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 Vor Biopharma, an oncology company pioneering engineered hematopoietic stem cells (eHSCs) for the treatment of cancer, reported it has raised $110 million in a Series B financing (Press release, Vor BioPharma, JUL 7, 2020, View Source [SID1234561713]). Proceeds will advance the company’s lead candidate VOR33 into clinical trials, deepen its portfolio, and accelerate the validation of additional targets for its scientific platform, which is designed to remove redundant proteins so that transplanted stem cells become invisible to targeted therapies while leaving diseased cells vulnerable. Vor’s treatment strategy has the potential to bring a revolutionary treatment paradigm for patients with acute myeloid leukemia and other hematologic malignancies.

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"Vor has an elegant approach to engineering hematopoietic stem cells that we believe is amongst the most promising innovations in oncology," said Joshua Resnick, MD, Managing Director at RA Capital Management. "We are proud to support the efforts of their impressive team of experienced leaders and drug developers as they work aggressively to establish a new standard of care in stem cell transplants and forge ahead into first-in-human clinical studies."

RA Capital Management led the Series B financing, along with a diverse group of well-respected new investors including Fidelity Management & Research Company, LLC, Pagliuca Family Office, Alexandria Venture Investments, and other undisclosed investors, including additional institutional crossover investors. Existing investors 5AM Ventures, Johnson & Johnson Innovation — JJDC, Inc. (JJDC), Osage University Partners, and co-founder PureTech Health participated in the financing.

"The high caliber of investors participating in this financing underscores the tremendous potential of our eHSC platform," said Robert Ang, MBBS, MBA, Vor’s President and Chief Executive Officer. "We have ambitious goals for the coming year, and this financing is an important step as we prepare to treat cancer patients in our first clinical trials."

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 July 7, 2020 HiberCell, a biotechnology company developing novel therapeutics for cancer relapse and metastasis, reported the acquisition of Biothera Pharmaceuticals’ (Biothera) Imprime PGG program (Press release, HiberCell, JUL 7, 2020, View Source [SID1234561714]). HiberCell will integrate Biothera’s Minnesota-based staff, operations and other assets into the company.

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Imprime PGG is a novel innate immune activator that binds to the dectin-1 receptor and activates innate immunity, reprogramming the immunosuppressive tumor microenvironment to enhance antigen presentation, trigger T cell activation and ultimately enhance the immune response against tumors. Phase II clinical studies of Imprime PGG in combination with checkpoint inhibition demonstrated compelling mechanistic proof-of-concept data including the activation of innate and adaptive immunity resulting in improved overall survival, overall response and disease control rates in metastatic triple negative breast cancer (mTNBC).

"Imprime PGG has provided meaningful responses in Phase 2 clinical trials for metastatic cancer patients. HiberCell will build on these data and their potential to transform the lives of people living with metastatic breast cancer," said Alan C. Rigby, Ph.D., co-founder and chief executive officer of HiberCell. "This acquisition signifies HiberCell’s transition into a clinical stage company with a broad portfolio of assets targeting cancer relapse and metastasis."

HiberCell’s scientific approach focuses on three mechanistic pillars of cancer dormancy: adaptive stress biology, disseminated tumor cells and the tumor microenvironment. By exploring each, the company continues to assemble a pipeline of differentiated therapeutic opportunities for relapsed and metastatic cancer. Importantly, the Imprime PGG program adds to the HiberCell pipeline a later-stage innate immune activator supported by a robust translational oncology platform that has demonstrated a ‘reprogramming’ and activation of the tumor microenvironment.

In Phase II clinical studies, Imprime PGG paired with the checkpoint inhibitor Keytruda resulted in encouraging benefits across all clinical measures in patients with metastatic breast cancer, including TNBC. HiberCell will initiate additional clinical studies in TNBC and other indications to further demonstrate the safety and efficacy of various Imprime PGG combination therapies.

"We are very proud of the translational platform and science behind Imprime PGG," said Jeremy R. Graff, Ph.D., chief development officer of HiberCell. "We look forward to building a robust clinical pipeline in support of the meaningful data Imprime PGG has generated to date and are thrilled to continue this work at HiberCell."

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.