25
Nov
2025

London Life Sciences Week Shows UK Biotech is Open and Thriving

Rosie Rodriguez, senior vice president of growth, Relation Therapeutics

London has always been multicultural, multidisciplinary, and in constant motion. It is a global mosaic where academia, entrepreneurship, finance, policy, and creative arts intersect with ease.

That character was evident during London Life Sciences Week, which has grown far beyond its origins around the Jefferies London Healthcare Conference.

What began as a finance event has become something broader and more meaningful: a week in which scientific, entrepreneurial and investment communities come together across the city with a shared sense of purpose.

This evolution has happened both organically and with intention. While London Life Sciences Week (LLSW) emerged from the longstanding cluster of activity surrounding Jefferies, it is now also formally supported and jointly hosted by the UK BioIndustry Association (BIA), MedCity, London & Partners, the Mayor of London, and the UK Government. Their combined support has created something coordinated and substantial, an effort to amplify London’s strengths and reinforce its position as a global centre for life sciences.

Patrick Vallance

Sadiq Khan, Mayor of London, and Lord Patrick Vallance, Minister for Science, Innovation and Nuclear, started off the week with a simple and confident message: London is open for innovation, and everyone building the future of science is welcome here.

While some large pharma companies have recently paused major UK investments, the conversations across the week suggested that this pullback may be out of step with what is happening on the ground. London has real momentum. Especially when scientific expertise is being challenged in some parts of the world and anti-immigrant policies are on the rise, London’s stance was reassuring to the many immigrants in the city and a shrewd countermove in the global competition for scientific talent.

London’s life sciences community has reasons for optimism. The city attracted £1.6 billion of venture investment into life sciences over the past year, more than Paris, Stockholm and Berlin combined and leads continental Europe by over a billion pounds. During the typically gray and chilly third week of November, LLSW attracted more than 70 events, 1,300+ investors, and 2,400 participating companies.

Conversations from coffee meetings in King’s Cross to evenings in Soho had a grounded optimism. JPM now has real competition, people often remarked while taking in the scene.

London is not replacing San Francisco, but the value of being here, the density of science and talent, the productivity of meetings, the sense of community, is no longer in question. People spoke not about hype but about substance: good science, strong teams, and collaboration that feels natural rather than forced.

The deals and company updates around Jefferies were extensively covered, BiotechTV tracked and covered them fantastically in real time. The part that sits between the headlines, and what I wanted to capture here, was the atmosphere across London: the people, the conversations, and the sense of community that defined the week.

Emma Tinsley, CEO, Weatherden

London Bio stood out among the many great events of the week for how clearly it reflected the spirit running through LLSW and offered a moment that quietly captured the sector’s resilience. Led by Emma Tinsley (Weatherden, Elevara), Yasin Siraj, BACKED VC, and Jack O’Meara (Aerska), it had a relaxed but purposeful atmosphere.

Emma opened by noting that between the three organizers their ventures had collectively raised almost £200 million in the past year, BACKED VC’s £100 million seed fund, Elevara’s £70 million round, and Aerska’s £21 million raise. It was not shared as a boast, but as a reminder that thoughtful, science-led companies continue to be backed, even in a year often described as difficult.

Their guests brought that same tone to the room. As he steps down as CEO of Recursion, Chris Gibson reflected on the past, present and future, thoughtful and candid, with light moments of humour, including his plan to climb Kilimanjaro with Luke in February.

When Sir Jonathan Symonds, GSK Chairman, spoke about the importance of building partnerships rather than transactions, I realized I was nodding more vigorously than intended. Reader, if you permit, a small and shameless plug follows: at Relation, where I have the privilege of helping shape and grow the organization, our collaborations with GSK reflect exactly that spirit.

Jack O’Meara, CEO, Aerska

Throughout the rest of the week, what stood out was how naturally people interacted. Researchers, investors, engineers, founders and industry leaders moved fluidly between discussions. There was a sense of community, not aspirational, but real, built slowly and deliberately over time.

People were focused not only on their own companies but on strengthening the wider ecosystem and making London an even better place to do impactful science. The city’s strength lies in its people: biologists, chemists, machine learning scientists, experimentalists, engineers, and computational scientists who choose to build here.

Without this talent, innovation is not possible, and London continues to attract and cultivate exceptional people.

As a dual European-British national and as a Londoner, I felt pride throughout the week. The pride came from seeing how far the ecosystem has come, how collaborative and open it feels, and how committed people are to building something of long-term value. London Life Sciences Week showed that London is not aspiring to become a global center for life sciences; it is already operating as one.

What feels most exciting is that its future is being shaped not by any single institution, but by a collective, a community choosing, together, to build something meaningful for the patients that are waiting.

24
Nov
2025

Recommended Podcasts (and A Few Books), 2025 Year-End Edition

David Shaywitz

It’s time for my annual feature: recommended podcasts (and a few books) for TR readers to consider. As usual, these suggestions generally steer clear of politics; they also aren’t the only podcasts I listen to, but they’re the ones I’m least likely to skip.

Biotech and Health Care

Of course, everyone in biotech should listen to Luke’s interview series, The Long Run – that’s always been a given.

For regular updates on the state of the industry, my quirky favorite is BioCentury This Week – it’s unpretentious, well-informed, and has a distinct personality.

I also appreciate the quality of the conversations Dr. Eric Topol has on his Ground Truths podcast; his insights offer a reliable window into the part of the biomedical establishment that is rigorous and cautious yet still forward-leaning and innovation-curious, and how it makes sense of our rapidly evolving landscape. 

Perhaps my favorite health podcast is Dr. Lisa Rosenbaum’s Not Otherwise Specified (from the NEJM), driven entirely by the strength of Rosenbaum’s insights, the candor of her questions, and the capacity of her heart. This season she focuses on the challenges of primary care, and every episode has been brilliant.

Also worthwhile, engaging and from the NEJM: the monthly NEJM-AI Grand Rounds podcast, hosted by Raj Manrai and Andrew Beam, addressing issues at the intersection of AI innovation and clinical medicine.

Two other podcasts in this category you should know about: first is Carl Zimmer’s limited-run, characteristically thoughtful series about aging. Second is an upcoming series I’m excited about from journalist and writer Thomas Goetz, called Drug Story – preview here.

Business

My favorite daily business podcast, for a long time, has been The Journal, from (wait for it) The Wall Street Journal, and featuring a close, accessible look at a major business story in the news.

Another must is the less frequent and far longer podcast Acquired, described by the WSJ as the show “the smartest people in the room are all listening to.”  It offers a detailed look at the evolution of a prominent company; TR readers should check out the April episode on Epic.

I continue to enjoy episodes of Patrick O’Shaughnessy’s Invest Like the Best and Harry Stebbings’s Twenty Minute VC.  Regrettably, I’ve largely stopped listening to podcasts from a16z once it started to feel as if they’d adopted a “flood the zone” approach to content domination.

In contrast, I’ve really enjoyed the first few episodes I’ve heard of the recently launched Business History podcast (clearly inspired by Acquired, but fun-sized rather than family-sized).

History

I love learning about history.  While most of my listening here has been through audiobooks, I’ve also been really enjoying The Rest Is History, with Tom Holland and Dominic Sandbrook, and Breaking History, with Eli Lake. Both offer context and narrative verve in an engaging and appealing manner.

Psychology

There’s no shortage of podcasts focused on psychology and behavioral health; over the past year I’ve especially enjoyed (and frequently cited) excellence, actually, hosted by Steve Magness, Brad Stulberg, and Clay Skipper.

The Glue Guys podcast has also offered some quality content here, exploring the overlap between sports, leadership, and “the subtle art of making other people better.”

Fun

Not surprisingly, some of my favorite shows from previous years have remained regular parts of my line-up. These include 99% Invisible, with Roman Mars; Across the Movie Aisle, with Sonny Bunch, Peter Suderman, and Alyssa Rosenberg; and The Bulwark Goes To Hollywood, hosted by Sonny Bunch.

Finally, while perhaps politics-adjacent, I continue to love The Focus Group podcast hosted by Sarah Longwell, which each week features extended clips from voters representing a range of demographics.

Books

I’ve been unusually fortunate this year in having the opportunity to review a number of books, and enjoyed aspects of many of them. Particular recommendations include the Bill Gates autobiography Source Code and Sam Arbesman’s charming The Magic of Code.

Related to my interest in health and flourishing, I’d suggest Super Agers by Eric Topol, Why Brains Need Friends by Ben Rein, and Food Intelligence by Kevin Hall and Julia Belluz.

For readers keen to explore more on health and flourishing, this resource page at KindWellHealth might be of interest.

Happy Thanksgiving!

 

22
Nov
2025

Why Patients – And Many Innovative Doctors – Are Pursuing Health Outside the System

David Shaywitz

Our current system of delivering care is awful from the perspective of seemingly every stakeholder. It frustrates, enrages, saddens, and depletes patients and physicians alike. No one designed it this way. It evolved through a series of choices and contingencies that perhaps made sense at the time but now seem to have led us down an evolutionary dead end.

While there’s no shortage of examples, I was especially struck by an anecdote I heard in Dr. Lisa Rosenbaum’s brilliant “Not Otherwise Specified” podcast series for the New England Journal of Medicine. Her focus this season is primary care, and in one episode she speaks with a Denver family physician named Larry Green.

“I practiced in the oldest family practice in Denver, for years,” Green explains. “I was the chair of that department, I directed that residency, and I’m now a patient in that practice. I cannot call it. It’s impossible. Because when I call the practice, I get diverted to a call center…”

From the perspective of what he calls the “medical-industrial complex,” he says, longitudinal relationships are “totally unimportant in healthcare.”

Yet these relationships – developed with care over time – tend to be what many patients crave and what effective doctoring typically requires.

Green’s experience won’t surprise anyone who has tried to get care lately. In November 2023, Mass General Brigham announced it would not be accepting new primary care patients. At hospitals everywhere, it’s not unusual for patients to spend hours on gurneys in emergency-department hallways, waiting for an inpatient bed.

I don’t know many physicians who haven’t struggled to get care for themselves or a loved one – often at the very institutions where they trained and to which they’ve devoted years of their lives. If even insiders can’t reliably access timely, compassionate care, what chance does anyone else have?

The miserableness of the system has been well documented, and physician burnout has sadly become a dog-bites-man story.

Applicants Are Still Flocking to Medical Schools

What’s perhaps more surprising is how many people are still desperate to enter the system and become physicians, fueling an application process that, as Drs. Rochelle and Loren Walensky have documented in The New England Journal of Medicine (NEJM), has become increasingly competitive, expensive, and time-consuming. Premed students routinely take an extra year (or more) to tick all the expected boxes and jump through the hoops that are perceived as mandatory.

This highlights something that’s easy to forget: the ideal of medicine remains deeply attractive. I wrote about this almost thirty years ago in a New York Times op-ed, and it’s still true today.

The notion of doctoring – of being trusted at the intersection of science and human stories – retains a powerful hold on young people. If only the actual experience could live up to the hope of these applicants, the well-worn quotes from Osler and Peabody, the promise of the profession, and the expectations of patients.

Searching For A Better Alternative

The idea that there must be a better alternative is at once familiar and evergreen.

If you’re a cynic, you channel Homer Simpson and conclude, “We tried our best and failed miserably. The lesson is: never try.”

I see it differently.

The persistence of attempts to build something better – despite repeated disappointment – captures both how entrenched the current flawed system is and how deeply people yearn for something appreciably better.

At this point, I don’t know many people who seriously expect incumbents – whether health systems or their core technology vendors – to deliver radical change. Most are too busy trying to squeeze more juice from the existing machinery to welcome disruption.

Without a meaningful incentive, you wouldn’t expect organizations exquisitely tuned to the current equilibrium to dismantle or restructure it.

Even so, some of the most committed innovators I know are doubling down inside health systems, trying  heroically — like George C. Scott’s beleaguered chief of medicine in The Hospital — to wrestle these institutions back toward the care they were meant to provide.

Others are exploring promising paths outside.

Starting With an Obvious Gap: Preemptive Care

In the absence of an established alternative, many patients – and many doctors – are trying to assemble at least components of a better system. For a lot of people, that begins with focusing on an aspect our existing system overlooks and undervalues: preemptive care – sustaining our health rather than simply caring for our illness.

Longevity Panel-HBS Healthcare Alumni Conference at the Treehouse in Boston, MA November 6, 2025. From L to R: Anant Vinjamoori, MD, MBA, David Shaywitz, MD, PhD, Rich Joseph, MD, MBA, Sooah Cho, MPP, MBA (moderator & partner at SignalFire VC), Matt Vail, MS, and Julia Klim, MBA

As I recently discussed in a Wall Street Journal op-ed and at a Harvard Business School panel on healthy aging, the current fascination with “longevity” sits on top of something more interesting than recovery pods and rejuvenation Olympics. It’s easy, and appropriate, to roll your eyes at anti-aging drips and supplement stacks.

Underneath the spectacle, though, I’ve been struck by a quieter shift.  More people seem to believe that the deterioration they’ve observed in older relatives, friends, and cherished mentors isn’t inevitable, and they’re organizing their lives accordingly — an effort, in Bart Giamatti’s phrase (riffing on Milton), to fend off “the ruin of our grandparents.”

Science has helped here. Geroscience has moved from backwater to frontier, and the message it carries is surprisingly simple: movement, sleep, decent food, and warm human connection are not lifestyle accessories, they’re central levers of healthy aging. GLP-1 medicines, as I described in STAT this summer, have added an unexpected assist, giving many people who’d been defeated by years of yo-yo dieting a first experience of real traction.

At the same time, advances in measurement have made the body feel newly legible. Population-scale data have given rise to ideas like “biological age” – an assessment approach not yet validated for clinical use in individuals, but powerful in the story they tell.

Concepts like “biological age” invite people to see aging as at least partially malleable, as something you can potentially inflect.

Even some of the more dubious offerings – supplement rituals, for example – often function less as biochemistry and more as daily expressions of intent.

In the op-ed, I argued that this is the real through-line: a refusal to retreat passively into decline, and a growing appetite for preemptive moves that might tilt the odds, even a little, in our favor.

Aspiring Longevity Contenders: Fitness, Wearable, & Testing Companies

Not surprisingly, this perceived opportunity has attracted several categories of companies into the “health” space. You can roughly sort them into three overlapping buckets:

  • Fitness platforms like Peloton and Tonal that started as movement motivators and now increasingly wrap their offerings in a longevity narrative.
  • Wearable-centric companies like Oura and Whoop that focus on performance metrics around activity, strain, and recovery, again increasingly framed as healthy-aging tools.
  • Comprehensive testing platforms like Function Health, Superpower, and others, which offer large batteries of laboratory tests (often accompanied by imaging) marketed as opportunities to identify vulnerabilities early.

All of these companies are working feverishly on AI-enabled data plays and promise some version of personalized recommendation. Many are led by serious people who genuinely want to help.

Yet taken as a group, they also reveal the limits of an engineering mindset applied to human flourishing.  As I argued in a recent STAT column, we’ve become very good at harvesting data and building dashboards, and much less good at building platforms that support the experience of living a fuller, more agentic life.

Fitness & Wearable Companies: An Obsession with Performance Metrics

Today’s digital health tools, as I discussed in the Boston Globe this summer, tend to optimize what’s easy to count and, in the process, miss what most of us actually value: connection, purpose, and the sense that our choices are beginning to add up.

Image source: Wikipedia

The fitness and metric-heavy companies also illustrate a classic analytic trap (“survivorship bias”) that has been on my mind a lot lately – the “airplane problem.”

During World War II, analysts studying bombers returning from missions noticed that certain parts of the planes were riddled with bullet holes, and proposed adding armor to those areas. Statistician Abraham Wald pointed out the mistake: the bullet holes marked the places a plane could be hit and still make it home. The planes that didn’t return had likely been hit elsewhere. That’s where the armor was needed.

Most fitness and wearable companies are obsessed with retaining the people who already sign up – generally highly engaged, data-hungry users who enjoy tracking their VO₂ max, heart-rate variability, and step counts. These are the planes that make it back.

What these companies don’t see are the people who try once or twice, feel judged or overwhelmed or bored, and bounce off – people like New York Times op-ed contributor Rachel Feintzeig, who memorably describes her exercise experience:

“I get on my Peloton and am confronted with a veritable dashboard of my inadequacies: cadence (sluggish), resistance level (embarrassing), output (am I even alive?). There is my prior, surely eternal, personal record, highlighted so that I never forget exactly how much better I was three years ago. Suddenly I’m grappling with the passage of time, in my basement, as an Instagram influencer in a coordinating spandex set beseeches me to pedal faster.”

People like Feintzeig – and those who never even bother with platforms like Peloton –are the missing planes, as well as the untapped opportunity.

Early on, I was drawn to the idea of starting with movement as the foundation for a broader vision of flourishing, in part because it’s so concrete, palpable, and obviously useful for health on its own terms, even before it connects to anything deeper.It reminds me of the famous exchange from Woody Allen’s 1975 film Love and Death:

Sonja (Diane Keaton): “Sex without love is an empty experience.”
Boris (Allen): “Yes, but as empty experiences go, it’s one of the best.”

Movement without any larger sense of meaning can feel a bit like that. Even if it doesn’t yet connect to purpose, agency, or community, it’s still one of the healthier “empty experiences” we have – especially for those who aren’t exercising at all, since the health benefits of going from nothing to something can be as significant as going from something to a lot more.

I still think movement is a great place to start.

Unfortunately, I don’t see much (any) evidence that today’s fitness platforms view longevity as more than a marketing gloss, or that they are preparing seriously to serve the far larger group of people who want to lead richer lives, not dominate reductive leaderboards.

At the end of the day, it seems, fitness companies are gonna fitness. The longevity branding is kosher-style at best, and often closer to a BLT on a bagel.

Comprehensive Testing Companies: False Positives & Sterile Precision?

The comprehensive testing companies raise a different set of concerns. Large panels of lab tests and imaging sound appealing – who wouldn’t want to “know everything” and catch problems early?

In practice, as Dr. Eric Topol has critically reviewed at Ground Truths, the risks of false positives and incidentalomas are substantial, especially when testing is decoupled from clear, evidence-based action plans.

I’ve spent years following the arc from genetics to “personalized” to “precision” medicine and since high school have been deeply engaged in the science. I have a real appreciation for the promise, as well as for the practical limitations.

I recognize that the opportunities for truly precise, individualized interventions tend to be wildly overstated – even the ones that don’t come bundled with the hard sell of supplements.

The same goes for metabolomic and nutritional profiling. As Kevin Hall and others have pointed out, much of what’s been sold as precision nutrition turns out to be better marketing than science.

So where are the rays of hope?  Mostly, they center around talent as much as vision.

Green Shoot 1: Talent Redefining Testing Companies

When Function Health announced its recent fundraise, most of the attention focused on the celebrity investors and marketing sizzle.

What caught my eye was something else entirely: the decision by Dr. Daniel Sodickson –- a serious scientist and imaging innovator, long a leader in MRI at NYU, and recently an author –- to join as Chief Medical Scientist.

Dr. Daniel Sodickson

Dan, also a medical school classmate and friend, is the opposite of a hype merchant. He is thoughtful, technically deep, and obsessed with context and longitudinal understanding. His move signaled to me that Function was serious about building an engine for interpreting multimodal, longitudinal data in a way that could, over time, support genuinely more precise, personalized recommendations.

Professor Nathan Price

This aligns closely with ideas the exceptionally innovative medical scientists Lee Hood and Nathan Price have been articulating for years (including in their visionary 2023 book, The Age of Scientific Wellness), and that efforts like Arivale tried to operationalize. I’m excited about this direction and have been working with Dan and Nathan on some of these concepts – stay tuned.

Green Shoot 2: Talent Focused on Leveraging Agency & Personal Health Data

A second source of energy and inspiration for me, also connected to talent, has been the caliber of physicians and physician–scientists who’ve reached out to me as I’ve been developing and championing the concept of agency as the “motivational currency of behavior change,” ideas provisionally, and loosely, organized at KindWellHealth.  

In just the last few weeks, I’ve heard from clinicians, informatics leaders, former regulators, and population-health experts who said some version of: “Your focus on agency is exactly what I’ve been circling; I’m trying to build my next chapter around something like this.”

These are not people chasing the latest wellness fad. They are serious medical innovators who care deeply about science and patients and are trying to find a way to enhance health that feels truer to both, supported by rigorous, credible evidence.

One direction this naturally leads is towards a health system built around a data-empowered person who becomes the central locus of both control and information. In this vision, you would control your data the way you control your money. You might have accounts at many institutions, but you see everything in one place and can direct it where you want.

This idea has been around for a while, but it has acquired new urgency as patients are increasingly handed more responsibility without real visibility.

A personal “health data cloud” (Nathan Price has been using the more expansive phrase, “personal, dense, dynamic data cloud”) isn’t a cure-all, but it feels like it could be a vital first step towards a more enlightened, informed, person-centric, and humane health future.

It’s important to emphasize that “person-centric” doesn’t mean a series of dispassionate transactions with healthcare providers, which arguably is already the status quo. Nor does it mean dumping a stack of options and PDFs on patients and congratulating ourselves for “empowering” them.

As Atul Gawande has described so eloquently, in appropriately pushing back against medical paternalism, the pendulum in some settings has swung too far the other way.

Some physicians, trying to be sensitive, have misunderstood the assignment. They present a neutral menu and maintain distance at moments when some patients are desperate for a clinician to share the decision-making burden – to listen carefully, offer a considered recommendation, and shoulder some of the responsibility. 

As Gawande wrote in 1999, with his usual magnificence,

“The new orthodoxy about patient autonomy has a hard time acknowledging an awkward truth: patients frequently don’t want the freedom that we’ve given them. That is, they’re glad to have their autonomy respected, but the exercise of that autonomy means being able to relinquish it.”

While we might substitute the term “agency” for “autonomy,” Gawande’s point is essential and should be reflected in any future vision of an improved health system.

Green Shoot 3: Talent Focused on Enhancing Agency Itself

A third promising area involves focusing explicitly on agency itself – which is how I view the efforts of companies like Lore (where I serve as an advisor), SlingshotAI, and others. These groups (who often have attracted exceptional talent) start from the psychology of behavior change. They ask how we might help people feel more able to influence their future for the better, and how we might compound that sense of agency over time.

Moving Forward

My own conviction is that maximal impact will require integrating this agency focus with two other elements I’ve been writing about: the quantitative side of biometrics and the qualitative, often neglected sphere of connection and meaning.

Source: D. Shaywitz

As I see it (see diagram), our shared goal is flourishing health, supported by three mutually reinforcing domains: physical function, meaningful connection, and personal agency. A few companies touch pieces of this map. Almost no one designs against the whole thing.

To me, the combination of a strong sense of conviction that this is what the future of health needs to encompass, together with a sense of uncertainty about how we’ll get there, is what’s so exciting, particularly given the remarkable amount of talent that seems to be drawn in this direction.  Certainly, this pursuit feels more satisfying than developing innovations aimed at maximizing billing, or escalating the AI battle between health systems seeking reimbursement and payors seeking to deny it.

Patients – and those who are eager to avoid becoming patients – are (as usual) leading the way. 

We owe it to them to meet them where they are and — with technology as an aid, evidence as our guide, and compassion as our soul — build an approach to health and healing worthy of the ideals that drew, and continues to draw, so many of us into medicine.

20
Nov
2025

Building a Rare Disease Company: Neil Kumar on The Long Run

Neil Kumar is today’s guest on The Long Run.

Neil is the founder and CEO of Palo Alto, Calif.-based BridgeBio Pharma.

Neil Kumar, CEO, BridgeBio

BridgeBio got started a little more than 10 years ago with an idea of creating what it calls a “hub and spoke” business model for rare disease drug development. The hope was to find opportunities that were biologically compelling, but didn’t neatly fit into one of the existing platform technology companies of the time. Neil and colleagues hoped to package them together in a portfolio to improve the risk/reward ratio for investors.  

It’s worked out. The company has an FDA-approved product on the market that’s generating blockbuster sales — $108 million in revenue in its third quarter on the market. The drug is acoramidis (brand name Attruby) for transthyretin-mediated amyloidosis with cardiomyopathy, sometimes called cardiac amyloidosis.

That drug has quite a story on its own. But BridgeBio isn’t turning out to be a one-hit wonder. A couple of positive clinical trial readouts this year show it has a chance to become a truly unusual creature – a truly diversified, independent biotech company with multiple cash-flow generating FDA approved products.

Neil has thought long and hard about how to mitigate risk, and how to create value for investors in this most challenging of scientific businesses.

Before we get started, a word from the sponsor of The Long Run.

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Visit www.dash.bio and see how fast bioanalysis can be.

 

Please enjoy this conversation with Neil Kumar on The Long Run.

17
Nov
2025

The Dark Side of the GLP-1 Weight Loss Drugs: Eating Disorders

Amanda Banks, MD

There has been much fanfare about the acquisition by Pfizer of Metsera, the developer of injectable and oral GLP-1 agonists and other peptides for the treatment of obesity.

The $10 billion price tag, the bidding war with Novo Nordisk, the lawsuits, it all made for high drama. It was a moment of vindication for biotechs that have struggled for years through a harsh downturn.

At the same time, Secretary of Health and Human Services Robert F. Kennedy Jr. and President Trump have secured commitments from Eli Lilly and Novo Nordisk that would limit the cost of GLP-1 drugs to $150 per month. The stated intent is to dramatically increase access for patients who need to lose weight.

Constraining the growth of the obesity epidemic has undeniable benefits for health and healthcare at the individual and population levels, linked to lower blood pressure, lower risk of heart attack and stroke, improved control of blood sugar, lower risk of kidney disease, blunted desire for alcohol and maybe even protective effects against neurodegenerative diseases.

There’s a long list of benefits.

It’s easy, in this context, to understand the frenzy that has led to vast investment in this space and an expectation for outsized returns. This feels like a wonder drug: for patients, investors and for companies.

And yet, there are two sides to every story.

The Risks

These drugs were FDA-approved to treat type 2 diabetes and obesity, but they are increasingly used to achieve and maintain slimness in the absence of either. A growing proportion of people using GLP-1s are healthy people with normal weight, or even who are underweight. And perhaps most disturbingly, while GLP-1 drugs show anecdotal evidence in the treatment of binge eating disorder, these drugs are also widely recognized to exacerbate eating disorders characterized by restriction, most notably anorexia nervosa.

GLP-1 agonists have a complex mechanism of action, but in essence they are effective weight loss medications because they mimic satiety signals in the brain and slow gastric emptying, making people feel full, and often nauseated, with very small meals. It isn’t uncommon for patients to consume a fraction of the calories required for their age over months or years. People on GLP-1 agonists frequently develop nutrient deficiencies, electrolyte abnormalities, orthostatic hypotension, osteopenia, sarcopenia, thinning hair and other signs of malnutrition.

It is not surprising then, that some people who either have a history of disordered eating or who are biologically predisposed to anorexia, spiral quickly into a dangerous cycle of restriction, weight loss and positive societal reinforcement for their new thinness. Complicating the picture is the fact that only 6% of eating disorder diagnoses occur in people who are medically recognized as being underweight; indeed those with higher BMIs are at very high risk of both developing eating disorders on GLP-1s and of not rising to the attention of medical providers who receive little to no training in eating disorders and do not typically think of people in larger bodies when they conjure what an eating disorder “looks like”.

How Much Access is Too Much?

More troubling is the ease with which women with already thin bodies can obtain GLP-1 agonists without ever seeing or speaking to a healthcare professional. Online sites like hers.com will ship semaglutide and other drugs without requiring patients to ever communicate with a healthcare professional or confirming that patients fulfill labeling requirements (it took me less than two minutes to get to the payment page after providing false information about my weight, age, medical history and goals at every step to get there). 

With little oversight, compound pharmacies have also sprung up to help fill the growing demand of GLP-1 agonists as “lifestyle drugs”. Instagram and TikTok abound with videos of young women with normal size bodies extoling the values of slimming down even further with GLP-1 agonists or “microdosing” to achieve weight loss in the setting of a low or normal BMI.

Anorexia nervosa is defined by the DSM-5 as the restriction of energy intake relative to requirements, leading to a significant low body weight in the context of age, sex, developmental trajectory, and physical health, with an intense fear of gaining weight or becoming fat, or persistent behavior that interferes with weight gain. The documented prevalence of anorexia nervosa, a dramatic underestimation, is about 4% globally – or 150 million people. 

Of all the neuropsychiatric disorders we know of, anorexia nervosa has the highest mortality rate with 5% of those affected dying within four years of initial diagnosis. It affects mainly girls, mainly around puberty, and can kill them directly via acute effects of starvation, including dangerous abnormal heart rhythms, inability to maintain sufficient blood sugar, blood pressure and heart rate, or by taking its toll chronically on the heart, brain, bones, and muscles. Or, at any time, simply by suicide.

Rigorous studies about the incidence of eating disorders in people taking GLP-1 agonists are lacking, but the risk of these drugs driving restrictive eating disorders is broadly recognized, with some estimates as high as one-third (35 percent) of new diagnoses of eating disorders coming from people on GLP-1 agonists. In a large sample of de-identified health records in people taking GLP-1 agonists, patients with any pre-existing mental health condition had more than double the risk of those who did not of developing an eating disorder in two years. The cumulative incidence in both groups of a new eating disorder diagnosis (mainly anorexia nervosa) was 1.275%. With one in 8 Americans – or approximately 43 million people – now taking GLP-1 agonists, this translates to over 500,000 people.

With increased access, cheaper prices and the growing off-label use of these drugs in vulnerable populations to achieve thinness, we’re going to see more people with eating disorders.

Seeking the Other Side of the Story

As physicians, trialists, regulators, policymakers and indeed as an industry, we are completely unprepared for this oncoming wave. There is no standard protocol to screen people for a history of eating disorders or disordered eating behaviors prior to prescribing these drugs. As far as I can tell, there is no safety database or real-world evidence study that is specifically targeted to assess this outcome, which, by virtue of its complexity, would not be expected to be passively captured in a typical adverse event assessment.

Novo Nordisk’s semaglutide (Wegovy) and similar drug labels do not include a warning for the risk of triggering restrictive eating disorders. There is no structure in practice for routine clinical follow-up that would capture these events in a systematic way so as to add to a safety database. Many of our patients may be taking these drugs without our knowledge, having obtained them online from any number of willing suppliers.

How is it, that as an industry, we have invested trillions of dollars in GLP-1 agonists and related drugs without paying attention to what this pandora’s box has unleashed? How do we have multiple approved products, dozens in late-stage clinical trials, new companies getting funded in the space seemingly every day and a frenzy of M&A activity, but not a single approved medication to help the millions of people who struggle with, and die from, anorexia nervosa every year?

Like all stories with two sides, one is typically not true to the exclusion of the other. The good stories, the ones with really compelling endings, strike a balance. The GLP-1 medicines can be a godsend for some people, and a nightmare for others.

The increasing understanding of the underlying GLP-1 biology may also point us in surprising new directions. Anorexia nervosa is not the inverse of obesity, but like obesity, it is now recognized as a complex medical and psychiatric illness. There are important areas of mechanistic overlap in the underlying biology. In a time of growing ubiquity of GLP-1 drugs, we can learn from this shared foundation to help identify druggable targets.

In a world that chronically underinvests in women’s health, could we leverage the GLP-1 wins to put effort into minimizing the devastating consequences of obesity’s metabolic cousin, anorexia, that ironically has been exacerbated by the use and abuse of GLP-1 agonists? As an industry, could we provide support to change a culture that values thinness at any cost?

As a physician, a drug developer and a mom of a daughter in recovery for anorexia nervosa, I remain hopeful that the answer is yes.

17
Nov
2025

Seattle’s AI-Biotech Leaders See Hype, Hope, and Hard Problems

Chris Picardo, partner, Madrona Venture Group

AI is reshaping the foundations of biotechnology, but progress isn’t uniform. While some breakthroughs such as generative protein design models and AI-based target identification are transforming drug discovery, others are overhyped or held back by stubborn infrastructure and data barriers.

At last month’s AI Leadership Summit in Seattle, co-hosted by Life Science Washington and Madrona, a group of founders, CEOs, and investors from across biotech and tech dug into the realities behind the rhetoric.

Many of the leaders in the room began their careers in Nobel laureate Dr. David Baker’s lab at the University of Washington while others helped build large-scale AI systems at Amazon and Microsoft. This grounded the conversations in a practical view of how tech and biotech are converging. Speakers were optimistic, yet pragmatic about where the field is going and the challenges that need to be addressed to realize the potential for AI-powered drug development.

The shared perspective: AI is already changing how we discover and develop drugs, but the bottlenecks, particularly around data, culture, and validation, remain the industry’s defining challenges.

The Data Problem

For all the attention on large language models, the biggest barrier isn’t which model you use, it’s the types of data and quality of data needed to customize and fine tune these models to make them actually useful.

“Garbage in, garbage out,” summed up the mood.

Unlike tech, it takes years to gather high-quality biological and clinical data. Once you have it, it is often fragmented across wet labs, clinical trial sites, and institutions. Real progress will come from data standardization and closed-loop data generation, not just from models that vacuum up more and more fragmented data sets.

The most innovative companies are constantly producing their own differentiated data and tying these processes directly to their AI infrastructure. This new integrated discovery loop is what will drive progress and new category defining drugs.

A few bright spots are emerging on the data generation front. Fred Hutch’s Cancer AI Alliance is a coalition of five major cancer centers alongside major tech companies such as Amazon, Microsoft, NVIDIA, Google, and others. The Cancer AI Alliance is building standardized, multi-modal, oncology datasets designed for machine learning.

It’s still in the early days, but panelists said this kind of data harmonization is what it will take to make AI truly predictive and useful.

Models Help, But Validation Rules

The first panel of the day began with fast pitches from early-stage Seattle-based AI-biotech companies, including Outpace Bio, Archon Bio, Cyrus Biotech, and Talus Bio. Each company leverages AI to design and optimize therapeutics in ways that were impossible even a few years ago.

Each also relies on tools born in Seattle’s ecosystem, from revolutionary protein design models to automated wet lab systems to cloud-based data infrastructure fit for life sciences. All emphasized the same principle: AI is only as good as the experimental feedback loop that validates it.

AI models alone will not solve drug discovery. There must be deep investment in the loop data generation and validation to leverage models and understand the quality of their outputs. Drug development is still hard and requires iteration and experimentation to get to the best drug candidates.

Culture: When Tech and Biotech Teams Converge

Seattle’s combination of research universities, clinical institutions, and cloud-scale AI expertise makes it one of the few regions in the world where the tech–biotech convergence is happening organically.

But tech and biotech teams don’t always speak the same language. Software engineers are trained to ship fast and iterate often based on real-world customer feedback. Life scientists are trained by their principal investigators to spend years on research that will stand up to scrutiny under peer review before ever seeing the light of day in a scientific publication. These rhythms can clash.

Companies that succeed at the interface of AI and life sciences are learning to merge those mindsets, adopting agile practices from tech while preserving the scientific rigor of biotech. Productivity platforms from the tech world are now being used to track cross-functional workflows between computational and experimental teams, while coding is a core job at all AI-enabled biotech companies.

Attendees also emphasized the importance of AI literacy across all levels of their organizations. It’s not something that can be siloed off into an “AI department.” While early-career and forward-thinking scientists are already natively adopting AI tools, the next leap forward will depend on experienced biotech leaders engaging deeply with these systems, not delegating their understanding of AI to others.

From 10% to 20% Success Rates

Attendees pointed to two areas where the next turn of innovation will come from.

First: personalized medicine. As patient data becomes more structured, algorithms can better match individuals to existing treatments much more granularly than today. This will meaningfully improve human health. In the short term, development (vs. research) functions are ripe for applying AI to increasing efficiency. Those processes also tend to have more standardized data.    

Second: the drug discovery process will accelerate. The industry is going to be revolutionized when we go from less than 10% of drug candidates succeeding in clinical development to FDA approval to 20%.

Focusing on the Long-Term Matters

Seattle’s biotech founders and investors share a distinctive mindset: They tend to be missionaries, not mercenaries. The region’s culture prizes deep technical work and long-term value creation over short-term hype. That pragmatism, paired with world-class research institutions, a preeminent AI ecosystem, and the world’s leading cloud companies, creates fertile ground for building the next generation of AI-driven biotech companies.

The bottom line: AI won’t make biology easy, but it will make the impossible achievable. The companies that win will be those that combine scientific depth, computational scale, and cultural fluency across both domains.

12
Nov
2025

Reinventing Drug Discovery with AI: Marc Tessier-Lavigne on The Long Run

Marc Tessier-Lavigne is today’s guest on The Long Run.

Marc is the chairman and CEO of South San Francisco-based Xaira Therapeutics.

Marc Tessier-Lavigne, chairman and CEO, Xaira therapeutics

Xaira is using computers to design protein drugs from scratch, building on work from co-founder David Baker’s lab at the University of Washington.

Designing protein drugs on computers with ideal properties is a plenty big idea that won Baker the Nobel Prize in 2024. But there’s more to the company. Xaira is building a platform for drug discovery that gathers multiple types of biological data – genomic, proteomic, etc. – and feeds that into AI models to hopefully tease apart what’s causing disease, versus what’s merely hanging along for the ride. That information on what’s causing disease is supposed to help guide the design of these new targeted protein drugs from the ground up.

The hope at Xaira, and all other AI-assisted drug discovery companies, is ultimately to create a system that can make drug R&D faster, less expensive, and more predictable.

Xaira was co-founded and incubated by Arch Venture Partners and Foresite Labs. It debuted with $1 billion in committed capital in April 2024.

Marc is a neuroscientist by training. He was on the faculty at UCSF before he took an R&D leadership role at Genentech during its storied ascent as the leading cancer drug developer of the early 2000s. He returned to academia as president at Rockefeller University and then Stanford University. He left Stanford in 2023 amid some controversy, before he came back to industry with Xaira in 2024. Right now, he has the advantage of being in a startup at a moment of technological possibility – Xaira has a lot of money, brilliant people, and a clean slate to do something consequential for all of biopharma R&D. It doesn’t need to unlearn a lot of things to start doing them a different way.

Before we get started, a word from the sponsor of The Long Run.

 

 

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Please enjoy this conversation with Marc Tessier-Lavigne on The Long Run.

3
Nov
2025

China Learned from Us — and We Can Learn from Them

Leslie Williams, biotech entrepreneur and board member

Over the last decade, China-based biotech companies learned from the best —us.

They studied how the US biotech ecosystem was built: a fusion of basic science, venture capital, and entrepreneurial risk-taking. They learned how our scientists turned NIH-funded discoveries into startups, how our venture model backed innovation years before potential profit, and how collaboration between academia, biotech, and pharma fueled breakthroughs from recombinant proteins to RNA medicines.

They saw how a science-based regulatory agency fostered confidence in marketed products, and how transparent stock markets protected investors and helped them best allocate capital toward promising companies. They saw the key infrastructure at work and sought to build it for themselves.

Through it all, they followed the science.

They observed how U.S. biotech created platform companies around novel modalities — mRNA, gene editing, t-RNA therapeutics, and CAR-T — and they built their own. They watched how we used CROs to increase efficiency and flexibility, then scaled that concept into global networks that now serve the entire industry. They understood that innovation requires speed, capital efficiency, and quality — and they applied those lessons with relentless intensity. They brought a can-do engineering mindset to the task.

While Chinabuilt up its innovative capacity, it also played to its existing strengths. China continued to invest in large-scale global manufacturing capacity that the US once dominated, but no longer does. While the US was debating drug pricing and health insurance policy over the past decade, China was building bioparks, GMP facilities, and end-to-end supply chains that operate 24 hours a day, seven days a week.

They trained their scientists abroad in the US and Europe, and recruited many to return home with a deep understanding of the science — and a national mission to lead in it.

Now, 10 years later, they are good. Very good.

They are not just manufacturing efficiently; they are developing medicines faster. Chinese biotech companies are aggressively licensing assets to the West — antibodies, cell therapies, and novel oncology drugs — moving them into patients at a pace that outstrips the US regulatory and development cycle. Take bispecific antibodies: while we’ve spent years refining and testing our constructs, Chinese developers can take a similar design, tweak the sequence, and advance to first-in-human studies within months. They’ve turned speed into a strategic advantage.

And it’s time we learn from them.

From China, we can learn how to prioritize scale and speed without losing sight of science. We can learn how to move a molecule from concept to clinic in half the time, through coordinated teams, decisive leadership, and streamlined regulatory alignment. They’ve shown what’s possible when national strategy, capital, and execution converge behind a scientific goal.

But we must not forget what makes the US unique — our freedom to think differently. Innovation here comes from friction: the clash of ideas, the courage to challenge convention, the belief that failure is part of discovery. If we spend the next decade simply trying to compete with China on cost or manufacturing capacity, we’ll lose sight of what we are good at — that creative spark.

The reasons we struggle to compete in manufacturing are deeply woven into our national fabric — labor unions, complex zoning, and a society that still sees biopharma with some suspicion. We value individual rights and environmental safeguards — and we should — but they make it challenging to match China’s speed and efficiency. That’s not a weakness; it’s a reflection of who we are. But we must be honest about what that means.

Yet this dependence on China for manufacturing has a cost. The COVID-19 pandemic exposed how fragile global supply chains can be — and how vulnerable we become when critical drug components or manufacturing capabilities lie overseas. We can’t afford that risk again.

To safeguard national security and ensure access to essential medicines, we must invest in building and maintaining advanced biomanufacturing capacity here at home — not to replace global partnerships, but to create redundancy and resilience. Backup plants, regional hubs, and flexible production networks across the US could protect both innovation and preparedness.

This will require public–private coordination, new incentives, and policy frameworks that make it viable to build and sustain manufacturing on US soil. This means leveraging strengths of world-leading biotech clusters like Boston, San Francisco and San Diego, while building stronger alliances with other US regions that have their own scientific assets and room to ramp up domestic manufacturing. We should approach this not as isolationism, but as smart insurance — ensuring that when global systems falter, our science and supply remain strong.

Our challenge is to protect our innovation engine while ensuring biosecurity and maintaining global leadership. Recent US policies designed to limit Chinese investment and partnerships may improve national security — but if applied too broadly, they could isolate our science, fragment our supply chains, and slow our ability to deliver life-saving medicines. Meanwhile, the capital markets in Hong Kong are robust, and Chinese biotech doesn’t need capital from American investors to continue making progress.

Let’s remember what’s at stake. Many of today’s breakthrough therapies — from PD-1 antibodies to RNA vaccines to cell therapies — were developed through global collaboration. Manufacturing in Shenzhen, clinical trials in Australia, reagents from Shanghai, analytics from San Diego — these efforts save lives, not based on nationality or race, but on shared human purpose. The medicine your child, spouse, or parent may need tomorrow could be born from both American discovery and Chinese delivery.

A wise leader knows what they are good at and what they are not — and partners to fill the gaps. The US excels at discovery, translational and clinical insight, and the courage to pioneer. China excels at speed, cost, and execution. We should protect what’s uniquely ours — our innovation — while respecting and leveraging what they’ve built.

If we choose to compete wisely and collaborate thoughtfully, we can create a symbiosis that accelerates global health. That’s not naïveté — that’s pragmatism rooted in hope.

Because in the end, the true competition isn’t between nations.
It’s between disease and time.

And I, for one, am holding on to a hope that won’t fade.

30
Oct
2025

The Outsized Significance of A New Study of AI in Diabetes Prevention

David Shaywitz

A lifestyle intervention delivered by AI was found to be as effective as validated traditional interventions delivered by trained experts in a carefully conducted implementation study conducted by Johns Hopkins researchers and just published in JAMA.

These results have broad significance and speak to the promise of AI to deliver promising behavior-change interventions at unprecedented scale.

Context: The DPP

The core of the study involved a striking and unexpected finding from a classic study, the Diabetes Prevention Program (DPP), conducted two decades ago, and led by Dr. David Nathan of the MGH Diabetes Center.

Dr. David M. Nathan

The DPP was designed to examine whether one of three potential interventions administered to patients at high risk for diabetes could prevent or delayed their progression to the full-blown disease, compared to placebo. 

The interventions examined by the DPP originally included one of two medicines (metformin or troglitazone), although the troglitazone was soon dropped due to safety concerns.  The third intervention evaluated was intensive lifestyle coaching.

In 2002, the DPP investigators reported that intensive lifestyle coaching reduced incidence of diabetes by a staggering 58% compared to placebo over three years; metformin reduced incidence by 31% compared to placebo over the same time.

This 58% reduction has become the benchmark – a consistently elusive benchmark – that researchers and companies have chased ever since. 

As I discussed in Forbes in 2012, in piece about the (at the time, nascent) digital health company, Omada Health leveraging digital tools to try to emulate the DPP success, the secret sauce of the DPP is the intensity and dedication of the coaching provided. 

I had particular visibility into the nature of this coaching since my endocrinology training was at MGH, where I was mentored in diabetes by Dr. Nathan and his colleagues at the MGH Diabetes Center, and learned about the nature of the DPP lifestyle interventions directly from some of the coaches who administered them.

My takeaway: these coaches were determined and relentless, deeply dedicated to connecting with their patients individually, understanding their challenges, and urging them onwards.  From what I saw, there was nothing pro-forma or box-checking about any of it – the coaches (compassionately) pestered patients, exhorted them, humored them, listened to them, and believed in them – ultimately to great effect.

But duplicating these efforts – and this commitment – has been challenging. 

Even when the same protocol has been followed, and coaches appropriately trained, the results have never been quite as impressive, and usually come in at about half the efficacy seen in the original DPP.  This impact is still clinically meaningful, to be sure, but not at the level seen in the DPP.

Challenges include matching the original intensity (particularly when trying to deliver the program with less resources to larger populations) and maintaining participant engagement and retention.

AI- vs Human-Delivered DPP

The latest study randomized patients at high risk of diabetes into two groups: one received a DPP-style intervention administered by AI, while patients in the other group received an DPP-protocol intensive intervention delivered by human coaches.  The initial intent was for these sessions to be in person, but this was changed to virtual sessions due to COVID, a change that may have actually helped the study, since as an excellent editorial by Dr. Leigh Perreault accompanying the JAMA publication observed, “the human-led DPP group saw higher-than-typical participation rates when delivered virtually compared with historical in-person rates.”  

As the study authors note, “The AI used in the intervention consisted of a reinforcement learning algorithm that did not use large language models. It personalized messaging by continuously learning which prompts, timing, and content elicited greater user engagement.”

The result of the non-inferiority study, using a composite endpoint incorporating measures of glucose control, physical activity, and weight loss, was a tie: the two approaches delivered similar outcomes: about 32% of patients in each group achieved the pre-specified outcome, suggesting that for this population, the AI intervention did as well as the human coaches.

A closer look at the results highlights an important nuance: fewer patients randomized to the human coaches actually initiated the program (only about 83%), while more than 93% of patients allocated to AI coach started that intervention.  Doing the math, this means that the human coaches were slightly more effective on the patients they actually reached – but the AI reached more people, and these effects netted out to the same impact.

Why This Matters

The ability of AI to achieve the same efficacy for a study population as human coaches using a well-validated approach has significance for at least three reasons that take us far beyond an encouraging proof of principle. 

  1. Scale: AI was built to scale; the cost for delivering an AI intervention to ten patients, 100 patients, or 10,000 patients almost certainly will be far less expensive than human coaches would be, coaches who must be individually trained, organized, supported, etc. The AI will also be far more consistent in its content delivery.
  2. Constant learning and improvement: an AI system also will facilitate the rapid, continuous learning upon which medical progress often depends. Not only can new best practices be identified, but they can be incorporated immediately at scale.  It is also much easier to set up comparisons between slightly different approaches, enabling ongoing refinement.  Thus, whatever level of performance the AI achieves at the start is likely to improve significantly over time.
  3. Supercharging promising local approaches: it is not uncommon in medicine (or in any other pursuit) for a motivated provider, craftsperson, or inventor somewhere to figure out a better way of doing something, such as caring for patients with a particular type of condition. Their solution might be highly effective in the provider’s hands, but hard to transmit outside their local practice. The promise of AI-delivered interventions is to enable these insights to be systematized (perhaps in partnerships with a motivated startup), deployed as a pilot, evaluated, iteratively improved, and if effective, rapidly scaled, potentially benefiting far more patients.

An important question I continue to have is whether this approach will plateau at a point that is still below the level of the most expert practitioners who deliver the intervention in person. 

I think about the next-level DPP coaches at the MGH Diabetes Center, for example, or the late, next level cystic fibrosis doctor Warren Warwick at Fairview-University Children’s Hospital, in Minneapolis, so memorably profiled in The New Yorker by Atul Gawande. 

In theory, it might be possible to capture and systematize much of what the MGH diabetes coaches and Dr. Warwick have done so well, and to use technology to deliver at scale, and iteratively improve the approach to a level that matches or even exceeds that of these exemplars.

I’m curious about this possibility, but skeptical. 

Gawande writes about other medical centers trying to replicate Warwick’s CF success, and reflects,

“Yet you have to wonder whether it is possible to replicate people like Warwick, with their intense drive and constant experimenting. In the two years since the Cystic Fibrosis Foundation began bringing together centers willing to share their data, certain patterns have begun to emerge, according to Bruce Marshall, the head of quality improvement for the foundation. All the centers appear to have made significant progress. None, however, have progressed more than centers like Fairview.”

The ability of technology to scale means that reasonably effective interventions delivered consistently can benefit large swaths of patients.

But it feels comforting to know, or at least to believe, that there may be something special, powerful, ineffable and deeply human that lies beyond the reach of even the most impressive digital technologies.

 

28
Oct
2025

Innate Immune System Activators for Cancer: Art Krieg on The Long Run

Art Krieg is today’s guest on The Long Run.

Art is the founder and CEO of a Cambridge, Mass.-based startup called Zola Therapeutics.

Art Krieg, founder and CEO, Zola Therapeutics

Zola is developing an oligonucleotide drug candidate to activate a family of Toll-like receptors known as TLR7 TLR8 and TLR9. Activating these receptors is thought to spur the innate immune system to attack cancer cells.

Art designed the molecule himself and believes it could be the biggest thing he’s done in a long and distinguished career. He is a physician-scientist who’s considered one of the founders of the field of oligonucleotide therapies. These drugs consist of short strands of synthetic RNA or DNA to do some specific job. 

Art became enthralled with this type of medicine when he was a rheumatologist, thinking about how oligos might modulate the immune system. When he was on the faculty at the University of Iowa in the 1990s, Art discovered the immune stimulatory CpG DNA motif, which led to a new approach to immunotherapy and vaccine adjuvants. He then moved over from academia to industry, living through a historic boom in cancer immunotherapy in the 2010s. His most recent company, Checkmate Pharmaceuticals, developed a TLR9 agonist for cancer which was acquired by Regeneron Pharmaceuticals for $250 million in 2022.

Before we get started, a word from the sponsor of The Long Run…Dash Bio.

Are you tired of inconsistent bioanalysis results and waiting months for data that should take days?

Dash is the only bioanalysis CRO built from the ground up with a tech-first approach, designed to deliver better, faster, and cheaper than anyone else.

With Dash, you get:

  • Faster turnaround, with results in days, not months. 
  • High-quality data across major assay types including ELISA/MSD, LC-MS, and PCR, supporting all modalities and therapeutic areas 
  • Customer-first policies, like guaranteed outcomes and transparent pricing.

From preclinical to late-stage studies, Dash helps you move from assay development and validation to sample analysis with unmatched speed. Founded by industry veterans who’ve felt the pain of traditional CROs, Dash is the partner researchers and clinical leaders actually need: reliable, fast, and easy to work with.

So if slow bioanalysis CROs are costing you money and missed deadlines—put Dash to the test.

Visit www.dash.bio and see how fast bioanalysis can be.

 

Now, please enjoy this conversation with Art Krieg on The Long Run.

27
Oct
2025

Report from China: Setting Sight on New Modalities and Global Markets

David Li, co-founder and CEO, Meliora Therapeutics

Chinese biotechs opened 2025 with a bang at JPM week, and the momentum has continued.

Much of the conversation early this year was about how the US could rise to the challenge, and hold onto its historic position as the world leader in biotech innovation (see my Jan. 8, 2025 editorial in TR).

The evidence of a China biotech renaissance was overwhelming and could no longer be downplayed. Recall a flurry of deals from January totaling billions in upfront and milestone payments, including Innovent / Roche, Kelun / Harbour – Windward Bio, Keymed / Innocare – Prolium, Duality Bio – Avenzo, KeyMed – Timberlyne, among others.

Six months later, a Jefferies report showed that one in three licensing deals for all new drug candidates — 32 percent — trace their origins to China. Even as US biotech has shown signs of recovery this fall, Chinese biotechs are maintaining a competitive pace.

Last month, I traveled to Beijing, Shanghai, and surrounding areas on a 10-day business trip to see with my own eyes. I wanted to explore opportunities for my company, San Francisco-based Meliora Therapeutics, and spot the latest trends. I met with local biotech startups, established pharmas, and Chinese VC funds.

Here are my top impressions:

First Came Antibodies and Bispecifics, Now Come Genetic Medicines

Chinese biotechs have burst on the scene the past five years to become a dominant force in antibody engineering and biologics development. This is mainly attributable to their advantages in cost, efficiency, and speed.

The deals speak for themselves: BioNTech’s $800 million upfront deal value with Biotheus for their PD-L1/VEGF bispecific, and Merck’s acquisition of a PD-1/VEGF bispecific from LaNova Medicines for $588 million upfront and up to $2.7 billion in milestone payments are a couple recent examples.

This year, we have seen Chinese biotechs pursue with in vivo CAR T-cell therapies and other genetic engineering technologies with a similar fervor.

This is exemplified by recent deals like Vitalgen licensing a lipid nanoparticle (LNP) construct from GRIT Biotechnology for in vivo CAR-T applications and Porton Advanced partnering with RongCan Biotech to develop ionizable LNPs aimed at mRNA, gene editing, and in vivo CAR-T payloads. This is just the tip of the spear. By latest count, there are over *150* China-based in vivo CAR-T companies now.

Most of these companies will not survive, but such is the market in China. The Darwinian selection pressure is intense, but it also drives breathtaking speed.

China’s advantages in cost and velocity are even more apparent in this modality, with some companies claiming timelines of nine months to development candidate for RNA and other genetic medicine programs. This is perhaps 3X+ faster than the norm in the US.

Novel Translational Biology Is In Sight

For many years, the critique of Chinese biotech has been they are fast followers, not innovators. This narrative is beginning to shift, albeit slowly.

On my trip in September 2025, I counted at least a dozen instances of startups genuinely pursuing novel biology, from novel rare disease targets identified through proprietary human genetic databases to first-in-class oncology programs that are not simply leveraging Western academic & industry publications as starting points for scaffolds and molecules.

The competition among biotechs inside China is intense. The CEOs leading these biopharma companies understand that novel biology is the one differentiator that can help them stand out in a field of many me-toos seeking investment dollars.

The larger pharmas in China all now have R&D groups that are exploring novel targets and mechanisms via small molecules, antibody-drug conjugates, bispecific T-cell engaging antibodies, and more. Most of Chinese biotech still operates in the validated target space. But the desire and capability to explore novel biology is evident. Green shoots are visible.

The constraint, as always, is talent. China has extraordinary depth in antibody engineering, chemistry, process development, formulation, and manufacturing science. It has growing – but still limited – talent depth in translational medicine and disease biology. The companies making the leap into novel biology are typically those that have successfully recruited native-born Chinese scientists who were educated in the US and Europe, and who are now returning to China to lead their R&D efforts.

Fewer Newcos, But Business Development Still Humming

In 2024, newco activities were all the rage. Windward Bio, Prolium Bioscience, and Timberlyne Therapeutics were a few of the startups that debuted, each raising substantial rounds of venture capital. At the time, Western VCs were looking for clinical stage assets that could reach clinical value inflection points quickly, and Chinese biotechs were willing sellers of assets given financing difficulties in their market.

Fewer new companies are being formed in China with assets to out-license to the US and Europe this year, but it’s still happening.

First, the financing environments in China have recovered faster than in the US, meaning existing biotechs in China are not desperate to do outlicensing deals to stay alive. Second, valuation expectations are higher after substantial deals like those mentioned earlier have set the high-water mark. Third, and perhaps most importantly, many of the obvious targets and clinic-ready assets are gone.

While newco activity as slowed, it hasn’t gone away completely. San Francisco-based Expedition Therapeutics recently raised a $165 million round, and Boston-based Bambusa Therapeutics raised a $90 million Series A. Both companies are built around assets from China.

Additionally, licensing activity remains robust as mentioned by the Jefferies report. The difference is that deals are increasingly happening at earlier stages and with more creative structures. For example, there are now meaningful examples of Western biotechs licensing Chinese platform technologies for speed and cost advantages in manufacturing and formulation, e.g. Kite / Gilead & Pregene, rather than licensing specific assets.

This is still early innings, but the trend is notable in that it demonstrates Western pharma’s interest in leveraging Chinese platform capabilities broadly.

Chinese Pharma Has a New Slogan: “Go Global”

During my visit, it became apparent there is a new slogan for the major Chinese biopharma companies today, whether Hengrui, Sino Biopharma, Simcere, or Innovent: “go global.”

Their model? Takeda, which over decades built a truly global R&D and commercial presence that transcended its Japanese origins.

The aspiration is clear and understandable. After spending the better part of two decades building innovative R&D capabilities and seeing those capabilities validated through licensing deals and promising clinical data, Chinese pharmas are asking the logical next question: why stop at outlicensing when we could capture the full value ourselves? The domestic market, while large, is hyper competitive and subject to aggressive volume-based procurement policies from the main buyer of its products – the Chinese central government. That squeezes profit margins. Global expansion is seen as both a growth opportunity and a strategic hedge.

While this aspiration is clear, there are still challenges that should not be underestimated. The capital intensity of global registrational trials is much higher than domestic or regional studies. Clinical development expertise for navigating FDA, EMA, and other global regulatory authorities has not been fully developed internally yet, and hiring clinical development organizations internationally represents a significant commitment in both cost and management attention.

Only the best financed and profitable of the Chinese biopharma are likely to make the jump successfully, but make no mistake, this is an industrywide goal that was uttered many times on this most recent trip.

As China’s home-grown pharma companies start generating meaningful cash flow domestically from innovative therapeutics, they have set their sights on commercializing that innovation in global markets. This will be a key theme to watch in the coming quarters and years. The first Chinese biopharma to successfully launch and commercialize a novel drug in the US or Europe without a partner will be a watershed moment.

The Relentless March Continues

The pace of China’s development continues to astound. Every quarter the Chinese biotech ecosystem has a new “feel,” and progress is relentless if uneven. Some areas surge ahead while others stumble, but the overall trajectory is unmistakable.

For observers in the West, particularly those making capital allocation or partnership decisions, the imperative is clear: the world would benefit from continuing to watch this market closely as Chinese biotech continues to make strides.

24
Oct
2025

The Biology of Belonging: Social Connection Meets Geroscience

David Shaywitz

Digital health, fitness, and longevity platforms have focused on the constant measurement and relentless optimization of biometric parameters, an often-valuable effort but one that has systematically left behind vital components of health and flourishing – such as social connection — that are more difficult to measure. 

The Health Value of Social Connection

Robust longitudinal studies, including the Harvard Study of Adult Development, and Northwestern’s Super Agers study, have demonstrated that a critical determinant of longevity is warm human relationships.  The Harvard research, for example, “found that the people who stayed healthiest and lived longest were the people who had the strongest connections to others,” according to a Harvard School of Public Health summary of the work.

Moreover, a 2021 review by Jaime Vila of 23 meta-analyses of studies conducted over the last sixty years, involving over a billion subjects, found a “significant association of functional and structural measures of social support with health and longevity.” 

Vila continues, “The strength of this association is equivalent to that documented for other well-documented risk factors such as smoking or obesity.”

The health importance of social connection is also a key theme of Why Brains Need Friends, a new book by neurobiologist (and social media phenomenon) Ben Rein that I recently reviewed for the Wall Street Journal

Rein’s bottom line: “I really think you should spend more time socializing.”  He adds, “Your brain is counting on you.”

Geroscience pioneer Steve Horvath

This message is reinforced by a pair of just-published papers that used “aging clocks” to explore the impact of social connection.  One of these papers was highlighted by geroscience researcher Steve Horvath at the 2025 Biomarkers of Aging conference held this week at Harvard Medical School.

Before we get to these papers, I thought it might be useful to share a few thoughts from this meeting with TR readers.

Biomarkers of Aging Conference: Reflections

As a first-time attendee (and I only was able to make it to some of the sessions), I was struck by the remarkable (and welcome!) degree of energy, hope, and optimism among so many of the speakers, including many (like Horvath) who were toiling in the field long before it became so trendy. 

Much of the work presented involved various measures of aging, so-called “aging clocks” that relate specific patterns of biological or structural measurements to estimates of age and health.  For example, patterns of DNA methylation accumulate as individuals age, and seem to build up faster in less healthy people; thus, this measurement can reveal someone is “older” or “younger” than their chronological age would otherwise suggest.

The first multi-tissue aging clock, based on DNA methylation, was developed by Horvath back when he was a geneticist at UCLA; today, he works at Altos Labs.  (This 2024 interview of Horvath by Dr. Eric Topol on the Ground Truths podcast explores the fascinating origin story, rich in serendipity, of aging clocks, and is highly recommended.)  Perhaps not surprisingly, a colleague referred to Horvath as the “King of Clocks” in a discussion at the conference.

The attraction of ever more researchers to geroscience is easy to understand.  As Nobel Laureate Venki Ramakrishnan writes in Why We Die, “aging is connected intimately with so many biological processes,” and captures the attention of scientists in so many disciplines.

These connections weren’t always so apparent.  Ramakrishnan, an RNA biologist (see his wonderful first book, Gene Machine), explains “when I started my career, I had no idea that anything I did would be connect with the problem of why we age and die.” 

But more recently, Ramakrishnan says, he’s learned that his life’s research on “the problems of how proteins are made” is highly relevant to aging, since “much of aging has to do with how our body regulates the production and destruction of proteins.”

As palpable as the attendees’ excitement, however, was a frustration, perhaps even impatience, with a nagging sense that their work is still not quite taken seriously by the biomedical “establishment” – even as they appreciate that many patients (or more precisely, individuals who are hoping to forestall becoming patients) are drawn to the field looking for answers. 

Among the promising initiatives to integrate longevity into medicine were:

Professor Andrea Maier, National University of Singapore

  • Healthy Longevity Medicine Society,” discussed by professor Andrea Meier of the National University of Singapore. Meier was the founding President of the organization, which was established in 2022 “to build a clinically credible framework and platform for longevity medicine that promotes the highest standards of interdisciplinary collaboration in the field.”

    Dr. Evelyne Bischof

  • Sheba Longevity Center,” discussed by medical director Evelyne Bischof. Sheba, located in the Tel Aviv metropolitan area in Israel, describes itself as “the first longevity center within an academic medical institution,” and is focused on “integrating the latest research and innovations in longevity into patient care.”

Other prominent centers in geroscience include the Buck Institute in Novato, California, “an independent biomedical research institute that researches aging and age-related disease,” and was founded in 1999; and the Abu Dhabi-based Institute for Healthier Living, which characterizes itself as “the world’s first specialized healthy longevity medicine center.”

Professor Terrie Moffitt, Duke University

On many levels, I especially appreciated the presentation from Duke’s Terrie Moffitt, a psychologist who first pursued the roots of antisocial behavior, and who — by following the Dunedin birth cohort across five decades — has helped redefine how we understand biological aging. 

Her group’s DunedinPACE clock, now widely regarded as one of the most rigorous measures of biological aging, is even featured in the Rejuvenation Olympics (although, as Open Evidence reminds us, Dunedin aging measures “are not yet established for routine clinical practice”).

In her talk, Moffitt described a range of new clocks the team is developing, including one based on neuroimaging (the DunedInPACENI) that aims to predict overall aging rate (not the aging rate of the brain, specifically).

The conference presenters included several leaders from several emerging biotechs focused on aging, and with established pharma partnerships. These include:

Kristen Fortney, CEO BioAge

  • BioAge, represented by CEO and co-founder Kristen Fortney.  The company has ongoing relationships with Lilly (focused on therapeutic antibody discovery) and Novartis (focused on target discovery, with an eye towards therapeutics that can mimic some of the benefits of exercise).

    Alex Zhavoronkov, CEO Insilico Medicine

  • Insilico Medicine, represented by founder and CEO Alex Zhavoronkov. The company’s active partnerships include a target discovery relationship with Sanofi, earning a milestone payment in 2024.

The only speaker from an established and comparatively large biopharma was David Glass,  a world expert in muscle biology who is now Vice President, Research, Aging/Age-Related Disorders, at Regeneron.  Glass thoughtfully discussed important (and easily-overlooked) nuances of the molecular study of sarcopenia in rats vs mice.

David Glass, VP Research, Aging/Age-Related Disorders, Regeneron

A final observation from this conference is simply that as I considered the ever-increasing number of biological clocks available, their remarkable ease of use, and the tendency to use multiple clocks in single studies, I found it all too easy to imagine p-hacking efforts (whether deliberate or just self-deception) where, if you test enough clocks in enough conditions, eventually you find some association, and then can persuade yourself (or others) that you’ve found a way to reverse aging – or have discovered a factor that accelerates it.  If most everything can be tied to alterations in some biomarker of aging, then it will be increasingly challenging to identify meaningful signal beneath the volume of noise.

Fortunately, while one of studies we’re about to discuss does consider multiple measures of aging, it was performed rigorously, and accounts for multiple comparisons in their statistical analysis.

Social Connection and Biological Aging

Social connection, as we’ve discussed, is good for your health.  Two research groups have recently published findings reflecting their efforts to relate measures of biological aging to social connection and dissect the most impactful components.  Interesting, the teams both analyzed the same basic dataset — a well-characterized cohort, the Midlife in the United States (MIDUS) project that includes extensive self-report data as well as biobanked samples — but approached their analyses in slightly different, fairly complementary fashions.

One team — Anthony Ong of Cornell, Frank Mann of Stony Brook, and senior author Laura Kubzansky of Harvardanalyzed data from over 2000 MIDUS subjects, with an average age of about 55.

Professor Laura Kubzansky, Harvard School of Public Health

The authors utilized a measure – “cumulative social advantage” (CSA) – they previous developed, intended to capture and integrate social resources across four broad domains:

  • Religious and faith-based support
  • Parent-child relationship quality
  • Community Engagement
  • Extended emotional support.

These were assessed by self-report, using several questions for each domain.

Then, the researchers analyzed samples by using a range of stress and aging, including several biological clocks, serum measures of inflammation, and urine measures of neuroendocrine function. The numbers were then crunched, comparing the singular, composite assessment of connection (CSA) to each of these measures of stress and aging, explicitly correcting for the multiple comparisons. 

The result: higher CSA scores were linked in statistically significant manner to slower biological aging, and also with lower levels of IL-6 (a marker of inflammation), even after accounting for a comprehensive set of sociodemographic (eg socioeconomic status) and health-related (eg smoking history) confounders.

Within the CSA construct, the component of social integration–measured by the self-reported response to ‘I feel close to other people in my community’–accounted for much of the variability in CSA scores. The contribution of perceived community closeness to the observed association between CSA and slower biological aging and lower inflammation was inferred from its central role within the CSA composite.

The second team of scientists – Holly Prigerson and Paul Maciejewski of Cornell, together David Russell of Appalachian State Universityexamined data from 1309 MIDUS subjects, average age about 51.

Professor Holly Prigerson, Cornell University

This team explored the relationship between (presumptive) positive social experiences (such as volunteering for organizations) and negative social experiences (eg dropping out of school), on the one hand and two measures of biological aging on the others.  The intention was to determine, after adjusting for known confounders (critical!), which experiences most impact aging, and also to explore whether there was a relationship between the net ratio of positive/negative experiences and aging.

The key findings: engaging in social meetings had the strongest (and highly significant) positive effect on aging; also scoring well: marriage and giving assistance to others.  On the negative side, a strikingly deleterious effect on aging was associated with dropping out of school and with the subject’s parents experiencing drug problems. 

Perhaps not surprisingly, a respondent’s total number of positive experiences were associated with slower aging, and total number of negative experiences were associated with accelerated aging.  Comparison of subjects with “net positive” ratio of experiences to those with “net negative” revealed a profound difference between these two groups, with the “net negative” group aging much faster.

Interestingly, perceived social support was not found to be associated with aging in this publication.

While both studies link aspects of social connection with aging, they don’t speak directly either to causation (the social factors measured may reflect a deeper underlying driver of stress and aging, say) or to the biological mechanisms by which social connectivity exerts its putative effect on the biology. 

Also not addressed: the potential impact on aging of interventions focused on enhancing social connectivity – a critical question for those seeking to improve health rather than just measure it.

Bottom Line

Social connection exerts a powerful effect on health and aging, with robust evidence linking greater social engagement and support to reduced morbidity, mortality, and slower biological aging. These relationships deserve greater attention in longevity-promoting efforts, including digital health and wellness platforms. Geroscience research is experiencing a remarkable intensification of interest, partly due to the availability of biological aging measures, though consumer enthusiasm for these tools often exceeds their current scientific validation. The ability to connect social connection to biological aging, and to use these measures to dissect and optimize social interventions, represents an exciting but still nascent approach to developing meaningful, targeted strategies for healthy aging.

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