On September 9, 2015 Chugai Pharmaceutical Co., Ltd. [Main Office: Chuo-ku, Tokyo. Chairman & CEO: Osamu Nagayama] (Chugai) (TOKYO: 4519) and F. Hoffmann-La Roche Ltd. [Head Office: Basel, Switzerland. CEO: Severin Schwan] (Roche) reported that Genentech, Inc. [Head Office: California, U.S., CEO: Ian T. Clark], a member of the Roche Group, has filed a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) and the FDA has accepted the NDA, for ALK (Anaplastic Lymphoma Kinase) inhibitor "alectinib hydrochloride" (alectinib) for the treatment of patient with ALK positive advanced non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib in September (Press release, Chugai, SEP 8, 2015, View Source [SID:1234507419]).

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Alectinib was granted Breakthrough Therapy Designation by FDA in June 2013 for patients with ALK positive NSCLC who have progressed on crizotinib.

Alectinib is a highly selective, CNS-active ALK inhibitor created by Chugai. Alectinib matches with the Personalized Healthcare Strategy promoted by Chugai and Roche. It has been reported that 2 to 5 percent of patients with NSCLC express a chromosomal rearrangement which leads to fusion of the ALK gene with another gene1. ALK kinase signaling is constantly active in cells with such fusion genes, resulting in uncontrolled growth of tumor cells and transforming the cells into tumor cells2, 3. Alectinib exerts its anti-tumor effect by selectively inhibiting ALK kinase activity to inhibit tumor cell proliferation and induce cell death4. In addition, alectinib is not recognized by the transporter proteins in the blood brain barrier that actively pump molecules out of the brain.

Alectinib is active in the central nervous system and has proven activity against brain metastases.

In Japan, alectinib [brand name; Alecensa capsule 20mg and 40mg] was become available to patients with "ALK fusion gene positive unresectable, recurrent/advanced NSCLC" in September 2014 and is marketed by Chugai. The rights for Alecensa in overseas countries including Europe and the US were out-licensed to Roche, and clinical trials of Alecensa (Roche Development Code: RG7853) for patients with NSCLC who have ALK mutation are currently ongoing in the US, Europe and other countries.

Two pivotal clinical phase I/II trials formed the basis for the new drug application.

NP28673 study
NP28673 is a phase I/II global, single arm, open-label, multicentre trial evaluating the safety and efficacy of alectinib in 138 people with ALK positive NSCLC whose disease progressed on crizotinib.

The study showed by assessment of an independent review committee an ORR in 50.0% of people treated with alectinib, as measured by RECIST criteria.

An investigator assessment also showed tumours shrank in 47.8% of people who received alectinib.

CNS tumours shrank in response to alectinib in 57.1% of people whose disease had spread to the brain or other parts of the CNS.
In addition, the people whose tumours shrank in response to alectinib continued to respond for a median of 11.2 months (Duration of Response (DOR), immature data).

The median progression-free survival (PFS) for people who received alectinib was 8.9 months.

Alectinib demonstrated a safety profile consistent with that observed in previous studies.

The most common (occurring in at least 2% of people) Grade 3 or higher adverse event was shortness of breath (dyspnoea; 4%).
NP28761 study
NP28761 is a phase I/II North American, single arm, open-label, multicentre trial evaluating the safety and efficacy of alectinib in 87 people with ALK positive NSCLC whose disease progressed on crizotinib.

The study showed by assessment of an independent review committee an ORR in 47.8% of people treated with alectinib, as measured by RECIST criteria.

An investigator assessment showed tumours shrank in 46.0% of people who received alectinib.

CNS tumours shrank in response to alectinib in 68.8% of people whose disease had spread to the brain or other parts of the CNS.
In addition, the people whose tumours shrank in response to alectinib continued to respond for a median of 7.5 months (DOR, immature data).

The immature median PFS was 6.3 months.
Alectinib demonstrated a safety profile consistent with that observed in previous studies.
The most common (occurring in at least 2% of people) Grade 3 or higher adverse events were an increase in muscle enzymes (increased blood levels of creatine phosphokinase; 8%), increased liver enzymes (alanine aminotransferase; 6%, and aspartate aminotransferase; 5%) and shortness of breath (dysponea; 3%).

On September 8, 2015 Cellectis S.A. (Alternext: ALCLS; Nasdaq: CLLS), a biopharmaceutical company focused on developing immunotherapies based on gene edited CAR-T cells (UCART), reported its results for the three- and six-month periods ended June 30, 2015 (Filing, 6-K, Cellectis, SEP 8, 2015, View Source [SID:1234507418]).

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Recent Corporate Highlights

Completed U.S. IPO in March 2015 raising more than $228 million of proceeds.

Opened U.S. research facility at the Alexandria Center in New York City, with more than 12,000 sq. ft. of state-of-the-art laboratories and 15 full time staff, in proximity to Cellectis’s U.S. partners and investors.

Entered into a strategic collaboration with Weill Cornell Medical College to accelerate the development of targeted immunotherapy for patients with acute myeloid leukemia (AML). This alliance will foster the development of our lead product candidate, UCART123, for treatment of AML.

Achieved a significant milestone under our collaboration agreement with Servier.

Entered into a broad preclinical and clinical strategic alliance with MD Anderson Cancer Center to pursue the development of Cellectis’ candidate products UCARTCS1, UCART22, UCART38 in T-cell ALL and UCART123 in a rare non curable disease BPDCN.

Development Update

Ongoing manufacturing of GMP-compatible CAR T-cell batches in line.

Presented additional study results on gene-edited allogeneic ("off-the-shelf") CAR T-cells, strengthening the pre-clinical proof of concept in lead development programs. In particular, Cellectis presented the following results at ASCO (Free ASCO Whitepaper) and ASGCT (Free ASGCT Whitepaper):
"UCART19, an allogeneic "off-the-shelf" adoptive T-cell immunotherapy against CD19+ B-cell leukemias"
"Adoptive immunotherapy of acute myeloid leukemia (AML) with allogeneic CAR T-cells targeting CD123"
"A multidrug resistant engineered CAR T-cell for allogeneic combination immunotherapy"
Publication of a study in Molecular Therapy, a Nature Publishing Group journal, describing the development of the next generation of engineered CAR T-cells compatible with allogeneic adoptive transfer immunotherapy.

Publication of an article in Cancer Research describing the applicability of TALEN-mediated genome editing to a scalable process, enabling the manufacturing of non-alloreactive T-cells from third-party donors in a robust, scalable process, thus allowing "off-the-shelf" CAR T-cell immunotherapies.

Our plant sciences subsidiary, which changed its name to Calyxt, Inc., continues to show promising developments and commenced field trials of cold storable potatoes in the United States of America and high oleic/low transfat soybean varieties in Argentina and the United States of America.

Financial Results

Since Cellectis did not have consolidated financial statements for individual quarters during fiscal year 2014, no comparative quarterly 2014 figures will be presented during 2015. Cellectis will publish quarter-over-quarter comparative figures starting with the first quarter of 2016.

Cellectis’s consolidated financial statements have been prepared in accordance with International Financial Reporting Standards, or IFRS, as issued by the International Accounting Standards Board ("GAAP").

Second Quarter 2015 Financial Results

Cash Position: As of June 30, 2015 Cellectis had €283.9 million in cash and cash equivalents compared to €112.3 million as of December 31, 2014. This increase is primarily attributable to the $228 million of proceeds from the U.S. initial public offering in March 2015.

Revenues and Other Income: Total revenues and other income were €8.0 million for the second quarter 2015 and primarily comprised €6.6 million of collaboration revenues and €0.9 million of license revenues.

Total Operating Expenses and Other Operating Income: Total operating expenses for the second quarter of 2015 were €20.1 million, which includes non-cash stock-based compensation expenses of €7.2 million.

R&D Expenses: Research and development expenses for the second quarter of 2015 were €10.6 million, including personnel expenses of €7.6 million and external purchases and other expenses of €3.0 million. Research and development expenses for the second quarter notably reflected the impacts of (i) non-cash stock-based compensation expense of €3.3 million and (ii) social charges related to free shares granted during the second quarter of €1.8 million.

SG&A Expenses: Selling, general and administrative expenses were €9.1 million for the second quarter of 2015, and included personnel expenses of €6.3 million and external purchases and other expenses of €2.8 million. SG&A expenses for the second quarter notably reflected the impacts of (i) non-cash stock-based compensation expense of €3.8 million and (ii) social charges related to free shares granted during the second quarter of €1.8 million.

Financial Loss: Financial loss was €10.0 million for the second quarter of 2015, which is primarily attributable to an unfavorable Euro-Dollar exchange rate applied to U.S. dollar-denominated cash and cash equivalents during the quarter.

Net Loss Attributable to Shareholders of Cellectis: Net loss attributable to shareholders of Cellectis was €22.2 million, or €0.63 per share, for the second quarter of 2015. The decrease of €28.3 million in net earnings, compared to the first quarter 2015 net gain attributable to shareholders of Cellectis of €6.1 million, notably reflects the effects of unfavorable Euro-Dollar exchange rates with respect to our U.S. Dollar cash and cash equivalent accounts and to a lesser extent the impact of non-cash stock-based compensations during the second quarter of 2015. Adjusted net loss attributable to shareholders of Cellectis for the second quarter of 2015, which excludes a non-cash stock-based compensation expense of €7.1 million, was €15.0 million, or €0.43 per share. Please see "Note Regarding Use of Non-GAAP Financial Measures" for a reconciliation of GAAP net income to adjusted net income.

First Half Year 2015 Financial Results

Revenues and Other Income: During the six months ended June 30, 2015 and 2014, Cellectis recorded €17.2 million and €10.3 million, respectively, in revenues and other income. The increase of €7.1 million primarily reflects an increase of €13.2 million in revenues under our collaboration agreements with Servier and Pfizer which were partially offset by a decrease in license, R&D services and Product and Services revenues.

Total Operating Expenses and Other Operating Income: Total operating expenses and other operating income for the first half of 2015 was €32.9 million (€15.3 million for the same period in 2014). Total operating expenses and other operating income for first half of 2015 and 2014 include non-cash stock-based compensation expenses of €8.0 million and €0.4 million, respectively.

R&D Expenses: Cellectis recorded research and development expenses of €16.2 million in the first half of 2015 and €7.7 million in the first half of 2014. These amounts include personnel expenses of €11.1 million and €3.1 million in 2015 and in 2014, respectively, and purchases and external expenses and other expenses of €5.1 million and €4.6 million, respectively. The increase in research and development expenses also reflects expenditures for the development of UCART programs toward their entry into Phase 1 clinical trials, expenses related to the opening of our facility in New York, non-cash stock-based compensation expense of €3.8 million and social charges on stock options and free share grants of €4.1 million in 2015.

SG&A Expenses: SG&A expenses were €16.3 million in the first half year of 2015 compared to €6.2 million in the corresponding period of 2014. SG&A expenses included personnel expenses of €11.2 million in 2015 compared to €3.0 million in 2014, and purchases and external expenses and other expenses of €5.1 million in 2015 compared to €3.2 million in 2014. The increase in SG&A expenses in 2015 was attributable, among other things, to €4.3 million of non-cash stock-based compensation expense, €4.6 million of social charges on stock options and free share grants and an increase in professional costs, in each case in connection with our U.S. IPO in March 2015.

Financial result: Financial loss was €0.2 million for the first half year of 2015 compared to €16,000 financial gain for the corresponding period in 2014. This increase was primarily attributable to an unfavorable Euro-Dollar exchange rate applied to U.S. dollar-denominated cash and cash equivalents during 2015.

Net Loss Attributable to Shareholders of Cellectis: Net loss attributable to shareholders of Cellectis was of €16.0 million, or €0.48 per share, for the first half year of 2015 compared to a net loss attributable to shareholders of Cellectis of €7.4 million, or €0.32 per share, for the corresponding period in 2014. Adjusted net loss attributable to shareholders of Cellectis for the first half year of 2015 was €8.2 million, or €0.25 per share, compared to adjusted net loss attributable to shareholders of Cellectis of €7.1 million, or €0.31 per share, for the corresponding period in 2014. Adjusted net loss attributable to shareholders of Cellectis for the first half year of 2015 and 2014 excludes a non-cash stock-based compensation expense of €7.9 million and €0.3 million, respectively. Please see "Note Regarding Use of Non-GAAP Financial Measures" for a reconciliation of GAAP net income to adjusted net income.

On September 8, 2015 Synta Pharmaceuticals Corp. (NASDAQ: SNTA) reported that presentations related to ganetespib, a novel, potent small molecule inhibitor of heat shock protein 90 (Hsp90) in Phase 3 development, and STA-12-8666, the Company’s leading candidate from its proprietary Hsp90 inhibitor Drug Conjugate (HDC) Program, will be presented at the 16th Annual World Conference on Lung Cancer at the Colorado Convention Center in Denver, Colorado (Press release, Synta Pharmaceuticals, SEP 8, 2015, View Source;p=RssLanding&cat=news&id=2085888 [SID:1234507416]).

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Details of the presentations are provided below:

Mini Oral Presentations:

HSP90 Inhibitor Ganetespib Radiosensitizes Human Lung Adenocarcinoma Cells and Inhibits Lung Cancer Stem Cells

Date and Time: Tuesday, September 8, 10:45 AM – 12:15 PM MT
Location: Mile High Ballroom 2c – 3c, MINI14.08
Presenter: Vera Levina, Ph.D., University of Pittsburgh

The Novel HSP90 Inhibitor-SN-38 Conjugate (STA-12-8666), Is Highly Active in Preclinical Models of Small Cell Lung Cancer (SCLC)

Date and Time: Wednesday, September 9, 6:30 -8:00 PM MT
Location: Rooms 605+607, MINI37.02
Presenter: Yanis Boumber, M.D., Ph.D., University of New Mexico

Poster Presentations:

Ganetespib Resistance in KRAS Mutant NSCLC Is Mediated through Reactivation of the RAF/MEK/ERK and PI3K/MTOR Pathways

Date and Time: Tuesday, September 8, 9:30AM – 5:00 PM MT
Location: Exhibit Hall (Hall B+C), Poster P2.04-101
Presenter: Timothy F. Burns, M.D., University of Pittsburgh

A Phase Ib/II Trial of Doxorubicin with Ganetespib, a Novel Hsp90 Inhibitor, in Advanced Solid Tumors, with Dose Expansion in Small Cell Lung Cancer

Date and Time: Wednesday, September 9, 9:30 AM – 5:00 PM MT
Location: Exhibit Hall (Hall B+C), Poster P3.07-003
Presenter: Deepa Subramaniam, M.D., Georgetown University

On September 8, 2015 Celsion Corporation (NASDAQ: CLSN), an oncology drug development company, reported highlights from presentations by three leading experts in the treatment of intermediate primary liver cancer, also known as hepatocellular carcinoma (HCC) and Celsion’s pivotal Phase III OPTIMA Study of ThermoDox, the Company’s proprietary heat-activated liposomal encapsulation of doxorubicin, in combination with optimized radiofrequency ablation (RFA) (Press release, Celsion, SEP 8, 2015, View Source [SID:1234507414]). The symposium, entitled "Intermediate HCC: Cure vs. Palliation," was held on September 5, 2015 at the International Liver Cancer Association (ILCA) 9th Annual Conference in Paris, France and was moderated by Professor Riccardo Lencioni, MD, FSIR, EBIR, Executive Committee member of the ILCA Governing Board.

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The three presentations included:

"Current Management of Intermediate HCC: Unmet Medical Needs," by Ronnie T.P. Poon, MD, MBBS, MS, PhD, FRCS (Edin), FACS, Medical Director at the Hong Kong Integrated Oncology Center, Honorary Professor of Surgery at the University of Hong Kong Queen Mary Hospital, and member of the ILCA Governing Board. Dr. Poon discussed strategies for treating different stages of HCC including intermediate stage HCC which has been previously thought to be incurable. New treatment strategies, most notably an optimized RFA procedure with the investigational drug, ThermoDox, show clear promise as a potential cure for intermediate HCC in the years ahead.

"Intermediate HCC Treatment Paradigms and Lessons Learned," by Ghassan K. Abou-Alfa, MD, Professor at Memorial Sloan Kettering Cancer Center. Dr. Abou-Alfa reviewed results from recent clinical studies in intermediate stage primary liver cancer patients, including recent data from Celsion’s latest HEAT Study post-hoc analysis which suggests an overall survival benefit of more than two years in the large subgroup of patients treated with ThermoDox plus optimized RFA (RFA ≥ 45 minutes).

"OPTIMA Phase III Clinical Trial: Study Design and Protocols," by Riccardo Lencioni, MD, FSIR, EBIR, Professor and Director of Diagnostic Imaging and Intervention at Pisa University School of Medicine in Pisa, Italy, Lead European Principal Investigator for Celsion’s HEAT Study and member of the ILCA Governing Board. Dr. Lencioni reviewed the latest findings from the HEAT Study post-hoc analysis, which strongly supports the rationale for a minimum 45 minute ablation time when using ThermoDox and suggests that there could be an important curative role for optimized RFA and ThermoDox in intermediate HCC. Celsion is currently evaluating ThermoDox plus optimized RFA in its ongoing Phase III OPTIMA Study, currently enrolling patients in over 75 clinical sites globally.

"Results from the HEAT Study, one of the largest clinical trials ever conducted in primary liver cancer, reinforce the potential for ThermoDox in combination with an optimized RFA regimen as a curative treatment for this deadly cancer," said Professor Lencioni. "With median overall survival of more than 6.5 years, or 79 months, data from the HEAT Study post-hoc analysis suggest a greater than two year median survival advantage for treatment with ThermoDox plus optimized RFA, a meaningful finding given that few treatments are effective in prolonging survival in HCC."

As of July 15, 2015, data from the latest HEAT Study post-hoc overall survival analysis demonstrated that in a large, well bounded subgroup of patients (n=285, 41% of the HEAT Study patients), treatment with a combination of ThermoDox and optimized RFA provided an average 58% improvement in overall survival compared to optimized RFA alone. The Hazard Ratio (HR) at this analysis was 0.63 (95% CI 0.43 – 0.93) with a p-value of 0.0198. Median overall survival for the ThermoDox group has been reached, which translates into a 2.1 year survival benefit over the optimized RFA group (79 months for the ThermoDox plus optimized RFA group versus 53.6 months for the optimized RFA only group).

The presentations are available on Celsion’s website at View Source

About The International Liver Cancer Association

The International Liver Cancer Association (ILCA) is the only international organization devoted exclusively to liver cancer research for experts from all related disciplines – medical, interventional and surgical oncology as well as hepatology. ILCA aspires to advance research in the pathogenesis, prevention and treatment of liver cancer.

About Celsion’s Phase III OPTIMA Study

Celsion’s Phase III OPTIMA Study is a global pivotal, double-blind, placebo-controlled study evaluating ThermoDox, its proprietary heat-activated liposomal encapsulation of doxorubicin, in combination with optimized radiofrequency ablation (RFA) in HCC. The study is expected to enroll up to 550 patients in over 75 clinical sites in the North America, 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 standardized 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 for the OPTIMA Study calls for two interim efficacy analyses by an independent Data Monitoring Committee (iDMC).

On September 08, 2015 ArQule, Inc. (Nasdaq:ARQL) reported that additional analyses of plasma biomarkers support the prognostic and predictive role of MET status in this previously reported phase 2 trial in hepatocellular carcinoma (HCC) (Press release, ArQule, SEP 8, 2015, View Source [SID:1234507413]). The data was presented at the International Liver Cancer Association (ILCA) 9th Annual Conference on September 6th, 2015.

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The phase 2 study, completed in the third quarter of 2011 and published in The Lancet Oncology medical journal in November 2012, enrolled 107 HCC patients who progressed or were intolerant to one prior systemic therapy. Multiple biomarkers were evaluated as part of the study, and MET status as determined by immunohistochemistry emerged as the strongest predictor of tivantinib benefit. In addition, the presentation noted that biopsies were more likely to be categorized as MET-high when taken after sorafenib therapy than before therapy. The presentation can be accessed in the "Investor and Media" section of our website, www.arqule.com, under "Recent Data Presentations."

"The biomarker data from this trial demonstrates that patients with MET-high tumors are more likely to benefit from tivantinib therapy," said Dr. Brian Schwartz, head of research and development at ArQule. "On the basis of the results from the phase 2 trial and in partnership with Daiichi Sankyo, we are conducting the pivotal phase 3 METIV-HCC trial that is enrolling MET-high HCC patients as determined by a required companion diagnostic test."

By the end of 2015 the pivotal phase 3 trial, METIV-HCC, is expected to complete enrollment of approximately 300 patients, randomized 2:1 treatment to best supportive care, with the primary end-point of overall survival.

About hepatocellular carcinoma (HCC)

Globally, liver cancer is the sixth most common cancer according to the World Cancer Research Fund International (782,000 new cases in 2012) and is the second cause of cancer related death (746,000 deaths in 2012). HCC accounts for about 90 percent of primary liver cancers. Cirrhosis, chronic hepatitis B and C and smoking are recognized worldwide as factors increasing the risk of HCC.

About MET and tivantinib (ARQ 197)

Tivantinib is an orally administered, selective inhibitor of MET, a receptor tyrosine kinase, which is currently in Phase 2 and Phase 3 clinical trials. In healthy adult cells, MET can be present in normal levels to support natural cellular function, but in cancer cells, MET can be inappropriately and continuously activated. When abnormally activated, MET plays multiple roles in aspects of human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis. The activation of certain cell signaling pathways, including MET, has also been associated with the development of resistance to anti-EGFR (epidermal growth factor receptor) antibodies such as cetuximab and panitumumab.

Pre-clinical data have demonstrated that tivantinib inhibits MET activation in a range of human tumor cell lines and shows anti-tumor activity against several human tumor xenografts. In clinical trials to date, treatment with tivantinib has been generally well tolerated and has shown clinical activity in the tumors studied. Tivantinib has not yet been approved for any indication in any country.

In December 2008, ArQule and Daiichi Sankyo signed a license, co-development and co-commercialization agreement for tivantinib in the U.S., Europe, South America and the rest of the world, excluding Japan, China (including Hong Kong), South Korea and Taiwan.