On August 10, 2023 Cantex Pharmaceuticals, Inc., a clinical-stage pharmaceutical company focused on developing transformative therapies for cancer and other life-threatening medical conditions for which new treatments are urgently needed, reported the publication in the peer-reviewed journal, npj Breast Cancer, a Nature Portfolio journal published in partnership with Breast Cancer Research Foundation, with results from in vitro and in vivo models for triple-negative breast cancer showing suppression of metastasis and tumor progression by RAGE inhibition (Press release, Cantex, AUG 10, 2023, View Source [SID1234634238]). Cantex’s azeliragon, currently in phase 2/3 development for the treatment of major cancers, complications of cancer treatment, and the treatment of other life-threatening illnesses, is a RAGE inhibitor that is orally administered and taken once daily.

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In the paper titled, "RAGE inhibitor TTP488 (Azeliragon) suppresses metastasis in triple-negative breast cancer," researchers investigated whether azeliragon impairs triple-negative breast cancer progression and metastasis and the mechanisms by which RAGE inhibition by azeliragon mediates breast cancer progression and metastasis. The authors showed that azeliragon exerts a potent anti-metastatic effect in orthotopic xenograft and experimental metastasis models of triple-negative breast cancer, which they corroborated by demonstrating that RAGE inhibition impairs biological mechanisms that drive cancer metastasis.

"This is a major publication supporting the role of RAGE inhibition in progressive and deadly cancers like triple-negative breast cancer," said Stephen G. Marcus, M.D., Cantex’s Chief Executive Officer. "We congratulate the authors on their critically important work and look forward to collaborating with them as we seek to unlock the potential of azeliragon and RAGE inhibition to treat triple-negative breast cancer and other major cancers, for which improved treatment is greatly needed."

"Our results show that azeliragon impairs metastasis of triple-negative breast cancer, clarifying signaling and cellular mechanisms through which RAGE mediates metastasis," said Barry Hudson, PhD, associate professor of oncology at Georgetown University’s Lombardi Comprehensive Cancer Center and senior author of the study. "Importantly, given the favorable safety profile that azeliragon has displayed in human studies, we believe there is strong rationale for studying its potential in clinical trials to treat or prevent metastatic triple-negative breast cancer."

The authors of the peer-reviewed article were comprised of cell and cancer biology researchers at the University of Miami, Miller School of Medicine, and Georgetown University. Cantex recently announced the expansion of collaboration with researchers at Georgetown’s Lombardi Comprehensive Cancer Center and the licensing from Georgetown University of intellectual property related to the potential use of azeliragon to treat, prevent or alleviate cancer-treatment related cognitive decline. Hudson and study co-author Marc Lippman, at Georgetown University, are named inventors on the patent application related to the Georgetown license.

About Azeliragon
Azeliragon is an orally administered capsule, taken once daily, that inhibits interactions of the receptor for advanced glycation end products (known as RAGE) with certain ligands, including HMGB1 and S100 proteins in the tumor microenvironment. Azeliragon was originally under development for Alzheimer’s disease by vTv Therapeutics Inc. (NASDAQ: VTVT) from which Cantex licensed worldwide rights to azeliragon. Clinical safety data from these trials, involving more than 2000 individuals dosed for periods up to 18 months, indicate that azeliragon is very well tolerated. Cantex has ongoing clinical trials in neoadjuvant therapy of breast cancer, metastatic pancreatic cancer, and hospitalized COVID-19 patients to prevent acute kidney injury and will soon initiate FDA-approved phase 2 clinical trials of azeliragon in newly diagnosed glioblastoma, and in brain metastases in combination with stereotactic radiosurgery as well as in combination with whole brain radiation therapy. These trials are based on robust pre-clinical data as well as the extensive clinical safety information from randomized placebo-controlled clinical trials.

On August 10, 2023 Oricell Therapeutics Co., Ltd. ("Oricell") reported that it has received the green light for its Investigational New Drug (IND) application of OriCAR-017, a cutting-edge CAR-T cell therapy targeting GPRC5D to combat relapsed or refractory multiple myeloma (R/R MM) (Press release, OriCell Therapeutics, AUG 10, 2023, View Source [SID1234634237]). This remarkable milestone not only marks the world’s first tier GPRC5D-targeting CAR-T therapy approved in China but also underlines Oricells prowess as a frontrunner in the biotech industry.

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About GPRC5D target

GPRC5D, a G protein-coupled receptor that boasts high expression on multiple myeloma cells while maintaining low levels in normal tissues, has emerged as a promising therapeutic target for multiple myeloma. The revolutionary approach of independently targeting GPRC5D, regardless of BCMA expression levels, opens up new possibilities for patients who have exhausted conventional treatments or shown limited response to BCMA-targeting therapies.

Earlier, data from the investigator initiated trial of OriCAR-017 (POLARIS) were presented at the 2022 ASCO (Free ASCO Whitepaper) (American Society of Clinical Oncology Annual Meeting) and the 2022 EHA (Free EHA Whitepaper) (European Hematology Association Annual Meeting), attracting widespread attention due to its efficacy and safety advantages. The study enrolled 10 patients, included five patients who were previously treated with BCMA-targeted CAR T-cell therapy and four patients with extramedullary disease (EMD). According to the latest data, at a median follow-up time of 280 days (217 ~ 459 days), OriCAR-017 is turning heads with an impressive overall response rate (ORR) of 100% and a stringent complete response rate (sCR) of 80%. Additionally, compared to other therapies targeting the same antigen, OriCAR-017 demonstrated significant safety advantages, with only one case of grade 2 cytokine release syndrome (CRS) observed after treatment, while the rest were grade 1. Notably, no instances of immune effector cell-associated neurotoxicity syndrome (ICANS) and no grade 3 or higher skin toxicities or nail changes were reported, nor infection events were observed during long-term follow-up after treatment. Such reassuring safety data paves the way for reduced post-treatment clinical interventions, ultimately lightening the burden on healthcare providers and enhancing patient experiences.

Oricell’s Chairman and CEO, Helen Yang expressed, "OriCAR-017’s approval as China’s first and the world’s leading GPRC5D-targeting CAR-T therapy is a pivotal moment for the biotech landscape. We are bridging the gap in late-line treatments for R/R MM, providing new hope to patients who have failed or responded poorly to different therapies targeting BCMA. The potential global impact of OriCAR-017 is undeniable, as we have been developing a global development plan for OriCAR-017 and are systematically advancing its registration for clinical trials in the United States. We have already obtained the ‘Orphan Drug’ designation from the Office of Orphan Products Development (OOPD) of the U.S. FDA." Helen is confident about the development prospects of this product and further stated, "with the IND clearance in China and seamless progress in overseas registrations and technology transfer, the stage is set for OriCAR-017 to become a game-changer in the fight against multiple myeloma. As Oricell continues to make strides in ground-breaking innovation, the future of cancer treatment looks more promising than ever before."

On August 10, 2023 Researchers with City of Hope, one of the largest cancer research and treatment organizations in the nation, reported preclinical research in Nature Communications demonstrating that a chimeric antigen receptor (CAR)-engineered T cell therapy worked against ovarian cancer in the laboratory and in preclinical models (Press release, City of Hope, AUG 10, 2023, View Source [SID1234634236]).

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City of Hope’s Saul Priceman, Ph.D., is conducting research on chimeric antigen receptor (CAR)-engineered T cell therapy and has demonstrated in the laboratory and in preclinical models that the investigational cell therapy can work against ovarian cancer. The preclinical study was published in Nature Communications.
City of Hope’s Saul Priceman, Ph.D., is conducting research on chimeric antigen receptor (CAR)-engineered T cell therapy and has demonstrated in the laboratory and in preclinical models that the investigational cell therapy can work against ovarian cancer. The preclinical study was published in Nature Communications.
"City of Hope’s research helped develop CAR T cell therapies for blood cancers, and these patients are now seeing long-term benefits from the therapy, but we can’t stop there," said Saul Priceman, Ph.D., associate professor in the Department of Hematology & Hematopoietic Cell Transplantation and associate director of Translational Sciences & Technologies in the T Cell Therapeutics Research Laboratories at City of Hope. "The next frontier is solid tumors, and City of Hope is taking on that challenge."

The therapy is currently in a first-in-human Phase 1 trial at City of Hope for patients with advanced epithelial ovarian cancer who have already received platinum-based chemotherapy. The trial, led by Lorna Rodriguez-Rodriguez, M.D., Ph.D., City of Hope professor in its Division of Gynecologic Oncology, Department of Surgery, is testing the therapy’s safety, side effects and activity of the therapy in patients. The trial is currently enrolling patients for treatment.

Developing a CAR T cell therapy for solid tumors is particularly challenging because the therapy needs to first reach the solid tumor and then survive in a harsh microenvironment that is filled with cancer cells and other cells that prevent attack by the CAR T cells. But Priceman and his team have made significant progress in overcoming these challenges.

The team’s most recent research found that a CAR T cell therapy targeting TAG72, a target found on the surface of ovarian cancer cells, eradicates cancer cells in mouse models.

"What’s exciting about this is that TAG72 is also found on other cancer cells, including pancreatic, colorectal, breast and brain tumors, so if the clinical trial in ovarian does well, we can investigate expanding this to other patients," he added.

CAR T cell therapy involves taking a patient’s T cells, a white blood cell that helps fight disease, from the bloodstream. T cells are then reprogrammed with a CAR in a City of Hope laboratory to recognize and attack a specific cancer-causing protein, such as TAG72, and reintroduced into the patient’s bloodstream. CAR T cells should then eradicate cancer cells. Patients are closely monitored for any side effects.

Priceman and his team also found that by adding the cytokine Interleukin-12 (IL-12), a protein that sends signals to the immune system, to the CAR T cell therapy, the treatment worked more effectively against cancer cells in the lab. The co-first authors Eric Hee Jun Lee and John P. Murad, Ph.D., along with the rest of the team, showed that IL-12 also enabled the T cells to both fight the cancer and leave the tumor area, enter the bloodstream and target other cancer cells around the body. Priceman noted that IL-12 is not currently part of the current Phase 1 clinical trial.

The preclinical research also found that delivering the CAR T cell therapy via an injection where the cancer is located, regionally, is also effective in enabling CAR T cells to target cancer elsewhere. This technology allows for both safety and improved anti-tumor activity in several cancer types tested to date.

"This therapy has been years in the making at City of Hope, so we are excited to finally see it in patients whose cancer is advanced and are in need of more treatments," Priceman added.

On August 10, 2023 Antengene Corporation Limited ("Antengene" SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class therapeutics in hematology and oncology, and Hansoh Pharmaceutical Group Company Limited ("Hansoh Pharma" SEHK: 3692.HK), a leading innovation-driven pharmaceutical company with a focus on the treatment of major diseases including oncology, infectious diseases, CNS disorders, metabolic diseases, and autoimmune diseases, reported the entrance into a collaboration agreement between Antengene and Hansoh Pharma for the commercialization of XPOVIO in the mainland of China (Press release, Antengene, AUG 10, 2023, View Source [SID1234634235]).

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"Our collaboration with Hansoh Pharma further strengthens our confidence in the market potential of the First and Only-in-class XPO1 inhibitor XPOVIO in the mainland of China," said Dr. Jay Mei, Founder, Chairman, and Chief Executive Officer of Antengene. "Through collaborating with Hansoh Pharma, we will leverage their well-established commercialization infrastructure to make XPOVIO more accessible to patients in the mainland of China. Given Antengene’s plans to apply for inclusion into the National Reimbursement Drug List (NRDL) for XPOVIO in the near future, and the broad indication expansion potential of XPOVIO, it is crucial to ensure that XPOVIO could reach as many cities, hospitals and prescribers, and benefit as many patients as possible. We believe this collaboration with Hansoh Pharma will not only enhance assess of XPOVIO but also lead to commercial success in the mainland of China."

"Hansoh Pharma is excited to enter into this partnership with Antengene and is committed to bringing XPOVIO to more patients in China," said Ms. Yuan Sun, Executive Director of Hansoh Pharma. "We believe that XPOVIO is a drug with great commercial potential, addressing huge unmet medical needs for those hematologic patients in China. In addition to obtaining approvals in multiple countries and regions globally for multiple myeloma and diffuse large B-cell lymphoma, XPOVIO has indication expansion potential in myelofibrosis, endometrial cancer, as well as T/NK-cell lymphoma. We look forward to collaborating with Antengene and make XPOVIO available to the widest possible number of Chinese patients with hematological malignancies."

Under the terms of the agreement, Antengene will continue to be responsible for research and development, regulatory approvals and affairs, product supply, and distribution of XPOVIO, while Hansoh Pharma will be exclusively responsible for commercialization of XPOVIO in the mainland of China. Antengene will receive up to RMB200 million of upfront payments, RMB100 million of which shall be received upon signing, and pursuant to the Agreement and subject to the terms and conditions thereof, Antengene shall be eligible to receive up to RMB100 million of the remaining upfront payments, and up to RMB535 million in milestone payments from Hansoh Pharma. Antengene will continue to record revenues from sales of XPOVIO in the mainland of China and Hansoh Pharma will charge a service fee to Antengene.

About Multiple Myeloma

Multiple myeloma (MM) is caused by the dysregulated proliferation of plasma cells. It is the second most common hematologic malignancy in many countries. Despite availability of a number of treatments for relapsed patients, MM is prone to relapse and most patients still succumb to their disease. MM is the second most common hematologic malignancy in China, with an estimated about 15,000 to 20,000 new MM patients and 10,300 deaths per year.1

About XPOVIO (selinexor)

XPOVIO is the world’s first approved orally-available, selective inhibitor of the nuclear export protein XPO1. It offers a novel mechanism of action, synergistic effects in combination regimens, fast onset of action, and durable responses.

By blocking the nuclear export protein XPO1, XPOVIO can promote the intranuclear accumulation and activation of tumor suppressor proteins and growth regulating proteins, and down-regulate the levels of multiple oncogenic proteins. XPOVIO delivers its antitumor effects through three mechanistic pathways: 1) exerting antitumor effects by inducing the intranuclear accumulation of tumor suppressor proteins; 2) reducing the level of oncogenic proteins in the cytoplasm by inducing the intranuclear accumulation of oncogenic mRNAs; 3) restoring hormone sensitivity by activating the glucocorticoid receptors (GR) pathway. To utilize its unique mechanism of actions, XPOVIO is being evaluated for use in multiple combination regimens in a range of indications. At present, Antengene is conducting 8 clinical studies of XPOVIO in mainland of China for the treatment of relapsed/refractory hematologic malignancies and solid tumors (3 of these studies are being jointly conducted by Antengene and Karyopharm Therapeutics Inc. [Nasdaq:KPTI]).

XPOVIO is approved in South Korea for the following two indications:

In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.
As a monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy.
XPOVIO is approved in mainland of China for the following indication:

In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received prior therapies and whose disease is refractory to at least one proteasome inhibitor, at least one immunomodulatory agent, and an anti-CD38 monoclonal antibody.
XPOVIO is approved in Taiwan China for the following three indications:

In combination with dexamethasone (Xd) for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors (PIs), at least two immunomodulatory agents (IMiDs), and an anti-CD38 monoclonal antibody.
In combination with bortezomib and dexamethasone (XVd) for the treatment of adult patients with MM who have received at least one prior therapy.
As a monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy.
XPOVIO is approved in Hong Kong China, for the following indication:

In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors (PIs), two immunomodulatory agents (IMiDs), an anti-CD38 monoclonal antibody (mAb), and who have demonstrated disease progression on the last therapy.
XPOVIO is approved in Australia for the following two indications:

In combination with bortezomib and dexamethasone (XVd) for the treatment of adult patients with multiple myeloma (MM) who have received at least one prior therapy.
In combination with dexamethasone (Xd) for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received at least three prior therapies and whose disease is refractory to at least one proteasome inhibitor (PI), at least one immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody (mAb).
XPOVIO is approved in Singapore for the following three indications:

In combination with bortezomib and dexamethasone for treatment of adult patients with multiple myeloma (MM) who have received at least one prior therapy.
In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.
As a monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy who are not eligible for haematopoietic cell transplant.

On August 10, 2023 WuXi Biologics ("WuXi Bio") (2269.HK), a leading global Contract Research, Development and Manufacturing Organization (CRDMO), and Boostimmune, a biotech company dedicated to developing next-generation anti-cancer therapies modulating the tumor immune microenvironment and ADCs to novel targets, reported a Memorandum of Understanding (MOU) had been signed for research and discovery services for Boostimmune’s pipeline (Press release, WuXi Biologics, AUG 10, 2023, View Source [SID1234634234]).

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Under the collaboration, Boostimmune will have access to WuXi Biologics’ integrated discovery services and extensive expertise in antibody discovery, lead optimization, in vitro screening and characterization, as well as in vivo tests. WuXi Biologics will be the exclusive service partner to support Boostimmune in generating different modality candidates, including monoclonal antibodies, bispecific antibodies and recombinant proteins.

Dr. Gwanghee Lee, Co-founder and CEO of Boostimmune, commented, "Collaborating with WuXi Biologics – and accessing their comprehensive antibody generation technology platform – offers an opportunity to discover novel biological candidates and explore the science of complex proteins. We look forward to working with WuXi Biologics to build a compelling pipeline with the potential to meaningfully improve the lives of patients."

Dr. Chris Chen, CEO of WuXi Biologics, commented, "We are very pleased to partner with Boostimmune to advance their innovative pipeline. The biotech industry in South Korea is flourishing, and there is increasing demand for end-to-end discovery and development services. WuXi Biologics is proud to support our global and Asia partners in bringing innovative biologics solutions to market for patients around the world."