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.

On November 30, 2021 Intensity Therapeutics, Inc. ("Intensity"), a clinical-stage biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumoral cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported that new breast cancer data from its phase 1/2 study IT-01 using novel lead asset, INT230-6, will be presented at the San Antonio Breast Cancer Symposium (SABCS) being held virtually and in-person at the Henry B. Gonzales Convention Center in San Antonio, Texas from December 7-10, 2021 (Press release, Intensity Therapeutics, NOV 30, 2021, View Source [SID1234596297]).

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Presentation Title: Safety and efficacy of INT230-6, a potential first-in-class intratumoral therapy, in monotherapy and in combination with pembrolizumab: Results from the IT-01 study [KEYNOTE-A10] in subjects with locally advanced, unresectable and metastatic breast cancer
Abstract: 541
Poster Number: P-5-16-13
First Author: Philippe Bedard, MD, FRCPC, Princess Margaret Cancer Centre, Toronto, ON, Canada.
Full Authors Block: Philippe Bedard1, Lillian L Siu1, Jacob Thomas2, Diana Hanna3, Anthony J Olszanski4, Nilofer Azad5, Giles Whalen6, Matthew Ingham7, Syed Mahmood8, Lewis H Bender8, Ian B Walters8 and Anthony El-Khoueiry2. 1Princess Margaret Cancer Centre, Toronto, ON, Canada2USC Norris Comprehensive Cancer Center, Los Angeles, CA;3USC Hoag Memorial Hospital Presbyterian, Newport Beach, CA;4Fox Chase Cancer Center, Philadelphia, PA;5Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD;6UMass Memorial Medical Center – University Campus, Worcester, MA;7New York Presbyterian Hospital/Columbia University Medical Center, New York, NY;8Intensity Therapeutics, Inc., Westport, CT,
Session: Treatment: Therapeutic Strategies – New Drugs and Treatment Strategies
Date: Friday, December 10, 2021
Time: 7:00AM – 8:30AM Central Standard Time

The presentation shall be accessible on the "Publications, Papers and Posters" section of Intensity’s website at: View Source on December 10, 2021.

About INT230-6

INT230-6, Intensity’s lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRx℠ technology platform. The drug is composed of two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule that helps disperse the drugs throughout tumors for diffusion into cancer cells. In addition to local disease control, direct killing of the tumor by INT230-6 releases a bolus of neoantigens specific to the patient’s malignancy, leading to engagement of the immune system and systemic anti-tumor effects. Importantly, these effects are mediated without the immunosuppression of concomitant systemic chemotherapy.

INT230-6 is currently being evaluated in several phase 2 cohorts (NCT03058289) in patients with various advanced solid tumors as part of Study IT-01. In 2019, the Company signed a clinical collaboration agreement with Merck Sharpe & Dohme (Merck) to evaluate the combination of INT230-6 and KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 (programmed death receptor-1) therapy, in patients with advanced pancreatic, colon, squamous cell and bile duct malignancies. In 2020, the Company executed a clinical collaboration agreement with Bristol-Myers Squibb Company to evaluate the combination of INT230-6 with Bristol-Myers Squibb’s anti-CTLA-4 antibody, Yervoy (ipilimumab), in patients with advanced liver, breast and sarcoma cancers. In 2021, the Company executed agreements with the Ottawa Hospital Research Institute and the Ontario Institute of Cancer Research to study INT230-6 in a randomized controlled neoadjuvant phase 2 study in women with early stage breast cancer (the INVINCIBLE study) (NCT04781725).