Are Autologous Therapies Here to Stay? Are Allogeneic Therapies the Future?

The pros, cons and future of allogeneic versus autologous therapies are explored as Rachel Smith, Portfolio Director for Veristat, shares her observations on the impact of these techniques on advanced cell-based therapies and what the next decade may hold. Factors spanning patient safety, manufacturing, costs and regulations are considered as Rachel responds to the question whether an autologous approach for rare disease therapies is sustainable long-term.

Transcript

Speaker 1: 0:00

Bringing a cell or gene therapy to market is an art here. Vera stat thought leaders, as they draw on their specialized expertise to offer insight on timely relevant clinical development topics. Welcome

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To art podcasts, advancing revolutionary therapies, a podcast presented by the center for excellence for cell and gene therapies by Veta. My name is Rachel Smith. I'm a portfolio director here at Veta, working with our clients in cell and gene therapies, providing operational excellence from strategic consulting to clinical trials. And post-marketing commitments today, I'll be touching on the future direction of cell and gene therapies, focusing on all versus allogeneic technologies. Autologous is defined as cells or tissues, which are collected from the individual patient. So therapy using this approach are specifically tailored for the same patient and cannot be used to treat anyone else. Whereas allergenic cells or tissues are from the same species, but are nonspecific to an individual patient. Currently the most commonly used approach is auto autologous cells as the start of material for many cell and cell based gene therapies. Looking back over the past 19 years of advanced therapy approvals both in the us and Europe, all approved cell based gene therapies utilizes paradigm as you, several of these cell therapies such as Macy, and for good reason, this approach is considered lower risk than alle as we are using the patient's own cells. So the risk of autoimmune events, post transplant, such as graft versus host disease. It's very low. In addition to this, we know this technology works. It's proven technology and has the potential to significantly improve clinical outcomes or even cure disease, particularly in the rare or ultra red is setting. However, autologous therapies do have a relatively long list of negatives. These therapies, for example, rely on a starting material cells from already diseased patients. And what that means for manufacturing is you already have variability at the very start of the process. And so the final product quality also has high variability and low predict you of the end product quality. So essentially you are producing inconsistent product and we are routinely seeing out spec end products in our clinical trials for this reason. Most of the time we do end up administering these out spec product, but we've limited success. And the reason for that is due to the adverse risk of not administering these to our patients. For example, if we've already put a patient through the conditioning regimen, um, and therefore they need, um, cells to be reinfused added to this is the cost of the variable manufacturing process. Um, it's extremely high. So we're talking about one batch providing enough doses for just one patient. And so these are expensive and it brings into question the commercial viability of these therapies outside of the disease space, as manufacturing can take up to 12 weeks. In some cases, particularly when we're thinking about Europe, the COVID 19 pandemic has highlighted how limited our manufacturing capabilities are. In reality companies may only be able to treat a handful of patients post year, each year, post market, as a result of the cost of these therapies. We're also seeing low engagement with payers. So those insurance companies and national healthcare providers who fund the cost of these treatments takes in Telo. For example, this will not be available in Germany. As the healthcare provider is only willing to purchase the therapy for 50% of the target market price, making it a non-viable option in that country. All of this leads to issues with patient accessibility is generally there are only one or two centers globally who are actually offering these therapies and what this means for the patients and their caregivers is that they're having to fund travel and accommodation and take extended areas out of work to receive these treatments. So the question really is if this autologous approach is sustainable long term, particularly as we continue to see technology for cell and gene therapies evolve when new possibilities, which come with our greater understanding of the immune system and how these therapies work, for example, immune cloaking and hyper techniques to address you mean rejection risk and the use of armors or switching off mechanisms to address long term safety risks with non Atologous approaches. So will we be switching to an allergenic approach in future? I would say yes, not only with the evolution of the science around making this product safer or this approach safer. We're also starting to see progress in manufacturing EF and the development of allergenic cell banks, which will make this approach significantly more viable in the next five to 10 years. When we talk about allergenic therapies, we are talking about our cell source from either the healthy donors, stem cell sources or cell banks, rather than using the patient's own sales, the starting material, the starting material then goes through for various differentiation, expansion modification and activation steps. Before the final product is released for administration to the patient. In these cases, the cost is significantly lower per dose, primarily because one batch may yield hundreds or in the future, even thousands of doses for hundreds or thousands of patients. And mostly you are using a consistent starting material. End product quality is much more predictable and much more consistent than with an autologous product as a result of this. Plus the bonus that the patient does not have to go through earlier. Cell collection steps like bone marrow harvest through surgery, which has an incredible burden on the patient. You could in theory, an off the shelf final allergenic product to any center in the world for administration, meaning that the potential for patient accessibility, as well as parent engagement is anticipated to be increased. That said we do have a potentially higher safety risk with allergenic product that we do expect solutions to these risks to come to light over the next few years. As many of these are already been tested pre clinically like immune cloaking or in the early stages of clinical trials, such as HLA engineering or HLA knockouts in induced pluripotent stem cells, or I PSCs. So were mentioned that we have seen some improvements. Downstream manufacturing processes are still relatively inefficient and companies are working on higher throughput technology to increase the commercial viability of this approach. On top of that, starting material is currently high cost unlimited, and that's simply down to the lack of availability of clinical grade cell lines. And companies are really having to invest the else into the development of cell libraries and cell banks. But again, we expect the number of commercial sale banks to write significantly in the next five to 10 years, addressing this problem head on finally, ille regulations are someway behind autologous products. Guidance is under development by the major regulatory agencies, but for now this really somewhat of a gray area and requires constant communication by sponsors developing these therapies with the agencies on top of this, there is a lack of consensus on residual cell assays or assays to confirm the final product only contains the modified cells and has a low or zero percentage of non-modified cells remaining, which pose the highest. So where are we headed for cell based therapies? Don't get me wrong. Autologous therapies are absolutely here to stay. We have established processes, known safety profiles and clear regulations, but given the complexity of the scale out manufacturing model and high cost, low yield approach, these therapies are only likely to continue to be commercially viable in the rare disease setting where only are allergenic therapies today is where we were over autologous therapies five to 10 years ago. So we're not too far behind. And if we've learned anything from the pandemic, it's absolutely possible for us to see rapid development and improvements in clinical research. And we can expect the lessons learned during the pandemic to be applied to this field, as well as we anticipate moving to rare disease for these types of therapies, we will absolutely should see a shift towards allergenic therapies of the field advances, processes improve. And cell banks are established both with the traditional monogenetic and cell therapies. And I also expect with multigenic and gene editing techniques. So the podcast today is intended to be a high level overview of the pro and cons world autologous versus allogenetic techniques in advanced cell based therapies, as well as to give our view on where we're headed into the future of this field, Rista managed clinical trials for the first gene therapy to be approved in the Western world. And as trailblazers, we continue to be actively involved at the cutting edge of this field. We encourage you to listen to future episodes of this podcast, as we do love deeper into some of these issues and other important topics in cell and gene therapy, I hope this has been valuable to you. Please reach out to our expert teams through the links available on the various step website. Should you have any questions and we'll be back talking to you very soon.

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