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News Article | March 1, 2017
Site: globenewswire.com

Heidelberg, Germany, March 1, 2017 - Affimed N.V. (Nasdaq: AFMD), a clinical stage biopharmaceutical company focused on discovering and developing highly targeted cancer immunotherapies, announced today that preclinical data for Affimed's lead candidate AFM13, the Company's preclinical programs AFM24 and AFM26, as well as data on its MHC-peptide-targeting discovery program will be presented at the American Association for Cancer Research (AACR) 2017 Annual Meeting being held April 1 - 5, 2017 in Washington, D.C. Abstract: The tetravalent bispecific antibody AFM13 engages and primes innate immune cells for anti-cancer immunity (#2997) Presentation (Minisymposium): Monday April 3, 2017, 4:05 - 4:20 PM; Room 152, Level 1 AFM13 is a high affinity tetravalent bispecific antibody with bivalent binding to both CD30 and CD16A, which is currently being tested as monotherapy in Phase 2 and in combination with Merck's Keytruda® in Phase 1b clinical trials. Affimed has previously shown that AFM13 enhances the sensitivity of NK-cells to low doses of IL-2 and IL-15, leading to an increased NK-cell proliferative potential. In the present study, the Company describes an expanded panel of phenotypic NK-cell markers modulated after exposure to CD30+ tumor cells in the presence of AFM13. In addition, Affimed presents data on the kinetics of NK-cell responses to AFM13 exposure, demonstrating in vitro that the transiently reduced potency induced by long-term AFM13 exposure can be rescued via cytokine stimulation. Taken together, AFM13 specifically enhances the cytotoxic, proliferative and cytokine-producing potential of NK-cells, which are parameters that can be utilized to monitor NK-cell responses during AFM13 therapy. Based on Affimed's data, recruiting of CD16A+ cells to the tumor site might enable several immune effector functions for synergistic anti-tumoral activity. Abstract: EGFR/CD16A TandAbs are efficacious NK-cell engagers with favorable biological properties which potently kill EGFR+ tumors with and without Ras mutation (#3641/14) Presentation (Poster): Tuesday April 4, 2017 8:00 AM - 12:00 PM; Poster Section 26 Constitutive EGFR activation plays an important role in the pathophysiology of various solid cancers. Although molecules modulating signal transduction and activation of EGFR, such as tyrosine kinase inhibitors and monoclonal antibodies (mAbs), are approved for treatment of EGFR+ cancers, intrinsic or acquired resistance to these agents has been described for a larger number of patients. Utilizing the cytotoxic potential of NK-cells to eliminate EGFR-expressing tumors, Affimed has developed AFM24, a tetravalent, bispecific EGFR/CD16A-targeting antibody. In the present study, AFM24's cytotoxic activity was tested against several EGFR+ tumor cell lines with and without Ras mutation, which is a negative prognostic biomarker for mAbs such as cetuximab or panitumumab. AFM24 induced efficient killing of cetuximab-resistant cells in vitro and in vivo. Importantly, AFM24 did not activate NK-cells without target cell-binding. A further differentiating feature of AFM24 is that its binding to CD16A and cytotoxic efficacy is virtually unaffected by serum IgG, resulting in higher efficacy compared to monoclonal antibodies. These data demonstrate that AFM24 has the potential to exhibit a favorable side effect profile, reduce toxicity and overcome resistance to other targeted anti-EGFR therapeutic agents. Abstract: AFM26 - A novel CD16A-directed bispecific TandAb targeting BCMA for multiple myeloma (#5671/25) Presentation (Poster): Wednesday April 5, 2017 8:00 AM - 12:00 PM; Poster Section 28 Multiple myeloma (MM) is the second most common hematological cancer and is characterized by the accumulation of neoplastic plasma cells in the bone marrow and production of high levels of monoclonal immunoglobulin (M-protein). While new treatments of MM have been developed recently, an unmet need remains as most patients eventually relapse and/or become refractory to currently available treatments. B-cell maturation antigen (BCMA, CD269) has emerged as a particularly attractive target due to its limited expression on healthy tissues and almost universal expression on myeloma cells in the majority of patients. In the present study, Affimed describes the characterization of AFM26, a novel tetravalent bispecific NK-cell engager targeting BCMA and CD16A. AFM26 interacts bivalently with NK-cells, resulting in high avidity, prolonged cell surface retention and potent induction of NK-cell-mediated in vitro lysis of target cells. Binding and cytotoxicity are not impaired at high levels of polyclonal IgG, suggesting that, AFM26, in contrast to classical mAbs, retains full ADCC activity at high serum IgG levels. This is particularly important as about half of MM patients present with high levels of IgG-type M-protein. These data support development of AFM26 as a promising and highly potent drug candidate for MM treatment. Abstract: Identification of antibodies against a novel tumor-associated MHC/peptide-target and generation of highly specific and potent HLA-A*02MMP1-003/CD3 TandAbs (#3753/9) Presentation (Poster): Tuesday April 4, 2017 8:00 AM - 12:00 PM; Poster Section 30 Tumor-specific antigens for effective and safe T-cell engagement are very limited, leaving a high need to widen the therapeutic target space. Targeting disease-specific MHC/peptide complexes with bispecific T-cell-recruiting antibodies is a highly attractive strategy to address this need. However, so far, generation of antibodies against these peptides has been reported to be challenging. Together with its collaboration partner Immatics, Affimed has identified a novel tumor-associated MHC/peptide complex, the HLA-A*02-binding peptide MMP1-003, originating from matrix metalloproteinase 1 (MMP1). Overcoming the barrier of developing antibodies targeting specific MHC/peptide complexes, Affimed has generated and characterized highly specific and potent T-cell-recruiting tetravalent bispecific antibodies directed towards MMP1-003. In a panel of endogenously target-expressing cancer cell lines, the lead molecule demonstrated excellent target specificity as well as potent cytotoxicity with EC50 values in the pM range. Thus, Affimed's antibody technology holds the potential for opening up the therapeutic target space for T-cell engagement by providing access to intracellular target antigens that are presented in a disease-specific manner as MHC/peptide complexes. Full abstracts of the presentations can be accessed on the AACR website at www.aacr.org Affimed (Nasdaq: AFMD) engineers targeted immunotherapies, seeking to cure patients by harnessing the power of innate and adaptive immunity (NK- and T-cells). We are developing single and combination therapies to treat cancers and other life-threatening diseases. For more information, please visit www.affimed.com. This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as "anticipate," "believe," "could," "estimate," "expect," "goal," "intend," "look forward to", "may," "plan," "potential," "predict," "project," "should," "will," "would" and similar expressions. Forward-looking statements appear in a number of places throughout this release and include statements regarding our intentions, beliefs, projections, outlook, analyses and current expectations concerning, among other things, our ongoing and planned preclinical development and clinical trials, our collaborations and development of our products in combination with other therapies, the timing of and our ability to make regulatory filings and obtain and maintain regulatory approvals for our product candidates our intellectual property position, our collaboration activities, our ability to develop commercial functions, expectations regarding clinical trial data, our results of operations, cash needs, financial condition, liquidity, prospects, future transactions, growth and strategies, the industry in which we operate, the trends that may affect the industry or us and the risks uncertainties and other factors described under the heading "Risk Factors" in Affimed's filings with the Securities and Exchange Commission. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these forward-looking statements, even if new information becomes available in the future.


News Article | March 1, 2017
Site: globenewswire.com

Heidelberg, Germany, March 1, 2017 - Affimed N.V. (Nasdaq: AFMD), a clinical stage biopharmaceutical company focused on discovering and developing highly targeted cancer immunotherapies, announced today that preclinical data for Affimed's lead candidate AFM13, the Company's preclinical programs AFM24 and AFM26, as well as data on its MHC-peptide-targeting discovery program will be presented at the American Association for Cancer Research (AACR) 2017 Annual Meeting being held April 1 - 5, 2017 in Washington, D.C. Abstract: The tetravalent bispecific antibody AFM13 engages and primes innate immune cells for anti-cancer immunity (#2997) Presentation (Minisymposium): Monday April 3, 2017, 4:05 - 4:20 PM; Room 152, Level 1 AFM13 is a high affinity tetravalent bispecific antibody with bivalent binding to both CD30 and CD16A, which is currently being tested as monotherapy in Phase 2 and in combination with Merck's Keytruda® in Phase 1b clinical trials. Affimed has previously shown that AFM13 enhances the sensitivity of NK-cells to low doses of IL-2 and IL-15, leading to an increased NK-cell proliferative potential. In the present study, the Company describes an expanded panel of phenotypic NK-cell markers modulated after exposure to CD30+ tumor cells in the presence of AFM13. In addition, Affimed presents data on the kinetics of NK-cell responses to AFM13 exposure, demonstrating in vitro that the transiently reduced potency induced by long-term AFM13 exposure can be rescued via cytokine stimulation. Taken together, AFM13 specifically enhances the cytotoxic, proliferative and cytokine-producing potential of NK-cells, which are parameters that can be utilized to monitor NK-cell responses during AFM13 therapy. Based on Affimed's data, recruiting of CD16A+ cells to the tumor site might enable several immune effector functions for synergistic anti-tumoral activity. Abstract: EGFR/CD16A TandAbs are efficacious NK-cell engagers with favorable biological properties which potently kill EGFR+ tumors with and without Ras mutation (#3641/14) Presentation (Poster): Tuesday April 4, 2017 8:00 AM - 12:00 PM; Poster Section 26 Constitutive EGFR activation plays an important role in the pathophysiology of various solid cancers. Although molecules modulating signal transduction and activation of EGFR, such as tyrosine kinase inhibitors and monoclonal antibodies (mAbs), are approved for treatment of EGFR+ cancers, intrinsic or acquired resistance to these agents has been described for a larger number of patients. Utilizing the cytotoxic potential of NK-cells to eliminate EGFR-expressing tumors, Affimed has developed AFM24, a tetravalent, bispecific EGFR/CD16A-targeting antibody. In the present study, AFM24's cytotoxic activity was tested against several EGFR+ tumor cell lines with and without Ras mutation, which is a negative prognostic biomarker for mAbs such as cetuximab or panitumumab. AFM24 induced efficient killing of cetuximab-resistant cells in vitro and in vivo. Importantly, AFM24 did not activate NK-cells without target cell-binding. A further differentiating feature of AFM24 is that its binding to CD16A and cytotoxic efficacy is virtually unaffected by serum IgG, resulting in higher efficacy compared to monoclonal antibodies. These data demonstrate that AFM24 has the potential to exhibit a favorable side effect profile, reduce toxicity and overcome resistance to other targeted anti-EGFR therapeutic agents. Abstract: AFM26 - A novel CD16A-directed bispecific TandAb targeting BCMA for multiple myeloma (#5671/25) Presentation (Poster): Wednesday April 5, 2017 8:00 AM - 12:00 PM; Poster Section 28 Multiple myeloma (MM) is the second most common hematological cancer and is characterized by the accumulation of neoplastic plasma cells in the bone marrow and production of high levels of monoclonal immunoglobulin (M-protein). While new treatments of MM have been developed recently, an unmet need remains as most patients eventually relapse and/or become refractory to currently available treatments. B-cell maturation antigen (BCMA, CD269) has emerged as a particularly attractive target due to its limited expression on healthy tissues and almost universal expression on myeloma cells in the majority of patients. In the present study, Affimed describes the characterization of AFM26, a novel tetravalent bispecific NK-cell engager targeting BCMA and CD16A. AFM26 interacts bivalently with NK-cells, resulting in high avidity, prolonged cell surface retention and potent induction of NK-cell-mediated in vitro lysis of target cells. Binding and cytotoxicity are not impaired at high levels of polyclonal IgG, suggesting that, AFM26, in contrast to classical mAbs, retains full ADCC activity at high serum IgG levels. This is particularly important as about half of MM patients present with high levels of IgG-type M-protein. These data support development of AFM26 as a promising and highly potent drug candidate for MM treatment. Abstract: Identification of antibodies against a novel tumor-associated MHC/peptide-target and generation of highly specific and potent HLA-A*02MMP1-003/CD3 TandAbs (#3753/9) Presentation (Poster): Tuesday April 4, 2017 8:00 AM - 12:00 PM; Poster Section 30 Tumor-specific antigens for effective and safe T-cell engagement are very limited, leaving a high need to widen the therapeutic target space. Targeting disease-specific MHC/peptide complexes with bispecific T-cell-recruiting antibodies is a highly attractive strategy to address this need. However, so far, generation of antibodies against these peptides has been reported to be challenging. Together with its collaboration partner Immatics, Affimed has identified a novel tumor-associated MHC/peptide complex, the HLA-A*02-binding peptide MMP1-003, originating from matrix metalloproteinase 1 (MMP1). Overcoming the barrier of developing antibodies targeting specific MHC/peptide complexes, Affimed has generated and characterized highly specific and potent T-cell-recruiting tetravalent bispecific antibodies directed towards MMP1-003. In a panel of endogenously target-expressing cancer cell lines, the lead molecule demonstrated excellent target specificity as well as potent cytotoxicity with EC50 values in the pM range. Thus, Affimed's antibody technology holds the potential for opening up the therapeutic target space for T-cell engagement by providing access to intracellular target antigens that are presented in a disease-specific manner as MHC/peptide complexes. Full abstracts of the presentations can be accessed on the AACR website at www.aacr.org Affimed (Nasdaq: AFMD) engineers targeted immunotherapies, seeking to cure patients by harnessing the power of innate and adaptive immunity (NK- and T-cells). We are developing single and combination therapies to treat cancers and other life-threatening diseases. For more information, please visit www.affimed.com. This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as "anticipate," "believe," "could," "estimate," "expect," "goal," "intend," "look forward to", "may," "plan," "potential," "predict," "project," "should," "will," "would" and similar expressions. Forward-looking statements appear in a number of places throughout this release and include statements regarding our intentions, beliefs, projections, outlook, analyses and current expectations concerning, among other things, our ongoing and planned preclinical development and clinical trials, our collaborations and development of our products in combination with other therapies, the timing of and our ability to make regulatory filings and obtain and maintain regulatory approvals for our product candidates our intellectual property position, our collaboration activities, our ability to develop commercial functions, expectations regarding clinical trial data, our results of operations, cash needs, financial condition, liquidity, prospects, future transactions, growth and strategies, the industry in which we operate, the trends that may affect the industry or us and the risks uncertainties and other factors described under the heading "Risk Factors" in Affimed's filings with the Securities and Exchange Commission. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these forward-looking statements, even if new information becomes available in the future.


News Article | February 17, 2017
Site: globenewswire.com

NORCROSS, Ga., Feb. 17, 2017 (GLOBE NEWSWIRE) -- Immucor, Inc., a global leader in transfusion and transplantation diagnostics, today announced the launch of Pak Lx™, a qualitative Luminex®-based immunoassay that brings high-definition to platelet antibody testing. While the assay is CE marked and has previously been available in international markets, Pak Lx is now available as a research use only (RUO) kit in the United States. Platelets express a variety of polymorphic proteins that may become targets for antibodies as a result of pregnancy or transfusion. The presence of antibodies that bind to platelet glycoproteins is associated with life-threatening bleeding disorders, such as refractoriness to platelet transfusions, post-transfusion purpura (PTP), and fetal and neonatal alloimmune thrombocytopenia (FNAIT). The Pak Lx assay may be used to detect and differentiate IgG antibodies to Human Platelet Antigens (HPA-1, HPA-2, HPA-3, HPA-4, HPA-5), Glycoprotein (GPIV), and Human Leukocyte Antigen (HLA Class I).  Once validated for use, Pak Lx may be used to support the selection of antigen negative or HLA-matched platelets for transfusion, providing a better matched unit to improve patient care. “Immucor is pleased to expand the offering of Pak Lx to the US market,” stated Christie Otis, Senior Transfusion Franchise Director at Immucor. “Pak Lx is an important addition to our platelet compatibility portfolio and provides another tool to enable laboratories to select antigen negative or HLA-matched platelets for transfusion. The availability of Pak Lx further supports Immucor’s portfolio for red cell and platelet compatibility testing.” Pak Lx availability demonstrates Immucor’s commitment to transfusion and transplant diagnostics.  Immucor’s total solution extends beyond platelet compatibility testing and includes a full line of automated immunohematology instruments including the NEO® and Echo® analyzers, PreciseType® (the only FDA licensed molecular immunohematology solution), and a broad portfolio of transplant solutions, including LIFECODES® for HLA typing and antibody screening, MIA FORA® for NGS HLA typing, and kSORT™ for post-transplant surveillance. Request a Demonstration To schedule a demonstration of Pak Lx, or any Immucor solution, Immucor clients may contact their local Molecular and Specialty Diagnostics Business Manager.  For more information about Immucor products, please contact your local Immucor representative or visit www.immucor.com. About Immucor Founded in 1982, Immucor is a global leader in transfusion and transplantation diagnostics that facilitate patient-donor compatibility. Our mission is to ensure that patients in need of blood, organs or stem cells get the right match that is safe, accessible and affordable. With the right match, we can transform a life together. For more information on Immucor, visit www.immucor.com.


News Article | February 15, 2017
Site: www.nature.com

The discovery cohort consisted of 147 studies comprising 458,927 adult individuals of the following ancestries: (1) European descent (n = 381,625); (2) African (n = 27,494); (3) South Asian (n = 29,591); (4) East Asian (n = 8,767); (5) Hispanic (n = 10,776) and (6) Saudi Arabian (n = 695). All participating institutions and coordinating centres approved this project, and informed consent was obtained from all subjects. Discovery meta-analysis was carried out in each ancestry group (except the Saudi Arabian) separately as well as in the All group. Validation was undertaken in individuals of European ancestry only (Supplementary Tables 1–3). Conditional analyses were undertaken only in the European descent group (106 studies, n = 381,625). The SNPs we identify are available from the NCBI dbSNP database of short genetic variations (https://www.ncbi.nlm.nih.gov/projects/SNP/). No statistical methods were used to predetermine sample size. The experiments were not randomized and the investigators were not blinded to allocation during experiments and outcome assessment. Height (in centimetres) was corrected for age and the genomic principal components (derived from GWAS data, the variants with a MAF > 1% on ExomeChip (http://genome.sph.umich.edu/wiki/Exome_Chip_Design), or ancestry-informative markers available on the ExomeChip), as well as any additional study-specific covariates (for example, recruiting centre), in a linear regression model. For studies with non-related individuals, residuals were calculated separately by sex, whereas for family-based studies sex was included as a covariate in the model. Additionally, residuals for case/control studies were calculated separately. Finally, residuals were subject to inverse normal transformation. The majority of studies followed a standardized protocol and performed genotype calling using the designated manufacturer’s software, which was then followed by zCall30. For ten studies participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, the raw intensity data for the samples from seven genotyping centres were assembled into a single project for joint calling11. Study-specific quality-control measures of the genotyped variants was implemented before association analysis (Supplementary Tables 1–2). Individual cohorts were analysed separately for each ancestry population, with either RAREMETALWORKER (http://genome.sph.umich.edu/wiki/RAREMETALWORKER) or RVTEST (http://zhanxw.github.io/rvtests/), to associate inverse normal transformed height data with genotype data taking potential cryptic relatedness (kinship matrix) into account in a linear mixed model. These software are designed to perform score-statistics based rare-variant association analysis, can accommodate both unrelated and related individuals, and provide single-variant results and variance-covariance matrix. The covariance matrix captures linkage disequilibrium relationships between markers within 1 Mb, which is used for gene-level meta-analyses and conditional analyses31. Single-variant analyses were performed for both additive and recessive models (for the alternate allele). The individual study data were investigated for potential existence of ancestry population outliers based on the 1000 Genome Project phase 1 ancestry reference populations. A centralized quality control procedure implemented in EasyQC32 was applied to individual study association summary statistics to identify outlying studies: (1) assessment of possible problems in height transformation; (2) comparison of allele frequency alignment against 1000 Genomes Project phase 1 reference data to pinpoint any potential strand issues; and (3) examination of quantile–quantile plots per study to identify any problems arising from population stratification, cryptic relatedness and genotype biases. We excluded variants if they had a call rate <95%, Hardy–Weinberg equilibrium P < 1 × 10−7, or large allele frequency deviations from reference populations (>0.6 for all ancestry analyses and >0.3 for ancestry-specific population analyses). We also excluded from downstream analyses markers not present on the Illumina ExomeChip array 1.0, variants on the Y chromosome or the mitochondrial genome, indels, multiallelic variants, and problematic variants based on the Blat-based sequence alignment analyses. Meta-analyses were carried out in parallel by two different analysts at two sites. We conducted single-variant meta-analyses in a discovery sample of 458,927 individuals of different ancestries using both additive and recessive genetic models (Extended Data Fig. 1 and Supplementary Tables 1–4). Significance for single-variant analyses was defined at an array-wide level (P < 2 × 10−7, Bonferroni correction for 250,000 variants). The combined additive analyses identified 1,455 unique variants that reached array-wide significance (P < 2 × 10−7), including 578 non-synonymous and splice-site variants (Supplementary Tables 5–7). Under the additive model, we observed a high genomic inflation of the test statistics (for example, a λ of 2.7 in European ancestry studies for common markers, Extended Data Fig. 2 and Supplementary Table 8), although validation results (see below) and additional sensitivity analyses (see below) suggested that it is consistent with polygenic inheritance as opposed to population stratification, cryptic relatedness, or technical artefacts (Extended Data Fig. 2). The majority of these 1,455 association signals (1,241; 85.3%) were found in the European ancestry meta-analysis (85.5% of the discovery sample size) (Extended Data Fig. 2). Nevertheless, we discovered eight associations within five loci in our all-ancestry analyses that are driven by African studies (including one missense variant in the growth hormone gene GH1 (rs151263636), Extended Data Fig. 3), three height variants found only in African studies, and one rare missense marker associated with height in South Asians only (Supplementary Table 7). We observed a marked genomic inflation of the test statistics even after adequate control for population stratification (linear mixed model) arising mainly from common markers; λ in European ancestry was 1.2 and 2.7 for all and common markers, respectively (Extended Data Fig. 2 and Supplementary Table 8). Such inflation is expected for a highly polygenic trait like height, and is consistent with our very large sample size3, 33. To confirm this, we applied the recently developed linkage disequilibrium score regression method to our height ExomeChip results34, with the caveats that the method was developed (and tested) with >200,000 common markers available. We restricted our analyses to 15,848 common variants (MAF ≥ 5%) from the European-ancestry meta-analysis, and matched them to pre-computed linkage disequilibrium scores for the European reference dataset34. The intercept of the regression of the χ2 statistics from the height meta-analysis on the linkage disequilibrium score estimates that the inflation in the mean χ2 is due to confounding bias, such as cryptic relatedness or population stratification. The intercept was 1.4 (s.e.m. = 0.07), which is small when compared to the λ of 2.7. Furthermore, we also confirmed that the linkage disequilibrium score regression intercept is estimated upward because of the small number of variants on the ExomeChip and the selection criteria for these variants (that is, known GWAS hits). The ratio statistic of (intercept − 1)/(mean χ2 − 1) is 0.067 (s.e.m. = 0.012), well within the normal range34, suggesting that most of the inflation (~93%) observed in the height association statistics is due to polygenic effects (Extended Data Fig. 2). Furthermore, to exclude the possibility that some of the observed associations between height and rare and low-frequency variants could be due to allele calling problems in the smaller studies, we performed a sensitivity meta-analysis with primarily European ancestry studies totalling >5,000 participants. We found very concordant effect sizes, suggesting that smaller studies do not bias our results (Extended Data Fig. 2). The RAREMETAL R package35 and the GCTA v1.24 (ref. 36) software were used to identify independent height association signals across the European descent meta-analysis results. RAREMETAL performs conditional analyses by using covariance matrices in order to distinguish true signals from those driven by linkage disequilibrium at adjacent known variants. First, we identified the lead variants (P < 2 × 10−7) based on a 1-Mb window centred on the most significantly associated variant and performed linkage disequilibrium pruning (r2 < 0.3) to avoid downstream problems in the conditional analyses due to co-linearity. We then conditioned on the linkage disequilibrium-pruned set of lead variants in RAREMETAL and kept new lead signals at P < 2 × 10−7. The process was repeated until no additional signal emerged below the pre-specified P-value threshold. The use of a 1-Mb window in RAREMETAL can obscure dependence between conditional signals in adjacent intervals in regions of extended linkage disequilibrium. To detect such instances, we performed joint analyses using GCTA with the ARIC and UK ExomeChip reference panels, both of which comprise >10,000 individuals of European descent. With the exception of a handful of variants in a few genomic regions with extended linkage disequilibrium (for example, the HLA region on chromosome 6), the two pieces of software identified the same independent signals (at P < 2 × 10−7). To discover new height variants, we conditioned the height variants found in our ExomeChip study on the previously published GWAS height variants3 using the first release of the UK Biobank imputed dataset and regression methodology implemented in BOLT-LMM37. Because of the difference between the sample size of our discovery set (n = 458,927) and the UK Biobank (first release, n = 120,084), we applied a threshold of P  < 0.05 to declare a height variant as independent in this analysis. We also explored an alternative approach based on approximate conditional analysis36. This latter method (SSimp) relies on summary statistics available from the same cohort, thus we first imputed summary statistics38 for exome variants, using summary statistics from a previous study3. Conversely, we imputed the top variants from this study3 using the summary statistics from the ExomeChip. Subsequently, we calculated effect sizes for each exome variant conditioned on the top variants of this study3 in two ways. First, we conditioned the imputed summary statistics of the exome variant on the summary statistics of the top variants that fell within 5 Mb of the target ExomeChip variant. Second, we conditioned the summary statistics of the ExomeChip variant on the imputed summary statistics of the hits of this study3. We then selected the option that yielded a higher imputation quality. For poorly tagged variants (  < 0.8), we simply used up-sampled HapMap summary statistics for the approximate conditional analysis. Pairwise SNP-by-SNP correlations were estimated from the UK10K data (TwinsUK39 and ALSPAC40 studies, n = 3,781). Several studies, totalling 252,501 independent individuals of European ancestry, became available after the completion of the discovery analyses, and were thus used for validation of our experiment. We validated the single-variant association results in eight studies, totalling 59,804 participants, genotyped on the ExomeChip using RAREMETAL31. We sought additional evidence for association for the top signals in two independent studies in the UK (UK Biobank) and Iceland (deCODE), comprising 120,084 and 72,613 individuals, respectively. We used the same quality control and analytical methodology as described above. Genotyping and study descriptions are provided in Supplementary Tables 1–3. For the combined analysis, we used the inverse-variance-weighted fixed effects meta-analysis method using METAL41. Significant associations were defined as those with a combined meta-analysis (discovery and validation) P  < 2 × 10−7. We considered 81 variants with suggestive association in the discovery analyses (2 × 10−7 < P  ≤ 2 × 10−6). Of those 81 variants, 55 reached significance after combining discovery and replication results based on a P  < 2 × 10−7 (Supplementary Table 9). Furthermore, recessive modelling confirmed seven new independent markers with a P  < 2 × 10−7 (Supplementary Table 10). One of these recessive signals is due to a rare X-linked variant in the AR gene (rs137852591, MAF = 0.21%). Because of its frequency, we only tested hemizygous men (we did not identify homozygous women for the minor allele) so we cannot distinguish between a true recessive mode of inheritance or a sex-specific effect for this variant. To test the independence and integrate all height markers from the discovery and validation phase, we used conditional analyses and GCTA ‘joint’ modelling36 in the combined discovery and validation set. This resulted in the identification of 606 independent height variants, including 252 non-synonymous or splice-site variants (Supplementary Table 11). If we consider only the initial set of lead SNPs with P < 2 × 10−7, we identified 561 independent variants. Of these 561 variants (selected without the validation studies), 560 have concordant direction of effect between the discovery and validation studies, and 548 variants have a P  < 0.05 (466 variants with P  < 8.9 × 10−5, Bonferroni correction for 561 tests), suggesting a very low false discovery rate (Supplementary Table 11). For the gene-based analyses, we applied two different sets of criteria to select variants, based on coding variant annotation from five prediction algorithms (PolyPhen2 HumDiv and HumVar, LRT, MutationTaster and SIFT)42. The mask labelled ‘broad’ included variants with a MAF < 0.05 that are nonsense, stop-loss, splice site, as well as missense variants that are annotated as damaging by at least one program mentioned above. The mask labelled ‘strict’ included only variants with a MAF < 0.05 that are nonsense, stop-loss, splice-site, as well as missense variants annotated as damaging by all five algorithms. We used two tests for gene-based testing, namely the SKAT43 and VT44 tests. Statistical significance for gene-based tests was set at a Bonferroni-corrected threshold of P < 5 × 10−7 (threshold for 25,000 genes and four tests). The gene-based discovery results were validated (same test and variants, when possible) in the same eight studies genotyped on the ExomeChip (n = 59,804 participants) that were used for the validation of the single-variant results (see above, and Supplementary Tables 1–3). Gene-based conditional analyses were performed in RAREMETAL. We accessed ExomeChip data from GIANT (BMI, waist:hip ratio), GLGC (total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol), IBPC (systolic and diastolic blood pressure), MAGIC (glycaemic traits), REPROGEN (age at menarche and menopause), and DIAGRAM (type 2 diabetes) consortia. For coronary artery disease, we accessed 1000 Genomes Project-imputed GWAS data released by CARDIoGRAMplusC4D45. DEPICT (http://www.broadinstitute.org/mpg/depict/) is a computational framework that uses probabilistically defined reconstituted gene sets to perform gene set enrichment and gene prioritization15. For a description of gene set reconstitution, refer to refs 15, 46. In brief, reconstitution was performed by extending pre-defined gene sets (such as Gene Ontology terms, canonical pathways, protein-protein interaction subnetworks and rodent phenotypes) with genes co-regulated with genes in these pre-defined gene set using large-scale microarray-based transcriptomics data. In order to adapt the gene set enrichment part of DEPICT for ExomeChip data (https://github.com/RebeccaFine/height-ec-depict), we made two principal changes. First, because DEPICT for GWAS incorporates all genes within a given linkage disequilibrium block around each index SNP, we modified DEPICT to take as input only the gene directly impacted by the coding SNP. Second, we adapted the way DEPICT adjusts for confounders (such as gene length) by generating null ExomeChip association results using Swedish ExomeChip data (Malmö Diet and Cancer (MDC), All New Diabetics in Scania (ANDIS), and Scania Diabetes Registry (SDR) cohorts, n = 11,899) and randomly assigning phenotypes from a normal distribution before conducting association analysis (see Supplementary Information). For the gene set enrichment analysis of the ExomeChip data, we used significant non-synonymous variants statistically independent of known GWAS hits (and that were present in the null ExomeChip data; see Supplementary Information for details). For gene set enrichment analysis of the GWAS data, we used all loci with a non-coding index SNP and that did not contain any of the novel ExomeChip genes. In visualizing the analysis, we used affinity propagation clustering47 to group the most similar reconstituted gene sets based on their gene memberships (see Supplementary Information). Within a ‘meta-gene set’, the best P value of any member gene set was used as representative for comparison. DEPICT for ExomeChip was written using the Python programming language and the code can be found at https://github.com/RebeccaFine/height-ec-depict. We also applied the PASCAL (http://www2.unil.ch/cbg/index.php?title=Pascal) pathway analysis tool16 to association summary statistics for all coding variants. In brief, the method derives gene-based scores (both SUM and MAX statistics) and subsequently tests for the over-representation of high gene scores in predefined biological pathways. We used standard pathway libraries from KEGG, REACTOME and BIOCARTA, and also added dichotomized (Z score > 3) reconstituted gene sets from DEPICT15. To accurately estimate SNP-by-SNP correlations even for rare variants, we used the UK10K data (TwinsUK39 and ALSPAC40 studies, n = 3781). To separate the contribution of regulatory variants from the coding variants, we also applied PASCAL to association summary statistics of only regulatory variants (20 kb upstream, gene body excluded) from a previous study3. In this way, we could classify pathways driven principally by coding, regulatory or mixed signals. For the generation of STC2 mutants (R44L and M86I), wild-type STC2 cDNA contained in pcDNA3.1/Myc-His(−) (Invitrogen)23 was used as a template. Mutagenesis was carried out using Quickchange (Stratagene), and all constructs were verified by sequence analysis. Recombinant wild-type STC2 and variants were expressed in human embryonic kidney (HEK) 293T cells (293tsA1609neo, ATCC CRL-3216) maintained in high-glucose DMEM supplemented 10% fetal bovine serum, 2 mM glutamine, nonessential amino acids, and gentamicin. The cells are routinely tested for mycoplasma contamination. Cells (6 × 106) were plated onto 10-cm dishes and transfected 18 h later by calcium phosphate co-precipitation using 10 μg plasmid DNA. Medium was collected 48 h after transfection, cleared by centrifugation, and stored at −20 °C until use. Protein concentrations (58–66 nM) were determined by TRIFMA using antibodies described previously23. PAPP-A was expressed stably in HEK293T cells as previously reported48. Expressed levels of PAPP-A (27.5 nM) were determined by a commercial ELISA (AL-101, Ansh Labs). Culture supernatants containing wild-type STC2 or variants were adjusted to 58 nM, added an equal volume of culture supernatant containing PAPP-A corresponding to a 2.1-fold molar excess, and incubated at 37 °C. Samples were taken at 1, 2, 4, 6, 8, 16, and 24 h and stored at −20 °C. Specific proteolytic cleavage of 125I-labeled IGFBP-4 is described in detail elsewhere49. In brief, the PAPP-A–STC2 complex mixtures were diluted (1:190) to a concentration of 72.5 pM PAPP-A and mixed with pre-incubated 125I-IGFBP4 (10 nM) and IGF-1 (100 nM) in 50 mM Tris-HCl, 100 mM NaCl, 1 mM CaCl . Following 1 h incubation at 37 °C, reactions were terminated by the addition of SDS–PAGE sample buffer supplemented with 25 mM EDTA. Substrate and co-migrating cleavage products were separated by 12% non-reducing SDS–PAGE and visualized by autoradiography using a storage phosphor screen (GE Healthcare) and a Typhoon imaging system (GE Healthcare). Band intensities were quantified using ImageQuant TL 8.1 software (GE Healthcare). STC2 and covalent complexes between STC2 and PAPP-A were blotted onto PVDF membranes (Millipore) following separation by 3–8% SDS–PAGE. The membranes were blocked with 2% Tween-20, and equilibrated in 50 mM Tris-HCl, 500 mM NaCl, 0.1% Tween-20; pH 9 (TST). For STC2, the membranes were incubated with goat polyclonal anti-STC2 (R&D systems, AF2830) at 0.5 μg ml−1 in TST supplemented with 2% skimmed milk for 1 h at 20 °C. For PAPP-A–STC2 complexes, the membranes were incubated with rabbit polyclonal anti-PAPP-A50 at 0.63 μg ml−1 in TST supplemented with 2% skimmed milk for 16 h at 20 °C. Membranes were washed with TST and subsequently incubated with polyclonal rabbit anti-goat IgG[en rule]horseradish peroxidase (DAKO, P0449) or polyclonal swine anti-rabbit IgG[en rule]horseradish peroxidase (DAKO, P0217), respectively, diluted 1:2,000 in TST supplemented with 2% skimmed milk for 1 h at 20 °C. Following washing with TST, membranes were developed using enhanced chemiluminescence (ECL Prime, GE Healthcare). Images were captured using an ImageQuant LAS 4000 instrument (GE Healthcare). Summary genetic association results are available on the GIANT website (http://portals.broadinstitute.org/collaboration/giant/index.php/GIANT_consortium).


News Article | February 17, 2017
Site: globenewswire.com

NORCROSS, Ga., Feb. 17, 2017 (GLOBE NEWSWIRE) -- Immucor, Inc., a global leader in transfusion and transplantation diagnostics, today announced the launch of Pak Lx™, a qualitative Luminex®-based immunoassay that brings high-definition to platelet antibody testing. While the assay is CE marked and has previously been available in international markets, Pak Lx is now available as a research use only (RUO) kit in the United States. Platelets express a variety of polymorphic proteins that may become targets for antibodies as a result of pregnancy or transfusion. The presence of antibodies that bind to platelet glycoproteins is associated with life-threatening bleeding disorders, such as refractoriness to platelet transfusions, post-transfusion purpura (PTP), and fetal and neonatal alloimmune thrombocytopenia (FNAIT). The Pak Lx assay may be used to detect and differentiate IgG antibodies to Human Platelet Antigens (HPA-1, HPA-2, HPA-3, HPA-4, HPA-5), Glycoprotein (GPIV), and Human Leukocyte Antigen (HLA Class I).  Once validated for use, Pak Lx may be used to support the selection of antigen negative or HLA-matched platelets for transfusion, providing a better matched unit to improve patient care. “Immucor is pleased to expand the offering of Pak Lx to the US market,” stated Christie Otis, Senior Transfusion Franchise Director at Immucor. “Pak Lx is an important addition to our platelet compatibility portfolio and provides another tool to enable laboratories to select antigen negative or HLA-matched platelets for transfusion. The availability of Pak Lx further supports Immucor’s portfolio for red cell and platelet compatibility testing.” Pak Lx availability demonstrates Immucor’s commitment to transfusion and transplant diagnostics.  Immucor’s total solution extends beyond platelet compatibility testing and includes a full line of automated immunohematology instruments including the NEO® and Echo® analyzers, PreciseType® (the only FDA licensed molecular immunohematology solution), and a broad portfolio of transplant solutions, including LIFECODES® for HLA typing and antibody screening, MIA FORA® for NGS HLA typing, and kSORT™ for post-transplant surveillance. Request a Demonstration To schedule a demonstration of Pak Lx, or any Immucor solution, Immucor clients may contact their local Molecular and Specialty Diagnostics Business Manager.  For more information about Immucor products, please contact your local Immucor representative or visit www.immucor.com. About Immucor Founded in 1982, Immucor is a global leader in transfusion and transplantation diagnostics that facilitate patient-donor compatibility. Our mission is to ensure that patients in need of blood, organs or stem cells get the right match that is safe, accessible and affordable. With the right match, we can transform a life together. For more information on Immucor, visit www.immucor.com.


News Article | February 14, 2017
Site: globenewswire.com

NORCROSS, Ga., Feb. 14, 2017 (GLOBE NEWSWIRE) -- Immucor, Inc., a global leader in transfusion and transplantation diagnostics, today announced the launch of the new MIA FORA® NGS FLEX HLA Typing Assay that provides comprehensive coverage of up to 11 HLA genes. The MIA FORA NGS FLEX HLA Typing Assay is the only high resolution next generation sequencing (“NGS”) solution that delivers comprehensive, flexible coverage and an optimized laboratory workflow without compromising performance. The MIA FORA NGS FLEX HLA Typing Assay has been validated on the Illumina MiSeq and MiniSeq platforms using multiple flow cell options.  It is now available as Research Use Only (RUO) in the United States, and is CE Marked. The MIA FORA NGS FLEX HLA Typing Assay provides superior whole gene coverage of all major HLA gene regions, including whole gene coverage for HLA-A,B, C, DPA1, DQA1, and DQB1; all exons and introns for HLA-DRB1,3,4,5 except partial coverage for exon 6 and intron 1; and all exons and introns between exons 2 and 4 for HLA-DPB1. This broad coverage minimizes ambiguities, in particular for DRB1,3,4,5, which uses a unique approach to primer design to maximize coverage. The software that powers the MIA FORA NGS FLEX analysis was developed based on Immucor’s extensive experience with HLA typing. With an intuitive user interface, the MIA FORA FLEX 3.0 software is the only HLA analysis solution that uses three algorithms for analysis of genotyping calls, a proprietary database for precise mapping and alignment, and a smart flagging system that alerts users and allows them to make confident allele calls rapidly. Data is automatically transferred and analyzed from the sequencing platform with no user intervention, so results are analyzed as soon as the data is available.  MIA FORA FLEX 3.0 software is the next generation of informatics optimizing both laboratory technologist ease-of-use and data analytics. “The launch of the MIA FORA NGS FLEX HLA Typing Assay shows the ability and dedication of the Immucor MIA FORA team to quickly develop a significantly enhanced product that will meet the demands of the HLA testing community,” stated Michael Mindrinos Ph.D., President and co-founder of Sirona Genomics, now a part of Immucor. Keith Chaitoff, Immucor’s Chief Marketing Officer added, “The improvements to the MIA FORA workflow demonstrate Immucor’s commitment to the transplant market and all stakeholders, from the laboratory and transplant teams to the patients and their families. The MIA FORA NGS FLEX HLA Typing Assay combines with the LIFECODES transplant products and the kSORT post-transplant monitoring test to offer Immucor customers the broadest high quality transplant product line available in the market today.” About Immucor Founded in 1982, Immucor is a global leader in transfusion and transplantation diagnostics that facilitate patient-donor compatibility. Our mission is to ensure that patients in need of blood, organs or stem cells get the right match that is safe, accessible and affordable. With the right match, we can transform a life together. For more information on Immucor, please visit our website at www.immucor.com.


News Article | February 14, 2017
Site: globenewswire.com

NORCROSS, Ga., Feb. 14, 2017 (GLOBE NEWSWIRE) -- Immucor, Inc., a global leader in transfusion and transplantation diagnostics, today announced the launch of the new MIA FORA® NGS FLEX HLA Typing Assay that provides comprehensive coverage of up to 11 HLA genes. The MIA FORA NGS FLEX HLA Typing Assay is the only high resolution next generation sequencing (“NGS”) solution that delivers comprehensive, flexible coverage and an optimized laboratory workflow without compromising performance. The MIA FORA NGS FLEX HLA Typing Assay has been validated on the Illumina MiSeq and MiniSeq platforms using multiple flow cell options.  It is now available as Research Use Only (RUO) in the United States, and is CE Marked. The MIA FORA NGS FLEX HLA Typing Assay provides superior whole gene coverage of all major HLA gene regions, including whole gene coverage for HLA-A,B, C, DPA1, DQA1, and DQB1; all exons and introns for HLA-DRB1,3,4,5 except partial coverage for exon 6 and intron 1; and all exons and introns between exons 2 and 4 for HLA-DPB1. This broad coverage minimizes ambiguities, in particular for DRB1,3,4,5, which uses a unique approach to primer design to maximize coverage. The software that powers the MIA FORA NGS FLEX analysis was developed based on Immucor’s extensive experience with HLA typing. With an intuitive user interface, the MIA FORA FLEX 3.0 software is the only HLA analysis solution that uses three algorithms for analysis of genotyping calls, a proprietary database for precise mapping and alignment, and a smart flagging system that alerts users and allows them to make confident allele calls rapidly. Data is automatically transferred and analyzed from the sequencing platform with no user intervention, so results are analyzed as soon as the data is available.  MIA FORA FLEX 3.0 software is the next generation of informatics optimizing both laboratory technologist ease-of-use and data analytics. “The launch of the MIA FORA NGS FLEX HLA Typing Assay shows the ability and dedication of the Immucor MIA FORA team to quickly develop a significantly enhanced product that will meet the demands of the HLA testing community,” stated Michael Mindrinos Ph.D., President and co-founder of Sirona Genomics, now a part of Immucor. Keith Chaitoff, Immucor’s Chief Marketing Officer added, “The improvements to the MIA FORA workflow demonstrate Immucor’s commitment to the transplant market and all stakeholders, from the laboratory and transplant teams to the patients and their families. The MIA FORA NGS FLEX HLA Typing Assay combines with the LIFECODES transplant products and the kSORT post-transplant monitoring test to offer Immucor customers the broadest high quality transplant product line available in the market today.” About Immucor Founded in 1982, Immucor is a global leader in transfusion and transplantation diagnostics that facilitate patient-donor compatibility. Our mission is to ensure that patients in need of blood, organs or stem cells get the right match that is safe, accessible and affordable. With the right match, we can transform a life together. For more information on Immucor, please visit our website at www.immucor.com.


News Article | February 17, 2017
Site: globenewswire.com

NORCROSS, Ga., Feb. 17, 2017 (GLOBE NEWSWIRE) -- Immucor, Inc., a global leader in transfusion and transplantation diagnostics, today announced the launch of Pak Lx™, a qualitative Luminex®-based immunoassay that brings high-definition to platelet antibody testing. While the assay is CE marked and has previously been available in international markets, Pak Lx is now available as a research use only (RUO) kit in the United States. Platelets express a variety of polymorphic proteins that may become targets for antibodies as a result of pregnancy or transfusion. The presence of antibodies that bind to platelet glycoproteins is associated with life-threatening bleeding disorders, such as refractoriness to platelet transfusions, post-transfusion purpura (PTP), and fetal and neonatal alloimmune thrombocytopenia (FNAIT). The Pak Lx assay may be used to detect and differentiate IgG antibodies to Human Platelet Antigens (HPA-1, HPA-2, HPA-3, HPA-4, HPA-5), Glycoprotein (GPIV), and Human Leukocyte Antigen (HLA Class I).  Once validated for use, Pak Lx may be used to support the selection of antigen negative or HLA-matched platelets for transfusion, providing a better matched unit to improve patient care. “Immucor is pleased to expand the offering of Pak Lx to the US market,” stated Christie Otis, Senior Transfusion Franchise Director at Immucor. “Pak Lx is an important addition to our platelet compatibility portfolio and provides another tool to enable laboratories to select antigen negative or HLA-matched platelets for transfusion. The availability of Pak Lx further supports Immucor’s portfolio for red cell and platelet compatibility testing.” Pak Lx availability demonstrates Immucor’s commitment to transfusion and transplant diagnostics.  Immucor’s total solution extends beyond platelet compatibility testing and includes a full line of automated immunohematology instruments including the NEO® and Echo® analyzers, PreciseType® (the only FDA licensed molecular immunohematology solution), and a broad portfolio of transplant solutions, including LIFECODES® for HLA typing and antibody screening, MIA FORA® for NGS HLA typing, and kSORT™ for post-transplant surveillance. Request a Demonstration To schedule a demonstration of Pak Lx, or any Immucor solution, Immucor clients may contact their local Molecular and Specialty Diagnostics Business Manager.  For more information about Immucor products, please contact your local Immucor representative or visit www.immucor.com. About Immucor Founded in 1982, Immucor is a global leader in transfusion and transplantation diagnostics that facilitate patient-donor compatibility. Our mission is to ensure that patients in need of blood, organs or stem cells get the right match that is safe, accessible and affordable. With the right match, we can transform a life together. For more information on Immucor, visit www.immucor.com.


PRINCETON, N.J., and HAMILTON, Bermuda, Feb. 27, 2017 (GLOBE NEWSWIRE) -- Advaxis, Inc. (NASDAQ:ADXS) and SELLAS Life Sciences Group, both late-stage biopharmaceutical companies focused on developing cancer immunotherapies, today announced that Advaxis has granted SELLAS a license to develop a novel cancer immunotherapy agent using Advaxis’ proprietary Lm-based antigen delivery technology with SELLAS’ patented WT1 targeted heteroclitic peptide antigen mixture (galinpepimut-S). Advaxis’ proprietary technology generates innate immune stimulation, alongside potent and sustained T-cell responses. When combined with SELLAS’ WT1 antigens, this has the potential to precisely direct an immune response, yielding improved clinical activity against many cancer types that express WT1. SELLAS’ future clinical studies will investigate this capability in the presence of measurable residual or recurrent disease. Galinpepimut-S has demonstrated positive phase 2 clinical results in acute myeloid leukemia and malignant pleural mesothelioma and positive early clinical data in multiple myeloma. It has been shown to induce strong immune responses (CD4+/CD8+) against the WT1 antigen and to access a broad range of HLA types. Advaxis’ Lm-based antigen delivery technology has demonstrated the potential to induce an enhanced innate immune stimulation and generate specific T cells while reducing immune tolerance in the tumor microenvironment. Under the terms of the collaboration, Advaxis will conduct all pre-clinical activities required for an IND filing. Thereafter, SELLAS will be responsible for all clinical development and commercial activities. Advaxis will receive future payments of up to $358 million from SELLAS if certain development, regulatory, and commercial milestones are met.  Following any regulatory approval of the product candidate emanating from this particular program, SELLAS has agreed to pay Advaxis single-digit to low double-digit royalties based on worldwide net sales upon commercialization. “WT1 is one of the most widely expressed cancer antigens and was named a top target for cancer immunotherapy by the National Cancer Institute,” said Daniel J. O’Connor, President and Chief Executive Officer of Advaxis. “SELLAS’ proprietary galinpepimut-S therapy has already demonstrated clinical benefit and a strong immune response against WT1 expressing cancer cells. We believe that the use of our proprietary Lm-based antigen delivery technology with SELLAS’ proprietary technology could result in a very compelling WT1-targeted cancer immunotherapy.” Angelos Stergiou, MD, ScD h.c., Vice Chairman and Chief Executive Officer of SELLAS, added: “The combined Advaxis-SELLAS Lm-WT1 active immunotherapy candidate has the potential to deliver SELLAS’ WT1 proprietary peptide antigens in a novel way, taking advantage of our antigen’s ability to target a wide variety of tumors of diverse immune system HLA genotypes. The delivery afforded by the Advaxis technology expands upon our current programs and should substantially enhance the clinical utility seen with galinpepimut-S, and eventually, the cancer immunotherapy armamentarium for a variety of tumors.” SELLAS Life Sciences is a late-stage biopharmaceutical company focused on the development of novel cancer immunotherapies and therapeutics for a broad range of cancer indications. The Company’s lead product candidate, galinpepimut-S, is a cancer immunotherapeutic agent licensed from Memorial Sloan Kettering Cancer Center that targets a broad spectrum of hematologic cancers and solid tumor indications. Galinpepimut-S is poised to enter Phase 3 clinical trials in patients with acute myeloid leukemia (AML) and mesothelioma in the first and second half of 2017, respectively. SELLAS recently received orphan drug designations by the US FDA, as well as the EMA, for galinpepimut-S in AML and MPM; as well as Fast Track Designation for AML and mesothelioma (MPM) by the US FDA. Galinpepimut-S also is in various development phases in multiple myeloma, ovarian cancer, and soon in other indications as monotherapy or in combination with other immuno-oncology agents. SELLAS was founded in 2012 and is headquartered in Bermuda, with additional offices in New York. For more information, visit www.sellaslifesciences.com. SELLAS’ WT1 immunotherapeutic anti-cancer treatment, galinpepimut-S, which was licensed by Sellas from Memorial Sloan Kettering Cancer Center, is a clinical-stage cancer immunotherapy being developed to target hematologic cancers and solid tumors, including AML, MPM, multiple myeloma, ovarian cancer, and multiple other cancers. The WT1 antigen is a transcription factor that is not generally expressed in normal adult cells, but appears in a large number of cancers, as well as in certain cancer stem cells. WT1 has been ranked by the NCI as the number 1 target for cancer immunotherapy. While WT1 has not been druggable by traditional approaches, it can be targeted by the immune system. Specifically, a number of different peptide sequences from the WT1 antigen have been identified as immunogenic and capable of stimulating cytotoxic T cells that can target and kill WT1-expressing cancer cells. Studies also have shown that WT1 does not provoke tolerization and that patients’ T cells can remain reactive to the antigen over time. Galinpepimut-S, originally developed by MSK and licensed to SELLAS, comprises four modified heteroclitic peptide chains that induce a strong innate immune response (CD4+/CD8+ T cells) against the WT1 antigen. Galinpepimut-S is administered in combination with an adjuvant and an immune modulator to improve the immune response to the target. Based on its mechanism and the accumulating evidence of activity in mid-stage trials, galinpepimut-S may have the potential to complement currently available therapies by destroying residual tumor cells of cancers in remission and providing ongoing immune surveillance for recurrent tumors. Overall, SELLAS’ galinpepimut-S could target over 20 cancers that over-express WT1, many of which are associated with relapse rates of up to 80 percent or more, as seen in patients with AML and MPM. Located in Princeton, N.J., Advaxis, Inc. is a clinical-stage biotechnology company developing multiple cancer immunotherapies based on its proprietary Lm Technology™. The Lm Technology, using bioengineered live attenuated Listeria monocytogenes (Lm) bacteria, is the only known cancer immunotherapy agent shown in preclinical studies to both generate cancer fighting T cells directed against cancer antigens and neutralize Tregs and myeloid-derived suppressor cells (MDSCs) that protect the tumor microenvironment from immunologic attack and contribute to tumor growth. Advaxis' lead Lm Technology immunotherapy, AXAL, targets HPV-associated cancers and is in clinical trials for three potential indications: Phase 3 in invasive cervical cancer, Phase 2 in head and neck cancer, and Phase 2 in anal cancer. The FDA has granted AXAL orphan drug designation for each of these three clinical settings, as well as Fast Track designation for adjuvant therapy for high-risk locally advanced cervical cancer (HRLACC) patients and a Special Protocol Assessment for the Phase 3 AIM2CERV trial in HRLACC patients. AXAL has also been classified as an advanced therapy medicinal product for the treatment of cervical cancer by the European Medicines Agency's Committee for Advanced Therapies. Advaxis has two additional immunotherapy products: ADXS-PSA in prostate cancer and ADXS-HER2 in HER2 expressing solid tumors, in human clinical development. In addition, Advaxis and Amgen are developing ADXS-NEO, a preclinical investigational cancer immunotherapy treatment designed to activate a patient's immune system to respond against the unique mutations, or neoepitopes, contained in and identified from each individual patient's tumor, with plans to enter the clinic in 2017. For additional information on Advaxis, visit http://www.advaxis.com/ and connect on Twitter, LinkedIn, Facebook, and YouTube. This press release contains forward-looking statements, including, but not limited to, statements regarding Advaxis’ ability to develop the next generation of cancer immunotherapies, and the safety and efficacy of Advaxis’ proprietary immunotherapy, axalimogene filolisbac. These forward-looking statements are subject to a number of risks including the risk factors set forth from time to time in Advaxis’ SEC filings including, but not limited to, its report on Form 10-K for the fiscal year ended October 31, 2016, which is available at http://www.sec.gov. Any forward-looking statements set forth in this presentation speak only as of the date of this presentation. We do not intend to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof other than as required by law. You are cautioned not to place undue reliance on any forward-looking statements.


SEATTLE, Feb. 14, 2017 (GLOBE NEWSWIRE) -- Nohla Therapeutics Inc. (Nohla), a leading innovator in the development of universal donor cellular therapies for the treatment of patients with blood cancers, announced today that it will present at the Cowen and Company 37th Annual Health Care Conference in Boston, MA. Dr. Colleen Delaney, Nohla’s Scientific Founder and Chief Medical Officer, is scheduled to present on Tuesday, March 7th at 2:00pm ET.  Dr. Delaney’s presentation will provide an overview of the Company’s ex vivo expansion platform, which enables expansion and directed differentiation of cord blood stem/progenitor cells resulting in “off-the-shelf” universal donor cellular therapies (which can be used on demand without the need for HLA matching). In addition, Dr. Delaney will profile Nohla’s two lead programs evaluating the ability of these products to reduce infection and other complications of neutropenia in multi-center, randomized clinical trials: a Phase IIb study in the setting of cord blood transplant and a global Phase II study in the setting of high dose chemotherapy for acute myelogenous leukemia (AML). Nohla Therapeutics Inc. (Nohla) is a clinical stage company dedicated to the development of universal donor cellular therapies for the treatment of patients with life threatening blood cancers. The Company is leveraging a platform developed over the past two decades at Fred Hutchinson Cancer Research Center which enables the ex vivo expansion and directed differentiation of cord blood stem/progenitor cells resulting in “off-the-shelf” universal donor cellular therapies (which can be used on demand without the need for HLA matching). Nohla is evaluating the ability of these “off-the-shelf” cryopreserved expanded cell products to reduce infection and other complications of neutropenia in several clinical settings including two lead programs involving multi-center, randomized clinical trials: a Phase IIb study in the setting of cord blood transplant and a global Phase II study in the setting of high dose chemotherapy for acute myelogenous leukemia (AML). Nohla is supported by top-tier healthcare dedicated institutional investors including ARCH Venture Partners, 5AM Ventures, and Jagen Group.

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