9
Apr
2021

Timmerman Traverse for LSC: A Biotech Community Drive to Fight Poverty

Luke Timmerman, founder & editor, Timmerman Report

Like many people, I’m itching to get outside.

Today, I’m excited to announce a new outdoor experience for a good cause: The Timmerman Traverse for Life Science Cares.

It’s a Presidential Traverse hike scheduled for Sept. 13-15, 2021.

A fantastic group of 20 biotech leaders — 10 women and 10 men — will hit the trails. We’ll cover the iconic 20-mile hike over Mt. Washington, Mt. Adams, and Mt. Jefferson. All told, we’ll experience 8,000 feet of elevation gain up and over 7 summits in the White Mountains of New Hampshire.

Each team member on this trip is committing to raise at least $25,000 for Life Science Cares.

Team goal: $500,000 to fight poverty.

We are well on our way to crushing this goal, with more than $225,000 raised.

For those unfamiliar, Life Science Cares is a fantastic organization that mobilizes the biotech community to support antipoverty nonprofit organizations, education groups and job training programs. The work began in Boston and has now expanded to chapters in Philadelphia, San Diego and the Bay Area.

The inaugural Timmerman Traverse team includes:

This team is showing tremendous spirit in the early days, having already helped secure a deeply committed group of sponsors to support Life Science Cares.

Sponsors:

Mt Washington

 

 

Mt. Jefferson

 

 

Mt. Pierce

 

 

 

Trailhead

 

 

You can show your support a few different ways.

DONATE: Go to the JustGiving.com page for Timmerman Traverse, and find a hiker you know. They’ll appreciate whatever you feel comfortable giving — $100, $500 or $1,000 or more – to help them hit their goal of $25,000.

SPONSOR: If you’re thinking big as an organization, and able to donate between $5,000 and $50,000, you could join that outstanding group of sponsors above. See a team member you know, or contact Sarah MacDonald and Christine Casalini at Life Science Cares for more about sponsorship opportunities.

LACE UP YOUR BOOTS: Would you enjoy an outdoor experience with biotech leaders? Are you willing to work hard to support Life Science Cares? I am compiling a list of alternates, and also gauging interest in future expeditions. luke@timmermanreport.com.

This will be a wonderful way to appreciate nature, give back to community, and build relationships with tremendous biotech people.

Let’s show what the biotech community is capable of when it sets its mind to supporting the most vulnerable members of our society.

The Team

7
Apr
2021

The Long Run Mentality for Diversity and Inclusion in Biotech

Bill Newell, CEO, Sutro Biopharma

I can never forget the video of George Floyd, a black man, being suffocated to death under the knee of a white police officer.

My worldview was changed by it.

As the CEO of a mid-sized public biotech company, I supported equal rights and opportunities. In my day job, it mainly meant hiring and promoting a diverse team, and supporting industry initiatives to promote diversity in employment and in clinical trials. As a citizen, I tried to do things consistent with these values – donating to charities, voting, treating others with respect and decency.

Watching that video and hearing the cries of protest that followed led me to the realization that more needed to be done.

George Floyd’s murder resonated because it cast a spotlight on police brutality that has been going on for so long, against so many of our fellow Black Americans. Too many of us just hadn’t been able to see it, to fully reckon with it, until that video made it impossible to miss.

It changed the way I think about race in America, and how I think about what to do about it within my own sphere of influence as a corporate leader.

The recent spotlight on hate crimes against Asian Americans has further broadened my perspective. I have come to the inescapable conclusion that simply trying to be color blind is no longer enough. 

So, I started a personal change process last summer. I sought to be more proactive, to use my role as a leader to do more to recognize and actively work to tackle systemic racism.

As I discussed this with good friends, one challenged me and others following a similar path.

Could we truly sustain this newly energized engagement for the many years it would take?

To me, the answer is yes. This is the biopharma industry. We need to have a long run mentality to be successful in our work. We can channel that same mentality toward diversity and inclusion in our industry.

Listening & Self-Reflection

Last June at an all hands meeting to discuss George Floyd’s murder and systemic racism, I said this:

I am a 62-year-old well-to-do white male – my life experience is limited in so many ways and even though I like to think I have led a good life where I do not judge anyone by the color of their skin or for any other difference they may have from me – have I? Have I? I have many questions to ask myself about how I have behaved in the past and how I behave today. These are not easy questions to ask oneself, let alone answer. 

Since then, I have found that, while self-reflection is valuable, I also needed new and different inputs. So I have started to learn more about systemic racism, to listen more to different voices, perspectives and histories and to engage in discussions about racism. I can recommend the works of Ibram X. Kendi, including “How to be an Antiracist,” to start. 

If you are interested in diving deeper, our Sutro team has suggested some additional resources on our website (see our Diversity, Inclusion & Social Justice web page).

By continuing to read and learn more about systemic racism, I hope to avoid complacency and to sustain efforts to dismantle it.

Active Engagement & Empowering Others

While not being a racist is important, that alone will never get our society to equality and justice. I believe we should heed Kendi’s call that we should do more, we should be antiracists. That word requires taking actions and engaging actively. 

As a company leader, taking actions and engaging actively are part of my DNA. I have been directly involved in diversity issues on the relevant committees at both BIO and California Life Sciences Association (CLSA), our national and state trade associations.  

The Sutro senior leadership team includes six women. Our 17-person senior team also includes two LGBTQ individuals, three Latinx and three Asian members. Our Board is well on its way to California’s AB 979 compliance with two women directors, one of whom is Board Chair, both of whom are also people of color.

As our company evolves, I am committed to fostering even more diversity across the staff over time.

If one individual can effect change, then how much more impactful is it if many individuals are actively committed to change? 

Leaders of companies can empower others to be change agents as well. We can start by setting policy, and channeling it through the organization with the tone and example we set. 

For example, as we planned our 2021 summer internship program, our team has again set the objective to have a diverse group of interns, including those from economically disadvantaged backgrounds. We intend to have a group of 12 interns, and our diversity goal is 75%.

These interns will work in person where possible, and remotely when necessary, with our staff of approximately 200 employees dedicated to targeted therapies for cancer. It’s a valuable real-life drug development experience for the interns, and an on-ramp for their careers. It’s also an opportunity for us to learn a few things from a younger generation.

We are also working to encourage young people to think about the future possibilities in biotech. Our team has promoted and supported our employees’ participation as volunteers in South San Francisco STEM education.   

We have committed funding to a variety of industry-based initiatives, including CLSA’s Racial & Social Equity Initiative – We Commit to Change. We have supported and sponsored employees to attend educational experiences that broaden their knowledge of systemic racism and healthcare inequalities, such as programming from Impact Experience.

The Importance of Leading Publicly

Is it enough to lean in personally and support efforts by your employees to lean in themselves? I would argue it is not. I believe it is in a company’s best interest, and in society’s best interest, for leaders to be vocal and demonstrate leadership on issues of equality.

Historically, few leaders have been willing to do so. It seemed disconnected from pure business interests. 

Merck CEO Ken Frazier has rejected the notion that equality is not a matter for business leaders to address. He has set an example for us all in recent years. Last summer, he said businesses have to “go beyond just statements” and that “businesses have to use every instrument at their disposal to reduce these barriers that existed.”  

I agree. I have begun to use my and Sutro’s social media platform to reflect and advocate for equality and to denounce inequality. 

Some investors may be uncomfortable seeing that sort of visible leadership. Shouldn’t we keep our heads down? I hope they will come to embrace the wave of environmental, social and governance (ESG) awareness that is growing in the investment community. All of us should be leaning into that wave.

The Long Run & Accountability

There is no simple fix that will end systemic racism. Its roots run deep and are pervasive. Even when we believe we have made progress, as recent events have shown, back sliding happens too easily and too rapidly.

We need to acknowledge that being antiracist is to be on a long run. We need to acknowledge there will always be more to do. That may seem daunting and occasionally discouraging. Even so, I believe our industry’s long run mentality will serve us well as we strive for equality. 

How do I plan to ensure that my efforts at Sutro are sustainable? I believe commitments and accountability are at the core of sustainability.

At Sutro, we have made our commitments public. In coming months, we will add a process of transparency and accountability that will also be public.

We will aspire. We will measure and we will report. We will do so for all to see.  

We are far from perfect. But we are committed to continuous learning and improvement. Progress may come slowly but we are used to that in our industry. 

Let’s remember Lao Tzu: “The journey of a thousand miles begins with a single step.”

Bill Newell is CEO of South San Francisco-based Sutro Biopharma.

5
Apr
2021

The Glory of John Martin: an Understated Leader Who Built a Biotech Powerhouse

Chris Garabedian, chairman and CEO, Xontogeny

John C. Martin was an unassuming man with an ordinary name. But his leadership qualities and accomplishments as a biopharma CEO were extraordinary.

Martin, the CEO of Foster City, Calif.-based Gilead Sciences from 1996 to 2016, didn’t seek to dominate the room or inspire legions with a charismatic personality. He didn’t make the cover of magazines, even when he led the company that did more than any other to transform HIV into a chronic, manageable disease.

When he died last week at age 70, Martin was essentially unknown to the public and not very well understood within his own industry. Yet he left a legacy of having built one of biotech’s most successful and enduring companies.

I’m fortunate to have seen Martin work at close range, and consider him a mentor. When I was serving in several roles as part of a lean and aspirational management team at Gilead in the late 1990s and early 2000s, Martin was the boss. I got to see how he set direction and how the organization responded. Long after I moved on, I saw how this quiet leader continued to envision and execute on the big, long-term strategies that he set in motion in Gilead’s adolescent years.

John C. Martin, former chairman and CEO, Gilead Sciences

Humble Appearances

John did not dress to impress, only donning a conservative suit and tie when it was necessary as a respectful obligation for an important meeting or an investment conference. His business casual attire of neutral colors and pattern-less sport coats seemed intended to not allow any distraction from his words and the ideas he wanted to convey.  

He didn’t focus on selling a future vision of Gilead. He was more likely to be touting the latest approved drug or the importance of a recent company initiative. John didn’t try to persuade with a dynamic or stylized narrative, but rather by clearly communicating a core idea in the simplest and most straight-forward manner possible, often with just a short statement or a Socratic question. 

He was a leader who listened and observed far more than he spoke. When he spoke, he did it with piercing intent.

When John asked you a question in a meeting, it sometimes felt like a test. John likely already knew the answer or had a better answer than what you might muster up. John could make one comment or a short statement in a meeting and change the entire trajectory of the conversation. 

He displayed an efficiency of words that was focused on communicating with clarity about a key concept or an action to be taken. At the end of a meeting with John, there was little room for interpretation or doubt about what to do next.

He was uninterested in the spotlight. He let other executives do the talking for Gilead. He never sought awards. He let the company’s results speak volumes. 

These performance metrics led Harvard Business Review in 2010 to rank Martin #6 in their first edition of “Best Performing CEOs in the World” (Steve Jobs was #1). A few years later, Martin moved up to #2 behind Amazon’s Jeff Bezos.

During John’s tenure, Gilead went from a company valued in the hundreds of millions to one of the few biotech companies to achieve a $100 billion-plus valuation. Today, it’s the second highest-valued biopharma company ranking behind only Amgen.

During my tenure at Gilead (1997-2005), Martin’s office was austere. He worked at a simple uncluttered desk. Framed group photos highlighting Gilead’s history decorated the walls. A few sample bottles of Gilead’s approved products sat on the windowsill. There was a small conference table where I remember weekly tactical meetings would be held with selected members of the management team to go through John’s questions and tasks that he would accumulate over the week and would write down as a to-do list on a yellow legal pad.

If John was not in team meetings or walking around the corporate campus dropping in people’s offices, he was often at his desk tapping away at his laptop. 

I saw his routines out of the corner of my eye. My office was two doors down from John and next door to the “other John,” John F. Milligan – the longtime chief operating officer and eventual CEO of Gilead. Early employees, to make sure they didn’t confuse one for the other, sometimes referred, with brevity, to ‘JCM’ and ‘JFM.’   

I was an early riser, often arriving at work between 6 am and 6:30 am. That meant I was often first in the office. Let me correct that: I was often second, because John was already there. If he wasn’t, it probably meant he was traveling. 

I didn’t want to leave that office next to John, even for a promotion. When I was tasked with leading Gilead Medical Affairs, I was supposed to move to the R&D building where my new boss, Norbert Bischofberger, was located. I dragged my feet for a year, with the lame excuse that I was too busy to move my things to a new office.

A Tireless Work Ethic

John loved to work. One Saturday morning on the day of Gilead’s annual company picnic, a beach event at Half Moon Bay, I stopped by the office in Foster City first to get a little work done. I was surprised to see John in the office. 

I tried to make some small talk, which was always a bit awkward. That wasn’t his forte.

“Are you excited to go to the company picnic?” I asked.

He shrugged. 

“I’d rather be spending the day working, but I guess people are expecting me to be there,” he said. 

John would later be seen at the picnic chatting with employees, watching others play volleyball and eating barbecue. But the small talk of those huddled around him inevitably turned, and as most casual conversations almost always did with John, to the excitement of the work.

Yes, we talked shop at the company picnic.

Never have I experienced anyone with the tireless work ethic and persistent drive as John. His dedication to the vision of Gilead and getting quality products to the patients that needed them was an inspiration to all of us who worked for him. 

John started his career on the science side. He received a PhD in Organic Chemistry from University of Chicago. He then worked at Syntex and Bristol Myers as a medicinal chemist leading antiviral drug programs. 

While at Syntex, he decided to strengthen his business understanding and pursued an MBA in Marketing from Golden Gate University. John’s understanding of business and marketing along with his grounding in antiviral chemistry proved to be a potent combination.

A Strategic Masterstroke

Martin came to work at Gilead in 1990, when it was a startup working on antisense oligonucleotide drug candidates. He was named CEO in 1996. One of the first things he did was drop the antisense oligonucleotide work. The delivery challenges and high cost of goods meant it would probably take 20 years for these therapies to pan out, he reasoned.

That decision to stop doing antisense work was just as important as his decision shortly thereafter to bet the company on antivirals.

While thinking through this strategic pivot, John saw that antiretroviral cocktail therapies were emerging as the most potent weapons yet in the AIDS epidemic. The multi-drug combinations had turned the disease into a manageable chronic condition.

But many of the drugs required multiple pills taken several times throughout the day. Some had to be taken with food, some without. Patients had a pill burden of more than 20 pills taken at multiple time points over the day. Simply scheduling a daily regimen was a burdensome task and made it difficult for patients to fully adhere to prescriptions needed to keep the virus in check.

John unified Gilead around the easy-to-understand vision of “one pill, once a day.” It became the north star for the company. With that vision in mind, Gilead acquired Triangle Pharmaceuticals to obtain a second “backbone” nucleoside analogue to combine with Gilead’s own tenofovir. Rounding out the plan, Gilead formed a collaboration with BMS for the third drug component, the NNRTI efavirenz, and later for another BMS drug, the protease inhibitor atazanavir.

With those pieces in place, Gilead was on its way to dominating the HIV marketplace. Gilead’s drugs worked against the virus. That was clear. But they won in the marketplace because they enriched patient quality of life and made it easier for patients to stick to the instructions on the prescribing label. 

In the mid-90s, almost every pharmaceutical company was seeking a piece of the HIV therapeutics market. Competitors included GSK, BMS, Pfizer, Abbott, Roche, and Merck. But the little biotech from Foster City, California, over the course of a decade, reigned supreme as the world’s largest maker of HIV medicines. 

John didn’t stop there. The next clear goal was to develop or find the best-in-class treatment for HCV (hepatitis C virus). Gilead toiled on this work for more than a decade before acquiring Pharmasset and finishing work on what became the dominant cure for HCV. 

Pricing and access to medicines were perennial thorny issues at Gilead. The critics were relentless and vocal. John handled these issues with aplomb — working methodically behind the scenes. He saw to it that Gilead’s HIV drugs could be manufactured at cost by local manufacturers in developing countries. He pressed teams to develop a pre-exposure prophylaxis, or PrEP, strategy to prevent HIV in high-risk individuals.

He persisted in multiple attempts to diversify Gilead beyond its core antiviral franchises. Not all of these acquisitions were successful – cardiovascular disease and pulmonary hypertension were a couple of areas where Gilead struggled to gain traction.

In his last major act as CEO, Martin oversaw the acquisition of Kite Pharma and its CAR-T platform to strengthen the company’s oncology and cell therapy bona fides. It’s a bold bet on the future that will take years to pay off.

Focus on the Customer

Throughout, John emphasized that Gilead be outward-looking. This was exemplified during the development and commercialization of Gilead’s initial HIV and HBV drugs. John expected that the top researchers and clinicians would personally know the top managers at Gilead. 

John set the example himself. Every month, he would visit clinicians, often with a Gilead sales rep. He used the opportunity to conduct his own market research to help the drive the company’s clinical development pipeline strategy, anticipate objections to product adoption or exploit opportunities to position Gilead’s products more favorably vis-à-vis our competitors. 

My first few months at Gilead were spent traveling the world visiting every top expert HBV clinician to learn about the disease, the current state of treatment and what outcomes would be most meaningful. This was market intel we would use to shape clinical development strategy. 

John hungered for this kind of market knowledge so much, that he wanted it woven into the company’s cultural fabric.

When I was asked to lead Medical Affairs a few months before the introduction of Gilead’s first HIV drug, tenofovir (Viread), John handed me a business card of a physician he had recently met in one of the largest HIV-treating practices in New York’s Greenwich Village. 

Fly to New York the next weekend to meet him, John said. And don’t come back until the doctor agrees to join us as a medical science liaison, he added.

“How do I do that?” I blurted out.

John told me he had planted the seed and that I just needed to convince the doctor that he could impact more patient lives by helping to educate other clinicians on his experience and how they could treat their patients optimally using Gilead’s drugs.

That was the first of many MDs, PhDs and PharmDs that were hired to build credible relationships between Gilead and the medical community.

This close working relationship extended beyond researchers and clinicians to the patient community. While almost every rare disease company knows the power of engaging with patient advocates, John was doing it with many HIV advocates in a thoughtful, sensitive and collaborative manner long before it was vogue. We discussed access, pricing, and feedback on marketing messages.

I took many of these principles with me in meetings with Duchenne Muscular Dystrophy patients and advocates when I later became CEO of Sarepta Therapeutics.

A Man of Ideas

John Martin didn’t feel compelled to show everyone how smart he was, but he had a fierce intellect. He was a man of ideas. It seemed as if his mind never stopped working and he was always 10 steps ahead of everyone else. He read philosophy with practical aims in mind.

A few days after a meeting on organizational effectiveness, John gave me a copy of Nietzsche’s “Beyond Good and Evil.” He explained the dynamics of managers and subordinates and how those in authority are often perceived wrongly in terms of ethics and intention by those who work for them. 

A couple weeks later, I gave him Hobbes’ “Leviathan.” We discussed how to best tame a growing organization and keep it from getting unwieldy and unmanageable. Every discussion of ideas was anchored in application to our day-to-day work. 

There is a long list of Gilead alumni and current employees, like me, who would call John their most influential mentor. While some of us left Gilead prior to John’s departure at the end of 2018 (I left in 2005), there was quite an exodus in recent years of senior leaders who spent the bulk of their careers at Gilead and have now moved on to be CEOs and board members for other companies. They are carrying forward John’s legacy.

John never sought glory, but was glorified by so many of us who knew him and had the pleasure of working with him. Glory is defined in numerous ways but the word most commonly means “high renown or honor won by notable achievements” and “magnificence or great beauty,” as well as “praise, worship and thanksgiving offered to a deity.”  

As I read about his death last week, I realized that his understated and humble style did not allow him to receive the glory that he deserved from the industry that benefited so much from his contributions. But he has provided a tremendous legacy for those that learned from him and a beautiful standard for us to strive toward, to measure ourselves against, and to carry forward.

5
Apr
2021

Compassionate Use Policy Has Everything We Need…Except Policy and Compassion

Daniel McIntyre, biopharma public affairs consultant

Biogen is in a bind. The way it navigates a tricky compassionate use situation today could reverberate across the industry for years to come.

Full disclosure before diving in — I used to work at Biogen, but left there five years ago. I hold the company in high regard, and am hopeful the company will find a way to solve this predicament.

The story centers on tofersen, an antisense oligonucleotide designed to block production of the SOD1 protein that drives a rare type of amyotrophic lateral sclerosis – the neurodegenerative disease also known as Lou Gehrig’s disease. There are no effective drugs for ALS, but there is considerable enthusiasm for this drug candidate – Phase I/II results were published in the New England Journal of Medicine last July.

Biogen’s plan for this ALS treatment has collided with one patient’s desperate battle. Pressure is mounting on Biogen to provide compassionate-use access to the experimental drug for Lisa Stockman Mauriello.

Ms. Stockman Mauriello is a biopharma industry insider, forced by ALS to retire as president of Syneos Health’s public relations, medical communications and advertising agencies.  Her diagnosis came just days after enrollment closed for VALOR, the Phase 3 clinical trial for tofersen (BIIB0067).

Her physician requested the drug under FDA’s expanded access policy and was denied. Ms. Stockman Mauriello then contacted the company directly. Denied again. 

Biogen issued a public statement explaining the reasons for its decision but, by then, a loose coalition of Ms. Stockman Mauriello’s network had mounted a campaign including a Change.org petition (100,000 signatures and counting), national print, broadcast and online media coverage, social media, and an advocacy grassroots movement that has taken on a life of its own.

It’s a heartbreaking situation for Ms. Stockman Mauriello, but simply giving her the drug in this instance isn’t the answer. The concept of providing pre-approval access to investigational therapies has been with us for decades, under the terms Compassionate Use, Expanded Access and more recently Right to Try. It’s followed the usual cycle of outrage-and-amnesia, erupting over therapies for cancer, HIV and, more recently, rare disorders.

Often, an application for compassionate use outside the usual context of a clinical trial is made by a physician to a company on behalf of a single patient. Other times, a formal expanded access program is operated by the sponsor, in which dozens or even hundreds of patients may be eligible to receive a drug prior to when the FDA allows a treatment to be made available on the market. There are other methods that represent a middle ground on the continuum of pre-market access.

And there lies the problem. The process often resembles a game of “hot potato”:  Companies have expressed worries that providing access to experimental drugs outside of controlled clinical trials raises the risk that their drug candidates could be unfairly tainted if the patient has a bad outcome and suspects it was a drug-related adverse event. If that were to happen, then a good drug could be derailed. That would end up harming patients who might otherwise benefit.

Advocacy groups struggle to balance the interests of their broad constituent base — people who generally want to see good new therapies become widely available through FDA approval — against a few desperate members of their communities who want immediate access to the latest experimental compound, no matter the consequences.

Patients desperately seeking help confront a world where the decision on access always seems to be “someone else’s” decision. The FDA has repeatedly stated its support for the concept and has published data to corroborate this support, while stressing the decision to provide therapy under compassionate use is each company’s alone.

It’s sadly ironic that Biogen finds itself in this position. It has been steadfast in ALS drug research and development, even when things didn’t appear to be going well. When Biogen’s previous clinical effort failed, the company shared the community’s anguish. Biogen responded by rededicating its efforts: funding research, supporting a genome mapping project, establishing a research consortium, and doubling down on R&D.

This work sowed the seed of the current challenge. The plight of Lisa Stockman Mauriello shines a light on a problem likely to grow, as public policy fails to keep pace with science, communication and expectations.

This is not just about Biogen and Ms. Stockman Mauriello.

If Biogen can find itself in this predicament, any company working on rare, hard-to-treat diseases can – and likely will. A lack of clear regulatory guidance means that each company will be left to establish its own path for each compound, in each population, at each point in time with little help.

Something must change.

There is no doubt that Biogen wants to do the most good for the most people in the shortest time possible. But those goals are inherently subjective, and there’s no policy framework or consensus on how best to achieve them. Great care is needed to ensure that the process of determining compassionate use is—and is seen as—transparent, resistant to abuse and, at minimum, not unjust.

To begin to think about a clear and consistent policy framework, it helps to ask, what are the critical diseases, drug candidates and patient populations that cry out for a tragically scarce resource to be made available prior to full FDA evaluation and market availability?

  • Start by acknowledging that no one will have “the answer”. Companies must learn the views of those who live with the problem. Insights can be gained here, but no hard answers.
  • Seek good-faith decision criteria based on clinically relevant, transparent and widely recognized factors that reflect the most current knowledge, while eliminating social, economic and other ethically inappropriate factors.
  • Practice ethical behavior in allocation. While no perfect methods exist, there are morally inferior methods of providing treatment that should be rejected – for example, preferential access to a drug based on ability to pay, social status and political connections.
  • Communicate transparently and honestly always. Keep quiet periods as short as possible and speak clearly and with confidence as soon as it is possible to do so.

Any company facing Biogen’s dilemma will have to confront a difficult truth: It is not that there is no right answer to this tragic dilemma; it is that every answer is wrong, one way or another. Deny the application and you look like a cold-hearted corporation. Approve the application, and you run the risk of shooting your company in the foot while potentially harming patients who might otherwise benefit.

Faced with this reality, the search is not for the right answer but rather deciding how to act in a way that is honorable and humane, regardless of the decision. Every company should be paying close attention: It is a horrible state of affairs for one company and one family, but it is likely a harbinger of what is to come for many biotech companies and families. The fact that we have so many excellent treatments in the industry pipeline, especially for rare genetic diseases with no current available treatments, makes situations like this inevitable.

Biogen, a respected biotech pioneer, has the chance to take a pioneering role yet again, this time shaping a future for compassionate use that affirms its core values, and aligning them to the values of current society. This is how we declare the values to be preserved at great cost and those to be sacrificed at equally great cost, in order to be clear about our society’s fundamental character.

I have known Lisa Stockman Mauriello for 30 years. I’m well aware she does not want her life to be seen as more important than others in her circumstances but, as things stand now, it appears to be valued less. For a company so deeply committed to patients and the ALS community, finding a solution for all patients it is working to serve is essential.

Daniel McIntyre was senior vice president of Corporate Affairs for Biogen from 2011 – 2016. He is now a Boston-based public affairs consultant.

5
Apr
2021

COVID-19 Testing: Going to the Dogs?

Mara Aspinall, managing director, BlueStone Venture Partners; professor of the practice, biomedical diagnostics, Arizona State University.

For at least the 15,000 years since the first-known burial of two humans with their dog, dogs and humans have cooperated intimately. Dogs get food and shelter in exchange for performing work they can do uniquely well.

Working dogs use capabilities, such as strength, speed, alertness and willingness to please (trainability).

From the very beginning, it is likely that it has been the dog’s uniquely sensitive sense of smell that is the superpower that fed the relationship, in which dogs help humans by tracking prey, avoiding threats and being willing and able to learn any new smell-related task. 

Estimates are that dogs can detect one particle in 1,012 to 1,015. That is equivalent to detecting a single drop diluted into 13 million gallons of water (i.e. 20 Olympic size swimming pools).

Genie Joseph, dog trainer, Emmy-Award winning filmmaker and Executive Director of The Human-Animal Connection

Dogs achieve this exquisitely sensitive sense of smell with only one-third more smell receptors than humans. The big difference is that evolution has tuned every part of their nervous system and their brains to enable a sense of smell that is up to 1 million times better than humans.

Dog stories are always popular — especially with dog owners! — and several scientific papers from the past year examined whether dogs might be able to help detect COVID-19.

Using dogs in scent detection work is not new. They are used at airports to detect contraband and foods not allowed entry. They are used in prisons to find drugs, cell phones and stashes of cash. They are used by law enforcement to detect drugs, in search and rescue missions, and by the military to find bombs and landmines.

Airports are a logical place to start with dogs attempting to sniff whether a human has COVID-19. A government-sponsored test program at Finland’s Helsinki-Vantaa Airport had dogs examine 4,000 sweat samples on cloth. This way, no direct dog/human contact was required, posing no risk of transmission to the dogs.

When the dogs called out a potential positive case, the passenger was taken to the health office for a follow-up PCR confirmation test.

Officials at the Beirut airport designed a similar experiment. They used the two best of 18 trained dogs to screen 1,680 passengers. Of that cohort, 158 positive cases were found – and  92% of those positive cases were confirmed as positive by PCR.

Negative results were 100% accurate (unpublished results).

“This is very accurate, feasible, cheap, and reproducible,” says Riad Sarkis, a surgeon and researcher at Saint Joseph University in Beirut quoted in a Nature commentary.

Intriguing as the results are, they shouldn’t come as a surprise.

There is a long recent history of reports of canine abilities in diagnosing human cancers, including lung and ovarian cancers and melanoma; as well as clostridium difficile intestinal infection, among others.

Medical alert dogs can anticipate seizures, high or low blood sugar, and perform many other life-saving functions in a companion role. There are many advantages to asking dogs to serve us in this way. Dogs can survey large numbers of people over large areas, results are immediately available and, in a high traffic location such as an airport, one dog can perform hundreds of “tests” per hour.

They don’t cost much either – a little food, water and human companionship can go a long way in a day’s work.

What is it that dogs are actually detecting through smell? The human body is a biological “factory” that changes its internal operations in the presence of disease. These operations emit a dynamic mixture of about 1,000 separate volatile organic compounds (VOCs) in breath, sputum, saliva, feces, urine and in sweat, the chemical composition of which reflects the changed metabolism of cells infected by virus combined with the immune system’s attempts to eradicate it. These volatile organic compounds are what alert the dog to something being amiss.

The biggest differences dogs can detect are between healthy and infected individuals. The specific nature of the infection they’re detecting is less clear to us – they can’t deliver to us a distinct bark for COVID vs. HIV, for instance.

None of the scientific research published to date tries to tease out this cross-reactivity, only asking dogs to distinguish COVID-19 samples from healthy controls. It will be essential to explore how disease-specific canine discrimination is before adopting it as an official COVID-19 identification technique.

Unfortunately, and in spite of strong but intermittent interest by the medical community, there are only small pilot studies and anecdotes because very few scale, controlled studies have been funded and performed. Careful experimental design would be required, but it’s conceivable that a large study could tell us whether dogs can specifically detect a COVID-19 signal in an otherwise “noisy” environment of other potential co-morbidities.

Scientists have a long history of thinking about canine smell. The first scientific paper on canine scent capabilities appeared in Nature in 1887. Since then, interest has ebbed and flowed, but no serious systematic investigation of canine capabilities in medicine has been carried out.

In January, 2021 a brief meta-study found only three original peer-reviewed research papers: Grandjean et al; Jendrny et al; Vesga et al; plus a plan for future research by Robert Jones and colleagues at the London School of Hygiene & Tropical Medicine. All three of these are small proof-of-concept pilot studies, with similar COVID versus healthy controls trial design.

Even in this limited context, however, these studies show promise.

They uniformly concur that dogs are almost as accurate as conventional RTqPCR and about equal to the best antigen tests for COVID-19.

To review:

  • Paula Jendrny and colleagues at University of Veterinary Medicine Hannover in Germany selected eight previously trained detection dogs and spent one week training them with saliva and sputum from positive and negative individuals. (Watch this 37-second video of the dogs in action). Some dogs were better than others. The all-out champion was a 12-year-old retired explosives female who was correct in 96% of 115 trials. Overall, all eight together correctly identified 157 of 190 true positives and 792 of 822 true negatives for a sensitivity of 83% and specificity of 96%. In other words, positives were 84% correct (Positive Predictive Value — PPV) and negatives were 96% correct (Negative Predictive Value–NPV). This is not RTqPCR territory in terms of gold-standard accuracy, but it’s well-within the range of accuracy we see with single-use antigen tests. It is likely that volatile organic compounds (VOC) generation is correlated with viral load and infectivity so, in a small feasibility study like this, we cannot know how many of the false positives were pre-symptomatic or asymptomatic true positives, nor to what extent reported false negatives were caused by later post-infection patients who were no longer contagious.
  • Omar Vesga and colleagues at Hospital Universitario San Vicente Fundación in Medellín, Colombia selected six non-working dogs of three different breeds and trained them for a longer time period – 49 days in all. The testing set up was less automated, but the results were consistent with but even better than achieved by Jendrny: 95% sensitivity; 100% specificity; 86% PPV; and 100% NPV.
  • Dominique Grandjean and colleagues at the national veterinary school at the University of Paris studied auxiliary sweat (armpit) carried out in three separate locations with eight experienced search and rescue or explosive detection dogs. Reported accuracy was high: Four of the eight dogs made no errors in 176 trials, and the others were correct in 83-94% of 192 trials.  Interestingly, two of the seemingly “false” positives were referred back to the patients’ hospitals and were found to be positive on RTqPCR re-testing.

Since the dawn of the scientific age, humans have discounted canine help with tasks connected to clinical diagnosis. Our new tools of the molecular biology age must be vastly superior to a dog’s scent, right?

In certain cases, yes.

Then again, seeing results like those above begs a question — why, after 134 years of interest and investigation, has essentially no progress been made on systematically using dogs to help us detect disease? 

It is broadly acknowledged that dogs accurately sense human distress and disease, even the changes of scent that distinguish stress from an innate inflammatory response. But can they be trained to detect the very subtle differences between human pathologies, and can they do it sufficiently consistently, repeatedly and accurately? 

Can they do this with COVID-19?

Increasingly, the answer appears to be “yes.” Dogs are already patrolling high-traffic public spaces today. Adding COVID-19 testing to their work would be a highly cost-effective and practical solution that could allow a return to some degree of normalcy.

2
Apr
2021

Building An Easy On-Ramp For Consumer Fitness

David Shaywitz

A comprehensive 2018 review of the scientific literature commissioned by the Department of Health and Human Services reported that physical activity not only helps you “sleep better, feel better, and function better,” but also “reduces the risk of a large number of diseases and conditions,” including dementia, hypertension, diabetes, and a range of cancers.

The report specifically highlights the benefits to individuals who “perform no or little moderate-to-vigorous physical activity.” 

Just adding light-intensity physical activity, the report notes, “reduces the risk of all-cause mortality, cardiovascular disease incidence and mortality, and the incidence of type 2 diabetes.” Similarly, sedentary individuals who gradually add at least some moderate intensity physical activity “can reduce their health risks.”

(Moderate intensity activities like brisk walking, gardening, and biking under 10 MPH raise your heart rate but still allow conversation; vigorous intensity activities like hiking uphill or running are difficult to do while talking. Light intensity activities include cooking and walking at a leisurely pace.)

This again leads us back to the opportunity of digital fitness, technology platforms like Peloton that seem incredibly good at engaging and motivating users – but generally users who already are at least “exercise-curious,” and often trying to decide between one form of exercise and another.

But how do you motivate exercise in the first place?

I had the chance this week to pose this question directly to executives from three leading digital fitness companies, at a Wharton digital fitness panel moderated by legendary Wharton marketing professor (and self-described fitness enthusiast) Americus Reed. You can watch a recording here.

Americus Reed, Whitney M. Young Jr. Professor
Professor of Marketing, University of Pennsylvania Wharton School of Business

The companies represented were Nike (in the context of their digital platforms like the popular Nike running club app), Tonal (the digital strength training company that just this week announced a $250M series E raise, at an associated valuation of $1.6B), and WHOOP (the physiological parameter monitoring company used by many elite athletes; Lisa Suennen and I interviewed the founder, Will Ahmed, on Tech Tonics in 2016, here.

The question I submitted, and posed by Reed to the group, was, as I recently discussed, how these platforms think about reaching beyond the already-athletic, to speak to “future former couch potatoes.”

Chris Stadler, head of marketing at Tonal, frames the opportunity this way: “76% of Americans,” he says, “believe strength training is important,” yet most don’t do it. 

Why not?

“Most of them,” Stadler continues, “are either intimidated to go to the gym or don’t have the equipment or knowledge to strength train at home. [The traditional equipment required is] big and bulky.” By enabling strength training from the privacy and comfort of home, and using equipment that occupies a much smaller footprint, he believes Tonal can serve this unmet need. 

This seems logical, though I imagine it’s one thing for survey respondents to passively agree with a statement asserting “strength training is important” and quite another for that same person to feel sufficiently motivated to consider it for themselves. 

Kristen Holmes, the VP of Performance Science at WHOOP, highlighted the health-promoting values she sees in the rich physiological data (including heart rate variability, respiratory rate, sleep dynamics) the program offers.   

This information provides “the keys to the kingdom,” Holmes said, adding, “To the extent that you can understand how your body’s adapting, you increase longevity, you stave off disease, you have higher level of cognitive functioning, physical functioning….”

Fundamentally, Holmes argues, “this isn’t just about athletic performance. This is about owning your health. That is 100 percent what this is about. And every human is responsible for owning their health.”

The hope of improving performance through rich personal data sounds a lot like what drove many “quantified selfers” to embrace wearables a decade ago; yet many (such as, famously, Wired editor Chris Anderson) were disappointed by the lack of utility and value. 

As reviewers of WHOOP such as Mashable’s Tim Marcin point out, there may be too much data for the casual user, leading to what he described as “information overload.” Others have cautioned about confusing information with insight, and worry the platform over-extrapolates from the data it collects, leading to oversimplified conclusions and recommendations.  

In short, while WHOOP may highlight the benefit outside of sports to general users, it’s not immediately clear that the casual user, and particularly the sedentary user, would gravitate to, benefit from, or enjoy this powerful data collection and analysis platform.

In Reed’s framing of the original question, there are three segments to consider: “super hardcore athletes,” “people that are interested in wellness,” and “a group of people who are even before the interest in wellness.” 

This third group, in principle, could benefit the most from activity, and it wasn’t yet clear to me how the emerging technology platforms were speaking to them. 

Then there was Nike.

At first, I had considered it charmingly old school to include a speaker — Vikas Mehta, the CFO of Nike’s $15B direct to consumer business — from this (relatively) venerable shoe company.

Vikas Mehta, chief financial officer, Nike Direct

But as he spoke, I was reminded that this popular consumer brand, famous for encouraging us to “just do it,” clearly knows a thing or two about how to attract and bring into the fold even the most sedentary among us.

According to Mehta, Nike is especially focused on targeting three important population segments: kids, women, and the underserved. 

Kids, he pointed out, have been moving less and less since the pandemic began. It’s also in childhood where life-long interest in and attitudes towards activity may be first formed. The Nike apps offer specific programs for parent/son and parent/daughter dyads, to encourage intergenerational participation.

Mehta also seemed concerned about ensuring women remain engaged in athletics, engagement Nike seeks to sustain and promote with its app. Mehta was particularly pleased to report that during the pandemic, more women than men reported completing runs on the Nike App.

Finally, Mehta emphasized the importance of engagement with underserved communities, and the need to create “resources and opportunities where we can see a higher involvement.”

While reflecting on what was said, I was reminded of the same dialog we hear about digital in the context of biopharma. 

Digital technology offers tremendous potential to transform the industry, but who will drive the change? Will it be digitally-native upstarts, who really understand their technology, and hope to find a focused, useful application, or will it be the incumbent behemoths, who have extensive experience in drug development, and are trying to figure out how to adapt to and embrace the new, less familiar digital technologies.

It’s difficult — especially as someone already excited about fitness — not to be intrigued by the sexy, tech-enabled, still somewhat niche offerings of WHOOP and Tonal, but from a population health perspective, you can’t help but think companies like Nike and Apple may be onto something.

I’m especially intrigued and excited by the promise of pilot efforts like Time To Walk, offered by Apple Fitness+. I can easily envision this deliberately constructed audio walk accompaniment expanding into an important “fitness media” category of its own, including video (including VR) as well as audio; this has exceptional promise for sustained consumer engagement.

Finally, it’s interesting to think how companies might encourage consumers to progressively ramp up their participation and engagement. Peloton provides a particularly informative example of how this might work. While of course best known for their expensive stationary bikes (and associated, engaging classes), they have expanded not only to include other expensive exercise machines like their treadmill, but, significantly, to welcome consumers who may not own any exercise equipment. 

Peloton bike owners need to fork over about $39 a month to subscribe to classes, but anyone can subscribe to the Peloton app for $13/month. This app, like its competitor, the Apple Fitness+ app, offers a range of exercises for all levels of users. Moreover, to get the most out of the Apple app, you need an Apple Watch; Peloton, one imagines, hopes to use the standalone app to draw users in, then collect the big money later on, when the customers are engaged, motivated, and ready to upgrade.

As captured so vividly by Reed’s palpable excitement, this is a remarkably exciting moment for digital fitness – and perhaps, ultimately, for population health. The sheer volume of chronic disease – heart disease, diabetes, depression and more – shows us the value in even a little bit of prevention that could come from improved physical fitness.

It’s encouraging to see the velocity and variety of innovation, embracing software and hardware, technology and media. It will be even more encouraging to see these technologies impact our happiness and health at scale.

31
Mar
2021

Asian Americans in Biotech: Breaking the Silence

Nancy Hong, managing director, RiverVest Venture Partners

As a first generation Asian-American working in biotech in San Diego, I identified with the many good points in Kevin Kwok’s piece on Mar. 9 about the rise in hate crimes.

Fast forward to the end of March, and we have seen more horrific attacks. The element of race (and gender) in these attacks is sometimes overtly declared; at other times it’s an unavoidable subtext. But the pattern is clear.

There were the shootings in Atlanta. Then came reports of violent attacks in New York, including one against an elderly Asian American woman on a sidewalk while witnesses stood by and did nothing.

As Kevin wrote here, many Asian Americans have remained silent for reasons that are deeply ingrained in family and the immigrant experience. But as he said, silence doesn’t mean everything is OK.

Today more and more Asian Americans are bringing an end to the silence. We are thinking about what to do.

A fellow investor, Dave Lu at Hyphen Capital, has organized 1,000 Asian American business leaders to sign on to his effort to show ourselves, see each other, and take positive action against Asian hate.

This group has bought a full-page ad in the Wall Street Journal today and created a website, standwithasianamericans.com. Our goal is to build public support, both through the power of names attached to prominent companies in the US and the dollars to organize. We are asking allies to join us in this effort. Zoom, DoorDash, Peloton, BMS, JNJ are already there – it would be great to add some more biopharma names as well.

To me, the question boils down to the American dream, which isn’t so much about buying a home with a white picket fence (sadly too expensive for too many today).

Instead, it’s about meritocracy. Which America do we believe in, the one where your talents and spirit drive your achievements or the one that uses racism to devalue other humans and hold them back? I believe the biotech community sees how immensely difficult our goal to improve human health is and largely welcomes people from all over the world to the challenge.

There are biases at work, some overt and some implicit. We have work to do. Have we conquered microaggressions, hiring for fit as a code for lack of diversity, bias against non-native English speakers, or even the (over)reliance on past performance when predicting future success?

All of these tendencies reinforce the status quo – supporting the people in power and those who look like them. These biases undermine a true meritocracy.

These problems are deeply embedded in our broader culture. It’s not a problem we can outsource to one activist group or another. It takes conscious behavior change in school, work, government and organizations of all kinds. Biopharma’s mission is to use science to alleviate suffering of all people. It’s a humanistic enterprise at the core. This work includes us.

Friendly reminder to colleagues: while we go about our work creating and testing new medical treatments, remember your Asian American colleagues — people who often play crucial roles in this work — may be feeling unsafe.

As a California resident surrounded by plenty of Asians, I think I may have been in denial until recently about the rising tide of anti-Asian hostility in the US. I bought into a “safety in numbers” mindset. It’s a feeling of security knowing people are used to seeing a lot of Asian Americans. That clearly doesn’t work if bystanders are not around or unable or unwilling to help in a moment of crisis.

Since these most recent attacks, I took off the blinders. I have heard from Asian friends about hate incidents — way too many hate incidents — even where I live in sunny, chill San Diego.

Please consider checking in on your Asian American co-worker to lend a caring ear or other show of support. Showing some empathy is a start. It’s meaningful.

The pandemic has broken down some walls between work and home. This might be a good time to send some love to your fellow human at work, even if you can’t yet give your colleague a hug. I know I’ve had some despondent moments, when this rising tide of hate feels overwhelming.

The care I have lately received from fellow biotech people has buoyed my mood and helped renew my hope for the America I cherish.

29
Mar
2021

Flying Blind on the Origin of a Pandemic

Ruth Etzioni, Full Member, Division of Public Health Sciences, Fred Hutch Cancer Center

I was always curious. 

An early elementary school memory is my mother returning from a parent-teacher conference to report that my teacher thought I had “an enquiring mind.”

Curiosity is what led me to a life of research, as a biostatistician and population scientist. Because in research, the questions you ask are just as important as their answers. The questions I ask have to do with the inevitable gaps in evidence that get in the way of making well-informed medical decisions. 

So I am having a hard time fathoming why people around me are not more curious about how on earth this pandemic began. Without knowing where the SARS-CoV-2 virus came from or how it began to infect people, it’s hard to be strategic about preventing the next pandemic.

The standard explanation is that the virus started in a bat, a bat transmitted the virus to another animal, and then at some point the virus began to infect humans. Scientists call this a zoonotic event, transmission of a pathogen from animals to humans.

But there are gaps in the evidence.

A recent New York Times article by Thomas Friedman titled, “One Year Later, We Still Have No Plan to Prevent the Next Pandemic,” focuses squarely on the illicit wildlife trade and how it facilitates the leap of viruses from wildlife to humans. While Friedman interviews some wildlife veterinarians, the prevailing zoonotic explanation involves an intermediate animal host.

Virologists believe an intermediate species is critical, because bat viruses need to have an opportunity to adapt so that they are able to infect and transmit between non-native species such as humans.

But natural zoonosis is not the only possible explanation. 

Another explanation is that the SARS-CoV-2 virus could have accidentally escaped from a laboratory. This was posited by former CDC director Robert Redfield in an interview with CNN’s medical correspondent, Dr. Sanjay Gupta. It’s his view, Redfield said, the virus escaped from a lab in Wuhan where genetic research was being done on coronaviruses.

Although Redfield is not alone in suggesting lab escape, the newly published WHO report termed this possibility “highly unlikely.” And CNN immediately labeled his comments as “a controversial theory without evidence.” Other media outlets were quick to jump in to the fray, dismissing Redfield’s assertion as “baseless.”

Since theory, evidence and likelihood are my bread and butter, I started thinking about whether CNN’s characterization was appropriate. What is a theory? What is evidence? And how would one even begin to assess how likely any explanation might be when thinking about how the pandemic began?

My goal is not to try and convince you about what happened, because I don’t know. Rather, I hope to convince you that the question is important, that the evidence about every explanation is lacking, and that healthy curiosity is warranted. 

Like many of you I spent hours every day last year reading news stories and research articles about the coronavirus, yet I saw relatively little about the question of its origins, at least in the mainstream media. 

That may be changing. More voices are clamoring for answers. In addition to CNN’s reporting, CBS just aired a 60 Minutes segment, “What happened in Wuhan? Why questions still linger on the origin of the coronavirus.” (Watch segment here).

According to Merriam-Webster, a theory is “a hypothesis assumed for the sake of argument or investigation,” or “an unproved assumption.” But both zoonosis and lab escape are more than assumptions. Rather, they are potential explanations that are made plausible by our experience in other settings.

Avian influenza viruses have been definitively isolated from animals, shown via genetic sequencing to be the source of human infections among exposed individuals such as poultry workers, and then implicated in human-to-human transmission as household members and other contacts of these workers have fallen ill.

Lab escape, even from supposedly secure facilities working with dangerous and highly contagious pathogens, has been documented in labs across the globe. As it turns out, there was a lab — the Wuhan Institute of Virology — doing genetic research on bat coronaviruses just a few miles away from the wet market originally suspected to be the site where the zoonotic leap happened. 

Evidence, on the other hand, is defined by Merriam-Webster rather vaguely, as, “something that furnishes proof.” The Oxford Dictionary is more specific here, defining evidence as, “facts, signs, or objects that make you believe that something is true.”

Here things get fuzzy. 

While bats are known to harbor coronaviruses, the original bat virus that was the definitive source has not been found, there is no clear sequencing trail that matches what has informed our understanding of avian influenza, and there is no identified intermediate host. Civet cats were implicated as the source of the 2002 SARS-CoV-1 outbreak, and were immediately considered suspects this time around, along with pangolins, mink, and ferrets. 

More than a year into this pandemic, none of the extensive sampling of animals at the market has yielded any useful “facts, signs or objects” that would have confirmed the market to be ground zero. So far, that natural zoonosis generated the pandemic seems therefore to be largely an argument of precedent — it happened before so it could happen again.

Records from the Wuhan lab and its collaborators have been blocked from the scientific community so any evidence that might confirm a lab escape as being the source of the pandemic is missing. Documentation of the types of bat viruses being held in the Wuhan Institute of Virology and the experiments being conducted there would be useful “facts, signs or objects” that could discredit or support this explanation.

We just don’t know, because these data are being kept away from the international scientific community. While lab escape has precedence in other settings, in this case the argument seems to be largely one of mechanism — the existence of such a lab could have led to a chain of events that could have seeded a pandemic.

When evidence is lacking, uncertainty reigns, and it becomes natural to start thinking in terms of probabilities. The new report from the WHO calls the lab escape explanation highly unlikely and dismisses it as the least plausible of four possible explanations. (The report finds natural zoonosis to be most likely despite the evidence gaps.) But whether something is likely or unlikely is an assessment of probability.

To know the probability of lab escape would require meticulous documentation of the number of times per year such escapes happen – in labs like the the one in Wuhan and, more specifically in the Wuhan lab itself.  The number of escapes would need to be normalized by the number of pathogens being handled or experiments being carried out, further complicating the calculation. There is no register of lab escapes and there likely never will be.

And to know the probability of a zoonotic event seeding a coronavirus pandemic like the one we are still living through would require identifying all possible encounters of humans with animals carrying such viruses and counting the ones that succeeded – not only in infecting humans but infecting humans in a manner that makes them contagious to one another. It’s hard to imagine getting any idea of this probability.

In summary, we have at least two origins for the pandemic that are more than theories. One seems to rest largely on precedent, the other on mechanism. Both are lacking definitive evidence.  And the likelihood of either is impossible to assess. 

Are you curious yet?

29
Mar
2021

Writing with DNA at Scale: Emily Leproust on The Long Run

Today’s guest on The Long Run is Emily Leproust.

Emily is the co-founder and CEO of South San Francisco-based Twist Bioscience. It’s a DNA synthesis company. It uses a silicon-based system to “write” in the language of DNA – that is, make synthetic genes to test ideas in a lab, or to perform some basic biomedical or industrial workhorse function.

Emily Leproust, co-founder and CEO, Twist Bioscience

Many people have heard of “reading” DNA with high-speed, low-cost sequencing. That opens up a lot of possibilities in biotech. Fewer may be familiar with the “writing” part, but it goes hand-in-hand.

Twist Bioscience has been on a wild growth run. The 52-week range for the stock is between $25 and $214. Investors can debate what the right near-term valuation ought to be, but there’s no question there’s a secular trend in the upward direction, in which Twist is a key enabler of both medical and industrial progress.

In this episode, Emily talks about her life story growing up in France, coming to America to become a scientist, and then becoming a scientific entrepreneur.

Enjoy this episode with Emily Leproust on The Long Run.

28
Mar
2021

Needed: Planet Fitness for The Digital World

David Shaywitz

Digital platforms such as Peloton and Tonal have clearly learned how to use emerging technologies to cultivate healthy exercise habits and a loyal base of fitness-focused customers.

These same technologies would seem ideally suited – if presented in the right way – to coax more people off the couch in the first place. 

This represents an enormous health — and market — opportunity, as well as a notoriously difficult challenge, one that remains largely unsolved.

The digital fitness world I see reminds me so much of the academic sports medicine and “human performance lab” world: inhabited largely by the already-fit and exercise committed. 

The concern is whether there’s something a bit hermetic about this – if you spend your life living among the fit and fit-obsessed, it may be easy to lose touch with the many who avoid exercise but desperately could use some. 

Research efforts aimed at exploring and extending the extremes of human fitness, say, or reducing injuries in athletes may uncover principles and insights that apply to the rest of us, but there may also be important learnings that require dedicated focus on the exercise-avoidant, who are unlikely to find their way into a sports medicine clinical center.

To adapt a phrase, and a mindset, from Pete Buttigieg: both sports medicine and digital fitness need to spend a lot more time thinking about how to embrace “future former couch potatoes.”

Pete Buttigieg, Secretary of Transportation

While campaigning for the 2020 Democratic nomination for President (he now serves in the Biden Administration as Transportation Secretary), Buttigieg famously emphasized the importance of speaking not just to Democrats and swing voters, but also to traditional GOP voters – or as he termed them, “future former Republicans.” 

For Buttigieg, this wasn’t just a slogan but a strategy. Unlike the many candidates from both parties who tended to cling to media perceived as friendly, Buttigieg enthusiastically, and deliberately, appeared on Fox, for example, which he described as an opportunity to get in front of voters who might not otherwise have a chance to hear his views directly.

The analogy to fitness feels especially apt. While nominally embracing all comers, many digital fitness platforms – and sport medicine researchers – remind me of the Republicans who do appearance after appearance on Fox, or the Democrats doing the same on MSNBC or CNN. In both cases, the politicians are targeting their appeal to viewers most likely to respond. 

While I understand the appeal of such “fan service” from a business perspective (essentially, the customer acquisition cost is far lower), ultimately both industry growth and population-level health impact will require broadening the outreach.

Moreover, unlike with politics, where evidence suggests we cling incredibly tightly to political affiliation as a core part of our identity, fitness status identification is likely to prove far more malleable. Many exercise-avoidant people, I suspect, might be even happier to re-identify themselves as exercise initiates if they found an activity that sufficiently engaged them.

In summary, from a health perspective, it seems like there’s a huge segment of the population that could benefit from digital fitness if only they were deliberately approached.

Remarkably, the view from Wall Street seems strikingly similar. 

Aarti Kapoor, who follows the health and wellness space closely at a top investment bank (you can catch an enlightening discussion with her here) tells me that “the majority of institutional capital over the last few years has gone towards digital fitness concepts in the premium segment, which are targeting consumers who are already focused on fitness (if not ‘fitness enthusiasts’ or athletes).” 

The category has attracted significant interest from investors. In 2020 alone,” Kapoor reports, “digital fitness concepts that received significant capital investments included Hydrow (June 2020), Mirror (June 2020), Tempo (July 2020), Tonal (September 2020), Zwift (September 2020), Strava (November 2020), and Echelon (December 2020) among others.” 

She notes that most of these companies sell a platform that requires “a hefty multi-thousand dollar upfront purchase of equipment / hardware followed by ongoing monthly subscription fees.” 

Wirecutter (the go-to product review website, owned by New York Times) reports similar figures, noting that between the initial equipment cost and recurring monthly subscription feeds, “Becoming a member of the Peloton pack is an investment: roughly $2,500 for the first year and nearly $500 each year thereafter. And that’s for the base model.”

Kapoor adds that institutional investors were comfortable with these companies because the investors felt that “the ‘sunk cost’ of the upfront hardware purchase … makes for a stickier consumer base in the long-term.” 

In contrast, she points out, institutional investors remain wary of digital fitness offerings that involve “content only” (i.e. no equipment like a Peloton bike). While content-only offerings come in at a more manageable price point for customers, and are relatively easy to scale, Kapoor says investors worry these products won’t be especially sticky, leading to lots of churn as customers surf from platform to platform to platform.  

One brick-and-mortar company that has done incredibly well by targeting first-time fitness customers is Planet Fitness. Kapoor says the company has built “robust brand equity on the premise of a welcoming, non-intimidating environment (coined the ‘Judgment Free Zone’).” 

According to Kapoor, Planet Fitness, with more than 2,000 locations and more than 15.5 million members, “has demonstrated an unmatched ability to offer broad demographic appeal catering to 80% of the U.S. population that does not belong to a gym — for example, approximately 35% of new members have indicated that they are first-time gymgoers.”

Planet Fitness relies both on local marketing as well as a well-conceived national campaign that astutely targets new customers through commercials that position the brand as an approachable alternative to competitive boutique cycling classes (this “Bike of shame” ad) and high-end gyms populated by buff narcissists (this “Mirror guy” ad).

Looking at the category as a whole, Kapoor ultimately lands on the exact question that I’ve been fixating on: “Where is the Planet Fitness of the digital world?” 

Such an offering, in targeting “future former couch potatoes,” seems remarkably promising from both the perspective of both health and economics. 

It’s an opportunity that’s in plain sight, for those who are looking.

27
Mar
2021

Digital Health: From Pharma To…Fitness?

David Shaywitz

Astute TR readers might have noticed that I’ve been writing a lot about digital fitness lately, in contrast to digital pharma. 

This is deliberate, and represents an evolution of my thinking.

I was first drawn to digital health over a decade ago, in the context of a translational medicine training program for medical scientists that I developed with Dr. Denny Ausiello at Massachusetts General Hospital.  This initiative was called PASTEUR – Patient-Associated Science: Training, Education, Understanding, and Research. The core tenet was an emphasis on the patient-participant in medical science.  Our tagline was “Our patients as partners in discovery.”

Our focus on better understanding the patient experience led us to an early interest in digital health and digital technologies. Here seemed like an excellent way to connect with patients, leveraging their smartphones and other digital tools to help advance clinical understanding and accelerate biomedical discovery. We established CATCH – the Center for Assessment Technology and Continuous Health — to explore applications of these emerging technologies.

When I moved to California in 2010 for a biotech role, I was also really excited about the opportunity to immerse myself in the culture and expertise of the Valley.  I was especially eager to explore how my sense of the needs of healthcare matched up with the possibilities afforded by the emerging technologies that were being developed all around me.  You couldn’t grab a coffee in town without overhearing energetic pitches and animated discussions; so many smart engineers and entrepreneurs were seeking to extend technology into new markets, including healthcare.

Yet I was struck almost immediately by what felt like a disconnect between my understanding of biology and medicine and the view that seemed so prevalent out here, a solutionist perspective that often underestimated the messiness of biology, the deep humanity of medicine, and the often perverse market incentives of various healthcare stakeholders. I said as much in 2011, with a shot across the bow entitled “What Silicon Valley Doesn’t Understand About Medicine,” and have returned to this theme quite often since.

The potential for digital technologies in healthcare remains extraordinary – and extraordinarily difficult to harness, at least in some of the areas we care most about: using digital technologies to come up with important new drugs, on the pharma side, and iteratively leveraging experience to continuously improve the care of patients (the ideal of the learning healthcare system), on the care delivery side. 

Despite some important, authentic progress (protein folding prediction comes to mind) – and an almost unfathomable amount of extravagant expectation and incessant, endlessly escalating hype, the goals remain largely aspirational, as Derek Lowe, in particular, has expertly chronicled.

In a range of roles – including chief medical officer of a healthtech startup, senior partner at a pharma corporate venture group to which I tried (unsuccessfully) to add a digital vertical, and my current work advising senior pharma execs about digital and data – I’ve developed a deep appreciation of how difficult it is to bring emerging digital technology into legacy organizations. Change is hard. Especially at more senior levels, pharma tends to be extremely cautious and skeptical.

I’ve come away with a particular sense of awe and admiration for the digital/data champions within pharma organizations, who often have nominal, high-level organizational blessing but typically very little ground-level buy-in.  Not only are their efforts often received with polite skepticism, but when something does succeed, there are often others who immediately rush in to take credit. This is the exact response to innovation Safi Bahcall describes perfectly in Loonshots

It’s also, by the way, exactly – exactly – the same thing I’ve heard from top doctors working in leading tech companies.

Stanford Business School professor Jeffery Pfeffer would surely shake his head knowingly and say this represents typical organizational power dynamics. As usual, Pfeffer would be right. The inconvenient truth: if you’re a data science person in a biopharma organization, or a medical person in a tech company, you can find yourself without a meaningful power base, and struggle accordingly.

I remain extremely bullish on the long-term opportunity for digital and data in biopharma and healthcare, though it promises to remain a brutal and painful struggle for the next decade. The good news – the best news – is that we are beginning to train a cohort of physician/data-scientists and biologist/data-scientists, experts who are intrinsically bilingual and who recognize and incorporate data science as an intrinsic and vital component of the medical science of the future.

Erik Reinertsen, director of data science and engineering, Prometheus Biosciences

An example in biopharma is Dr. Erik Reinertsen, a whip-smart physician/data scientist from Emory and Georgia Tech who interned with me in venture capital, went on to do some fine work at the Broad Institute, and is now leading data science efforts at Prometheus Biosciences.

Or consider Dr. Griffin Weber, a physician-data-scientist from Harvard and a standout example in care delivery who Lisa Suennen and I interviewed on our last Tech Tonics episode.

Perhaps not surprisingly, my advisory work has tended to focus less on product strategy than on organizational executive coaching, and I plan to continue counseling data science champions within biopharmas. 

At the same time, I am finding myself increasingly drawn to consumer health in general, and digital fitness in particular, as it seems to represent an expression of digital health that is already positively and palpably impacting lives – right now, today — and seems poised to meaningfully impact so many more people in the future.

Griffin Weber, Associate Professor of Medicine, Beth Israel Deaconess Medical Center
Associate Professor of Biomedical Informatics, Harvard Medical School

It’s difficult not to be struck by the foundational role regular exercise plays in the lives of so many physicians, scientists, and entrepreneurs I know and admire – and the role exercise has played in my own life – including helping me lose 80 pounds several years ago (and keep it off), as well as helping me stay both fit and centered during this last tumultuous pandemic year.

I’ve also been impressed both by the engagement so many have with exercise, as well as by the opportunity that exists to use technology to bring exercise and a sense of community to the many people who’d benefit from exercise but find it difficult or daunting.

The opportunity to leverage emerging digital technologies to improve both physical and mental health by offering engaging and compelling fitness experiences seems too powerful to ignore, and too promising to be reserved only for those who are already athletic.   

For years, doctors have advised their patients to exercise more, with almost zero expectation that anyone actually would. As Harvard anthropologist Daniel Lieberman points out in Exercised, we didn’t evolve to pursue pointless activity. 

Even so, the many physical and psychological benefits associated with exercise (after all, we didn’t evolve to sit at desks all day long either) suggest the wisdom of this timeless medical advice. 

The challenge and the opportunity before us: leveraging digital fitness technology to turn the tedium of prescriptive exercise into engaging, delightful, and healthy activity.

We can do this. Eye of the tiger.

25
Mar
2021

Can Digital Fitness Extend Beyond Hardy Base To Reach Those Who May Benefit Most?

David Shaywitz

Whether you are an “exercist,” who relentlessly talks up the benefits of regular exercise to anyone who will listen, or instead are like the vast majority of people and conscientiously avoid exercise, you will find something appealing in the recently published Exercised, by Harvard anthropologist Daniel Lieberman.

Those who assiduously avoid unnecessary exertion – pretty much the definition of exercise – turn out to have years of evolution on their side. According to Lieberman, “let’s go strenuously exert ourselves for the next half hour, just for the heck of it” is a sentiment no living creature has ever expressed (at least until quite recently). 

Instead, movement was always purpose driven – to find food, escape predators, procreate, celebrate, socialize. No wonder, then, that few are thrilled to hop on a treadmill and plod drearily, step by tedious step, to absolutely nowhere.

On the other hand, throughout the history of our species, a lot of activity was baked into life –including through old age.  (Yes, old age. “Contrary to the widespread assumptions that hunter-gatherers die young,” Lieberman writes, “foragers who survive the precarious first few years of infancy are most likely to live to be 68-78 years old.”)  

Today, with the ubiquity (at least in the United States) of electricity, running water, and grocery stores, you can meet many of your essential needs with little physical effort. 

The problem, Lieberman argues, is that there is now an overwhelming amount of data pointing out that exercise is good for you – really, really good for you. While not a magic bullet (cue Jim Fixx invocation, as Lieberman dutifully acknowledges), exercise seems to help forestall a surprising range of diseases, and can improve cognitive performance (including perhaps through improved sleep) and elevate your overall sense of well-being.

While the mechanisms underlying these benefits remain to be worked out (unless you accept the reductionist explanations offered by Lieberman, which I suspect even he might acknowledge are frequently tidy and simplistic), the underlying message is compelling. 

As Lieberman summarizes, Michael Pollan style:

  • “Make exercise necessary and fun
  • Do mostly cardio but also some weights
  • Some is better than none
  • Keep it up as you age.”

Given the pronounced benefits of exercise across the lifespan – and the particular benefit for those who may be older, less fit, or both – it seems mystifying that leading digital fitness programs seem intent on targeting primarily those who are young and already fit, or at worst, fit-adjacent. The toned models who famously (or infamously) grace Peloton ads are clearly positioned as aspirational examples – “This could be you if you sign up today!”

While some non-exercisers have surely been inspired to join Peloton, many users (especially during the pandemic) would otherwise be exercising in a boutique class. Home cycling may be more convenient, but it’s attracting many of the same customers, or at least seems to be pulling from the same pool of (relatively young, fit — and affluent) customers.

My mind keeps returning to the vast majority of people to whom these ads are clearly not speaking, and who, when they see these ads, are likely put off by and discouraged by depictions of such dissimilar people.

Yet many of these same disaffected viewers, as Lieberman reminds us, could benefit profoundly from exercising more, and while fancy digital fitness equipment is hardly required, the ability of technology to afford users an engaging, compelling experience and a sense of community also should be utilized to serve the enormous population of older and/or less fit customers as well. 

This feels like an obvious and compelling business and health opportunity that so far seems to have been all but ignored.

One physician who has locked onto this need is Dr. James Beckerman, a cardiologist in Oregon who I knew from my internal medicine training at Massachusetts General Hospital in Boston, although we had largely lost track of each other since then. It turns out, he is now focusing his efforts on encouraging exercise and building communities – including an inspirational and apparently highly impactful effort known as “Heart to Start.”

As you watch this video – and you should – not only will you feel authentically inspired, but the contrast between the very real participants in this video, and those featured in the typical digital fitness commercial couldn’t be more striking.

(And if you find yourself thinking “Gosh this could be the basis for a TED talk,” turns out – you’re right. Beckerman gave one on the topic, in 2017 – enjoy it here.)

You don’t have to be Yenta the Matchmaker to see the possibilities. 

  • Imagine if the cutting-edge technology that has delivered transformative products like Peloton could be channeled toward the millions of far less fit people who might be interested in getting healthier.
  • Imagine also that such a platform could help foster the sense of community and connection that Beckerman’s participants clearly savor — and that Peloton’s current user base, for example, already enjoys.
  • Imagine what could be accomplished just by bringing these existing technologies to an established population – the remarkable possibilities for the health and well-being of participants. 
  • Imagine the upside for the business able to deliver this.

Seems time to stop imagining and start working.

25
Mar
2021

A Glimpse Into a Price-Controlled Future

Luke Timmerman, founder & editor, Timmerman Report

Imagine if H.R. 3 — the drug price-control bill that has significant support in the House of Representatives — were to become law.

What would it look like if some of the bill’s provisions, like indexing US prices to 120 percent of prices in Europe, were enacted?

How would entrepreneurs adapt? What types of drug discovery programs might be prioritized, and which ones cast aside as impractical? How would management teams have to adjust their strategy, and pitches, to successfully attract investors? How would certain patient groups be affected? What would it mean for the sector?

There are many questions. It’s fascinating, when you dig in, to think through the implications of this thought experiment.

Students at the University of Texas Southwestern Medical Center were challenged to think along these lines through a business plan competition on Mar. 20. Small teams of postdocs, grad students and MBAs were asked to think of a product profile, a relevant disease indication, and — assuming success in clinical development and regulatory approval — a price that could withstand the hard calculations of Incremental Cost-Effectiveness Ratios (ICER) and Quality-Adjusted Life Years (QALY).

The goal was to come out with an investment pitch that investors might buy into.

RA Capital Management, the Office for Technology Development at UTSW, Biotech+ Hub at Pegasus Park and McKinsey supported the competition. RA Capital managing partner Peter Kolchinsky served as a judge with Jeb Keiper, CEO of Nimbus Therapeutics, and Sara Nayeem, partner at Avoro Ventures. I observed.

The students clearly did their homework.

The results were eye-opening.

One group imagined it had an antibody-drug conjugate for lung cancer that delivered an 85 percent Complete Response rate, few side effects, and an average improvement in life expectancy of 10-11 years. Such a drug could be administered for about two years on average, and priced at $210,000 a year in Europe and $250,000 a year in the US, they figured. At that price, the fictional company would beat existing PD-1 inhibitors from Merck and Bristol Myers Squibb on a QALY-based comparison.

Kolchinsky shook his head. Sure, payers would pay for that. But there is no such drug on the market, or in R&D.

Peter Kolchinsky, managing partner, RA Capital

“We never see this kind of efficacy,” Kolchinsky told the students. Turning to his fellow judges, he said: “What they are asking us to do is stop investing in plausible, realistic science and start investing in fantasy.”

Another group sized up a new treatment for irritable bowel syndrome with constipation or diarrhea, and imagined generating three times as much sales volume in Europe to make up for an anticipated shortfall in the US.

Next came a team with an mRNA vaccine for HIV that elicits broadly neutralizing antibodies. The students thought the vaccine could be given to everyone in the US. They considered a low price for a national population and a higher price for a subpopulation deemed to be “high risk.”

The team concluded that it didn’t make sense to develop such a product as a low-volume/high-priced ($9,000) product for the high risk population. Forget about it.

A few days later, I asked the judges to reflect. How were students forced to adapt to the new environment? What did it tell us?

Kolchinsky wrote:

“The participants made an admirable effort, but every single team was forced to make unrealistic assumptions to try to make their business pitches seem fundable despite the limitations of price controls.

“A lot of the submissions were based on actual drugs in development by real companies. But the actual programs are funded because those companies and investors have an expectation that, if successful, those drugs will get reimbursed at prices close to those drugs we have on the market now, which are all higher than prices that HR-3 would allow. And when these teams tried to win funding for these programs but asked investors to accept a much lower price, they couldn’t. Some teams resorted to asking the judges to imagine that these drugs were better than they actually were, had a higher chance of succeeding that they actually have, or would treat more patients than could possibly be true. Bottom line, price controls killed investment in the R&D that is actually possible and forced teams to resort to making promises they couldn’t keep…”

If health economists who run conventional cost-effectiveness are put in charge of setting price, innovators probably won’t be able to win funding from any knowledgeable investors. There may some investors who fall for a pitch claiming a high probability of success and larger market than is real, but in time they will lose enough money to realize the price controls set rewards too low for the risks involved in making new medicines.”

Jeb Keiper, CEO, Nimbus Therapeutics

Jeb Keiper of Nimbus said the pressures would cause entrepreneurs to overpromise. “Like snake oil salesmen, [they] promise a cure in every bottle,” he said. “The constraints forced business plan competitors’ strategies to subvert price-control legislation by promising miracles.” 

That was one survival strategy. The winning team had a different plan. It pitched a reformulation of a proven drug. But in a hostile pricing environment, the students said they would need to accept a lower valuation in the next funding round — crushing the ownership stakes of earlier investors.

Keiper ruefully asked the team who was the CEO. That person would likely be fired.

“The implications are chilling,” Keiper wrote. “Existing biotech investors (including large scale mutual funds and pensions which many Americans have their savings in) get gutted, new medicines stop being developed for patients that need them, and the public only gets incremental improvements that industry watchdogs rightly hound against.”

Pain would be spread among entrepreneurs, investors, and patients. The patients most likely to bear the brunt, though, would be ones with the greatest needs.

Sara Nayeem, partner, Avoro Ventures

Sara Nayeem of Avoro Ventures wrote:

“Drug development for diseases where there have been many historic failures would be especially hard to fund.  For instance, pancreatic cancer is a devastating diagnosis for which we need breakthrough drugs; but because the historical probability of success is much lower than in other areas of oncology (per BIO, a drug for pancreatic cancer entering Phase 1 trials has only a 1.1% chance of approval), investors would need to know that a drug that shows needle-moving efficacy would be reimbursed at a higher price than the average cancer drug…groups like ICER don’t take into account the low success rates in certain diseases; nor do they quantify the value to society into perpetuity of branded drugs going generic.”

Some readers might think this boils down to the same old industry talking points about price controls causing investment to dry up.

But the students weren’t trying to score political points. They were imagining a future drug pricing environment, and trying to prepare.

It was a useful and humbling exercise. Lawmakers would be wise to think a few steps ahead, like this, when considering big changes to a complex market like this with so much at stake.

That’s not to say we should slavishly stick with the status quo. Biotech as an industry is creative and resilient under pressure. Management teams were forced to cut expenses and operate in more lean ways in the Great Recession years of 2008-2012. People in Congress warned the Affordable Care Act would crush incentives for innovation. That didn’t happen.

Instead, a crop of battle-tested, productive companies emerged. We have reaped the harvest of those innovations from the early 2010s. Year by year, the FDA approvals tell the story.

Markets have their vicissitudes. But the secular trend in biomedicine is upward. There’s a lot here in academia, government and industry that’s worth preserving and building upon.

Our elected leaders ought to guide regulations and set guardrails that keep companies honest, with an eye toward preserving a dynamic environment where startups can come along and knock off incumbents.

Kolchinsky, in his book “The Great American Drug Deal,” advocates for contractual genericization as one way to provide balance to pharmaceutical markets that are too often dominated by companies with incentives to primarily protect aging franchises. Many of these aging franchises should have gone generic years ago. Too many drugs, because of patenting games or other perverse incentives that involve middlemen, command sky-high prices that can’t be justified. All of these shenanigans end up wasting money, harming patients and discouraging entrepreneurs.

This publication believes in standing up for the proverbial little guy. Policymakers, health economists, and industry leaders should take action to rein in the excesses of the big guys, without forgetting that little guy (or gal) with a startup dream. That person should have an incentive, and a chance. That person shouldn’t become collateral damage.

If we want to create an environment where scientific entrepreneurs can flourish, we can do it. With scalpels, not sledgehammers.

 

Damaged Public Trust

If you missed Tuesday’s Frontpoints, it predicted this week’s AstraZeneca vaccine debacle. The NIH statement of Mar. 23 pointed out the company’s press release claiming 79 percent efficacy was based on outdated data. The NYT and Washington Post got ahold of a seething letter from the Data Safety Monitoring Board. AZ tried to do some damage control in a revised press release on Mar. 25, which dragged efficacy down to 76 percent. Given the company’s recent pattern of bad behavior and incompetence, I plan to read every line of the FDA briefing documents, and listen to every minute of the FDA advisory committee hearing for this vaccine candidate.

This is a test. Regulators, doing their jobs, will go over everything with a fine-toothed comb and review the application with full transparency. Then we can make informed decisions.

A lot of leeway has been granted to companies in this emergency, born from necessity and a generous spirit of “we’re all in this together.” Some standards about not doing science by press release, and not accepting company statements at face value, have gone out the window in the name of expediency. We put a lot of trust in companies and they have mostly delivered the past year.

But when a company abuses trust repeatedly, the credibility of science and industry itself gets called into question. AstraZeneca needs to make things right. This isn’t one of those cases where PR window dressing or a carpet-bombing of advertisements will make controversy go away. They need to fix things.

This Week in Drug Pricing

Are you a biopharma executive who breathed a sigh of relief about how the drug pricing pit bulls snarling at the industry have been neutered during the glory days of vaccine development?

Not so fast. Public opinion can be fickle.

The AZ imbroglio (see above) feeds into the confirmation bias of the industry’s harshest critics. While a majority are grateful for the vaccines, we still have perverse incentives in our health insurance system, healthcare profiteering, millions of our most vulnerable are being left in the cold, and we still have an information commons that downgrades fact-based discourse and amplifies conspiracy mongering.

Without systemic fixes to how we pay for healthcare — and how we provide fair access to healthcare for everyone — we could easily fall back into the brain-dead rhetorical rut about sticking it to those evil price-gouging drugmakers.

See this NYT op-ed, headlined “Taxpayers Fund Research and Drug Companies Make a Fortune” in which a patient advocate imagines a day when COVID-19 vaccines might cost money (the horror!).

I agree individuals shouldn’t be paying out of pocket for this most valuable preventive medicine. We should be paying for it with our tax dollars. We should be grateful about it because we’re getting an amazing bargain from vaccines that will get the global economy moving again and bring tremendous peace of mind.

Science Policy

President Biden is showing vision and guts. Who says we can’t solve problems, so why bother trying? Biden isn’t buying that nihilistic garbage. He’s acting like a young man in a hurry. Let’s ask serious questions that citizens in a serious participatory democracy ought to ask. Like whether we invest enough in science as a country. What more could we be doing to advance cures, fight climate change, and create meaningful career opportunities for younger generations?

A big investment like the one suggested below inspire a new generation to be drawn to science, and to value science.

Science Features
  • Pandemic whistle-blower: we need a non-political way to track viruses. Interview with Rick Bright. Nature. Mar. 19. (Amy Maxmen)
  • What scientists do and don’t know about the Oxford–AstraZeneca COVID vaccine. Nature. Mar. 24. (Smriti Mallapaty and Ewen Callaway)
  • Unlocking the COVID Code. NYT Magazine. Mar. 25. (Jon Gertner)
Science of SARS-CoV-2
  • Dynamics of SARS-CoV-2 neutralising antibody responses and duration of immunity: a longitudinal study. The Lancet Microbe. Mar. 23. (Wan Chia et al Duke-NUS Medical School, Singapore)
  • Early Evidence of the Effect of SARS-CoV-2 Vaccine at One Medical Center. NEJM. Mar. 23. (William Daniel et al UT Southwestern)
Data That Mattered

Bristol Myers Squibb said it met the primary endpoint – progression free survival — in a Phase III clinical trial with its LAG-3 targeting antibody, relatlimab, in combination with nivolumab (Opdivo), the PD-1 directed antibody. The study looked at patients newly diagnosed with metastatic or unresectable melanoma. Overall survival data aren’t yet available. It’s the first time a checkpoint inhibitor for LAG-3 has passed a pivotal study.

Financings

Eric Schmidt, the former Google CEO, donated $150 million to establish a new center at the Broad Institute to support machine learning analysis of emerging biological datasets, including next-generation DNA sequencing, single-cell genomics, and advanced medical imaging. The Schmidt Center will be co-directed by Caroline Uhler, Associate Professor of Electrical Engineering and Computer Science and the Institute for Data, Systems, and Society at MIT and an associate member of the Broad Institute; and Anthony Philippakis, Broad’s chief data officer. 

Rivervest Venture Partners, with offices in St. Louis and San Diego, said it raised $275 million for Fund V to invest in early stage biopharma and medical device companies.

Seattle-based Eliem Therapeutics raised $80 million in a Series A financing led by RA Capital Management to develop treatments for chronic pain and depression. (TR coverage).

Emeryville, Calif.-based Zymergen, an industrial biotech company, filed an IPO prospectus to raise up to $100 million.

Cambridge, Mass.-based Apnimed raised $25 million in a Series B financing to develop a once-daily oral pill for obstructive sleep apnea. Morningside Ventures led.

San Francisco-based Ginger said it raised $100 million in a Series E financing led by Blackstone to improve mental healthcare offerings for employers, health plans, and strategic partners. (TR Frontpoints column on mental health, Mar. 4, 2021)

Cambridge, Mass.-based 1910 Genetics said it raised $26 million to advance its technology to design small molecules and protein drugs with AI and automated tools. M12 – Microsoft’s Venture Fund and Playground Global co-led.

Personnel File

Moncef Slaoui, the former head of R&D at GSK and leader of the Operation Warp Speed program for COVID-19 vaccines, was fired from the board of a GSK / Verily entity (Galvani Bioelectronics), and stepped down immediately from a new job as chief scientific officer of Centessa Pharmaceuticals, after GSK said it had learned of sexual harassment allegations and an outside law firm investigated the claim.

Amy Abernethy, the principal deputy commissioner of the FDA, will step down from her position next month. She has overseen a push to modernize the agency’s data practices.

Novartis said it’s closing down a factory in Colorado where it was planning to manufacture Zolgensma, the gene therapy for spinal muscular atrophy type 1. The company plans to shut down the plant in July, and lay off 400 workers. It apparently overestimated demand for the therapy, which it obtained through the acquisition of AveXis for $8.7 billion. (FiercePharma coverage).

Atul Dandekar joined South San Francisco-based Maze Therapeutics, a precision medicine company, as chief strategy officer. (TR coverage of Maze, Feb. 2019)

Josh Makower was named the new director of the Stanford Byers Center for Biodesign. He replaces the legendary founder of the center, Paul Yock, a medical device innovator. Makower will retain a relationship with NEA, in keeping with the center’s longstanding focus on academic-industry partnerships.

Merck promoted Caroline Litchfield from treasurer to CFO. She replaces Robert Davis, who is being promoted to president on Apr. 1 as part of a succession plan for him to take over from Ken Frazier as CEO on July 1.

Regulatory Action

Takeda Pharmaceuticals said its submitted an application for its dengue vaccine to regulators in Europe, and in dengue-endemic countries.

Our Shared Humanity

Bruce Booth of Atlas Venture wrote an unusually personal piece on his LifeSciVC blog Mar. 16. I let some time pass before asking him about the feedback from this article about divorce.

It was a rare example of a powerful business leader showing vulnerability.

If you missed it, this is a message that bears repeating. We should all try to be a little more empathetic to friends and colleagues at work who may be stressed by personal issues just beneath the surface. By listening a little more, and extending some understanding and grace, we do ourselves a favor and everyone around us.

I was really happy to hear Booth tell me yesterday that the feedback has been “uniformly positive.”

Hundreds of emails poured in. These weren’t the usual “Hey, nice article” notes that writers sometimes get.

Many of these correspondents got specific and personal, Booth said.

“They went on for paragraphs about a sick kid, a sick spouse, feeling unable to talk about it at work. There were other people who went through divorces, and talked about making it through. They were just sharing their stories. I got very emotional reading all the responses. It was really powerful.”

It took courage to write the article.

We men are taught to be brave from an early age, in a gladiatorial, competitive sense. Never let ‘em see you sweat. Bullies on the playground will bury you at the slightest hint of “weakness.” But at some point in life, we realize that “putting on your game face” at work, as Booth put it, isn’t always a show of strength.

Showing some vulnerability, and allowing people to be human beings with each other in your midst, can be a source of leadership strength.

The positive reaction to Booth’s article lifts my spirits. It reminds me that people in this industry are capable of many good things, in science and beyond.

22
Mar
2021

AZ Tells Us Its Vaccine is OK. Rebuilding Trust Will Take a While

Luke Timmerman, founder & editor, Timmerman Report

Credibility can be lost in a heartbeat.

It can take years to rebuild.

That maxim kept running through the back of my mind when reading the press release on the AstraZeneca Phase III clinical trial conducted with 32,449 participants in the US, Peru and Chile, in partnership with the NIH’s COVID-19 Prevention Network.

The top line was encouraging — 79 percent efficacy at preventing COVID-19 and 100 percent efficacy at preventing severe illness and hospitalization.

The company, following a rough couple weeks of rumors and innuendo, said independent data monitors found no increased risk of blood clots in people who got the vaccine.

“I’m thrilled,” said Ashish Jha, dean of Brown University’s School of Public Health, in reacting to the breaking news in Science. “This is the vaccine that I had always assumed would vaccinate a large chunk of the world.”

It’s a view rooted in practical reality. AZ’s is an adenoviral vector vaccine, given in two doses four weeks apart (or potentially further apart, according to UK officials). It’s manufacturable at global scale, easy to ship in refrigerators, and cheap — $2 to $6 a dose.

So far, so good.

I hope that everything in the company statement is right, and that there are no serious flies in the ointment. But despite our yearning for positive vaccine news, we have reason to withhold judgment until we get a good, hard look at the data.

This company has shot itself in the foot multiple times, damaging its credibility in the past year.

Consider the sequence of vaccine events:

May 21—company says it’s getting $1 billion from the Biomedical Advanced Research and Development Authority (BARDA) to develop, produce and deliver its COVID-19 vaccine in the US. Plan is to run a 30,000-participant Phase III trial, and deliver at least 400 million doses in 2020 and 2021. This was an assuring sign of a major league pharma company with a major league academic partner (Oxford), getting a major league vote of confidence from the richest and most scientifically powerful country in the world. At a time when mRNA was still seen as fairly speculative, this looked like a safe bet.

Sept. 6—company receives a report of an adverse event — transverse myelitis, an inflammation of the spine — in a vaccine participant in Britain. The company halts enrollment while investigating the adverse event, looking to see if its vaccine might have played a causative role.

Sept. 8—company has conference call with FDA officials, seeking clarity on what’s necessary for US regulatory approval. Company neglects to mention the transverse myelitis adverse event in the UK, and the decision to halt trial enrollment. The FDA was blindsided a few hours later when it heard about the revelations on the news. (The only reason we know this is because of a New York Times report from four months later). This confirms the absolute worst impressions critics have of the pharmaceutical industry. Not only that, but if you were working for the FDA and in the room that day, wouldn’t you be fuming that the company didn’t disclose the event, and didn’t discuss how to get to the bottom of the issue in partnership?

Sept. 9—As reports of the adverse event swirl, AstraZeneca CEO Pascal Soriot goes into a private conference call organized by J.P. Morgan for clients of the investment bank. From this well-controlled safe space, he assures everyone that the woman who suffered the severe spinal inflammation was improving and likely to be discharged from the hospital soon. We only learned this because STAT broke the story that day. Again, this was news of international biomedical significance, given in private to wealthy clients of JP Morgan — before the public.

Sept. 9—All AstraZeneca COVID-19 vaccine trials go on clinical hold as researchers seek to suss out what happened with the woman who got transverse myelitis.

Sept. 12—AstraZeneca vaccine trial resumes enrollment in the UK. Importantly, the big 30,000-participant study in the US, the one designed to yield the most rigorous evidence, remains on hold.

Oct. 23—the US FDA lifts the clinical hold, allowing AZ to resume enrollment of the 30,000-participant vaccine study. The clinical hold lasted more than six weeks – an eternity in a fast-moving pandemic. Pfizer/BioNTech, Moderna and J&J leaped ahead.

Nov. 23—AZ reports on a pooled analysis of 23,000 participants who got the vaccine in the UK and Brazil. Because of a dosing screw-up, a half-dose appeared to be 90 percent effective in a subpopulation of 2,100 subjects, while the full dose appeared to be 62 percent effective. The dataset, on its own, was a mess. Regulators here, in the best-resourced drug regulatory agency, already had good reason to be suspicious at the company for hiding a crucial piece of information. Now AZ is telling the world that its trial was bungled? There was no realistic path forward for the company to seek FDA Emergency Use Authorization on the basis of this unconvincing dataset.

Dec. 8—The NYT publishes its expose on AstraZeneca’s failure to disclose the adverse event to the FDA in September. Days later, the FDA approved the first two COVID-19 vaccines – one from Pfizer/BioNTech, the other from Moderna.  

Feb. 8.—South Africa health officials halt administration of the AZ vaccine, saying it was offering “minimal protection” against the B.1.351 variant of SARS-CoV-2 that was in wide circulation by then.

Feb.15—the World Health Organization authorizes the AZ vaccine for use in low and middle-income countries.

Mar. 15—European countries temporarily halt administration of the AZ vaccine amid anecdotal scary reports of blood clots in people who received the vaccine. Despite no compelling evidence to point to the vaccine causing those adverse events, health authorities in multiple countries, fearing the worst, shut down mass vaccinations with the AZ product, partly to allay public fears.

Mar. 22—AZ reports the long-awaited results from the US, Peru and Chile, in 32,000 participants. The top-line efficacy of 79 percent looks solid, if not spectacular. Some public health experts, like Ashish Jha at Brown University, cheer this development as a step toward vaccinating the world.  

For sure, 79 percent is solid efficacy. The more vaccines we have, the better. But before getting too excited, I want to see some more details on how the vaccine is performing against the variants and in subpopulations and what the immunogenicity data look like.

Part of me really prefers to withhold judgment for now, wondering if there’s another shoe to drop. Given the track record, it makes sense to wait and see for what the FDA staff come up with when they comb through the dataset with a kind of rigor that makes peer-review look like a stroll in the park.

Not only is the FDA rigorous, it has a long institutional memory. It can really put the screws to companies behind the scenes in multiple ways.

That’s one of the important lessons I learned many years ago in an FDA law class at Harvard Law School taught by Peter Barton Hutt, the attorney at Covington and a legendary former FDA counsel. (I’m not a Harvard Law graduate, but was able to audit classes at MIT and Harvard during the 2005-2006 academic year via the Knight Science Journalism Fellowship at MIT).

I practically heard shades of Peter Barton Hutt and FDA staff sharpening their pencils this morning when I watched a TV appearance by Anthony Fauci.

The FDA is going to very, very carefully go over all of these data,” Fauci said, “You can rest assured, that the FDA will apply a great deal of scrutiny in every aspect of these data.”

Fauci is surely aware that while the US public may have forgotten some of AZ’s missteps, the FDA has not.

Even if the company turns in a thorough and squeaky-clean application and regulators agree that it deserves an Emergency Use Authorization (the most likely outcome), that will be just one step in building back public trust.

Yesterday morning, on cue with the company press release, the NYT published an op-ed from Heidi Larson, the preeminent voice on vaccine hesitancy.  

There’s a lot of work to do in building vaccine trust, she wrote.

Indeed.

[Update 6:45 am PT, Mar. 23: After this column was published, the National Institute of Allergy and Infectious Disease issued the following statement: “AstraZeneca may have included outdated information from that trial, which may have provided an incomplete view of the efficacy data. We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible.” AstraZeneca responded with its own statement, saying it would provide more updated data within 48 hours.

Financings

Taicang, China and San Diego-based Connect Biopharma raised $191 million in an IPO at $17 a share. The company is working on T-cell driven inflammatory diseases. Qiming Venture Partners, RA Capital Management, and Advantech Capital were among the principal shareholders heading into the liquidity event. Shares inched up to $18.61 at yesterday’s close.

Dallas, Texas-based Instil Bio, the developer of T-infiltrating lymphocyte therapies for cancer, raised $320 million in an IPO at $20 a share. It climbed to $26.80 at yesterday’s close, with a market valuation of $3.3 billion. CEO Bronson Crouch controls the Curative Ventures entity that holds 29.7 percent ownership in the company after the IPO. The other big stakeholders in the company include Venrock, CPMG and Vivo Capital.

Somerville, Mass.-based Finch Therapeutics, a microbiome therapeutics developer, raised $128 million in an IPO at $17 a share. A member of the Walton family, heirs to the Walmart fortune, is among the big winners in this IPO. Shares traded up to $19.15 at yesterday’s close.

Boston Immune Technologies and Therapeutics (BITT) said it completed a $10 million Series A/A1 financing to develop novel antibodies against members of the TNF superfamily. BeiGene participated, along with Hatteras Venture Partners and EGP Investments.

Malvern, Penn.-based Xylocor Therapeutics said it completed a $41.9 million Series A round to advance its gene therapy for coronary artery disease. Fountain Healthcare Partners led and was joined by new investors Longwood Fund and Lumira Ventures.

Seattle-based Dexcare, a new digital health startup, said it raised $20 million in investment led by Define Ventures. The round included Frist Cressey Ventures, Kaiser Permanente Ventures, SpringRock Ventures and Providence Ventures. DexCare describes itself in a statement as “an intelligent digital care operating system that manages health system capacity and demand across all lines of care.” It was developed internally at Providence, a large hospital chain on the West Coast, in 2016 and is now being spun out aas a business with a half-dozen customers.

Cambridge, Mass.-based Aura Biosciences said it raised $80 million in financing to advance virus-like drug conjugate therapies for cancer. Matrix Capital Management and Surveyor Capital led.

Legal Corner

The SEC brought charges against uBiome for allegedly defrauding investors out of $60 million. The complaint was brought in the US District Court in Northern California.

Science Policy
  • Put this one in the ‘Never Forget’ Folder: Tom Frieden on the ‘Mind-Boggling’ Interference of the Trump Administration in COVID-19. The BMJ. Mar. 17. (Joanne Silberner)
  • Where’s the Science Behind CDC’s 6-Foot Decree and Transmissability? WSJ. Mar. 21. (Scott Gottlieb)
  • The Pandemic Year: The Hyper-Acceleration of the Life Sciences. WSJ. Mar. 19. (Eric Topol)
  • Five Myths About Coronavirus Vaccines. Washington Post. Mar. 19. (Peter Hotez and Maria Elena Bottazzi)
Science of SARS-CoV-2
  • Post-acute COVID-19 syndrome. Nature Medicine. Mar. 22. (Ani Nalbandian et al New York-Presbyterian/Columbia University Irving Medical Center)
  • Neutralizing Antibodies Against SARS-CoV-2 Variants After Infection and Vaccination. JAMA. Mar. 19 (Venkata Viswanadh Edara et al Emory University).
  • Infection and vaccine-induced antibody binding and neutralization of the B.1.351 SARS-CoV-2 variant. Cell. Mar. 20. (Venkata Viswanadh Edara et al Emory University).
  • SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies. Cell. Mar. 20. (Markus Hoffmann et al University Gottingen)
  • Difference in SARS-CoV-2 attack rate between children and adults may reflect bias. Oxford Clinical Infectious Diseases preprint. Feb. 26. (Zoe Hyde et al University of Western Australia)
  • Transmissibility and transmission of respiratory viruses. Nature Reviews Microbiology. Mar. 22. (Nancy Leung)
  • Single-component, self-assembling, protein nanoparticles presenting the receptor binding domain and stabilized spike as SARS-CoV-2 vaccine candidates. Science Advances. Mar. 19. (Linling He et al The Scripps Research Institute)
Data That Mattered

Roche/Genentech said its PD-L1 directed antibody atezolizumab (Tecentriq), hit the primary endpoint of extending disease-free survival in the Phase III Impower010 study. The trial looked at patients getting adjuvant therapy after surgery and chemotherapy for Stage II-IIIA populations with non-small cell lung cancer. Participants were randomized to the drug group, or best supportive care. The company said the magnitude of disease-free survival benefit “was particularly pronounced in the PD-L1-positive population.” The company said it doesn’t yet have mature data on Overall Survival.

Roche/Genentech also said it shut down a Phase III clinical trial for tominersen, an antisense oligonucleotide for Huntington’s disease in-licensed from Ionis Pharmaceuticals. The drug was designed to reduce production of huntingtin protein (HTT), including its mutated variant, mHTT. An independent data monitoring committee made the recommendation. See Sek Kathiresan’s succinct summary of this head-scratcher below. (Phase I results in NEJM, 2019).

Exton, Penn.-based Idera Pharmaceuticals failed in a pivotal trial of tilsotolimod in combination with ipilimumab versus ipilimumab alone in patients with anti-PD-1 refractory advanced melanoma. The drug is a Toll-like receptor 9 agonist, being combined with the CTLA-4 inhibitor in this case. Shares lost two-thirds of their value.

Our Broken US Healthcare System

Major donors to South Florida hospital foundation got early vaccine access. Politico. Mar. 19. (Arek Sarkissian and Matt Dixon)

RIP

Jose Baselga, the prominent cancer researcher and leader of oncology R&D at AstraZeneca, died at age 61. (STAT obituary).

Personnel File

Diana Brainard was hired as CEO at Cambridge, Mass.-based AlloVir, a cell therapy company focused on viral diseases patients with weakened immune systems. She starts May 17. Brainard is currently senior vice president of virology therapeutics at Gilead Sciences. She oversaw teams that developed curative therapies for hepatitis C and remdesivir for COVID-19, among other areas. She replaces David Hallal, who is moving upstairs to be executive chairman. Hallal is also CEO of ElevateBio, the largest shareholder in AlloVir. (Disclosure: Brainard is married to TR healthtech columnist David Shaywitz.)

Jean-Frédéric Viret was hired as chief financial officer at South San Francisco-based Blade Therapeutics, a developer of treatments for fibrotic diseases. He was previously CFO at Coherus Biosciences.

South San Francisco-based Sutro Biopharma, the developer of treatments for cancer and autoimmunity, promoted David Pauling to General Counsel and Robert Kiss was promoted to senior vice president of process and analytical development.

South San Francisco-based Veracyte, a molecular diagnostics company, added Muna Bhanji to its board of directors.

Chart of the Day

The data out of Brazil are a concern.

Source: Outbreak.info, based on data from Johns Hopkins University Center for Systems Science and Engineering, New York Times, COVID Tracking Project, GISAID Initiative

20
Mar
2021

Enticing Some With Social Cues, Others With Health, Exercise Rewards Body And Mind

David Shaywitz

I recently discussed the rise of digital fitness, and specifically how companies like Peloton are succeeding by delivering an engaging experience.

The new crop of digital fitness companies have figured out how to make health-promoting activities that are intrinsically tedious – like riding a stationary bike – into something compelling and sustaining. A New York Times writer, Amanda Hess, captures the essence of this magnificently in her piece, “Your Brain on Peloton.”

I was reminded of another important component of healthy activities this week when I was chatting with my barber (as one does), and asked about his fitness routine. He told me he goes to his gym 3-4 times a week, and has for years. 

I wondered what gets him there each day. Simple, he said. He has a group of buddies there.  Sometimes, he says, they’ll go for drinks afterwards, or their families will go over to one another’s house afterward for dinner. 

In short: he’s motivated by a sense of community.

An anecdote is hardly data, but the idea that healthy behaviors may be linked to interpersonal influences is well established. 

An influential paper published by Nicholas Christakis and James Fowler in the New England Journal of Medicine in 2007, for example, examined decades of Framingham Heart Study data, and concluded that “obesity may spread in social networks.” They note “people are embedded in social networks,” which “suggests that both bad and good behaviors might spread over a range of social ties.”

Another Christakis paper, from 2016, looked at two years of Gallup surveys for clues about the influence of social networks. Analyzing the data, Christakis and colleagues concluded that individuals who tend to associate with a lot of heavy people are more likely to want to lose weight, but are less likely to be successful. Conversely, associating with thinner people is linked to more successful weight loss.   

“Gains and losses of even a single social tie with a thinner or heavier individual show important links to the probability of obesity,” the authors of the 2016 paper wrote. In other words: the probability of obesity increases with additional ties to heavier people and decreases with additional ties to thinner people, and vice-versa.

A very readable overview of the “power of community” in cultivating consistent healthy fitness behaviors, by industry analyst Anthony Vennare, can be found here.

My barber’s story also reminds us of Clay Christensen’s advice: make sure you understand the problem to be solved. In Christensen’s classic (and perhaps not so healthy) milkshake example, many customers purchasing a shake from a fast-food drive-through turned out not to be looking for a tasty beverage so much as for something to occupy them in the morning, while they were driving to work. 

By recognizing this initially obscure need, the vendor was able to increase sales by making the shakes thicker (to last longer) and adding bits of fruit (to make it more interesting).

Which brings me back to what the real issue is for the barber at the gym. He’s apparently not looking for the most efficient or effective workout. Instead, he’s looking for camaraderie, while engaged in a healthy activity. These social factors are often what draw customers to the gym, and keeps them coming back.  While these individuals may achieve a healthy outcome, their pursuit of physical health is only one motivator, and often not the primary one.

Of course, not everyone is motivated in the same way. Many people are drawn to exercise explicitly for the physical benefits (such as better endurance, an improved cardiovascular risk profile, a beach body, or wanting to keep up with the grandkids). Some then discover significant mental health dividends along the way.

As modern life becomes increasingly busy, with ever more demands on our attention, “exercise time” may represent our last protected space, a cocoon of time we give to ourselves.

Over the last several years (as I’ve discussed here and here), and continuing through the pandemic, I have savored my morning exercise routine. I’ve used that time — whether sweating inside on the treadmill, elliptical, or weight machine, or outside on my bike — to lose myself in audiobooks and podcasts. I avoid work during this early hour, never checking email or text messages, and avoid all but the most essential calls. I love this daily routine. I find it grounds me, and puts me in a relaxed and positive mindset – an ideal headspace – to start the day. 

I’m certainly not alone.

I also recognize that many people — including me — would have a really tough time taking an hour out of each day for reflection, meditation, or other self-soothing activities. For many similar Type A’s, it would feel difficult to justify, and easy to encroach upon. 

Yet because the time is allocated for an activity that’s both nominally health promoting and physically unpleasant (at least compared to sitting on the couch), it somehow seems easier to rationalize – a modestly uncomfortable sacrifice made in the name of disease prevention. 

In short, exercise creates the permission structure to give ourselves the headspace we so desperately need.

In short, exercise creates the permission structure to give ourselves the headspace we so desperately need.

This also makes me wonder how much of the benefits attributed to the physical aspects of exercise may actually come from the state of mind that exercise enables us to inhabit. Parsing the relative contribution of each seems difficult. 

The bottom line is less ambiguous. Whether you go to the gym to socialize and wind up exercising (delighting your cardiologist), or jump on the bike to stay fit and wind up rejuvenated because of your protected “me-time,” (pleasing your psychiatrist), the results are joyously similar: a healthier body, a happier mind, and a better you.

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