Category: Science

Daiichi Sankyo showcases latest research towards creating new standards of care for patients with cancer with data at ASCO and EHA

DESTINY-PanTumor02 late-breaking interim data and DESTINY-CRC02 primary results further support potential of ENHERTU across multiple HER2 expressing cancers
TROPION-Lung02 updated results continue to demonstrate promising clinical activity of datopotamab deruxtecan-based combinations in patients with non-small cell lung cancer
Investor meeting to discuss ASCO presentations and oncology development updates

BASKING RIDGE, N.J. — (BUSINESS WIRE) — Daiichi Sankyo (TSE: 4568) will present new clinical research across its oncology portfolio at the 2023 American Society of Clinical Oncology Scientific Program (#ASCO23) and the European Hematology Association Congress (#EHA23).

Presentations at ASCO showcasing the company’s leadership in developing multiple innovative medicines for patients with cancer will include the DESTINY-PanTumor02 late-breaking (LBA #3000) and DESTINY-CRC02 oral presentations (#3501) evaluating ENHERTU^® (trastuzumab deruxtecan) across multiple HER2 expressing cancers. Data from DESTINY-PanTumor02 will be featured in an ASCO press briefing.

Additional data from Daiichi Sankyo’s DXd antibody drug conjugate (ADC) portfolio at ASCO include oral presentations featuring TROPION-Lung02 updated results of datopotamab deruxtecan (Dato-DXd)-based combinations in patients with advanced or metastatic non-small cell lung cancer (NSCLC) and the first results from BRE-354, a collaborative trial with Sarah Cannon Research Institute, evaluating patritumab deruxtecan (HER3-DXd) in patients with metastatic breast cancer.

Two analyses from the QuANTUM-First trial evaluating the addition of quizartinib to standard induction and consolidation chemotherapy followed by continuation monotherapy for the treatment of patients with newly diagnosed FLT3-ITD positive acute myeloid leukemia (AML) will be highlighted at EHA.

“Our data at ASCO and EHA represent another step forward in realizing our vision to create new standards of care for patients with cancer. Data from our ENHERTU clinical development program will be presented at ASCO showcasing how this medicine potentially may change the way HER2 targetable solid tumors are treated beyond breast, gastric and lung cancer,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “New datopotamab deruxtecan-based combination data from our TROPION-Lung02 trial will be reported at ASCO along with analyses from our QuANTUM-First trial of quizartinib in newly diagnosed acute myeloid leukemia at EHA.”

ENHERTU Redefining HER2 Targetable Cancers

Data from an interim analysis of the DESTINY-PanTumor02 phase 2 trial evaluating ENHERTU in patients with pre-treated metastatic HER2 expressing solid tumors, including biliary tract, bladder, cervical, endometrial, ovarian, pancreatic and other rare cancers will be presented as a late-breaking presentation and included in an ASCO press briefing on Sunday, June 4.

In topline results from DESTINY-PanTumor02, ENHERTU demonstrated clinically meaningful and durable responses across many of these HER2 expressing cancers, potentially redefining how these tumors may be treated. The safety profile observed in the DESTINY-PanTumor02 trial was consistent with that seen in other trials of ENHERTU with no new safety signals identified.

Other ENHERTU data being presented include two oral presentations featuring the primary results from the DESTINY-CRC02 phase 2 trial evaluating ENHERTU in patients with previously treated HER2 overexpressing metastatic colorectal cancer and age-specific pooled analysis of ENHERTU from three global breast cancer trials (DESTINY-Breast01, DESTINY-Breast02 and DESTINY-Breast03).

Datopotamab Deruxtecan-Based Combinations Continuing to Show Promise in NSCLC

Updated results from the TROPION-Lung02 phase 1b trial evaluating datopotamab deruxtecan in combination with pembrolizumab with or without platinum-based chemotherapy in patients with previously untreated or pretreated advanced or metastatic NSCLC without actionable genomic alterations will be featured in an ASCO oral presentation.

Trials-in-progress presentations also will be featured including the TROPION-Lung04 phase 1b trial evaluating datopotamab deruxtecan in various immunotherapy combinations with or without carboplatin in patients with advanced or metastatic NSCLC, and the TROPION-PanTumor03 phase 2 trial evaluating datopotamab deruxtecan monotherapy as well as combination therapy with other anticancer treatments (immunotherapy, PARP inhibitor, VEGF inhibitor or chemotherapy) in patients with advanced/metastatic endometrial, gastric, ovarian, colorectal and castration-resistant prostate cancer.

Daiichi Sankyo will hold a hybrid investor meeting/conference call for investors on Monday, June 5, 2023 from 7:30 to 9:00 pm CDT / Tuesday, June 6, 2023 from 9:30 to 11:00 am JST. Executives from Daiichi Sankyo will provide an overview of the ASCO research data and address questions.

Highlights of data from Daiichi Sankyo’s DXd ADC portfolio at 2023 ASCO include:

Presentation Title		Author	Abstract #	Presentation
ENHERTU (trastuzumab deruxtecan; T-DXd)
Pan-Tumor	Efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with HER2 expressing solid tumors: DESTINY-PanTumor02 (DP-02) interim results	F. Meric-Bernstam	LBA 3000	Oral Presentation Monday, June 5 8:00 – 11:00 am CDT
GI	Trastuzumab deruxtecan (T-DXd) in patients with HER2 overexpressing/amplified (HER2+) metastatic colorectal cancer: primary results from the multicenter, randomized, phase 2 DESTINY-CRC02 study	K. Raghav	3501	Oral Presentation Sunday, June 4 8:00 – 11:00 am CDT
Breast	An age-specific pooled analysis of trastuzumab deruxtecan (T-DXd) in patients with HER2 positive metastatic breast cancer from DESTINY-Breast01, 02, and 03	I. Krop	1006	Oral Presentation Monday, June 5 11:30 am – 2:30 pm CDT
	Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice in patients with HER2 low, hormone receptor-positive unresectable and/or metastatic breast cancer: exploratory biomarker analysis of DESTINY-Breast04	S. Modi	1020	Poster Presentation Sunday, June 4 11:30 am – 1:00 pm CDT
	Interim real-world treatment patterns in patients with HER2+ unresectable or metastatic breast cancer: interim results from HER2 REAL Asia cohort	S. Lee	1047	Poster Presentation Sunday, June 4 8:00 – 11:00 am CDT
Lung	Analytical and clinical validation of Oncomine Dx Target (ODxT) test and local testing for identifying patients with HER2 (ERBB2) mutant non-small cell lung cancer for treatment with trastuzumab deruxtecan (T-DXd) in DESTINY-Lung01/02 (DL-01/02)	B. Li	9033	Poster Presentation Sunday, June 4 8:00 – 11:00 am CDT
Datopotamab Deruxtecan (Dato-DXd)
Lung	TROPION-Lung02: datopotamab deruxtecan (Dato-DXd) plus pembrolizumab with or without platinum chemotherapy in advanced non-small cell lung cancer	Y. Goto	9004	Oral Presentation Tuesday, June 6 9:45 am – 12:45 pm CDT
Lung	TROPION-Lung04: phase 1b, multicenter study of datopotamab deruxtecan (Dato-DXd) in combination with immunotherapy ± carboplatin in advanced/metastatic non-small cell lung cancer	H. Borghaei	TPS3158	Poster Presentation Saturday, June 3 8:00 – 11:00 am CDT
Pan-Tumor	TROPION-PanTumor03: phase 2, multicenter study of datopotamab deruxtecan (Dato-DXd) as monotherapy and in combination with anticancer agents in patients with advanced/metastatic solid tumors	Y. Janjigian	TPS3153	Poster Presentation Saturday, June 3 8:00 – 11:00 am CDT
Patritumab Deruxtecan (HER3-DXd)
Breast	A phase 2 study of HER3-DXd in patients with metastatic breast cancer	E. Hamilton	1004		Oral Presentation Monday, June 5 11:30 am – 2:30 pm CDT

Quizartinib Analyses in Newly Diagnosed FLT3-ITD Positive AML

Two analyses of data from the QuANTUM-First phase 3 trial of quizartinib in combination with standard induction and consolidation chemotherapy and as continuation monotherapy in patients with newly diagnosed FLT3-ITD positive AML will be presented at EHA. An oral presentation will feature data reporting the impact of hematopoietic stem cell transplantation (HSCT) following first complete remission followed by up to three years of quizartinib monotherapy. An analysis of FLT3-ITD-specific measurable residual disease (MRD) and how it

impacted patient outcomes in QuANTUM-First will be reported in a poster presentation. The primary manuscript of the QuANTUM-First trial was recently published online in The Lancet along with approval received in Japan today for use in this AML patient population.

Highlights of data from Daiichi Sankyo at 2023 EHA include:

Presentation Title		Author	Abstract #	Presentation
Quizartinib
AML	Impact of allogeneic hematopoietic cell transplantation in first complete remission plus FLT3 inhibition with quizartinib in acute myeloid leukemia with FLT3-ITD: results from QuANTUM-First	R. Schlenk	S137	Oral Presentation Sunday, June 11 12:00 – 12:15 pm CEST
AML	QuANTUM-First trial: FLT3-ITD-specific measurable residual disease (MRD) clearance is associated with improved overall survival	M. Levis	P483	Poster Presentation Friday, June 9 6:00 – 7:00 pm CEST

About the DXd ADC Portfolio of Daiichi Sankyo

The DXd ADC portfolio of Daiichi Sankyo currently consists of five ADCs in clinical development across multiple types of cancer. The company’s clinical trial stage DXd ADCs include ENHERTU, a HER2 directed ADC and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca; and patritumab deruxtecan (HER3-DXd), a HER3 directed ADC. Two additional ADCs including ifinatamab deruxtecan (I-DXd; DS-7300), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd; DS-6000), a CDH6 directed ADC, are being developed through a strategic early-stage research collaboration with Sarah Cannon Research Institute.

Designed using Daiichi Sankyo’s proprietary DXd ADC technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen, each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan and raludotatug deruxtecan are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.

ENHERTU U.S. Important Safety Information

Indications

ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

Unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either:– In the metastatic setting, or– In the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy

Unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy
Unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapyThis indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen

WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms.
Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.

Contraindications

None.

Warnings and Precautions

Interstitial Lung Disease / Pneumonitis

Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.

Metastatic Breast Cancer and HER2-Mutant NSCLC (5.4 mg/kg)

In patients with metastatic breast cancer and HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 1.0% of patients treated with ENHERTU. Median time to first onset was 5 months (range: 0.9 to 23).

Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21).

Neutropenia

Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 10⁹/L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 10⁹/L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by one level. For febrile neutropenia (ANC <1.0 x 10⁹/L and temperature >38.3º C or a sustained temperature of ≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by one level.

Metastatic Breast Cancer and HER2-Mutant NSCLC (5.4 mg/kg)

In patients with metastatic breast cancer and HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Sixteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 664). Febrile neutropenia was reported in 1.1% of patients.

Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients.

Left Ventricular Dysfunction

Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.

Metastatic Breast Cancer and HER2-Mutant NSCLC (5.4 mg/kg)

In patients with metastatic breast cancer and HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, LVEF decrease was reported in 3.6% of patients, of which 0.4% were Grade 3.

Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF.

Embryo-Fetal Toxicity

ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU.

Additional Dose Modifications

Thrombocytopenia

For Grade 3 thrombocytopenia (platelets <50 to 25 x 10⁹/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 10⁹/L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by one level.

Adverse Reactions

Metastatic Breast Cancer and HER2-Mutant NSCLC (5.4 mg/kg)

The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 984 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast03, DESTINY-Breast04, and DESTINY-Lung02. Among these patients 65% were exposed for >6 months and 39% were exposed for >1 year. In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (71%), decreased hemoglobin (66%), decreased neutrophil count (65%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (47%), increased aspartate aminotransferase (48%), vomiting (44%), increased alanine aminotransferase (42%), alopecia (39%), increased blood alkaline phosphatase (39%), constipation (34%), musculoskeletal pain (32%), decreased appetite (32%), hypokalemia (28%), diarrhea (28%), and respiratory infection (24%).

HER2-Positive Metastatic Breast Cancer

DESTINY-Breast03

The safety of ENHERTU was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg intravenously every three weeks in DESTINY-Breast03. The median duration of treatment was 14 months (range: 0.7 to 30).

Serious adverse reactions occurred in 19% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were vomiting, interstitial lung disease, pneumonia, pyrexia, and urinary tract infection. Fatalities due to adverse reactions occurred in 0.8% of patients including COVID-19 and sudden death (one patient each).

ENHERTU was permanently discontinued in 14% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 44% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, leukopenia, anemia, thrombocytopenia, pneumonia, nausea, fatigue, and ILD/pneumonitis. Dose reductions occurred in 21% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, neutropenia, and fatigue.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (74%), decreased neutrophil count (70%), increased aspartate aminotransferase (67%), decreased hemoglobin (64%), decreased lymphocyte count (55%), increased alanine aminotransferase (53%), decreased platelet count (52%), fatigue (49%), vomiting (49%), increased blood alkaline phosphatase (49%), alopecia (37%), hypokalemia (35%), constipation (34%), musculoskeletal pain (31%), diarrhea (29%), decreased appetite (29%), respiratory infection (22%), headache (22%), abdominal pain (21%), increased blood bilirubin (20%), and stomatitis (20%).

HER2-Low Metastatic Breast Cancer

DESTINY-Breast04

The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU 5.4 mg/kg intravenously every 3 weeks in DESTINY-Breast04. The median duration of treatment was 8 months (range: 0.2 to 33) for patients who received ENHERTU.

Serious adverse reactions occurred in 28% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia, febrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to adverse reactions occurred in 4% of patients including ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural effusion, and respiratory failure (1 patient each).

ENHERTU was permanently discontinued in 16% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 39% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, fatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased transaminases, and hyperbilirubinemia. Dose reductions occurred in 23% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, thrombocytopenia, and neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (70%), decreased hemoglobin (64%), decreased neutrophil count (64%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (44%), alopecia (40%), vomiting (40%), increased aspartate aminotransferase (38%), increased alanine aminotransferase (36%), constipation (34%), increased blood alkaline phosphatase (34%), decreased appetite (32%), musculoskeletal pain (32%), diarrhea (27%), and hypokalemia (25%).

Contacts

Global:
Jennifer Brennan

Daiichi Sankyo, Inc.

jbrennan2@dsi.com
+ 1 908 900 3183 (mobile)

Japan:
Koji Ogiwara

Daiichi Sankyo Co., Ltd.

ogiwara.koji.ay@daiichisankyo.co.jp
+81 3 6225 1126 (office)

Investor Relations Contact:
DaiichiSankyoIR@daiichisankyo.co.jp

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Celltrion USA announces U.S. FDA approval of Yuflyma® (adalimumab-aaty), a high-concentration and citrate-free formulation of Humira® (adalimumab) biosimilar

Yuflyma is FDA approved to treat eight conditions including Crohn’s disease and ulcerative colitis

Yuflyma is the first high-concentration and citrate-free adalimumab biosimilar to gain EU marketing authorization

Yuflyma offers citrate-free and high-concentration adalimumab formulation, providing an alternative treatment option for patients

JERSEY CITY, N.J. — (BUSINESS WIRE) — Celltrion USA today announced that the U.S. Food and Drug Administration (FDA) has approved Yuflyma^® (adalimumab-aaty), a high-concentration (100mg/mL) and citrate-free formulation of Humira^® (adalimumab) biosimilar. The FDA granted approval for the treatment of eight conditions: rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, and hidradenitis suppurativa.¹

Yuflyma is Celltrion’s fifth biosimilar and second anti-TNF biosimilar approved for use in the United States. Yuflyma will offer patients pre-filled syringe and autoinjector administration options to meet different preferences and needs.

“Yuflyma offers patients a high-concentration and citrate-free formulation of adalimumab biosimilar, providing an alternative treatment option for patients. It represents a key treatment option in patient care and patient choice,” said Tom Nusbickel, Chief Commercial Officer at Celltrion USA. “As a leading global biopharmaceutical company, we are leveraging our unique heritage in biotechnology, supply chain excellence, and best-in-class sales capabilities to expand the availability of high-quality biosimilars for U.S. patients.”

“Currently, more than 80% of patients treated with Humira in the United States rely on a high-concentration and citrate-free formulation of this medication. The availability of a high-concentration and citrate-free formulation adalimumab biosimilar provides an important treatment option for patients with inflammatory diseases who benefit from this effective therapy,” said Professor Jonathan Kay of UMass Chan Medical School.

The approval of Yuflyma was based on a comprehensive data package of analytical, preclinical, and clinical studies, demonstrating that Yuflyma is comparable to the reference product in terms of efficacy, safety, pharmacokinetics, and immunogenicity up to 24 weeks and one year following treatment.^2,3,4

Yuflyma will be available to patients in the U.S. starting July 2023.

Celltrion is also seeking an interchangeability designation from the U.S. FDA for Yuflyma, which is tentatively expected Q4 2024.

Notes to Editors:

About Yuflyma^® (CT-P17, biosimilar adalimumab-aaty)¹

Yuflyma was the world’s first proposed high-concentration, low-volume and citrate-free adalimumab biosimilar to receive European Commission approval in Europe. Yuflyma is FDA approved for the treatment of patients with rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, and Hidradenitis Suppurativa. Yuflyma is a recombinant fully human anti–tumour necrosis factor α (anti-TNFα) monoclonal antibody. Following the launch of 40mg/0.4mL, in the U.S. in July 2023, Celltrion additionally plans to launch two different types of dosage forms 80mg/0.8mL, 20mg/0.2mL.

About Interchangeability

An interchangeable biosimilar product is a biosimilar that meets additional requirements outlined by law, and often require additional clinical studies, which demonstrate that there is no additional risk or reduced drug effectiveness if a patient switches back and forth between an interchangeable biosimilar and a reference product, as compared to receiving treatment with just the reference product. When a biosimilar receives an interchangeability designation by the FDA, that means the biosimilar product may be substituted for the reference product without the prescriber having to change the prescription. The substitution may occur at the pharmacy, subject to state pharmacy laws which vary by state, a practice commonly called “pharmacy-level substitution” — similar to how generic drugs are substituted for brand name drugs.

Yuflyma^® IMPORTANT SAFETY INFORMATION¹

SERIOUS INFECTIONS

Patients treated with YUFLYMA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

Discontinue YUFLYMA if a patient develops a serious infection or sepsis.

Reported infections include:

Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before YUFLYMA use and during therapy. Initiate treatment for latent TB prior to YUFLYMA use.
Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric antifungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.
Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

Carefully consider the risks and benefits of treatment with YUFLYMA prior to initiating therapy in patients with chronic or recurrent infection.

Monitor patients closely for the development of signs and symptoms of infection during and after treatment with YUFLYMA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

Treatment with YUFLYMA should not be initiated in patients with an active infection, including localized infections.
Patients over 65 years of age, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants (such as corticosteroids or methotrexate), may be at greater risk of infection. Discontinue YUFLYMA if a patient develops a serious infection or sepsis. For a patient who develops a new infection during treatment with YUFLYMA, closely monitor them, perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and initiate appropriate antimicrobial therapy.
Drug interactions with biologic products: In clinical studies in patients with RA, an increased risk of serious infections has been observed with the combination of TNF blockers with anakinra or abatacept, with no added benefit; therefore, use of YUFLYMA with abatacept or anakinra is not recommended in patients with RA. A higher rate of serious infections has also been observed in patients with RA treated with rituximab who received subsequent treatment with a TNF blocker. There is insufficient information regarding the concomitant use of YUFLYMA and other biologic products for the treatment of RA, PsA, AS, CD, UC, PS, and HS. Concomitant administration of YUFLYMA with other biologic DMARDS (e.g., anakinra and abatacept) or other TNF blockers is not recommended based upon the possible increased risk for infections and other potential pharmacological interactions. A higher rate of serious infections has been observed in RA patients treated with rituximab who received subsequent treatment with a TNF blocker.

MALIGNANCY

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including adalimumab products. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including adalimumab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn’s disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants.

Consider the risks and benefits of TNF blocker treatment including YUFLYMA prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC), or when considering continuing a TNF blocker in patients who develop a malignancy.
In controlled portions of clinical trials of some adalimumab products, more cases of malignancies have been observed compared to control-treated adult patients.
Non-melanoma skin cancer (NMSC) was reported during clinical trials for patients treated with adalimumab products. During the controlled portions of 39 global adalimumab clinical trials in adult patients with RA, PsA, AS, CD, UC, PS and HS, the rate (95% confidence interval) of NMSC was 0.8 (0.52, 1.09) per 100 patient-years among adalimumab-treated patients and 0.2 (0.10, 0.59) per 100 patient-years among control-treated patients. Examine all patients, particularly those with a medical history of prior prolonged immunosuppressant therapy or psoriasis patients with a history of PUVA treatment, for the presence of NMSC prior to and during treatment with YUFLYMA.
In clinical trials of some adalimumab products, there was an approximate threefold higher rate of lymphoma than expected in the general U.S. population. Patients with RA and other chronic inflammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to several fold) than the general population for the development of lymphoma, even in the absence of TNF blockers.
Postmarketing cases of acute and chronic leukemia were reported with use of a TNF blocker in RA and other indications. Approximately half of the postmarketing cases of malignancies in children, adolescents, and young adults receiving adalimumab were lymphomas; other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents.

HYPERSENSITIVITY

Anaphylaxis and angioneurotic edema have been reported following administration of adalimumab products. If an anaphylactic or other serious allergic reaction occurs, immediately discontinue administration of YUFLYMA and institute appropriate therapy.

HEPATITIS B VIRUS REACTIVATION

Use of TNF blockers, including YUFLYMA, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. In some instances, HBV reactivation occurring in conjunction with TNF blocker therapy has been fatal.
Evaluate patients at risk for HBV infection for prior evidence of HBV infection before initiating TNF blocker therapy.
Exercise caution in prescribing TNF blockers for patients identified as carriers of HBV and closely monitor such patients for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy.
In patients who develop HBV reactivation, stop YUFLYMA and initiate effective antiviral therapy with appropriate supportive treatment. The safety of resuming TNF blocker therapy after HBV reactivation is controlled is not known. Therefore, exercise caution when considering resumption of YUFLYMA therapy in this situation and monitor patients closely.

NEUROLOGIC REACTIONS

Use of TNF blocking agents, including adalimumab products, has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease, including multiple sclerosis (MS) and optic neuritis, and peripheral demyelinating disease, including Guillain-Barré syndrome.
Exercise caution in considering the use of YUFLYMA in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of YUFLYMA should be considered if any of these disorders develop.
There is a known association between intermediate uveitis and central demyelinating disorders.

HEMATOLOGIC REACTIONS

Rare reports of pancytopenia including aplastic anemia have been reported with TNF blocking agents.
Adverse reactions of the hematologic system, including medically significant cytopenia, have been infrequently reported with adalimumab products.
Consider discontinuation of YUFLYMA therapy in patients with confirmed significant hematologic abnormalities.

HEART FAILURE

Cases of worsening congestive heart failure (CHF) and new-onset CHF have been reported with TNF blockers. Cases of worsening CHF have also been observed with adalimumab products.
Exercise caution when using YUFLYMA in patients who have heart failure and monitor them carefully.

AUTOIMMUNITY

Treatment with adalimumab products may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with YUFLYMA, discontinue treatment.

IMMUNIZATIONS

Patients on YUFLYMA may receive concurrent vaccinations, except for live vaccines.
It is recommended that pediatric patients, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating YUFLYMA therapy.
No data are available on the secondary transmission of infection by live vaccines in patients receiving adalimumab products.
The safety of administering live or live-attenuated vaccines in infants exposed to adalimumab in utero is unknown. Risks and benefits should be considered prior to vaccinating (live or live-attenuated) exposed infants.

ADVERSE REACTIONS

The most common adverse reactions in adalimumab clinical trials (>10%) were: infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash.

INDICATIONS

YUFLYMA is a tumor necrosis factor (TNF) blocker indicated for:

Rheumatoid Arthritis (RA): reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA
Juvenile Idiopathic Arthritis (JIA): reducing signs and symptoms of moderately to severely active polyarticular JIA in patients 2 years of age and older
Psoriatic Arthritis (PsA): reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active PsA
Ankylosing Spondylitis (AS): reducing signs and symptoms in adult patients with active AS
Crohn’s Disease (CD): treatment of moderately to severely active Crohn’s disease in adults and pediatric patients 6 years of age and older
Ulcerative Colitis (UC): treatment of moderately to severely active ulcerative colitis in adults

Limitations of Use: Effectiveness has not been established in patients who have lost response to or were intolerant to TNF blockers

Plaque Psoriasis (Ps): treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate
Hidradenitis Suppurativa (HS): treatment of adult patients with moderate to severe hidradenitis suppurativa

Please see full Prescribing Information for Yuflyma^® (adalimumab-aaty)

About Celltrion Healthcare

Celltrion Healthcare is committed to delivering innovative and affordable medications to promote patients’ access to advanced therapies. Its products are manufactured at state-of-the-art mammalian cell culture facilities, designed and built to comply with the US FDA Current Good Manufacturing Practice (cGMP) and the EU GMP guidelines. Celltrion Healthcare endeavors to offer high-quality, cost-effective solutions through an extensive global network that spans more than 110 different countries. For more information, please visit: https://www.celltrionhealthcare.com/en-us.

About Celltrion USA

Celltrion USA is Celltrion Healthcare’s U.S. subsidiary established in 2018. Headquartered in New Jersey, Celltrion USA is committed to expanding access to innovative biologics to improve care for U.S. patients. Celltrion currently has five biosimilars approved by the U.S. FDA: Inflectra^® (infliximab-dyyb), Truxima^® (rituximab-abbs), Herzuma^® (trastuzumab-pkrb), Vegzelma^® (bevacizumab-adcd), and Yuflyma^®(adalimumab-aaty). Celltrion USA will continue to leverage Celltrion Healthcare’s unique heritage in biotechnology, supply chain excellence, and best-in-class sales capabilities to improve access to high-quality biopharmaceuticals for U.S. patients.

FORWARD-LOOKING STATEMENT

Certain information set forth in this press release contains statements related to our future business and financial performance and future events or developments involving Celltrion/Celltrion Healthcare that may constitute forward-looking statements, under pertinent securities laws.

These statements may be identified by words such as “prepares”, “hopes to”, “upcoming”, ”plans to”, “aims to”, “to be launched”, “is preparing, “once gained”, “could”, “with the aim of”, “may”, “once identified”, “will”, “working towards”, “is due”, “become available”, “has potential to”, the negative of these words or such other variations thereon or comparable terminology.

In addition, our representatives may make oral forward-looking statements. Such statements are based on the current expectations and certain assumptions of Celltrion/Celltrion Healthcare’s management, of which many are beyond its control.

Forward-looking statements are provided to allow potential investors the opportunity to understand management’s beliefs and opinions in respect of the future so that they may use such beliefs and opinions as one factor in evaluating an investment. These statements are not guarantees of future performance and undue reliance should not be placed on them.

Such forward-looking statements necessarily involve known and unknown risks and uncertainties, which may cause actual performance and financial results in future periods to differ materially from any projections of future performance or result expressed or implied by such forward-looking statements.

Such Risks and uncertainties may include, among other things, uncertainties regarding the launch timing and commercial success of Celltrion in the United States; the uncertainties inherent in supply chain, manufacturing, research and development, and the possibility of unfavorable new clinical data and further analyses of existing clinical data as it relates to Celltrion products; intellectual property and/or litigation/settlement implications; decisions by the FDA impacting labeling, manufacturing processes, safety, promotion, and/or other matters that could affect the availability or commercial potential of Celltrion products; and uncertainties regarding access challenges for our biosimilar products where our product may not receive appropriate formulary access or remains in a disadvantaged position relative to competitive products; and competitive developments. A further description of risks and uncertainties can be found in Celltrion’s Annual Report.

Although forward-looking statements contained in this presentation are based upon what management of Celltrion/Celltrion Healthcare believes are reasonable assumptions, there can be no assurance that forward-looking statements will prove to be accurate, as actual results and future events could differ materially from those anticipated in such statements. Celltrion/Celltrion Healthcare undertakes no obligation to update forward-looking statements if circumstances or management’s estimates or opinions should change except as required by applicable securities laws. The reader is cautioned not to place undue reliance on forward-looking statements.

Trademarks

Humira is a registered trademark of AbbVie.

Yuflyma^® is a registered trademark of Celltrion, Inc., used under license.

References

¹ Yuflyma US prescribing information (2023)

² Yu K et al., Pharmacokinetic Equivalence of CT‐P17 to High‐Concentration (100 mg/mL) Reference Adalimumab: A Randomized Phase I Study in Healthy Subjects. Clin Transl Sci. 2021;14:1280-91.

³ Kay J et al., Efficacy and safety of biosimilar CT-P17 versus reference adalimumab in subjects with rheumatoid arthritis: 24-week results from a randomized study. Arthritis Res Ther. 2021;23(1):51.

⁴ Furst D et al., Efficacy and safety of switching from reference adalimumab to CT-P17 (100 mg/ml): 52-week randomised study in rheumatoid arthritis. Rheumatology. 2022;61(3):1385-95.

Contacts

For further information please contact:

Lindsey Lucenta

llucenta@apcoworldwide.com
+1 260-444-1306

Tags Business, New Jersey

Art & Life Culture International & World Lifestyle Science

Chris Rivers: Satellite now opens at Friedrichs Pontone in NYC

Post author By Editor
Post date May 25, 2023
No Comments on Chris Rivers: Satellite now opens at Friedrichs Pontone in NYC

Friedrichs Pontone art gallery in New York City is thrilled to present Satellite, a solo exhibition of works by British artist Chris Rivers, featuring a mesmerizing selection of his otherworldly, stellar skyscapes. The display opens May 18 until June 18.

Rivers’ large-scale paintings are inspired by the natural world and his fascination with the cosmos. His works capture the beauty and majesty of the sky, from the swirling clouds to the shimmering stars. These paintings are not simply depictions of the natural world, but rather a reflection of Rivers’ own emotional response to it. Rendered in a sumptuous palette of rich color and a welter of expressive, gestural handling that is at once abstract and representational, Rivers conveys the awe-inspiring power of nature and the limitless potential of the universe.

Born in 1983 in Manchester, England, Chris Rivers began his artistic journey in 2014. As a self-taught painter, Rivers brings a fresh perspective to the art world. Formerly a professional drummer for UK rock band Heaven’s Basement, his work is rooted in his background as a musician, which he infuses into his art through the use of rhythm and movement, treating the canvas as a drum. Every painting maintains an energetic, almost frenzied tempo, tempered by subtle manipulations of technique and pace that captivate and enchant the viewer with their strange and beautiful ambience.

His works are a testament to his dedication to exploring and exploiting the pictorial possibilities generated by the physicality of his painting process. Rivers creates sumptuous, surrealistic, fantastical scenes of otherworldly, stellar landscapes with saturated washes of vibrant color that develop into lowering skyscapes, clots, and accretions of impasto that turn into mountain ranges, scattered and scumbled paint fields tha become the detritus of volcanic explosions, and swirling billows of translucent medium that suggest protean

clouds of gas. The contrast of light and dark elements presents a dichotomy that invites the viewer to explore the interplay between opposing forces, evoking at once a sense of innocence and treachery, harmony and dissonance, serenity and turbulence, order and chaos.

He carefully inserts small figures, often astronauts and cherubs, into his galactic turmoil to establish a sense of innocence and isolation, struggle and survival. Indistinguishable at first glance, the figures are subsumed in fiery, elemental vortices of turbulent paint, carried through time and space, desperate voyagers in an alien world. They exist on the edge of the sublime, in awe of the terrifying universe surrounding them. Rivers seems keen to emphasize human vulnerability and at the same time hail the pioneering spirit, inviting the viewer on a fantastic voyage, in anticipation of being lost and found in space.

Through his alchemical and self-described “alternative” process, Rivers transforms mundane material into visionary images. Satellite showcases Rivers’ mastery of the language of painterly abstraction to create pictures of notional and imaginary places and is a testament to Rivers’ artistry and passion for exploring the beauty and wonder of the cosmos, the complexities and contradictions of the human experience, and the

infinite possibilities of the universe.

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American Water recognized on Fortune’s Modern Board 25 ranking

Post author By Michelle Dryden
Post date May 24, 2023
No Comments on American Water recognized on Fortune’s Modern Board 25 ranking

First utility to be honored on the ranking

CAMDEN, N.J.–(BUSINESS WIRE)–American Water (NYSE: AWK), the nation’s largest publicly traded water and wastewater utility company, announced today that it has been named on Fortune’s Modern Board 25 ranking, recognizing the most innovative Boards of Directors among S&P 500 companies.

“American Water is honored to be recognized on Fortune’s Modern Board 25, a testament to the strength of our diverse Board,” said M. Susan Hardwick, President and CEO, American Water. “Achieving and maintaining gender parity and diversity at the Board level is important for the company and we are proud that American Water’s Board of Directors reflects diversity on several levels.”

The 25 companies included in the Fortune Modern Board 25 ranking were in the top quartile of the S&P 500 in board effectiveness, diversity, tenure, financial performance, and vulnerability to activism, positioning them well strategically for long-term, sustainable growth. Learn more about the methodology here.

Additionally, American Water was recently recognized by 50/50 Women on Boards™ for its Gender-Balanced Board of Directors and in 2022 named Champion of Board Diversity by The Forum of Executive Women for the sixth consecutive year. Learn more about American Water’s Inclusion, Diversity and Equity strategy here.

About American Water

With a history dating back to 1886, American Water is the largest and most geographically diverse U.S. publicly traded water and wastewater utility company. The company employs approximately 6,500 dedicated professionals who provide regulated and regulated-like drinking water and wastewater services to an estimated 14 million people in 24 states. American Water provides safe, clean, affordable and reliable water services to our customers to help keep their lives flowing. For more information, visit amwater.com and diversityataw.com. Follow American Water on Twitter, Facebook and LinkedIn.

Contacts

Media Contact

Alicia Barbieri

Manager, Corporate Communications

American Water

856-676-8103

alicia.barbieri@amwater.com

Tags Business, New Jersey

Business Lifestyle News Now! Programs & Events Science Technology

Construction begins on ‘The District at 15fifteen’ in Parsippany, NJ

Post author By Michelle Dryden
Post date May 24, 2023
No Comments on Construction begins on ‘The District at 15fifteen’ in Parsippany, NJ

New mixed-use development will bring 60,000 SF of retail space and 498 apartments to the heart of Morris County, N.J.

PARSIPPANY, N.J. — (BUSINESS WIRE) — A joint venture of Stanbery Development Group, Claremont Development, and PCCP, LLC has broken ground on The District at 15fifteen — a master-planned, mixed-use development in the heart of Morris County, New Jersey. New York Life Insurance Company is providing the construction loan for the project.

Located at 1515 Route 10 in Parsippany, N.J., The District at 15fifteen will feature approximately 60,000 square feet of high-end and local retailers, full and quick-service restaurants, boutique fitness and specialty services, along with a 498-unit luxury apartment community. The three-building, streetscape-style complex will serve as a one-of-a-kind destination that encourages community gatherings with year-round programming such as farmer’s markets, music in the park, food trucks, and family movie nights.

“By bringing new job, commercial, and housing opportunities to Parsippany, this exciting project takes a stagnant property and creates unique and vibrant possibilities that are part of the fabric making Parsippany one of the best places to live, work, and play in NJ,” said Mayor James R. Barberio.

The District at 15fifteen will feature 498 thoughtfully designed luxury rental homes, including 42 affordable units and 49 age-restricted units for residents 55 and over. Spread across two buildings and comprising a mix of studio, one- and two-bedroom units, phase one will be a four-story, wood-framed building with two exterior courtyards and phase two will be a five-story, wood-framed building wrapping an 853-space parking deck with one exterior courtyard. An additional 209 surface parking spaces will also be available with the option of valet parking. Both areas will service the entire development, offering easy access for both residents, retail customers and visitors.

The District at 15fifteen will feature high-end interior finishes and amenitized common spaces tailored to the work-from-home lifestyle. Residents will enjoy access to a full suite of resort-style, modern amenities including a fitness center, yoga studio, pool, lounge area, conference center, co-working/work-from-home options, and dog spa. The 49 age-restricted units will also include access to their own private lobby and amenities including a fitness center, co-working area, party room, and roof deck.

“Over the last several years we have seen Parsippany, and specifically the stretch of Route 10 between Interstate 287 and Route 202, experience an immense transformation with an influx of national retail, restaurant, and hotel options aimed at serving both residents and the large daytime worker population in Morris County,” said Marc Hays, Partner, Acquisitions and Leasing at Stanbery Development Group. “We, alongside our partners at Claremont Development and PCCP, saw an opportunity to cater to that growing need and anchor this bustling section of the Route 10 corridor with not only a high-quality, mixed-use environment, but a new, vibrant town center that cannot be found anywhere else in the region.”

The “pedestrian first” town center design of The District at 15fifteen will provide access for vehicles as well as pedestrian crosswalks that create a livable and walkable design for locals, visitors and the tens of thousands of workers whose headquarters and offices can be found in the area, including Wyndham Worldwide, Avis/Budget Group, Tiffany & Co. and Zoetis, among others.

“As young working professionals continue to seek out accommodations in nearby urban centers, suburban-based companies have been challenged with attracting and retaining a talented workforce,” said Maximilian Dorne, Partner at Claremont Development. “The District at 15fifteen will provide the amenities and modern living options millennials crave and serve as a significant tool for attracting and retaining a qualified pool of employees and employers in Parsippany and the surrounding area. The ability to seamlessly walk to the community’s commercial core for a cup of coffee, morning yoga class, business lunch, or dinner and drinks with friends, caters to this group as well as the active lifestyles of 55 and older residents. The District at 15fifteen has something for everyone.”

The District at 15fifteen has been approved by the New Jersey Department of Transportation to complete roadway improvements that will enhance vehicular circulation to both Route 10 East and West, as well as provide a tie-in to the Dryden Way jug handle. The road improvement will provide a direct connection to the Dryden Way ramps at Route 10 and to the office park immediately across Route 10, formerly known as the Mack-Cali office park, without so much as hitting a traffic light. The direct connection will provide a regional benefit by removing vehicle trips through the intersection of Route 10 and Route 202 while opening an alternative point of access for several other commercial properties.

First move-ins are slated for Fall 2024 with the retail and restaurant portions slated for completion in Fall 2025.

To learn more about The District at 15fifteen please visit: https://www.district1515.com/

About Stanbery Development Group

Stanbery Development Group is a real estate development firm specializing in the acquisition, development and redevelopment, leasing, and asset management of retail driven projects. Since our founding in 2000, Stanbery has been focused on real estate throughout the eastern United States and has developed approximately $1 billion of commercial real estate. Stanbery’s success has been built on a team with a unique blend of talent that covers all aspects of the development and redevelopment life cycle. We couple our agility and quick decision making, with the full range of industry experience and knowledge found in a large firm. As the retail climate has changed, Stanbery has adapted its core focus and now concentrates on mixed-use development, highlighting the synergies between various commercial uses such as multifamily, hotel and retail.

About Claremont Development

Claremont Development is a real estate development firm that focuses primarily on ground-up development of multifamily, industrial, and mixed-use projects throughout New Jersey. We leverage our in-house expertise and strategic partnerships to navigate all elements of the development and construction process in order to minimize our risks and maximize returns. Our ability to identify, acquire, entitle, design, finance and construct projects has set Claremont apart from our competitors. Our core investment strategy focuses on transit-oriented multi-family development opportunities in strong demographic locations, adaptive re-use projects in underutilized urban downtowns, strategic development projects that require substantial environmental remediation efforts, as well as underutilized / off-market properties that can be transitioned into higher density community centers or industrial space.

Claremont Development is responsible for over $2.0 billion of ground up development projects.

About PCCP, LLC

PCCP, LLC is a real estate finance and investment management firm focused on commercial real estate debt and equity investments. PCCP has $21.0 billion in assets under management on behalf of institutional investors. With offices in New York, San Francisco, Atlanta, and Los Angeles, PCCP has a 24-year track record of providing real estate owners and investors with a broad range of funding options to meet capital requirements. PCCP underwrites the entire capital stack to exploit inefficiencies in the market and provide investors with attractive risk-adjusted returns. Since its inception in 1998, PCCP has managed, raised or invested over $36.8 billion of capital through a series of investment vehicles including private equity funds, separate accounts and joint ventures. PCCP continues to seek investment opportunities with experienced operators seeking fast and reliable capital. Learn more about PCCP at www.pccpllc.com.

About New York Life Insurance Company

New York Life Insurance Company (www.newyorklife.com), a Fortune 100 company founded in 1845, is the largest¹ mutual life insurance company in the United States and one of the largest life insurers in the world. Headquartered in New York City, New York Life’s family of companies offers life insurance, retirement income, investments, and long-term care insurance. New York Life has the highest financial strength ratings currently awarded to any U.S. life insurer from all four of the major credit rating agencies.²

¹Based on revenue as reported by “Fortune 500 ranked within Industries, Insurance: Life, Health (Mutual),” Fortune magazine, 5/23/2022. For methodology, please see http://fortune.com/fortune500/.

²Individual independent rating agency commentary as of 10/18/2022: A.M. Best (A++), Fitch (AAA), Moody’s Investors Service (Aaa), Standard & Poor’s (AA+).

Contacts

MEDIA:
Sam DePasquale

Antenna | Spaces

districtat1515@antennagroup.com
(646) 935-3558

Tags Business, New Jersey

Art & Life Education Lifestyle Science

NYC artist Landon Metz releases his first album, ‘Six Days at the Orange House’

Post author By Editor
Post date May 24, 2023
No Comments on NYC artist Landon Metz releases his first album, ‘Six Days at the Orange House’

Landon Metz, is a transdisciplinary, conceptual artist living and working in New York City. His work investigates ontological questions of space, duration, and movement.

Throughout his career thus far, Metz has garnered critical attention for his painting-based practice, often implementing architectural interventions, produced in dye and canvas, advancing traditions of American abstraction. In Metz’s images, forms span multiple panels wrapping impossibly from one border of the canvas to the other – top to bottom, or left to right – hanging in adjoining sequences.

The arrangements trace the contours of architecture with occasional disregard for its surface, portals, or obstructions. They invite the viewer to reflect on how they process and inhabit space, both visually and bodily.

“My practice is largely about breaking down polarities, and I think that’s apparent in the way I present space. It’s about negotiating between setting and subject, public and private.”

In the wake of the birth of his son and the passing of his father, Metz returns to a powerful mode of communication he learned early in life – music.

Releasing on May 26th, Six Days At The Orange House is a deeply personal piece, a sonic catalog of a week Metz spent in Copenhagen during the autumn of 2022. Throughout the work, Metz explores similar themes in music as an extension of his painting and installation practice.

Six Days At The Orange House is a record – a personal narrative made transcendent, juxtaposing pain and longing with hope and gratitude. Like his paintings, each track is produced by hand with care, evidenced in its occasionally irregular metre and organic repetitions. The overall enveloping texture of its sound speaks to Metz’s ability to immerse the listener in a distinctly human, poetic narrative. The album is both immensely personal and universal – a rendering of place with story through tonal sequences, memories, echos, emotions.

Art & Life Business Healthcare Lifestyle News Now! Science

Tevogen Bio will present positive proof-of-concept trial findings at the 5th Annual Allogeneic Cell Therapies Summit in Boston, MA

Tevogen’s ExacTcell platform is designed to produce off-the-shelf, genetically unmodified, allogeneic cytotoxic CD8+ T lymphocyte (CTL) products that can be targeted against malignancies and viruses.
TVGN 489 is the first clinical product from Tevogen’s ExacTcell platform.
TVGN 489 is an off-the-shelf, genetically unmodified, allogeneic CTL product with precise targets across the SARS-CoV-2 genome.
The safety and feasibility of TVGN 489 was successfully tested in high-risk ambulatory patients with COVID-19.

WARREN, N.J. — (BUSINESS WIRE) — #ASCGT2023 — Tevogen Bio is pleased to announce that it will present the proof-of-concept clinical trial results of TVGN 489, the company’s first clinical product from its ExacTcell platform, at the 5th Annual Allogeneic Therapies Summit in Boston, MA.

ExacTcell, Tevogen’s precision T cell platform, utilizes CD8+ Cytotoxic T Lymphocytes (CTLs) also known as Killer T Cells, one of nature’s most powerful weapons against cancer and infection. Unlike currently available genetically engineered T cell therapies, the ExacTcell platform is based on careful selection of naturally occurring T cells that recognize targets of interest from the body’s native T cell receptor pool to provide enhanced safety. CD8+ CTLs in ExacTcell based products target multiple and distinct antigens to overcome potential mutational challenges, such as TVGN 489.

TVGN 489 precisely targets multiple areas across the COVID-19 genome – not just the Spike protein.
To date, these TVGN 489 targets, which were identified early in the pandemic, have persisted through the most recent Omicron derived SARS-CoV-2 variants.
Conducted at Thomas Jefferson University Hospital in Philadelphia, the trial assessed the safety and feasibility of TVGN 489 when given at one of four escalating doses to patients who were at high-risk for COVID-19-related complications due to their age and other medical conditions.
Each patient in the treatment arm received a single infusion of TVGN 489.

Positive Proof-of-Concept Clinical Trial Results:

No dose-limiting toxicities or significant adverse events related to TVGN 489, including Cytokine Release Syndrome, were observed in any patient at any dose level.
Every patient in treatment arm returned to their baseline health status within 14 days.
Following TVGN 489 treatment, no incidence of COVID-19 reinfection or Long COVID was observed in any treated patient at the time of the six (6) month follow up.
Symptom improvement was reported by all patients receiving TVGN 489 within 2 to 3 days of treatment, which corresponded to a significant decrease in COVID-19 viral load on nasal swab PCR testing in the majority of patients.

“TVGN 489 has shown promise as a safe therapy in our proof-of-concept trial, warranting continued development for patients who are vulnerable to poor COVID-19 outcomes, such as the immune-compromised, elderly, and infirm,” stated Dolores Grosso, DNP, the trial’s Principal Investigator.

“These proof-of-concept trial results have illustrated the immense potential of Tevogen’s ExacTcell platform, providing a foundation for the future product development for other viral diseases and various cancers. In addition, we are exploring the potential of TVGN 489 for the treatment and prevention of Long COVID,” said Neal Flomenberg, MD, Tevogen’s Chief Scientific Officer.

“We believe that cell therapies are expected to be the norm, not the exception,” said Tevogen CEO Ryan Saadi, M.D., M.P.H. “Tevogen aspires and is designed to be the very first biotech to achieve commercial success and patient affordability through advanced science and efficient business models.”

About Tevogen’s Next Generation Precision T Cell Platform

Tevogen’s next generation precision T cell platform is designed to provide increased immunologic specificity to eliminate malignant and virally infected cells, while allowing healthy cells to remain intact. Multiple, precise candidate targets on viral or malignant cells are selected in advance for T cell sensitization and effector functions with the goal of overcoming the mutational escape capacity of cancer cells and viruses while limiting cross-reactivity.

Tevogen is investigating its technology’s potential to overcome the primary barriers to the broad application of personalized T cell therapies: potency, purity, production-at-scale, and patient-pairing, without the limitations of current approaches. Tevogen’s goal is to provide access to the vast and unprecedented potential of developing personalized immunotherapies for large patient populations impacted by common cancers and viral infections. The ability to administer TVGN-489 in the outpatient setting and the ongoing work by Tevogen scientists to use this product in diverse patient populations, highlights Tevogen Bio’s commitment to patient accessibility.

About Tevogen Bio

Tevogen Bio is driven by a team of highly experienced industry leaders and distinguished scientists with drug development and global product launch experience. Tevogen’s leadership believes that accessible personalized immunotherapies are the next frontier of medicine, and that disruptive business models are required to sustain medical innovation in the post-pandemic world.

Forward Looking Statements

This press release contains certain forward-looking statements relating to Tevogen Bio™ Inc (the “Company)” and its business. These statements are based on management’s current expectations and beliefs as of the date of this release and are subject to several factors which involve known and unknown risks, delays, uncertainties, and other factors not under the Company’s control that may cause actual results, performance or achievements to be materially different from the results, performance or other expectations implied by these forward-looking statements. Forward-looking statements can sometimes be identified by terminology such as “may,” “will,” “should,” “intend,” “expect,” “believe,” “potential,” and “possible,” or their negatives or comparable terminology, as well as other words and expressions referencing future events, conditions, or circumstances. In any forward-looking statement in which the Company expresses an expectation or belief as to future results, there can be no assurance that the statement or expectation or belief will be achieved. Various factors may cause differences between the Company’s expectations and actual results, including, among others: the Company’s limited operating history; uncertainties inherent in the execution, cost, and completion of preclinical studies and clinical trials; risks related to regulatory review, and approval and commercial development; risks associated with intellectual property protection; and risks related to matters that could affect the Company’s future financial results, including the commercial potential, sales, and pricing of the Company’s products. Except as required by law, the Company undertakes no obligation to update the forward-looking statements or any of the information in this release, or provide additional information, and expressly disclaims any and all liability and makes no representations or warranties in connection herewith or with respect to any omissions therefrom.

Contacts

Tevogen Communications

T: 1 877 TEVOGEN, Ext 701

Communications@Tevogen.com

Tags Business, New Jersey

Business Lifestyle Science Technology

Fuji Electric launches new MONITOUCH V10 series

Post author By Michelle Dryden
Post date May 23, 2023
No Comments on Fuji Electric launches new MONITOUCH V10 series

EDISON, N.J. — (BUSINESS WIRE) — #HMI — Fuji Electric Corp is excited to announce the launch of the NEW MONITOUCH V10 HMI Series. The V10 joins the MONITOUCH V9, TechnoShot, and X1 series of HMI products available from Fuji Electric Corp. The new MONITOUCH V10 Series offers the high-speed processing of a quad-core CPU, allowing for stable operation and communication on high-load screens, an advanced storage device (eMMC) reducing startup/transfer time and man-hours, and the panel cutout size and functions are fully compatible with existing V series!

The new MONITOUCH V10 focuses on the six basic performance aspects of HMIs: Rendering and Operation, offering the highest screen switching speed and quickest input response time. Start-up and Transfer speed for the shortest power on time and highest screen data transfer speed. Communication speed reduces the read and write time of device data. Custom Code at the highest processing speed for rapid macro command execution. These features benefit designers, operators, and maintenance engineers in every application.

Fuji Electric Corp. of America is a wholly owned subsidiary of Fuji Electric Co., Ltd., headquartered in Tokyo, Japan and has been responsible for sales and distribution of the company’s products since 1970. Fuji Electric Co., Ltd. began developing power electronics equipment in 1923, and is a global leader in industrial products ranging from semiconductors, HMIs, contactors, relays, and power generation equipment to AC drives and uninterruptible power supply systems. For more information, please visit https://americas.fujielectric.com/or follow us on LinkedIn and Twitter.

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Healthcare Lifestyle Programs & Events Science

Teva to present data demonstrating UZEDY™ (risperidone) extended-release injectable suspension significantly prolonged time to impending relapse for adults with schizophrenia at the American Psychiatric Association’s 2023 Annual Meeting

UZEDY significantly reduced the risk of relapse by up to 80% and prolonged the time to impending relapse by up to 5.0 times while having a similar safety profile to other formulations of risperidone^1,2
The U.S. Food and Drug Administration (FDA) approved UZEDY on April 28, 2023 for the treatment of schizophrenia in adults as a subcutaneous injection every one or two months using a pre-filled syringe
Symposia on IMPACT-TD scale for tardive dyskinesia (TD) progression measurement and clinical education tool for schizophrenia, S.C.O.P.E., are also to be presented

TEL AVIV, Israel & PARSIPPANY, N.J. — (BUSINESS WIRE) — Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA),today announced that four studies across its neuroscience portfolio will be presented during the American Psychiatric Association’s (APA) 2023 Annual Meeting taking place on May 20-24, 2023. Abstracts include data for UZEDY (risperidone) extended-release injectable suspension for subcutaneous use, which was recently approved by the FDA for the treatment of schizophrenia in adults. Additional abstracts being presented include data on characteristics that impact TD diagnosis and machine-learning to identify unique patient segments for TD. TD is a chronic movement disorder that affects one in four people who take certain mental health treatments.^3-5

Of the data being presented, Teva will share findings from two trials that supported the FDA approval of UZEDY, the RISE Study (The Risperidone Subcutaneous Extended-Release Study) and the SHINE Study (A Study to Test TV-46000 for Maintenance Treatment of Schizophrenia).^6,7 The RISE data demonstrated that UZEDY significantly prolonged time to impending relapse by 5.0 (once-monthly dosing) and 2.7 (once-every-two-months dosing) times versus placebo in patients with schizophrenia.² Additionally, the SHINE data confirmed the safety profile of UZEDY is consistent with other formulations of risperidone.²

“We’re pleased to present the foundational data that supported the FDA’s approval of UZEDY,an important new treatment option for adults with schizophrenia,” said Eric Hughes, MD, PhD, Executive Vice President of Global R&D and Chief Medical Officer at Teva. “We know schizophrenia patients experience a number of challenges when it comes to this condition, and are optimistic that UZEDY can help address the unmet needs of patients, their caregivers, and physicians.”

Findings from the RISE and SHINE studies demonstrate that UZEDY is efficacious with the known safety profile of risperidone. The innovative long-acting formulation of UZEDY allows for both absorption and sustained release after subcutaneous injection and is available with a range of dosing options. UZEDY utilizes SteadyTeq™, a copolymer technology proprietary to MedinCell, that controls the rate and duration of risperidone release. With this delivery system, therapeutic blood concentrations are reached within 6-24 hours of a single dose.¹

In addition to the data, Teva will also be holding a symposium on the newly developed IMPACT-TD scale, featuring Richard Jackson, MD, Assistant Clinical Adjunct Professor, University of Michigan School of Medicine Department of Psychiatry, that may help better measure disease progression of those living with TD by taking a holistic approach to tracking social, vocational, psychological and psychiatric challenges the condition poses over time. A symposium on S.C.O.P.E. featuring John Kane, MD, Professor and Chairman, Department of Psychiatry, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, will also be presented – an educational tool for schizophrenia that helps teach physicians about common myths and misconceptions, manage frequent clinical dilemmas and identify the latest therapeutic options.

This year’s annual APA meeting is being offered both in person and virtually. Abstracts can be accessed here.

The full set of data sponsored by Teva includes:

Symposium: Saturday, May 20, 2:00 PM – 3:00 PM PT

Guiding the S.C.O.P.E. of schizophrenia care forward through interactive digital education for clinicians

Symposium: Monday, May 22, 12:15 PM – 12:45 PM PT

IMPACT-TD scale: A novel tool to assess the true story of the impact of TD in our patients

Poster Session 12: Tuesday, May 23, 1:30 PM – 3:00 PM PT

(De novo) Use of Machine-Learning to Identify Unique Patient Segments Within the Tardive Dyskinesia Population (5040)
(De novo) Assessment of Underdiagnosis of Tardive Dyskinesia (TD) by Geographic Region, Social Determinants, and Other Patient Characteristics (4939)

Poster Session 13: Tuesday, May 23, 3:45 PM – 5:15 PM PT

(De novo) TV-46000, a Long-Acting Subcutaneous Antipsychotic (LASCA) in Schizophrenia: Phase 3 Study (RISE) and Long-Term Safety and Tolerability Study (SHINE) (5523)
(De novo) Myths, Misconceptions, and Clinical Dilemmas Surrounding the Use of Long-acting Injectable Antipsychotic Agents for Treatment of Schizophrenia (4779)

About Tardive Dyskinesia (TD)

Tardive dyskinesia (TD) is a highly debilitating, chronic movement disorder that affects one in four people who take certain mental health treatments and is characterized by uncontrollable, abnormal, and repetitive movements of the face, torso, and/or other body parts, which may be disruptive and negatively impact individuals.^3-5

About Schizophrenia

Schizophrenia is a chronic, progressive and severely debilitating mental disorder that affects how one thinks, feels and acts.⁸ Patients experience an array of symptoms, which may include delusions, hallucinations, disorganized speech or behavior and impaired cognitive ability.^8-10 Approximately 1% of the world’s population will develop schizophrenia in their lifetime, and 3.5 million people in the U.S. are currently diagnosed with the condition.^9,10 Although schizophrenia can occur at any age, the average age of onset tends to be in the late teens to the early 20s for men, and the late 20s to early 30s for women.⁸ The long-term course of schizophrenia is marked by episodes of partial or full remission broken by relapses that often occur in the context of psychiatric emergency and require hospitalization.⁸ Approximately 80% of patients experience multiple relapses over the first five years of treatment, and each relapse carries a biological risk of loss of function, treatment refractoriness, and changes in brain morphology.^11-13 Patients are often unaware of their illness and its consequences, contributing to treatment nonadherence, high discontinuation rates, and ultimately, significant direct and indirect healthcare costs from subsequent relapses and hospitalizations.^8-13

About UZEDY

UZEDY (risperidone) extended-release injectable suspension, for subcutaneous use, is indicated for the treatment of schizophrenia in adults. In clinical trials, UZEDY reduced the risk of relapse by up to 80%.¹ UZEDY administers risperidone through copolymer technology under license from MedinCell that allows for absorption and sustained release after subcutaneous injection. UZEDY is the only long-acting, subcutaneous formulation of risperidone available in both one- and two-month dosing intervals.¹ For full prescribing information, visit https://www.uzedy.com/globalassets/uzedy/prescribing-information.pdf.

INDICATION AND USAGE

UZEDY (risperidone) extended-release injectable suspension for subcutaneous use is indicated for the treatment of schizophrenia in adults.

IMPORTANT SAFETY INFORMATION

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. UZEDY is not approved for use in patients with dementia-related psychosis and has not been studied in this patient population.

CONTRAINDICATIONS: UZEDY is contraindicated in patients with a known hypersensitivity to risperidone, its metabolite, paliperidone, or to any of its components. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone or paliperidone.

WARNINGS AND PRECAUTIONS

Cerebrovascular Adverse Reactions: In trials of elderly patients with dementia-related psychosis, there was a significantly higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, in patients treated with oral risperidone compared to placebo. UZEDY is not approved for use in patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status including delirium, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If NMS is suspected, immediately discontinue UZEDY and provide symptomatic treatment and monitoring.

Tardive Dyskinesia (TD): TD, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to predict which patients will develop the syndrome. Whether antipsychotic drug products differ in their potential to cause TD is unknown.

The risk of developing TD and the likelihood that it will become irreversible are believed to increase with the duration of treatment and the cumulative dose. The syndrome can develop, after relatively brief treatment periods, even at low doses. It may also occur after discontinuation. TD may remit, partially or completely, if antipsychotic treatment is discontinued. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome, possibly masking the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.

If signs and symptoms of TD appear in a patient treated with UZEDY, drug discontinuation should be considered. However, some patients may require treatment with UZEDY despite the presence of the syndrome. In patients who do require chronic treatment, use the lowest dose and the shortest duration of treatment producing a satisfactory clinical response. Periodically reassess the need for continued treatment.

Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain. While all of the drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile.

Hyperglycemia and diabetes mellitus (DM), in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, have been reported in patients treated with atypical antipsychotics, including risperidone. Patients with an established diagnosis of DM who are started on atypical antipsychotics, including UZEDY, should be monitored regularly for worsening of glucose control. Patients with risk factors for DM (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics, including UZEDY, should undergo fasting blood glucose (FBG) testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics, including UZEDY, should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics, including UZEDY, should undergo FBG testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic, including risperidone, was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of risperidone.

Dyslipidemia has been observed in patients treated with atypical antipsychotics.

Weight gain has been observed with atypical antipsychotic use. Monitoring weight is recommended.

Hyperprolactinemia: As with other drugs that antagonize dopamine D₂ receptors, risperidone elevates prolactin levels and the elevation persists during chronic administration. Risperidone is associated with higher levels of prolactin elevation than other antipsychotic agents.

Orthostatic Hypotension and Syncope: UZEDY may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope. UZEDY should be used with particular caution in patients with known cardiovascular disease, cerebrovascular disease, and conditions which would predispose patients to hypotension and in the elderly and patients with renal or hepatic impairment. Monitoring of orthostatic vital signs should be considered in all such patients, and a dose reduction should be considered if hypotension occurs. Clinically significant hypotension has been observed with concomitant use of oral risperidone and antihypertensive medication.

Falls: Antipsychotics, including UZEDY, may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other fall-related injuries. Somnolence, postural hypotension, motor and sensory instability have been reported with the use of risperidone. For patients, particularly the elderly, with diseases, conditions, or medications that could exacerbate these effects, assess the risk of falls when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.

Leukopenia, Neutropenia, and Agranulocytosis have been reported with antipsychotic agents, including risperidone. In patients with a pre-existing history of a clinically significant low white blood cell count (WBC) or absolute neutrophil count (ANC) or a history of drug-induced leukopenia or neutropenia, perform a complete blood count (CBC) frequently during the first few months of therapy. In such patients, consider discontinuation of UZEDY at the first sign of a clinically significant decline in WBC in the absence of other causative factors. Monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection and treat promptly if such symptoms or signs occur. Discontinue UZEDY in patients with ANC < 1000/mm³) and follow their WBC until recovery.

Potential for Cognitive and Motor Impairment: UZEDY, like other antipsychotics, may cause somnolence and has the potential to impair judgement, thinking, and motor skills. Somnolence was a commonly reported adverse reaction associated with oral risperidone treatment. Caution patients about operating hazardous machinery, including motor vehicles, until they are reasonably certain that treatment with UZEDY does not affect them adversely.

Seizures During premarketing studies of oral risperidone in adult patients with schizophrenia, seizures occurred in 0.3% of patients (9 out of 2,607 patients), two in association with hyponatremia. Use UZEDY cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold.

Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Antipsychotic drugs, including UZEDY, should be used cautiously in patients at risk for aspiration.

Priapism has been reported during postmarketing surveillance for other risperidone products. A case of priapism was reported in premarket studies of UZEDY. Severe priapism may require surgical intervention.

Body temperature regulation. Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotic agents. Both hyperthermia and hypothermia have been reported in association with oral risperidone use. Strenuous exercise, exposure to extreme heat, dehydration, and anticholinergic medications may contribute to an elevation in core body temperature; use UZEDY with caution in patients who experience these conditions.

ADVERSE REACTIONS

The most common adverse reactions with risperidone (≥5% and greater than placebo) were parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, anxiety, blurred vision, nausea, vomiting, upper abdominal pain, stomach discomfort, dyspepsia, diarrhea, salivary hypersecretion, constipation, dry mouth, increased appetite, increased weight, fatigue, rash, nasal congestion, upper respiratory tract infection, nasopharyngitis, and pharyngolaryngeal pain.

The most common injection site reactions with UZEDY (≥5% and greater than placebo) were pruritus and nodule.

DRUG INTERACTIONS

Carbamazepine and other strong CYP3A4 inducers decrease plasma concentrations of risperidone.
Fluoxetine, paroxetine, and other strong CYP2D6 inhibitors increase risperidone plasma concentration.
Due to additive pharmacologic effects, the concomitant use of centrally-acting drugs, including alcohol, may increase nervous system disorders.
UZEDY may enhance the hypotensive effects of other therapeutic agents with this potential.
UZEDY may antagonize the pharmacologic effects of dopamine agonists.
Concomitant use with methylphenidate, when there is change in dosage of either medication, may increase the risk of extrapyramidal symptoms (EPS)

USE IN SPECIFIC POPULATIONS

Pregnancy: May cause EPS and/or withdrawal symptoms in neonates with third trimester exposure. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including UZEDY, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinicaland-research-programs/pregnancyregistry/.

Lactation: Infants exposed to risperidone through breastmilk should be monitored for excess sedation, failure to thrive, jitteriness, and EPS.

Fertility: UZEDY may cause a reversible reduction in fertility in females.

Pediatric Use: Safety and effectiveness of UZEDY have not been established in pediatric patients.

Renal or Hepatic Impairment: Carefully titrate on oral risperidone up to at least 2 mg daily before initiating treatment with UZEDY.

Patients with Parkinson’s disease or dementia with Lewy bodies can experience increased sensitivity to UZEDY. Manifestations and features are consistent with NMS.

Please see the full Prescribing Information for UZEDY, including Boxed WARNING.

About Teva

Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) has been developing and producing medicines to improve people’s lives for more than a century. We are a global leader in generic and innovative medicines with a portfolio consisting of over 3,500 products in nearly every therapeutic area. Around 200 million people around the world take a Teva medicine every day, and are served by one of the largest and most complex supply chains in the pharmaceutical industry. Along with our established presence in generics, we have significant innovative research and operations supporting our growing portfolio of innovative and biopharmaceutical products. Learn more at www.tevapharm.com.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, which are based on management’s current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. You can identify these forward-looking statements by the use of words such as “should,” “expect,” “anticipate,” “estimate,” “target,” “may,” “project,” “guidance,” “intend,” “plan,” “believe” and other words and terms of similar meaning and expression in connection with any discussion of future operating or financial performance. Important factors that could cause or contribute to such differences include risks relating to the development and commercial success of UZEDY (risperidone) extended-release injectable suspension for the treatment of schizophrenia; our ability to successfully compete in the marketplace, including our ability to develop and commercialize competition for our innovative medicines, our ability to achieve expected results from investments in our product pipeline, our ability to develop and commercialize additional pharmaceutical products, and the effectiveness of our patents and other measures to protect our intellectual property rights; our substantial indebtedness; our business and operations in general, including, the impact of global economic conditions and other macroeconomic developments and the governmental and societal responses thereto, and costs and delays resulting from the extensive pharmaceutical regulation to which we are subject; compliance, regulatory and litigation matters, including failure to comply with complex legal and regulatory environments; other financial and economic risks; and other factors discussed in our Quarterly Report on Form 10-Q for the first quarter of 2023 and in our Annual Report on Form 10-K for the year ended December 31, 2022, including in the section captioned “Risk Factors.” Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements.

________________________

¹ UZEDY™ (risperidone) extended-release injectable suspension, for subcutaneous injection Current Prescribing Information. Parsippany, NJ. Teva Neuroscience, Inc.

² Kane J, Sharon N. TV-46000, a Long-Acting Subcutaneous Antipsychotic (LASCA) in Schizophrenia: Phase 3 Study (RISE) and Long-Term Safety and Tolerability Study (SHINE). American Psychiatric Association’s 2023 Annual Meeting; 2023. May 20-24. Hybrid congress.

³ Warikoo N, Schwartz T, Citrome L. Tardive dyskinesia. In: Schwartz TL, Megna J, Topel ME, eds. Antipsychotic Drugs. Hauppauge, NY: Nova Science Publishers. 2013:235-258.

⁴ Waln O, Jankovic J. An Update on Tardive Dyskinesia: From Phenomenology to Treatment. Tremor Other Hyperkinet Mov. 2013;3:1-11.

⁵Tardive dyskinesia. National Alliance on Mental Illness website. https://www.nami.org/Learn-More/Treatment/Mental-Health-Medications/Tardive-Dyskinesia. Accessed May 4, 2023.

⁶“A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Risperidone Extended-Release Injectable Suspension (TV-46000) for Subcutaneous Use as Maintenance Treatment in Adult and Adolescent Patients With Schizophrenia. ClinicalTrials.gov, U.S. National Institutes of Health, 2018 (NCT03503318).

Contacts

IR Contacts
Ran Meir +1 (267) 468-4475

Yael Ashman, +972 (3) 914 8262

Sanjeev Sharma +1 (973) 658 2700

PR Contacts
Kelley Dougherty +1 (973) 832-2810

Eden Klein +972 (3) 906 2645

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Healthcare Science

Legend Biotech to demonstrate progress in advancing potential treatment options for patients with multiple myeloma at ASCO and EHA Annual Meetings

Eight presentations at ASCO and EHA 2023 Annual Meetings showcase continued leadership in CAR-T cell therapy research for patients with multiple myeloma across various clinical settings
First analysis from the CARTITUDE-4 Phase 3 study in relapsed and lenalidomide-refractory multiple myeloma patients with one to three earlier lines of therapy to be presented as an oral presentation at ASCO and in a plenary session at EHA
Data from the final analysis of the CARTITUDE-1 study

SOMERSET, N.J. — (BUSINESS WIRE) — $LEGN–Legend Biotech Corporation (“Legend Biotech” or the “Company”) (NASDAQ: LEGN), a global biotechnology company developing, manufacturing and commercializing novel therapies to treat life-threatening diseases, today announced that new and updated data from the CARTITUDE Clinical Development Program evaluating ciltacabtagene autoleucel (cilta-cel) will be presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting and the European Hematology Association’s (EHA) 2023 Hybrid Congress. Five-year follow-up data from Legend-2 (NCT03090659), an investigator-initiated trial that has been assessing a similar CAR construct since 2015, will also be presented at the meetings.

From the CARTITUDE Clinical Development Program, the first analysis of the Phase 3 CARTITUDE-4 study was accepted as a late breaking abstract at ASCO and will be presented as an oral presentation at both ASCO and in a plenary session at EHA. CARTITUDE-4 (NCT04181827) is the first international, randomized, open-label Phase 3 study investigating the treatment of adult patients with relapsed and lenalidomide-refractory multiple myeloma who have received cilta-cel vs standard-of-care regimens, including pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd), following one to three prior lines of therapy.

“We are pleased that the latest data from the CARTITUDE-4 study will be officially presented at the meetings. We are continuing to investigate cilta-cel in earlier lines of treatment and the readout from this study is crucial to how we move forward,” said Ying Huang, Ph.D., Chief Executive Officer of Legend Biotech. “We also eagerly anticipate the presentation of the five-year follow-up data from Legend-2 at ASCO. This was the study that showed — in front of the international community back in 2017 —promising results in heavily pretreated patients with multiple myeloma. Since then, we have taken significant steps toward advancing the treatment landscape for myeloma patients in the CARTITUDE Development Program and are exploring the potential of other agents in our pipeline for this and other indications.”

Additional data at this year’s meetings will include longer-term results from the final protocol-specified analysis of the CARTITUDE-1 study (NCT03548207), which will be shared as a poster presentation at ASCO and an oral presentation at EHA. CARTITUDE-1 is a Phase 1b/2 study evaluating cilta-cel for the treatment of heavily pretreated patients with relapsed or refractory multiple myeloma. The study’s 18-month follow-up data supported the U.S. Food and Drug Administration (FDA) approval of CARVYKTI^® (ciltacabtagene autoleucel; cilta-cel) in February 2022.

Data from the 5-year follow-up analysis of LEGEND-2 will be presented as a poster at ASCO and EHA. This first-in-human, Phase 1 study evaluates LCAR-B38M CAR-T cells in patients with relapsed and refractory multiple myeloma. It is the longest follow-up for any BCMA-targeted CAR-T cell therapy study to be presented at the meetings.

A select list of abstracts from the meetings can be found below.

ASCO Presentations (June 2-6, 2023)

Abstract Number	Title	Information
Abstract #106 Oral Presentation	First Phase 3 results from CARTITUDE-4: Cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma	Session Title: Clinical Science Symposium – Moving Cellular Therapy into Earlier Lines of Treatment in Hematologic Malignancies: Latest Efficacy Data and The Need to Improve Access Date/Time: June 5, 2023, 9:45 am – 11:15 am CDT Location: Hall D1 & On Demand
Abstract #8009 Poster Discussion	CARTITUDE-1 final results: Phase 1b/2 study of ciltacabtagene autoleucel in heavily pretreated patients with relapsed/refractory multiple myeloma	Session Title: Hematologic Malignancies – Plasma Cell Dyscrasia Date/Time: June 5, 2023, 8:00 am – 11:00 am CDT (poster), 3:00 pm – 4:30 pm (discussion) Location: Hall A & On Demand
Abstract #8010 Poster Discussion	Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment of LCAR-B38M CAR-T – at least 5-year follow-up in LEGEND-2	Session Title: Hematologic Malignancies – Plasma Cell Dyscrasia Date/Time: June 5, 2023, 8:00 am – 11:00 am CDT (poster), 3:00 pm – 4:30 pm (discussion) Location: Hall A & On Demand

EHA Presentations (June 8-11, 2023)

Abstract Number

Title

Information

Abstract #P904

Poster Presentation

LocoMMotion: A prospective, observational, multinational study of real-life current standards of care in patients with relapsed/refractory multiple myeloma – final analysis at 2-year follow-up

Friday June 9, 2023

18:00 – 19:00 CEST

Abstract #S100

Plenary Session

Encore: First Phase 3 results from CARTITUDE-4: cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma

Saturday June 10, 2023

14:45-15:00 CEST

Abstract #S202

Oral Presentation

Encore: CARTITUDE-1 final results: Phase 1b/2 study of ciltacabtagene autoleucel in heavily pretreated patients with relapsed/refractory multiple myeloma

Sunday, June 11, 2023

12:00 –12:15 CEST

Abstract #P874

Poster Presentation

Encore: Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment of LCAR-B38M CAR-T – at least 5-year follow-up in LEGEND-2

Friday June 9, 2023

18:00 – 19:00 CEST

Abstract #P922

Poster Presentation

Adjusted comparisons of ciltacabtagene autoleucel with therapies from real-world clinical practice: two-year follow-up analysis from CARTITUDE-1 and the prospective LocoMMotion study

Friday, June 9, 2023

18:00 – 19:00 CEST

ABOUT CARVYKTI^® (CILTACABTAGENE AUTOLEUCEL; CILTA-CEL)

Ciltacabtagene autoleucel is a 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.¹

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.

In February 2022, cilta-cel was approved by the U.S. Food and Drug Administration (FDA) under the brand name CARVYKTI^® for the treatment of adults with relapsed or refractory multiple myeloma.² In May 2022, the European Commission (EC) granted conditional marketing authorization of CARVYKTI^®for the treatment of adults with relapsed and refractory multiple myeloma.³ In September 2022, Japan’s Ministry of Health, Labour and Welfare (MHLW) approved CARVYKTI^®.⁴Cilta-cel was granted Breakthrough Therapy Designation in the U.S. in December 2019 and in China in August 2020. In addition, cilta-cel received a PRIority MEdicines (PRIME) designation from the European Commission in April 2019. Cilta-cel also received Orphan Drug Designation from the U.S. FDA in February 2019, from the European Commission in February 2020, and from the Pharmaceuticals and Medicinal Devices Agency (PMDA) in Japan in June 2020. In March 2022, the European Medicines Agency’s Committee for Orphan Medicinal Products recommended by consensus that the orphan designation for cilta-cel be maintained on the basis of clinical data demonstrating improved and sustained complete response rates following treatment.⁵

ABOUT CARTITUDE-1

CARTITUDE-1 (NCT03548207) is a Phase 1b/2, open-label, single arm, multi-center trial evaluating cilta-cel for the treatment of adult patients with relapsed or refractory multiple myeloma, who previously received at least three prior lines of therapy including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and an anti-CD38 monoclonal antibody. Of the 97 patients enrolled in the trial, 99 percent were refractory to the last line of treatment and 88 percent were triple-class refractory, meaning their cancer did not respond, or no longer responds, to an IMiD, a PI and an anti-CD38 monoclonal antibody.

ABOUT CARTITUDE-4

CARTITUDE-4 (NCT04181827) is the first 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.

ABOUT LEGEND-2

LEGEND-2 (NCT03090659) is a single arm, open-label, multi-center, Phase 1/2 study, to determine the safety and efficacy of LCAR-B38M CAR-T cells in treating patients diagnosed with refractory/relapsed multiple myeloma.

ABOUT LOCOMMOTION

LocoMMotion (NCT04035226) is a prospective, multinational, observational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma who received at least 3 prior lines of therapy including a PI, IMiD and CD38 monoclonal antibody treatment.

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.⁶ 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.⁷ While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.⁸ Although treatment may result in remission, unfortunately, patients will most likely relapse.⁹Patients who relapse after treatment with standard therapies, including protease inhibitors, immunomodulatory agents, and an anti-CD38 monoclonal antibody, have poor prognoses and few treatment options available.^10,11

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 and hemorrhage, HLH/MAS, angina pectoris, supraventricular and ventricular tachycardia, malaise, myalgias, increased Creactive protein, ferritin, blood alkaline phosphatase and gamma-glutamyl transferase.

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. One patient with CRS and suspected HLH/MAS developed a fatal retroperitoneal hemorrhage in the setting of thrombocytopenia, coagulopathy and anticoagulation.

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, immune mediated myelitis, 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%).

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.

Immune Mediated Myelitis: Grade 3 myelitis has occurred 25 days following treatment in another ongoing study. Symptoms reported included hypoesthesia of the lower extremities and the lower abdomen with impaired sphincter control. Symptoms improved with the use of corticosteroids and intravenous immune globulin. Myelitis was ongoing at the time of death from other cause.

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. Monitor patients for signs and symptoms of peripheral neuropathies.

Cranial Nerve Palsies: Three patients (3.1%) experienced cranial nerve palsies in CARTITUDE-1. All three patients had 7^th cranial nerve palsy; one patient had 5^th cranial nerve palsy as well. Median time to onset was 26 days (range 21-101 days) following infusion of ciltacabtagene autoleucel. Occurrence of 3^rd and 6^th cranial nerve palsy, bilateral 7^th 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.

One patient with grade 4 HLH/MAS developed fatal intracerebral and gastrointestinal hemorrhage in the setting of coagulopathy and thrombocytopenia 12 days after treatment in another ongoing study. Patients who develop HLH/MAS have an increased risk of severe bleeding. Monitor hematological parameters in patients with HLH/MAS and transfuse per institutional guidelines.

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.

Further information is available at https://www.carvyktirems.com/ or 1-844-672-0067.

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.

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.

Contacts

PRESS CONTACT:
Tina Carter, Corporate Communications Lead, Legend Biotech

tina.carter@legendbiotech.com
(908) 331-5025

INVESTOR CONTACTS:
Joanne Choi, Senior Manager, Investor Relations, Legend Biotech

joanne.choi@legendbiotech.com

Crystal Chen, Manager, Investor Relations, Legend Biotech

crystal.chen@legendbiotech.cn

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