Dr Fiona McLaughlin is the new Chief Scientific Officer of Avacta’s Therapeutics Division. She talks to Karen Southern about her mission to develop first and best-in-class cancer drugs.

From the day that Dr McLaughlin – then a biochemistry student – volunteered for a one-off industrial placement at ICI, her ‘fate’ was sealed.

“I have worked in cancer research throughout my career,” she explains, “including at university, where my final year project was conducted at The Beatson Institute working on a metabolism project, now a very hot area of research.

“My PhD was in Stem Cell Leukaemia, and in industry I have worked throughout in oncology (and inflammatory) drug development, covering small molecules, biologics, and radiopharmaceuticals.

“I am very fortunate to have always loved science and biological sciences in particular. Working with world-class physicians and scientists is always inspirational because you know that what you do is going to contribute towards either greater understanding of disease biology, or ultimately in a new oncology therapeutic.”

After completing a year at ICI (now AZ), she finished her BSc at Glasgow University, and a PhD in Haematology at Cambridge. Twenty-five years on, her impressive pharma and biotech portfolio in research and translational drug development includes stints at GlaxoSmithKline, and leadership positions such as vice-president, Translational Research at Antisoma plc and director of Pre-clinical Development at BTG plc (now part of Boston Scientific).

Other roles include Head of Biology at TopoTarget A/S, where she was responsible for the pre-clinical development of belinostat which went on to gain FDA approval to treat peripheral T-cell lymphoma. Most recently, she was vice-president of New Opportunities at Algeta ASA (acquired by Bayer), a Norwegian biotech developing alpha radio-pharmaceuticals, that gained FDA approval of Xofigo to treat castration resistant prostate cancer.

Now she is responsible for helping to develop innovative cancer therapies and powerful diagnostics at Avacta, as Chief Scientific Officer of the Company’s Therapeutics Division. This intensive body of work focuses on addressing a critical gap in cancer treatment – the lack of a durable response to current immunotherapies experienced by most patients. By combining its two platforms, Affimer® and pre|CISION™, the Group is building a pipeline of novel cancer therapies.

The Affimer® platform is an alternative to antibodies derived from a small human protein. Despite their shortcomings, antibodies currently dominate markets, such as diagnostics and therapeutics, worth in excess of $100bn. Affimer® technology has been designed to address many of their negative performance issues, principally: the time taken to generate new antibodies and the reliance on an animal’s immune response; poor specificity in many cases; their large size, complexity and high cost of manufacture.

Avacta’s pre|CISION™ targeted chemotherapy platform releases active chemotherapy in the tumour, which limits the systemic exposure that causes damage to healthy tissues, and improves the safety and therapeutic potential of these powerful anti-cancer treatments.

So what attracted Fiona to the role? “I had been working as a consultant for the last few years, which gave me a great amount of flexibility to work with a number of different types of organisations, from biotechs, to venture capitalists and not for profit organisations such as Cancer Research UK.

“Working as a consultant, you build up a fantastic network, especially in the Cambridge area. As a next step, I wanted to move to an Oncology-focused biotech, where I could take my expertise gained over 25 years in drug development, together with my strong network in the oncology field, to really develop the science and bring new, innovative drugs to the market.

“Avacta is a company that is just starting its journey as a clinical development organisation, and I could see the potential to really shape the portfolio and help steer the company into a new phase.”

There is also however, a more personal element for Fiona: “I have an identical twin sister who was diagnosed with breast cancer in 2018, while still in her 40’s. I have known many people who have had cancer, but not anyone this close. She was diagnosed with a type of tumour for which there was an antibody therapy, and we hoped that meant she would be spared from the side-effects of chemotherapy. Unfortunately, the best result in trials came from the antibody given in combination with chemotherapy and so she underwent 12 months of chemo, antibody treatment, surgery and radiotherapy.

“I saw first-hand the side effects of having three chemotherapeutic drugs given at the same time, and I appreciated more than ever the need to get better tolerated drugs to patients. One of the drugs she was given is called an anthracycline, and I am now working on developing a better tolerated version of an anthracycline in my new role at Avacta.”

For now, Fiona sees her main challenge being access to high quality patient material and “the heterogeneity of tumours which makes statistically significant comparisons challenging.”

However, she singles out the timely advances in AI for rapid breakthroughs in oncology drug development, diagnosis, precision oncology and ultimately prevention. “The ability to process huge amounts of data, and recognise patterns in the data, allows us to potentially identify novel areas of research and new drug targets, but also to repurpose existing therapeutics.

“Furthermore, in advancing these therapies in the past five years, cutting-edge research areas have been established that hold huge potential to expand the efficacy and safety of current therapy options. By harnessing these discoveries, the benefits of standard chemotherapies can be expanded to more patients, without the debilitating side-effects.

“This means we can collaborate with first class academic labs to help translate our research (for example exploratory biomarker analysis) to the clinic and back to the bench. We design our clinical trials to be as data rich as possible, so that we get a better understanding of our drugs and how they work and identify which patients are likely to respond, using state of the art methodology.”

Fiona and her team have already prioritised assets in their portfolio, driving them faster towards the clinic. “We have also built up the translational science team to ensure we design the most effective clinical studies, expand the pipeline using our two platform technologies and increase our interactions with world-class academic labs and industries, to deliver first-in-class therapeutics.”

However, she is also pragmatic about the challenges ahead: “There are more than 100 different types of cancer, some are solid and some are liquid (haematological) which makes our work incredibly challenging. Each tumour type has a different genetic background, and that genetic background can change over time and with treatment. Gaining an understanding of this complex environment such that we then understand which targets to go after is a massive challenge.

“I think one of my greatest frustrations, so to speak, is that there are still so many potential drug targets that are un-druggable using current technologies, for example transcription factors.

“This is why everything that we do in the lab has to be tangible. We are making drugs to deliver to patients, or developing companion diagnostics to help deliver a precision medicine approach to cancer treatment.

Our ultimate goal is to continue bringing novel, effective therapies to patients, in particular in areas of high unmet need such as pancreatic cancer and to help make cancer a disease that people die with, not from.”

How does Dr McLaughlin see treatment progressing in the next few years? “Immuno-oncology agents have been transformational for many patients, but sadly not all. A number of disruptive technologies, such as in the cell and gene therapy area, could significantly alter cancer outcomes, but I suspect chemotherapy will still have a role to play in patient care for many years to come.”

And finally, any advice for aspiring R&D graduates? “Don’t give up! Attrition in early stage drug development is high, because of the complexities of what we do. You need to be able to problem solve constantly, but the more experience you gain, the more you are able to bring that experience to bear on the problem in hand.”