On April 17, 2018 VBI Vaccines Inc. (Nasdaq: VBIV) ("VBI"), a commercial-stage biopharmaceutical company developing next-generation infectious disease and immuno-oncology vaccines, reported that, upon review of all safety data from the fully enrolled, low-dose patient cohort of the ongoing Phase 1/2a clinical study of VBI-1901 in recurrent Glioblastoma (GBM), the independent Data and Safety Monitoring Board (DSMB) unanimously recommended the continuation of the study without modification (Press release, VBI Vaccines, APR 17, 2018, View Source [SID1234525443]).

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Following this recommendation, VBI has initiated enrollment in the intermediate-dose arm of the dose-escalation phase of this study. Two additional, pre-specified DSMB reviews will occur after the completion of enrollment in the intermediate-dose study arm and the high-dose study arm, respectively.
"We are encouraged by the safety profile of this candidate so far and are excited to continue enrollment in the intermediate dose cohort of this Phase 1/2a study, our first clinical study in immuno-oncology," said Jeff Baxter, VBI’s president and CEO. "In recurrent GBM, a devastating CMV-associated tumor, patients have few effective treatment options, and we believe that VBI-1901 has the potential to stimulate immune responses critical to boosting anti-tumor immunity."

About the Phase 1/2a Study Design
VBI’s two-part Phase 1/2a study is a multi-center, open-label, dose-escalation study of VBI-1901 in approximately 28 patients with recurrent GBM:

Part A: Dose-escalation phase to define the safety, tolerability, and optimal dose level of VBI-1901 in recurrent GBM patients. This phase is expected to enroll up to 18 patients in three dose cohorts.

Part B: A subsequent extension of the optimal dose level, as defined in the dose escalation phase. This phase is expected to enroll an expanded cohort of approximately 10 additional patients.
VBI-1901 is administered intradermally and is adjuvanted with granulocyte-macrophage colony-stimulating factor (GM-CSF), a potent adjuvant that mobilizes dendritic cell function. Patients in both phases of the study will receive vaccine every four weeks until tumor progression.
Additional information, including a detailed description of the study design, eligibility criteria, and investigator sites, is available at ClinicalTrials.gov using identifier NCT03382977.
About VBI-1901 and GBM
VBI-1901 is a novel immunotherapy developed using VBI’s eVLP technology to target two highly immunogenic cytomegalovirus (CMV) antigens, gB and pp65. Scientific literature suggests CMV infection is prevalent in multiple solid tumors, and recent research has demonstrated that an anti-CMV dendritic cell vaccination regimen may extend overall survival in patients with GBM. Additionally, recent preclinical studies confirmed that VBI-1901 may be a potent, "off-the-shelf" therapeutic vaccine.
Glioblastoma is among the most common and aggressive malignant primary brain tumors in humans. In the U.S. alone, 12,000 new cases are diagnosed each year. The current standard of care for treating GBM is surgical resection, followed by radiation and chemotherapy. Even with aggressive treatment, GBM progresses rapidly and is exceptionally lethal, with median patient survival of less than 16 months.

Genprex has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission (Filing, 10-K, Genprex, 2018, APR 17, 2018, View Source [SID1234527531]).

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On April 17, 2018 Euronext Paris: FR0010331421 – IPH) reported that new preclinical data of the Company’s broad and innovative portfolio of next generation immunotherapies have been presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, April 14-18, in Chicago (Press release, Innate Pharma, APR 17, 2018, View Source [SID1234525405]).

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Eric Vivier, Chief Scientific Officer of Innate Pharma, said: "Innate Pharma has always been driven by innovation and we are very proud to present new preclinical data from our broad and innovative portfolio of next generation immunotherapies. These data not only underpin our ongoing clinical program but also highlight the next wave of immunotherapies in cancer."

Innate Pharma has presented four posters featuring new preclinical data at the Immune Checkpoints sessions on 16 April.

Monalizumab in combination with cetuximab:
Data (ID: 1690) demonstrates that squamous cell carcinoma of the head & neck (SCCHN) tumor cells are infiltrated by NK and CD8+ T cells expressing CD94/NKG2A and that these cancer cells express the natural ligand of NKG2A, HLA-E. Blockade of NKG2A potentiated cetuximab induced antibody-dependent cell-mediated cytotoxicity (ADCC) towards SCCHN cell lines. Overall, the data support the Company’s ongoing Phase I/II trial for the combination of monalizumab and cetuximab in recurrent and/or metastatic SCCHN for which first clinical activity data will be presented today at 1:00 PM Chicago time during the "Phase I/II, II, and III Trials in Progress" poster session.

Monalizumab in combination with durvalumab:
New preclinical data (ID: 2714) suggest the combination of monalizumab and durvalumab is a potent immunotherapy for solid tumors. Tumor infiltrating NK and CD8+ T cells expressing NKG2A and/or PD-1 are present in several cancer types.

Blocking both NKG2A/HLA-E and PD-1/PD-L1 pathways enhanced anti-tumor responses of NK and CD8+ T cells in vitro and in vivo in mice. Taken together, these data support the rationale for ongoing clinical trials investigating the monalizumab/durvalumab combination in various solid tumors
.
IPH52 and IPH53, targeting the adenosine pathway:
Additionally, preclinical data (ID: 2718) support the development of anti-CD39 (IPH52) and anti-CD73 (IPH53) neutralizing antibodies targeting the ATP/Adenosine immune checkpoint pathway for cancer immunotherapy, potentially in combination with chemotherapy or immune checkpoint blockade.
These antibodies potently inhibit the enzymatic activity of both the soluble and membrane-associated forms of their respective target enzymes. In vitro, both antibodies efficiently reverse adenosine-mediated T cell suppression in the presence of ATP. IPH52, a first-in-class CD39 blocking antibody, sustains high concentrations of extracellular ATP that promotes immune responses by enhancing dendritic cell (DC) activation and subsequent T cell proliferation. IPH53 is more potent in vitro than benchmark anti-CD73 antibodies currently under clinical development. Additionally, combining IPH52 and IPH53 lead to a strong reversion of immune cell inhibition in the presence of ATP. Humanized IPH52 and IPH53 are currently in preclinical development.

Siglec-9, a new checkpoint for cancer immunotherapy:
In another highlight, preclinical findings (ID: 2713) for a first-in-class antibody program targeting Siglec-9 were presented. Siglecs comprise a family of 15 members of sialic acid-binding receptors. Siglec-9 is an inhibitory receptor of the family that is expressed on a broad range of immune cells of both lymphoid and myeloid origin. Siglec-9 can interact with sialic acids expressed by tumors, leading to dampened immune cell functions. Thus, Siglec-9-sialic acid interaction disruption may promote anti-tumor immunity.
Data show that antibodies against Siglec-9 generated by Innate Pharma enhance NK cell cytotoxicity. This anti-tumor response is improved by the blockade of the immune checkpoint NKG2A. Further, data demonstrate that Siglec-9 is highly expressed on tumor-infiltrating myeloid cells and upregulated on T cells in cancer, suggesting a potential additional role as an inhibitory checkpoint agent.

On April 17, 2018 Sierra Oncology, Inc. (Nasdaq: SRRA), a clinical stage drug development company focused on advancing next generation DNA Damage Response (DDR) therapeutics for the treatment of patients with cancer, reported preclinical results in two posters, including late-breaking data being presented today, for its Checkpoint kinase 1 (Chk1) inhibitor SRA737, at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018 in Chicago, Illinois (Press release, Sierra Oncology, APR 17, 2018, View Source [SID1234525426]).

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"The data presented within these posters demonstrate that SRA737, as monotherapy and in combination with a poly ADP-ribose polymerase inhibitor (PARPi) such as niraparib, has anti-tumor activity across a broad range of settings. Anti-tumor activity was observed both in homologous recombination repair (HRR) proficient cancers which are poor candidates for PARPi alone, and in HRR deficient tumor cells that have acquired resistance to either PARPi and/or platinum agents," said Dr. Christian Hassig, Chief Scientific Officer of Sierra Oncology. "We also observed inhibition of tumor growth in aggressive CCNE1-driven high grade serous ovarian cancer (HGSOC) patient-derived xenografts. CCNE1 amplification is known to increase replication stress and genomic instability, leading to increased reliance on Chk1. Analogous to PARPi, which first exhibited robust activity in patients harboring BRCA mutations, Chk1 inhibitors such as SRA737 may prove effective in defined genetic backgrounds of high replication stress, such as CCNE1 amplification."
The efficacy of SRA737 monotherapy is currently being investigated in an ongoing Phase 1/2 clinical trial (NCT02797964) in replication stress-driven cancer including a patient cohort with CCNE1 amplified HGSOC.
Sierra is also planning to investigate SRA737 in combination with niraparib in a multicenter Phase 1b/2 study in subjects with metastatic castration-resistant prostate cancer (mCRPC), anticipated to be initiated in the fourth quarter of 2018. Janssen Research & Development, LLC will supply TESARO’s ZEJULA (niraparib) for the trial, which is to be led by Professor Johann de Bono, Regius Professor of Cancer Research, Head of the Division of Clinical Studies and Professor in Experimental Cancer Medicine at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.
The two posters will be available on the company’s website at www.sierraoncology.com.
SRA737 AACR (Free AACR Whitepaper) 2018 Late-Breaker: The Novel Oral Chk1 Inhibitor, SRA737, Is Active in Both PARP Inhibitor Resistant and CCNE1 Amplified High Grade Serous Ovarian Cancers
Data being presented in this late-breaking poster is from research conducted in the laboratory of Dr. Fiona Simpkins, Assistant Professor of Obstetrics and Gynecology at The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Approximately 20% of HGSOCs harbor CCNE1 gene amplification. CCNE1 amplification is known to increase replication stress and genomic instability, leading to increased reliance on Chk1. These tumors show intrinsic resistance to PARPi and frequently are, or become resistant to, platinum therapy, leaving patients without effective treatment options. In this research, Chk1 inhibition by SRA737 as monotherapy in CCNE1 amplified ovarian cancer models was shown to: a) increase levels of replication stress and DNA double strand breaks, b) in turn leading to excessive genomic instability, c) resulting in subsequent tumor cell death, tumor regression and a profound survival benefit.

A distinct subgroup comprising approximately 50% of HGSOC have defective HRR genes (e.g. BRCA1/2 mutation). HRR deficient HGSOC are initially sensitive to PARPi but drug resistance ultimately emerges, frequently involving genetic reversion of BRCA mutated genes and partial restoration of HRR. HRR deficiency may also elevate sensitivity to Chk1 inhibition, given the well-established role of Chk1 in HRR, as well as other aspects of the replication stress response. In this research, SRA737 demonstrated activity as a single agent, as well as in combination with PARPi, in acquired PARPi-resistant cells. Furthermore, SRA737 in combination with PARPi demonstrated preliminary evidence of synergistic tumor growth inhibition in a HGSOC patient-derived xenograft model.

SRA737 AACR (Free AACR Whitepaper) 2018 Poster: The Chk1 Inhibitor, SRA737, Synergizes with the PARP Inhibitor, Niraparib, to Kill Carcinoma Cells via Multiple Cell Death Pathways
Sierra presented a second poster at AACR (Free AACR Whitepaper) with data from research conducted in the laboratory of Dr. Paul Dent, Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia. The results demonstrate that the combination of SRA737 and niraparib was effective in HRR proficient ovarian and breast tumor cell lines and that both autophagic cell death and apoptotic pathways contribute to SRA737/niraparib-induced tumor cell killing. PARPi monotherapy is known to be substantially less effective in treating patients with HRR proficient tumors, making the combination with SRA737 a novel and potentially more effective treatment option. Moreover, the involvement of multiple cell death mechanisms may decrease the potential for tumors to develop resistance to these agents.

On April 17, 2018 Novocure (NASDAQ: NVCR) reported positive top-line results from its STELLAR phase 2 pilot trial in mesothelioma demonstrating clinically meaningful improvements in overall survival and progression free survival among patients who received Tumor Treating Fields plus standard of care chemotherapy, pemetrexed and cisplatin or carboplatin, compared to historical control data of patients who received standard of care chemotherapy alone (Press release, NovoCure, APR 17, 2018, View Source [SID1234525444]).

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The final data exceeded the results of the interim analysis presented in December 2016 at the International Association for the Study of Lung Cancer (IASLC) 17th World Conference on Lung Cancer for all efficacy endpoints. No device-related serious adverse events were reported. Novocure will submit the full data for presentation at an upcoming medical conference.

"We are extremely pleased with these top-line results, which bring us one step closer to realizing the potential for a new treatment for mesothelioma patients in desperate need," said Dr. Eilon Kirson, Novocure’s Chief Science Officer and Head of Research and Development. "Mesothelioma is the first torso indication for which Novocure will pursue FDA approval. The STELLAR data reinforce our belief that Tumor Treating Fields may be a broadly applicable platform technology for the treatment of solid tumors. We look forward to sharing the detailed results of the study with the lung cancer community at an upcoming medical conference."

Novocure previously received Humanitarian Use Device (HUD) designation for the use of Tumor Treating Fields for the treatment of pleural mesothelioma. Based upon the final STELLAR data, Novocure plans to submit a Humanitarian Device Exemption (HDE) application to the FDA for approval. An approved HDE would allow Novocure to market Tumor Treating Fields in combination with standard of care chemotherapy as a treatment for pleural mesothelioma in the United States.

Tumor Treating Fields in combination with standard of care chemotherapy is an investigational treatment for pleural mesothelioma and is not approved for this indication. These results are preliminary top-line data and are subject to further analysis.

About STELLAR

The STELLAR trial is a phase 2 pilot single-arm, open-label, multi-center trial designed to test the efficacy and safety of Tumor Treating Fields in combination with standard of care chemotherapy, pemetrexed combined with cisplatin or carboplatin, in 80 patients with unresectable, previously untreated malignant pleural mesothelioma. The historical control for this trial is the results of the 2003 pemetrexed phase 3 FDA registration trial.

An interim analysis of the first 42 patients enrolled in the trial with an average follow-up time of 11.5 months was presented at the International Association for the Study of Lung Cancer in December 2016. The one-year survival rate of patients treated with Tumor Treating Fields combined with pemetrexed and cisplatin or carboplatin was 80 percent (compared to 50 percent in pemetrexed and cisplatin-alone historical controls). Median progression free survival in the Tumor Treating Fields-treated group was 7.3 months (compared to 5.7 months in pemetrexed and cisplatin-alone historical controls) and one-year survival rate was 79.7 percent (compared to 50.3 percent in pemetrexed and cisplatin-alone historical controls). Median overall survival had not yet been reached. No device-related serious adverse events had been reported to date.

About Mesothelioma

Malignant mesothelioma is a rare thoracic solid tumor cancer that has been strongly linked to asbestos exposure. It has a long latency period of at least 20-30 years following exposure, and global incidence is still increasing in countries where asbestos is still in use. There are approximately 3,000 new cases of mesothelioma annually in the United States. The prognosis of mesothelioma patients is very poor, with a median overall survival of approximately 12 months in most reported studies.