On September 5, 2022 Bertis, a proteomics-based precision medicine technology development company (CEOs Dong-young Noh, Seung-man Han), reported on the 5th that the research results of their search for protein biomarkers for early diagnosis of high-grade serous ovarian cancer (HGSOC) were published in the September issue of the international scientific journal, Journal of Proteome Research (Press release, Bertis, SEP 5, 2022, View Source [SID1234619000]).1

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Ovarian cancer is the first leading cause of death among gynecological cancers. Most patients are asymptomatic in early stages, and as effective early diagnosis methods have not yet been secured, 70% of the cases are not detected until the cancer develops into stage 3 or higher.2, 3 After stage 3, the survival rate of the patient is drastically reduced. The 5-year survival rate is more than 76% in stage 1 and approximately 60% to 74% in stage 2, while the 5-year survival rate in early stage 3 is known to be 41%, 23% in late stage 3, and just 11% in stage 4.4 In particular, HGSOC is the most common type of ovarian cancer, accounting for 70% of all ovarian cancers. For decades, the overall survival rate of HGSOC has barely improved, and the need for the introduction of a standard testing method for early diagnosis has been emphasized.5, 6

The research team at Bertis presented a new multi-biomarker panel candidate with 95% accuracy (100% sensitivity, 91% specificity) for the diagnosis of stage 1 to 3 HGSOC. The results of this research were published in the September issue of the Journal of Proteome Research on the 2nd by the American Chemical Society. In particular, the results were included as one of the supplementary cover articles in this issue with 16 papers listed.

In this study, the research team identified 18 candidate proteins after quantifying 1,847 serum proteins, the highest number ever reported as ovarian cancer biomarker research results, through Bertis’ technology platform to discover biomarker candidates. As a result of developing and evaluating a predictive model, the accuracy of the diagnostic value for stages 1 to 37 HGSOC was 95% (sensitivity 100%, specificity 91%) when 18 candidate proteins were combined with multiple biomarkers.

Un-beom Kang, Head of Bertis Biomarker Research Institute, who led this study, explained, "This study is significant in that it secured the results of in-depth blood proteome research based on Bertis’ advanced proteomics analysis technology, as well as presented a new biomarker panel with high accuracy for ovarian cancer," and added that, "We expect that based on data from this study, research and development to provide standardized testing for early diagnosis of ovarian cancer will be expedited and the creation of results will be accelerated."

"Proteomics analysis is an incredibly effective tool for understanding cancer and discovering new biomarkers for diagnosis and prognosis," said, Seung-man Han, Bertis’ CEO. "As a company that has led the discovery of biomarkers based on proteomics technology as well as the development of clinical solutions using it, we will do our best to contribute to the improvement of the diagnosis and treatment of major diseases through continuous research and development."

Bertis is a company that combines proteomics and bioinformatics to develop biomarkers for cancer and other various major diseases, as well as provides diagnosis and analysis solutions. It succeeded in commercializing proteomics technology with Mastocheck, the world’s first proteomics-based blood testing solution for early breast cancer diagnosis, and PASS (Pan-omics Analysis Service & Solution), an integrated analysis solution for Panomics. Currently, Bertis is researching and developing early diagnosis solutions for pancreatic cancer, ovarian cancer, etc.

On September 5, 2022 Avacta Group plc (AIM: AVCT), a clinical stage oncology drug company and developer of powerful diagnostics based on its innovative Affimer and pre|CISION platforms, reported that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to the company’s lead pre|CISION drug candidate, AVA6000, for treatment of soft tissue sarcoma (Press release, Avacta, SEP 5, 2022, View Source [SID1234618997]).

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AVA6000 is a form of the generic chemotherapy doxorubicin that has been modified using the pre|CISION technology so that it is activated predominantly in the tumour with the aim of sparing healthy tissue from exposure and improving the safety, tolerability and efficacy of the drug. Doxorubicin has a market size that is expected to grow to $1.38bn by 2024, and is widely used as part of the standard of care in several cancer types. Avacta has an ongoing Phase 1 clinical trial to assess the safety and pharmacokinetics of AVA6000 which has potential as a treatment for patients with a range of cancer types, including soft tissue sarcoma.

The FDA can grant ODD based on a review of preclinical data from investigational treatments for rare diseases, such as soft tissue sarcoma, which are defined as conditions affecting fewer than 200,000 people in the US. This designation qualifies the developer of the drug for certain incentives, including, seven years of market exclusivity upon drug approval from the FDA.

Soft-tissue sarcoma is a rare mesenchymal malignancy which accounts for less than 1% of all adult tumours. Despite the successful advancement of localised therapies, such as surgery and radiotherapy, these tumours can recur, often with metastatic disease. The American Cancer Society estimates that, in 2022 approximately 13,190 new soft tissue sarcomas will be diagnosed, and about 5,130 people are expected to die of the disease in the US.

Dr Alastair Smith, Chief Executive Officer of Avacta, commented: "We are delighted to receive Orphan Drug Designation from the FDA for AVA6000, which is a reflection of the high quality of the preclinical data and the potential benefit the pre|CISION platform can bring to cancer patients."

"This designation provides tax credits and other incentives for drug developers addressing rare diseases. Most notably the Orphan Drug Designation will give Avacta, if AVA6000 is approved for treatment of soft tissue sarcoma, seven years of market exclusivity in the US, which is a significant commercial advantage."

On September 5, 2022 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported that the following presentations will be presented at the ESMO (Free ESMO Whitepaper) (European Society for Medical Oncology) Annual Meeting 2022 taking place from 9 to 13 September 2022, in Paris, France (Press release, Innate Pharma, SEP 5, 2022, View Source [SID1234618996]).

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A multi-center Phase Ib trial evaluating the safety and efficacy of lacutamab in patients with relapsed/refractory peripheral T-cell lymphoma that express KIR3DL2
– Abstract Number: 647TiP
– Session Type: Trial In Progress Poster
– Session Title: Haematological malignancies
– Session Date: Sunday Sept 11, 2022
– Presenter: Marianna Muller, MD, PharmD, Clinical Development Director at Innate Pharma
Oral presentation: Designing multispecific antibodies: ANKET for antigen-specific activation of NK cells
– Session Type: Special session
– Session Title: Next frontiers in drug discoveries
– Date and Time: Monday Sept 12, 2022 9:05 AM – 9:20 AM CEST
– Location: 7.3.U – Urval Auditorium
– Presenter: Eric Vivier, DVM, PhD, Chief Scientific Officer of Innate Pharma
Oral presentation: Platform study of neoadjuvant durvalumab (D) alone or combined with novel agents in patients (pts) with resectable, early-stage non-small-cell lung cancer (NSCLC): pharmacodynamic correlates and circulating tumor DNA (ctDNA) dynamics in the NeoCOAST study [AstraZeneca-sponsored]
– Presentation #929MO
– Session Type: Mini Oral Session
– Session Title: Non-metastatic NSCLC and other thoracic malignancies
– Date and Time: Monday Sept 12, 2022 3:15 PM CEST
– Location: 7.3.O – Orléans Auditorium
– Presenter: Jonathan Spicer (Montreal, Canada)
The poster and presentations will be available on the Publications section of innate-pharma.com following the presentation.

About Lacutamab:

Lacutamab (IPH4102) is a first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody that is currently in clinical trials for treatment of cutaneous T-cell lymphoma (CTCL), an orphan disease, and peripheral T cell lymphoma (PTCL). Rare cutaneous lymphomas of T lymphocytes has a poor prognosis with few efficacious and safe therapeutic options at advanced stages.

KIR3DL2 is an inhibitory receptor of the KIR family, expressed by approximately 65% of patients across all CTCL subtypes and expressed by up 90% of patients with certain aggressive CTCL subtypes, in particular, Sézary syndrome. It is expressed by up to 50% of patients with mycosis fungoides and peripheral T-cell lymphoma (PTCL). It has a restricted expression on normal tissues.

About ANKET:

ANKET (Antibody-based NK cell Engager Therapeutics) is Innate’s proprietary platform for developing next-generation, multi-specific natural killer (NK) cell engagers to treat certain types of cancer.

This versatile, fit-for-purpose technology is creating an entirely new class of molecules to induce synthetic immunity against cancer. It leverages the advantages of harnessing NK cell effector functions against cancer cells and also provides proliferation and activation signals targeted to NK cells.

Our latest innovation, the tetra-specific ANKET molecule, is the first NK cell engager technology to engage activating receptors (NKp46 and CD16), a tumor antigen and an interleukin-2 receptor (via an IL-2 variant, IL-2v) via a single molecule.

About Monalizumab:

Monalizumab is a potentially first-in-class immune checkpoint inhibitor targeting NKG2A receptors expressed on tumor infiltrating cytotoxic CD8+ T cells and NK cells.

NKG2A is an inhibitory checkpoint receptor for HLA-E. By expressing HLA-E, cancer cells can protect themselves from killing by NKG2A+ immune cells. HLA-E is frequently overexpressed in the cancer cells of many solid tumors and hematological malignancies. Monalizumab may reestablish a broad anti-tumor response mediated by NK and T cells, and may enhance the cytotoxic potential of other therapeutic antibodies1.

The ongoing development for monalizumab is focused on investigating monalizumab in various combination strategies in different malignancies, including, in early lung cancer, the Phase 3 PACIFIC-9 study in adults with locally advanced (Stage III), unresectable NSCLC, who have not progressed following platinum-based concurrent chemoradiotherapy, and the Phase 2 NeoCOAST-2 study in the neoadjuvant early-stage setting of NSCLC.

On September 5, 2022 Synthetic Biologics, Inc. (NYSE American: SYN), a diversified clinical-stage company developing therapeutics designed to treat diseases in areas of high unmet need, reported a presentation of initial data from a Phase 1 investigator-sponsored study evaluating VCN-01 in combination with durvalumab for patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) (Press release, Synthetic Biologics, SEP 5, 2022, View Source [SID1234618995]). Data will be featured in a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, being held both virtually and in Paris from September 9-13, 2022.

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"We are encouraged by the acceptable safety profile seen in the sequential arm of this study as well as the biological activity observed in R/M HNSCC patients previously treated with anti-PD(L)-1 agents, which speak to the promise of VCN-01-based combination approaches for devastating cancers with high unmet need," said Manel Cascallό, Ph.D., General Director of Synthetic Biologics’ European Subsidiary. "Further, these results provide valuable dose-finding context and build upon our compelling foundation of data that highlight VCN-01’s differentiated mechanism of action that may transform cancer therapy. We look forward to leveraging our findings as we advance VCN-01 through clinical development and we remain on track to deliver on several value-driving milestones, including the initiation of our Phase 2 study in patients with metastatic pancreatic adenocarcinoma in the fourth quarter of 2022 and our Phase 2/3 study in retinoblastoma in the second half of 2023."

Key data and conclusions featured in the ESMO (Free ESMO Whitepaper) presentation include:

Safety: Treatment with VCN-01 had an acceptable safety profile when administered with durvalumab in the sequential regimen (single dose of VCN-01 administered 14 days prior to the first dose of durvalumab; n=14).
The most common treatment-related adverse events (TRAEs) were pyrexia, flu-like symptoms and increases in liver transaminases.
TRAEs were dose-dependent, reversible and consistent with TRAEs previously described for other adenovirus-based products.
Pharmacokinetics (PK) and pharmacodynamics (PD): Based on toxicology and PK/PD analysis the recommended Phase 2 dose is 1×1013 viral particles (vp)/patient.
Biological activity: Sustained blood levels of VCN-01 viral genomes and increased serum hyaluronidase levels were maintained for over six weeks.
Observed an increase in CD8 T cells, a marker of tumor inflammation and an upregulation of PD-L1 in tumors.
Analysis of serial tumor biopsies revealed differential gene expression profiles and downregulation of matrix-related pathways after VCN-01 administration.
The full abstract (#1231P) is accessible on the ESMO (Free ESMO Whitepaper) Congress portal and the e-Poster will be available on-demand starting Saturday, September 10 at 9:00 a.m. CEST. Additional details of the poster are provided below.

Title: Phase I Study to Evaluate the Safety, Tolerability, and Efficacy of VCN-01 in Combination With Durvalumab (MEDI4736) in Subjects With Recurrent/ Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M HNSCC)
Presenting Author: Dr. Ricard Mesia (Head of the Medical Oncology Department at Institut Català d’Oncologia- Barcelona, Spain)
Poster Session Date and Time: Monday, September 12 at 12:00 p.m. CEST

On September 5, 2022 AstraZeneca reported it’s Imfinzi (durvalumab) has been approved in the US for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC) in combination with chemotherapy (gemcitabine plus cisplatin) (Press release, AstraZeneca, SEP 5, 2022, View Source [SID1234618994]).

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The approval by the Food and Drug Administration (FDA) was based on the results from the TOPAZ-1 Phase III trial. In an interim analysis of TOPAZ-1, Imfinzi plus chemotherapy reduced the risk of death by 20% versus chemotherapy alone (hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.66-0.97; p=0.021). An estimated one in four (25%) patients treated with Imfinzi plus chemotherapy were still alive at two years compared to one in 10 (10%) treated with chemotherapy alone. Results were consistent across all prespecified subgroups, regardless of PD-L1 expression or tumour location.

BTC is a group of rare and aggressive cancers that occur in the bile ducts and gallbladder.1,2 Approximately 23,000 people in the US are diagnosed with BTC each year.1 These patients have a poor prognosis, with approximately 5% to 15% of patients with BTC surviving five years.3

Aiwu Ruth He, MD, PhD, Associate Professor of Medicine, Leader of the GI Cancer Program, Georgetown Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington DC, and a lead investigator in the TOPAZ-1 Phase III trial, said: "This approval represents a major step forward for patients with advanced biliary tract cancer, who urgently need new, well-tolerated and effective treatment options after more than a decade of limited innovation. The combination of durvalumab and chemotherapy should become a new standard of care in this setting, having demonstrated significantly improved survival for these patients who have historically faced a poor prognosis."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "For the first time, patients in the US with advanced biliary tract cancer have an immunotherapy-based treatment option that meaningfully extends survival and is well-tolerated. This approval for Imfinzi and chemotherapy advances our ambition to challenge treatment expectations and transform care for patients with gastrointestinal cancers with high unmet need."

Stacie Lindsey, CEO, Cholangiocarcinoma Foundation, said: "Patients have been waiting a long time for a new, first-line treatment option for biliary tract cancer. The Foundation congratulates AstraZeneca for engaging in rare cancer research, which impacts patients and families nationwide. We are especially grateful to the patients who participated in this trial making it possible for the broader rare disease community to benefit from this treatment."

The TOPAZ-1 Phase III trial results were presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers (ASCO GI) Symposium and published in the New England Journal of Medicine Evidence. Imfinzi plus chemotherapy was generally well tolerated and did not increase the discontinuation rate due to adverse events compared to chemotherapy alone.

In July 2022, Imfinzi plus chemotherapy was added to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) as a Category 1 preferred regimen as 1st-line therapy for locally advanced or metastatic BTC based on the data from TOPAZ-1.4

The US regulatory submission for TOPAZ-1 was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, Imfinzi plus chemotherapy is also under regulatory review for the same indication by the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency (ANVISA), Health Canada, Israel’s Ministry of Health Pharmaceutical Administration, Singapore’s Health Sciences Authority, Switzerland’s Swissmedic and the UK’s Medicines and Healthcare products Regulatory Agency.

The approval was granted after securing Priority Review and Orphan Drug Designation for Imfinzi in the US in this setting. Regulatory applications are also currently under review in Europe, Japan and several other countries based on the TOPAZ-1 results.

Notes

Biliary tract cancer
BTC is a group of rare and aggressive gastrointestinal (GI) cancers that form in the cells of the bile ducts (cholangiocarcinoma), gallbladder or ampulla of Vater (where the bile duct and pancreatic duct connect to the small intestine).1,2

Cholangiocarcinoma is more common in China and South-East Asia and is on the rise in Western countries.1,3 Gallbladder cancer is more common in certain regions of South America, India and Japan.5

Early-stage BTC affecting the bile ducts and gallbladder often presents without clear symptoms and most new cases of BTC are therefore diagnosed at an advanced stage, when treatment options are limited and the prognosis is poor.3,5,6

TOPAZ-1
TOPAZ-1 is a randomised, double-blind, placebo controlled, multicentre, global Phase III trial of Imfinzi in combination with chemotherapy (gemcitabine plus cisplatin) versus placebo in combination with chemotherapy as a 1st-line treatment in 685 patients with unresectable advanced or metastatic BTC including intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer. Patients with ampullary carcinoma were excluded.

The primary endpoint is overall survival and key secondary endpoints included progression-free survival, objective response rate and safety. The trial was conducted in 105 centres across 17 countries including in the US, Europe, South America and several countries in Asia including South Korea, Thailand, Japan and China.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

In addition to the approval in BTC, Imfinzi is the only approved immunotherapy in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy and is the global standard of care in this setting based on the PACIFIC Phase III trial.

Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage small cell lung cancer (ES-SCLC) based on the CASPIAN Phase III trial. In 2021, updated results from the CASPIAN trial showed Imfinzi plus chemotherapy tripled patient survival at three years versus chemotherapy alone.

Imfinzi is also approved for previously treated patients with advanced bladder cancer in several countries.

Since the first approval in May 2017, more than 100,000 patients have been treated with Imfinzi.

As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, several GI cancers, ovarian cancer, endometrial cancer, and other solid tumours.

Imfinzi combinations have demonstrated clinical benefit in multiple additional cancer settings with positive Phase III trials in unresectable advanced liver cancer (HIMALAYA) and metastatic NSCLC (POSEIDON).

AstraZeneca in GI cancers
AstraZeneca has a broad development programme for the treatment of GI cancers across several medicines and a variety of tumour types and stages of disease. In 2020, GI cancers collectively represented approximately 5.1 million new cancer cases leading to approximately 3.6 million deaths.6

Within this programme, the Company is committed to improving outcomes in gastric, liver, BTC, oesophageal, pancreatic, and colorectal cancers.

Imfinzi is being assessed in combinations in liver, BTC, oesophageal and gastric cancers in an extensive development programme spanning early to late-stage disease.

The Company aims to understand the potential of Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate, in the two most common GI cancers, colorectal and gastric cancers. Enhertu is jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Lynparza (olaparib) is a first-in-class PARP inhibitor with a broad and advanced clinical trial programme across multiple GI tumour types including pancreatic and colorectal cancers. Lynparza is developed and commercialised in collaboration with MSD (Merck & Co., Inc. inside the US and Canada).

AstraZeneca in immunotherapy
Immunotherapy is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. The Company’s Immuno-Oncology (IO) portfolio is anchored in immunotherapies that have been designed to overcome evasion of the anti-tumour immune response. AstraZeneca is invested in using IO approaches that deliver long-term survival for new groups of patients across tumour types.

The Company is pursuing a comprehensive clinical-trial programme that includes Imfinzi as a single treatment and in combination with tremelimumab and other novel antibodies in multiple tumour types, stages of disease, and lines of treatment, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient.

In addition, the ability to combine the IO portfolio with radiation, chemotherapy, and targeted small molecules from across AstraZeneca’s oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumours.

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.