On April 17, 2018 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology Company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, reported a poster presentation of data from preclinical and clinical studies evaluating poziotinib in HER2 exon 20 mutations in non-small cell lung cancer (NSCLC) and summarizing a dataset of the prevalence of HER2 exon 20 across solid tumors by scientists from the University of Texas MD Anderson Cancer Center at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) which is taking place in Chicago, Illinois, April 14-18, 2018 (Press release, Spectrum Pharmaceuticals, APR 17, 2018, View Source [SID1234525442]).

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"We are excited to see the first presentation of data for poziotinib in HER2 exon 20 mutations in NSCLC," said Joe Turgeon, President and Chief Executive Officer of Spectrum Pharmaceuticals. "These data build upon previous results from poziotinib studies and indicate that this drug could be effective in treating both EGFR and HER2 exon 20 mutations. Furthermore, new data from MD Anderson reveal that these mutations are found across a variety of solid tumors and there is strong rationale for evaluating poziotinib in a basket study."
"The pre-clinical and early clinical activity of poziotinib in EGFR and HER2 exon 20 mutant NSCLC suggests poziotinib could be a promising agent for the numerous cancer types driven by HER2 exon 20 mutations," said Jacqulyne Robichaux, Ph.D, Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center. "We have previously shown that poziotinib is an effective inhibitor of EGFR exon 20 insertion mutations in vitro and in vivo. These data show that poziotinib overcomes de novo resistance of HER2 exon 20 mutations in NSCLC and other cancers. Further evaluation of poziotinib in solid tumors is warranted."

About Poziotinib
Poziotinib is a novel, Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) that inhibits the tyrosine kinase activity of EGFR as well as HER2 and HER4. Importantly this, in turn, leads to the inhibition of the proliferation of tumor cells that overexpress these receptors. Mutations or overexpression/amplification of EGFR family receptors have been associated with a number of different cancers, including non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer. Spectrum received exclusive license to develop, manufacture, and commercialize worldwide excluding Korea and China from Hanmi Pharmaceuticals. Poziotinib is currently being investigated by Spectrum and Hanmi in several mid-stage trials in multiple solid tumor indications.

On April 17, 2018 NewLink Genetics Corporation (NASDAQ:NLNK) reported that it presented a poster entitled "Indoximod modulates AhR-driven transcription of genes that control immune function" in the Immunomodulatory Agents and Interventions session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2018 Annual Meeting in Chicago (Press release, NewLink Genetics, APR 17, 2018, View Source [SID1234525425]).

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"The data demonstrate that indoximod has a unique mechanism of action, remarkably differentiated from IDO enzymatic inhibitors. This different mechanism may contribute to antitumor immune responses in the IDO pathway and through activity independent of IDO," said Charles J. Link, Jr., M.D., Chairman and Chief Executive Officer.

The data suggest that indoximod regulates the differentiation of helper T cells toward an immuno-stimulatory helper function and downregulates genes that control the differentiation of T cells into immuno-suppressive regulatory T cells (Tregs) in an AhR dependent manner. This leads to an increase in the ratio of helper T cells to Tregs. Additionally, it was shown that indoximod reduces the level of IDO protein in dendritic cells in vitro, leading to increased stimulation of CD8 T cell proliferation and reduced production of kynurenine. Moreover, indoximod stimulation of mTOR in T cells appears to increase the proliferation of effector T cells in an IDO and TDO-independent manner. Through this mechanism, indoximod may be able overcome the effects of Trp degradation mediated by both IDO and TDO. Thus, in addition to opposing immunosuppression mediated by the IDO pathway, indoximod may drive antitumor immune responses independent from IDO.

In summary, indoximod has immunostimulatory effects involving 4 main cell types: CD8+ T cells, T helper cells, T regulatory cells, and dendritic cells. Indoximod appears to function through three main mechanisms to inhibit the IDO pathway:

Reversing the effects of low tryptophan by increasing proliferation of effector T cells

Increasing the ratio of T helper to T regulatory cells by both favoring differentiation of activated CD4 T cells into helper T cells and directly reprogramming T regulatory cells into helper T cells

Downregulating IDO expression in dendritic cells

About Indoximod

Indoximod is an investigational, orally available small molecule targeting the IDO pathway. The IDO pathway is a key immuno-oncology target involved in regulating the tumor microenvironment and immune escape. Indoximod is being evaluated in combination with treatment regimens including anti-PD-1/PD-L1 agents, cancer vaccines, radiation and chemotherapy across solid and liquid tumors.

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.

On April 17, 2018 Seres Therapeutics, Inc. (NASDAQ:MCRB) reported that new preclinical data supporting the development of microbiome therapeutics for immuno-oncology (leveraging gut microbiota to impact tumor immunotherapy)1 will be presented today by Sceneay et al in the late breaking poster session at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (AACR) (Free AACR Whitepaper) in Chicago (Press release, Seres Therapeutics, APR 17, 2018, View Source [SID1234530893]). The data presented provide new insights on the potential mechanism by which Seres’ microbiome therapies could improve the outcomes of cancer patients treated with immune checkpoint inhibitors.

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"The data presented at AACR (Free AACR Whitepaper) provide important new models and mechanistic insights that inform our planned development efforts to evaluate the ability of microbiome therapy to augment immune checkpoint inhibitors," said David Cook, Ph.D., Chief Scientific Officer and Executive Vice President of Research at Seres. "The insights described in this presentation will guide the continued development of SER-401, which we expect to enter clinical development later this year. Our objective is to use our microbiome therapeutic approach to improve the efficacy of immunotherapy in patients with life-threatening cancers."

Seres presented results from preclinical studies designed to evaluate the impact of various consortia of bacterial species on the anti-tumor immune response in murine models following treatment with an anti-PD-1 checkpoint inhibitor. Results demonstrated that both germ-free mice lacking a microbiome and antibiotics-treated mice with a dysbiotic microbiome, failed to mount an effective anti-tumor response following treatment with an anti-PD-1 checkpoint inhibitor. The response to anti-PD-1 was restored in germ-free as well as antibiotics-treated mice by introducing a diverse microbiome, and was driven by increased entry of tumor-infiltrating lymphocytes into the tumor; specifically, CD8+ T effector cells. Current pre-clinical efforts are focused on optimizing specific microbiome compositions based on functional and phylogenetic information to inform the development of therapeutic candidates.

Seres is developing SER-401, a preclinical stage oral microbiome therapy comprising a consortium of live bacteria to improve the efficacy and safety of immunotherapy. Through a collaboration with The University of Texas MD Anderson Cancer Center and the Parker Institute for Cancer Immunotherapy, Seres plans to initiate a clinical study in patients with advanced metastatic melanoma later this year. In a 2017 study published in Science, the MD Anderson research team, led by Dr. Jennifer Wargo, described a microbiome signature associated with response to checkpoint inhibitor therapy. A planned clinical trial will evaluate the impact of an anti-PD-1 checkpoint inhibitor with adjunctive microbiome therapy on patient outcomes.

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.