In this interview, John Hood recounts his journey from a ranch in East Texas to becoming a biotech founder. He describes his education at Texas A&M and a postdoctoral fellowship at Scripps where he studied angiogenesis and published in Science. A key paper on gene delivery targeting RAP led to the creation of TARGENT, where he pursued JAK2 inhibition for myeloproliferative neoplasms. Hood explains the discovery of fedratinib, a selective JAK2 inhibitor he calls the “Goldilocks molecule,” and its early promise. After a verbal agreement with Sanofi, unexpected safety concerns caused a break with the company, prompting Hood to leave and co‑found Samumed/Impact Bio to rescue the drug. He shares the personal motivation of meeting patients like Teresa, whose death underscored the urgency to bring fedratinib back. Hood details the extensive effort to persuade the FDA that adverse events were disease‑related, not drug‑related, and ultimately succeeded, restoring fedratinib to market and improving lives of myelofibrosis patients.
Chapters
I grew up on a ranch in East Texas in the middle of nowhere. It was outside of a little town called Gladewater, which is where I went to high school, and went from there to Texas A&M for both my undergrad and graduate studies, and left Texas A&M to come out here for a postdoc at Scripps Research Institute. I was always interested in sciences growing up, and Essentially, it was— it's a unique form of problem solving. You can just do essentially logic puzzles and problems and try to reason out underlying causes and how to fit the right piece into the puzzle so you can truly solve something. In life sciences, the payoff is being able to help patients live longer and feel better, which is in many ways the ultimate payoff. That's what we really want to do. So you— that, that was very appealing to me from the very beginning. So after I finished my PhD, we looked at a number of different places. I had a postdoctoral opportunity at Genentech up in the Bay, some great professors in New York and Washington, and we came to San Diego, me and my wife, and stayed in La Jolla, visited Scripps, visited UCSD, and there was just something resonant about it. We knew from right then that this is a place we had to be. Uh, we're at Scripps Research Institute. I was a postdoc in David Cherish's lab there. We were focused on angiogenesis, the growth of new blood vessels, and the underlying notion with that is if you can stop the new blood vessels from growing, the tumor can't get new food, it will die out from starvation. So we were looking at the VEGF pathway and the role of integrins and intercellular signaling molecules to control it. And it was great. I got a couple papers in Science. I was first author on it. It was a very successful postdoc.
And how did you go to Targagen?
So one of those papers in Science that we did became very interesting. We had profound effects with a gene delivery targeting a specific intracellular protein called RAP. And the science behind that was really the key science that led to the foundation of TARGENT. So it was the stuff I was doing as a postdoc ported right over into commercial. Because ultimately, being able— the notion of basic science, being able to understand how things work is great, but you try to understand how things work in order to build a new therapy for man. So we wanted to take that next step. So, I moved directly from Targogen, became director of research at— I mean, I moved directly from Scripps, became director of research at Targogen, and we were going to try to develop the things I did as a postdoc by inhibiting specific intercellular signaling proteins, get a profound benefit to tumor patients bearing tumors. So, there was a series of papers that came out that implicated JAK2 as a driving mutation for myeloproliferative neoplasms, including myelofibrosis. And literally the day those papers came out, me and the CMO, Charles Theurer, met and we both said we've got to start this program. We started the program the day the papers came out. Drug discovery and development is a tough business. It's not 40-hour weeks. You spend a lot of time finding what you believe is the just right molecule. It's very much a Goldilocks phenomenon. It can't be a little too much of that. It's not just potency, but you have to have pharmacokinetics, very clean tox profile. You have to have something that patients can actually take, that drug gets to the disease site, and has a benefit. And by the time you whittle down, you screen through thousands and thousands of molecules to find the one that's just right, that Goldilocks molecule, it becomes kind of a child to you. It's— you give birth to this thing, and it's very resonant, and you know everything about it. When we found a molecule that had the selectivity profile and had a good pharmacokinetics, that was the epiphany. That was the hands-up celebration touchdown dance. We knew that this thing was actually— had the potential to be a drug that helped a lot of people. So what fedratinib does is it selectively inhibits a protein called JAK2, Janus kinase 2, that when mutated drives this disease. These diseases create an overgrowth overproduction of red blood cells or platelets, or at the end stage, the bone marrow actually fibroses out and you have marrow failure. That's what actually causes death. But by inhibiting JAK2, you kill out the cells that are driving the tumor, driving the cancer. And it does it very selectively, and single dose, one pill a day knocks it out for the full day. So that really treats the underlying cause of the disease. When Sanofi— when we just reached verbal agreement with them They had asked me to stay on, and I thought it was in good hands, and I actually resigned on that day and moved on to found Samumed, become one of the founders of that company, because I thought it was in good hands. This was a huge pharmaceutical company that had a lot of competent people in running clinical trials. What happened was so non-predicted based on non-clinical toxicology and based on what I knew from the Phase 1 and Phase 2 studies. That it, it, it didn't make sense. There was cognitive dissonance. I knew this, what they said was out of nowhere. This, it just couldn't be.
And then at Sanumed, after hearing from oncologists about their patients that are failing, you took that leap. You decided, I'm going to go back, quit my job, and bring this drug back. I'm going to put all my ability to work, communicate my case, raise money. And what was it like when you decided that and what did your wife say?
It was, it actually wasn't as hard a decision as you might think because it was the right thing to do. We, uh, and Simi was going well. We raised a lot of money. We had programs going into clinical trials, but we knew these patients. We knew Teresa. We, I had the pleasure of meeting her. And when we couldn't get the drug back for her in time and she passed away, and I knew there was a lot of other patients just like it, it— there wasn't really a decision to be made. It's just what you had to do. Knowing this molecule as well as I did, it made it a lot easier because I knew that the reported AEs didn't make sense. I knew that some of the things that were being reported in the literature were artifacts. So, because I know the molecule.
And it was simply a matter of getting each patient's history, looking it over with Katrina and others, and figuring out what really happened.
That is correct.
But then you actually had to convince the FDA.
That is correct.
And that took a little bit more persuading.
It took a lot of persuading. It was, it's a challenge because the FDA's primary mantra is to do no harm. And there were adverse events that came up during the course of the trial. My impression is that they were adverse events associated with their underlying disease as opposed to the therapy, but they want to make sure, and I understand that. And you have to make the case that this compound, this drug, based on its activity, provides profound benefit for the patients, and the risk real or not, just if the theoretical risks are not too great. I go to UCSD or I visited the Mayo or Anderson and get to meet patients who are around today because this drug is on the market. There's nothing better. That's, that's knowing that you played a key role in saving people's lives. That's why we do the job.
