James Noble, CEO of Adaptimmune, explains where the industry is with attacking solid tumors and sheds light on the ever-present pricing issue.
What does the next generation of immuno-oncology mean for the patient?
Noble: It is difficult to attack solid tumors, which represent 90% of all tumors. Potentially, we can expand the targets from a small number of hematological indications.
The question is can we expand beyond a very limited number of tumors? Right now, we have data in synovial sarcoma and MRCLS. We have tumor reductions in lung, ovarian, and melanoma, but not enough to be RECIST responses. The next challenge is how to convert the data that we have for sarcoma into other solid tumors? We’re working extremely hard on this.
There’s been quite a bit of news as of late regarding the cost of therapies. What’s your take on how pricing is currently handled?
Noble: That’s a very good question. I have to say, research costs a great deal of money, so to be honest, I don’t think there is any argument that a high price must be charged to get a return. The treatments are quite expensive even once you get them onto the market. They’re not getting 99% margins, even charging $400,000, but I do completely understand the point.
I think two things will happen. There will be an increasing acceptance that you only pay for therapies if you can prove they work. That’s done by staggering the payments. Instead of charging $400,000 on day one, you charge $40,000 a year for ten years and, if the patient dies, then they stop paying. If the patient relapses, payment stops.
The second thing is the price of these cell therapies will come down. Consider the cost of goods for clinical purposes from two years ago — prices were high.
Consider the vector, which is costly. At one point, one of our vector runs could cost $400,000, and it only produced vector for three patients. So, it’s obviously not a commercial enterprise. But we can now produce dozens upon dozens of patients at much lower cost.
The input costs of production will go down because people will develop ways to produce vector more cost effectively. The other big component of the cost is the cell manufacturing. Right now, manufacturing is very highly manual, requires ultra clean rooms, etc. That process will evolve toward completely different manufacturing methods.
In fact, although we haven't disclosed exactly what we’ve changed in the manufacturing methods for our next generation, we filed the IND including a completely different system. If that system works, that will dramatically reduce the cell manufacturing costs.
I think the reason that the costs are so high for companies is essentially every program, including our own, has taken manufacturing methods from an academic setting, which obviously is not related to commercial conditions.
What are the biggest challenges facing cell therapy?
Noble: The biggest challenge is reaching solid tumors and destroying them. We have made some very good progress with this, because the learnings we get from patients tell us what to do next. We’re finding new information almost every day.
We are very interested in combinations. We just completed a technology deal with Alpine Immune Sciences in order to provide further types of t-cells. The challenges and the solutions are the same. The t-cell will kill something. If it recognizes the antigen, it will kill the cell, undoubtedly.
We need to make sure that we can get t-cells which are still capable of killing the tumor. So, all the effort is going to be in finding methods of enhancing the ability of that t-cell to survive until they see the antigen. We’re working to uncover methods to essentially knock out the tumors’ defenses.
I think those are the areas which everybody is going to focus on, but you can only work out which way to go using data received from patients, because that's how you know what the defense mechanisms are and then you adjust your product accordingly.
Success will require a mixture of refining the t-cell product to ensure the t-cells are more active; putting new elements into the t-cells, such as our next generation. We have many more next generation programs. Perhaps we will use other companies’ technologies to penetrate the tumor effectively.