For this month’s CFFN Spotlight, we spoke with Zahra Jawad, Founder & CEO of Creasallis – a Cambridge biotech re-engineering antibody drugs to reach solid tumours more effectively.
Drawing on nearly two decades in antibody development, Zahra and her team have built CreaTap, a plug-in that helps existing antibody drugs penetrate deeper into tumours by harnessing the tumour’s own biology. In this conversation, you’ll hear why so little of an antibody dose ever reaches the tumour, how CreaTap borrows from rocket design, and what it could mean for the next wave of cancer drugs.
For those unfamiliar with Creasallis, what are you building, and how does it change the way we think about antibody-based cancer therapies?
Creasallis stands for “Creative Antibody Solutions”, and that’s really the premise behind what we do. We’re looking for creative solutions to alleviate some of the biggest bottlenecks in antibody-based therapies.
Our first focus is cancer therapeutics. Monoclonal antibodies have been amazing: we’ve moved the needle for some cancer patients, and we can make antibodies that bind tumours and shrink them down. But only around 20% of people benefit. The majority either don’t respond or can’t tolerate the toxicities that come with these drugs.
We’re trying to tackle that problem: can we get more of the drug to penetrate into the tumour so that more patients can benefit, without making them really unwell in the process?
How big is the tumour-penetration problem in reality, and what does that mean for patients?
Maybe around 0.001% of what you give a patient actually makes it into the tumour. The vast majority goes elsewhere in the body.
The tumour has tightly packed cells and abnormal vasculature. When you give a treatment into the bloodstream, the antibody can’t diffuse very far out of the vessel and into this dense mass of cells. Very little actually gets in.
So the typical response has been: give the patient more drug. You do get a tiny bit more into the tumour, but you’re not really moving the needle. What you are doing is bathing all the other organs in a lot more drug. That’s where you see toxicity.
The majority of patients exhibit some form of toxicity from antibody-based drugs. The question is whether they can tolerate it enough to stay on treatment or whether they have to come off and move to something else.
What we want to do is really change that picture: increase the fraction of drug that reaches the tumour so more patients respond; potentially reduce the dose, so toxicity decreases and treatment is easier to tolerate; and, crucially, reach patients who currently can’t be treated because their tumours are simply too big or too hard to penetrate.
CreaTap is ultimately aimed at most cancer patients treated with antibody-based drugs, not just a narrow subgroup. Today only a small proportion of patients respond to these therapies, and many can’t tolerate the toxicity, so large numbers end up effectively on palliative care – in lung cancer, for example, global deaths are still rising year on year. By improving how antibodies reach solid tumours, Creasallis aims to make these drugs far more inclusive. Over time, the same approach could also extend beyond oncology into diseases like fibrosis, atherosclerosis, and Crohn’s disease, where antibody penetration is already recognised as a problem.
You’ve spent nearly 20 years designing antibody drugs in industry. What made you step back and decide the field needed a different approach?
I’ve spent almost two decades in industry making antibody-based drugs – in big pharma and in smaller biotechs. I know what it takes to get a drug to patients.
For a long time I thought we were making great drugs. Then I realised we were hitting the same wall over and over again. We were pouring huge effort into discovering new targets. A few were fantastic, genuine magic bullets. But the “new target” model wasn’t transforming outcomes the way we’d hoped.
So I started asking: do we really need yet another new target? Tumours are made of our own cells, so the biology is shared; people have been looking for something truly tumour-only for 20-30 years and it hasn’t really materialised. And when you do discover something, it’s a huge amount of work to get from that discovery to a drug in a patient.
That’s when I began to think that maybe the real opportunity is in engineering, not discovery. We already have a lot of good drugs. They’re just not benefiting enough people. If we collectively focused on improving how those drugs behave – where they go in the body, how they penetrate tumours – we might create a much bigger shift for patients than by chasing the next “perfect” target.
What really crystallised it for me was how we think about the body. The industry is used to thinking in terms of stability: you make a drug, you characterise it, you give it to humans, and then you’re surprised when biology modifies it; the liver metabolises, tissues process it, and suddenly the molecule is altered. Then you go back and engineer it not to change.
Our proposition is: we know biology is going to do things to the drug. Instead of fighting that, let’s use it. Let’s design a better drug by deliberately harnessing those changes. That mindset – of accepting that the body will interact with your drug and asking how to turn that to your advantage – is really at the core of Creasallis, and it’s what eventually pushed me to leave a comfortable job, after about five years of thinking it through, and build a company around this idea.
How does your core technology – CreaTap – actually work?
We engineer antibodies in a very specific way.
Antibodies are large macromolecules. Their size is part of what gives them a long half-life in the bloodstream; they’re too big to be filtered quickly by the kidney. But that same size makes it hard for them to diffuse into the tumour.
People have tried to solve this by making smaller antibody fragments, just the binding part. Those diffuse much better through the tumour, but they’re so small that they’re rapidly filtered by the kidney and cleared from the blood in minutes.
We took inspiration from the space industry.
Think about a rocket: it takes off with lots of fuselage, fuel tanks, stages, and as it gets closer to its destination it sheds the parts it no longer needs so the lander can reach the moon.
We applied that principle to antibodies. We re-engineered the antibody so that it contains a tumour-specific protease site in its hinge region.
Proteases are proteins that cut other proteins at specific sites. Tumours often have high expression of certain proteases. So what we’ve done with CreaTap is this: in the bloodstream, the antibody behaves like a normal, large antibody. It avoids kidney filtration and has a long half-life. As soon as it enters the tumour microenvironment – where those proteases are highly expressed – they recognise the engineered site and cut there. The antibody splits into smaller fragments. Inside the tumour, these smaller pieces have a diffusion advantage, so they penetrate deeper into the tumour mass.
The region we engineer is the hinge – a universal region that’s the same in every IgG antibody. It’s traditionally been a bit of a taboo area to touch, but we’ve figured out where the best protease sites are and how to plug them in in a way that’s consistent and predictable.
The result? In our models, we see just over double the amount of antibody in the tumour compared with the unmodified version, while maintaining normal behaviour in the blood.
Antibodies now sit at the heart of a lot of cancer drugs. At one end you’ve got “plain” monoclonals; at the other, antibody–drug conjugates (ADCs), where the antibody carries a toxic payload into the tumour. In that landscape, where do you see CreaTap having the biggest impact first – and what could that unlock?
ADCs are where we see the most immediate need. Adding a linker and a payload onto an antibody, and making it more hydrophobic, tends to make penetration worse, and yet these are some of the most powerful agents in oncology.
So ADCs are in greatest need of improvement, and that’s where CreaTap can make a big difference early on.
Applying CreaTap to entirely new therapeutics – for instance, going back to very toxic drugs that failed in phase 2 because patients couldn’t tolerate them, and seeing if we can “rescue” them – is a longer-term play. There you have two unknowns: the therapy itself and our engineering.
Right now the lowest-hanging fruit, and the route to the fastest impact for patients, is improving existing ADCs and, more broadly, antibody-based drugs that are already known to work but are held back by penetration and toxicity.
As more of these engineering approaches come alive, I think we’ll see people thinking much more creatively about improving what we already have. One company might have a technology that improves penetration, another might have something that enhances binding, and a third might have a way to reduce off-target toxicity. Taken alone, each is an incremental improvement. Combined, they could create a genuine paradigm shift: a sort of “super-drug” that really moves the needle for patients.
What needs to change in the wider ecosystem – from pharma to ecosystems like Cambridge – to unlock that kind of collaboration?
We need each part of the system to do what it does best.
Pharma is excellent at getting drugs to patients: moving methodically through regulatory steps, running large clinical trials, navigating reimbursement, marketing to doctors and hospitals. They are not, and don’t need to be, the primary innovators.
Start-ups and small biotechs – the “crazy people” who are willing to take the early risk – are where real innovation often happens. The system works best when those innovators can plug into pharma rather than be subsumed or replicated.
Practically, we need more mergers and structured collaborations, rather than everyone trying to copy each other’s ideas and go it alone; less fear around IP being “stolen” and more recognition that one plus one can equal three when you combine technologies; and a more secure funding environment, so founders and teams aren’t constantly operating from a place of fear.
We’ve found collaboration in Cambridge harder than we’d like. In Boston, the attitude is more: “We love what you’re doing. We could try to do it ourselves, but why not just work together and create something new?”
In Cambridge, people are more guarded. I understand it. People want to protect themselves and their ideas – but that fear can really get in the way. From my point of view, I’m busy enough trying to get my idea off the ground. I’m not here to steal anyone else’s. We’ve patented, they’ve patented. The real opportunity is in figuring out how our technologies might complement each other instead of hiding them away.
When I meet another founder, I’m not thinking, “How do I copy you?” I’m thinking: “What are you doing? What are we doing? Could those things together become something more powerful for patients?” If we can shift the culture even slightly away from defensiveness and towards that kind of curiosity and co-building, we’ll move much faster – and patients will feel the benefit.
We’re very grateful to Zahra Jawad for sharing the story and technology behind Creasallis and CreaTap – an engineering-led approach that is reshaping how antibody drugs are designed for solid tumours, and pointing to a future where many more patients can benefit.
🔗 Learn more about Creasallis here.
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