Leading a Renaissance in Alzheimer's

FORUM Pharmaceuticals CEO and President Deborah Dunsire made the move from the oncology sphere into dementia-related illnesses. She tells Danielle Barron why she likes to stay at the cutting edge of research, while always keeping her eye on the prize – better outcomes for patients.

Industry veteran Deborah Dunsire had been involved in some of the most pivotal discoveries in the oncology field. That makes her move in 2013 to FORUM Pharmaceuticals to work on the development of therapies for Alzheimer’s and other neurological conditions even more surprising. Originally a physician, she has spent over 25 years in the industry, including lengthy spells with Novartis and then Millennium Pharmaceuticals, and was involved in the development of several ground-breaking drugs, including the chronic myeloid leukemia game-changer Gleevec and the multiple myeloma therapy Velcade.

There was a personal driver for the reasons behind her move, however. With her father-in-law currently in a nursing home in South Africa suffering from a dementia-related illness, Dunsire explains that to see this once-brilliant man become a shadow of himself gave her first-hand experience of the unmet need in this area.

“He was head of the obstetrics and gynecology at a regional hospital and to see how the brain function deteriorates as dementia takes hold is pretty scary, not to mention the impact on the family. Having had that experience made the move to FORUM more attractive. I wouldn’t have imagined leaving oncology, but this fit a lot with my personal desires to be in a therapeutic space where there isn’t adequate therapy and where we really can bring forward performing medicines.”

An inflection point

Efficacious, disease-modifying therapies in Alzheimer’s disease have indeed remained elusive, and according to Dunsire, it hasn’t been ignored by the research community; rather, the research to date has been unsuccessful as scientists fought to get a handle on the underlying biology of the condition. That is all set to change, despite recent cutbacks in funding for neurological and neurodegenerative disease research, she says.

“A tremendous amount of money has been invested by pharmaceutical companies in the past decade in disease-modifying drugs for Alzheimer’s disease. The challenge is that they have all gone after the same target, which is primarily beta-amyloid and using the same technology and nothing definitive has come out of it as yet. If you look at psychiatry and neurological diseases in general, investment in those areas has been really cut back, partly because pharmaceutical companies are saying that biology isn’t well enough understood.”

Now, however, things are about to change, asserts Dunsire.

“I feel we are at an inflection point in these diseases in the coming five years, that we will understand the biology better and we will be getting a better handle on the genetics. I see some of the dementias and some neurological diseases being able to be much better served, and I think we will see a return on the investment in the CNS areas.”

A learning curve

They are artists essentially; they are incredibly creative because they have to be able to imagine futures that don’t exist yet".

Dunsire explains that her first foray into “true organizational leadership” was when she moved to Millennium Pharmaceuticals as CEO in 2005. Prior to this, she worked as one of many key cogs in the much larger corporate wheel of Novartis, where she admits she was somewhat constrained by processes and protocol, however necessary these may have been. This led to a very different experience of leadership within the much smaller Millennium, as she worked alongside researchers and developers for the first time. She admits it was a learning curve, emphasizing the contrast between the creative and visionary personalities of the scientists in a cutting-edge biotech company and the corporate atmosphere of the big multinationals.

“With a large global company, processes and procedures are very necessary, while in smaller companies, there has to be order and processes, but not too much – otherwise it is stifling and it makes it difficult to get things done. I had to figure out how to work with scientists, who for the most part, when you think about drug discovery and development, are at the very early part of that process where there is more failure than there is success, given that only one in 100 medicines will eventually make it to market. It is a mix of optimism, determination, and fascination that comes from all the scientists in the organization working on drug discovery. They are artists essentially; they are incredibly creative because they have to be able to imagine futures that don’t exist yet,” Dunsire muses.

“Commercial organizations are much more linear, they are about process and all about execution and they are more easily measurable – while individual scientific experiments can have their own precise measurements, the trajectory of what all the experiments add up to is not always easy to predict.”

Effecting change

The move in 2013 to the relatively diminutive FORUM was another significant change for Dunsire, and meant she again had to re-evaluate the leadership skills she had spent years honing. What she has found particularly pleasurable is the personal relationships she has been able to build with her co-workers.

“One of the things that is very enjoyable about a smaller company is knowing everyone, which I do at FORUM; we are only 165 people, whereas at Millennium we were 1,500, and at Novartis you know your work group and immediate group but your connection to the rest of the company can be limited. That’s been a fun part of moving to a smaller company.”

Effecting organisational change is much easier, she admits.

“You can enrol people in the why and the wherefore of change more easily because there is a personal interaction and the ability to have a very direct communication. Effecting change takes a lot more energy, effort and process at a larger company.”

Intrinsic curiosity

Given that Dunsire has proven her ability to lead in very different environments within the pharmaceutical industry, what does she think are the key personality traits that have led to her success?












"The one I would have to identify first is curiosity – I just find it immensely interesting to learn and explore different areas. If you are intrinsically curious about how things work and you are willing to dial in and learn, things that are outside of your initial comfort zone and understanding - aspects such as legal issues, patents, organizational structures, that type of curiosity and that thirst for learning is a priority.”

Another aspect she also thinks has contributed to her many years spent in high-level positions is an ability to make tough decisions despite the threat of several unknown parameters.

“There are always so many unknowns in this business that we have to be able to make progress and pick a path even though not everything that you’d like to know is known at the time. You have to move down a path and then adjust as more information becomes available. If you are somebody who really requires a full dataset to be able to decide and move, it would be very hard.”

Making a difference

I have used my medical training to make a difference by helping to deliver medicines that allow people live who otherwise would have died".

As well as the ability to make tough decisions in the boardroom, and her inherent thirst for knowledge, it is clear from her stellar career trajectory that Dunsire prefers to be at the forefront of innovation. Her background as a physician, however, means that the patient is always her motivation. In fact, she says what first attracted her to working in the pharmaceutical industry is the potential to truly help patients.

“That’s why all the years spent in oncology were so satisfying in terms of seeing how the lives of patients were truly transformed in a way that wasn’t possible before. I have used my medical training to make a difference by helping to deliver medicines that allow people live who otherwise would have died.”

Playing a part

In fact, Dunsire defines success not in terms of her personal accomplishments, but rather knowing she has played a pivotal role in efforts to prolong and save people’s lives.

“When I look back at my career, I think about patients, actually. One patient who was a on a Phase I clinical trial of Glivec - I got to know her while I was working at Novartis – this was a lady who was dying. She was put on the trial in 1998 and over 15 years later she is alive – I had a part to play in that with a huge team of people. Together over many years, that medicine was discovered, developed and delivered to patients. Being able to be a part of that and see the outcome to me defines what I am proud of and, therefore, what I consider successful.”

The gender question

The elephant in the room is that while Dunsire speaks confidently and passionately about leading companies as they tread the precarious path of drug development, she is almost unique, in that she is one of the very few women who have managed to reach such dizzying heights within a traditionally male-dominated industry.

Why is the gender balance so off within pharmaceutical companies? She believes that women have a better chance of succeeding within the flexible and progressive culture of the modern biotechnology enterprises.

“When you look at biotech, you do see a better gender balance throughout the organization. The question is why can’t the big companies do this – they are getting better but not at a rate that is good enough. In the smaller companies, there is an ability to be more flexible so for women to be able to better balance the demands of their family life and their work life, not by taking time off or by being out of the workforce for long periods of time, but just flexibility to their work practice – being able to bring work home and not having to be in the office at specific hours – and not having the perception that the number of hours you are in the office reflects your commitment to the company.”

An interesting point by Dunsire is that women are prone to feeling guiltier about any errors of judgment they may make, and she says this may affect them being viewed as competent leaders.

“Women are more likely to be harder on themselves than a man will – that’s a generalization, but there are more women that will be devastated by a mistake they have made, and apologize and criticize themselves than there will be men who will take that path. That also contributes to why women may be seen differently if they make a perceived error.”

A forced evolution

Gender balance notwithstanding, Dunsire asserts that the recent avalanche of patent expiry has forced the pharmaceutical industry to evolve and she believes that the new world opened up by the leaps forward in pharmacogenomics holds the key to the next generation of medicines. In her opinion, this will require active collaboration between the pharmaceutical behemoths of old, and the younger, daredevil biotech start-ups.

“With the mapping of the human genome and the understanding of better gene sequencing, we have got so many more tools now to understand what really is going on and actually driving the disease. Many more pathways and targets are becoming available and what I think that does to evolution in the pharma industry is make it really clear that no one company can do it all internally. The bigger companies need to see these external forces in drug discovery and development and smaller, newer companies taking a different approach and then big pharma either partnering with them or acquiring them. That’s the new evolution.”

Transforming therapeutics in Alzheimer’s disease

FORUM’s most advanced compound, encenicline, is currently being investigated as part of two global phase III clinical trial programs, one in Alzheimer’s disease and one in schizophrenia, but also within its pipeline is a compound that just entered a phase II biomarker trial for use in a rare genetically-determined dementia.

The genomics revolution is particularly pertinent for Alzheimer’s disease and other dementias, and Dunsire’s desire to transform therapeutics in the field is evident as she passionately concludes: “It’s exciting because if we can define genetic subsets of dementia, we can start to make some of the progress we have seen in oncology; lung cancer used to be one disease but now we know there are different genetic drivers, and if you address those you get a much better clinical outcome. The same is now happening in dementia.”

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