On November 22, 2016 Opsona Therapeutics Ltd (‘Opsona’), the innate immune drug development company focused on novel therapeutic approaches to treat oncology, autoimmune and other inflammatory diseases, reported that it will present preliminary results from its ongoing prospective, open label Phase I/II study being conducted with OPN-305 in second-line lower (Low and intermediate-1) risk myelodysplastic syndrome (MDS) (Press release, Opsona Therapeutics, NOV 22, 2016, View Source [SID1234516770]). The presentation will take place on Saturday, 3 December at the 58th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Myelodysplastic syndromes are a complex and heterogeneous group of bone marrow failure disorders characterized by ineffective hematopoiesis and poor prognosis. There is an urgent need for the development of novel therapies in the treatment of MDS which can delay progression, improve patient survival and quality of life, and which have fewer adverse effects. Opsona has recently received orphan drug designation (ODD) from the United States Food and Drug Administration for MDS.

OPN-305 is a novel proprietary humanized IgG4 monoclonal antibody (MAb) against Toll-Like Receptor 2 (TLR2), a key target within the innate immune system.

The study in patients with lower risk MDS who have failed hypomethylating agents is ongoing in collaboration with MD Anderson Cancer Center in Houston USA with additional sites now being added in the USA. The lead principal investigator Professor Guillermo Garcia-Manero will present the preliminary data at ASH (Free ASH Whitepaper) and commenting on today’s announcement said "Inhibition of TLR2 with OPN-305 is safe and is currently demonstrating strong clinical activity in patients with lower risk MDS after hypomethylating agent therapy"

Details of the presentation are as follows:

A Clinical Study of OPN-305, a Toll-like receptor 2 (TLR-2) antibody, in patients with Lower Risk Myelodysplastic Syndromes (MDS) that have received prior Hypomethylating Agent (HMA) Therapy

Abstract # 227

Session Name: 637. Myelodysplastic Syndromes—Clinical Studies: Lower Risk MDS Clinical Studies

Session Date: Saturday, December 3, 2016

Session Time: 4:00 PM – 5:30 PM

Presentation Time: 5:00 PM

Room: Manchester Grand Hyatt San Diego, Grand Hall C

The ASH (Free ASH Whitepaper) abstract is now online can be accessed here:

View Source

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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 21, 2016 Mustang Bio, Inc. ("Mustang"), a Fortress Biotech (NASDAQ: FBIO) Company, reported that Phase 1 clinical data and pre‐clinical data on its MB‐101 (IL13Rα2‐specific Chimeric Antigen Receptor–engineered CAR T cells (CAR T cells)) product candidate in development for the treatment of glioblastoma were presented by investigators from the City of Hope ("COH") in oral sessions at the 21st Annual Meeting and Education Day of the Society for Neuro‐Oncology ("SNO") in Scottsdale, AZ (Press release, Fortress Biotech, NOV 21, 2016, View Source;FID=1500093635 [SID1234516780]).   

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Dr. Lindsay A. Rosenwald, Fortress Biotech’s Chairman, President and Chief Executive Officer commented, "CAR T cell therapy has shown promise in treating certain forms of hematological cancers.  However, translating that activity into solid tumors has been challenging to date.  The clinical data presented at SNO by the investigators from COH suggest MB‐101 is safe and well‐tolerated, and capable of eliciting a potent anti‐tumor response in patients with glioblastoma (GBM), a disease that is almost universally fatal.  We believe this is the first evidence of activity of CAR T cells in the treatment of GBM.  We are very encouraged by the early evidence of anti‐tumor activity with MB‐101 with five of seven post‐surgical resection patients showing stable disease for >8 weeks and, in particular, one patient showing complete response for 7.5 months. Interestingly, this patient was the only patient of the seven to receive, on a compassionate use basis, the dual delivery of CAR T cells by both intracavitary and via intraventricular administration, which provides systemic CNS delivery of the CAR T cells.  We look forward to continuing to advance MB‐101 in Phase 1 studies and further exploring the dual delivery approach beyond this single patient experience."

The following summarizes the oral presentations on November 18, 2016 at SNO:

Phase I Study of Chimeric Antigen Receptor–Engineered T cells Targeting IL13Rα2 for the Treatment of Glioblastoma

Presenter: Christine E. Brown, PhD, Heritage Provider Network Professor of Immunotherapy, Associate Director, T Cell Therapeutics Research Laboratory, City of Hope National Medical Center/Beckman Research Institute

The Phase I study presented showed early clinical data evaluating IL13Rα2‐targeted CAR T cell therapy for the treatment of glioblastoma.  On this study, patients are treated on a four‐week therapeutic regimen consisting of three weekly intracranial infusions of IL13Rα2‐specific CAR T cells followed by one rest week for toxicity and disease assessment.  To date, seven patients have been treated with local intracavitary delivery of the CAR T cells following surgical resection.
Some highlights from the presentation included:
The treatment was well‐tolerated in all patients treated – with No DLTs or therapy‐related SAEs
No grade 3 or higher toxicities attributed to the therapy were observed
No CRS or Neurotoxicity was observed
Only grade  < 2 fevers, headaches, myalgia, chills
Best Response: 2 PD, 4 SD for >8‐weeks, 1 SD CR following intraventricular CAR T therapy for 7.5 months

Development of murine IL13Rα2‐targeted CAR T cells (mIL13BBζ) for assessment of CAR T cell therapy in syngeneic glioma models

Presenter: Darya Alizadeh, PhD, City of Hope National Medical Center/Beckman Research Institute

The pre‐clinical research program presented discussed a murine IL13Rα2‐targeted CAR T cell platform that was developed to evaluate parameters that impact the efficacy of CAR T cell therapy. Overall, the development of mIL13BBζ CAR T cells and its applications will allow researchers to assess factors that may impact the efficacy of CAR T cells and provide invaluable information critical for combination therapies and clinical trial design.  These studies may also provide important insights for improving therapeutic outcomes for patients with glioblastoma.

About Glioblastoma multiforme (GBM)
Glioblastomas (GBM) are tumors that arise from astrocytes cells that make up the supportive tissue of the brain. These tumors are usually highly malignant (cancerous) because the cellsreproduce quickly and they are supported by a large network of blood vessels. GBM isthe most common brain and central nervoussystem (CNS) malignancy, accounting for 15.1 percent of all primary brain tumors and 55.1 percent of all gliomas. There will be an estimated 12,120 new glioblastoma casesin the U.S. in 2016. Malignant brain tumors are the most common cause of cancer‐ related deaths in adolescents and young adults aged 15‐39, and the most common cancer occurring among 15‐19 year olds in the U.S. (Brain Tumor Statistics. American Brain Tumor Association.  December 2015). While GBM is a rare disease (2‐3 cases per 100,000 person life years in the U.S. and EU), it is quite lethal with five‐year survival rates historically lessthan 10 percent. Chemotherapy with temozolomide and radiation are shown to extend mean survival from approximately 12 to 15 months, while surgery remains the standard of care. GBM remains difficult to treat due to the inherent resistance of the tumor to conventional therapies. Treatment is further complicated by the susceptibility of the brain to damage, difficulty of the brain to repair itself and limitation to drugs crossing the blood brain barrier. Immunotherapy approaches targeting brain tumors offer promise over conventional treatments.

About MB‐101 (IL13Rα2‐specific CAR T cells)
IL13Rα2 is an attractive target for CAR T therapy as it has limited expression in normal tissue but is over‐expressed on the surface of the majority of GBM. CAR T cells are designed to express a membrane‐tethered IL‐13 receptor ligand (IL‐13) incorporating a single point mutation that provides high affinity for IL13Rα2 and reduces binding to IL13Rα1 in order to reduce healthy tissue targeting.  

Mustang is developing an optimized CAR T product incorporating enhancements in CAR design and T cell engineering to improve antitumor potency and T cell persistence. We include a second‐generation hinge optimized CAR containing mutations in the IgG4 linker to reduce off‐target Fc interactions, as well as the 41BB (CD137) co‐stimulatory signaling domain forimproved persistence of CAR T cells, and extracellular domain of CD19 as a selection/safety marker. In order to further improve persistence, central memory T cells are enriched and genetically engineered using a manufacturing process that limits ex vivo expansion in order to reduce T cell exhaustion and maintain a memory T cell phenotype.

On November 21, 2016 Syros Pharmaceuticals (NASDAQ: SYRS) reported that new data on its lead candidate, SY-1425, a selective retinoic acid receptor alpha (RARα) agonist, will be highlighted in a late-breaking presentation at the San Antonio Breast Cancer Symposium (SABCS) taking place December 6-10, 2016, in San Antonio (Press release, Syros Pharmaceuticals, NOV 21, 2016, View Source;p=irol-newsArticle&ID=2224844 [SID1234516732]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The presentation will feature new preclinical data showing that SY-1425 represents a potentially promising therapeutic approach for defined subsets of breast cancer patients whose tumors are driven by abnormally high expression of the RARA gene.

Details on the presentations are as follow:

Date & Time: Saturday, December 10, from 7:30 – 9:00 am CST
Presentation Title: A novel subgroup of estrogen receptor positive breast cancer may benefit from super-enhancer guided patient selection for retinoic acid receptor α agonist treatment
Session: Treatment: Novel Targets and Targeted Agents
Presenter: Michael R. McKeown, Ph.D., Senior Scientist, Syros Pharmaceuticals
Program Number: P6-11-18
Location: Henry B. Gonzalez Convention Center, Hall 1

SY-1425 is currently in a Phase 2 clinical trial in genomically defined subsets of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients. Using its gene control platform, Syros discovered subsets of AML, MDS and breast cancer patients whose tumors have a highly specialized regulatory region of non-coding DNA, known as a super-enhancer, associated with the RARA gene, which codes for the RARα transcription factor. The super-enhancer is believed to lead to over-expression of the RARA gene, locking cells in an immature, undifferentiated and proliferative state. Treatment with SY-1425 in cancer cells with this super-enhancer promotes differentiation of these cells.

About Syros Pharmaceuticals

Syros Pharmaceuticals is pioneering the understanding of the non-coding region of the genome to advance a new wave of medicines that control expression of disease-driving genes. Syros has built a proprietary platform that is designed to systematically and efficiently analyze this unexploited region of DNA in human disease tissue to identify and drug novel targets linked to genomically defined patient populations. Because gene expression is fundamental to the function of all cells, Syros’ gene control platform has broad potential to create medicines that achieve profound and durable benefit across a range of diseases. Syros is currently focused on cancer and immune-mediated diseases and is advancing a growing pipeline of gene control medicines. Syros’ lead drug candidates are SY-1425, a selective RARα agonist in a Phase 2 clinical trial for genomically defined subsets of patients with acute myeloid leukemia and myelodysplastic syndrome, and SY-1365, a selective CDK7 inhibitor with potential in a range of solid tumors and blood cancers. Led by a team with deep experience in drug discovery, development and commercialization, Syros is located in Cambridge, Mass.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, including without limitation statements regarding the potential therapeutic benefits of treatment with SY-1425 in genomically defined subsets of AML, MDS and breast cancer patients. The words ‘‘anticipate,’’ ‘‘believe,’’ ‘‘continue,’’ ‘‘could,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘plan,’’ ‘‘potential,’’ ‘‘predict,’’ ‘‘project,’’ ‘‘target,’’ ‘‘should,’’ ‘‘would,’’ and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including: Syros’ ability to: advance the development of its programs, including SY-1425, under the timelines it projects in current and future clinical trials; obtain and maintain patent protection for its drug candidates and the freedom to operate under third party intellectual property; demonstrate in any current and future clinical trials the requisite safety, efficacy and combinability of its drug candidates; replicate scientific and non-clinical data in clinical trials; successfully develop a companion diagnostic test to identify patients with biomarkers associated with the RARA super-enhancer; obtain and maintain necessary regulatory approvals; identify, enter into and maintain collaboration agreements with third parties; manage competition; manage expenses; raise the substantial additional capital needed to achieve its business objectives; attract and retain qualified personnel; and successfully execute on its business strategies; risks described under the caption "Risk Factors" in the company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2016, which is on file with the Securities and Exchange Commission; and risks described in other filings that the company makes with the Securities and Exchange Commission in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Syros expressly disclaims any obligation to update any forward-looking statements, whether because of new information, future events or otherwise.

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.