ISR Platform®
A unique research tool for injection site reaction studies
Human response to your vaccine and drug candidates
First-in-human data without harming humans or animals
Local adverse events are too often discovered upon injection during clinical trials, causing unexpected pain to volunteers and resulting in lower patient compliance. Genoskin has designed a unique platform to study inflammatory side-effects to injections prior to clinical trials. Our ISR Platform® helps you assess and predict inflammatory response to subcutaneous, transdermal and intradermal vaccines, drugs and medical devices. A quick overview of the platform’s features and benefits:
Cutting-edge
Unbiased automated machine-learning based analysis of immunotoxicity and cytotoxicity.
Characterization
Deep knowledge of drug-induced pseudo-allergic reactions to better prevent and mitigate them.
Injections
Local biological response to self-injected drugs from live, immunocompetent human skin.
Adverse events
Predict the number one complaint from patients upon injection of biologics, prior to clinical trials.
What are injection site reactions?
Injection site reactions (ISRs) are fast, localized inflammatory reactions, characterized by pain, itch, swelling, and erythema. They are one of the most commonly reported adverse effects upon injection of a biologic drug. ISRs are known as “pseudo-allergic responses” as these reactions are not mediated through the classical IgE-mediated mast cell degranulation pathway.
Corbière, A, Loste, A, Gaudenzio, N.- Exp Dermatol. 2021; 30: 193– 200.
Why study injection site reactions?
With the rapid growth of the biologic drugs class over the past two decades, a massive increase in unwanted immunogenic response has been reported. Too often, local adverse effects are only discovered at the clinical trial stage or when a drug is already on the market. As a consequence, they may delay the drug development process and increase associated costs or negatively affect patient compliance when discovered after the drug is put on the market.
Obtain data from our unique injectable platform
Live response from immunocompetent human skin
Genoskin offers an innovative first-in-human approach to help you detect and understand potential injection site reactions in order to select the best drug candidate and secure your development process. We inject your drug or vaccine into a healthy, biostabilized and immunocompetent human HypoSkin® model to characterize potential ISRs.
The HypoSkin® platform contains real human epidermis, dermis and adipose tissue and all native human skin appendages and immune cells. The model is particularly suited to test injection site reactions ex vivo and observe mast cell degranulation in situ. Moreover, it allows to observe response from live human skin to your vaccine, needle or drug for an entire week.
Study human immunotoxicity and cytotoxicity in response to your drug
Custom experiments to help you move forward
Genoskin’s ISR platform® helps biotech and pharmaceutical companies understand and mitigate injection site reactions and determine the right formulation for their drug candidate, biosimilar or marketed drug. Depending on your needs, our expert immunologists design custom experiments to provide reliable answers and help you move forward safely.
Immunotoxicity
Local immune burst & inflammatory event associated with skin-resident immune cell or mast cell activation is mostly caused upon injection of biologic drugs.
Cytotoxicity
Local toxicity causing cell death and necrosis is mostly caused upon injection of small molecule drugs.
First-in-human data on immunotoxicity
Study in situ mast cell degranulation & cytokine release
Genoskin helps you understand how likely your molecule or device is to trigger mast cell-dependent or -independent inflammatory reactions. We study the immunotoxicity of subcutaneous or intradermal drugs, vaccines and medical devices by introducing them in our HypoSkin® models. This unique approach helps you obtain live immune response in order to analyze in situ mast cell degranulation and/or cytokine release to better understand immune reactions. It is also possible to evaluate different formulations on a cohort of skin models from healthy donors to measure dose response.
In Situ Mast Cell Degranulation
Characterize off-target inflammatory response
In situ mast cell activation and degranulation assays help you predict and characterize off-target inflammatory reactions. The generated data are analyzed using our proprietary machine-learning software for unbiased and automated quantification of the presence and level of degranulation. To take characterization even further, we also provide a unique in vitro human primary mast cells platform.
Unbiased Multiplex Cytokine Assays
Profile inflammatory response at the proteomic level
We simultaneously measure the proteins released in the HypoSkin® culture medium and matrix. Cytokines are dosed using the MesoScale technology. The data are then clustered using our proprietary Audacy (AUtomated Data Analysis of CYtokines) application, to profile inflammation at the proteomic level, highlight the mechanisms involved and associate real-world evidence to better predict clinical outcomes.
First-in-human data on cytotoxicity
Predict local toxicity for self-injected drugs
Genoskin’s ISR platform® helps you de-risk clinical trials via cytotoxicity studies on living human skin from a cohort of healthy donors. Genoskin’s ISR platform® helps biotech and pharmaceutical companies understand and mitigate injection site reactions and determine the right dosage for their drug candidate, biosimilar or marketed drug. When it comes to research on immunotoxicity, the platform generates first-in-human data on loss of cell viability, signs of cell death and cytokine release.
Identify loss of cell viability
To provide reliable data on loss of cell viability in human skin, our skin biology experts perform histological analyses to quantify pyknosis, epidermal detachment, papillary dermis alteration or breaks in adipocyte membranes.
Detect signs of cell death
Our experts perform a range of immunofluorescence assays, such as TUNEL assays, to detect DNA breaks. We also conduct spectrometry analyses of LDH release to measure cell death.
Explore cytokine release
To generate an injected drug’s proteomic signature and better characterise off-target events, we combine multiplex cytokine assays with Audacy, our proprietary software that allows automated clustering of cytokines for unbiased analysis.
Study reactions for multiple donors
Include donor diversity to increase data relevance
Since our human data generation platforms only contain donated skin, it is possible to conduct studies on multiple donors to represent the diversity of the human population or of your target audience. The characteristics of our skin models are donor-dependent and reflect the natural biological diversity of the general population, allowing for more accurate and relevant study results. Our human data platforms are one of the great strengths of our approach, which offers the added possibility of mimicking small clinical trials. In order to generate statistically relevant results, Genoskin recommends 3 to 5 donors and 3 replicates.
Multiple donors of different age, gender and ethnicity
Parallel testing of different compounds in the same donor
Take your research one step further
Discover what triggered the adverse event
Genoskin associates cutting-edge technology with proprietary AI-based analytical applications to help you understand the mechanism of action behind the adverse effect we observed in situ or following a clinical trial. We generate the unique biological signature left behind by your biotherapeutic agent to select the drug candidate or formulation that is least likely to trigger injection site reactions, combining our MANTIS® spatial biology platform and RNA sequencing.
MANTIS® Spatial Biology Platform
Our MANTIS® spatial biology platform provides complete immune profiling in response to your drug or formulation to better understand the immune cell interactions associated with the adverse event.
Next Generation RNA Sequencing
Our experts also conduct next generation RNA-Sequencing to help you understand the off-target effects of your drug on the human transcriptome, a good addition to further characterize a drug’s mechanism of action.
Interested in seeing how others use our ISR® Platform?
Feel free to have a look at this case study to see how one of our customers mitigated injection site reactions using the ISR Platform®.
