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You led a medicinal chemistry group responsible for two commercially successful cardiovascular drugs: the blood pressure pill Cozaar and the anticoagulant Eliquis. That puts you in rarified air. What sort of things need to fall into place to achieve that kind of success? 

Thank you for your very kind words. To achieve success, it is crucial to have high achieving teams “following the science�� from the earliest days of a drug discovery program all the way thru clinical trials. In fact, sometimes it’s a matter of pushing back frontiers in science, as was the case in both of the programs which led to these two drugs, wherein our teams were leading the way in the science both in the Angiotensin II and Factor Xa fields. One also needs to take advantage of “serendipity�� which sometimes accompanies hard work and innovation. 

To be successful there are three essential strategic aspects that one needs to get right, and they are: selecting the right therapeutic target, selecting the right compound to move into development, and thirdly conducting the right clinical trial. This I learned while at DuPont Pharma from the head of our Chemistry organization, and I have found it to be key to successful discovery and development. First, and most important to ultimate success culminating in a drug, is selecting the right target: a molecular target that is linked to a defined mechanism of biological action, that has the potential to be transformational, i.e. targets that focus on a high unmet medical need, and has the potential to differentiate in a meaningful way from the standard of care (if one exists), and from compounds that are ahead in clinical trials. Target validation is essential in selecting the right target; preclinical data showing that the target has the potential to show strong efficacy and an excellent therapeutic index which is expected to translate into clinical trials, ultimately with the ability to demonstrate target engagement and biomarkers for efficacy and safety that can be translational into clinical studies, and then back to preclinical work are of key importance in target selection. 

Second, once there is confidence in the selected target, it is critical to select the highest quality compound for advancement that can be identified. High quality in terms of biological profile and chemical structure, with a limited potential for off-target effects, excellent pharmacokinetic and safety profiles, such that the drug has the potential to deliver fully on the promise of the molecular target. 

Third is conducting the right clinical trials that follow the science, focused on the right patient population at the right dose. Success requires all three: identifying the right target, the right compound, and the right clinical plan. Both losartan, an Angiotensin II receptor antagonist, and Eliquis, a Factor Xa inhibitor -- drugs resulting from our team -- clearly met all three. 

As indicated earlier, none of this would be possible, without high performing teams who are passionate about drug discovery and development, who are focused and work with a sense of urgency and who have the perseverance to deliver. It takes a village of dedicated scientists working together. Dedicated people are the secret sauce that drives success. 

Based on your experience, what are the hallmarks of a high achieving team in medicinal chemistry?

There are hallmarks of high achieving teams in medicinal chemistry that are in common with high performing teams in drug discovery, and some hallmarks that are specific to the discipline of medicinal chemistry. In general, a hallmark of a high achieving team is a team that has a shared vision and shared objectives that are tied to the overall goals and priorities of the organization. High achieving teams in medicinal chemistry are composed of talented individuals who are passionate about discovering medicines that improve the lives of patients. They understand how their work fits in to that overall mission of the organization and are able to work closely together to deliver on this mission, and/or on developing new technologies or synthetic methods that will be used to advance the science of Medicinal Chemistry. 

Individuals on high achieving teams are highly engaged in their work, and they manage their work with a sense of urgency, focusing their work on the highest priorities and are always looking for the next break-thru to capitalize on. Essential to high achieving teams is strong trust and respect between team members, and open communication as well as a strong sense of shared accountability and the desire to consistently deliver superior results. 

High achieving teams have a leader who sets the team up for success by taking responsibility for communicating the vision for the team, clarifies roles and responsibilities for all members of the team, and empowers team members to make decisions. Importantly, high achieving teams have a leader who commits to identifying team members who have both the needed technical skills and can collaborate well in a highly matrixed environment. It is well documented, and I have seen over and over again during my career, that when teams are diverse, in terms of individual background, gender, race, ethnicity, nationality, and thinking style, there is a greater level of healthy debate, giving rise to a higher level of success. Diversity saves teams from “group-think�� and fosters greater engagement and a higher level of innovation. 

Individuals on high achieving teams are focused on hypothesis testing and problem solving, and challenge assumptions as well as challenge each other scientifically, which results in an enhanced level of creativity. Individuals on high achieving teams are not afraid to ask questions of more experienced drug hunters, and they seek out mentors and, and later, become mentors. They are resilient and forward thinking. The culture is one where individuals learn and grow together (a culture of continuous learning), and one where team members collaborate and innovate together. Another hallmark of high achieving teams is that they celebrate their successes and have fun together.

High performing medicinal chemistry teams have all of the above traits. Specific to medicinal chemists, they are able to match the best chemical modality to the specific target they are working on. They are open to trying new things, and are able to incorporate all of the tools and technologies available to medicinal chemists into their work flow to help with the design and synthesis of their target compounds. They aren’t afraid of challenging syntheses, but at the same time are practical in their target design, avoiding unneeded complexity. They are very familiar with the competition and prior art in areas that they are working, and they focus on innovative ways to break ahead of the competition, and/or for ways to identify compounds that are differentiated from the prior art both on structure and properties. 

Medicinal chemists who are on high achieving teams are quite skilled at managing multiple properties simultaneously and are skilled at integrating large amounts of data during this iterative multi-parameter optimization process required in drug discovery while simultaneously tackling new issues as they arise. I often liken the optimization process in drug discovery to the game of “Wack-a-Mole�� wherein just as one problem is solved, another, or in some cases many others pop up. High achieving medicinal chemists are nimble and are able to pivot quickly to other ideas and targets as data emerges that suggest a change in direction is needed. 

In terms of new technologies, I believe the potential for high performing teams to benefit from application of machine learning to accelerate drug discovery, as well as design synthetic routes to target molecules holds tremendous promise. Medicinal chemists on high achieving teams are able to work well across seams in a matrix environment with internal and external collaborators in other disciplines who have complementary skills/expertise required to be successful in drug discovery, such as biologists, crystallographers, computer modelers, computational scientists, ADME scientists, toxicologists, amongst other disciplines and delve deeply into understanding the science around the target being pursued, so as to jointly push their programs forward. 

When you think back, what traits did you most highly value among your medicinal chemist group members?

Thinking back, there are many traits that I highly value from the medicinal chemists that I have had the pleasure to work with over the years. For starters, I want to call out passion, perseverance, and trust/respect for each other. In terms of passion, I am referring to a shared passion that the team had for drug hunting, for innovation, for scientific excellence, and a passion for working together. The later included challenging one another scientifically, which resulted in a high level of productivity and innovation. Along with this shared passion for conducting excellent science, was a passion for continuous learning, a growth mindset, and a desire to both integrate and share knowledge with the rest of the team. 

Delivering “first in class drugs” as well as “best in class drugs” required not only creativity but perseverance, which was a shared value amongst the team, as many of the targets we tackled were challenging. In addition, the ability to take advantage of serendipity is also important, as sometimes science is unpredictable. Since every second matters to patients in need, and because drug discovery is incredibly competitive, I highly value being nimble, resilient, and working with a sense of urgency. The strong willingness of team members to remain focused on the science even in times when the science is difficult, or in times of challenging change in the environment, both within the company and more globally, enabled an ability to control what was within the team’s ability to control and a sense of ownership. 

Another key trait that I valued was scientific confidence and curiosity, and along with that came the willingness to take risks, to try new things, for example new synthetic methodology, and/or using new technologies, and then integrating the successful tools and strategies into their work flow. It is often what we learn from failed studies that catapults us forward in drug discovery. Lastly, and perhaps most important is that individuals on our team valued each other, they supported each other, took risks together, they shared with each other, they innovated together, and they genuinely cared about each other which enabled them to succeed together.

If you had to break it out in rough percentages, how much of your career success do you owe to (a) your formal academic schooling, (b) the professional training provided by your employers, and (c) general ‘on the job�� experience?

It is challenging to answer in rough percentages, as my answer to this has changed over time, depending on what stage of my career I was in. My formal academic training helped me to decide on a career path and in many ways is largely responsible for my earliest successes. While doing undergraduate research at Boston University, I realized I was passionate about research: it was in my blood, I enjoyed problem solving, I loved the challenge, the opportunity to be creative, the opportunity to ask and answer important scientific questions. While in graduate school at the University of Pennsylvania, I decided I wanted to pursue a career in the pharmaceutical industry, so I could marry my passion for research with my desire to try to improve the lives of patients as a way of making a difference in the world. The strong synthetic organic chemistry training I received at UPenn gave me the pedigree to land the job that I wanted and prepared me to be successful in the lab in the early part of my career at DuPont. 

After those initial years, I would say that 90 percent of my training to be a medicinal chemist, and then to become a leader was tied to “on the job�� training, with the remainder coming from formal training courses, seminars, and scientific meetings while at DuPont, and later at Bristol Myers Squibb. I was privileged to work with many teams of talented scientists and leaders throughout my career: both internal and external collaborators. I learned from their experiences and expertise, by watching and listening, by asking questions, and by participating in many, many project discussions. Most important, as I am an experiential learner, I learned the most by “doing” from the many opportunities I was given over my career. In terms of leadership behaviors, I tried to take the best of what I learned from my leaders and mentors, and melded it into a leadership style that was comfortable for me and that felt uniquely mine. 

What have you learned about your decades in leadership positions that you would like to pass along to the next generation of leaders in biopharma?

I would like to pass on the following thoughts to next generation of leaders in biopharma: Believe in your team members’ ability to deliver; inspire your team by showing them you believe in them. Communicate, communicate, communicate! One cannot over-communicate. Ensure that everyone understands the overall goals and what they are accountable for, empower individuals and teams, ask good questions as a way of guiding the team leads and teams, and then serve as a resource. More productivity and innovation will result when people are empowered rather than directed. People grow when they are responsible for their work and own their decisions. Successful leaders encourage growth and see and bring out greatness in others. Building for the future, it is important to hire the strongest talent, and invest in training, and providing opportunities for the future. Set the tone for the culture you want the group to have, and lead by example. 

Make sure all individuals in the group are focused on science and focused on work that, if successful will make a difference in the lives of patients. If it’s a drug discovery group, encourage the group to match the right modalities to the therapeutic targets of choice, and to use all available technology to drive the science. Focusing on the science, and focusing on how the group can achieve their goals is the best way a leader can engage scientists since science is the shared passion of the group. People thrive best when they are doing what they love; for chemists this is conducting science. 

By promoting an environment focused on science, the chemists on their team(s) are more likely to feel empowered and have the confidence to take risks, to be creative, and not to worry as much about the many things going on around them that are outside of their control. Shared passion(s) creates energy, makes the improbable seem possible, and helps people keep going during challenging times. Expect scientific excellence and rigor. Create a culture of accountability, where everyone on the team knows what they are accountable for. Hold yourself and your team accountable and be seen as doing so. Give feedback both good and bad.

If the latter is done in a constructive way, it can be just as important as positive feedback, as it will likely be beneficial to the individual’s growth. Promote resilience, and perseverance, as in drug discovery there is a lot of failure. Encourage leaders on your teams to help their team members view failure as acceptable, and more than that, encourage them to learn from the failures to push themselves closer to success. Recognize, and let the team know that you, as a leader, will also make mistakes; when that happens, share lessons learned where applicable. Encourage them to create an inclusive and collaborative environment, where creativity, diversity, teamwork and mutual respect are key values. Provide opportunity for life-long learning and mentoring of the next generation of talent. 

Encourage mentoring and be a mentor. Recruit strong talent and provide opportunity. Recognize that as a leader, it is not necessary to be the “smartest person in the room��, but rather, it is important to find, hire, train, and surround oneself with individuals that are as smart or smarter than you are. Admit when you don’t know something, or when you need to get more information. Put significant effort and commitment into forming high performing teams, and who you recruit for each team. Diversity is a key on high performing teams. 

Ensure that all voices are heard; encourage inclusive and collaborative thinking. Challenge your teams to be creative, foster curiosity, encourage new and different ways of thinking, and enable folks to try out their ideas as this will enhance productivity and innovation. Spend a significant amount of time listening, not only to learn but because when people are listened to, they are more motivated. Seek input before you make decisions, make it clear that you value input, and then work to make crisp decisions and don’t look back. Get to know all members of their group(s), show genuine interest in each individual, build authentic relationships, and foster an environment where career development is important. Encourage all team members to do the same. Express gratitude! While this may seem like a lot to pass on, I believe all of it is essential to enable new leaders to be successful.

If I had told you in 2019 that the biopharma industry was capable of developing, producing, and launching a vaccine for world-wide use �� and receive full FDA approval �� in a total of about 18 months, you would have responded how? What are some noteworthy implications of this achievement for the future of biopharma? 

In 2019, I would have been very skeptical that a COVID-19 vaccine could be developed and approved in 18 months. Certainly, when COVID-19 vaccine research was initiated, many experts also viewed 18 months as unrealistic, relative to the development of earlier vaccines, which typically took 8-10 years, with the fastest being the development of the mumps vaccine, which took four years. On the other hand, there had been significant new scientific advances and vaccine platforms (mRNA and viral vector technologies) that were ready to be evaluated in developing a COVID vaccine based on the prior research towards the development of vaccines for diseases such as SARS, EBOLA and MERS which resulted in vaccines which were already in clinical trials; so if successful, acceleration was feasible, although these technologies had not previously resulted in an approved vaccine. 

The successful development of the COVID-19 vaccine is likely to be a game changer for future vaccine development. Given that the mRNA and viral vector technology has successfully been employed in vaccines against COVID-19, it is highly likely that we will see a lot more vaccines using these platforms in the future. For example, we are already hearing about R&D towards vaccines for HIV, flu, and other viruses using the mRNA platforms. It is expected that using these technologies, future vaccines will also be developed at an accelerated pace, and at a cheaper price to manufacture than traditional vaccines. In addition, using the mRNA and viral vector technology, efforts are ongoing towards developing cancer vaccines, and mRNA-based medicines may be on the horizon, for example, towards localized regenerative therapeutics, and towards systemic therapeutics for multiple diseases. In addition to vaccines, viral vectors are used for gene therapy which is a new modality showing considerable promise.

How would you characterize the current state of the industry-academic partnership environment in the biopharma arena? Is it working well? How could it work better? 

Over the past decade, I have seen enhanced levels of collaboration between pharma and academia to the point where in some instances pharma and academic researchers are working side by side rather than simply providing consultancy, or transferring new science and technologies. The need to identify novel molecular targets, the increased complexity of the drug targets being pursued, the highly competitive nature of our business, and the high cost of bringing a drug to the market has resulted in new models for drug discovery. These include closer ties between academia with pharma to harvest and validate new targets, and leveraging cutting edge science and technologies being developed in academia to accelerate the drug discovery process. 

At the same time, academic researchers are more and more reliant on industry for funding faculty and students. In addition to new science and new technology, the upside of building these relationships for pharma is that it enables companies to keep track of emerging science, and talented students forming excellent pipelines for recruiting talent. 

Another benefit of these collaborations is more open communication, wherein the engaged industrial partners are helping to shape the direction of academic research programs, and academic researchers have a better understanding of drug discovery, which ultimately results in a more productive collaboration between researchers, with a greater level of trust. 

Historically some of the challenges have been that the cultures between pharma and industry have been quite different. In pharma the focus is on teamwork towards shared therapeutic goals, and in academia, students are trained to be independent thinkers. In pharma, intellectual property is a highly valued and managed asset, whereas in academia, interest in rapid publication has often times been an issue for pharma. 

Another issue has been insufficient ways to share data and platforms for open innovation. Pharma and academia are coming closer together in each of these areas, for example in the case of intellectual property (IP), academia has a greater focus on filing IP, and industry works to ensure more publication at the appropriate time.

In terms of areas for further improvement, to increase diversity of thought within research teams, pharma ought to collaborate and recruit more with schools with a higher number of under-represented minorities. In addition, while many schools now have courses and/or seminars on drug discovery and understanding intellectual property, there is further to go in this regard. There would be less “siloing” and more partnering, if there was greater career mobility across pharma and industry at all levels, and if more internship and sabbatical programs existed. In addition, better and more cost-effective data management platforms would be beneficial for data sharing.

Talk about the metaphorical “one that got away��. Is there a project that eluded you? Why? And if you could return to it, what would you do differently?

This is a tough one to answer, most of the “ones�� that got away were drug candidates that we discovered that were halted in clinical trials rather than our inability to identify the candidate. There were some real heart-breakers over the years: several high-quality compounds were stopped for “strategic reasons��; those were always the toughest to lose. We lost a couple compounds because we weren’t able to achieve the desired efficacy profile in clinical evaluation, even though they looked very good in pre-clinical models; these were novel mechanisms which hadn’t been previously tested clinically, and we lost a compound in Phase III trials because of a lack of a sufficient safety margin. 

However, in each of these cases, we did our best in discovery to put forward the highest quality compounds we could identify. Preclinically, the one area that we were not successful in delivering in, was our efforts at DuPont Pharma focused on both beta and gamma-secretase inhibitors directed at Alzheimer’s disease, two targets that industry-wide have really not yielded clinical success with small molecule compounds. This is a devastating disease, which has seen a tremendous number of preclinical and clinical failures. It is challenging to say what we would do differently today; clearly the science is continuing to evolve: some companies are again working on beta-secretase, and there are some new mechanisms of action that look like they could be good targets for combatting Alzheimer’s disease.

The biopharma industry, despite its significant contributions to society, is often attacked by many in the media and in government. Add to that, a public that often doesn’t seem to fully appreciate the industry’s contributions to health with such medicines as statins, vaccines, antibiotics, and more. As one who has devoted a career in this area, how do you feel about this? 

I find it extremely frustrating that the media often attacks the pharma industry and that the efforts in the pharma industry to develop drugs is frequently not appreciated by the public. It is unfortunate that the public doesn’t understand that the heart of what we do in pharma is to use science to discover new drugs that improve patients�� lives. 

Some of this bad press is due to a lack of knowledge. The pharma industry should continue to invest in educating the media and the consumer, both on the science around new drugs, and the value these drugs have on society. Pharma should describe where possible how the drug is uniquely beneficial in a way that the patient understands how the therapeutic is differentiated. From my perspective, this is not done aggressively enough, but of course there is a fine line between education and promotion, the latter of which cannot be done ethically by pharma companies. 

Another issue is related to the public criticism of high drug pricing, and the accusation that the pharma industry is only interested in profit, rather than the public good. Again, the public needs to be more educated on the cost of bringing drugs to the market, so that there is a better understanding of why drugs are expensive. In terms of improved education, and communication, pharma needs to speak directly to consumers, and articulate effectively to consumers so they understand the value of the drugs to them, and why they are priced the way they are. Interestingly, I recently read an article that said the Covid-19 vaccine has improved public perspective to some extent, as the public saw companies, universities and the government working together to develop and distribute the vaccine, which might offer an opportunity to help reset the public perception of pharma companies. 

Mentoring seems to be a source of pride to you. How did mentoring come to be important to you? What makes for an effective mentor/mentee relationship? 

Yes, I am very passionate about mentoring; it is a key tool for investing in the next generation of scientists. My passion for mentoring stems from relatively early in my career, when I had some terrific mentors who helped me develop from an early career synthetic organic chemist to a medicinal chemist and “drug hunter��, and then others who later helped me to develop leadership skills, all of which had a long-lasting impact on my career. 

What I learned from my mentors played a significant role in helping me to achieve my professional career goals, and in helping me to develop as a leader. Times when my career accelerated the most, or when I felt most empowered were often linked to times when I had a strong mentor that I could use as a sounding board. This resulted in my desire to pay it forward as a way of “giving back��, and at the same time investing in the future. As drug discovery and development is fraught with challenges, learning from a diverse set of mentors over one’s career is highly beneficial. It is also sometimes valuable for individuals to simultaneously have multiple mentors.

For example, early in my career, I simultaneously had a mentor who helped me think through short and mid-term career goals and navigate being new in a large company, and another mentor who helped me navigate the issues of being both a young professional and young mother (i.e. work/life balance). 

In answer to what makes an effective mentor/mentee relationship, the foundation is one of mutual trust and respect. Trust takes time and effort to build; both mentor and mentee must be committed to spend the time getting to know each other. The mentee should set clear goals for the area(s) the mentee wants to develop in, seek advice, help to cultivate the relationship, and follow up on actions that come out of the mentoring discussions. Being a mentee is not a passive role, i.e. this should be a mentee driven process. Finding the right pairings is important as there needs to be the right “chemistry�� between mentor and mentee so that frank and honest communication can take place. For this reason, it is best if the mentee selects the mentor(s), other than for new hires who have not yet built a network. 

A successful mentor needs to have the expertise to help the mentee in the area the mentee chooses for further development, whether it be subject matter expertise, leadership skills, organizational savvy or otherwise. The mentor listens, shares experiences and expertise, provides feedback, motivates, guides, and helps build confidence. The mentor should not solve problems/challenges for the mentee, but rather provide the mentee with the tools to solve their own problems/challenges. It is important that the mentor instill in the mentee the importance of owning one’s career, (i.e. this is the responsibility of the mentee). As stated by Steven Spielberg “The delicate balance of mentoring someone is not creating them in your own image, but giving them the opportunity to create themselves.��

In the decade starting in 2030, what would you project will be the ratio of FDA-approved drugs manufactured in living organisms such as bacteria, yeast, and mammalian cells vs. through chemical synthesis? What leads you to that conclusion?

My guess is the ratio may not be very different from what it has been over the past 3-5 years wherein drug approvals have ranged from 63%-71% small molecules (i.e. chemical synthesis) versus 29-37% biologics, and for 2021 year to date, the ratio appears to have remained pretty much the same. It takes on average 10 years for a drug to be developed and approved for prescription, so for a drug to be marketed in the early 2030’s, it would likely need to be moving into development in the very near term if not already in development, and for later in the decade, it is likely that discovery efforts towards the target would have already been initiated. 

Over the past decade, there have been a number of new technologies and computational methods building on the strengths of small molecule therapeutics which has made it possible to pursue an expanded number of novel synthetic modalities and innovative strategies enabling pursuit of previously undruggable and hard to drug targets, which is resulting in a small molecule renaissance. 

The increasing understanding of biological systems at the molecular level, and the ability to explore new areas of chemical space to tackle increasing complex targets such as protein-protein interactions, transcription factors, E3 ligases, RNA targets and the like with small molecules, and new modalities such nucleic acid-based therapeutics and molecular conjugates is resulting in a resurgence in small molecule and/or synthetics as drug candidates. 

Rapidly expanding areas of small molecule drug discovery, such as targeted protein degraders, and the fact that more machine learning including AI start-ups at present are focused on small molecule drug discovery are also driving growth in small molecule drug discovery. Therefore, it is even possible that this expansion in modalities could result in an increase in small molecule/ synthetic drug approvals in the next decade. Also, at least at present, biologics are generally not orally bioavailable, are often unable to access intramolecular targets across multiple tissue types, and are more expensive to prepare, suggesting that for chronic care, synthetics will remain prevalent as next generation medicines. 

You have received many professional honors throughout your career. Is there one or two that have special meaning for you?

The two awards that are the most special to me are the EB Hershberg Award for Important Discoveries in Medicinally Active Substances, which I received in 2015, and being inducted into the ACS Medicinal Chemistry Hall of Fame in 2014. The EB Hershberg Award was particularly important to me because it was made possible by our team’s discovery of Eliquis. When we started the Factor Xa program, which culminated in Eliquis, finding orally bioavailable inhibitors of serine proteases was a world class problem, and solving this challenge and multiple other issues during the optimization process required a tremendous amount of scientific innovation, perseverance and team work. I am extremely proud of the team that discovered Eliquis! I believe I was the first woman to achieve this award; many of the previous awardees were leaders that I greatly admired, and giants in the field of medicinal chemistry. 

Similarly, when I was inducted into the ACS Medicinal Chemistry Hall of Fame, I was one of the first few women to receive this honor, and was hopeful that at least in part I would be helping to pave the way for additional women to receive this honor in future years. I am also extremely proud of the awardees that have been selected for awards which I have nominated them for, as it is more important to me to give than to receive. Awards and invited lectureships that I have received from universities have also been especially important to me, as when I visit schools, I have the opportunity to speak with and encourage many students in terms of their career paths.

What’s a travel destination you can’t wait to get back to? 

This is a tough one, I love traveling and I am fortunate to have visited many really fantastic places. It’s tough because when I travel, I really enjoy going to new places, and exploring new things. However, in answer to the question, I would pick Aruba. We have had two wonderful family vacations there. It’s a wonderful island. Going back to Aruba would mean we are in a better place with regard to COVID-19, as we haven’t flown since the pandemic started.