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Zahra Jawad, CEO and founder of Creasallis, caught up with Onyx for a feature-length interview on re-engineering antibodies to get inside solid tumours, and on what she learned raising a seed round in the US after Cambridge said no.
Give us the short version — what problem is Creasallis solving?
The one line is that we re-engineer antibodies to improve how they penetrate tumours, because really very, very little gets into a tumour for all these therapies that are being developed at the moment. That's the problem we're trying to solve.
Can you talk through the science behind the CreaTap platform in more detail?
Antibodies are very large molecules. They have a binding site that binds really specifically to its target, which in oncology is the cancer cell. But because they're so big, and because a tumour is so dense, the antibody doesn't actually penetrate very well. It leaves the blood vessel and then it loiters there.
The solutions currently are to make them smaller. Really cutting down the antibody to the binding unit and inject that, because it will penetrate deeper. But then you have another problem in the body: the kidney. The kidney filters anything that's small. We find that these small fragments filter out within 20 minutes of being injected, and not enough can accumulate near the tumour for it to diffuse in meaningfully. That's the dilemma we've been stuck in for many years.
What we do is re-engineer the antibody so that when it hits the tumour microenvironment, the unique conditions there cause it to fragment — almost like a grenade going off. You get smaller fragments formed inside the tumour, and now they're able to diffuse deeper in. But you still benefit from the molecule staying large in circulation, so it keeps bypassing the kidney. You take the best of both worlds by taking advantage of some of the hostile conditions of the tumour.
How does that compare with other attempts to fix poor penetration in solid tumours?
The first group of people tackling poor penetration make the molecule smaller and dose it more frequently, which hasn't really made it through for oncology, because you do need recirculation of the drug to hit the tumour several times over. Those technologies work great for eye delivery, topical delivery, local delivery — where you can just leave it there and not worry about the kidney clearing it.
The other option is injecting directly into the tumour, which comes with its own set of problems. It isn't favourable for the drug payer, because you need a surgeon to administer the drug in a specialist environment. And a lot of these tumours are hard to reach, so they can't be injected at all.
What we're trying to do is improve antibody therapy for oncology in a setting that is identical to how it's made before. So the drug is administered in the outpatients department, by nurses, by IV. And we don't have the problem of fast clearance, because it's a full antibody until it gets into the tumour, and that's where it changes form. Our innovation is a paradigm shift that we've introduced: that manufacturing can happen at the site of the disease, rather than outside the body with the expectation that the molecule stays the same during the course of treatment.
You're seed stage. What milestones have you hit, and what do you need before a Series A?
I started the company unusually, without any data, as my background is purely industrial, from pharma and biotech. I have been engineering antibodies as drugs for a couple of decades, thinking they were great drugs but came to realise that they are quite toxic to patients, so made it my mission to focus on improving that. Even though I am a seasoned drug hunter, starting up from industry has its own set of issues — data generation. You cannot spend your weekends working in a lab to prove it; that won't protect your IP.
So the first milestone was to prove the idea works, and prove it works in an animal. That is quite a high milestone for a pre-seed, but the biotech climate has shifted and animal data is now needed earlier. For seed, the focus now needs to move away from the platform and into developing an asset to demonstrate the platform is viable. That milestone is called candidate nomination, or DC (drug candidate), where you are committed to taking that drug towards the clinic. That is what is needed to raise a Series A. We are close to our DC, so we are starting to think more about manufacturing, regulatory, and where we're going to run our first clinical trial. That's the exciting part — actually seeing your drug being put into a human is quite a life-changing moment.
Have you decided where the first trials will run?
We're still exploring a few territories. The UK has really stepped up in terms of getting things through faster, which is really important for a startup. We also need a territory where there are willing patients. Our lead indication is lung cancer, so we have to be sure we have patients willing to enrol. And we need enough diversity in our Phase 1 population to understand whether it's working, rather than only working in a subset. Of course, we also need somewhere the regulator is fast to approve. China is another interesting regulatory territory, mostly down to its large population and the speed at which they move.
You're Cambridge-based, but Creasallis isn't a university spin-out — and you ended up raising in the US. What was that journey like?
I have been in Cambridge for 26 years, from my PhD all through my industrial career, so Cambridge is very dear to me. So of course the Cambridge and UK ecosystem was the first place I went to look for money. But when you come from an industrial background, when you don't have academic backing, you look atypical to the community here — particularly in Cambridge, where it's very much the academic spin-out type. I came to realise quite quickly that I was getting a lot of nos, very rapidly, because I didn't fit that prototype.
So I thought I've got to try the US, and I went on a few road trips. This involves pre-setting up meetings with as many investors as possible (which is difficult!) — but if I get two or three then I book a ticket for a few days and meet them for a coffee. But I also have several hours to spare, so I filled that time with reaching out to my network — anyone I worked or studied with — and that helped me learn about the ecosystem. One conversation leads to "you should go and talk to this person", which leads to "you should talk to my investor". That led to the success of raising in the US. In addition, in the US you have to be persistent and try several ways to get into the ecosystem. And since this comes naturally to me, it made it a successful path.
Once you had US backing, did UK investors become more interested?
Yes. I think it's always the case with investment that people want to work with people. Investors want to work with you and help you build the company, and investors also want to work with other investors. If you can bring in credible investors, some people go: oh, actually, these are great investors you've brought on board — yes, I'm interested. It's like hiring a team. When you bring in good people, it escalates, and it brings in more good people.
But the attitude is still different. In the US people want you to build fast and furious, whereas in the UK we are more cautious, so US investor bases may not suit every startup and what they are trying to build. When fundraising, that difference is really stark. Conversations in the UK were more like "you're raising a £5 million seed, what can you do with £3 million?", whereas in the US it's "you're raising a £5 million seed, what can you do with £7 million?". It demonstrates that when there is a good idea, the US want you to move faster and think better, whereas in the UK we still worry all the time whether we backed the right idea, science and team.
Is the UK funding picture improving?
I think there's a lot of noise, and a lot of people are speaking up. A lot of UK companies are finding investment in the US, which initially felt great — and then people found that those companies gravitate towards the US, move operations there, and we lose the talent. It might be nice to get US or foreign investment, but what does that mean later for that company? You're losing your best companies to foreign entities.
The UK knows it's a problem. The investment community is definitely hustling the government on opening up early-stage funding, like Mansion House for early investment. But I don't think we're there yet. There are a few examples of big British rounds happening in the last year, but early-stage funding is still suffering. Everything is just more amplified in the US, and we do really need to move faster to stimulate the industry.
How big is the team, and what has hiring been like?
Our team is quite small — we're three people, all scientists, all drug developers, all from industry. I'd say finding the right people has been the biggest challenge for me in the UK, 100%, especially when you've got big dreams and big visions and you want to grow. We have very, very competent people in the UK. But urgency, speed and passion are more difficult to find.
We're also very conservative in drug discovery, I feel. We know what the key experiments are, and we don't reach them fast enough. We've got to take the best bets from our collective experience and move faster. That's where the US is really good — taking the shortcuts and getting there faster. And yes, sometimes it all backfires, and in the UK it probably backfires less because we're more thorough. Let's get to the key experiment fast and backfill the nice-to-haves later, rather than putting the nice-to-haves on the critical path and never getting to the key experiment.
Do you think the average person working in US biotech is hungrier — and if so, why?
They're definitely hungrier. People are hungry to build something, to be part of something, and to use that as a success. I am unsure why the UK doesn't have that hunger — it could be because we don't reward hard work and those who go above and beyond. Or maybe in the UK people are not patient enough to stick around to see what their impact is, and get disillusioned and switch off.
But there are pockets where that hunger does exist here. You can definitely see it strongly among the founders community.
What are you actually looking for in the people who do have it?
We're looking for a very rare skill set: people who are experienced, who know their field really well so they know what the critical path needs to be, but who are also hungry to be part of some revolution and build a company. I can't explain it better than a spark in someone's eye. You can tell within the first 20 minutes of sitting across from somebody whether what you're saying excites them, or whether they're just excited by having another job.
In the early stages of a startup, everyone needs to have the builder mentality — the willingness to be scrappy, the thinking outside the box. Someone who says, we could do it this way, but we could also get the same result this other way, and it would be faster and cheaper. That wheeler-dealer, business-development type of mentality. It isn't about being pushy. It's about understanding who you're talking to, going into that energy and driving it forward. So that's what I look for: the drive and the spark.
If Creasallis goes from three people to 30, or 300, what culture are you trying to build?
I spend a lot of time thinking about the culture of the company I want to build. Part of hiring people with that spark is giving them accountability and responsibility, so they feel part of it and feel like they're building it. That means a very flat hierarchy — not managers telling you what to do, but self-motivation, knowing what needs to be done and getting it done in the best way possible with the knowledge we have today.
I also believe small teams work better than very large teams. Even at 300 people, we'd still run the company in sprints, with smaller project teams leading things. We already run in a scrum-type way at Creasallis: we touch base for 15 minutes every week, look at the plan, where we're at, what's blocking, what's moving, and make it really clear what we all need to do by the end of the week. People who are self-motivated are really important to that.
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