Legend Biotech Shares Updated Data from Comprehensive Cilta-Cel Clinical Development Program at ASH 2022 Seven accepted poster presentations showcase our continued leadership in CAR-T cell therapy research for patients w

Seven accepted poster presentations showcase our continued leadership in CAR-T cell therapy research for patients with multiple myeloma

New analysis of sustained minimal residual disease (MRD) negativity from the pivotal CARTITUDE-1 study of CARVYKTI (ciltacabtagene autoleucel, cilta-cel) in heavily pretreated adults with relapsed or refractory multiple

First conference presentation of data from the CARTIFAN-1 study of cilta-cel in heavily pretreated Chinese patients with RRMM

SOMERSET, N.J.--(BUSINESS WIRE)--November 3, 2022--Legend Biotech Corporation (NASDAQ: LEGN), a global biotechnology company developing, manufacturing and commercializing novel therapies to treat life-threatening diseases, announced today that

seven company-sponsored studies were accepted for presentation at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition in New Orleans.

The presentations deliver the latest on the clinical development program for ciltacabtagene autoleucel (cilta-cel), the B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of multiple

myeloma (RRMM). The poster presentations will detail an analysis from the Phase 1b/2 CARTITUDE-1 study assessing patients with sustained minimal residual disease (MRD) negativity ( 6 months, and 12 months), as well as updated data from

CARTIFAN-1, a Phase 2 confirmatory trial of cilta-cel in China for the treatment of heavily pretreated Chinese patients with relapsed or refractory multiple myeloma (RRMM). This is the first time that data from CARTIFAN-1 will be presented at a

conference (an earlier data cut has been published in Journal of Clinical Oncology).1

Longer-term follow-up data from the ongoing multicohort Phase 2 study, CARTITUDE-2, will also be presented, communicating results from Cohort B, which is comprised of patients who had early relapse ( 12 months following autologous stem cell

transplant [ASCT] or 12 months following the start of initial treatment with anti-myeloma therapy) and Cohort C, which includes patients with progressive multiple myeloma and previous exposure to a non-cellular anti-BCMA immunotherapy.

The study design of CARTITUDE-6/EMagine will also be presented at the meeting. This Phase 3 study seeks to evaluate the safety and efficacy of daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd) followed by cilta-cel vs DVRd

followed by ASCT in newly diagnosed multiple myeloma patients.

"Cilta-cel's comprehensive clinical development program, which is conducted in collaboration with Janssen, demonstrates our continuous commitment to multiple myeloma research. We're encouraged by the longer-term results from the CARTIFAN-1

study in heavily pretreated patients with RRMM in China," Ying Huang, Ph.D., Chief Executive Officer of Legend Biotech, said. "We look forward to the presentations of the latest cilta-cel data at ASH. We believe that this therapy has the

potential to play an important role for patients suffering from this serious disease."

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

ASH Presentations (December 10-13, 2022)

About CARVYKTI (ciltacabtagene autoleucel; cilta-cel)

CARVYKTI 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 CARVYKTI 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.2

In December 2017, Legend Biotech Corporation entered into an exclusive worldwide license and collaboration agreement with Janssen Pharmaceuticals (Janssen) to develop and commercialize cilta-cel.

In February 2022, CARVYKTI was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with relapsed or refractory multiple myeloma.3 In May 2022, the European Commission (EC) granted

conditional marketing authorization of CARVYKTI for the treatment of adults with relapsed and refractory multiple myeloma.4 In September 2022, Japan's Ministry of Health, Labour and Welfare (MHLW) approved CARVYKTI .5

Cilta-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 May 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.6

CARTITUDE-1 (NCT03548207)7 is a Phase 1b/2, open-label, multicenter study evaluating the safety and efficacy of cilta-cel in adults with relapsed and/or refractory with multiple myeloma who have received at least 3 prior lines of

therapy or are double refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), received a PI, an IMiD, and anti-CD38 antibody and documented disease progression within 12 months of starting the most recent therapy. The

primary objective of the Phase 1b portion of the study was to characterize the safety and confirm the recommended Phase 2 dose of cilta-cel, informed by the first-in-human study with LCAR-B38M CAR-T cells (LEGEND-2). The Phase 2 portion further

evaluated the efficacy of cilta-cel with overall response rate as the primary endpoint.

CARTITUDE-2 (NCT04133636)8 is an ongoing Phase 2 multicohort study evaluating the safety and efficacy of cilta-cel in various clinical settings. Cohort A included patients who had progressive multiple myeloma after 1-3 prior lines

of therapy, including a PI and an IMiD, were lenalidomide refractory, and had no prior exposure to BCMA-targeting agents. Cohort B included patients with early relapse after initial therapy that included a PI and an IMiD. Cohort C included

patients with progressive MM after treatment with a PI, IMiD, anti-CD38 antibody, and non-cellular BCMA-targeting agent. The primary study objective was to measure the percentage of patients with negative minimal residual disease (MRD).

About CARTITUDE-6/EMagine

CARTITUDE-6 (NCT05257083)9 is a Phase 3, randomized, open-label, global study comparing the efficacy and safety of DVRd followed by cilta-cel and lenalidomide vs DVRd followed by ASCT, DVRd, and lenalidomide in patients with newly

diagnosed multiple myeloma. The dual primary endpoints are progression-free survival (PFS) and minimal residual disease (MRD)-negative CR sustained for 12 months.

CARTIFAN-1 (NCT03758417)10 is a Phase 2 open-label, confirmatory trial evaluating the efficacy and safety of cilta-cel in Chinese patients with RRMM who have received at least three prior lines of treatments including a PI and

IMiD. The primary endpoint is overall response rate.

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.11 In 2022, it is estimated that more than 34,000 people will be diagnosed with

multiple myeloma, and more than 12,000 people will die from the disease in the U.S.12 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.13 Although treatment may result in remission, unfortunately, patients will most likely relapse.14 Patients 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.15,16

U.S. CARVYKTI Important Safety Information

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.

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-Barr 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

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: 1 12 days). The most common manifestations of CRS included pyrexia (100%), hypotension (43%), increased

aspartate aminotransferase (AST) (22%), chills (15%), increased alanine aminotransferase (ALT) (14%) and sinus tachycardia (11%). Grade 3 or higher events associated with CRS included increased AST and ALT, hyperbilirubinemia, hypotension,

pyrexia, hypoxia, respiratory failure, acute kidney injury, disseminated intravascular coagulation, HLH/MAS, angina pectoris, supraventricular and ventricular tachycardia, malaise, myalgias, increased C reactive protein, ferritin, blood

alkaline phosphatase and gamma-glutamyl transferase.

Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is

a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS.

Sixty-nine of 97 (71%) patients received tocilizumab and/or a corticosteroid for CRS after infusion of ciltacabtagene autoleucel. Forty-four (45%) patients received only tocilizumab, of whom 33 (34%) received a single dose and 11 (11%)

received more than one dose; 24 patients (25%) received tocilizumab and a corticosteroid, and one patient (1%) received only corticosteroids. Ensure that a minimum of two doses of tocilizumab are available prior to infusion of CARVYKTI .

Monitor patients at least daily for 10 days following CARVYKTI infusion at a REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion. At

the first sign of CRS, immediately institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids.

Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.

Neurologic toxicities, which may be severe, life-threatening or fatal, occurred following treatment with CARVYKTI . Neurologic toxicities included ICANS, neurologic toxicity with signs and symptoms of parkinsonism,

Guillain-Barr Syndrome, peripheral neuropathies, and cranial nerve palsies. Counsel patients on the signs and symptoms of these neurologic toxicities, and on the delayed nature of onset of some of these toxicities. Instruct patients to seek

immediate medical attention for further assessment and management if signs or symptoms of any of these neurologic toxicities occur at any time.

Overall, one or more subtypes of neurologic toxicity described below occurred following ciltacabtagene autoleucel in 26% (25/97) of patients, of which 11% (11/97) of patients experienced Grade 3 or higher events. These subtypes of neurologic

toxicities were also observed in two ongoing studies.

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): Patients may experience fatal or life-threatening ICANS following treatment with CARVYKTI , including before CRS onset, concurrently with

CRS, after CRS resolution, or in the absence of CRS. ICANS occurred in 23% (22/97) of patients receiving ciltacabtagene autoleucel including Grade 3 or 4 events in 3% (3/97) and Grade 5 (fatal) events in 2% (2/97). The median time to onset of

ICANS was 8 days (range 1-28 days). All 22 patients with ICANS had CRS. The most frequent ( 5%) manifestation of ICANS included encephalopathy (23%), aphasia (8%) and headache (6%).

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-Barr Syndrome: A fatal outcome following Guillain-Barr 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.

Peripheral Neuropathy: Six patients in CARTITUDE-1 developed peripheral neuropathy. These neuropathies presented as sensory, motor or sensorimotor neuropathies. Median time of onset of symptoms was 62 days (range

4-136 days), median duration of peripheral neuropathies was 256 days (range 2-465 days) including those with ongoing neuropathy. Patients who experienced peripheral neuropathy also experienced cranial nerve palsies or GBS in other ongoing

trials of ciltacabtagene autoleucel.

Cranial Nerve Palsies: Three patients (3.1%) experienced cranial nerve palsies in CARTITUDE 1. All three patients had 7th cranial nerve palsy; one patient had 5th cranial nerve palsy as well. Median time to onset

was 26 days (range 21-101 days) following infusion of ciltacabtagene autoleucel. Occurrence of 3rd and 6th cranial nerve palsy, bilateral 7th cranial nerve palsy, worsening of cranial nerve palsy after improvement, and occurrence of peripheral

neuropathy in patients with cranial nerve palsy have also been reported in ongoing trials of ciltacabtagene autoleucel. Monitor patients for signs and symptoms of cranial nerve palsies. Consider management with systemic corticosteroids,