On September 26, 2017 Mateon Therapeutics, Inc. (OTCQX:MATN), a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, reported results from its third scheduled interim analysis of the phase 2/3 FOCUS study evaluating CA4P in combination with bevacizumab (Avastin) and physician’s choice chemotherapy in patients with platinum-resistant ovarian cancer (Press release, Mateon Therapeutics, SEP 27, 2017, View Source [SID1234520671]).

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FOCUS was designed to evaluate whether the addition of CA4P improved progression-free survival (PFS), the primary endpoint of the study, as well as objective response rate (ORR) and other measures. All patients enrolled in the FOCUS study received either CA4P or placebo plus the current standard-of-care for platinum-resistant ovarian cancer: bevacizumab (Avastin) and chemotherapy. The current analysis is based on initial results from the first 70 patients in the study who have been treated for at least two months or discontinued from the trial. A total of 91 patients were enrolled in FOCUS.

Efficacy Results

ORR data is summarized in the table below.

CA4P Control
Complete Response
0 (0%) 0 (0%)
Partial Response
8 (23.5%) 13 (36.1%)
Stable Disease
16 (47.1%) 17 (47.2%)
Progressive Disease
5 (14.7%) 3(8.3%)
Not Evaluable
5 (14.7%) 3(8.3%)

PFS, the primary endpoint of the study, favored the CA4P group, with a 32 day increase in median PFS for the patients receiving CA4P compared to patients receiving control (202 days vs. 170 days; HR=0.844; p=0.688). Progression events are available from 24 of 70 (34.3%) patients: 12 patients (35.3%) in the CA4P arm and 12 (33.3%) patients in the control arm progressed or died while in the study.

Due to the lack of a meaningful improvement in PFS, combined with the unfavorable partial response data, the company does not believe that continuation of the study is appropriate. Therefore, Mateon is immediately terminating the FOCUS Study and further development of CA4P. Mateon will continue to support investigator-sponsored studies and preclinical studies in combination with immuno-oncology agents.

"We are clearly disappointed that CA4P did not show a clinically meaningful benefit when it was added to the current standard of care in platinum-resistant ovarian cancer," said William D. Schwieterman, M.D., President and Chief Executive Officer. "I want to thank our investigators and advisors, as well as the patients that we treated, for their efforts to advance future cancer care. These external participants, along with our internal team, did a great job planning and executing the study, but the outcome is clear, and unfortunately negative."

Safety Results

The safety profile of CA4P was favorable. Similar to prior analyses, most patients receiving CA4P experienced transient increases in blood pressure compared to the control arm. Other adverse events occurring more often in the CA4P arm than in the control arm included: hypertension, fatigue, nausea, vomiting, and abdominal pain. Most adverse events were mild or moderate in severity, with blood pressure increase being the only adverse event with a
significant increase in Grade 3 or above (29.4% in CA4P arm versus 5.6% in control). Six patients in the treatment arm (17.6%) withdrew from the study for adverse events compared to three in the control arm (8.3%).
Reduction in Expenses

Given the company’s limited financial resources, Mateon is implementing various near-term cost reduction measures, which include a significant reduction in personnel, representing a decrease in the company’s workforce of approximately 60% since the beginning of the year. The remaining members of the senior management team will take 50% salary reductions, effective immediately.

"We assembled a great team that, within the last two years, has planned, initiated and completed the FOCUS Study ahead of schedule. The team has also planned, initiated and completed five cohorts of an on-going OXi4503 study for relapsed/refractory AML. With the company’s needs now very different, it is disheartening to terminate most of these employees following their solid work performances," concluded Dr. Schwieterman. "Going forward, our immediate focus is to obtain value from our OXi4503 program in AML, which, within the last two months, has shown clear positive clinical outcomes in relapsed/refractory patients. As always, we are exploring all options for additional fundraising and adding value for our stockholders, which includes continuing to look for buyers for any or all of our assets."

On September 27, 2017 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") has announced that the application submitted for an additional indication of its in-house discovered and developed anticancer agent Lenvima (generic name: lenvatinib mesylate) for the treatment of hepatocellular carcinoma (HCC) has been accepted for review by the U.S. Food and Drug Administration (FDA). Lenvatinib for the treatment of HCC is designated as an orphan drug by the FDA (Press release, Eisai, SEP 27, 2017, View Source [SID1234528956]).

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This application is based on the results of the REFLECT study (Study 304), a multicenter, open-label, randomized, global Phase Ⅲ trial comparing the efficacy and safety of Lenvima versus sorafenib, a standard treatment for HCC, as a first-line treatment for patients with unresectable HCC.1

In the REFLECT study, Lenvima met the primary endpoint and demonstrated an overall survival (OS) treatment effect by the statistical confirmation of non-inferiority compared to sorafenib. Developing first-line treatments for HCC is challenging, and over the past 10 years, four previous first-line Phase Ⅲ studies investigating other agents compared to sorafenib have failed to achieve their endpoints in OS.2
Additionally, Lenvima showed highly statistically significant and clinically meaningful improvements in the secondary endpoints of Progression Free Survival (PFS), Time To Progression (TTP), and Objective Response Rate (ORR). In this study, the five most common adverse events observed in the Lenvima arm were hypertension, diarrhea, decreased appetite, weight loss and fatigue, which is consistent with the known side-effect profile of Lenvima.

Liver cancer is the second leading cause of cancer related death and is estimated to be responsible for 750,000 deaths per year globally (27,000 per year in the US), with 780,000 cases newly diagnosed each year (30,000 per year in the US).3 HCC accounts for 85% to 90% of liver cancer cases. Treatment options for unresectable HCC are limited and the prognosis is very poor, making this an area of high unmet medical need.

Eisai positions oncology as a key therapeutic area, and is aiming to discover revolutionary new medicines with the potential to cure cancer. Eisai is committed to exploring the potential clinical benefits of Lenvima as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to patients with cancer, their families, and healthcare providers.

On September 26, 2017 Asterias Biotherapeutics, Inc. (NYSE MKT:AST), a biotechnology company pioneering the field of regenerative medicine, reported that the Medicines and Healthcare Products Regulatory Agency (MHRA) and the NHS Research Ethics Committee (REC) have provided the necessary approvals to initiate the first-in-human (FIH) clinical trial of AST-VAC2 in the United Kingdom (UK) (Press release, Asterias Biotherapeutics, SEP 26, 2017, View Source;p=RssLanding&cat=news&id=2302817 [SID1234520634]). The trial, which is being sponsored and managed by Cancer Research UK, will examine the safety, tolerability, immunogenicity and activity of AST-VAC2 in non-small cell lung cancer (NSCLC) patients and is expected to be initiated later this year.

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AST-VAC2 is a "first-in-class" allogeneic cancer immunotherapy that is composed of mature dendritic cells which are designed to kill tumor cells by stimulating immune responses to telomerase, a tumor antigen expressed by over 85% of malignant tumor cells. AST-VAC2 is available for "on demand" patient use because it is produced from allogeneic pluripotent stem cells that can be manufactured in scale and then cryopreserved. The AST-VAC2 to be used in this trial has been manufactured by Cancer Research UK’s Biotherapeutics Development Unit.

AST-VAC2 is a platform cancer immunotherapy that could be investigated as a potential therapeutic for many cancer indications and for targeting of many antigens. The results from the clinical trial sponsored by Cancer Research UK could be used to support advanced clinical studies in one or more of the following areas:

Non-small cell lung cancer
Other indications showing high levels of telomerase activity and susceptibility to immunotherapy
In combination with check point or immune pathway inhibitors
In combination with additional antigens, including those arising from the exciting new field of tumor neoantigens
"The recently announced acquisition of Kite Pharma by Gilead for $11.9 billion provides strong validation for the cell therapy industry generally and especially in oncology," said Mike Mulroy, President and Chief Executive Officer. "With its potential as a ready-to-administer, off-the-shelf cancer immunotherapy, AST-VAC2 represents an exciting opportunity for Asterias in the rapidly evolving immuno-oncology sector and the approvals received from MHRA and REC to commence clinical testing represent an important milestone in the development of AST-VAC2."

The clinical trial will administer AST-VAC2 in up to twenty-four patients in two cohorts. In the first cohort, up to 12 patients with advanced non-small cell lung cancer and a specific immunological marker called HLA-A2 will receive AST-VAC2, and will be followed for safety, immune responses to telomerase, and overall clinical survival. The second cohort will evaluate AST-VAC2 in up to 12 patients with the HLA-A2 marker who have had successful resection of their tumor with no evidence of metastasis and each patient will be followed for safety, immune responses to telomerase, overall clinical survival and time to relapse. Both cohorts will have a control group consisting of patients that meet all inclusion/exclusion criteria for the study except those patients do not have the HLA-A2 marker.

"The design of the trial will allow us to assess many features of AST-VAC2 and how to best position its use in future trials," said Jane Lebkowski, Chief Scientific Officer. "We will be testing immune responses invoked by AST-VAC2 in the settings of advanced disease and resected disease and perform intermediate assessments of immune response during the course of AST-VAC2 dosing. Clinical outcome and immune response data will help confirm whether AST-VAC2 is most beneficial for patients in an active or minimal residual disease setting and inform determination of the optimal dosing regimen for future trials. The trial will also have a concurrent control group to provide real-time assessment of the safety and activity of the product. We are very excited to begin the clinical development of AST-VAC2 which could become a cornerstone agent in the immunotherapy of cancer."

"The AST-VAC2 study is an exciting step towards improving our tools in cancer immunotherapy," said Professor Christian Ottensmeier, the study’s principal investigator. "Not only does the Asterias approach already have a track record in Acute Myeloid Leukemia (AML), but an ‘off the shelf’ dendritic cell vaccine opens the path towards making dendritic cell vaccination easily deliverable in the clinic. We are very excited to be working towards opening this study in the second half of 2017."

The partnership between Asterias and Cancer Research UK is being conducted under Cancer Research UK’s Clinical Development Partnerships (CDP) scheme, which allows the first clinical trial of AST-VAC2 to be initiated without significant Asterias resources being allocated to the trial and the manufacturing of the product. On completion of the clinical trial, Asterias will have an exclusive first option to acquire the data from the trial.

About AST-VAC2

AST-VAC2 is an innovative immunotherapy product that contains mature dendritic cells derived from pluripotent stem cells. These non-patient specific (allogeneic) AST-VAC2 cells are engineered to express a modified form of telomerase, a protein widely expressed in tumor cells, but rarely found in normal cells. The modified form of telomerase invokes enhanced stimulation of immune responses to the protein. Similar to an earlier, Asterias-sponsored, hematological cancer program which provided proof-of-concept data, the AST-VAC2 dendritic cells instruct the immune system to generate responses against telomerase which will target tumor cells. AST-VAC2 is based on a specific mode of action that is complementary to and potentially synergistic with other immune therapies such as checkpoint inhibitors or other immune pathway inhibitors.

About Non-Small Cell Lung Cancer and the AST-VAC2 Trial

Lung cancer (both small cell and non-small cell) is the leading cause of cancer-related death, accounting for about one-quarter of all cancer deaths and more than colorectal, breast, and prostate cancers combined. Non-small cell lung cancer (NSCLC) accounts for about 80% to 85% of lung cancers, according to the American Cancer Society. The three main types of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. The American Cancer Society’s estimates for lung cancer in the United States for 2017 are: about 222,500 new cases of lung cancer, and about 155,870 deaths from lung cancer. Despite the large number of people afflicted by non-small cell lung cancer, patients remain vastly underserved due to a scarcity of effective treatments. According to statistics published by Cancer Research UK, the five year survival rate for lung cancer patients in England and Wales is less than 10%.

The AST-VAC2 clinical trial will enroll up to twenty-four patients into one of two cohorts, depending on the stage of their non-small cell lung cancer. The first cohort will evaluate AST-VAC2 in up to 12 patients with advanced non-small cell lung cancer for whom only palliative treatments are available. Subjects in this cohort, who carry the major histocompatibility gene, HLA-A2, will receive six weekly injections of AST-VAC2 and will be followed for safety, immune responses to telomerase, impact on tumor burden and overall clinical survival. These safety and activity results will be compared directly to a control group who meet all of the other inclusion/exclusion criteria but do not possess the HLA-A2 gene. Assuming safety is demonstrated in the first cohort, enrollment will advance to a second cohort. In the second cohort, early stage patients who have had successful resection of their tumor with no evidence of metastasis will be enrolled. Up to 12 subjects in this second cohort who carry the major histocompatibility allele HLA-A2 will receive six, weekly injections of AST-VAC2 and will be followed for safety, immune responses to telomerase, and relapse. These safety and activity results will again be compared directly to a control group who meet all of the inclusion/exclusion criteria of cohort 2 but are not HLA-A2+. For their key endpoints, patients will be followed for one year.

On September 26, 2017 Glythera Limited (Glythera), the next generation antibody drug conjugate (ADC) development company, and Cancer Research UK* reported an agreement giving Glythera exclusive, worldwide rights to the charity’s novel CDK11 inhibitor payload series for the development of multiple ADCs conjugated using Glythera’s proprietary PermaLink conjugation platform (Press release, Cancer Research Technology, SEP 26, 2017, View Source [SID1234523160]).

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According to the agreement, Glythera and Cancer Research UK will select and optimise toxins from the inhibitor payload series for development in ADCs. Glythera will then progress multiple ADCs, optimised according to cancer cell-kill profiles, for difficult-to-treat tumours. Glythera is currently evaluating a range of clinically important antibody targets and intends to identify its first clinical ADC candidate by 2019.

This agreement follows a successful period of collaboration between the parties during which the viability of selected low molecular weight CDK11 molecules was demonstrated in relevant ADC models.

The CDK11 inhibitor programme has identified a series of low molecular weight, synthetically tractable compounds which potently inhibit and are selective against other kinase targets. The series demonstrates highly potent anti-proliferative activity in dividing and non-dividing tumour cells and represents an exciting approach for ADCs.

Under the Terms of the agreement, Cancer Research UK will receive an undisclosed up-front fee, milestone payments on programme success for each resulting ADC, and royalties on worldwide product sales. Glythera is responsible for the development, manufacturing and commercialisation of any ADC products resulting from the agreement.

Dr Hamish Ryder, Director of Cancer Research UK’s Therapeutic Discovery Laboratories, said: "This collaboration highlights the success of our drug discovery approach in translating the most promising early stage research into new cancer treatments."

"We’re excited to work with Glythera to identify and advance the very best novel agents and develop targeted treatments for cancer patients. By continuing to bring together industry and world leading academics in this field, we hope to transform the outlook for people with cancers that are the hardest to treat."

Dr Dave Simpson, Chief Executive Officer, Glythera, said: "I am delighted that Glythera is working with Cancer Research UK as we look to identify and develop CDK11 inhibitor payloads and antibody conjugates to combat difficult-to-treat solid tumours and improve the lives of patients living with cancer."

On September 26, 2017 Amgen (NASDAQ: AMGN) and Simcere Pharmaceutical Group reported the execution of an exclusive agreement to co-develop and commercialize four biosimilars in China (Press release, Amgen, SEP 26, 2017, View Source;p=RssLanding&cat=news&id=2302973 [SID1234520648]). The collaboration includes undisclosed biosimilars in the areas of inflammation and oncology.

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Under the terms of the agreement, Amgen will remain responsible for the co-development, marketing approval applications and manufacturing of the biosimilars. Simcere will be responsible for distribution and commercialization in China, while Amgen will have a limited right to co-promote the products. The biosimilars included in the agreement are a part of Amgen’s existing biosimilars portfolio.

"We are pleased to enter this strategic collaboration with Simcere as we continue to enhance patient access through broader adoption of more competitive therapeutic options worldwide," said Scott Foraker, vice president and general manager of Biosimilars at Amgen. "This agreement brings together Amgen’s long-standing development and biologics manufacturing expertise with Simcere’s local development experience and strong commercial presence in China in the areas of inflammation and oncology."

"This agreement furthers Amgen’s efforts to reach more patients in Asia by bringing high quality biosimilars medicines to patients suffering from debilitating and potentially life-threatening conditions," said Penny Wan, regional vice president and general manager of Amgen’s Japan and Asia-Pacific Region. "We look forward to working with Simcere on these four biosimilar programs where we can build on their network and experience in China to make a big difference for patients."

"This strategic partnership between a world-renowned biotechnology company and a leading Chinese pharma will help to accelerate development and launch of United States and European approved biosimilars in China. By leveraging our sales network, it will also help to improve the accessibility of high quality therapeutic antibodies for Chinese patients," said Honggang Feng, president of Simcere. "This collaboration will allow both companies to further penetrate inflammation and oncology markets in China."

Dr. Hua Mu, chief scientific officer of Simcere said, "Recently, China Food and Drug Administration (CFDA) has formally joined the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and implemented major reforms on drug evaluation and approval systems, encouraging and supporting research and development of innovative, high quality medicines. This strategic alliance combines Amgen’s leading global research and development capabilities in biosimilars and Simcere’s domestic drug development and registration experience. It aims to bring more high quality and effective medicines to Chinese patients to meet the pressing unmet medical needs. It is also another important milestone in our international collaboration strategy to enrich Simcere’s biologics pipeline."

Specific financial terms of the agreement were not disclosed.