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."

On January 15, 2020 Celltrion reported the company’s vision for the next decade at the 38th Annual J.P. Morgan Healthcare Conference in San Francisco, USA (Press release, Celltrion, JAN 15, 2020, View Source [SID1234553240]). Celltrion’s Chairman Jung Jin Seo outlined the company’s strategic transition: Celltrion expects to transform from a ‘first mover’ to a ‘game changer’ by 2030.

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Celltrion’s strategy is anticipated to differentiate the company in the biosimilars landscape, building on its existing portfolio of treatments, including value added medicines or bioinnovatives such as Remsima SC, the world’s first subcutaneous formulation of infliximab. Remsima SC has the potential to offer an alternative personalised and convenient treatment option and was approved by the European Commission for patients with rheumatoid arthritis in November 2019. Celltrion Healthcare, the distribution arm of Celltrion, has also applied for a further extension to the marketing authorization of Remsima SC, to include the inflammatory bowel disease indication. This approval decision is expected in mid-2020.

Jung Jin Seo, Celltrion’s Chairman, said ‘‘Celltrion boasts a strong and dynamic product portfolio and pipeline. As we chart the company’s 2030 vision, the company hopes to launch one biosimilar product every year, reaching a total number of 18 products by 2030. Biosimilars and value added medicines which we call ‘bioinnovatives’ (innovative biosimilars) are set to be our key growth drivers in 2020. We plan to enter the new drugs and ubiquitous-healthcare business sector towards 2030."

Celltrion expects a number of significant factors will positively influence biosimilar uptake and the company’s growth in the coming years, including healthcare budgetary pressures; growing demand for low-cost alternative medicines and an increase in prescriptions for biologics. These factors have played a role in the growth of the biosimilar industry in recent years. Celltrion’s Chairman highlighted that increasingly positive sentiment from key stakeholders has contributed to Celltrion Healthcare’s growth in sales over the course of 2019 and is set to continue.

As demonstrated by the findings of a recent report from healthcare consulting firm IQVIAi, the company’s market share in major European markets has continued to grow. Remsima, the world’s first approved monoclonal antibody biosimilar has continued to overtake the market share of its reference drug, Janssen’s Remicade, with Remsima owning 59% of the market. Celltrion has also seen growth in the uptake of its rituximab biosimilar, Truxima and trastuzumab biosimilar, Herzuma, with their market shares reaching 38% and 15% respectively. These figures place Truxima and Herzuma as the leading biosimilars in terms of market share within the rituximab and trastuzumab markets.

Ho Ung Kim, Head of the Medical and Marketing Division at Celltrion Healthcare said, "As a ‘first mover’, Celltrion Healthcare has gained extensive experience in the biopharmaceutical field and is now ready to initiate a direct sales model. Celltrion Healthcare has set up its own sales network and overseas offices in 14 countries throughout Europe to secure price competitiveness, and strives to lead the global tumour necrosis factor alpha (TNF-α) inhibitors market with its innovative infliximab Remsima SC, which is projected to be worth approximately $50 billion."

As Celltrion enters the next decade, its ambitions reach beyond biosimilars and into new drug development. At the conference, Jung Jin Seo also outlined the company’s new drug development plan which is set to combine new platform technology and drug repositioning. This platform technology – the Antibody Delivery Enhancing Domain – is designed to increase the delivery efficiency of antibody-drug conjugates and their cell penetration, which has the potential to enhance cancer treatments. The company is set to create a new paradigm following innovation trends throughout the healthcare sector from 2020 to 2030.

On January 15, 2019 NanoString Technologies, Inc. (NASDAQ:NSTG), a leading provider of life science tools for translational research, reported the publication of two peer-reviewed studies using the GeoMx Digital Spatial Profiler (DSP) in the journal Nature (Press release, NanoString Technologies, JAN 15, 2020, View Source [SID1234553239]). The two independent papers published by groups at the MD Anderson Cancer Center and Lund University used GeoMx DSP for deep molecular profiling of immune cells critical for understanding response to immunotherapy in patients with metastatic melanoma.

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The first publication, "B-cells and tertiary lymphoid structures (TLS) contribute to immune checkpoint blockade response," from the team of Dr. Jennifer Wargo at The University of Texas MD Anderson Cancer Center in Houston, TX. The study combines data from GeoMx DSP, RNA-sequencing, and mass cytometry to establish the presence of clonally expanded and memory-switched B-cells in patients responding to immune checkpoint blockade. This is the second publication by the Wargo group utilizing DSP, and it follows up observations in the earlier Nature Medicine paper that used the technology to identify B-cells as predictors of response to neoadjuvant immunotherapy (View Source).

B-cells are adaptive immune cells that produce antibodies and mediate T-cell activation. Recently, the presence of B-cells in the tumor microenvironment has been recognized as a prognostic marker for immunotherapy response. However, the mechanisms by which they contribute to anti-tumor immunity are difficult to determine as their phenotype and behavior differ significantly based on location within the tumor. Notably, B-cells can concentrate in specialized lymphoid organs known as tertiary lymphoid structures (TLS). The B-cells, T-cells, and antigen presenting cells comprising the TLS have distinct phenotypes and functions when compared to non-TLS immune cells. Dissection of the roles and mechanisms that these cells play in the tumor immune environment requires the use of spatially driven multiplex technology such as GeoMx DSP.

"The multiplex GeoMx DSP platform enabled us to specifically define the immune phenotype of tumor-infiltrating and TLS-localized B-cells and T-cells in the tumor sample," said Sarah Warren, Ph.D, Senior Director, Translational Science at NanoString. "By exclusively profiling the B-cells and T-cells within the TLS, we gained insights into the specific mechanisms by which these structures influence immunotherapy outcomes."

The second study, "Tertiary lymphoid structures improve melanoma survival and immunotherapy response," led by Dr. Göran Jönsson at the Lund University in Sweden, used the GeoMx DSP platform to conduct high-plex proteomic characterization of B- and T-cells in melanoma tumors with and without Tertiary Lymphoid Structures (TLS).

"We used the GeoMx platform to better understand the mechanism by which the presence of TLS lead to improved outcomes," said Dr. Jönsson. "We found that infiltrating T-cells in tumors without TLS show a dysfunctional molecular phenotype, suggesting that distinct patterns of intratumoral adaptive immune activation may be partly driven by B-cells."

"These concurrent studies demonstrate the ability of GeoMx DSP to deliver unique and impactful biological insights that advance the field on immuno-oncology," said Brad Gray, NanoString’s president and chief executive officer.

The GeoMx Digital Spatial Profiler enables researchers to rapidly and quantitatively characterize tissue morphology with a high-throughput, high-plex RNA and protein profiling system that preserves samples for future analyses. NanoString and its collaborators have published DSP data in 12 peer-reviewed papers and presented DSP data in more than 35 abstracts at major scientific meetings, demonstrating the utility of DSP technology to address a wide range of biological questions in Formalin-Fixed Paraffin-Embedded (FFPE) tissues.