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Times are tough in biotech, but this is an industry where we learn, adapt, and move forward.
I’m proud to announce that the 2025 Timmerman Traverse for Damon Runyon Cancer Research Foundation has hit its fundraising goal of $700,000 to support high-risk / high-reward cancer research. We stand at $702,555 in closed donations.
Our team of 16 hikers is now packing bags and gearing up to trek to Everest Base Camp at 17,500 feet / 5,364 meters. We will hike in Nepal Apr. 15-25.
This Timmerman Traverse campaign, like all others, required sweat and sacrifice. We had to overcome adversity. It took creativity and relentlessness. We kept working because it’s important to uplift the next generation of outstanding cancer researchers, especially in a moment of so much potential.
We did it together.
Now we will enjoy some quiet time, away from the daily work world. We will come together as a community of men and women united in shared purpose.
We will slow down, unplug. We will stare up in awe at one of the marvelous mountain ranges of the world. We will feel the challenge of hiking uphill, on dirt and rock, breathing thin air. We will sip warm tea in rustic lodges, around a wood burning stove. We will play card games and tell stories. We will shiver when sliding into our sleeping bags at night.
We will form friendships to last a lifetime.
Thanks to our top-tier sponsors – Bristol Myers Squibb; Kite, a Gilead company; and Alnylam Pharmaceuticals.
Thanks also to Cooley, Higgins Group, HLX Life Sciences, KMAK Capital, Latham & Watkins, Lincswitch Therapeutics, Lumanity, Lyfe Capital, NeoGenomics, Nucleate, PH Foundation, PhaseV, Relation Therapeutics, TD Securities and WilmerHale.
Thanks to Aragen, Argot Partners, Bain Capital Life Sciences, BioInvent, British Land, Causaly, DH Life Sciences, Emily Whitehead Foundation, ImmunoPrecise Antibodies, Lonza, Nurix Therapeutics, OrbiMed, Recursion, Saras Capital, Singular Biotech, and TCG Life Sciences.
For a full list of corporate sponsors, click here.
Thanks to this year’s team:
Friends, family, and colleagues can follow our progress on the expedition here.
Finally, thanks for everyone who donated, and everyone who makes it their life mission to alleviate suffering from cancer.
We may come up with a few ideas on the trail to share with you later. — Luke
L to R: Henry Kilgore of the Whitehead Institute, Luke Timmerman, and Will Chen of the University of Washington on Kilimanjaro, Feb. 2024. Henry and Will are Damon Runyon Fellows who participated in the inaugural Timmerman Traverse for Damon Runyon on Kilimanjaro, Feb. 2024. They are a couple of the brilliant young scientists that our donations support.
Enjoy a few more photos from my Everest and Everest Base Camp archives.
Monks in training, Thame Monastery.
The legendary Lakpa Rita Sherpa, 17-time Everest summiter, in front of a Tibetan Buddhist stupa, with Ama Dablam in the background.
Hiking into and above the clouds.
Spinning the prayer wheels, paying respects to the local culture, sending forth good vibrations through the Khumbu Valley.
Luke Timmerman with mountain guide Jangbu Sherpa at Everest Base Camp. 2018.
David Roblin is today’s guest on The Long Run podcast.
David is the CEO of London-based Relation Therapeutics. The company uses multi-omic tools to look for drug targets in human tissue samples. It seeks to find the relationships between perturbed biological states and disease, with the help of machine learning.
Relation emphasizes relationships in another sense as well – the cultural kind among biologists, engineers, physicians and other professionals who need to find ways to meld their disciplines together to improve biopharma R&D success rates.
David Roblin, CEO, Relation Therapeutics
The startup has raised more than $80 million to date from a diverse group of tech and biotech investors. Late last year, it announced a preclinical partnership with GSK in which the pharma giant is supporting Relation’s work to discover novel drugs for fibrosis and osteoarthritis.
David comes to this work after a long career as a physician, then as an R&D executive at large biopharma companies Bayer and Pfizer, and in translational research from The Francis Crick Institute..
I met David and the team in London in late January. I was wearing another hat there, as part of a fundraising event for the Timmerman Traverse for Damon Runyon Cancer Research Foundation. I learned about the London biotech community, and how the many players – academia, hospitals, startups, and large tech and pharma companies – are seeking to work together and put the pieces together to improve the biopharma R&D enterprise. I hope you will learn something too.
Now, please join me and David Roblin on The Long Run.
Sam Blackman, MD, PhD; entrepreneur-in-residence, GV
It’s been a rough week (again) for those of us within the biotech ecosystem. Actually, it’s been a rough month. Hell, let’s just say it’s been a hard year. Or two.
Rather than writing about the negatives – there will be plenty of time for that, I suspect – I’d like to share a delightful little story.
I recently returned from a meeting on pediatric sarcomas held at Cold Spring Harbor Laboratory. I’ve never been before, and it was hard to not be awed by the campus and the sense of legacy you have in the buildings and on the grounds and by the innumerable photographic reminders of the role that CSHL has played, as a physical place, in the history of molecular biology and biotechnology.
Not only was the physical place inspiring, and so were the people at the conference. I felt fortunate to refresh long-standing connections that included Alejandro Sweet-Cordero and Kim Stegmaier. Both were young faculty members in the Pediatric Hematology/Oncology division at Dana-Farber back when I was but a wee fellow.
The combination of photographic history and personal re-connections was a reminder that one of the enduring joys provided by a life in science and medicine are the career-spanning, or sometimes life-spanning, relationships that you can build. It is this joy that will make so many of us flock to Chicago this year (twice!) for AACR and ASCO.
Returning to my home on Orcas Island after the CSHL meeting, I got back to one of the more mundane tasks that I’ve been tackling during my recent “retirement” from Day One Biopharmaceuticals – cleaning out the storage room. Absolute joy and delight came from cleaning out an old filing cabinet.
There was a dusty drawer full of papers and certificates, many dating back to my medical and graduate school years (mid-1990s), and some dating back to my undergraduate years. I found a photocopy of the first journal article I co-authored, a stack of old student and hospital IDs from medical school (which serve only to remind me that I somehow managed to transform hair follicle stem cells into adipose-derived stem cells over the past 30 years), letters of recommendations from former college professors, and other ephemera that reminded me of exactly how long I’ve been a denizen of the medical and scientific ecosystem.
One surprising treasure was a program booklet from the 1998 MD/PhD National Student Conference. That year I was midway through my MD/PhD program at the University of Illinois Chicago and was lucky to have somehow managed to have my abstract selected for this conference, which was held every year, hosted by the University of Colorado Health Sciences Center (the conference is still ongoing and is in its 40th year this year).
The 1998 conference featured lectures by Carol Greider, Michael Welsh, Richard Klausner, Mark Groudine, and Michael Brown. In addition to hearing 5 incredible keynote talks, I remember that a number of us went mountain biking with Carol Greider. Looking back it was quite a reminder that I had the privilege of sharing a few days with a current Nobel Laureate, a future Nobel Laureate, a future NCI director, and multiple National Academy of Medicine members.
Perusing the list of attendees, I realized that for those 3 days in Aspen, not only was I sitting in the same room with then current luminaries, but many of the young scientists at that meeting ended up becoming highly accomplished future colleagues.
It turns out that I was sitting in the same room with Mike Thompson, MD, PhD, FASCO, who I’ve gotten to know through the years (on Twitter and in real life), Shannon Morris, who I would end up working together with in oncology clinical development at GSK, with James LaBelle, who I’d get to know and befriend as fellow fellows in pediatric oncology at Dana-Farber Cancer Institute, David Berman, who I would meet and interview in 2007 when he was at BMS, and who would be the person who inspired me to go into a career in drug development, and, most amazingly, Jeremy Bender, who would in 2020 become my CEO, my dear friend and partner, and with whom I would continue to build Day One Biopharmaceuticals into the success that it has become.
This week, my “retirement” is coming – unsurprisingly – to a premature end, as I am in Cambridge to begin the next chapter of my career as an entrepreneur-in-residence at GV. The time for looking back has concluded, and now it’s time to again look forward. But the past and future remain inextricably linked.
Robert Copeland
Much to my delight, and in keeping with the theme, I learned that Robert Copeland has also recently joined GV as an advisor. He and I are being reunited as colleagues. Many of you will know Bob from his innumerable scientific accomplishments, including the discovery and development of the first approved EZH2 inhibitor tazemetostat. But I have the privilege of also knowing Bob first as my biochemistry professor at the University of Chicago back in 1991 when he co-taught a course with the legendary Herbert Friedmann. And while I don’t remember the specifics from 30-plus years ago, I suspect that my introduction to the lac operon and the fundamental concepts of molecular biology came to me first via Bob Copeland.
Once again, Shakespeare was right: what’s past is prologue (a statement that is, ironically, inscribed on a statue found at the National Archives building in Washington, D.C. and an important reminder for all of us, today).
As Gary Gilliland, an incredible physician-scientist and my former department head at Merck, told me in my last meeting with him before I left to take new job, “Remember, Sam, it’s a long dance.”
Gary was, of course, absolutely correct.
We occupy an incredibly small world, and an even smaller one for those of us lucky to have a career in science and medicine and biopharmaceutical R&D. Our future is, of course, profoundly influenced by those who teach, train, and collaborate with us over the years. But unlike so many other fields, the long, if not epic, arcs of science and medicine all but guarantee that we accumulate a lifetime of colleagues, as well as colleagues for life.
In a world that is so fractured, I feel the need to cling even more tightly to the threads that connect people across space and time, like the ones tucked away in that filing cabinet drawer. Especially the threads that connect the remarkable people in our biotech community — people who have dedicated themselves to the pursuit of truth and the insatiable desire to positively impact human health.
I save them and treasure the threads that connect us much like I treasure those old papers and pictures, knowing that it is the connections that will sustain and hold us together, admixing and sometimes reconnecting us at unexpected points, so we can continue working together towards the greater good.
David Shaywitz
The arrival of generative AI prompted many to worry about the adverse impact on human agency; after all, if the technology can effectively do what we’re doing, where does that leave us?
This concern was the central focus of Reid Hoffman’s “Superagency,” which I reviewed for the WSJ earlier this year – see here. Essentially, Hoffman argues that new technologies can take some time to adjust to, but ultimately they empower us to do more things and greater things.
In the moment, however, that’s not how many experience the technology; in the review, I discuss a 2024 research paper out of MIT exploring the impact of generative AI on material scientists. The technology seemed to make the researchers more productive – and apparently even more creative – but also robbed them of the aspect of their work that provided them the most satisfaction.
As I wrote,
Mr. Hoffman, presumably, would argue that future scientists, accustomed to partnering with AI, will experience an enhanced sense of agency based on all they will be able to accomplish. Whether this forecast ultimately accords with our lived experience is the unanswered question upon which Mr. Hoffman’s cheery thesis depends.
Reid Hoffman
Recently, I’ve been thinking a lot about agency in the context of another remarkably powerful emerging technology – GLP-1 receptor agonists, the wildly popular anti-obesity medicines developed by Lilly and Novo.
According to the most recent CDC data, over 40% of Americans are categorized as suffering from obesity (defined, however imperfectly, as a BMI of 30 or higher); 9.2% of Americans suffered from extreme obesity (BMI 40 or higher). As the CDC points outs, “This means that more than 100 million adults have obesity, and more than 22 million adults have severe obesity.”
These numbers are climbing; twenty years earlier, about 30% of Americans were classified as suffering from obesity, and 4.7% suffered from extreme obesity, according to the CDC.
Prior to the arrival of GLP-1 medicines, durably losing weight in the extraordinarily obesogenic environment that we inhabit was virtually impossible without bariatric surgery. But not for lack of effort; millions of Americans endured cycle after cycle of desperately trying to lose weight, only to fail entirely, or to briefly succeed and then regain the weight rapidly. I can relate (see here, here).
One consequence of this pattern was a sense of futility around lifestyle changes for health. Yes, doctors preached the benefits of “diet and exercise,” and everyone is familiar with this advice. However, the sad reality is that the constant failure of the diet component often resulted in a broader sense of demoralization. What’s the point of sweating on the treadmill for half an hour if you’re just going to undo the apparent benefit by scarfing down some oreos later that day? (To be sure: there are many important intrinsic benefits of exercise, but it could be a difficult argument to make when someone is watching themselves get heavier day after day.)
The demoralization associated with failed (or being failed by) diet/nutrition programs (presumably coupled with the increased difficulty of exercising when you are heavier) thus had a cascading effect, depriving many of the absolutely extraordinary health benefits associated with physical activity, as I’ve discussed here and just this week here.
Enter the GLP-1s. In addition to all the remarkably positive effects they seem to have on their own (including some that appear independent of weight loss, as endocrinologist Daniel Drucker notes in a recent review, here), I suspect that among the greatest health opportunities associated with GLP-1 medicines will be their enhancement of our sense of agency.
According to University of Pennsylvannia professor Martin Seligman (see my discussion here) agency boils down to the belief that “I can make a positive difference in the world.” As I wrote,
Referencing what he describes as an extensive literature, Seligman argues that “people who have high agency are physically healthier,” adding “If you look at people with high agency holding constant the traditional risk factors, they live on average 6-8 years longer,” compared to people with low agency.
He continues, “Optimistic people—people who believe that they can control things far into the future, bounce back. They resist depression. They succeed. They try harder and give up less at school.” They do better in college than their SATs predict, he says, and do better at work. In contrast, “pessimistic people are less productive than their talents predict.”
From a health perspective, he says “about 20 well-done studies” have shown that after accounting for “the usual risk factors,” it turns out that “being in the bottom quartile of pessimism is roughly equivalent to smoking 2-3 packs of cigarettes a day for longevity. “
The point is that according to Seligman, enhanced agency is associated with better health. The massive opportunity I suspect GLP-1s may represent is that by allowing people – finally – to achieve mastery of their diet and appetite, these medicines might profoundly enhance our sense of agency.
Martin Seligman, Zellerbach Family Professor of Psychology, University of Pennsylvania; Founding Director, Positive Psychology Center
In addition to this being intrinsically beneficially to our health as Seligman suggests, it’s easy to imagine that success in the nutrition management will motivate many to embrace other health enhancing behaviors, including in particular exercise, which presumably will generate still more positive feedback and enhance our sense of agency even further.
In short, GLP-1s will generate what I’d call an agentic dividend that can be — and should be — leveraged to drive other healthy behaviors.
A bit optimistic? Only if GLP-1s prove financially inaccessible to most people – unfortunately, a very real possibility.
A skeptic might also argue that GLP-1s are fundamentally a cheat – in helping us lose weight without the suffering, we don’t really acquire the mastery, and perhaps the sense of enhanced agency, that weight loss without medical assistance might provide.
This is an understandable argument (if also somewhat dated with its emphasis on raw willpower). It’s also arguably moot since so few people were durably successful this way. I suspect that without the psychological burden of serial diet/nutrition failures, we will be far more enthusiastic about embracing additional healthy activities.
I am particularly excited by the profound opportunity here to recognize and leverage the agency enhancement that GLP-1s will provide and use it to fuel additional health-positive behaviors, starting with exercise, and building out from that foundation.
David Shaywitz
Dying, with few exceptions, has never been especially popular, and our shared interest in not dying hardly constitutes breaking news. Nevertheless, the aspiration of living longer — and remaining healthier while doing it — appears to be all the rage.
Consider these recent headlines:
There have also been a slew of longevity-focused books over the last several years; Outlive, by Dr. Peter Attia, is perhaps the best known, and has spent over ninety weeks on the New York Times Bestsellers list. Also relevant: Dr. Howard Luks’s Longevity…Simplified: Living A Longer, Healthier Life Shouldn’t Be Complicated.
What’s going on – what accounts for this apparent surge of interest?
To oversimplify, there are two general (and not entirely distinct) lines of work that seem to account for this.
First, there’s the biological study of longevity itself – what accounts for the intrinsic limits of lifespan, and how might this be extended? Much of this biology, as Dockser Marcus describes in the WSJ, originated from studies in the Guarente Lab at MIT, and has been pursued by researchers including David Sinclair (now Professor in the Department of Genetics at Harvard Medical School) and Brian Kennedy (former CEO of Buck Institute for Aging, currently Distinguished Professor in Biochemistry and Physiology at the National University of Singapore).
Leonard Gaurente, Novartis professor of biology, MIT
Similar to many frontier areas, the underlying science of aging has proved particularly challenging. As Dr. Eric Verdin, CEO and president of the Buck Institute for Research on Aging in Novato, California told Dockser Marcus,
“…the more you study something, the more you understand the complexity. There is no magic pill—even though we all would love the idea that there’s going to be something magical that solves all of your problems and prevents you from aging.”
The second area of work involves the factors that cause us to get sick and frail when we age. Attia describes four “chronic diseases of aging,” which he calls “the Four Horsemen”:
Dr. Attia’s framework, shared by others, is that each of these diseases develops very slowly over time, yet we tend to intervene only relatively late in the process.
The “goal should be to act as early as possible,” Dr. Attia argues. “We should be proactive instead of reactive in our approach. Changing that mindset must be the first step in attacking slow death.”
There also appears to be a shared belief that a key factor contributing to all four Horsemen (to various degrees) is metabolic dysfunction – essentially the idea that through excessive and unhealthy eating, and insufficient exercise, we develop insulin resistance, and our bodies enter a generalized pro-inflammatory state.
This contributes not only to cardiovascular disease and type 2 diabetes, but (at least to some extent) to cancer and neurodegeneration as well. Through focusing early on improved diet and more exercise, and monitoring progress closely, the hope is that we might delay, perhaps for many years, the arrival of the Horsemen.
One common attribute of many (but not all) researchers and entrepreneurs focused on either the biology of longevity or the prevention of chronic disease (or both) is a sense that action is required and warranted before definitive proof (in the form of randomized controlled trials, the gold standard of medical science) has been documented.
For example, Dockser Marcus writes,
Dismissing promising results because they aren’t definitive isn’t fair, Guarente said: “It is moving in the direction where there will be stronger and stronger data, maybe not in everything, but in some significant human health areas in the future.”
Similarly, Attia argues (in a section titled “From evidence based to evidence informed”) that while the “purists of evidence-based medicine demand data from RCTs before doing anything (emphasis in original),” the study of longevity isn’t particularly amenable to tradition RCTs because “it would take too long to do the study” and “the interventions are very complex, particularly if they involve exercise, nutrition, and sleep.”
Thus, he says, rather than wait for definitive proof that might never come, he argues we should extrapolate aggressively and thoughtfully from what we know, and recognize we’ll not achieve “absolute certainty,” but rather it’s about managing risk.
He argues we should think about approaching our health like an investment strategy, “seeking the tactics, based on what we know now, to deliver a better-than-average return on our capital, while operating within our own tolerance of risk.”
With this context, we can appreciate the rationale underlying both the consumer longevity companies (generally focused on extensive testing) profiled in depth by Dr. Topol and the supplements promoted by some of the longevity biologists interviewed by Dockser Marcus. Many longevity biologists are also working on developing what they hope will be FDA-approved medicines to combat aging.
We can also start to appreciate some of the critical dynamics associated with the surge in interest in longevity. If you believe traditional medicine is either excessively conservative about assessing risk or insufficiently proactive, or both, and if you are sufficiently well-off to afford the additional testing, then longevity companies are here to serve you.
On the other hand, Dr. Topol observes, “As is the case with the companies attempting to reverse aging, the ones marketing longevity, healthspan and advanced prevention to consumers have not yet provided any evidence for benefit.”
He continues,
That is not to say the concept behind these companies— a much broader collection of data— is wrong. My contention is that it is flawed because it is indiscriminate as to who undergoes testing and what tests (such as total body MRI or multi-cancer early detection) and when they are performed.
As Dr. Topol points out, according to Bayes Theorem, “if the pre-test probability is low, the accuracy of the test is substantially reduced.”
In short, the testing approach utilized by many longevity companies seems likely to generate a plethora of false positives, as well as additional testing, procedures, and anxiety. That’s a key concern for both physicians and payers — that we’ll run all these tests and waste a lot of time and money searching for problems that aren’t really there, and potentially generating new, iatrogenic problems in the process.
(Dr. Zak Kohane and colleagues described the challenge of “incidentalomas” in 2006, here; I’ve recently reviewed a book about Bayes Theorem for the WSJ here; the topic is also covered in another book I recently reviewed for the WSJ – Sir David Spiegelhalter’s The Art of Uncertainty – here.)
While today’s consumer-focused longevity companies focus on testing, the research around longevity science, while complex, as Dr. Verdin noted, remains exciting and promising. The work could ultimately lead to FDA-approved medicines capable of resetting our intrinsic rate of aging and significantly increasing our potential lifespan.
Despite differences in thresholds for various diagnostic tests, there seems to be remarkable alignment around lifestyle interventions that can promote longevity. As Dr. Luks nicely summarizes (recommendations with which Attia and others seem to largely agree), key elements include:
Dr. Howard Luks, author, “Longevity… Simplified”
As longtime TR readers recognize, I’m especially impressed by the impact of exercise, and I’m hardly the only one. As Attia writes, “The data demonstrating the effectiveness of exercise on lifespan are as close to irrefutable as one can find in all human biology.”
The disproportional impact of getting the sedentary to move even a little (as I’ve discussed here) is striking:
I am especially attracted to the idea of a healthspan platform that’s rooted less in arcane laboratory testing, and more in promoting a combination of activity and agency (which I suspect GLP-1RA medicines can help propel), particularly among the motivated tech-savvy highly agentic 50+ generation I’ve referred to as “The Vanguard.”
Longevity is having a moment, driven both by decades of research into the biology of aging and by research suggesting metabolic dysfunction leading to chronic inflammation may contribute to major diseases of aging, exerting a deleterious effect over a very long time. The hope is that earlier intervention (perhaps prompted by a suggestive value on a laboratory test or imaging study) could mitigate the damage. One concern is that if testing is performed without consideration of pre-test probabilities, many false positives will be identified and pursued. On the other hand, GLP-1 medicines provide a profound opportunity, particularly when combined with suitable physical activity, for individuals to significantly enhance their years of healthy life. In addition, with continued research, longevity science may one day deliver FDA-approved medicines capable of significantly increasing intrinsic human lifespan.
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Eddie Pauline, President and CEO, Ohio Life Sciences
The current debate over capping federal research overhead rates misses the forest for the trees.
Federal investments in medical research have built a thriving U.S. biotech sector that employs 2.3 million people. Funding from the National Institutes of Health (NIH) provides the foundation for this success, supporting universities and research institutions that attract top scientists and foster innovation.
Laura Gunter, President, North Carolina Life Sciences Organization
The Trump Administration’s proposed cuts to NIH’s indirect cost reimbursement—dismissed by some as mere “overhead”—threaten to undermine American exceptionalism, ceding our leadership in life sciences, global health and biosecurity to China.
After World War II, the U.S. created the world’s greatest research enterprise, which has driven American innovation for decades.
Rather than centralizing federal research, the U.S. made the decision to conduct research at universities and institutes throughout the country by co-investing in the development of research infrastructure.
Marc Cummings, President and CEO, Life Science Washington
By funding world-class facilities, the U.S. attracted the best scientists to conduct breakthrough research, which, in turn, secured private investment to turn that research into life-saving medicines. Today, life science companies invest $65 for every dollar the NIH contributes to a successful drug. That’s an incredible return on investment.
So, this debate isn’t really about overhead. It’s about maintaining the partnership between the federal government, universities, and medical research institutions that have allowed the United States to be the global leader in science and innovation for decades.
Stephen Rapundalo, President and CEO, Michigan Biosciences Industry Association
These funds keep the lights on, maintain state-of-the-art labs and enable cutting-edge research that powers America’s biotech industry. Reducing them may seem like a well-intended cost-cutting measure, but it’s a dangerous step toward dismantling the very infrastructure that allowed the United States to be the global leader in biotech investment and new drug development.
Meanwhile, China isn’t debating overhead rates. It’s investing aggressively in universities, research parks and industry partnerships. It subsidizes companies conducting research within its borders, making it cheaper to conduct research, clinical trials, and innovate there. The results are staggering: In less than a decade, China has gone from a non-player to licensing nearly one-third of all new molecules acquired by large pharma last year.
Simply put, our economic, health and national security depends on maintaining leadership in developing new treatments, cures and defenses against biothreats. We cannot afford to rely on a foreign competitor—and potential adversary—for the health and safety of the American people.
For generations, our nation’s early investments in research created new industries like biotechnology and precision medicine, transforming lives and driving the U.S. economy. These investments didn’t just benefit coastal research hubs. Universities and research institutions in red, blue and purple states alike depend on NIH funding to fuel local economies, support jobs and drive scientific discovery.
From biotech clusters in North Carolina and Washington to leading research universities in Ohio and Michigan, this funding is critical to maintaining American competitiveness across the country. The argument for capping Facilities & Administrative rates is that institutions can cover the gap in funding through endowments.
The reality is that most institutions, particularly public universities, will need to look to their states, which means increased state taxes, to find the funding — or simply forgo the funding altogether.
This isn’t a distant threat. It’s already hurting U.S. institutions and companies. Research institutions have already started to pause hiring, curb spending and rescind offers to graduate students, risking the loss of the best and brightest talents to other countries that have sought for years to replicate the American innovation engine.
Meanwhile, stock prices of companies supplying research tools plummeted 15-20% after the proposed NIH cuts were announced. The message from the market was clear: Weakening America’s research enterprise has immediate economic consequences.
China understands that. While we debate cuts, it’s doubling down on building facilities, attracting top talent and fostering partnerships with the goal of becoming a global leader in life sciences innovation.
We still have the advantage, but it won’t last without action. Protecting America’s leadership in life sciences isn’t just about national pride—it’s about economic strength, global health and national security.
Think of it this way: Taxpayers could save money by cutting “indirect costs” like fire trucks and fire stations. But no firefighter wants to work without a truck, and no one wants their fire department to arrive on a bicycle. Cutting indirect costs would leave our research system similarly unprepared.
A federal judge has issued a preliminary injunction in the case. Rather than placing a cloud of uncertainty over every research project and forcing our most innovative minds to look abroad for opportunities, we’re calling on the Trump Administration to drop the case regarding NIH overhead cuts and start a meaningful dialogue with industry and research leaders to identify opportunities for efficiency while maintaining our position as the world’s dominant life science powerhouse.
The choice is clear: We can invest to maintain our leadership or watch it slip away to China. America cannot afford to get this wrong.
This editorial was co-authored by the leaders of four state biotech associations:
Joe Horsman, biotech investor, Madrona Venture Group
Before Roche officially announced their new sequencer in a pre-AGBT webinar in February 2025, only true sequencing aficionados had heard of Stratos Genomics or Sequencing by Expansion (SBX).
The SBX chemistry underlying Roche’s new sequencer was developed by Stratos Genomics, which Roche acquired in 2020 and paired with nanopore sensors from Genia Technologies, which Roche acquired way back in 2014.
Stratos Genomics has an unlikely origin story, starting from a skunkworks operation in Seattle-based Stratos Product Development. The now defunct Stratos Product Development worked on a range of technical products, including Microsoft Xbox controllers, Apple laptops, and Nike sunglasses.
In 2007, Stratos Genomics was born in a closet-sized lab based on a napkin sketch outlining the fundamental idea behind SBX: copying DNA into an expandable, surrogate molecule for easy nanopore sequencing. Over the intervening 18 years, a relatively unknown group of scientists and engineers painstakingly developed the chemistry that brought the initial SBX napkin sketch to life.
Stratos Genomics is perhaps one of the most unlikely candidates to develop technology that is now taking on sequencing giant Illumina. The leadership is devoid of ex-Illumina stars and academic luminaries. Group leaders inside Stratos (and now Roche) often lack long academic or industry accolades—or even PhDs—instead spending years working their way up from research associates inside the organization.
There was no mega-round from a brand name Silicon Valley VC to generate buzz. Very little capital went into the company at all. Stratos only raised around $60 million during its entire 15-year history prior to acquisition.
Mark Kokoris, former CEO, Stratos Genomics; VP and head of SBX Technology, Roche Diagnostics Seattle
The CEO, Mark Kokoris, likewise eschews the limelight—you won’t find him at many conferences or sitting on panels. Instead, he is laser-focused on building the next generation of sequencing in a Seattle office building converted into a lab. With this profile, it is not surprising that the sequencing world was taken by surprise when Roche announced an SBX-driven sequencer that seems poised to upend the status quo—they quite literally did not see it coming.
The sequencing world is buzzing about it now. Roche announced at the AGBT conference last month that the SBX technology reduces the time from sample to genome from days to hours—a potentially big leap in R&D productivity. It could also provide useful differentiation in the type of data it throws off as a “midi-read” instrument, positioned between the short-read (Illumina) and long-read (PacBio and Oxford Nanopore Technologies) players.
SBX is a novel approach to nanopore sequencing, giving high accuracy short reads—almost a hybrid between Illumina-like SBS (sequencing by synthesis with short reads of DNA) and Oxford Nanopore which directly detect DNA and can give reads length of over 4 million bases.
With SBX, the DNA sequence is copied into a synthetic, surrogate molecule. A highly modified polymerase copies the DNA sequence, incorporating expandable nucleotides (XNTPs) instead of dNTPs, each of the 4 XNTPs contains a reporter molecule corresponding to its DNA base identity. After the DNA template is copied, the surrogate molecule is cleaved at the alpha phosphate, causing the molecule to expand 50X the length of the native DNA.
This “Xpandomer” is then sequenced through a nanopore. Because of the large sizes of the surrogate molecule only one base is read at a time, and the reporter molecule gives a clear, distinct signal for each base.
This was a heroic undertaking, requiring the combination of world-class chemistry, protein engineering, biochemistry and lots of determination. I saw some of this work firsthand, as I worked at the company from 2018-2022. For example, the polymerase evolution and engineering to specifically incorporate XNTP could barely begin until you had designed, generated and purified all 4 XNTPs! This could easily have been a cost and time prohibitive barrier to even starting.
So how did this dark horse bring this wild sequencing chemistry into the real world? Essentially, through one thing: grit. Long hours (11-hour days were completely normal), meticulous attention to every detail of the sequencing chemistry (Mark Kokoris will talk for days about chemical minutiae at every step of the process), and an unwavering belief that SBX could—and would—happen.
Over almost 20 years, SBX was willed into existence with (sometimes literal) blood, sweat, and tears.
But SBX is the type of scientific breakthrough that every scientist should be rooting for. When you hear about accurately copying DNA into a synthetic polymer 50 times the length of DNA—let alone see the chemical structures in the preprint (below)—every scientific bone in your body yells, “No way that works!” And yet, it works, and works really well, claiming a world record for DNA sequencing speed.
Look at this thing! Yikes
Expandable nucleotide structure. From Fig. 3, BioRxiv preprint. https://www.biorxiv.org/content/10.1101/2025.02.19.639056v2
However, big questions remain. Early access starts in 2025, but full commercialization won’t be until 2026, and there are still no hints on pricing. So, any predictions of disruption must come with an asterisk.
SBX brings two new (and underappreciated) axes to the sequencing discussion: flexibility and speed. These are tailor-made to solve pain points for clinical-facing customers.
With an instrument that offers flexible throughputs, large diagnostic providers no longer need to wait to fill up a sequencing lane—potentially bringing down clinical turnaround-times. SBX also uncouples read length from sequencing time, sequencing run times can be tailored to the amount of data needed. Obtaining 2X150 reads (300bp) on Illumina’s NovaSeq at the most cost-effective, high throughput can take up to 48 hours.
With Roche’s pedigree in diagnostics, Illumina is now being attacked on all sides. Element Biosciences is coming from the bottom up with a flexible sequencer accessible to many academic labs. Ultima Genomics is gunning straight at the mega-core, hyperscaler labs like the Broad Institute with an unquenchable thirst for raw read numbers, at below $100 per genome.
Even future growth markets like China are slipping away, with Illumina recently placed on an import ban list by the Chinese government, in favor of homegrown MGI. Now Roche steps into the fray, poised to take a shot at one of Illumina’s future bright spots, the clinical diagnostics market, with a full sample-to-answer offering and a large sales force capable of competing with Illumina around the world.
Illumina will be forced to respond. The big question is, “does Illumina still have enough scrappy, startup DNA left to fight, or will they retrench to service a dedicated install base?”
Illumina isn’t likely going anywhere. This dominant sequencing giant built the NGS market and ecosystem, embedding sticky workflows and customer relationships. The switching costs are high for these long-term customers. Illumina has a high-quality, well-known commodity, and a generation of scientists has been trained on its instruments. That will be hard to unseat. If you have an iPhone, and all your apps and data have been on it for years, what would it take to switch to an Android phone?
Entrenched as Illumina is, its growth prospects are very much in question. Illumina has been reducing its revenue forecasts as the entire biopharma industry grapples with a stagnant investment environment and now sweeping cuts to the NIH. New competitors in the sequencing field will make a return to growth much more challenging.
Illumina is also looking to break into adjacent fields like spatial biology, but these are far from green fields and incumbents won’t just roll over. Illumina’s new XLEAP sequencing chemistry is a nice, incremental improvement but perhaps a sign of a shift away from the ambitious, step-change innovations that drove the cost of sequencing from millions of dollars per genome to under $100.
For Roche, diagnostics will likely be the primary focus. There will certainly be research- and academic-focused instruments, but Roche’s greatest strength is its ability to offer a fully integrated solution for diagnostics. Roche has a checkered reputation in the academic sequencing world since discontinuing the 454 pyrosequencing platform in 2016. They will likely have to commit real resources to demonstrate SBX’s commitment to researchers. In contrast, Roche boasts a world-class molecular diagnostic sales force and end-to-end clinical solutions, positioning it to become the leader in clinical sequencing.
Roche’s SBX entrant poses an even bigger threat to Thermo Fisher Scientific and its Ion Torrent sequencer. While Ion Torrent doesn’t receive much attention, it has quietly built a strong business serving a largely clinical customer base. Roche poses an existential threat to Ion Torrent.
Among all the hype, what Is Roche’s weak spot? Expect to hear a lot about accuracy and Q scores from rivals as SBX’s launch date approaches. Single-read accuracy has been the Achilles’ heel of every single-molecule sequencing method. While Oxford Nanopore and PacBio have each developed solutions, Roche will face criticism that their raw read accuracy doesn’t measure up especially as PacBio’s Onso (the product of another sequencing acquisition—Omniome) and Element compete for ever-higher Q scores. Q50+, anyone?
Will Roche’s big announcement spur further consolidation? Will large diagnostic players view a sequencer as a must-have, spurring Abbott, Thermo Fisher, Danaher, or Qiagen to buy one of the up-and-coming players? Singular Genomics was recently taken private by Deerfield—perhaps expect their sequencing box to quietly find a diagnostics-focused home.
Alternatively, will Illumina position itself as the “white knight,” the neutral platform for diagnostic companies to standardize on? Upwards of 50% of its revenue is likely clinical-focused, a space it can’t afford to concede to Roche. This is perhaps the most bullish opportunity for the beleaguered sequencing incumbent facing a seemingly never-ending stream of challenges.
Disclosure: the author was previously an employee of both Stratos Genomics and Roche.
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Thanks to everyone who attended the TR10 anniversary party Mar. 13 at Adaptive Biotechnologies.
The toasts and roasts were funny, perceptive and heartfelt. It was a joyous occasion.
Enjoy a few photos. Click to enlarge.
Photos by Robert Wade.
Thanks to everyone who attended the TR10 anniversary party Mar. 6 at Alnylam Pharmaceuticals. The toasts and roasts were funny, perceptive and heartfelt.
There was a joyful community spirit in the room.
Enjoy a few photos. Click to enlarge.
Photos by Mike Mejia.
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Tim Hunt, CEO, Alliance for Regenerative Medicine
As the CEO of the cell and gene therapy advocacy organization the Alliance for Regenerative Medicine (ARM), I’ve been asked one question more than any other amid the constant barrage of news headlines the past two months.
How are you approaching the Trump Administration?
I hear it from across our community, including biotechnology companies, academic and medical research institutions, patient advocacy groups, investors, and our Board of Directors.
Here is how I explain it, starting with important context. For many of our major stakeholders, cell and gene therapy (CGT) represents highly disruptive technology, much more akin to AI than small molecules. It elicits tremendous hope but also raises justifiable questions and concerns — from patients, payors, policy leaders, and religious leaders. So, we engage with everyone to share our views on the technology and meet people where they are. Everyone gets our respect and our time.
We are treating the new Administration and Congress the exact same way.
I first came to Washington, DC, as a young man during the George H.W. Bush Administration and I’ve seen challenges and opportunities associated with every administration since. At ARM, it’s our duty to recognize — and operate within — this reality and advocate for the patients we serve.
During the first Trump Administration, the FDA approved the first gene therapies for rare genetic diseases and the first CAR-Ts for blood cancers and proposed a rule that encouraged the use of outcomes-based payment arrangements in Medicaid. But the same administration proposed tying the prices of physician-administered drugs in Medicare Part B to the prices paid in foreign countries, which would have dramatically reduced prices and discouraged further investment in cell and gene therapy startups. The Trump Administration also implemented an immigration ban that harmed the biotechnology workforce.
The Biden Administration took similar positions with regard to our industry. It started the Centers for Medicare and Medicaid Services’ Cell and Gene Therapy Access Model, a welcome effort to modernize Medicaid by facilitating the use of outcomes-based agreements for the FDA-approved gene therapies for sickle cell disease. But skyrocketing inflation — and the rise in interest rates that came with it — depressed investment in development-stage biotechnology companies that create many of the most innovative therapies. And the Inflation Reduction Act, which gave Medicare the ability to drive down prices it pays for a certain number of medicines each year, hit the large biopharmaceutical companies that are often the engines of commercialization for cell and gene therapies through partnerships and acquisitions.
So, with that understanding, when the opportunity arose last week to meet with US Health and Human Services Secretary Robert F. Kennedy, Jr., with a small group of healthcare stakeholders on regenerative medicine, I jumped at the opportunity.
While it wouldn’t be appropriate for me to share specific details about an off-the-record meeting, I can say Secretary Kennedy and his team were highly engaged, asked good questions, and appeared eager to support the field on behalf of the patients we serve. I left the meeting thinking there is important work we can do together to fine-tune the federal regulatory and reimbursement approaches to CGTs to balance safety, efficacy, and speed, and to break down barriers to access.
Beyond that particular meeting, we generally think there is a philosophical alignment between CGTs and aspects of the Make America Healthy Again (MAHA) movement. CGTs address the root cause of disease and can reduce the need for ongoing chronic interventions. Indeed, when the Trump Administration announced the MAHA Commission in February, it cited the work it did during the first term to accelerate advancements in genetic treatments for sickle cell disease.
For CGTs to flourish and reach patients in need, and for the US to outcompete rising powers like China, we need an ecosystem that combines trailblazing science, flexible regulation, modernized healthcare systems, and robust capital markets.
There are three priority areas that we’re discussing with the Administration and Congress:
We strive to find common ground with this, and any other, administration because our patients for the most part do not have other treatment options they can turn to. As the father of a young man with a rare brain condition (Dandy-Walker Syndrome), I am aware of the joys, but also the many juggles and struggles that take place in our community. I’ve met countless CGT patients who have benefitted from our advanced therapies, but also many families who have lost loved ones to cancer and rare genetic diseases.
When it’s about the future of CGT and our patients, not engaging is never an option.
Tim Hunt is CEO of the Alliance for Regenerative Medicine
Andy Scharenberg is today’s guest on The Long Run.
Andy is the co-founder and CEO of Seattle-based Umoja Biopharma. The company is developing in vivo CAR-T cell therapies. The idea is to use gene therapy, delivered in a single shot, that can reprogram T cells of the immune system to recognize markers on cancer cells and then hunt down cancer cells and kill them like an invading virus.
Andy Scharenberg, co-founder and CEO, Umoja Biopharma
CAR-T cell therapies have been around for years, and they have delivered remarkable, lifesaving results for patients with certain forms of blood cancer. But these treatments are engineered in a complex, time-consuming, and expensive process. It depends on carefully controlled lab environments where a patient’s precious T cells get engineered, then shipped back to the patient and re-infused. Umoja is hoping to sidestep this so-called “ex-vivo” work – outside the body – and save everyone a lot of time and money by coaxing the body to achieve a similar result “in vivo” or inside the body.
Umoja raised $100 million in a Series C financing at the start of 2025 and is advancing programs through early clinical testing for cancer and autoimmunity. The company and its R&D partners hope to have an early glimpse of clinical trial results before the end of 2025. If successful, this could represent a paradigm shift in the field of cell therapy.
Now before we get started, a word from the sponsor of The Long Run.
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Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $199 per year, you reward quality independent biotech reporting, and encourage more.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $199 per year, you reward quality independent biotech reporting, and encourage more.
David Baker, professor of biochemistry, University of Washington; director, Institute for Protein Design
[Editor’s note: David Baker gave this speech to Seattle community leaders Mar. 10, at a celebration of his 2024 Nobel Prize in Chemistry.]
Let me just briefly tell you how innovation arises in biomedicine and where drug discoveries come from.
A large percentage of the innovation is made at universities by graduate students and postdocs. Often, they take their ideas and spin out biotech companies, and the biotech companies further develop these and the ideas eventually transition to pharmaceutical companies.
It might be surprising to many people that most of the innovation doesn’t happen in the big companies. It happens at universities. The universities also train the workforce for the biotech and the pharmaceutical companies.
So there’s this idea that cutting funding can maybe revitalize a company.
My main message tonight is that exactly the opposite is true for science. That’s because of the critical role that graduate students and postdocs play.
In face of uncertainty about funding, universities are cutting way back on graduate school admissions. For example, in my department, the acceptance rate, the number of students admitted has gone down by more than a factor of two. That’s true across the country.
It’s going to be much harder for students next year who want to pursue careers in science to become scientists. Next, because of the way in which program managers have been fired, there’s a lapse in renewing the flow of funding, so labs are stuck without funding, which makes it very, very hard for the graduates and postdocs in research labs.
Now, because of the uncertainty, universities are imposing hiring freezes. That’s happened in the University of Washington School of Medicine. It is a very reasonable response, because we don’t know where the money is coming from.
That means new postdocs can’t be hired. It’s also means individual labs don’t know if they’re going to have funding. And then finally, for postdocs transitioning to become faculty members, faculty job searches are being canceled across the country. Again because of this uncertainty.
The cumulative effect of this uncertainty is way out of proportion to the amount of funding saved. It doesn’t actually save that much money to have all this uncertainty. It just wreaks havoc on a system which then has to behave conservatively, because it can’t pay people if there isn’t money coming in.
There’s a final aspect to this, which is, many, many outstanding researchers come to the United States from foreign countries. With this uncertainty, the US is getting less attractive as a place to stay. So people are having to return to their home countries. So the US is losing out on all this talent.
I’m telling you this to give you a few more talking points with people that you’re speaking with. I think these things could really have a very long-term effect, a negative effect, not just in biomedicine, but across science overall.
The bottom line is that uncertainty is really bad for science. It hits people at the most delicate time in their career. It hits early on, like when undergraduate students want to become graduate students, or graduate students want to become postdocs or postdocs who want to become faculty members.
That’s the message to spread. Now we’ll move on to more positive things.
David Baker is a professor of biochemistry at the University of Washington and director of the Institute for Protein Design.
Arjun Kumar
Several thousand scientists gathered Friday in Seattle for one of the nationwide “Stand Up for Science” protests. People studying a range of disciplines — biology, climate change, public health and more — took a break from the lab to protest cuts to federal spending on science and mass firings.
Morale had been low for weeks among many attendees, but Friday had a different mood. Scientists and their allies of all ages gathered on the amphitheater grass under a rare sunny Seattle day.
Speakers stood below the iconic Space Needle and drew thunderous applause. Some wore white lab coats while others waved American flags. Many brought their dogs. Two protestors even dressed in chicken costumes, calling attention to the rising outbreak of bird flu in the U.S.
Despite the lighter aspects, participants had a serious purpose. Carrying signs with messages like “Science Saves Lives”, “No Science, No Cures”, and “Dump DOGE, Defend Our Data”, they had three core policy demands:
Protestors at Space Needle on Friday, March 7 (Photo by Arjun Kumar)
Chetan Seshadri, a tuberculosis researcher at the University of Washington, described the NIH funding cuts in material terms. He’d initially declined the speaking invitation from the rally organizers until the NIH grant review panel he was scheduled to participate in was abruptly canceled.
“We’ve been told it’s about budgets,” he said. “If it was about budgets, they wouldn’t have canceled my nonrefundable flight.”
Seshadri pointed to the NIH’s proposal to cap indirect costs on grants at 15% as particularly impactful for researchers. For example, the University of Washington doesn’t own the building that houses his lab and instead pays rent through a high indirect cost rate. The proposed change to indirect costs would lead to an estimated $90 million loss for the university.
The UW secures more federal research dollars than any other US public university. Now, with grant funding withheld and grant review panels canceled, Seshadri said he’s worried about making payroll for his lab.
Many of the cuts to federal agencies are being challenged in court. Washington Gov. Bob Ferguson expressed his support and described lawsuits the state has joined. He expressed confidence in the ongoing lawsuits, pointing to his record as the state’s Attorney General when he won 58 cases while losing 3 against the first Trump Administration. That line drew cheers.
Stand Up for Science in Seattle. Mar. 7. (Photo by Kelsey Woodruff).
A look at the audience, however, revealed mixed support for the Washington Governor, who has proposed $4 billion in cuts to the state budget after inheriting a deficit. Signs like “Bob focus on the revenue” and “Furloughs are BAD for Science!” criticized the governor’s proposal to furlough state employees (including public university workers) to address an estimated $15 billion state budget shortfall.
In a nod to conservatives, pediatric oncologist Jim Olson of Seattle Children’s Hospital described growing up and “pulling himself up by the bootstraps.” He finished college in three years while simultaneously working and being supported by federal Pell Grants for low-income students. Olson earned his MD/PhD at the University of Michigan (again with the support of federal funding) before becoming a leading researcher of brain cancer in children.
Federal research funding fueled his work, and it eventually translated into his co-founding of three biotech companies — Presage Biosciences, Blaze Bioscience, and Link Immunotherapeutics. Those companies collectively raised over $200 million in venture capital and created dozens of high-paying jobs.
Government and industry each have roles to play, Olson said. Government, he said, “is intended to do what companies cannot do” – including supporting the training of young scientists.
Jim Olson, professor, Seattle Children’s Research Institute; program director, Invent@SC
Many such trainees have felt heightened anxieties because of these cuts. I ran into a friend, a first-year graduate student, who was rotating between professors to choose a permanent lab. There aren’t many choices, as few professors have enough funding flexibility to accept a new student.
As a third-year graduate student working on immunotherapies, my own collaboration with the National Cancer Institute has also been effectively frozen, first by a ban on external communication from the Department of Health and Human Services and then by cuts to the NIH’s intramural research funding. Each of my classmates has a similar story.
Many people were sharing their stories at the protest. An estimated 4,200 people attended the Seattle event alone, with sister rallies in over 30 U.S. cities and several other countries.
Kelsey Woodruff, a graduate student and one of the rally’s organizers, noted the event came together in just three weeks. She joined the organizing effort after feeling disillusioned with government and federal funding, saying “the rally felt like a place to put my frustration and anger in a productive way.” Woodruff wanted to “restore a sense of agency” and remind her fellow scientists and allies that “you can keep advocating for science and calling your representatives.” In a time when many feel powerless, she said this rally was one way to “feel like you can do something about it.”
Such advocacy was new to many scientists, with the recent turmoil inspiring them to write to their legislators for the first time.
But trying new things is itself a practice of science. As Seshadri said, “the founding fathers were scientists – political scientists – who tried something new. They didn’t know if it would last, and it’s now being put to the test.” The current administration, he said, “wants people to give up and look away.” It was time for people to “use their voice and speak truth to power.”
Arjun Kumar is a graduate student in Molecular & Cellular Biology at the University of Washington who participated in the rally.
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