On December 21, 2020 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the company has initiated the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking marketing approval for JZP-458 for use as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) in adult and pediatric patients who have developed hypersensitivity or silent inactivation to E. coli-derived asparaginase (Press release, Jazz Pharmaceuticals, DEC 21, 2020, View Source [SID1234573184]).

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The BLA was initiated and will be reviewed under the Real-Time Oncology Review (RTOR) pilot program, an initiative of the FDA’s Oncology Center of Excellence designed to expedite the delivery of safe and effective cancer treatments to patients.

"Given the urgent need for a reliable and high-quality recombinant asparaginase option for patients with hypersensitivity to E. coli-derived asparaginase, we are committed to bringing JZP-458 to market as quickly as possible and pleased to be initiating our BLA submission," said Robert Iannone, M.D., M.S.C.E., executive vice president, research and development of Jazz Pharmaceuticals. "Receiving a Fast Track designation for JZP-458 from the FDA in October 2019 and being able to submit the BLA under the RTOR program is significant, potentially allowing us to more quickly address patient need with a new asparaginase option."

The company continues to plan for a mid-2021 launch of JZP-458 following completion of the BLA submission and FDA review and approval.

An ongoing Phase 2/3 study is being conducted in collaboration with the Children’s Oncology Group (COG) to evaluate JZP-458 as a potential treatment option for pediatric and adult patients with ALL or LBL who are hypersensitive to E. coli-derived asparaginases. Hypersensitivity reactions affect up to 30 percent of patients with ALL and LBL who are treated with E. coli-derived asparaginase.1

About JZP-458
JZP-458 is a recombinant Erwinia asparaginase that uses a novel Pseudomonas fluorescens expression platform. It is being developed for use as a component of a multi-agent chemotherapeutic regimen in the treatment of pediatric and adult patients with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) who are hypersensitive to E. coli-derived asparaginase products. JZP-458 was granted Fast Track designation by the U.S. Food and Drug Administration in October 2019 for the treatment of this patient population.

About Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) is a cancer of the blood and bone marrow that can progress quickly if not treated.2 Leukemia is the most common cancer in children, and about three out of four of these cases are ALL.3 Although it is one of the most common cancers in children, ALL is among the most curable of the pediatric malignancies due to recent advancements in treatment.4,5 Adults can also develop ALL, and about four of every 10 cases of ALL diagnosed are in adults.6 The American Cancer Society estimates that almost 6,000 new cases of ALL will be diagnosed in the United States in 2019.6 Asparaginase is a core component of multi-agent chemotherapeutic regimens in ALL.7 However, asparaginase treatments derived from E. coli are associated with the potential for development of hypersensitivity reactions.8

On December 21, 2020 GT Biopharma, Inc. (OTCQB: GTBP) (GTBP.PA) an immuno-oncology company focused on innovative therapies based on the Company’s proprietary NK cell engager (TriKE) technology platform reported the presentation of additional interim data results for the Company’s lead therapeutic candidate, GTB-3550, for the treatment of high-risk myelodysplastic syndromes (HR-MDS) (Press release, GT Biopharma, DEC 21, 2020, View Source;gtb-3550-trike-reduces-cancer-cells-by-61-7-for-a-high-risk-myelodysplastic-syndromes-hr-mds-patient-301196659.html [SID1234573183]).

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Erica Warlick, M.D, Principal Investigator for the GTB-3550 clinical trial, presented additional clinical data results with the treatment with HR-MDS patient #7 of its TriKE GTB-3550 during the Q&A session following her presentation at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. Dr. Warlick’s HR-MDS patient presentation can be viewed on the GT Biopharma web site at View Source

Mr. Anthony Cataldo, the Chairman and Chief Executive Officer of GT Biopharma commented, "Our clinical data demonstrates that our proprietary TriKE (CD16/IL15/CD33), safely activated and harnessed the patient’s native NK cell’s cancer killing ability in a target-directed fashion without side effects. Which is not the case with highly expensive and intrusive supplemental NK cell therapies. We look forward to progressing to the next level."

Clinical Benefit Achieved

Prior to being treated with TriKE GTB-3550, the HR-MDS patient failed hypomethylating agent (HMA) and Luspatercept therapies. With TriKE GTB-3550 at 50mcg/kg/day (three consecutive 96-hour continuous infusions), the patient achieved a successful bone marrow blast level reduction from 12% before GTB-3550 therapy to 4.6% post GTB-3550 therapy determined by morphological assessment, Additionally, the patient achieved stable hematologic parameters including normal platelet counts throughout therapy. Following this single course of GTB-3550 TriKE therapy causing significant reduction in bone marrow blast levels, the patient achieved clinical benefit from GTB-3550 therapy, which qualified patient #7 to receive a hematopoietic stem cell transplant (HSCT).

No Toxicities / Potent Native NK Cell Activation and Proliferation achieved without Supplemental NK Cell Therapy

The patient exhibited NO SIDE AFFECTS or signs of clinical immune activation, and NO DOSE LIMITING TOXICITY such as cytokine release syndrome (CRS) or serious adverse events (SAEs) or fevers, tachycardia or constitutional symptoms which are synonymous with other NK Cell Therapy and NK Engagers. Correlative studies showed no shedding of CD16 from patient’s NK cells, and potent NK cell activation, proliferation and target cell killing without the need for supplemental autologous NK cell therapy.

Targeted delivery of IL-15 to NK cells via GTB-3550 TriKE therapy showed preferential proliferation of NK cells, significantly less effect on CD8+ T-cells, and no observed toxicity at 25x the previous reported MTD for continuous infusion of recombinant human IL-15. GTB-3550 TriKE is a single-chain, tri-specific scFv recombinant fusion protein conjugate composed of the variable regions of the heavy and light chains of anti-CD16 and anti-CD33 antibodies, and a modified form of IL-15.

GTB-3550 Therapy Prior to Hematopoietic Stem Cell Transplant (HSCT)

The only treatment with curative intent for a majority of elderly HR-MDS or relapsed/refractory AML patients is allogeneic hematopoietic stem cell transplant (HSCT). Age is one of the strongest risk factors associated with poor outcome. Difficulties in treating elderly patients include comorbidities, reduced performance status, and a disease biology with more frequent aberrant cytogenetics and multidrug resistance. There is a significant gap between elderly patients in need of HSCT, and those actually receiving HSCT due to their failure to meet the eligibility requirements. TriKEGTB-3550 represents a novel, low intensity therapeutic option which has the potential to increase HSCT eligibility for elderly HR-MDS and relapsed/refractory AML patients.

Mr. Anthony Cataldo, the Chairman and Chief Executive Officer of GT Biopharma commented "we are gratified that GTB-3550 TriKE achieved the threshold of clinical benefit, and the HR-MDS patient became eligible for HSCT." Mr. Cataldo further stated "we believe our clinical data demonstrates that our proprietary CD16 and IL-15 incorporated in TriKE safely activates and harnesses the patient’s native NK cell’s cancer killing ability in a target-directed fashion without the need for highly expensive and intrusive supplemental NK cell therapies. The TriKE platform biologic technology is demonstrating its capabilities as a first in class drug never before done technology."

About High-Risk Myelodysplastic Syndromes (MDS)

MDS is a rare form of bone marrow-related cancer caused by irregular blood cell production within the bone marrow. As a result of this irregular production, MDS patients do not have sufficient normal red blood cells, white blood cells and/or platelets in circulation. High-risk MDS is associated with poor prognosis, diminished quality of life, and a higher chance of transformation to acute myeloid leukemia. Approximately 40% of patients with High-Risk MDS transform to acute myeloid leukemia (AML), another aggressive cancer with poor outcomes.

About GTB-3550 TriKE Clinical Trial

Patients with CD33+ malignancies (primary induction failure or relapsed AML with failure of one reinduction attempt or high-risk MDS progressed on two lines of therapy) age 18 and older are eligible (NCT03214666). The primary endpoint is to identify the maximum tolerated dose (MTD) of GTB-3550 TriKE. Correlative objectives include the number, phenotype, activation status and function of NK cells and T cells.

About GTB-3550 TriKE

GTB-3550 is the Company’s first TriKE product candidate being initially developed for the treatment or relapsed/refractory acute myeloid leukemia (AML), high-risk myelodysplastic syndrome (HR-MDS). GTB-3550 is a single-chain, tri-specific scFv recombinant fusion protein conjugate composed of the variable regions of the heavy and light chains of anti-CD16 and anti-CD33 antibodies and a modified form of IL-15. The natural killer (NK) cell stimulating cytokine human IL-15 portion of the molecule provides a self-sustaining signal that activates NK cells and enhances their ability to kill cancer cells.

On December 21, 2020 Avidity Biosciences, Inc. (Nasdaq: RNA), a biopharmaceutical company pioneering a new class of oligonucleotide-based therapies called Antibody Oligonucleotide Conjugates (AOCs), reported that it has been added to the Nasdaq Biotechnology Index (Nasdaq: NBI), which became effective prior to market open on Monday, December 21, 2020 (Press release, Avidity Biosciences, DEC 21, 2020, View Source [SID1234573182]).

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The NASDAQ Biotechnology Index is designed to track the performance of a set of securities listed on the NASDAQ Stock Market (NASDAQ) that are classified as either biotechnology or pharmaceutical according to the Industry Classification Benchmark (ICB). The NASDAQ Biotechnology Index is re-ranked annually and all securities in the index are listed on the NASDAQ Global Market or the NASDAQ Global Select Market and meet minimum market value and share volume requirements among other criteria. The NASDAQ Biotechnology Index is the basis for the iShares NASDAQ Biotechnology IndexSM Fund. In addition, options based on the iShares NASDAQ Biotechnology Index Fund trade on various exchanges. For more information about the NASDAQ Biotechnology Index visit View Source

On December 21, 2020 Exicure, Inc. (Nasdaq: XCUR), a pioneer in gene regulatory and immunotherapeutic drugs utilizing spherical nucleic acid (SNA) constructs, reported that the U.S. Patent and Trademark Office has issued two new patents, No.10,792,251 (the ‘251 patent) and No. 10,837,018 (the ‘018 patent), and allowed U.S. patent application 14/907,430 (the ‘430 application), further strengthening the Company’s intellectual property position and coverage for the Company’s therapeutic product candidate, cavrotolimod (Press release, Exicure, DEC 21, 2020, View Source [SID1234573180]).

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The ‘018 patent and the ‘430 application, both titled, "Spherical Nucleic Acid-based Constructs as Immunostimulatory Agents for Prophylactic and Therapeutic Use," covers nanoparticles with a corona of CpG oligonucleotides and their methods for treating cancer.

The ‘251 patent, jointly owned by the Company and Northwestern University, titled, "Liposomal Particles, Methods of Making Same and Uses Thereof," is directed to liposomal nanoparticles with toll-like receptor 9 (TLR9) agonist oligonucleotides and methods for treating cancer.

"The two issued patents and the soon-to-be-issued patent demonstrate our commitment to developing cavrotolimod, which is currently in a Phase 2 clinical trial for the potential treatment of Merkel cell carcinoma and cutaneous squamous cell carcinoma," said David Giljohann, Chief Executive Officer of Exicure. "We are pleased with cavrotolimod’s development to date and excited about its potential to address unmet need for patients living with these rare forms of skin cancers."

On December 21, 2020 Legend Biotech Corporation (NASDAQ: LEGN) ("Legend Biotech"), a global clinical-stage biopharmaceutical company engaged in the discovery and development of novel cell therapies for oncology and other indications, reported the initiation of a rolling submission of a Biologics License Application (BLA) to the Food and Drug Administration (FDA) for ciltacabtagene autoleucel (cilta-cel), an investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell therapy, for the treatment of adults with relapsed and/or refractory multiple myeloma (Press release, Legend Biotech, DEC 21, 2020, View Source [SID1234573179]).

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The submission is based on results from the pivotal Phase 1b/2 CARTITUDE-1 study which evaluated the efficacy and safety of cilta-cel in the treatment of patients with relapsed and/or refractory multiple myeloma.1 The latest data from the study were recently presented (Abstract #177) at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

"Initiation of the BLA submission is an important milestone in advancing this therapy for patients with multiple myeloma who are heavily pretreated and in need of treatment options," said Ying Huang, PhD, CEO and CFO of Legend Biotech. "Together with our collaborator Janssen, we look forward to working with the FDA to fulfill this unmet medical need with the goal of making this breakthrough treatment available to patients and healthcare providers in the future."

Based on this submission, Legend Biotech also announced, according to the terms and conditions of an agreement with Janssen Biotech, Inc. (Janssen), achievement of a $75M milestone payment relating to the clinical development of cilta-cel. Janssen, Legend Biotech’s collaboration partner, initiated the submission of the BLA for cilta-cel. The FDA previously granted Breakthrough Therapy Designation (BTD) for cilta-cel and has agreed to a rolling review of the BLA in which completed portions of the application will be submitted and reviewed on an ongoing basis.

About CARTITUDE-1

CARTITUDE-1 (NCT03548207) is an ongoing Phase 1b/2, open-label, multicenter study evaluating the safety and efficacy of cilta-cel in adults with relapsed and/or refractory multiple myeloma, 99 percent of whom were refractory to the last line of treatment; 88 percent of whom were triple-class refractory (to at least 1 immunomodulatory drug [IMiD], 1 proteasome inhibitor [PI] and 1 anti-CD38 antibody).1

The primary objective of the Phase 1b portion of the study was to characterize the safety and confirm the 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.1

About Ciltacabtagene autoleucel (cilta-cel)

Cilta-cel is an investigational chimeric antigen receptor T cell (CAR-T) therapy, formerly identified as JNJ-4528 outside of China and LCAR-B38M CAR-T cells in China, that is being studied in a comprehensive clinical development program for the treatment of patients with relapsed and/or refractory multiple myeloma and in earlier lines of treatment. The design consists of a structurally differentiated CAR-T with two BCMA-targeting single domain antibodies. In December 2017, Legend Biotech, Inc. entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. to develop and commercialize cilta-cel.

In addition to a Breakthrough Therapy Designation (BTD) granted in the U.S. in December 2019, cilta-cel received a PRIority MEdicines (PRiME) designation from the European Commission in April 2019, and a BTD in China in August 2020. In addition, Orphan Drug Designation was granted for cilta-cel by the U.S. FDA in February 2019, and by the European Commission in February 2020.

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.2 Although treatment may result in remission, unfortunately, patients will most likely relapse. 3 Relapsed myeloma is when the disease has returned after a period of initial, partial or complete remission and does not meet the definition of being refractory.4 Refractory multiple myeloma is when a patient’s disease is non-responsive or progresses within 60 days of their last therapy.5,6 While some patients with multiple myeloma have no symptoms until later stages of the disease, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.7 Patients who relapse after treatment with standard therapies, including protease inhibitors and immunomodulatory agents, have poor prognoses and few treatment options.8