Axol Bioscience - March Newsletter

This month's highlights

As warmer weather starts to creep in and the UK prepares for Daylight Savings Time, we've found ourselves casting an optimistic eye into the (near) future of iPSC technology.

• This month saw us visit the Society of Toxicology (SOT) 63rd Annual Meeting where we discussed our work building better in vitro neurotoxicity and cardiotoxicity models with human iPSCs. SOT also saw us launch our new axoCells? Atrial Cardiomyocytes Kit (see below) and discuss two exciting concepts for the future of cardiotoxicity models
• We've also been discussing developing areas of Alzheimer's Disease drug discovery, including the role of TREM2 mutations in human iPSC-based Alzheimer's Disease models. We're excited about the concept of complex neurodegenerative disease models, including co-culture and "clinical trial in a dish" formats
• Promising developments in the FDA Modernization Act 3.0 and wider regulatory drivers are bolstering the global iPSC market (read more below). We've been keeping our finger on the pulse at in-person events (including SOT and World Organoid Research Day+) and have launched a poll to get our community's thoughts on where iPSCs will have the greatest impact. Details below- make sure to vote!

New cardiac kit launch for better models of AF

The major benefit of close engagement with our iPSC community is understanding where the needs are, which is why we've developed our new axoCells Atrial Cardiomyocytes Kit for more useful in vitro atrial fibrillation models.

We were delighted to officially launch our new axoCells Atrial Kit at the SOT 63rd Annual Meeting, with an opportunity to discuss the benefits of the kit with experts in cardiac safety pharmacology.

Key features of this axoCells Atrial Cardiomyocyte kit include:

• Tailored culture medium and optimized coating solution for maximal cell viability and growth
• Validated functional performance in a range of assays, including patch clamp, electrophysiology and contractility on the InnoVitro FLEXcyte 96
• Chamber-specific pharmacological responses demonstrated

And all in a handy kit format, saving you time and money!

You can read more about our axoCells Atrial Kit here.

Exploring two exciting concepts for in vitro cardiotoxicity models

At Axol Bioscience, we've been looking into the key questions of utility and relevance for iPSC-derived cardiotoxicity models. We've therefore produced two discussion documents based on our research in this space:

1. Our ongoing work licensing an innovative protocol developed by a team at The Crick Institute, which aims to produce purer populations of left ventricular cardiomyocytes (click here to read)
2. The identification of a metabolic maturation media to enhance cardiomyocyte maturity (click here to read)

We enjoyed discussing these concepts at SOT as part of our wider work in the cardiac and cardiotoxicity space. You can read more about how we're supporting in vitro cardiac safety pharmacology projects in our 2024 Cardiac Guide.

TREM2 for in vitro Alzheimer's Disease models

Alzheimer's Disease is the most common form of dementia worldwide, affecting over 40 million people. But despite this prevalence, we still have limited treatments and a staggering 99.6% failure rate for promising pre-clinical therapies.

One gene that is of increasing interest to AD researchers is TREM2 (triggering receptor expressed on myeloid cells 2), which plays an important role in microglial function. TREM2 mutations have been linked to the development of abnormal microglial behavior, potentially driving neurodegenerative diseases including AD.

At Axol Bioscience, we're excited about the potential of TREM2 for AD drug discovery and have been exploring it as part of our wider AD disease model focus.

We've therefore produced a discussion document to outline:

• Why TREM2 could be a major target for AD drug discovery
• The work we've done investigating TREM2 mutations in microglia
• How we can support researchers looking to build in vitro TREM2 AD models

Click here to access our discussion document. If you'd like to discuss an Alzheimer's Disease/TREM2 project, please get in contact at [email protected]

Unlock the benefits of iPSC-based co-culture models

Looking to use iPSC-derived co-culture models in your research? We can help!

Stepping up from mono-culture to co-culture experiments can be technically challenging, which is why we're offering our expertise to groups looking to benefit from more complex in vitro models.

Two examples of our work in this space include:

• The impressive data behind the testing of an axoModel? built as a complex tri-culture model for compound screening. In partnership with Sumitomo Pharma America Inc., we used axoCells cortical excitatory neurons, inhibitory interneurons and astrocytes to produce a cortical tri-culture model that was successfully tested against a blinded panel of compounds, demonstrating its value as a compound screening platform and paving the way for future testing of neurotoxic liability
• The generation of AD patient cell lines homozygous for the APOE4 allele or with mutations in presenilin-1 (PSEN1) and presenilin-2 (PSEN2), which we differentiated into iPSC-derived astrocytes, cortical neurons, and microglia and characterized with ICC, transcriptomics and/or flow cytometry

If you'd like to unlock the benefits of iPSC-derived co-culture models, get in touch with us at [email protected] to see how we can best help you.

Key regulatory drivers for the widespread adoption of iPSC technology

Last year, the FDA Modernization Act 2.0 made history by allowing cell-based assays and related technologies to replace animal models in pre-clinical research. This provided the catalyst for industry change, with an increasing number of biopharma organizations transitioning to in vitro models- some for the very first time.

We're delighted to see three key regulatory drivers continue that momentum in 2024:

• The UK Government announced increased funding (doubled from ￡10 million to ￡20 million) into non-animal alternatives, alongside an action plan to enhance the "development, validation and uptake of technologies and methods to reduce reliance on the use of animals in science"
• We also saw the approval of the NIH?Common Fund’s Complement Animal Research In Experimentation (Complement-ARIE)?program which seeks to "speed [up]?the development, standardization, validation, and use" of NAMs, bringing together the expertise of industry scientists to drive progress in research models.
• Staying in the US, the FDA Modernization Act 3.0 was introduced in the US House of Representatives, building on the momentum from the FDA Modernization Act 2.0 to expand alternatives to animal models (including stem cell-based assays) for pre-clinical drug testing. The FDA Modernization Act 3.0 aims to introduce a qualification process for alternative methods and widen the definition of "non-clinical test" to incorporate innovative technologies including cell-based assays, organoids and organ-on-chip models.

We're excited to see the downstream impact of these regulatory drivers and welcome the recognition of in vitro technology at the government/policy level.

This is also a great opportunity to revisit our interview with Elizabeth Baker, Esq., an award-winning attorney who played an active role in laying the foundations for the FDA Modernization Act 2.0.

Have your say! Where will iPSC models have the great impact?

2024 is shaping up to be "the year of iPSCs" with human iPSC technology shooting up the biopharma priority list. There's an exciting array of applications from ALS and Alzheimer's Disease to pain models, sensory studies and sophisticated cardiotoxicity models.

So we've launched a poll to gauge our community's views on where iPSC-based models will have the greatest impact, out of:

• Early drug discovery (*currently in the lead*)
• Compound screening
• Patient stratification models
• Toxicity studies

Click here to have your say and make sure to follow us on LinkedIn to never miss our polls, surveys and opportunities to get involved with our work.