On October 24, 2024 NiKang Therapeutics Inc. ("NiKang") is a clinical stage biotech company focused on developing innovative small molecule oncology medicines to bring transformative therapies to patients in need, reported the unveiling of NKT3964 at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics ("Triple Meeting") during a Poster Spotlight Session (Press release, NiKang Therapeutics, OCT 24, 2024, View Source [SID1234647389]). The conference is being held October 23-25, 2024, in Barcelona, Spain. NKT3964 is a first-in-class, orally bioavailable small molecule CDK2 degrader that selectively degrades CDK2, demonstrating high specificity over CDK1 and other CDK family members. Its high potency and unique mechanism of action result in sustained inhibition of CDK2 pathway without causing cyclin E accumulation. NKT3964 is designed to treat patients with aberrant CDK2/cyclin E pathway activation, including those with ovarian, endometrial, gastric and HR+HER2- breast cancers.

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NiKang has initiated a phase 1, open-label, dose escalation study of NKT3964 as a single agent. This first-in-human study (NCT06586957) is designed to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity to determine the preliminary recommended dose for expansion of NKT3964 in adults with advanced or metastatic solid tumors.

"We are excited to share the discovery of NKT3964, a first-in-class oral CDK2 degrader at this year’s Triple Meeting," said Zhenhai Gao, Ph.D., co-founder, president, and CEO of NiKang. "This is the second of three programs targeting the cell cycle (CDK2 inhibitor NKT3447, CDK2 degrader NKT3964, and a CDK2/4 selective dual degrader) that we have advanced to the clinic. We believe CDK2 plays a critical role in driving tumor growth. Recent clinical data presented at ESMO (Free ESMO Whitepaper) further validates CDK2 as a key oncology target. We are developing a cutting-edge portfolio of CDK2 and CDK2/4 degraders that can achieve sustained CDK pathway inhibition while avoiding paradoxical cyclin E increase. Our multi-pronged approach allows us to thoroughly and deeply interrogate this pathway. We look forward to exploring NKT3964’s potential in treating patients with advanced or metastatic solid tumors."

Poster Presentation Details:

Title:

Discovery of NKT3964: a first-in-class, highly potent and selective, orally bioavailable CDK2 PROTAC degrader for cancer therapy

Presenter:

Jianlin Geng, Ph.D.

Abstract Number:

PB002

Session:

Posters in the Spotlight

Date/Time:

2:00 p.m.-2:40 p.m. CEST on October 24, 2024

About NKT3964

NKT3964 is a first-in-class, highly potent and selective, orally bioavailable CDK2 PROTAC degrader, causing prolonged CDK2 pathway inhibition without cyclin E accumulation. It has the potential to maximally inhibit the CDK2 pathway, fully harnessing the therapeutic benefits of CDK2 inhibition. NKT3964 is currently under evaluation in a Phase 1 clinical study in advanced or metastatic solid tumors as a single agent (NCT06586957).

On October 24, 2024 Matica Biotechnology Inc. (Matica Bio), a CDMO specializing in viral vector development and manufacturing, reported the signing of a Letter of Intent (LOI) with KaliVir Immunotherapeutics, a U.S.-based clinical-stage biotechnology company developing cutting-edge, multi-mechanistic oncolytic viral immunotherapies (Press release, KaliVir Immunotherapeutics, OCT 24, 2024, View Source [SID1234647388]).

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KaliVir is at the forefront of developing novel cancer therapies using its proprietary Vaccinia Enhanced Template (VET) platform. This platform allows for the expression and systemic delivery of multiple therapeutic transgenes. KaliVir’s lead clinical candidate, VET3-TGI, expresses interleukin-12 and a TGFbeta inhibitor.

Under this new partnership, Matica Bio will utilize its proprietary cell line, MatiMax, to explore a new manufacturing process for KaliVir’s oncolytic virus product.

Helena Chaye, CEO of KaliVir, stated, "Our collaboration with Matica Bio allows us to accelerate the development of our oncolytic virus therapies. This agreement is expected to expand our strategic partnership across all phases of product development."

"The development of production processes for viral vectors is crucial for the stable production of high-quality therapeutics. Through this agreement, we aim to leverage our high-performance MatiMax cell line and CGT manufacturing expertise to actively support KaliVir’s oncolytic virus program," said Paul Kim, CEO of Matica Bio.

Matica Biotechnology has viral vector facilities in College Station, Texas, purpose-built and equipped with single-use system to develop and produce viral vectors, a key raw material for cell and gene therapies. In June 2023, Matica successfully developed its proprietary MatiMax cell line, enhancing viral vector production efficiency. The company continues to expand its contract service orders while advancing biomanufacturing technologies.

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.