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OncoSec Announces Positive Interim Response Data at the Society for Immunotherapy of Cancer (SITC) Annual Meeting 2016

On November 8, 2016 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported that new clinical data are being presented from a Phase II Investigator Sponsored Trial led by the University of California, San Francisco (UCSF) (Press release, OncoSec Medical, NOV 8, 2016, View Source [SID1234516470]). This single-arm, open-label trial assessed the combination of OncoSec’s investigational intratumoral therapy, ImmunoPulse IL-12, and Merck’s KEYTRUDA (pembrolizumab) in patients with unresectable metastatic melanoma. A predictive biomarker was used to enroll patients that have a low likelihood of response to an anti-PD1 agent alone, and the purpose of the trial is to assess whether the addition of ImmunoPulse IL-12 can increase response rates in these patients. The data will be presented at an oral poster presentation (#466) by Dr. Alain Algazi at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) ("SITC") Annual Meeting in National Harbor, MD on November 11, 2016 at 12:50 PM EST.

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In August 2016, OncoSec announced the publication of a research assay in the Journal of Clinical Investigation that might be used as a predicative biomarker in melanoma patients. The assay shows that patients with a low frequency of a certain phenotype of CD8 T cells, pre-disposes them to low response rates to PD-1 inhibitor therapy alone. The Company is using this biomarker assay to select patients considered to be PD-1 non responders for this ongoing combination study. The key endpoints of the study include: best overall response rate by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune-related Response Criteria; safety and tolerability; duration of response; 24-week landmark progression-free survival; median progression-free survival; and overall survival.

Results
Interim efficacy and safety data are available on 15 patients. In patients considered unable to respond to PD-1 we measured an overall response rate of 40% (6 /15), consisting of 4 complete responses and 2 partial responses by RECISTv1.1 criteria. Additionally, the therapy has an acceptable safety profile and was well tolerated. Analysis of tumor biopsies and blood correlated with patients’ responsiveness and demonstrated correlative immunological changes including an increased number of CD8+ tumor-infiltrating lymphocytes, tumoral RNA signatures and concordant immune phenotypes in the periphery. Investigators concluded that the combination of ImmunoPulse IL-12 with pembrolizumab in patients with an anti-PD-1 non-responsive phenotype enables an effective anti-PD-1 response.

Punit Dhillon, CEO of OncoSec, stated: "These results validate our therapeutic hypothesis for the ability of ImmunoPulse IL-12 to improve response rates in advanced melanoma. We wish to thank the investigators and patients for their continued participation in this study. We are working diligently to advance this agent towards registration-enabling studies, and we look forward to providing additional details regarding the Company’s operations and strategy at our upcoming Investor and Analyst Day on November 17, 2016."

Alain Algazi, M.D., Principal Investigator from UCSF, stated: "Although this open-label study is still ongoing and data are maturing, I am encouraged by the meaningful interim response rates that the combination of ImmunoPulse IL-12 and pembrolizumab has been able to achieve in a patient population otherwise expected to respond poorly to pembrolizumab alone. While checkpoint inhibition has conferred meaningful clinical benefit for advanced melanoma patients, there remains an urgent need to increase these agents’ efficacy through the rational combination with other immunotherapies. I look forward to the continued maturation of this data and to further reporting on the trial’s progress."

For more information about this trial, please visit: View Source;rank=3

LION BIOTECHNOLOGIES PRESENTS ENCOURAGING TIL TECHNOLOGY DATA IN FOUR POSTERS AT 2016 SITC ANNUAL MEETING

On November 8 Lion Biotechnologies, Inc. (NASDAQ: LBIO), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte technology (TIL), reported encouraging data in four poster presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 31st Annual Meeting & Associated Programs in National Harbor, Maryland taking place November 9-13, 2016.

"The data to be presented at SITC (Free SITC Whitepaper) is reflective of our progress in two main directions at Lion; process optimization and expansion of utilization of the TIL technology in new indications. In one abstract, data is provided demonstrating successful culturing of TIL cells from non-melanoma solid tumors, potentially expanding application of the Lion TIL technology in new indications. Additionally, we show progress in process optimization including development of cryopreservation methodology and a more efficient assay to assess potency of TIL cells," said Maria Fardis, PhD, MBA, Lion Biotechnologies President and Chief Executive Officer.

Poster Presentation: "Successful Expansion and Characterization of Tumor Infiltrating Lymphocytes (TILs) from Non-melanoma Tumors"

This study demonstrated the feasibility of culturing and expanding TILs isolated from non-melanoma tumors including bladder, cervical, head and neck, lung and triple negative breast cancer (TNBC).
TILs were harvested to assess cell count and viability, followed by immunophenotyping and cryopreservation for future studies.
Phenotypic characterization of TIL from bladder, cervical and lung cancer were > 60-70% CD8+ T cells whereas TILs from head and neck demonstrated variable distribution of CD8+ and CD4+ T cells. TIL propagated from TNBC were > 80% CD4+ T cells. Regardless of the tumors, most cultures had < 20% CD56+ NK cells.
Based on the successful culturing of TILs, clinical feasibility of adoptive cellular therapy for patients with non-melanoma solid tumors will be investigated.
Poster Presentation: "Artificial Antigen Presenting Cells Promote Expansion of Tumor Infiltrating Lymphocytes (TILs)"

The study evaluated artificial antigen presenting cells (aAPC) as a potential substitute for allogeneic peripheral blood mononuclear cells (PBMC) which are currently required for the expansion of TIL. The benefit of using aAPC is to reduce the price of the manufacturing process as well to turn the process into a more reproducible and scalable one.
A novel aAPC was developed from the CD64+ MOLM-14 human leukemia cell line, genetically engineered to express recombinant CD86 (B7-2) and CD137-L (41BBL) (MOLM14-86/137).
The study showed that co-culture of TILs with MOLM-14-86/137 aAPC resulted in expansion, metabolic activity and cytotoxicity that were sufficiently similar to that obtained with PBMC.
TIL differentiation, cellular respiration (OXPHOS) and redirected cytotoxicity were also within the range expected via co-culture with PBMC.
This data suggests that the expansion protocol using the novel MOLM14-86/137 aAPC can be tested in a clinical setting.
Poster Presentation: "Bioluminescent Redirected Lysis Assay (BRLA) as an Efficient Potency Assay to Assess Tumor-Infiltrating Lymphocytes (TILs) for Immunotherapy"

TIL therapy involves culturing and expanding T cells isolated from a patient’s tumor and then reinfusing them into the patient. TIL antitumor activity is commonly measured using tumor cells from the patient’s tumor, when available.
In order to test the potency of TILs, a BRLA assay was developed using an engineered P815 cell line. It requires no radionuclides and is more efficient than traditional cytotoxicity assays.
The assay was shown to measure TIL cytotoxicity in a highly sensitive dose dependent manner.
Poster Presentation: "Stable Tumor-Infiltrating Lymphocytes (TIL) Phenotype Following Cryopreservation"

Cryopreservation is a beneficial process which allows cell products to be shipped in a safe manner with less time constraints. In this study, the data show that cryopreservation did not affect the measured phenotypic characteristics of TIL, enabling Lion to further investigate the possibility of using cryopreserved TIL in a clinical setting.
Clinical studies using cryopreserved TIL have not been conducted so far.
In this study, fresh versus frozen/thawed TIL samples were tested to evaluate the expression of phenotypic markers.
Cryopreservation did not affect the measured phenotypic characteristics of TIL, with the exception of some regulatory molecules. Lion will further investigate the possibility of using cryopreserved TIL in a clinical setting.

Affimed to Present Preclinical Data on Bi- and Trispecific Immune Cell Engagers at ASH

On November 8, 2016 Affimed N.V. (Nasdaq: AFMD), a clinical stage biopharmaceutical company focused on discovering and developing highly targeted cancer immunotherapies, reported that three of the Company’s abstracts have been chosen for poster presentations at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, being held December 3-6, 2016 in San Diego, California (Press release, Affimed, NOV 8, 2016, View Source [SID1234516419]).

Poster Information

AFM13 Is the Most Advanced Bispecific NK-Cell Engaging Antibody in Clinical Development Substantially Enhancing NK-Cell Effector Function and Proliferation (Abstract #1764)
Session: 622. Lymphoma Biology – Non-Genetic Studies: Poster I
Date: Saturday, December 3, 2016: 5:30-7:30 p.m. (PT)
Location: Hall GH (San Diego Convention Center)

Functional Defects of T Cells of NHL Patients after Different Chemotherapy Regimens Activated By CD19/CD3 Tetravalent Bispecific TandAb AFM11 (Abstract #4130)
Session: 622. Lymphoma Biology – Non-Genetic Studies: Poster III
Date: Monday, December 5, 2016: 6:00-8:00 p.m. Pacific Time
Location: Hall GH (San Diego Convention Center)

Trispecific Antibodies for Selective CD16A-Directed NK-Cell Engagement in Multiple Myeloma (Abstract #4513)
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster III
Date: Monday, December 5, 2016: 6:00-8:00 p.m. Pacific Time
Location: Hall GH (San Diego Convention Center)

About AFM13
AFM13 is a bispecific NK-cell TandAb simultaneously targeting CD16A on NK-cells and CD30 on tumor cells. AFM13 is designed to treat CD30-positive malignancies including Hodgkin lymphoma (HL) and T-cell lymphoma (TCL) and is currently in Phase 2 studies in HL patients. Based on its appropriate safety profile, AFM13 is being developed both as monotherapy and in combination with other therapeutics such as our collaboration partner Merck’s checkpoint inhibitor KEYTRUDA.

About AFM11
AFM11 is a bispecific T-cell TandAb simultaneously targeting CD3 on T-cells and CD19 on tumor cells. AFM11 is specifically designed to treat B-cell malignancies including non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL), in which CD19 is expressed at abnormally high levels. AFM11 is currently in Phase 1 clinical development for NHL and ALL.

About NK- and T-Cell TandAbs and Trispecific Antibodies
TandAbs and Trispecific Abs are immune cell-engaging antibodies with a tetravalent architecture characterized by four binding domains. Affimed develops products from three proprietary platforms:
Bispecific TandAbs engaging NK-cells (via CD16A)
Bispecific TandAbs engaging T-cells (via CD3)
Trispecific Abs engaging either NK- or T-cells
Affimed develops TandAbs and Trispecific Abs to substantially increase the efficacy, specificity and/or extend the therapeutic window of current therapeutics. Binding to targets on both the immune and the tumor cell, they redirect immune cells and establish a bridge between either NK-cells or T-cells and cancer cells, triggering a signal cascade that leads to the destruction of cancer cells. In clinical studies, our TandAb products have already demonstrated promising signs of therapeutic activity in patients.

Galectin Therapeutics Reports Third Quarter 2016
Financial Results and Provides Business Update

On November 8, 2016 Galectin Therapeutics Inc. (NASDAQ: GALT), the leading developer of therapeutics that target galectin proteins to treat fibrosis and cancer, reported financial results for the three and nine months ended September 30, 2016 (Filing, Q3, Galectin Therapeutics, 2016, NOV 8, 2016, View Source [SID1234516417]). These results are included in the Company’s Form 10-Q, which has been filed with the U.S. Securities and Exchange Commission and is available at www.sec.gov.
Summary of Key Development Programs, Updates and Anticipated Milestones

• At The Liver Meeting in Boston, Massachusetts on November 11-15, 2016, Dr. Peter Traber, president, chief executive officer and chief medical officer of Galectin Therapeutics and co-investigator of these studies, will present two posters that demonstrate the use of alternative non-invasive tests on the progression of cirrhosis and fibrosis in patients with nonalcoholic steatohepatitis (NASH), highlighting the potential utility of non-invasive imaging methods in the development of novel therapies in this patient population and adding momentum in this area of medicine.

• In the recently completed NASH-FX study, GR-MD-02 was found to be safe and well tolerated among the patient population with no serious adverse events.

• In August, the Company reported on a study that demonstrated clinically meaningful results in a human disease with GR-MD-02, where four patients who received 24 weeks of therapy experienced an average of 48% improvement in their plaque psoriasis. In October, a fifth patient reached 72% improvement at his 13th infusion visit with one more assessment to be completed by the end of November. Dr. Stephen Harrison, the co-chief investigator in our NASH-CX trial, stated that he was especially encouraged that GR-MD-02 has demonstrated an improved clinical effect in moderate-to-severe psoriasis, suggesting the compound has activity in a human disease that can occur in association with NASH.

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• The full report of our Phase 1 study in NASH patients with advanced fibrosis, which demonstrated GR-MD-02 was safe and defined dosing for Phase 2 trials, was published on October 25, 2015 in the peer-reviewed scientific journal, Alimentary Pharmacology and Therapeutics (http://bit.ly/2f3Znq3).

• In support for continued funding of the NASH-CX trial, a private placement financing for $1.5 million was secured from a single source.

• Dr. William L. Redmond, Ph.D., of Earle A. Chiles Research Institute of Providence Portland Medical Center will present pre-clinical and clinical data regarding use of GR-MD-02 in combination with immunotherapy, specifically with Yervoy and Ketruda, at the GTCbio 9th Immunotherapeutics & Immunomonitoring Conference, to be held on February 6-7, 2017 in San Diego, CA.
Management Commentary
"As noted by our co-lead investigators, Dr. Stephen Harrison and Dr. Naga Chalasani, it is important to complete our ongoing NASH-CX Phase 2b trial focused on the treatment of NASH cirrhosis as one year may provide an appropriate length of therapy and the endpoints may serve as a surrogate for outcomes for registration trials in this patient population," said Peter G. Traber, M.D., president, chief executive officer and chief medical officer of Galectin Therapeutics. "NASH cirrhosis has always been, and remains, the lead indication for GR-MD-02. Presently, we are the only company with a compound for NASH cirrhosis in an active Phase 2 clinical trial.
"The market seemingly recognizes the concerns about the rising incidence of NASH and the need for therapies to counter a potential health epidemic as Allergan’s $1.7 billion purchase of Tobira appears to have been motivated by a NASH drug in clinical trials.
"The NASH-CX trial is a one-year of treatment, multi-center trial in patients with NASH cirrhosis that is being conducted at 36 outstanding liver centers in the United States. It completed enrollment one month early with 162 well-compensated patients with NASH cirrhosis (Child-Pugh-Turcotte Class A) with elevated portal pressure (HVPG ³ 6 mmHg). Only five patients of the 162 enrolled have dropped out of the trial thus far,

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with this low attrition rate highlighting the importance, urgency, and need for patients suffering from NASH-cirrhosis to find an effective medical treatment. And, a total of 2,240 drug infusions (including placebo) have been given in this trial, representing 53% of the total number of infusions in the entire trial. So we are quite pleased that this study is well along in its development and on track for reporting of top-line results in December of 2017.
"As a company, Galectin Therapeutics’ attention has always been focused on completing the NASH-CX clinical trial and reporting results in a timely fashion. With an outstanding safety profile, inhibition of galectin-3 with GR-MD-02 remains a potential treatment of NASH cirrhosis and provides us encouragement about our continuation of the NASH-CX clinical trial."
Financial Results
For the three months ended September 30, 2016, the Company reported a net loss applicable to common stockholders of $5.6 million, or $0.19 per share, compared with a net loss applicable to common stockholders of $6.2 million, or $0.26 per share, for the three months ended September 30, 2015. The decrease is largely due to lower non-cash stock based compensation expense and timing of research and development expenses related to the Phase 2 clinical program in NASH.
Research and development expense for the three months ended September 30, 2016 was $3.3 million, compared with $4.4 million for the three months ended September 30, 2015. The decrease primarily relates to timing of research and development expenses related to the Phase 2 clinical program in NASH.
General and administrative expense for this quarter was $1.2 million, compared with $1.4 million for the prior year, with the decrease being primarily related to non-cash stock compensation. As of September 30, 2016, the Company had $16.1 million of non-restricted cash and cash equivalents. The Company believes it has sufficient cash to fund currently planned operations and research and development activities through August 2017.

Endo Reports Third Quarter 2016 Financial Results

On November 8, 2016 Endo International plc (NASDAQ: ENDP) (TSX: ENL) reported third quarter 2016 financial results, including:
Revenues of $884 million including the addition of sales from its 2015 acquisition of Par Pharmaceutical, a 19 percent increase compared to third quarter 2015 revenues of $746 million(Press release, Endo, NOV 8, 2016, View Source;p=RssLanding&cat=news&id=2220454 [SID1234516401]).

Reported net loss from continuing operations of $191 million compared to third quarter 2015 reported net loss from continuing operations of $804 million.

Reported diluted loss per share from continuing operations of $0.86 compared to third quarter 2015 reported diluted loss per share from continuing operations of $3.84.

Adjusted net income from continuing operations of $226 million, a 5 percent increase compared to third quarter 2015 adjusted net income from continuing operations of $214 million.1

Adjusted diluted EPS from continuing operations of $1.01 compared to third quarter 2015 adjusted diluted EPS from continuing operations of $1.02.1

"During the third quarter 2016, Endo further sharpened its focus on operational execution. We have continued to deliver results across all of our businesses that are on-track or ahead of Company expectations for the quarter. Today we are reaffirming our full year 2016 revenue and adjusted diluted EPS financial guidance," said Paul Campanelli, President and CEO of Endo. "This is an important time for Endo. The leadership team is working closely and collaboratively to build on our strengths and develop a go-forward strategy that best positions the Company to improve the lives of the patients and customers we serve."
FINANCIAL PERFORMANCE

(in thousands, except per share amounts)

Three Months Ended
September 30,

Nine Months Ended
September 30,

2016

2015

Change

2016

2015

Change
Total Revenues
$
884,335

$
745,727

19
%

$
2,768,761

$
2,195,021

26
%
Reported Income (Loss) from
Continuing Operations
$
(191,496)

$
(803,706)

(76)
%

$
109,553

$
(744,108)

NM
Reported Diluted Weighted Average
Shares
222,767

209,274

6
%

223,060

188,085

19
%
Reported Diluted Income (Loss) per
Share from Continuing Operations
$
(0.86)

$
(3.84)

(78)
%

$
0.49

$
(3.96)

NM
Adjusted Income from Continuing
Operations
$
225,519

$
214,110
1

5
%

$
658,591

$
625,805
1

5
%
Adjusted Diluted Weighted Average
Shares
223,139

210,787

6
%

223,060

192,144

16
%
Adjusted Diluted EPS from
Continuing Operations
$
1.01

$
1.02
1

(1)
%

$
2.95

$
3.26
1

(10)
%

(1) Refer to footnote 12 and 14 in the Reconciliation of GAAP and Non-GAAP Financial Measures tables for three and nine months ended September 30, 2015, respectively, for further discussion.
CONSOLIDATED RESULTS
Total revenues increased by 19 percent to $884 million in third quarter 2016 compared to the same period in 2015, primarily attributable to revenues related to the September 2015 Par acquisition. GAAP net loss from continuing operations in third quarter 2016 decreased to $191 million compared to a GAAP net loss from continuing operations of $804 million during the same period in 2015, primarily attributable to the amount of goodwill and intangible asset impairment charges recorded during the third quarter 2015. GAAP net loss per share from continuing operations for the three months ended September 30, 2016 was $0.86, compared to a GAAP net loss from continuing operations of $3.84 in third quarter 2015.
Adjusted net income from continuing operations for third quarter 2016 increased by 5 percent to $226 million compared to third quarter 2015, driven primarily by the contribution of Par, offset partially by an increase in interest expense. Adjusted net income per share from continuing operations for the three months ended September 30, 2016 decreased 1 percent to $1.01 compared to third quarter 2015.
U.S. BRANDED PHARMACEUTICALS
During third quarter 2016, the U.S. Branded Pharmaceuticals business unit continued to focus on supporting demand growth for XIAFLEX in both the Dupuytren’s contracture and Peyronie’s disease indications and the BELBUCA launch continues to progress.
Third quarter 2016 U.S. Branded Pharmaceuticals results include:
Revenues of $280 million, an 8 percent decrease compared to third quarter 2015; this decrease was primarily attributable to a generic entrant for Voltaren Gel in March 2016 and volume contraction across our established pain products.
Net sales of XIAFLEX increased 19 percent compared to third quarter 2015; this increase reflects high single-digit demand growth for the product and expected inventory build in the quarter.
U.S. GENERIC PHARMACEUTICALS
During third quarter 2016, the U.S. Generic Pharmaceuticals business unit continued to execute on its sales and marketing, research and development (R&D), and manufacturing plans for the year.
Third quarter and recent 2016 U.S. Generic Pharmaceuticals results include:
Revenues of $534 million, a 45 percent increase compared to third quarter 2015; this increase was primarily attributable to growth from the addition of sales by Par.
Generics Base business revenues declined approximately 20 percent sequentially compared to the second quarter 2016, due to deepening consortium pricing pressures and additional competitive entrants and product discontinuations as well as discrete factors, including destocking and shifts in purchase timing due to market conditions. The sequential decline would have been approximately 15 percent without these discrete factors and this deeper decline may continue into 2017.
On November 1, 2016, the Company launched the generic form of SEROQUEL XR, for which it has first-to-file status and 180 days of marketing exclusivity.
INTERNATIONAL PHARMACEUTICALS
During third quarter 2016, the International Pharmaceuticals business unit continued to focus on expanding adjusted margins for its emerging markets businesses, while in-licensing new products and managing the expected loss of exclusivity for certain products at Paladin.
Third quarter 2016 International Pharmaceuticals results include:
Revenues of $71 million, a 3 percent decrease compared to third quarter 2015.
Paladin revenues of $28 million, a 10 percent increase compared to third quarter 2015, due primarily to solid performance across the base business, the Canadian launch of Nucynta and the continuing management of the expected loss of exclusivity for two products.
Emerging market revenues from Litha and Somar of $38 million, a 4 percent decrease compared to third quarter 2015, driven primarily by a decrease in Litha revenues as it manages its recent divestiture of non-core assets and integrates its new portfolio of products and pipeline programs acquired from Aspen.
2016 Financial Guidance
For the full twelve months ended December 31, 2016, at current exchange rates, Endo is reaffirming its full year revenue and adjusted diluted EPS financial guidance. The Company estimates:
Total revenues to be between $3.87 billion and $4.03 billion;
Diluted GAAP EPS from continuing operations is now expected to be between $0.98 and $1.28; and
Adjusted diluted EPS from continuing operations to be between $4.50 and $4.80.
The Company’s 2016 financial guidance is based on the following assumptions:
Adjusted gross margin of approximately 60 percent;
Adjusted operating expenses as a percentage of revenues to be approximately 22.5 percent;
Adjusted interest expense of approximately $450 million;
Adjusted effective tax rate of approximately zero to 2 percent; and
Adjusted diluted EPS from continuing operations assumes full year adjusted diluted shares outstanding of approximately 223 million shares.
Balance Sheet, Liquidity and Other Updates
As of September 30, 2016, the Company had $561.6 million in unrestricted cash; net debt of approximately $7.7 billion and a net debt to adjusted EBITDA ratio of 4.9.
Third quarter 2016 cash used in operating activities was $111.3 million, primarily attributable to the funding of mesh payments, offset partially by improved cash collections.
During third quarter 2016, the Company recorded impairment charges of $93.5 million primarily related to unfavorable formulary changes and market conditions impacting its Sumavel DosePro product.