On October 17, 2017 Diffusion Pharmaceuticals Inc. (NASDAQ:DFFN) (“Diffusion” or “the Company”), a clinical-stage biotechnology company focused on extending the life expectancy of cancer patients, reported that it has received final protocol guidance from the U.S. Food and Drug Administration (FDA) for a Phase 3 clinical trial with the Company’s lead compound trans sodium crocetinate (TSC) in patients newly diagnosed with inoperable glioblastoma multiforme (GBM), a type of brain cancer (Press release, Diffusion Pharmaceuticals, OCT 17, 2017, View Source [SID1234520978]). The Company has responded to all outstanding points raised by the FDA and plans to begin the trial under the protocol agreed to by the FDA by the end of 2017. The trial will compare survival at two years of patients receiving TSC concurrent with chemotherapy and radiation (standard of care, or SOC), with patients receiving SOC alone.

“Following a series of interactions with the FDA, we are gratified to have an agreed-upon protocol and to be preparing to start our TSC Phase 3 trial in patients newly diagnosed with inoperable GBM,” said David Kalergis, Chief Executive Officer of Diffusion Pharmaceuticals. “As previously announced, we have engaged the contract research organization to oversee this trial and have completed the Phase 3 TSC drug production run to FDA standards. On our way to opening an anticipated total of 100 sites across the U.S. and Europe, we have 17 initial sites selected in the U.S., all under one Institutional Review Board, and first patients are expected to be enrolled this year.”

Mr. Kalergis continued, “This Phase 3 study will focus on treating newly diagnosed GBM patients who have been judged by their medical team to be inoperable because of the size or location of the tumor. In Diffusion’s Phase 2 proof-of-concept trial, the inoperable GBM patients who were treated with TSC plus standard of care showed a nearly four-fold increase in survival at two years compared with standard of care patients only. Due to their poor prognoses, inoperable patients are often excluded from GBM clinical trials and have usually been treated with radiation and chemotherapy only. We are excited to bring a new treatment possibility to patients with inoperable GBM, and look forward to beginning the trial.”

About the Glioblastoma Multiforme Phase 3 Trial

The Phase 3 trial is a randomized, controlled registration trial with TSC and SOC chemotherapy and radiation, compared with SOC alone in newly diagnosed inoperable GBM patients. The primary endpoint is overall survival, either after a predetermined number of patient deaths or following successful results of an optional interim analysis. Secondary endpoints include progression-free survival (PFS) and objective response rate (ORR; tumor response) using RANO criteria, as well as patient performance scoring (Karnofsky Performance Scale; KPS), Quality of Life (EQ-5D-5L questionnaire) and corticosteroid and anticonvulsant usage.

A total of 236 patients will be randomized 1:1 at 100 clinical sites (54 U.S., 46 EU). TSC will be dosed three times each week for six weeks concurrent with standard radiation and chemotherapy as initial treatment. This will be followed by one month of rest and then adjuvant chemotherapy consisting of six monthly cycles of TSC and temozolomide given for the first week of each cycle. As such, 18 doses of TSC will be administered during initial treatment and another 18 doses will be administered during adjuvant treatment to those so randomized.

About Treatment-Resistant Cancers and TSC

Oxygen deprivation at the cellular level (hypoxia) is the result of rapid tumor growth, causing the tumor to outgrow its blood supply. Cancerous tumor cells thrive with hypoxia and the resultant changes in the tumor microenvironment cause the tumor to become resistant to radiation therapy and chemotherapy. Using a novel, proprietary mechanism of action, Diffusion’s lead drug TSC counteracts tumor hypoxia – and therefore treatment-resistance – by safely re-oxygenating tumor tissue, thus enhancing tumor kill and potentially prolonging patient life expectancy. Oxygen levels of normal tissue remain unaffected upon administration of TSC, thereby avoiding the introduction of harmful side effects.

On October 17, 2017 Celsion Corporation (NASDAQ:CLSN), an oncology development company, reported a summary of ThermoDox related presentations made during the Company’s Research and Development (R&D) Day held on Thursday, October 12, 2017 (Press release, Celsion, OCT 17, 2017, View Source [SID1234520977]). This summary is intended to provide easy access to pertinent, top line information discussed during the conference. A complete webcast of the presentations is available on Celsion’s website at www.celsion.com under the heading News & Investors / Financial Events / Featured Events – October 12, 2017 – Celsion to Host Research and Development Update.

The presentations focused on the Company’s research and development program using ThermoDox, Celsion’s proprietary heat-activated liposomal encapsulation of doxorubicin, for the treatment of primary liver cancer, also known as hepatocellular carcinoma or HCC. Leading OPTIMA Study clinical investigators representing various geographical regions (Asia-Pacific and Europe) and multiple medical disciplines (hepatology, interventional radiology and surgery) presented their past and current experiences with ThermoDox for the treatment of primary liver cancer.

— Nicholas Borys, M.D., Celsion’s Senior Vice President & Chief Medical Officer, presented the following:
ThermoDox’s mechanism of action and how it utilizes tumor biology to deliver high concentrations of drug (Doxorubicin) directly to the tumor site and the importance of heating time.

Key learnings from the Company’s 701 patient HEAT Study including results from (i) computer simulation studies, (ii) preclinical animal studies and (iii) a post hoc subgroup analysis, all of which establishes a clear understanding of a key ThermoDox heat-based mechanism of action: the longer the target tissue is heated, the greater the doxorubicin tissue concentration.

Hypothesis prompted by the HEAT Study post-hoc findings: ThermoDox, when used in combination with Radiofrequency Ablation (RFA) standardized to a minimum dwell time of 45 minutes (sRFA > 45 min), appears to increase the overall survival (OS) of patients with HCC.

Results from an independent retrospective analysis conducted by the National Institutes of Health on the intent-to-treat population of the HEAT Study which sought to evaluate the correlation between RFA burn time per tumor volume (min/ml) and clinical outcome. The analysis concluded that increased RFA “burn time” per tumor volume significantly improved overall survival (OS) in patients with solitary lesions treated with sRFA + ThermoDox compared to patients treated with sRFA alone.

Update on the current enrollment status of the OPTIMA Study which is approaching 70% of the 550 patients necessary to ensure that its primary end point, overall survival, can be evaluated with statistical significance. The statistical plan for the OPTIMA Study calls for two interim efficacy analyses by the IDMC. The Company projects full patient enrollment by mid-2018 and the first pre-planned efficacy analysis after 118 overall survival events by the first quarter of 2019.

— Won Young Tak, M.D., Ph.D., Professor Internal Medicine, GI & Hepatology Kyungpook National University Hospital Daegu, Republic of Korea presented the following:

RFA has limited efficacy in larger tumors due to microsatellite nodules or viable tumors.
Patients treated with ThermoDox in the HEAT Study had excellent survival outcome. Two cases presented for the HEAT Study showed five and nine year survival benefit for patients treated with ThermoDox plus sRFA.

— Stephen N. Wong, M.D., Principal Investigator OPTIMA, Chinese General Hospital, Philippines presented the following:

HEAT Study patients treated with ThermoDox demonstrated a high complete response rate compared to other studies

A strong correlation exists between complete response and better survival.

— Robert M. Eisele, M.D., Deputy Head of Department, Dept. of General, Visceral, Vascular and Pediatric Surgery, Medical Faculty of the University of Saarland, Homburg, Germany presented the following:
HCC is a worldwide problem with high incidence that continues to rise.

Treatment strategies for treating HCC should be tailored.

Until ThermoDox, RFA was insufficient in treating intermediate to large tumors.
Data from the HEAT Study suggests a new role for RFA plus ThermoDox in HCC – a “promising option.”

About the OPTIMA Study
The Phase III OPTIMA Study is expected to enroll up to 550 patients in up to 70 clinical sites in the United States, Europe, China and Asia Pacific, and will evaluate ThermoDox in combination with optimized RFA, which will be standardized to a minimum of 45 minutes across all investigators and clinical sites for treating lesions three to seven centimeters, versus optimized RFA alone. The primary endpoint for the trial is Overall Survival, which is supported by post-hoc analysis of data from the Company’s 701 patient HEAT Study, where optimized RFA has demonstrated the potential to significantly improve survival when combined with ThermoDox. The statistical plan calls for two interim efficacy analyses by an independent Data Monitoring Committee.

ThermoDox has received U.S. FDA Fast Track Designation and has been granted orphan drug designation for primary liver cancer in both the U.S. and Europe. Further, the U.S. FDA has provided ThermoDox with a 505(b)(2) registration pathway. Subject to a successful trial, the OPTIMA Study has been designed to support registration in all key primary liver cancer markets. Celsion fully expects to submit registrational applications in the USA, Europe and China. The Company believes that applications will be accepted in South Korea, Taiwan and Vietnam, three other large and important markets for ThermoDox subject to approval in Europe, China or the USA.

On October 17, 2017 Aduro Biotech, Inc. (Nasdaq:ADRO), a biopharmaceutical company with three distinct immunotherapy technologies, reported that its license partner, Janssen Biotech, Inc., presented a poster with initial data from an ongoing first-in-human Phase 1 dose finding trial to evaluate JNJ-64041757 (also known as ADU-214 ), a live, attenuated double-deleted Listeria monocytogenes (LADD)-based immunotherapy in development for the treatment of advanced or metastatic non-small cell lung cancer (Press release, Aduro Biotech, OCT 17, 2017, View Source [SID1234520976]). The data were presented at the International Association for the Study of Lung Cancer’s World Conference being held in Yokohama, Japan.

The Phase 1 first-in-human, open label dose-finding trial included nine patients with advanced stage relapsed or refractory non-small cell lung cancer. Patients were administered either 1×108 or 1×109 colony-forming units infused intravenously over one hour every 21 days. Of the nine patients treated with JNJ-64041757 monotherapy, five experienced a best response of stable disease. The maximum number of cycles administered to a single patient was 25 cycles at the time of the clinical data cut off. Additionally, biomarker data showed evidence of activation of innate immunity with transient cytokine increases in all patients as well as induction of mesothelin-specific T cell immunity in a subset of patients. The immunotherapy was generally well-tolerated with transient mild to moderate adverse events, including headache, nausea, pyrexia and vomiting.

“These are encouraging early data which we believe may support clinical activity of our listeria-based immunotherapy for lung cancer,” said Dirk Brockstedt, executive vice president of research and development at Aduro Biotech. “We look forward to Janssen initiating a combination trial of JNJ-64041757 with other agents, based on synergistic combination data from preclinical mouse tumor models.”

In October 2014, Aduro entered into its second agreement with Janssen Biotech, Inc., part of the Janssen Pharmaceutical Companies of Johnson & Johnson, granting an exclusive, worldwide license to JNJ-64041757 and other product candidates engineered for the treatment of lung cancer and certain other cancers based on its novel LADD immunotherapy platform. Under the agreement facilitated by the Johnson & Johnson Innovation center in California, Aduro received a $30 million up-front payment and has received $21 million in milestone payments upon the completion of various development activities. Aduro is eligible to receive future development, regulatory and commercialization milestone payments up to a potential total of $766 million. In addition, Aduro is eligible to receive royalties at a rate ranging from high single-digits to low teens on worldwide net sales upon successful launch and commercialization.

About LADD
LADD is Aduro’s proprietary platform of live-attenuated double-deleted Listeria monocytogenes strains that have been engineered to induce a potent innate immune response and to express tumor-associated antigens to induce tumor-specific T cell-mediated immunity.

On October 17, 2017 Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to improve the survival and quality of life of cancer patients, reported payment of a $6 million milestone to Infinity Pharmaceuticals, Inc., representing the first milestone under the duvelisib license agreement between Verastem and Infinity (Press release, Verastem, OCT 17, 2017, View Source [SID1234520973]). This milestone is based on the achievement of positive top-line results from the Phase 3 DUO study evaluating the efficacy and safety of duvelisib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

In addition, Verastem drew an additional advance of $7.5 million from its existing $25 million loan and security agreement, dated March 21 2017, with Hercules Capital, Inc. (the Term Loan Facility). The proceeds will be used to pay the $6 million milestone payment to Infinity, for ongoing research and development programs, and for general corporate purposes. Verastem has drawn a total of $10 million under the Term Loan Facility, leaving $15 million in available additional advances, subject to certain conditions of funding.

“Payment of this milestone to Infinity reflects the attainment of a critical milestone for the duvelisib development program, positive data from the Phase 3 DUO study in CLL/SLL,” said Julie B. Feder, Chief Financial Officer of Verastem. “We have elected to employ the non-dilutive option of drawing a second tranche of funding under our Term Loan Facility. We believe this approach is a prudent use of the strategic financial tools that we have at hand as we advance the program towards a potential NDA filing in H1 2018.”

In September 2017, Verastem reported that the Phase 3 DUO study met its primary endpoint with oral duvelisib monotherapy demonstrating superiority over ofatumumab for progression free survival (PFS) in patients with CLL/SLL. In this study, duvelisib achieved a statistically significant improvement in median PFS of 13.3 months, compared to 9.9 months for ofatumumab with a hazard ratio (HR) of 0.52 (p<0.0001), representing a 48% reduction in the risk of progression or death. Verastem plans to share these clinical data with the U.S. Food and Drug Administration (FDA) during Q4 2017 with the goal of filing a New Drug Application (NDA) with the FDA during the first half of 2018. The duvelisib NDA submission will also be supported by favorable results from the Phase 2 DYNAMO study in indolent non-Hodgkin’s lymphoma (iNHL), which also achieved its primary endpoint with an ORR of 46% (p<0.0001).

On October 17, 2017 AstraZeneca and MedImmune, its global biologics research and development arm, reported that the US Food and Drug Administration (FDA) has accepted a supplemental Biologics License Application (sBLA) for Imfinzi (durvalumab) for the treatment of patients with locally advanced (Stage III) unresectable non-small cell lung cancer (NSCLC) whose disease has not progressed following platinum-based chemoradiation therapy (Press release, AstraZeneca
, OCT 17, 2017, View Source [SID1234520970]). The FDA has granted Imfinzi Priority Review status.

The US FDA sBLA submission acceptance is an important milestone for Imfinzi in a disease state where patients need better treatment options and outcomes. Currently, the standard of care for patients with this earlier stage of lung disease is active monitoring following concurrent chemoradiation.

The sBLA submission is based on positive progression-free survival (PFS) data from the Phase III PACIFIC trial. The trial continues to evaluate overall survival (OS), its other primary endpoint. Detailed results of the PACIFIC trial, including additional safety information, were published online in the New England Journal of Medicine.

On 28 September 2017, the US NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) were updated to include Imfinzi for the treatment of patients with locally-advanced unresectable NSCLC with no disease progression after two or more cycles of definitive chemoradiation, based on the data from the PACIFIC Phase III trial. This indication is not yet FDA-approved.

NOTES TO EDITORS

About Locally Advanced (Stage III) NSCLC

Locally advanced (Stage III) lung cancer is commonly divided into two stages (IIIA and IIIB), which are defined by how much the cancer has spread locally and the possibility of surgery. This differentiates it from Stage IV disease, when the cancer has spread (metastasised) to distant organs.

Stage III lung cancer represents approximately one-third of NSCLC incidence and was estimated to affect around 105,000 patients in the top-7 countries in 20161. More than 70% of these patients have tumours that are unresectable. The current standard of care is chemotherapy and radiation followed by active surveillance to monitor for progression. The prognosis remains poor and long-term survival rates are low.

1. France, Germany, Italy, Japan, Spain, United Kingdom, United States

About PACIFIC

The PACIFIC trial is a randomised, double-blinded, placebo-controlled, multi-centre trial of Imfinzi as treatment in unselected patients with locally-advanced, unresectable (Stage III) NSCLC who have not progressed following platinum-based chemotherapy concurrent with radiation therapy.

The trial is being conducted in 235 centres across 26 countries involving approximately 700 patients. The primary endpoints of the trial are progression-free survival (PFS) and overall survival (OS), and secondary endpoints include landmark PFS and OS, objective response rate (ORR) and duration of response.

About Imfinzi

Imfinzi (durvalumab), a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumour’s immune-evading tactics and inducing an immune response.

Imfinzi has already received accelerated approval in the US for the treatment of patients with locally advanced or metastatic urothelial carcinoma, who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery.

As part of a broad development programme, Imfinzi is also being investigated for the adjuvant treatment of patients with NSCLC in the CCTG (Canadian Cancer Trials Group) trial ADJUVANT (BR31). In the MYSTIC, NEPTUNE, and PEARL Phase III trials, Imfinzi is being studied for 1st-line treatment as monotherapy and/or in combination with tremelimumab, an anti-CTLA-4 monoclonal antibody, for the treatment of metastatic NSCLC. The POSEIDON trial is investigating Imfinzi with and without tremelimumab in combination with chemotherapy in the same population.

About AstraZeneca in Lung Cancer

AstraZeneca is committed to developing medicines to help every patient with lung cancer. We have two approved medicines and a growing pipeline that targets genetic changes in tumour cells and boosts the power of the immune response against cancer. Our unrelenting pursuit of science aims to deliver more breakthrough therapies with the goal of extending and improving the lives of patients across all stages of disease and lines of therapy.

About AstraZeneca’s Approach to Immuno-Oncology (IO)

Immuno-Oncology (IO) is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. At AstraZeneca and MedImmune, our biologics research and development arm, our IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. We believe that IO-based therapies will offer the potential for life-changing cancer treatments for the vast majority of patients.

We are pursuing a comprehensive clinical trial programme that includes Imfinzi (anti-PD-L1) monotherapy and in combination with tremelimumab (anti-CTLA-4) in multiple tumour types, stages of disease, and lines of therapy, using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine our IO portfolio with small, targeted molecules from across our oncology pipeline, and with those of our research partners, may provide new treatment options across a broad range of tumours.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms–Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates–and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.