Team Julie: Fighting Back Against Glioblastoma

Scott Rakestraw

Thirty-seven years ago, I met a lovely and talented young woman while we were both pursuing our PhDs.

We were married during our last year in graduate school, and have spent every day since raising a family; working in STEM-Medicine careers; and engaging with our communities.

We had just retired in 2019 and begun making plans to travel and enjoy life when COVID hit.

Then came the “Big One.”  

Last December, my wife Julie was diagnosed with glioblastoma multiforme (GBM), the same aggressive brain cancer that killed President Biden’s son Beau, and Senators Ted Kennedy and John McCain.

Our lives changed forever. Where do we go from here?

The instant the MRI came back, it was clear that Julie had glioblastoma. That image delivered a gut punch. My experience as a biotech executive, investor and advisor has taught me that standard treatments of the past 30 years offer only marginal effectiveness, and most experimental agents fail. Julie’s case looked particularly grim at first glance: the tumor was large enough (5 centimeters in diameter) that it was pushing a significant portion of Julie’s left cerebral hemisphere into the emergent Danger Zone of fatal brain herniation.

We would have to act fast. But first, I had to make a phone call no father ever wants to make. 

I stepped out of the ER to call our children, Dr. Stephanie Rakestraw, a general surgeon in Alabama, and Alex Rakestraw, an advertising strategist and writer in New York. Videos of Julie’s MRI scans popped into our “Dad and Kids” group text as I told them what those scans showed. You could hear a pin drop. They weren’t going to wait for Christmas to see their Mom. The kids quickly booked predawn flights – they would be home in Bucks County, Pennsylvania, no matter what.

Well after midnight, I drove home from Princeton, NJ. I pulled some leftovers out of the fridge, poured a stiff drink, and lay down alone in bed for a few minutes. Sleep was impossible. I had to clear my head enough to start critically thinking about the road ahead as a caregiver, husband, father and patient advocate.

The amazing Joanne Smith-Farrell, CEO of Be Biopharma and a friend, calls this process “The Journey,” a road traveled by all spouses/partners of a critically ill cancer patient. Early the next morning, The Journey began.

The kids drove straight from the Philadelphia airport to the Thomas Jefferson University Neuro ICU. I met them in the lobby and filled them in with all the composure I could muster: Mom had been transferred overnight from the local hospital ER, and was being evaluated for emergency neurosurgery. Given the tumor size and location, we would be fortunate to have Julie recover from the surgery without severely compromised speech/language and executive function capabilities. A world-class neurosurgeon might be able to perform a maximal safe resection that would remove perhaps 90% of the tumor. David W. Andrews, MD is one of the best: the surgery was a success.

That bought us some time. But there wasn’t time to waste. We had to think about what to do about the cancer cells that remained, and how to best neutralize the threat they posed.

It is useful to keep in mind that cancer is a deeply personal disease – that is, in fact, part of its wickedness. Each cancer displays its own cellular and molecular profile. That means that even while we rely on well-controlled clinical trials to guide best treatment practices, those studies only provide us with rough guidelines based on the best odds in fairly heterogeneous patient populations. The true therapeutic protocol for every individual cancer patient is essentially an “N-of-1” uncontrolled clinical experiment, usually involving multi-agent combination therapy. There are always adverse events to consider, especially with cancer treatment. They need to be managed carefully, because quality of life matters. No one wants to live a few extra months if those extra months are utterly miserable.

To find the right path for Julie, we leaned on all of our knowledge and contacts from the past 30 years in biotech. First, we had to send a tissue sample taken during Julie’s neurosurgery to multiple labs for extensive molecular and genetic profiling.

While we waited for results, the family made the best of a holiday no one had planned: both kids, their significant others, and Tony the Cat unwrapped presents Christmas morning. Even though our lives had changed, life itself was worth celebrating. We savored every minute.

The results came back right after the New Year. I had some idea of where to begin, but quickly needed the counsel of experts to efficiently “Boil the Ocean” to map out Julie’s treatment plan. Dozens of emails and text messages were sent out worldwide asking for quick turnaround Zoom sessions and telephone calls. Team Julie began to respond immediately, often within minutes. Senior life sciences leaders across both industry and academia, usually asked a simple question: “How can I help?” And, without requests from me, they took their own initiative, inviting their colleagues to help chart the best course for Julie.

Behold: The true power of knowledge and empathy within our industry.

Upon seeing the molecular and genetic profiling of Julie’s tumor, #TeamJulie quickly crafted a plan to venture “off the map.” 

Simply put, sticking with the post-radiation adjuvant portion of the standard of care Stupp protocol alone was not going to be a winning strategy given the molecular and genetic data. A multi-component treatment plan was crafted based on the tumor profile data.

One key component is the Optune device, a cap that sends alternating electrical pulses through the brain to slow or stop the out-of-control cell division of the tumor. Because Julie’s tumors appeared to express high levels of PD-L1, she was a good candidate for treatment with the PD-1 inhibitor pembrolizumab (marketed by Merck as Keytruda). She also got fluoxetine, a generic selective serotonin reuptake inhibitor that’s commonly taken by brain cancer patients to stabilize mood (and has recently been shown to inhibit EGFR signaling in GBM cells), and also infliximab, the Tumor Necrosis Factor inhibitor marketed by Johnson & Johnson as Remicade. (For more about the specifics of the treatment plan, visit MissionGBM.)

This treatment plan has not been without its setbacks – after all, there is nothing more complex than human biology, especially when that biology is being turned against itself by cancer. 

Julie has a hyper-sensitive innate immune system. While checkpoint inhibitor immunotherapy is generally well tolerated, we managed to blow up Julie’s thyroid and sigmoid colon with Grade 3+ immune-related serious adverse events on Cycle 1 of immunotherapy. But she recovered and we kept our eyes on the horizon. The silver lining: extensive published clinical research regarding immunotherapy of cancer patients shows that the patients displaying the most aggressive immune-related adverse events are also the ones who tend to have the best objective tumor responses.

Some breathtaking science led us to create this personalized treatment plan. The tools of diagnosis and treatment are far more advanced than they were a decade ago. Even so, as good as it all sounds on paper, it took a lot of Julie’s courage to continue trusting the same knucklehead (#Husband) who hospitalized her early in her treatment.

Our Journey is now approaching the one-year mark. Julie is clinically stable, active, feels good, walks 3-4 miles per day with occasional Peloton cycling sessions. She is enjoying each day despite the constant presence of her tumor (now lovingly nicknamed “Glio”). In September, Stephanie and Alex made an emotional trip home to celebrate their Mom’s 59th birthday with cake, laughter, and joy.

The big smiles underscore commemoration of a birthday that few people believed Julie would see. Those smiles are a direct result of some incredible and selfless work performed by countless many in our industry. You know who you are, and what you have done. We invite the reader to read “An Open Letter to Team Julie” to learn more about the people and leading-edge science behind Julie’s customized therapeutic protocol. You are all #BeyondGreat. We are forever in your debt.

That said, we are not naïve: GBM has a one-year survival rate around 20 percent with a five-year survival rate in the single digits. The Journey will undoubtedly be tortuous. However, how we live between now and then is not up to a disease. It is up to us. And we get by with a little help from our amazing friends and colleagues in the biopharma and biomedical industries.

Julie and I have increased our focus on spending time with family and friends, and making every day count. In addition, I have come out of retirement and am riding herd to inject significant new scientific and capital resources into brain cancer therapeutics innovation.

Julie’s cancer makes it clear that none of us are guaranteed tomorrow. Be sure to live your life, enjoy each day, and pay it forward if you are able. Julie has embraced her love of photography. Her daily walks are now spent with camera in hand, capturing the turtles, wildflowers, and Great Blue Herons that surround our home. 

One day, there may be no more cards to play – and yet, we will be at the final table. You will know it is us: I will be the player betting all his chips on each hand, and Julie will be right there with me. None of this would be possible without the dedicated people who answer the call every day in our chosen industry.


To follow Scott and Julie’s Journey, visit MissionGBM. At MissionGBM, the objectives are (1) to raise awareness of advances in the development of brain cancer treatment options; and (2) to actively engage worldwide resources to drive innovation and investment to battle brain cancer.


ICYMI – Recommended Reading and Listening for Biotech Innovators

David Shaywitz

Searching for a good listen or an interesting read? Here are my latest suggestions.

Everything is awesome!

Looking for something thoughtful and uplifting? A great place to start is this recent interview with tech VC Marc Andreessen, who discusses, persuasively, why he is still so optimistic about technology. Particularly useful: Andreessen’s ability to contextualize the evolution of technology, including the predictable critique, which as he points out was associated with even such radical advances as the teddy bear and the bicycle (celebrated at this website, “The Pessimist’s Archive”). 

Citing the classic (1966) writing of MIT professor Elting Morrison, Andreessen notes that most transformative technologies go through stages where they’re first ignored, then rationally criticized. When this fails, Morrison says, “the name calling begins.” Of course, as Andreessen acknowledges, every new technology doesn’t represent a good idea – although he argues many failed ideas are simply “too early.”

Marc Andreesen

Famously, Andreessen believes in founder-CEOs (versus professional managers who might assume a CEO role). As Andreessen has presumably discovered, there’s actually a podcast that focuses exclusively on the story of founders – specifically founders who have created businesses that have stood the test of time. The podcast, appropriately called “Founders,” is the brainchild of innovation enthusiast David Senra, and the premise is remarkably simple: Senra reads biographies (often autobiographies) of founders, or essays about founders, and then discusses what he’s learned, in exquisite and engaging detail, week after week. It’s an exceptional resource, and highly recommended.

Surveying the Landscape

At their best, good management consultants leverage their breadth of industry experience to offer relevant insights to perpetually overwhelmed executives trying to keep their heads above water. Three recent contributions (all open access) from McKinsey that are worth your time include:

  • The Helix Report – an assessment of the current state of biopharma, with an eye towards future challenges. The disconnect between areas of pharma focus and areas of unmet need, while not surprising, is one particularly striking finding.  Another: the remarkable growth of companies McKinsey describes as “ecosystem players” – essentially, toolmakers, like Thermo Fisher and Danaher, that provide many of the core technologies upon which pharma relies.

    Anne Klibanski, president and CEO, Mass General Brigham

  • Interview of Dr. Anne Klibanski – a captivating discussion with the CEO of Mass General Brigham. Admittedly, I am somewhat biased – Anne, a distinguished neuroendocrinologist, was my clinical mentor during my endocrinology training at MGH, and is an extraordinary teacher, researcher, clinician, and human being.  The McKinsey interview captures these qualities, as Anne discusses her career journey, and the critical need in both medicine and science for multiple different perspectives, values she authentically lives and has consistently exemplified and championed.
  • AI in biopharma research – perhaps my most ambivalent recommendation of the three. Essentially, the premise of the article is that AI needs to be incorporated into research workflows, and when biopharmas do this, “we have observed significant impact along the value chain.” Since generally biopharmas are just beginning to figure out how to leverage AI systematically in research, I suspect early reports of effective practices may be greatly exaggerated. (See also my last TR piece on the failure of AI, so far, to meaningfully impact the area of greatest need in biopharma – improved translational models.)  Nevertheless, my hunch is that the advice offered by McKinsey is directionally correct: there’s a huge opportunity for biopharmas to incorporate AI systematically in research. It will be particularly interesting to follow the progress at Genentech, where Aviv Regev, formerly of the Broad Institute, is leading early research efforts. She brings what might be called a digitally native mindset to the South San Francisco operation.

Although venture capitalist Bruce Booth left McKinsey years ago, the clarity of his annual Atlas Venture year-in-review presentations does his alma mater proud. This year’s talk – available on YouTube – is once again exemplary, stepping us through the macrotrends and market pressures, and providing insights into how Bruce and the team at Atlas see the opportunity space for future early-stage biotech investments.  One particularly striking slide presented the cash individual large pharmas have on hand; it turns out that J&J and Pfizer are each sitting on around $33B of cash, potentially available for future acquisitions.

Bruce Booth, partner, Atlas Venture

Given the outsized contribution of externally-sourced products to pharma revenue (another remarkable slide), one wonders if this will become another example of accumulated advantage, where those who start with the most to begin with will be best positioned to accrue still more. (Also striking: a slide showing the swarming behavior of biopharmas, in this case, the more than 110 CD-19 CAR-T products in the pipeline).  

Think Different

If there’s one thing business executives and technologists can agree on, it’s that the best way to make progress is to set ambitious goals, then monitor progress, adjusting course as necessary along the way.  Right? Well, maybe not. While this approach may work for relatively straightforward goals, AI scholar Ken Stanley argues, it actually doesn’t really work for super ambitious goals, where we don’t even know what the stepping stones are. “Almost no prerequisite to any major invention was invented with that invention in mind,” Stanley asserts. In essence, he argues – based on captivating examples from AI research – that if you want to achieve something profound, you’re more likely to get there by the pursuit of the interesting; “honor interestingness,” he advises. While this approach may not lead you to a specific goal, it is more likely to lead to something profound than more direct attempts to arrive as the same ambitious destination.  Listen to Stanley make his case in this interview with Patrick O’Shaughnessy, host of “Invest Like The Best,” here.

Bedside Rounds describes itself, accurately, as a podcast “about fascinating stories in clinical medicine.  Hosted by internist Adam Rodman, a hospitalist at Boston’s Beth Israel Deaconess Medical Center, the show offers a thoughtful, humanistic, generally historical perspective on topics in medicine. A pair of recent episodes – here and here – stand out, as they focus on the way doctors have approached and attempted to systematize the collection of information from patients. Rodman is joined on these two episodes by one of medicine’s most gifted diagnosticians, UCSF’s Gurpreet Dhaliwal. Of particular relevance to healthtech readers, Rodman and Dhaliwal describe subtleties of medical data that may not be obvious to data scientists. For example, Dhaliwal describes the difference between information gathered from a questionnaire (for example, a patient checking a box next to the statement “I do not have a fever”) and information Dhaliwal elicits from a patient. Dhaliwal says this is the difference between “building truth with the patient” and “accepting it as a binary construct.” Dhaliwal clearly understands the concept of data empathy — and of empathy more generally.

Most everyone today recognizes the importance of cybersecurity, including in healthcare, as Eric Perakslis, among others, has eloquently reminded us. Even so, we’re not likely to be drawn to podcasts focused on cybersecurity – which is what makes “Click Here” so extraordinary.  Hosted by NPR veteran Dina Temple-Raston (she is also the executive producer), Click Here features captivating, well-constructed narrative-driven stories that relate to cybersecurity, but focus on people, taking us from Ukraine to digital health surveillance to violence-as-a-service (!) to cold war espionage, educating, entertaining, and gently terrifying us along the way, even as we eagerly await the next installment.

Meet Me At Camera 3

As long-time Daily Show fans may remember, when Jon Stewart had an important message to convey with brutal honestly to viewers, he’d urge them to meet him at Camera 3 (see this classic example).   For those seeking this spirit of uncomfortable candor, here are several considerations.

Among the most memorable experiences I’ve had in consulting and in biopharma have been the opportunities to observe, through a one-way mirror, a focus group, individuals who are convened to discuss (in a facilitated conversation) a particular condition or product. Frequently, their actual experiences and priorities are vastly different than what conventional wisdom might have dictated.  You can get a feel for this in “The Focus Group” podcast, featuring political strategist Sarah Longwell. The appeal of the podcast is that it provides a relatively unfiltered opportunity to hear what people actually think, including people you might not typically encounter, discussing perspectives you might not typically hear expressed, on all sides of the political spectrum. 

In the gauzy world of LinkedIn (“… humbled to be honored…”), effusive corporate PR, and giddy entrepreneurs (“crushing it!”), it can be easy to lose perspective on some of the grueling verities of our work. I can imagine no better tonic than this blog post, describing in excruciatingly painful, all-too-familiar detail the preposterous dance biopharmas do with contract research organizations (CROs) in the course of preparing to conduct clinical trials. As we watch the author’s vitality and ambition slowly extinguished by inexorable bureaucratic processes, we share the author’s sentiment that there must be a better way.

Jeffrey Pfeffer, Thomas D. Dee II Professor of Organizational Behavior, Stanford Graduate School of Business

Finally, there is Stanford Professor Jeffrey Pfeffer, who has managed to write a series of utterly essential business books (including Power, Leadership BS, and his latest, 7 Rules of Power) that effectively have been banned from the corporate canon. No HR exec is going to pay thousands of dollars to bring in a distinguished speaker who will tell employees that their bosses probably got there through the skillful deployment of self-serving, often inauthentic behaviors – behaviors the same leaders now actively discourage as they seek to preserve the status quo. It’s not that Pfeffer encourages such distasteful behavior; rather, his view is that if you are, or are planning to be, part of any organization, then the data suggest these are behaviors you are likely to encounter and will need to be ready to handle. Pfeffer offers the critical business books (and now, podcast series) you need, even if – and precisely because – they are the ones you are least likely to be told about by senior management. 


Delivery of Genetic Medicines: Shehnaaz Suliman on The Long Run

Today’s guest on The Long Run is Shehnaaz Suliman.

Shehnaaz is the CEO of Menlo Park, California-based ReCode Therapeutics.

Shehnaaz Suliman, CEO, ReCode Therapeutics

Recode is working on lipid nanoparticles to improve the delivery of genetic medicines. These little packages have made it possible to deliver billions of mRNA COVID vaccines in people’s arms, saving millions of lives.

It’s been two decades of hard work. The strides ahead in delivery have fired imaginations of how to do even more. ReCode is based on technology from the lab of Daniel Siegwart at the University of Texas Southwestern in Dallas, where he and colleagues have worked on a fifth biochemically distinct lipid, in addition to the four commonly used in Moderna’s COVID vaccine, to allow for targeted delivery to tissues and to bypass the liver where so many LNP-delivered therapies end up.

ReCode raised a $120 million Series B extension announced in June 2022, and that money will help advance the work into clinical trials. The first application at ReCode is with mRNA constructs delivered via aerosol to the lungs. It’s starting with primary ciliary dyskinesia, and has another program for cystic fibrosis.

With new therapeutic modalities – antisense, RNA interference, and messenger RNA among them – one of the key lessons of history is the importance of getting delivery right.

It usually takes longer, and requires more creativity, than most people expect.

Shehnaaz comes to this opportunity after overcoming some significant obstacles in life. She grew up in apartheid-era South Africa. She fought against injustice. She saw medicine as a field in which she could address health inequities. She went on to the pharmaceutical industry, and one of the things she did was work to help make life-saving HIV medicines more accessible around the world. Today, she’s using her platform as a biotech CEO to speak up in defense of women’s reproductive rights, and making policies at her company consistent with this view.

Please join me and Shehnaaz Suliman on The Long Run.


It Ain’t Over Til It’s Over

Larry Corey, MD

If you’re still curious about COVID-19, then good for you. Many people apparently have stopped paying attention, but COVID-19 remains a relevant topic.

Here’s where things stand this fall with viral variants and our countermeasures.

We are starting a period of the Omicron epidemic in which the numbering is no longer B1, B2, B3, B4, B5. We’re into the Omicron subvariants—BA.5, BA.4.6, BQ.1.1, BQ.1, BF.7, BA.2.75.2, BA.2.75, BA.4.6., and XBB.

All of this nomenclature which, of course doesn’t make much sense to any of us, indicates that we’re getting the strain variation that we saw in South America early on with Lambda. When you look at the diversity of the viruses with these Omicron subtypes, we’re starting to see some commonality of changes in the spike protein, especially in regions associated with immune escape. This is a phenomenon called convergent evolution. These alterations are happening in many places around the world. Localized variants are acquiring unique but sometimes common mutations, indicating the virus is evolving in an effort to escape immunity.

We’re probably at the time now where we need to just track the mutational changes in the spike protein and give less credibility to the names. What seems more meaningful are the strains that “take over” geographically that have high reproductive rates. Some of these variants possess reproductive numbers that are remarkably fast — similar to what we saw at the beginning of the Omicron wave in November/December 2021. Genomic surveillance is telling us about localized outbreaks such as BQ1.1 in Europe and some parts of the US and XBB in Singapore.

To date, the pattern has been for each local outbreak to grow for a few weeks. These outbreaks appear to be shorter in duration than what we saw with the Delta wave from 2021, and certainly the first part of Omicron.

A Better Prepared Population

This makes sense when you consider the overall increase in COVID-19 immunity in the population. There are fewer and fewer people immunologically naive to SARS-CoV-2; more and more people are seeing reinfection; and more and more reinfections on top of vaccination. The likelihood is that on a population basis, we would see an immune response threshold that cuts down the duration of shedding and therefore a reduced rate of transmissibility. The level of immunity that shuts down transmissibility is now being reached much sooner. I suspect we will see epidemic waves in most countries that are measured in 2 to 3 months rather than 4  to 8 months.

United States, the Outlier?

My one caveat on this is when you consider the United States: we as a country have had sustained outbreaks with each of the variants. Delta lasted a long time, six to nine months; Omicron BA.1, six months; B4/5, six months. Whether we see the peak and fall, like Singapore, or chronic lingering outbreaks this winter remains to be seen.

We’re already seeing this fall, and I predict will be true for winter also, an uptick of what some are already calling the “tridemic” of RSV converging with COVID-19 and the flu. Mask-wearing has gone back to being a stigmatizing behavior and people have gone back to pre-pandemic activity—just walk around any US airport, restaurant, or urban public space.

When kids were wearing masks, RSV and influenza were close to non-existent in the school setting.

Why? Because masks are effective. Now, we’re seeing our pediatric hospitals flooded with RSV because children haven’t had it in two and a half years. Older kids are getting their primary infection, and secondary transmission is occurring in families with higher inoculum loads. Those who are involved in the respiratory care of children, and their parents, are going to have a banner year in taking care of people. And COVID-19 will still be around.

Winter Surge

I suspect that we will see — in mid-to-late December — a pretty significant upswing in hospitalizations and deaths in the adult population mostly related to COVID-19. I fully expect that hospitalizations will go from 3,500 to 7,000 a day and deaths likely from 350 to 600 each day. Some of this may be due to Influenza A and RSV, but most will, in my opinion, be COVID-19/Omicron.

Omicron has silently impacted the very elderly (75 and over) with hospitalizations, especially if they aren’t boosted. So, if we don’t see more uptake of boosting, we’ll see a fair amount of hospitalization and some mortality from Omicron and even perhaps flu, although this year’s flu vaccine seems to be reasonably matched to what we expect to see as the circulating strains of influenza A.

Understanding the population impact between COVID-19, RSV, and influenza will be interesting and valuable. We haven’t had to do that yet because there’s been only COVID-19 the past two winters. Now we have a multifactorial issue.

What about COVID-19 Vaccination?

All the data say that the bivalent vaccine gets you to produce new antibody-producing cells to Omicron strains, and yes, you will also make antibodies to the ancestral strain. But it also starts you off with Omicron B cells. There are data that show a full monovalent Omicron boost gives better antibody magnitude than the bivalent booster, and those neutralizing antibody titers likely that will be matched and surpassed with a second monovalent Omicron boost. Some of the cross-reacting ancestral antibodies still bind to Omicron virions so they might not neutralize, but binding antibodies can also be useful making it less transmissible and in making immune complexes which help enhance T cell responses.

So, I can see no reason not to get vaccinated with the new bivalent vaccine.

People talk a lot about where the next variant will be coming from. In the past, each major variant has come from something we call “saltational” evolution. That means that someone with persistent COVID-19 developed an inadequate immune response and the variant escaped with a large number of mutations. Omicron clearly came from clade C SARS-CoV-2 variant 8 to 12 months after its emergence; it had 18 mutational changes from its nearest relative, and it didn’t have these intermediary cousins prior to its appearance. That indicates it emerged from a single person or a small number of individuals.

What’s the probability of this happening again? We don’t know, but there are precious few SARS-CoV-2 viruses from outside the Omicron family circulating in the world at the moment. It doesn’t mean they aren’t there—and that there isn’t a possibility that another zoonotic jump to humans couldn’t occur—but all of the data suggest that the strains that are going to occur are emanating from Omicron, because it’s the only thing around. Thus, I think we need to concentrate on Omicron. Maybe it can accommodate another massive “saltational jump” of say 10 or more mutations that introduce a dominant new variant; or maybe the virus can sustain this constant evolution to escape from immune responses incrementally.

Monoclonal Antibodies Lost

The biggest danger I see now is the dwindling availability of monoclonal antibodies to treat serious infections. A combination of monoclonal antibodies, tixagevimab and cilgavimab (Evusheld), has been a valuable tool for protecting immune compromised patients.

Unfortunately, it has been lost. The new Omicron subvariants escape it. This is an incredible loss—one that I think has been underappreciated by the public. AstraZeneca’s Evusheld has played a vital role in prophylaxis for the highly immunocompromised patients who will never respond to vaccination. Evusheld has been effective in reducing infections, keeping these people healthy, keeping them out of the hospital, and alive. Many can’t take effective antivirals when they get infected, so they have a double whammy—no response to vaccination and they face potential organ loss because they need to come off immune suppressive medications for extended time periods in order to use Paxlovid. 

I’m concerned. When you look at the monoclonal antibody field, every single monoclonal antibody within the last three years has dropped out: the Lilly monoclonals, bamlanivimab/etesevimab and also bebletovimab; Regeneron’s casirivimab/imdevimab (brand name REGEN-COV); VIR/GSK’s sotrovimab; and now AZ’s Evusheld.

It’s very tough for a company to financially invest in a product that only has a market shelf life of a year or year and a half. The only way we can handle that is to have society—and the government—underwrite the manufacturing of the monoclonals for this important population. Evusheld, at its peak, averaged a million doses a month; and it’s probably been underutilized.

My philosophy for the severely immunocompromised and the frail elderly is to give them effective antibodies; quit flogging them with a vaccine with limited efficacy.

So, settle in this winter, get the Omicron bivalent vaccine booster shot, keep the antivirals close, get tested when you feel sick to determine what you have, and don’t be ashamed to wear a mask. 

Dr. Larry Corey is the leader of the COVID-19 Prevention Network (CoVPN) Operations Center, which was formed by the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health to respond to the global pandemic and the Chair of the ACTIV COVID-19 Vaccine Clinical Trials Working Group. He is a Professor of Medicine and Virology at University of Washington and a Professor in the Vaccine and Infectious Disease Division and past President and Director of Fred Hutchinson Cancer Center.


You Have Chosen … Poorly: Why Drug Developers Make Bad Decisions

David Shaywitz

Drug development remains an incredibly expensive endeavor. Much of the cost can be attributed to late-stage clinical trial failures. 

The burden is borne first and foremost by clinical trial participants who aren’t helped by the experimental medicine. It also significantly impacts the companies sponsoring these studies. Everyone would like to improve the chances that a novel medicine that advances into clinical studies ultimately will prove successful and earn approval from regulators around the world.

Yet the odds of success remain stubbornly low.

What’s the problem? (And: is AI likely to help? We’ll return to this briefly at the end.)

Let’s consider two recent perspectives on the topic.

David Grainger: remove organizational bias

We’ll start with David Grainger, a scientist, entrepreneur and VC (now Venture Advisor) at Medicxi. I’ve admired and discussed Grainger’s work for years (here, here, here). Writing in his always worthwhile “Drug Baron” blog, Grainger argues that drug developers have the data to make much smarter decisions than they actually do; the problem, he suggests, are the biases that consistently lead developers astray.

David Grainger

Among the examples Grainger cites:

Infrastructure bias – “if you have a team of employees, a lease on a building and so forth, it can be painful to call a halt even if the enthusiasm is draining away.”  Since “there nearly always is” some potential path forward, “further investment becomes almost inevitable.”  This is sometimes termed “inertia bias” or “status quo bias,” reflecting our shared tendency to stick with, and justify, decisions we’ve already made.

Narrative bias – the story “that companies, particularly biotechs, tend to weave around their assets to make them palatable to investors.”  Grainer notes the narrative can involve technology (e.g. DNA editing), deep expertise in a particular indication (e.g. endometriosis), or a focus on a particular biological mechanism (e.g. caspases). 

The problem with this thematic approach, Grainger says, is that there can be a reluctance to discontinue development of a lead asset (despite bad data), for fear of besmirching the broader narrative. It can also lead to a failure to consider promising programs outside the narrative, even if they might have a higher probability of success.

Commercial bias – large pharma companies, Grainger observes, “are usually phenomenally good” at sales, adding that “selling drugs, rather than discovering or developing them, is arguably the core competence of the biggest and best in our industry.” Because of commercial commitment to a finite number of areas and indications, Grainger writes, “the ‘gravitational pull’ from the commercial hub starts to dominate R&D decisions.” Thus, to meet the need for new products in a given area, an R&D team may “risk choosing to buy or progress inferior assets, in order to meet that imperative.”

The answer, according to Grainger, is to develop drugs in a strictly asset-focused way, deliberately seeking to avoid the biases he has described.  He’s pursuing this through a Medicixi-backed company called Centessa (he’s the Chief Innovation Officer). 

While Grainger is right about the existence of these biases, such as the drive to fill therapeutic area pipelines, he may underestimate the value that comes from working intensively, over time, in a given therapeutic area, and the expertise and judgement that comes from this hard-won experience. 

It’s reminiscent of the logic that leads some to suggest pharma should ditch research and early development entirely, and just focus on in-licensing promising assets for late-stage development.  The problem, of course, is that if you’re not actively trying to develop your own drugs in a particular area, you tend not to know what you don’t know, and absent this organic expertise – likely including the learning associated with previous failures — your ability to make informed, nuanced decisions can be limited.  Perhaps this might be termed “ignorance bias.”

Another challenge with Grainger’s approach is that bias-free drug development, much like a learning health system, is an entity that’s often discussed, invariably praised, yet rarely if ever seen in the wild.  Blame human nature. 

Grainger, certainly, is as aware of these caveats as anyone. So credit him for not just writing about a solution but actually trying to build and inhabit it. Let’s see how it goes.

Jack Scannell: improve translational models

Next, let’s turn to Jack Scannell, whose thoughtful, scholarly musings on drug development I’ve admired for more than a decade (see here). 

Jack Scannell

In his latest article, in Nature Reviews Drug Discovery, Scannell argues that the key success factor in drug development is “predictive validity” – how well the success of a given preclinical or translational model predicts ultimate success in clinical trials. 

Everyone recognizes predictive validity is important, Scannell acknowledges, but argues we may underestimate just how important.  A slight improvement in the predictive validity of a model  – say increasing the correlation coefficient from 0.5 to 0.6, he says – can “often have a bigger impact on the probability of selecting a clinically useful drug candidate … than a 10x or sometimes a 100x change in the number of candidates tested.”

Phrased differently: if we had the choice, we’d be smarter to invest in a slightly better translational model than in a much larger drug screen.

Scannell points to the exploitation of translational models as one reason why pharma productivity famously declined between 1950 and 2010, despite profound advances in science and technology. 

His argument is that it was precisely the ability to efficiently pursue existing translational models – he cites models of stomach acid secretion as an example – that led to an explosion of effective drugs for these conditions (e.g. H2 receptor antagonists, proton pump inhibitors), medicines that eventually went generic and raised the bar for future products . 

The development of a good translational model can transform therapy, Scannell observes. He points to “the invention of the hepatitis C virus replicons” as an example, noting this approach “made it possible to produce reliable, high-titre, viral RNA replication in cell cultures, and to screen and optimize drugs.”

Pragmatically, what are drug developers to do?  Scannell offers several suggestions, which, as he distilled in an email with me, include:

  • Devote a lot more time and effort to evaluating models and to improving models.
  • Focus on “model-able” diseases (as Vertex does, he says) and avoid those with bad models
  • Think harder about calibrating models and assembling sets of complementary models.
  • Fix financial incentives

The financial incentives comments reflect the observation, developed in the article, that “it is easier to capture financial value from novel drug structures than from novel decision tools,” essentially because “much of the value of the innovation can spill over to other firms at low cost.”  While acknowledging “this is a difficult problem to fix,” Scannell suggests perhaps pre-competitive consortia, focused on developing decision tools (translational models) in areas of shared interest could make sense.

While immediately implementable solutions don’t leap from the pages of Scannell’s manuscript, he is almost certainly right about:

(1) the problem with inadequate predictive translational models;

(2) the undervaluing of incremental improvements in such models; and

(3) the need to pay meticulous attention to the performance of these models; otherwise, it will remain challenging to deploy them thoughtfully and to detect small but meaningful enhancements.

What about AI?

Predictably, neither Grainger nor Scannell believe AI is on the threshold of offering a solution to the fundamental problem in biopharma R&D: the need to increase the odds of success in late-stage clinical development.  

For Grainger, the contribution of bias towards poor decision-making swamps any positive contribution AI might make.  In his view, we don’t need AI – we have the information in hand today to make far better decisions, if only we could disentangle the many entrenched biases.

Scannell, for his part, also doesn’t believe AI is about to revolutionize drug R&D, and cites the work of Andreas Bender (whose work I’ve frequently discussed in this column – see here, here). Bender argues that AI researchers focus on computational models that don’t reflect that actual challenge that’s bedeviling R&D researchers: predicting safety and efficacy in advance of late-phase clinical development. 

Academic researchers, Bender suggests, tend to focus on abstractions of drug development, artificial quantitative models that can be interrogated easily, and which produce publishable results. However, these mathematical models are largely removed from the actual questions and needs of real-world drug development, which tend to be closely enmeshed with the detailed context of the specific project.  (For more on Bender’s arguments, see the slides here, and the references to which he links.)

If AI is to meaningfully impact drug development, Bender contends, we’ll need not just more data overall, but also, data that are directly relevant to the specific needs and nuances of  particular drug development programs. Like Scannell, Bender proposes a role for large precompetitive consortia, though neither sound especially optimistic.

If AI isn’t likely to resolve the fundamental challenge of biopharma R&D, why is there so much excitement around (and investment in) the promise of emerging digital and data technologies? 

Let me briefly suggest several possibilities:

  • As I’ve previously described, the most significant impact of digital and data on biopharma, as in many other industries, appears to be in industrial efficiency, making repeatable processes, from manufacturing to shipping, flow better. Your drug may not have a higher chance of clinical success because of digital technologies (success or failure is largely baked into the molecule by the time it enters clinical studies), but you may find this out faster, and at less cost.
  • Shared visibility of your data can serve as a powerful management tool, helping to align teams around a common set of information, enabling better execution. This appears to have been a critical factor (as I’ve discussed here) in Pfizer’s rapid development of their COVID vaccine.
  • Technologies can help increase patient engagement (for example, in the context of decentralized clinical trials, as Lisa Suennen (now President of Digital and Data Solutions at Canary Medical) and I discussed with Craig Lipset on our Tech Tonics podcast in 2020). Deeper knowledge of patients, coupled with the savvy application of AI, can also enable earlier identification of patients who might benefit from a medication or a relevant clinical trial. One compelling example: a collaboration between the Mayo Clinic, an AI company (Anumana, a spinout of nference), and Janssen’s data science team, led by Najat Khan, revealed that patients with pulmonary artery hypertension could be flagged through a pattern identified by AI on routine electrocardiograms.  This algorithm received a breakthrough device designation from the FDA in May.
  • Improved data management can facilitate the collection and analysis of datasets that can generate future insights. Ideally, data around the predictive validity of translational models, as Scannell has proposed, might be evaluated rigorously, so that the models could be optimized iteratively, and applied thoughtfully.
Bottom Line

A critical challenge for drug developers is to improve their rate of clinical trial success. One cause for the low success rate: organizational biases that lead projects to continue far longer than they should. Another cause: inadequate (poorly predictive) translational models. In the short term at least, digital technologies are unlikely to meaningfully impact the success of clinical development, although programs are likely to be prosecuted more efficiently. Digital technologies are already contributing to drug development in other ways, including promoting alignment through dashboards; making trials more convenient for patients; and facilitating earlier disease diagnosis and patient identification. Eventually, improved data management and the application of appropriate analytics may lead to the generation of insights that truly make drug development smarter, so we can succeed more often, rather than fail more efficiently.


Single-Cell Analysis for Precision Medicine: Tariq Kassum on The Long Run

Today’s guest on The Long Run is Tariq Kassum.

Tariq is the CEO of Cambridge, Mass.-based Celsius Therapeutics.

Tariq Kassum, CEO, Celsius Therapeutics

Celsius emerged on the scene in May 2018 with a $65 million Series A led by Third Rock Ventures. It was built on the conviction that single cell analysis will shed light on new targets for the treatment of cancer, autoimmunity and other diseases.

Single-cell analysis is one of the big trends in biology.

As I wrote about Celsius in December 2020:

Whatever layer of information being looked at – genomics, proteomics, metabolomics – molecular activity comes into sharper resolution with single cell analysis than with traditional techniques that depend on information averaging from samples.

By looking carefully at single cells, gathered from patients with a given disease, Celsius is wagering that it will find abnormalities that can’t be seen by looking at just one particular type of biological information – like genetic mutations.

Four years after its debut, Celsius has a lead program being prepped for clinical trials in 2023. It’s an antibody directed against TREM-1 for the treatment of inflammatory bowel disease. The company also has a partnership with France-based Servier to discover new targets for the treatment of colorectal cancer.

Tariq comes to this challenge with an interesting set of experiences. He’s a physician by training, got early experience on Wall Street, and then made his way into biopharma business development. He’s drawing on those experiences now, in thinking about how to build a company that can take these enabling technologies, and apply them in a clever way to help people who need help.

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

Calgary is home to more than 120 life sciences companies, from emerging startups to established firms. With this critical mass of research, technical talent and expertise, the city is an active hub for life sciences innovation.

Technologies homegrown in Calgary are changing the face of healthcare. Syantra is revolutionizing breast cancer detection using artificial intelligence-derived algorithms. NanoTess is harnessing the power of nanotechnology to tackle chronic wounds and skin conditions. And this is only the beginning. Calgary’s life sciences sector is projected to spend $428 million on digital transformation by 2024.

If you’re a bright mind or bright company solving global health challenges, Calgary is the place for you. 

Take a closer look at why at calgarylifesciences.com

Now, please join me and Tariq Kassum on The Long Run.


Biotech Executives Call for Action on Reproductive Health Rights

Shehnaaz Suliman, CEO, ReCode Therapeutics

Dear Friends and Biopharma colleagues, 

The rapidly approaching midterm elections carry the potential to dramatically reshape the political landscape in myriad ways. The importance of the US Supreme Court’s Dobbs decision in June, overturning Roe v. Wade, looms large. 

At this critical time, we must be clear that Dobbs was about more than abortion

Amanda Banks, MD

With the decision to eliminate a Constitutional right to abortion, a powerful few stripped a majority – women – of the right to make basic decisions affecting their healthcare and their lives. It marks the beginning of a broader loss of autonomy and privacy for all Americans.

As a result, in many states in our country, women no longer have the legal right to openly consult with their doctors, to make decisions informed by facts and receive the best care possible, without their actions subject to criminalization.

Julia Owens, CEO, Ananke Therapeutics

The impact of the Court’s ruling disproportionately affects the least powerful among us: the poor, the less educated, minority women, primarily in historically red states. 

The Dobbs decision undermines essential principles that underpin medical ethics, and that we as a healthcare industry hold as guiding principles: beneficence (doing good), non-maleficence (do no harm), autonomy (giving the patient the freedom to choose for themselves), and justice (ensuring fairness). 

Sheila Gujrathi, Executive Chair and Chair
Ventyx Biosciences, ImmPACT Bio, ADARx

Beyond abortion, this erosion of basic rights impacts miscarriage care, access to birth control and ironically fertility services, and this is just the beginning. As an industry dedicated to improving human health, we stand united in opposition to Dobbs and in support of people impacted by this decision.

In a July 2022 letter signed by hundreds of biotech leaders we emphasized that abortion is reproductive healthcare and denounced the Court’s decision. We emphasized that a woman’s decision to be pregnant or unpregnant are fundamental rights and personal choices.

Today we ask our industry to support four calls to action:

  1. Provide financial support and time off to employees who need to travel to obtain reproductive healthcare services.
  2. For any medicine that has been approved as safe and effective by the FDA for abortion care, treatment of miscarriage, or prevention of pregnancy, we call on FDA to work with sponsors to remove unnecessary barriers to access. Specifically, we call upon the FDA to remove the REMS restrictions for mifepristone, and to allow oral contraceptive pills to be sold over the counter. We commend FDA’s efforts to consider both actions.
  3. Any drug company that manufactures products used for abortion care, treatment of miscarriage, or prevention of pregnancy is called upon to make these medicines as widely accessible as possible.
  4. With the midterm elections upon us, we commit to making accommodations for our employees to take time off to vote.

We cannot, as an industry, or as a nation and regardless of gender, stay silent while our fundamental health rights are negated. By signing this letter, we as individuals and as organizations commit to these calls to action, and to maintaining continuous vigilance in our collective fight to improve human health for all.

The Biotech Sisterhood and Allies


Shehnaaz Suliman, MD


Recode Therapeutics

Amanda Banks, MD

Advisor, Board Member, Physician



Grace Colón, PhD

Former CEO

InCarda Therapeutics

Julia Owens

President & CEO

Ananke Therapeutics

Sheila Gujrathi, MD

Executive Chair and Chair

Ventyx Biosciences, ImmPACT Bio, ADARx


Paula Soteropoulos




Rekha Hemrajani


Jiya Acquisition Corp


Sabrina Martucci Johnson


Daré Bioscience, Inc.

Peter Kolchinsky

Managing Partner

RA Capital Management, LP

Andrew Goldberg

HealthVerity, Inc


Deborah Palestrant


5AM Ventures

Robert Poole 


NW Biomedical Consulting Inc.

Julie Sunderland


Oriane Consulting


Catherine Riesen

VP, Finance

RA Ventures


Rita Balice-Gordon


Muna Therapeutics

Nina Kjellson

General Partner



William Newell

Sutro Biopharma 

Nancy Whiting, PharmD


Recludix Pharma

Rosana Kapeller

President and CEO

ROME Therapeutics 


Amy Burroughs


Cleave Therapeutics

Jeffrey D. Marrazzo

Co-founder and former founding CEO, Spark Therapeutics

Marrazzo Ventures


Jeremy Levin, MD

Chairman and CEO


Daphne Koller

CEO and Founder


Martina Roos



Alex Martin



Samantha Miller

Co-founder and co-CEO

Cadence OTC Inc.


Ramona Doyle MD

Clinical Professor


JeenJoo (JJ) Kang


Appia Bio


Cameron Pitt


Quanta Therapeutics

Art Krieg

Adjunct Professor

UMass Chan Medical School RNA Therapeutics Institute


Samantha S. Truex


Upstream Bio


Alex Harding, MD

SVP Business Development and Corporate Strategy

Remix Therapeutics


Wendye Robbins, MD

President & CEO

Blade Therapeutics, Inc.

Scott Wasserman


Latigo Biotherapeutics, Inc.


Ivana Magovcevic-Liebisch

Vigil Neuroscience

Jodie Morrison

Acting CEO and Board member


Sarah Boyce




Jennifer Beachell


Upstream Bio 


Aoife Brennan



Peter Smith


Remix Therapeutics



Dave Melville


The Bowdoin Group


Carol L. Brosgart, MD

Clinical Professor of Medicine, Biostatistics and Epidemiology


Kate Yen


Auron Therapeutics 

Nancy Stagliano



Joanne Kotz


Jnana Therapeutics 


Yael Weiss


Mahzi Therpaeutics


Hanadie Yousef

CEO and co-founder

Juvena Therapeutics, inc. 

Alice Valder Curran


Hogan Lovells

Simone Azevedo


Xingu Health Inc


Karen Larochelle


LaRochelle Advisors, LLC

Tanya Joseph

Managing Director, Biotech Investment Banking



Ramani Varanasi 

Managing Director

ReVive Advisors


Sarah Kurz


Partner Therapeutics

Blake Wise


Novome Biotechnologies


Shi Yin Foo


Arvada Therapeutics


Deborah S Kelly, MD

Executive Medical Director, Global Risk Mngt & Safety Surveillance

Incyte Corporation


Kristen Fortney

CEO and Co-founder


Carol Marzetta 

Retired biopharma exec



Chris Conley

Biotech Consultant

DNA Consulting

Daniella Ishimaru

Principal Scientist

ReCode Therapeutics, Inc

Samantha S. Truex


Upstream Bio


Christine Zedelmayer


Equillium, Inc. 

Andre Turenne


Matchpoint Therapeutics

Adam Keeney




Kitty Wu

VP, Head of BD and Strategy 

Fosun Pharma USA

Laura Kahn

Executive director of R&D Strategy and Operations

ReCode Therapeutics


Erika Smith


ReNetX Bio


Richard Gaster

Managing Partner

venBio Partners

Eleanor Quin

Senior Director, Total Rewards and People

Totus Medicines

Pamela Michelle Klein, M.D.

Founder and Managing Director

PMK BioConsulting

Nathaniel Horwitz

President (Mayday) & Venture Partner (RA) 

Amber Brown

Chief of Staff

RA Capital

Karla Loken

Disease Area partner 


Laura Berner



Donna Higgins


The Higgins Group Inc


Maria Fardis

Venture Partner



Kenneth Drazan

Chairman & CEO

Arsenal Bio

Caryn Peterson


DSC Associates, LLC

Emily Drabant Conley


Federation Bio


Ashleigh Farver



Jay Hagan


Regulus Therapeutics

Rajeev Shah

Managing Partner

RA Capital Management, LP

Cindy Xiong


Foresite Capital 


Aaron Royston

Managing Partner

venBio Partners

Vickie Capps



Michael Blash

Communications Consultant

BlashComm LLC


Ellen Lubman

Chief Business Officer and Head of Investor Relations

Werewolf Therapeutics, Inc.


Kelly C. Huang

Leadership/Executive Coach

Genesis Advisers


Elaine Sun


Mammoth Biosciences

Clarissa Shen

COO and Board Member

Q Bio, Inc.

Shelia M. Violette

Chief Scientific Officer and Founder

Q32 Bio


Michael Saulnier


RA Capital

Bernat Olle


Vedanta Biosciences

Karl Kieburtz, MD, MPH

Managing Partner

Hoover Brown, LLC

Becki Filice

SVP, Portfolio and Program Leadership



Adam Rosenberg


Aliada Therapeutics

Rene Russo


Xilio Therapeutics


Sarah Reed

General Counsel

RA Capital Management

Mary Thistle


Deborah Geraghty




Safia K Rizvi


CILA Therapeutics, Inc.

Maria Soloveychik




Laure Nucci 

Executive Director, BD



Melissa Shaw

V.P., Legal and IP

Annexon, Inc.

Catherine Stehman-Breen


Chroma Medicine

Asina Gant

Division Counsel

Annexon Biosciences



Melita Sun Jung

Chief Business Officer

Structure Therapeutics Inc.

Jake Simson


RA Capital Management


Phyllis Loud Gray

SVP, Human Resources

Annexon Biosciences


Joseph O’Neill


RA Capital

Karpagam Srinivasan

Associate Director

Alector LLC

Jay Lichter

Managing Director

Avalon Ventures


Laura Stoppel


RA Capital

Cony D Cruz

Venture Partner

RA Ventures

Thomas Culman

Engagement Associate

RA Capital Management


Ernesto Gonzalez Jr.

Senior Business Systems Analyst

RA Capital


Fuad Naser


RA Capital Management

Alex Strasser


RA Capital Management

Daniel Slesinski


RA Capital Management

Megan Lipcsey

Healthcare associate, former physician

RA Capital


Edward Monaghan

Chief Development Officer

Lusaris Therapeutics, Inc.


Meghan Petrowski

Business Operations Manager / Recruiting Coordinator

RA Ventures


Cameron Decker

Research Assistant

RA Capital

Kaleen Sullivan

Sr Research Project Coordinator 

RA Capital


Jack Vailas

Senior Associate

RA Capital

Lauren Walrath

VP, Public Affairs

RA Capital

Jamie Donovan

Executive Assistant

RA Capital

Gunes Bozkurt

Venture Analyst

RA Capital

Simos Simeonidis

co-CEO/co-CIO, Managing Partner

Ally Bridge Group


Zach Scheiner


RA Capital


Nate Davis


RA Capital

Emily Gransky

VP, Head of Recruiting

RA Capital

Anurag Kondapalli


RA Capital

Angela Pontius

VP, Clinical Operations

RA Capital


Julie Hambleton

Retired Pharma/Biotech Executive; Chief Medical Officer

Julie Krop

Chief Medical Officer, PureTech Health


Lori Rudolph-Owen


Senda Biosciences

Diana Bernstein


Northpond Ventures

Jasmine Ferrer

Managing Partner

Korn Ferry


Sharon Ayd



Ekaterine Kortkhonjia

Early Innovation Partnering

Johnson & Johnson

Jennifer Fang


Wilson Sonsini 



Aimee Raleigh

Sr Associate

Atlas Ventures

Alexander Martinez-Forte

Strategic Finance, Analyst

RA Capital

Matthew Hammond


RA Capital



Christina Lilliehook

Scientific Writer

RA Capital

Kate Moreau

Associate Director

RA Capital Management


Priya Patel

Business Development



Gisela Paulsen


Oncocyte Corporation

Gina Patel

President and CEO

Patel Kwan Consultancy LLC

Joanne L Viney


Seismic Therapeutic


Scott Garland


PACT Pharma

Nerissa Kreher

Chief Medical Officer

Entrada Therapeutics

Sophie Chapelle

VP Corporate Development

Sherlock Biosciences


Monica Stanciu

Associate Director, TechAtlas

RA Capital

Kristine C. Mechem

VP Precision Medicine

Health Advances

Derek DiRocco


RA Capital Management


Monika Trzcinska 


Bluestar Bioadvisors 

Kate Haviland


Blueprint Medicines

Cyriac Roeding

Co-founder, CEO

Earli Inc.


Lori Taylor


Annexon Biosciences

Emilie Besnard

Senior Scientist

Dorian Therapeutics 

Erez Chimovits 



Cristina Montero

Associate Director

RA Capital, LP

Leslie J Williams

Founder President & CEO

hC Bioscience, Inc.

Kate Hermans

Interim CEO and President 



Harvey Chan


RA Capital

Bahija Jallal



Katherine Terranova

Healthcare Associate

RA Capital


Maria Radu

Principal Scientist


Robin Toft

Senior Advisor, Boardroom Diversity

ZRG Partners


Rebecca Silberman

Senior Associate

RA Capital


Hilary Malone


Certego Therapeutics

Catherine Flaherty

Executive Assistant

RA Capital


Sevgi Gurkan

Venture Partner and CEO

OrbiMed and Perfuse Therapeutics 


Nikole Kimes


Siolta Therapeutics, Inc.


Michael Varnum

Research Assistant

RA Capital

Mariagrace Houllahan

Executive Assistant

RA Capital Management



Akash Datwani


Shikha Barman, PhD

Founder, President and CEO

Integral BioSystems

Saundra Pelletier


Evofem Biosciences


Dennis A. Dean, II

Principal Investigator

Seven Bridges

Rachel Bedenbaugh

Project Manager – Vaccines

RA Capital

Morgen Alden


FirstThought, LLC


James Schneider

Associate General Counsel

RA Capital

Rachel Haurwitz

President & CEO

Caribou Biosciences, Inc.

Maria Soloveychik




Angie You


Frazier Healthcare and Casdin Capital


Dolca Thomas

Director; Board of Directors


Elizabeth Aluck

Director Biopharma Partnering

Siemens Healthineers


Aetna Wun Trombley


Lycia Therapeutics

Sarah Bhagat

Biotech Investor

Yvonne Linney

Independent Board Member

Bionano Genomics


Bernard Coulie

President & CEO

Pliant Therapeutics

Kate Hermans

Interim CEO and President 


Alyssa Larson

Associate Director

RA Capital 


Amy DuRoss

Senior Advisor 

Frazier Healthcare Partners

Lauren La Rue

Head of Early CMC

GIVAX Inc. (Incubated under RA Capital Management)


David Carter Hoffman

Head of Intellectual Property

Bit Bio Inc.


Elaine Hamm



Osvaldo Flores


Century Therapeutics

Katherine Vega Stultz

President and CEO 

Ocelot Bio


Alana McNulty


Janux Therapeutics

Rhona O’Leary

Senior Vice President, Portfolio Strategy and Execution



Liz Guthridge

Leadership coach

Connect Consulting Group


Michael Curtis



Florian Brand

CEO & Co-Founder

atai Life Sciences

Stephen Klasko

Executive in Residence

General Catalyst


Owen Richfield 

Postdoctoral Fellow

Yale University 

Smriti Jain

Project Manager


Sibylle Hauser

Executive Director, Innovation & Entrepreneurship



Amy Lurier

SVP People and Talent

Carbon Biosviences

Jennifer Kane

Sr Director of PV

Arcus Biosciences

Susan Nemetz

CEO and Founder

The NemetzGroup LLC


Julie Martin Walker






Protein Degraders For Outside the Cell: Aetna Wun Trombley on The Long Run

Today’s guest on The Long Run is Aetna Wun Trombley.

Aetna is the CEO of South San Francisco-based Lycia Therapeutics.

Aetna Wun Trombley, CEO, Lycia Therapeutics

Many in biotech know about targeted protein degraders. Arvinas and Kymera Therapeutics are a couple of the well-known companies that make these drugs which work to inhibit intracellular proteins. This approach has drawn a lot of excitement because it can access previous ‘undruggable’ proteins, by essentially dragging them into the cellular garbage bin.

Fascinating as this is, there are many other proteins that can’t be targeted this way because they are secreted outside cells, or reside on the cell membrane. This requires a different approach. That’s where Lycia comes in.

The company is working on lysosomal targeting chimeras, known as “Lytacs” for short. Carolyn Bertozzi, the chemist who won the Nobel Prize earlier this month, has her fingerprints all over this one. Her team at Stanford University devised a method for binding both a cell surface lysosome targeting receptor and the extracellular domain of a target protein.

That work was posted in a preprint in 2019, and then a year later in Nature. Versant Ventures was among the many groups who read the preprint and wanted to get to work developing a potentially new class of medicines. They agreed to work together, Versant committed $50 million, Aetna was recruited as CEO, and the company was off and running. A little over a year ago, Lycia struck a multi-year research collaboration with Eli Lilly that brought in a $35 million upfront payment.

This is a big idea for drug discovery.

Program note: This conversation was recorded in early September, before Bertozzi won the Nobel Prize for her work on biorthogonal chemistry. Listeners may want to go back and listen to a Long Run podcast I did with Bertozzi in April 2019.

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

Calgary is home to more than 120 life sciences companies, from emerging startups to established firms. With this critical mass of research, technical talent and expertise, the city is an active hub for life sciences innovation.

Technologies homegrown in Calgary are changing the face of healthcare. Syantra is revolutionizing breast cancer detection using artificial intelligence-derived algorithms. NanoTess is harnessing the power of nanotechnology to tackle chronic wounds and skin conditions. And this is only the beginning. Calgary’s life sciences sector is projected to spend $428 million on digital transformation by 2024.

If you’re a bright mind or bright company solving global health challenges, Calgary is the place for you. 

Take a closer look at why at calgarylifesciences.com

Now, please join me and Aetna Wun Trombley on The Long Run.


The Kilimanjaro Climb to Fight Cancer Is Back

Luke Timmerman, founder & editor, Timmerman Report

I’m taking another biotech team to the highest peak in Africa.

Four years after the first team expedition, the Kilimanjaro Climb to Fight Cancer is back with a new crew of 28 biotech executives and investors. Together, we’re going to push ourselves physically, and raise more than $1 million for research at the Fred Hutch Cancer Center.

The expedition is set for Feb. 9-20, 2023.

Most people on the team don’t know each other, and don’t know what it’s like to hike in the thin air of 19,000 feet. A couple are veterans of previous expeditions. Everyone is training to get ready.

They love nature. They love science. They dislike cancer. They are making a big commitment to others in need, raising at least $50,000 apiece.

Here’s who is coming together for this challenging and memorable adventure:

  • Luke Timmerman, founder & editor, Timmerman Report
  • Nathan Trinklein, co-founder and CSO, Rondo Therapeutics
  • Bharatt Chowrira, president, Puretech Health
  • Jens Eckstein, managing partner, Apollo Health Ventures
  • Mark Mendel, venture partner, Sozo Ventures 
  • Wendy Nelson, president and founder, Boston Biotech Forum; corporate development Danforth Advisors
  • Brian Gallagher Jr., biotech investor and entrepreneur
  • Soufiane Aboulhouda, PhD candidate, Church Lab, Wyss Institute, Harvard University, co-founder and president, Nucleate
  • Melinda Richter, global head of Johnson & Johnson Innovation JLABS
  • Paul Biondi, president, Pioneering Medicines at Flagship Pioneering
  • Ben Vollrath, COO, Amprion
  • Ramani Varanasi, managing director, ReVive Advisors
  • Ram Aiyar, CEO, Korro Bio
  • Greg Verdine, co-founder and CEO, LifeMine Therapeutics
  • Kamal Puri, CSO, OncoResponse
  • Nerissa Kreher, chief medical officer, Entrada Therapeutics
  • Saul Fink, SVP, pharmaceutical & nonclinical development, Normunity
  • Alex Federation, co-founder and CEO, Talus Bio
  • Amber Kaplan, consultant, Amber Lab LLC, MBA candidate USC Marshall School of Business
  • Laurie Halloran, founder and CEO, Halloran Consulting Group
  • Joanne Smith-Farrell, CEO, Be Biopharma
  • Jeff Leek, vice president, chief data officer, professor; Fred Hutch Cancer Center
  • Ginger Cooper, associate vice president, Agilent Technologies
  • Jung Choi, chief business and strategy officer, Global Blood Therapeutics
  • Joe Budman, vice president of biology, Vicinitas Therapeutics

The first Kilimanjaro trip in 2019 was a huge success, raising more than $1.5 million for cancer research at Fred Hutch. People on that trip formed lifelong friendships. They open doors for each other.

One of the people from that team summed up the experience:

“The proposition: join Luke and equal numbers of men & women in our industry to raise money for cancer research at the Fred Hutch and climb Mt. Kilimanjaro. This was the experience of a lifetime. Breathtaking scenery – yes. Challenging physically – yes. Outstanding guides & support personnel – yes. Life-long bonding experiences – yes!”  — Bill Newell, CEO, Sutro Biopharma

You can do a couple things to help.

First, go to the Kilimanjaro 2023 team fundraising page on FredHutch.org and find a member of the team you want to support. You can click on their name to open their personal fundraising page, and donate. That will help them hit their $50,000 goal. They’ll appreciate it!

Second, if your company is interested in raising awareness of your support for cancer research, ask us about team sponsorship opportunities. See me at luke@timmermanreport.com and Elizabeth ‘Za’ Martin at eamartin@fredhutch.org.

The biotech community has tremendous capacity for scientific genius and human generosity. When we exercise these muscles, we get stronger.

I’m eager to see what this next Kilimanjaro team, with your help, will do to propel science and improve the lives of cancer patients.

The Kilimanjaro 2023 team