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Immuno-Oncology Presentation, dated November 2018

On November 19, 2018 Pieris Pharmaceuticals, Inc presented its Immuno-Oncology Presentation 2018 (Presentation, Pieris Pharmaceuticals, NOV 19, 2018, View Source [SID1234531426]).

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MSB Provides Q1 Financial Results and Operational Highlights

On November 16, 2018 Mesoblast Limited (ASX:MSB; Nasdaq:MESO) reported strong financial results and provided operational highlights for the first quarter ended September 30, 2018 (Press release, Mesoblast, NOV 16, 2018, View Source;item=o8hHt16027g9XhJTr8+weNRYaV9bFc2rMd0Q/AXw4zsnDXGHIhg1Zo6OdZ/mQ8xDmNwG+8nCjWUi3+8AQHHPCXcVikgZW6js6ORaqvd2+bjcttGnteaZ9Jpj4yScdpgCNFAltwkTyd4RE/yXEZRb1w==&cb=636779123550696247 [SID1234531524]).

Key financial results for the three months ended September 30, 2018 (first quarter FY2019)
• Significant increase in revenues to US$11.6 million in the first quarter FY2019, compared with US$1.2 million in the first quarter FY2018
• 66% increase in commercialization revenue from royalty income on sales of TEMCELL1 HS. Inj. for the quarter, compared with first quarter FY2018
• Reduction in operating cash outflows in first quarter FY2019 of US$0.8 million (4%) compared with first quarter FY2018
• Loss after tax increased by $12.5 million compared to the first quarter FY2018, $10.1 million of which is due to non-cash remeasurement of contingent consideration in the comparative quarter
• Pro-forma cash on September 30, 2018 was US$95.1 million including:
o US$55.1 million balance sheet cash, and
o US$40.0 million from Tasly Pharmaceutical Group (Tasly) received in October 2018 in relation to the strategic cardiovascular partnership in China announced in July 2018
• An additional US$50.0 million may be available under existing arrangements with Hercules Capital and NovaQuest, subject to achievement of certain milestones.

Corporate Highlights
• Results of a 159-patient randomized placebo-controlled Phase 2 trial, sponsored and conducted by United States National Institutes of Health (NIH), evaluating MPC-150-IM in the treatment of end-stage heart failure patients implanted with a left ventricular assist device (LVAD) were presented at the 2018 American Heart Association Scientific Sessions.
• The trial succeeded in achieving the clinically meaningful outcome of reduction in gastrointestinal (GI) bleeding and related hospitalizations
• Results confirm the previous pilot trial, which also demonstrated significant reduction in GI bleeding and related hospitalizations in MPC-150-IM treated LVAD patients
• Pilot trial results formed the basis for the FDA Regenerative Medicine Advanced Therapy (RMAT) designation granted in December 2017
• The RMAT designation under the 21st Century Cures Act aims to expedite the development of regenerative medicine therapies intended for the treatment of serious diseases and lifethreatening conditions
• Company intends to meet with the FDA in 1H CY2019 to provide full study data and discuss pathway to potential Biologics License Application (BLA) filing using reduction in GI bleeding and related hospitalizations as an approvable regulatory endpoint
• While the trial did not meet the overall primary endpoint of temporary weaning, MPC-150- IM treatment did significantly improve weaning in the 44% of patients with chr
• Mesoblast’s Phase 3 trial of its product candidate remestemcel-L in children with steroidrefractory acute Graft Versus Host Disease (aGVHD) demonstrated strong survival outcomes through Day 180. Mesoblast is preparing for a pre-BLA meeting to initiate filing of a marketing authorization for this product candidate in the United States.
• Mesoblast expanded its partnership with JCR Pharmaceuticals Co. Ltd. (JCR) for the treatment of wound healing in epidermolysis bullosa (EB). Having been granted Orphan Regenerative Medical Product designation for EB in October, JCR now intends to seek a label extension for TEMCELL in Japan for EB beyond its existing approval for the treatment of aGVHD.
• Mesoblast completed its transaction with Tasly to establish a strategic cardiovascular partnership in China. In addition to US$40 million received on closing the transaction, Mesoblast is eligible to receive up to US$25 million on product regulatory approval in China, double-digit escalating royalties on net product sales as well as six escalating milestone
payments upon the achievement of certain product sales thresholds in China.

Operational Highlights and Anticipated Upcoming Milestones
MPC-150-IM for Moderate to Advanced Heart Failure:
• The ongoing Phase 3 trial received a recommendation in October 2018 from the unblinded Independent Data Monitoring Committee to continue without modification after an evaluation of clinical safety data in the first 526 randomized patients. MSC-100-IV (remestemcel-L) for pediatric steroid-refractory acute Graft Versus Host Disease
(aGVHD):
• Mesoblast will seek a pre-BLA meeting to initiate filing of a marketing authorization for remestemcel-L in the United States, where there are currently no approved therapies for aGVHD.
• An existing Fast Track designation from the FDA allows eligibility for priority review and a rolling BLA review process.
MPC-06-ID for Chronic Low Back Pain:
• Mesoblast’s Phase 3 trial in patients with chronic low back pain who have failed conservative therapy completed enrollment in March 2018, with a total of 404 patients across 48 sites being followed out for evaluation of treatment-related improvement in pain and function.
Financial Results for the Three Months Ended September 30, 2018 (first quarter FY2019) (in U.S. Dollars)
• Revenues were US$11.6 million for the first quarter FY2019, compared with US$1.2 million for the first quarter FY2018, an increase of US$10.5 million. These revenues primarily consisted of:
o US$1.5 million in royalties and milestones from sales of TEMCELL by our licensee in Japan, JCR Pharmaceuticals Co. Ltd. Royalties from TEMCELL increased by 66% for first quarter FY2019 compared with the first quarter FY2018
o US$10.0 million milestone revenue in relation to establishing a strategic cardiovascular
partnership with Tasly in China
• Research and Development expenses were US$18.5 million for the first quarter FY2019, compared with US$15.4 million for the first quarter FY2018, an increase of US$3.1 million (20%) as the Company invested in its Tier 1 clinical programs
• Manufacturing expenses were US$4.3 million for the first quarter FY2019, compared with US$0.9 million for the first quarter FY2018, an increase of US$3.4 million due to an increase in manufacturing activities in preparation for filing the Biologics License Application (BLA) for MSC100-IV
• Management and Administration expenses were US$5.6 million for the first quarter FY2019, compared with US$5.0 million for the first quarter FY2018, an increase of US$0.6 million (12%) primarily due to increased legal and professional fees associated with establishing the strategic cardiovascular partnership with Tasly
• Finance Costs of US$2.6 million in interest expenses were recognized in first quarter FY2019 in relation to loan and security agreements entered into with Hercules Capital in March 2018 and NovaQuest Capital in June 2018. No interest expense was recognized in the first quarter FY2018

Additional components of loss after income tax also include movements in other items which did not impact current cash reserves, such as: fair value remeasurement of contingent consideration, and foreign exchange movements within other operating income and expenses.

A non-cash income tax benefit of US$0.7 million was recognized in the first quarter FY2019 in relation to the net change in deferred tax assets and liabilities recognized on the balance sheet during the period. On December 22, 2017, the United States signed into law the Tax Cuts and Jobs Act (the Tax Act), which changed many aspects of United States corporate income taxation, including a reduction in the corporate income tax rate from 35% to 21%. In the first quarter FY2018 deferred tax assets in the United States were recognized at 35% compared with 21% in the first quarter FY2019.

A non-cash income tax benefit of US$2.9 million was recognized in first quarter FY2018 in relation to the net change in deferred tax assets and liabilities recognized on the balance sheet during the period.

The net loss attributable to ordinary shareholders was US$19.5 million, or 4.07 cents loss per share, for the first quarter FY2019, compared with US$7.0 million, or 1.58 cents loss per share, for the first quarter FY2018.
1TEMCELL HS Inj. is a registered trademark of JCR Pharmaceuticals Co. Ltd.
Conference Call Details
There will be a webcast today on the financial results beginning at 4.30pm on Thursday, November
15, 2018 EST; 8:30 am on Friday, November 16, 2018 AEDT.
The live webcast can be accessed via
View Source
To access the call only, dial 1 855 881 1339 (U.S.), 1 800 558 698 (toll-free Australia) or +61 2 9007
3187 (outside of the U.S. and Australia). The conference identification code is 667811.
The archived webcast will be available on the Investor page of the Company’s website:
www.mesoblast.com

AstraZeneca provides update on the Phase III MYSTIC trial of Imfinzi and tremelimumab in Stage IV non-small cell lung cancer

On November 16, 2018 AstraZeneca and MedImmune, its global biologics research and development arm, reported final overall survival (OS) results for the Phase III MYSTIC trial, a randomised, open-label, multi-centre, global trial of Imfinzi (durvalumab) monotherapy and the combination of Imfinziand tremelimumab, an anti-CTLA4 antibody, versus standard-of-care (SoC) platinum-based chemotherapy in previously-untreated patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, NOV 16, 2018, View Source [SID1234531487]).

In the primary analysis population of patients, whose tumours express PD-L1 on 25% or more of their cancer cells as determined by the VENTANA PD-L1 (SP263) Assay, Imfinzi monotherapy and the combination of Imfinzi plus tremelimumab did not meet the primary endpoints of improving OS compared to SoC chemotherapy. While the OS result did not meet statistical significance, a hazard ratio (HR) of 0.76 (97.54% CI 0.564-1.019; nominal p=0.036) was observed with Imfinzimonotherapy. The combination therapy had an HR of 0.85 (98.77% CI 0.611-1.173; nominal p=0.202); the data support further analysis in exploratory subgroups.

The safety and tolerability profiles for Imfinzi and the Imfinzi plus tremelimumab combination were consistent with previous trials.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, said: "We are encouraged to see that Imfinzi monotherapy activity is in-line with that of the anti-PD-1 class in previously-untreated patients with Stage IV non-small cell lung cancer; however, we are disappointed that these results missed statistical significance. We remain confident in Imfinzias the cornerstone of our IO programme and continue to evaluate its potential in ongoing non-small cell lung cancer trials, including Imfinzi and Imfinzi plus tremelimumab in combination with chemotherapy."

Imfinzi is approved for unresectable, Stage III NSCLC in more than 40 countries, including the US, EU and Japan, based on the Phase III PACIFIC trial. Imfinzi is currently being tested in a range of Phase III trials for Stage IV NSCLC.

Immuno-oncology Phase III trials in Stage IV, 1st-line NSCLC

PEARL

Imfinzi monotherapy vs SoC chemotherapy
NEPTUNE

Imfinzi + tremelimumab vs SoC chemotherapy
POSEIDON

Imfinzi + chemotherapy or Imfinzi + tremelimumab + chemotherapy
vs SoC chemotherapy

About MYSTIC
The MYSTIC trial is a randomised, open-label, multi-centre, global Phase III trial of Imfinzi(durvalumab) monotherapy or Imfinzi in combination with tremelimumab versus SoC chemotherapy in the 1st-line treatment of patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type, locally-advanced or metastatic (Stage IV) non-small cell lung cancer.

The trial was conducted in 167 centres across 17 countries, including the US, Canada, Europe, Russia, Australia and parts of Asia, including Japan, Korea, Thailand, Taiwan and Vietnam. Primary endpoints included progression-free survival (PFS) for the combination, and OS in monotherapy and in combination therapy. The combination of Imfinzi and tremelimumab did not meet the primary endpoint of improving PFS compared to SoC in patients whose tumours express PD-L1 on 25% or more of their cancer cells in July 2017.

About Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is approved for unresectable, Stage III NSCLC in more than 40 countries including the US, EU, and Japan based on the Phase III PACIFIC trial. Imfinzi is also approved for previously-treated patients with advanced bladder cancer in the US, Canada, Brazil, Israel, India, United Arab Emirates, Australia and Hong Kong.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, small-cell lung cancer (SCLC), bladder cancer, head and neck cancer and other solid tumours.

About tremelimumab
Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4, contributing to T cell activation and boosting the immune response to cancer. Tremelimumab is being tested in a clinical trial programme in combination with Imfinzi in NSCLC, urothelial carcinoma, head and neck squamous cell carcinoma, hepatocellular carcinoma and blood cancers.

About Stage IV NSCLC
Lung cancer is the leading cause of cancer death among both men and women and accounts for about one-fifth of all cancer deaths: more than breast, prostate and colorectal cancers combined. Lung cancer is broadly split into NSCLC and SCLC, with 80-85% classified as NSCLC. Stage IV is the most advanced form of lung cancer and is often referred to as metastatic disease. Approximately 85% of Stage IV patients are diagnosed after the tumour has spread outside of the lung. For these patients, prognosis is particularly poor, as only 1 in 10 will be alive five years after diagnosis.

About AstraZeneca in lung cancer
AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage clinical development for the treatment of different forms of lung cancer spanning several stages of disease and lines of therapy. We aim to address the unmet needs of patients with EGFR-mutated tumours as a genetic driver of disease, which occur in 10-15% of NSCLC patients in the US and EU and 30-40% of NSCLC patients in Asia, with our approved medicines Iressa and Tagrisso and ongoing FLAURA, ADAURA and LAURA Phase III trials.

Our extensive late-stage Immuno-Oncology programme focuses on 75-80% of patients with lung cancer without a known genetic mutation. Imfinzi, an anti-PDL1 antibody is in development as monotherapy (ADJUVANT BR.31, PACIFIC-2, PACIFIC-5, MYSTIC and PEARL Phase III trials) and in combination with tremelimumab and/or chemotherapy (MYSTIC, NEPTUNE, POSEIDON, ADRIATIC and CASPIAN Phase III trials).

About AstraZeneca’s approach to immuno-oncology
IO is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. At AstraZeneca and MedImmune, our biologics research and development arm, our IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. We believe that IO-based therapies offer the potential for life-changing cancer treatments for the clear majority of patients.

We are pursuing a comprehensive clinical-trial programme that includes Imfinzi (anti-PDL1) as monotherapy and in combination with tremelimumab (anti-CTLA4) in multiple tumour types, stages of disease, and lines of therapy, using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine our IO portfolio with small, targeted molecules from across our Oncology pipeline, and from our research partners, may provide new treatment options across a broad range of tumours.

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 driver 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.

Chi-Med Announces Phase III FALUCA Trial Results for Fruquintinib in Third-Line, Advanced Non-Small Cell Lung Cancer in China

On November 16, 2018 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) reported the outcome of FALUCA, its Phase III trial of fruquintinib in advanced non-small cell lung cancer ("NSCLC") patients in China who have failed two lines of systemic chemotherapy (Press release, Hutchison China MediTech, NOV 16, 2018, https://www.chi-med.com/phase-iii-faluca-results/ [SID1234531461]). The trial did not meet the primary endpoint to demonstrate a statistically significant increase in overall survival ("OS") compared to placebo.

Fruquintinib demonstrated, in FALUCA, a statistically significant improvement in all secondary endpoints including progression-free survival ("PFS"), objective response rate ("ORR"), disease control rate ("DCR") and duration of response ("DoR") as compared to the placebo. The safety profile of the trial was in line with that observed in prior clinical studies. Full detailed results are expected to be disclosed at an upcoming scientific meeting.

"While the study demonstrates a significant reduction in disease progression in this challenging lung cancer patient population, we are disappointed that this benefit did not translate into an increase in overall survival," commented Simon To, Chairman of Chi-Med. He added, "We remain confident that the high selectivity and lower off-target toxicities of fruquintinib are major points of differentiation. The recent first approval of fruquintinib monotherapy for advanced colorectal cancer, the imminent launch in China, and the commencement of several combination collaborations with immunotherapies both in China and in the U.S., reinforces our belief in fruquintinib."

Fruquintinib was first approved by the National Medical Products Administration of China (NMPA) in September 2018, for the treatment of advanced colorectal cancer, becoming the first China-discovered and developed pharmaceutical for a mainstream oncology indication to be unconditionally approved in China. Chi-Med has established a manufacturing facility in Suzhou, China, to produce fruquintinib. The market launch of fruquintinib in CRC in China, in collaboration with Eli Lilly and Company ("Lilly"), is now imminent.

Fruquintinib is also in multiple ongoing clinical trials in the U.S. and China, including in combination with checkpoint inhibitors, chemotherapy, and other targeted therapy agents.

About Other Fruquintinib Development Programs
Global Development
Phase I monotherapy in the U.S.: In December 2017, Chi-Med initiated a multi-center, open-label, Phase I clinical study to evaluate the safety, tolerability and pharmacokinetics of fruquintinib in U.S. patients with advanced solid tumors (clinicaltrials.gov identifier NCT03251378). This study is almost complete, and proof-of-concept ("POC") studies are expected to begin in 2019.

China Development
Colorectal cancer in China: The NMPA approved the first NDA for fruquintinib for the treatment of patients with advanced colorectal cancer in September 2018. The NDA is supported by data from the successful FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with advanced colorectal cancer in China, which was highlighted in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held on June 5, 2017 (clinicaltrials.gov identifier NCT02314819).

Gastric cancer in China: In October 2017, Chi-Med initiated a pivotal Phase III clinical trial of fruquintinib in combination with Taxol (paclitaxel), known as the FRUTIGA study, in approximately 500 patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma who have progressed after first-line standard chemotherapy (clinicaltrials.gov identifier NCT03223376). An interim analysis on FRUTIGA, to establish POC, is anticipated during the first half of 2019 and if successful could trigger a POC milestone from Lilly. The FRUTIGA study followed a Phase I/II clinical trial in 34 patients with gastric cancer that demonstrated that combination therapy of fruquintinib and Taxol was generally well-tolerated with promising tumor response (clinicaltrials.gov identifier NCT02415023).

Lung cancer in China: Fruquintinib is being studied in a Phase II study in combination with Iressa (gefitinib) in patients with untreated advanced or metastatic NSCLC (clinicaltrials.gov identifier NCT02976116). Preliminary results were highlighted in an oral presentation at the 18th World Conference on Lung Cancer on October 16, 2017.

Programmed cell death protein-1 ("PD-1") checkpoint inhibitor combination: It is an important part of Chi-Med’s strategy to explore the potential synergies of its drug candidates in combination with other anti-cancer treatments in several solid tumor settings. In October 2018, Chi-Med entered into a further collaboration in China to evaluate the combination of fruquintinib with genolimzumab (GB226), a PD-1 inhibitor being developed by Genor Biopharma Company Limited.

About FALUCA
The FALUCA trial is a randomized, double-blind, placebo-controlled, multi-center, Phase III registration study targeted at treating patients with advanced non-squamous NSCLC, who have failed two lines of systemic chemotherapy. 527 patients were randomized at a 2:1 ratio to receive either: 5mg of fruquintinib orally once per day, on a three-weeks-on / one-week-off cycle, plus best supportive care ("BSC"); or placebo plus BSC. The primary endpoint is OS, with secondary endpoints including PFS, ORR, DCR and DoR. Additional details about this study can be found at clinicaltrials.gov, using identifier NCT02691299.

About Fruquintinib
Fruquintinib (brand name: Elunate) is a small molecule, selective and highly potent inhibitor of VEGFR 1, 2 and 3. VEGFR inhibitors play a pivotal role in tumor-related angiogenesis, cutting off the blood supply that a tumor needs to grow rapidly. The global market for anti-angiogenesis therapies was estimated at over US$18 billion in 2017, including both monoclonal antibodies and small molecules approved in around 30 tumor settings. During the discovery research process, which began at Chi-Med in 2007, fruquintinib was successfully designed to be differentiated by improving kinase selectivity in comparison to other approved small molecule tyrosine kinase inhibitors (TKIs), to minimize off-target toxicities, improve tolerability and provide more consistent target coverage, resulting in better clinical efficacy. The superior tolerability, along with fruquintinib’s low potential for drug-drug interaction based on preclinical assessment, suggests that it may be highly suitable for innovative combinations with other anti-cancer therapies.

In October 2013, Chi-Med entered into a licensing, co-development and commercialization agreement in China with Lilly for fruquintinib. Under the terms of the agreement, the costs of development of fruquintinib, carried out by Chi-Med, are shared; Chi-Med has received upfront payments and development and regulatory approval milestone payments; and upon commercialization in China, Chi-Med would receive royalties. Chi-Med and Lilly agreed to develop fruquintinib in three initial solid tumor indications, including CRC, NSCLC and gastric cancer.

The most common adverse reactions included hypertension, hand-foot syndrome and proteinuria. Clinically effective management of these adverse effects is feasible. For important safety information about fruquintinib, please see www.chi-med.com.

Agios Presents Updated Data from Phase 1 Dose-Escalation Study of AG-881 in Patients with IDH Mutant Positive Advanced Glioma

On November 16, 2018 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported its updated data from the ongoing Phase 1 study evaluating single agent AG-881 in advanced glioma (Press release, Agios Pharmaceuticals, NOV 16, 2018, View Source [SID1234531460]). The data were featured in an oral presentation at the Society for Neuro-Oncology (SNO) Annual Meeting in New Orleans. AG-881 is an investigational, oral, selective, potent inhibitor of the mutant isocitrate dehydrogenase-1 (IDH1) and IDH2 enzymes and was designed for enhanced brain penetrance for development in IDH-mutant glioma.

"With additional follow-up, the AG-881 Phase 1 dose-escalation data continue to show a favorable safety profile at the doses selected for the perioperative study. Longer treatment duration and a reduction in tumor growth rates are encouraging signs of clinical activity in low-grade glioma," said Ingo Mellinghoff, M.D., Memorial Sloan Kettering Cancer Center, an investigator for the study. "Ultimately, use of an IDH inhibitor in this difficult-to-treat disease has the potential to improve the current treatment paradigm by delaying the multiple rounds of surgery, radiation and chemotherapy that many patients endure."

"With no curative or approved targeted therapies and a high frequency of IDH1 mutations in low-grade glioma, we are committed to advancing one of our IDH inhibitors to a registrational study in this disease," said Chris Bowden, M.D., chief medical officer at Agios. "We are continuing to collect clinical data for both ivosidenib and AG-881, along with feedback from regulators and the neuro-oncology community, to make an internal decision on our glioma pivotal strategy by the end of this year."

Study Status

AG-881 is being evaluated as a single agent in an ongoing Phase 1 dose-escalation trial in IDH1/2 mutant advanced solid tumors, including glioma. Enrollment was completed in June 2017. Dose escalation data as of March 29, 2018 were presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. As of the updated July 20, 2018 data cut-off, study design, enrollment and baseline characteristics of the 52 glioma patients remain unchanged, as reported below.

Forty-eight percent of patients (n=25) had World Health Organization (WHO) classified Grade 2 tumors, 42% (n=22) had Grade 3 tumors, 8% (n=4) had Grade 4 tumors and 2% (n=1) was unknown.
The median age of these patients is 42.5 years (ranging from 16-73 years).
Patients received a median of two prior systemic therapies (ranging from one to six).
Seventy-three percent of patients (n=38) had previously received temozolomide and 58% percent (n=30) had previously received radiotherapy.
Patients received daily doses of AG-881 ranging from 10 mg to 300 mg.
Updated safety and efficacy data on the 52 patients with enhancing and non-enhancing glioma, including an exploratory tumor volume growth rate analysis, are reported below.

Fourteen patients remain on treatment, including 13 patients with non-enhancing disease.
Of the 38 patients who discontinued treatment, 76.3% (n=29) discontinued for disease progression and 5.2% (n=2) discontinued due to an AE.
The median treatment duration was 6.3 months (ranging from 0.2-32 months) for all glioma patients, 15 months (ranging from 1-32 months) for non-enhancing glioma and 3.25 months (ranging from 0.2- 32 months) for patients with enhancing disease.
Thirty-seven percent of patients (n=19, including 15 patients with non-enhancing disease) remained on treatment for ≥1 year.
Safety Data

The safety analysis conducted for all 52 glioma patients as of the data cut-off demonstrated that AG-881 continues to have a favorable safety profile at dose levels below 100 mg.

The majority of adverse events (AEs) reported by investigators were mild to moderate, with the most common (>30%) being increases in alanine aminotransferase (ALT) (n=23), increases in aspartate aminotransferase (AST) (n=21), headache (n=19) and fatigue (n=17).
Grade 3 or higher AEs were observed in 19% of all patients (n=10). AEs occurring in more than one patient included seizure (n=4), ALT increases (n=3) and AST increases (n=2).
As reported in June, dose limiting toxicities (DLTs) of Grade 2 or higher elevated transaminases occurred in five glioma patients at the higher dose levels (≥100 mg) and resolved to Grade ≤1 with dose modification or discontinuation. There were no new DLTs reported as of the new data cut-off or any treatment-related on-treatment deaths.
Doses of 10 mg and 50 mg are under evaluation in an ongoing perioperative study in non-enhancing glioma.
Efficacy Data

Efficacy data from the 52 glioma patients (22 with non-enhancing and 30 with enhancing disease) as of the data cut-off showed:

One patient with non-enhancing disease and a 1p19q co-deletion had a confirmed / sustained partial response according to the investigator by Response Assessment in Neuro-Oncology for low grade glioma (RANO-LGG) and remains on treatment.
One patient with non-enhancing disease and a 1p19q co-deletion had a confirmed / sustained minor response according to the investigator by RANO-LGG and remains on treatment.
Sixty-nine percent of patients (n=36) had a best response of stable disease, including 82% (n=18) patients with non-enhancing disease.
For non-enhancing patients with available data (n=18), the average volumetric six-month tumor growth was 6.8% following treatment with AG-881; pre-treatment volumetric growth rates were not available for these patients. For a similar population of IDHm low-grade glioma patients in the ongoing Natural History study, the average six-month volumetric growth prior to treatment was 24.5%.
Ongoing Glioma Perioperative Study Presented in Trials in Progress Poster
A perioperative ‘window’ trial with ivosidenib and AG-881 (10 mg and 50 mg) in up to 45 IDH1m non-enhancing low-grade glioma patients is ongoing and being presented today as part of a trials in progress poster. The goal of the trial is to confirm CNS penetrance and tumor 2-HG suppression of ivosidenib and AG-881 as part of the strategy to finalize internal pivotal development plans by year-end 2018.

About Glioma
Glioma presents in varying degrees of tumor aggressiveness, ranging from slower growing (low-grade glioma) to rapidly progressing (high-grade glioma-Glioblastoma Multiforme). Common symptoms include seizures, memory disturbance, sensory impairment and neurologic deficits. The long-term prognosis is poor with a five-year survival rate of 33 percent. Approximately 11,000 low-grade glioma patients are diagnosed annually in the U.S. and EU and approximately 80 percent have an IDH1 mutation.