On December 7, 2022 KSQ Therapeutics, a clinical-stage biotechnology company developing therapies to treat cancer and autoimmune diseases using its proprietary, integrated discovery CRISPRomics platform, reported the initiation of dosing in the combination therapy portion of Study KSQ-4279-1101, a Phase 1 clinical study of KSQ-4279 in patients with advanced solid tumors (Press release, KSQ Therapeutics, DEC 7, 2022, View Source [SID1234624922]). This stage of the clinical study will investigate KSQ-4279 across multiple indications, both in combination with a PARP inhibitor and in combination with chemotherapy.

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"The initiation of the combination therapy portion of the study is a significant milestone for KSQ. We are excited by the strong combination activity that we observed across multiple preclinical models in both BRCA-mutant ovarian and triple-negative breast cancers, including models from patients that relapsed after multiple rounds of chemotherapy and treatment with PARP inhibitors," said Andrew Wylie, Ph.D., Senior Vice President, Head of Oncology at KSQ. "We continue to see strong evidence of the promise and potential of our CRISPRomics platform, and believe we are just beginning to realize the tremendous opportunities to develop therapies with true curative potential for a wide range of cancers, in particular solid tumors, as well as autoimmune diseases."

"The preclinical data suggests there is a broad opportunity to combine KSQ-4279 with PARP inhibitors and with chemotherapy," said Qasim Rizvi, Chief Executive Officer of KSQ. "The safety profile was favorable in preclinical studies, and KSQ-4279 has been well-tolerated in the ongoing Phase 1 clinical trial. No dose-limiting toxicities have been reported to date in the monotherapy dose escalation portion of the clinical trial. In addition, KSQ-4279 has demonstrated tumor growth inhibition as a single agent and led to deep and durable tumor regressions when administered in combination with a PARP inhibitor in multiple preclinical tumor models."

KSQ-4279 preclinical data highlights:

KSQ-4279 is active as a monotherapy in BRCA1-mutant ovarian PDX models, with tumor regressions observed at doses well below its maximum tolerated dose.
KSQ-4279 activity is seen in cancers that harbor defects in homologous recombination (HR), a genetic driver event prevalent in several solid tumor types.
In patient-derived TNBC xenograft models resistant to PARP inhibitor treatment, combining KSQ-4279 with a PARP inhibitor led to durable tumor regressions.
Data presented at the recent ENA 2022 conference described the activity of KSQ-4279 in ovarian tumor ascites models derived from patient tumors that had relapsed after multiple rounds of chemotherapy, including, in some cases, PARP inhibitor therapy.
Four of the ovarian models tested had BRCA1 mutations but were resistant to PARP inhibitor therapy, yet all four were sensitive to KSQ-4279 when used in combination with a PARP inhibitor.
KSQ utilized its proprietary CRISPRomics platform to identify the deubiquitinating enzyme USP1 as an attractive cancer target with established roles in DNA damage repair processes that are distinct from PARP inhibitors and other approaches currently being tested in the clinic. Potent and highly selective inhibitors of USP1 were developed, and profiling of the clinical development candidate KSQ-4279 across a large collection of tumor models confirmed an enriched response rate in cancers with genetic alterations in BRCA1/2 or other HRD lesions.

Study KSQ-4279-1101 is a Phase 1 clinical trial expected to enroll approximately 140 patients with advanced solid tumors. It is a dose-escalation and expansion trial of KSQ-4279 as a monotherapy and in combination. The study’s primary endpoint is to assess the safety of KSQ-4279 both alone and in combination, determine the maximum tolerated dose, and establish a recommended Phase 2 dose. Secondary endpoints include characterizing the pharmacokinetics of KSQ-4279 and evaluating its preliminary antitumor activity alone and in combination. The trial will also explore potential predictive biomarkers and other genetic factors and their correlation with clinical outcomes.

KSQ-4279

KSQ-4279 is a first-in-class small molecule targeting USP1, a protein regulating DNA damage response (DDR). USP1 was identified by KSQ’s CRISPRomics platform as a novel synthetic lethal target in cancers with certain types of genomic instability. KSQ-4279 is currently being evaluated in a Phase 1 study in patients with advanced solid tumors.

On December 7, 2022 Updated results from the DESTINY-Breast03 phase 3 trial (Abstract #GS2-02) reported that ENHERTU (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared to trastuzumab emtansine (T-DM1) in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane (Press release, AstraZeneca, DEC 7, 2022, View Source [SID1234624921]). These results and primary results from the DESTINY-Breast02 phase 3 trial (Abstract #GS2-01) will be presented today at the 2022 San Antonio Breast Cancer Symposium (#SABCS22), with the updated results from DESTINY-Breast03 simultaneously published in The Lancet.

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ENHERTU is a specifically engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo (TSE:4568) and AstraZeneca (LSE/STO/Nasdaq: AZN).

In the key secondary endpoint analysis of OS in DESTINY-Breast03, ENHERTU demonstrated a 36% reduction in risk of death versus T-DM1 (hazard ratio [HR] = 0.64; 95% confidence interval [CI] 0.47-0.87; p=0.0037). In both treatment arms, median OS was not yet reached (ENHERTU [40.5-NE] versus T-DM1 [34.0-NE]) after a median duration of follow-up of 28.4 months for ENHERTU and 26.5 months for T-DM1. In the ENHERTU arm, an estimated 77.4% of patients were alive at two years (95% CI: 71.7-81.2) compared to 69.9% of patients treated with T-DM1 (95% CI: 63.7-75.2). The observed survival benefit was consistent across all analyzed subgroups, including patients with or without baseline brain metastases, with or without baseline visceral disease, those who were hormone receptor (HR) positive or HR negative and patients regardless of prior pertuzumab or lines of systemic therapy.

"The main goals of therapy for advanced breast cancer are to control the disease and improve survival, and it is therefore critical to continue to improve upon existing treatment options, particularly in the metastatic setting," said Sara Hurvitz, MD, Medical Oncologist, Professor of Medicine and Director of the Breast Cancer Clinical Trials Program in the Division of Hematology-Oncology at the David Geffen School of Medicine at UCLA, and Medical Director for the Clinical Research Unit at the UCLA Jonsson Comprehensive Cancer Center in Santa Monica, CA. "For patients with HER2 positive breast cancer who experience disease progression following initial treatment in the metastatic setting, ENHERTU has shown significant improvement in survival compared to T-DM1, further confirming this medicine as the new standard of care."

With the additional follow-up in DESTINY-Breast03, ENHERTU also continued to demonstrate a clinically meaningful improvement in progression-free survival (PFS) with a 22 month improvement in median PFS over T-DM1, reaffirming the statistically significant finding at the previous interim analysis. The updated exploratory analysis was not tested for statistical significance and not powered to show differences between treatment arms. The median PFS for patients in the ENHERTU arm was 28.8 months (HR=0.33; 95% CI: 22.4-37.9) compared to 6.8 months for T-DM1 (95% CI: 5.6-8.2) as assessed by blinded independent central review (BICR). Confirmed objective response rate (ORR) was 78.5% in the ENHERTU arm with 21.1% of patients demonstrating a complete response (CR) versus an ORR of 35.0% in the T-DM1 arm where 9.5% of patients achieved a CR. The median duration of response (DoR) was 36.6 months in the ENHERTU arm and 23.8 months in the T-DM1 arm.

The safety profile observed with ENHERTU in DESTINY-Breast03 was consistent with previous clinical trials with no new safety concerns identified. Grade 3 or higher treatment-related treatment emergent adverse events (TEAEs) occurred in 47.1% of patients receiving ENHERTU. The most common grade 3 or higher treatment-related TEAEs in the ENHERTU arm were decreased neutrophil count (16.0%), anemia (9.3%), decreased platelet count (7.8%), nausea (7.0%), decreased white blood cell count (6.2%) and fatigue (5.8%). In the ENHERTU arm, 15.2% of patients (n=39) experienced interstitial lung disease (ILD) or pneumonitis related to treatment as determined by an independent adjudication committee. The majority of ILD or pneumonitis events were low grade (grade 1 or grade 2) with two grade 3 events and no grade 4 or grade 5 events observed in patients treated with ENHERTU.

"The overall survival benefits shown in both the DESTINY-Breast03 and DESTINY-Breast02 trials further validate the role of ENHERTU in potentially extending the lives of patients with previously treated HER2 positive breast cancer," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "Additionally, median progression-free survival was four times longer with one in five patients showing no detectable signs of disease when treated with ENHERTU compared to T-DM1 in DESTINY-Breast03, which is particularly impressive in the metastatic setting of HER2 positive breast cancer."

"The updated results for DESTINY-Breast03 showing that ENHERTU extends patients’ lives and also delays progression by nearly two years reinforces our belief that this medicine has the potential to set a new standard of care for patients with HER2 positive metastatic breast cancer treated in the second-line setting," said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. "Complemented by DESTINY-Breast02, we now have two phase 3 trials in HER2 positive metastatic breast cancer showing patients in these trials have more disease-free time and live longer when they receive ENHERTU versus the previous standard of care."

All patients in DESTINY-Breast03 received at least one prior cancer therapy, including trastuzumab (ENHERTU = 99.6%; T-DM1 = 99.6%) or pertuzumab (ENHERTU = 62.1%; T-DM1 = 60.1%). In the ENHERTU arm, 41.4% of patients had received one prior line of therapy in the metastatic setting. At baseline, 16.5% of patients in the ENHERTU arm and 14.8% of patients in the T-DM1 arm had a history of brain metastases. As of data cut-off on July 25, 2022, 75 patients remained on treatment with ENHERTU and 18 patients on T-DM1.

Summary of Updated DESTINY-Breast03 Results

Efficacy Measure

ENHERTU (5.4 mg/kg)

n=261

Trastuzumab Emtansine
(T-DM1; 3.6 mg/kg)

n=263

Median OS, months (95% CI)

Not reached (40.5-NE)

Not reached (34.0-NE)

HR=0.64 (0.47-0.87) p=0.0037i

OS rate (%) (95% CI)

12 months

94.1% (90.4-96.4)

86.0% (81.1-89.8)

24 months

77.4 % (71.7-82.1)

69.9% (63.7-75.2)

Median PFS by BICR, months (95% CI)

28.8 months (22.4-37.9)

6.8 months (5.6-8.2)

HR=0.33 (0.26-0.43) p<000001i,ii

Median PFS2 by investigator, months (95% CI)iii

40.5 months (40.5-NE)

25.7 months (18.5-34.0)

HR=0.47 (0.35-0.62) p=0.000001i,ii

Confirmed ORR, % (95% CI)

78.5% (73.1-83.4)

35.0% (29.2-41.1)

p<0.0001i,ii

CR (%)

21.1% (n=55)

9.5% (n=25)

PR (%)

57.5% (n=150)

25.5% (n=67)

SD (%)

18.0% (n=47)

41.8% (n=110)

PD (%)

1.1% (n=3)

17.9% (n=47)

Median DoR, months (95% CI)iv

36.6 months (22.4-NE)

23.8 months (12.6-34.7)

BICR, blinded independent central review; CI, confidence interval; CR, complete response, DoR, duration of response; ORR, objective response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PFS2, second progression-free survival; PR, partial response; SD, stable disease

i Two-sided

ii Nominal p value. Updated exploratory analysis was not tested for statistical significance and not powered to show differences between treatment arms

iii From the time of randomization to second progression

iv Based on BICR

DESTINY-Breast02 Primary Results
In the primary results from the DESTINY-Breast02 phase 3 trial, ENHERTU demonstrated a 64% reduction in the risk of disease progression or death in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with T-DM1 compared to physician’s choice of treatment (trastuzumab plus capecitabine or lapatinib plus capecitabine) (HR=0.36; 95% CI: 0.28-0.45; p<0.000001). The median PFS for patients in the ENHERTU arm was 17.8 months (95% CI: 14.3-20.8) compared to 6.9 months (95% CI: 5.5-8.4) for those treated with physician’s choice of therapy as assessed by BICR. Treatment with ENHERTU also showed a 34% reduction in the risk of death compared to physician’s choice of treatment (HR=0.66; 95% CI: 0.50-0.86; p=0.0021) with a median OS of 39.2 months with ENHERTU (95% CI: 32.7-NE) versus 26.5 months with physician’s choice of therapy (95% CI: 21.0-NE).

The data from DESTINY-Breast02 confirm the data seen in the DESTINY-Breast01 phase 2 trial, which supported the first approvals of ENHERTU in patients with HER2 positive metastatic breast cancer who received two or more prior anti-HER2-based regimens.

The safety profile observed with ENHERTU in DESTINY-Breast02 was consistent with previous clinical trials with no new safety concerns identified. Grade 3 or higher treatment-related TEAEs occurred in 41.3% of patients receiving ENHERTU. The most common grade 3 or higher treatment-related TEAEs in the ENHERTU arm were decreased neutrophil count (10.6%), anemia (7.9%), neutropenia (7.7%), nausea (6.7%) and asthenia (5.0%). In the ENHERTU arm, 10.4% of patients (n=42) experienced ILD or pneumonitis related to treatment as determined by an independent adjudication committee. The majority of ILD or pneumonitis events were low grade (grade 1 or grade 2), with three grade 3 events, no grade 4 events and two grade 5 events observed.

About DESTINY-Breast03
DESTINY-Breast03 is a global, head-to-head, randomized, open-label, pivotal phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus T-DM1 in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The primary efficacy endpoint of DESTINY-Breast03 is PFS based on BICR. OS is a key secondary efficacy outcome measure. Other secondary endpoints include ORR, DoR, PFS based on investigator assessment and safety. DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia, Europe, North America, Oceania and South America. Primary results from DESTINY-Breast03 were published in The New England Journal of Medicine, with updated OS results published in The Lancet. For more information about the trial, visit ClinicalTrials.gov.

About DESTINY-Breast02
DESTINY-Breast02 is a global, randomized, open-label, pivotal phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus physician’s choice of treatment (trastuzumab/capecitabine or lapatinib/capecitabine) in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with T-DM1. Patients were randomized 2:1 to receive either ENHERTU or physician’s choice of treatment. The primary endpoint of DESTINY-Breast02 is PFS based on BICR. The key secondary endpoint is OS. Other secondary endpoints include ORR based on BICR and investigator assessment, DoR based on BICR, PFS based on investigator assessment and safety. DESTINY-Breast02 enrolled approximately 600 patients at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

About HER2 Positive Breast Cancer
Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2020, with nearly 685,000 deaths globally.1 Approximately one in five cases of breast cancer are considered HER2 positive.2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers.3 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.4

Despite initial treatment with trastuzumab and a taxane, patients with HER2 positive metastatic breast cancer will often experience disease progression.5,6

About ENHERTU
ENHERTU (trastuzumab deruxtecan, fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

ENHERTU (5.4 mg/kg) is approved in more than 35 countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received a (or one or more) 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 based on the results from the DESTINY-Breast03 trial. ENHERTU also is approved in several countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.

ENHERTU (5.4 mg/kg) is approved in Brazil and the U.S. for the treatment of adult patients with unresectable or metastatic HER2 low (immunohistochemistry (IHC) 1+ or IHC 2+/in-situ hybridization (ISH)-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

ENHERTU (5.4 mg/kg) is approved under accelerated approval in the U.S. for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a FDA-approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (6.4 mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

ENHERTU is approved in the U.S. with Boxed WARNINGS for Interstitial Lung Disease and Embryo-Fetal Toxicity. For more information, please see the accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

About the ENHERTU Clinical Development Program
A comprehensive global development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway.

Regulatory applications for ENHERTU in breast and gastric cancer are currently under review in several countries.

On December 7, 2022 Aarvik Therapeutics reported a global license and assignment Agreement with NJ Bio, Inc. to secure a class of novel proprietary payloads with a wide range of potencies (Press release, Aarvik Therapeutics, DEC 7, 2022, View Source [SID1234624920]).

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Aarvik has an exclusive license to commercialize the novel proprietary payloads from NJ Bio, as well as any materials or products containing the payloads, and can acquire ownership and all rights upon completion of option payments. As part of the agreement, Aarvik will pay NJ Bio an upfront payment, option payments, as well as future success-based milestone and royalty payments for products utilizing the payloads. NJ Bio will also provide all conjugation services for the payloads. Aarvik will partner with NJ Bio to manufacture materials for preclinical studies and clinical trials.

"We are excited to secure a set of novel payloads for our ADC programs from NJ Bio and to benefit from NJ Bio’s deep chemistry and bioconjugation expertise with ADCs," said Jagath Reddy Junutula, Ph.D., Co-founder, President, and CEO of Aarvik Therapeutics. "NJ Bio will be an excellent research, development, and manufacturing partner for Aarvik. The payloads from NJ Bio complement the novel therapeutic antibodies from Aarvik."

"We are thrilled to provide Aarvik with a class of novel payloads for their next-generation ADC program. The ADC development experience and innovative antibodies from Aarvik combined with our bioconjugation and novel linker-payload synthesis expertise can be synergistic. We look forward to a very exciting time with Aarvik to revolutionize ADC therapies for patients with cancer," said Nareshkumar Jain, President, and CEO of NJ Bio.

On December 7, 2022 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported updated findings from the Translational Breast Cancer Research Consortium (TBCRC) Trial 022 at the ongoing 2022 San Antonio Breast Cancer Symposium in San Antonio, Texas (Press release, Puma Biotechnology, DEC 7, 2022, View Source [SID1234624919]). The poster (PD7-03), entitled "Neratinib and ado-Trastuzumab-Emtansine (T-DM1) for HER2+ Breast Cancer Brain Metastases (BCBM): Translational Breast Cancer Research Consortium (TBCRC) Trial 022," was presented by Rachel A Freedman, MD, MPH, Breast Oncology Center, Susan F. Smith Center for Women’s Cancers, Dana Farber Cancer Institute, at Spotlight Poster Session 7 on December 7 from 5:00 p.m. – 6:15 p.m. CT.

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TBCRC-022 is a prospective, multicenter, Phase II study to evaluate the effect of neratinib plus T-DM1 in patients with HER2-positive breast cancer brain metastases. This presentation outlined updates from three cohorts: 4A – patients with previously untreated BCBM; 4B – patients with BCBM progressing after prior local CNS-directed therapy without prior T-DM1 exposure; and 4C – patients with BCBM progressing after prior local CNS-directed therapy with previous T-DM1 exposure. Data from previous cohorts from this study were reported at the 2017 ASCO (Free ASCO Whitepaper) Annual Meeting. Patients with measurable HER2-positive BCBM received neratinib 160 mg orally once daily plus T-DM1 3.6 mg/kg intravenously every 21 days in the three parallel-enrolling cohorts. Diarrhea prophylaxis with colestipol and loperamide was required during cycle 1. All enrolled patients underwent a brain MRI plus CT scan of the chest/abdomen/pelvis every 6 weeks for 18 weeks, followed by every 9 weeks thereafter.

The primary endpoint, Response Assessment in Neuro-Oncology-Brain Metastases (RANO-BM), was evaluated in each cohort separately. The efficacy results from the trial showed that CNS Objective Response Rate by RANO-BM was 33.3% of patients in cohort 4A, 29.4% in cohort 4B, and 28.6% in cohort 4C. Rates of response + stable disease greater than or equal to 6 months were 50% in cohort 4A, 35.3% in cohort 4B, and 33.3% in cohort 4C.

Intracranial activity was observed for the combination of neratinib plus T-DM1 in all three cohorts, including in patients with prior T-DM1 exposure, suggesting a reversal of resistance to T-DM1. Overall, the most frequently observed adverse event was diarrhea, grade 2 (32%) and grade 3 (23%). These data provide additional evidence for the consideration of neratinib-based combinations in patients with HER2-positive BCBM.

"Neratinib given in combination with T-DM1 showed promising activity in patients with heavily pre-treated HER2-positive disease metastatic to the CNS including patients with prior T-DM1 exposure, which may suggest that neratinib is playing a role in reversing resistance to T-DM1," said Rachel A. Freedman, MD, MPH, Breast Oncology Center, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute. "Despite the introduction of several new treatments for patients with HER2-positive metastatic breast cancer, CNS progression events remain a major source of patient morbidity and mortality. The data from this study provide additional evidence for consideration of neratinib- based combinations in patients with HER2-positive breast cancer brain metastases."

Alan H. Auerbach, CEO and President of Puma Biotechnology, added, "We are pleased with the results from the TBCRC-022 trial on the combination of neratinib and T-DM1. As a small molecule that can cross the blood brain barrier, neratinib potentially offers patients with HER2-positive metastatic breast cancer that has metastasized to the CNS a novel HER2 targeted treatment option. This data adds to the existing body of data that we have from the other previously presented arms from the TBCRC-022 trial that continue to demonstrate that neratinib is active in patients with HER2-positive breast cancer brain metastases."

On December 7, 2022 Kite Pharma, Inc., a Gilead Company, (hereafter Kite) and Daiichi Sankyo Co., Ltd. (hereafter, Daiichi Sankyo) jointly reported the revision of their 2017 partnership agreement, which gave Daiichi Sankyo exclusive rights to develop, manufacture and commercialize Yescarta (axicabtagene ciloleucel) in Japan (Press release, Kite Pharma, DEC 7, 2022, https://www.businesswire.com/news/home/20221207005859/en/Kite-and-Daiichi-Sankyo-Announce-Changes-to-YESCARTA%C2%AE-CAR-T-Cell-Therapy-Licensing-Agreement-in-Japan [SID1234624918]). Kite was acquired by Gilead Sciences, Inc. later in 2017 after the Daiichi Sankyo partnership agreement. Daiichi Sankyo and Kite have now agreed that the Marketing Authorization for Yescarta will be transferred to Gilead Sciences K.K., the Japan subsidiary of Gilead Sciences, Inc., in 2023. A Kite Cell Therapy Business Unit at Gilead Sciences K.K. will manage the sales and promotion activities of the product in Japan after the Marketing Authorization transfer.

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Kite’s manufacturing facility in El Segundo, California, U.S., has been approved by Japanese regulatory authorities to manufacture Yescarta for the Japanese market, and it is expected that supply will commence in early 2023. The first axicabtagene ciloleucel treatment center in Japan was authorized in December 2021, and there are now six hospitals in Japan authorized to administer the therapy.

"We are confident that these changes will benefit patients in Japan by increasing capacity and support broader patient access to this important treatment for blood cancer patients and we remain committed to working together with Kite to ensure a smooth transfer during this transitional period," said Shoji Hirashima, Senior Executive Officer, Head of Japan Business Unit of Daiichi Sankyo.

"As the global leader in cell therapy, we are pleased that our partnership with Daiichi Sankyo has brought this innovative therapy to patients in Japan. We look forward to building on the momentum to accelerate efforts in Japan to maximize access and impact for patients as part of Gilead and Kite’s expansion into oncology in Japan," said Christi Shaw, CEO of Kite.

About YESCARTA

YESCARTA (axicabtagene ciloleucel) is a CAR T-cell therapy directed against CD19 (a cell membrane protein), which harnesses a patient’s own immune system to fight cancer. Axicabtagene ciloleucel is made by removing a patient’s T cells from their blood and engineering them in the lab to express chimeric antigen receptors so that they can recognize and destroy cancer cells when they are infused back to the patient’s body. The CAR T therapy is manufactured specifically for each patient and administered only once. Axicabtagene ciloleucel received Orphan Drug Designation from the Japan Ministry of Health, Labour, and Welfare in 2018 for the treatment of diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, transformed follicular lymphoma and high-grade B-cell lymphoma. Yescarta was approved in Japan for the treatment of patients with relapsed or refractory large B-cell lymphomas1, a type of non-Hodgkin lymphoma, in January 2021. Japan has the second-largest number of people diagnosed with non-Hodgkin lymphoma globally2.

YESCARTA is approved in the U.S. and Europe for patients with certain types of relapsed or refractory B-cell lymphoma, where it is developed, manufactured and commercialized by Kite.

Please see full U.S. Prescribing Information, including BOXED WARNING and Medication Guide.

Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:

Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. (1.1)
Adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
Limitations of Use: Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma. (1.1)

Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). (1.2)
For the full European Prescribing Information, please visit: View Source