On November 6, 2019 TG Therapeutics, Inc. (NASDAQ: TGTX), reported that data for the triple combination of U2 (umbralisib and ublituximab) plus venetoclax has been accepted for oral presentation, and Phase 1 data for TG-1701, the Company’s novel BTK inhibitor, monotherapy and in combination with U2, has been accepted for poster presentation, at the upcoming 61stAmerican Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting and exposition, to be held December 7 – 10, 2019, at the Orange County Convention Center in Orlando, FL (Press release, TG Therapeutics, NOV 6, 2019, View Source [SID1234550556]). Abstracts are now available online and can be accessed on the ASH (Free ASH Whitepaper) meeting website at www.hematology.org. Abstract highlights and presentation details are outlined below.

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Michael S. Weiss, Executive Chairman and Chief Executive Officer, stated, "We are looking forward to an exciting ASH (Free ASH Whitepaper) conference as we continue to present data highlighting the unique combinability of the U2 doublet as the backbone for triple therapy combinations. We believe the combination of U2 plus venetoclax offers a well-tolerated, highly-active, treatment option potentially offering CLL patients an opportunity to achieve bone marrow MRD negativity and cease treatment after 12 months." Mr. Weiss continued, "We are also extremely pleased to see the preliminary results for our BTK inhibitor, TG-1701, both as a single agent and in combination with U2. We have previously presented compelling results from the combination of U2 plus ibrutinib and believe a proprietary triplet can offer a better outcome for patients than U2 or a BTK alone, across multiple B-cell cancers. We look forward to sharing these data at the upcoming meeting as we continue to drive towards the initiation of our first NDA filing for umbralisib monotherapy, as well as the PFS readout for U2 from our UNITY-CLL Phase 3 trial."

Abstract Highlights

Oral Presentation: A Phase 1/2 Study of Umbralisib, Ublituximab and Venetoclax in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Regimen was administered with 3 cycles of U2 induction to reduce risk of tumor lysis syndrome (TLS) followed by addition of venetoclax in cycle 4. Patients that were bone marrow MRD negative after cycle 12 were permitted to stop all therapy.
Overall response rate (ORR) of 85% (11/13) after U2 induction period, prior to introduction of venetoclax, in relapsed/refractory CLL patients, including patients refractory to ibrutinib
At the time of the abstract, 9 patients had been treated for >7 cycles and 5 patients for > 12 cycles:
◦ 100% ORR (9/9) after cycle 7 for the triple combination
◦ 100% (5/5) of patients who reached 12 cycles of therapy had undetectable minimal residual disease (MRD) (<0.01%) in peripheral blood; and
◦ 80% (4/5) of patients who reached 12 cycles of therapy had undetectable MRD in bone marrow and have stopped therapy
Triple combination was well tolerated with no events of TLS observed
Preliminary results suggest that the chemotherapy-free triple regimen of U2 plus venetoclax can provide undetectable MRD after only 12 cycles, representing an effective treatment plan for these heavily pre-treated CLL patients
Poster Presentation: Phase 1 Study of TG-1701, a Selective Irreversible Inhibitor of Bruton’s Tyrosine Kinase (BTK), in Patients with Relapsed/Refractory B-Cell Malignancies

TG-1701, a once daily BTK inhibitor, has an encouraging preliminary safety profile, with clinical and pharmacodynamic activity at all dose levels evaluated
19 patients have been treated with TG-1701: 3 patients at 100 mg QD, 9 patients at 200 mg QD (expansion before opening combination), 3 patients at 300 mg QD single agent arm, and 4 patients at 100 mg QD combination arm
All 3 patients treated with 100 mg TG-1701 plus U2 have achieved a response at the first response assessment: 1 Complete Response (CR) in a follicular lymphoma (FL) patient and 2 Partial Responses (PR), a FL patient with 88% reduction in tumor burden, and a marginal zone lymphoma (MZL) patient with 65% reduction in tumor burden
Presentation Details

Title: A Phase 1/2 Study of Umbralisib, Ublituximab and Venetoclax in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
◦ Publication Number: 360
◦ Oral Session: 642. CLL: Therapy, excluding Transplantation: Combination and Novel Treatment
◦ Session Date and Time: Sunday, December 8, 2019; 7:30 AM – 9:00 AM ET
• Presentation Time: 8:45 AM ET
◦ Location: Orange County Convention Center, Hall E1
◦ Presenter: Paul M. Barr, MD, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY

Title: Phase 1 Study of TG-1701, a Selective Irreversible Inhibitor of Bruton’s Tyrosine Kinase (BTK), in Patients with Relapsed/Refractory B-Cell Malignancies
◦ Publication Number: 4001
◦ Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Poster III
◦ Date and Time: Monday, December 9, 2019; 6:00 PM – 8:00 PM ET
◦ Location: Orange County Convention Center, Hall B
◦ Presenter: Chan Cheah, MD, Sir Charles Gairdner Hospital, Hollywood Private Hospital, University of Western Australia, Blood Cancer Research Western Australia
Following each presentation, the data presented will be available on the Publications page of the Company’s website at View Source

TG THERAPEUTICS INVESTOR & ANALYST EVENT
TG Therapeutics will host an event on Monday, December 9, 2019 beginning at 7:30 PM ET with a featured fireside chat beginning promptly at 8:00 PM ET. The event will take place at the Hyatt Regency Orlando. A live webcast will be available on the Events page, located within the Investors & Media section of the Company’s website at View Source, as well as archived for future review. This event will also be broadcast via conference call. To access the conference line, please call 1-877-407-8029 (U.S.), 1-201-689-8029 (outside the U.S.), and reference Conference Title: TG TherapeuticsDecember 2019 Investor & Analyst Event.

On November 6, 2019 Teneobio, Inc., a clinical-stage biotechnology company developing engineered bispecific antibodies for the treatment of cancer reported that it has received orphan drug designation by the U.S. Food and Drug Administration (FDA) for the treatment of multiple myeloma (Press release, TeneoBio, NOV 6, 2019, View Source [SID1234550555]).

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"New and better treatment options are needed for multiple myeloma. While there are a number of BCMA-targeting agents currently in clinical development, TNB-383B, an anti-BCMAxCD3 currently in Phase I, is a bispecific comprised of a unique T-cell engager designed to maximize the therapeutic window for this class of drugs," said Roland Buelow, CEO of Teneobio.

The FDA’s Orphan Drug Designation program provides orphan status to drugs defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases that affect fewer than 200,000 people in the U.S. Orphan designation qualifies the sponsor of the drug for certain development incentives, including tax credits for qualified clinical testing, prescription drug user fee exemptions and seven-year marketing exclusivity upon FDA approval.

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 Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) reported its third quarter 2019 financial results and highlights (Press release, Synta Pharmaceuticals, NOV 6, 2019, View Source [SID1234550553]):

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"Madrigal continued to execute its clinical development strategy in non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD) during the third quarter. We opened clinical sites and enrolled subjects in accordance with the plan for our Phase 3 study of MGL-3196 (resmetirom) in patients with biopsy-proven NASH and liver fibrosis (MAESTRO-NASH)," stated Paul Friedman, M.D., Chief Executive Officer of Madrigal. "We also made progress toward initiating a second Phase 3 clinical study in a broader segment of NASH patients, many of whom also have hyperlipidemia, MAESTRO-NAFLD-1. These patients, like the later stage NASH patients, are at high risk of cardiovascular disease. In this regard, we are pleased that Seth Baum, M.D., Immediate Past President, American Society for Preventive Cardiology, will present "Managing Cardiovascular Risk in NAFLD/NASH" from 1:30 – 2:00 PM ET on Monday, November 11, 2019, during the AASLD Annual Meeting."

Becky Taub, M.D.,CMO, President, Research & Development of Madrigal, added, "We are pleased to announce that The Lancet has accepted for publication Madrigal’s Phase 2 study results in patients with NASH. We are also pleased to announce that FDA has granted Madrigal’s request for Fast Track designation of resmetirom for NASH. We look forward to the upcoming Liver Meeting AASLD 2019 in Boston this month, where our abstract "Effects of Resmetirom (MGL-3196) on Hepatic Fat, Lipids, Liver Enzymes and Markers of Liver Fibrosis in an Open-Label 36-Week Extension Study in NASH Patients" has been selected for oral presentation, and our poster, "Steatosis and Fibrosis Measured as Continuous Variables on Paired, Serial Liver Biopsies in the Resmetirom (MGL-3196) 36-Week Phase 2 NASH Study" will also be presented."

Details of the presentations mentioned above are as follows:

Seth Baum, M.D., Immediate Past President, American Society for Preventive Cardiology, will present "Managing Cardiovascular Risk in NAFLD/NASH," Monday November 11, 1:30 – 2:00 PM, Product Theater, Exhibition Floor.

Stephen Harrison, M.D. TITLE: "Effects of Resmetirom (MGL-3196) on Hepatic Fat, Lipids, Liver Enzymes and Markers of Liver Fibrosis in an Open-Label 36-Week Extension Study in NASH Patients" Parallel Session 39 (oral) (4:30-6:00 PM) Hynes Convention Center Ballroom BC, Monday November 11, 5:30 PM.

Poster 2133 "Steatosis and Fibrosis Measured as Continuous Variables on Paired, Serial Liver Biopsies in the Resmetirom (MGL-3196) 36-Week Phase 2 NASH Study," Monday November 11, 8:00 AM, Poster Hall. NAFLD and NASH Therapeutics: Pharmacologic and Other.

Madrigal will also have a medical information booth – #513 on the exhibition floor.

Additional information about Madrigal’s Phase 3 study in patients with NASH [NCT03900429] can be obtained at www.clinicaltrials.gov.

Financial Results for the Three and Nine Months Ended September 30, 2019

As of September 30, 2019, Madrigal had cash, cash equivalents and marketable securities of $453.6 million, compared to $483.7 million at December 31, 2018. The decrease of $30.1 million was largely the result of $29.3 million cash used in operating activities during the first nine months of 2019.

Operating expenses were $24.2 million and $65.0 million for the three and nine month periods ended September 30, 2019, compared to $11.3 million and $26.2 million in the comparable prior year periods.

Research and development expenses for the three and nine month periods ended September 30, 2019 were $19.4 million and $47.4 million compared to $6.2 million and $16.5 million in the comparable prior year periods. The increases are primarily attributable to additional activities related to initiation of our Phase 3 clinical trial in NASH, including a payment due related to a milestone achieved under our agreement with Roche, an increase in headcount and increased non-cash stock compensation from stock option awards.

General and administrative expenses for the three and nine month periods ended September 30, 2019 were $4.7 million and $17.6 million compared to $5.1 million and $9.7 million in the comparable prior year periods. The decrease for the three month period is due primarily to lower non-cash stock compensation expense from stock option awards. The increase for the nine month period is due primarily to increased non-cash stock compensation from stock option awards.

Interest income for the three and nine month periods ended September 30, 2019 was $2.8 million and $8.8 million compared to $2.8 million and $4.7 million in the comparable prior year periods. The change in interest income for the nine month period was due primarily to a higher average principal balance in our investment portfolio in 2019, and increased interest rates.

About resmetirom (MGL-3196)

Among its many functions in the human body, thyroid hormone, through activation of its beta receptor, plays a central role in controlling lipid metabolism, impacting a range of health parameters from levels of serum cholesterol and triglycerides to the pathological buildup of fat in the liver. Attempts to exploit this pathway for therapeutic purposes in cardio-metabolic and liver diseases have been hampered by the lack of selectivity of older compounds for the thyroid hormone receptor (THR)-ß, chemically-related toxicities and undesirable distribution in the body.

Madrigal recognized that greater selectivity for thyroid hormone receptor (THR)-ß and liver targeting might overcome these challenges and deliver the full therapeutic potential of THR-ß agonism. Madrigal believes that resmetirom is the first orally administered, small-molecule, liver- directed, truly ß-selective THR agonist.

Based on the positive Phase 2 clinical study results in patients with NASH (Phase 2 36-Week Results Press Release), Madrigal initiated a Phase 3 multinational, double-blind, randomized, placebo-controlled study of resmetirom in patients with non-alcoholic steatohepatitis (NASH) and fibrosis to resolve NASH and reduce progression to cirrhosis and/or hepatic decompensation (Phase 3 Initiation Press Release and ClinicalTrials.gov NCT03900429). Additionally, in both the NASH Phase 2 study, and a second positive Phase 2 clinical study in patients with heterozygous familial hypercholesterolemia (Phase 2 HeFH Results Press Release), significant reductions in multiple atherogenic lipids were observed. Madrigal is planning a Phase 3 study in NASH and NAFLD patients to further assess effects on LDL-cholesterol, other atherogenic lipids, biomarkers of fibrosis, MRI-PDFF and fibroscans to better characterize potential clinical benefits of resmetirom on cardiovascular and liver related endpoints using noninvasive measures.

On November 6, 2019 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that the first patient has been dosed in AUGMENT-101, a Phase 1/2 clinical trial evaluating SNDX-5613, Syndax’s potent, highly selective oral Menin inhibitor, in patients with relapsed/refractory (R/R) acute leukemias (Press release, Syndax, NOV 6, 2019, View Source [SID1234550552]).

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"Dosing of the first patient in AUGMENT-101 represents an important milestone, both for the SNDX-5613 program and, importantly, for patients with genetically-defined acute leukemias, many of whom often do not achieve durable benefit from currently available treatment regimens," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "Preclinical data strongly support our belief that SNDX-5613 has the potential to address a significant unmet need as a treatment for patients with MLL-r and NPM1 mutant leukemias."

AUGMENT-101 is a Phase 1/2 open-label trial designed to evaluate the efficacy, safety, tolerability and pharmacokinetics of orally administered SNDX-5613. The Phase 1 dose escalation portion of AUGMENT-101 will enroll adults with R/R acute leukemias and establish a recommended Phase 2 dose. The Phase 2 portion will evaluate efficacy, as defined by Complete Response rate (per International Working Group response criteria), across three expansion cohorts: MLL-rearranged (MLL-r) acute lymphoblastic leukemia (ALL), MLL-r AML and NPM1 mutant AML. The Company expects to report initial clinical data from the trial in 2020.

Additional information about the AUGMENT-101 trial is available via Clinicaltrials.gov (NCT 04065399).

About SNDX-5613

SNDX-5613 is a potent, selective, small molecule inhibitor of the Menin-MLL binding interaction that is being developed for the treatment of MLL-rearranged (MLL-r) acute leukemias, including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). MLL rearrangements occur in approximately 80% of acute leukemia cases in infants and up to 10% of all leukemias. In preclinical models of MLL-r acute leukemias, SNDX-5613 demonstrated robust, dose-dependent inhibition of tumor growth, resulting in a marked survival benefit. Menin-MLL interaction inhibitors have also demonstrated robust treatment benefit in multiple preclinical models of NPM1 mutant AML, which represents the most frequent genetic abnormality in adult AML. SNDX-5613 is currently being evaluated in the Company’s AUGMENT-101 Phase 1/2 open-label clinical trial for the treatment of relapsed/refractory acute leukemias.

About Mixed Lineage Leukemia Rearranged (MLL-r)

Rearrangements of the MLL gene give rise to MLL-r acute leukemias, known to have a poor prognosis, with less than 55% of patients surviving past 5 years. MLL rearrangements produce fusion proteins that require interaction with the protein called Menin to drive leukemic cancer growth. Disruption of the Menin-MLL-r interaction has been shown to halt the growth of MLL-r leukemic cells. MLL-r leukemias, which are routinely diagnosed through currently available cytogenetic or molecular diagnostic techniques, occur in approximately 80% of infant acute leukemias and up to 10% of all acute leukemias. There are currently no approved therapies indicated for MLL-r leukemias.

About NPM1 Mutant Acute Myeloid Leukemia

NPM1 mutant AML, which is distinguished by point mutations in the NPM1 gene that drive the leukemic phenotype, is the most common type of cytogenetically normal adult AML and represents approximately 30% of all adult AML cases. This subtype of AML has a 5-year overall survival rate of approximately 50%. Similar to MLL-r leukemias, NPM1 mutant AML is highly dependent on the expression of specific developmental genes, shown to be negatively impacted by inhibitors of the Menin-MLL interaction. NPM1 mutant AML is routinely diagnosed through currently available screening techniques. There are currently no approved therapies indicated for NPM1 mutant AML.