On July 11, 2024 Thermo Fisher Scientific Inc. (NYSE: TMO), the world leader in serving science reported that to help accelerate research into new treatments for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), it is partnering with the National Cancer Institute (NCI) – part of the National Institutes of Health – on the myeloMATCH (Molecular Analysis for Therapy Choice) precision medicine umbrella trial (Press release, Thermo Fisher Scientific, JUL 11, 2024, View Source [SID1234644800]). By testing patients’ bone marrow and blood for certain genetic biomarkers using Thermo Fisher’s next-generation sequencing (NGS) technology, clinical sites can more quickly match patients with an appropriate clinical trial that tests a treatment designed to target specific mutations present in the samples.

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AML is an aggressive cancer of the bone marrow and blood and is one of the most common types of leukemia. Because it can advance quickly with a five-year survival rate of only 30-40% for people under age 60, rapid detection and effective treatment are essential to improve patient outcomes. Further, clinical practice guidelines note the importance of rapid genetic analysis to identify biomarkers that may help match patients with optimal treatments based on their unique cancer profile.

"myeloMATCH breaks new ground in many ways, not least by assembling a portfolio of sub-studies to treat patients with specific subtypes of AML and MDS through all stages of their treatment journey," said Dr. Harry P. Erba, chair of the Southwest Oncology Group (SWOG) Leukemia Committee and co-chair of the myeloMATCH Senior Science Council. "Many more treatment options are available for people with AML and MDS than just 5-10 years ago, and many more targeted therapies are being developed. However, to choose the best treatment option for our patients requires knowledge of the genetic changes that underly the disease, which vary between patients. This information is needed quickly in order to begin effective therapy for very aggressive cancers. Our partnership with Thermo Fisher allows us to obtain the required genomic profiling rapidly and begin therapies specific for each subtype of the disease. Through this personalized approach to treatment, we believe we will increase the number of people who are leukemia survivors."

The study aims to complete genomic testing and deliver complete results within a few days across testing modalities to help quickly enroll patients into specific sub-studies based on their biomarker profile at time of diagnosis. As the first turnkey NGS solution that automates the specimen-to-report workflow designed to deliver results in a single day with just two user touchpoints, the Ion Torrent Genexus System* will help accelerate the process of matching patients with appropriate clinical trials.

myeloMATCH will be open in the U.S. and Canadian sites of the NCI National Clinical Trials Network, which includes more than 2,200 sites. Further, the NCI’s Division of Cancer Treatment and Diagnosis has developed cooperative research and development agreements with many pharmaceutical companies that will provide different drugs to support myeloMATCH. By conducting multiple treatment sub-studies specific to genomic types, myeloMATCH may help fuel the development of promising new therapies.

"myeloMATCH is an immense step forward for patients with aggressive and rapidly advancing cancers who need better treatment options," said John Sos, senior vice president and president, life sciences solutions at Thermo Fisher Scientific. "Using the Genexus System, clinical teams across sites can quickly match eligible patients with the right trials to ultimately better understand the clinical impact of these therapies. By helping to expedite this process, we can ensure that more patients have access to appropriate precision oncology treatments."

Patient samples will be sequenced in the myeloMATCH Molecular Diagnostics Laboratory Network (MDNet) using the Genexus System and reagents along with the Oncomine-based NCI Myeloid Assay as part of an approved Investigational Device Exemption (IDE) to assign participants to myeloMATCH treatment studies and has received Investigational New Drug authorization by the U.S. Federal Drug Administration. The MDNet sites at the Molecular Characterization Laboratory, part of the Frederick National Laboratory for Cancer Research, and the Fred Hutchinson Cancer Center in Seattle, Wash., are funded by NCI for this activity. As presented during the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting, the assay demonstrated high sensitivity and reproducibility between sites.

To learn more about myeloMATCH, please visit View Source

On July 11, 2024 ADM Korea, a subsidiary of Hyundai Bioscience, reported on the 8th that the first clinical trial target population for its niclosamide-based oral metabolic anticancer drug will be ‘prostate cancer patients resistant to hormone therapy (Press release, Hyundai Bioscience, JUL 11, 2024, View Source [SID1234644799]).’

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Metabolic anticancer drugs regulate the metabolic pathways of cancer cells to induce their death. The niclosamide-based metabolic anticancer drug not only regulates the metabolic pathways of cancer cells to induce their death but also blocks the signaling pathways of cancer cells that avoid anticancer effects, thus inhibiting drug resistance.

Currently used anticancer drugs, including hormone therapies, chemotherapies, targeted therapies, and immunotherapies, all fail to resolve the issue of cancer cell drug resistance that arises with long-term treatment. Cancer cell resistance refers to the phenomenon where cancer cells activate cell signaling pathways that help them evade the effects of anticancer agents through repeated drug administration, thereby decreasing the efficacy of the drugs. The biggest challenge in anti-cancer treatment is solving the problem of cancer cell drug resistance, but no drug has yet been developed to address this.

Niclosamide is a drug that has been identified to inhibit the Wnt/β-catenin and STAT3 cell signaling pathways, which are activated when cancer cells develop resistance to anticancer drugs, thereby suppressing cancer cell drug resistance. Numerous studies have shown that when niclosamide is used in combination with chemotherapies (such as SN38 and azacitidine), immunotherapies (PD-L1 Ab), targeted therapies (erlotinib), and hormone therapies (enzalutamide), the anticancer effects are superior to those of single-agent treatments. However, due to the longstanding issues of low absorption and short half-life, niclosamide has not been repurposed as an anticancer drug over the past 60 years.

CNPharm, which plans to enter into an exclusive license agreement with ADM Korea, has overcome these two issues with its patented technology, successfully repurposing niclosamide as an oral metabolic anticancer drug.

In a triple-negative breast cancer model animal study conducted by CNPharm, the combination treatment of the chemotherapeutic agent docetaxel and the niclosamide-based metabolic anticancer drug showed 67% greater anticancer effects compared to the docetaxel-only treatment group. Additionally, in a three-month animal toxicity study of the oral niclosamide-based metabolic anticancer drug, the blood concentration at the NOAEL (No Observable Adverse Effect Level) of niclosamide was 7,888 ng/mL, and cancer cell proliferation was found to be reduced by 50% at a concentration of less than one-tenth of NOAEL level (65~654 ng/mL) in in vitro study, confirming the drug’s safety. The niclosamide-based drug is an oral medication offering convenience and ease of administration.

ADM Korea plans to conduct clinical trials combining existing treatments with the oral niclosamide-based metabolic anticancer drug for all terminal cancer patients who have developed resistance to existing anticancer drugs. Initially, in August, ADM Korea will submit an IND to the Ministry of Food and Drug Safety of the Republic of Korea for a clinical study combining hormone therapy and the niclosamide-based metabolic anticancer drug in prostate cancer patients resistant to hormone therapy. ADM Korea received a proposal for this combination therapy clinical study from a domestic prostate cancer expert in mid-May. ADM Korea decided to conduct the clinical trial on prostate cancer patients first, as the number of prostate cancer patients is steadily increasing, there is no suitable treatment for patients resistant to hormone therapy, the clinical trial period for prostate cancer is relatively shorter (taking about four weeks), and higher therapeutic effects compared to other cancers can be expected.

According to a recent paper published in the Lancet, the number of prostate cancer patients worldwide is expected to more than double from 1.4 million in 2020 to 2.9 million in 2040. The global prostate cancer market is predicted to reach approximately 29.8 trillion KRW by 2025.

Combining niclosamide with existing anticancer treatments is expected to solve the problem of drug resistance, significantly enhancing the effectiveness of anticancer therapy compared to single-agent treatments, and drastically improving the quality of life for cancer patients.

Vice President of ADM Korea Jin Geun-woo said, "The clinical trial is designed to verify the safety and efficacy of combining niclosamide-based metabolic anticancer drug and hormone therapy in prostate cancer patients over four weeks by observing PSA levels. According to Clinical Cancer Research article {20.12 (2014)}, in animal models with tumors resistant to secondary hormone therapies for prostate cancer, enzalutamide alone reduced tumors by only about 5%, while the combination of niclosamide and enzalutamide resulted in a tumor reduction of about 72%. The niclosamide-based metabolic anticancer drug will mark a historic turning point in prostate cancer treatment."

On July 11, 2024 MEKanistic Therapeutics Inc., a biotechnology company pioneering the development of next-generation kinase inhibitors for cancer treatment, reported the peer-reviewed publication of new preclinical research on its lead candidate, MTX-531, an investigational dual-targeting therapy, in Nature Cancer (Press release, Mekanistic Therapeutics, JUL 11, 2024, View Source [SID1234644798]). MTX-531 is a potential first-in-class therapy uniquely designed to inhibit both EGFR (Epidermal Growth Factor Receptor) and PI3K (Phosphoinositide 3-kinase), two critical proteins involved in cancer cell survival and proliferation.

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"We are excited to share the positive MTX-531 preclinical research published in Nature Cancer, which we believe show promising signals toward a novel solution to addressing the root cause of resistance to current cancer treatments," said Danny Cunagin, chief executive officer, MEKanistic Therapeutics. "By targeting critical adaptive resistance mechanisms with a dual inhibition strategy, we aim to significantly halt cancer progression compared to single-target treatments, and look forward to advancing this innovative therapy to patients in clinical trials."

Key Findings of MTX-531 Study

High Potency, Selectivity Leading to First of Its Kind Tolerability

Preclinical studies demonstrated that MTX-531 exhibits nanomolar potency against both EGFR and PI3K (14.7 nM for EGFR, 6.44 nM for PI3K), with a high degree of selectivity as determined by broad kinome testing. In addition, MTX-531 did not cause hyperglycemia in mice at therapeutic doses, unlike other known pan-PI3K inhibitors, which have been reported to significantly increase blood glucose and insulin levels both in preclinical and clinical settings.

Judith Sebolt-Leopold, PhD, chief scientific officer, MEKanistic Therapeutics, commented, "MTX-531 is the first PI3K inhibitor capable of selectively co-targeting EGFR and the first known pan-PI3K inhibitor that does not induce hyperglycemia, a known challenge with PI3K inhibitors that often leads to treatment discontinuation. This unique feature, achieved through precise targeting enabled by MTX-531’s computational design, confers a favorable therapeutic index and resilience to adaptive resistance mechanisms not observed in prior PI3K inhibitor clinical programs."

Robust Tumor Suppression as Monotherapy and in Combination Therapy

MTX-531 monotherapy led to significant tumor regression in preclinical models of head and neck squamous cell carcinoma (HNSCC). Oral therapy effectively inhibited PI3K and EGFR signaling in a balanced fashion, achieving objective responses in every HNSCC model evaluated. Complete tumor regressions were observed across a broad dose range, with survival improvement ranging from 62% to >500% across models.

In addition, when combined with a MEK inhibitor (trametinib) or a KRAS inhibitor (sotorasib), treatment with MTX-531 more than doubled the incidence of tumor regressions achieving a 100% objective response rate in multiple KRAS mutant colorectal (CRC) and pancreatic tumor models.

Dr. Sebolt-Leopold added, "Our collective preclinical data show that MTX-531 effectively inhibits tumor growth in cancers with PIK3CA and KRAS mutations, which often lead to aggressive behavior and resistance to standard therapies. MTX-531 was well tolerated and outperformed the combination of drugs that individually target EGFR and PI3K. These findings highlight the versatility and broader potential of MTX-531 in treating hard-to-treat cancers."

The scientific paper can be accessed at the following link: View Source

About MTX-531 Development

Investigational new drug-enabling toxicology studies sponsored by the National Cancer Institute’s Experimental Therapeutics (NExT) Program are currently underway. The NExT Program aims to advance clinical practice by supporting promising new drug discovery and development projects. Through this program, MEKanistic Therapeutics collaborates with NCI staff and contractors on a milestone-driven project team to conduct these studies and assess MTX-531’s safety and efficacy in patients with cancer.

"Our partnership with the NCI is a testament to the promising potential of MTX-531," said Christopher Whitehead, PhD, co-founder and chief operating officer, MEKanistic Therapeutics. "With their support and our focused efforts on GMP manufacturing and drug product development, we are poised to make significant strides in bringing this innovative therapy closer to clinical trials and ultimately to patients in need."

On July 11, 2024 Senhwa Biosciences, Inc. (TPEx: 6492), reported IND Submission to US FDA for the Phase I/II study of Silmitasertib (CX-4945) in combination with chemotherapy in children and young adults with relapsed refractory solid tumors (Press release, Senhwa Biosciences, JUL 11, 2024, View Source [SID1234644797]). This investigator-initiated trial (IIT) will be conducted by the Penn State Health Children’s Hospital and the prestigious Beat Childhood Cancer Research Consortium, a group of over 50 universities and children’s hospitals, based at Penn State College of Medicine in Hershey, Pa., that offers a worldwide network of pediatric cancer clinical trials. The funding is sponsored by the Four Diamonds Foundation, with Senhwa Biosciences providing the investigational drug, Silmitasertib (CX-4945).

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The clinical trial is conducted in two phases: the first phase focuses on establishing the safety and dosage of Silmitasertib (CX-4945) in pediatric patients with relapsed or refractory solid tumors, while the second phase evaluates its efficacy and potential as a novel treatment option.

As high CK2 activity is noted across several pediatric cancers, including neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, osteosarcoma, medulloblastoma, and liposarcoma. Recent study has shown that CK2 is one of the key kinases that is essential for maintaining the stabilization of MYCN protein, the oncogenic driver in neuroblastoma. In view of the anti-tumor activity of CK2 inhibitor, the Beat Childhood Cancer Research Consortium at The Pennsylvania State University regards Silmitasertib (CX-4945) high therapeutic potential of treating pediatric cancers.

Neuroblastoma is the most common type of solid malignant tumor in children, aside from brain tumors and lymphomas. Over 90% of cases are diagnosed before the age of 5. 70% of patients already have metastatic disease by the time symptoms appear, and the 20-year survival rate is only around 30%. In the US, there are 700-800 new cases each year, accounting for about 6% of childhood cancers, meeting the definition of a rare disease.

Senhwa Biosciences is planning to apply for Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPD) for Silmitasertib (CX-4945) for the treatment of neuroblastoma. If these designations are granted and the drug is successfully commercialized, the company would obtain a Priority Review Voucher (PRV). The holder of a PRV can designate any future human drug application to receive priority review, potentially shortening the review time to 6 months, which could accelerate the timeline for the company (or its partners) to bring other products to market.

The clinical trial design also includes Ewing’s sarcoma and osteosarcoma, which are common pediatric bone cancers with poor prognoses, representing unmet medical needs.

On July 11, 2024 Dynamic Cell Therapies (DCT) reported an investment of $1M from the Myeloma Investment Fund (MIF), the venture philanthropy subsidiary of the Multiple Myeloma Research Foundation (MMRF), to accelerate the development of novel CAR-T cell technologies for patients with multiple myeloma (Press release, Dynamic Cell Therapies, JUL 11, 2024, View Source [SID1234644796]). DCT is developing technology platforms that will allow CAR-T cells to attack unique and differentiated tumor targets that will allow for durable responses to treatment, and DCT’s proprietary CAR-T cells have demonstrated superiority to FDA-approved CAR-T cells in animal models. These technology platforms will improve the safety and efficacy of CAR-T cell therapies and have immediate application for patients with hematological cancers, including multiple myeloma. Supported by this recent investment, DCT is on track to advance a product into patients within the next two years.

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"Despite current successes in treating patients with CAR-T cells, many patients with multiple myeloma still relapse after therapy," said Fred Mermelstein, Ph.D., Chief Executive Officer of DCT. "The support of the MMRF & the Myeloma Investment Fund provides key expertise that will enable us to hasten the development of novel and best-in-class CAR-T cell therapies for patients with relapsed and refractory multiple myeloma."

"At the MMRF, we are deeply committed to advancing novel treatments intended to improve patient outcomes and get us closer to cures. We are energized by DCT’s cutting-edge cell therapy approach as a potentially transformative answer to patients with relapsed or refractory myeloma," said Michael Andreini, President and CEO of the Multiple Myeloma Research Foundation (MMRF).