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 26, 2017, View Source [SID1234520637]).

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 26, 2017 Moleculin Biotech, Inc., (NASDAQ: MBRX) (“Moleculin” or the “Company”), a clinical stage pharmaceutical company focused on the development of anti-cancer drug candidates, some of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported that the Food and Drug Administration (FDA) has advised Moleculin it may begin clinical trials of Annamycin in the treatment of relapsed or refractory Acute Myeloid Leukemia (AML) (Press release, Moleculin, SEP 26, 2017, View Source [SID1234520635]). The FDA’s determination came after the agency completed its safety review of information and a proposed protocol submitted by Moleculin in an Investigational New Drug application (IND).

“This represents a tremendous milestone for Moleculin,” commented Walter Klemp, Chairman and CEO of Moleculin. “Our primary focus has been to get Annamycin back into the clinic so we can begin optimizing the dosing of the drug as the next step in evaluating its potential to become the first 2nd line therapy suitable for the majority of relapsed or refractory AML patients. It is a thrill to now refer to Moleculin as a ‘clinical stage’ company.”

Dr. Don Picker, Chief Science Officer for Moleculin, added, “We are grateful for the FDA’s thorough and comprehensive review of our IND, and for the manner in which they worked with us to address some key technical issues in the area of Chemistry, Manufacturing and Control.”

Moleculin’s Chief Medical Officer, Dr. Robert Shepard, added: “Responding to comments from the FDA, we have adopted additional patient safeguards that will be implemented while we seek to establish the ‘Recommended Phase 2 Dose.’ This will include reporting interim safety data to FDA before allowing US patients to progress beyond initial agreed-upon dosing limits. After seeing indications of what Annamycin may be capable of from earlier clinical trials, I made it a career goal to get the drug back into the proper clinical trials to determine its potential.”

The US IND going into effect also allows Moleculin to make a submission to Polish authorities necessary for the planned Annamycin clinical trial to also be conducted in Poland.

On September 26, 2017 (GLOBE NEWSWIRE) — 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, BioTime, SEP 26, 2017, View Source [SID1234520633]). 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.

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.

On September 26, 2017 Aduro Biotech, Inc. (Nasdaq:ADRO), a biopharmaceutical company with three distinct immunotherapy technologies, reported that the first patient has been dosed in the Phase 1b dose escalation and dose expansion clinical trial (see www.clinicaltrials.gov, identifier NCT03172936) designed to evaluate the safety and efficacy of ADU-S100 (also known as MIW815), a novel STING pathway activator, in combination with PDR001, Novartis’ investigational PD-1 checkpoint inhibitor, for the treatment of advanced/metastatic solid tumors or lymphomas (Press release, Aduro Biotech, SEP 26, 2017, View Source [SID1234520631]). The trial, which is being conducted in collaboration with Aduro’s partner, Novartis, is expected to enroll approximately 175 patients at sites located in the United States, Europe, Canada, Australia and Japan.

“We are pleased with our early progress in the ongoing Phase 1 dose escalation trial of ADU-S100 as a single agent and are eager to expand our investigation into a separate clinical trial to evaluate the effect of ADU-S100 used in combination with the PDR001 checkpoint inhibitor,” said Natalie Sacks, M.D., chief medical officer of Aduro Biotech. “As a leader in STING activation, we look forward to gaining more insight into the potential therapeutic application of this novel combination therapy.”

Clinical Design of Phase 1b ADU-S100 (MIW815)/PDR100
The Phase 1b multi-center, open-label study is designed to evaluate the safety and efficacy of ADU-S100 (MIW815) in combination with PDR001 in patients with accessible solid tumors or lymphomas. The trial will evaluate two treatment schedules of ADU-S100 in dose escalation. One group will receive a fixed dose of intravenous PDR001 on day 1 and an intratumoral injection of ADU-S100 three times in a 28-day cycle. Another group will receive a fixed dose of intravenous PDR001 on day 1 and intratumoral injection of MIW815 (ADU-S100) on day 1 of every 28-day cycle. Once the maximum tolerated dose and/or recommended dose for expansion is determined, the expansion part of the study will open.

Ongoing Phase 1 Dose Escalation Trial of ADU-S100 (MIW815) in Multiple Tumor Types
In May 2016, Aduro announced the initiation of the ongoing Phase 1, multicenter, dose escalation study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of ADU-S100 (MIW815) in patients with cutaneously accessible metastatic solid tumors or lymphomas (see www.clinicaltrials.gov, identifier NCT02675439). The trial is ongoing.

About STING Pathway Activator Platform
The Aduro-proprietary STING pathway activator product candidates, including ADU-S100 (MIW815), are synthetic small molecule immune modulators that are designed to target and activate human STING. STING is generally expressed at high levels in immune cells, including dendritic cells. Once activated, the STING receptor initiates a profound innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines. This subsequently leads to the development of a systemic tumor antigen-specific T cell adaptive immune response.

About Aduro/Novartis Collaboration
In March 2015, Aduro and Novartis entered into a collaboration and license agreement relating to the global research, development and commercialization of immuno-oncology products derived from Aduro’s proprietary STING pathway activator platform technology. Under the terms of the agreement, Aduro received an upfront payment from Novartis of $200 million and a $35 million development milestone upon initiation of the Phase 1 trial for ADU-S100 in May 2016, and if all development and regulatory milestones are met, is eligible to receive up to an additional aggregate amount of $465 million. The collaboration is guided by a joint steering committee with both Aduro and Novartis having final decision making authority regarding specified areas of development or commercialization. Pending regulatory approval, Aduro will lead commercialization activities and will book sales in the United States for any products developed and commercialized pursuant to this collaboration, and Novartis will lead commercialization activities in all other regions. The companies will share in profits, if any, in the United States, Japan and major European countries. Novartis will pay Aduro a mid-teens royalty for sales in the rest of the world. Aduro maintains rights to its STING platform technology in all therapeutic areas outside of oncology, including infectious disease and autoimmunity, among others.

On September 26, 2017 BioLineRx Ltd. (NASDAQ/TASE:BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported the initiation of a Phase 1b/2 trial for BL-8040 in combination with atezolizumab (TECENTRIQ), an anti-PDL1 cancer immunotherapy from Genentech, a member of the Roche Group (Press release, BioLineRx, SEP 26, 2017, View Source [SID1234520628]). The trial, known as the BATTLE study (NCT03154827), will focus on the maintenance treatment of patients with intermediate- and high-risk acute myeloid leukemia (AML) who have achieved a complete response (CR) following induction and consolidation therapy.

Up to 60 patients are planned to be enrolled in this multicenter, single arm, open-label study, to evaluate the relapse-free survival, minimal residual disease status, safety and tolerability of the combination of BL-8040 and atezolizumab for maintenance treatment in AML patients. The study’s primary endpoint is to assess whether the combination of BL-8040 and atezolizumab prolongs relapse free survival. In addition, the effect of the combination therapy on minimal residual disease, multiple immunological parameters, and potential biomarkers will be evaluated. The trial is planned to take place at approximately 22 sites in the US, Europe and Israel.

The BATTLE study is part of BioLineRx’s cancer immunotherapy collaboration with Genentech to conduct several Phase 1b/2 studies investigating the combination of BL-8040 with atezolizumab in multiple cancer indications, announced in September 2016.

Philip Serlin, Chief Executive Officer of BioLineRx, stated, “We are excited to commence yet another clinical study under this significant immuno-oncology collaboration, following the recent initiation of a study to evaluate the combination of the same two drugs for the treatment of pancreatic cancer. The BATTLE study is the first study under our collaboration in hematologic malignancies, and we are hopeful that combining atezolizumab with BL-8040 will demonstrate the potential to establish a new treatment for AML patients that would extend the duration of remission following induction treatment, in particular for patients for whom stem-cell transplantation is inappropriate. We look forward to the initiation of additional combination studies under this collaboration, all planned by the end of this year.”

BL-8040, BioLineRx’s lead oncology platform, is a CXCR4 antagonist that has been shown, in a successful Phase 2a study in relapsed and refractory AML patients, to be a robust mobilizer of immune and tumor cells and to be effective in inducing direct tumor cell death.

These two effects, when combined with atezolizumab-induced blockade of the interaction between PD-L1 with PD-1 and B7.1, are hypothesized to have a beneficial effect on the minimal residual disease (MRD) status of AML patients. Specifically, this combined approach could potentially reduce an AML patient’s MRD status from positive to negative, and possibly have a favorable effect on disease outcome. This study’s regimen aims at further prolonging the period of remission, exploring a novel maintenance approach to these patients.

About BL-8040
BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and stem cell mobilization. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells from the bone marrow, thereby sensitizing these cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing cell death (apoptosis). In addition, BL-8040 has also demonstrated robust stem-cell mobilization, including the mobilization of colony-forming cells, T, B and NK cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

About Acute Myeloid Leukemia (AML)
Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow and is the most common type of acute leukemia in adults. According to the American Cancer Society, approximately 20,000 new cases of AML were diagnosed in the United States in 2016, and the median age of AML patients was 67 years old. The first treatment line for patients with AML includes a combination of chemotherapy drugs and is called induction treatment. The median survival for AML patients receiving induction chemotherapy is less than two years, with shorter survival for patients over the age of 60 or for those with certain gene or chromosome aberrations. Due to relapsed or refractory disease (where the disease is not responsive to standard treatments), the overall five-year survival rate for AML is between 10 and 40 percent.