In fast-growing KRAS field, this oncology veteran is chasing the toughest cancer targets
Loïc Vincent watched his mother face cancer three times: Once in 1988 when he was 12 years old, and then again in 1996 and 2012.
During her third battle with the disease, Vincent was already well into his career as an oncology scientist and was head of pharmacology for Sanofi’s oncology drug development and preclinical development team. Despite having early hope his mother would once again beat cancer, Vincent soon learned differently.
“I knew there was no therapeutic options for my mom,” he said. “So she went into all of this palliative chemotherapy that extends your life a little bit, but the quality of your life is really poor. That was the most painful experience of my life.”
Vincent spent nine years at Sanofi and nearly five years at Takeda, where he eventually headed up its oncology drug discovery and immunology units. Over the course of his career, he said his teams advanced more than 20 oncology drugs in the clinic.
Vincent was happy at Takeda and not looking to jump ship, but was drawn to Affini-T Therapeutics in August 2021 by its strong scientific foundation and ambitious goal to use T cell receptor engineered T cell (TCR-T) therapies for oncology targets such as KRAS.
“Targets matter a lot in cancer. If you go after oncogenic drivers you have the opportunity to eradicate tumor cells in a much more efficient manner.”
Loïc Vincent
Chief scientific officer, Affini-T Therapeutics
Although it’s one of the most common gene mutations linked to cancer, KRAS was believed to be undruggable for decades. All that changed in May 2021, when the FDA granted accelerated approval to the first KRAS-targeted therapy, Amgen’s Lumakras. In December 2022, Mirati Therapeutics received accelerated approval for its KRAS inhibitor, Krazati. Now, other companies are attempting to follow in those footsteps, including Eli Lilly and Genentech.
Now as chief scientific officer at Affini-T, Vincent is advancing the company’s precision immunotherapy approach to targeting core oncogenic driver mutations and developing durable therapies for solid tumors. Affini-T has three preclinical programs targeting KRAS G12V and KRAS G12D and several others in discovery.
Throughout his career, Vincent said he’s been acutely aware that when it comes to cancer treatments, the clock is always ticking for patients.
“Patients don’t have time. So we as scientists advancing drugs should think about this,” he said. “We shouldn’t forget in biotech and pharma (about) trying to have this sense of urgency.”
He said he’s also at the point in his career where he wants to work on drugs he believes could be truly “transformative.”
“At my age — I’m 47 — I don’t want to work on me-too drugs,” he said. “After two years, we are a few weeks away from our first IND submission … we are going to be a clinical stage company. I have goosebumps as I’m talking to you. We are going to advance those programs to patients in the coming months, which is really exciting for the company, but more importantly for the patients who are waiting for novel therapeutic options.”
Here, Vincent discusses his leadership philosophy and what makes Affini-T’s work stand out.
This interview has been edited for brevity and style.
PHARMAVOICE: Affini-T is going after challenging cancers. Is that intentional?
LOÏC VINCENT: Yes. If you look at the field of targets and indications, a lot of pharmas and even biotechs work on what I call the ‘usual suspect’ targets that you know can work in the clinic. What we want to do at Affini-T is work on the most difficult targets. Targets matter a lot in cancer. If you go after oncogenic drivers you have the opportunity to eradicate tumor cells in a much more efficient manner as opposed to other targets.
And (as far as) the most challenging cancers, this is what we have to do. If you look at some indications now in 2023, there are plenty of therapies available for patients … and cancer is becoming a chronic disease.
For some other cancers there are no therapeutic options. We think about how we can have the greatest impact on patients by going after those very difficult, hard to treat indications. At Affini-T, we want to change the paradigm and set up a new way of treatment for patients.
How is Affini-T’s approach different?
When you see all the progress that is happening, almost every month, there’s a lot of hope for patients not only in cancer, in all therapeutic areas, even rare diseases.
That said, it’s still unacceptable to not have treatment for some of the cancers. At Affini-T we’re going after colorectal cancer, pancreatic cancer and lung cancer. We have lined up the potential challenges that our cell therapies are going to face and we are coming up with specific strategies to overcome those challenges in our T cell products.
For example when you inject T cells in a patient, those cells are not going to persist for a long time. So we are doing two things for our T cell product. The first thing is the phenotype. With all the learning that we have … from different studies, we know that if you want to have persistence of our T cell product, you need to have the right phenotype. In particular a memory phenotype. So our T cell products have 95% of this memory phenotype.
The second thing is that we are leveraging synthetic biology. We have a novel construct that we use to improve proliferation, survival and persistence of our T cell product. We have validated that in vitro and in vivo, and now the next step is to take those constructs into the clinic and try to validate that in patients. We are going to be the first to advance that particular construct in our T cell product this year. That could be a game changer in the field.
What’s your leadership philosophy as you build this company and team?
My role is being a catalyst in the organization for the discovery and preclinical team, setting the strategy of the products we are advancing. My role is to enable people … I don’t want a team to be struggling … thinking about finance (and wondering) can I buy this? Should I do that? No, just do it.
I’m trying to build an environment where people have no fears. They can be creative, they can advance the program, and (make) sure there’s this sense of urgency.
Scientists can be very creative. They can go really deep in something and do hundreds of studies. What I’m trying to (tell them is to) do the studies that help you answer specific questions and to advance to the next milestone. You don’t need to do everything but you need to do the right studies.
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