On July 7, 2020 Myriad Genetics, Inc. (NASDAQ: MYGN), a leader in molecular diagnostics and precision medicine, reported two recent publications validating the polygenic risk score (PRS) component of Myriad’s breast cancer risk stratification tool riskScore (Press release, Myriad Genetics, JUL 7, 2020, View Source [SID1234561739]). The publications clinically validate both the ability of the PRS component of riskScore to predict breast cancer risk in asymptomatic women and modify risk estimations for patients identified with pathogenic mutations.

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"Historically we’ve considered breast cancer risk most significant for women diagnosed with pathogenic mutations in hereditary cancer genes. These studies demonstrate clearly that other genetic factors evaluated through Myriad’s riskScore test can dramatically alter breast cancer risk both independent of, and in combination with, gene mutations," said Nicole Lambert, president of Myriad International, Oncology and Women’s Health. "This information can dramatically change patient clinical management and Myriad is currently working diligently to provide access to this important information for all women."

The first study published in JCO Precision Oncology described the PRS component of riskScore in over 150,000 women. It showed that independent of other hereditary breast cancer gene mutations (e.g., BRCA1), Myriad’s polygenic risk score can add great value and precision to breast cancer risk estimates. The PRS was highly associated with breast cancer risk with an odds ratio of 1.47 (95% confidence interval 1.45 to 1.49) per unit standard deviation in the PRS. This translated to women in the top PRS percentile having a three-fold higher risk of breast cancer than an average risk patient.

The second study published in the Journal of the American Medical Association Network Open demonstrates the ability of Myriad’s polygenic risk score to improve breast cancer risk stratification in women diagnosed with pathogenic mutations in common breast cancer genes. The study evaluated over 150,000 patients and approximately 10,000 patients who were carriers of pathogenic mutations in the BRCA1, BRCA2, CHEK2, ATM and PALB2 genes who were tested at Myriad. The study demonstrated that patients with high penetrant genes such as BRCA1 and BRCA2 did not warrant changes in clinical management; however, breast cancer risks in patients with moderate penetrant genes such as CHEK2, ATM, and PALB2 could vary significantly, warranting different clinical management considerations. For example, patients with a PALB2 mutation historically have been assessed to have an approximately 50 percent lifetime risk for breast cancer. However, after incorporating the data from Myriad’s 86 single nucleotide polymporphism (SNP) riskScore test, patient risks varied between 26 percent to 79 percent (see Graph 1 below).

"These are some of the largest polygenic risk score studies ever published. Patient medical management can vary dramatically depending on where patients with and without pathogenic mutations fall within the risk spectrum," said Thomas P. Slavin M.D., senior vice president for Medical Affairs in Oncology at Myriad Genetic Laboratories. "This information will help empower patients and clinicians to make more informed decisions based upon the most precise breast cancer risk estimates availiable."

About riskScore
riskScore is a new clinically validated personalized medicine tool that enhances Myriad’s myRisk Hereditary Cancer test. riskScore helps to further predict a women’s lifetime risk of developing breast cancer using clinical risk factors and genetic-markers throughout the genome. The test incorporates data from more than 80 single nucleotide polymorphisms identified through 20 years of genome wide association studies in breast cancer and was prospectively validated in our laboratory to predict breast cancer risk in women of European descent. This data is then combined with a best-in-class family and personal history algorithm, the Tyrer-Cuzick model, to provide every patient with individualized breast cancer risk.

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.