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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]).

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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.

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]).

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.

Biota Commences Dosing in Phase 2 Trial of Antiviral Therapy BTA074 for Topical Treatment of Condyloma

On February 8, 2016 Biota Pharmaceuticals, Inc. (NASDAQ:BOTA), a biopharmaceutical company focused on the discovery and development of direct-acting antivirals that address infections that have limited therapeutic options, reported that the first patient has been dosed in a Phase 2 double-blind, randomized, placebo-controlled trial to evaluate the safety, tolerability and efficacy of BTA074 5% gel in male and female patients with condyloma, or anogenital warts, caused by human papillomavirus (HPV) types 6 & 11 (Press release, Nabi Biopharmaceuticals, FEB 8, 2016, View Source [SID:1234508993]).

"We are excited to progress BTA074 into a well-powered proof-of-concept study. The currently approved topical treatments for condyloma lack consistent efficacy and cause a considerable amount of undesirable local skin reactions, such as erosions and edema, often leading to the need to stop treatment. With this larger Phase 2 study, we hope to further validate the clinical activity of BTA074 seen in its earlier Phase 2 trial, which showed evidence of overall clearance and a benign side effect profile," remarked Joseph M. Patti, PhD, president and chief executive officer at Biota. "We now have three direct-acting antiviral programs in the clinic, each of which has the potential to help patients by attacking the root cause of their viral infections."

BTA074 is a potent and selective inhibitor of the interaction between two viral proteins from HPV6 and HPV11, and is designed to prevent HPV DNA replication. The Phase 2 trial is expected to enroll approximately 210 patients with anogenital warts and will have a 2-to-1 randomization of BTA074 5% gel to placebo gel. The patients will be dosed twice daily for up to 16 weeks. The primary efficacy objective is to determine the complete clearance rate for baseline anogenital warts from the commencement of therapy to the end of the treatment period. Secondary efficacy endpoints include various assessments of clearance and wart area reduction for both baseline warts and post-baseline emergent warts.

OncoMed Provides Update on Tarextumab Phase 2 Programs

On February 08, 2016 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported updates on the tarextumab (anti-Notch 2/3, OMP-59R5) Phase 2 programs in pancreatic cancer (the "ALPINE" study) and small cell lung cancer (the "PINNACLE" study) (Press release, OncoMed, FEB 8, 2016, View Source [SID:1234509000]). OncoMed will continue the PINNACLE Phase 2 trial of tarextumab in small cell lung cancer following a review of unblinded safety and efficacy data from both the ALPINE and PINNACLE studies by the U.S. Food and Drug Administration (FDA) and the PINNACLE Data Safety Monitoring Board (DSMB). The PINNACLE study remains blinded to OncoMed, investigators and patients. OncoMed has discontinued dosing of tarextumab in the Phase 2 ALPINE clinical study.

"After communicating with the FDA and the PINNACLE trial DSMB we have received feedback that appropriate safety monitoring is in place to continue the PINNACLE trial," said Paul J. Hastings, Chairman and Chief Executive Officer of OncoMed. "While we remain blinded to the PINNACLE trial data, differences in pancreatic and small cell lung cancer biology, combined with our understanding of the potential mechanisms of tarextumab, give us confidence to continue the PINNACLE Phase 2 clinical trial."

ALPINE Analysis

On January 25, OncoMed announced feedback received from a pre-planned DSMB analysis of the ALPINE Phase 2 clinical trial. Following receipt of that feedback, OncoMed promptly discontinued patient dosing in the ALPINE trial and proceeded to unblind the study. Subsequently, based on its own initial analysis of unblinded interim Phase 2 data, OncoMed confirmed key findings by the DSMB regarding futility of the ALPINE trial. Post-hoc, exploratory, and ongoing analyses conducted by OncoMed revealed subgroups of patients with decreased survival and a subgroup which appears to exhibit improved survival with tarextumab. OncoMed will continue to analyze the ALPINE data, and present the data at a future medical meeting.

"We have obtained a good understanding of the results from the ALPINE trial. We believe there are important differences in effects that are unique and specific to tarextumab inhibition of Notch signaling within different tumor types that may have significant impact on the drug’s anti-tumor activity. As such, we feel that there is evidence that tarextumab may behave differently in the small cell lung cancer setting than in the pancreatic cancer setting," said Jakob Dupont, M.D., Chief Medical Officer. "We are encouraged that the PINNACLE study will continue after a careful assessment in collaboration with the independent DSMB, the FDA and the investigators. We hope to make a difference for patients with small cell lung cancer who are in need of new and improved therapies. We thank our tarextumab investigators, their teams, the patients, their families, and caregivers for participating in the ALPINE and PINNACLE clinical trials. Their efforts are advancing our understanding of pancreatic and small cell lung cancer treatment."

Impact on PINNACLE

Following notification of the ALPINE DSMB’s findings, OncoMed initiated interactions with tarextumab clinical investigators, partner GlaxoSmithKline, the FDA and the PINNACLE trial’s DSMB chairperson to assess potential impact of these results on the overall development program, including the ongoing Phase 2 PINNACLE trial in small-cell lung cancer patients.

PINNACLE trial investigators received an addendum to the informed consent form that included a description of the interim analysis from ALPINE. The FDA and the PINNACLE DSMB were provided unblinded data from both Phase 2 trials, a description of OncoMed’s exploratory analysis of the ALPINE results and related trial materials for review. The independent analyses of the FDA and PINNACLE DSMB indicated that the PINNACLE trial could continue under the supervision of the PINNACLE DSMB monitoring for safety and efficacy and that appropriate safeguards are in place.

OncoMed is conducting the PINNACLE Phase 1b/2 clinical trial of tarextumab for the treatment of small cell lung cancer. The randomized Phase 2 trial is comparing progression-free survival (PFS) outcomes for patients treated with tarextumab administered at 15 mg/kg every three weeks in combination with etoposide and cisplatin or carboplatin versus patients who receive placebo plus chemotherapy. Additionally, PFS will be assessed using a predictive biomarker for high tumor Notch3 expression. Secondary endpoints for the Phase 2 study include overall survival, overall response rate, pharmacokinetics, safety and other biomarkers. The PINNACLE study is being conducted at about 40 sites in the U.S. and is expected to enroll approximately 130 patients. Results from the Phase 2 PINNACLE trial are anticipated in 2017.

OncoMed plans to present updated PINNACLE Phase 1b data at the 16th Annual Targeted Therapies of the Treatment of Lung Cancer in Santa Monica, California taking place February 17-20, 2016.

About Tarextumab (anti-Notch2/3, OMP-59R5)

Tarextumab (anti-Notch2/3, OMP-59R5) is a fully human monoclonal antibody that targets the Notch2 and Notch3 receptors. Preclinical studies have suggested that tarextumab exhibits two mechanisms of action: (1) by downregulating Notch pathway signaling, tarextumab appears to have anti-cancer stem cell effects, and (2) tarextumab affects pericytes, impacting stromal and tumor microenvironment.

Tarextumab is part of OncoMed’s collaboration with GlaxoSmithKline (GSK). GSK has an option to obtain an exclusive license to tarextumab during certain time periods through completion of the proof-of-concept Phase 2 trials.