Scaling up: The need for human cells to give better access to cell therapies

Cells under a microscope

Reece Armstrong speaks to Kathryn Golden, SVP Technical Operations and Manufacturing, bit.bio, about novel technologies, and methods to manufacture human cells for therapies so more patients can access these treatments.

Cell therapies have emerged as transformative and potentially curative treatments across a range of disease areas. These therapies, which utilise human cells to replace diseased or damaged cells or use engineered cells to act as therapies for a specific disease, have become more common in recent years, with approvals and clinical trials increasing.

Perhaps the greatest example of this has come from CAR-T cell therapies, which have developed as treatments for aggressive lymphomas, particularly in childhood cancers. In fact, long-term follow-up data in children with relapsed acute lymphoblastic leukaemia who were treated with CAR-T cells showed promising complete remission rates, with 60% of the patients still being alive after five years and without their cancer coming back1.

These successes in cell therapies are exciting and the future potential for these treatments is something that Golden says brought her to bit.bio, as the company’s focus on cellular reprogramming means that it can expand past T-cells, which have been the primary focus of a lot of cell therapies and are the cell type used in CAR-T. She and bit.bio are going beyond this cell type and looking at producing other cell types which may provide answers to a range of diseases beyond blood cancers.

And it’s not just bit.bio – there are many other companies exploring different cell types within clinical research. For example, Vertex Pharmaceuticals’ stem-cell treatment for sickle-cell disease and transfusion-dependent β-thalassemia was authorised by the Medicines and Healthcare products Regulatory Agency (MHRA) in November 2023, making it the first licensed therapy that uses the gene-editing tool CRISPR to help treat patients. Moreso, research using natural killer cells blossomed in 2023 with a number of companies targeting use-cases in Alzheimer’s oncology, and even diabetes.

It’s safe to say there is a lot of potential for cell therapies. But they face several major challenges that the industry needs to address if they are to be brought to more patients. One of these is cost, driven largely by the bespoke and expensive manufacturing processes.

Challenges

“There are some cell therapies on the market but the cost of those is maybe $500,000 a dose. And although they’re life changing therapies, the issue at the moment is they are just not going to be accessible to everyone who might need them,” Golden explains.

Specifically, one of the problems that drives up the costs of these therapies is that all those that have been approved are autologous – meaning it’s the patient’s own cells which are used within the treatment.

“When it comes to autologous therapies, in the ideal situation you have the patient in the hospital, you’re pulling their cells out, you transport that somewhere, you do a manipulation on those cells, you transport them back, and then you get them back to the patient,” Golden adds, going onto mention that it’s this logistical process which is in part due to the reason for the high costs of these treatments.

More so, ex vivo cell therapies can exhibit short half-lives of only a few hours, meaning production facilities must be located close to the healthcare system in order to deliver treatments to patients as quickly as possible. It’s a laborious process to deliver a single dose of treatment to one patient.

To date, cell therapy approvals have largely been for oncology treatments, and whilst the production and delivery on a single-use autologous product makes sense in terms of a patient’s cancer, scaling up production will be essential if cell therapies are developed to treat other prevalent diseases.

If drug developers had a way to access cells that aren’t required to be taken from the patient, they could potentially develop off-the-shelf therapies that would be available to patients and that had fewer logistical or manufacturing burdens than autologous treatments. This allogeneic approach is something Golden states is key to both reducing the cost of cell therapies and increasing their access to patients. In fact, it’s something that forms part of her passion for being at bit.bio.

bit.bio has positioned itself as a synthetic biology company dedicated to democratising access to human cells. It’s been doing this through its opti-ox platform – which is used to execute genetic programs in human induced pluripotent stem cells (iPSCs), effectively reprogramming them into any human cell of choice.

Why is this important?

Stem cells act as the only other alternative to donor cells when developers want to take an allogeneic approach to their therapies. Donor cells – where the cells are not taken from the patient but from a healthy donor – are also being used to develop allogeneic therapies. But whilst donor cells are more difficult to scale, stem cells are not – if you have the right technology – which is where bit.bio’s opti-ox comes in.

“opti-ox results in a really homogeneous culture of iPSCs that we can control well and scale up with the reprogramming technology engineered in and ready to go,” Golden says.

And whilst a single run for a stem cell treatment for a blood cancer patient might cost around $500,000, Golden says an allogeneic approach where opti-ox is used to reprogram stem cells could potentially supply 1,000 patients in a single run.

“The cost of goods when we take this reprogramming approach is going to go down one to two orders of magnitude. And that’s a game changer for access. That’s my passion. That’s why I’m here,” she adds.

Expanding outside of cancer

In November 2023, bit.bio announced its cell therapy pipeline, placing a focus on its lead candidate, bbHEP01, which is being developed as a treatment for patients suffering from acute liver failure (ALF) and acute-on-chronic liver failure (ACLF).

The company’s lead programme was chosen based on “minimal clinical risk”, according to Golden. “It’s going to focus on getting the cells to patients and showing strong efficacy and also safety.”

bbHEP01 is made up of allogeneic induced hepatocyte- like cells (txHepatocytes) which are developed using the opti-ox technology. Essentially, these cells will support liver function in the wait for a transplant, or in some patients, could offer a means to native liver recovery. The treatment, whilst only in early stages, is a good example of the possibilities cell therapies offer outside of cancer. The wait for a transplant can be lengthy due to the scarcity of organ donors, and patients also have to consider surgical risks and the requirement that they’ll need to take immunosuppression drugs, potentially for life, to reduce the risk of liver rejection.

Bit.bio plans to generate initial clinical data in 2026 but is basing its approach for bbHEP01 on preclinical and clinical data2 that show the feasibility of this type of cell therapy. The process starts with the creation of an iPSC line which is then expanded and made into the txHepatocytes. The benefit with the approach is that it could treat hundreds of patients but starts with just one donor to create the initial iPSC line. The txHepatocytes can also be cryopreserved, enabling the kind of off-the- shelf therapies that are much needed in this space, essentially enabling access to a potentially life-preserving treatment for patients.

Beyond this treatment, bit. bio is looking to explore broader cell therapy options announced in its therapeutic cell pipeline which includes pancreatic islet cells, GABAergic neurons and immune cells such as myeloid and natural killer (NK) cells. With each cell type having the potential to lead to multiple therapy candidates, the company is looking to expand into areas of neurology, immunology, endocrinology and metabolic studies.

It will be interesting to see what kinds of indications can truly benefit from cell therapies in the same way that certain cancers have. These are avenues that are driving Golden in her position at bit.bio.

“I think for us, it’s limitless.”

DDW Volume 25 – Issue 1, Winter 2023/2024

References:

  1. Shah NN, Lee DW, Yates B, et al. Long-Term Follow-Up of CD19-CAR T-Cell Therapy in Children and Young Adults With B-ALL. J Clin Oncol. 2021 May 20;39(15):1650-1659.
  2. Dhawan A, Chaijitraruch N, Fitzpatrick E, et al. Alginate microencapsulated human hepatocytes for the treatment of acute liver failure in children. J Hepatol. 2020 May;72(5):877-884.

Kathryn GoldenBiography

Kathryn Golden is SVP Technical Operations and Manufacturing at bit.bio. She has a track record of shepherding complex drug candidates from discovery to pivotal trials. Her expertise includes integrated process development, phase-appropriate quality and regulatory coordination, and management of contract manufacturing organisations.

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