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The flow of capital and scientific acuity irrigates this pharm system.
True breakthroughs are never in plentiful supply. Recognizing reality, Uwe Schoenbeck, PhD, senior vice president and chief scientific officer for Emerging Science & Innovation (ES&I) at Pfizer, has synthesized and made functional core lessons from two of the past decade’s best business books: Creativity, Inc. (1) and Loonshots (2). His ES&I group, through the power of independent invention and collaboration, applies methods described in these books to the tasks of uncovering, cultivating, and nurturing novel drugs and therapies. No two trees in his orchard are exactly alike, and some bear fruit only when many seasons of doubt, change, and struggle have passed by. But as the COVID-19 vaccine and messenger RNA (mRNA) success stories illustrate, early adoption of new technologies can establish substantial long-term gains—as well as provide emergency solutions when needed. Whatever the season, there is always something taking root and growing at Pfizer.
Each morning, a vast landscape of activity and invention to sift confronts the ES&I team. This team’s X-axis is a challenge that can be described as identifying the right partnering opportunity particularly for less known early science developments and technologies. Pfizer relies on its Emerging Science Leads (ESLs), a team of seasoned PhD/MDs to search for and evaluate opportunities from academia and the biotech industry for Pfizer’s R&D organization. According to Schoenbeck, ESLs are highly experienced in the relevant disease area and embedded within the respective therapeutic areas, resulting in high strategic alignment of the opportunity being sourced and avoiding opportunities that are not a strategic fit (1). Schoenbeck adds, “It’s easier to identify what’s complementary if you have an understanding of the therapeutic area and what’s not on the typical partnering list that might be cutting edge.”
Each afternoon that same team takes what they’ve uncovered, turns it sideways, and overlays this onto their Y-axis—an $80 billion dollar a year enterprise already populated with 80,000 competitive busy staff (3, 4). The ES&I team, in conjunction with colleagues working in Business Development, has stood out for bringing genuinely creative partnership ideas and innovations into an already creative and crowded environment. “They’re not just the typical corporate venture type of series A, B, or C,” continues Schoenbeck from a Pharmaceutical Technology Drug Solutions podcast (5). “Increasingly, we’re doing more seed investments, new company formations, really trying to enable cutting-edge, emerging science areas that we see on one hand strong strategic fit to Pfizer. On the other hand, [areas] also holding a lot of potential—but really early, needing more work before you could fully implement them.” A long, successful track record has cleared the decks for Pfizer to go earlier than most, to uncover exciting advances as they happen, before first bloom.
To augment integration capability on the Y-axis, Pfizer brings internal expertise, capabilities, and resources. Discussing Pfizer’s Centers for Therapeutic Innovation (CTI), for example—a collaboration model that helps translate early scientific concepts into potential drugs—Schoenbeck says, “We do have a number of wet bench capabilities, our own labs through which we run a portfolio of about 25 or so projects, and these projects are partnered with academic or very early stage biotech companies, which focus on cutting edge new projects.”
Using its many flexible partnering and collaboration vehicles, Pfizer has been identifying strong partners in both the academic world and in the biotech industry to help its scientific engine and company at large make changes it needs in the gene therapy, mRNA, and degrader spaces. The most recent and most notable example would be the multi-year partnership Pfizer established with German biotech company, BioNTech, to deliver the world’s first COVID-19 vaccine in 2020. But before the pandemic arrived, the two companies had been in discussions since the early 2010s, first about the use of mRNA for oncology and later establishing an agreement for influenza.
While COVID has been on the frontlines of the company both in headlines and scientific delivery, Schoenbeck’s team has continued to plant and grow its roots in other areas. For example, in early 2022 Pfizer announced several collaborations designed to augment its leadership in mRNA. Their agreement with Beam Therapeutics will leverage Beam’s base editing platform in support of potential therapies for rare diseases. A collaboration with Acuitas will allow Pfizer to explore the use of their lipid nanoparticles (LNPs) to deliver a variety of vaccines or therapeutics. Finally, a collaboration with Codex DNA will potentially streamline the mRNA production process by facilitating synthetic DNA assembly, another notable fruit of the team’s labor to bring forth a competitive pipeline in gene therapy. Through gene therapy partnerships, such as 2019’s deal with Vivet Therapeutics to advance a treatment for Wilson disease, Pfizer now has one of the most competitive pipelines in gene therapy in the industry.
Increasingly, Pfizer’s focus is on a “true first-in-class mechanism, if not only in class kind of programs, that would allow us to bring real breakthroughs to patients.” Schoenbeck continues, “So these are by definition a higher-risk approach, a higher-risk kind of biology, but they hold a lot of promise and could provide a very strong fit to the Pfizer R&D organization, if we can then build a pipeline and portfolio around those areas … So, you really need to start thinking early and clearly about where do you want to focus your search? Where do you want to place your bets? And what’s important to us is actually that when we partner, we really partner in the true sense of doing things jointly … not just to bring in the intellectual property in-house or anything like that. It’s really about identifying an academic or biotech partner, that can bring something to the table that would be very complementary … allowing us to do something to benefit patients that neither of us could do alone.”
Many approaches sound great on paper, or even anecdotally, so how does ES&I manage risk? “I think each company might take a different approach, but the way we have thought about it is that you want to have a balance in your portfolio when it comes to risk. Risk can be defined as risk in biology, risk in development, risk in therapeutic modality. If you have a mature modality, but you go for a new target, that’s one level of risk. If you go for a novel target and a new therapeutic modality and invention in your development direction, then you’re really multiplying your risk. Obviously, the COVID-19 vaccine was one of these examples that fortunately has been quite successful but really was a high-risk approach. You can do this where you really see the need for patients, where you really see the potential for breakthrough, but you can’t do it for every single program in your pipeline obviously. Now on top of that, as I said earlier, you want to make sure you get a good feel for the cutting edge for anything that’s emerging, really promising on the horizon. And for that we have for example this ES&I team here at Pfizer. Some of the areas that we’re focusing in on include repeat expansion disorders, senescence, DNA damage response and nucleic acid sensing, deubiquitinase pathways, and neuroinflammation. Pfizer feels these hold special promise for new innovative therapies.”
All of the fields mentioned previously are newly emerging and require technical bravery and alongside special care. The book Loonshots mainspring metaphor borrows from material science concerning phase transition as applied to both creative (artistic) and execution (soldier) teams (2). Within that framework, the author, by examining a multitude of examples, asserts that structure may matter more than culture. Transplanting this to Pfizer’s orchard, Schoenbeck has successfully practiced a version of companion planting, where seedlings of different crops are carefully placed in proximity to lower certain technical or resource barriers, while simultaneously raising pollination and nutrient availability. Reduced footprint along these guidelines is seen as a feature, not a bug. The concept itself sprouted within the garden walls of the Mesopotamian proto palaces, where, “The oldest written evidence of medicinal plants’ usage for preparation of drugs has been found on a Sumerian clay slab from Nagpur, approximately 5000 years old. It comprised 12 recipes for drug preparation referring to over 250 various plants, some of them alkaloid such as poppy, henbane, and mandrake” (6). These alkaloid drugs were far from mild, and great care was taken not only in their application, but also in raising their yield, by careful germination and cultivation techniques.
So, the essential oil for the ES&I group stems from the orchard structure itself, enabling them to identify and nurture pharmaceutical creativity well before first florescence. These orchard rules follow a pattern laid out in the book Creativity Inc., by Ed Catmull, who founded Pixar in 1986 with John Lasseter and Steve Jobs (1). Their philosophies, or planting scheme, defied convention and protected the creative process by institutionalizing concepts such as “the cost of preventing errors is often far greater than the cost of fixing them” and, “It’s not the manager’s job to prevent risk, it’s the manager’s job to make it safe for others to take them.”
This is a pragmatic view of what enhances the creative process, in line with that practiced by Schoenbeck. One of the strongest but subtle suggestions, being “don’t assume that general agreement will lead to change it takes substantial energy to move a group, even when all are on board” (1). This is certainly a precept worth following up on when dealing with large organizations such as big pharmaceutical companies. Catmull, however, is not above advice on pruning to promote optimal health.
His sections on recognizing “you are not your idea” point to the constant need for reality checks, and his postmortems are as important as any other section in the book. Pfizer’s ES&I team, who by their outward facing role interact with anyone performing interesting material, pharmaceutical, or manufacturing science, have perhaps taken to heart the inner core message of this book, that, “The companies communication structure should not mirror its organizational structure; everybody should be able to talk with anybody.” Last year by any measure was a bumper crop for the ES&I team, and indeed they currently top a patient group survey (7) for best reputation. Even amidst a widespread drought, Pfizer’s orchard remains well irrigated.
Chris Spivey is the editorial director of Pharmaceutical Technology.
Vol. 46, No. 9
When referring to this article, please cite it as C. Spivey, “Pfizer’s Idea Orchard,” Pharmaceutical Technology 46 (9) 2022.