The field of immuno-oncology promises to make anti-cancer treatments more effective than ever. But in this crowded field, many companies struggle to make therapies that not only are effective and safe, but that can also be scaled-up, manufactured and commercialized. Helen Tayton-Martin, Chief Business Officer at the biotech company Adaptimmune, shares her advice on how to approach the commercialization of new technologies in this competitive space.
Immuno-oncology, or the science of making the immune system fight against cancer, is booming. Checkpoint inhibitors, a type of drug that releases the “brakes” of immune cells attacking tumors, have had a big success in the market. And a new generation of treatments known as CAR-T cell therapies are now changing the whole cancer field.
“What really changed the field was when Carl June published data on three leukemia patients, who were cured with his CD19 CAR-T cells. Once he demonstrated that, the whole world woke up,” Tayton-Martin told me.
“That was a seminal moment because the industry historically has not really taken too much notice of T-cell therapy, and that changed everything. Novartis signed a deal with the University of Pennsylvania to take the whole technology platform forward. Investors were also beginning to take notice.”
Still, these therapies are not infallible. In particular, CAR-T cells have so far been limited to treating rare types of blood cancers, have presented issues with toxicity and have raised concerns on whether their six-figure price tags are in line with the benefits they bring.
Since the immuno-oncology boom started by checkpoint inhibitors and CAR-T cells, researchers worldwide have started developing new immuno-oncology approaches that could solve some of these issues. However, it can be especially challenging in this field to develop viable therapies that are feasible beyond the test tube.
Bring an advantage to the table
Based in the UK, Adaptimmune is one of the most advanced players working in another form of T-cell therapy that is based on T-cell receptors, or TCRs for short. With several of its therapies being tested in clinical trials, and a big deal signed with GSK, the company is on its way to commercializing the technology.
“T-cell receptors are natural receptor molecules that the T-cells use to scan the body and look for foreign or invading cells,” explained Tayton-Martin. “We identify and isolate T-cell receptor molecules that are relevant for cancer. We then increase their affinity and put them back into T-cells, obtaining a powerful T-cell that uses a natural mechanism to identify cancer cells.”
“The key thing is that these target proteins are involved in cancer development, and they are all inside the cell. That’s very different to the chimeric antibody receptor therapies that have seen such great success, which basically recognize surface proteins.”
According to Tayton-Martin, Adaptimmune’s TCRs have not shown anywhere near the levels of toxicity of CAR-T cells, which can reach life-threatening levels of systemic and brain inflammation. However, she warns, proving you can bring a significant advantage is not enough. You also have to prove it is viable as a commercial therapy.
“Data is king. The ability to execute is incredibly important. Having a cool scientific approach and being able to have in vitro or preclinical data is exciting, but you need to prove that it is specific, that it is safe. And that you can actually manufacture the products and deliver them safely, robustly, and consistently.
Safety is key. Efficacy is key. But so are manufacturing improvements, and thinking about reimbursement and patient access almost from the very beginning. I don’t think a lot of early innovators really think about that. ”
When seeking to commercialize a new therapy, she believes the end user needs to be kept in mind at all times. “You really have to understand the product and what it’s like for the clinician and the patient trying to get access to that product. That might sound like a simple thing to say, but while clinicians in the hematological centers were reasonably familiar with the idea of T cell therapy, as soon as you go into a solid tumor setting you’re dealing with a very different mindset and experience.”
“To understand what you need to show to the regulators, you have to build up experience in the real world, in our case solid tumor centers. The data, the experience, and the input from clinicians and patient groups you get are all incredibly important to generate the data that supports pricing, and valuation, and access down the line.”
Fund the pipeline
Funding all the steps required to reach commercialization can be a major challenge. Adaptimmune has been supported by a partnership it signed with GSK back in 2014 for the development of its lead program.
“With that significant validation from GSK in June 2014, we were able to then bring our own proprietary programs into the clinic. We raised over a hundred million dollars in October of the same year, which then enabled us to make the company public in May 2015.”
Though challenging, a technology can be taken a long way without a partner. “It is possible, Kite obviously demonstrated that very effectively, taking a product right through to the verge of approval.”
In the end, it is about proving that a therapy is viable, either to a partner or to investors. “It’s all very new, there are very few who actually have those capabilities in place and there is a lot to do. Whether it’s with a partner or self-financing, there is a lot to think about on how to do that effectively and efficiently. It’s possible though, for sure.”
As with any relatively new field, there is not an established way of getting to the finish line. However, commercializing a new therapy requires a plan that takes into account, from the very beginning all the challenges that it will encounter. Not only in the clinic but also in the manufacturing site and the hospital bed.
Whether it’s antibodies, cell therapy, mRNA or any of the new technologies seeking to harness the immune system to fight cancer, only those who can overcome all those challenges will be able to make it through in a space as competitive as immuno-oncology.