On November 22, 2016 Cellectis S.A. (Paris:ALCLS) (NASDAQ:CLLS) (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-month period ended September 30, 2016 and for the nine-month period ended September 30, 2016 (Filing, Q3, Cellectis, 2016, NOV 22, 2016, View Source [SID1234516771]).

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Recent Corporate Highlights

UCART19 in collaboration with Servier / Pfizer

On June 20, 2016, Cellectis announced that the first patient in Servier’s UCART19 Phase 1 clinical trial had been dosed. The UCART19 Phase 1 clinical trial in ALL and CLL patients is conducted at two clinical sites in the UK – at the Great Ormond Street Hospital (GOSH), part of UCL, for the pediatric arm of the trial, and at Kings College London for the adult arm of the study.
Interim data from the UCART19 Phase 1 clinical trial is expected to be announced at a scientific meeting in H1 2017.
UCART123

On November 15, 2016, Cellectis announced the successful completion of large scale production runs of UCART123, according to cGMP standards. Cellectis is planning to file an IND for a Phase 1 clinical trial in AML and BPDCN patients by YE 2016 in collaboration with the Weill Cornell Medical College and the MD Anderson Cancer Center.
Weill Cornell will present pre-clinical data on UCART123 in an oral presentation at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. The meeting will be held from December 3 to 6, 2016 in San Diego.
Pfizer Partnership

Cellectis and Pfizer are making advances in their partnered programs. Notably, Pfizer will present on the "Preclinical Evaluation of Allogeneic Anti-BCMA Chimeric Antigen Receptor T Cells with Safety Switch Domains and Lymphodepletion Resistance for the Treatment of Multiple Myeloma" in an oral presentation at ASH (Free ASH Whitepaper) in December 2016.
IP / Patent Portfolio

Issuance of U.S. patent 9,458,439 – which claims gene inactivation by use of chimeric restriction endonucleases. This patent, granted by the USPTO to the Institut Pasteur and Boston Children’s Hospital, naming Dr. André Choulika and Pr. Richard C. Mulligan as co-inventors, is exclusively licensed to Cellectis.
Award

Cellectis won EuropaBio’s 2016 Most Innovative European Biotech SME Award for the healthcare category. The Awards program is a unique annual initiative that recognizes innovative biotech small- and medium-sized enterprises (SMEs) in Europe and the crucial role that they play in answering some of society’s greatest challenges through biotechnology.
Conferences

Cellectis will participate in the upcoming Oppenheimer Life Sciences Summit being held in NYC on November 29, 2016 and will be presenting at the Piper Jaffray 28th Annual Health Care Conference on November 30, 2016 in NYC.
Calyxt – Cellectis’ plant science subsidiary

Calyxt expanded its patent portfolio with U.S. patent 9,458,439, which encompasses broad uses of technologies such as CRISPR/Cas9, Zinc Finger Nucleases and TAL-effector Nucleases for plant gene editing.
On October 20, 2016 Cellectis hosted, along with its agricultural biotech subsidiary Calyxt, the world’s first dinner made with gene edited foods in New York.
Calyxt has completed the 2016 expansion of its high-oleic/no trans-fat soybean variety (CAL1501) in the U.S. with a production of 1,200 tons of beans. In Spring 2016, Calyxt planted 942 acres (381 hectares) in six U.S. states – Illinois, Iowa, Michigan, Minnesota, South Dakota and Wisconsin. To date, the Company has harvested approximately 45,000 bushels with the intent to use a substantial portion of the harvest for its first industrial scale crush.
Financial Results

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

Third Quarter 2016 Financial Results

Cash: As of September 30, 2016, Cellectis had €264.0 million in total cash, cash equivalents and current financial assets compared to €269.7 million as of June 30, 2016. This decrease of €5.7 million notably reflects (i) the net cash flows used in operating activities of €1.7 million, which includes €9.2 million of cash receipts in the third quarter of 2016 in connection with the achievement of two milestones under our collaboration agreement with Servier that occurred during the second quarter of 2016, and (ii) capital expenditures of €2.2 million. The change was also attributable to the unrealized negative translation effect of exchange rate fluctuations on our U.S. dollar cash, cash equivalents and current financial assets of €1.6 million.

Revenues and Other Income: During the quarters ended September 30, 2015 and 2016, we recorded €10.0 million and €11.3 million, respectively, in revenues and other income. This is mainly due to (i) the increase of €2.5 million in collaboration revenues, notably due to the agreement to provide Servier with raw materials and batches of UCART19 products, partly offset by (ii) the decrease of €0.3 million in research tax credit and €0.8 million in subsidies.

Total Operating Expenses and Other Operating Income: Total operating expenses and other operating income for the third quarter of 2016 were €22.9 million, compared to €23.4 million for the third quarter of 2015. The non-cash stock-based compensation expenses included in these amounts were €12.1 million and €9.5 million, respectively.

R&D Expenses: For the quarters ended 2015 and 2016, research and development expenses decreased by €2.3 million from €16.2 million in 2015 to €13.8 million in 2016. Personnel expenses decreased by €1.1 million from €10.3 million in 2015 to €9.2 million in 2016, notably due to a €2.5 million decrease in social charges on stock options and free share grants, partly offset by a €0.4 million increase in wages and salaries, and a €0.9 million increase in non-cash stock based compensation expense. Purchases and external expenses and other expenses decreased by €1.2 million from €5.8 million in 2015 to €4.6 million in 2016.

SG&A Expenses: During the quarters ended 2015 and 2016, we recorded €6.9 million and €8.7 million, respectively, of selling, general and administrative expenses. The increase of €1.8 million primarily reflects (i) an increase of €0.9 million in personnel expenses from €5.7 million to €6.7 million, attributable, among other things, to an increase of €1.7 million of non-cash stock-based compensation expense, partly offset by a decrease of €1.0 million of social charges on stock options and free share grants, and (ii) an increase of €0.9 million in purchases and external expenses and other charges.

Financial Gain (Loss): The financial gain was €0.7 million for the third quarter of 2015 compared with a financial loss of €1.0 million for the third quarter of 2016. The change in financial result was primarily attributable to the effect of exchange rate fluctuations on our U.S. dollar cash and cash equivalent accounts.

Net Income (Loss) Attributable to Shareholders of Cellectis: During the three months ended September 30, 2015 and 2016, we recorded a net loss of €12.8 million (or €0.36 per share on both a basic and a diluted basis) and net loss of €12.6 million (or €0.36 per share on both a basic and a diluted basis), respectively. Adjusted loss attributable to shareholders of Cellectis for the third quarter of 2016 was €0.5 million (€0.01 per share on both a basic and a diluted basis) compared to adjusted loss attributable to shareholders of Cellectis of €3.3 million (€0.09 per share on both a basic and a diluted basis), for the third quarter of 2015. Adjusted loss attributable to shareholders of Cellectis for the third quarter of 2016 and 2015 excludes non-cash stock-based compensation expense of €12.1 million and €9.5 million, respectively. Please see "Note Regarding Use of Non-GAAP Financial Measures" for reconciliation of GAAP net income (loss) attributable to shareholders of Cellectis to Adjusted income (loss) attributable to shareholders of Cellectis.

First Nine Months 2016 Financial Results

Cash: As of September 30, 2016, Cellectis had €264.0 million in total cash, cash equivalents and current financial assets compared to € 314.2 million as of December 31, 2015. This decrease of €50.3 million was primarily driven by (i) €30.8 million of cash used in operating activities, notably in connection with the initiation of industrial Good Manufacturing Practice ("GMP") production of UCART123, increased expenses in materials required of GMP production of UCART 123 and other targets, a payment of €7.2 million of value added taxes related to proceeds received in the fourth quarter of 2015 from Servier, partly offset by cash receipts of €9.2 million in connection with the achievement of two milestones under our collaboration agreement with Servier that occurred during the second quarter of 2016 and (ii) €11.3 million of cash used in investment activities, primarily through Calyxt’s land acquisition and greenhouse construction in an aggregate amount of €8.9 million. The decrease was also partially attributable to the negative unrealized translation effect of exchange rate fluctuations on our U.S. dollar cash, cash equivalents and current financial assets accounts of €7.4 million.

Cellectis expects that its cash, cash equivalents and Current financial assets of €264.0 million as of September 30, 2016 will be sufficient to fund its current operations through the end of 2018.

Revenues and Other Income: During the nine-month periods ended September 30, 2015 and 2016, we recorded €27.2 million and €38.9 million, respectively, in revenues and other income. This is mainly due to the increase of (i) €9.6 million in collaboration revenues mainly due to both the agreement to provide Servier with raw materials and additional batches of UCART19 products and the achievement of two milestones (totaling €11.7 million) under our collaboration agreement with Servier and (ii) €3.1 million in research tax credit, partly offset by a decrease of €0.9 million in research subsidies, resulting from the termination of research programs.

Total Operating Expenses and Other Operating Income: Total operating expenses and other operating income for the nine-month period ended September 30, 2016 were €80.9 million, compared to €56.3 million for the nine months ended September 30, 2015. The non-cash stock-based compensation expenses included in these amounts were €39.9 million and €17.5 million, respectively.

R&D Expenses: For the nine months ended September 30, 2015 and 2016, research and development expenses increased by €15.8 million from €36.4 million in 2015 to €52.2 million in 2016. Personnel expenses increased by €8.4 million from €24.3 million in 2015 to €32.7 million in 2016, notably due to a €1.9 million increase in wages and salaries, and a €12.6 million increase in non-cash stock based compensation expense, partly offset by a €6.1 million decrease in social charges on stock options and free share grants. Purchases and external expenses increased by €7.6 million from €11.0 million in 2015 to €18.6 million in 2016, due to increased expenses related to innovation and platform development, including payments to third parties participating in product development, purchases of biological raw materials and expenses associated with the use of laboratories and other facilities.

SG&A Expenses: During the nine months ended September 30, 2015 and 2016, we recorded €19.1 million and €27.8 million, respectively, of selling, general and administrative expenses. The increase of €8.7 million primarily reflects (i) an increase of €7.4 million in personnel expenses from €14.0 million to €21.4 million, attributable, among other things, to a €0.5 million increase in wages and salaries, and an increase of €9.9 million of non-cash stock-based compensation expense, partly offset by a decrease of €3.0 million of social charges on stock options and free share grants, and (ii) an increase of €1.0 million in purchases and external expenses.

Financial Gain (Loss): The financial gain was €0.5 million for the nine months ended September 30, 2015 compared with financial loss of €6.3 million for the nine months ended September 30, 2016. The change in financial result was primarily attributable to the effect of exchange rate fluctuations on our U.S. dollar cash and cash equivalent accounts.

Net Income (Loss) Attributable to Shareholders of Cellectis: During the nine months ended September 30, 2015 and 2016, we recorded a net loss of €28.8 million (or € 0.85 per share on both a basic and a diluted basis) and a net loss of €48.3 million (or €1.37 per share on both a basic and diluted basis), respectively. Adjusted loss attributable to shareholders of Cellectis for the nine months ended September 30, 2016 was €8.4 million (€0.24 per share on both a basic and a diluted basis) compared to adjusted loss attributable to shareholders of Cellectis of € 11.3 million (€0.33 per share on both a basic and a diluted basis), for the nine months ended September 30, 2015. Adjusted loss attributable to shareholders of Cellectis for the nine months ended September 30, 2016 and 2015 excludes a non-cash stock-based compensation expense of €39.9 million and €17.5 million, respectively. Please see "Note Regarding Use of Non-GAAP Financial Measures" for a reconciliation of GAAP net income (loss) attributable to shareholders of Cellectis to Adjusted income (loss) attributable to shareholders of Cellectis.

CELLECTIS S.A.
STATEMENT OF CONSOLIDATED FINANCIAL POSITION
(unaudited)
(€ in thousands, except per share data)

As of
December 31, 2015 September 30, 2016

ASSETS
Non-current assets
Intangible assets 956 1 180
Property, plant, and equipment 5 043 15 141
Other non-current financial assets 845 612
Total non-current assets 6 844 16 933

Current assets
Inventories and accumulated costs on orders in process 158 106
Trade receivables 6 035 11 382
Subsidies receivables 9 102 14 535
Other current assets 4 685 7 252
Cash and cash equivalent and Current financial assets 314 238 263 968
Total current assets 334 218 297 243
TOTAL ASSETS 341 062 314 177

LIABILITIES
Shareholders’ equity
Share capital 1 759 1 767
Premiums related to the share capital 420 682 460 474
Treasury share reserve (184) (373)
Currency translation adjustment (1 631) (1 933)
Retained earnings (137 188) (158 032)
Net income (loss) (20 544) (48 309)
Total shareholders’ equity – Group Share 262 894 253 595
Non-controlling interests 725 1 471
Total shareholders’ equity 263 619 255 066

Non-current liabilities
Non-current financial liabilities 66 37
Non-current provisions 437 581
Total non-current liabilities 503 619

Current liabilities
Current financial liabilities 1 921 1 922
Trade payables 6 611 9 176
Deferred revenues and deferred income 54 758 41 893
Current provisions 953 467
Other current liabilities 12 697 5 034
Total current liabilities 76 940 58 492
TOTAL LIABILITIES AND SHAREHOLDERS’ EQUITY 341 062 314 177

CELLECTIS S.A.
STATEMENT OF CONSOLIDATED OPERATIONS – Third quarter
(unaudited)
(€ in thousands, except per share data)

For the three-month period
ended September 30,
2015 2016

Revenues and other income
Revenues 7 600 10 091
Other income 2 379 1 215
Total revenues and other income 9 978 11 306

Operating expenses and other operating income (expenses)
Royalty expenses (334) (311)
Research and development expenses (1) (16 156) (13 824)
Selling, general and administrative expenses (1) (6 921) (8 712)
Other operating income 0 (6)
Redundancy plan 24 3
Other operating expenses (37) (10)
Total operating expenses and other operating income (expenses) (23 425) (22 860)

Operating income (loss) (13 447) (11 555)

Financial gain (loss) 680 (1 035)

Income (loss) from continuing operations (12 766) (12 590)
Net income (loss) (12 766) (12 590)
Attributable to shareholders of Cellectis (12 766) (12 590)
Attributable to non-controlling interests
–

-

Basic earnings attributable to shareholders of Cellectis per share (€/share) (0.36) (0.36)

Diluted earnings attributable to shareholders of Cellectis per share (€/share) (0.36) (0.36)

___________________

(1) Cellectis reclassified certain expenses related to the year ended December 31, 2015 from SG&A expenses to R&D expenses in the fourth quarter of 2015. This reclassification is effective starting in 2015, and is due to the increased level of efforts towards our R&D activities in order to develop product candidates and work toward clinical phases. Starting in 2015, we classify personnel and other costs related to information technology, human resources, business development, legal, intellectual property and general management in Research and development expense based on the time that employees spent contributing to research and development activities versus general and administrative activities. We approved the reclassification in Q4 2015 and assess the performance of the consolidated company based on this new classification.

CELLECTIS S.A.
STATEMENT OF CONSOLIDATED OPERATIONS – First Nine Months
(unaudited)
(€ in thousands, except per share data)

For the nine-month period
ended September 30,
2015 2016

Revenues and other income
Revenues 23 356 32 892
Other income 3 845 6 053
Total revenues and other income 27 201 38 945

Operating expenses and other operating income (expenses)
Royalty expenses (1 153) (1 035)
Research and development expenses (1) (36 375) (52 220)
Selling, general and administrative expenses (1) (19 145) (27 839)
Other operating income 515 380
Redundancy plan 259 3
Other operating expenses (432) (216)
Total operating expenses and other operating income (expenses) (56 331) (80 926)

Operating income (loss) (29 130) (41 981)

Financial gain (loss) 515 (6 328)

Income (loss) from continuing operations (28 615) (48 309)
Net income (loss) (28 615) (48 309)
Attributable to shareholders of Cellectis (28 786) (48 309)
Attributable to non-controlling interests 171 -

Basic earnings attributable to shareholders of Cellectis per share (€/share) (0.85) (1.37)

Diluted earnings attributable to shareholders of Cellectis per share (€/share) (0.85) (1.37)

___________________

(1) Cellectis reclassified certain expenses related to the year ended December 31, 2015 from SG&A expenses to R&D expenses in the fourth quarter of 2015. This reclassification is effective starting in 2015, and is due to the increased level of efforts towards our R&D activities in order to develop product candidates and work toward clinical phases. Starting in 2015, we classify personnel and other costs related to information technology, human resources, business development, legal, intellectual property and general management in Research and development expense based on the time that employees spent contributing to research and development activities versus general and administrative activities. We approved the reclassification in Q4 2015 and assess the performance of the consolidated company based on this new classification.

Note Regarding Use of Non-GAAP Financial Measures

Cellectis S.A. presents Adjusted Income (Loss) attributable to shareholders of Cellectis in this press release. Adjusted Income (Loss) attributable to shareholders of Cellectis is not a measure calculated in accordance with IFRS. We have included in this press release a reconciliation of this figure to Net Income (Loss) attributable to shareholders of Cellectis, the most directly comparable financial measure calculated in accordance with IFRS. Because Adjusted Income (Loss) attributable to shareholders of Cellectis excludes Non-cash stock-based compensation expense—a non-cash expense, we believe that this financial measure, when considered together with our IFRS financial statements, can enhance an overall understanding of Cellectis’ financial performance. Moreover, our management views the Company’s operations, and manages its business, based, in part, on this financial measure. In particular, we believe that the elimination of Non-cash stock-based expenses from Net Income (Loss) attributable to shareholders of Cellectis can provide a useful measure for period-to-period comparisons of our core businesses. Our use of Adjusted Income (Loss) attributable to shareholders of Cellectis has limitations as an analytical tool, and you should not consider it in isolation or as a substitute for analysis of our financial results as reported under IFRS. Some of these limitations are: (a) other companies, including companies in our industry which use similar stock-based compensation, may address the impact of Non-cash stock-based compensation expense differently; and (b) other companies may report Adjusted Income (Loss) attributable to shareholders or similarly titled measures but calculate them differently, which reduces their usefulness as a comparative measure. Because of these and other limitations, you should consider Adjusted Income (Loss) attributable to shareholders of Cellectis alongside our IFRS financial results, including Net Income (Loss) attributable to shareholders of Cellectis.

RECONCILIATION OF GAAP TO NON-GAAP NET INCOME – Third quarter
(unaudited)
(€ in thousands, except per share data)

For the three-month period
ended September 30,
2015 2016

Net Income (Loss) attributable to shareholders of Cellectis (12 766) (12 590)
Adjustment:
Non-cash stock-based compensation expense
9 464 12 114
Adjusted Income (Loss) attributable to shareholders of Cellectis (3 301) (475)

Basic Adjusted Income (Loss) attributable to shareholders of Cellectis (€/share) (0.09) (0.01)

Weighted average number of outstanding shares, basic (units) 35 094 503 35 333 572

Diluted Adjusted Income (Loss) attributable to shareholders of Cellectis (€/share) (0.09) (0.01)

Weighted average number of outstanding shares, diluted (units) 35 475 034 35 713 432

RECONCILIATION OF GAAP TO NON-GAAP NET INCOME – First nine months
(unaudited)
(€ in thousands, except per share data)

For the nine-month period
ended September 30,

2015 2016

Net Income (Loss) attributable to shareholders of Cellectis (28 786) (48 309)
Adjustment:
Non-cash stock-based compensation expense
17 481 39 911
Adjusted Income (Loss) attributable to shareholders of Cellectis (11 305) (8 398)

Basic Adjusted Income (Loss) attributable to shareholders of Cellectis (€/share) (0.33) (0.24)

Weighted average number of outstanding shares, basic (units) 33 819 191 35 274 890

Diluted Adjusted Income (Loss) attributable to shareholders of Cellectis (€/share) (0.33) (0.24)

Weighted average number of outstanding shares, diluted (units) 34 152 422 35 695 907

As a foreign private issuer, we are not required under the Exchange Act to file periodic reports and financial statements with the SEC as frequently or as promptly as United States companies whose securities are registered under the Exchange Act. Notwithstanding the foregoing, we currently provide quarterly interim consolidated financial data to the SEC, and commencing with our first quarter interim report for the 2017 fiscal year, we intend to file our periodic reports within the deadlines applicable to domestic reporting companies.

On November 22, 2016 NantKwest Inc. (Nasdaq:NK), a pioneering, next-generation, clinical-stage immunotherapy company focused on harnessing the unique power of our immune system using natural killer (NK) cells to treat cancer, infectious diseases and inflammatory diseases, reported that the Company’s abstract reviewing data on the company’s CD19.taNK program has been accepted for an oral presentation at the upcoming 58th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, CA, December 3-6, 2016 (Press release, NantKwest, NOV 22, 2016, http://ir.nantkwest.com/phoenix.zhtml?c=254059&p=RssLanding&cat=news&id=2225427 [SID1234516781]).

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"NantKwest’s transition from preclinical to clinical studies continues to make significant progress," said Patrick Soon-Shiong, MD, Chairman and CEO of NantKwest. "In these preclinical studies, aNK cells expressing a CD19-CAR (CD19.taNK) demonstrated strong killing of CD19-positive cancer cells. In addition, direct tumor injections of CD19.taNK into a fully immunocompetent mouse model induces tumor clearance and protection from tumor re-challenge, suggesting the induction of a memory (‘vaccine’) protective effect after the injection of the CD19.taNK cell."

Presentation Summary

Intra-Tumor Injection of CAR-Engineered NK Cells Induces Tumor Regression and Protection Against Tumor Re-Challenge

Abstract #466, View Source
Presenter: Laurent Boissel, PhD, NantKwest, Woburn, MA
Sunday, December 4, 2016, 5:15 PM, Room 5AB
This poster will review the potential use of CD19.taNK cells to effectively kill cancer cells. In vivo preclinical studies of direct tumor injection of CD19.taNK cells induces significant tumor regression and significantly improved survival, with 75% of the mice showing complete tumor regression at day 32 (p<0.05). Upon re-challenge with A20 lymphoma cells, >80% mice remained free of tumor after 14 days.

On November 21, 2016 Ruga Corporation reported the company’s name change to Aravive Biologics, Inc., and the relocation of its business operations to Houston, Texas (Press release, Aravive Biologics, NOV 21, 2016, View Source [SID1234516733]). The move follows the company’s award of a $20 million grant from the Cancer Prevention & Research Institute of Texas (CPRIT), which is supporting the development of a novel drug candidate, Aravive-S6, as a potential treatment for acute myelogenous leukemia (AML) and solid tumors including ovarian, pancreatic, and breast cancers.

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"We are very pleased to be selected to receive this significant funding from CPRIT and look forward to building our business in Houston’s Texas Medical Center," said Ray Tabibiazar, M.D., President and Chief Executive Officer of Aravive Biologics. "Houston’s vibrant biomedical community is home to many of the top cancer researchers in the United States, including noted experts on AML, our lead hematologic cancer indication. We look forward to accessing this outstanding expertise and growing our presence within the local biomedical community as we advance Aravive-S6 into clinical trials."

"Investing in Aravive Biologics’ clinical development program was an easy decision for CPRIT," said Michael Lang, Chief Product Development Officer of CPRIT. "Aravive-S6 is an innovative compound that has exhibited strong preclinical proof-of-principal, and it addresses a critical unmet medical need. The company also has experienced management with an excellent track record in oncology drug development. Aravive team members are well positioned for success, and we welcome them to the Houston biomedical community."

Aravive-S6 is a novel high-affinity, soluble Fc-fusion protein designed to block the activation of the GAS6- AXL signaling pathway by serving as a decoy that prevents the binding of GAS6 to the AXL receptor on the surface of tumor cells. The AXL receptor, when activated through GAS6 binding, has been shown to act as a "survival switch," a key driver of invasiveness and metastasis, and a critical regulator of therapeutic resistance to cytotoxic chemotherapeutic drugs.

Aravive Biologics has robust and compelling data demonstrating the in vivo efficacy and tolerability of its lead drug candidate in preclinical models of ovarian, renal, breast, and pancreatic cancer, and AML. Aravive-S6 provides high specificity and selectivity for the AXL/GAS6 pathway that other anti-AXL and anti-GAS6 inhibitors have been unable to match; it has greater than 100-fold tighter affinity for GAS6 compared to other anti-AXL and anti-GAS6 antibody candidates in development. Aravive Biologics has also developed a proprietary complementary diagnostic tool that may enable the identification of patients with cancers exhibiting elevated GAS6 levels, which would allow the company to match its drug candidate to those patients most likely to benefit from therapy.

AML is a cancer that begins in bone marrow and affects cells intended to mature into different types of blood cells. Research shows that interaction between the AXL receptor and its GAS6 ligand leads to more severe and invasive cases of AML.

"As patients with AML tend to be older (over 60 years of age) and possibly also in poorer health, they are often unable to tolerate standard, intensive chemotherapy regimens and thus must undergo less rigorous treatment, said Amato Giaccia, Ph.D., Chief Scientific Officer and co-founder of Aravive. "We envision that Aravive-S6 might be administered either as a single agent or as a complement to standard chemotherapy that assists in reducing the survival of cancer cells, which have become "addicted" to AXL/GAS6 signaling, while attempting to achieve or maintain remission."

Each year, approximately 19,950 new cases of AML are diagnosed, primarily in adults, and about 10,430 deaths from the disease, nearly all in adults. About 35% of AML cases exhibit active GAS6/AXL signaling, an incidence which may potentially qualify Aravive-S6 for Orphan Drug Designation.

On November 21, 2016 ImmunoCellular Therapeutics, Ltd. ("ImmunoCellular") (NYSE MKT:IMUC) reported the presentation of updated immune monitoring data from the phase 2 trial of ICT-107 in patients with newly diagnosed glioblastoma (Press release, ImmunoCellular Therapeutics, NOV 21, 2016, View Source [SID1234516718]). Also presented were updated long-term survival data from the phase 1 trial of ICT-107. ICT-107 is a dendritic cell-based immunotherapy targeting multiple tumor-associated antigens on glioblastoma stem cells. ICT-107 is currently being tested in a phase 3 registration trial in patients with newly diagnosed glioblastoma. The updated phase 1 and phase 2 data were presented in two oral sessions on Friday, November 18th, at the 21st Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology, held in Scottsdale, AZ.

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The ICT-107 phase 2 trial was a randomized, double-blind, placebo-controlled phase 2 study of the safety and efficacy of ICT-107 in patients with newly diagnosed glioblastoma following resection and chemoradiation. ICT-107 is an intradermally administered autologous immunotherapy consisting of the patient’s own dendritic cells pulsed with six synthetic tumor-associated antigens: AIM-2, MAGE-1, TRP-2, gp100, HER-2, IL-13Rα2. The placebo control consisted of the patient’s unpulsed dendritic cells. The data from the phase 2 trial indicated a survival advantage in the ICT-107 treated group compared to the control group. The data also showed an association between immune response and survival, especially in HLA-A2 positive (HLA-A2+) patients, which is the target patient population for the ongoing phase 3 registration trial.

The updated immune response data from the phase 2 trial showed that treatment with ICT-107 resulted in the development of a measurable anti-tumor T cell response in some patients, which was associated with survival. Patients that developed the anti-tumor T cell response which was measurable by both ELISpot (to detect viable T cells capable of binding to a target antigen) and multimer testing (to detect T cell binding with higher sensitivity than ELISpot) had improved survival. The data demonstrated that immuno-monitoring can provide an early indication of patients responding to immunotherapy. In the current ongoing phase 3 registration trial of ICT-107, ImmunoCellular plans to perform immuno-monitoring to support the trial.

The data were presented at SNO by Steven J. Swanson, PhD, Senior Vice President, Research, ImmunoCellular Therapeutics, in a presentation titled, "Categorizing immune responders with fusion metrics and simulation for association to survival and progression-free survival with immune response in HLA-A2+ patients with GBM from a phase 2 trial of dendritic cell (DC) immunotherapy (ICT-107)."

Dr. Swanson commented: "ICT-107 is designed to deliver therapeutic benefit by stimulating the patient’s immune system to attack tumor tissue. A first indicator that the immunotherapeutic is active is the production of tumor-specific T cells by the patient. In our SNO presentation, we described our ability to more clearly interpret the immune-monitoring data from the phase 2 trial. The ability to accurately identify negative and positive responses enabled us to better understand which of the patients in our trial generated T cells capable of attacking the tumor. We determined that patients with a T cell response measureable in both the ELIspot assay and through multimer analysis achieved longer survival as compared with patients who did not show a positive response. These data should enable us to better interpret the results of our ongoing phase 3 trial."

Andrew Gengos, ImmunoCellular Chief Executive Officer, said: "The phase 2 trial immune monitoring results indicate that patients who mount a T cell response appear to have improved survival over those without a detectable response. In designing the phase 3 trial, we have made important changes in the protocol to potentially enhance the immune response in ICT-107 treated patients with the goal of optimizing the potential survival outcomes in the trial."

Data from the phase 1 trial of ICT-107 were presented by Surasak Phuphanich, MD, Department of Neurology, Cedars-Sinai in Los Angeles, in a presentation titled "Ten-year follow up with long term remission in patients with newly diagnosed glioblastoma (GBM) treated with ICT-107 vaccine (phase 1)." The phase 1 open-label, single institution trial, which was completed in 2010, included 16 evaluable patients with newly diagnosed glioblastoma. Results of the study were initially published in 2012 (Cancer Immunol Immunother).

Updated survival data presented by Dr. Phuphanich at the 2016 SNO meeting showed that 19% of patients had long-term remission of greater than 8 years, with the longest remission being 9.6 years. Also, 38% of patients demonstrated long-term survival of greater than 8 years, with the longest survivor greater than 10.2 years. Immune response data showed a correlation between survival and cancer-stem-associated expression, and a trend toward greater CD8 T cell cytokine responses in long-term survivors.

ICT-107 Phase 3 Registration Trial Underway

The ongoing phase 3 registrational trial of ICT-107 is designed as a randomized, double-blind, placebo-controlled study of HLA-A2+ subjects, which is being conducted at about 120 sites in the US, Canada and the EU, with plans to randomize at least 500 patients with newly diagnosed glioblastoma. The primary endpoint in the trial is overall survival. Secondary endpoints include progression-free survival and safety, as well as overall survival in the two pre-specified MGMT subgroups.

For patients, families and physicians seeking additional information about the ICT-107 phase 3 trial, please consult www.clinicaltrials.gov.

About ImmunoCellular Therapeutics, Ltd.

On November 21, 2016 RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) ("RedHill" or the "Company"), a biopharmaceutical company primarily focused on development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, reported the presentation of a poster relating to YELIVA (ABC294640), the Company’s proprietary, first-in-class, orally-administered sphingosine kinase-2 (SK2) selective inhibitor, at the 2016 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium, on November 29, 2016, in Munich, Germany (Press release, RedHill Biopharma, NOV 21, 2016, View Source [SID1234516722]).

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The poster, entitled ‘Antitumor and Anti-Inflammatory Effects of the Sphingosine Kinase-2 Inhibitor ABC294640 in Combination with Radiation,’ was authored by scientists from Apogee Biotechnology Corporation ("Apogee"), the original developers of YELIVA.

By inhibiting the SK2 enzyme, YELIVA blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid signaling molecule that promotes cancer growth and pathological inflammation.

RedHill is pursuing and evaluating, with YELIVA, multiple clinical programs in oncology, inflammatory and gastrointestinal indications, as well as potential collaboration opportunities with larger pharmaceutical companies to evaluate YELIVA as an add-on therapy to their existing oncology treatments.

Results from a Phase I study with YELIVA in patients with advanced solid tumors confirmed that the study, conducted at the Medical University of South Carolina Hollings Cancer Center (MUSC), successfully met its primary and secondary endpoints, demonstrating that the drug is well-tolerated and can be safely administered to cancer patients at doses that provide circulating drug levels that are predicted to have therapeutic activity.

A Phase II study with YELIVA for the treatment of advanced hepatocellular carcinoma (HCC) was initiated at MUSC Hollings Cancer Center. The study protocol is under FDA review and enrolment is expected to begin by year end 2016. The study is supported by a $1.8 million grant from the National Cancer Institute (NCI) awarded to MUSC and is intended to fund a broad range of studies on the feasibility of targeting sphingolipid metabolism for the treatment of a variety of solid tumor cancers, with additional funding from RedHill.

A Phase Ib/II study with YELIVA for the treatment of refractory or relapsed multiple myeloma was initiated at Duke University Medical Center. The study is supported by a $2 million grant from the NCI Small Business Innovation Research Program (SBIR) awarded to Apogee, in conjunction with Duke University, with additional support from RedHill.

A Phase I/II clinical study evaluating YELIVA in patients with refractory/relapsed diffuse large B-cell lymphoma was initiated at the Louisiana State University Health Sciences Center in New Orleans in June 2015 and was recently amended to address overall recruitment prospects. The study, which will now also include Kaposi sarcoma patients, is expected to resume by the end of 2016, pending regulatory approval. The study is supported by a grant from the NCI, as well as additional support from RedHill.

A Phase Ib study to evaluate YELIVA as a radioprotectant for prevention of mucositis in head and neck cancer patients undergoing therapeutic radiotherapy is planned to be initiated in the first quarter of 2017.

The ongoing studies with YELIVA (ABC294640) are registered on www.ClinicalTrials.gov, a web-based service by the U.S. National Institute of Health, which provides public access to information on publicly and privately supported clinical studies.

About YELIVA (ABC294640):
YELIVA (ABC294640) is a Phase II-stage, proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with anti-cancer and anti-inflammatory activities. RedHill is pursuing with YELIVA multiple clinical programs in oncology, inflammatory and gastrointestinal indications. By inhibiting the SK2 enzyme, YELIVA blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid signaling molecule that promotes cancer growth and pathological inflammation. SK2 is an innovative molecular target for anticancer therapy because of its critical role in catalyzing the formation of S1P, which is known to regulate cell proliferation and activation of inflammatory pathways. YELIVA was originally developed by U.S.-based Apogee Biotechnology Corp. and completed multiple successful pre-clinical studies in oncology, inflammation, GI and radioprotection models, as well as the ABC-101 Phase I clinical study in cancer patients with advanced solid tumors. The development of YELIVA was funded to date primarily by grants and contracts from U.S. federal and state government agencies awarded to Apogee Biotechnology Corp., including the U.S. National Cancer Institute, the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA), the U.S. Department of Defense and the FDA Office of Orphan Products Development.