On September 26, 2017 Selexis SA and OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnémo: OSE) reported the signing of two commercial license agreements (CLAs) that provide OSE with access to high-performance research cell banks (RCBs) developed using the Selexis SUREtechnology Platform (Press release, Selexis, SEP 26, 2017, View Source [SID1234520640]). The agreements are designed to support the advancement of the clinical development of OSE-172 (Effi-DEM), OSE’s new generation immune myeloid checkpoint inhibitor, as well as OSE-703 (Effi-3), OSE’s cancer immunotherapy, which is a cytotoxic monoclonal antibody targeting the IL-7 receptor.

“This is our third signed CLA with OSE this year, and we believe the rapid expansion of our relationship is a direct result of the utility and flexibility of our cell-line expression technology across protein therapeutics and development stages,” said Marco Bocci, PhD, DPharm, Selexis vice president, licensing and business development. “One of the most fulfilling aspects of our work at Selexis is that we are able to play a role in our partners’ success, which means the possibility of new therapeutic options for patients with many life-threatening diseases. Selexis’ technology can scale with OSE’s developmental needs, and provide the company with a fast, stable and reliable method of protein expression. This is critical for the development of recombinant, protein-based medicines like OSE-172 and OSE-703.”
“Our work with Selexis has been instrumental in advancing our investigational therapeutic candidates toward clinical development,” said Alexis Peyroles, chief operating officer of OSE Immunotherapeutics. “OSE and Selexis are focused on quickly advancing delivery of treatment options to patients facing life-threatening diseases. It’s exciting to watch the evolution of our relationship with Selexis, knowing the impact their technology is having on our research and development activities.”
Selexis’ proprietary SUREtechnology Platform facilitates the rapid, stable, and cost-effective production of virtually any recombinant protein and provides seamless integration of the biologics development continuum, spanning discovery to commercialization.

A new generation immune checkpoint inhibitor, OSE-172 (Effi-DEM) is a monoclonal antibody targeting SIRP-α, expressed on suppressive myeloid cells involved in the tumor microenvironment. As selective antagonist of SIRP-α, OSE-172 transforms the tumour microenvironment by blocking suppressor cells and activating anti-tumour effector cells. OSE-172 is planned to enter Phase 1/2 clinical phase in 2018.

OSE-703 (Effi-3) is a humanized monoclonal antibody directed against the extracellular domain of the alpha-chain of the receptor for interleukin-7, cytotoxic for human cells expressing CD127. Under a research collaboration with Memorial Sloan Kettering Cancer Center, the cancer immunotherapy is in preclinical studies for solid tumors with non-small cell lung cancer (NSCLC) as the primary cancer model.

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, Glythera, SEP 26, 2017, View Source [SID1234520639]).

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 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.