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AVEO Oncology Announces $2M Milestone Payment from EUSA Pharma Related to German Commercialization of FOTIVDA®

On November 15, 2018 AVEO Oncology (NASDAQ: AVEO) reported the triggering of a $2 million milestone payment to AVEO from EUSA Pharma (Press release, AVEO, NOV 15, 2018, View Source [SID1234531364]). The milestone payment relates to the commercial launch and reimbursement in Germany of FOTIVDA (tivozanib) as a first line treatment of adult patients with advanced renal cell carcinoma (RCC). In the European Union, Norway and Iceland, tivozanib is indicated for the first line treatment of adult patients with RCC and for adult patients who are vascular endothelial growth factor receptor (VEGFR) and mTOR pathway inhibitor-naïve following disease progression after one prior treatment with cytokine therapy for RCC. Tivozanib is an oral, once-daily, potent and highly-selective vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI).

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EUSA Pharma is the licensee for tivozanib in Europe, North and South Africa, Latin America and Australasia. The milestone payment is subject to a 30% sublicense fee due to AVEO’s partner Kyowa Hakko Kirin and is incremental to the previously-disclosed cash, cash equivalents and marketable securities at September 30, 2018, which AVEO reported would fund operations into the second quarter of 2019.

"Germany is among a growing list of countries in the European Union that recognize the benefit of expanding patient access to FOTIVDA," said Michael Bailey, president and chief executive officer. "As our partner EUSA continues to advance FOTIVDA in the approved European commercial market, we continue to work toward retrieving overall survival data not yet collected at the preliminary OS analysis of our pivotal TIVO-3 study, and toward the potential submission of a New Drug Application with the FDA for tivozanib as a treatment for advanced or metastatic RCC, a milestone we expect to reach in the first half of 2019."

Under the terms of their December 2015 agreement, EUSA Pharma has agreed to pay AVEO up to $384 million in future research and development funding and milestone payments, assuming successful achievement of specified development, regulatory and commercialization objectives, as well as a tiered royalty ranging from a low double-digit up to mid-twenty percent on net sales of tivozanib in the agreement’s territories. Thirty percent of milestone and royalty payments received by AVEO, excluding research and development funding, are due to Kyowa Hakko Kirin (KHK) as a sublicensing fee in Europe. In the United States, the royalty obligation to KHK ranges from the low- to mid-teens on net sales.

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.1,2 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.3 Tivozanib has been investigated in several tumors types, including renal cell, hepatocellular, colorectal and breast cancers.

Immunomic Therapeutics to Present at the 2018 World Vaccine & Immunotherapy Congress

On November 15, 2018 Immunomic Therapeutics, Inc. (ITI) reported that the company will present and participate at the 2018 World Vaccine & Immunotherapy Congress West Coast, being held November 28-29 in San Diego, CA (Press release, Immunomic Therapeutics, NOV 15, 2018, View Source [SID1234531363]).

Dr. Teri Heiland, Senior Vice President of R&D, and Sia Anagnostou, Senior Director of Corporate Development, will discuss ITI’s investigational UNiversal Intracellular Targeted Expression (UNITE) technology platform, designed to utilize the body’s natural biochemistry to generate broad immune responses, during a presentation and panel discussion. ITI’s UNITE platform has potentially broad therapeutic applications in oncology, including viral antigens, cancer antigens, neoantigens and antigen-derived antibodies as biologics. ITI has built a large pipeline from UNITE with seven oncology programs, with its lead program in Phase II for GBM, and an allergy program which is fully licensed to ITI’s partner, Astellas Pharma, Inc.

Details of ITI’s presentation and panel participation are listed below:

Presentation: "Immunomic is Addressing the Challenges of Viral Targets in Cancer"

When: Wednesday, November 28, at 12:50 p.m. PST
Who: Teri Heiland, Ph.D., Co-Founder and Senior Vice President of Research and Development at Immunomic Therapeutics, Inc.
Where: Loews Coronado Bay Resort, 4000 Coronado Bay Road, Coronado, CA 92118

Panel: "Immunotherapy in Cancer – Combinations Are Key"

When: Thursday, November 29, at 9:10 a.m. PST
Who: Moderated by Sia Anagnostou, Senior Director of Corporate Development at Immunomic Therapeutics, Inc.
Participants include:

Teri Heiland, Ph.D., Co-Founder and Senior Vice President of Research and Development at Immunomic Therapeutics
Sylvaine Cases, Ph.D., Vice President of Oncology Scientific Innovation at Janssen Research & Development
Peter Emtage, Ph.D., Senior Vice President and Global Head of Cell Therapy Research at Kite, a Gilead Company
Amy Conrad, Founder and CEO of Juniper Point
Raghuram Selvaraju, Ph.D., MBA, Managing Director & Head of Equity Research, H.C. Wainwright & Co.
Where: Loews Coronado Bay Resort, 4000 Coronado Bay Road, Coronado, CA 92118

About UNITE

ITI’s investigational UNITE platform, or UNiversal Intracellular Targeted Expression, is thought to work by encoding the Lysosomal Associated Membrane Protein, an endogenous protein in humans. In this way, ITI’s vaccines (DNA or RNA) have the potential to utilize the body’s natural biochemistry to develop a broad immune response including antibody production, cytokine release and critical immunological memory. This approach could put UNITE technology at the crossroads of immunotherapies in a number of illnesses, including cancer, allergy and infectious diseases. UNITE is currently being employed in Phase II clinical trials as a cancer immunotherapy. ITI is also collaborating with academic centers and biotechnology companies to study the use of UNITE in cancer types of high mortality, including cases where there are limited treatment options like glioblastoma and acute myeloid leukemia. ITI believes that these early clinical studies may provide a proof of concept for UNITE therapy in cancer, and if successful, set the stage for future studies, including combinations in these tumor types and others. Preclinical data is currently being developed to explore whether LAMP nucleic acid constructs may amplify and activate the immune response in highly immunogenic tumor types and be used to create immune responses to tumor types that otherwise do not provoke an immune response.

Epizyme Announces Conference Call to Discuss Corporate Updates

On November 15, 2018 Epizyme, Inc. (Nasdaq: EPZM), a clinical-stage company developing novel epigenetic therapies, reported that management will host a conference call to discuss corporate updates today at 8:30 a.m. ET (Press release, Epizyme, NOV 15, 2018, View Source [SID1234531362]).

To participate in the conference call, please dial (877) 844-6886 (domestic) or (970) 315-0315 (international) and refer to conference ID 5172457. A live webcast will be available in the investor section of the company’s website at www.epizyme.com. The webcast also will be archived for 60 days following the call and presentation

Boehringer Ingelheim and Epizyme Announce Worldwide Collaboration to Develop Novel Epigenetic Oncology Therapies

On November 15, 2018 Boehringer Ingelheim and Epizyme, Inc. (Nasdaq: EPZM) reported a new global collaboration focused on the research, development and commercialization of novel small molecule inhibitors directed toward two previously unaddressed epigenetic targets as potential therapies for people with cancer (Press release, Boehringer Ingelheim, NOV 15, 2018, View Source [SID1234531361]). Specifically, these targets are enzymes within the helicase and histone acetyltransferase (HAT) families that when dysregulated have been linked to the development of cancers that currently lack therapeutic options.

"Boehringer Ingelheim’s collaboration with Epizyme furthers our strategic vision to profoundly impact the oncology treatment landscape by enabling a new generation of precision medicines," said Clive R. Wood, Ph.D., Senior Corporate Vice President, Discovery Research, Boehringer Ingelheim. "We are excited to launch this partnership with Epizyme and to work together with them to advance epigenetic inhibitors that have the potential to transform the lives of patients and help win the fight against difficult-to-treat cancers."

Epigenetic modification affects how genes are biologically regulated. More than half of cancers can stem from functional errors in epigenetic modification. In particular cases, epigenetic dysregulation is associated with alterations in specific components of gene regulation, which can be used to identify patients most likely to benefit from the therapy. What makes both targets compelling is not only the clear role they play in cancer but that both targets have patient stratification biomarkers, which will enable a focus on the patients most likely to benefit from these potential treatments. Epizyme is a leader in the discovery of the roles of such enzymes and their development as therapy targets.

"This partnership with Boehringer Ingelheim to develop treatments for two novel epigenetic targets, which have been historically viewed as undruggable, further validates the promise of epigenetics for oncology and our pioneering leadership in this field," said Robert Bazemore, president and chief executive officer of Epizyme. "By combining our innovative target identification and research capabilities with Boehringer Ingelheim’s world-class drug development and commercialization expertise, we are aiming to realize the full potential of these targets and our platform, while continuing to focus on executing development of our lead program in multiple ongoing and planned clinical trials."

The collaboration has a strategic goal to focus on lung and other solid tumor cancers in patients with defined mutations, sub-populations that currently lack precision medicine treatments. Under the terms of the agreement, Boehringer Ingelheim and Epizyme will jointly research and develop a helicase program, with both parties sharing U.S. commercialization responsibilities and Boehringer Ingelheim assuming responsibility for commercialization outside the U.S. Epizyme and Boehringer Ingelheim will share research responsibilities for the HAT program, with Boehringer Ingelheim assuming responsibility for worldwide development and commercialization.

Epizyme will receive an upfront payment of $15 million and an additional $5 million in research funding in 2019. Epizyme is eligible to receive more than $280 million in additional payments for research, development, regulatory and commercial milestones. For the helicase program, Epizyme will fund a portion of the global development costs, retain a share of U.S. profits and receive tiered royalties on ex-U.S. sales. For the HAT program, Epizyme is eligible to receive tiered royalties on worldwide sales.

European Commission approves Ipsen’s Cabometyx® (cabozantinib) for the treatment of hepatocellular carcinoma in adults previously treated with sorafenib

On November 15, 2018 Ipsen (Euronext: IPN; ADR: IPSEY) reported that the European Commission (EC) has approved Cabometyx (cabozantinib) 20, 40, 60 mg as a monotherapy for hepatocellular carcinoma (HCC) in adults who have previously been treated with sorafenib (Press release, Ipsen, NOV 15, 2018, View Source [SID1234531360]). This approval allows for the marketing of Cabometyx (cabozantinib) in this indication in all 28 member states of the European Union, Norway and Iceland.

"Today’s EC approval for the use of Cabometyx provides a much needed new option for HCC patients. Until now, physicians in Europe had only one approved therapy for the 2nd line treatment of this aggressive and difficult-to-treat cancer.1,2 We are proud to offer Cabometyx as an innovative treatment that has been shown to extend survival in previously treated patients with HCC," said Harout Semerjian, Chief Commercial Officer, Ipsen. "This new indication reinforces Ipsen’s commitment to improve patients’ lives through the expansion of the clinical benefit of Cabometyx in the treatment of solid tumors."

Philippe Merle, M.D., Ph.D., Hepatology and Gastroenterology specialist at La Croix-Rousse Hospital, Lyon, stated: "Patients with HCC in Europe can now benefit from a treatment that has, through the CELESTIAL trial, proven effective in prolonging life and delaying disease progression. This is a very encouraging development for liver cancer patients, and provides physicians with a new therapeutic option for this complex disease."

The EC approval is based on the results of the global placebo-controlled CELESTIAL phase 3 pivotal trial which met its primary endpoint of overall survival (OS), with cabozantinib providing a statistically significant and clinically meaningful improvement in OS compared with placebo in patients with advanced HCC who have been previously treated with sorafenib.3 In July 2018, CELESTIAL phase 3 pivotal trial results were published in the New England Journal of Medicine.3

The EC has also approved Cabometyx for the treatment of advanced renal cell carcinoma (aRCC) both in treatment-naïve adults with intermediate or poor risk (May 2018) and in adults following prior vascular endothelial growth factor (VEGF)-targeted therapy (September 2016).

The detailed recommendations for the use of this product are described in the Summary of Product Characteristics (SmPC), available here.

About CELESTIAL

CELESTIAL is a randomized, double-blind, placebo-controlled global phase 3 study of cabozantinib versus placebo in patients with advanced HCC who have been previously treated with sorafenib. The study was conducted at more than 100 sites globally in 19 countries. The trial was designed to enroll 760 patients with advanced HCC who previously received sorafenib and may have received up to two prior systemic cancer therapies for HCC and had adequate liver function. Enrollment of the trial was completed in September 2017, and 773 patients were ultimately randomized. Patients were randomized 2:1 to receive 60 mg of cabozantinib once daily or placebo and were stratified based on etiology of the disease (hepatitis C, hepatitis B or other), geographic region (Asia versus other regions) and presence of extrahepatic spread and/or macrovascular invasion (yes or no). No cross-over was allowed between the study arms.

The primary endpoint for the trial is OS, and secondary endpoints include objective response rate (ORR) and progression-free survival (PFS). Exploratory endpoints include patient-reported outcomes, biomarkers and safety.

Based on available clinical trial data from various published trials conducted in the second-line setting of advanced HCC, the CELESTIAL trial statistics for the primary endpoint of OS assumed a median OS of 8.2 months for the placebo arm. A total of 621 events provide the study with 90 percent power to detect a 32 percent increase in median OS (HR = 0.76) at the final analysis. Two interim analyses were planned and conducted at 50 percent and 75 percent of the planned 621 events. The independent data monitoring committee for the study recommended that the trial should be stopped for efficacy following review of the second planned interim analysis. CELESTIAL trial met its primary endpoint, with cabozantinib providing a statistically significant and clinically meaningful improvement in OS compared to placebo in patients with advanced HCC. The safety data in the study were consistent with the established profile of cabozantinib.

About Hepatocellular Carcinoma (HCC)

Hepatocellular carcinoma is the most common form of liver cancer in adults.4 The disease originates in cells called hepatocytes found in the liver. With approximately 800’000 new cases diagnosed each year, HCC is the sixth most common cancer and the second-leading cause of cancer deaths worldwide.5,6 According to the GLOBOCAN data, it is estimated that across the European Union (EU-28) nearly 60’000 new patients will be diagnosed with liver cancer in 2020.7 Without treatment, patients with the disease in advanced stage usually survive between 4 and 8 months.8

About Cabometyx (cabozantinib)

Cabometyx is an oral small molecule inhibitor of tyrosine kinase receptors, including VEGFR, MET, AXL and RET. In preclinical models, cabozantinib has been shown to inhibit the activity of these receptors, which are involved in normal cellular function and pathologic processes such as tumor angiogenesis, invasiveness, metastasis and drug resistance.

In February of 2016, Exelixis and Ipsen jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications outside of the United States, Canada and Japan. This agreement was amended in December of 2016 to include commercialization rights for Ipsen in Canada.

Cabometyx tablets are approved in the United States for the treatment of patients with advanced RCC. On September 9, 2016, the European Commission approved Cabometyx tablets for the treatment of advanced RCC in adults who have received prior vascular endothelial growth factor (VEGF)-targeted therapy in the European Union, Norway and Iceland. Cabometyx is also approved in Australia, Brazil, Canada, Hong Kong, South Korea, Switzerland, Taiwan and Ukraine. Cabometyx is available in 20 mg, 40 mg or 60 mg doses. The recommended dose is 60 mg orally, once daily.

On May 17, 2018, Ipsen announced that the European Commission approved Cabometyx for the first-line treatment of adults with intermediate- or poor- risk advanced renal cell carcinoma in the European Union, Norway and Iceland.

On November 15, 2018, Ipsen announced that the European Commission approved Cabometyx for the second-line treatment of hepatocellular carcinoma in adults who have previously been treated with sorafenib in the European Union, Norway and Iceland.