Worldwide, numerous urgent initiatives have been started with the aim to repurposing approved drugs for the treatment of COVID-19. Hopefully, this fast-track approach will serve to cure affected patients in the near future, as clinical safety of this approved drugs has already been demonstrated. In addition, research teams in industry and academia are unleashing many antiviral drug development programs to identify new treatment modalities (e.g., RNA-based vaccines) or develop novel therapeutic viral targets.

To join the fight against the COVID-19 pandemic, InSphero has decided to support these efforts by providing free access to our 3D in vitro liver toxicology platform for the assessment of drug-induced liver injury (DILI) as part of the preclinical risk assessment.

New therapeutic modalities, such as RNA-based vaccines, are not always suitable for classical safety testing, which typically includes translational testing using animal models.

InSphero’s 3D in vitro human liver models can mimic liver function for up to four weeks in the lab. These co-culture models, comprised of primary human hepatocytes and NPCs (which are important for capturing the immune response), represent the smallest functional unit of a human liver and are highly predictive for identifying safety hazards.

Our testing technology is fast (typically, a three-week turnaround) to ensure drug development programs move forward swiftly and offer a new, efficient way to test novel modalities as well as classical compounds.

The InSphero 3D InSight™ Liver Toxicology Platform is well suited for hepatotoxic risk assessment of most therapeutic agents relevant to the treatment of COVID-19. Here's why:

• Human cell-based models
• Biological relevant. 3D InSight™ Human Liver models mimic human liver function for up to four weeks in the lab
• Highly predictive in identifying safety hazards
• Fast turnaround times (typically within three weeks) to ensure drug development programs proceed swiftly
• Suitable for testing viral disease-combating modalities as well as classical small molecule compounds, such as recombinant, polysaccharide, or nucleic-acid-based antigen vaccines (based on results of our internal R&D pilots)

This offer is directed globally to any pharmaceutical or biotech industry as well as academic, governmental or NGO research entity engaging in drug/vaccine development programs targeted to treat and foster immunity against COVID-19

Long-term toxicity testing on 3D InSight™ Liver Microtissues with most therapeutic agents. A full concentration-response is assessed using human liver microtissues, composed of primary human hepatocytes and NPCs (primarily Kupffer cells), conferring innate immunity. Three repeated treatments are provided over a period of 14 days to mimic chronic exposure. For more information, click on the links below:

• DILI testing overview
• 3D human liver models
• A comprehensive evaluation study published in Arch. Toxicol

Per program, each project order is limited to max. 3 test items of the above indicated therapeutic classes. Timing is at InSphero’s discretion, with the fastest turnaround possible (approx. 3-4 weeks). Due to the current situation, we cannot offer a processing guarantee for your samples at this time.

• Measurement of ATP levels after 14 days of exposure
• Measurement of LDH release (a marker for membrane damage) at three-time points
• Concentration-response curve for 7 concentrations, positive control (chlorpromazine)
• A written report summarizing results

Maximum of 3 (three) test items per program, dissolved at 200x max. dosing concentration, provided in screw cap tubes.

• Small molecules should be delivered in 100% DMSO solutions, with other solvents possible upon request (e.g., for antibodies or ASOs)
• Volume 50-100 μl
• Please note that neither volatile substances nor powders will be accepted.

• 1. InSphero covers the full cost of testing, including handling, data analysis, and reporting
  2. Requests are served on a first-come, first-served basis
  3. This offer is subject to availability and can be terminated at any time
  4. InSphero cannot guarantee the execution of testing as circumstances due to the Covid-19 outbreak may prohibit to maintain of lab services due to governmental lockdown decree or supply shortage
  5. InSphero has no interest in participating in potential future revenues related to tested drug candidates (no IPR, license fees, or other payments)
  6. All information regarding customer relationships, compound specifications, and experimental data will be handled strictly confidential. Experimental data are owned by the project partner
  7. Partner allows InSphero to list its organization name as a member of the Covid-19 DILI initiative
  8. InSphero shall under no circumstances be liable for direct or indirect damage or loss of any kind, including any contract penalties that the Partner may have to pay to a third party, nor for the Partner's operating loss, time loss, lost supplies, or similar losses.
  9. The Partner shall indemnify and hold harmless InSphero from and against any and all third-party losses, claims, damages, or liabilities, to the extent caused by, arising from, or in connection with (i) any use, including but not limited to clinical trials, or sale or transfer by the Partner to any third party or any product or information provided by InSphero to the Partner under these Terms & Conditions, or (ii) any use or storage by InSphero of any materials supplied by the Partner to InSphero under these Terms & Conditions.
  10. Force majeure: InSphero shall not be liable for failing or delayed fulfillment of supplies if the cause is force majeure, such as fire, government intervention or intervention by other public authorities, strike, lockout, export and/or import bans, vandalism, currency restrictions, delayed and/or defective supplies from subcontractors or any other cause beyond the control of InSphero.

March 24, 2020