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

On December 21, 2020 ImmunityBio, Inc., a privately-held immunotherapy company, reported positive data from the first cohort of a pivotal Phase 2/3 trial (QUILT 3.032) for non-muscle invasive bladder cancer in high risk carcinoma in situ (CIS) disease (Press release, ImmunityBio, DEC 21, 2020, View Source [SID1234573178]). The data showed 51 out of 71 evaluable patients (72%) had a complete response (at any time) to intravesical BCG plus N-803 (Anktiva), with 59% probability of these patients maintaining a complete response for at least 12 months, with a median duration of complete response of 19.2 months to date.

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With the observed efficacy and only 1% of patients reporting treatment emergent serious adverse events, but none of which were treatment-related, the data support the potential for Anktiva plus BCG as a novel option for BCG unresponsive CIS, a therapeutically challenging disease. Patients with BCG unresponsive CIS disease face surgical removal of the bladder, a procedure fraught with high morbidity and mortality.

Bladder cancer has a high incidence worldwide; it caused 212,536 deaths and an estimated 573,278 new cases were diagnosed in 20201. In the United States, bladder cancer is the fourth most commonly diagnosed solid malignancy in men and the twelfth for women; The American Cancer Society estimates 80,470 new cases and 17,670 deaths in 20192. Approximately 75-85% of all newly diagnosed cases of bladder cancer are non-muscle invasive bladder cancer (NMIBC)3.

The open-label, three cohort multicenter Phase 2/3 study of intravesical BCG plus Anktiva (N-803) in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) was opened in 2017. The primary endpoint for Cohort A of this Phase 2/3 study is incidence of complete response (CR) of CIS at any time. The FDA had granted Fast Track Designation to the pivotal trial based on Phase I data. In December 2019, the FDA granted ImmunityBio Breakthrough Therapy Designation based on interim Phase 2 data indicating the primary endpoint of the trial was already met.

"The high rates of progression and recurrence for NMIBC make it one of the most expensive cancers to treat. This preliminary data is heartening and provides additional evidence of the potential for ImmunityBio’s Anktiva in treating a serious and potentially fatal cancer, for which the alternative is a highly invasive radical cystectomy," said Patrick Soon-Shiong, M.D., Chairman and CEO of ImmunityBio. "We expect to file a Biologics License Application following a meeting with the FDA in 2021."

ImmunityBio’s IL-15 superagonist Anktiva (N-803)

The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of the natural killer (NK) and T cells. N-803 is a novel IL-15 superagonist complex consisting of an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. N-803 has improved pharmacokinetic properties, longer persistence in lymphoid tissues and enhanced anti-tumor activity compared to native, non-complexed IL-15 in vivo.

N-803 is currently being evaluated for adult patients in two clinical NMIBC trials. QUILT 2.005 is investigating use of N-803 in combination with BCG for patients with BCG-naïve NMIBC; QUILT 3.032 is studying N-803 in combination with BCG in patients with BCG-unresponsive NMIBC.

The Urgent, Unmet Need to Treat NMIBC and Avoid Cystectomy

For the last 30 years, BCG immunotherapy has been the standard for treating NMIBC. However, disease recurrence and progression rates remain unacceptably high. Standard of care recommendations for these patients include lifetime invasive surveillance and rapid treatment of recurrences, creating a substantial financial burden and drastic impact on quality of life. Of those patients who experience recurrence, approximately 30% will progress and succumb to their disease over a 15-year period, and another 50% will undergo radical cystectomy of the bladder in an attempt to control their disease4.

For high-risk NMIBC patients who are BCG-unresponsive with persistent or recurrent disease, treatment guidelines recommend a surgical procedure called radical cystectomy, a surgery to remove the entire bladder that may require removal of other surrounding organs. In men, removal of the prostate may be necessary, and in women, surgeons may also remove the uterus, fallopian tubes, ovaries and cervix, and occasionally a portion of the vagina. Despite the advent of minimally invasive procedures and robotic techniques, the 90-day mortality and morbidity rates in patients who undergo cystectomy remain unacceptably high at 5.1-8.1% and 28-64%, respectively5. Based on this urgent need, FDA published guidance in February 2018 to address BCG unresponsive non-muscle invasive bladder cancer (NMIBC), stating that the goal of therapy in patients with BCG-unresponsive NMIBC is to avoid cystectomy.

NantKwest Transaction

ImmunityBio separately announced today that it has entered into an agreement to combine in a stock-for-stock transaction with NantKwest, Inc. (NASDAQ: NK). The combination will create a leading immunotherapy and cell therapy companies focused on oncology and infectious disease.

On December 21, 2020 Sesen Bio (Nasdaq: SESN), a late-stage clinical company developing targeted fusion protein therapeutics for the treatment of patients with cancer, reported submission of the completed Biologics License Application (BLA) to the FDA for Vicineum for the treatment of high-risk, BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) on December 18, 2020 (Press release, Sesen Bio, DEC 21, 2020, View Source [SID1234573177]).

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Within 60 days after receipt of the completed application, the FDA will issue a decision to the Company on the acceptance of the filing, and whether the BLA has received Priority Review (six-month target PDUFA date) under its existing Fast Track designation.

The BLA is supported by the pivotal Phase 3 VISTA trial, which the Company believes demonstrates a strong benefit-risk profile. The BLA also includes positive chemistry, manufacturing and controls (CMC) data that the Company believes validates the analytical comparability between clinical and commercial supply.

"There remains a significant unmet need for high-risk NMIBC, and we believe the differentiated clinical profile of Vicineum will provide a best-in-class option for physicians and their patients," said Dr. Thomas Cannell, president and chief executive officer of Sesen Bio. "Our strong non-clinical and clinical data, in addition to our positive comparability data, give us confidence in the regulatory path forward. I would like to thank the entire Sesen Bio team and our regulatory and manufacturing partners for their tireless dedication in helping us to complete the BLA submission. We look forward to continuing our regulatory progress by submitting a Marketing Authorization Application in Europe, which we anticipate in early 2021."

Bladder cancer is the sixth most commonly diagnosed cancer in the US, in which approximately 80% of patients are diagnosed with NMIBC. For patients who do not respond to BCG, the recommended option for treatment is radical cystectomy (the complete removal of the bladder) or Keytruda. Results of market research conducted by the Company show that when given the choice between Vicineum and Keytruda, doctors will choose Vicineum over 80% of the time. If approved by the FDA, Vicineum could be a best-in-class treatment option for patients, and a critical step in Sesen Bio realizing its mission to save and improve the lives of patients.

About Vicineum

Vicineum, a locally administered fusion protein, is Sesen Bio’s lead product candidate being developed for the treatment of high-risk non-muscle invasive bladder cancer (NMIBC). Vicineum is comprised of a recombinant fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent protein payload, Pseudomonas Exotoxin A. Vicineum is constructed with a stable, genetically engineered peptide tether to ensure the payload remains attached until it is internalized by the cancer cell, which is believed to decrease the risk of toxicity to healthy tissues, thereby improving its safety. In prior clinical trials conducted by Sesen Bio, EpCAM has been shown to be overexpressed in NMIBC cells with minimal to no EpCAM expression observed on normal bladder cells. Sesen Bio is currently conducting the Phase 3 VISTA trial, designed to support the registration of Vicineum for the treatment of high-risk NMIBC in patients who have previously received a minimum of two courses of bacillus Calmette-Guérin (BCG) and whose disease is now BCG-unresponsive. Additionally, Sesen Bio believes that cancer cell-killing properties of Vicineum promote an anti-tumor immune response that may potentially combine well with immuno-oncology drugs, such as checkpoint inhibitors. The activity of Vicineum in BCG-unresponsive NMIBC is also being explored at the US National Cancer Institute in combination with AstraZeneca’s immune checkpoint inhibitor durvalumab.

About Non-Muscle Invasive Bladder Cancer

Bladder cancer is the sixth most commonly diagnosed cancer in the United States, and approximately 80 percent of patients have non-muscle invasive bladder cancer (NMIBC). In NMIBC, cancer cells are in the lining of the bladder or have grown into the lumen of the bladder but have not spread into muscle or other tissue. NMIBC primarily affects men and is associated with carcinogen exposure. Initial treatment includes surgical resection; however, there is a high rate of recurrence and more than 60 percent of all patients diagnosed with NMIBC will receive bacillus Calmette-Guérin (BCG) immunotherapy. While BCG is effective in many patients, challenges with tolerability have been observed and many patients will experience recurrence of disease. If BCG is not effective or a patient can longer receive BCG, the recommended option for treatment is radical cystectomy, the complete removal of the bladder.