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Sysmex Obtains First Manufacturing and Marketing Approval in Japan for Blood-Based RAS Gene Mutation Testing for Colorectal Cancer

On August 2, 2019 Sysmex Corporation (HQ: Kobe, Japan; Chairman and CEO: Hisashi Ietsugu) reported that it has obtained Japanese manufacturing and marketing approval for the OncoBEAM1 RAS CRC Kit, used for blood-based circulating tumor DNA molecular testing of mutations in the RAS gene2 for colorectal cancer patients (Press release, Sysmex, AUG 2, 2019, View Source [SID1234538074]). This product is the first in vitro diagnostic reagent in Japan to be used for RAS gene mutation testing for colorectal cancer using liquid biopsy. Minimally invasive and simpler than conventional physical biopsies of tumor tissue, the new testing method provides detection results on a par with the use of tumor tissue.3 As a result, this testing method reduces the physical and mental burden on patients, expands testing opportunities, and contributes to the early-stage determination of treatment methods.

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In recent years, demand has grown for the use of liquid biopsy in the diagnosis and selection of treatment methods for cancer and other diseases. Liquid biopsy refers to using blood or other bodily fluids, which place little burden on the patient, rather than physical biopsies, which require taking samples of a cancer tumor or other tissue.4 Sysmex has defined the "resolution of medical issues through products and services" as one of the priority issues (materiality) for realizing a sustainable society and sustainable growth in corporate value for Sysmex through the creation of new technologies and markets. As one aspect of these activities, Sysmex is pursuing R&D toward the realization of personalized medicine, which involves the provision of healthcare optimized for individual patients, and the proliferation of testing to reduce the physical burden on patients.

The OncoBEAM RAS CRC Kit is used to test samples of tumor-derived DNA (circulating tumor DNA, or ctDNA) suspended in the blood of colorectal cancer patients. To help doctors determine treatment methods, this product provides auxiliary test data to determine the appropriateness for patients with colorectal cancer of the molecularly targeted drags—Cetuximab and Panitumumab (gene recombination)—, using BEAMing technology5 that detects RAS gene mutations to a high degree of sensitivity. Jointly developed between Merck KGaA, Darmstadt, Germany, and our subsidiary Sysmex Inostics, the product received CE Marking certification in March 2016, which indicates the product complies with the European IVD Directive, and is already being used for clinical applications in Europe. For the approval as an in vitro diagnostic reagent in Japan, eight medical facilities were involved in a multi-facility evaluation, including the National Cancer Center Hospital East. Gene testing using this product can be used to provide appropriate treatment opportunities for patients that would have difficulty with testing using conventional tumor tissue. Furthermore, rather than physical biopsies, this type of testing allows samples to be obtained from blood samples in a simple and minimally invasive manner. This helps reduce the physical and mental burden on the patient, shortens the time required from the start of testing, and contributes to the early-stage determination of treatment methods.

Going forward, we plan to launch the OncoBEAM RAS CRC Assay Service, an assay service for colorectal cancer using liquid biopsy to detect RAS gene mutations in the blood, at the Sysmex IMP laboratory, located in the Kobe Biomedical Innovation Cluster. To increase the opportunities for more patients to receive the testing, we plan to apply for Japan’s national insurance coverage for this product.

By providing new cancer diagnostic methods to patients at the earliest possible date, such as the OncoBEAM RAS CRC Kit, as well as the OncoGuideTM NCC Oncopanel System,5 which received insurance coverage in Japan on June 1, 2019 for use in cancer genome profiling, Sysmex aims to take the global lead in realizing personalized medicine, contributing to patient quality of life and the advancement of healthcare.

Name: OncoBEAM RAS CRC Kit
Use: To detect RAS (KRAS and NRAS) gene mutations in genomic DNA extracted from plasma
(Auxiliary use to determine the appropriateness of Cetuximab and Panitumumab (gene recombination) for patients with colorectal cancer)
Target market: Japan
Target institutions: Healthcare institutions and clinical testing centers in Japan, other
In vitro diagnostics manufacturing and marketing approval number: 30100EZX00010000 (Obtained on July 19, 2019)
Reference

・
April 6, 2016 press release entitled "New Liquid Biopsy RAS Testing for metastatic colorectal cancer patients now available for clinical practices"
View Source

Terminology

OncoBEAM:
The name of Sysmex’s technology to detect minute gene mutations circulating in the blood with a high degree of sensitivity using BEAMing technology. BEAMing technology is an acronym for "bead, emulsion, amplification and magnetics", a gene analysis method developed at Johns Hopkins University combining digital PCR and flow cytometry technologies for highly sensitive analysis of genetic mutations.

RAS gene:
As the likelihood is high that patients with RAS gene (KRAS/NRAS gene) mutations will not benefit (prolongation of life, tumor reduction) from the administration of anti-EGFR drugs, companion diagnostics may be performed to treat the gene mutation first.

According to the results of multi-facility evaluation, determination results using this method are on a par with those of conventional RAS gene mutation testing using tumor tissue. Source: British Journal of Cancer volume 120, pages 982–986 (2019)

The Guidance on Genetic Testing in the Treatment of Coloretal Cancer Vol. 4.1 (May 2019), published by the Japanese Society of Medical Oncology, indicates the necessity of using liquid biopsy for colorectal cancer and the clinical utility of ctDNA testing.

OncoGuide NCC Oncopanel System (medical device manufacturing and marketing approval No.:23000BZX00398000):
(Reference) May 31, 2019 press release entitled "The OncoGuide NCC Oncopanel System Receives Insurance Coverage for Use in Cancer Genome Profiling" View Source

PFIZER ANNOUNCES CLOSING OF JOINT VENTURE WITH GLAXOSMITHKLINE TO CREATE A PREMIER GLOBAL CONSUMER HEALTHCARE COMPANY

On August 1, 2019 Pfizer Inc. (NYSE: PFE) reported the closing of its joint venture with GlaxoSmithKline plc (NYSE: GSK) to combine the parties’ respective consumer healthcare businesses to create the world’s largest over-the-counter (OTC) business with robust iconic brands (Press release, Pfizer, AUG 1, 2019, View Source [SID1234553276]). As previously announced, under the terms of the transaction, Pfizer owns a 32% equity stake in the joint venture and GSK owns 68%. The combined business, which will operate globally as GSK Consumer Healthcare, will be led by CEO Brian McNamara.

"The successful closing of the joint venture represents an important and exciting step in forming a world-class pure-play consumer healthcare business," said Albert Bourla, Chief Executive Officer, Pfizer. "It also furthers Pfizer’s evolution to be a more focused, global leader in science-based, innovative medicines that delivers breakthroughs that change patients’ lives and creates long-term value for shareholders."

The combined brand portfolio forms the world’s largest OTC business with leadership positions in pain relief, respiratory and vitamins, minerals and supplements, and therapeutic oral health. In addition, operating together, the two business will hold the number one OTC position in the U.S. and the number two OTC position in China – the two biggest OTC markets in the world.

As part of the agreement, three out of the nine members of the joint venture’s board have been appointed by Pfizer and include John Young, Group President, Chief Business Officer; Douglas Giordano, Senior Vice President, Worldwide Business Development and Bryan Supran, Senior Vice President, Deputy General Counsel. The transaction is expected to deliver $650 million in peak cost synergies and to be slightly accretive on a full-year basis for Pfizer in each of the first three years following the closing.

GSK intends to separate the joint venture as an independent company via a demerger of its equity interest to its shareholders and a listing of the joint venture on the UK equity market. GSK will have the sole right to decide whether and when to initiate a separation and listing for a period of five years following the closing. GSK may also sell all or part of its stake in the joint venture in a contemporaneous IPO.

Should a separation and listing occur during the first five years after closing, Pfizer has the option to participate through the distribution of its equity interest in the joint venture to its shareholders or the sale of its equity interest in a contemporaneous IPO. After the fifth anniversary of the closing, both GSK and Pfizer will have the right to decide whether and when to initiate a separation and public listing of the joint venture.

Kaleido Biosciences Reports Second Quarter 2019 Financial Results and Provides Corporate Update

On August 1, 2019 Kaleido Biosciences, Inc. (Nasdaq: KLDO), a clinical-stage healthcare company with a chemistry-driven approach to leveraging the potential of the microbiome organ to treat disease and improve human health, reported financial results for the second quarter ended June 30, 2019, and provided a corporate update (Press release, Kaleido Biosciences, AUG 1, 2019, View Source [SID1234540067]).

"In the second quarter we made important progress with our pipeline and now have five clinical studies underway with our Microbiome Metabolic Therapy (MMT) candidates," said Alison Lawton, President and Chief Executive Officer of Kaleido. "We initiated Kaleido’s first Phase 2 clinical trial with the advancement of KB195 for urea cycle disorders (UCD) under an IND. For our KB174 program, we completed enrollment in a dosing study in healthy subjects and continued to progress our clinical study in patients with cirrhosis. We also advanced a third MMT, KB109, into a clinical study in patients colonized with multi-drug resistant pathogens. We look forward to a number of key milestones expected during the second half of the year, including data from three clinical studies in two different patient populations."

Recent Highlights

Received approval from regulatory authorities in the United Kingdom and Belgium for the Company’s clinical trial application (CTA) for its Phase 2 clinical trial of KB195 in UCD

Initiated the Phase 2 clinical trial evaluating KB195 in patients with UCD

Initiated a non-IND clinical study of KB109 in patients colonized with multi-drug resistant pathogens

Expanded Kaleido’s Scientific Advisory Board to include six leading experts in microbiology, chemistry and microbiome research across a variety of therapeutic areas:

Laurie H. Glimcher, M.D., President and CEO, Dana-Farber Cancer Institute, Director, Dana-Farber/Harvard Cancer Center, and Richard and Susan Smith Professor of Medicine, Harvard Medical School;

Robert Jenq, M.D., Assistant Professor in the Department of Genomic Medicine, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center;

C. Ronald Kahn, M.D., Head of the Section on Integrative Physiology and Metabolism, Past President & CEO, Joslin Diabetes Center, and Mary K. Iacocca Professor of Medicine, Harvard Medical School;

Laura L. Kiessling, Ph.D., Novartis Professor of Chemistry, Massachusetts Institute of Technology;

Max Nieuwdorp, M.D., Professor of Internal Medicine and endocrinologist, University of Amsterdam’s Faculty of Medicine (AMC-UvA); and

Peter J. Turnbaugh, Ph.D., Associate Professor, Department of Microbiology and Immunology, G.W. Hooper Research Foundation, and Investigator, Chan Zuckerberg Biohub, University of California, San Francisco.

Appointed Jerald Korn as General Counsel and Corporate Secretary

Members of Kaleido’s leadership team were featured speakers at the 4th Microbiome Movement – Drug Development Summit held June 26-28, 2019 in Boston

Anticipated Key Milestones
Safety and tolerability data from a non-IND clinical study of KB195 in patients with UCD accepted for presentation at the annual Society for the Study of Inborn Errors of Metabolism Symposium, Sept 3-6, 2019

Data from a non-IND clinical study of KB174 in healthy subjects to explore dosing expected in Q4 2019

Data from a non-IND clinical study of KB174 in patients with well-compensated cirrhosis expected in Q4 2019
Second Quarter 2019 Financial Results
For the second quarter ended June 30, 2019, Kaleido reported a net loss of approximately $24.6 million, or $0.83 per share, basic and diluted, compared to a net loss for the quarter ended June 30, 2018 of $12.3 million, or $2.57 per share, basic and diluted.
Total operating expenses for the quarter ended June 30, 2019 were $25.0 million compared to $12.4 million for the quarter ended June 30, 2018.
Research and development expenses for the quarter ended June 30, 2019 were $18.8 million, compared to $9.1 million for the quarter ended June 30, 2018. The increase in expense for the quarter was driven by an increase in external manufacturing and research costs to support the production of study material used in preclinical studies, human clinical studies, and clinical trials as well as clinical research organizations costs associated with MMT candidates for 2019.
General and administrative expenses were $6.2 million for the quarter ended June 30, 2019, compared to $3.2 million for the quarter ended June 30, 2018. The increase in general and administrative expenses compared to the same quarter last year was driven by increased professional services and employee-related costs as the Company continues to expand its infrastructure to support its growth.
Total operating expenses for the quarter ended June 30, 2019 include non-cash stock-based compensation expense of $2.4 million compared to $0.5 million of non-cash stock-based compensation expense for the quarter ended June 30, 2018.
Cash and cash equivalents were $100.0 million as of June 30, 2019.

About Microbiome Metabolic Therapies (MMT)
Kaleido’s Microbiome Metabolic Therapies, or MMTs, are designed to drive the function and distribution of the microbiome organ’s existing microbes in order to decrease or increase the production of metabolites, or to advantage or disadvantage certain bacteria in the microbiome community. The Company’s initial MMT candidates are targeted glycans that are orally administered, have limited systemic exposure, and are selectively-metabolized by enzymes in the microbiome. Kaleido utilizes its human-centric discovery and development platform to study MMTs in microbiome samples from healthy subjects and patients in an ex vivo setting, followed by advancing MMT candidates rapidly into non-Investigational New Drug (non-IND) clinical studies in healthy subjects and patients. These non-IND human clinical studies are conducted under regulations supporting research with food, measuring safety, tolerability and potential markers of effect. For MMT candidates that are further developed as therapeutics, the Company conducts clinical trials under an IND or regulatory equivalent outside the U.S., and in Phase 2 or later development.

Pfenex and Arcellx Announce a Development, Evaluation and License Agreement

On August 1, 2019 Pfenex Inc. (NYSE American: PFNX) and Arcellx, Inc. reported a Development, Evaluation and License agreement under which Arcellx gains access to the proprietary Pfenex Expression Technology platform to advance multiple proprietary sparX proteins that activate, silence and reprogram Antigen- Receptor Complex T cell based therapies (Press release, Pfenex, AUG 1, 2019, View Source [SID1234538434]). Pfenex has successfully completed expression screening and process development activities for the first sparX program. Technology transfer of the program to a cGMP manufacturing facility is underway. The success of the first program has encouraged both parties to initiate a second sparX program, both programs are focused on the treatment of hematologic malignancies.

Under the terms of the agreement, Pfenex is eligible to receive development funding in addition to development, regulatory and commercial milestones ranging from $2.6M up to $18M for each product incorporating a SparX protein expressed using the Pfenex Expression Technology as well as royalties on worldwide sales of any such products.

"Our collaboration with Arcellx fits our strategy of leveraging the Pfenex protein production platform to advance our products and those of our collaborators. Pfenex’s success with the first sparX program further validates the versatility of our proprietary protein expression platform and the quality of our development capabilities. We look forward to collaborating with Arcellx through the combination of our respective platforms in support of developing new therapies for patients in need." said Eef Schimmelpennink, chief executive officer of Pfenex.

"The uniquely efficient protein expression technologies and process expertise developed by Pfenex have been critical in accelerating development of our first sparX program," said David Hilbert, chief executive officer of Arcellx. "Our continued development of new sparX programs provides the basis for a forward looking Pfenex collaboration involving multiple sparX proteins with the potential to revolutionize immune cell therapies."

La Jolla Pharmaceutical Company Announces Financial Results for the
Three and Six Months Ended June 30, 2019 and Highlights Recent Corporate Progress

On August 1, 2019 La Jolla Pharmaceutical Company (Nasdaq: LJPC), a leader in the discovery, development and commercialization of innovative therapies intended to significantly improve outcomes in patients suffering from life-threatening diseases, reported financial results for the three and six months ended June 30, 2019 and highlighted recent corporate progress (Press release, La Jolla Pharmaceutical, AUG 1, 2019, View Source [SID1234538315]).

Recent Corporate Progress

GIAPREZATM (angiotensin II)

Net Sales: For the three months ended June 30, 2019, GIAPREZA net sales were $5.7 million, up 258% from the same period in 2018, and up 30% from the three months ended March 31, 2019. For the six months ended June 30, 2019, GIAPREZA net sales were $10.1 million, up 320% from the same period in 2018.

Positive CHMP Opinion: In June 2019, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for La Jolla’s Marketing Authorisation Application (MAA) for GIAPREZA for the treatment of refractory hypotension in adults with septic or other distributive shock. The CHMP’s positive opinion was sent to the European Commission (EC), which has the authority to approve medicines for the 28 European Union member countries. Approval would also be recognized in Iceland, Norway and Liechtenstein. We expect a final approval decision on the GIAPREZA MAA by the EC in the third quarter of 2019.

Investigational Products

Breakthrough Therapy Designation and Orphan Drug Designation Received from the FDA for LJPC-0118 (artesunate): The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation and Orphan Drug designation for LJPC-0118 for the treatment of malaria in April 2019 and July 2019, respectively. The active pharmaceutical ingredient in LJPC-0118, artesunate, was demonstrated to be superior to quinine in reducing mortality in patients with severe falciparum malaria infection in two randomized, controlled, clinical studies. We plan to file a New Drug Application (NDA) for LJPC-0118 with the FDA in the fourth quarter of 2019.

Positive Results Announced from Pre-Specified Interim Analysis of Phase 2 Study of LJPC-401 in Patients with Hereditary Hemochromatosis: In June 2019, we announced positive results from the pre-specified interim analysis of our Phase 2 study of LJPC-401 (synthetic human hepcidin) in patients with hereditary hemochromatosis (HH). The interim analysis of efficacy included 26 patients who had reached the end of the 16-week treatment period, and the interim analysis of safety included 60 randomized patients. Treatment with LJPC-401 resulted in a statistically significant reduction in transferrin saturation (TSAT) from baseline to the end of treatment (16 weeks), the primary efficacy endpoint of the study: LJPC‑401‑treated patients had a mean reduction in TSAT of 42% compared to placebo-treated patients who had a mean reduction of 6% (p<0.0001). The requirement for and frequency of phlebotomy procedures, a key secondary endpoint of the study, also was statistically significant: LJPC-401-treated patients had 0.06 phlebotomies per month compared to placebo-treated patients who had 0.41 phlebotomies per month (p=0.003). There were 3 phlebotomies in 2 LJPC-401-treated patients and 24 phlebotomies in 9 placebo-treated patients. LJPC-401 was well tolerated. The most frequent treatment-emergent adverse events (TEAEs) were injection site reactions (ISRs). The ISRs were all mild or moderate in severity, and no ISRs resulted in treatment discontinuation. As of the interim analysis, there were no serious TEAEs reported. We expect to announce top-line results of LJ401-HH01 in the fourth quarter of 2019.

"We are pleased with the progress made in the first half of 2019, which included the achievement of significant milestones for each of GIAPREZA, LJPC-0118 and LJPC-401," said George Tidmarsh, M.D., Ph.D., La Jolla’s President and Chief Executive Officer. "In the second half of 2019, we look forward to continued growth in GIAPREZA net sales, the final approval decision

on the GIAPREZA MAA by the EC, our filing of an NDA for LJPC-0118 with the FDA and top-line results of our Phase 2 study of LJPC-401 in patients with HH."

Financial Results

For the three and six months ended June 30, 2019, GIAPREZA net sales were $5.7 million and $10.1 million, respectively, compared to $1.6 million and $2.4 million, respectively, for the same periods in 2018. La Jolla’s net loss for the three and six months ended June 30, 2019 was $30.4 million and $62.1 million, or $1.12 per share and $2.29 per share, respectively, compared to $52.8 million and $103.3 million, or $2.02 per share and $4.22 per share, respectively, for the same periods in 2018. La Jolla continues to expect full-year 2019 GIAPREZA net sales of $24 million to $28 million.

As of June 30, 2019, La Jolla had $123.4 million in cash, compared to $172.6 million as of December 31, 2018. Net cash used in operating activities for the three and six months ended June 30, 2019 was $16.5 million and $49.2 million, respectively, compared to $37.5 million and $83.4 million, respectively, for the same periods in 2018. La Jolla has no debt. La Jolla continues to expect that its net cash used in operating activities in 2019 will be $89 million to $94 million.

About GIAPREZA

In December 2017, GIAPREZA (angiotensin II) was approved by the U.S. Food and Drug Administration (FDA) as a vasoconstrictor indicated to increase blood pressure in adults with septic or other distributive shock. GIAPREZA mimics the body’s endogenous regulatory peptide that is central to the renin-angiotensin-aldosterone system to increase blood pressure. Prescribing information for GIAPREZA is available at www.giapreza.com. GIAPREZA is marketed by La Jolla Pharmaceutical Company on behalf of La Jolla Pharma, LLC, its wholly owned subsidiary.

IMPORTANT SAFETY INFORMATION

Contraindications

None

Warnings and Precautions

There is a potential for venous and arterial thrombotic and thromboembolic events in patients who receive GIAPREZA. Use concurrent venous thromboembolism (VTE) prophylaxis.

Adverse Reactions

The most common adverse reactions that were reported in greater than 10% of GIAPREZA-treated patients were thromboembolic events.

Drug Interactions

Angiotensin converting enzyme (ACE) inhibitors may increase response to GIAPREZA. Angiotensin II receptor blockers (ARB) may reduce response to GIAPREZA.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

For additional information, please see Full Prescribing Information for the United States.

About LJPC-0118

LJPC-0118 is La Jolla’s investigational product for the treatment of severe malaria. The active pharmaceutical ingredient in LJPC-0118, artesunate, was demonstrated to be superior to quinine in reducing mortality in patients with severe falciparum malaria infection in two randomized, controlled, clinical studies. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation and Orphan Drug designation for LJPC-0118 for the treatment of malaria in April 2019 and July 2019, respectively. La Jolla plans to file a New Drug Application (NDA) for LJPC-0118 with the FDA in the fourth quarter of 2019 for the treatment of severe malaria. Severe malaria is a serious and sometimes fatal disease caused by a parasite that

commonly infects a certain type of mosquito, which feeds on humans. Symptoms include but are not limited to: fever, chills, sweating, hypoglycemia and shock. Severe malaria is often complicated by central nervous system infections that may lead to delirium, which may progress to coma. Infections usually occur a few weeks after being bitten. In 2017, an estimated 219 million cases of malaria occurred worldwide, with an estimated 200 million of these cases occurring in the World Health Organization (WHO) African Region, and, in 2013, the global annual incidence of severe malaria was estimated to be 2 million cases. In 2017, an estimated 435,000 people died from malaria worldwide.

About LJPC-401

LJPC-401, a clinical-stage investigational product, is La Jolla’s proprietary formulation of synthetic human hepcidin. Hepcidin, an endogenous peptide hormone, is the body’s naturally occurring regulator of iron absorption and distribution. In healthy individuals, hepcidin prevents excessive iron accumulation in vital organs, such as the liver and heart, where it can cause significant damage and even result in death. La Jolla is developing LJPC-401 for the potential treatment of iron overload, which occurs as a result of primary iron overload diseases such as hereditary hemochromatosis (HH), or secondary iron overload diseases such as beta thalassemia (BT), sickle cell disease (SCD), myelodysplastic syndrome (MDS) and polycythemia vera. The European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) has designated LJPC‑401 as an orphan medicinal product for the treatment of beta thalassemia intermedia and major and SCD.