Ellipses Pharma: the drug development model that minimizes risk

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Guaranteed success in drug development does not exist, such are the inherent risks, potential pitfalls and costs involved.

But UK-based Ellipses Pharma has developed a model that - if its founder’s convictions prove accurate - will maximize the probability of success and lead to a host of new oncology drugs being brought to market by big pharma.

That man is Professor Sir Chris Evans (pictured, above), a scientist and entrepreneur in his fourth decade in the industry. During that time, he has been involved in the inception and development of more than 50 companies. Several have gone on to attain billion-dollar unicorn status including Biovex, Chiroscience and Vectura.

Garnering global expertise

In this period, Sir Chris noticed a huge opportunity for a new type of drug development company, that will avoid the stumbling blocks that impede many others.

“The whole point of Ellipses, the real vision from about 10 years ago, was how to create a cancer-focused drug development company, where we could get multiple successful hits and multiple wins in clinical trials,” he told The Pharma Letter.

“How am I going to do that? My big idea, and it’s an idea that has evolved over these four decades of working with different people - experts with different views on different things - that I realized that I can’t really rely on six or seven or eight really smart world-leading oncologists to statistically give me all of the comfort that I want.

“What I mean is, where am I going to get the drug and, when I’ve found it, how do I know it’s going to be any good and how do you design the trials and how do you develop the trials and when do you do them? All these things, I’d done in the past, and I’d built these companies and laboratories and [worked with] thousands of scientists.”

‘Don’t cut corners’ early on

When it came to the first step of ensuring that Ellipses could find and select the best cancer drugs anywhere, the company chose prospects that had not been research candidates but had been in existence somewhere. Their source varies from major charities like Cancer Research UK, biotech companies, leading universities and more. Then, the company makes sure that the preclinical, formulation work is done in full where consideration is given to all aspects of clinical trial design.

“What are the things we should be looking for in those trials, before we even start?” Sir Chris explained. “What are biomarkers, how are going to do patient selection, using those biomarkers? How do we maximise what I call patient responders? Because that’s how you get good results, and what does all this mean in terms of commerciality, in terms of market value?”

Even when you have something unique with a great mechanism and every belief that it should work, doing the pre-clinical work and managing the formulation in full is critical, Sir Chris believes.

“My experience is that even to this day, a lot of biotechs underestimate and rush through their preclinical work and it comes back to haunt them in Phase I and Phase II, in terms of bioavailability and efficiency and success rate,” he said. “In other words, don’t cut corners in the first place.”

With all of this work done at the outset, Ellipses will know when it has a potentially successful molecule. This inflection point may arise at various stages but most likely during or at the end of a Phase II trial, when it is apparent what the data means and how best it can be positioned as a commercial package to big pharma.

“Our model is to out-license the drug at that point,” Sir Chris explained. “Either sell it outright or out-license it to various parties. It will go into the hands of the big boys, who know how to finish the Phase III and the registration and get it into cancer patients around the world. I will get on and find the next 10 and the next 10 and the next 10. That’s the machine, that’s the vision.

An advisory board with 300 plus world-leading KOLs

“But the key, the unique selling point, which I knew no-one had ever done, was I’m not going to rely on six or eight people, I’m not going to rely on a classic 12- or 14-member scientific advisory board that a lot of big pharmas have, with world experts on them, though we do use some of those same people because they’re world experts in particular areas of oncology,” Sir Chris added.

“My big plan was to build an advisory board with 300 world leaders on it in every category, breast cancer, colorectal, everything. To do that, it’s going to take me years - getting around, convincing these world experts they’re not going to be wasting their time with some biotech, they’re going to be using their time very valuably to look at brand new molecules that have not run through clinical trials, that probably have fantastic futures and need to be properly formulated and designed into proper clinical trials.

“That appealed to all these world-leading KOLs, who are all practising clinicians in major hospitals and institutions, all around the world in over 25 different countries.”

As well as these hundreds of experts involved in the company’s Scientific Affairs Group, Ellipses has the expertise of Sir Chris and an experienced team of 30 employees, many with big pharma experience, looking at the projects early on to help choose which ones to back, and which ones not to.

“We’ve got over 300 world-leading KOLs in our platform,” Sir Chris explained. “Any 50 or so may be utilized on a particular compound. Their input is provided anonymously and the data is blinded before being reviewed internally. The platform helps prevent groupthink and stimulates more open expression of views and mitigates the risk of relying on favored opinions. By actively encouraging and appreciating heterodox views we do in effect create the equivalent of a finely tuned peer review system.

The nature of this type of group increases confidence in the feedback process, welcoming those who challenge assumptions in the pursuit of better outcomes.

However, it is important to realise that it is not simply the volume of KOLs that matters, but the quality and granularity of individual contributions. Their feedback can also identify new and bespoke opportunities for drug candidates.

“If too many concerns and issues are raised, I don’t care even it’s 50-50, it’s dead.”

Serving the needs of big pharma

If a compound is to be taken forward, the KOLs - who in some cases have helped to find it in the first place - remain involved throughout its entire journey, from preclinical trial design, clinical study design, and so on.

“They help with the Phase I, the Phase IIs, designing everything particularly the markers, the responders, the key blood analyses you need to do, and then as we’re implementing the trial they also help with developing protocols, including patient selection criteria” Sir Chris said.

“When the trial is run for a year, two years, three years, the data’s processed, when things are ready for out-license, it’s packaged up. I will lead the team in the presentation to big pharma, on very sensible commercial terms. We know what we’re doing, we know what we have and we know the market.

“This is what big pharma wants, they want people to bring them these high-quality compounds in oncology.”

‘It’s working as we’d hoped’

Sir Chris believes that this model, with plenty of finance and great care invested in drugs at the outset, is the best way to develop oncology candidates.

“We design our trials the same way as big pharma,” he said. “Where big pharma may spend $9 million to $15 million on preclinical work, most biotechs run a mile from spending that. But if I have to spend it, then I will. And so on through Phase I and Phase II. I don’t shy away from it, and it’s all done in incredible detail, overseen by these 300 plus world experts and run by my very experienced clinical team who, with their big pharma experience, are used to running things this way.

“The end product is a substance that’s been in a substantial number of patients and which you can present to big pharma. They can recognize the quality of the way we’ve done this, the quality of all the steps in the journey, and they don’t have to repeat them.”

Currently, Ellipses has three drugs in Phase ll, one that enter the clinic later in 2025, one preclinical stage and others under consideration.

All assets that are in current development are progressing well to date, which has been very encouraging.

“I’m very pleased and optimistic, and so are the KOLs in our Scientific Affairs Group," Sir Chris said. "Our model is working as we hoped it would.”

‘A leading oncology development company’

Despite significant progress over the last 50 years, the process from discovery to patient access to new cancer drugs remains slow and fraught with challenges.

Ellipses believes it is on course to accelerate the development of cancer medicines and treatments.

“We all know the challenges that cancer presents, but we are very confident that we are on course to be a leading oncology development company,” Sir Chris said.