On July 7, 2020 Nucleai (www.Nucleaimd.com), an Israeli start-up providing an artificial intelligence-powered precision oncology platform for research and treatment decisions and Debiopharm (www.debiopharm.com), a Swiss-based biopharmaceutical company specializing in drug development, manufacturing and digital health investment, reported the Series-A initial closing of $6.5M (Press release, Nucleai, JUL 7, 2020, View Source [SID1234561733]).

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In recent years, cancer immunotherapies have revolutionized cancer treatment, providing long term benefits to certain patient populations. However, the efficacy of these treatments is often observed in only a small subset of patients. Without an adequate way to predict drug response, patients risk receiving ineffective treatment accompanied by unnecessary payor coverage. In light of the high percentage of clinical trial failure, this lack of predictive precision can also have a heavy impact on pharmaceutical companies conducting costly clinical research. Nucleai’s core technology analyzes large and unique datasets of tissue images using computer vision and machine learning methods to model the spatial characteristics of both the tumor and the patient’s immune system, creating unique signatures that are predictive of patient response. In a recent work performed in collaboration with leading researchers and published at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 conference, Nucleai has demonstrated the predictive power of tumor microenvironment AI-based spatial analysis for breast cancer.

Through this investment, Debiopharm and Nucleai will collaborate in order to leverage Debiopharm’s 40 years of pharmaceutical expertise towards an acceleration of predictive biomarker discovery for drug response and the improvement of data from clinical trials involving cancer patients. The company intends to use the funds to further progress the development of its advanced platform for use in Immuno-oncology and other diseases. The funds will be used also to further progress its commercial reach to pharmaceutical and biotech companies.

"We are excited to have Debiopharm’s corporate VC as our lead investor along with our longterm partner investors Vertex Ventures and Grove Ventures. Debiopharm is bringing decades of pharmaceutical expertise which will assist in accelerating our development and market reach," explained Avi Veidman, Nucleai’s CEO. "Nucleai has multiple revenue-generating, commercial partnerships, with leading Immunotherapies pharma companies and US-based payors. We plan to use these funds to expand our offering to additional indications and diseases as well as to increase our commercial footprint substantially."

Founded in Israel, a growing hotspot for computational biology innovation, Nucleai was founded by former members of an elite technological unit of Israeli intelligence corps specializing in artificial intelligence and big data: Avi Veidman (CEO), Eliron Amir (COO), and Lotan Chorev (VP R&D). This Tel Aviv hub positions the start-up to leverage a wealth of valuable resources including a centralized medical system, 25 years of EMR data, and top AI talents.

"Our team is thrilled to embark on this adventure to develop and further understand the extent to which AI can help pathologists and oncologists become more precise in both diagnosis and prediction," explained Tanja Dowe, CEO of Debiopharm Innovation Fund. "We recognize the huge impact that Nucleai’s AI-powered platform, could have on clinical research for pharmaceutical treatments."

Avi Veidman, Nucleai’s CEO added, "The battle between the tumor and the immune cells is clearly visible by inspecting the pathology slide, just like a satellite image of a battlefield. Our AI platform analyzes the hundreds of thousands of cells in a slide, examines the interplay between the tumor and the immune system and matches the right patient to the right drug based on these characteristics".

"Our solution is purely based on software which is embedded into the biomarker researcher workflow. This allows us to scale our solution rapidly, to provide service to a large number of pharmaceutical and biotech partners as well as to patients," expressed Eliron Amir, COO of Nucleai. "It is an elegant solution to a complex problem. There is no need for an expensive wet-lab biology operation. Our cloud-based solution allows us to gather huge amounts of immuno-oncology data from different sources, creating complex insights that a single pharma or institute cannot generate by itself."

On July 7, 2020 Quantum Leap Healthcare Collaborative (Quantum Leap) reorted the initiation of an investigational treatment arm with Byondis’ [vic-]trastuzumab duocarmazine (SYD985) in the ongoing I-SPY 2 TRIAL for neoadjuvant treatment of locally advanced breast cancer (Press release, QuantumLeap, JUL 7, 2020, View Source [SID1234561732]). This treatment arm will focus on treatment for HER2 low early-stage breast cancer.

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This study arm will evaluate if SYD985 will limit tumor growth in a population of patients whose tumors are not normally treated with HER2-targeted therapies. Specifically, these tumors have low expression of HER2, and require better HER2-targeted drugs in order to be as effectively treated as HER2+ patients.

SYD985 is being developed for the treatment of HER2 expressing or HER2 mutant tumors. In nonclinical and clinical studies, SYD985 has demonstrated potent antitumor activity. Based on the preliminary clinical observations in a Phase 1 study, SYD985 demonstrated antitumor activity in HER2-expressing cancers including breast cancer. Researchers and clinicians believe SYD985 inhibits tumor growth for the following reasons: SYD985 is a next generation ADC, comprised of the mAb (monoclonal antibody) trastuzumab and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA). The antibody part of SYD895 binds to HER2 on the surface of the cancer cell and is internalized by the cell. After proteolytic cleavage of the linker, the inactive cytotoxin is activated and DNA damage is induced, resulting in death of dividing and non-dividing tumor cells. An earlier phase I study (SYD985.001) in patients with histologically-confirmed, locally advanced or metastatic tumors, concluded that SYD985 is effective in patients with high HER2 levels in their tumor, as well as in a subset of patients with lower levels of expression of the HER2 protein (HER2- low).

The SYD985 arm of the I-SPY 2 clinical trial will be open for randomization to the HER2-low subset of the HER2- I-SPY 2 population, further defined as HER2-low by HER2 immuno histo-chemical staining (i.e. IHC 1+ and 2+) and in-situ hybridization. Tumors will be further characterized by genetic testing employing MammaPrint (MP1 or MP2) and by hormone receptor status (HR+ or HR-). Within the HER2 negative population, patients will be excluded for HER2 IHC 0 and ISH negative.

"This I-SPY 2 TRIAL arm is designed to test a less toxic and a potentially highly effective approach where we need better options for patients." stated Dr. Laura Esserman, Lead PI for the I SPY 2 TRIALs. "Low levels of HER2 protein expression are not sufficient to generate a response to traditional HER 2 treatment currently on the market. This particular agent works differently and is a promising way to deliver a targeted toxin. We need to continue to push to find better therapies. The I-SPY investigators are excited to partner with Byondis to test this agent in I-SPY 2."

The I-SPY 2 TRIAL, sponsored by Quantum Leap, is a standing phase 2 randomized, controlled, multicenter study with an innovative Bayesian adaptive design aimed to rapidly screen and identify promising new treatments in specific subgroups of women with newly-diagnosed, high-risk (high likelihood of recurrence), locally-advanced breast cancer (Stage II/III).

Byondis will supply the investigational drug and provide financial and regulatory support. Quantum Leap, as sponsor, will provide the clinical sites and clinical expertise.

On July 7, 2020 Senhwa Biosciences, Inc. (TPEx: 6492), a clinical-stage biopharmaceutical company focused on Next Generation DNA Damage Response (DDR) therapeutics for the treatment of cancer, reported that the U.S. Food and Drug Administration (FDA) granted Rare Pediatric Disease (RPD) Designation for its drug Silmitasertib, a Casein Kinase 2 (CK2) inhibitor, being developed as a treatment for recurrent sonic hedgehog (SHH) medulloblastoma (Press release, Senhwa Biosciences, JUL 7, 2020, View Source [SID1234561730]). With the RPD designation, Senhwa Biosciences is eligible for a Priority Review Voucher (PRV) which can be used for a subsequent marketing application, and may be sold or transferred. In August 2015, AbbVie bought a PRV from United Therapeutics Corp for $350 million which allowed AbbVie to accelerate one of its drug’s FDA review process.

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Medulloblastoma is the most common cancerous brain tumor in children. Treatment for medulloblastoma usually includes surgery, followed by radiation or chemotherapy, or both. Currently there is no targeted drug available. Recurrent SHH medulloblastoma is recognized as one of the four major sub-groups of medulloblastoma, with about 80-100 new cases per year. The FDA grants RPD Designation for serious or life-threatening diseases that primarily affect people from birth to 18 years old and which affect fewer than 200,000 people in the U.S.

Senhwa’s clinical partner, the Pediatric Brain Tumor Consortium (PBTC, www.pbtc.org) is currently conducting a Phase I/II and Surgical study of Silmitasertib, in both children and adults with recurrent SHH medulloblastoma, at its participating member academic medical centers and children’s hospitals across the United States. This clinical trial is sponsored by the PBTC and funded through the Consortium grant awarded by the National Institute of Health (NIH) – Cancer Therapy Evaluation Program (CTEP).

Silmitasertib is safe and well-tolerated in humans. To date, three Phase I trials of Silmitasertib in cancer patients have been completed; currently, there are one ongoing Phase I and two ongoing Phase II studies of Silmitasertib.

About Silmitasertib
Silmitasertib is a first-in-class small molecule drug which targets CK2 and acts as a CK2-inhibitor. A Phase I/II study has shown that Silmitasertib achieved clinical benefit, resulting in stable disease and extending the duration of treatment in patients who are unresponsive to standard of care therapy. The combination of Silmitasertib with DNA-damaging agents such as gemcitabine (Gemzar) plus cisplatin (Platinol) has been shown to synergistically improve the efficacy of cholangiocarcinoma (CCA) treatments. In December 2016, Silmitasertib was granted Orphan Drug Designation by the US FDA for the treatment of CCA.

On Juy 7, 2020 Natera, Inc. (NASDAQ: NTRA), a pioneer and global leader in cell-free DNA testing, along with its collaborators, reported two distinct studies (one oral and one poster presentation) at the recent 2020 virtual ESMO (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer that took place July 1-4, 2020 (Press release, Natera, JUL 7, 2020, View Source [SID1234561729]).

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The studies highlight: a) the clinical validity of Signatera, a personalized and tumor-informed circulating tumor DNA (ctDNA) assay for identifying molecular residual disease (MRD) in patients with oligometastatic CRC; and b) a prospective trial, already in progress, that will measure the clinical outcomes of MRD-guided treatment in stage II-III CRC patients.

These presentations build upon a fast-growing set of evidence that Signatera MRD testing is valid and useful for guiding post-surgical treatment decisions in colorectal cancer (escalation or de-escalation of therapy), including for late-stage oligometastatic patients where surgical resection may lead to cure.

"Now that Signatera is being used in prospective interventional trials, we’re seeing confirmation that it can help inform treatment decisions after oligometastatic resection in the 20 percent to 30 percent of patients with metastatic CRC,"1-3 said Alexey Aleshin, M.D., M.B.A., Natera’s Senior Medical Director for Oncology. "This clinical data suggest ctDNA testing is a highly accurate tool in guiding treatment and supports the advancement of our efforts with Signatera to improve cancer management."

Details about the abstracts are as follows:

Assigned ID: SO-34 | Oral Presentation

Presenter: Stacey A. Cohen, M.D.

Clinical Experience of a Personalized and Tumor-Informed Circulating Tumor DNA Assay for Minimal Residual Disease Detection in Oligometastatic Colorectal Cancer Patients

This study is a sub-analysis of the first large, real-world study using personalized MRD in 535 unique patients with Stage I-IV CRC, and is one of the first studies to evaluate ctDNA detection rates in late-stage oligometastatic CRC. The study found that ctDNA detection was significantly associated with stage of disease, demonstrating a detection rate of 100 percent in patients with active metastatic disease in a pre-surgical setting.

Assigned ID: P-120 | Poster Presentation

Presenter: Hiroki Yukami, M.D.

Prospective observational study monitoring circulating tumor DNA in resectable colorectal cancer patients undergoing radical surgery: GALAXY study in CIRCULATE-Japan (Trial in Progress)

The poster presentation highlighted the GALAXY study design, a prospective, observational study, which is part of the CIRCULATE-Japan trial, organized by the National Cancer Center (NCC) Japan. The CIRCULATE-Japan trial is a multicenter, randomized trial that will investigate optimal ctDNA-guided treatment strategies for patients with Stage II-III CRC, particularly adjuvant chemotherapy decisions based on MRD status.

About Signatera

Signatera is a custom-built ctDNA test for treatment monitoring and MRD assessment in patients previously diagnosed with cancer. The test is available for clinical and research use, and it was granted Breakthrough Device Designation by the FDA in 2019. The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual’s tumor. This maximizes accuracy for detecting the presence or absence of residual disease in a blood sample, even at levels down to a single tumor molecule in a tube of blood. Unlike a standard liquid biopsy, Signatera is not intended to match patients with any particular therapy. Rather, it is intended to detect and quantify how much cancer is left in the body, to detect recurrence earlier and to help optimize treatment decisions. Signatera’s test performance has been clinically validated in multiple cancer types including colorectal, non-small cell lung, breast, and bladder cancers. Medicare has proposed insurance coverage for the use of Signatera in patients with Stage II or III colorectal cancer, and it is expected to finalize that coverage decision in mid-2020. Signatera has been developed and its performance characteristics determined by the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA). Although FDA is exercising enforcement discretion of premarket review and other FDA legal requirements for laboratory-developed tests in the US, certification of the laboratory is required under CLIA to ensure the quality and validity of the tests. CAP accredited, ISO 13485 certified, and CLIA certified. © 2020 Natera, Inc. All Rights Reserved.

On July 7, 2020 MAIA Biotechnology, Inc., a targeted therapy, immuno-oncology company focused on development of first-in-class drugs, reported that encouraging preclinical results supporting newly-identified immunogenic effects of the company’s lead product candidate, investigational THIO (6-thio-dG), the only telomere-by-telomerase targeting agent in development for the treatment of cancer, has been published in Cancer Cell, a renowned peer-reviewed scientific journal covering major advances in cancer research (Press release, MAIA Biotechnology, JUL 7, 2020, View Source [SID1234561728]). The manuscript entitled: "Telomere Stress Potentiates STING-Dependent Anti-tumor Immunity," Mender et al., is now featured online and will also be published in the September 2020 edition of Cancer Cell, Volume 38, pages 1-12.

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Telomerase is the enzyme responsible for the maintenance of telomeres. While inactive in most normal cells, telomerase is activated in the majority of cancer cells, making it an attractive target for cancer therapy. Preclinical data have demonstrated that THIO kills cancer cells by targeting and uncapping telomeres thereby inducing DNA damage. The latest preclinical data showed this is complemented by an immunogenic effect, which may allow for more durable outcomes when used sequentially with immunotherapy. THIO’s activity was shown to be cancer-specific in tumor types with active telomerase. Since up to 35 million patients have telomerase-positive cancers, MAIA Biotech believes these results suggest that THIO holds significant potential to treat large patient populations across many types of cancers.

In these preclinical studies published in Cancer Cell, investigators demonstrated that THIO leads to tumor regression through induction of innate and adaptive host immune system responses. THIO was shown to be directly incorporated into telomeres by telomerase, where it rapidly induced telomeric DNA damage responses, which is selective to telomerase-positive TERT(+) cancer cells without affecting normal telomerase-silent cells. The findings also indicated that THIO induces DNA-mediated innate sensing and activation of immune responses in a host cGAS/STING-dependent manner, leading to improved anti-tumor efficacy. Low doses of THIO, followed by anti-PD-L1 therapy, completely eliminated advanced tumors in preclinical models and produced cancer cell specific immune memory where the immune system continued to be active against the cancer cells after extended periods of time with no additional treatment. These results are significant as they demonstrate how the THIO-produced telomere stress increases innate sensing and adaptive anti-tumor immunity, which provides a strong rationale for sequentially combining telomere-targeted therapy with immunotherapy.

"We believe THIO has the potential to transform the immuno-oncology landscape and change the cancer treatment paradigm, and these most recent findings provide a strong rationale for combining telomere-targeted therapy with immunotherapy," stated Vlad Vitoc, MD, MAIA’s Chief Executive Officer and President. "We believe the publication of these unprecedented immunogenic effects of THIO in Cancer Cell provides additional validation for this innovative program. We are highly encouraged by these promising findings of tumor elimination, cancer specific immune responses, and stimulation of immune memory, which build upon prior positive preclinical results. These findings provide further support for the company’s plans to advance THIO into Phase 1 clinical studies in 2021."

About THIO

THIO (6-thio-dG) is a small molecule in preclinical development and is the only telomere-by-telomerase targeting agent currently in development. THIO is designed to selectively kill cancer cells by modifying telomeric DNA structure and function utilizing telomerase. Telomerase is present in >85% of human cancers and contributes significantly to proliferation and immortality of cancer cells. THIO is recognized by telomerase and incorporated into telomeres selectively in cancer cells. Once incorporated, it compromises the telomere structure and function, leading to ‘uncapping’ of the chromosome ends and thus resulting in rapid tumor cell death. In preclinical studies, this rapid cancer cell death occurred without impacting normal cells. THIO is investigational and has not been approved for any use anywhere in the world.

About Cancer Cell

Cancer Cell provides a high-profile forum to promote major advances in cancer research and oncology. The primary criterion for considering manuscripts is whether the studies provide major advances into answering important questions relevant to naturally occurring cancers. Cancer Cell is also interested in publishing clinical investigations, in particular those that lead to establishing new paradigms in the treatment, diagnosis, or prevention of cancers; those that provide important insights into cancer biology beyond what has been revealed by preclinical studies; and those that are mechanism-based proof-of-principle clinical studies. For more information, please visit www.cell.com/cancer-cell or follow the journal on Twitter: @Cancer_Cell.