On May 4, 2017 Eleven Biotherapeutics, Inc. (NASDAQ:EBIO), a late-stage clinical oncology company advancing a broad pipeline of novel product candidates based on its Targeted Protein Therapeutics (TPTs) platform, reported financial results for the quarter ended March 31, 2017, and provided a corporate update (Press release, Eleven Biotherapeutics, MAY 4, 2017, View Source [SID1234518830]).

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"During our first quarter of 2017, we made meaningful progress, advancing our Phase 3 registration clinical trial of Vicinium and continuing development efforts with Proxinium and VB6-845d," said Stephen Hurly, President and Chief Executive Officer of Eleven Biotherapeutics. "Importantly, we also presented new preclinical data supporting the potential of our locally- and systemically-administered drug candidates not just as monotherapies, but also in combination with immuno-oncology products, including checkpoint inhibitors. These results accord with our clinical development strategies, and we look forward to further exploring TPTs as new medicines with the potential to offer considerable improvements over existing options."

First Quarter and Recent Business Highlights and Anticipated Upcoming Milestones:

Vicinium: Vicinium is a single protein anti-epithelial cell adhesion molecule (anti-EpCAM) antibody fragment fused with Pseudomonas Exotoxin A (ETA) that is designed to specifically target and deliver a potent anti-cancer payload directly into tumor cells. Vicinium is currently in a Phase 3 registration clinical trial for the treatment of high-grade non-muscle invasive bladder cancer (NMIBC) in subjects who have previously received two courses of Bacillus Calmette-Guérin (BCG) and whose disease is now BCG-unresponsive.

Complete enrollment for Phase 3 registration clinical trial expected in second half of 2017
Topline data from Phase 3 registration clinical trial expected in 2018
Proxinium: Proxinium is a single protein anti-EpCAM antibody fragment fused with ETA for the treatment of late-stage squamous cell carcinoma of the head and neck (SCCHN). Proxinium has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), and Fast Track designation from the FDA. Proxinium has demonstrated anti-tumor activity in prior Phase 1 and 2 clinical trials.

Initiation of Phase 1/2a clinical trial evaluating Proxinium in combination with a checkpoint inhibitor expected in second half of 2017
At the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April, Eleven presented new preclinical results with VB4-845, the active pharmaceutical ingredient used to formulate both Vicinium and Proxinium. Data suggest that VB4-845 induces the expression of HMGB1 in tumor treated cells; HMGB1 is one of three damage-associated molecular patterns (DAMPs) indicative of immunogenic cell death (ICD). Eleven has previously disclosed observations of the other two DAMPs markers – cell surface expression of calreticulin and extracellular release of ATP – following treatment with VB4-845. Together, these results suggest that product candidates formulated with VB4-845 are capable of driving host anti-tumor immune responses that can potentiate the activity of immuno-oncology agents.

As part of the same poster presentation, Eleven shared data from a preclinical model in patient-derived xenograft tumor-bearing mice reconstituted with a human immune system, which was used to assess the combination of intratumoral injection of VB4-845 with the anti-PD1 antibody, nivolumab. Treatment with VB4-845 alone suppressed the growth of injected tumors, while monotherapy nivolumab had little effect. In contralateral, non-injected tumors, responses from mice treated with both VB4-845 and nivolumab were more pronounced than responses in mice treated with either product as a monotherapy. Based on these results, Eleven believes that VB4-845 killing of tumor cells could facilitate and augment checkpoint inhibitor anti-tumor activity.

Systemically-administered TPT Pipeline: Eleven’s initial systemically-administered TPTs leverage a proprietary, highly potent, de-immunized, plant toxin, deBouganin. DeBouganin has picomolar killing of cancer cells and may be effective against cancer stem cells. In preclinical studies, deBouganin demonstrated the ability to avoid multi-drug resistance mechanisms that can decrease the efficacy of small molecule payloads. Based on these results, Eleven believes that deBouganin-based therapies may be effective against a wide spectrum of cancers.

Investigational New Drug Application (IND) submission for VB6-845d planned for first quarter of 2018
At the AACR (Free AACR Whitepaper) Annual Meeting, Eleven presented preclinical data suggesting that its deBouganin payload is capable of effectively killing tumor cells that are resistant to treatment with antibody drug conjugates (ADCs) composed of DM-1 and MMAE payloads when conjugated to the same monoclonal antibody, trastuzumab. The Company believes this is due, in part, to deBouganin’s lack of sensitivity to both the multidrug resistance pumps and the changes in phosphorylation status of proteins involved in cell proliferation and survival that allow some cancers to escape the action of anti-mitotic ADCs.

Corporate: Eleven further expanded its internal clinical development team with two key hires: Gary Conboy as Executive Director, Clinical Sciences and Mary Rohrer as Associate Director, Clinical Operations.

First Quarter 2017 Financial Results:

Cash Position: Cash and cash equivalents were $20.3 million as of March 31, 2017, compared to $25.3 million as of December 31, 2016.
Revenue: Revenue was $0.4 million for the three months ended March 31, 2017, compared to $0.2 million for the same period in 2016. This increase was due to revenue recognized from the License Agreement (License Agreement) with F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc. (Roche).
R&D Expenses: Research and development expenses were $2.9 million for the three months ended March 31, 2017, compared to $4.6 million for the same period in 2016. The decrease was due primarily to a reduction in isunakinra and EBI-031 related development expenses, partially offset by an increase in Vicinium related development expenses.
G&A Expenses: General and administrative expenses were $2.2 million for the three months ended March 31, 2017, compared to $2.1 million for the same period in 2016.
Net Loss: Net loss was $6.1 million, or $0.25 per share, for the three months ended March 31, 2017, compared to net loss of $7.6 million, or $0.39 per share, for the same period in 2016.
Financial Guidance: Based on current operating plans, Eleven expects to have cash to fund research and development programs and operations into early 2018.
Upcoming Events and Presentations:

American Urological Association 2017 Annual Meeting, May 12-16, 2017 in Boston, Massachusetts

On May 4, 2017 Novocure (NASDAQ:NVCR) reported two pilot trials are open and actively recruiting pediatric patients with high grade gliomas to evaluate the safety and feasibility of Tumor Treating Fields (TTFields) in this population (Press release, NovoCure, MAY 4, 2017, View Source [SID1234518829]). The trials are sponsored by the Pediatric Brain Tumor Consortium and Hackensack University Medical Center.

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"Although solid tumor cancers are generally rare in children, brain and spinal cord tumors are the third most common type of childhood cancer," said Dr. Stewart Goldman, Professor of Pediatrics at the Ann & Robert H. Lurie Children Hospital of Chicago. "In order to make a meaningful impact in the lives of these children, we need ongoing research to test the safety and feasibility of potential treatments. We are pleased to see trials testing TTFields in this underserved population."

The first trial, sponsored by the Pediatric Brain Tumor Consortium in collaboration with the National Cancer Institute, will study the feasibility of using TTFields for children with recurrent or progressive suptratentorial high-grade glioma and ependymoma. This study will primarily assess patients’ compliance and number of treatment-related toxicities with secondary outcome measures including the response rate and event-free survival. This trial is actively recruiting an estimated 25 patients.

In the second study, the safety, tolerability and preliminary efficacy of TTFields will be tested in pediatric high-grade gliomas in two cohorts. The initial cohort of patients will receive TTFields alone and will consist of children with recurrent high-grade gliomas. The second cohort of patients will receive TTFields in combination with temozolomide and bevacizumab and is open to children with both newly diagnosed and recurrent gliomas. The trial, sponsored by Hackensack University Medical Center, is actively recruiting and is estimated to enroll 12 patients.

For more information on the trial designs, visit clinicaltrials.gov and reference NCT03033992 and NCT03128047. Treatment with TTFields is not approved for the treatment of pediatric gliomas by the U.S. Food and Drug Administration. The safety and effectiveness of TTFields therapy for pediatric gliomas has not been established.

On May 4, 2017 Syros Pharmaceuticals (NASDAQ: SYRS), a biopharmaceutical company pioneering the discovery and development of medicines to control the expression of disease-driving genes, reported new data generated using its gene control platform, including the discovery of 14 new drug targets in triple negative breast cancer (Press release, Syros Pharmaceuticals, MAY 4, 2017, View Source [SID1234518828]). These discoveries demonstrate the power of Syros’ pioneering approach for systematically analyzing regulatory regions of the genome to identify novel targets for defined subsets of patients with diseases that have eluded other genomics-based approaches. These data were presented at the IMPAKT 2017 Breast Cancer Conference in Brussels, Belgium.

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"Targeted drug discovery in cancer has focused on mutations in protein-coding regions of the genome, and while some cancers have been well served by this approach, many other cancers, including triple negative breast cancer, remain unaddressed," said Eric Olson, Ph.D., Chief Scientific Officer of Syros. "By analyzing the non-coding regulatory region of the genome of tumor cells, we have uncovered new targets in subsets of triple negative breast cancer. Our focus on the regulatory genome, coupled with our expertise in drugging transcriptional targets to control the expression of genes, positions us to develop a new wave of genomic-based medicines for patients with diseases that have remained beyond the reach of other targeted approaches."

Using its proprietary gene control platform to analyze the regulatory genomes from 43 breast cancer patients’ tissue samples, Syros scientists identified highly specialized regions of non-coding regulatory DNA, known as super-enhancers, that drive the expression of genes critical for tumor growth and survival in defined subsets of breast cancer patients. Analysis of the super-enhancers and their associated genes revealed:

Known cancer drivers and patient subsets, with HER2+ patients having a super-enhancer associated with the HER2 gene and ER+ patients having a super-enhancer associated with the ESR1 gene, providing validation that super-enhancer analysis can be used to identify clinically relevant disease drivers in defined patient subsets.
Enhancer-linked genes that were validated as essential for triple negative tumor cell proliferation by CRISPR-mediated gene disruption.

Of those genes, 14 code for newly identified drug targets for triple negative breast cancer across a range of druggable target types, including enzymes, surface receptors, and signaling and metabolic proteins.
A super-enhancer associated with the RARA gene that is predictive of response to SY-1425, a first-in-class selective retinoic acid receptor alpha (RARα) agonist, in multiple preclinical models of breast cancer, including those resistant to treatment with standard-of-care therapies. Notably, the RARA super-enhancer is present across known subtypes of breast cancer, and Syros estimates it is present in about 35 percent of breast cancer patients. SY-1425 is currently in a Phase 2 clinical trial for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who are positive for biomarkers for super-enhancers linked to RARA pathway-associated genes, including RARA and IRF8. Upon achieving clinical proof-of-concept in that trial, Syros plans to expand development of SY-1425 into genomically defined subsets of breast cancer patients.

Syros’ drug discovery and development platform is the first to focus solely on the regulatory genome to systematically and efficiently identify disease-causing alterations in gene expression and create medicines to selectively target transcription to control the expression of genes with the aim of treating cancer, as well as autoimmune and rare genetic diseases. Using its platform, Syros is advancing a growing pipeline of drug candidates, including SY-1425 and SY-1365, a first-in-class selective inhibitor of cyclin-dependent kinase 7 (CDK7), that is on track to begin a Phase 1 clinical trial in the second quarter of this year in patients with transcriptionally dependent solid tumors, including triple negative breast, small cell lung and ovarian cancers.

One May 4, 2017 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology (I-O) company with a pipeline of immune checkpoint antibodies and cancer vaccines, provided a corporate update and reported financial results for the first quarter ended March 31, 2017 (Filing, Q1, Agenus, 2017, MAY 4, 2017, View Source [SID1234518827]).

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"In the first quarter we amended our agreement with Incyte and streamlined and optimized our R&D operations; our balance sheet has been strengthened and our projected burn reduced. Importantly, these steps allow us to focus on clinical programs that support our path to commercialization. In the forefront are our antibodies targeting CTLA-4 and PD-1," said Garo H. Armen, Ph.D., Chairman and CEO of Agenus.

"These initiatives also provide us with the ability to advance our other assets on an accelerated path, including our innovative programs which include next generation immune targets, such as TIGIT and 4-1BB, our neoantigen vaccine, AutoSynVax and our cell therapy programs which we anticipate will be advanced through an externally funded subsidiary."

Cell Therapy Program
Agenus unveils previously undisclosed I-O cell therapy discovery program. This program has been advanced over the last 18 months, including the identification of at least one potential development candidate. The Company plans to pursue its cell therapy assets with the formation of a separate business entity to be majority owned by Agenus and funded externally.

Anticipated Clinical Milestones for H2 2017:

AGEN1884 (anti-CTLA-4) Phase 1 trial: dose-escalation to be completed with safety and pharmacodynamic data compiled; ASCO (Free ASCO Whitepaper) poster presentation in June
AGEN2034 (anti-PD-1) Phase1/2 trial:
Dose-escalation with monotherapy and combination doses
Patient recruitment in a second line cervical cancer trial.
AGEN1884+AGEN2034: commencement of a Phase 1b combination trial, paving the way for a rapid path to registration
AutoSynVax (neoantigen vaccine): readouts for immunogenicity expected in patients with advanced malignancies
Recent Highlights:

Incyte agreement:
Cash infusion of $80 million; projected cost savings of $70M over an 18-month time period
Incyte responsible for fully funding GITR and OX40 clinical programs
Agenus eligible for royalties at 15%
TIGIT reverted to Agenus
Organizational streamlining:
Basel, Switzerland site to close-down later this year; key functions to transition to Cambridge, UK.
Patient enrollment commenced for Phase 1/2 clinical trial for anti-PD-1 antagonist AGEN2034
Initiated Phase 1 clinical trial for AutoSynVax; patient accrual complete
QS-21 milestones:
GSK’s shingles vaccine containing Agenus’ QS-21 filed for regulatory approval in Japan in addition to existing filings for US, Canada and EU
Regulatory approvals anticipated in H2
GSK’s malaria vaccine containing QS-21 to be distributed in select African countries as per WHO’s recommendation.
Identification of next generation anti-CTLA-4 antibody:
Novel differentiated candidate targeting CTLA-4
Manufacturing readiness:
Agenus West successful GMP production of AGEN1884 at 1,000L scale
First Quarter 2017 Financial Results
Cash, cash equivalents and short-term investments were $124 million as of March 31, 2017 compared to $76 million as of December 31, 2016. For the first quarter ended March 31 2017, Agenus reported a net loss of $17.1 million, or $0.18 per share, compared with a net loss for the first quarter of 2016 of $31.8 million, or $0.37 per share. The decrease in net loss for the three months ended March 31, 2017, compared to the net loss for the same period in 2016, was primarily due to the accelerated milestone payment received from Incyte. Our operating expenses increased $6.1 million over the same period in 2016 primarily due to the later stage advancement of our programs.

On May 04, 2017 OncoMed Pharmaceuticals, a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer therapeutics, reported that the first patient has been dosed in the company’s Phase 1a clinical trial of anti-TIGIT (OMP-313M32). Anti-TIGIT is an investigational immuno-oncology therapeutic candidate intended to block suppression of the immune system in tumors and enable immune system anti-tumor activity, similar to marketed checkpoint inhibitors that target the PD-L1-PD-1 axis.

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"The first wave of immuno-oncology agents demonstrated that disabling immune suppression mechanisms in tumors can enable the body’s immune system to fight cancers with good efficacy. Still, available immunotherapies have limited results for many cancer patients, and there remains a pressing need for new agents and combinations to improve outcomes," said Johanna Bendell, M.D., Associate Director of the Drug Development Program at Sarah Cannon Research Institute and a lead investigator for the Phase 1a anti-TIGIT study. "The immuno-suppressive receptor TIGIT is expressed on many different tumor types, giving us reason to believe that an anti-TIGIT antibody, such as OncoMed’s OMP-313M32, has potential for broad activity in cancer patients. I look forward to seeing its performance in the clinic."

The Phase 1 open-label clinical trial is designed to assess the safety and tolerability of escalating doses of anti-TIGIT in patients with advanced or metastatic solid tumors. Secondary objectives for the trial include characterization of the pharmacokinetics, immunogenicity and anti-tumor efficacy of single-agent anti-TIGIT. Pharmacodynamic and potential predictive biomarkers focused on changes in immune system activation will also be explored. Anti-TIGIT will be administered as a single agent every two weeks at escalating dose levels. Once a maximum-tolerated dose has been achieved, an expansion cohort will enroll patients with certain tumor types. The trial will be conducted at five centers in the U.S. and is expected to enroll approximately 30 patients.

"In multiple preclinical studies of anti-TIGIT antibodies, we have observed immune activation and single-agent as well as combination anti-tumor activity, including indications that an anti-TIGIT antibody induced a long-term immune memory response." said Robert Stagg, Pharm.D., OncoMed’s Senior Vice President of Clinical Research and Development. "The initiation of this Phase 1a anti-TIGIT study represents the first of our novel immuno-oncology therapeutics to enter clinical trials. We believe that by blocking TIGIT signaling, our anti-TIGIT antibody may enable T-cell activation and facilitate anti-tumor immune responses with the potential to impact tumor growth."

About Anti-TIGIT
TIGIT (T cell immunoreceptor with Ig and ITIM domains) blocks T cells from attacking tumor cells and is similar in structure and function to the inhibitory protein PD-1. OncoMed’s anti-TIGIT antibody (OMP-313M32) is intended to activate the immune system through multiple mechanisms and enable anti-tumor activity. At the 2017 AACR (Free AACR Whitepaper) Annual Meeting, OncoMed presented data from several studies characterizing anti-TIGIT’s mechanism, identifying pharmacodynamics biomarkers and demonstrating potent anti-tumor responses in in-vivo models. In preclinical studies, anti-TIGIT antibodies increased cytotoxic T-cell activity against tumor cells and decreased T-cell suppression. A surrogate anti-TIGIT antibody used in syngeneic mouse models of different solid tumors demonstrated dose-dependent, potent single-agent anti-tumor efficacy. Anti-TIGIT antibodies also demonstrated combination activity with checkpoint inhibitors anti-PD1 and anti-PD-L1 in preclinical models. When mice whose tumors achieved complete regression following treatment with anti-TIGIT, anti-TIGIT plus anti-PD1 or anti-TIGIT plus anti-PD-L1 were re-challenged with increasing number of tumor cells, they remained protected from tumor growth, suggesting the induction of immunologic memory against the tumor cells. This program is part of OncoMed’s Celgene collaboration.