On November 30, 2021 Treadwell Therapeutics, a clinical stage biotechnology company developing novel therapeutics for highly aggressive cancers, reported that the U.S. Food and Drug Administration (FDA) has approved its Investigational New Drug (IND) application to evaluate CFI-402257, an oral, first-in-class inhibitor of Threonine Tyrosine Kinase (TTK, also as MPS1) in advanced solid tumors and breast cancer (Press release, Treadwell Therapeutics, NOV 30, 2021, View Source [SID1234596246]).

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"TTK is a critical component of the Spindle Assembly Checkpoint and potentially represents a tumor specific vulnerability. Pharmacologic inhibition of TTK using CFI-402257 causes tumor cells to prematurely exit mitosis, leading to increased genomic instability and cell death," said Dr. Mark Bray, Treadwell Chief Scientific Officer and Co-Founder. "CFI-402257 was developed from concept to clinic by our world class team. Preclinical studies and emerging clinical evidence support the use of CFI-402257 in the context of CDK4/6 inhibitor failure in ER+/Her2- breast cancer, a segment where there is a strong unmet need. We are excited by the promise of the molecule in advanced breast cancer and beyond" added Dr. Michael Tusche, Treadwell co-Chief Executive Officer.

Under this IND, Treadwell intends to initiate a Phase 2 clinical trial of CFI-402257 in the first quarter of 2022. This clinical trial is designed to confirm previously efficacious doses and to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of CFI-402257 as a single agent in advanced solid tumors, and in combination with fulvestrant in patients with ER+/HER2- advanced breast cancer after disease progression on prior CDK4/6 inhibitor and endocrine therapy. Start-up activities are currently underway.

CFI-402257 is a highly bioavailable, potent and selective inhibitor of TTK. Preclinical studies showed robust inhibition of tumor growth in a wide variety of xenograft models. CFI-402257 also demonstrated durable activity and a manageable safety profile as a single agent and in combination with fulvestrant in advanced ER+ breast cancer in studies conducted at select Canadian sites.

On November 30, 2021 Athenex, Inc., (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies for the treatment of cancer and related conditions, reported that it will host a virtual key opinion leader (KOL) event on its CAR-NKT technology on Monday, December 13th, at 9:00 am ET (Press release, Athenex, NOV 30, 2021, View Source [SID1234596245]).

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The webinar will feature presentations by KOLs Leonid Metelitsa, M.D., and Carlos Ramos, M.D., both from Baylor College of Medicine, and Sattva Neelapu, M.D., from MD Anderson Cancer Center. Dr. Metelitsa will provide an overview of Athenex’s CAR-NKT cell-based approaches. Dr. Ramos will discuss the interim data from the ongoing ANCHOR study evaluating KUR-502 in relapsed or refractory lymphoma and leukemia. These data will also be featured in a poster presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, being held from December 11th to December 14th. Dr. Neelapu will discuss the current treatment landscape and unmet medical needs in lymphoma/myeloma.

Presentations from Kurt Gunter, M.D., Chief Medical Officer for Cell Therapy at Athenex, and Daniel Lang, M.D. President, Athenex Cell Therapy, will follow. Dr. Gunter will discuss clinical milestones and company objectives.

A question-and-answer session will follow the formal presentations. To register for the webinar, please click here.

Presenting Key Opinion Leaders:

Dr. Carlos Ramos is currently an Associate Professor of Medicine in the Center for Cell and Gene Therapy at the Baylor College of Medicine, and an Attending Physician in the Blood and Marrow Transplantation Service at the Houston Methodist Hospital. As a faculty member, he has focused his research efforts on T-cell therapy for malignancies and viral infections. He has broad experience in cellular therapy for hematologic cancers, being the principal investigator in trials using chimeric antigen receptor (CAR)-modified T cells targeting CD19, CD30 and kappa light chain as therapy for non-Hodgkin and Hodgkin lymphoma and multiple myeloma. He is also implementing cellular therapy approaches for patients with Human Papilloma Virus (HPV)-associated malignancies, using HPV-specific T cells. Dr. Ramos earned his Medical Degree with Honors from the University of Lisbon, Portugal, and was a Resident in Internal Medicine at the Baylor College of Medicine, in Houston. He completed Fellowships in Hematology and Medical Oncology at the Memorial Sloan-Kettering Cancer Center, in New York, and in Blood and Marrow Transplantation at the University of Texas M. D. Anderson Cancer Center, in Houston.

Dr. Leonid Metelitsa is involved in research focused on understanding the role of Vα24-invariant natural killer T cells (iNKTs) in tumor immunity. Using clinical samples from neuroblastoma patients, his lab demonstrated for the first time that iNKTs localize to primary tumors and their presence at the tumor site is associated with good outcome. In the pursuit of the underlying mechanistic basis for the observed association between iNKTs and clinical outcome, Dr. Metelitsa’s group has published a series of high-impact papers that revealed the mechanisms of iNKT cell tumor localization and function in the tumor microenvironment. In one of these studies, they discovered the mechanism by which iNKTs attack tumor-associated macrophages (TAMs). That study has had a major impact in the fields of NKT cell and neuroblastoma research. First, it explained how iNKTs can mediate antitumor activity against CD1d-negative tumors, the majority of solid tumors in humans. Second, it showed for the first time that macrophages infiltrate primary tumors in a subset of neuroblastoma patients, their products directly support tumor growth, and their presence at the tumor site is associated with poor clinical outcome. This discovery has been validated in large international study validated using large independent cohorts of patients, concluding that the presence of M2-like macrophages is associated with a novel inflammatory signature in neuroblastoma that serves as an independent prognostic factor of extremely poor outcome. Most recently, Dr. Metelitsa has been focused on the development of therapeutic applications using iNKTs and their synthetic ligands.

Dr. Sattva Neelapu is professor and deputy chair of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center in Houston, Texas. As a physician-scientist at MD Anderson, Dr. Neelapu is focused on clinical and translational development of novel immunotherapies for B-cell malignancies. His laboratory characterized some of the major immunosuppressive mechanisms in the tumor microenvironment of B-cell malignancies, identified TCL1 as a novel shared tumor-associated antigen for B-cell lymphomas, and investigated novel targets for CAR T-cell therapy in lymphoma and myeloma. His work on the pivotal trial of axicabtagene ciloleucel CD19 CAR T-cell therapy in aggressive B-cell lymphomas led to its FDA approval as the first CAR T therapy for lymphoma. Dr. Neelapu has authored or co-authored over 150 publications.

Presenting Athenex Cell Therapy Management:

Dr. Dan Lang has over 25 years of medicine, healthcare investment as well as leadership and business experience. Prior to joining Athenex, Dan was the Chief Investment Officer of the RS Value franchise focused on domestic equity strategies. Dan was on the executive team of RS Investment Management (RSIM) that led the sale of RSIM to Victory Capital in 2016. Prior to joining RSIM in 2009, he was an analyst at Farallon Capital Management covering biotech, medical device, pharma, and healthcare services globally. Previously, he was a senior associate at a venture capital firm, Brilleon Capital and the co-founder and CFO of Sapient Medical Group. Dan’s 25+ years of business and investment experience is preceded by a distinguished career in medicine. He was a post-doctoral research and clinical fellow in cardiology at the University of California, San Francisco and the Gladstone Cardiovascular Research Institute. He was board certified in internal medicine and a Chief Medical Resident at Mount Sinai Hospital in New York. Dan holds a BA in Chemistry from Cornell University and an MD from Cornell University Medical College.

Dr. Kurt Gunter has devoted his career to the development of cell and gene therapies and brings significant experience to Athenex from his previous positions at Kuur Therapeutics, Hospira, ViaCell, and Transkaryotic Therapies. As past President of the International Society for Cellular Therapy (ISCT), Dr. Gunter played a worldwide leadership role in promoting understanding of the clinical, regulatory, manufacturing, and marketing requirements for the successful development of cell and gene therapies. Prior to his biotech career, he worked at the United States Food and Drug Administration as a Medical Officer in the Center for Biologics and was appointed Acting Deputy Director of the Division of Cell and Gene Therapy within the Center for Biologics Evaluation and Research. He also served for 5 years on FDA’s Cellular, Tissue and Gene Therapies Advisory Committee. He earned his MD from the University of Kansas and also has a BS in biological sciences, with distinction, from Stanford University. His postdoctoral training included Johns Hopkins and the US National Institutes of Health.

ASH Poster Presentation:

Session Name: 704. Cellular Immunotherapies: Clinical: Poster II
Date: Sunday, December 12, 2021
Presentation Time: 6:00 PM – 8:00 PM
Location: Georgia World Congress Center, Hall B5

About the Phase I Study of KUR-502 (Allogeneic CD19 CAR-NKT Cells) in Patients with Relapsed or Refractory B-Cell Malignancies (ANCHOR)

The phase I study is an open-label, dose-escalation study. NKT cells were isolated from the leukapheresis product of one HLA-unmatched healthy individual, transduced with the CAR, expanded ex vivo for 14 days (99.8% NKT purity), and cryopreserved. Patients received 107 (DL 1) or 3×107 (DL 2) CAR-NKT cells per square meter of body surface area following lymphodepleting conditioning with cyclophosphamide/fludarabine. Adverse events were evaluated per NCI criteria. When accessible, patients underwent core biopsies of an involved site at 2-5 weeks post-infusion. Response to therapy was assessed at 4 weeks per Lugano Criteria (for NHL) or NCCN guidelines (for ALL).

For further information about the study, visit ClinicalTrials.gov, identifier: NCT03774654.

On November 30, 2021 Hamlet Pharma reported that it is proceeding with the development of BAMLET for pharmaceutical use (Press release, HAMLET Pharma, NOV 30, 2021, View Source;utm_medium=rss&utm_campaign=hamlet-pharma-has-signed-a-collaboration-agreement-with-galenica [SID1234596241]). A necessary first step is to establish technology for large-scale production of BAMLET. A new production method has been developed and patented and will be used as a basis for scaling up the production process together with Galenica AB.

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Galenica AB is a contract research organisation (CRO) providing services in the field of pharmaceutical technology. The company has broad skills and experience in formulation, production and quality control of pharmaceuticals.

The parties have agreed to a development plan, including production technology transfer, testing of biological activity of the product and development of suitable formulations.

‘’BAMLET is a fascinating molecule with potent effects on tumor cells and in animal models of cancer’’ says Catharina Svanborg, Chairman, Hamlet Pharma.

‘’We are pleased to move forward with our second drug candidate and extend the Hamlet Pharma portfolio’’, says Mats Persson, CEO, Hamlet Pharma.

This disclosure contains information that Hamlet is obliged to make public pursuant to the EU Market Abuse Regulation (EU nr 596/2014). The information was submitted for publication, through the agency of the contact person, on 30-11-2021 08:50 CET.

On November 30, 2021 AstraZeneca reported its supplemental New Drug Application (sNDA) for Lynparza (olaparib) has been accepted and granted Priority Review in the US for the adjuvant treatment of patients with BRCA-mutated (BRCAm) HER2-negative high-risk early breast cancer who have already been treated with chemotherapy either before or after surgery (Press release, AstraZeneca, NOV 30, 2021, View Source [SID1234596240]).

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Lynparza is being jointly developed and commercialised by AstraZeneca and MSD.

The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that offer significant advantages over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance.1 The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is during the first quarter of 2022.

Breast cancer is now the most diagnosed cancer worldwide with an estimated 2.3 million patients diagnosed in 2020.2 Nearly 91% of all breast cancer patients are diagnosed at an early stage of disease and BRCA mutations are found in approximately 5% of patients.3,4,5

The sNDA was based on results from the OlympiA Phase III trial presented during the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and simultaneously published in The New England Journal of Medicine.

These results showed Lynparza demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival (iDFS), reducing the risk of invasive breast cancer recurrence, second cancers or death by 42% versus placebo (based on a hazard ratio of 0.58; 99.5% confidence interval 0.41-0.82; p<0.0001). The safety and tolerability profile of Lynparza in this trial was in line with that observed in prior clinical trials.

Lynparza is approved in the US, EU, Japan and several other countries for the treatment of patients with germline BRCAm, HER2-negative, metastatic breast cancer previously treated with chemotherapy based on results from the OlympiAD Phase III trial. In the EU, this indication also includes patients with locally advanced breast cancer.

Notes

Early breast cancer
Early breast cancer is defined as disease confined to the breast with or without regional lymph node involvement, and the absence of distant metastatic disease.6 The 5-year survival rate is 99% for localised breast cancer (only found in the breast area) and 86% for regional breast cancer (cancer that has spread outside the breast to nearby structures or lymph nodes).3 Despite advancements in the treatment of early breast cancer, up to 30% of patients with high-risk clinical and/or pathologic features, such as BRCA mutations, recur within the first few years.7,8

Breast cancer is one of the most biologically diverse tumour types with various factors fuelling its development and progression.9 The discovery of biomarkers in the development of breast cancer has greatly impacted scientific understanding of the disease.10

OlympiA
OlympiA is a Phase III, double-blind, parallel group, placebo-controlled, multicentre trial testing the efficacy and safety of Lynparza tablets versus placebo as adjuvant treatment in patients with germline BRCAm high-risk HER2-negative early breast cancer, who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy.11

The primary endpoint of the trial is iDFS defined as time from randomisation to date of first loco-regional or distant recurrence or new cancer or death from any cause.11

The OlympiA Phase III trial is led by the Breast International Group (BIG) in partnership with the Frontier Science & Technology Research Foundation (FSTRF), NRG Oncology, AstraZeneca and MSD.11

BRCA
BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role maintaining the genetic stability of cells.11

When either of these genes is mutated or altered such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer and confer sensitivity to PARP inhibitors including Lynparza.12-15

Lynparza
Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), such as those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as new hormonal agents).

Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza is being tested in a range of PARP-dependent tumour types with defects and dependencies in the DDR pathway.

Lynparza is currently approved in a number of countries, including those in the EU, for the maintenance treatment of platinum-sensitive relapsed ovarian cancer. It is approved in the US, the EU, Japan, China, and several other countries as 1st-line maintenance treatment of BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy.

It is also approved in the US, EU and Japan as a 1st-line maintenance treatment with bevacizumab for patients with HRD-positive advanced ovarian cancer (BRCAm and/or genomic instability).

Lynparza is approved in the US, Japan, and a number of other countries for germline BRCA-mutated, HER2-negative, metastatic breast cancer, previously treated with chemotherapy; in the EU, this includes locally advanced breast cancer.

It is also approved in the US, the EU, Japan and several other countries for the treatment of germline BRCAm metastatic pancreatic cancer.

Lynparza is approved in the US for HRR gene-mutated metastatic castration-resistant prostate cancer (BRCAm and other HRR gene mutations) and in the EU and Japan for BRCAm metastatic castration-resistant prostate cancer.

Regulatory reviews are underway in several countries for ovarian, breast, pancreatic and prostate cancers. Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, has been used to treat over 40,000 patients worldwide.

Lynparza has the broadest and most advanced clinical trial development programme of any PARP inhibitor, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types.

Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

The AstraZeneca and MSD strategic oncology collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US (known as MSD outside the US and Canada) announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the world’s first PARP inhibitor, and Koselugo (selumetinib), a mitogen-activated protein kinase (MEK) inhibitor, for multiple cancer types.

Working together, the companies will develop Lynparza and Koselugo in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and Koselugo in combination with their respective PD-L1 and PD-1 medicines.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.

AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and the next-generation selective estrogen receptor degraders (SERD) and potential new medicine camizestrant (formerly known as AZD9833).

Lynparza is a targeted treatment option for metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD continue to research Lynparza in early and metastatic breast cancer patients with a BRCA mutation.

Building on the first approval of Enhertu (trastuzumab deruxtecan), a HER2-directed antibody-drug conjugate (ADC), in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential in earlier lines of treatment and in new breast cancer settings. Results from the DESTINY-Breast03 Phase III trial showed that Enhertu significantly improved progression-free survival in patients with HER2-positive metastatic breast cancer.

To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy Imfinzi (durvalumab) in combination with other oncology medicines, including Lynparza and Enhertu, assessing the potential of AKT kinase inhibitor, capivasertib, in combination with chemotherapy, and collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On November 30, 2021 THERADIAG (Paris:ALTER) (ISIN: FR0004197747, Ticker: ALTER), a company specializing in in vitro diagnostics and Theranostics, reported that it has received yesterday a letter from BIOSYNEX informing it of its acquisition of a stake in its capital and the crossing of statutory thresholds, in accordance with article 12.3 of THERADIAG’s articles of association (Press release, Theradiag, NOV 30, 2021, View Source [SID1234596230]).

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Following acquisitions on the market and its participation in the Rights Issue, BIOSYNEX held 2,468,932 shares, i.e. 18.82% of THERADIAG’s share capital and 18.89% of its voting rights, as at 29 November 2021 at 8:00 a.m.