On April 13, 2018 Syndax Pharmaceuticals, Inc. ("Syndax,"the "Company" or "we") (Nasdaq:SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported twelve oral and poster presentations at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 14-18, 2018 in Chicago, Illinois (Press release, Syndax, APR 13, 2018, View Source [SID1234525305]).

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Details on Presentations
Oral Presentations:
Title: Safety, efficacy, and immune correlates of alternative doses and schedules of entinostat combined with pembrolizumab in patients with advanced solid tumors – results from SNDX-275- 0141 phase I trial
Presenter: Anthony W. Tolcher, M.D.
Category: Clinical Trials
Session: Biomarkers in Immuno-oncology
Abstract Number: CT179
Location: N Hall C – McCormick Place North (Level 1)
Date and Time: Tuesday April 17, 2018; 3:50 PM – 4:05 PM C.T.
Title: VTP-50469 is a novel, orally-available Menin-MLL1 targeted inhibitor effective against MLL-Rearranged and NPM1-mutant leukemia
Presenter: Andrei V. Krivtsov, PhD
Category: Experimental and Molecular Therapeutics
Session: Early Novel Drug Development
Abstract Number: 4958
Location: McCormick Place South, Room S102 (Level 1)
Date and Time: Tuesday April 17, 2018; 3:50 PM – 4:05 PM C.T.
Title: Entinostat transforms the suppressive tumor microenvironment of breast

Title: Epigenetic reprogramming of the tumor microenvironment by Entinostat increases tumor sensitivity to multivalent immunotherapy combinations with an IL-15 superagonist plus vaccine or immune checkpoint blockade
Category: Immunology
Session: Modifiers of the Tumor Microenvironment 2
Abstract Number: 1740
Location: McCormick Place South, Exhibit Hall A, Poster Section 33
Date and Time: Monday April 16, 2018; 8:00 AM – 12:00 PM C.T.
Title: Epigenetic modulation of the tumor microenvironment enhances immune checkpoint
efficacy in a murine model of pancreatic cancer
Category: Immunology
Session: Modifiers of the Tumor Microenvironment 2
Abstract Number: 1746
Location: McCormick Place South, Exhibit Hall A, Poster Section 33
Date and Time: Monday April 16, 2018; 8:00 AM – 12:00 PM C.T.
Title: Activity of entinostat alone and in combination with cisplatin in a panel of low passage adenoid cystic carcinoma patient-derived xenograft (PDX) models
Category: Tumor Biology
Session: Translational Therapeutics in Cancer Models 2
Abstract Number: 2146
Location: McCormick Place South, Exhibit Hall A, Poster Section 7
Date and Time: Monday April 16, 2018; 1:00 PM – 5:00 PM C.T.
Title: Antitumor activity of HDAC inhibition in bladder cancer mouse models correlates with enhanced immune response
Category: Immunology
Session: Immune Mechanisms Invoked by Therapies 1
Abstract Number: 2748
Location: McCormick Place South, Exhibit Hall A, Poster Section 33
Date and Time: Monday April 16, 2018; 1:00 PM – 5:00 PM C.T.
Title: Overcoming resistance to DNA targeted agents by epigenetic activation of Schlafen 11
(SLFN11) expression with class I histone deacetylase inhibitors
Category: Molecular and Cellular Biology/Genetics
Session: Late-Breaking Research: Molecular and Cellular Biology / Genetics 2
Abstract Number: LB-244
Location: McCormick Place South, Exhibit Hall A, Poster Section 45
Date and Time: Tuesday April 17, 2018; 8:00 AM – 12:00 PM C.T.
Title: Pediatric Preclinical Testing Consortium evaluation of the menin inhibitor, VTP-50469, against xenograft models of MLL-rearranged infant acute lymphoblastic leukemia
Category: Tumor Biology
Session: Pediatrics 2: Preclinical Therapies, Resistance, and Stem Cells
Abstract Number: 3187
Location: McCormick Place South, Exhibit Hall A, Poster Section 7
Date and Time: Tuesday April 17, 2018; 8:00 AM – 12:00 PM C.T.

Title: Histone deacetylase inhibitor, Entinostat enhances the tumor specific immune response by generating T-cell central memory in the TME
Category: Immunology
Session: Immunomodulatory Agents and Interventions 1
Abstract Number: 3761
Location: McCormick Place South, Exhibit Hall A, Poster Section 32
Date and Time: Tuesday April 17, 2018; 8:00 AM – 12:00 PM C.T.
Title: Manipulating the breast tumor microenvironment with histone deacetylase inhibitors for
more robust and durable T cell responses
Category: Immunology
Session: Immunomodulatory Agents and Interventions 2
Abstract Number: 4700
Location: McCormick Place South, Exhibit Hall A, Poster Section 33
Date and Time: Tuesday April 17, 2018; 1:00 PM – 5:00 PM C.T.
All accepted abstracts will be published in the 2018 Proceedings of the AACR (Free AACR Whitepaper). Session
information is available online via the Annual Meeting Itinerary Planner through the AACR (Free AACR Whitepaper) website
at www.aacr.org.

On April 13, 2018 Hanmi Pharmaceutical reported thst it’s long and turbulent development of lung cancer drug olmutinib came to an end this week after the company abandoned the program (Press release, FierceBiotech, APR 13, 2018, View Source [SID1234573812]).

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The South Korean drugmaker took the decision after struggling to recruit patients into clinical trials and concluding that the third-generation EGFR inhibitor was too far behind Tagrisso (osimertinib), AstraZeneca’s fast-growing rival, to make a commercial success of the drug, according to a Korea Biomedical Review report.

Back in 2015, the olmutinib program was riding high on the back of a promising midstage data in T790M-mutated non-small cell lung cancer (NSCLC) and a $730 million licensing deal with Boehringer Ingelheim. The German company described the drug as a possible best-in-class candidate that it was hoping to pair with Merck & Co’s immuno-oncology blockbuster Keytruda in a combination trial.

Just over a year later, Boehringer backed out of the deal after taking another look at the clinical data for the drug and the increasingly crowded EGFR inhibitor market, even though olmutinib had already picked up its first approval—as Olita—in Hanmi’s home market.

Things went from bad to worse last year when the Korean authorities rapped the company for not acting quickly enough to disclose a fatality in a patient treated with the drug who developed life-threatening skin condition Stevens-Johnson syndrome (SJS). All told, the drug was linked to three cases of SJS, two of which proved fatal.

Yet more controversy ensued after Hanmi employees were accused of insider trading relating to the termination of the Boehringer deal, and the Korean firm also lost another partner for olmutinib when Chinese licensee Zai Lab returned rights to the drug.

Meanwhile, olmutinib isn’t the only Hanmi drug to run into trouble of late. Its Eli Lilly-partnered BTK inhibitor LY3337641 failed to hit its objectives in a phase 2 trial in rheumatoid arthritis, leaving the future of the program in other indications under a cloud, while at the end of 2016 a $4.2 billion, three-drug deal with Sanofi for diabetes therapies was trimmed down to two candidates.

Other partnerships with Spectrum for Rolontis (eflapegrastim) and pan-HER drug poziotinib, Johnson & Johnson for diabetes and obesity candidate HM12525A and Roche/Genentech for RAF-targeted cancer drugs currently remain on track.

On April 13,2018 MabSpace Biosciences reported that the first subject has been dosed in a Phase 1 clinical study of MSB2311 , for the treatment of advanced solid tumors (Press release, Mabspace, APR 13, 2018, View Source [SID1234525306]). MSB2311 is a 2nd Generation PD-L1 antibody with a unique pH-dependent antigen binding property that enables intra-tumor recycling and potentiates tumor penetration. It is the first clinical asset generated by MabSpace’s proprietary Immune Tolerance Breaking Technology (IMTB) platform.

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Yuntao Wan, vice president and head of clinical development operations at MabSpace, said, "With seamless execution we moved quickly from IND clearance by FDA to first patient dosed in less than 2 months, by Dr. Papadopoulos and his team at the START clinic of San Antonio, Texas. We’d also like to thank Dr. Adjei from Mayo Clinic, for his expert input into the trial design from the very beginning. He will lead a group of prominent Mayo investigators to join the study soon. Of course, we couldn’t have achieved such a speedy and quality start without the strong support from our CRO partners Syneos Healthcare and Q2 Solutions."

This study, MSB2311-CSP-001, is a first-in-human, open-label, Phase 1 dose-escalation study of MSB2311, a humanized anti-PD-L1 monoclonal antibody in patients with advanced solid tumors. More information can be found at www.clinicaltrials.gov (NCT03463473). A separate China Phase 1 study with several disease expansion cohorts to evaluate preliminary efficacy is at the final stage of regulatory review, and is expected to be initiated soon upon CFDA approval.

"We are excited to start the testing of MSB2311 in cancer patients and can’t wait to see how well the superior pre-clinical efficacy of MSB2311 will translate in clinical setting," said Xueming Qian, Founder and CEO, MabSpace Biosciences

On April !3, 2018 AstraZeneca reported that presented new post-progression outcomes data from an exploratory analysis of the global Phase III FLAURA trial, which assessed the efficacy and safety of Tagrisso (osimertinib) as 1st-line therapy in patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, APR 13, 2018, View Source [SID1234525369]). The presentation at the European Lung Cancer Conference (ELCC) in Geneva during the "Best of ELCC" session showed that the progression-free survival (PFS) benefit of 1st-line Tagrisso over the EGFR tyrosine kinase inhibitors (TKIs), erlotinib or gefitinib, was sustained throughout post-progression outcomes [Abstract #128O].

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Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "The new analysis from the FLAURA trial shows that 1st-line treatment with Tagrisso has a sustained effect beyond subsequent therapy by almost halving the risk of a second progression or death. These findings build on the clinically-meaningful PFS benefit of Tagrisso and reinforce its potential as a new standard of care.
"
At the time of data cut-off, fewer patients on 1st-line Tagrisso had discontinued treatment compared to patients on the EGFR-TKI comparator arm (49% vs. 77%) and 29% received a subsequent treatment compared to 46% on the comparator arm. Median time to first subsequent therapy or death was 23.5 months (95% confidence interval [CI] 22.0, NC) for those treated with 1st-line Tagrisso vs. 13.8 months (95% CI 12.3, 15.7) for patients on erlotinib or gefitinib (hazard ratio [HR] 0.51, 95% CI 0.40, 0.64, p<0.0001).

Patients treated with 1st-line Tagrisso experienced a longer time before discontinuation of EGFR-TKI therapy (median 23.0 months (95% CI 19.5, NC), compared to a median of 16.0 months (95% CI 14.8, 18.6) for comparator arm patients, which included patients who had crossed over to Tagrisso in the 2nd line. 1st-line Tagrisso patients had almost half the risk of second progression or death (PFS2) compared to the comparator arm (HR 0.58, 95% CI 0.44, 0.78, p<0.001).

Dr. David Planchard, Associate Professor of Medicine, Thoracic Tumour Board, Gustave Roussy, France, said: "Post-progression outcomes are increasingly recognised as important measures of efficacy for 1st-line cancer therapies, and the consistency in risk reduction across these endpoints in FLAURA provides confidence in the data from the interim overall survival analysis."

Safety data for 1st-line Tagrisso in FLAURA were in line with those observed in prior clinical trials. It was well tolerated, with fewer Grade 3 or higher adverse events (AEs) than with standard EGFR-TKIs (34% vs. 45%). In patients treated, the most common adverse reactions were rash (58% [1.1% Grade ≥3] for Tagrisso vs. 78% [6.9% Grade ≥3] for the comparator arm), diarrhoea (58% [2.2% Grade ≥3] for Tagrisso vs. 57% [2.5% Grade ≥3] for the comparator arm) and dry skin (36% [<1% Grade ≥3] for Tagrisso vs. 36% [1.1% Grade ≥3] for the comparator arm).

NOTES TO EDITORS
About NSCLC
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths, more than breast, prostate and colorectal cancers combined. Approximately 10-15% of patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC. These patients are particularly sensitive to treatment with EGFR-TKIs, which block the cell-signalling pathways that drive the growth of tumour cells. Tumours almost always develop resistance to EGFR-TKI treatment, however, leading to disease progression. Approximately half of patients develop resistance to approved EGFR-TKIs such as gefitinib, erlotinib and afatinib due to the EGFR T790M resistance mutation. There is also a need for medicines with improved CNS efficacy, since approximately 25% of patients with EGFRm NSCLC have brain metastases at diagnosis, increasing to approximately 40% within two years of diagnosis.

About Tagrisso
Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI designed to inhibit both EGFR-sensitising and EGFR T790M-resistance mutations, with improved clinical activity against CNS metastases. Tagrisso 40mg and 80mg once-daily oral tablets have been approved in more than 75 countries, including the US, EU, Japan and China for patients with EGFR T790M mutation-positive advanced NSCLC. Tagrisso is also being investigated in the adjuvant setting and in combination with other treatments.

About the FLAURA trial
The FLAURA trial assessed the efficacy and safety of 1st-line Tagrisso 80mg once daily vs. standard-of-care EGFR-TKIs (either erlotinib [150mg orally, once daily] or gefitinib [250mg orally, once daily]) in previously-untreated patients with locally-advanced or metastatic EGFRm NSCLC. The trial was double-blinded and randomised, with 556 patients across 29 countries.

About AstraZeneca in Lung Cancer
AstraZeneca is committed to developing medicines to help every patient with lung cancer. We have three approved medicines and a growing pipeline that targets genetic changes in tumour cells and boosts the power of the immune response against cancer. Our unrelenting pursuit of science aims to deliver more breakthrough therapies with the goal of extending and improving the lives of patients across all stages of disease and lines of therapy.
About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance Oncology as a key growth platform for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On April 13, 2018 Novocure (NASDAQ: NVCR) reported that new data on Tumor Treating Fields will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018, which will be held April 14 through April 18, in Chicago (Press release, NovoCure, APR 13, 2018, View Source [SID1234525307]). Tumor Treating Fields is a cancer therapy that uses electric fields tuned to specific frequencies to disrupt cell division, inhibiting tumor growth and causing affected cancer cells to die.

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A total of 35 presentations on the application of Tumor Treating Fields in seven cancer types will be presented. Of the 35 presentations, 18 are externally led research. Highlights include data demonstrating the utility of Tumor Treating Fields in various applications and include the following:

A phase 2 pilot study is assessing the safety of Tumor Treating Fields when administered concomitant to radiation therapy in newly diagnosed glioblastoma patients. The interim results found that newly diagnosed GBM patients who received Tumor Treating Fields at the same time of radiation therapy reported similar proportions of Tumor Treating Fields-related skin toxicity as reported by patients in a phase 3 pivotal study of newly diagnosed GBM patients who received Tumor Treating Fields plus temozolomide four weeks or more after radiation therapy (40 percent versus 52 percent). No other toxicities related to Tumor Treating Fields were reported.

A retrospective safety analysis of Novocure’s EF-14 phase 3 pivotal trial found that the combination of Tumor Treating Fields and the chemotherapy lomustine was a feasible combination in glioblastoma patients who had a recurrence.

Novocure has conducted four phase 2 pilot trials of Tumor Treating Fields in solid tumors located outside of the brain: non small-cell lung cancer, mesothelioma, pancreatic cancer and ovarian cancer. A meta-analysis of 176 patients from these trials found that Tumor Treating Fields applied to the lungs, abdomen and upper pelvis did not result in treatment-related pulmonary, cardiac, hematological or gastrointestinal toxicities. The only common adverse event related to Tumor Treating Fields was skin irritation beneath the device transducer arrays.

"In our preclinical studies to date, Tumor Treating Fields has shown promise in multiple solid tumor types, and we believe it may provide additive or synergistic benefits when combined with certain other anti-cancer agents, which may lead to greater efficacy without significantly increasing the side effects," said Dr. Eilon Kirson, Novocure’s Chief Science Officer and Head of Research and Development. "We must first determine the safety of Tumor Treating Fields in any new application before we can explore potential efficacy. These data support the mild side effect profile of Tumor Treating Fields that we have seen to date."