On September 15, 2021 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported the publication of preclinical data demonstrating that its off-the-shelf, multiplexed-engineered, iPSC-derived NK cell product candidate FT538 exhibits significantly enhanced serial killing and functional persistence compared to peripheral blood NK cells (Press release, Fate Therapeutics, SEP 15, 2021, View Source [SID1234587737]). The superior anti-tumor activity of FT538 was attributable to its novel engineered components, including the knockout of CD38 and the expression of IL-15/IL-15R fusion protein, which were shown to improve metabolic fitness, increase resistance to oxidative stress, and induce transcription of proteins that control NK cell activation and effector function. The data were published in Cell Stem Cell in an online article entitled "Harnessing features of adaptive NK cells to generate iPSC-derived NK cells for enhanced immunotherapy".

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"The NK cell community has long sought to improve NK cell activation, cytotoxicity, functional persistence, and tumor targeting for cancer immunotherapy. Our preclinical data demonstrate that the synthetic features of FT538 uniquely harness all these therapeutic attributes and significantly improve NK cell anti-tumor activity," said Bob Valamehr, Ph.D., Chief Research and Development Officer of Fate Therapeutics. "We are excited to bring FT538 to patients for off-the-shelf treatment of hematologic malignancies and solid tumors, and to continue to leverage its multiplexed engineered backbone as the foundation for development of multi-antigen, CAR-targeted product candidates."

The studies in the Cell Stem Cell publication were conducted as part of a collaboration between scientists at Fate Therapeutics and the laboratory of Jeffrey S. Miller, M.D., University of Minnesota, and were led by Frank Cichocki, Ph.D., University of Minnesota. The Miller laboratory has previously shown that a rare subset of NK cells with memory-like properties that arise in response to cytomegalovirus, known as adaptive NK cells, have a genome-wide epigenetic profile and recall response that parallel cytotoxic effector CD8+ T cells. These adaptive NK cells persist long term, exhibit a unique metabolic profile with elevated mitochondrial oxidative phosphorylation and glycolysis as well as increased levels of ATP, and have enhanced cytotoxicity.

The peer-reviewed paper describes preclinical studies showing that FT538 shares metabolic, transcriptional, and functional features with adaptive NK cells. The data demonstrate that FT538 persists in vivo at high levels for more than six weeks in the absence of cytokine support after adoptive transfer, whereas adoptively-transferred peripheral blood NK cells required the co-infusion of either IL-2 or IL-15 to achieve low-level persistence for up to two weeks. Additionally, in sequential killing assays, FT538 was shown to have robust serial killing and functional persistence, which were not observed with peripheral blood NK cells. FT538 also incorporates a novel high-affinity, non-cleavable CD16 Fc receptor as a third functional component, which was shown to mediate potent in vivo anti-tumor activity in combination with the CD38-targeted monoclonal antibody daratumumab against MM.1S myeloma cells.

FT538 is being investigated in a multi-dose Phase 1 clinical trial for the treatment of acute myeloid leukemia and in combination with daratumumab for the treatment of multiple myeloma (NCT04614636). In addition, the Company has initiated patient enrollment in a multi-dose Phase 1 clinical trial of FT538 in combination with certain monoclonal antibodies targeting EGFR, HER2, and PDL1 for the treatment of solid tumors.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT538
FT538 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three functional components: a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments. FT538 is designed to enhance innate immunity in cancer patients, where endogenous NK cells are typically diminished in both number and function due to prior treatment regimens and tumor suppressive mechanisms. In preclinical studies, FT538 has shown superior NK cell effector function, as compared to peripheral blood NK cells, with the potential to confer significant anti-tumor activity to patients through multiple mechanisms of action. FT538 is being investigated in a multi-dose Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and in combination with daratumumab, a CD38-targeted monoclonal antibody therapy, for the treatment of multiple myeloma (NCT04614636).

On September 15, 2021 Coherus BioSciences, Inc. ("Coherus", Nasdaq: CHRS) and Shanghai Junshi Biosciences Co., Ltd ("Junshi Biosciences", HKEX: 1877; SSE: 688180) reported publication of a cover article in the September issue of Nature Medicine featuring clinical data from the pivotal study "JUPITER-02", a randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating toripalimab plus chemotherapy for the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma (NPC) (Press release, Coherus Biosciences, SEP 15, 2021, View Source [SID1234587736]).

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Titled Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial, the paper highlights that the addition of toripalimab to standard of care gemcitabine-cisplatin (GP) chemotherapy as a first-line treatment for patients with recurrent or metastatic NPC provided superior progression free survival (PFS) compared to GP alone [median PFS of 11.7 vs 8.0 months, hazard ratio (HR) = 0.52 (95% confidence interval (CI): 0.36–0.74), P = 0.0003], and with a manageable safety profile. The impact of the addition of toripalimab on PFS was demonstrated in patients regardless of PD-L1 expression status. Although overall survival data were not yet mature, as of February 18, 2021, a 40% reduction in risk of death was observed in the toripalimab arm compared to the placebo arm (HR = 0.603 (95% CI: 0.364–0.997)). The incidence of grade ≥3 treatment emergent adverse events (TEAEs) (89.0% vs 89.5%), TEAEs leading to discontinuation of toripalimab/placebo (7.5% vs 4.9%), and fatal TEAEs (2.7% vs 2.8%) was similar between both arms. Immune-related adverse events (irAEs) (39.7% vs. 18.9%) and Grade ≥3 irAEs (7.5% vs. 0.7%) were more frequent in the toripalimab arm. The full results can be found in the on-line edition of Nature Medicine.

"There are currently no PD-1 blocking antibodies approved for NPC in the United States. We are pleased that this study has been selected for cover article publication in this highly-respected journal," said Dr. Patricia Keegan, Chief Medical Officer of Junshi Biosciences. "This is a strong signal that further validates the potential advance that toripalimab in combination with chemotherapy would represent as a new standard-of-care first-line therapy for patients with advanced NPC, an aggressive and difficult-to-treat cancer."

A biologics license application has been submitted to the U.S. Food and Drug Administration ("FDA") for toripalimab in combination with gemcitabine and cisplatin for first-line treatment for patients with advanced recurrent or metastatic NPC and toripalimab monotherapy for second-line or above treatment of recurrent or metastatic NPC after platinum-containing chemotherapy.

About JUPITER-02
The JUPITER-02 Study (ClinicalTrials.gov identifier: NCT03581786) is a randomized, double-blind, placebo-controlled, international multi-center Phase 3 clinical trial comparing the efficacy and safety of toripalimab versus placebo in combination with Gemcitabine/Cisplatin, as a first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma. Professor Ruihua Xu from Sun Yat-sen University Cancer Centre is the lead principal investigator of the study. The largest Phase 3 clinical trial to date evaluating a checkpoint inhibitor plus chemotherapy for the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma, JUPITER-02 was conducted in mainland China, Taiwan and Singapore and enrolled a total of 289 patients.

About Toripalimab
Toripalimab is an anti-PD-1 monoclonal antibody developed for its ability to block PD-1 interactions with its ligands, PD-L1 and PD-L2, and for enhanced receptor internalization (endocytosis function). Blocking PD-1 interactions with PD-L1 and PD-L2 is thought to recharge the immune system’s ability to attack and kill tumor cells. More than thirty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally, including in China and the United States. Ongoing or completed pivotal clinical trials are evaluating the safety and efficacy of toripalimab for a broad range of tumor types including cancers of the lung, nasopharynx, esophagus, stomach, bladder, breast, liver, kidney and skin.

In China, toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (approved in China as TUOYI). On December 17, 2018, toripalimab was granted a conditional approval by the National Medical Products Administration (NMPA) for the second-line treatment of unresectable or metastatic melanoma. In December 2020, toripalimab was successfully included in the updated National Reimbursement Drug List. In February 2021, the NMPA granted a conditional approval to toripalimab for the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) after failure of at least two lines of prior systemic therapy. In April 2021, NMPA granted a conditional approval to toripalimab for the treatment of patients with locally advanced or metastatic urothelial carcinoma who failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. In addition, two supplemental NDAs for toripalimab in combination with chemotherapy for the first-line treatment of patients with advanced, recurrent or metastatic NPC or for the first-line treatment of patients with advanced, or metastatic esophageal squamous cell carcinoma were accepted by the NMPA for review in February and July 2021 respectively.

In the United States, the first toripalimab BLA has been submitted to the FDA for the treatment of recurrent or metastatic NPC. The FDA has granted Breakthrough Therapy designations for toripalimab in combination with chemotherapy for the 1st line treatment of recurrent or metastatic NPC and for toripalimab monotherapy in the 2nd line and subsequent treatment of recurrent or metastatic NPC. There are currently no PD-1 blocking antibodies approved for use in NPC in the United States. Additionally, FDA has granted Fast Track designation for toripalimab for the treatment of mucosal melanoma and orphan drug designation for NPC, mucosal melanoma and soft tissue sarcoma. Earlier in 2021 Coherus in-licensed rights to develop and commercialize toripalimab in the United States and Canada. Coherus and Junshi Biosciences plan to file additional toripalimab BLAs with the FDA over the next three years for multiple rare cancers and highly prevalent cancers.

On September 15, 2021 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage clinical biopharmaceutical company focused on the discovery and development of drugs for the treatment of cancer, reported that James Caruso, president and CEO, will present a company overview at the following upcoming conference (Press release, Cellectar Biosciences, SEP 15, 2021, View Source [SID1234587734]):

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Oppenheimer Fall Healthcare Life Sciences & MedTech Summit

Presentation Date: Monday, September 20, 2021
Presentation Time: 12:25PM Eastern Time
Webcast Link: View Source

A replay of the presentation will be available on the Events Page of the company’s website (www.cellectar.com).

On September 15, 2021 Researchers from the Case Comprehensive Cancer Center reported that uncovered the potentially important role of the protein-coding gene, MYO10, in tumor development and immune therapy response (Press release, Case Western Reserve University, SEP 15, 2021, View Source [SID1234587733]). Their findings were published today in Science Advances.

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The team, led by Youwei Zhang, an associate professor of pharmacology at the Case Western Reserve University School of Medicine, found breast tumors with high levels of MYO10—including the most malignant triple-negative breast cancers—responded favorably to immune checkpoint blockade (ICB) therapy, supporting the use of this therapy to treat these types of tumors.

ICB is an innovative treatment that uses medications known as immune checkpoint inhibitors—medications that can help the body’s immune system recognize and attack cancerous cells.

The team’s findings also suggest that the use of ICBs should be avoided in breast tumors with low MYO10 because these tumors actually grew larger after ICB therapy.

Studies found that high levels of MYO10 induce chronic inflammation in tumors, which reduces the ability of key immune cells—known as T cells—to slow tumor growth.

At the same time, however, this inflammatory environment in the tumor increased the ability of immune cells to provoke an immune response. This eventually allowed tumor cells to respond to ICB therapy, improving outcomes.

Proteins called interferon and interleukin—and other factors that regulate their production—are part of the body’s natural defenses. When they sense germs or cancer cells in the body, they boost the immune system, triggering killer immune cells to fight these invaders.

A model showing how the MYO10 protein regulates the inflammation and creates a favorable situation for immune checkpoint blockades.
A model showing how the MYO10 protein regulates the inflammation and creates a favorable situation for immune checkpoint blockades.
In this study, the researchers found that high levels of MYO10 increased the presence of interferons; conversely, low levels of MYO10 correlated with reduced production of interferons. These findings at least partly explain why MYO10-low tumors failed to respond to ICB therapy, the researchers explained.

Consistent with a chronic inflammation environment in tumors with high levels of MYO10 that led to loss of T cell function, treatment with aspirin to reduce inflammation significantly reduced the growth of breast tumors overexpressing MYO10.

This is consistent with studies showing that long-term use of aspirin or nonsteroidal anti-inflammatory drugs significantly reduced tumor risk for esophageal, colorectal and stomach cancers, as well as—to a smaller degree—in breast, lung and prostate cancers.

The team members further uncovered how MYO10 drives tumor growth. They found that MYO10 regulates the genome stability and cancer growth through mediating the nucleus shape. They also discovered that the protein level of MYO10 is critical for this function.

They went on to show how the protein recycling system tightly controls the expression level of MYO10. These findings support the tumor studies, highlighting the importance of MYO10 in tumor development and immune therapy response.

"This is the first study to link MYO10 with genomic instability and to validate the role of MYO10 in tumor development and immune therapy response," said Zhang, a member of the Molecular Oncology Program of the Case Comprehensive Cancer Center. "We will continue these studies and are eager to see how this knowledge can have a clinical impact on patient care. In addition, we hope that these findings will lead to more effective therapy options for breast cancer patients and the elimination of less effective treatments."

Study co-authors include: Mark Jackson, at the Case Comprehensive Cancer Center and Case Western Reserve School of Medicine; Franklin Mayca Pozo, Xinran Geng and Ilaria Tamagno from the Case Western Reserve School of Medicine; Ernest G. Heimsath and Richard Cheney from University of North Carolina Chapel Hill; and John Hammer, from National Heart, Lung and Blood Institute.

On September 15, 2021 Aurinia Pharmaceuticals Inc. (NASDAQ: AUPH) (the "Company") reported that members of the senior management team will present at the following upcoming virtual investor conferences (Press release, Aurinia Pharmaceuticals, SEP 15, 2021, View Source [SID1234587732]):

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Oppenheimer Fall Healthcare Life Sciences & MedTech Summit Monday, September 20, 2021 at 2:55 pm ET. (access here)
Cantor Global Healthcare Conference on September 30, 2021 at 12:40 pm ET. (access here)
In order to participate in the audio webcasts, interested parties can also register and access presentations under "News/Events" through the "Investors" section of the Aurinia corporate website at www.auriniapharma.com. A replay of the webcasts will be available on Aurinia’s website.