On October 16, 2022 Akeso, Inc. (9926. HK) ("Akeso"), a China-based biopharmaceutical company focusing on the development and commercialization of innovative therapeutic antibodies for Oncology & Immunology, reported the Phase Ib/II clinical trial of its in-house developed Ivonescimab (PD-1/VEGF bi-specific, AK112) combined with its Drebuxelimab (CD73, AK119) for the treatment of advanced solid tumors, has been approved by the National Medical Products Administration (NMPA) (Press release, Akeso Biopharma, OCT 16, 2022, View Source [SID1234622044]).

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AK112 is the first PD-1/VEGF bi-specific antibody that entered Phase III clinical research. The PD-1 antibody and VEGF blocker combination therapy has shown strong efficacy in various tumor types. AK119 targets the key node of CD73 through the adenosine pathway, and its inhibitor has broad therapeutic prospects for tumors that are quite sensitive to the adenosine pathway. Combination with immune checkpoint drugs such as AK112 can strengthen the synergistic effect of tumor therapy.

AK119 combined with AK112 has demonstrated well in vivo pharmacodynamic activity and safety in relevant pre-clinical studies. This unique combination therapy strategy will bring breakthroughs in tumor therapy.

About Ivonescimab(PD-1/VEGF, Ak112)
Ivonescimab is a first-in-class and the first to enter phase III clinical trial PD-1/VEGF bi-specific antibody independently developed by the Company. Engineered with our unique Tetrabody technology, Ivonescimab blocks PD-1 binding to PD-L1 and PD-L2, and blocks VEGF binding to VEGF receptors. PD-1 antibodies combined with VEGF-blocking agents have shown robust efficacy in various tumor types (including renal cell carcinoma, non-small cell lung cancer, and hepatocellular carcinoma). Given the co-expression of VEGF and PD-1 in the tumor microenvironment, Ivonescimab, as a single agent to block these two targets, may block these two pathways more effectively and enhance the antitumor activity, as compared to combination therapy.

Currently, Akeso is conducting a phase III clinical trial of AK112 monotherapy versus Pembrolizumab monotherapy as the first-line treatment for NSCLC patients with positive PD-L1 expression. In addition, a phase III clinical trial of AK112 plus chemotherapy versus chemotherapy in EGFR mutated advanced non-squamous NSCLC that failed in prior EGFR-TKI therapy is ongoing. AK112 has started multiple clinical trials for various stages of treatment of indications, including non-small cell lung cancer and small cell lung cancer.

About Drebuxelimab (CD73, AK119)
Drebuxelimab is a humanized monoclonal antibody self-developed by the Company with a unique mechanism to activate B-cells to generate immune responses to tumor antigens and viruses. It can significantly inhibit the enzymatic activity of CD73 and block the production of immunosuppressive adenosine. No similar product has been successfully developed and commercialized in the global market.

On October 16, 2022 At the European Association of Nuclear Medicine (EANM) Annual Meeting, GE Healthcare reported Omni Legendi, the first system on its all-new, all-digital PET/CT platform (Press release, GE Healthcare, OCT 16, 2022, View Source [SID1234622043]). This cutting-edge system features a brand-new category of digital BGO (dBGO) detector material with a small crystal size that delivers more than two times the sensitivity of prior digital scannersii, enabling faster total scan timesiii and impressive small lesion detectabilityiv. It is designed to improve operational efficiency, enhance the patient experience, and increase diagnostic power, ideally helping to enable improved patient outcomes.

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Additionally, the system’s theranosticsv capabilities and ability to image short life tracers, as well as dynamic protocolsvi, help empower clinicians with greater clinical information across more oncology, cardiology, and neurology procedure types than ever before.

"Sensitivity and image quality are everything in PET/CT," explains John Kennedy, Ph.D., Chief Physicist, Nuclear Medicine Department, Rambam Health Care Campus, and Lecturer at Technion – Israel Institute of Technologyvii. "Omni Legend delivers on both – meeting all our image quality criteria for oncology and providing impressive sensitivity to image high count tracers for cardiac and neuro imaging, which helps better inform patient diagnoses and monitoring. Also, we have been able to increase patient throughput by more than a third thanks to the system’s fast total scan times – even achieving 35 patient scans in a 9.5-hour shift – and reduce dose by 40% versus the previous equipment that was installed. This not only enables better patient access and experience but also allows us to increase overall hospital efficiencyviii."

As the pace of change in healthcare continues to increase, health plan leaders cite managing costs and driving operational efficiency as the top two challenges they face todayix. This is consistent with comments by global Molecular Imaging departments, which note operational efficiency as a top barrier to growing PET/CT procedure volumesx.

Omni Legend is GE Healthcare’s response to these growing challenges, helping healthcare systems overcome today’s barriers with a collection of intuitive workflow solutions enhanced by artificial intelligence (AI), including its new Precision DLi solution for deep learning image processing in PET/CT as well as its AI-based Auto Positioning Camera.

"Having access to high-quality images to determine patient care is foundational to administering quality healthcare," adds Prof. Zohar Keidar, Director of Nuclear Medicine & the PET/CT Department at Rambam and an Associate Clinical Professor at the Technion Faculty of Medicinevii. "With this in mind, a department like ours – which has a very heavy workload – requires a system that enables flexibility for emergency cases, in addition to our already packed schedules. Omni Legend provides that flexibility. Within a few short weeks/months, we were able to increase our number of scans by 150 percent – going from 30 to 45 patient scans per day. We used to have a long wait list; but today, if something is urgent, we can quickly scan a patient while keeping our other scheduled appointmentsviii. And the system’s clinical protocols afford us additional flexibility, allowing us to stage patients on any scanner, regardless of the system the patients was previously scanned on – affording us new opportunities in fleet management."

More than a new processing technique, Precision DLi is engineered using Deep Learning with a sophisticated deep neural network trained on thousands of images created with different reconstruction methods. It was designed to provide the image quality performance benefits most associated with hardware-based Time-of-Flight, such as better contrast-to-noise ratio, contrast recovery, and quantitative accuracy.

The capabilities of Omni Legend are further elevated by the inclusion of Q.Clear (BSREM), GE Healthcare’s pioneering PET image reconstruction technology, and MotionFree, the company’s proven, deviceless respiratory motion correction technology. Q.Clear helps to ensure reliable quantification, while MotionFree operates seamlessly in the background to correct respiratory motion artifacts for all patient types.

Furthermore, the new system’s operational efficiency solutions help improve the PET/CT imaging experience for both the technologist and the patient with convenient features that provide:

A fast data quality assurance process that saves time with streamlined calibration;
Simplified protocol selection on the gantry touchscreen and a new user interface to enable an easy PET/CT process from start to finish; and
Enhanced patient positioning capabilities as a result of AI-based Auto Positioning that automatically centers the patient for a completely hands-free positioning experience.
This streamlined patient setup frees up technologists to focus on making patients feel more comfortable. Omni Legend also features LED ambient lighting to encourage a calming mood as well as a graphic pattern for the patient to view in the system to help in both alleviating stress and reducing movement for nervous patients.

"We built our scalable Omni platform from the ground up to meet the needs of our customers and their patients today and in the future," shares Jean-Luc Procaccini, President & CEO, Molecular Imaging & Computed Tomography, GE Healthcare. "With the patient in mind, we leaned on our longstanding technological leadership and strong clinical collaborations to enhance the scan experience with entirely new components designed to help improve clinical outcomes. The result is an all-digital detector, a cutting-edge deep learning solution, and workflow enhancements to help enable more personalized care."

Omni Legend was designed with theranostics in mind, enabling clinicians to reach new levels of sensitivity and detectability for incredibly clear images. Already, the system boasts the highest sensitivity per cm in the marketxi and images Gallium 68 for diagnosis, staging, or restaging.

Future-ready capabilities include a multi-directional, upgradable platform that can potentially expand in each of the core dimensions of PET/CT imaging, including axial field-of-view, digital detector technology, software, CT capabilities, and imaging of new tracers.

On October 14, 2022 Pacylex reported that the U.S. Food and Drug Administration (FDA) granted PCLX-001 Orphan Drug Designation for "treatment of patients with acute myeloid leukemia (Press release, Pacylex Pharmaceuticals, OCT 14, 2022, View Source [SID1234645060])." PCLX-001 is a first-in-class N-myristoylation inhibitor in clinical development by Pacylex. PCLX-001 is currently being studied in non-Hodgkin lymphoma (NHL) and solid tumor cancer patients at 4 sites in Canada. Pacylex has filed an IND to study PCLX-001 in the U.S. in AML patients.

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Dr. Michael Weickert, Pacylex’s President and CEO commented, "The 5-year survival rate for AML patients 20 and older is only 27%. Patients relapse despite existing therapies. We are developing a first-in-class therapy that tackles AML in a new way that has been very effective in disease models and may be synergistic with other approaches. Our trial will offer relapsed patients another option. This Orphan Drug Designation for PCLX-001 recognizes the importance of this potential new therapy for these patients."

The planned US study will be the first time an NMT inhibitor is tested in AML patients. The U.S. Department of Defense recently awarded a grant of $1.4 million to treat AML patients with PCLX-001. "Our ongoing clinical trial in people with NHL and solid tumors showed PCLX-001 was well-tolerated and achieved drug exposures likely to benefit AML patients," said Dr. John Mackey, CMO of Pacylex. "We look forward to treating AML patients with PCLX-001 in the near future."

In animal models of AML, PCLX-001 monotherapy produced complete remissions in subcutaneous AML cell line derived xenografts (CDXs). In tail-vein injected AML patient derived xenografts (PDXs), PCLX-001 treatment resulted in up to 95% reduction of human peripheral blood and bone marrow CD45+ cells, which include the malignant stem cell population responsible for disease relapse.

The ongoing clinical PCLX-001 trial in NHL and solid tumor patients is registered at ClinicalTrials.gov Identifier: NCT04836195.

The U.S. FDA Orphan Drug Designation is only granted to investigational therapies addressing medical diseases or conditions that affect fewer than 200,000 people in the United States. Orphan drug designation provides several benefits to drug developers, including assistance in the drug development process, tax credits for clinical costs, exemptions from certain FDA fees and seven years of post-approval marketing exclusivity.

PCLX-001
PCLX-001 (aka DDD86481) is a first-in-class, small molecule NMT inhibitor originally developed by the University of Dundee Drug Discovery Unit as part of a program to treat African sleeping sickness, funded by Welcome Trust. Pacylex is developing PCLX-001 in the form of a once-a-day pill initially to treat leukemia and lymphoma. PCLX-001 has also been shown to inhibit the growth of lung and breast cancer tumors in animal models. In leukemia, lymphoma and breast cancer patients, the levels of NMT2 is correlated with survival, suggesting an important biological role in these cancers. In tests using cultured cancer cells in vitro, PCLX-001 is at least ten times as potent as ibrutinib (Imbruvica) and dasatinib (Sprycel), two clinically approved drugs currently used to treat hematologic malignancies.

On October 14, 2022 Genor Biopharma (Stock code: 6998.HK) reported that the first patient has been successfully dosed in a Phase I/II clinical trial of GB263T, a novel EGFR/cMET/cMET trispecific therapeutic antibody, in China for the treatment of patients with advanced Non-Small Cell Lung Cancer (NSCLC) and other solid tumors (Press release, Genor Biopharma, OCT 14, 2022, View Source [SID1234629909]).

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Previously, the first patient has been successfully dosed in this GB263T FIH study in Australia.

About GB263T（EGFR/cMET/cMET）

GB263T is the world’s first EGFR/cMET/cMET tri-specific antibody targeting EGFR and two different epitopes of cMET and has been designed with the goal of improving safety and efficacy. Thus, GB263T is a highly differentiated tri-specific antibody that exhibits multiple mechanisms of action to inhibit primary and secondary EGFR mutations and cMET signaling pathway simultaneously. The unique sequential binding feature whereby c-MET VHH2 binding depends on c-MET VHH1 binding expands the safety and efficacy window.

Preclinical studies showed that GB263T potently blocked ligand-induced phosphorylation of EGFR and cMET, and demonstrated better dual inhibition of EGFR and cMET signaling pathways compared to the JNJ-372 analogue. GB263T effectively induced enhanced internalization of EGFR and cMET, and downregulated the expression levels of both EGFR and cMET proteins. The in vivo anti-cancer efficacy of GB263T was demonstrated in several different tumor models, such as those with EGFR exon 20 insertion, EGFR exon 19 deletion, including C797S mutation, and various cMET alteration models. In all the models studied, GB263T demonstrated significant and dose-dependent tumor inhibition. In addition, GB263T did not show any major toxicities in monkeys, even at a high dose given for four weeks in a GLP tox study.

On October 14, 2022 Pacylex reported that the U.S. Food and Drug Administration (FDA) granted PCLX-001 Orphan Drug Designation for "treatment of patients with acute myeloid leukemia (Press release, Greenfire, OCT 14, 2022, View Source [SID1234624500])." PCLX-001 is a first-in-class N-myristoylation inhibitor in clinical development by Pacylex. PCLX-001 is currently being studied in non-Hodgkin lymphoma (NHL) and solid tumor cancer patients at 4 sites in Canada. Pacylex has filed an IND to study PCLX-001 in the U.S. in AML patients.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Dr. Michael Weickert, Pacylex’s President and CEO commented, "The 5-year survival rate for AML patients 20 and older is only 27%. Patients relapse despite existing therapies. We are developing a first-in-class therapy that tackles AML in a new way that has been very effective in disease models and may be synergistic with other approaches. Our trial will offer relapsed patients another option. This Orphan Drug Designation for PCLX-001 recognizes the importance of this potential new therapy for these patients."

The planned US study will be the first time an NMT inhibitor is tested in AML patients. The U.S. Department of Defense recently awarded a grant of $1.4 million to treat AML patients with PCLX-001. "Our ongoing clinical trial in people with NHL and solid tumors showed PCLX-001 was well-tolerated and achieved drug exposures likely to benefit AML patients," said Dr. John Mackey, CMO of Pacylex. "We look forward to treating AML patients with PCLX-001 in the near future."

In animal models of AML, PCLX-001 monotherapy produced complete remissions in subcutaneous AML cell line derived xenografts (CDXs). In tail-vein injected AML patient derived xenografts (PDXs), PCLX-001 treatment resulted in up to 95% reduction of human peripheral blood and bone marrow CD45+ cells, which include the malignant stem cell population responsible for disease relapse.

The ongoing clinical PCLX-001 trial in NHL and solid tumor patients is registered at ClinicalTrials.gov Identifier: NCT04836195.

The U.S. FDA Orphan Drug Designation is only granted to investigational therapies addressing medical diseases or conditions that affect fewer than 200,000 people in the United States. Orphan drug designation provides several benefits to drug developers, including assistance in the drug development process, tax credits for clinical costs, exemptions from certain FDA fees and seven years of post-approval marketing exclusivity.

PCLX-001
PCLX-001 (aka DDD86481) is a first-in-class, small molecule NMT inhibitor originally developed by the University of Dundee Drug Discovery Unit as part of a program to treat African sleeping sickness, funded by Welcome Trust. Pacylex is developing PCLX-001 in the form of a once-a-day pill initially to treat leukemia and lymphoma. PCLX-001 has also been shown to inhibit the growth of lung and breast cancer tumors in animal models. In leukemia, lymphoma and breast cancer patients, the levels of NMT2 is correlated with survival, suggesting an important biological role in these cancers. In tests using cultured cancer cells in vitro, PCLX-001 is at least ten times as potent as ibrutinib (Imbruvica) and dasatinib (Sprycel), two clinically approved drugs currently used to treat hematologic malignancies.