When Jacob Becraft was developing programmable mRNA technology at MIT, most of the world wasn’t thinking about mRNA, let alone imagining it as a therapeutic platform. Fast forward a few years, and he is cofounder and CEO of Strand Therapeutics, which is already reporting promising phase I results from their first-in-human clinical trial.
Jake joined me to reflect on making bold bets in mRNA, why medicine is the best investment, and the state of science today. — Sajith Wickramasekara
* Editor’s note: The conversation has been edited for length and clarity.
Betting big on mRNA — before it was a proven modality
Sajith Wickramasekara: Strand was started in 2017, when mRNA was still unproven and met with skepticism. What was the turning point in your PhD when you knew it could be a company?
Jake Becraft: The entire reason that I went to do a PhD was this fundamental belief about where genetic medicine was going.
I went to MIT with the idea that I would become a professor. I'd done a summer in Bob Langer's lab as an undergrad. Bob's got this beautiful job: he gets to do science, spin it out, and the science goes out into the world.
Then I found out what academia really was like for 99.99% professors. Most of them aren’t Bob Langer. You see the gaps in how science gets out to the world.
There was a startup upstairs from my lab that had just come out of stealth: Moderna. They and BioNTech were developing this really beautiful technology for vaccines.
We were working on mRNA and thought the big gap would be: how are we going to deliver it to other areas of the body? So that's what I started working on as a scientist. I had no idea I’d start a company.
In 2017, we realized we were onto something. We began pitching this company, where I’d say, we’re mRNA 2.0 — next-generation mRNA. So many investors weren’t even convinced there was a 1.0.
Sajith: So investors were pretty skeptical?
Jake: It took me 18 months to raise our seed round. I'm not from that world; I didn't know what investors wanted to see. My original pitch deck was basically my thesis defense. I've looked at it — it’s so incredibly bad. The pitch is essentially all the technology we had developed, without any applications.
Sajith: It was a science project.
Jake: In my head, it was clear what we needed to work on, but I had no idea how to boil that down, to tell a story around it.
“In my mind, everyone would just get it, like we did.”
Sajith: How did you end up convincing investors?
Jake: The investor that ended up leading the round was Playground Global. Jory Bell is a partner there.
Sajith: So you went to Silicon Valley, actually.
Jake: We tried to go here [in Boston] first. We were laughed out of most offices. I mean, most people weren't overtly rude to us. But I was 26, and it's not exactly your typical biotech CEO. This is pre- people making a push around founder-led biotech as well. There was a lot of, “You're not remotely in the decade where you can be CEO of this company.”
Our pitch was a little bit different: We want to deliver the protein that the mRNA makes. The mRNA is just a means to an end. If you can control expression, then you essentially control protein delivery.
That, to this day, still really annoys some more traditional-thinking biotech and pharma folks. The mRNA is going all over, but I don't care because it’s getting degraded and is non-toxic.
This is a way to solve the issue that people have been literally banging their head against the wall for 20+ years: specificity of delivery. We were trying to showcase that idea.
It wasn't well received because it was new. I was still in graduate school and hadn't defended yet. I was finishing up a paper on this that ended up going into Nature Chemical Biology. We were just getting off the ground.
One of the reasons Playground worked out is because they're a venture firm that's deeply technical. They take a lot of time to understand things. Because of that, they were able to see the forest for the trees.
Sajith: Was there a moment where things flipped and everyone believed in mRNA? Did the pandemic fix everything?
Jake: I imagine it’s what people who have been in machine learning for the past 10 years must feel like. It's very surreal.
I'll give you an example. I met Uğur Şahin (who's a founder of BioNTech) and Kati Karikó (who was SVP at BioNTech and now a Nobel Prize winner), at an mRNA conference. Tasuku Kitada, my cofounder, and I had snuck our poster into the poster session at this industry conference.
Sajith: You snuck it in?
Jake: There was an extra poster board, so we just hung it up and stood in front of it during the poster session. So we're standing there and Uğur and Kati come and talk to us. They invited us to BioNTech to give a seminar. So I know these people.
Then, there's a pandemic. The biotech industry was mobilized. We were doing everything: therapeutics, vaccines, preventatives, anti-infectives, everything we could think of. As time went on, mRNA vaccines emerged as this faster, more efficient solution. All of a sudden, these people I know are being interviewed by Anderson Cooper.
“It was a very surreal moment. But all it did was accelerate the inevitable.”
mRNA was going to come as a future cornerstone of medicine. COVID pulled that timeline up and shoved it into the forefront of society.
Getting your drugs to patients
Sajith: It's been eight years since Strand was founded, and now you have positive phase I results. Tell me about the journey.
Jake: Despite being CEO, I think of myself, first and foremost, as a scientist. There's no bigger professional joy than seeing science from the earliest ideation — literally pipette in hand, working on that science at the bench — and taking that all the way into a patient in need that we then helped.
The very first patient that was treated on our trial, we gave the drug and they came in after one cycle. They were metastasizing so fast that after three weeks, the disease was way worse. The momentum was still going.
We continued to treat them, because there were no other options for them. When they came in after that second cycle, that was when we got a call: a bunch of these tumors were gone.
As more patients responded to the drug, we started to hear more — as a scientist, I don't know that there's a greater feeling than being able to move that there.
Sajith: Were there times it seemed like the program wouldn't work?
Jake: That drug that's expanding into a phase II now, multiple times people have hated on it. They said, “It's the same mechanism as we've seen before. It's just new because you're using mRNA. We don’t care.” It was really hard to get certain investors excited about it.
But it's not that cytokines don't work — it's that we haven't delivered them correctly. And now with mRNA, we have a better approach to deliver these signaling molecules.
We had so many different stutter steps. We had all of these mRNA manufacturers that we were trying to line up — at the same time that the mRNA industry went from making a thousand doses a year for a few clinical trials, to making ten billion doses and vaccinating the entire world. Every raw material was zapped out of existence.
Sajith: So it’s not that there wasn’t capacity?
Jake: It was both. The Defense Production Act was rolled out. Even if we had contracts signed, if they needed to make vaccines, they could kick us out. Every place needed excess capacity for the COVID vaccines.
One of the components of most lipid nanoparticles was produced by one family-owned company in rural Germany. There just wasn't demand for it. But all of a sudden, we went from 1,000-10,000 doses per year, to needing to vaccinate 6-7 billion people.
The markets went crazy. You couldn’t get raw materials.
Sajith: Many founder-led biotechs have struggled to survive and advance. What has enabled Strand to break through and deliver, and so spectacularly, to date?
Jake: At the end of the day, if you are a drug development company, your job is to bring drugs to patients. That’s it.
“Your job is not to make mice happier or to generate cool data sets. It’s to get drugs into patients, get data from that, and inform yourself how to move forward or make new drugs.”
There's a disconnect, where we've seen a lot of companies just continue. They're five or seven years old and don't have development candidates. At the end of the day, your platform needs to create a pipeline asset — and it needs to go into patients.
Sajith: Do people lose sight of that because they love their technology too much?
Jake: Cool science gets everyone excited. But I'm still looking at the data, and it excites me because it tells me where our science is going into the future.
Every time we reevaluate what we are investing in, it’s about how this is becoming a drug that we’re going to put in patients.
“Our model does not allow for us to do science for the sake of science. I think people lose sight of what they are building.”
Sajith: Was there a point when you realized all this? Because they definitely don’t teach you this in grad school.
Jake: It was this fundamental belief that we were on to something. The data convinced me, but other people weren’t convinced by it. So there's one way to show it — just get this drug to patients.
Obviously, we had supply chain delays, manufacturing delays, all these things that happened because of COVID, and just getting your first drug approved to start a clinical trial. I've always said, speed is the message.
“Our very first patient, we got to just in time. They were supposed to go to hospice last summer — and over a year in, they're almost disease free.”
Sajith: That's unbelievable. Your team must be so proud.
Jake: We are. But if your drug is effective, that means every time you’re delayed, someone is going to miss an opportunity for that drug. I think that we're still not doing good enough — as a company, as an industry, as a country. It takes way too long.
The state of modern biomanufacturing
Sajith: Biomanufacturing is a big topic these days. You grew up in rural Illinois, near Peoria. I heard you're trying to help revitalize it into a modern biomanufacturing hub?
Jake: I’m all in on reshoring biomanufacturing to the United States. It's embarrassing the level of critical technologies that we don't manufacture here in the United States as a “global superpower” — medicines being one of them.
We manufacture no broad-spectrum antibiotics in the United States, none of the critical components that go into COVID vaccines, and very little genetic medicine components. We manufacture very little biologics.
Sajith: So this isn’t just for the sake of manufacturing here, it's actually critical to the health of the United States population that we have at least some control over the supply chain of lifesaving medicines.
Jake: Imagine a pandemic that hits the same way [as COVID], and how fast supply chains constrict. Imagine that there's a global conflict and it becomes harder to import things — a lot comes from China and Southeast Asia. We don’t have the biomanufacturing capacity here.
Sajith: What sparked the effort in Peoria?
Jake: I grew up in a small farm town of about 1,800 people, outside of a midwestern city called Peoria. Peoria used to be where Caterpillar is headquartered. They also discovered how to mass-produce penicillin during World War II at a USDA research site there. So there's this history of advanced manufacturing.
Like most Midwestern cities, it's been hollowed out by globalization, and manufacturing has left. As I was looking at this hollowed-out manufacturing infrastructure, I thought, why not here?
I started a foundation to think about what biomanufacturing in Peoria would look like, just as a test case. For Peoria and many other cities to be advanced manufacturing juggernauts, like they were 50 years ago, would take continued investment from the federal government, state government, and companies.
You can incentivize companies in both “carrot and stick” ways. The current president has taken a lot of “sticks” to people not manufacturing domestically. I think you should apply that policy at both ends.
Sajith: How do you see the state of biomanufacturing today? Have we made progress?
Jake: No, unfortunately. We definitely manufactured more vaccines during COVID, and that was the government dumping money in to solve the problem as an emergency.
We're beginning to see signs. Some pharma and biotech companies are announcing more biomanufacturing in the United States. But we're lacking a lot of raw material production, which is gonna take a large investment probably from the federal government. And we're missing early stage manufacturing.
Regulatory reforms need to come forward. From the patient perspective, they need the drug sooner than later. From the company perspective, the faster you get to an answer, the faster investment capital can flow to the next stage.
For example, lower those CMC (Chemistry, Manufacturing, and Controls) requirements and combine that with an incentive to manufacture here in the United States, whether that's regulatory or commercial. There's a lot of different options.
Medicine is the best investment — and we need policy that reflects that
Sajith: You were formerly a science technology adviser to the Massachusetts state legislator — what should the government be doing more today?
Jake: Biotech needs the three R's: risk capital, access to revenue, and regulatory reforms.
What happened during COVID was actually the three R's. Regulatory action cleared out the bureaucracy. There was regular conversation between the FDA, companies, researchers, and clinicians. You could get feedback immediately.
There was risk capital provided by the government early on that flew money into not just Moderna, but a number of companies trying to solve the COVID pandemic.
Finally, there was revenue, which was purchase agreements. That can be transformative for a company that's trying to bridge the gap between a proof-of-concept and commercial launch.
Sajith: Totally. I'm sure everyone looks back and thinks Operation Warp Speed was a great deal for the world.
Jake: Medicine is the best investment we make in health care because it's a mortgage and not a rent. All medicine goes generic.
Statins are a great example. Lipitor was a very expensive drug when it came out. It decreased spending by trillions of dollars on heart disease and decreased early deaths — because statins were a huge success for decreasing cardiovascular risk.
Now statins, because they're off-patent and generic, are basically a free drug. So you pay for the patent period, which is usually, at most, about 13 years. After that, you have this, like, free drug. It's an incredible investment.
Whereas knee surgery today is going to be three times as much 10 years from now. If you create a drug that decreases the need for knee surgeries, you pay for it for 10 years, and then it's free.
Sajith: You've been involved in policy for a while. Even in grad school, you were part of MIT's Science Policy Initiative. What drew you to it?
Jake: Scientists need to have regular dialogue with elected officials. We need more scientists to run for office. I think there's one scientific PhD out of 435 members of Congress. There's 23 members of Congress whose highest degree is a high school diploma.
That's not a judgment on people who only have a high school diploma or a GED. That's the highest level of education that my father has.
Sajith: I dropped out of college. I feel called out right now.
Jake: It's more about the juxtaposition of that. Less than 0.25% of Congress is represented by actual scientists. We need more scientists to run for office.
“Whether you're a startup executive or academic, if you're at the forefront of discovery in any way, you have an obligation to communicate that to others.”
What’s happening with various calls to cut funding within the federal government, I think, all stems from a lack of understanding of what scientists do.
Ten years ago, there was a congressman from Texas who was famous for finding grants that sounded the most ridiculous, like a million dollars to study shrimp walking. But you go into the fine print, they were studying the impact of the Gulf oil spill on shrimp mobility, for how we could better recapitulate those fisheries and return business to the Gulf states — including his own state of Texas.
“But it becomes very easy to make science sound ridiculous when taken out of context.”
I think part of the blame lies with scientists. Not everyone needs to be as involved as I try to be, being a resource for members in Congress or their staff.
You don't get credit when an emergency happens and you show up and say, “I'm the scientist, trust me.” You get credit over time when you help people understand.
At the end of the day, I don't know anyone who doesn’t want cancer to be cured, or says “I love Alzheimer's.” No one thinks that. But there are people who are pro cutting certain programs that can help those sorts of research. And it behooves us to be better communicators — I feel very passionately about that.
Sajith: It’s a shame the industry is not better at telling its story. The industry should be celebrated for vaccinating against COVID and things like that.
Jake: Again, I think it falls on us. If you look at the biotech industry, we don't tell our story. You don't watch the Super Bowl to see the final score. You watch the Super Bowl to see how you got to the final score.
“As an industry, we don't take people outside of our bubble along for the journey.“
We don't show them the failures that happen, the people who invest a decade of their life just to fail a phase III trial, the heartbreak that comes from that, and how you pick yourself back up.
My family has no hardcore scientists. My dad sells pagers and beepers, and my mom was a public high school special ed teacher. But as I've been building Strand, they love being along for that journey. Not just because I'm their son, but because they want to hear how the science is doing.
The general public wants to hear it. It's on us to tell that story better.
Rising to the challenge, as CEO
Sajith: There are many challenges that come with developing a new modality. Were there any other big, unexpected hurdles trying to make an mRNA medicine?
Jake: Not for mRNA or genetic medicine — just that the capital requirements on companies are super hard. The markets for biotech have been very challenging for risk capital.
“Biotech companies professionally set money on fire, hoping that the warmth of the fire would be worth more than the money that fueled it.”
Every day is a new challenge. We've been in operations at Strand for about six and a half years, and every year, it's a different company — and the different company actually needs a different CEO. I either have to grow into that position, or I need to get out of the way for whoever can do the job.
It’s like the first year of graduate school. The first year you're drinking from a fire hose and trying not to drown. The learning curve approaches an asymptote by the third or fourth year of graduate school, where you're not really learning new skills — you're just trying to get the data out so you can write your thesis.
Every year of being the CEO of Strand has been like the first year of graduate school. The thing about being a founder is: you have to love that constant learning and development. You have to lean into it. It's an “always on” scenario.
There's a lie that founders tell themselves: It'll get easier once we close this round, get that piece of data, or have that customer.
I talked to a founder, a current executive of a large drug development company who's still running the company 30 years later.
I asked, when does it get easier? He said, it's challenging every year. I've just come to embrace it.
Secrets to a healthy cofounder relationship
Sajith: Let’s talk about cofounders. How did you decide to work together?
Jake: I met Tasuku my first week of graduate school. He is the smartest scientist I've ever worked with in my life. When I first came to MIT, he was about a year into his postdoc, and we started working together.
We were very intense people. I would sleep in the lab sometimes — he would sleep in the lab almost every day. He lived three blocks down the street in a crappy apartment so he could be closer to lab. We were obsessed with science.
But he taught me a lot. I didn't even know how to clone, how to do a mini prep. He trained me on that early stuff, and through to being a good scientist.
He ended up working at this hedge fund, which is where he started to see some insight into how our technology could be leveraged. That's how we ended up becoming a company.
Sajith: Today, you're CEO and he's president. How did you divide up the responsibilities?
Jake: Early on, our business cards both said cofounder, because that's all we were.
I remember one investor pulled me aside and said, “You can't both be cofounder. Who am I investing in?”
So Tasuku and I had this conversation around our skill sets and how to build from that. He’s a great scientific leader, in terms of thinking about complex scientific topics and then building a team and different innovations all the way down to the lowest level. So we knew that he would be very internally focused.
It was probably clear, even back then, that I was a little more communication-oriented between the two of us — and not as good of a scientist.
So I wanted to build an environment where we could unleash his scientific creativity. I’ll be externally focused and talk to investors. That is a CEO's job.
Sajith: Any lessons about keeping a strong cofounder relationship? A lot of people don't think about how critical that relationship is to the company's success when they start.
Jake: We had the benefit of six years of working experience beforehand. It was helpful for us, because there's a lot of trust in that. There’s trust that we’re aligned on what we’re trying to build.
There’s an understanding of how you communicate that to each other, because the two of us can be very blunt with each other. Sometimes I'll fire off a text like, “This is the stupidest sh**. We're not gonna do this, it’s dumb.”
We have a relationship where we can be very blunt. We understand that I don’t want his job, and he doesn’t want my job. We’re not trying to compete for any sort of influence. We’re just trying to make a better company.
That level of alignment is critical for a well-functioning team. And it allows you to rely on another person through the very difficult journey of building a company.
Parenting and advice for the next generation
Sajith: Let’s talk about your personal life. How has becoming a parent this year shifted how you run Strand?
Jake: This is probably the same for any new parent, but for me, it really crystallizes the importance of time management.
I can lie to myself about the company and think, “If I just get this done, then it'll all free up.” You and I have been running companies long enough to know that's a lie. If I take three months to solve that one problem, I've missed three months — that's a different kid.
My son just turned sixteen months. And every few months, he acquires new skills or stops doing something. Sometimes they’re things that you don’t like, like waking up through the night, and sometimes they’re things that I loved — things he did as a baby that he just doesn’t do anymore.
For me, that’s really refined how present I want to be in my personal life. I work crazy hard, and I have a wonderful team behind me. But my son is going to have only one sixteenth month and one seventeenth month in life.
It just helped me understand how to better enjoy my personal life while I'm on this journey. I want to build an enduring generational biotech company. I'm not pushing for an M&A next year, or trying to flip some data set so I can buy a house in Nantucket. I'm trying to build something that's sustainable. That means making time to smell the roses (or poopy diapers).
Sajith: I heard you gave the commencement speech last year at your alma mater. What did you tell them?
Jake: The University of Illinois, where I did my bachelor's degree, is such an incredible university. I went from the cornfields I grew up in, and in less than an hour and a half down the interstate there’s this mecca of scientific research. It’s where I learned how to be a researcher.
For me, the message that I wanted to convey is that this is the ultimate gift — it's made you who you are today. But in a year or five years from now, no one's gonna care who you were today. Every day is a fresh day. Your GPA defines you for exactly one job application.
This was something that I used to think about when I was starting my company and my classmates at MIT were like, “You're not even the smartest kid in our class. Why do you think you can start a company?” And I was like, “I don't know, but I'm just gonna do it.”
For kids coming from the University of Illinois, growing up in the Midwest, it seems like a place that has been forgotten by the coast to a certain extent. But you can just go out and do things. You already have permission.
