On January 15, 2020 Natera, Inc. (NASDAQ: NTRA) reported an agreement with the National Cancer Center (NCC) Japan to launch the CIRCULATE-IDEA trial in Japan, a prospective, multi-center, randomized trial to investigate ctDNA-guided treatment strategies for patients with Stage II-III colon cancer, based on the results of molecular residual disease (MRD) testing with Signatera (Press release, Natera, JAN 15, 2020, View Source [SID1234553245]). The trial is organized by the NCC and national in scope, and it is expected to include approximately 1500 patients from over 100 cancer centers across Japan.

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The CIRCULATE-IDEA trial was unveiled in September 2019 at the annual congress of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper),1 introduced as a sequel to the pivotal IDEA collaboration of 2007-2017 which compared outcomes from 3 months vs. 6 months of adjuvant chemotherapy in patients with Stage III colon cancer. The CIRCULATE-IDEA trial picks up where the IDEA trial left off, with groups across Japan, the U.S. and Europe collaborating to explore optimal treatment strategies in the era of personalized, tumor-informed MRD testing.

There will be multiple investigational arms in the Japanese CIRCULATE-IDEA trial, including treatment escalation (experimental therapies) in patients who test MRD-positive after surgery, and treatment de-escalation (no chemotherapy at all) in patients who test MRD-negative after surgery. The study’s primary objective is to demonstrate that MRD-negative patients derive no significant clinical benefit from adjuvant chemotherapy and thus may safely avoid it. This outcome, if achieved, would result in a significant change to current medical practice, in which adjuvant chemotherapy is standard for all Stage III patients despite the fact that most patients are cured by surgery alone.

In Japan, CIRCULATE-IDEA is the centerpiece of a new platform study called SCRUM-Japan MONSTAR-SCREEN. If successful, the platform study is expected to support widespread adoption and reimbursement of MRD testing in Japan.

"There are many thousands of colon cancer patients each year who receive unnecessary chemotherapy," said the study’s Principal Investigator, Dr. Takayuki Yoshino of the NCC East, Kashiwa, Japan. "We believe the Signatera technology offers a breakthrough solution to differentiating which patients need further treatment and which do not."

In a published validation study, Signatera detected relapse in patients with Stage II-III colorectal cancer up to 16.5 months earlier (average 8.7 months earlier) than standard diagnostic tools including CT imaging and CEA. Patients who remained MRD-negative throughout the study had significantly reduced risk of relapse, as low as 3%.2

"We are proud to partner with the NCC and the Japanese oncology community on this important trial," said Alexey Aleshin, M.D., M.B.A., Natera’s Senior Medical Director for Oncology. "Helping patients avoid unnecessary treatment is a cornerstone of our vision for Signatera across many cancer types, and we believe this collaboration is an early example of how that story will unfold globally."

About Signatera
Signatera is a custom-built circulating tumor DNA (ctDNA) test for treatment monitoring and molecular residual disease (MRD) assessment in patients previously diagnosed with cancer. The test is available for clinical and research use, and in 2019 it was granted Breakthrough Device Designation by the FDA. 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 may be left in the body, to detect recurrence earlier, and to help optimize treatment decisions. Signatera test performance has been clinically validated in multiple cancer types including colorectal, non-small cell lung, breast, and bladder cancers.

Signatera was developed by Natera, Inc. a laboratory certified under the Clinical Laboratory Improvement Amendments (CLIA). This test has not been cleared or approved by the U.S. Food and Drug Administration (FDA). Although FDA does not currently clear or approve laboratory-developed tests in the U.S., certification of the laboratory is required under CLIA to ensure the quality and validity of the tests.

On January 15, 2020 BerGenBio ASA (OSE: BGBIO) a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for multiple cancer indications, reported meeting the clinical efficacy endpoint of stage 1 of Cohort B in the phase II trial (BGBC008) evaluating bemcentinib in combination with MSD’s Keytruda (pembrolizumab) in previously treated non-small cell lung cancer (NSCLC) patients with confirmed progression on prior immune checkpoint therapy (Press release, BerGenBio, JAN 15, 2020, View Source [SID1234553244]). The trial will advance into the second stage.

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The company reports that the Cohort B, stage 1 efficacy analysis has met the confirmed response of one or more patients therefore continuation to stage two evaluation is planned.

The second stage will enroll a further 16 patients to confirm the safety and clinical efficacy of the combination in NSCLC patients that have confirmed progression on prior immune checkpoint therapy.

Comprehensive exploratory biomarker studies of tumor and blood samples are ongoing to measure of AXL expression and immune modulation. Further results from the trial are expected during 2020 and will be presented at appropriate scientific conferences.

The BGBC008 trial (ClinicalTrials.gov Identifier: NCT03184571) is being sponsored by BerGenBio. MSD, a tradename of Merck & Co., Inc., Kenilworth, New Jersey, USA, will continue to supply Keytruda for use in the study under a collaboration agreement signed in March 2017.

Richard Godfrey, Chief Executive Officer of BerGenBio, said: "Reversing resistance to immune checkpoint inhibitors in patients who have relapsed on immunotherapy is a highly desirable alternative to the second-line chemotherapy standard-of-care. We are very excited with these early results in this challenging setting and look forward to expanding the study to confirm these findings and reporting comprehensive translational insight. Furthermore, Cohort C in NSCLC patients having failed 1L chemo-checkpoint inhibitor combination is now recruiting, and top line data should be available in the coming months."

About AXL

AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases. In cancer, AXL suppresses the body’s immune response to tumours and drives cancer treatment failure across many indications. AXL inhibitors, therefore, have potential high value at the centre 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.

About Bemcentinib

Bemcentinib (formerly known as BGB324), is a potentially first-in-class selective AXL inhibitor in a broad phase II clinical development programme. Ongoing clinical trials are investigating bemcentinib in 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. Increase in AXL function has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers.

On January 15, 2020 John Theurer Cancer Center at Hackensack University Medical Center in New Jersey reported are participating in a first-in-patients clinical trial assessing VE800, a novel bacteria-containing therapy, in combination with the immunotherapy drug nivolumab (Press release, John Theurer Cancer Center, JAN 15, 2020, View Source [SID1234553243]). Laboratory research has suggested that VE800 may enhance the effectiveness of drugs like nivolumab.

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Nivolumab belongs to a class of drugs called checkpoint inhibitors, which also include pembrolizumab and ipilimumab. Cancer cells use certain proteins to hide from or block the immune system, preventing the elimination of cancer cells by the immune system. The category of drugs called checkpoint inhibitors can take the brakes off the immune response and enable the it to detect and destroy cancer cells. Based on their impressive activity, checkpoint inhibitors have been approved by the FDA and become part of the standard of care for more than 14 different types of cancer, including melanoma, lung cancer, head and neck cancer, bladder cancer, cervical cancer, liver cancer, stomach cancer, breast cancer, and lymphoma.

Though immune blockade has been a game-changer, some patients still do not respond to this treatment or eventually relapse. Efforts to understand why some patients respond more than others have revealed that the answer might be in the microbiome: the trillions of bacteria and other tiny organisms that live in our bodies, the bulk of it being the intestinal flora or "gut microbiome." Growing evidence has shown that the microbiome is an important contributor to human health, playing a role in a number of diseases or conditions including obesity, diabetes, and inflammation, among others. Remarkably, studies have revealed differences in microbiome composition between responders and non-responders to checkpoint inhibitors. This is due to the ability of the microbiome to modulate the immune system and affect the microenvironment of tumors and the immune response.

VE800 is an investigational therapy made up of 11 "friendly" bacterial strains that act in concert to activate cytotoxic CD8+ T cells — immune cells which form the vanguard of the immune system’s response to tumors and a key driver of effective immunotherapies. In preclinical studies, VE800 enhanced the ability of these T cells to get into tumors, promoting the suppression of tumor growth and potentially enhancing survival.

The phase I study, which is being conducted at John Theurer Cancer Center and other centers across the United States, will evaluate the safety and clinical activity of VE800 in combination with nivolumab in patients with advanced or metastatic melanoma, gastric/gastroesophageal junction adenocarcinoma (esophagus/stomach cancer), or a type of colon cancer called microsatellite-stable colorectal cancer. The first results are anticipated in 2021.

"While immunotherapy has revolutionized cancer care, there are still many patients who are not doing as well as we would like with these treatments," explained Martin E. Gutierrez, M.D., Director of Drug Discovery and the Phase I Unit and Chief of Thoracic Oncology at John Theurer Cancer Center. "Modifying the microbiome in combination with immunotherapy is a provocative concept. John Theurer Cancer Center is excited to be part of this pivotal study."

On January 15, 2020 Diverse Biotech, Inc. www.diversebiotech.com has reported it was preferentially selected to make a presentation at 3pm Pacific Time today at the Biotech Showcase in San Francisco, which is a key Healthcare conference running in parallel to the JP Morgan Healthcare Conference (Press release, Diverse Biotech, JAN 15, 2020, View Source [SID1234553242]).

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"Presenting at such an important congress is critical for our company and we were honored to be selected so soon into our clinical development program. The potential of our CuSP-C2 technology is extremely disruptive, validating the high interest level in our innovative chemistry," said Stella Vnook, Diverse Biotech’s Chief Executive Officer.

On January 15, 2020 Hanmi Pharmaceutical reported, led by President and CEO Se-chang Kwon and co-representative Jong-soo Woo, participated in the 38th J.P. Morgan Healthcare Conference in San Francisco during Jan. 13-15, which it presented its vision and major R&D strategies for 2020 (Press release, Hanmi, JAN 15, 2020, View Source [SID1234553241]).

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Kwon delivered the presentation at a session on Jan. 15 with key executives including Vice Chairman Gwan-sun Lee and Head of R&D center Kwee-hyun Suh attending.

Kwon highlighted significant pipelines on which the company would focus throughout 2020. He presented eight novel drug candidates among 29 pipelines as key programs, promising the company would make all-out efforts to make successful achievements, including out-licensing.

What are Hanmi’s key R&D pipelines?
The key pipelines highlighted during Kwon’s presentation included first-in-class novel drug candidates such as anti-NASH drug candidate HM15211(LAPSTriple Agonist), dual-acting anti-obesity drug candidate HM12525A(LAPSGlucagon/GLP-1 Dual Agonist) and innovative anti-obesity drug candidate HM15136(LAPSGlucagon Analog) that treats obesity with a once-weekly injection.

Attendees paid close attention to anti-NASH drug candidate HM15211(LAPSTriple Agonist) with its innovative differentiation points.

NASH is a complex chronic liver disease, which there is no currently approved therapies. An effective treatment, if any, needs to act simultaneously on multiple indices including steatosis, inflammation and fibrosis. HM15211 showed rapid and potent effect by reducing liver fat in Phase 1 multiple ascending dose study.

It is also effective in suppressing hepatic stellate cell activation and reducing pro-inflammatory cytokines. Hanmi plans to initiate Phase 2 study of HM15211 in the second quarter of this year with biopsy-proven NASH patients around the world.

Another highlighted program, HM12525A(LAPSGlucagon/GLP-1 Dual Agonist), also drew attention which Janssen has returned back its out-licensed rights last year after finishing Phase 2 study. Unlike Janssen, which tried to develop a dual-acting agonist to treat both obesity and diabetes, Hanmi is developing a first-in-class dual-acting anti-obesity drug with stronger efficacy compared to currently existing anti-obesity drug.

Especially, HM12525A is the world’s first anti-obesity treatment that works as a once-weekly injection. Its efficacy was proven to be higher than currently existing daily-injection obesity treatment in Phase 2 global trials. In a Head-to-Head comparative study with Liraglutide (branded "Saxenda"), HM12525A achieved double-digit percentage of weight loss, significant blood lipid reduction, blood pressure reduction and a tolerable safety profile.

HM15136, an innovative anti-obesity drug under development with a new mechanism of action, also drew attention. In the obese animal model, HM15136 was twice as effective as currently available drugs in weight loss and shown significant body-weight reduction when administered in combination with the anti-diabetic drug DPP-4. HM15136 targets to reduce approximately 20 percent of body weight. HM15136 completed Phase 1 single ascending dose (SAD) clinical study and the multiple ascending doses, and (MAD) trial is expected to be completed by the third quarter of this year.

Open Innovation in oncology area
Hanmi plans to expand the oncology pipeline through open innovation, including licensing-in innovative drug-making technologies from external global partners.

Last year, Hanmi has licensed in FLX475 — an oral immune-oncology asset, CCR4 antagonist developed by U.S. Biopharmaceutical Company RAPT Therapeutics, Hanmi is also developing an immune-oncology bispecific and a multi-specific antibody programs, using an antibody sequence form licensed in from another biopharmaceutical company, Phanes Therapeutics. These open innovation activities reflect Hanmi’s commitment to expanding the scope of application for in-house bispecific antibody platform technology called Pentambody.

While a clinical trial of Pan-RAF inhibitor Belvarafenib (HM95573, solid tumors), out-licensed to Genentech, is progressing smoothly, a strategy to expand the treatment indication is under review. Another clinical trial of HM43239, a FLT3 inhibitor for the treatment of acute myeloid leukemia, is going forward smoothly.

The NDA application for the oral anti-cancer drug Oraxol will be submitted in the first half of this year. Rolontis, a biologic drug to treat chemotherapy-induced neutropenia, is expected to obtain FDA approval for commercialization by October of this year, which FDA’s review of biologic license application (BLA) is already under way.

Drugs for rare diseases seen as new growth engines
Hanmi has been aggressively expanding R&D pipelines on rare diseases with high unmet medical needs, believing innovative drugs in this area will become the company’s new growth engines.

Among nearly 30 pipeline assets developed by Hanmi, 30 percent (or 8 assets) of them are developed as rare diseases treatment, having five assets have obtained the total of 12 Orphan Drug Designations (also called ODD) from the Ministry of Food and Drug Safety of Korea (MFDS), the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA) and the Medicines and Healthcare products Regulatory Agency of the United Kingdom (MHRA).

HM15136(LAPSGlucagon Analog) and HM15912(LAPSGLP-2 Analog) were designated as orphan drugs for the treatment of Congenital Hyperinsulinism (CHI) and short bowel syndrome (SBS) in the U.S. and Europe, respectively.

HM43239, a FLT3 inhibitor, was designated as a drug for Acute Myeloid Leukemia (AML) by the U.S. FDA. Furthermore, Hanmi is developing a monthly enzyme replacement treatment for patients suffering from fabry & maroteaux-lamy syndrome.

"We are developing various innovative drugs through open innovation and keeping our robust commitment to R&D amid environmental changes that are increasingly challenging to us," said Kwon. "We will do our best to strengthen Korean pharmaceutical Industry’s competitiveness with consistent, performance-based R&D and collaboration with overseas partners."