On October 24, 2024 Havah Therapeutics, a clinical stage biopharmaceutical company developing innovative, proprietary hormonal implant therapies for prevention and treatment of breast cancers, reported the formation of their Clinical Advisory Board Chaired by Havah Therapeutics founder Stephen Birrell, MD, PhD (Press release, HavaH Therapeutics, OCT 24, 2024, View Source [SID1234647387]).

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"The scientific and clinical guidance of this esteemed group will be invaluable as we advance our androgen targeted therapy into late-stage clinical studies for Ductal Carcinoma In-Situ (DCIS) and investigator-sponsored combination studies in more advanced disease," said, Matthew Brewer, CEO of Havah Therapeutics.

Shelley Hwang, MD, MPH, Breast Cancer Research Foundation (BCRF) Investigator and internationally recognized expert in pre-invasive disease and DCIS, added: "I am thrilled to be involved with Havah Therapeutics at this critical stage of their development. Insights gained from their ongoing Phase 2 study (RECAST DCIS), coupled with my experience as the principal investigator of the COMET Study, will potentially enable the company’s androgen receptor targeting therapy to provide a much needed treatment alternative to invasive surgery and radiation treatment."

The members of Havah Therapeutics’ Clinical Advisory Board include:

Stephen Birrell, MD, PhD (Chair), is founder of Havah Therapeutics and Chief Medical Officer of Wellend Health, an Australia-wide clinic that specializes in breast hormone-health, women at high-risk breast cancer and clinical trials. He is a Clinical Affiliate academic at the University of Adelaide Dame Roma Mitchell Cancer Research Laboratories.

Shelley Hwang, MD, MPH is the Mary and Deryl Hart Distinguished Professor of Surgical Oncology and Radiology, Vice Chair of Research and Disease Group Leader for the Breast Cancer Program at Duke University Comprehensive Cancer Center. Her research focus includes breast cancer prevention, identifying less invasive treatments for early-stage breast cancers including DCIS and addressing and mitigating health care disparities in breast cancer.

Seema A. Khan, MD is Professor of Surgery in the Feinberg School of Medicine at Northwestern University, and the Bluhm Family Professor of Cancer Research. She is the Co-Leader of the Cancer Prevention Research Program at the Robert H. Lurie Comprehensive Cancer Center. Her research focuses on applying biomarker knowledge to improve breast cancer risk stratification and develop preventive interventions for high-risk women. Her research is funded by the National Institutes of Health, The Breast Cancer Research Foundation, the Avon Foundation, and the Susan G. Komen Foundation

Professor Wayne Tilley, PhD is the Inaugural Director of the Dame Roma Mitchell Cancer Research Laboratories, University of Adelaide. He completed a Fellowship at UT Southwestern in Dallas Texas in the late 1980s where he was one of the first to clone the human androgen receptor (AR) with Professor Jean Wilson, MD. A current major research focus of Professor Tilley’s lab is the development of new treatments for breast cancer that stimulate the tumor suppressive activity of the AR in the breast (Nature Medicine 2021; Lancet Oncology 2024) to counter the proliferative effects of estrogen.

Additional background information on the CAB members can be found on the company’s website: www.havahtx.com

About RECAST DCIS

Havah Therapeutics is currently participating in the Re-Evaluating Conditions for Active Surveillance Suitability as Treatment: Ductal Carcinoma In Situ (RECAST DCIS), a Phase 2 platform study aimed at preventing the progression of DCIS to breast cancer. Havah Therapeutics’ HAVAH T+Ai, a proprietary combination of testosterone (T) and anastrozole (Ai) that targets the androgen and estrogen receptor pathways, is being evaluated alongside two other endocrine therapy arms.

On October 24, 2024 Qurient Co. Ltd. (KRX: 115180) reported the commencement of a clinical trial for adrixetinib (formerly named Q702), following the clearance of its investigational new drug (IND) application by the U.S. FDA (Press release, Qurient Therapeutics, OCT 24, 2024, View Source [SID1234647386]).

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The trial is a Phase 1 dose escalation and expansion study designed to assess the safety and preliminary efficacy of Q702 as a single agent and in a triplet combination with venetoclax and azacitidine for patients with relapsed/refractory acute myeloid leukemia (AML) (ClinicalTrials.gov Identifier: NCT06445907). Adrixetinib, an orally administered, selective inhibitor of AXL/MER/CSF1R kinases, has demonstrated significant anti-tumor activities, enhancing chemo-sensitivity and immune response across various tumor models. The innovative combination therapy is expected to work synergistically, potentially improving patient outcomes in AML treatment.

The trial’s principal investigator is Abhishek Maiti, M.D., assistant professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston.

The expression of AXL and MER (TAM family kinases) and CSF1R has been linked to a poorer prognosis in AML, positioning them as critical therapeutic targets within the cell and tumor microenvironment. Preclinical studies have shown the efficacy of AXL/MER inhibition, both as a standalone treatment and in combination with venetoclax, in various AML models, including aggressive FLT3-ITD bearing AML and venetoclax-resistant primary AML samples. CSF1R inhibition also targets AML by disrupting supportive microenvironmental signals, while AXL inhibition in macrophages may enhance the myeloid-centered anti-leukemia immune response.

Dr. Kiyean Nam, CEO of Qurient, conveyed his enthusiasm for the company’s strategic trajectory, stating, "The establishment of adrixetinib’s Phase 2 recommended dosage has set the stage for further clinical collaboration with leading American medical institutions for patients diagnosed with AML, but who may not be eligible for intensive chemotherapy. I believe that adrixetinib’s unique underlying biology can help these patients in combination with venetoclax and azacitidine."

About Adrixetinib (Q702)

Adrixetinib, an innovative immunotherapy conceived by Qurient, is a selective triple kinase inhibitor that targets AXL, MER, and CSF1R. It enhances the body’s innate immune defenses and increases the susceptibility of cancer cells to therapeutic interventions. Q702 is currently in clinical development for the treatment of select advanced solid tumors and hematologic malignancies.

On October 24, 2024 Researchers at Children’s Hospital of Philadelphia (CHOP) reported significant findings in the treatment of neuroblastoma, a cancer of the peripheral nervous system that usually occurs as a solid tumor in a child’s chest or abdomen (Press release, CHOP, OCT 24, 2024, View Source [SID1234647385]). The study offers insights that could lead to new, personalized medicine approaches in immunotherapy treatment. The findings were published today in the journal Cancer Cell.

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Neuroblastoma is the most common cancer in infants, accounting for a disproportionate share of pediatric cancer deaths. Currently, monoclonal antibody-based immunotherapy is the only Food and Drug Administration (FDA) approved treatment for neuroblastoma. However, this type of immunotherapy can cause painful side effects, and patients often relapse. All these factors led researchers to seek new and innovative approaches to treating this disease and safely improve cure rates.

In this study, researchers used a multi-omics approach to analyze and identify potential new targets for immunotherapy, integrating proteomic, transcriptomic, and epigenomic data to pinpoint biologically relevant proteins on the surfaces of cancer cells that are visible to the immune system. Reviewing comprehensive data helps scientists understand how cells function and what goes wrong in diseases like cancer.

Based on their findings, the researchers prioritized the protein, Delta-like canonical notch ligand 1 (DLK1). They showed that high expression of DLK1 in cancer cells promotes tumor growth and discovered how neuroblastoma cells increase DLK1 levels. They also found that DLK1 is produced at a higher rate in many childhood and adult cancers.

"Our study demonstrates the power of an integrative multi-omics approach to identify immunotherapeutic targets," said senior author, Sharon J. Diskin, PhD, a member of the Center for Childhood Cancer Research and Department of Biomedical and Health Informatics at CHOP and an Associate Professor of Pediatrics in the Perelman School of Medicine at the University of Pennsylvania.

The researchers subsequently studied a novel treatment called ADCT-701, an antibody-drug conjugate (ADC) that delivers a potent therapy targeting DLK1-expressing cancer cells, as part of the National Cancer Institute’s (NCI) Pediatric Preclinical in Vivo Testing (PIVOT) Program. They demonstrated that ADCT-701 was highly effective in eradicating highly resistant patient-derived tumors. The NCI is currently conducting a phase 1 clinical trial for treatment of neuroendocrine neoplasms with ADCT-701 in adults 18 and older.

"Our findings provided important validation and preclinical data to support an ongoing first-in-human DLK1-directed immunotherapy clinical trial for adult patients diagnosed with neuroendocrine neoplasms, including neuroblastoma," said the study’s primary author, Amber Hamilton, PhD, a post-doctoral fellow at CHOP. "This research brings hope to families, offering the potential for more effective treatments."

The research was supported by a grant from the W.W. Smith Charitable Trust, an Innovation Award from Alex’s Lemonade Stand Foundation, and a Stand Up 2 Cancer-St. Baldrick’s Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT1113). This work was also supported by National Institutes of Health (NIH) grants U54-CA232568, R01-CA204974, R01-CA237562, R03-CA230366, U01-CA199287, R35-CA220500, U01-CA263957, U01-CA199222, F31-CA225069 and T32-CA009140. The work was delivered in part by the NexTGen Cancer Grand Challenges partnership funded by Cancer Research UK (CGCATF-2021/100002), the National Cancer Institute (CA278687-01) and The Mark Foundation for Cancer Research.

On October 24, 2024 J INTS BIO, a pioneering biopharmaceutical company, reported that it has unveiled promising interim results from the Phase 1/2 clinical trial of its novel 4th-generation EGFR Tyrosine Kinase Inhibitor (TKI), JIN-A02, aimed at EGFR-mutated non-small cell lung cancer (NSCLC) patients who developed resistance and progressive diseases despite treatments (Press release, J INTS BIO, OCT 24, 2024, View Source [SID1234647384]). The data was presented at this year’s edition of ENA (EORTC-NCI-AACR) (Free EORTC-NCI-AACR Whitepaper) Symposium, held in Barcelona, Spain, from October 23-25, 2024, drawing significant attention from the global oncology community.

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Mutations in the epidermal growth factor receptor (EGFR) is a key driver in the pathogenesis of NSCLC, with 3rd Generation EGFR-TKIs like osimertinib serving as the cornerstone of treatment. Unfortunately, eventually resistance to this treatment will occur, leading to cancer relapse and disease progression. JIN-A02, developed by J INTS BIO, is the 4th-generation EGFR-TKI specifically designed to address this. By targeting both the original mutations and those acquired subsequently as a result of cancer treatments, it offers a therapeutic solution for these patients.

The ongoing Phase 1/2 clinical trial evaluates JIN-A02 in patients with advanced or metastatic NSCLC who have developed resistance and disease progression after 3rd-generation EGFR-TKIs use. The study consist of 3 parts: dose escalation (Part A), dose exploration (Part B), and dose expansion (Part C). The data generated so far in Part A has been encouraging with a good safety profile and early efficacy signals, underscoring JIN-A02’s position as a novel treatment for EGFR-TKI-resistant NSCLC.

J INTS BIO said, "New treatment are urgently needed for lung cancer patients whose disease has worsened or relapsed after treatment with 3rd-generation EGFR-TKI. JIN-A02 is potentially one such treatment option that can bring hope to patients world wide."

Study Design and Interim Results:

To date, the Part A of the study has enrolled 16 patients who received increasing doses of JIN-A02, starting with a low dose of 12.5mg daily to 150 mg daily, with the primary objective of determining the maximum tolerated dose (MTD). This Part also look at safety, pharmacokinetics, and anti-tumor activity as secondary objectives. Doses higher than 150mg are currently being studied in this Part.

Key Interim Findings:

Safety: JIN-A02 demonstrated a very favorable tolerability across all dose levels studied so far, with no dose-limiting toxicities (DLTs) observed up to 150mg daily. There has been no myelosuppression and more importantly, no adverse events commonly associated with EGFR TKI such as rash, diarrhea and cardiotoxicity and this despite tumor reduction already being observed. This is the reason higher doses are being studied.
Efficacy: Tumor control were reported early in this study at lower doses. The first instance occurring at a relative low dose of 50mg. In this cohort, Partial Response of the lung lesions with stable disease in brain metastases was reported. Another Partial Response of the lung lesions was reported in the next cohort of 100mg, in a patient with similar primary EGFR mutation. These findings highlight JIN-A02’s potency as a therapeutic agent, even in patients with progressive diseases and who were heavily treated prior to entering this study.
Central Nervous System (CNS): Of interest is JIN-A02 activity against brain metastases, a potentially fatal complication of progressive lung disease. Reduction in the brain metastases was first reported with JIN-A02 in the 100mg Cohort, although stable disease was reported in the 50mg Cohort. These results points to JIN-A02 not only penetrating the tough Blood-Brain Barrier, but also exerting its anti-tumor effects.
Progression to Subsequent Trial Phases:

Once we have the final doses to be used in Phase 2, the dose-expansion part of the study (Part B) will begin, and two doses will be selected and studied in bigger groups of patient to verify its safety, pharmacokinetics, and anti-tumor activity. Part B is essential for the selection of the final dose level to be used in Phase 2 or Part C of this study.

In this final part (Part C), we will investigate JIN-A02 in specific patient populations who are stratified by EGFR mutation subtypes and the presence of CNS metastases. Part C is critical for generating a bigger dataset on the drug’s therapeutic potential across distinct NSCLC patient groups for regulatory approval purposes.

Implications for Future Therapeutic Development

Professor Byeong Cheol Cho of Severance Hospital’s Division of Medical Oncology, South Korea, commented on the significance of these findings, stating, "JIN-A02’s demonstrated efficacy against both lung and its associated CNS disease underscores its potential as a groundbreaking treatment for patients with EGFR-TKI-resistant NSCLC, including and especially those with brain metastases."

JIN-A02’s ability to effectively target CNS lesions represents a notable advancement and as a 4th generation EGFR-TKI, offers hope for patients with very limited options as a result of progression after 3rd-generation TKIs use.

Next Steps in Clinical Development:

J INTS BIO is fully committed to accelerating the clinical development of JIN-A02. And as the clinical study continues to enroll patients ahead of schedule, JIN-A02, is poised to shape the treatment landscape of NSCLC and to offer hope to lung cancer patients worldwide.

On October 24, 2024 Pierre Fabre Laboratories reported that the first patient has been dosed with PFL-002/VERT-002, a monoclonal antibody acting as a degrader of c-MET, in a phase I/II first-in-human dose-escalation, dose-optimization and dose-expansion trial, for patients with Non-Small Cell Lung Cancer (NSCLC) harbouring MET alterations (Press release, Pierre Fabre, OCT 24, 2024, View Source [SID1234647383]).

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The PFL-002/VERT-002 phase I/II trial is an open label, multi-centre study that aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary clinical efficacy of PFL-002/VERT-002, as a monotherapy for patients with MET-dependent tumors, including those emerging with acquired resistance to other treatments.

Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer, accounting for approximately 85% of newly diagnosed lung cancer cases, and MET, also known as hepatocyte growth factor receptor (HGFR), is an oncogene driver in subsets of patients suffering from NSCLC.1-4 MET exon 14 skipping mutation and MET amplification are found as primary oncogenic drivers and MET amplification as a resistance mechanism to selected targeted therapies.

"PFL-002/VERT-002 targets a clinically validated oncogenic driver with a unique and differentiated mechanism of action, triggering the degradation of the c-MET oncogene. Thus, it provides the opportunity to test a novel therapeutic approach for patients with MET driven tumors. We are looking forward to collaborating with the investigators participating in the first-in-human trial to assess the safety and efficacy of this new agent." said Francesco Hofmann, Head of Research and Development for Medical Care at Pierre Fabre Laboratories.