On January 10, 2024 Dxcover Limited, a clinical-stage diagnostics company pioneering multi-omic spectral analysis (MOSA) for early detection of multiple cancers, reported that it is initiating three pivotal clinical trials measuring efficacy of the company’s liquid biopsy technology for the detection of brain, colorectal and lung cancer (Press release, Dxcover, JAN 10, 2024, View Source [SID1234639195]).

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The company has launched its EMBRACE study, a 2,200-patient trial focused on the early detection of brain cancer. Dxcover Brain Cancer is a qualitative in vitro diagnostic (IVD) test analyzing blood serum by infrared spectroscopy to detect the signals indicative of brain cancer. This highly sensitive test is to help determine the necessary treatment of patients presenting vague symptoms in primary care environments. The results of the test would prioritize individuals who require a confirmatory brain scan, potentially enabling earlier detection to save lives and reduce healthcare costs. The Dxcover Brain Cancer test has been developed over four years with clinical support from NHS Lothian. This pivotal study is partially funded by a €2.5m grant from the European Innovation Council.

The CREATE2 trial will be conducted to evaluate diagnostic accuracy for colorectal cancer and high-risk adenoma in patients undergoing a colonoscopy. The study will have two recruitment pathways, one in the US and one in the UK, each with 700 patients. The US cohort will be assessed in the average risk population 45-84 who are intending to undergo a screening colonoscopy, while the UK cohort will be assessed post-referral at colonoscopy. CREATE2 aims to validate the previous CREATE study which showed Dxcover’s ability to achieve accurate detection of pre-cancerous lesions and stage 1 colorectal cancer, detection at these stages will enable a positive impact on patients’ lives.

The SPIRALS trial is focused on the management of indeterminant pulmonary nodules by scanning for nodules in the size range between 0.8 – 3.0 mm range. At this size range the nodules are small, however 80% have an intermediate risk score where next steps are unclear resulting in unnecessary surgery and missed cancer diagnoses. Dxcover will be analyzing more than 1,800 samples in order to provide a rapid, cost-effective tool that can help patients receive the correct next steps in their journey.

"Each cancer follows a unique development path, and these are important trials to assess brain, colorectal and lung cancer separately to zero in on the distinct triggers of each disease and, based on the results, identify the most effective treatment for each patient," said Professor Matthew Baker, Founder and CEO, Dxcover. "As the medical community gathers this week in San Francisco for what is always one of the most significant gatherings in the healthcare industry, I’m looking forward to meeting with like-minded partners whose mission is to eradicate the devastating effects of cancers. At Dxcover, we are firm believers that the key to improving patient outcomes lies in the early detection of cancer, expanding intervention and treatment options. Not only does this have the potential to enhance the efficacy of medical intervention, but also contributes to prolonging and promoting healthier lives."

The Dxcover Cancer Liquid Biopsy test uses Fourier transform infrared (FTIR) spectroscopy and machine learning algorithms to build a classifier of the resultant spectral profiles to detect cancer and can be fine-tuned to maximize either sensitivity or specificity depending on the requirements of specific disease pathway.

On January 10, 2024 Debiopharm, an independent biopharmaceutical company headquartered in Switzerland, and ThinkingNodeLife.ai (TNL), a trailblazer in AI Digital Cells Lab in USA, reported a collaborative partnership aimed at advancing the development of a cutting-edge cancer drug (Press release, Debiopharm, JAN 10, 2024, View Source [SID1234639194]). This strategic alliance leverages the unique capabilities of TNL’s AI Digital Cells Lab platform and Debiopharm’s deep pharmaceutical expertise to bring cancer drugs into new frontiers of innovation.

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Key Highlights of the Partnership: 1) Expanding Indications: The partnership will harness TNL’s AI Digital Cells Lab platform to explore additional indications for one of Debiopharm’s cancer drugs. 2) Drugs’ Combination Identification: Utilizing TNL’s AI digital knockdowns, it will identify valuable combinations with other drugs in development, enhancing the therapeutic potential of Debiopharm’s cancer drug. 3) Mechanism of Action Validation: TNL’s mechanistic digital cell clones will be instrumental in validating the mechanism of action of Debiopharm’s cancer drug, ensuring a deep understanding of its efficacy. 4) Drugs’ Comparison: TNL’s digital cell clones will provide comparative analysis, allowing Debiopharm to assess its cancer drug against other existing cancer treatments. 5) Biomarker Discovery: TNL partnership will focus on identifying valuable predictive biomarkers.

"We’re intrigued to discover what this collaboration with ThinkingNodeLife.ai will bring to the advancement of our oncology drug programs. Integrating AI-powered solutions into our research processes, such as TNL’s AI-Enabled Digital Cells Lab platform, aligns with our aim to adopt smarter practices in our R&D, in order to broaden drug application to more cancer types and speed up the time it takes to bring new drugs to patients," explained Bertrand Ducrey, CEO of Debiopharm.

"We are excited to start this strategic partnership with Debiopharm, a highly esteemed and innovative Swiss pharmaceutical company. We are confident that the synergy between TNL’s unique Digital Cell Clones Lab platform and Debiopharm’s profound expertise in drug R&D will show the transformative potential of AI-enabled Digital Labs from disease-target discovery to the optimization of clinical trials. As we look forward to an exhilarating 2024, we believe this partnership will pave the way for significant advancements in the field of drug R&D for the benefit of the patients," explained Khai Pham, CEO of ThinkingNodeLife.ai

On January 10, 2024 According to preclinical research published online today in Cell, one of the world’s premier scientific journals, researchers with City of Hope, one of the largest cancer treatment and research organizations in the United States, reported that a type of immune cell in the human body known to be important for allergy and other immune responses can also attack cancer (Press release, City of Hope, JAN 10, 2024, View Source [SID1234639193]).

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Furthermore, these cells, called human type 2 innate lymphoid cells (ILC2s), can be expanded outside of the body and applied in larger numbers to overpower a tumor’s defenses and eliminate malignant cells in mouse models with cancer.

"The City of Hope team has identified human ILC2 cells as a new member of the cell family capable of directly killing all types of cancers, including blood cancers and solid tumors," said Jianhua Yu, Ph.D., a professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope and the study’s senior author. "In the future, these cells could be manufactured, preserved by freezing, and then administered to patients. Unlike T cell-based therapies, such as CAR T cells, which necessitate using the patient’s own cells due to their specific characteristics, ILC2s might be sourced from healthy donors, presenting a distinct potential therapeutic approach as an allogeneic and ‘off-the-shelf’ product."

In previous research focused on mouse cells, ILC2s had not consistently shown promise when tested for their cancer-killing abilities.

However in the highly translational labs at City of Hope, researchers prioritized the examination of human cells and found that human ILC2s do not work the same as mouse ILC2s.

"Typically, mice are reliable models for predicting human immunity, so it was a real surprise in the field to find that human ILC2s function as direct cancer killers while their mouse counterparts do not," said Michael Caligiuri, M.D., who is a co-senior author of the study and also a City of Hope professor in the Department of Hematology & Hematopoietic Cell Transplantation. "It is remarkable that something has evolved so distinctly in going from mouse to human."

Finding a New Function

To test human ILC2s, Yu and the team first isolated the cells from a blood sample. Then, they developed a novel platform, which in four weeks can expand ILC2s 2000-fold from those harvested in the body. They next injected these ex-vivo expanded ILC2s into mice engrafted with human acute myeloid leukemia (AML) or solid tumors, including pancreatic cancer, lung cancer, and glioblastoma. The results showed that this ILC2 population could kill these tumors via a previously unknown cancer-killing mechanism.

"One convincing and direct piece of evidence appeared when we placed one ILC2 and one tumor cell directly together and found that the tumor cell died, but the ILC2 cell survived," explained Yu. "This proves that the ILC2s directly killed the cancer cell in that absence of any other cell."

Yu noted that the ILC2s do not need to come from the cancer patient’s own cells, meaning that there may be the possibility of harvesting and freezing ILC2s from healthy donors for ILC2 treatment options in the future.

Investigating Killer Cells

Yu and Caligiuri have been investigating a different type of cancer killer called natural killer cells, or NK cells, for decades. In fact, Yu is founding director of the Natural Killer Cell Biology Research Program at City of Hope, a national leader in the field.

Yu and Caligiuri said ILC2s now represent a new member of the cytotoxic immune effector cell family, alongside NK cells and CD8+ T cells, which help the body fight against cancer. They are excited to see how researchers might be able to harness the collective power of these different killer cells to better fight other diseases as well.

Next Steps

Yu and Caligiuri caution that because they are still in the early days of understanding ILC2s’ cancer-killing functions, many questions remain. However, they plan to continue to work with their collaborators to understand and learn more about human ILC2s now that they know the cells are killers.

"We aim to really expand the applications of these findings, potentially beyond cancer treatments," Yu said, noting that ILC2s may even work against viruses, such as COVID-19. "Additionally, we are working towards translating our discovery into tangible clinical benefits."

The team has already jumped at least one hurdle in getting ILC2s to clinical trials, which is having enough of the product to test. ILC2s are rare in the body, Caligiuri said. The team has a platform to grow them quickly.

"You have to be able to expand these cells for human clinical trials and one of the exciting things is that we are on the right track," Caligiuri said. "At City of Hope, we have the advantage of access to our good manufacturing practices-compliant facilities that can manufacture cells for us and speed discoveries into clinical trials."

The study team also included lead authors Zhenlong Li, Rui Ma, and Hejun Tang from the Yu and Caligiuri labs, as well as David Artis, Ph.D., the Michael Kors Professor of Immunology and director of the Jill Roberts Institute for Inflammatory Bowel Disease Research at Weill Cornell Medicine. The work was supported by grants from the National Institutes of Health and The Leukemia & Lymphoma Society.

On January 10, 2024 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported The New England Journal of Medicine (NEJM) has published data from the registrational Phase 1/2 TRIDENT-1 study evaluating repotrectinib (TPX-0005) in patients with ROS1 fusion-positive (ROS1+) non-small cell lung cancers (NSCLCs) (Press release, Zai Laboratory, JAN 10, 2024, View Source [SID1234639192]). Repotrectinib is a tyrosine kinase inhibitor (TKI) that has shown robust anti-tumor activity against ROS1+ cancers in preclinical models. In the TRIDENT-1 study, repotrectinib demonstrated high response rates and durable activity in patients with ROS1+ NSCLC, including patients with TKI-naïve and TKI-pretreated tumors, ROS1 G2032R resistance mutations and brain metastases. Treatment with repotrectinib was generally well tolerated with a manageable safety profile compatible with long-term administration.

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Turning Point Therapeutics, a wholly owned subsidiary of the Bristol-Myers Squibb Company, sponsored and designed the global, registrational TRIDENT-1 study. In August 2022, Bristol Myers Squibb acquired the company, including its asset repotrectinib. As part of its exclusive license agreement with Turning Point Therapeutics to develop and commercialize repotrectinib in Greater China (mainland China, Hong Kong, Taiwan, and Macau), Zai Lab participated and enrolled 81 patients for this trial.

Every year in China, more than 800,000 people are newly diagnosed with lung cancer, and NSCLC accounts for approximately 85% of the cases. ROS1 rearrangements occur in ≤2% of patients with NSCLC1. Brain metastases are common among patients with ROS1+ NSCLC and intracranial activity of approved ROS1 TKIs can be suboptimal.

"The results from the TRIDENT-1 study suggest repotrectinib results in high and durable response rates in patients with ROS1+ NSCLC, in the settings of both treatment naïve, treatment resistant, and intracranial disease, which may address the limitations of first-generation TKIs," said Rafael G. Amado, M.D., president, head of Global Oncology Research and Development, Zai Lab. "We look forward to advancing the development of repotrectinib in Greater China as a next generation treatment in this clinical setting."

TRIDENT-1 is a registrational, first-in-human Phase 1/2 study assessing the efficacy and safety of repotrectinib in patients with advanced solid tumors, including ROS1+ NSCLC. In the study, 519 patients received one or more doses of repotrectinib, with 103 treated in Phase 1 and 416 treated in Phase 2. Primary endpoints were maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) and confirmed objective response rate (ORR), as assessed by blinded independent central review (BICR) using RECIST v1.1 (Phase 2). Secondary endpoints included duration of response (DOR), progression-free survival (PFS) and safety.

Based on the results of this trial, the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) accepted the New Drug Application (NDA) for repotrectinib submitted by Zai Lab for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC, after granting priority review in May 2023. In November 2023, the U.S. Food and Drug Administration approved repotrectinib for use in adult patients with locally advanced or metastatic ROS1+ NSCLC in the United States.

About Repotrectinib

Repotrectinib is a next-generation tyrosine kinase inhibitor (TKI) targeting the ROS1 and NTRK oncogenic drivers of advanced solid tumors, including non-small cell lung cancer (NSCLC). Patients with tumor harboring ROS1 and NTRK gene fusions treated with approved targeted therapies often develop resistance mutations, eventually leading to tumor progression. Repotrectinib is the first next-generation TKI for ROS1-positive metastatic NSCLC and tumors with NTRK fusions, uniquely designed to address key drivers of disease progression.

In China, repotrectinib has been granted four Breakthrough Therapy Designations from the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in ROS1-positive metastatic NSCLC patients who have not been treated with a ROS1 TKI; ROS1-positive metastatic NSCLC patients who have previously been treated with a ROS1 TKI and who have not received prior platinum-based chemotherapy; ROS1-positive metastatic NSCLC patients who have previously been treated with a ROS1 TKI and one prior line of platinum-based chemotherapy; and patients with advanced solid tumors that have an NTRK gene fusion who have progressed following treatment with prior TRK tyrosine kinase inhibitors (TKIs).

Zai Lab has an exclusive license agreement with Turning Point Therapeutics, a wholly owned subsidiary of the Bristol-Myers Squibb Company, to develop and commercialize repotrectinib in Greater China (mainland China, Hong Kong, Taiwan and Macau).

On January 10, 2024 WuXi Biologics ("WuXi Bio") (2269. HK), a leading global Contract Research, Development, and Manufacturing Organization (CRDMO), reported that its Research Service Unit (R in CRDMO) has signed a research service agreement with BioNTech SE (Nasdaq: BNTX, "BioNTech"), a next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases (Press release, WuXi Biologics, JAN 10, 2024, View Source [SID1234639191]).

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Under the terms of the agreement, WuXi Biologics leverages its proprietary antibody discovery technology platforms (R in CRDMO) to discover two undisclosed targets of preclinical investigational monoclonal antibodies for BioNTech to develop next-generation therapeutic product candidates. WuXi Biologics will receive a $20 million upfront payment for granting exclusive rights to these investigational monoclonal antibodies to BioNTech and is eligible to receive additional payments, including payments for research, development, regulatory, and commercial milestones, as well as tiered royalties.

Dr. Chris Chen, CEO of WuXi Biologics, commented, "Our unique CRDMO model is proven again. We are very pleased to support BioNTech’s growing innovative pipeline with antibodies discovered through our leading integrated discovery platforms. This agreement demonstrates our continued recognition as an industry leader in discovery service solutions, and further validates our ability to provide integrated discovery technology platforms for global partners to develop new modalities. We are looking forward to working with BioNTech with the aim of bringing potential new therapeutics with improved outcomes to patients worldwide."

WuXi Biologics offers a full spectrum of both end-to-end and modular discovery services – from idea to preclinical candidate identification – using industry-leading technology platforms and comprehensive discovery capabilities. The company’s discovery technology platforms for the generation, characterization, engineering, optimization and selection of novel antibody and biologic therapeutics include: hybridoma technology; single B cell cloning technology; phage display and yeast display technology; immune and synthetic human scFv and VHH libraries; human IgG transgenic platforms through an OmniAb and Alloy partnership; WuXiBody and SDarBody bispecific/multispecific antibody platforms; and other antibody and biologics generation and optimization technologies. All technology platforms are supported by WuXi Biologics’ comprehensive research material generation and assay development capabilities.