A biochemist, engineer and serial inventor, Philip Roche has spent the last two decades following his curiosity. Moving through fields that include cancer biology, protein engineering, nanomedicine and biometrics, led him to work on nanoparticles, ultra-fast diagnostics, biomedical devices and wearables. Now, as the CEO and chief scientific officer at Jenthera Therapeutics, Roche is focused on pushing CRISPR gene editing beyond something done at a bench in a tube to a process regularly conducted in vivo — within a living organism.
Less labour intensive and more cost-effective than extracting cells, editing them ex vivo (“out of the living”) and then transplanting them, in vivo gene editing can directly modify a person’s DNA and fine-tune immune cells to find and attack specific types of cancer. But to be effective, they need to get to the right place — that’s where Roche and his colleagues come in.
Founded in Montreal in 2019, Jenthera has created a gene-editing platform that will help deliver, via intravenous injection, protein-based anti-cancer drugs. In doing so, the company has created an alternative that is cheaper to produce, safer and — by virtue of doing away with large manufacturing facilities — more viable in the long term than viruses, lipids and nanoparticles. Through a collaboration with the Edmonton-based biotechnology company Future Fields, Jenthera is evaluating how to best produce these cancer-fighting proteins and is moving ever closer to a sustainable technology that could transform oncology.
Here, Roche talks about cellular intelligence, the trap of million-dollar gene therapies and why Jenthera’s trials may succeed where many others have failed (spoiler: he refuses to rush).
I’m a former cancer patient, so I’ve been interested in the subject for three decades. It’s a fascinating disease. Deadly, but endlessly fascinating in its dynamics, its behaviours and the treatment methods. I had follow-up appointments where I’d realize I wasn’t seeing people from my last appointment or from the year before. Rather than just say “Oh dear, someone died,” I wanted to know why people continued to die at such rates. Rather than think about how unlucky or how fortunate I was, I focused on the intellectual challenge of looking at the cancer itself.
I think you have to be reasonably humble about your ability to help. There is a very long path for any therapeutic, methodology or device to reach the point where it helps someone. There’s a more practical thing you can do: You can make sure that every step in the development of the thing you hope could be helpful is done correctly and is as efficient as possible. And, critically, that it is scalable economically. It’s no good being yet another $1-million, $2-million, $3-million gene therapy.
We keep things very simple: CRISPR is an enzyme that cuts DNA, so let’s engineer that enzyme to actually deliver itself to the cells that are needing it.
Everything. What cell do you want? Is your system stable enough? How do you pick the right cell? Over the last few years, we’ve been able to solve the challenges of selecting the right cell and we’ve been able to do it not only in a tube, but also off an IV injection into animals targeting specific cell types or tumours, and we’ve even passed the blood-brain barrier.
We looked at the cells first. Cells are very intelligent — they have all the answers. Look at CAR-T, which is this incredible adoptive cell therapy whereby you grow a patient’s immune cells and adapt them with the chimeric antigen receptor, and it targets tumours. The problem is that the manufacturing takes too long. So we looked at the cells that are being edited: the T-cells. Most importantly, you’re driving efficiency at every step so by the time you get to that nucleus where it can integrate the DNA-encoded receptor — it’s done efficiently. We’ve been pretty good at that.
That’s of key relevance in glioblastoma, a brain cancer solid tumor. One current clinical trial method of introducing CAR-T to the brain involves drilling a cannula. I’m no surgeon, but drilling a hole in someone’s head to then introduce a treatment that gets outmoded by the cancer’s own development seems interventionist to me. So we looked for a better way.
We’re delivering an enzyme. That’s very different from what other people are doing. They’ll try to deliver a virus or some mRNA in lipids. Great stuff, but they are difficult to target. Plus, our solution is more economical and our efficacy is better. Everything always comes down to delivery, the effectiveness and how that actually results in the therapeutic editing that you design.
We’re not going into clinical trials until 18 to 24 months from now. In the long term, what we want is for gene therapies to not only be cost-effective but open to major diseases just as much as they are for rare conditions. But critically, I think we need to look at how we’re going to pay for these things.
I don’t think it’s sufficient to lay the cost completely on customers, regulatory agencies or Big Pharma companies. It’s got to start with the development of molecules that are scalable in production. There are always commercial pressures, but taking a longer route instead of a shorter one will put you in a better position to be successful in the clinic.
When I started my PhD in the U.K. in 2004, it was a program whereby you had to do all the MBA courses at the Manchester Business School. So I was primed for this, but that’s not the same as doing it. Ultimately, you’ve got to realize what you’re good at and what you’re crap at. When you’re not good at something, you have to find friends who are. That’s where Jenthera’s COO Laurent Ziri and CFO Sandra Azoulay — my co-founders — come in. You don’t need a massive team. You need a close team, one that is willing to say, “Wait a minute, you haven’t thought of this” along every path you’re on, whether it be the challenge of the financing, the challenge of the marketing or the challenge of the therapeutics you’re attempting to develop.
Don’t rush. It’s better to defer judgment until you’ve had time for consideration. Talk through every decision with your trusted core team. For example, it’s very easy to get carried away if you have a contract in front of you. The same is true for a piece of IP. It’s better to just step back, read things carefully, think them through, consult and then make a decision. When it came to structuring Jenthera, we’ve taken our time to work out the best fit for not only the technology, but also how it fits with the market. And how the development of the preclinical to clinical should go and why. If we’d rushed that, we would have been left with gaping holes in our credibility. Finally, you’ve got to make your company yours. You can take advice from everyone else but you have to plot your own path.
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