On January 16, 2024 Promega reported that a research published today in Nature Communications demonstrates a new potential approach for managing multiple myeloma and other hematological cancers (Press release, Promega, JAN 16, 2024, View Source [SID1234639279]). The molecule, called SJ3149, demonstrates potent anti-proliferative activity in a variety of human cancer cell lines through selective degradation of the cancer-causing protein CK1α. The authors suggest that this degrader shows great promise for broad-spectrum anti-cancer applications.

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

                  Schedule Your 30 min Free Demo!

"The rapid and robust degradation of CK1α affects the target’s cellular pathway, leading to broad killing in a variety of cancer cell models," says Promega Research Scientist Elizabeth Caine. "We believe the research in this paper will provide valuable insights to researchers developing all types of degrader molecules."

Targeted protein degradation is an emerging form of treatment in which a therapeutic molecule recruits the cell’s own machinery to destroy defective proteins. In this study, the team primarily focused on degrading a protein called CK1α, which is linked to uncontrolled cell proliferation. They report that SJ3149 potently and selectively degrades CK1α and limits the proliferation of multiple cancer cell lines spanning a wide range of disease subtypes. Their results strongly support future research on applying selective CK1α degraders to many different cancer types.

Promega scientists collaborated with researchers at St. Jude Children’s Research Hospital on this study. The paper is available open access from Nature Communications at View Source

Learn more about how Promega technologies are used to study targeted protein degradation here.

On January 16, 2024 MEI Pharma, Inc. (Nasdaq: MEIP), a clinical-stage pharmaceutical company evaluating novel drug candidates to address known resistance mechanisms to standard-of-care cancer therapies, reported the design of the ongoing Phase 1b study of the mitochondrial oxidative phosphorylation (OXPHOS) inhibitor ME-344 in combination with bevacizumab (Avastin) in refractory metastatic colorectal cancer patients will be presented during a poster session at the 2024 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium to be held January 18 – 20, 2024 (Press release, MEI Pharma, JAN 16, 2024, View Source [SID1234639278]).

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

                  Schedule Your 30 min Free Demo!

Presentation Title: A Phase 1b Study of the OXPHOS Inhibitor ME-344 in Combination with Bevacizumab in Refractory Metastatic Colorectal Cancer
Session Title: Trials in Progress Poster Session C: Cancers of the Colon, Rectum, and Anus
Presenter: Patrick M. Boland
Date: Saturday, January 20, 2024, 6:30-7:45 AM (Pacific Time)
Abstract Number: TPS222

The poster can be viewed on the MEI Pharma website here:
View Source

About the Phase 1b Study

The ongoing Phase 1b study is evaluating ME-344 plus bevacizumab across two cohorts in patients with metastatic colorectal cancer after failure of standard therapies. The combination of ME-344 and bevacizumab is intended to create metabolic synthetic lethality by leveraging the ability of antiangiogenics like bevacizumab to reduce glycolysis, forcing tumors to switch to mitochondrial respiration via OXPHOS, which is inhibited by ME-344.

In the first cohort of approximately 20 patients ME-344 is administered at 10 mg/kg once weekly for 3 weeks in combination with bevacizumab every two weeks, with cycles repeated every 4 weeks. If the rate of non-progression in Cohort 1 reaches a predetermined progression free survival threshold, Cohort 2 will enroll an additional 20 patients. Patients will be treated until disease progression or intolerability. The primary endpoint of the study is progression free survival. Secondary endpoints include overall response rate, duration of response, overall survival and safety.

The study is being conducted at member centers of the Academic GI Cancer Consortium (AGICC), an oncology consortium dedicated to identifying new drugs to treat gastrointestinal (GI) cancers.

About ME-344

ME-344 is a novel drug candidate that inhibits mitochondrial oxidative phosphorylation (OXPHOS), a fundamental metabolic pathway involved in the production of adenosine triphosphate (ATP) in the mitochondria. ATP provides energy to drive many metabolic cell processes, including division, proliferation, and growth. By disrupting the production of ATP, ME-344 has been shown to induce cancer cell death in nonclinical models and was associated with antitumor activity in clinical studies.

The two main sources of ATP production in cells are OXPHOS and glycolysis; the latter is highly active in most tumors. Anti-angiogenics, like the vascular endothelial growth factor (VEGF) inhibitor bevacizumab (AVASTIN), have the potential to normalize vasculature and decrease reliance on glycolysis. The resulting reduction in glycolysis may trigger an increased dependence on mitochondrial ATP production for energy to support continued tumor proliferation.

In such cases of tumor plasticity, the combination of ME-344 and bevacizumab may induce metabolic synthetic lethality, providing a novel therapeutic strategy. Specifically, leveraging the ability of antiangiogenics like bevacizumab to reduce glycolysis and force tumor cells to switch to mitochondrial respiration via OXPHOS, which is inhibited by ME-344, may reduce access to ATP needed for cell division and growth in tumors.

This approach was first clinically evaluated in a multicenter, investigator-initiated, randomized, open-label, window of opportunity clinical study, evaluating ME-344 (3 doses) plus bevacizumab (1 dose) in 42 women with early HER2-negative breast cancer. Study results demonstrated significant biological antitumor activity as measured by a reduction in the proliferative biomarker Ki-67 compared to placebo. The combination appeared to be generally well tolerated. The data from this study were consistent with preclinical data suggesting that combining ME-344 can augment anti-angiogenic therapy and provided validation for continued evaluation of the combination of ME-344 with bevacizumab and other VEGF inhibitors.

An earlier Phase 1 clinical study evaluating ME-344 as a single-agent in patients with refractory solid tumors also demonstrated anti-tumor activity, further validating the potential of mitochondrial inhibition as a promising therapeutic modality.

On January 16, 2024 Presage Biosciences, a biotechnology company whose mission is to enable precision drug response evaluation in the human tumor microenvironment (TME), reported that the U.S. Food and Drug Administration (FDA) has issued a Study May Proceed notification for testing a pre-GMP drug candidate with the CIVO platform (Press release, Presage Biosciences, JAN 16, 2024, View Source [SID1234639277]). The drug candidate, PBA-0405, is owned by Poland-based biopharmaceutical company, Pure Biologics, and represents the earliest stage material to date that will be evaluated in patients in a CIVO Phase 0 clinical trial. PBA-0405 is a ROR1-targeting compound that has been engineered to induce tumor cell killing by cytotoxic immune cells.

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

                  Schedule Your 30 min Free Demo!

"We are very excited by this first opportunity to evaluate pre-GMP material in partnership with Pure Biologics," said Patrick Gray, PhD, Presage CEO. "This is a tremendous step forward for both Presage and overall drug development. We continue to push the bounds on finding alternatives to using preclinical models that fail to capture the effects of novel agents in the intact TME."

"The Pure Biologics team is incredibly proud of this momentous achievement," said Dr. Filip Jelen, Pure Biologics Co-Founder and President of the Management Board." "Our partnership with Presage was key in achieving this milestone and we eagerly await the first insights into drug efficacy and impact on the tumor microenvironment."

About CIVO
Comparative In Vivo Oncology (CIVO) is Presage’s patented platform that enables multiplexed intratumoral microdosing and generation of detailed tumor profiling. The CIVO device can deliver up to eight different drugs or drug combinations simultaneously into trackable drug columns. Presage’s CIVO technology and analysis capabilities are unparalleled at providing insight into drug-exposed areas of the intact tumor microenvironment. Presage is pairing the use of CIVO with molecular profiling technologies in both preclinical and Phase 0 trials in order to inform and de-risk oncology drug development.

On January 16, 2024 Halozyme Therapeutics, Inc. (NASDAQ: HALO) ("Halozyme") reported that Roche received European Commission (EC) marketing authorization of Tecentriq SC (atezolizumab) co-formulated with ENHANZE, Halozyme’s proprietary recombinant human hyaluronidase enzyme, rHuPH20 (Press release, Halozyme, JAN 16, 2024, View Source [SID1234639276]). The approval applies to all approved indications of Tecentriq IV and represents the European Union (EU)’s first PD-(L)1 cancer immunotherapy for subcutaneous injection.

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

                  Schedule Your 30 min Free Demo!

Tecentriq SC reduces treatment time to approximately 7 minutes, compared to an IV infusion which can take approximately 30 to 60 minutes. In addition, it may be administered by a healthcare professional outside of the hospital, in a community care setting or at home, depending on national regulations and health systems.

"As the first subcutaneous PD-(L)1 cancer immunotherapy in Europe, Tecentriq SC can provide a new treatment option that can enhance the treatment experience for patients and caregivers while freeing up resources in constrained healthcare systems," said Dr. Helen Torley, president and chief executive officer of Halozyme.

The EC approval follows pivotal data from the Phase IB/III IMscin001 study, which showed comparable levels of Tecentriq in the blood, when administered subcutaneously, and a safety and efficacy profile consistent with the IV formulation. The study found 90% of healthcare professionals agreed that the SC formulation is easy to administer and 75% said it could save time for healthcare teams compared with the IV formulation.

On January 16, 2024 Chengdu Chipscreen NewWay Biosciences Co., Ltd. (NewWay) reported that on January 5, 2024, the dosing of the first patient for a phase I clinical trial of a PD-1/CD40 bispecific antibody (bsAb), NWY001, at Sun Yat-Sen University Cancer Center in China, the trial-leading institution (Press release, Shenzhen Chipscreen Biosciences, JAN 16, 2024, View Source [SID1234639275]). The trial is a multi-center, non-randomized, open-label, multi-dose phase I clinical trial designed to evaluate the safety, tolerability, preliminary efficacy, pharmacokinetic properties, and potential biomarkers associated with NWY001 treatment in patients with advanced solid tumors.

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

                  Schedule Your 30 min Free Demo!

NWY001 is world’s first PD-1/CD40 bispecific antibody entering clinical study. Mechanistically, the bsAb targets two targets synergistically and can activate the CD40 pathway in a PD-1 dependent manner, reducing the potential toxicity commonly associated with CD40 agonistic monoclonal antibody (mAb). It is expected that this bsAb can transform "cold" tumors into "hot" tumors, thereby increasing cancer patients’ sensitivity to PD-(L)1 immune checkpoint inhibitors, especially PD-(L)1 antibody resistant cancer patients.

Dr. Bin Liu, Scientific Director of Chipscreen NewWay, said:

"Dosing of the first patient marks a significant milestone for the clinical development of NWY001. Its unique mechanism is expected to circumvent the ineffectiveness or toxicity caused by PD-(L)1 immune checkpoint inhibitor monotherapy, CD40 agonists, or their combination therapy, therefore benefiting more cancer patients. We thank the experts at Sun Yat-Sen University Cancer Center for their great support, the clinical and related teams at Chipscreen for their efforts, and the patients enrolled in this NWY001 clinical trial and their families."

February 27th, 2023 – Biocytogen Pharmaceuticals (Beijing) Co., Ltd. announced that its wholly owned subsidiary, Eucure (Beijing) Biopharma Co., Ltd., has reached an exclusive licensing agreement with Chipscreen NewWay Biosciences, a holding subsidiary of Shenzhen Chipscreen Biosciences Co., Ltd. ("Chipscreen Biosciences", SSE: 688321) for the clinical development and commercialization of bispecific antibody YH008 (NWY001) in Greater China (including Mainland China, Hong Kong, Macau and Taiwan).