Charlottesville, VA, United States
Charlottesville, VA, United States

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Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.20M | Year: 2015

DESCRIPTION provided by applicant Drug induced vascular injury DIVI is a common phenomenon in pre clinical animal studies and is typically characterized by hemorrhage vascular endothelial and smooth muscle cell necrosis medial blood cell infiltration and inflammation Mechanisms underlying DIVI are not well understood for several reasons A DIVI result in a preclinical GLP animal study can interrupt or stop the progression of a promising drug to the clinic In addition GLP safety studies in non human primates required to de risk early DIVI findings in lower species are costly HemoShear LLC is a biotechnology research company that utilizes patented methodologies US to restore in vivo biology to animal and human primary cells in co culture in vitro The HemoShear vascular system exposes primary endothelial cells to vascular region specific hemodynamics in co culture with primary smooth muscle cells In this system vascular cells are rescued from a non physiological andquot stateandquot as indicated by restoration of region specific in vivo morphology and function Importantly cells in the HemoShear system demonstrate an efficacious or toxic response to drugs at concentrations that approximate in vivo animal or human exposure levels which are often to orders of magnitude different from standard D static cell culture systems HemoShearandapos s preliminary data with known DIVI compounds show that our science can predict unforeseen DIVI in vitro and prior to pre clinical GLP studies In HemoShear received the Tibbetts SBIR Award from the Small Business Administration for commercialization of innovation The purpose of this SBIR is to further validate the HemoShear DIVI platform for routine commercial application and prospective decision making in pre clinical drug discovery and development PUBLIC HEALTH RELEVANCE Drug induced vascular injury DIVI is a common phenomenon in pre clinical animal studies and is typically characterized by hemorrhage vascular endothelial and smooth muscle cell necrosis medial blood cell infiltration and inflammation Mechanisms underlying DIVI are not well understood for several reasons A DIVI result in a preclinical GLP animal study can interrupt or stop the progression of a promising drug to the clinic HemoShear LLC is a biotechnology research company that utilizes patented methodologies US to restore in vivo biology to animal and human primary cells in co culture in vitro HemoShearandapos s preliminary data with known DIVI compounds show that our science can predict unforeseen DIVI in vitro and prior to pre clinical GLP studies In HemoShear received the Tibbetts SBIR Award from the Small Business Administration for commercialization of innovation The purpose of this SBIR is to further validate the HemoShear DIVI platform for routine commercial application and prospective decision making in pre clinical drug discovery and development


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.69M | Year: 2015

DESCRIPTION provided by applicant Human inducible pluripotent stem cells iPSCs proliferate readily and can be terminally differentiated into hepatocytes which potentially makes them an attractive cost effective resource compared to primary human hepatocytes Moreover the ability to standardize a platform to a single human donor or donor s who may include known genetic drug metabolism polymorphism s can eliminate or greatly reduce donor donor variability associated with primary hepatocytes Unfortunately it has been clearly demonstrated that differentiated iPSC derived hepatocytes iHCs though similar to primary hepatocytes in many ways retain certain andquot fetalandquot like aspects This includes increased expression of fetal like proteins e g fetal protein and decreased activity of specific cytochrome p enzymes e g the CYP A family which is responsible for metabolizing over of drugs Thus the pharmaceutical industry and regulatory agencies view the use of iHCs as promising but currently limited Attempts to andquot matureandquot these cells in novel hepatocyte platforms have not proven successful HemoShear is a biotechnology research company that utilizes patented methodologies to restore in vivo responsiveness to human primary cells in vitro We commercialized a human primary hepatocyte platform that combines physiological principles of controlled hemodynamics and transport to restore and maintain mature in vivo like differentiated phenotype morphology and metabolic function Hepatocytes in this platform respond to drugs and hormones at in vivo concentrations The purpose of this Fast Track SBIR is to develop an iHC platform using the HemoShear technology to mature iHC differentiated function and drug responses at physiological levels providing the framework for commercializing a much needed platform for drug safety and efficacy assessment PUBLIC HEALTH RELEVANCE Human inducible pluripotent stem cells iPSCs proliferate readily and can be terminally differentiated into hepatocytes which potentially makes them an attractive cost effective resource compared to primary human hepatocytes for drug discovery and development Unfortunately it has been clearly demonstrated that differentiated iPSC derived hepatocytes iHCs though similar to primary hepatocytes in many ways retain certain andquot fetalandquot like aspects Thus the pharmaceutical industry and regulatory agencies view the use of iHCs as promising but currently limited HemoShear is a biotechnology research company that utilizes patented methodologies to restore in vivo responsiveness to human primary cells in vitro The purpose of this Fast Track SBIR is to develop an iHC platform using the HemoShear technology to mature iHC differentiated function and drug responses at physiological levels providing the framework for commercializing a much needed platform for drug safety and efficacy assessment


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 255.13K | Year: 2015

DESCRIPTION provided by applicant Non alcoholic fatty liver disease NAFLD is a rapidly emerging public health crisis affecting up to of Type diabetics and of obese individuals Glucose and insulin regulate de novo lipogenesis in the liver Glucose and insulin regulate de novo lipogenesis in the liver High glucose and insulin in human diabetics and animal models stimulate fat buildup in the liver that progresses to steatohepatitis However there are no in vitro hepatocyte models that possess an adequate insulin glucose response to induce steatohepatitis through a similar signaling pathway HemoShear is a biotechnology research company that utilizes patented methodologies US to restore in vivo biology and responsiveness to primary cells in vitro In HemoShear received the Tibbetts SBIR Award from the Small Business Administration for commercialization of innovation In the HemoShear primary hepatocyte system the presence of high glucose and insulin results in de novo hepatocyte lipogenesis and lipid accumulation histologically similar to primary human hepatocytes from a steatotic liver This is unprecedented The purpose of this Phase I SBIR is to further investigate induction of steatosis and progressive steatohepatitic changes in response to known risk factors at clinically relevant levels within HemoShearandapos s human primary hepatocyte system providing the framework a much needed platform to assess the efficacy of drugs and biomarkers under development identify new targets and biomarkers and support investigative toxicology in steatohepatitis PUBLIC HEALTH RELEVANCE Non alcoholic fatty liver disease NAFLD is a rapidly emerging public health crisis affecting up to of Type diabetics and of obese individuals There are no meaningful in vitro systems to study human steatosis HemoShear is a biotechnology research company that utilizes patented methodologies US to restore in vivo biology and responsiveness to primary cells in vitro In HemoShear received the Tibbetts SBIR Award from the Small Business Administration for commercialization of innovation The purpose of this Phase I SBIR is to further investigate induction of steatosis and progressive steatohepatitic changes in response to known risk factors at clinically relevant levels within HemoShearandapos s human primary hepatocyte system providing the framework a much needed platform to assess the efficacy of drugs and biomarkers under development identify new targets and biomarkers and support investigative toxicology in steatohepatitis


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.99M | Year: 2015

Not Available


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 463.48K | Year: 2015

DESCRIPTION provided by applicant Liver cell based systems are widely used to study drug metabolism toxicity and liver disease However the poor correlation between in vitro data and clinical outcomes is very real and attributed in part to the missing physiological context of the hepatic microenvironment sinusoidal flow and transport three dimensional architecture and heterotypic cell cell interactions HemoShear LLC is a biotechnology research company that utilizes patented methodologies US to restore in vivo biology to animal and human primary cells in co culture in vitro Recently under the SBIR mechanism HemoShear has commercialized in vitro rat and human primary hepatocyte systems that combine physiological principles of hemodynamics and transport to restore and maintain in vivo like differentiated hepatocyte phenotype and function Primary hepatocytes in this system respond to drugs and risk factors at concentrations that approximate in vivo and clinical response levels a major advantage for our commercial partners see Letters of Support However in spite of the rapid commercial uptake of this single cell type system primary hepatocytes only this platform could fail to capture drug toxicities requiring the involvement of multiple liver cell types e g non parenchymal cells NPCs resulting in preclinical false negatives that manifest toxicity in the clinic The purpose of this Fast Track SBIR is to develop a human physiological hepatocyte NPC multi cellular liver system and validate drugs that are known to cause drug induced liver injury through an NPC mediated process for which there are currently no such preclinical human based systems PUBLIC HEALTH RELEVANCE Liver cell based systems are widely used to study drug metabolism toxicity and liver disease However the poor correlation between in vitro data and clinical outcomes is very real and attributed in part to the missing physiological context of the hepatic microenvironment sinusoidal flow and transport three dimensional architecture and heterotypic cell cell interactions HemoShear LLC is a biotechnology research company that utilizes patented methodologies US to restore in vivo biology to animal and human primary cells in co culture in vitro HemoShear has commercialized in vitro rat and human primary hepatocyte systems that combine physiological principles of hemodynamics and transport to restore and maintain in vivo like differentiated hepatocyte phenotype and function The purpose of this Fast Track SBIR is to develop a human physiological hepatocyte NPC multi cellular liver system and validate drugs that are known to cause drug induced liver injury through an NPC mediated process for which there are currently no such preclinical human based systems


Patent
HemoShear | Date: 2014-10-21

Methods for mimicking a tumor microenvironment in vitro are provided. The methods comprise indirectly applying a shear stress upon at least one tumor cell type plated on a surface within a cell culture container. Methods for mimicking tumor metastasis and methods for testing drugs or compounds in such systems are also provided.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 249.01K | Year: 2014

DESCRIPTION (provided by applicant): R43 SBIR: Development of an iPSC-derived human vascular system for drug development. ABSTRACT Human inducible pluripotent stem cells (iPSCs) can be differentiated into vascular endothelial (iEC) and smooth muscle (iSMC)cells and hold immense potential for developing drugs in genetically defined subpopulations and for patients with vascular rare diseases, such as Marfan's syndrome, from which iPSCs can be acquired. However, it has not been clearly demonstrated that iECsand iSMCs are phenotypically similar to differentiated human primary adult vascular cells, including disease risk factor and drug responsiveness. This cannot be understated as recent studies with iPSC-derived hepatocytes have shown that these cells provide limited utility to the FDA and pharmaceutical industry for drug discovery as they retain many fetal -like characteristics, failin to express primary hepatocyte levels of many cytochrome p450 enzymes, including the CYP3A family, which is responsible


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 281.94K | Year: 2014

DESCRIPTION (provided by applicant): Human inducible pluripotent stem cells (iPSCs) proliferate readily and can be terminally differentiated into hepatocytes, which potentially makes them an attractive, cost-effective resource compared to primary human hepatocytes. Moreover, the ability to standardize a platform to a single human donor, or donor(s) who may include known genetic drug metabolism polymorphism(s), can eliminate or greatly reduce donor-donor variability associated with primary hepatocytes. Unfortunately, it has been clearly demonstrated that differentiated iPSC-derived hepatocytes (iHCs), though similar to primary hepatocytes in many ways, retain certain fetal -like aspects. This includes increased expression of fetal-like proteins, e.g.??fetalprotein, and decreased activity of specific cytochrome p450 enzymes, e.g. the CYP3A family, which is responsible for metabolizing over 60% of drugs. Thus, the pharmaceutical industry and regulatory agencies view the use of iHCs as promising but curren


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.21M | Year: 2016

Phase II SBIR Validation of a human in vitro system of hepatic steatohepatitis ABSTRACT Non alcoholic steatohepatitis NASH is part of the progressive disease spectrum of non alcoholic fatty liver disease NAFLD a public health crisis affecting of type diabetics and of obese individuals Glucose and insulin regulated de novo lipogenesis in the liver a critical step in the disease process is severely compromised in cellular hepatocyte systems typically used for drug discovery and development due to dedifferentiation in vitro and the requirement for supra physiological high levels of insulin X in vivo and glucose X in vivo to sustain viability The consequent lack of insulin sensitivity and responsiveness challenges the relevance of disease and target biology limiting the confidence in target discoveries made using these systems This along with the use of mouse models that do not mimic human disease pathogenesis may explain the current landscape of over drugs for NASH in preclinical clinical development without any consensus on the optimal human targets This lack of human relevance drives high failure rates for this indication HemoShear Therapeutics is a biotechnology company that utilizes a patented technology to recreate human liver disease biology using human primary cells In our Phase I SBIR we developed a steatohepatitis system using hepatocytes cultured in more physiological levels of glucose and insulin Since our last submission we have further matured the liver system to include human stellate cells and macrophages in addition to hepatocytes The resulting disease model exhibits progressive steatohepatitic changes in response to a pathological milieu based on human disease risk factors and demonstrates the ability of the HemoShear liver system to assess the therapeutic efficacy and mechanisms of promising new drug candidates at clinically relevant concentrations The purpose of the Phase II SBIR is to validate the disease relevance of the HemoShear multi cellular model by benchmarking against clinical liver tissue samples from NASH patients and to evaluate the effect of a diverse set of pharmacological pathway inhibitors on each of the core biological pathways impacted by the NASH phenotype !Phase II SBIR Validation of a human in vitro system of hepatic steatohepatitis NARRATIVE Non alcoholic steatohepatitis NASH is part of the progressive disease spectrum of non alcoholic fatty liver disease NAFLD a public health crisis affecting of type diabetics and of obese individuals In vitro cell culture and in vivo mouse models of NAFLD NASH do not recapitulate the human disease and may explain the current landscape of over drugs for NASH in preclinical clinical development without any consensus on the optimal human targets This lack of human relevance drives high failure rates for this indication HemoShear Therapeutics is a biotechnology company that utilizes a patented technology to recreate human liver disease biology using human primary cells Our Phase I SBIR and subsequent studies developed a multi cellular steatohepatitis system that exhibits progressive steatohepatitic changes in response to a pathological milieu that demonstrates the ability to assess the therapeutic efficacy and mechanisms of promising new drug candidates The purpose of the Phase II SBIR is to validate the disease relevance of the HemoShear multi cellular model by benchmarking against clinical liver tissue samples from NASH patients and to evaluate the effect of a diverse set of pharmacological pathway inhibitors on each of the core biological pathways impacted by the NASH phenotype


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 433.82K | Year: 2016

Fast Track SBIR Identification and validation of targets for therapeutic intervention in rare diseases of intermediary metabolism defects ABSTRACT There are very few reliable methods to study and understand the biology of liver rare diseases in the laboratory for the purpose of drug discovery and development which contributes to a dismal record for development of new treatments First genetic mouse models do not faithfully mimic human rare diseases Second modeling liver diseases in vitro is challenging on account of the rapid loss of the liver like phenotype of primary hepatocytes in vitro For these reasons target ID validation and prioritization can be misleading and costly In HemoShear LLC and Childrenandapos s National Health System formed a strategic partnership to systematize and accelerate discovery and treatments for rare diseases of the liver HemoShear is an early stage biotechnology company with a patented technology for recreating human liver disease biology in the laboratory using human primary cells The Division of Genetics and Metabolism at Childrenandapos s is a premier research center with the nationandapos s largest clinical program that studies and treats patients with liver rare diseases Under this partnership we have already shown that biomaterial from patients treated at Childrenandapos s can be used to validate the rare disease system developed at HemoShear for the identification of targets for therapeutic development Chapman et al Mol Gen Metab This study will focus on the biochemical group of diseases called organic acidemias specifically propionic acidemia and methylmalonic acidemia These rare diseases have high early and late mortality rates there are no primary therapies for these conditions and patients often undergo liver transplant to control symptoms The purpose of this FastTrack SBIR is to identify validate and prioritize targets for the future development of therapies to treat patients with intermediary metabolism defects in the liver Fast Track SBIR Identification and validation of targets for therapeutic intervention in rare diseases of intermediary metabolism defects NARRATIVE There are very few reliable methods to study and understand the biology of liver rare diseases in the laboratory for the purpose of drug discovery and development which contributes to a dismal record for development of new treatments In HemoShear LLC and Childrenandapos s National Health System formed a strategic partnership to systematize and accelerate discovery and treatments for rare diseases of the liver Under this partnership tissue and biomaterial from patients treated at Childrenandapos s can be used to validate the rare disease system developed at HemoShear for the identification of targets for therapeutic development This study will focus on the biochemical group of diseases called organic acidemias These rare diseases have high early and late mortality rates there are no primary therapies for these conditions and patients often undergo liver transplant to control symptoms The purpose of this FastTrack SBIR is to identify validate and prioritize targets for the future development of therapies to treat patients with intermediary metabolism defects in the liver

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