On November 5, 2018 Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of autoimmune disease, asthma and allergic diseases, and cancer, reported financial results for the third quarter ended September 30, 2018 and provided a review of recent business and clinical highlights (Press release, Xencor, NOV 5, 2018, View Source [SID1234530746]).

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"Our recent data readouts represent advancement across our pipeline of wholly owned and partnered XmAb-based therapeutics for autoimmune disorders and cancer," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "In particular, we are encouraged by initial data from the ongoing Phase 1 study of our lead bispecific oncology candidate, XmAb14045, in AML, which will be presented in an oral session at ASH (Free ASH Whitepaper) next month. These data show complete remissions on a weekly dosing schedule in heavily pretreated patients as we continue to optimize dosing regimen."

Dr. Dahiyat added, "This is the first clinical data to emerge from our bispecific oncology programs and reflects the potential of our novel bispecific Fc domains to enable stable, long-lived bispecific antibodies in which their potencies are tuned to potentially improve tolerability and effectiveness. Our broad pipeline now includes seven bispecific candidates in addition to our lead autoimmune disease candidate, XmAb5871, which is expected to enter into a Phase 3 study in IgG4-RD by early 2019."

Recent Business Highlights and Upcoming Clinical Plans

XmAb5871: XmAb5871 is a first-in-class monoclonal antibody that targets CD19 with its variable domain and uses Xencor’s XmAb immune inhibitor Fc domain to target FcγRIIb, a receptor that inhibits B-cell function. XmAb5871 is currently in clinical development for IgG4-Related Disease (IgG4-RD) and Systemic Lupus Erythematosus (SLE), and it has received Orphan Drug designation from the FDA and Orphan Medicinal Product designation from the European Commission for the treatment of IgG4-RD.

Based on promising Phase 2 results and ongoing discussions with the regulatory authorities, Xencor is designing a randomized, placebo-controlled, double-blind Phase 3 trial of XmAb5871 in approximately 200 to 250 patients and is defining the novel endpoint in order to evaluate the addition of XmAb5871 to standard of care. Initiation of the study is expected by early 2019.
In October 2018, Xencor presented topline results from its randomized, double-blind, placebo-controlled Phase 2 study in patients with SLE at the American College of Rheumatology (ACR) Annual Meeting. A positive trend was observed in the primary endpoint of the study, proportion of efficacy-evaluable patients who did not experience loss of improvement (LOI) by Day 225, though it did not achieve statistical significance. The study achieved the prespecified secondary endpoint, time to LOI, and patients treated with XmAb5871 experienced a 76% improvement in median time to LOI compared to patients treated with placebo. Given these encouraging results, Xencor believes that XmAb5871 warrants further development in SLE and is seeking a partner to continue such development.

Bispecific Oncology Pipeline: Xencor’s bispecific Fc domains are being used to develop several classes of novel drug candidates, including: CD3 bispecific antibodies, tumor microenvironment (TME) activator bispecific antibodies and bispecific cytokines. Xencor’s XmAb Fc domains confer long circulating half-lives, stability and ease of manufacture.

CD3 Bispecific Antibodies: Xencor’s initial bispecific antibody programs are tumor-targeted antibodies that contain both a tumor antigen binding domain and a cytotoxic T-cell binding domain (CD3). These bispecific antibodies activate T cells for highly potent and targeted killing of malignant cells.

Presentation of initial data from Phase 1 study of XmAb14045 (CD123 x CD3) in patients with acute myeloid leukemia (AML) on December 3, 2018 at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.
Initial data from Phase 1 study of XmAb13676 (CD20 x CD3) in B-cell malignancies, expected in 2019, pending alignment on timing with Novartis.
Initial data from Phase 1 study of XmAb18087 (SSTR2 x CD3) in neuroendocrine tumors and gastrointestinal stromal tumors, expected in 2019.
TME Activator Bispecific Antibodies: Xencor’s bispecific pipeline includes a suite of TME activators that engage multiple targets, such as T-cell checkpoints or agonists.

Initial data from DUET-2, a Phase 1 study of XmAb20717 (PD-1 x CTLA-4) in advanced solid tumors, expected in 2019.
IND application for XmAb23104 (PD-1 x ICOS) allowed by the FDA in November 2018; initiation of Phase 1 study in select solid tumors expected in 2019.
IND submission for XmAb22841 (CTLA-4 x LAG-3) in multiple oncology indications, expected by year-end 2018; initiation of Phase 1 trial expected in 2019.
Bispecific Cytokines: Xencor is developing a candidate that contains cytokine and cytokine receptor domains to selectively expand and activate immune cells that can be recruited against tumors.

IND submission for XmAb24306 (IL15/IL15Rα-Fc) in multiple oncology indications expected in 2019.
XmAb7195: XmAb7195 is a first-in-class monoclonal antibody that targets IgE with its variable domain and uses Xencor’s XmAb immune inhibitor Fc domain to target FcyRIIb, resulting in three distinct mechanisms of action for reducing IgE. In a Phase 1b study, subcutaneously-administered XmAb7195 induced potent IgE reduction with improved tolerability. Xencor is currently seeking a development partner for XmAb7195.

Partnered XmAb Programs: Eight pharmaceutical companies and the National Institutes of Health are advancing novel drug candidates either discovered at Xencor or that rely on Xencor’s proprietary XmAb technology. Four such programs are currently undergoing clinical testing, including MOR208, which is in Phase 3 development as a combination agent for the treatment of relapsed or refractory diffuse large B-cell lymphoma, and AMG 424, a CD38 x CD3 bispecific antibody, which Amgen announced had entered into a Phase 1 study for the treatment of patients with multiple myeloma in the third quarter of 2018.

In the third quarter of 2018, Xencor received $9 million in milestone payments from Alexion in connection with their submission of marketing authorizations for ALXN1210 to the FDA and EMA for the treatment of patients with paroxysmal nocturnal hemoglobinuria. In October 2018, Alexion announced that they had submitted a marketing authorization to regulatory authorities in Japan and that the FDA had set the review date for its application for February 2019.

Third Quarter Ended September 30, 2018 Financial Results

Effective January 1, 2018, Xencor adopted the new revenue recognition standard, Accounting Standard Codification 606 (ASC 606). In addition to adopting the standard for 2018, revenue reported for the prior period ending September 30, 2017 has been revised to reflect the new standard.

Cash, cash equivalents and marketable securities totaled $547.8 million as of September 30, 2018, compared to $363.3 million at December 31, 2017. The increase reflects net proceeds of $245.5 million from Xencor’s sale of additional stock in March 2018, partially offset by cash used to fund operating activities in the nine months ended September 30, 2018.

Total revenue for the three- and nine-month periods ended September 30, 2018 was $29 million, compared to zero and $16 million of revenue reported for the same periods in 2017. Revenues in the three and nine-month periods ended September 30, 2018 included revenue recognized under the Company’s Novartis collaboration and milestone payments received from the Company’s Alexion collaboration.

Research and development expenditures for the third quarter ended September 30, 2018 were $21.0 million, compared to $19.4 million for the same period in 2017. Total research and development expenditures for the nine-month period ended September 30, 2018 were $70.4 million, compared to $51.4 million for the same period in 2017. The increased research and development spending for the three and nine months ended September 30, 2018 reflects additional spending on Xencor’s expanding pipeline of bispecific oncology candidates.

General and administrative expenses for the third quarter ended September 30, 2018 were $7.4 million, compared to $4.2 million in the same period in 2017. Total general and administrative expenditures for the nine-month period ended September 30, 2018 were $17.0 million, compared to $13.1 million for the same period in 2017. The increased spending on general and administrative expenses for the three and nine months ended September 30, 2018 reflects increased compensation costs including increased stock-based compensation charges.

Non-cash, stock-based compensation expense for the nine months ended September 30, 2018 was $15.5 million, compared to $10.2 million for same period in 2017.

Net income for the third quarter ended September 30, 2018 was $3.2 million, or $0.05 on a fully diluted per share basis, compared to a net loss of $22.7 million, or $(0.48) on a fully diluted per share basis, for the same period in 2017. The net income reported for three months ended September 30, 2018 over the loss for the same period in 2017 is primarily due to revenue recognized from Xencor’s Novartis and Alexion collaborations in 2018. For the nine months ended September 30, 2018, net loss was $52.2 million, or $(0.98) on a fully diluted per share basis, compared to a net loss of $45.9 million, which was also $(0.98) on a fully diluted per share basis, for the same period in 2017. The increased revenue for the nine months ended September 30, 2018 over amounts for the same period in 2017 was offset by increased spending in research and development in 2018. The earnings per share loss for the nine months ended September 2018 was equal to the earnings per share loss in 2017 due to the increase in shares outstanding in 2018.

The total shares outstanding were 56,212,449 as of September 30, 2018, compared to 46,955,365 as of September 30, 2017. The additional shares outstanding at September 30, 2018 reflect the 8,395,000 shares sold in Xencor’s March financing.

Financial Guidance

Based on current operating plans, Xencor expects to have cash to fund research and development programs and operations into 2023. Xencor expects to end 2018 with approximately $525 million in cash, cash equivalents and marketable securities.

Conference Call and Webcast

Xencor will host a conference call today at 4:30 p.m. ET (1:30 p.m. PT) to discuss these third quarter 2018 financial results and provide a corporate update.

The live call may be accessed by dialing (877) 359-9508 for domestic callers or (224) 357-2393 for international callers and referencing conference ID number 5577136. A live webcast of the conference call will be available online from the Investors section of the Company’s website at www.xencor.com. The webcast will be archived on the company’s website for 90 days.

On November 5, 2018 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported its financial results for the third quarter ended September 30, 2018 (Press release, Syndax, NOV 5, 2018, View Source [SID1234530745]). In addition, the Company provided a clinical and business update. As of September 30, 2018, Syndax had $89.6 million in cash, cash equivalents and short-term investments.

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"The last several months have been marked by exciting progress across multiple programs, culminating with our recent announcement of plans to commence what will become our second registration study: a focused, biomarker-driven registration trial to evaluate entinostat in combination with pembrolizumab in patients with non-small cell lung cancer whose disease has progressed after PD-1 therapy," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "We remain highly encouraged by the potential for a positive overall survival readout for E2112, our Phase 3 registration trial of entinostat plus exemestane in HR+, HER2- breast cancer, which would allow us to file for full regulatory approval in this indication. We look forward to reporting on multiple exciting value inflection points across our ENCORE I/O combination trials in the coming months."

Pipeline Updates

Entinostat

At the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer (WCLC) in September, the Company presented data from the full cohort of PD-(L)1 refractory non-small cell lung cancer (NSCLC) patients enrolled in the ENCORE 601 trial of entinostat in combination with KEYTRUDA (pembrolizumab). The data continued to support the prior observation of enhanced clinical benefit in a subpopulation of patients with elevated baseline levels of peripheral classical blood monocytes. In October, the Company announced plans to commence a focused, biomarker-driven, randomized registration trial comparing the entinostat-pembrolizumab combination to standard of care chemotherapy in patients whose disease has progressed after both platinum-based chemotherapy and PD-1 antagonist therapy. The trial will seek to validate peripheral classical monocytes as a marker of response to the combination and to determine whether the combination can improve progression free survival (PFS) over standard of care chemotherapy in the high monocyte population. The Company anticipates beginning the trial in the first half of 2019.
In October, Syndax announced that enrollment has concluded in E2112, the Phase 3 registration trial of entinostat plus exemestane in advanced hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+, HER2-) breast cancer, with a total of 608 patients enrolled. ECOG-ACRIN Cancer Research Group and the National Cancer Institute informed the Company that the trial did not meet the statistical hurdle for the first primary endpoint of improving PFS, which would have provided the earliest regulatory filing opportunity. Following the most recent interim overall survival (OS) analysis conducted by the trial’s Data Safety Monitoring Committee, ECOG-ACRIN also informed Syndax that the trial is continuing as planned, with the next interim analysis for the OS primary endpoint scheduled for the second quarter of 2019. Additional interim analyses will be conducted every six months until either an OS benefit is observed, or the final target number of events occur. E2112 was designed, and obtained Breakthrough Therapy Designation for this indication, based on positive Phase 2b OS results. Any positive OS assessment would enable the Company to file for full regulatory approval.
The Company will make a decision later this year on next steps for entinostat in combination with KEYTRUDA in melanoma patients whose disease has progressed following PD-1 therapy.
Enrollment in the expanded stage 1 ENCORE 601 cohort of patients with microsatellite stable colorectal cancer (MSS-CRC, n = 37) is now complete. A decision on whether to continue to the second stage of this cohort is expected in the first quarter of 2019.
As previously communicated, target enrollment is complete in both the Phase 2 portion of ENCORE 602, the Phase 1b/2 clinical trial evaluating the combination of entinostat plus Genentech’s PD-(L)1 inhibitor, TECENTRIQ (atezolizumab), in patients with triple negative breast cancer, and the Phase 2 portion of ENCORE 603, evaluating entinostat in combination with Pfizer/Merck KGaA’s PD-(L)1 inhibitor, BAVENCIO (avelumab), in patients with ovarian cancer. Topline results for ENCORE 603 are expected in the first quarter of 2019, with topline results from ENCORE 602 to follow in the second quarter of 2019.
ENCORE 606, the Phase 1b/2 trial evaluating entinostat in combination with NKTR-214, Nektar’s CD122-biased agonist, is expected to begin enrolling patients with melanoma whose disease has progressed after PD-1 antagonist therapy in the second quarter of 2019.
SNDX-6352

Enrollment has recently been initiated in the Phase 1 dose escalation trial of SNDX-6352, the Company’s anti-CSF-1R monoclonal antibody, in patients with chronic graft versus host disease (cGVHD). The objectives of this trial are to evaluate the safety and preliminary efficacy of SNDX-6352 in cGVHD and to identify a recommended Phase 2 dose and schedule. Initial results are anticipated in the second half of 2019.
A Phase 1/1b dose escalation study evaluating the safety of SNDX-6352 remains ongoing with patients continuing to receive doses of SNDX-6352 alone or in combination with IMFINZI (durvalumab), AstraZeneca’s human monoclonal antibody directed against PD-L1. The Company anticipates identifying the recommended Phase 2 dose and schedule for SNDX-6352 monotherapy and in combination with durvalumab in the second quarter of 2019.
Menin-MLLr Inhibitor Portfolio

Development of the Company’s portfolio of Menin-Mixed Lineage Leukemia (MLLr) inhibitors is ongoing, and the Company has selected a lead compound, SNDX-5613, to continue through Investigational New Drug (IND)-enabling studies. The Company expects to file an IND with the FDA and initiate a Phase 1 clinical trial in patients with a defined subset of acute leukemias in the second quarter of 2019.
Syndax’s Menin-MLLr program will be featured in two presentations at the upcoming 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition being held December 1-4, 2018 in San Diego.
Third Quarter 2018 Financial Results

As of September 30, 2018, Syndax had cash, cash equivalents and short-term investments of $89.6 million and 26.1 million shares issued and outstanding (including a prefunded warrant for 2.0 million shares).

In the third quarter of 2018 and through November 2, 2018, the Company sold 2.1 million shares of its common stock with net proceeds of approximately $15.5 million pursuant to its at-the-market arrangement.

Third quarter 2018 research and development expenses increased to $14.1 million from $12.2 million for the comparable period in the prior year, an increase of $1.9 million, or 16%, due to an increase in development activities of $0.8 million and increased employee compensation expense of $1.1 million. The increase in development activities was primarily related to the development of the Menin-MMLr program and increased activities in the 602 ENCORE trial partly offset by the completion of Phase 1 clinical pharmacology trials and decrease in E2112 costs. The increase in employee compensation costs was primarily due to increased headcount.

General and administrative expenses increased to $4.1 million during the third quarter of 2018, compared to $3.6 million for the comparable period in the prior year, an increase of $0.6 million, or 16%. The increase in general and administrative expenses was primarily due to an increase employee related expenses of $0.3 million and in professional and legal fees of $0.2 million.

For the three months ended September 30, 2018, Syndax reported a net loss attributable to common stockholders of $17.3 million or $0.68 per share compared to $15.1 million or $0.68 per share for the comparable prior year period.

Financial Guidance

Today, the Company provided operating expense guidance for the fourth quarter and full year 2019. For the fourth quarter of 2018, research and development expenses are expected to be $13 to $15 million and total operating expenses are expected to be $17 to $19 million. Total operating expenses for the fourth quarter of 2018 are expected to include approximately $1.5 million of non-cash stock compensation expense. The year-end 2018 cash balance is expected to be approximately $80 million.

For the full year 2019, research and development expenses are expected to be $54 to $58 million, and total operating expenses are expected to be $68 to $73 million. Total operating expenses for 2019 are expected to include approximately $6 million of non-cash stock compensation expense.

Conference Call and Webcast

In connection with the earnings release, Syndax’s management team will host a conference call and live audio webcast at 4:30 p.m. ET today, Monday, November 5, 2018.

The live audio webcast and accompanying slides may be accessed through the Events & Presentations page in the Investors section of the Company’s website at www.syndax.com. Alternatively, the conference call may be accessed through the following:

Conference ID: 8397904
Domestic Dial-in Number: 855-251-6663
International Dial-in Number: 281-542-4259
Live Webcast: View Source

For those unable to participate in the conference call or webcast, a replay will be available for 30 days on the Investors section of the Company’s website, www.syndax.com.

On November 5, 2018 Eli Lilly and Company (NYSE: LLY) and NextCure, Inc. reported a multi-year collaboration focused on the discovery and development of immuno-oncology therapies (Press release, Eli Lilly, NOV 5, 2018, View Source [SID1234530744]). The collaboration seeks to discover novel cancer targets utilizing NextCure’s proprietary FIND-IO platform.

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Under the terms of the agreement, Lilly and NextCure will each receive options to exclusively license antibodies resulting from the collaboration. NextCure will receive an upfront payment of $25 million, and will be eligible for development and commercial milestones and royalty payments, should Lilly successfully develop and commercialize new cancer therapies resulting from the collaboration. Additionally, Lilly has made a $15 million equity investment in NextCure.

"The emerging field of immuno-oncology is offering new treatment options and hope to cancer patients," said Greg Plowman, M.D., Ph.D., vice president of oncology research at Lilly. "Through this collaboration, we hope to leverage NextCure’s discovery platform to expand the reach of this class of groundbreaking treatments by identifying novel cancer targets that could enable the development of a new generation of immuno-oncology therapies."

"Partnering with Lilly, a world leader in drug development, to advance the next generation immuno-oncology therapies is important validation of our FIND-IO discovery platform and our approach to discovering and developing immunomedicines," said Michael Richman, NextCure’s president & CEO. "FIND-IO has the potential to identify and rapidly translate immune cell interactions into disease modifying immunomedicines. We look forward to working with Lilly to discover novel targets that will further enhance both companies’ growing immuno-oncology pipelines."

This transaction will be reflected in Lilly’s reported results and financial guidance according to Generally Accepted Accounting Principles (GAAP). There will be no change to Lilly’s 2018 non-GAAP earnings per share guidance as a result of this transaction.

About FIND-IO
The FIND-IO platform is designed to identify novel cell surface molecular interactions that drive functional immune responses in the tumor microenvironment and other disease sites. NextCure has developed proprietary approaches to assess immune pathways in primary immune cells and established cell lines from immune lineages, including T cells, NK cells, macrophages, myeloid-derived suppressor cells, dendritic cells, as well as cancer cells. NextCure is utilizing FIND-IO technology to identify targets that impact immune function, addressing the major challenge of supplying next generation immunomedicines for patients that do not respond to current cancer therapies.

On November 5, 2018 NantKwest (NASDAQ: NK), a leading, clinical-stage natural killer cell-based therapeutics company, reported that the company will be making multiple presentations associated with the company’s off-the-shelf CD16 targeted NK cell (hanK) and NANT Cancer Vaccine platform at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference which runs from November 7 – 11 in Washington D.C (Press release, NantKwest, NOV 5, 2018, View Source [SID1234530743]).

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SITC Conference Details:

Title:
First in human data in advanced solid tumors of NANT Cancer Vaccine: A novel temporospatial orchestration of the innate (NK) & adaptive immune system to induce antigen cascade & immunogenic cell death

Session: Immune Escape: Currently Understanding of Mechanisms and Advances in Therapeutics Approaches

Date/Time: Wednesday, November 7, 2018, 5:45pm EST

Type: Oral Presentation

Title:
NANT Cancer Vaccine an orchestration of immunogenic cell death by overcoming immune suppression and activate NK and T cell therapy in patients with third-line or greater metastatic pancreatic cancer

Date: Friday, November 9, 2018

Type: Poster Presentation/Abstract #P713

Location: Hall E

Title:
NANT Cancer Vaccine an orchestration of immunogenic cell death by overcoming immune suppression and activate NK and T cell therapy in patients with third-line or greater TNBC and head & neck cancer

Date: Saturday, November 10, 2018

Type: Poster Presentation/Abstract #P310

Location: Hall E

On November 5, 2018 AVEO Oncology (NASDAQ: AVEO) reported positive topline results from the primary analysis of the TIVO-3 trial, the Company’s Phase 3 randomized, controlled, multi-center, open-label study to compare tivozanib (FOTIVDA) to sorafenib in 351 subjects with highly refractory advanced or metastatic renal cell carcinoma (RCC) (Press release, AVEO, NOV 5, 2018, View Source [SID1234530742]).

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The trial met its primary endpoint of demonstrating a statistically significant benefit in progression-free survival (PFS). Tivozanib demonstrated a 44% improvement in median PFS and 26% reduction in risk of progression or death (Hazard Ratio [HR]=0.74, p=0.02). Median PFS was 5.6 months for tivozanib compared to 3.9 months for sorafenib. The TIVO-3 trial enrolled patients with RCC who have failed at least two prior regimens. Among these, approximately 26% of patients received checkpoint inhibitor therapy in earlier lines of treatment. Tivozanib PFS was longer than sorafenib both in patients who received prior checkpoint inhibitor therapy and those who did not.

The analysis of the secondary endpoint of overall survival (OS) was not mature at the time of the final PFS analysis, with only 46% of potential OS events having been reported. At the time of the preliminary OS analysis, no statistically significant difference in OS was observed (HR=1.06, p=0.69). The final survival analysis per protocol is planned for August 2019, two years following the last patient enrolled. Detailed results of the trial will also be submitted for presentation at an upcoming major medical meeting. The secondary endpoint of overall response rate for patients receiving tivozanib was 18% compared to 8% for patients receiving sorafenib (p=0.02).

Tivozanib was generally well-tolerated, with grade 3 or higher adverse events consistent with those observed in previous tivozanib trials. Infrequent but severe adverse events reported in greater number in the tivozanib arm were thrombotic events similar to those observed in previous tivozanib studies. The most common adverse event in patients receiving tivozanib was hypertension, an adverse event known to reflect effective VEGF pathway inhibition.2

Based on results from the TIVO-3 trial, together with the previously completed Phase 3 TIVO-1 trial of tivozanib in the first line treatment of RCC, the Company’s goal is to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in approximately six months.

"Tivozanib’s therapeutic profile is distinct among VEGF TKIs as a treatment for RCC, with the TIVO-3 trial demonstrating a significant PFS benefit and a favorable tolerability profile," said Brian Rini, MD, Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Director, Cleveland Clinic Genitourinary Cancer Program, and principal investigator of the TIVO-3 trial. "In the advanced disease setting, these outcomes are particularly meaningful, providing the first large, pivotal dataset that shows sequencing of treatment following earlier TKI and immunotherapy treatment. This profile suggests an important place for tivozanib in the evolving treatment paradigm for RCC and, taken together with early combination data, the need to study tivozanib further in combination with immunotherapies."

"Our determination to fight for tivozanib in 2015, when AVEO faced an important strategic crossroads, came from our belief that it could have a meaningful impact not just on how a disease was treated, but also what the patient experiences through that treatment. Today’s outcome is the culmination of that multi-year effort, and a first step in our goal to improve both outcomes and patient experience," said Michael Bailey, president and chief executive officer of AVEO. "We owe our deepest gratitude to the healthcare professionals, many of whom long believed in the potential of tivozanib, and to the patients and their families for participating in our pivotal studies."

Conference Call and Webcast

In connection with this announcement, AVEO will host a conference call and slide webcast today, November 5, 2018 at 5:00 pm Eastern Time. The call can be accessed by dialing (844) 882-7841 (U.S. and Canada) or (574) 990-9828 (international). The passcode for the conference call is 7078805. To access the live audio webcast, or the subsequent archived recording, please visit the Investors section of the AVEO website at www.aveooncology.com. The webcast will be recorded and available for replay on AVEO’s website for two weeks.

About TIVO-3

The TIVO-3 trial was designed to enroll patients with RCC who have failed at least two prior regimens, including VEGFR-TKI therapy. Eligible patients may also have received checkpoint inhibitor therapy in earlier lines of treatment. Patients are randomized 1:1 to receive either tivozanib or sorafenib, with no crossover between arms. The primary endpoint of the study is progression free survival (PFS). Secondary endpoints include overall survival (OS), overall response rate (ORR), and safety and tolerability. TIVO-3, together with the previously completed TIVO-1 trial of tivozanib in the first line treatment of RCC, is designed to support a regulatory submission of tivozanib in the U.S. as a treatment for RCC in multiple lines of therapy. TIVO-3 patients were exclusively enrolled in North America, Western Europe, and Central Europe.

About Tivozanib (FOTIVDA)

Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) discovered by Kyowa Hakko Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.3,4 Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models, enabling potentially enhanced activity when used in combination with immune modulating therapy.5 Tivozanib has been investigated in several tumors types, including renal cell, hepatocellular, colorectal and breast cancers.