On July 12, 2024 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, reported a poster presentation at the upcoming ESMO (Free ESMO Whitepaper) Congress, taking place in Barcelona, Spain, 13-17 September 2024 (Press release, Adagene, JUL 12, 2024, View Source [SID1234644801]).

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 poster will report results of an ongoing phase 1b/2 trial of Adagene’s masked anti-CTLA-4 SAFEbody in combination with the anti-PD-1 treatment pembrolizumab. The title is:

Increased Therapeutic Index of Muzastotug (Muza, ADG126), a Masked Anti-CTLA-4 SAFEbody, in Combination with Pembrolizumab (Pembro) Enables Significant Clinical Benefits and Supports Further Clinical Development in Patients with Metastatic MSS CRC

The poster will be published in accordance with the ESMO (Free ESMO Whitepaper) embargo policy on the company’s website at www.adagene.com/pipeline/publications.

On July 11, 2024, Relay Therapeutics, Inc. (the "Company") reported to have received notice of termination of the Collaboration and License Agreement, dated December 11, 2020, as amended from time to time (the "Agreement"), with Genentech, Inc. and F. Hoffmann-La Roche Ltd (collectively, "Genentech"). Genentech elected to terminate the Agreement without cause, and the termination will become effective 180 days after the date of receipt of the notice of termination (the "Termination Date") (Filing, Relay Therapeutics, JUL 11, 2024, View Source [SID1234644893]).

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!

Under the Agreement, the Company and Genentech (each a "Party" and together, the "Parties") collaborate on the development and commercialization of RLY-1971 (now referred to as migoprotafib or GDC-1971), the Company’s oral, small molecule inhibitor of Src homology region 2 domain-containing phosphatase-2. Under the terms of the Agreement, the Company received aggregate consideration of $121.8 million from Genentech, including $75.0 million in an upfront payment, $45.0 million in milestone payments as well as reimbursement of certain research and development costs.

As a result of the termination of the Agreement, the Company will not be entitled to receive any further milestones or other payments due after the Termination Date. The Parties will also cease to have any development or commercialization obligations after the Termination Date and the licenses the Company granted to Genentech pursuant to the Agreement will cease to be in effect as of the Termination Date. Other material terms of the Agreement not related to termination are set forth in the Company’s Annual Report on Form 10-K for the year ended December 31, 2023.

The foregoing description of the termination of the Agreement is only a summary of the material terms thereof, and does not purport to be complete. The description is qualified in its entirety by reference to the Agreement which the Company filed as Exhibits 10.17 and 10.18 to its Annual Report on Form 10-K for the year ending December 31, 2023.

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.

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!

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]).’

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!

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.

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 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."