Nymox Announces Prostate Cancer Clinical Trial Results From Completed 18 Month Endpoint Study

On February 09, 2016 Nymox Pharmaceutical Corporation (NASDAQ:NYMX) reported results from the completion of the Company’s U.S. 40 month (18 month outcomes) localized prostate cancer Phase 2 NX03-0040 clinical trial of fexapotide triflutate (NX-1207) (Press release, Nymox, FEB 9, 2016, View Source [SID:1234509016]). The study successfully met its pre-determined endpoints. Cancer progression clinical outcomes were significantly improved in the fexapotide treated patient groups.

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 clinical trial commenced in February 2012 at 28 U.S. investigational clinical trial sites and enrolled 147 patients with low grade localized (T1c) prostate cancer. The study lasted 40 months overall from the first patient randomized to the last patient 18 month endpoints.

Results from the completed 18 month outcome study after a single injection of fexapotide included the following:

Absence of tumors (Primary Endpoint) controlled for size in baseline area: fexapotide 15 mg superior to control (p=.035); crossover fexapotide 15 mg superior to control (p=.002); crossover fexapotide overall superior to control (p=.014).

75.5% reduction in biopsy proven prostate cancer Gleason upgrades (pathological progression) after 18 months in fexapotide 15 mg treated patients compared to control (p=.0055). 71.7% reduction in prostate cancer Gleason upgrades in fexapotide treated patients overall (p=.0045 vs controls).

84.8% reduction after 18 months in surgery or radiotherapy instituted for prostate cancer Gleason upgrade (biopsy worsening) in fexapotide treated patients overall compared to control group (p=.014).

54.8% reduction after 18 months in surgery or radiotherapy instituted for all causes with or without prostate cancer Gleason upgrade in fexapotide 15 mg treated patients compared to control (p=.026).

Significant improvement for fexapotide patients compared to controls in 4 out of 4 Secondary Endpoints. Tumor volume reduction in the treated area, combined dosages (p=.04); tumor volume change in prostate overall, fexapotide patients overall (p=.014); median tumor grade outcome in the treated area, all dosages (fexapotide median benign, vs control median Gleason 3+3), and superior median tumor grade in prostate overall, fexapotide 15 mg vs controls.

Consistent safety results with no significant drug-related adverse events and no significant related sexual adverse events.

Overall superior results for the fexapotide 15 mg dose compared to the 2.5 mg dose (dose-response).

Other statistically significant improvement outcomes in fexapotide patients compared to controls, to be presented comprehensively at medical meetings.
"These results demonstrate that a single targeted office injection of fexapotide has led to statistically significant improvement in outcomes with much less surgery or radiotherapy required after 18 months. This means a reduction in patient discomfort, and a reduction in permanent side effects and life changes when the more invasive treatments are required," said Paul Averback, CEO of Nymox.

Dr. Averback added, "Based on these outcomes, we believe there are exciting potential patient benefits from one or more painless fexapotide office injections for this common and distressing condition."

The Company will report at a later date concerning its plans for moving the compound forward toward the market for this important medical problem.

U.S. Food and Drug Administration Grants Breakthrough Therapy Designation for Adaptimmune’s Affinity Enhanced T-cell Therapy Targeting NY-ESO in Synovial Sarcoma

On February 9, 2016 Adaptimmune Therapeutics plc (Nasdaq: ADAP), a leader in the use of TCR engineered T-cell therapy to treat cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for the company’s affinity enhanced T-cell therapy targeting NY-ESO in synovial sarcoma for HLA-A*201, HLAA*205 or HLA-A*206 allele-positive patients with inoperable or metastatic synovial sarcoma who have received prior chemotherapy and whose tumor expresses the NY-ESO-1 tumor antigen (Press release, Adaptimmune, FEB 9, 2016, View Source [SID:1234509015]).

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 committed to investigating the potential of our NY-ESO-1-T cell therapy across a variety of cancers. We are pleased that the FDA has granted Breakthrough Therapy designation for our T-cell therapy in synovial sarcoma, recognizing both the unmet need for patients suffering from this disease as well as the promise of these early data," said Dr. Rafael Amado, Adaptimmune’s Chief Medical Officer. "We look forward to working closely with the FDA to expedite the clinical development of this therapeutic candidate."

The Breakthrough Therapy designation was based on the results of a phase I/II trial in patients with unresectable, metastatic or recurrent synovial sarcoma who have received prior chemotherapy. Patients were treated with lymphodepleting chemotherapy followed by immunotherapy with T-cells engineered to recognize an HLA-A2 restricted NY-ESO-1 peptide.

Data from this study were most recently presented at the 2015 Annual Meeting of the Society of Immunotherapy for Cancer (SITC) (Free SITC Whitepaper) in November 2015. In the primary efficacy analysis, 60 percent of the 10 patients receiving the target dose of cells responded, and there was a 50 percent overall response rate in the 12 patients receiving any dose of cells. 90 percent (9/10) of those patients who received the target dose and 75 percent (9/12) of all patients were alive and on long term follow-up. The most common adverse events included nausea, anemia, pyrexia, lymphophenia and neutropenia. Cytokine release syndrome (CRS) was seen in four of twelve subjects, with grade 3 CRS observed in two subjects; no grade 4 CRS events were observed.

Adaptimmune recently announced that it will aim to initiate pivotal studies with its affinity enhanced Tcell therapy targeting NY-ESO in synovial sarcoma around year end 2016, and that it will also explore development in myxoid round cell liposarcoma. Studies with this therapy are also under way in myeloma, melanoma, ovarian cancer and non-small cell lung cancer.

About Breakthrough Therapy Designation
The breakthrough therapy designation was enacted as part of the Food and Drug Administration Safety and Innovation Act of 2012 and is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for breakthrough therapy designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy. According to the FDA, breakthrough therapy designation conveys all of the fast track program features, more intensive FDA guidance on an efficient drug development program, an organizational commitment involving senior managers, and eligibility for rolling review and priority review of the company’s Biologic License Application when submitted.

About Soft Tissue Sarcoma
Soft tissue sarcomas can develop from soft tissues like fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues. There are approximately 50 types of soft tissue sarcomas, including synovial sarcoma, a cancer of the connective tissue around joints. Soft tissue sarcomas can develop at almost any anatomic site, such as the extremities, trunk or thorax, abdomen and retroperitoneum, pelvis and the head and neck region. The more common soft tissue sarcomas originate from muscle, nerve tissue, fat or deep skin tissue. For a number of sarcomas, such as synovial sarcoma, the tissue origin is not well characterized. Surgical resection is the standard therapy for localized disease and radiation therapy (preoperative or postoperative) is added in selected cases. The American Cancer Society estimates 11,930 new soft tissue sarcoma diagnoses (6,610 cases in males and 5,320 cases in females) in the United States in 2015, representing approximately 2 percent of all cancers, and approximately 4,870 Americans (2,600 males and 2,270 females) are expected to die of soft tissue sarcomas.

Immune Design Announces Positive Topline Data From Three Phase 1 Clinical Trials of Immuno-oncology Product Candidates

On February 09, 2016 Immune Design (Nasdaq:IMDZ), a clinical-stage immunotherapy company focused on oncology, reported positive topline data from three ongoing Phase 1 oncology studies that support continued development of its two primary in vivo immuno-oncology product candidates, CMB305 and G100 (Press release, Immune Design, FEB 9, 2016, View Source [SID:1234509012]).

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!

CMB305: First-in-class Prime-boost Immunotherapy Targeting NY-ESO-1 Tumors

Data from a completed first-in-human dose-escalation study and an early subset of patients from an expansion study of CMB305 as a single agent in patients with cancers expressing the NY-ESO-1 tumor antigen revealed:

CMB305 was safe, without dose-limiting toxicities, as reviewed by an independent data safety monitoring board (DSMB);
A significant subset of CMB305-treated patients had NY-ESO-1-specific CD8 T cell responses that were generated or increased after therapy;
Patients who did respond immunologically had a greater degree of antigen-specific T cell response than that previously reported in a Phase 1 study of LV305 alone, which is consistent with the intent of the prime-boost approach; and
Preliminary clinical benefit in the form of progression-free rate (PFR) was observed in patients with soft tissue sarcoma.
LV305: Novel Vector Delivering NY-ESO-1 RNA Specifically to Dendritic Cells in vivo Maintains Safety and Immunogenicity with Improved Clinical Benefit Profile

Data from the expansion study following the previously-reported dose escalation study of LV305 in patients with tumors expressing NY-ESO-1 revealed:

A consistently favorable safety profile, as reviewed by an independent DSMB;
A consistent immune response rate; and
An improved clinical benefit profile.
G100: Intratumoral Administration of aTLR4 Agonist Significantly Modifies the Tumor Microenvironment (TME) and Maintains Clinical Benefit

New data from the completed pilot trial of G100 with local radiation in patients with Merkel cell carcinoma revealed:

Safety was consistent with that originally reported, demonstrating an acceptable profile alone or in combination with local radiation;
G100 significantly altered the TME, causing inflammation and transforming tumors to a "hot" state in G100 responding patients; and
Clinical benefit remained constant with the full patient set.
Abstracts for each of these three Phase 1 studies have been submitted for presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (June 3-7, 2016). If afforded the opportunity to present, it is the company’s intent to work with the Principal Investigator for each product candidate to present a more complete data set at the Conference.

"The accumulating data, including this new set, clearly supports proceeding with the clinical development of our two first products, CMB305 and G100, each activating the anti-tumor immune response by targeting a predefined tumor antigen or neo-antigens, respectively," said Carlos Paya, M.D., Ph.D, President and Chief Executive Officer of Immune Design. "The initiation of randomized studies in which we are combining our two products with inhibitors of the PD-1/L1 axis through our collaborations with Genentech and Merck will provide the evidence as to how novel products that activate the immune system and aim to make tumors "hot" add or synergize with check-point inhibitors."

Additional Information on Immune Design’s Distinct Immuno-oncology Approaches

About CMB305

CMB305 is an immuno-oncology product candidate that involves the sequential dosing of two active agents, LV305 and G305. LV305 is a hybrid vector from the ZVex discovery platform that specifically targets dendritic cells (DCs) in vivo and delivers the RNA for NY-ESO-1, enabling the DCs to express the entire tumor antigen and potentially induce a diverse set of CTLs targeting NY-ESO-1 in tumors. G305, in contrast, is designed to boost the CTL response via the induction of antigen-specific CD4 "helper" T cells. G305 consists of recombinant NY-ESO-1 protein formulated with a proprietary synthetic small molecule called glucopyranosyl lipid A (GLA), the novel TLR4 agonist at the core of the GLAAS platform. CMB305 is intended to be an "off-the shelf" therapy that does not require patient-specific manufacturing or ex vivo manipulation of patient samples. Immune Design has conducted prior studies to establish the safety and individual immunologic activity of LV305 and G305. CMB305 is currently being evaluated in a Phase 1B trial in patients with locally advanced, relapsed or metastatic solid cancers whose tumors express NY-ESO-1 and a randomized Phase 2 trial of CMB305 combined with Genentech’s investigational cancer immunotherapy, atezolizumab (anti-PD-L1), in patients with soft tissue sarcoma, pursuant to a collaboration with Genentech.

About G100

G100 is Immune Design’s intratumoral Immune Activation approach to treating cancer and is expected to directly activate dendritic and other antigen presenting cells near the tumor, which may enhance the function of pre-existing cytotoxic T lymphocytes (CTLs) and create both a local and systemic immune response against neo-antigens. G100 is a product of the company’s GLAAS platform and recently completed a Phase 1 study in patients with Merkel cell carcinoma. G100 also has potential therapeutic utility in any accessible tumor and will be investigated in combination with local radiation and Merck’s anti-PD-1 agent, KEYTRUDA, in a randomized study in patients with follicular Non-Hodgkin lymphoma, pursuant to a collaboration with Merck.

ZIOPHARM Announces First Patient Enrolled in Phase 1 Study of Second Generation Non-Viral CD19-Specific CAR T-Cell Therapy for Advanced Lymphoid Malignancies

On February 09, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new cancer immunotherapies, reported that the first patient has been enrolled in a Phase 1 clinical study of its second generation non-viral CD19-specific chimeric antigen receptor (CAR) modified T-cell therapy in patients with advance lymphoid malignancies (Press release, Ziopharm, FEB 9, 2016, View Source [SID:1234509011]). The CD19-specific T cells were modified using the Sleeping Beauty system to stably express the CAR in T cells.

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 Sleeping Beauty transposon-transposase is a unique non-viral system for introducing genes encoding CARs and T-cell receptors (TCRs) into lymphocytes and is exclusively licensed by Intrexon Corporation (NYSE:XON) through The University of Texas MD Anderson Cancer Center and accessed as part of ZIOPHARM’s collaboration. This non-viral approach may play an important role in immunotherapy and has several potential advantages over viral delivery systems, including:

Lower cost of generating genetically modified T cells
Generate T cells with minimal ex vivo processing
Conduit to targeting solid tumor neo-antigens using TCRs
Pathway to overcome regulatory hurdles

"The survival benefit seen in early clinical results with our first generation CD19-specific CAR+ T cells were highly encouraging, and preclinical results to date suggest that our next generation CAR structure may improve upon these outcomes," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. "These studies continue to strengthen our understanding of the application and benefit of the Sleeping Beauty platform, the only efficient non-viral gene transfer system in clinical application. Sleeping Beauty offers the potential to significantly reduce the expense and simplify the implementation of genetically modified T cells, both of which are critical to the personalization and broad application of immunotherapies based on CARs and TCRs."

In two prior trials the first generation CD19-specific CAR+ T cells, patient-derived (autologous) or donor-derived (allogeneic) T cells were administered to recipients with advanced CD19-expressing leukemias and lymphomas after hematopoietic stem-cell transplantation (HSCT). Results demonstrated an apparent doubling of survivals compared to historical controls.

The second-generation Sleeping Beauty CAR+ T cells employ a revised CAR construct designed to improve persistence and anti-tumor response over the first generation therapy. Additionally, this investigational treatment is independent of HSCT. This trial is being conducted at MD Anderson.

Pfizer Names Executive Leadership Team for Combined Organization Upon Close of Proposed Allergan Transaction

On February 8, 2016 Pfizer Inc. (NYSE: PFE) reported the executive leadership team for the combined Pfizer and Allergan plc (NYSE: AGN) business following the close of the proposed transaction (Press release, Pfizer, FEB 8, 2016, View Source [SID:1234509009]).

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!

As previously announced, following the closing, Brent Saunders will become President and Chief Operating Officer of the combined company with responsibility for the oversight of Pfizer and Allergan’s combined commercial businesses, manufacturing and strategy functions.

Effective immediately and through the closing of the transaction Pfizer’s Global Innovative Pharma (GIP) business and its Vaccines, Oncology and Consumer (VOC) business will operate separately under the leadership of Albert Bourla, currently Group President, VOC. Upon the closing of the transaction, the Vaccines and Oncology businesses will be combined with the GIP business, and Albert Bourla will become Group President, Global Innovative Pharma, leading all of these businesses.

In addition, following the close of the transaction, the combined company will create a new operating segment named Global Specialty and Consumer Brands that will include Pfizer’s Consumer Healthcare unit and Allergan’s ophthalmology and aesthetics businesses, and Botox Therapeutic and Cosmetic. Bill Meury, currently Executive Vice President and President Branded Pharma at Allergan, will become Group President, Global Specialty and Consumer Brands, Pfizer.

After the close of the proposed transaction, Pfizer will continue to manage the combined company’s commercial operations through two distinct businesses: an Innovative Products business and an Established Products business. The Innovative Products business will be composed of two operating segments: the Global Innovative Pharmaceutical and the Global Specialty and Consumer Brands segment. The Established Products business will continue to be led by John Young, and consist of the Global Established Pharmaceutical segment, including all legacy Hospira commercial operations.

Upon the close of the transaction, the following executives will be members of the company’s executive leadership team, reporting to Brent Saunders:

Albert Bourla, Group President, Global Innovative Pharma
Tony Maddaluna, Executive Vice President, President Pfizer Global Supply
Bill Meury, Group President, Global Specialty and Consumer Brands
Laurie Olson, Executive Vice President, Strategy, Portfolio and Commercial Operations
John Young, Group President, Global Established Pharma
The following Pfizer executives are continuing in their roles reporting to Ian Read, Pfizer Chairman and Chief Executive Officer:

Frank D’Amelio – Executive Vice President, Business Operations and Chief Financial Officer
Mikael Dolsten – President, Worldwide Research and Development
Chuck Hill – Executive Vice President, Worldwide Human Resources
Rady Johnson – Executive Vice President, Chief Compliance and Risk Officer
Doug Lankler – Executive Vice President, General Counsel
Freda Lewis-Hall – Executive Vice President, Chief Medical Officer
Sally Susman – Executive Vice President, Corporate Affairs
"We are creating an executive team that has deep industry knowledge, a proven track record of success and an unwavering commitment to the patients we serve. I look forward to working with these outstanding leaders to achieve the full potential of this combination and fulfill our mission of becoming the premier biopharmaceutical company in our industry," said Ian Read, Chairman and Chief Executive Officer of Pfizer. "We are designing the combined company to preserve and enhance our option to potentially separate the innovative and established businesses into separate companies in the future, and continue to expect to make a decision about any potential separation by no later than the end of 2018."

Pfizer also announced that Geno Germano, Group President, Global Innovative Pharma Business, will be leaving the company.

"We thank Geno for his many contributions to Pfizer’s business over the past seven years," continued Read. "Under Geno’s leadership we have laid the foundation for the growth potential of our vaccines and oncology businesses, strengthened our in-line portfolio with products like Enbrel, Xeljanz and Eliquis and improved our innovative late-stage pipeline with programs like bococizumab and tanezumab."

Pfizer and Allergan will continue to operate as two separate companies until the close of the transaction, which is expected in the second half of 2016, and is subject to certain conditions, including: receipt of regulatory approval in certain jurisdictions, including the United States and European Union; the receipt of necessary approvals from both Pfizer and Allergan shareholders; and the completion of Allergan’s pending divestiture of its generics business to Teva Pharmaceuticals Industries Ltd.