Biotech Needs to Get Back to Work in Person. Now.

John Maraganore, former and founding CEO, Alnylam Pharmaceuticals

Companies at the frontiers of science and medicine, developing new therapies for patients, are working on one of the most challenging endeavors known to humanity. Most would agree it’s more difficult than putting a man on the moon.

The pandemic created a dramatic disruption to our globally networked economy. It will have far-ranging and long-lasting repercussions.

It started with quarantine.

We adapted quickly, managing to achieve business continuity on Zoom, Teams, and WebEx. We continued to file INDs and NDAs. Our lab and manufacturing workers kept coming to work in person to conduct their critical tasks and experiments.

Executives were able to continue to have conversations with investors which kept fueling our industry’s need for capital with venture rounds, IPOs, and follow-on offerings. Even our commercial colleagues discovered new and efficient ways to stay in touch with customers through digital means.

For a while, we appeared equally — if not more — productive than before.

We improved our work-life balance with no hair-tearing commutes, more time with kids and family, and a newfound flexibility to work from the beach or ski slopes.

Now as we approach the third full year of this work experiment, it is increasingly clear that the cost of hybrid/remote work greatly outweighs the benefits across multiple important dimensions: culture, engagement, creativity, and employee development.

For a mission-driven industry tackling some of the world’s greatest challenges, we need to get back to work, in person.

As I wrote in my 2022 Nature Biotech article “Reflections on Alnylam,” people and culture are the most critical elements of a biotech’s success. A company culture cannot be built effectively without interactions of people and teams; culture is defined by a set of core values that define desired behaviors, norms, and interpersonal interactions.

In Alnylam’s 20+ year history, culture and our core values underscored the commitment to persevere when we were up against many technical adversities. This culture is what enabled us to take the appropriate risks to advance early RNAi prototypes into development, and empowered our leadership team to make the quick, and necessary, data-driven decisions.

Virtually all aspects of drug discovery, development, and commercialization are part of a multi-disciplinary team sport. It requires the highest level of engagement with people working together in close proximity. This means constant communication, alignment, and coordination. Much of this work requires informal and spontaneous communication, such as the afterthought following a meeting.

High-performing teams are known to require stages of development including “forming, storming, and norming” prior to “performing.” It’s critical for teams to develop strong interpersonal engagement, and mutual trust and respect. Teams need to learn how to best interact with each other, and this is a continuously evolving dynamic as team membership often evolves over time. New employees need to be effectively “on-boarded” so they can contribute effectively to the goals and objectives.

With all the “mountain climbing” needed to bring medicines to patients, it’s hard to imagine doing it without the engagement of teams.

The third consequence of the post-pandemic work environment is the cost to creativity. More often than not, creativity emerges from the spontaneous engagement of colleagues in informal manners; it is the idea that’s sparked from an impromptu hallway or “water cooler” conversation. It’s the new plan that comes from coworkers chatting after a meeting, or the brilliance that can radiate from a team after simply grabbing lunch together.

While remote or hybrid work has enabled productivity, it has stifled creativity. I have had conversations with many CEOs and heads of R&D about this phenomenon. With fewer creative sparks, we run the risk of falling into a rut of the mundane. Without a doubt, the mission of bringing transformative medicines to patients requires creativity to solve the enumerable challenges and uncertainties of science and medicine.

Finally, the post-pandemic work environment could have stark consequences for employee and professional development. For newly-minted employees entering the workforce, where is the opportunity to learn from talking with experienced leaders? How do the experienced leaders get to benefit from the energy and fresh ideas of younger workers, and then help guide them to direct these energies in the most productive way? Where is the whiteboard talk that a manager often needs to deliver to their employee regarding work plans or business strategy?

It is hard to imagine how a young employee will learn the managerial and leadership skills and capabilities from a two-dimensional Zoom box. Will this result in different advancement and promotional consequences for on-site vs. hybrid employees? More seasoned employees also have their own obligation to provide mentorship and development to newer employees, ensuring a continuity and sustainability of the business over time as people move on in their careers.

There are some features of hybrid and/or remote work that are positive. But a physical return to work is needed for effective company cultures, engagement of workforce and teams, creativity and invention, and the development of future leaders. As an industry with a mission and responsibility of bringing medicines to patients, we need to get back to work in person, now!

The bottom line: we cannot sustainably deliver transformative medicines to patients from a virtual workplace.  


From Computational Discovery to a New Psoriasis Drug: Jeb Keiper on The Long Run

Today’s guest on The Long Run is Jeb Keiper.

Jeb is the CEO of Boston-based Nimbus Therapeutics.

Jeb Keiper, CEO, Nimbus Therapeutics

Nimbus made news in December 2022 when it sold its experimental Tyk2 inhibitor to Takeda Pharmaceuticals for $4 billion upfront and $2 billion in potential milestones. The drug’s value skyrocketed when it hit the primary endpoint of a Phase 2b clinical trial for psoriasis. Nimbus hasn’t disclosed the detailed results of that study, but the pill is said to have best-in-class potential when compared with a first-in-class molecule from Bristol Myers Squibb. Takeda is imagining all kinds of other possible uses of this anti-inflammatory medicine for psoriatic arthritis and inflammatory bowel disease.

This is quite a victory for any small biotech company. But there’s more to the story.

Nimbus got to this point after investing for more than a decade in its physics-based computational drug discovery platform. It was among the early adopters seeking to use high-performance computers to model the best possible small molecule drug candidates against a given target. The model didn’t just work one time – Nimbus sold a previous small molecule drug candidate for non-alcoholic steatohepatitis, a chronic liver disease, to Gilead Sciences.

Jeb is a chemist by training, spent a good early part of his career in pharmaceutical business development, and joined Nimbus as chief business officer in 2014. He became CEO in 2018. I’ve known Jeb for a number of years, and he was a member of the inaugural Timmerman Traverse for Life Science Cares in 2021. I’ve been trying to get him on the show for about a year, and am really glad I was able to sit down with him in person at the recent JP Morgan Healthcare Conference in San Francisco. I think this is an especially thoughtful and absorbing conversation that will be of interest to a wide range of people in biotech.

And now for a word from the sponsor of The Long Run – the BIO CEO & Investor Conference.

Now in its 25th year, the BIO CEO & Investor Conference is a premier event connecting biotech leaders from established and emerging public and private companies with the investor and banking communities.

You can expect limitless networking, on-point sessions crafted by impressive industry experts, polished company presentations, and making important connections powered by BIO One-on-One PartneringTM.

We look forward to seeing you February 6-9 in New York and virtually.

Register now

Now, please join me and Jeb Keiper on The Long Run.


From Musician to Tech to Biotech Investor: D.A. Wallach on The Long Run

Today’s guest on The Long Run is D.A. Wallach.

D.A. is the founder and general partner of Time BioVentures.

DA Wallach, founder and general partner, TIME BioVentures

Time BioVentures is a relative newcomer to the biotech world, investing out of a $100 million inaugural fund. The strategy is to invest in companies seeking to make a big impact in therapeutics, diagnostics, research tools, and healthcare delivery models.

D.A. says he seeks out companies with brilliant and driven founders, wants to let them have a meaningful ownership stake in the company, and then help them build great enduring companies. “If they’re successful, you’d want to own them forever,” D.A. told me a few months ago.

One early investment: Cambridge, Mass.-based Beam Therapeutics, the DNA base editing company.

D.A. assembled this fund with co-founder and general partner Tim Wright, a physician scientist with a long track record of developing medicines at Pfizer and then, Novartis.

D.A. finds himself in position to get in on the ground floor of some of biotech’s most exciting startups, after what can only be described as a unique personal journey. He grew up in Wisconsin, went to Harvard, majored in African-American studies there, became a successful musician, toured the world with Lady Gaga, Weezer and Blink 182, went to work for Spotify in the early days of the subscription music platform, and then set out to become an investor. He discovered the biotech revolution and dedicated the next chapter of his career to learning everything he could about how it could transform healthcare for the better.

One key takeaway from listening to D.A.’s story: People come to the biotech industry from a wide variety of backgrounds. Some of the most successful people never stop learning. They have an endless curiosity.

And now for a word from the sponsor of The Long Run – the BIO CEO & Investor Conference.

Now in its 25th year, the BIO CEO & Investor Conference is a premier event connecting biotech leaders from established and emerging public and private companies with the investor and banking communities.

You can expect limitless networking, on-point sessions crafted by impressive industry experts, polished company presentations, and making important connections powered by BIO One-on-One Partnering.

We look forward to seeing you February 6-9 in New York and virtually.

Register now at bio.org/ceo

I’ll add that I’ve attended BIO CEO a few times, most recently in Feb. 2020 in New York. I interviewed Jeremy Levin there for an episode of The Long Run podcast, when he was BIO chairman. It’s the kind of meeting where biotech newsmakers can have productive dialogues with investors and other key players.

Again, to register, go to bio.org/ceo

Now, please join me and D.A. Wallach on The Long Run.


A New Way to Treat Depression: Barry Greene on The Long Run

Today’s guest on The Long Run is Barry Greene.

Barry is the CEO of Cambridge, Mass.-based Sage Therapeutics.

Barry Greene, CEO, Sage Therapeutics

Sage is developing a new medicine for the treatment of major depressive disorder and postpartum depression. Sage, and its partner, Biogen, recently completed a New Drug Application to the FDA for permission to start marketing zuranolone. The drug is a once-daily oral medication that’s designed to be taken for two weeks.

Depression affects tens of millions of people worldwide. It’s been treated for decades with medicines that are given on a chronic basis. They help many people, but not everyone. Often, they take several weeks to kick in.

The Sage drug is worth talking about in depth because it provides a different mechanism of action than the traditional SSRIs and SNRIs. As an allosteric modulator of the GABA-A receptor, it has been shown to work quickly, within three days. Patients don’t need to take it on a chronic basis – two weeks will often get them back to feeling like themselves again. If something flares up in their life and they need it again for another crisis, it’s there if they need it. 

There has been some progress with different mechanisms of action for treating depression. Esketamine is one example, although there are a number of barriers to use that have kept that from having a big effect on how depression is treated. Sage and Biogen will be doing a lot of work to prepare for commercial rollout. The work happening behind the scenes this year will determine whether the product reaches a niche market, or whether it can alter the landscape for how physicians and patients think about the treatment of depression.

The challenges ahead are huge, which we talk about here.

Barry came to Sage as CEO two years ago, when the company had struggled with its first marketed medicine and had to lay off half its staff. The good news is that it has a fighting chance to rebuild the company around zuranolone. It’s given in a convenient oral pill, rather than the more problematic IV form that is part of what tripped up the company’s first product. Barry comes to the company with a successful career in operations and commercialization at AstraMerck, Millennium, and most notably, Alnylam Pharmaceuticals.

This is a pertinent conversation for anyone who thinks about how medicines can ultimately reach people in need, and for anyone personally interested in what’s coming down the road for this all-too-human malady that strikes so many people.

Now, if you like listening to The Long Run, you’ll love a subscription to Timmerman Report. This is where you can read my in-depth reports on the most interesting startups in biotech, my regular Friday Frontpoints column that concisely covers the issues of the week, plus insightful coverage of current topics in biotech from a rotating cast of contributing writers. Individual subscriptions are available on a monthly, quarterly, or annual basis. Group subscriptions provide a license to companies that have more than one reader.

For sponsorship opportunities on The Long Run podcast, or to inquire about bringing me to your company for a speaking engagement, see my business representative Stephanie Barnes. Stephanie@timmermanreport.com.

Testimonials here.

Now, please join me and Barry Greene on The Long Run.


Hot Topics in Biopharma: Initial Impact of Digital, Data Dilemmas in Clinical Studies, and the Search for ‘New Normal’

David ShaywitzFor today: topics relevant to many drug developers (and others):

For today: topics relevant to many drug developers (and others):

  • The initial impact of digital
  • The dilemma of data collection in early clinical studies
  • The elusive search for “new normal” ways of working
Initial impact of digital in biopharma

The sexy promise of digital/data/AI in biopharma was that emerging digital technologies were going to solve our most important and vexing problems. At the most breathless moments, some asked whether IBM’s Watson would cure cancer.  

AI, generally speaking, has continued to struggle in areas where the underlying data are a mess and/or where it’s difficult to aggregate adequate amounts of reasonably reliable data. One example where such insight is needed but not currently available: translational models.

As I discussed in a recent column, drug developers desperately need improved translational models, improved abilities to predict which candidate molecules are safe and effective. This would increase the success rate of large and costly Phase 2 and Phase 3 trials. While AI has proved remarkably helpful in domains such as predicting  protein folding, it’s currently difficult to imagine that in the near future, AI will be able to anticipate reliably what will happen — good and bad — when a molecule is introduced into the human body.

On the other hand – as I described in 2021 — emerging digital technologies are having an immediate impact in the “digital transformation” of how pharma functions, similar to the way other businesses have been transformed. The new direction tends to emphasize large platforms, repeatable processes, and real-time dashboards that enable teams, as well as the broader organization, to align around shared data. In short: business operations, including R&D operations.

(I’ve previously emphasized the value of dashboards as a valuable management tool for Pfizer in the development of their COVID-19 vaccine; separately, I have also discussed the downside of excessive reliance on dashboards and metrics.)

The emphasis on operations in pharma closely parallels areas of near-term progress in healthcare, where much of the initial effort, and low-hanging fruit, seem to be in what physician and venture capitalist Vineeta Agarwala calls “the workflow and administration category,” and highlights the intensive activity she’s seen in the “revenue cycle management and billing world.”  (The comments are from a recent podcast, featuring Agarwala, fellow VC Vijay Pande, and physician and digital champion Eric Topol; the episode, here, is highly recommended.)

Vineeta Agarwala, general partner, Andreesen Horowitz

Why operations? For one, these data tend to be plentiful, easily obtainable, and readily analyzable. For another, these data are consequential in a fashion business leaders intuitively understand, particularly when focused on parameters like efficiency.

A more interesting question is whether these efforts will ultimately enable higher-level inquiry, or will just enable drugs to fail slightly faster and cheaper. The optimistic view – which I favor — is that eventually the process of digitization will enable the thoughtful secondary analysis of large volumes of laboratory and clinical data. That sort of analysis could catalyze the development of novel and effective medicines. In the short term, though, most of the impact is likely to be on more prosaic measures of process efficiency.

One final point: a key aspect of the digital vision for biopharma is to maximize the opportunity for the organization to learn from every byte of data collected. This mirrors the much-discussed and often elusive (see here) vision for a learning healthcare system, where the goal is for each patient to benefit from the knowledge gleaned from each previous patient and aggregated for all previous institutional experience.  (Dr. Agarwala nicely discusses this aspiration in a recent McKinsey interview, here.)

Historically, pharma companies have struggled to comprehensively capture and leverage the totality of their data and experience, as both data and expertise tend to reside in hard-to-locate organizational silos.  The digitization of the enterprise offers the hope that more wisdom will be shared, allowing more insights to emerge.

Dilemma of data collection in early clinical studies

As much as drug developers try to understand a new molecule in pre-clinical studies and models, the introduction of a compound into a human being for the first time represents a profoundly important event, and contributes to a step-change increase in our understanding of the molecule.

The initial (Phase 1) clinical studies are focused on ensuring the new molecule is safe and well-tolerated; the product is given to healthy subjects (Phase 1a) and volunteer patients (Phase 1b) in carefully escalating doses in a controlled and monitored research environment.

Phase 2 studies, generally somewhat larger, are focused on starting to figure out whether the new medicine is likely to be acting the way you hoped in the body – does it seem like it might be working on treating the disease?

Broadly speaking, there are two schools of thought regarding how to approach early phase studies. Many researchers see these trials as an opportunity (some would say obligation) to learn as much about the medicine and the human body as possible. New molecules, they point out, are ultimately “perturbogens,” designed to poke certain parts of certain cells in certain ways. By analyzing in as comprehensive a way as possible how the body responds, there is the opportunity for extensive knowledge capture and insight generation. Thus, some scientists want to include in early phase studies a number of additional assays and evaluations.

The other school of thought – generally adopted by the folks responsible for the conduct and operation of clinical studies – emphasizes the value of parsimony. 

They argue clinical studies should be (and must be) as simple as possible, with the minimal number of tests required to achieve the trial’s primary objective. Reducing complexity, they point out, increases both study recruitment (a simpler study with fewer evaluations is generally more convenient and less burdensome for subjects) and study conduct, since there are fewer ways for things to go wrong. The much-lauded RECOVERY study in COVID is frequently cited as highlighting the value of parsimony in trial design. 

The truth is that it’s a very difficult balance to strike, and if (like me) you’ve been around long enough, you’ve lived through the ongoing struggles as well as the consequences. I’ve seen clinical teams lamenting the omission of data elements that they subsequently wished they had, but I’ve also seen clinical study protocols (often drafted by recent academic emigrees) that are incredibly clever and refined and complex – and then prove to be impossible to recruit and execute. 

Clearly, an elaborately designed scientific  study with zero subjects isn’t particularly useful – the phrase “succès d’estime” springs to mind. At the same time, an extremely simple study that fails to capture valuable data may represent a critical missed opportunity to advance the science and accelerate therapeutic development for the benefit of patients.

My increasing concern here is that just as we’re gaining the ability to leverage and contextualize increasing amounts of multimodal data, especially critical for translational science, drug development organizations find themselves under enormous pressure to make studies as lean as possible.  Short-term performance metrics (the vital signs intensively scrutinized by most companies) are relentlessly focused on efficiency – on how fast and cheaply a study is conducted. 

The consequences of this emphasis – the missed opportunity to capture meaningful insight – is far more difficult to measure, and is appreciated (if at all) only far later in development.

To summarize, the short-term corporate incentives to drive efficiency tend to be more palpable than the incentives to resist them in favor of more extensive data collection. Presumably, if or when the value of richer data collection – and the pragmatic utility of and necessity for translational research and data – becomes more readily apparent, the balance might change, and measures viewed as optional today might become essential in the future.

Elusive search for “new normal” ways of working

Finally, a few thoughts on the “new normal.” Despite the efforts of most corporate leaders across most sectors of the economy to return employees to the office, many are still choosing hybrid work, and are coming to the office only sporadically.

The surprise, perhaps, is just how effective groups comprised of many hybrid workers seem to be. Teams are functioning, the work is getting done, and the employees are on balance happy with the arrangement — even if management continues to grumble.

I was talking about this recently with a technology colleague, a long-time pharma industry veteran who only recently joined our company, and had actually started working remotely even before the pandemic.

My colleague emphasized – correctly, I think – how much everyone has learned about remote work during the pandemic. The combination of improved tools and extensive experience has enabled many employees to become phenomenally effective. Particularly when combined with occasional, high-value in-person team experiences, hybrid work seems like a promising alternative for many employees that seems here to stay.

Full disclosure — I remain a bit old-school here. As much as I dislike the commute and dread the Cambridge traffic each day, I still come to the office 4-5 days a week. I like running into people unexpectedly and serendipitously, and I appreciate the sense of place – however empty the place may often be.

When not driving my kids to and from school — moments I cherish — I use my time in the car to listen to podcasts and audiobooks, catch up with friends and family, and follow-up with colleagues at work. But could I use the hours I spend in bumper-to-bumper traffic more productively outside the confines of my automobile? I suspect the answer is yes.

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