative AI won’t wait for the economy, so it’s important that organisations invest in staff to oversee its development in order to secure their long-term business health.”
Sectors such as technology are already facing a shortage of skills, and when it comes to staff, organisations need digital recruits that can help boost efficiencies, stay on top of emerging trends in areas such as gen AI and data, and ultimately generate revenue for the business.
There are a number of different ways for businesses to hire digitally skilled staff without breaking the bank such as flexible contracts or hiring at an entry-level, but it’s important that organisations invest in people regardless of the economic situation. Unlocking the potential of people through their unique skillsets is key to success” he added.
Despite competition for skilled workers, budgetary pressures due to the economy meant that starting salaries and temporary pay saw slower rises compared to previous months.
The news comes ahead of the Bank of England’s decision on interest rates on December 14. The Bank is expected to keep interest rates unchanged at 5.25 per cent.
In this weekly post, I share with you my most interesting discoveries of the week, including the latest news on the fronts of fitness, nutrition, health, wellness, biohacking, and anti-aging research. I also recap my upcoming events and special announcements so you can keep up with opportunities to learn, giveaways, discounts, and more!
New Discoveries
Exciting News — My Latest Culinary Creation, Boundless Kitchen, Is Finally Here!
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Get ready to expand your cooking skills with dishes ranging from Carrot Cake Blender Waffles to Sous Vide Blueberry Brisket. You’ll not only master techniques like sous vide and air frying but also discover the science of clean eating and the restorative power of food.
Caffeine’s Effects On Exercise Performance Depends On Your Genes
Ever wondered if your genes play a role in how you respond to a pre-workout caffeine boost? A fascinating meta-analysis just shed some light on this, and the results are pretty intriguing…
Researchers dived into how different CYP1A2 genotypes (basically, your genetic makeup) affect your body’s response to caffeine, especially when it comes to exercise performance. Scientists looked at three different blood genotypes (AA, AC, and CC, which refer to the type of hemoglobin present in someone’s red blood cells) and analyzed how caffeine impacted each.
For the AAs and ACs out there: Good news! Caffeine generally improved exercise performance. AAs saw a more significant boost than ACs, but both groups benefited.
But, among the CCs, here’s where it gets interesting. Caffeine actually reduced performance in this group. Plus, the amount and timing of caffeine intake had a unique impact on CCs, affecting their physical performance more than those with other genotypes. For CCs, waiting longer after consuming caffeine led to better performance.
What does this mean for you?
If you’re into fitness and love your caffeine, your genetic makeup might be more important than you think.
While some can enjoy their caffeine boost worry-free, others might need to be more strategic about their caffeine intake, including how much they consume and when.
So, next time you reach for that cup of coffee or pre-workout supplement, remember — your genes might be playing a role in how effective that caffeine kick really is!
Most people don’t know which of these three genotypes they have, but this is useful information nonetheless. Pay attention to how caffeine makes you feel when you work out. Are you more pumped up or easily wiped out? Make adjustments based on your body’s feedback.
Note, if you do want to determine your genotype to better understand how you metabolize different substances, several methods are available, including the electrophoresis method, the Point of Care Test kit (POCT), and the High-Performance Liquid Chromatography (HPLC) method.
Want research hot off the presses as soon as I discover it? Follow me on Twitter.
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My new 16-week program will guide you from information overload to transformation enjoyment.
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Upcoming Events:
Elements of Vitality: December 8, 2023
Return to the Elements of Vitality: This will be the second time my good friend Dr. John Lieurance and I collaborate to bring you the most effective and cutting-edge health and wellness advice, protocols, and some of our favorite tools. If you’re into health and wellness and want to stay on top of all the cutting-edge, latest, and greatest innovations and protocols, you don’t want to miss this event. Learn more here and use code GREENFIELD for 5% off at checkout.
Listed logistics firm Express Kenya Limited has issued a profit warning for the year ending this month on slowed economic activities in the country which it says have significantly reduced demand for warehousing operations.
Coming just a day after another listed firm, Kakuzi Plc, issued a similar statement, the notice by Express Kenya brings to 12 the growing list of publicly traded companies that have issued earnings alerts to investors this year. A majority of them are citing a tough operating environment that includes the high cost of doing business.
Others that have issued the warnings since March include Sameer Africa, Crown Paints, WPP Scangroup, Longhorn Publishers, Sasini, Car & General, Nation Media Group, Centum Investment Company, Unga Group and Kenya Power.
Just like Kakuzi, Express projects that its earnings for the current financial year will be at least 25 percent lower than the income posted last year.
This means that its earnings for 2023 will not surpass Sh56.1 million, having reported a net income of Sh74.8 million last year.
“The warehousing operations of the company are still significantly low due to the decrease in demand and low economic activities leading to reduced income, further resulting to a negative impact on the business performance,” said the firm in a Thursday notice.
“Based on a review of the company’s financial performance, the board of directors has determined that the earnings for the financial year ending December 31, 2023 are projected to be lower than the earnings for the previous year by at least 25 percent.”
Last year, Express Kenya reversed a Sh82.9 million net loss that it had posted in the year ending December 2021.
Kakuzi, on the other hand, projected in a Wednesday statement a decline of at least 25 percent in net earnings from the Sh845.8 million profit posted last year, meaning the figure for this year will not exceed Sh634.4 million.
The agricultural firm attributed the forecast to expected losses arising from a significant decline in demand and price of macadamia on the global markets of China, Japan and the US.
“The anticipated drop in full year net earnings is mainly as a result of our macadamia business which is expected to post a loss due to a significant decline in demand and price in the global markets. However, our other crops are performing as per expectations with a strong performance expected from avocado,” said Kakuzi.
Last year, the firm declared a record dividend of Sh24 per share or a total of Sh470.3 million for the year ended December 2022, after its net income more than doubled from the Sh319.7 million posted in the year ended December 2021.
The payout marked a nine percent increase from the Sh22 per share amounting to Sh431.1 million that was paid for 2021.
The improved earnings were attributed to rising demand for commodities on recovery from the Covid-19 pandemic, as well as the weakening of the local shilling against major world currencies such as the US dollar.
In March this year, Kakuzi announced plans to grow avocado exports to the Chinese market that it said has the potential to become one of the largest destinations for the Kenyan fruit.
BANGKO SENTRAL ng Pilipinas (BSP) Governor Eli M. Remolona, Jr. said it is premature to discuss policy easing in 2024, with the Monetary Board still prepared to hike borrowing costs if needed to make sure inflation returns to the 2-4% target range.
“The risks are still there so we have to assess the situation. I think it’s premature to say we will start to ease,” he told reporters on Wednesday evening.
Mr. Remolona said the BSP remains hawkish as frequent supply shocks could lead to higher inflation expectations and second-round effects.
“We want to be sure (inflation) stays within the target range, comfortably within the target range, and then when we are comfortable about that, we can start to think about easing,” he said.
“If inflation is within the target range for one month, it’s not enough. It has to be there and it has to look like it will stay there until we can start to consider not being hawkish,” he said.
The BSP chief said the goal is to keep inflation expectations anchored to mitigate second-round effects.
Headline inflation slowed for a second straight month in November to 4.1%, its lowest in 20 months. Year to date, inflation averaged 6.2%, still above the central bank’s 6% forecast.
From May 2022 to October this year, the BSP has raised interest rates by 450 basis points (bps), bringing the benchmark interest rate to a 16-year high of 6.5%.
Mr. Remolona also said there will be no cut in banks’ reserve requirement ratio (RRR) while the central bank remains hawkish.
The RRR for big banks is currently at 9.5%, while the ratio for digital banks is at 6%. The BSP also set the RRR for thrift banks, and rural and cooperative banks to 2% and 1%, respectively.
Despite the aggressive rate increases since last year, Mr. Remolona noted Philippine economic growth is still very strong and robust. He noted the impact of policy tightening is gradual, with the effects taking some time to materialize due to prolonged lags.
“We wish (the lags) were shorter,” he said. “We have to improve the transmission mechanism of monetary policy.”
Mr. Remolona also said the central bank does not want to make any unnecessary tightening.
“We want to make just enough tightening so that we get within the target range and expectations remain anchored to our target,” he said.
However, monetary policy may be kept tighter for longer since inflation may go up again next year.
“It’s sort of tricky because we think inflation should be within the (2-4%) target range in the next month or so, and then there’s kind of a base effect then it will go up and maybe exceed the target range (again),” Mr. Remolona said. “Hopefully not, we hope we could settle within the target range for the rest of 2024.”
In early 2024, he noted inflation may ease to below 3% before picking up again to 4% by midyear.
At its November meeting, the BSP lowered its risk-adjusted inflation forecast for 2023 to 6.1% (from 6.2%), to 4.4% (from 4.7%) for 2024, and to 3.4% (from 3.5%) for 2025.
On the other hand, the BSP’s baseline inflation forecast stood at 6% in 2023 and at 3.7% in 2024, before easing to 3.2% in 2025.
Moving forward, Mr. Remolona said the BSP will use the risk-adjusted inflation forecast and emphasized that policy will be based on “likely events.”
Meanwhile, HSBC economist for ASEAN Aris Dacanay in a note said the BSP will keep its policy rate steady on Dec. 14 after inflation eased in November.
“All in all, the economy’s macroeconomic fundamentals are improving and there is no impending need to adjust monetary policy to be even more restrictive,” he said.
However, inflation may rise again and breach the 2-4% target in the second quarter of next year when the tariff rates for agricultural items could increase due to the expiration of Executive Order No. 10 on Dec. 31.
“With upside risks to inflation still heavily tilted to the upside, it may still be too early to put rate cuts on the table. The economy will need time to pause, to ensure that the BSP’s tight monetary stance filters through to the economy,” Mr. Dacanay said.
The BSP may also begin its easing cycle gradually after the US Federal Reserve does its first rate cut within the third quarter of 2024.
“By then, we expect headline CPI to be softening on a consistent basis. Cutting at the same rate as the Fed will also mitigate the volatility of the peso against the dollar given how wide the current account deficit still is for the Philippine economy,” Mr. Dacanay said.
The BSP projects the current account deficit to reach $11.1 billion, or equivalent to -2.5% of gross domestic product (GDP).
In the first semester, the current account deficit stood at $8.2 billion (-4% of GDP), 32.2% lower than the $12.1 billion deficit (-6.1% of GDP) a year ago.
Former Governor from South Carolina and UN ambassador Nikki Haley (L) and Florida Governor Ron DeSantis attend the third Republican presidential primary debate at the Knight Concert Hall at the Adrienne Arsht Center for the Performing Arts in Miami, Florida, on November 8, 2023.
Mandel Ngan | AFP | Getty Images
Florida Gov. Ron DeSantis slammed Nikki Haley’s economic views and financial ties ahead of the fourth Republican primary debate night.
“You see what some of the support she’s garnering from these Wall Street guys who’ve supported Hillary Clinton,” DeSantis said Tuesday in a radio interview. “She really represents that last gasp of the failed Republican establishment of yesteryear.”
The fresh line of attack from DeSantis hinted at what the former U.S. ambassador to the United Nations can expect at Wednesday’s debate in Tuscaloosa, Alabama. The event will be broadcast on NewsNation starting at 8:00 p.m. ET.
As President Joe Biden continues to poll poorly on the economy despite falling gas prices and inflation rates, Republicans see a golden opportunity.
But in order for DeSantis to claim the prize, he will need to stand apart from the rest of the field.
The debate could be one of his last chances to cut into Haley’s momentum before the first-in-the-nation Iowa caucuses next month.
Once seen as the top Republicans alternative to former President Donald Trump, DeSantis has seen his poll numbers slide in recent months, while Haley’s have steadily ticked up.
Some polls now show Haley in second place in the key primary states of New Hampshire and South Carolina — while edging up on DeSantis in Iowa, where he has focused his campaign.
Wall Street weighs in
Haley’s surge has sparked a recent wave of donations from Wall Street veterans and other high-profile donors.
Haley raised over $500,000 on Monday at a glitzy New York City penthouse event packed with financial heavies, CNBC’s Brian Schwartz reported.
Billionaire and LinkedIn co-founder Reid Hoffman also reportedly gave $250,000 to a super PAC backing Haley this week.
A Democrat who supports Biden, Hoffman said in a LinkedIn post that he donated to Haley because “my first priority is American democracy and the integrity of our legal system. That means my first priority is to defeat Trump, and the primary is the first of two chances to do so.”
Read more CNBC politics coverage
Hoffman’s party affiliation was not lost on the DeSantis campaign.
“It makes perfect sense that liberal Democrat billionaires would support Nikki Haley’s bid for the White House, because she is a liberal,” campaign press secretary Bryan Griffin said in a statement.
DeSantis’ campaign also resurfaced Haley’s reported meeting last month with Blackrock CEO Larry Fink, an attack focused on Haley’s stance on ESG.
Fink has championed the investing strategy that considers environmental, social and governance factors. But conservatives have decried it, and DeSantis has barred Florida state officials from using public funds to promote ESG goals.
Haley braces for impact
DeSantis isn’t the only Republican set to take aim at Haley Wednesday night.
Entrepreneur Vivek Ramaswamy has been Haley’s chief antagonist so far, and seemed poised to keep up his attacks in Alabama.
Haley has returned fire, most notably when she called him “scum” in the last debate after he made a remark about her adult daughter’s use of TikTok.
Meanwhile, former New Jersey Gov. Chris Christie has accused Haley of tiptoeing around any criticism of Trump, who leads in national polls by huge margins.
Trump will skip Wednesday’s debate just as he has all the others, leaving Haley and DeSantis to duke it out for the chance to be the top Republican alternative, heading into Iowa.
This may not be as empty of a trophy as it sounds. Trump, after all, lost to Biden in 2020, and faces an unprecedented four criminal cases that could go to trial in the next year.
Haley’s campaign shared a debate “cheat sheet” Wednesday that highlighted negative press coverage about DeSantis’ campaign’s personnel issues, and accused him of lying about her record.
NCAA President Charlie Baker is asking members to make one of the most dramatic shifts in the history of college sports by allowing highly resourced schools to pay some of their athletes.
In a letter sent to more than 350 Division I schools Tuesday, Baker said he wants the association to create a new tier of NCAA Division I sports where schools would be required to offer at least half their athletes a payment of at least $30,000 per year through a trust fund.
Baker also proposed allowing all Division I schools to offer unlimited educational benefits and enter into name, image and likeness licensing deals with athletes.
He said the disparity in resources between the wealthiest schools in the top tier of Division I called the Football Bowl Subdivision and other D-I members — along with the hundreds of Division II and III schools — is creating “a new series of challenges.”
“The challenges are competitive as well as financial and are complicated further by the intersection of name, image and likeness opportunities for student-athletes and the arrival of the Transfer Portal,” wrote Baker, the former Massachusetts governor who took over at the NCAA in March.
Baker is scheduled to speak Wednesday at the Sports Business Journal’s Intercollegiate Athletic Forum in Las Vegas.
Division I is currently divided for football into the FBS, which has 133 schools, and FCS (Football Championship Subdivision).
Baker’s proposal is aimed at creating a new subdivision, covering all sports, where the richest athletic departments in the so-called Power Five conferences — the Big Ten, Southeastern Conference, Big 12, Atlantic Coast Conference and Pac-12 — can operate differently than the rest, while still competing with the rest of Division I.
Conference realignment starting in 2024 will move the Pac-12 out of that group.
The proposed shift would not require all members of a conference to be part of the new subdivision. Schools would be allowed to make that determination individually.
Baker noted athletic budgets in Division I range from $5 million and $250 million annually, with 59 schools spending over $100 million annually and another 32 spending over $50 million. He said 259 Division I schools, however, spend less than $50 million on their athletic programs.
Baker said the difference in the way schools that participate in revenue-generating college sports such as major college football and basketball operate and the vast majority of college sports is complicating attempts to modernize the entire enterprise.
“The contextual environment is equally challenging, as the courts and other public entities continue to debate reform measures that in many cases would seriously damage parts or all of college athletics,” he wrote.
Mountain West Commissioner Gloria Nevarez said a during the Sports Business Journal’s Intercollegiate Sports Forum that subdivision can be a trigger word in the NCAA, stoking worries some schools will be shut out of championship events or lose out on revenue. Nevarez didn’t read Baker’s proposal that way.
“When I read it … it talked about space to make governance,” she said.
Baker and college sports leaders have been pleading with Congress to help the NCAA with a federal law to regulate the way athletes can be paid for NIL deals.
“I am 100% supportive of your efforts. Intercollegiate Athletics needs the proactive and forward thinking you are providing,” Ohio State athletic director Gene Smith said in a post on social media platform X.
Smith oversees one of the largest athletic departments in the country with operating expenses of above $225 million annually.
Former Southern California and NFL star Reggie Bush called schools paying athletes, “Long overdue.”
Bush, who was being inducted into the College Football Hall of Fame on Tuesday night in Las Vegas, was the focus of an NCAA impermissible benefits infractions case during his USC career that resulted in the vacation of a national title for the Trojans and Bush’s 2005 Heisman Trophy victory.
Baker’s letter is an aggressive first step toward a major shift for the NCAA. To turn his vision into detailed legislation will take member feedback, lots of work by the Division I Council and final approval from the Division I Board of Directors.
There is no timetable to bring the proposal to fruition.
The NCAA is also facing a new round of legal threats that could force its members to share some of the billions in revenue generated by major college football and basketball, along with giving athletes employees status. One antitrust case working its way through federal court could cost the NCAA billions in damages.
Baker called on NCAA member schools to create a new framework to make what he called “fundamental changes.”
“First, we should make it possible for all Division I colleges and universities to offer student-athletes any level of enhanced educational benefits they deem appropriate. Second, rules should change for any Division I school, at their choice, to enter into name, image and likeness licensing opportunities with their student-athletes,” he wrote. “These two changes will enhance the financial opportunities available to all Division I student-athletes.”
Currently, schools are allowed — though not required — to provide athletes $5,980 per year in educational benefits under NCAA rules.
Baker said the changes would help level the playing field between men’s and women’s athletics by forcing schools to abide by gender equity regulations as they invest.
He said schools in a new tier of Division I should be allowed, while staying compliant with Title IX, to “invest at least $30,000 per year into an enhanced educational trust fund for at least half of the institution’s eligible student-athletes.”
A new D-I subdivision should also allow members to create unique rules regarding “scholarship commitment and roster size, recruitment, transfers or NIL,” he said.
Mid-American Conference Commissioner Jon Steinbrecher said Baker’s proposal merely defines what already exists: The power conference schools have separated themselves financially, already provide greater benefits to athletes and have some autonomy in the NCAA legislative process.
“I think probably a lot of people are saying this is the precursor of the great breakaway (of power conferences from the NCAA),” Steinbrecher said. “I would suggest to you it’s exactly the opposite. It’s taking the pressure valve off.”
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Pornography websites must strengthen their age verification measures and use tools such as facial scanning software and credit card checks to protect children from their content, as part of the UK’s tough new online safety regime.
Ofcom, the UK’s media regulator tasked with enforcing the Online Safety Act, on Tuesday issued guidance to porn websites, forcing them to introduce stricter technical measures to ensure that their users are over the age of 18. Some websites are no more stringent than asking users whether they are over the age of 18.
Groups that fail to adhere to the rules could be fined up to 10 per cent of annual global revenue, be blocked from operating in the UK or face criminal liability for their named executives.
The UK’s legislation, many years in the making, is seen as among the strongest online regulations in the world, with Ofcom’s new guidance forming its first step in holding companies to account for breaches of the law.
“The heart of the Online Safety Act is around children continuing to enjoy the internet but doing so safely,” Gill Whitehead, Ofcom’s director of online safety, told the Financial Times.
“Children [are] seeing pornography that can be quite violent and quite aggressive,” she added. “The act is very clear that that experience must change.”
The average age at which children first encounter online pornography is 13, according to research by the children’s commissioner this year. However, 27 per cent come across it at 11.
Ofcom’s guidance said that age-assurance methods, which also include user information from banks and photo ID matches, must be “accurate, robust, reliable and fair”.
Facial age estimation, in which a user’s face is scanned to estimate their age, is also on the UK regulator’s list of suggestions. This type of software, however, has been criticised for lacking accuracy, with a greater degree of errors on non-white faces.
“There’s a lot of investment going into this area, and [it is being] improved upon all the time,” said Whitehead. “For example, in bias, there are increasing steps to make sure that the training data sets used are using diverse data.”
Critics, including the Open Rights Group and the Digital Policy Alliance, an internet and technology sector think-tank, argue age verification will create databases containing highly sensitive information that could expose individuals if leaked or hacked.
“Ofcom’s proposed guidelines create serious risks to everyone’s privacy and security,” said Abigail Burke of the Open Rights Group.
“The potential consequences of data being leaked are catastrophic and could include blackmail, fraud, relationship damage and the outing of people’s sexual preferences in very vulnerable circumstances.”
However, Iain Corby, executive director at the Age Verification Providers Association, a trade body for suppliers of age-assurance technologies, said data protection laws prevent this.
“Understandably, no one wants to give a porn site their personal data,” he said. “Our members are tightly regulated and have done over a billion online age checks without any data breaches because we don’t create any new central databases of personal information.”
Researchers dived into how different CYP1A2 genotypes (basically, your genetic makeup) affect your body’s response to caffeine, especially when it comes to exercise performance. Scientists looked at three different blood genotypes (AA, AC, and CC, which refer to the type of hemoglobin present in someone’s red blood cells) and analyzed how caffeine impacted each.
