On July 18, 2022 Byondis B.V., an independent, Dutch clinical stage biopharmaceutical company creating precision medicines, reported that the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for the company’s investigational next generation anti-HER2 antibody-drug conjugate (ADC) trastuzumab duocarmazine (SYD985) in patients with HER2-positive unresectable locally advanced or metastatic breast cancer (MBC) (Press release, Byondis, JUL 18, 2022, View Source [SID1234616743]).

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If granted, the marketing authorization applies to all EU member states, as well the European Economic Area (EEA) countries Iceland, Liechtenstein and Norway. SYD985 will be marketed by Byondis’ commercialization partner and marketing authorization applicant medac GmbH, a privately owned pharmaceutical company based in Germany. medac has an exclusive license to market SYD985 in all approved indications in the EU, UK and other European countries, including Iceland, Liechtenstein, Norway and Switzerland.

"The MAA validation is an important step forward in our mission to make hope real for patients," said Byondis CEO Marco Timmers, Ph.D. "About one in five breast cancers are HER2-positive, often resulting in a more aggressive disease. There is a dire need to provide an alternative treatment option to these patients."

"medac shares Byondis’ passion for delivering tolerable, more effective cancer treatment options," said medac Managing Director, CEO Jörg Hans. "This important milestone brings us closer to realizing this goal."

The MAA is supported by data from Byondis’ pivotal Phase III TULIP multi-center, open-label, randomized clinical trial comparing SYD985 to physician’s choice (PC) treatment in patients with pre-treated HER2-positive unresectable locally advanced or metastatic breast cancer (SYD985.002/NCT03262935). The study, of which the preliminary results were presented at the 2021 ESMO (Free ESMO Whitepaper) Congress, met its primary endpoint of progression-free survival (PFS), demonstrating a statistically significant improvement of 2.1 months over PC. TULIP also demonstrated supportive overall survival (OS) results.

This is the second regulatory submission for Byondis’ lead program SYD985. The therapy is currently under review by the U.S. Food & Drug Administration (FDA). The FDA granted the therapy fast track designation in January 2018 based on promising Phase I data involving heavily pre-treated last-line HER2-positive MBC patients (SYD985.001/NCT02277717). Byondis is also preparing the medac SYD985 dossier submission for the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Trastuzumab Duocarmazine (SYD985), a Next Generation Antibody-Drug Conjugate

Trastuzumab duocarmazine (SYD985) incorporates Byondis’ distinctive, proprietary duocarmazine linker-drug (LD) technology ByonZine. The ADC is comprised of the anti-HER2 monoclonal antibody trastuzumab and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA).

The antibody part of trastuzumab duocarmazine binds to HER2 on the surface of the cancer cell and the ADC is internalized by the cell. After proteolytic cleavage of the linker, the inactive cytotoxin is activated and DNA damage is induced, resulting in tumor cell death. SYD985 is considered a form of targeted therapy.

ByonZine, Byondis’ Distinctive, Proprietary Linker-Drug Technology

While earlier generation ADCs improved targeting and cell killing, they were unstable in the bloodstream, leading to premature release of the cytotoxic payload, impacting healthy tissue and narrowing the therapeutic window. Byondis’ next generation ADCs are highly stable in circulation and carry an intricate, inactivated and potent cytotoxic drug that rapidly self-destructs if it is prematurely released, limiting damage to healthy tissue and improving the therapeutic window.

Byondis’ differentiated linker-drug, vc-seco-DUBA, owes its potent antitumor activity to a synthetic duocarmycin-based cytotoxin. Duocarmycins, first isolated from Streptomyces bacteria in the 1970s, bind to the minor groove of DNA and disrupt the nucleic acid architecture, which eventually leads to tumor cell death.

The distinctive design of the selectively cleavable linker connecting the antibody to the duocarmycin drug leads to high stability in circulation and induces efficient release of the cytotoxin in the tumor. Uptake of the activated payload by neighboring tumor cells with lower HER2 expression may improve the efficacy potential, the so-called bystander effect.

On July 18, 2022 I-Mab (the "Company") (Nasdaq: IMAB), a clinical-stage biopharmaceutical company committed to the discovery, development, and commercialization of novel biologics, reported that an abstract reporting the latest clinical data from a Phase 2 study of lemzoparlimab (also known as TJC4) in combination with azacitidine (AZA) in patients with higher risk myelodysplastic syndrome (HR-MDS) will be presented in an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022, taking place September 9 – 13, 2022 (Press release, I-Mab Biopharma, JUL 18, 2022, View Source [SID1234616742]).

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Presentation details:

Abstract Title:

Lemzoparlimab, a Differentiated Anti-CD47 Monoclonal Antibody, in Combination with Azacitidine (AZA) in Patients with Newly Diagnosed Higher Risk Myelodysplastic Syndrome (HR-MDS): Initial Clinical Results

About CD47 and Lemzoparlimab

CD47 is a cell surface protein over-expressed in a wide variety of cancers and can act to protect tumors by delivering a "don’t eat me" signal to otherwise tumor-engulfing macrophages. CD47 antibody blocks this signal and enables macrophages to attack tumor cells. However, development of CD47 antibody as a cancer therapy has been hampered by its hematologic side effects, such as severe anemia, caused by natural binding of CD47 antibody to red blood cells. Scientists at I-Mab discovered a novel CD47 antibody, lemzoparlimab, that is designed to target tumor cells while exerting a minimal untoward effect on red blood cells.

Multiple clinical studies are ongoing in the Americas, Europe, Australia, and Asia to explore indications in treating both hematologic malignancies and solid tumors. Lemzoparlimab is being studied in patients with myelodysplastic syndrome (MDS), acute myelocytic leukemia (AML), and advanced solid tumors in combination with chemotherapy and immune checkpoint inhibitors.

In September 2020, I-Mab and AbbVie entered into a global strategic collaboration to develop and commercialize lemzoparlimab. This includes the design and conduct of further clinical trials to evaluate lemzoparlimab in multiple cancers in China and globally.

On July 18, 2022 Sumitomo Pharma Oncology, Inc., a clinical-stage company focused on novel cancer therapeutics, reported the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for DSP-0390, an investigational emopamil-binding protein (EBP) inhibitor for the treatment of brain cancer (Press release, Sumitomo Pharmaceuticals, JUL 18, 2022, View Source [SID1234616741]).

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"This designation for DSP-0390 underscores the profound need for novel brain cancer treatment options," said Patricia S. Andrews, CEO and Global Head of Oncology, Sumitomo Pharma Oncology, Inc. "We are excited to contribute to advancing critical research in brain cancer."

The FDA’s Orphan Drug Designation is granted to investigational therapies addressing rare medical diseases or conditions that affect fewer than 200,000 people in the United States. Brain cancer refers to brain tumors, made up of abnormal growth of cells in the brain, that are malignant. The exact cause of most brain cancer is unknown.1

"DSP-0390 is an emopamil-binding protein (EBP) inhibitor that mediates de novo cholesterol synthesis for cell membrane structure and signaling, enabling aberrant growth of tumors,"2-5 detailed Jatin J. Shah, M.D., Chief Medical Officer of Sumitomo Pharma Oncology, Inc. "Notably, in patients with glioblastoma multiforme (GBM), a form of high-grade glioma, increased de novo cholesterol synthesis is correlated with poor survival and preclinical evidence has shown that DSP-0390 has cytotoxic activity against GBM cell lines."6

DSP-0390 is currently being evaluated in a Phase 1 clinical trial to evaluate the safety and efficacy of DSP-0390 in patients with recurrent, high-grade glioma, which is being conducted in the United States and Japan. To learn more about the study and eligibility for enrollment, visit clinicaltrials.gov (NCT05023551).

This is the second recently announced Orphan Drug Designations from SMP Oncology. TP-3654, the company’s proprietary investigational oral inhibitor of PIM kinases, was also granted Orphan Drug Designation for the treatment of myelofibrosis (NCT04176198).

About DSP-0390

DSP-0390 is an investigational emopamil-binding protein (EBP) inhibitor. EBP is an endoplasmic reticulum membrane protein involved in cholesterol biosynthesis.2 DSP-0390 has shown cytotoxic activity against GBM, colorectal cancer, and triple-negative breast cancer in vitro. DSP-0390 is currently being evaluated in a Phase 1, interventional clinical trial to evaluate the safety and efficacy of DSP-0390 in patients with recurrent high-grade glioma (NCT05023551).

On July 18, 2022 Delfi Diagnostics, Inc., a pioneering developer of a new class of high-performance, accessible liquid biopsy tests for early cancer detection and monitoring, reported a Series B funding of $225 million (Press release, Delfi Diagnostics, JUL 18, 2022, View Source [SID1234616740]).

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This round of financing was led by DFJ Growth with participation from Eli Lilly and Company, Point72, Brown Advisory, Point Field Partners, Initiate Ventures, Open Field Capital, PTX Capital, and all existing investors including Cowen Healthcare Investments, Foresite Capital, Menlo Ventures, OrbiMed, funds and accounts advised by T. Rowe Price Associates, Inc., Northpond Ventures, Samsara BioCapital, Rock Springs Capital, AV8 Ventures, Illumina Ventures, Osage University Partners, and Windham Venture Partners.

"Cancer is a global public health problem and addressing it requires a solution that is accessible around the world," said Victor Velculescu, MD, PhD, Delfi’s CEO and Founder. "We believe our approach is uniquely capable of delivering high performing, cost effective, and clinically relevant tests for multiple applications to meet the needs of patients and providers everywhere."

This funding will support the continued development and commercialization of high-quality and accessible blood tests for single cancer early detection, multi-cancer early detection, and treatment monitoring.

"With this financing, Delfi is even better positioned to make high-quality liquid biopsy applications broadly available regardless of geographic and socioeconomic constraints," said Doug Schenkel, Delfi’s CFO. "We recognize that a fundraising of this magnitude is a notable achievement and with that comes great responsibility. Our focus on the Delfi mission to save lives through early cancer detection has never been higher."

Delfi’s platform is designed to efficiently develop high-quality liquid biopsy applications via a proprietary and uniquely scalable whole genome fragmentation approach. Rather than looking for relatively scarce signs of cancer found in DNA mutations or methylation changes within narrow regions of the genome, Delfi analyzes cell-free DNA fragments across the entire genome. This allows for a single, low-cost, and straightforward lab process for any test developed on the platform. When combined with breakthroughs in machine learning, the Delfi platform can deliver high-performing results for multiple applications.

Delfi is currently validating the technology for early detection of lung and other cancers in a 15,000-person prospective trial called CASCADE-LUNG, and is working with multiple research institutions to develop additional applications including screening for other cancer types, multi-cancer early detection, and treatment monitoring.

"Delfi has made incredible progress in a short amount of time," said DFJ Growth Partner Justin Kao, who joins Delfi’s board of directors. "We believe that Delfi’s low cost approach is critical to bringing early cancer detection to millions of patients globally. But the most exciting thing about Delfi is its potential to create a next-generation diagnostics company that innovates on data and analytics rather than focusing on ever-more complicated wet lab techniques. Delfi’s cutting-edge machine learning enables new products to be built on the same flexible assay, which has the potential to revolutionize the way we detect and manage cancer. I am thrilled to be joining this board to help Delfi fulfill this potential."

On July 18, 2022 GRAIL, LLC, a healthcare company whose mission is to detect cancer early when it can be cured, reported that the NHS-Galleri trial successfully completed enrollment in just over 10 months (Press release, Grail, JUL 18, 2022, View Source [SID1234616739]). The trial, which is the largest-ever study of a multi-cancer early detection (MCED) test, has enrolled 140,000 healthy volunteers aged 50-77 from select regions throughout England who have not had a cancer diagnosis or undergone treatment for cancer in the last three years.

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The NHS-Galleri trial is a randomized, controlled clinical trial being conducted in England alongside standard cancer screening with diagnostic follow-up in the NHS’ clinical practice setting. Regions were selected to include areas of high cancer mortality, socioeconomic disparities, and ethnic diversity, using innovative methods to enroll a study population with participants traditionally less likely to take part in medical research. Participants visited one of 150 mobile clinics operating at locations around England and were recruited through activities including community group briefings, leaflet distribution in community settings, engagement through community champions, and targeted social media campaigns.

"Meeting the goal of enrolling 140,000 people is a significant achievement, allowing us to evaluate an unprecedented number of volunteers without symptoms of cancer and representing diverse socio-economic and ethnic populations," said Charles Swanton, MD, PhD, a cancer researcher and oncologist at University College London and the Francis Crick Institute, chief clinician at Cancer Research UK, and co-chief investigator of the study. "Whilst the first year of the trial may pick up cancers that have existed for some time, the second and third years provide the best opportunity to explore the expected benefits of picking up new cancers at an early stage when treatment is generally more successful. By screening participants annually over three years, we will be able to explore how MCED tests can be used alongside existing NHS screening programs."

The study’s aim is to determine if the Galleri test, alongside standard cancer screening, can find asymptomatic cancers at earlier stages than they are found in clinical care today. The study will assess absolute numbers of stage 3 and 4 cancers diagnosed following three annual Galleri tests. The first screen will aim to identify the prevalent cancers in the population, while the second and third screens will aim to identify cancers that have newly emerged.

"NHS-Galleri has set a new standard in the speed of set-up and recruitment to clinical trials," said Professor Peter Sasieni, Director of The Cancer Research UK & King’s College London Cancer Prevention Trials Unit and one of the trial’s lead investigators. "Previous trials of this magnitude would typically have taken five times as long. Accelerating research means that we will find out sooner whether new technology has a role in the control of cancer and, if it does, introducing it within the NHS quickly so that more people can benefit."

This trial supports the NHS Long Term Plan ambition to catch three quarters of cancers at an early stage, when they are less advanced, and treatment has a higher chance of being successful and potentially curative. Based on initial results, the NHS may roll out the test to an additional 1 million people.

"Today marks an important milestone in our long-term efforts to catch and treat cancer earlier," said Amanda Pritchard, chief executive at NHS. "We know that certain cancers are harder to detect and a late diagnosis can be devastating for patients and their families, and this trial means thousands could benefit from a diagnosis even before symptoms appear."

In a previous clinical study, the Galleri test demonstrated the ability to detect a shared signal from more than 50 types of cancer, many of which lack recommended screening tests today in the UK. Early clinical trials report that GRAIL’s Galleri test has a false positive rate under 1% and can predict where a cancer signal originated with 89% accuracy.

"We are so grateful for the public’s enthusiasm for this trial and to all those who have volunteered," said Sir Harpal Kumar, president at GRAIL Europe. "We are hopeful Galleri will work well alongside existing cancer screening in the UK, can provide clinicians with an accurate prediction of where the cancer is located in the body, and help the NHS reduce the number of cancers detected at a late stage."

The study is sponsored by GRAIL and is being run by The Cancer Research UK and King’s College London Cancer Prevention Trials Unit (UK), in collaboration with eight cancer alliances in England. The study design of the trial was presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract #TPS6606) in June 2022.

About NHS-Galleri Trial

For the prospective, blinded, randomized controlled trial, study participants will provide a blood sample during three annual visits to a mobile health clinic—at baseline, year 1 and year 2. After the first visit, participants are randomized 1:1 into either the intervention or control arm. Participants in the intervention arm will have their blood tested by the Galleri test. Blood samples from subjects in the control arm will not be tested immediately, but will be stored for potential future testing. If a cancer signal is detected for those in the intervention arm, research staff will explain the result and schedule an appointment for follow-up tests at an NHS hospital local to the participant. All participants in the study will be followed for cancer and other related outcomes via NHS databases and will be reminded to continue to have guideline-recommended cancer screenings.