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3Brain AG CorePlate™ technology combines microchips and AI in a revolutionary new approach to drug discovery

On June 8, 2021 3Brain AG has reported a new technology based on a unique combination of microchips and AI that promises to change the way drug candidates are selected at the preclinical level to enter into clinical trials – and to maximize their chances of success (Press release, Lifescience Newswire, JUN 8, 2021, View Source [SID1234583739]).

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Using CorePlate technology, preclinical cell assays are performed in multiwell plates that integrate a microchip in each well to collect rich information from cells, pre-process cell data and streamline it to the paired software. As a result, much more and better data can be extracted, which can be referred to as cell big data. This is fed to an AI with the aim of simplifying interpretation and enabling researchers to discover more information about drugs being tested.

Preclinical studies are vital for early identification of any safety and efficacy issues, and for increasing the chance of success of those drugs entering clinical trials. However, common estimates show that there is still a lot to improve in this area as 90% of the drugs that enter into human trials fail and never reach the market. Among the factors responsible for this high failure rate are the limitations of conducting preclinical tests on animal models. The vast majority of drugs that pass tests on animals do not later work on humans because disease mechanisms vary significantly between species.

New biotechnologies like human stem cells offer more successful alternatives to animal models. These may be in the form of cell culture assays or more sophisticated spheroid and organoid assays that can be used as testbeds for drugs. Human cell-based assays hold the promise to revolutionize drug development, improving the success rate and pushing animal tests towards extinction.

Whatever cell-based assay one wants to investigate, traditional approaches extract cell information via optical systems or a few sensors embedded in plastic substrates. Typically, these substrates are multiwell plates with 24, 96 or even more wells, where each well houses the cell samples to be measured. From these wells, the acquired information travels on limited bandwidth across long distances (compared to the cell size) before reaching a CPU where it gets processed. Long distances and bandwidth issues affect the quality and quantity of information and, consequently, prevent an accurate inspection of cell networks. The CorePlate technology devised by 3Brain disrupts this paradigm by bringing the processing unit in contact with the cells.

20210604 CorePlate press release_other imgs_1"We want to radically change the way preclinical drug screening is performed, offering pharmaceutical companies the opportunity to manage their pipelines more efficiently," says Mauro Gandolfo, CEO and co-founder of 3Brain AG. "Basically, we take traditional plastic multiwell plates and we turn them into intelligent devices with multi-core processing power, which can be programmed according to research needs. Integrated intelligence is a remarkable distinction from other instruments in the preclinical space. Importantly, despite the large amounts of data CorePlate devices can process, the user can still easily generate results thanks to the AI-driven interpretation of data. With the CorePlate technology, pharmaceutical companies can save time and money by better filtering and prioritizing drug candidates. Our ultimate goal is to provide our users with tools that help them more readily identify new cures for diseases."

20210604 CorePlate press release_other imgs_23Brain AG has been working on microchip technology applied to life science for more than 15 years. Alessandro Maccione, CSO and co-founder of 3Brain AG, says, "We already have results showing that our technology is superior in identifying the effects of compounds on several disease models. We started focusing on brain diseases, such as Alzheimer’s and epilepsy, given the high burden that they represent for our society. In addition, we are expanding to other sectors such as cardiac safety, which is one of the main reasons drugs fail in clinical trials. At the same time, driven by our appetite for innovation, we are very attentive to the opportunities offered by advanced cell models such as spheroids and organoids. That’s why we plan to have our CorePlate devices shipped in two "flavors", a planar one that can work with more traditional cell assays and a three-dimensional one where the sensing layer of the microchip is on microneedles that can collect cell information from the inside of tissues and organoids."

Kilian Imfeld, CTO and co-founder of 3Brain AG, adds, "The processing power we have integrated into a CorePlate device is really striking. You can think of it as a modern multi-core CPU, but where the microchip is specifically designed for biological signals. Consequently, we call it BioSPU, BioSignal Processing Unit. Such power allows us to simultaneously process real-time information coming from hundreds of thousands of cells. This continuous data streaming allows for the observation of even subtle changes induced in the cells during the measurement session, such as those caused by the compound under investigation. At the moment we have developed a 6-well CorePlate and we are working on a 24-well and a 96-well format to be released over the coming years. Along the way, our microchips will continue to integrate more functionalities to align with the increased complexity while also maintaining an easy and efficient user experience."

Francis Medical Announces Positive Data from VAPOR 1 IDE Study for Water Vapor Ablation of Prostate Cancer

On June 8, 2021 Francis Medical, Inc., a privately held medical device company developing an innovative and proprietary water vapor ablation therapy for the treatment of prostate, kidney, and bladder cancer, reported positive results from the company’s VAPOR 1 clinical study evaluating the safety and efficacy of the company’s minimally invasive water vapor ablation therapy for treating prostate cancer (Press release, Francis Medical, JUN 8, 2021, View Source [SID1234583733]).

VAPOR 1 is a prospective, multicenter, single-arm study that treated 15 patients with intermediate- risk, localized prostate cancer at four U.S. clinical sites. The data is from the six-month primary endpoint, including safety and efficacy outcomes, and VAPOR 1 study patients will continue to be followed to one year. Study participants had unilateral cancer (one side of the prostate), with a treatment intent of ablating only the impacted side (hemi ablation). The VAPOR 1 six-month data reported no serious adverse events, no device-related adverse events, and no unanticipated adverse device effects. Additionally, the effectiveness results support findings that demonstrate water vapor technology can reach and treat all prostate regions (apex, mid, base, anterior, and posterior) and eradicate intermediate risk, Grade Group 2 (GG2, Gleason Score 3+4), prostate cancer. In 87% of patients, six-month biopsy results indicate no ≥ GG 2 (clinically significant) disease on the treated side. In three patients, results on the treated side showed a single positive biopsy core with ≤ 5% involvement (low volume) of GG1 (Gleason Score 3+3) disease.

The safety profile reflects low levels of adverse events for the patient population treated, with no patients reporting urinary incontinence requiring pad usage and one (6.7%) patient reporting moderate erectile dysfunction (with medication indicated). These promising results support the intent of this therapy to manage clinically significant disease while decreasing morbidities associated with currently used prostate cancer treatments. Francis Medical will use the safety and efficacy data from the VAPOR 1 study to support a pivotal trial with its next-generation device and U.S. regulatory approval.

"I am excited to be participating in the VAPOR 1 trial," said Dr. Christopher Warlick, head of the Department of Urology at the University of Minnesota and principal investigator in the VAPOR 1 study. "Currently, urologists commonly use water vapor to successfully treat benign prostatic hyperplasia (BPH). The VAPOR 1 results are very encouraging and suggest the viability of water vapor technology to treat prostate cancer as well. This approach has the potential to provide appropriate men a simple outpatient procedure to manage their prostate cancer with minimal risk of the debilitating side effects often seen with other therapies."

As the second most common cancer in U.S. men, the American Cancer Society estimates one in nine American men will be diagnosed with prostate cancer during their lifetime. Prostate cancer is a serious disease for which current treatment options often cause complications such as urinary incontinence and erectile dysfunction. Francis Medical’s water vapor energy technology applies the thermal energy stored in a few drops of sterile water to deliver targeted treatments to the cancerous tissue in a simple transurethral procedure. The therapy is designed to ablate cancer cells while protecting surrounding structures, lessening the likelihood of life-altering side effects common with other prostate cancer treatments.

"We are thrilled with the results from VAPOR 1," said Michael Kujak, Francis Medical president and chief executive officer. "We want to thank all of the VAPOR 1 investigators, their support staff and the patients suffering from prostate cancer who volunteered to participate for the extraordinary efforts required to execute this study through the worst of the COVID-19 pandemic. The excellent results of VAPOR 1 confirm our belief that this groundbreaking technology will ultimately become the first-line treatment of choice for men and their doctors."

"The VAPOR 1 results are the culmination of the hard work and shared vision of the entire Francis Medical team," said Michael Hoey, Francis Medical founder and chief technology officer. "At Francis Medical, the patient is always first and foremost in our minds. Therefore, it is extremely gratifying to provide the patients in VAPOR 1 with not only an effective treatment for their cancer, but also one that produced minimal pain and side effects, allowing them to quickly return to their normal activities. We continue to work hard every day to realize our shared goal to bring this therapy to every man who can benefit from it."

On the heels of these results, Francis Medical is currently in the process of raising Series B financing to fund their VAPOR 2 pivotal study.

BerGenBio Receives FDA Fast Track Designation For Bemcentinib / Anti-PD-(L)1 Combination In NSCLC

On June 8, 2021 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical need, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for Bemcentinib in combination with an anti-PD-(L)1 agent for the treatment of patients with AXL-positive advanced/metastatic non-small cell lung cancer (NSCLC) (Press release, BerGenBio, JUN 8, 2021, View Source;anti-pd-l1-combination-in-nsclc-301307422.html [SID1234583732]).

The FDA’s decision represents the first recognition by a regulator of AXL-positive patients as a molecular targetable patient population. This designation has been granted for patients without actionable mutations, with disease progression on or after treatment with an anti-PD-(L)-1 agent, with or without chemotherapy as their first line of therapy.

Fast Track designation is intended to facilitate the development and review of drugs used to treat serious conditions and to fill an unmet medical need. It will enable BerGenBio to have more frequent interactions with the FDA throughout the drug development process, so that an approved product can reach the market faster.

The designation also provides Eligibility for Accelerated Approval, enabling approval based on a surrogate clinical endpoint; Priority Review, which allows New Drug Application (NDA) review in six months instead of 10, if relevant criteria are met; and eligibility for Rolling Review, whereby the Company will be able to submit completed sections of its NDA for review by the FDA before complete application is submitted.

BerGenBio has developed proprietary biomarkers and companion diagnostic assays for selection of AXL positive patients, the cAXL assay is validated for clinical trial use. Retrospective analysis of patients in clinical trials suggest approximately 50% of patients are cAXL positive, and it is these patients that achieve the clinical responses and extended survival benefit previously reported.

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "Building on our encouraging clinical and translational data, we are excited to receive Fast Track designation from the FDA for the promising combination of bemcentinib in combination with a checkpoint inhibitor. This regulatory milestone is particularly meaningful for BerGenBio, as it represents the first formal recognition by a regulator of AXL-positive patients as a discernible patient population and serves as further validation of our belief that AXL inhibition has high potential as a cornerstone of cancer combination therapy. We look forward to working closely with the FDA on the continued clinical development of the combination."

About AXL

AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases.

In COVID-19, AXL has two synergistic mechanisms of action, it acts a co-receptor to ACE2, to which the spike protein of the SARS-CoV-2 virus attaches and enters the host cell, and AXL expression is upregulated that leads to suppression of the Type 1 Interferon immune response by host cells and in their environment. Research data confirms bemcentinib inhibits SARS-CoV-2 host cell entry and promotes the anti-viral Type I interferon response. Data from a Phase II in human clinical trial has shown that treatment with AXL inhibitor bemcentinib increased the rate ventilator free survival in hospitalised COVID-19 patients.

In cancer, increase in AXL expression has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers. AXL suppresses the body’s immune response to tumours and drives treatment failure across many cancers. High AXL expression defines a very poor prognosis subgroup in most cancers. AXL inhibitors, such as bemcentinib, therefore, have potential high value as monotherapy and as the cornerstone of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases including fibrosis

Composite AXL (cAXL) is a proprietary biomarker developed by BerGenBio that simultaneously scores AXL expression on tumour cells and immune cells in the tumour microenvironment, as determined by Immune Histo Chemistry (IHC) assay. Data from on-going clinical trials suggest ca. 50% of patients are high cAXL and this is predictive of improved clinical outcomes for patients receiving bemcentinib.

About Bemcentinib

Bemcentinib (formerly known as BGB324), is a potential first-in-class, potent and highly selective AXL inhibitor, currently in a broad phase II clinical development programme. It is administered as an oral capsule and taken once per day. Ongoing clinical trials are investigating bemcentinib in COVID-19, and multiple solid and haematological tumours, in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy), and as a single agent. Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity.

GT Biopharma to be Added to the Russell 2000® Index

On June 8, 2021 GT Biopharma, Inc. ("GT Biopharma" or the "Company") (NASDAQ: GTBP), a clinical stage immuno-oncology company focused on developing innovative therapeutics based on the Company’s proprietary natural killer (NK) cell engager (TriKE) protein biologic technology platform, reported that it is set to be added to the Russell 2000 Index at the conclusion of the Russell US Indexes annual reconstitution, effective at the opening of the U.S. equity markets on June 28, 2021 (Press release, GT Biopharma, JUN 8, 2021, View Source [SID1234583731]).

"Our inclusion in the Russell index is an important milestone for us as it reflects the continued progress we are making to develop and commercialize our first-in-class therapeutics. We welcome the enhanced visibility of our long-term growth potential and look forward to sharing our future milestones with a broader investment community," said Anthony J. Cataldo, GT Biopharma’s Chairman and Chief Executive Officer

FTSE Russell determines membership for its Russell indexes primarily by objective, market-capitalization rankings and style attributes. Membership in the small-cap Russell 2000 Index, which remains in place for one year, is based on membership in the broad-market Russell 3000Ò Index.

Russell’s U.S. indexes are widely used by investment managers and institutional investors for index funds and as benchmarks for active investment strategies. Approximately $9 trillion in assets are benchmarked against Russell’s U.S. indexes. Russell Indexes are part of FTSE Russell, a leading global index provider.

For more information about the Russell U.S. Indexes and the Russell Indexes reconstitution, visit the FTSE Russell website.

PathAI to Present Machine Learning-based Quality Control Tool for HER2 Testing in Breast Cancer at the American Society of Clinical Oncology Virtual Scientific Program 2021

On June 8, 2021 PathAI, a global leader of AI-powered technology applied to pathology, reported that new data highlighting a quality control tool for HER2 testing in digital pathology images captured in clinical trials will be presented in the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Scientific Program 2021, held from June 4-8, 2021 (Press release, PathAI, JUN 8, 2021, View Source [SID1234583730]). These results will be shared in the poster presentation, Machine learning models to quantify HER2 for real-time tissue image analysis in prospective clinical trials (Abstract #3061), in the session, Developmental Therapeutics —Molecularly Targeted Agents and Tumor Biology.

Together, PathAI, AstraZeneca (LSE/STO/Nasdaq: AZN) and Daiichi Sankyo Company, Limited have developed ML-based models for the automated quantification of HER2 IHC images in breast cancer tissue. Expression of HER2, a protein localized in the cell membrane, is typically assessed by pathologists to evaluate patient eligibility for anti-HER2 targeted therapies. ML-based models trained to identify and quantify tumor histology features can provide highly accurate and reproducible scores that are highly concordant with manual pathology.

The PathAI HER2 models were developed to generate HER2 scores consistent with the 2018 ASCO (Free ASCO Whitepaper)/CAP HER2 scoring guidelines. The models also produce metrics that reflect the quality of HER2 testing, such as the area and number of tumor cells, the presence of ductal carcinoma in situ (DCIS), background staining and artifact content. In a test set including diverse tissue-types across a wide range of breast cancer types, ML quantification of HER2 was consistent with manual scores from a consensus of pathologists (ICC 0.88, 95% CI 0.82-0.92). ML scores were even more closely aligned with pathologist scores after further training to learn pathologist scoring methods (ICC 0.91, 95% CI 0.89-0.94). By providing consistent, automated HER2 IHC image analysis, PathAI ML models can provide real-time QC read-outs enabling identification of drifts or inconsistencies in HER2 testing data and images captured during clinical trials.

PathAI’s broad approach towards integrating AI-powered tools into oncology clinical trial workflows is also represented by a separate study that PathAI is presenting at ASCO (Free ASCO Whitepaper) (Abstract #106). Both presentations are examples of how AI can enhance pathologist performance by generating accurate and reproducible clinically relevant scores that can be scaled to levels that are currently unachievable.