Planning For Perseverance
By Andrea Pfeifer
Creating and bringing new medicines to patients is a uniquely complicated process. It requires robust scientific research, business acumen, tremendous financial investment, and patience — even when all goes to plan. More often than not, it also necessitates the ability to absorb, learn from, pivot, and persist through setbacks.
Working in Alzheimer's disease (AD) for more than 20 years has provided many lessons in how to stay the course. In the time since I cofounded AC Immune in 2003, seven different clinical antibody therapies targeting beta amyloid have been set aside, including one of ours. Each round of setbacks and new beginnings set the pendulum of pharma and investor sentiment swinging from bearish to bullish and back again.
From a drug development perspective, the setbacks contributed valuable knowledge about optimal molecule characteristics, targets, patient selection, dosing, and clinical trial designs. In short, each “failure” was full of valuable learnings, and now, disease-modifying antibody therapies are approved for patients with AD in the U.S. and Europe.
From AC Immune’s perspective, two decades of perseverance, knowledge building, and invention have brought us within reach of realizing our vision for precision prevention of AD and other neurodegenerative diseases.
Arriving at this point depended upon maintaining focus on the need to help patients living with disease, communicating transparently about our setbacks and the adaptations we were making for future success, and most of all, steadfastly following and investing in the science.
The last is a difficult feat in uncertain times, but an absolute necessity for building a sustainable biotech, because long-term success very often requires a willingness to tackle the innovation that will sustain you in the future long before you’ve overcome the hurdles of the present.
The way we prepared for and persevered through our setbacks may provide learnings for other biotech leaders navigating turbulence and uncertainty today.
Innovate, Innovate, Innovate
At the first sign of a setback or when financial markets become volatile, investors often pressure management to deprioritize early programs in favor of advanced candidates that can increase valuation in the near to medium term. But if the aim is to build a company that is successful for the long term, then continual innovation is a necessity, not a nice-to-have.
Numerous companies, including ours, have repeatedly shown that investing in innovation — whether through platform development or drug discovery or licensing — is the more sustainable course. Having more shots on goal tips the odds of success in a company’s favor and also de-couples a company’s fate from that of a lead program that is delayed or doesn’t work as expected.
We set out to build a sustainable company that would become fully integrated. So, from day one, rather than focus on one lead asset, we worked in parallel on therapeutic antibodies against a specific conformation of amyloid beta, and an active immunotherapy to stimulate antibodies against the same target.
We soon realized that we could adapt our discovery platform technology to allow for small molecule drug discovery, too. Adding small molecule discovery capabilities in turn led us to invent a novel class of antibody-drug conjugates called morADCs. Each new modality offered differentiated and complementary applications, even when applied to the same therapeutic target.
Today our pipeline includes 14 candidates against five targets, including antibodies, active immunotherapies, small molecules, morADCs, and diagnostic imaging agents.
Pursuing different approaches in parallel and investing continuously in our platform provided several benefits. It insulated us from becoming a binary story for investors, rendered efficiencies in R&D, and generated more value. So, when one partner decided to discontinue an antibody program, we already had other partnerships, as well as wholly owned candidates that were ready for partnering or internal development.
Our steady stream of innovative new programs also kept our employees and investors engaged, and supported belief in our long-term future.
While setbacks are disappointing, we treated them as fuel for innovation, using the data to discover new insights about how to intervene in disease pathology. We added external learnings from oncology to our growing internal knowledge of neurodegeneration, which positioned us to tackle the next big challenge. We are now bringing precision medicine forward for Alzheimer’s, Parkinson’s, and other neurodegenerative diseases, and moving beyond treatment to prevention. Our precision prevention approach entails identifying and treating specific proteinopathies before the onset of clinical symptoms to prevent irreversible damage to neurons.
The overarching message is that investing in innovation is critical because it creates options that improve a biotech’s chances of success and instills in a company the resilience needed to withstand inevitable setbacks. But we didn’t do it alone.
The Value Of Partnerships In Perseverance
It would be hard to understate the role that a carefully calibrated mix of equity financings and strategic partnering has played in our ability to sustain innovation. We recognized early on that a partnering strategy can de-risk a company for its investors, accelerate the monetization of product candidates, and stack the odds in favor of success. So, as a start-up, we took the unusual approach to partner our lead programs early, licensing preclinical antibodies against beta amyloid to Genentech in 2006.
Even today, many investors would counsel management not to give away too much future potential. But there is no doubt it was a good decision for that stage of AC Immune’s development. That first partnership provided development experience and infrastructure that we did not have at the time, along with up-front payments, research funding, and milestones that enabled us to invest in future innovations. These innovations then fueled additional partnerships, creating a sustainable cycle of investment and value creation.
To date, we have secured half a dozen Big Pharma partnerships worth up to $4.75 billion combined. These partnerships have advanced our competencies and competitiveness, helping us through the ups and downs of product development and enabling us to extract more value from our R&D engine without the need to turn as often to the capital markets.
Patience For Patients
It must be acknowledged that investing in innovation becomes even more challenging when the financing, policy, and regulatory environments are as uncertain as they are today. In these times, it is crucial to keep one’s company and investors focused on a biotech’s true mission: to improve the lives of patients.
In our case, the needs of patients with neurodegenerative diseases was the motivation for continued expansion into new modalities and targets, even during periods when Big Pharma and investors were cold on neuroscience.
We understood early on that the complexity underlying Alzheimer’s, Parkinson’s, and other neurodegenerative diseases required us to expand our toolkit so that we could work toward matching the right patient to the right treatment or combination of treatments at the right time.
We also understood that even the most effective treatments, as much as they are needed, will still not be enough to serve the hundreds of millions of patients and families stricken by these diseases around the world. We simply had to tackle the next big challenge and think ambitiously, beyond treating and toward preventing neurodegenerative diseases by developing approaches like active immunotherapies that offered more convenience for dosing and distribution.
History has shown us that, sooner or later, sentiment always swings back toward those areas where the patient need is greatest. And let’s not forget that our products can often reduce overall healthcare costs.
Neurodegeneration is an area with a growing need, and the current standard of care incurs unacceptable human and financial costs. Patients with neurodegenerative diseases, and their families, must persevere in many cases through years of burden as progressive decline limits quality and length of life. They have shown exceptional patience as industry has strived to develop effective treatments. And they are counting on us to persevere and succeed in our quest to help them.
About The Author:
Andrea Pfeifer is cofounder and CEO of AC Immune SA, a clinical-stage Swiss biotech developing precision prevention therapies for neurodegenerative diseases including Alzheimer’s and Parkinson’s.