On November 30, 2021 Chimeric Therapeutics (ASX:CHM, "Chimeric" or the "Company"), a clinical-stage cell therapy company and the ASX leader in cell therapy, reported that it has entered into an exclusive option to license agreement with Case Western Reserve University (CWRU) for a Clinically validated, Off the shelf, Robust, Enhanced Natural Killer (CORE-NK) cell platform – a platform technology that provides the optimal foundation for the development of multiple next generation NK and CAR-NK products (Press release, Chimeric Therapeutics, NOV 30, 2021, View Source [SID1234596312]).

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Natural killer (NK) cells have innate safety features and the natural ability to target and destroy cancer cells through both indirect and direct mechanisms. The challenge with natural killer (NK) cells is that they are not naturally abundant or active enough to overcome cancer.

Dr. David Wald, a leading expert in immuno-oncology at Case Western Reserve University in Ohio, USA designed and developed the CORE-NK platform, enhancing the natural anti-cancer properties of NK cells to be robust and active enough to overcome cancer.

The CORE-NK platform utilizes a foundation of healthy donor NK cells, activating and expanding them to establish an enhanced, off the shelf NK cell platform that can provide an abundant supply of highly active NK cells. Preclinical data on the CORE-NK platform was published in the prestigious family of Nature publications in 2019.

In May 2018 a phase 1 clinical trial was initiated at the Case Comprehensive Cancer Center to study the CORE-NK platform in patients with both solid tumours and blood cancers. The phase 1 clinical trial of the CORE-NK platform was completed in June 2021 with clinical data expected in 2022. The trial examined the safety, bioactivity and efficacy of the CORE-NK platform cells at 3 dose levels in patients with both blood cancers and solid tumours.

With the clinical validation from the phase 1 trial complete, the CORE-NK platform provides the ideal off the shelf platform for the development of next generation NK and CAR-NK products.

Chimeric intends to begin a research collaboration with CWRU to further enhance and engineer the CORE-NK platform cells to develop a next generation CORE-NK platform and three initial CAR-NK products.

"The clinical experience we’ve had with the CORE-NK platform gives us tremendous confidence in the development path for optimized NK and CAR NK products. We look forward to working in close collaboration with Chimeric to bring forward the next generation of NK and CAR NK products to the clinic," said Dr. Wald, MD, PhD, Associate Professor of Pathology Case Western Reserve University School of Medicine and Member, Immune Oncology Program, Case Comprehensive Cancer Center, Associate Director for Basic Research, University Hospitals, Wesley Center for Immunotherapy.

The next generation CORE-NK platform will be developed with enhanced activation and expansion features with plans to study it as a combination therapy in blood cancers.

Three initial CAR-NK products will be developed using the next generation CORE-NK platform as a backbone leveraging Chimeric’s existing pipeline of chimeric antigen receptors (CARs); a CLTX CAR-NK (CHM 1301), a CDH17 CAR-NK (CHM 2301) and a currently undisclosed target CAR-NK (CHM 3301).

Chimeric will also explore additional opportunities to further leverage the CORE-NK platform to develop additional NK and CAR NK products through internal development and/or partnerships with other biotech and pharmaceutical companies.

This strategic agreement is transformative for Chimeric propelling the company forward as the Australian leader in cell therapy and as an emerging global cell therapy company with a robust and advanced portfolio of innovative autologous (personalized) and allogeneic (off the shelf) NK and T cell assets.

"The CORE-NK platform is truly transformative for Chimeric. It provides us with a platform technology that triples our current portfolio by enabling us to accelerate the development of multiple new, off the shelf, NK cell assets that work in perfect synergy with our existing pipeline. We could not be more excited to be bringing the CORE-NK platform into our portfolio and to be working in collaboration with Dr. Wald and the expert team at CWRU. Their clinical trial experience with the CORE-NK platform and their expertise in the development of NK cells will catapult our development forward," said Jennifer Chow, CEO Chimeric Therapeutics.

Under the terms of the option agreement, Chimeric has the exclusive right to license the CORE-NK platform for development and commercialization in cancer. Chimeric intends to rapidly move to complete full licensing of the platform and expects to pay CWRU development milestones and industry standard royalty payments based on commercial net sales. Upfront fees associated with the option agreement will be funded entirely from existing cash reserves.

The area of natural killer cells has seen widespread investment and partnership interest with numerous large transactions involving companies such as Merck, Takeda, Janssen and Kite.

Investor webinar

Chimeric Therapeutics CEO and Managing Director Jennifer Chow will hold an investor webinar today, Wednesday 1 December 2021, at 11am AEDT to elaborate on this announcement and take questions.

Click the link below to register:
View Source

After registering, you will receive a confirmation email about how to join the webinar. A recording of the webinar will be available at the same link shortly after the conclusion of the session.

On November 30, 2021 Mereo BioPharma Group plc (NASDAQ: MREO) ("Mereo" or the "Company"), a clinical stage biopharmaceutical company focused on oncology and rare diseases, reported promising interim efficacy, safety, and biomarker data on patients from ACTIVATE, a Phase 1b/2 study of its anti-TIGIT antibody, etigilimab, in combination with nivolumab in select recurrent advanced / metastatic solid tumors (Press release, Mereo BioPharma, NOV 30, 2021, View Source [SID1234596277]).

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"These early results from the ACTIVATE study are highly encouraging and support the further study of etigilimab in combination with an anti-PD-1 antibody in solid tumor types, especially in gynecologic malignancies," said Dr. Denise Scots-Knight, Chief Executive Officer of Mereo. "We are particularly excited by the complete response in the cervical cancer cohort and the partial response in one of the ovarian cancer patients treated to-date. In the efficacy analysis set, biomarker analysis showed a positive trend between baseline PVR expression and clinical benefit including in the absence of PD-L1 expression in the efficacy analysis population. Clinical benefit also occurred in tumor types with historically low response rates to anti-PD-1/PDL-1 antibodies. We look forward to providing additional updates on the study in 2022."

The ACTIVATE study aims to enroll approximately 125 patients across seven parallel cohorts. At the time of the data cut-off, 22 patients were included in the safety analysis set, 20 patients were evaluable with a minimum of at least one scan (as of November 8, 2021) and 15 patients were included in the efficacy analysis population.

As of the cut-off date, there are one complete response in cervical cancer, one partial response in ovarian cancer and four instances of stable disease in ovarian cancer, cervical cancer, and uveal melanoma. The ovarian cohort in ACTIVATE has now crossed futility for expansion into the second stage of the study (IDMC review pending). These results add to the earlier Phase 1b data of etigilimab in combination with nivolumab, with a partial response in the single ovarian cancer patient of the 8 patients evaluable and support the continued development of this dual checkpoint combination regimen.

The combination of etigilimab and nivolumab has been safe and well tolerated, with no new safety signals. The most common treatment-related adverse events were skin reactions, observed in seven patients. None of these reactions required treatment with systemic steroids. There was one case of immune diabetes mellitus.

Conference Call and Webcast

Mereo BioPharma will hold a conference call today, November 30, 2021, at 8:30am ET. To participate by telephone, please dial (866) 688-2942 (Domestic) or (561) 569-9224 (International). The conference ID number is 6585106. To view the slideshow please use the live webcast which can be accessed through the Investors section of the Company’s website at www.Mereobiopharma.com/investors. An archived replay of the webcast will be available on the Company’s website for two weeks following the live presentation.

On November 30, 2021 Navrogen, Inc., a biopharmaceutical company specialized in developing therapies for cancer and immune-related disorders, reported the publication of preclinical data regarding application of its proprietary Block–Removed Immunoglobulin Technology (BRITE) to enhance the efficacy of the CD20-targeting rituximab antibody in the presence of the immunosuppressive CA125 protein (Press release, Navrogen, NOV 30, 2021, View Source [SID1234596296]). The peer-reviewed study was published in Oncology Letters (www.spandidos-publications.com/10.3892/ol.2021.13120).

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The study results showed that CA125 can directly bind rituximab and suppress its immune-effector complement–dependent cytotoxicity (CDC) and antibody–dependent cellular cytotoxicity (ADCC) mechanisms of action. Recent clinical evidence suggests that high serum levels of CA125 reduce the effectiveness of rituximab’s clinical activity in patients with follicular lymphoma. In an attempt to overcome CA125-mediated suppression, BRITE was applied to generate antibody variants that were refractory to CA125 binding and retained efficient CDC and ADCC activity in the presence of CA125. BRITE is an engineering platform that generates and selects for proteins that are refractory to immunosuppressive factors. The application of BRITE resulted in the discovery of an antibody (NAV-006) with a single amino acid change that was refractory to CA125 immunosuppression while retaining similar antigen binding and immune-effector activities as the parental rituximab.

Dr. Luigi Grasso, Chief Scientific Officer of Navrogen said, "the findings here are another demonstration of the humoral immunosuppressive effects that proteins such as CA125 can have on antibody-mediated therapies and the opportunities that BRITE technology can bring to overcome their impact. Our BRITE-optimized rituximab NAV-006 will offer a new opportunity to treat CA125-positive follicular lymphoma patients in our efforts to combat this disease."

Navrogen is actively applying BRITE to improve other therapeutic antibodies affected by immunosuppressive factors for internal pipeline candidates and 3rd party collaborators.

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 Dr. Michael Shepard, President and Chief Scientific Officer of Enosi Life Sciences, a drug research and development company focused on providing industry-leading therapeutics for inflammatory autoimmune diseases and cancer, reported that as a guest of the World Laureates Association at its 4th World Laureates Forum in Shanghai, China earlier this month (Press release, Enosi Life Sciences, NOV 30, 2021, View Source [SID1234596259]).

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Dr. Shepard, an innovator in the field of biotechnology and pioneer in cancer research, won the 2019 Lasker-DeBakey Clinical Medical Research Award with colleagues Dr. Dennis J. Slamon and Axel Ullrich due to their work inventing Herceptin—a targeted antibody therapy for breast cancer. The treatment has saved over 500,000 women from aggressive breast cancer as a result of Dr. Shepard’s discovery and his collaborative approach to research.

"There’s no shortage of breakthroughs we can accomplish with open science," said Dr. Shepard. "We must take a look at what prevents this type of collaboration and address these causes so that we can realize our full potential."

The World Laureates Association, a non-political, non-religious, non-governmental organization is one of the world’s highest-profile organizations for laureates, having achieved the Nobel Prize, Wolf Prize, Lasker Award, Turing Award, MacArthur Fellowship, and Fields Medal. Both Dr. Shepard and the WLA are staunch advocates for international cooperation and the sharing of knowledge across borders.

Increasing knowledge and growing value thanks to cooperation with peers has been a recurring theme throughout Dr. Shepard’s career, and that philosophy of a united approach has guided him in his latest work with Enosi Life Sciences. His partnership with co-founder, Sir Marc Feldman who discovered anti-tumor necrosis factor (anti-TNF) therapy as an effective treatment for rheumatoid arthritis and other autoimmune diseases, combined with his own research in humanized antibodies has led to Enosi’s development of breakthrough biologics.

Beyond Dr. Shepard’s research, Enosi has embraced his collaborative approach as is reflected by Enosi’s executive team, including recently named CEO Dr. Patrick William Gray. Together, Enosi will continue its work to develop the next-generation of autoimmune, cancer and acute inflammation therapies that induce disease regression and prevent relapse, while dramatically-reducing patient side effects.