On March 12, 2018 Eleven Biotherapeutics, Inc. (NASDAQ: EBIO), a late-stage clinical company advancing next-generation antibody-drug conjugate (ADC) therapies for the treatment of cancer, reported that the company has completed enrollment in the VISTA Phase 3 registration trial of Vicinium in patients with non-muscle invasive bladder cancer (NMIBC) who have been previously treated with bacillus Calmette-Guérin (BCG) (Press release, Eleven Biotherapeutics, MAR 13, 2018, View Source [SID1234524701]). Bladder cancer is the sixth most common cancer in the United States and approximately 80 percent of bladder cancer patients are diagnosed with NMIBC. Vicinium is a fusion protein, designed to be a next-generation ADC, which specifically targets the epithelial cell adhesion molecule (EpCAM) antigens on the surface of bladder cancer cells to deliver a potent cytotoxin to those cells.
"Bladder cancer is one of the most prevalent cancers in the United States, yet there has been limited development of new therapeutic options for patients in more than 30 years," commented Donald Lamm, M.D., University of Arizona professor, director of BCG oncology and an investigator in the VISTA trial. "Today’s standard-of-care for NMIBC provides initial responses in many patients; however, after BCG is no longer effective, there are no meaningful FDA-approved options except surgical removal of the bladder in high-risk patients. I am encouraged by the data demonstrated with Vicinium in prior trials and its potential to offer my patients an alternative to radical cystectomy."

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"We believe Vicinium is the most advanced candidate in development for NMIBC and has the potential to be an effective and tolerable treatment for patients who have been previously treated with BCG," said Stephen Hurly, president and chief executive officer of Eleven Biotherapeutics. "The complete response rate and favorable safety seen in our Phase 2 trial were encouraging, and based on learnings from that trial, we modified the dosing regimen to potentially further enhance responses in the VISTA trial. With Phase 3 recruitment complete, we are on-track to report topline, three-month data in mid-2018, and look forward to further assessing Vicinium’s potential in treating patients with this devastating cancer."

About the VISTA Clinical Trial
The VISTA trial is an open-label, multicenter, single-arm Phase 3 clinical trial evaluating the efficacy and tolerability of Vicinium in patients with high-risk non-muscle invasive bladder cancer (NMIBC) that is carcinoma in situ (CIS, cancer found on the inner lining of the bladder that has not spread into muscle or other tissue) or papillary (cancer that has grown from the bladder lining out into the bladder but has not spread into muscle or other tissue), who have been previously treated with bacillus Calmette-Guérin (BCG). The primary endpoint of the trial is the complete response rate in patients with CIS with or without papillary disease. Patients in the

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study receive locally administered Vicinium twice a week for six weeks, followed by once-weekly treatment for another six weeks, then treatment every other week for up to two years. Topline data assessing responses and durability of responses at three-months on treatment are expected in mid-2018, with 12-month data anticipated in mid-2019. For more information, please visit www.mybladdercancer.com.

About Vicinium
Vicinium, Eleven Biotherapeutics’ lead product candidate, is a next-generation antibody-drug conjugate developed using the company’s proprietary Targeted Protein Therapeutics platform. Vicinium is comprised of a recombinant fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent protein payload, Pseudomonas Exotoxin A (ETA). Vicinium is constructed with a stable, genetically engineered linker to ensure the payload remains attached until it is internalized by the cancer cell, which is believed to decrease the risk of toxicity to healthy tissues, thereby improving its safety. In prior clinical studies conducted by Eleven Biotherapeutics, EpCAM has been shown to be overexpressed in non-muscle invasive bladder cancer (NMIBC) cells with minimal to no EpCAM expression observed on normal bladder cells. Eleven Biotherapeutics is currently conducting the Phase 3 VISTA trial, designed to support the registration of Vicinium for the treatment of NMIBC in patients who have previously received two courses of bacillus Calmette-Guérin (BCG) and whose disease is now BCG-unresponsive. Topline, three-month data from the trial are expected in mid-2018. The activity of Vicinium in BCG-unresponsive NMIBC is also being explored at the US National Cancer Institute in combination with AstraZeneca’s immune checkpoint inhibitor durvalumab.

About Non-Muscle Invasive Bladder Cancer
Bladder cancer is the sixth most commonly diagnosed cancer in the United States, and approximately 80 percent of patients have non-muscle invasive bladder cancer (NMIBC). In NMIBC, cancer cells are in the lining of the bladder or have grown into the lumen of the bladder, but have not spread into muscle or other tissue. NMIBC primarily affects men and is associated with carcinogen exposure. Initial treatment includes surgical resection; however, there is a high rate of recurrence and more than 60 percent of all patients diagnosed with NMIBC will receive bacillus Calmette-Guérin (BCG) immunotherapy. While BCG is effective in many patients, challenges with tolerability have been observed and many patients will experience recurrence of disease. If BCG is not effective or a patient can longer receive BCG, the recommended option for treatment is radical cystectomy, the complete removal of the bladder.

On March 13, 2018 IDEAYA Biosciences, Inc., an oncology-focused biotechnology company committed to the discovery of breakthrough synthetic lethality medicines and immuno-oncology therapies, reported the appointment of Julie Hambleton, M.D., as senior vice president and chief medical officer, head of development (Press release, Ideaya Biosciences, MAR 13, 2018, View Source [SID1234525130]). Dr. Hambleton brings more than 20 years of experience in clinical drug development, ranging from pre-clinical studies through Phase 4 and post-marketing studies. She has extensive experience working with regulatory agencies, including the U.S. FDA and the European Medicines Agency (EMA), and in filing of investigational new drug applications (INDs), biologics license applications (BLAs), and special protocol assessments (SPAs).

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"Dr. Hambleton is an accomplished industry executive and a leading oncology drug developer, and we welcome her to the leadership team at IDEAYA," said Yujiro S. Hata, chief executive officer of IDEAYA. "Dr. Hambleton’s unique clinical background in both immuno-oncology and synthetic lethality will strengthen our organization’s capabilities as we advance multiple first-in-class programs into the clinic, leveraging our clinical strategy in patient selection and combinations."

Julie Hambleton, M.D.

"Over the past two decades, I have been involved in the development of numerous targeted and biomarker enabled therapies, including Avastin and Rubraca, and first-in-class immuno-oncology agents that have been developed in combination with checkpoint inhibitors," said Dr. Hambleton. "IDEAYA’s diverse pipeline of biomarker enabled synthetic lethality programs and immunotherapies targeting immuno-metabolism and innate immunity have the potential to transform oncology care and deliver on our mission to bring innovative personalized therapies to cancer patients."

Dr. Hambleton was previously vice president, head of US medical at Bristol-Myers Squibb, overseeing medical & health economic and outcomes research activities in support of the oncology, immuno-oncology, specialty and cardiovascular marketed portfolios. From 2012 to 2016, she was executive vice president and chief medical officer at Five Prime Therapeutics, where she led clinical, clinical operations, regulatory, preclinical and translational and process development and was a member of the executive committee. From 2010 to 2012, Dr. Hambleton was vice president, clinical development, at Clovis Oncology, where she oversaw clinical development programs and managed clinical and pharmacokinetic functions, including the development of Rubraca, a PARP inhibitor, developed with a diagnostic for BRCA and HRD. From 2003 to 2010, she was at Genentech, most recently as group medical director, global clinical development, leading a cross-functional group conducting multiple Phase 2 and 3 trials of Avastin.

Prior to joining industry, Dr. Hambleton served from 1993 to 2003 in academic positions in the division of hematology-oncology at the University of California, San Francisco (UCSF), most recently as associate professor of clinical medicine. She completed post-graduate training at UCSF, where she served as medical resident, chief medical resident and fellow in the division of hematology-oncology. She received a B.S. from Duke University in nursing, an M.D. from Case Western Reserve University School of Medicine, and was board-certified in hematology and internal medicine.

GTx has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission (Filing, 10-K, GTx, 2018, MAR 13, 2018, View Source [SID1234524697]).

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On March 13, 2018 AVEO Oncology (NASDAQ:AVEO) today reported financial results for the full year ended December 31, 2017 and provided a business update (Press release, AVEO, MAR 13, 2018, View Source;p=RssLanding&cat=news&id=2337743 [SID1234524698]).

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"Last year was one of major progress for AVEO, with highlights including the first commercial launch of tivozanib (FOTIVDA); the completion of the enrollment for TIVO-3, our U.S. registration study; the receipt of promising results from the Phase 1b/2 TiNivo combination trial of tivozanib and nivolumab (OPDIVO); and progress across our earlier stage pipeline," said Michael Bailey, president and chief executive officer of AVEO. "These achievements are only the beginning of our effort to unlock the value of tivozanib through registration and development including combination therapy. We also are excited by the potential of our AVEO-developed pipeline candidates, including ficlatuzumab, AV-203, AV-380 and AV-353. Supporting our multifaceted goals, we have worked to strengthen our executive management team and Board with the appointment of experienced leaders and to reinforce our balance sheet through milestone payments, royalties, the renegotiation of our debt agreement and careful financial stewardship."

Tivozanib (FOTIVDA) European Union Update

Tivozanib (FOTIVDA) Launched in Germany, Granted Positive NICE Final Appraisal Determination for the Treatment of Advanced Renal Cell Carcinoma (aRCC) in the UK. In November 2017, AVEO and EUSA Pharma, the licensee for tivozanib in Europe, North and South Africa, Latin America and Australasia, announced the first commercial launch of FOTIVDA with the initiation of product sales in Germany. In February 2018, AVEO announced that the United Kingdom’s National Institute for Health and Care Excellence (NICE) published a Final Appraisal Determination recommending FOTIVDA for the first line treatment of adult patients with advanced renal cell carcinoma (aRCC). The positive recommendation was followed by the launch of FOTIVDA in the United Kingdom and triggered a $2M milestone payment to AVEO from EUSA Pharma. FOTIVDA was granted European Commission (EC) approval in August 2017 for the treatment of adult patients with aRCC in the European Union plus Norway and Iceland.
Tivozanib TIVO-3 Study North America Update

Successfully Completed the TIVO-3 Futility Analysis with No Changes to Study Protocol. In October 2017, AVEO announced the completion of a pre-planned interim futility analysis of the Phase 3 TIVO-3 trial, the Company’s randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib (NEXAVAR) in subjects with aRCC. Based on the results of the futility analysis, which were reviewed by an independent statistician, the study continued as planned without modification. The analysis did not allow for early stopping due to efficacy to assure adequate follow-up for the key secondary endpoint of overall survival. Based on the current rate of progression-free survival (PFS) events, the Company expects the TIVO-3 trial to read out in the second quarter of 2018. The TIVO-3 trial, together with the previously completed TIVO-1 trial of tivozanib in the first line treatment of aRCC, is designed to support a potential regulatory approval of tivozanib in the U.S. as a first- and third-line treatment for aRCC.
TiNivo Combination Study Clinical Update

Phase 1b/2 Results from the TiNivo Trial of Tivozanib and Nivolumab (OPDIVO) in aRCC presented at International KCS and ASCO (Free ASCO Whitepaper) GU. In November 2017, the results from the Phase 1b portion of the Phase 1b/2 TiNivo study were presented at the 16th International Kidney Cancer Symposium. In February 2018, Bernard Escudier, M.D., from the Institute Gustav Roussy in Paris, France presented preliminary results from the Phase 2 portion of the TiNivo study at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s Genitourinary Cancers Symposium (ASCO GU). TiNivo is a Phase 1b/2 multi-center trial of oral tivozanib in combination with intravenous nivolumab (OPDIVO, Bristol-Myers Squibb), an immune checkpoint, or PD-1, inhibitor, for the treatment of metastatic renal cell carcinoma (mRCC). The Phase 1b/2 study has enrolled a total of 28 patients. The Phase 2 portion of the study (n=22) was designed to assess the safety, tolerability, and anti-tumor activity of the full dose and schedule of oral tivozanib (1.5 mg/QD for 21 days followed by a 7-day rest period), as established in the Phase 1b portion of the study (n=6), in combination with intravenous nivolumab (240 mg every 2 weeks). The combination was generally well tolerated. Treatment-related Grade 3/4 adverse events occurred in 44% of patients, the most common of which was hypertension. Preliminary efficacy was assessed in 14 patients treated with the full dose and schedule of oral tivozanib in combination with intravenous nivolumab and enrolled at least 4 months prior to the data cutoff date. Of these, seven patients had received at least one prior systemic therapy and seven were treatment naive. A partial response was observed in 64% of patients, and a disease control rate (partial response + stable disease) was observed in 100% of patients. At the time of data collection, 11 of 14 evaluable patients remained on study. The Company and EUSA Pharma expect to present further updates to the TiNivo study at upcoming medical meetings in the second half of 2018.
TiNivo Combination Study Opt-in. In September 2017, AVEO announced that EUSA Pharma, under its multi-territory licensing agreement with AVEO for tivozanib, opted in to co-develop the Phase 1b/2 TiNivo study and potential future combination studies in exchange for research and development reimbursement payments totaling $2.0 million. Under terms of the agreement, EUSA will fund up to half of the Phase 1b/2 TiNivo study, not to exceed $2.0 million, and may utilize the data from the study for regulatory or commercial purposes.
Tivozanib Clinical Development in Hepatocellular Carcinoma

Phase 1b/2 Study Results of Tivozanib in Patients with Advanced Hepatocellular Carcinoma Presented at ASCO (Free ASCO Whitepaper) GI. In January 2018, AVEO announced the presentation of data from a multi-center, Phase 1b/2 study of tivozanib in previously untreated patients with advanced, unresectable hepatocellular carcinoma (HCC) at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI). The study, designed to evaluate the safety and efficacy of tivozanib in advanced HCC, enrolled a total of 21 patients at three study sites. Tivozanib at 1.0 mg daily was selected in the Phase 1b portion of the study as the dose for the Phase 2 expansion. Of 19 patients evaluable for efficacy, at a median follow up of 16.9 months, the study’s primary endpoint of PFS and PFS at week 24 were 5.5 months and 47%, respectively. A partial response (PR) was seen in 21% (4/19) of patients and stable disease (SD) was observed in 42% (8/19) of patients, for a disease control rate (DCR) of 63%. Overall survival (OS) at 6 and 12 months was 58% and 25%, respectively, with a median OS of 7.5 months. Notably, 4 patients have maintained SD for over two years. There were no significant changes in hepatitis B or hepatitis C viral load during study treatment. Tivozanib was generally well tolerated, with adverse events consistent with those observed in previous tivozanib trials. Findings from the study suggest that tivozanib has the potential to yield comparable PFS and a favorable response rate when compared to current first-line standards of care for HCC patients, and demonstrated a favorable safety profile which may enable therapeutic combinations with immunotherapy. The Phase 1b/2 study was led by Renuka Iyar, M.D., from the Roswell Park Cancer Center and was one of several studies funded by a grant provided to the National Comprehensive Cancer Network by AVEO.
Pipeline Updates

Phase 2 Study of Ficlatuzumab in Combination with Cetuximab in HNSCC Initiated. In December 2017, AVEO announced the initiation of an investigator-sponsored randomized, multi-center Phase 2 trial of ficlatuzumab and cetuximab (ERBITUX), an EGFR-targeted antibody, in patients with cetuximab-resistant, metastatic head and neck squamous cell carcinoma (HNSCC). AVEO has partnered with Biodesix, Inc. on the development of ficlatuzumab, a humanized IgG1 antibody that binds to the hepatocyte growth factor (HGF) ligand with high affinity and specificity to inhibit the biological activities of the HGF/c-Met pathway. The study will seek to confirm findings from a Phase 1 study where the addition of ficlatuzumab to cetuximab resulted in a disease control rate of 67%, and prolonged progression free and overall survival compared to historical controls, in addition to being well tolerated. This Phase 2 multi-center study, which is being conducted under the direction of Julie E. Bauman, M.D., M.P.H., Professor of Medicine, Chief, Division of Hematology/Oncology, Associate Director of Translational Research, University of Arizona Cancer Center, is expected to enroll approximately 70 patients randomized to receive either ficlatuzumab alone or ficlatuzumab and cetuximab.
Phase 1b Study of Ficlatuzumab in Combination with Gemcitabine and Nab-paclitaxel in Pancreatic Cancer Initiated. In December 2017, AVEO announced the initiation of an investigator-sponsored Phase 1b study to test the safety and tolerability of ficlatuzumab when combined with Nab-paclitaxel and Gemcitabine in previously untreated metastatic pancreatic ductal cancer (PDAC). The goal of the study, which is based on preclinical findings demonstrating a synergistic effect of these drugs in a preclinical model of PDAC, is designed to determine the maximum tolerated dose of ficlatuzumab when combined with gemcitabine and nab-paclitaxel. Secondary outcome measures include response rate and progression free survival. The study, which is being conducted under the direction of Kimberly Perez, M.D. at the Dana-Farber Cancer Institute, is expected to enroll approximately 30 patients.
IND Application for CAN017 (AV-203) Trial in Esophageal Squamous Cell Cancer (ESCC) Filed by CANbridge In China. In December 2017, CANbridge Life Sciences, the licensee for CAN017 (AV-203) outside of North America, announced that it filed an Investigational New Drug application with the China Food and Drug Administration for a Phase 1b/3 clinical study of CAN017 in esophageal squamous cell cancer (ESCC). CAN017 is an ErbB3 (HER3) inhibitory antibody candidate developed by AVEO. CANbridge also announced that it entered into a strategic partnership with Amoy Diagnostics Co., Ltd. to develop a CAN017 biomarker companion diagnostic.
Corporate Updates

Strengthened Executive Team and Board of Directors. In November 2017, AVEO announced the appointment of Nikhil Mehta, Ph.D., as Senior Vice President of Regulatory and Quality Assurance. In this role, Dr. Mehta oversees all aspects of regulatory, quality and technical operations for the Company’s portfolio. Dr. Mehta brings to AVEO more than 25 years of experience in the biotechnology and pharmaceutical industries.

AVEO also recently appointed Mike Ferraresso as Vice President, Business Analytics and Commercial Operations. Mr. Ferraresso brings more than 20 years of pharmaceutical industry experience in commercial strategy, sales operations and business analytics. He previously worked at AVEO from 2011 to 2013 as Senior Director of Business Analytics.

AVEO also announced today that Karuna Rubin has been named Senior Vice President and General Counsel, effective February 1, 2018. Ms. Rubin has more than 15 years of experience representing public companies in a variety of industries in securities, finance, mergers and acquisitions, litigation and other matters and has served as AVEO’s lead counsel since 2015. She received her J.D. from Columbia Law School and A.B. from Brown University.

In February 2018, AVEO announced the appointment of John H. Johnson to the Company’s Board of Directors. Mr. Johnson brings to AVEO over three decades of experience in the biotechnology and pharmaceuticals industries, having held commercial and executive management roles at leading global corporations that have a focus on oncology.
Refinanced Debt Facility, Extending Cash Runway into 2019. In January 2018, AVEO announced that it completed the refinancing of its existing $20.0 million debt facility with Hercules Capital, Inc. and its affiliates, the terms of which enable approximately an additional $12.1 million in cash flow over 2018 and 2019, when compared to the prior loan. The new $20.0 million facility has a 42-month maturity from closing, no financial covenants, a lower interest rate and an interest-only period of no less than 12 months, which could be extended up to a maximum of 24 months, assuming the achievement of specified milestones relating to the development of tivozanib. Extension of the interest-only period is expected to enable the Company to extend its cash runway into the first quarter of 2019. Proceeds of the new facility were used to retire the Company’s previous $20.0 million of secured debt with Hercules.
Full Year 2017 Financial Highlights

AVEO ended 2017 with $33.5 million in cash, cash equivalents and marketable securities as compared with $23.3 million at December 31, 2016.
Total collaboration revenue for 2017 was approximately $7.6 million compared with $2.5 million for 2016.
Research and development expense for 2017 was $25.2 million compared with $23.7 million for 2016.
General and administrative expense for 2017 was $9.1 million compared with $8.2 million for 2016.
Net loss for 2017 was $65.0 million, or a loss of $0.61 per basic and diluted share, compared with net loss of $26.9 million for 2016, or a loss of $0.39 per basic and diluted share. Approximately $33.7 million of the 2017 net loss was a non-cash loss attributable to the increase in the fair value of the warrant liability that principally resulted from the increase in the stock price that occurred within the year. In 2016, the non-cash gain attributable to the decrease in the fair value of the warrant liability was $4.8 million.
Updated Financial Guidance

We believe that our $33.5 million in cash resources would allow us to fund our planned operations into the first quarter of 2019. This estimate assumes no receipt of additional milestones from our partners or related payment of potential licensing milestones to third parties, no additional funding from new partnership agreements, no additional equity or debt financings, and no sales of equity through the exercise of our outstanding warrants issued in connection with our 2016 private placement.

On March 13, 2018 Medtronic plc (NYSE:MDT), the global leader in medical technology, reported it will participate in the Oppenheimer 28th Annual Healthcare Conference on Tuesday, March 20, 2018, in New York City (Press release, Medtronic, MAR 13, 2018, View Source;p=RssLanding&cat=news&id=2337864 [SID1234524735]).

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Hooman Hakami, executive vice president and group president of Medtronic’s Diabetes Group, will answer questions about the company beginning at 8:35 a.m. EDT (7:35 a.m. CDT).

A live audio webcast of the presentation will be available on March 20, 2018, by clicking on the Investor Events link at View Source An archive of the session will be available on the same webpage later in the day.