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PHASE II TRIAL RESULTS ON NOVEL ANTICANCER AGENT LENVIMA(R) IN RENAL CELL CARCINOMA PUBLISHED IN THE LANCET ONCOLOGY

On October 19, 2015 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that the results of a Phase II clinical trial (Study 205)(1) of its in-house developed novel anticancer agent Lenvima (lenvatinib mesylate, "lenvatinib") in advanced or metastatic renal cell carcinoma have been published in the online version of The Lancet Oncology(1), a leading clinical oncology research journal that is highly regarded worldwide (Press release, Eisai, OCT 19, 2015, View Source [SID:1234507729]).

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Study 205 was a Phase II clinical trial to compare the safety and efficacy among three groups including a combination of lenvatinib (18 mg) plus everolimus (5 mg), lenvatinib alone (24 mg) and everolimus alone (10 mg) in advanced or metastatic renal cell carcinoma following one prior vascular endothelial growth factor-targeted therapy. From the results of the study, the combination of lenvatinib plus everolimus group demonstrated a significant extension in progression free survival (PFS), the study’s primary endpoint, compared to the everolimus alone group. Additionally, the lenvatinib alone group demonstrated an extension in PFS compared to the everolimus alone group. Both the lenvatinib plus everolimus group and the lenvatinib alone group showed an improvement in objective response rate compared to the everolimus alone group. The most common treatment-emergent adverse events (TEAE) reported in the lenvatinib plus everolimus group were diarrhea, decreased appetite and fatigue. The most common TEAEs of Grade 3 or higher included diarrhea, hypertension and fatigue.

Renal cell carcinoma comprises more than 90% of all malignancies of the kidney.(2) For advanced or metastatic renal cell carcinoma that is difficult to treat with surgery, the standard treatment method is molecular targeted drug therapy, however with low 5-year survival rates, this remains a disease with significant unmet medical needs. According to the results of Study 205, the combination of lenvatinib plus everolimus showed superior PFS over everolimus alone, which is recommended by the National Comprehensive Cancer Network (NCCN) guidelines as a 2nd-line therapy for advanced or metastatic renal cell carcinoma.

Lenvatinib has received a breakthrough therapy designation from the U.S. Food and Drug Administration (FDA) for the potential indication of advanced and/or metastatic renal cell carcinoma. Eisai has shared the results of Study 205 with the U.S. FDA and the European Medicines Agency to discuss further steps regarding potential submission strategies for an indication covering renal cell carcinoma, and Eisai intends to have similar discussions with the regulatory authorities in Japan as well. Currently lenvatinib has been launched in the United States, Japan and Europe indicated for refractory thyroid cancer, and clinical trials of the agent in various types of cancer such as hepatocellular carcinoma are also underway.

Eisai is committed to exploring the potential clinical benefits of lenvatinib in order to further contribute to patients with cancer and their families.

1. About lenvatinib mesylate (product name: Lenvima) Lenvatinib is an orally administered multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other proangiogenic and oncogenic pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRalpha; KIT; and RET) involved in tumor proliferation. Lenvatinib has been confirmed through X-ray co-crystal structural analysis to demonstrate a new binding mode (Type V) to VEGFR2, and exhibits rapid binding to the target molecule and potent inhibition of kinase activity, according to kinetic analysis.(3)
Currently, Eisai has obtained approval for lenvatinib in the United States, Japan, Europe and Korea indicated for the treatment of refractory thyroid cancer. In addition, lenvatinib is undergoing regulatory review throughout the world including in Asia, Canada, Russia, Australia, Brazil and Mexico. Meanwhile, Eisai is conducting a global Phase III study of lenvatinib in hepatocellular carcinoma as well as Phase II studies of lenvatinib in several other tumor types such as endometrial carcinoma and non-small cell lung cancer. Furthermore, lenvatinib was granted Orphan Drug Designation by regulatory authorities in the United States, Japan and Europe for refractory thyroid cancer.

2. About Study 205(1)
Study 205 was a multicenter, randomized, open-label study of lenvatinib (18 mg) in combination with the anticancer agent everolimus (5 mg), lenvatinib alone (24 mg), and everolimus alone (10 mg) in patients with advanced or metastatic renal cell carcinoma following one prior VEGF-targeted therapy, and was conducted in Europe and the United States. 153 patients were randomized in a 1:1:1 ratio to one of three treatment arms to compare the safety and efficacy of these three regimens.
From the results of the study, the combination of lenvatinib plus everolimus group demonstrated a significant extension in the study’s primary endpoint of progression free survival (PFS) compared to the everolimus alone group (median PFS for the lenvatinib plus everolimus group: 14.6 months vs median PFS for the everolimus alone group: 5.5 months; Hazard Ratio (HR) 0.40 [95% CI: 0.24-0.68], p

Additionally, median PFS for the lenvatinib alone group was 7.4 months, demonstrating an extension in PFS compared to the everolimus alone group (HR: 0.61 [95% CI: 0.38-0.98]). The study also assessed objective response rate (ORR) and overall survival (OS) as secondary endpoints. Regarding ORR, both the lenvatinib plus everolimus group and the lenvatinib alone group showed an improvement in ORR compared to the everolimus alone group (lenvatinib plus everolimus: 43%, lenvatinib alone: 27%, everolimus alone: 6%). Furthermore, regarding OS, an updated analysis carried out in December 2014 suggested that lenvatinib plus everolimus extends OS compared to everolimus alone (HR 0.51 [95% CI=0.30-0.88]). The most common treatment-emergent adverse events (TEAE) reported in the lenvatinib plus everolimus group were diarrhea, decreased appetite and fatigue. The most common TEAEs of Grade 3 or higher (Common Terminology Criteria for Adverse Events) included diarrhea, hypertension and fatigue.

3. About Renal Cell Carcinoma
The number of patients with renal cancer was estimated to be approximately 338,000 worldwide, including approximately 58,000 in the United States, 17,000 in Japan and 115,000 in Europe.(4) Renal cell carcinoma comprises more than 90% of all malignancies of the kidney,(2) and occurs when malignant cells are found in the lining of the tubules of the kidney. The incidence of renal cell carcinoma in people aged in their late 50s is rising, and is more likely to affect men than women. For advanced or metastatic renal cell carcinoma that is difficult to treat with surgery, the standard treatment method is molecular targeted drug therapy, however with low 5-year survival rates, this remains a disease with significant unmet medical needs.
4. About The Lancet Oncology Highly regarded worldwide, The Lancet Oncology is an influential medical journal specialized in the field of oncology.

Agios Outlines Key Clinical Development & Research Strategies

On October 16, 2015 Agios Pharmaceuticals (NASDAQ:AGIO) reported its clinical development strategy for the company’s lead cancer metabolism and rare genetic metabolic disorders programs, along with insights into emerging research at its R&D Day today (Press release, Agios Pharmaceuticals, OCT 16, 2015, View Source [SID:1234507725]).

"With our lead IDH programs progressing through Phase 1 expansion cohorts and the initiation of the Phase 3 AG-221 study with our collaboration partner Celgene, we are moving closer to our goal of providing people with advanced AML with transformational new medicines as quickly as possible," said David Schenkein, M.D., chief executive officer at Agios. "We will share our long-term vision for these programs at today’s R&D Day, as we hope to one day provide benefit to every patient diagnosed with an IDH mutant-positive cancer."

"At our core, Agios is a research-driven organization, and I’m proud that our scientists have discovered AG-519, a novel PK activator, which represents our fifth new investigational medicine in just seven years. We continue to conduct research that we believe will enable us to make important advances for patients," Dr. Schenkein continued.

IDH Program Updates

In clinical studies to date, AG-221 and AG-120, which target mutated IDH2 and IDH1, respectively, have demonstrated positive clinical single-agent activity with durable complete and partial responses and manageable safety profiles in patients with AML. Together with our collaboration partner Celgene, Agios remains committed to bringing AG-221 and AG-120 to patients as quickly and efficiently as possible by leveraging a clinical development strategy that maximizes both speed and breadth.

Agios reported clinical development updates for AG-221 and AG-120 in AML, including:

Initiation of the AG-221 Phase 3 Study: The IDHENTIFY study of AG-221 is a Phase 3, international, multi-center, open-label, randomized clinical trial designed to compare the efficacy and safety of AG-221 versus conventional care regimens in patients 60 years or older with IDH2 mutant-positive AML that is refractory to or relapsed after second- or third-line therapy. Additional details can be found below and on www.clinicaltrials.gov. This study is being conducted by Celgene.

Novel Design of the AG-221 and AG-120 Frontline Trials in AML:
For Newly Diagnosed AML Patients Eligible for Intensive Chemotherapy: A Phase 1b combination study of either AG-221 or AG-120 with standard induction (7+3, Ara-C and idarubicin/daunorubicin) and consolidation (Ara-C, or mitoxantrone with etoposide) chemotherapy is planned for initiation by the end of 2015.

For Newly Diagnosed AML Patients Not Eligible for Intensive Chemotherapy: A Phase 1/2 combination study of either AG-221 or AG-120 with VIDAZA (azacitidine) is planned for initiation in the first quarter of 2016. This study has a Phase 1 component to determine the safety of the combinations, followed by a Phase 2 randomized component evaluating the safety and clinical activity of each investigational combination versus single-agent VIDAZA using a primary endpoint of overall response rate.
ASH Data Presentations: New data from the ongoing Phase 1 dose-escalation and expansion studies of AG-221 and AG-120 in advanced hematologic malignancies have been accepted for presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exhibition taking place December 5-8, 2015 in Orlando.

EORTC-NCI-AACR Data Presentation: The first data from the ongoing Phase 1 trial of AG-120 in advanced IDH1-mutant positive solid tumors have been accepted for oral presentation at EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) taking place November 5-9, 2015 in Boston.
Pyruvate Kinase (PK) Deficiency Program Updates

Agios is pioneering the development of its small molecule enzyme activators in PK deficiency, a rare genetic metabolic disorder with no disease-altering therapies.

AG-348: AG-348, a first-in-class orally available, potent, selective small molecule activator of pyruvate kinase-R (PKR), is on track and enrolling in DRIVE PK, a global Phase 2, open-label safety and efficacy trial in adult, transfusion-independent patients with PK deficiency.

AG-519: Agios announced today the development of its second PKR activator, AG-519. This program provides clinical development optionality for our PK activator portfolio and potentially opportunities in other hemolytic anemias where PK activation may be therapeutic. The development plan for AG-519 includes a placebo-controlled Phase 1 study in healthy volunteers, which is planned for the first quarter of 2016. This study will be an integrated single ascending dose (SAD) and multiple ascending dose (MAD) trial.
Research Program Updates

Agios has advanced and led the emerging field of cancer metabolism with its novel IDH1 and IDH2 programs, demonstrating significant potential benefit for AML patients whose cancers carry these mutations. Agios’ work in IDH exemplifies the company’s strategy of targeting metabolic vulnerabilities. The company continues to discover novel metabolic targets that meet a high bar for future development. Today at its R&D day, Agios will describe:

Its precision medicine strategy to discover novel cancer metabolism targets.
Novel research approach to rare genetic diseases using allosteric modulation to correct the underlying dysfunction in metabolic pathways.

The potential for PKR activators to provide clinical benefit in other indications, such as beta-thalassemia.

Webcast

A live webcast of the company’s R&D Day will begin today at 9:00 a.m. ET and can be accessed under "Events & Presentations" in the Investors and Media section of the company’s website at www.agios.com. A replay of the webcast will be archived on the Agios website for 30 days following the presentation.

About the IDHENTIFY Phase 3 Study of AG-221

The Phase 3, international, multicenter, open-label, randomized clinical trial is designed to compare the efficacy and safety of AG-221 versus conventional care regiments in subjects 60 years or older with IDH2 mutant-positive AML refractory to or relapsed after second- or third-line therapy. Patients will be randomly assigned to receive either AG-221, 100 mg orally once a day for 28 days, or one of the conventional care regiments. The conventional treatment options include best supportive care only, azacitidine, low-dose cytarabine or intermediate-dose cytarabine. The primary endpoint of the trial is overall survival. The study is expected to enroll approximately 280 patients and is being conducted by Celgene. Please refer to www.clinicaltrials.gov for additional clinical trial details.

About Acute Myelogenous Leukemia (AML)

AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly increases with age, and according to the American Cancer Society, the median age of onset is 66. Less than 10 percent of U.S. AML patients are eligible for bone marrow transplant and the vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. The five-year survival rate for AML is approximately 20 to 25 percent. IDH1 and IDH2 mutations are present in about 15 to 23 percent of AML cases.

About AG-348 and PK Deficiency

PKD is a rare inherited disease resulting from mutations in the PKR enzyme that result in hemolytic anemia, which is the accelerated destruction of red blood cells. The mutations in the PKR enzymes cause a deficit in cellular energy within the red blood cell, as evidenced by a decline in the energy metabolite ATP and a build-up of the metabolite 2,3-DPG. Agios scientists have previously reported that AG-348 is a potent activator of the wild-type and mutated PKR enzymes, resulting in restoration of ATP levels and a decrease in 2,3-DPG levels in patient blood ex vivo. The current standard of care for PK deficiency is supportive, including blood transfusions, splenectomy, chelation therapy to address iron overload and/or interventions for other treatment- and disease-related morbidities. Currently, there is no approved therapy to treat the underlying cause of PKD. AG-348, a first-in-class orally available, potent, selective small molecule activator of PKR, was discovered by Agios scientists, and the company retains worldwide development and commercialization rights.

10-Q – Quarterly report [Sections 13 or 15(d)]

Burzynski Research Institute has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

CU biotech start-up gets $1.5 million contract to develop head and neck cancer treatment

On October 15, 2015 SuviCa Inc. of Boulder, a University of Colorado Boulder biotech start-up company reported that it has been awarded roughly $1.5 million in federal funding to develop novel treatments for head and neck cancer (Press release, suvica, OCT 15, 2015, View Source [SID1234517395]).

The award to SuviCa is a Phase II Small Business Innovation Research (SBIR) contract from the National Cancer Institute, part of National Institutes of Health and the Department of Health and Human Services. SuviCa was founded in 2010 based on a novel drug-screening technology developed by CU-Boulder Professor Tin Tin Su, SuviCa co-founder and chief scientific officer.

The funding will allow SuviCa to continue development of the drug SVC112, a compound shown to enhance the anti-tumor effects of radiation in animal models of human head and neck cancer, said SuviCa CEO Judy Hemberger. While radiation is a regular therapy used to treat such cancers, it also is associated with potentially devastating side effects and tumor recurrence, she said.

New treatments under development by Su and her colleagues involve small molecules that work together with currently used cancer therapeutics to destroy cancerous tumors, said Hemberger. The lead candidate for treatment currently is a "radiation enhancer" molecule that inhibits a specific process that cancer cells rely on to recover from radiation damage.

The project is being directed by Su and Bert Pronk, SuviCa’s vice president of preclinical development. The team also includes clinicians and scientists at CU-Boulder, the University of Colorado Cancer Center and Colorado State University.

CU’s Technology Transfer Office (TTO) exclusively licensed SVC112, along with related technology, to SuviCa in 2011 and 2012.

"We have very talented researchers at each of these institutions that together are tackling the challenges involved with successfully developing novel treatment options for head and neck cancer," said Su, a professor in CU-Boulder’s Department of Molecular, Cellular and Developmental Biology.

"We are excited to receive continued support from the National Cancer Institute," said Hemberger. "Our goal as a company is to generate innovative ways to improve how we treat cancer patients, and we are pleased that the scientific and business communities recognize that we are working with an important technology."

The small molecules developed by SuviCa target ribosomes, which synthesize proteins inside of cells, said Hemberger. Ribosomes are becoming increasingly recognized as a potential therapeutic target in cancer treatment.

TTO pursues, protects, packages and licenses intellectual property generated from research at the university. Tech Transfer provides assistance to faculty, staff and students, as well as to businesses looking to license or invest in CU technology.

Open Monoclonal Technology and ARMO BioSciences Announce Anti-PD1 Antibody and OmniAbTM Platform License Agreement

On October 15, 2015 ARMO BioSciences, Inc. (ARMO), a leading developer of immuno-oncology therapeutics and Open Monoclonal Technology, Inc. (OMT ) reported a licensing agreement providing ARMO with exclusive rights to OMT’s Programmed Cell Death Protein 1 (PD-1) assets as well as unlimited access to OMT’s proprietary OmniRat, OmniMouse and OmniFlic human antibody generation platforms (Press release, ARMO BioSciences, 15 15, 2015, View Source [SID:1234513063]).

"This is an important transaction for ARMO as we transition to our next stage of corporate growth. In particular, securing a PD-1 targeting agent provides us with a complete, efficient and cost- effective combination therapy solution for our next generation cytokine therapies," commented Peter Van Vlasselaer, Ph.D., President and Chief Executive Officer of ARMO BioSciences.

The addition of an anti-PD-1 program to ARMO’s pipeline of cytokine immunotherapies reinforces the company’s commitment to the development of safe and effective treatments for cancer. ARMO’s clinical stage PEGylated form of recombinant human IL-10, known as AM0010, and anti- PD-1 antibodies work through complementary but distinct mechanisms on CD8+ T cells so the combination maximizes the activation, proliferation and survival of intratumoral, tumor-reactive, cytotoxic CD8+ T cells, which are considered to be central to clinical response. In ongoing clinical studies, AM0010 has already shown activity as a monotherapy and in combination with anti-PD-1 agents in immune-sensitive tumors such as melanoma, RCC, NSCLC and others not previously thought to be sensitive to immunotherapy such as colorectal and pancreatic cancers. Early results from these trials are suggestive of AM0010’s role in augmenting activated tumor infiltrating T cells and PD-1 expression, thereby bestowing anti-PD-1 sensitivity on tumors, including those that had been refractory to anti-PD-1 treatment.

Dr. Roland Buelow, OMT founder and CEO, said, "ARMO’s focus on discovery and development of novel therapies based on proprietary insights of dysregulated immune responses in cancer and atherosclerotic, fibrotic and inflammatory diseases are particularly amenable to human therapeutic antibodies. We are pleased to enable ARMO to access both OMT’s anti-PD1 antibodies and mono- and bi-specific antibody platforms to further the company’s therapeutic objectives."