On November 6, 2019 Moderna, Inc., (Nasdaq: MRNA) a clinical stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients,reported financial results for the third quarter of 2019 (Press release, Moderna Therapeutics, NOV 6, 2019, View Source [SID1234550523]).

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New updates and recent progress include:

Infectious Diseases

Positive interim results announced from Phase 1 CMV vaccine (mRNA-1647) study; Moderna is advancing mRNA-1647 to a dose-confirmation Phase 2 study in the near term while planning for a pivotal Phase 3 study
First participant dosed in Phase 1b age de-escalation study of hMPV+PIV3 vaccine (mRNA-1653)
FDA granted Fast Track designation for Zika vaccine (mRNA-1893)
Immuno-Oncology

First patient dosed in Phase 2 PCV (mRNA-4157) study in patients with resected melanoma
OX40L (mRNA-2416) Phase 2 expansion cohort in ovarian cancer to focus only on the combination with durvalumab (IMFINZI)
Rare Diseases

Positive interim results announced from Phase 1 chikungunya antibody (mRNA-1944) study; dosing of two additional cohorts planned to begin in the near term
Phase 1/2 MMA (mRNA-3704) study is actively recruiting patients at U.S. sites following a protocol amendment expanding the eligibility criteria to patients 8 years and older
FDA granted Fast Track designation for PA program (mRNA-3927); study start-up is ongoing for the open-label, multi-center Phase 1/2 study of multiple ascending doses of mRNA-3927 in pediatric patients with PA in the U.S.
Research

Moderna announced a multi-year mRNA immunotherapy research collaboration with Harvard University to explore fundamental immunological processes and identify potential therapeutic opportunities
"The positive Phase 1 cytomegalovirus vaccine results announced this quarter represent an important step toward the prevention of congenital CMV infections. These data resulted from investment in our mRNA technology platform, which has now generated six positive infectious disease vaccine clinical readouts. Additionally, the recent positive Phase 1 chikungunya antibody results help de-risk a delivery technology shared by our rare disease programs, further validating our approach into new areas where mRNA medicines have the potential to treat a wide range of diseases," said Stéphane Bancel, Moderna’s chief executive officer. "We ended the quarter with a strong cash balance of $1.34 billion and up to $187 million in additional untapped grant funding, giving us up to $1.5 billion to invest in the Company moving forward. We expect investment levels in 2020 to be approximately $500 million, similar to 2019. We intend to expand our group of biopharmaceutical partners and bring in additional non-dilutive grant and government funding as we advance our development pipeline and create new modalities."

Moderna currently has 21 mRNA development candidates in its portfolio with 13 in clinical studies. Across Moderna’s pipeline, more than 1,400 participants have been enrolled in clinical studies. The Company’s updated pipeline can be found at www.modernatx.com/pipeline. Moderna and collaborators have published more than 40 peer-reviewed papers, including 23 over the last 12 months.

The Company has established a wide range of strategic alliances with leading biopharmaceutical companies, as well as government-sponsored and private organizations focused on global health initiatives. Strategic collaborators contribute their therapeutic expertise, help to validate Moderna’s mRNA platform and have provided a quarter of the Company’s total capital to date. As of September 30, 2019, Moderna had up to $187 million in additional funding available from grants (including amounts not yet committed)1.

Summary of Program Highlights by Modality

Prophylactic vaccines: Moderna is developing vaccines against viral diseases where there is unmet medical need – including complex vaccines with multiple antigens for common diseases, as well as vaccines against epidemic and pandemic threats to global public health.

Cytomegalovirus (CMV) vaccine (mRNA-1647): At the Company’s annual R&D Day, Moderna announced positive data from the three-month interim analysis of safety and immunogenicity of the Phase 1 study of mRNA-1647. Vaccination immunized seronegative participants to levels consistent with or above seropositive titers and boosted baseline titers in seropositive participants. The vaccine was generally well-tolerated; the most common solicited local adverse event was injection site pain, and the most common systemic adverse events were headaches and chills. The next readout from the study will be from a seven-month interim analysis. Moderna also recently announced that it is advancing mRNA-1647 to a dose-confirmation Phase 2 study in the near term. Preparation has also begun for a pivotal Phase 3 study designed to evaluate the efficacy of mRNA-1647 against primary CMV infection. The Phase 2 study will test the intended Phase 3 formulation, which contains the same proprietary lipid nanoparticle (LNP) used in this Phase 1 study. mRNA-1647 is wholly owned by Moderna.
Human metapneumovirus (hMPV) and parainfluenza type 3 (PIV3) vaccine (mRNA-1653): The first participant in the Phase 1b age de-escalation study of hMPV+PIV3 vaccine (mRNA-1653) has been dosed. Moderna previously announced positive data from the second pre-planned interim analysis of the Phase 1 study of mRNA-1653. mRNA-1653 is wholly owned by Moderna.
Respiratory syncytial virus (RSV) vaccine (mRNA-1172 or V172): The Phase 1 study of mRNA-1172 led by Merck is ongoing.
Zika virus vaccine (mRNA-1893): In August, Moderna announced that the U.S. Food and Drug Administration (FDA) granted Fast Track designation for mRNA-1893. The Phase 1 study of mRNA-1893 is ongoing.
Presentations of note: Moderna presented data from its prophylactic vaccines at IDWeek, World Vaccine Congress Europe and the International Society of Vaccines Annual Congress, including interim Phase 1 hMPV+PIV3 vaccine (mRNA-1653) data, preclinical Zika vaccine (mRNA-1893) data and interim Phase 1 CMV vaccine (mRNA-1647) data.
Cancer Vaccines: These programs focus on stimulating a patient’s immune system with antigens derived from tumor-specific mutations to enable the immune system to elicit a more effective anti-tumor response.

Personalized cancer vaccine (PCV) (mRNA-4157): The first patients have been dosed in the randomized Phase 2 study investigating a 1 mg dose of mRNA-4157 in combination with Merck’s pembrolizumab (KEYTRUDA), compared to pembrolizumab alone, for the adjuvant treatment of high-risk resected melanoma. The Phase 1 study is ongoing.
PCV (NCI-4650): The National Cancer Institute (NCI) Phase 1 study of NCI-4650 as a monotherapy for patients with advanced metastatic cancers has completed enrollment with five participants. No responses to monotherapy in this heavily pretreated group were observed. NCI-4650 uses Moderna’s mRNA technology but uses a different neoantigen selection process and study design than Moderna’s Phase 1 mRNA-4157 study. Interim results from NCI-4650 were reported at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June and have been submitted for publication.
KRAS vaccine (mRNA-5671 or V941): The Phase 1 open-label, multi-center study to evaluate the safety and tolerability of mRNA-5671 both as a monotherapy and in combination with pembrolizumab, led by Merck, is ongoing.
Intratumoral Immuno-Oncology: These programs aim to drive anti-cancer T cell responses by injecting mRNA therapies directly into tumors.

OX40L (mRNA-2416): Based on available data, the Company has decided to focus its development of mRNA-2416 for the treatment of patients with ovarian cancer in combination with durvalumab (IMFINZI), a PD-L1 inhibitor. The safety cohort of the combination arm (mRNA-2416 and durvalumab) of this Phase 1/2 study is ongoing and will be followed by a Phase 2 expansion cohort in patients with advanced ovarian carcinoma. The Company will not move forward with the mRNA-2416 monotherapy ovarian cancer arm of this study.
OX40L + IL23 + IL36γ (Triplet) (mRNA-2752): The Phase 1 trial evaluating mRNA-2752 as a single agent and in combination with durvalumab in patients with accessible solid tumors and lymphomas is ongoing. mRNA-2752 is an investigational mRNA immuno-oncology therapy that encodes a novel combination of three immunomodulators.
IL12 (MEDI1191): The Phase 1 open-label, multi-center study of intratumoral injections of MEDI1191 alone and in combination with durvalumab in patients with advanced solid tumors, led by AstraZeneca, is ongoing. MEDI1191 is an mRNA encoding for IL12, a potent immunomodulatory cytokine.
Systemic Secreted Therapeutics: In this modality, mRNA is delivered systemically to create proteins that are secreted outside the cell with the aim of producing pharmaceutically active proteins with therapeutic effects across the human body.

Antibody against the chikungunya virus (mRNA-1944): Moderna recently announced positive interim data from the first analysis of safety and activity in the Phase 1 study evaluating escalating doses of mRNA-1944 administered via intravenous infusion in healthy adults. mRNA-1944 successfully encoded for functional antibody (CHKV-24) in humans at all dose levels tested (0.1, 0.3 and 0.6 mg/kg). Antibody level predicted to protect against chikungunya infection was achieved within hours and was projected to be maintained for at least 16 weeks at the middle and high doses. No significant adverse events were observed at the low and middle doses; infusion-related adverse events were observed at the high dose, which resolved spontaneously without treatment. These results mark the first systemic mRNA therapeutic to show production of therapeutic levels of a secreted protein in humans, demonstrating predictable translation from preclinical species. mRNA-1944 uses the same proprietary LNP delivery technology as the systemic intracellular therapeutics targeting MMA and PA. The safety and pharmacology of mRNA-1944 will continue to be explored in two additional cohorts: one cohort with steroid premedication at the 0.6 mg/kg dose and a second cohort with two doses of 0.3 mg/kg (without steroid premedication) given one week apart.
Presentation of note: In October, Moderna presented data from the Phase 1 study of its chikungunya antibody (mRNA-1944) at the Annual Meeting of the Oligonucleotide Therapeutics Society.
Systemic Intracellular Therapeutics: These programs aim to deliver mRNA into cells within target organs as a therapeutic approach for diseases caused by a missing or defective protein.

Methylmalonic acidemia (MMA) (mRNA-3704): The Phase 1/2 open-label, dose escalation study is actively recruiting patients for the first cohort at U.S. sites following a protocol amendment expanding the eligibility criteria to patients 8 years and older. This study is evaluating mRNA-3704 for the treatment of MMA due to methylmalonyl-CoA mutase (MUT) deficiency. The Company is planning to initiate several sites outside the U.S. and recently received Medicines and Healthcare products Regulatory Agency (MHRA) approval in the U.K. The objectives of this study are to evaluate safety and tolerability, assess the pharmacodynamic response and characterize the pharmacokinetic profile of mRNA-3704. This is Moderna’s first rare disease program to advance into clinical testing. The mRNA-3704 program uses the same LNP formulation as mRNA-1944.
Propionic acidemia (PA) (mRNA-3927): This quarter, Moderna announced an open Investigational New Drug (IND) and FDA Fast Track designation for mRNA-3927. Study start-up is ongoing for the open-label, multi-center Phase 1/2 study of multiple ascending doses of mRNA-3927 in pediatric patients with PA in the U.S. The objectives of this study are to evaluate the safety and tolerability of mRNA-3927 administered via IV infusion, assess the pharmacodynamic response as assessed by changes in plasma biomarkers and characterize the pharmacokinetic profile of mRNA-3927. The mRNA-3927 program uses the same LNP formulation as mRNA-1944.
MMA and PA Natural History Study (MaP): As of October 2019, a total of 87 patients have been enrolled in the study (37 MMA, 50 PA). This is a global, multi-center, non-interventional study for patients with confirmed diagnosis of MMA due to MUT deficiency or PA and is designed to identify and correlate clinical and biomarker endpoints for these disorders.
Information about each development candidate in Moderna’s pipeline, including those discussed in this press release, can be found on the investor relations page of its website: View Source

Research Update

In September, Moderna announced a multi-year research collaboration with Harvard University with the goal of identifying and developing novel therapeutic approaches that could improve the lives of patients with immunological diseases. Additional funding from Moderna to Harvard Medical School (HMS) has established an initiative at HMS called the Alliance for RNA Therapies for the Modulation of the Immune System (ARTiMIS), which will enable basic science research in the field of immunology using Moderna’s mRNA and nanoparticle delivery technology.
Corporate Updates

Moderna appointed Tracey Franklin as Chief Human Resources Officer.
Moderna was named a top biopharmaceutical employer by Science for the fifth consecutive year.
The Company will host its Manufacturing and Digital Day on March 4, 2020 at its Norwood, MA facility.
Financial Guidance

The Company expects to end 2019 with approximately $1.20 billion in cash, cash equivalents and investments.
For 2019, the Company expects net cash used in operating activities and purchases of property and equipment to total approximately $500 million.
In 2020, the Company expects net cash used in operating activities and purchases of property and equipment to be similar to 2019, between $490 million and $510 million.
Third Quarter 2019 Financial Results

Cash Position: Cash, cash equivalents and investments as of September 30, 2019 and December 31, 2018 were $1.34 billion and $1.69 billion, respectively.
Net Cash Used in Operating Activities: Net cash used in operating activities was $363.2 million for the nine months ended September 30, 2019 compared to $239.8 million for the same period in 2018. Net cash used in operating activities includes $22.0 million and $25.0 million for the nine months ended September 30, 2019 and 2018, respectively, of in-licensing payments to Cellscript, LLC and its affiliate, mRNA RiboTherapeutics, Inc., to sublicense certain patent rights. After the first quarter of 2019, we have no further in-licensing payment obligations to Cellscript and its affiliate.
Cash Used for Purchases of Property and Equipment: Cash used for purchases of property and equipment was $24.9 million for the nine months ended September 30, 2019 compared to $92.1 million for the same period in 2018.
Revenue: Total revenue was $17.0 million for the three months ended September 30, 2019 compared to $41.8 million for the same period in 2018. Total revenue was $46.2 million for the nine months ended September 30, 2019 compared to $99.6 million for the same period in 2018. On January 1, 2019, we adopted Accounting Standards Codification (ASC) Topic 606, Revenue from Contracts with Customers (ASC 606), using the modified retrospective transition method applied to those contracts which were not completed as of January 1, 2019. The total revenue decreases in 2019 were due to decreases in collaboration revenue across all our strategic alliances, particularly AstraZeneca and Merck, largely driven by our adoption of ASC 606. Total revenue under the previous revenue recognition standard would have been $24.7 million and $80.2 million for the three months and nine months ended September 30, 2019, respectively.
Research and Development Expenses: Research and development expenses were $119.7 million for the three months ended September 30, 2019 compared to $109.1 million for the same period in 2018. Research and development expenses were $378.8 million for the nine months ended September 30, 2019 compared to $303.7 million for the same period in 2018. The increases were primarily attributable to an increase in personnel related costs, including stock-based compensation, with additional increases for the nine months ended September 30, 2019 being driven by higher clinical trial and manufacturing costs, an increase in lab supplies and materials, and an increase in consulting and outside services.
General and Administrative Expenses: General and administrative expenses were $28.2 million for the three months ended September 30, 2019 compared to $18.5 million for the same period in 2018. General and administrative expenses were $84.0 million for the nine months ended September 30, 2019 compared to $56.2 million for the same period in 2018. These increases were mainly due to the additional costs of operating as a publicly traded company, including an increase in personnel related costs and stock-based compensation, consulting and outside services, legal and insurance related costs.
Net Loss: Net loss was $123.2 million for the three months ended September 30, 2019 compared to $80.3 million for the same period in 2018. Net loss was $390.9 million for the nine months ended September 30, 2019 compared to $243.3 million for the same period in 2018.
Investor Call and Webcast Information

Moderna will host a live conference call and webcast at 8:00 a.m. ET on Wednesday, November 6, 2019. To access the live conference call, please dial 866-922-5184 (domestic) or 409-937-8950 (international) and refer to conference ID 6287715. A webcast of the call will also be available under "Events and Presentations" in the Investors section of the Moderna website at View Source The archived webcast will be available on Moderna’s website approximately two hours after the conference call and will be available for 30 days following the call.

On November 6, 2019 FORMA Therapeutics, Inc., a clinical stage biopharmaceutical company focused on rare hematological diseases and cancers, reported that three abstracts have been accepted for presentation at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held in Orlando, Florida from December 7-10, 2019 (Press release, Forma Therapeutics, NOV 6, 2019, View Source [SID1234550538]).

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Three oral presentations on lead assets will feature data: olutasidenib, a next generation inhibitor of mutated isocitrate dehydrogenase 1 (IDH1m) in development for the treatment of patients with relapsed/refractory acute myeloid leukemia (RR/AML) or myelodysplastic syndrome (MDS), and patients with glioma and other solid tumors with an IDH1 mutation; and FT-4202, a novel selective red blood cell (RBC) pyruvate kinase (PKR) activator in development as a potentially disease-modifying therapy for the treatment of sickle cell disease (SCD). A poster presentation will feature data for a FORMA-discovered asset licensed to Celgene Corporation, FT-1101, an oral, structurally distinct and potent pan-inhibitor of the Bromodomain and Extra-Terminal (BET) epigenetic protein family.

The accepted abstracts are available online through the ASH (Free ASH Whitepaper) conference website, View Source, and include:

Oral Presentations

Title: Olutasidenib (FT-2102), an IDH1m Inhibitor As a Single Agent or in Combination with Azacitidine, Induces Deep Clinical Responses with Mutation Clearance in Patients with Acute Myeloid Leukemia Treated in a Phase 1 Dose Escalation and Expansion Study

Date/Time: Saturday, December 7, 2019 at 2:30 p.m. ET
Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Novel Targets and Combinations
Abstract: 231
Location: Orange County Convention Center, Chapin Theater (W320)
Presenter: Justin Watts, MD. Assistant Professor University of Miami, Sylvester Comprehensive Cancer Center

Title: Olutasidenib (FT-2102), Induces Rapid Remissions in Patients with IDH1-Mutant Myelodysplastic Syndrome: Results of Phase 1/2 Single Agent Treatment and Combination with Azacitidine

Date/Time: Monday, December 9, 2019 at 10:45 a.m. ET
Session: 637. Myelodysplastic Syndromes – Clinical Studies: Targeting Gene Mutations in MDS
Abstract: 674
Location: Orange County Convention Center, W311ABCD
Presenter: Jorge E. Cortes, MD. Professor, Augusta University, Director of the Georgia Cancer Center

Title: Phase 1 Single (SAD) and Multiple Ascending Dose (MAD) Studies of the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of FT-4202, an Allosteric Activator of Pyruvate Kinase-R, in Healthy and Sickle Cell Disease Subjects

The presentation will report the effects of FT-4202 on healthy subjects in this ongoing study.

Date/Time: Monday, December 9, 2019 at 11:15 a.m. ET
Session: 114. Hemoglobinopathies, Excluding Thalassemia—Clinical: Emerging Therapies: Reports from Recent Clinical Trials
Abstract: 616
Location: Orange County Convention Center, W304ABCD
Presenter: Theodosia Kalfa, MD, PhD. Associate Professor, University of Cincinnati Department of Pediatrics, Cincinnati Children’s Hospital Medical Center

Poster Presentation

Title: Phase 1 Dose Escalation and Expansion Study to Determine Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the BET Inhibitor FT-1101 As a Single Agent in Patients with Relapsed or Refractory Hematologic Malignancies

Date/Time: Monday, December 9, 2019 from 6:00 – 8:00 p.m. ET
Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster III
Abstract: 3907
Location: Orange County Convention Center, Hall B
Presenter: Manish Patel, MD. Director of Drug Development, Florida Cancer Specialists. Associate Director of Drug Development, Sarah Cannon Research Institute

About Olutasidenib (FT-2102)

FORMA’s most advanced clinical asset, olutasidenib, is a potent and selective next generation inhibitor of mutated isocitrate dehydrogenase 1 (IDH1) being investigated to treat patients with relapsed/refractory acute myeloid leukemia (RR/AML) or myelodysplastic syndrome (MDS), and patients with glioma and other solid tumors with an IDH1 mutation. IDH1 is a natural enzyme that is part of the normal metabolism of all cells. Mutations of IDH1 can produce excessive amounts of the oncometabolite 2-hydroxyglutarate (2-HG), which impairs cell differentiation and promotes blood malignancies and solid tumors. IDH1 mutations are present in 7-14% of patients with AML and 3-4% of patients with MDS.

About FT-4202

FT-4202 is a novel selective red blood cell (RBC) pyruvate kinase (PKR) activator designed to be a disease-modifying therapy for the treatment of sickle cell disease (SCD), with a multimodal approach. FT-4202 works upstream by activating the RBCs’ natural PKR activity to decrease 2,3-DPG levels, which leads hemoglobin to hold on to oxygen molecules longer to reduce RBC sickling. The downstream activity of FT-4202 increases ATP levels, the fuel that provides energy to cells, to improve RBC health and survival. Together, these effects are anticipated to increase hemoglobin levels and decrease painful vaso-occlusive crises. SCD is the most common disorder caused by a single gene mutation and affects approximately 100,000 people in the U.S., and millions globally.

About FT-1101 (also known as CC-95775)

FT-1101 (also known as CC-95775) is an oral, structurally distinct and potent pan-inhibitor of the Bromodomain and Extra-Terminal (BET) epigenetic protein family, which was discovered by FORMA and licensed to Celgene Corporation.

On November 6, 2019 Sysmex reported (Press release, Sysmex, NOV 6, 2019, View Source [SID1234550554])

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2. Dividend

3. Financial Forecast for the Year Ending March 31, 2020

4. Other Information

(1) Changes in significant consolidated subsidiaries (which resulted in changes in scope of consolidation): No

(2) Changes in accounting policies and accounting estimates 1) Changes in accounting policies required by IFRS: Yes 2) Other changes in accounting policies: No 3) Changes in accounting estimates: No

(3) Number of outstanding stock (common stock)

1) Number of outstanding stock at the end of each fiscal period (including treasury stock): 209,193,432 shares as of Sep. 30, 2019; 209,154,432 shares as of Mar. 31, 2019 2) Number of treasury stock at the end of each fiscal period: 446,444 shares as of Sep. 30, 2019; 446,168 shares as of Mar. 31, 2019 3) Average number of outstanding stock for each period (cumulative): 208,731,410 shares for the three months ended Sep. 30, 2019 208,580,388 shares for the three months ended Sep. 30, 2018 Note: Quarterly summaries of financial results are excluded from quarterly reviews. * Explanation regarding the appropriate use of financial forecast and other information

1. The forecasts and future projections contained herein have been prepared on the basis of rational decisions given the information available as of the date of announcement of this document. These forecasts do not represent a commitment by the Company, and actual performance may differ substantially from forecasts for a variety of reasons. Please refer to "3) Consolidated financial forecast" within "1. Qualitative information on quarterly financial results" on page 4 of the attachment to this document for cautionary statements concerning the conditions and performance forecasts that serve as the basis for these forecasts. 2. Supplementary financial materials (in Japanese and English) will be posted on the Sysmex website on Wednesday, November 6, 2019. －

1 － Content of Supplementary Materials 1. Qualitative information on quarterly financial results 2 1) Operating performance analysis 2 2) Financial conditions analysis 4 3) Consolidated financial forecast 4 2. Condensed quarterly consolidated financial statements and notes 5 1) Condensed quarterly consolidated statement of financial position 5

2) Condensed quarterly consolidated statement of income 7 3) Condensed quarterly consolidated statement of other comprehensive income 8 4) Condensed quarterly consolidated statement of changes in equity 9 5) Condensed quarterly consolidated statement of cash flows 10 6) Notes to the condensed quarterly consolidated financial statements 11 1. Notes related to the going concern assumption 11

2. Changes in accounting policies 11 3. Segment information 11 － 2 －

1. Qualitative information on quarterly financial results 1) Operating performance analysis Future-related information contained in the text below is based on the judgement as of the end of the fiscal period under review. During the first six months of the fiscal year ending March 31, 2020, the Japanese economy was affected in the manufacturing sector by worsening earnings due to trade friction and other uncertainties in the international situation, and yen appreciation, as well as a downturn in business confidence. However, the employment and income environments continued their modest recovery, and corporate investment remained firm as companies upgraded obsolete equipment and made streamlining and labor-saving investments against the backdrop of a labor shortage. Overseas, the economic outlook was characterized by a growing sense of caution, due to prolonged US–China trade friction, the United Kingdom’s exit from the European Union and rising geopolitical tension in the Middle East. On the healthcare front, in Japan the medical and healthcare field faces growing demand due to an aging society and increasingly diverse health and medical needs. The Japanese government is including the medical and healthcare industry in its growth strategies, which is expected to continue invigorating healthcare-related industries going forward. Looking overseas, the populations of developed countries are aging, while economic growth in emerging markets is causing healthcare demand to increase and prompting higher levels of healthcare quality and service enhancements. These trends are promoting efficient healthcare, with structural changes brought about by artificial intelligence, information and communications technology, and other breaking technologies. Against this backdrop, Sysmex obtained Japanese manufacturing and marketing approval for the OncoBEAM1 RAS CRC Kit, an RAS gene2 mutation testing kit. 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. 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. In addition, Sysmex launched its PS-10 sample preparation system in the North American market in August 2019. This system is for the clinical flow cytometry (FCM) testing market, which uses flow cytometry to perform detailed analyses of leukemia and malignant lymphoma diagnoses. By automating complicated sample preparation work for clinical laboratories, the PS-10 results in providing workflows which are more efficient and aids in standardizing clinical flow cytometry testing. In preparation for a global rollout, we will obtain necessary regulatory approval for flow cytometers as analyzers in various countries around the world. Since 2013, Sysmex and Tasuku Honjo, a general and distinguished professor at the Kyoto University Institute for Advanced Studies, have been conducting joint R&D on a fully automated measurement method for soluble immune checkpoint molecules (sPD-1, sPD-L1 and sCTLA-4) using the HI-1000, an automated, highly sensitive immunoassay system for research applications. In September 2019, Sysmex began providing assay services for research using this measurement method. The measurement method can be used in cancer immunotherapy and as a new method for diagnosing autoimmune diseases, and has the potential to help realize personalized medicine. Going forward, we will promote R&D with a view toward commercialization, contributing to advances in healthcare.

1 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, which was developed at Johns Hopkins University.

2 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. In Japan, instrument sales increased, mainly in the hematology and life science fields. As a result, sales in Japan rose 8.4% year on year, to ¥22,691 million. In overseas markets, reagent sales were down, chiefly in the hemostasis field, but reagent sales rose, centered on the hematology, urinalysis and immunochemistry fields. Consequently, overseas sales for the Sysmex Group rose 4.4% year on year, to ¥120,298 million. The overseas sales ratio fell 0.5 percentage point, to 84.1%. As a result, during the first six months of the fiscal year ending March 31, 2020, the Group recorded consolidated net sales of ¥142,990 million, up 5.0% year on year. Operating profit fell 2.5%, to ¥27,803 million; profit before tax decreased 5.1%, to ¥25,075 million; and profit attributable to owners of the parent fell 9.7%, to ¥17,593 million. Performance by segment

(1) Japan In Japan, sales increased 11.3% year on year, to ¥24,800 million, benefiting from such factors as higher instrument sales, principally in the hematology field. On the profit front, higher sales pushed up gross profit, but segment profit (operating profit) rose 2.1%, to ¥17,907 million, owing to higher SG&A and R&D expenses.

(2) Americas Instrument sales were down, mainly in the hemostasis field, but sales of reagents and maintenance services grew in the hematology field, pushing up sales 3.5% year on year, to ¥30,264 million. On the profit front, increased sales boosted gross profit. Nevertheless, segment profit (operating profit) declined 37.6% year on year, to ¥951 million, as a result of rising SG&A expenses.

(3) EMEA Sales in the EMEA region expanded 3.1% year on year, to ¥38,146 million, helped by higher reagent sales, mainly in the hematology and urinalysis fields. On the profit front, higher sales and a decrease in SG&A expenses led to higher gross profit and pushed segment profit (operating profit) up 21.7% year on year, to ¥3,812 million.

(4) China In China, reagent sales decreased, mainly in the hemostasis field, and instrument sales fell in the hematology field. However, instrument sales in the hemostasis field grew, as did reagent sales in the hematology field. As a result, sales increased 3.3% year on year, to ¥37,370 million. On the profit front, SG&A expenses decreased, but a worsening cost of sales ratio caused gross profit to decline. Consequently, segment profit (operating profit) dropped 25.2%, to ¥4,146 million. － 4 －

(5) Asia Pacific Instrument sales were down, mainly in the hemostasis and hematology fields, but reagent sales in the hematology field increased, leading to an 8.1% year on year rise in sales in the Asia Pacific region, to ¥12,408 million. On the profit front, despite worsening cost of sales ratio and higher SG&A expenses, higher sales led to a rise in gross profit and pushed segment profit (operating profit) up 10.0% year on year, to ¥1,610 million. 2)

Financial conditions analysis

(1) Financial conditions As of September 30, 2019, total assets amounted to ¥364,028 million, up ¥17,252 million from March 31, 2019. As principal factors, trade and other receivables (current assets) decreased ¥6,943 million, and other short-term financial assets fell ¥6,892 million, but property, plant and equipment increased ¥19,854 million, cash and cash equivalents expanded ¥5,923 million, and inventories grew ¥4,459 million. Meanwhile, total liabilities as of September 30, 2019, were ¥95,970 million, up ¥14,377 from their level on March 31, 2019. Principal factors included a ¥3,054 million decrease in trade and other payables and a ¥1,863 decline in accrued bonuses, but lease liabilities (current) rose ¥5,422 million, and lease liabilities (non-current) increased ¥16,826 million. Total equity came to ¥268,057 million, up ¥2,875 million from March 31, 2019. Among principal reasons, retained earnings rose ¥10,080 million, while other components of equity declined ¥7,217 million. Equity attributable to owners of the parent to total assets fell 2.8 percentage points, from 76.3% on March 31, 2019 to 73.5% on September 30, 2019.

(2) Cash flows As of September 30, 2019, cash and cash equivalents amounted to ¥56,985 million, up ¥5,923 million from March 31, 2019. Cash flows from various activities during the first six months of the fiscal year are described in more detail below. (Cash flows from operating activities) Net cash provided by operating activities was ¥26,908 million, up ¥7,481 million from the first six months of the previous fiscal year. As principal factors, profit before tax provided ¥25,075 million (¥1,335 million less than in the corresponding period of the preceding year), depreciation and amortization provided ¥11,510 million (¥3,889 million more than in the corresponding period of the preceding year), an increase in inventories used ¥5,851 million (up ¥3,980 million), a decrease in trade payables used ¥1,068 million (decrease of ¥1,851 million), and a decrease in consumption taxes receivable and others provided ¥2,058 million (increased ¥1,802 million). (Cash flows from investing activities) Net cash used in investing activities was ¥9,057 million (decrease of ¥13,671 million).

Among major factors, purchase of property, plant and equipment used ¥7,458 million (decrease of ¥1,967 million), purchase of intangible assets used ¥6,113 million (up ¥2,050 million), purchase of investments in equity instruments used ¥1,508 million (up ¥500 million), and proceeds from withdrawal of time deposits provided ¥7,221 million (up ¥7,221 million). (Cash flows from financing activities) Net cash used in financing activities was ¥10,195 million (up ¥2,942 million). This was mainly due to dividends paid of ¥7,513 million (up ¥6 million), and repayment of lease liabilities, which used ¥2,801 million. 3) Consolidated financial forecast For the Company’s consolidated financial forecast for the full fiscal year, please refer to the Announcement Regarding Differences between Actual and Forecast Figures for the Six Months Ended September 30, 2019, and Revision of Full-Year Financial Forecasts, announced today (November 6, 2019).the First Six Months of the Fiscal Year Ending March 31, 2020

On November 6, 2019 argenx (Euronext & Nasdaq: ARGX), a clinical-stage biotechnology company developing a deep pipeline of differentiated antibody-based therapies for the treatment of severe autoimmune diseases and cancer, reported the pricing of a global offering of ordinary shares in the form of American Depository Shares (ADSs) in the United States and certain other countries outside of European Economic Area and a simultaneous private placement of ordinary shares in the European Economic Area (Press release, argenx, NOV 6, 2019, View Source [SID1234550646]). The Company anticipates total gross proceeds of $484 million (approximately €437 million) from the sale of 1,410,057 ADSs at a price of $121.00 per ADS and the sale of 2,589,943 ordinary shares at a price of €109.18 per ordinary share. Each of the ADSs offered in the offering represents the right to receive one ordinary share, nominal value of €0.10 per share.

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In addition, argenx has granted the underwriters of the offering a 30-day option to purchase up to 600,000 ordinary shares (which may be in the form of ADSs) on the same terms and conditions. The U.S. offering and the European private placement are currently expected to close simultaneously on November 12, 2019, subject to customary closing conditions. On this timing, due to a public holiday in the United States, November 12, 2019 would count as T+2 settlement in the United States and a T+3 settlement for investors that purchase ordinary shares traded on Euronext Brussels. Accordingly, investors purchasing ordinary shares traded on Euronext Brussels should be aware that if they transact in the secondary market on T (November 7, 2019) they may not be able to settle those transactions on a T+2 basis, because they would only receive ordinary shares from argenx on a T+3 basis on November 12, 2019.

argenx’s ADSs are currently listed on the Nasdaq Global Select Market under the symbol "ARGX," and argenx’s ordinary shares are currently listed on Euronext Brussels under the symbol "ARGX."

Morgan Stanley, Cowen, BofA Securities and Evercore are acting as joint bookrunning managers for the offering. Kempen is acting as lead manager for the offering and Wolfe Capital Markets and Advisory is acting as co-manager.

The securities are being offered pursuant to an automatically effective shelf registration statement that was previously filed with the Securities and Exchange Commission (SEC). A preliminary prospectus supplement relating to the securities was filed with the SEC on November 6, 2019. The final prospectus supplement relating to the securities will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. When available, copies of the final prospectus supplement and the accompanying prospectus relating to the Offering may be obtained for free from Morgan Stanley & Co. LLC, 180 Varick Street, 2nd Floor, New York, New York 10014, United States, Attention: Prospectus Department; from Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, Attn: Prospectus Department, by email at [email protected], or by telephone at (833) 297-2926; BofA Securities, NC1-004-03-43, 200 North College Street, 3rd floor, Charlotte, North Carolina 28255-0001, Attn: Prospectus Department, or by email at [email protected]; or Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 36th Floor, New York, NY 10055, or by telephone at (888) 474-0200.

A request for the admission to listing and trading of the ordinary shares (including the ordinary shares underlying the ADSs) on the regulated market of Euronext Brussels will be made.

On November 6, 2019 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported that 15 abstracts featuring clinical and translational data from its oncology and rare genetic diseases programs will be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held December 7-10, 2019 in Orlando (Press release, Agios Pharmaceuticals, NOV 6, 2019, View Source [SID1234550433]).

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The accepted abstracts are listed below and are available online on the ASH (Free ASH Whitepaper) conference website: View Source

Oral Presentations

Abstract #541: Complex Polyclonal Resistance Mechanisms to Ivosidenib Monotherapy in IDH1-Mutant Relapsed or Refractory Acute Myeloid Leukemia Revealed By Single Cell Sequencing Analyses
Date & Time: Monday, December 9, 2019 at 7:00 a.m. ET
Oral Abstract Session: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Single-Cell and Clonal Approaches to Treatment Resistance in AML
Location: Orange County Convention Center, Valencia A (W415A)
Presenter: Hongfang Wang, Ph.D., Agios Pharmaceuticals

Abstract #545: Molecular Mechanisms Mediating Relapse Following Ivosidenib Monotherapy in Patients with IDH1-Mutant Relapsed or Refractory Acute Myeloid Leukemia
Date & Time: Monday, December 9, 2019 at 8:00 a.m. ET
Oral Abstract Session: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Single-Cell and Clonal Approaches to Treatment Resistance in AML
Location: Orange County Convention Center, Valencia A (W415A)
Presenter: Sung Choe, Ph.D., Agios Pharmaceuticals

Abstract #643: Enasidenib Plus Azacitidine Significantly Improves Complete Remission and Overall Response Compared with Azacitidine Alone in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) with Isocitrate Dehydrogenase 2 (IDH2) Mutations: Interim Phase II Results from an Ongoing, Randomized Study
Date & Time: Monday, December 9, 2019 at 10:30 a.m. ET
Oral Abstract Session: 613. Acute Myeloid Leukemia: Clinical Studies: Non-Intensive Therapy
Location: Orange County Convention Center, Valencia A (W415A)
Presenter: Courtney DiNardo, M.D., University of Texas MD Anderson Cancer Center

Poster Presentations

Abstract #2175: Comorbidities and Complications in Adults with Pyruvate Kinase Deficiency
Poster Session Date & Time: Saturday, December 7, 2019 from 5:30-7:30 p.m. ET
Poster Session: 904. Outcomes Research – Non-Malignant Conditions: Poster II

Abstract #1570: Hematologic Malignancies Exhibit Selective Vulnerability to Inhibition of De Novo Pyrimidine Biosynthesis By AG-636, a Novel Inhibitor of Dihydroorotate Dehydrogenase in Phase 1 Clinical Trials
Poster Session Date & Time: Saturday, December 7, 2019 from 5:30-7:30 p.m. ET
Poster Session: 625. Lymphoma: Pre-Clinical – Chemotherapy and Biologic Agents: Poster I

Abstract #1286: AG-636 for the Treatment of Adults with Advanced Lymphoma: Initiation of a Phase 1 Clinical Study
Poster Session Date & Time: Saturday, December 7, 2019 from 5:30-7:30 p.m. ET
Poster Session: 605. Molecular Pharmacology, Drug Resistance – Lymphoid and Other Diseases: Poster I

Abstract #2223: An Ongoing Global, Longitudinal, Observational Study of Patients with Pyruvate Kinase Deficiency: The PEAK Registry
Poster Session Date & Time: Sunday, December 8, 2019 from 6:00-8:00 p.m. ET
Poster Session: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster II

Abstract #2249: Mitapivat (AG-348), an Oral PK-R Activator, in Adults with Non-Transfusion Dependent Thalassemia: A Phase 2, Open-Label, Multicenter Study in Progress
Poster Session Date & Time: Sunday, December 8, 2019 from 6:00-8:00 p.m. ET
Poster Session: 112. Thalassemia and Globin Gene Regulation: Poster II

Abstract #3447: Development of Patient-Reported Outcome Measures (Symptoms and Impacts) in Adults with Pyruvate Kinase Deficiency
Poster Session Date & Time: Sunday, December 8, 2019 from 6:00-8:00 p.m. ET
Poster Session: 904. Outcomes Research – Non-Malignant Conditions: Poster II

Abstract #2593: AGILE: A Phase 3, Multicenter, Double‐Blind, Randomized, Placebo‐Controlled Study of Ivosidenib in Combination with Azacitidine in Adult Patients with Previously Untreated Acute Myeloid Leukemia with an IDH1 Mutation
Poster Session Date & Time: Sunday, December 8, 2019 from 6:00-8:00 p.m. ET
Poster Session: 613. Acute Myeloid Leukemia: Clinical Studies: Poster II

Abstract #2706: High Rate of IDH1 Mutation Clearance and Measurable Residual Disease Negativity in Patients with IDH1-Mutant Newly Diagnosed Acute Myeloid Leukemia Treated with Ivosidenib (AG-120) and Azacitidine
Poster Session Date & Time: Sunday, December 8, 2019 from 6:00-8:00 p.m. ET
Poster Session: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster II

Abstract #3512: Long-Term Safety and Efficacy of Mitapivat (AG-348), a Pyruvate Kinase Activator, in Patients with Pyruvate Kinase Deficiency: The DRIVE PK Study
Poster Session Date & Time: Monday, December 9, 2019 from 6:00-8:00 p.m. ET
Poster Session: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster III

Abstract #3526: Mitapivat (AG-348) in Adults with Pyruvate Kinase Deficiency Who Are Regularly Transfused: A Phase 3, Open-Label, Multicenter, Study (ACTIVATE-T) in Progress
Poster Session Date & Time: Monday, December 9, 2019 from 6:00-8:00 p.m. ET
Poster Session: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster III

Abstract #3513: Prevalence of Pyruvate Kinase Deficiency: A Systematic Literature Review
Poster Session Date & Time: Monday, December 9, 2019 from 6:00-8:00 p.m. ET
Poster Session: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster III

Abstract #4254: Ivosidenib (AG-120) in Patients with IDH1-Mutant Relapsed/Refractory Myelodysplastic Syndrome: Updated Enrollment of a Phase 1 Dose Escalation and Expansion Study
Poster Session Date & Time: Monday, December 9, 2019 from 6:00-8:00 p.m. ET
Poster Session: 637. Myelodysplastic Syndromes – Clinical Studies: Poster III

Event and Webcast Information
Agios will host an investor event on December 9, 2019 at 8:00 p.m. ET in Orlando to review the data from the company’s oncology and rare genetic diseases programs. The event will be webcast live and can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com. The archived webcast will be available on the company’s website beginning approximately two hours after the event.