Therapies using live cells offer the possibility of treatments for diseases and conditions that cannot be approached by conventional drugs.

Cells are being investigated for their abilities to reverse blindness, re-grow bone and nerves, restore the immune system and treat cancers for which there are no effective drugs.

Living cells, however, are fragile and short-lived outside their natural environment. A common approach to address these issues is to freeze the cells for storage but this causes problems when the cells are thawed again for injection into the patient. Many cell therapies simply cannot be frozen and for these products, complicated and expensive logistics are required to ensure their delivery to the hospital and the patient before their shelf life expires.

But how can logistics alone affect the commercial success or otherwise of a therapy?

The graphic below summarises the process for Sipuleucel-T to give an example.

The 18 hour shelf life of Provenge (Sipuluecel-T) meant that multiple GMP manufacturing plants needed to be built to address the geographical constraints of such a short time wondow before expiry of the therapy. Recovery of the extraordinarily high capital costs of building this manufacturing capacity impacted the price of the therapy. In turn, this affected reimbursement rates and prescriptions and, ultimately, the success of the business.

We believe that our cell encapsulation process would have had a dramatic impact on this therapy, by extending its shelf life so that a single manufacturing plant could have satisfied the entire market demand.

Cell-based models used in drug discovery and testing are moving away from simple, immortalized cell lines towards systems that more accurately recapitulate an in vivo setting.

There is a drive to using primary cells (including patient-specific cells from biopsy samples) and three-dimensional structures such as microtissues, organoids and spheroids. Cells derived from a stock of iPSC can provide a renewable source of complex cell types and the possibility of exploring patient variation by using multiple donors.

However, if there is a “rule of thumb” here it is that the more physiologically relevant the cell type, the more fragile they are. For the cell developer, this translates into the question “how do I ship my valuable products to my customer?”

Our customer came to us with a knotty problem. They can generate cortical neurons derived from iPSC and sell these as undifferentiated precursor cells for their customers to differentiate and mature into plated neurons after weeks in culture. A major customer wanted to buy a lot of these cells but didn’t want the headache of doing this laborious maturation – “you do the cell culture, and we’ll buy the plated, fully mature neurons from you. Lots of them.”

The problem? They could ship the precursors in deep frozen vials, but the mature neurons can’t be frozen and fall apart if transported fresh.

Using our WellReady™ product, we encapsulated the fully mature neurons in 96-well plates then shipped them by courier truck the 250 miles between our sites then kept them at room temperature for a further day before driving them back up to Newcastle.

The first image in the series of photos below shows the non-stored, non-transported control cells, and the axonal connections between these healthy cells are clearly visible as you would expect. The second image in the series below shows what happens when you try to ship these cells without encapsulation – 60% of them are dead, and those that remain have lost all the inter-cell connections and are no longer functional neurons.

By contrast, the cells that were encapsulated in WellReady™ and stored at room temperature for three days and transported twice (+WellReady™) are identical to the cells that hadn’t left the comfort of their incubator – healthy and alive, with mini-networks of nerves still in place.

We then extended this study to 7 days of room temperature storage with identical results, so these mature, plated neurons can now be shipped to wherever a customers wants them, anywhere in the world.

Problem solved.

If we were to intercept an asteroid on its icy, lonely trek through space and take samples from its surface, would we expect to isolate viable cells on warming the samples?

Maybe, maybe not – yet we expect that to happen routinely when we thaw cells from liquid nitrogen here on Earth.

But it is abundantly clear that many cells are deeply affected by such traumatic transitions in temperature. Some die, some change, and often you don’t realize this until it’s too late due to late onset apoptosis pathways and chromosomal rearrangements.

Some cells die, and others mutate!

Thawing cryopreserved products impairs cell functionality, potentially affecting product quality, efficacy and patient safety. It is well known that T-cells and MSC exhibit different functionalities upon thawing. It’s also known that they can regain their normal vitality after being returned to culture for 24-48 hours. So that’s OK, right?

The question is: where should this restoration of function be carried out?

Thawing your frozen cell therapy at the clinic and returning it to culture there before administering it to the patient, turns the clinic into a cGMP manufacturing site. And that’s true for each clinic or hospital, or each doctor’s office, where that process is carried out, with ALL the regulatory challenges that come with it.

We propose a better way, by using our room temperature encapsulation approach:

  • Store the cells frozen in your cell bank for as long as you need to
  • Thaw them at your processing site and remove the noxious cryoprotectants
  • Return to culture to regain full functionality and therapeutic efficacy
  • Encapsulate the cells in alginate and ship them “as fresh”
  • Dissolve the gel at the bedside and administer to the patient

Combine the benefits of cell banking with better logistics for addressing those “final miles”

When should I start worrying about this?

The short answer is: “as soon as possible”.

The slightly longer answer is: “as soon as possible in planning your clinical development pathway”.

As a therapy progresses through clinical stages it becomes increasingly difficult, complicated and expensive to make changes to elements in the Chemistry, Manufacturing and Controls (CMC) section of your filings. Changing processes, components, container/closures and storage methods can all affect patient safety and the efficacy of the therapy, and there is a clear need to think and plan ahead.

One of my favourite questions to someone just about to enter their experimental treatment into a Phase I trial is “have you thought about how to get the cells from and to the patient?”

The typical answer is “oh, that’s OK – all the patients will be treated here at this clinic so there’s no need to move the cells anywhere.”

“Mmm….that’s fine for the dozen or so patients in your Phase I trial, but what about when you need to open more clinical sites to enroll more patients in your Phase II or even Phase III trials?”

(Slowly dawning look of realisation) “Oh, I see – well, we’ll just change the……oh! I see!”

The short answer to the question is: “As soon as possible”

Cambridge and Newcastle, UK, 21st August 2019: Atelerix, pioneers in the storage and transport of cells at room temperature, today announces that it has been awarded a grant of £267,000 from Innovate UK, the UK’s innovation agency, with collaborators Rexgenero and the Cell and Gene Therapy Catapult.

The grant will be used to develop gel stabilisation technologies, developed by Atelerix, with the first objective of extending the shelf-life of Rexgenero’s cell-based therapies for storage and transport at room temperature. The project will initially focus on developing a stabilisation technology for REX-001, Rexgenero’s lead development candidate, but is expected to have broad applicability to a wide range of other cell therapies. The project will benefit from additional expertise and experience provided by the Cell and Gene Therapy Catapult.
Atelerix’s patented technology enables the storage and transport of human cells at temperatures between 4°C and 25°C, preserving and extending their functional viability from days to weeks. The technology encapsulates cells in a natural hydrogel for safe shipment and storage. The cells can be recovered when needed by the addition of a gentle, cell-friendly buffer.
REX-001 consists of bone marrow-derived white blood cells extracted from a patient’s own bone marrow (autologous). Rexgenero is currently recruiting 138 patients at 35 sites in countries across Europe for its Phase III SALAMANDER trials of REX-001 for the treatment of chronic limb threatening ischemia (CLI ) in diabetic patients.

CLI is a chronic condition and the most serious form of peripheral arterial disease (PAD) in which a build-up of fatty deposits in the arteries restricts blood supply to leg muscles, leading to chronic ischemic at-rest pain, ulcers, or gangrene in one or both legs. It is a major health and societal issue affecting an estimated 3-5 million people in Europe, growing at 1-2% p.a. due to the link with diabetes and ageing.
Extending the shelf-life of REX-001 will provide increased flexibility for transportation to and from the hospital and facilitate use for physicians treating patients with CLI.

Dr Mick McLean, CEO of Atelerix, commented, “We’re excited to be part of this collaboration with Rexgenero and the team at the Cell and Gene Therapy Catapult, and we deeply appreciate the support of Innovate UK to bring us together for this important project. The critical logistics of getting viable cell therapies to the patient are often overlooked, and extending the shelf life of therapies such as REX-001 at room temperature would open up an entirely new approach for this sector.”

Joe Dupere, CEO of Rexgenero added, “We look forward to initiating this project. Extending the shelf-life of our REX-001 autologous cell therapy is important to ensure that hospitals have the flexibility for less rigid scheduling of operating theatres, making it easier to treat patients and therefore enabling as many patients as possible to be treated with this novel, potentially curative therapy. Room temperature storage and transportation also widens our manufacturing options and should help to drive down cost.”

Keith Thompson, CEO of the Cell and Gene Therapy Catapult also added, “We have a long-standing relationship with Rexgenero and have collaborated with them previously to support the commercial manufacture of the REX-001 product. This collaboration underlines the strength of expertise that exists within the UK to support the cost-effective commercialization of cell therapies including in the important area of supply chain technologies. It is a great example of bringing together the capabilities of CGT Catapult and the expert companies that make up the complete UK cell and gene therapy ecosystem.”

9th May 2019 — Cambridge and Newcastle, UK – Atelerix, creators of an innovative cell encapsulation technology, today announces it has closed a second round of funding of £700,000 to accelerate development of its cell transport products to market.

Atelerix’s products are used for the storage and transport of human cells and tissues at room temperature, removing the need for cryopreservation and the potential for cell degradation or damage. Atelerix sells its products and services to customers in the cell therapy sector, as well as those developing cells, organoids and assays for use in drug discovery and development.

Atelerix was a spin-out from Newcastle University (UK) in 2017 and raised £425,000 in 2018 in a seed investment round led by specialist investor, UK Innovation & Science Seed Fund (UKI2S). This funding allowed the company to validate its technology, develop easy-to-use product formats for use with different cells and tissues and launch products onto the market. The follow-on investment announced today will be used to grow the team, increase revenues and expand the business, capitalising on the exciting opportunities in the cell therapy sector where delivery of viable cells to the patient remains a significant logistical challenge.

Atelerix CEO, Dr Mick McLean, commented “We’re delighted with the success of this fully subscribed funding round. I’m particularly pleased that all our existing investors chose to reinvest in this round, and glad to welcome several new investors. We’ve witnessed a lot of excitement for our products and technology since we launched a year ago and this latest investment will allow us to grow the business faster and reach new markets.”
The new investment round was led by existing investors UK Innovation & Science Seed Fund (UKI2S), Oxford Technology Management and Newable Private Investing with new investors also joining the round. Dr. Andrew Muir of UKI2S, who joined the board of Atelerix after the previous round, says “As a founding investor, UKI2S is delighted to see Atelerix well-positioned to complete the development of its proprietary platform and launch its products into two large markets. Based on great science, the company’s products have relevance to large growing markets of pre-clinical research and cell-based therapy.”

Prior to spinning the Company out of Newcastle University, founder Professor Che Connon’s academic research was supported by Biotechnology and Biological Sciences Research Council (BBSRC), a UKI2S partner. Professor Connon, commented “Encapsulating cells in the alginate hydrogel is a simple system capable of preserving the viability and functionality of cells at temperatures between 4°C and 21°C for extended periods of time. Used as a method of cell storage and transport, it overcomes the acknowledged problems associated with cryo-shipping. For shipping, cells are encapsulated by the in situ formation of the gel in plates or vials, and can be rapidly released from the gel by the addition of a simple buffer.”

Atelerix’s Impact

  • Predictability and reliability in drug discovery models and for cells used as therapies
  • Extended shelf life for currently short-lived cell therapy products
  • Customers can use cells and assays immediately on arrival
  • No need for cryopreservation, nor need for cytotoxic or animal-derived supplements
  • Cells retain their natural state and are not damaged or altered