7
Jun
2022

Rethinking Biotech Manufacturing: Rahul Singhvi on The Long Run

Today’s guest on The Long Run is Rahul Singhvi.

Rahul is the co-founder and CEO of Resilience.

The company made a splash in the fall of 2020, when it debuted with an $800 million Series A financing. Bob Nelsen of ARCH Venture Partners led the deal. The company has now raised a couple more rounds that add up to more than $2 billion.

Rahul Singhvi, co-founder and CEO, Resilience

Nelsen, a previous guest on The Long Run, saw what many others saw – a global supply chain for manufacturing that was suddenly vulnerable to disruptions from a pandemic, and, more recently, from war. He and other investors came together to found Resilience as a domestic manufacturing response to this vulnerability. They sought to build more capacity in the US and Canada for advanced biologics, and gene and cell therapies, with a network of high-tech facilities.

Rahul came to this moment with a wealth of pertinent experience. He had spent 25 years of his career working on vaccine manufacturing.

He’s been busy the past two years at this startup, acquiring existing biotech manufacturing facilities and re-tooling them. He and his team have been forming partnerships with large and small companies that need to manufacture advanced products, and could use help with sharpening their processes and technology for manufacturing at scale.

The vision of what Resilience is doing has become more clear, at least to an outside observer like me. I’ve written a fair bit about the opportunity for more domestic biotech manufacturing, for national security reasons, for national high-tech competitiveness, for regional economic development, for creating high-quality manufacturing jobs, and for creating stable businesses.

Rahul also points to a technology industry analogy, in which more specialized, sophisticated partners work together in an ecosystem, rather than each individual company trying to own every piece of the value chain. It’s an example of horizontal scaling that has worked in tech, and could now work for biotech.

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

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

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

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

Take a closer look at why at calgarylifesciences.com

 

Now, please join me and Rahul Singhvi on The Long Run.

2
Jun
2022

Out in the Community in 2022

Luke Timmerman, founder & editor, Timmerman Report

TR subscribers: I’m traveling more, and looking forward to seeing more of you in person.

I’ll be at the BIO Convention in San Diego, June 13-15. They have plenty of outdoor patio space overlooking the ocean at the San Diego Convention Center. Let’s chat.

While at BIO meeting people and gathering ideas, I’m also moderating a panel on improving diversity, equity and inclusion.

Time: 1:45-2:45 pm

Date: June 15

Place: Upper Level, Session Room 5A, San Diego Convention Center

Panelists:           

  • Michelle McMurry-Heath, president and CEO, BIO
  • Paul Hastings, CEO, Nkarta Therapeutics, chairman of BIO
  • Rob Perez, operating partner, General Atlantic, founder of Life Science Cares
  • Nancy Hong, managing director, RiverVest Venture Partners
  • Luke Timmerman, founder, Timmerman Report (moderator)

Emerging Frontiers in Oncology: I’ll be in Cambridge, Mass. June 30 to moderate at the Emerging Frontiers in Oncology meeting. It’s a half-day forum at the MassBio event center at Technology Square, followed by a networking reception at Catalyst.

Speakers include:

  • Keith Flaherty of MGH, co-founder of Loxo Oncology
  • Judy Lieberman of Boston Children’s Hospital
  • Doug Williams of Codiak Biosciences
  • Marian Nakada of J&J Innovation
  • Rosanna Kapeller of Rome Therapeutics

The event is organized by Uciane Scarlett of MPM Capital, as a fundraiser for the Timmerman Traverse for Life Science Cares. For tickets, ask Uciane (pronounced YOU-shuh-nee) uscarlett@mpmcapital.com.

Timmerman Traverse for Life Science Cares: My team of 20 biotech executives and investors is gearing up for a 20-mile hike of the Presidential Traverse in the White Mountains of New Hampshire Sept. 11-14. The team goal is on pace to hit the goal of $800,000 to fight poverty in Boston, San Francisco, San Diego and Philadelphia. SVB, SmartLabs and Goodwin are among the top sponsors.

Highlights of the Timmerman Traverse, 2021

This is a phenomenal way to give back to the wider communities where biotech operates, and there will be opportunities to mix and mingle with the stellar members of this team. To see who’s hiking and support someone you know, click here. For sponsorship opportunities, see Emily Stanford at LSC emily@lifesciencecares.org.

Kilimanjaro 2023. One way I seek to build community in biotech is by creating diverse and tight-knit teams for my philanthropic expeditions.

I’m now recruiting a team of 27 people to join me on the next Kilimanjaro Climb to Fight Cancer. It’s scheduled for Feb. 9-20, 2023. The goal is to raise $1.5 million for cancer research. Please let me know if you, or someone you know, might be a good candidate for this group expedition to the highest peak in Africa. I’m seeking biotech entrepreneurs and investors who have a thirst for adventure, are physically fit, and willing to raise a minimum of $50,000 for cancer research.

To request an invitation: luke@timmermanreport.com.

24
May
2022

Seeking Wellness Through More Data, Less Technology, and Better Habits

David Shaywitz

It only took a pandemic, but well-being has at last emphatically arrived in the corporate world.

Before the pandemic, wellness was often viewed as just another item on the HR benefit menu. Some companies offered limited reimbursement for fitness classes, or subsidized access to select health and wellness apps.

But in the turbulent wake of COVID-19, well-being is increasingly viewed as worthy of C-suite attention, and recognized as critical to company success.

As we collectively navigate our way towards improved well-being, we might consider two recent books that address the topic through two very different lenses.

Big Data Meets Well-Being

Several years ago, Seth Stephens-Davidowitz, a data scientist and New York Times columnist, wrote about what data science had to say about human behavior. His book, Everybody Lies, was a revealing and engaging read, as I discussed here.

Seth Stephens-Davidowitz, data scientist, author, and New York Times columnist.

Stephens-Davidowitz has now returned with Don’t Trust Your Gut, a delightful, quirky romp through the data science literature on self-improvement. 

Why self-improvement? Predictably, because Stephens-Davidowitz followed the data. He analyzed the reaction to his last book and noticed that readers told him they were most interested in the use of analytics to help others, particularly those less fortunate. 

Yet when he looked at the actual data (the passages underlined most in the Kindle version), he discovered readers were, in fact, most interested in themselves, and he aims to oblige. (This distinction between stated and revealed preference is a key theme of his last book, and a frequent topic of this column – eg here — since the ability to discern the difference is often critical to entrepreneurial success.)

Stephens-Davidowitz starts by demonstrating how data science can be used to study human relationships by mining dating sites, which turn out to contain a treasure trove of information. Some of the insights prove modestly surprising: for example, among those individuals seeking heterosexual relationships, tall men were especially prized, but tall women were not. 

At the same time, Stephens-Davidowitz writes, data scientists – despite extensive effort — have been utterly unable to predict whether two people will actually be happy in a relationship. The top lesson drawn by a researcher who exhaustively examined a dataset of 11,196 couples? “How unpredictable relationships seem to be.”

Ever the sabremetrician, Stephens-Davidowitz points out what he sees as the grand arbitrage opportunity here: since “good romantic partners are difficult to predict with data” but “desired romantic partners are easy to predict with data,” the winning move, he suggests, he to pursue the “Youkilis of love” (Kevin Youkilis was a famously undervalued baseball player because he didn’t look the part). He advises daters to “focus more of their attention on targets who the rest of the data market ignores, even though they are just as likely to be great romantic partners.”

Having shown us the approach, Stephens-Davidowitz applies this data-driven methodology to a range of subjects, from the impact of parenting (which may matter less than we think) to the role of genetics in sports success (genes are evidently far more determinative in basketball and track-and-field than in skiing and weightlifting) to activities that make us happier than we think (going to museums, exercising, gardening) to the importance for artists to aggressively maximize their opportunity to be discovered, rather than venturing forth timidly and in effect “pre-rejecting” themselves.   

Perhaps my favorite section focused on entrepreneurship, and the lessons learned from researchers analyzing massive datasets. For instance, a team analyzing every business created in the United States between 2007 and 2014 found that of the 2.7 million entrepreneurs represented, the average age of founders is about 42. They also learned that older people “succeed at creating highly profitable businesses more often than their younger peers” — a trend that continues “at least until the age of sixty.” In other words, the young tech geniuses the media often focus on are not representative – even in technology, where the average age of a founder of a highly profitable company was 42.3 years old.

Similarly, while we’re often told that industry outsiders have the independence to develop the most profitable startups, Stephens-Davidowitz cites research demonstrating that in reality,

“There is an enormous ‘Insider’s Advantage’ in entrepreneurship. Entrepreneurs are roughly twice as likely to build an extremely successful company if they previously worked in the field in which they started the company. The advantage gets larger the more directly the previous experience is related to the business.”

(Readers will note parallels between some of the findings Stephen-Davidowitz reports and those uncovered by VC and author Ali Tamaseb in Super Founders, as I’ve discussed.)

While not the definitive account of any of the topics it touches on, Don’t Trust Your Gut demonstrates the unreasonable power of empirical evaluation of extremely large datasets, including in the context of wellness, and reminds us of the many ways we can be deceived by selective sampling.  

Put Down Your Phone

Johann Hari is a journalist and writer who, like many of us, was struck by the outsized role technology – social media in particular – plays in our lives. In Stolen Focus, he explores the origins and dangers of this contemporary menace.

Hari starts with an anecdote – familiar to most parents – of watching his teenage godson Adam become increasing absorbed into the social media on his smartphone, to the point where he seemed to enter an almost dissociated state of scrolling and staring blankly at the screen. Eager to engage Adam in a real world experience – and because Adam had once been captivated by all things Elvis – Hari took his godson to Graceland, having secured from Adam, in advance, the promise of abstaining from technology once they got there.

Johann Hari, author, “Stolen Focus.”

Yet, the moment they arrive at Graceland, Hari and Adam are each handed….an iPad and headphones, for a self-guided tour of the mansion. 

But the most striking part, as Hari describes it, was when they arrived outside the famous “jungle room” (supposedly Elvis’s favorite place in the compound), Hari notices the middle-aged couple in front of him captivated by the ability to switch between images of the left and right side of the jungle room simply by flicking their fingers from side to side on the iPad. 

Flabbergasted, Hari points out to the couple that they can achieve the same effect by looking up from their iPads and looking at the actual room in front of them. We’ve become so entranced by our technology, he realizes, that we instinctively are drawn to the image of the jungle room even when the room itself exists before us.

Hari explains how we’ve become so addicted to our screens: the business model for tech companies like Google and Facebook means that their revenue is maximized by increasing our time and engagement on their platforms. Consequently, he says, the smartest engineers in the world leverage the most powerful AI and savviest user experience expertise to escalate our addiction. 

Hari also discusses why the constant beckoning of our smartphone apps is so destructive: it steals our ability to deeply and consistently focus. (Here, he echoes themes from Cal Newport’s Deep Work, which inspired me to quit Twitter in 2019.) It’s not that responding to a notification itself is so time consuming, but rather that it takes a shockingly long time – more than 20 minutes, he reports – to regain focus afterwards.  We tend to be closer to our best selves when we can deeply focus, and when we can’t, everything is worse. We may pride ourselves on our ability to multitask, he says, but in splitting our attention, we’re sabotaging ourselves, our work, and our happiness.

Hari writes that workplaces interested in worker well-being might do well to rely less on advocating wellness practices like meditation (which Hari says he personally enjoys and values), and more on creating intrinsically better environments for workers.  Essentially, he argues that instead of putting a band aid on the problem, companies should seek to provide greater opportunity to focus at work (i.e. fewer gratuitous distractions) and to relax at home (i.e. protected time and “right to disconnect” – now a legal protection in France).

While the book seemed to lose its way and go off the rails about halfway through (I couldn’t make it through to the end), the idea that we’re physically addicted – by design – to our apps is a crucial point worth amplifying.

Observations

When I thought about how I was interacting with my phone, and the number of times I reflexively checked it, I resolved to try to establish some new habits. 

For one, I re-quit Twitter (I had started up again in the context of Omicron) – with immediate satisfaction and minimal regret (sorry, Elon). I also now stow my phone when I drive, so I’m not even tempted to interact with it. This took a little adjusting, but I really appreciate this new habit as well.

I like the idea of seeing wellness through the lens of discrete, modifiable habits, as Hari alludes to and a number of authors have suggested; this seems like a pragmatic way of productively changing behavior.   The same science that has informed the development of smartphone apps that steal our focus and detract from our happiness can also be used to instantiate healthy habits.

In fact, it’s exactly the same science: many engineers designing today’s technology trained in B.J. Fogg’s legendary “persuasive technology lab” at Stanford (now known as the “behavioral design lab”). Fogg is also the author of the Tiny Habits, aimed at helping us use small changes to drive meaningful behavior change. (Good Habits Bad Habits, by USC professor Wendy Wood, is also highly recommended.)

Of course, not all apps are harmful, and some can even be a force for good. For example, I’ve been pleasantly surprised by impact of a corporate wellness initiative that simply involves signing up for an app that collects your daily steps from whatever device you select. You sign up in teams of four, and strive to average 7500 steps/day. Participants are encouraged to share photos of their walks with other participants through the app. 

Silly as it sounds, I’ve really appreciated this experience – it’s been lovely seeing where my colleagues are walking, and I find I’m getting out much more than I used to; I’m especially likely now to use short blocks of downtime as an opportunity to get in some additional steps.

Finally, I wanted to highlight a particularly positive recent experience I had attending an external two-day retreat with an exceptional group of biomedical leaders, innovators, entrepreneurs, and investors. The opportunity to engage with other colleagues in a relaxed setting — on hikes and over meals, in person and without masks — was extraordinary. 

The experience reminded me how much we’ve missed this human connection over the last two years.  It also emphasized how elevating and essential physical exercise and human connection are – not just for our health, but also for our happiness.

23
May
2022

Building a New Type of Drug Discovery Engine: Chris Gibson on The Long Run

Today’s guest on The Long Run is Chris Gibson.

Chris the co-founder and CEO of Salt Lake City-based Recursion.

Chris Gibson, co-founder and CEO, Recursion

The company was founded in 2013 when Chris was working in the lab of Dean Li at the University of Utah.

The idea at Recursion is to do what it calls “industrialized drug discovery.” It combines some of the common tools of drug discovery – CRISPR, synthetic biology, automated lab tools, high-powered computing, and Artificial Intelligence / Machine Learning to hopefully churn out more drug candidates faster, and with a higher probability of success. The company has a long history of phenotypic screening, and leans on that expertise, combined with the new tools, to create maps of biology that are supposed to help scientists predict how any two tested genes or molecules might interact with each other.

Recursion raised $436 million in an IPO in April 2021, which looks pretty well-timed based on the state of the biotech stock market today. It has a couple of partnerships – with Bayer and with Roche / Genentech. The Bayer deal is focused on treatments for fibrotic diseases, while the Roche / Genentech deal includes oncology and neuroscience indications.

Chris is a next-generation founder and industry leader who isn’t afraid to buck convention, and has a lot of interesting things to say about technology, about company building, and about creating a thriving ecosystem outside of the main industry hubs.

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

 

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

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

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

Take a closer look at why at calgarylifesciences.com

 

Alpenglow Biosciences sheds new light on pharmaceuticals with AI-powered, 3D spatial biology. Pathology is an essential component of drug development, yet it is stuck in archaic times by looking through 2D slides. Alpenglow has developed an end-to-end drug development solution with proprietary 3D imaging, cloud processing, and AI analysis to digitize entire 3D tissues, providing 250 times more data and deeper insights. Learn how Alpenglow can illuminate your path to breakthrough results at alpenglowbiosciences.com.

Now, please join me and Chris Gibson on The Long Run.

23
May
2022

Sachi Bioworks: Out of the University, Into Outer Space

Lisa Suennen

When they started their first venture together, Dr. Anushree Chatterjee and Dr. Prashant Nagpal were both leading research labs at the University of Colorado, Boulder. Prashant’s lab focused on nanotechnology and molecular biology: Anushree’s focused on building antibiotics for drug-resistant bacteria. 

That startup, Praan Biosciences, was founded in 2014 to develop improved genetic sequencing technology. Anushree and Prashant had one foot in the company and another on campus. By day they were academics in two separate labs, by night they were laboring to create a prototype gene sequencing instrument.

By 2015, it became evident to the founders that Praan was not going to be a success; they determined that there was no way to bring their vision to life with one foot in the academic lab and the other in a startup. 

“To fulfill the vision, we realized, we had to live the experience,” said Anushree.

Anushree Chatterjee, co-founder, chair & CEO, Sachi Bioworks

The shift in their thinking had begun.

Life in their respective research labs resumed. Time passed, but Prashant and Anushree, a married couple, realized how much they wanted to make an impact beyond academia.  They continued to learn and publish and get interviewed on their papers, but every time that happened, they would get letters from patients begging to try the drug upon which their research was focused. It became clear to these two individuals, long committed to scientific research, that there was no point, at least to them, in making a new medicine if it couldn’t translate into impact for patients.

New Startup, New Approach

They decided to make a change when Anushree took their one-year-old child to the doctor for an infection. The pediatrician wrote a prescription for an antibiotic.

“Let’s hope this works. If it doesn’t, we’ll try another,” the doctor said. 

Anushree wasn’t one to settle for this trial-and-error prescribing approach. She had spent her career working on drug development. Her thinking crystallized. “There are too many unknowns, even about approved drugs. There is a technology gap and we have to fill it,” she explained.

The pandemic drove the couple’s thought into action. As they sat at the dinner table, they realized what they had to do, “we need to change ourselves to change medicine.”

Prashant Nagpal, co-founder, COO, CTO; Sachi Bioworks

The two took a sabbatical from University of Colorado and shifted their attention to a new idea that could potentially drive faster identification of COVID-19 treatments, as a starting point.  

Prashant never went back to the academic lab. He decided to become a full-time entrepreneur. While Anushree has maintained her research position, she is an active thought partner with Prashant in how to move their new company, Sachi Bioworks (“Sachi”), into the emerging field of Space Medicine. The two say they have been far more productive in this arrangement.

Sachi, a word which means “miracle” in Japanese, is focused on creating a paradigm shift for the field of drug discovery. Their product has gone from concept to full manufacturing line in two years’ time. It’s a reflection of the change of clock speed required in industry as compared to academia.

In those two years, Sachi’s founders developed a system for making what they call Nanoligomers.  For those of us who are not chemical engineers, Nanoligomers are polymer molecules made up of a group of monomers (naturally!), which are themselves molecules that can be bonded to other identical molecules. 

By creating these Nanoligomers, Sachi aims to transform drug discovery with accelerated synthesis, validation, and production of specific nucleic acid therapies. They are using a robotic system to make candidate molecules per day that should be able to upregulate or downregulate any gene of interest, with high specificity.

The company already has four drug candidates in preclinical development for Parkinson’s, inflammatory bowel disease, an undisclosed neuroimmune disease, and one candidate designed to counteract radiation exposure. 

An Unusual Backer

The company has found an unusual backer in the drug discovery world — NASA. 

The company is advancing its work on radiation countermeasures under a NASA-funded SBIR grant. Astronauts in deep space are exposed in one day to the same amount of radiation that people on earth experience in one year. As early NASA-funded Translational Research Institute for Space Health (TRISH) experiments on SpaceX astronauts have shown, the impact of space travel has dramatically different impacts on each astronaut based on their genetic make-up, among other things.

Earth-bound medicine, Anushree noted, helps 50% or fewer of the people who are prescribed a particular drug. In deep space, there are a handful of astronauts on board. Each has their own genetic profile. They cannot stop at a local CVS. Ideally, they would have access to medicines that work for each person onboard.  

Space medicine, Anushree realized, was a perfect testing ground. The Sachi system could allow for the creation of thousands of drug candidates in real time. Existing pharmaceuticals rapidly degenerate in space, but Sachi thinks it can overcome that problem by enabling the astronauts to formulate their own personalized treatments onboard the spacecraft. 

Since the speed to a viable target is, at least in Sachi’s view, reducible to days instead of years, it is theoretically possible to send their miniaturized system into space to allow astronauts to rapidly design and deliver truly targeted, safe drugs on-the-fly (literally). 

In its first NASA space medicine project, the Sachi system was able to identify 17 target genes in 6 weeks and show an ability to turn proteins on and off as desired. They were able to do this in mice without needing a lipid to bind and deliver the treatment and without creating toxic concentrations of drug in the liver or other key organs. 

The goal is to be able to target any gene in any patient — on earth or in space — and create drugs for an audience of one (or more than one) at an order of magnitude lower cost and with less complexity.

The industry, and regulatory agencies, will need to make some significant changes to realize the value of what Sachi is doing. That includes regulatory pathway for new kinds of drug development; the business models if drug development costs plummet; and the methods of drug manufacturing, particularly if you can manufacture up to 1,600 drugs at the same time without a dedicated line and with no retooling. 

Changing Mindsets

The biggest risk Anushree sees? That many of the today’s players won’t be able to shift gears fast enough to keep up.

“The traditional drug development process focuses on risk reduction. Our approach switches the focus to impact maximization. With the ability to engage in rapid cycles of discovery, testing, learning and building, scientists no longer have to be afraid of the cost of failing,” says Anushree. “Creating a valuable drug for $10 billion is nice, but I’d rather deliver 100% biological impact at low cost and fast.”

Prashant noted that the move from academic to translational medicine required a dramatic change in thinking. 

“In the lab, people work in a very linear way based on how the money is targeted; in a company, you’re in the middle of the ocean and need to chart a path out without a map,” he said. In industry, he can’t just work on the science while neglecting other functions such as business operations, human resources, finance.

Perhaps most important, at least to Sachi’s co-founders, you can no longer measure your success by publications – you can only meaningfully measure success by getting to market and having an impact on patients. 

Anushree adds that having two small children has helped both founders switch mindset. The non-linear nature of parenting has helped them both use the pressure of managing career and family to become more flexible, less resistant to change, more open to new ways of getting things done. This has borne fruit for family and for their passion project, which is now garnering attention throughout industry.

Sachi has funded its work primarily through SBIR grants and other non-dilutive forms of funding. Even without big-name VC fund checks and the industry connections that come with them, Sachi says it will have its first drug ready for human testing in 2023, just three years after inception.

If it can achieve that goal, and continue to build a platform for fast, custom-manufactured precision genetic medicines, it would indeed represent a significant shift in drug discovery.

19
May
2022

A Path Forward for More Biotech Workers

Luke Timmerman, founder & editor, Timmerman Report

Biotech needs more workers. More people who don’t have PhDs and MDs.

The industry is 40 years old, and maturing. More companies are developing commercial products. Someone needs to make these products with precision, and at scale.

Given the sophisticated nature of the products (cell therapy, gene therapy, advanced biologics, RNA medicines), the fragile global supply chains, and the importance of steady supplies for patients, there’s a case to be made for manufacturing close to home. (See “Biotech’s Future off the Beaten Path, Feb. 2022.”)

Many companies see where this is going. One estimate by MassBio shows that 20 million square feet of lab and manufacturing space is coming online in Massachusetts by 2024. These facilities alone will create 40,000 net new jobs. That’s a lot of jobs for manufacturing technicians, lab managers, clinical trial associates, quality control, facilities managers and many other jobs that don’t require a PhD. There are currently about 85,000 biotech jobs in Massachusetts.

Who will do this all this extra work? Where will these people get the necessary skills and experience?

The good news: There are people who are willing and able to do this work, if companies are willing to put some skin in the game and invest in training.

Last week, I learned about a fascinating apprenticeship program run by MassBioEd, a branch of the local trade association. The early results are impressive. More on that in a minute.

The program was designed by Karla Talanian at MassBioEd, and based on models from Apprenti, a tech industry workforce development group.

Karla Talanian, senior director of life sciences apprenticeship program, MassBioEd

Here’s how the biotech program works.

People apply for a 4-month training program in biomanufacturing, or a 3-month training program to become a clinical trial associate. Students learn some fundamentals of industry.

For biomanufacturing, Northeastern University is the academic partner. Faculty teach 2 months online, and follow that up with 2 months of hands-on work at a Northeastern lab in Burlington, Mass. The clinical research track is taught online by faculty from the Association of Clinical Research Professionals — people who know how clinical trials work.

Tuition is free. When the apprentices complete their training, they are paired up with an employer for 1 year of work. Employers get to choose from a handful of graduates in an interview process. The biomanufacturing technicians start at $21 an hour, while clinical trial associates start at $27 an hour. There’s an opportunity for a raise at the halfway point.

The apprentices have a boss, but they are also matched with a workplace mentor – a seasoned employee who can answer questions. Once a month, the apprentices can meet with their peers and other program participants. At the end, there’s no obligation. The employer can hire the employee for a full-time permanent position, or let the employee walk away for a job elsewhere. But once a person has been trained at a company, if the person is doing well, there’s a natural incentive to want to retain the person.

The initial cohort of 30 people – 19 in biomanufacturing and 11 CTAs – have completed their training and are now embedded in the workforce.

Who are they? In their previous lives, they were restaurant workers, retail cashiers, Uber and Lyft drivers. One was a math teacher. MassBioEd does targeted outreach to immigrant support groups, adult education centers, veterans groups to find candidates.

The first group of apprentices had an average age of 33.

It’s a diverse group, in many ways.

  • 60 percent people of color
  • 63 percent female
  • 26 percent immigrants
  • 47 percent were unemployed

The one thing they all had in common? “None of them would have had a prayer of getting a job in the industry without this program,” MassBioEd’s Talanian said.

The program has been life-changing. Some of the program graduates had attended college for a while, but didn’t finish for whatever reason – couldn’t afford it, got pregnant, had to take care of an ailing family member. They’ve tried to get by, but struggle in low-wage/low-benefit/no future jobs. The idea of going to work in biotechnology is thrilling. It’s an industry with good salaries, good benefits, upward mobility, interesting colleagues, and making products that help people. It changes their outlook on life.

“Many of them didn’t think they’d ever have an opportunity to pursue their dreams,” Talanian said. “They are so grateful and excited to have this opportunity. They dive in.”

One professor from Northeastern University, with 20 years of experience, was blown away. The professor told Talanian that out of the 19 students in the initial biomanufacturing group, about 14-15 of were among the most motivated, dedicated students he’s ever taught.

The employers are impressed. All five of the employers that signed up for the pilot project have renewed their commitment for Year 2, agreeing to take on more apprentices, Talanian said. The group includes Pfizer, Bristol Myers Squibb, Alnylam Pharmaceuticals, MassBiologics, and Arranta Bio.

“If all five came back, it must be working well,” Talanian said.

Al Boyle, chief technical ops and quality officer, Alnylam Pharmaceuticals

Alnylam participated in the original cohort because it was good for the community, but it was also good for the company as it scales up manufacturing in Norton, Mass. “The level of energy and commitment to making this opportunity at a new career successful stood out the most for us,” said Al Boyle, chief technical ops and quality officer for Alnylam. “We knew the talent pool would be diverse, but I think the level of diversity was even larger than we thought we’d see.”

Word has gotten around the biotech community. After a couple of years working hard to persuade companies to commit to the program, Talanian now finds herself with the opposite problem. She has to shoo away some interested companies because she’s maxed out capacity for Year 2. The program is expanding from 30 spots for 5 companies to 100 spots for 11 companies. (Participants listed below).

Manufacturing and clinical trial associates are obvious places to start, but there are biotech functions that could benefit from filling up the entry level pipeline.

Talanian is hearing from companies that want apprentices who can get into lab operations support. These are jobs for people who order supplies, deal with environmental health and safety regs, cleaning, lab certifications, repairs. “We want to let the scientists do science, and take all that other stuff and professionalize it. Make it a respectable position to go into,” Talanian said.

Laurie Halloran, president and CEO, Halloran Consulting Group

Laurie Halloran, the CEO of Halloran Consulting Group, is a member of the MassBioEd board who has acted like a “godmother” to the program. Halloran told me she sees potential for similar apprenticeship programs for regulatory affairs – another area where it’s hard to hire.

“We can’t keep stealing each other’s people. We need to grow more people,” Halloran said.

There are still companies that are cautious, taking a wait-and-see approach, she said. “They don’t want to be the guinea pigs.”

This is a program that’s graduating from the experimental phase. It looks more like a train that’s leaving the station.

If the industry is serious about meeting its workforce needs, and about diversity/equity/inclusion, then it will consider programs like this one. The employees are motivated, curious, and likely to be loyal to the company that gave them their first shot.

There’s a lot of talent in this country, waiting to be tapped. Biotech could be a beacon for a new generation of young people starting their careers.

If the industry is willing to take a few chances, it could reach new heights.

Science Policy

  • The Answer to Stopping the Coronavirus May Be Up Your Nose. NYT. May 16. (Akiko Iwasaki, Yale University)
  • What COVID Hospitalization Numbers Are Missing. The Atlantic. May 18. (Ed Yong)
  • How Public Health Failed America. The Atlantic. May 15. (Jay Varma)
  • The COVID Capitulation. Substack. May 15. (Eric Topol)

Science

  • Unexplained post-acute infection syndromes. Nature Medicine. May 18. (Jan Choutka et al University of Chemistry and Technology, Prague, Czech Republic)
  • CRISPR’d CAR-T Cells in the Clinic. In the Pipeline. May 18. (Derek Lowe)

Strategy

  • Reflections on Alnylam. Nature Biotechnology. May 9. (John Maraganore)
  • Out On The (Cutting) Edge: How The Tools Of Extreme Survival Can Help Build A Biotech Company. LifeSciVC. May 18. (Aoife Brennan)
  • A new biotech investment firm, headed by Alexis Borisy and Zach Weinberg, to ‘free the founders’. STAT. May 11. (Alison De Angelis)
  • Healthcare hedge funds are in critical condition. Institutional Investor. May 11. (Stephen Taub)

Our Dysfunctional Healthcare System

  • Seven health insurance CEOs raked in a record $283 million in compensation last year, while profits grew and patients delayed getting treatment during the pandemic. STAT. May 12. (Bob Herman)

Financings

Cambridge, Mass.-based Remix Therapeutics, a company making small molecules aimed at RNA processing targets, raised $70 million in a Series B financing. (TR coverage)

The US government’s Biomedical Advanced Research & Development Authority (BARDA) and UK-based Wellcome committed another $370 million to CARB-X – a program at Boston University to fight antibiotic-resistant bacteria. The program was started with $355 million in 2016.

HealthQuest Capital raised $675 million for a growth equity fund. Garheng Kong founded the firm in 2013, and it now has $1.6 billion under management. The firm said it plans to use the new fund to back “commercial-stage companies that improve patient outcomes, or reduce cost and inefficiency in the healthcare system.”

Apollo and Sofinnova Partners announced a strategic partnership, in which Apollo is acquiring a minority stake in the European-based life science venture firm. Apollo is also committing up to 1 billion Euros to facilitate the venture firm’s growth.

Philadelphia-based SwanBio Therapeutics raised a $56 million Series B financing to develop gene therapy for neurological conditions. Syncona Limited and Mass General Brigham Ventures led. The lead program is an AAV gene therapy in clinical development for adrenomyeloneuropathy.

Research Triangle Park, NC-based Locus Biosciences said it raised $35 million to advance bacteriophage therapies for bacterial diseases.

Redwood City, Calif. and Research Triangle Park-based Kriya Therapeutics, a gene therapy company, raised $270 million in a Series C financing. Patient Square Capital led. Kriya plans to use the money to expand its pipeline, and scale up its engineering, manufacturing, and computational platforms.

Curie Bio, a new VC firm headed by Alexis Borisy and Zach Weinberg, has raised $250 million from a syndicate that includes GV, Casdin Capital and A16Z, according to STAT. The firm plans to “free the founders” as Borisy put it, allowing founders to hold onto a greater equity stake in startups than usual.

San Diego-based Aspen Neuroscience raised $147.5 million in a Series B financing. GV, LYFE Capital and Revelation Partners co-led. The company is developing an induced pluriopotent stem cell-derived autologous dopamine neuron replacement therapy for Parkinson’s Disease.

Morrisville, NC-based Inceptor Bio raised $37 million in a Series A financing to develop CAR-T, CAR-M, and CAR-NK therapies for cancer. Kineticos Ventures led.

Deals

Pfizer agreed to pay $11.6 billion to acquire Biohaven Pharmaceuticals, which had developed and begun to successfully commercialize an anti-migraine drug.

Cambridge, Mass.-based Be Biopharma, the developer of engineered B-cell therapies, announced a partnership with Resilience. Be Bio plans to lean on Resilience to manufacture viral vectors and cell therapies with personnel dedicated to its projects. Terms weren’t disclosed, but the companies described the arrangement as “a creative cost and risk-sharing model,” in which “Resilience will be responsible for manufacturing costs and receive potential future milestones and royalties.”

Cambridge, Mass.-based Myeloid Therapeutics formed a partnership with Acuitas to provide lipid nanoparticles for delivering the company’s in vivo mRNA programming therapies for cancer.

London-based RQ Bio came out of stealth mode, announcing it has outlicensed monoclonal antibodies to SARS-CoV-2 to AstraZeneca.

Menlo Park, Calif.-based GRAIL expanded its partnership with Intermountain Healthcare, the largest private employer in Utah. The company is now offering its test, designed to detect 50 different types of cancer at an early stage, to Intermountain employees and family members.

South San Francisco-based Atara Biotherapeutics said that Bayer intends to end its partnership in Sept. 2022. Atara will get back the full rights to allogeneic and autologous CAR-T cell therapy candidates directed against mesothelin-expressing tumors.

Japan-based Otsuka Pharmaceutical is ending its partnership with Akebia Therapeutics, the developer of vadadustat for anemia from chronic kidney disease. The drug application received a Complete Response Letter from the FDA earlier this year.

Personnel File

Seagen’s co-founder, chairman and CEO, Clay Siegall, is out of a job after 25 years. He resigned after being arrested and charged with 4th degree domestic assault, stemming from an incident at his home on Apr. 23. Days earlier, the company said Siegall was on a leave of absence, and that it had formed a special board committee to investigate the charges with an independent law firm. Roger Dansey, the chief medical officer, is serving as interim CEO while the board begins the search for a permanent CEO. It’s a troubling and sad chapter for a company that has long been a leader in antibody-drug conjugates for cancer. Seagen is the anchor company of the Seattle biotech community, with four marketed cancer drugs, nearly 3,000 employees worldwide, and a market valuation of $26 billion. People have been speculating about Seagen as a takeover candidate for at least 15 years, and rumors are spreading again. I think Seagen still could have a bright independent future under a new leader. Antibody-drug conjugates are maturing as a technology, and they are likely to be applied to many more tumor types in the near future. I also wrote here in February about the company’s shrewd bet on manufacturing in Everett, Wash. ‘Biotech’s Future Off the Beaten Path.’

Flagship Pioneering merged a couple of its portfolio companies, Inzen Therapeutics and Cygnal Therapeutics, into a new entity called Sonata Therapeutics. It will aim to use small molecules and genetic medicines against cancer, fibrosis and autoimmune disorders. Volker Herrmann, the former CEO of Inzen, will run the new company. Pearl Huang, the former CEO of Cygnal, is moving on to new opportunities.

Waltham, Mass.-based Xilio Therapeutics, the developer of tumor-selective immunotherapies, hired Stacey Davis as chief business officer. She comes from Novartis.

Eli Lilly said Mary Lynne Hedley is joining its board of directors. She is currently a senior scientific fellow at the Broad Institute, and previously was president and chief operating officer of Tesaro. That company was acquired by GSK.

Cambridge, Mass.-based Agios Pharmaceuticals said it’s cutting up to 50 jobs in research, and that chief scientific officer Bruce Car is stepping down in July. Sarah Gheuens, the chief medical officer, will keep that role and also take responsibility as head of R&D. The company said it expects to save $40-$50 million a year.

Cambridge, Mass.-based Scholar Rock said it’s cutting 25 percent of its workforce.

Switzerland and Cambridge, Mass.-based CRISPR Therapeutics hired Phuong Khanh Morrow as chief medical officer. She was previously with Amgen.

The Mark Foundation for Cancer Research, based in New York, promoted Ryan Schoenfeld to permanent CEO. He had been serving on an interim basis since August.

Waltham, Mass.-based Morphic Therapeutic, the developer of small molecule drugs against integrin targets, promoted Bruce Weber to president. He’s been chief scientific officer since Jan. 2016. Morphic also hired Joanne Gibbons as senior vice president of regulatory affairs. She previously worked with Codiak Biosciences.

Dublin, Ireland and Bridgewater, NJ-based Amarin announced a boardroom shakeup. Per Wold-Olsen is the new chairman of the board, and Erin Enright and Alfonso “Chito” Zulueta are new directors. David Stack and Joe Zakrzewski are stepping down from the board. Lars Ekman will no longer be chairman, but he will stay on the board.

Boston-based Odyssey Therapeutics, the developer of precision immunomodulators and cancer therapies, named Jeff Leiden as chairman of the board.

San Diego-based Ambrx Biopharma hired Janice Lu as chief medical officer.

Cambridge, Mass.-based Glympse hired Jonathan Wilde as chief scientific officer. The company is developing diagnostics that measure protein activity. He previously worked at Veracyte.

Hayward, Calif.-based Eikon Therapeutics, the developer of super-microscopy technology for drug discovery, added Robin Washington to its board as an independent director. She was the CFO of Gilead Sciences from 2008-2019. (TR coverage of Eikon, May 2021)

Our Shared Humanity

Immigrants are about 80 percent more likely to start a business than a US-born citizen, according to a recent study in American Economic Review: Insights. “The findings suggest that immigrants act more as “job creators” than “job takers” and play outsized roles in US high-growth entrepreneurship,” the authors wrote. (MIT news).

Regulatory Action

The FDA approved Eli Lilly’s application to market tirzepatide (Mounjaro) for adults with type 2 diabetes. The first-in-class GLP-1 and GIP agonist is given as a subcutaneous injection once a week. The drug not only beats others in the diabetes category on hemoglobin A1c scores, but has shown a consistent ability to help patients lose more weight. It recently showed that weight loss effect in a study of obese patients who don’t have type 2 diabetes. Analysts are predicting it will be a multi-billion dollar seller as it reaches its full potential in coming years. (See Apr. 2022 Frontpoints on “A Big Opportunity in Obesity.”)

The FDA gave Emergency Use Authorization to Labcorp for the first direct-to-consumer RT-PCR test that can detect both SARS-CoV-2 and influenza viruses. The patient can collect the nasal swab at home and send it in to Labcorp for testing.

The FDA gave Emergency Use Authorization to Pfizer/BioNTech’s COVID vaccine, in a low-dose form, as a booster for kids ages 5-11. The third shot can be given to kids at least five months after they get the first two shots. Fewer than one out of three kids in the US have gotten the vaccine at all, so demand for the booster is likely to be pretty low. The CDC’s Advisory Committee on Immunization Practices reviewed the data and recommended the booster shots for kids 5-11 a couple days later. (STAT) (See also “A Missed Opportunity for Grownups,” Dec. 2021). Meanwhile, parents of kids under age 5 are still waiting for any COVID vaccine to get authorized.

Cambridge, Mass.-based Foghorn Therapeutics said a Phase I study of its experimental treatment for acute myeloid leukemia and myelodysplastic syndrome was placed by the FDA on partial clinical hold. The hold was placed after a patient death, while investigators look into the cause.

The FDA lifted a clinical hold on Gilead Sciences’ lenacapavir for HIV treatment and HIV pre-exposure prophylaxis. All trials for the injectable medicine can now resume.

Data That Mattered

Watertown, Mass.-based Enanta Pharmaceuticals said it failed to hit the primary endpoint of a Phase IIb clinical trial of a small molecule drug for community-acquired RSV. The study enrolled otherwise healthy adults with community-acquired RSV. It did achieve statistical significance in knocking down viral RNA counts, but that didn’t translate to the desired effect on symptoms in this population. The company said it still plans to evaluate the drug, EDP-938, for high-risk patients.

Sometimes a chart is the best way to display data. See Verve Therapeutics’ results with a base editing therapy for cardiovascular disease targeting both PCSK9 and ANGPTL3. Cambridge, Mass.-based Verve also said it plans to start its first clinical trial with VERVE-101, a PCSK9-only edited therapy, in New Zealand in mid-2022.

 

12
May
2022

Changing the Balance of Power

Amanda Banks, MD

Early in my career as a physician, I took care of a woman who died from complications of an abortion procedure.

The patient had traveled to the blue state where I practiced, from a red state where she lived that restricted abortion access, to obtain care she couldn’t find or afford at home. She had previously gotten a procedure performed by a reckless physician who ultimately went to jail for several counts of murder.

She had survived being a refugee from a country that viciously and routinely violated human rights, only to die in an ICU a few months after her arrival in the US. Our team kept her on life support until her family could arrive, when care was withdrawn at their request.

As the US Supreme Court stands on the precipice of overturning Roe vs. Wade, and multiple states consider legislation criminalizing women who decide they must terminate their pregnancies, I cannot stop thinking about this woman and her family. We are about to enter a world where tragedies like this will become far more common.

What is this world, and how did we get here?

The degree to which our country has become polarized on the issue of a women’s right to determine her own reproductive health choices is extreme, but this isn’t about political views. It is about power.

We live in a country, and in a world, where power is concentrated in the hands of  very few. While there are many powerful people who use their influence for positive change, it only takes a few to make catastrophic decisions that affect people with no power, no voice. The powerful are usually men. The powerless are disproportionately women, people of color, poor people without resources.

The women who will most feel the pain and consequence of being stripped of their rights to decide whether, when and how to have children are mainly poor women, black and brown women. If Roe vs. Wade is overturned by the Supreme Court and many states follow through with plans to ban or greatly restrict access to legal abortion, women from these red states will consider traveling long distances to obtain reproductive health services in states that still have safe, legal access to abortion.

The hurdles may be insurmountable in many cases.

Rich women in blue states will likely continue to enjoy these rights, at least for now, perhaps until the powerful reach for even more control.

Look around the world and we see this dynamic playing out on a terrifying scale: In Ukraine, where Vladimir Putin’s thirst for power has made civilian targets of women and children, who are killed, orphaned, trafficked and sold. In Afghanistan, where last weekend the Taliban government ordered women to remain covered in public or their male relatives would be jailed. The list is long.

And yet, we have power too. We have platforms to galvanize our industry as a whole to stand up for those who cannot stand up for themselves.

It is our duty.

It is in fact also our mission (or should be) to improve the health of everyone equally.

We can and should offer generous benefits to our employees living in states that are likely to restrict abortion to obtain the care they need if they have to travel.

We can choose to open subsidiaries and start companies only in locations that will continue to provide reproductive healthcare, and shift away from those that do not.

We can donate money and time to organizations providing aid inside Ukraine and to Ukrainian refugees, and to those working to lift people out of poverty in our own communities.

We can diversify our own leadership by including more women and people with different racial, ethnic and socioeconomic backgrounds on our boards and in our C suites.

We can make our medications and technologies accessible to everyone regardless of their ability to pay.

We must vote.  

These actions may seem disjointed but they are not: they are tied together by giving power and resources back to people from whom it has been denied. They matter. They will add up. They will create a power counterbalance at a time where we cannot afford to stay silent.

I think of my son and daughter, and wonder, like all mothers do, what kind of country and world they will ultimately find themselves in, and how they might use their own power to help shape a better one.

Nothing I could have done would have changed the outcome for my patient or her family all those years ago. But I remember her, and tell her story, so that we can all remember how real this is, and how perilously close we are to a world where all choice is stripped away. Stand up.

11
May
2022

The Limits of Biomedical Innovation, and Why We Should Embrace Them

Alex Harding, MD., senior vice president, Remix Therapeutics; internal medicine physician, MGH.

Last October, I wrote for this publication about the emergence of Antibody-Drug Conjugates (ADCs) for cancer, based on my father’s experience being treated with Padcev for bladder cancer. A few months later, I posted on Twitter that, while Padcev had stopped working for my father, he had since started on another ADC called Trodelvy.

His tumors had shrunk. He was taking advantage of the time he had been given to do things he enjoyed. My editorial here and subsequent tweet were celebrations of biomedical innovation and all that has been achieved in the last 20 or so years to improve and extend patients’ lives.

The celebration ended in early April. I found myself sitting in an armchair pulled up alongside my father in his hospital bed at Johns Hopkins Hospital in Baltimore. While his cancer remained in check, bacteria had gotten into his bloodstream, causing him to develop the severe weakness, confusion, and low blood pressure characteristic of septic shock. Worse, some of those bacteria had deposited onto the aortic valve of his heart, a condition called endocarditis.

Even though the team at Johns Hopkins had given him antibiotics that eradicated the bacteria from his bloodstream, my dad’s condition did not improve. His blood pressure remained low. He began to accumulate fluid in his legs and lungs, an indication that his heart was not pumping effectively. The bacteria had damaged the aortic valve so much that, while his heart pumped blood out of the heart every time it contracted, the blood rushed right back into the heart through the leaky aortic valve each time the heart relaxed.

He was hospitalized for three weeks. While he improved over the first week with antibiotics and treatment for his low blood pressure, he got worse over the next two weeks. He began to grow weaker, and as fluid filled his lungs, he needed more and more oxygen support. My dad’s heart had failed.

He was dying.

Over the preceding year and a half, Dad had been on four different anti-cancer medication regimens. The treatments came with significant side effects, but most of them also worked effectively to shrink his tumors. He tenaciously coped with side effects from his treatments and continued to lead a fulfilling life. But now, with his heart failing him, that had changed. There would be no more ADCs, no genetically-targeted anti-cancer drugs, no medicine that would miraculously restore life. After being a beneficiary of the remarkable successes of today’s biomedical innovation efforts, he now faced its limits. My dad, Rob Harding, died on April 7. He was 75.

There are a couple of things you should know about me as you read this.

First, I love drugs (the legal kind). As a physician, the main tool at my disposal to treat patients is my electronic prescription pad. As a biotechnology professional, my singular goal is to help discover and develop new drugs. While some have critiqued modern cancer drugs for offering marginal benefit to patients at the expense of debilitating side effects, those critiques don’t apply to my father. His bladder cancer responded to the treatments he received in stunning ways. While he did have major side effects from the medicines, the benefits unequivocally outweighed the downsides for him.  I am not a luddite who resists technological advances. On the contrary, I yearn for more progress that can help patients live longer, better lives.

The second thing you should know about me is that I have spent a lot of time with dying people—not only my parents (my mother died of ALS one year ago), but also the countless patients I have treated as a physician who were approaching death. That experience has given me perspective on how to care for a dying person.

Patients are cared for at the bedside, not in the lab, and that aphorism certainly applies to dying patients. Sometimes, when a patient is facing death, the doctor’s job is to find a medicine to extend their life. Sometimes, a patient facing death needs a treatment that eases their suffering. And sometimes, when death is coming, what’s needed is not a medicine at all, but an attentive ear or a gentle hand—simply being there.

As someone who loves drugs, the hardest thing for me was knowing when to stop throwing new things at the problem. There was always one more drug we could try: a new anti-cancer drug that might erase his liver metastases more completely than the current therapy; perhaps a different antibiotic could better address the infection on his heart; maybe the right medical cocktail could restore his heart’s strength.

How could I step back from my reflex to reach for a new medicine?

As I sat facing my father in his hospital room, I thought through the events over the prior three weeks. I looked at my dad as he lay still in bed. Eventually, I could see that he did not need another medicine. His hand was cool to my touch and puffy with accumulating fluid. I squeezed his hand and he squeezed mine.

All doctors live for the opportunity to save a life. It’s what we dreamed about when we started medical school, and the thrill of making the right diagnosis and giving the right treatment to a patient teetering on the precipice is what spurs most of us to keep going. Indeed, the entire artifice of the biomedical innovation machine—academic labs, biotechnology start-ups, pharmaceutical companies—revolves around the ideal of saving a life. Sure, the FDA describes “Feels, Functions, or Survives” as the key criteria to determine whether a drug should be approved. “Feels” and “function”–in other words, improved quality of life—certainly matter a great deal, but we all know that drug discovery glory goes to increasing survival.

And yet, a universal, inescapable truth will eventually confound all our efforts to preserve life. It is a fact that is both utterly obvious and rarely discussed: Everyone we love will one day die.

If you are lucky enough to live a long life, you will probably accompany people you love on their journey toward death, too. It’s worth thinking about how you will handle such a situation.

In the biomedical professions, we tend to delude ourselves into thinking that most medical decisions have been studied with sufficient precision that they can be considered a matter of science. Often, such faith in science is exaggerated. The decision on when not to continue aggressive measures, in particular, remains firmly planted under the domain of art, detached from hard data.

In a world where data is king, letting go of scientific endeavor at the end of life can feel like a loss of control. It is difficult to concede that our scientific arsenal is no match for nature. And yet, doing so can be exactly what is needed to provide someone you love with comfort and dignity as they die. It does feel like losing control. But it is also a way to bring what’s important back into focus. All the sophisticated technologies—the drugs, devices, and equipment that form the apparatus of biomedical innovation and its efforts to prolong life, dissolve away. What’s left is the person you love.

Hard as it was, I had sat with enough sick patients to know. As I sat there with my father, I saw that it was time to embrace the limits of scientific progress. It was time to sit together, me and him. No more IVs or EKGs, no more pills or blood draws. Just two people.

In that hospital room, Dad and I talked about the summer vacations our family had taken when I was a kid. He had particularly fond memories of our trip to the Grand Canyon when I was 8, and when I was older, to Brazil. He mentioned a few people he wanted to make sure my brother and I invited to his memorial service. We reminisced about going to baseball games together at Camden Yards. He had taken me to the game in 1995 when Cal Ripken, Jr. tied Lou Gehrig’s record for consecutive games played.

After we talked for almost an hour, Dad needed a break. He dozed off. I squeezed his hand a little tighter.

9
May
2022

Fighting Cancer With Food and Drugs: Lew Cantley and Sid Mukherjee on The Long Run

Today’s guests on The Long Run are Lewis Cantley and Siddhartha Mukherjee.

They are co-founders of San Francisco-based Faeth Therapeutics.

Lewis Cantley

Cantley, who recently moved to Dana Farber Cancer Institute, is a scientist well-known for his work on cancer metabolism. He discovered the PI3kinase pathway that’s an important regulator of normal cell growth, proliferation, metabolism – and which can become activated to promote the survival and proliferation of cancer cells. This work inspired many cancer drug discovery efforts across the industry over the past 15 years.

Mukherjee is a physician-scientist at Columbia University. He runs a research lab, treats cancer patients, writes bestselling science books and also finds time to start biotech companies.

Cantley and Mukherjee have joined forces recently around a provocative idea.

Siddhartha Mukherjee

They are exploring the role of nutrition in the treatment of cancer. Through this startup company, they are betting that cancer patients will live longer and better lives on carefully calibrated diets. These diets are designed to be taken in combination with a PI3kinase inhibitor, some common chemotherapy, or a common diabetes treatment that lowers blood sugar.

Essentially, they want to reprogram metabolism to slow the growth of tumors and give conventional treatments a better chance to kill the cancer.

Nutritional science is a minefield for a bunch of reasons, which we touch on in this conversation. The company has a lot of work to do to prove its hypothesis. The company is beginning to enroll patients in clinical trials. It should know within a few years whether it’s on the right track.

For those who want to read up on the science, Faeth has compiled a list of five foundational research papers that were published in Nature and Science between 2013 and 2019. If you read them all back-to-back, at a bare minimum, it really makes you wonder how the world of cancer treatment might look different if everyone were put on managed diets in combination with standard treatments. You can see a link to those papers here.

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

 

Alpenglow sheds new light on pharmaceuticals with AI-powered, 3D spatial biology. Pathology is an essential component of drug development, yet it is stuck in archaic times by looking through 2D slides. Alpenglow has developed an end-to-end drug development solution with proprietary 3D imaging, cloud processing, and AI analysis to digitize entire 3D tissues, providing 250 times more data and deeper insights. Learn how Alpenglow can illuminate your path to breakthrough results at alpenglowbiosciences.com.

Now, please join me and Lew Cantley and Sid Mukherjee on The Long Run.

5
May
2022

An Old Idea Whose Time Has Come

Luke Timmerman, founder & editor, Timmerman Report

People are returning to the office. Many are rethinking the basics of work.

So many people are exhausted and anxious. Biotech leaders are thinking carefully about how to proceed. An R&D-based industry needs people in environments that allow them to be energized, creative, collaborative.

Here’s one simple idea: Walking meetings.

The “walk and talk” business meeting isn’t new. But we are learning more about its value in the workplace. We know from a growing body of psychological research that walking meetings spur creative thinking (see this 2014 paper from Stanford University researchers and this 2016 publication from Iowa State University psychologists). We also know sedentary lifestyles are unhealthy, and can be deadly over time (see this 2017 paper in the Annals of Internal Medicine).

The human body didn’t evolve to sit at desks, hunched over keyboards, for 10 hours a day. We are made to get outside, breathe fresh air, and get the blood flowing.

The philosopher Friedrich Nietzsche once wrote: “All truly great thoughts are conceived by walking.” Apple CEO Steve Jobs was a fan of the walking meeting. He inspired Silicon Valley leaders to follow. Some have designed campuses that encourage outdoor walking meetings, and discourage meetings in standard conference rooms.

Walking meetings might be an especially good idea at this moment in time, when so many workers have languished physically, and have been stressed emotionally by isolation.

Mostafa Ronaghi, the longtime chief technology officer of Illumina, co-founder of Grail, and now CEO of a SPAC affiliated with Senti Biosciences, has become a convert the past couple years. “I was tired of Zoom,” he said.

Mostafa Ronaghi

The realization came early in 2020, when he was still at Illumina, the DNA sequencing leader. For a dozen years, he oversaw a R&D team, which had grown to 230-240 people. The early pandemic was intense, with urgency to work on genomic surveillance of the new virus.

Instead of grinding away entirely on Zoom, he picked out long stretches of his day for walking meetings. Sometimes it would be 3 hours. Mostly, it was around his neighborhood in Silicon Valley. He’d wander around in a 4-mile loop, through a suburban cul de sac in Atherton, absorbed in conversation. Headset in place, Mute button On. Most of the time.

“There was no construction. The streets were very empty,” he said.

It was a welcome respite.

Was this a more creative and productive way to work? “I definitely listen better,” Ronaghi said. New ideas tend to flow when he’s walking outside – either with someone walking with him, or just walking and talking on a phone call. Either way, walking outside tends to focus the mind.

A big advantage is that it cuts out distractions from email, and websites clamoring for attention.

Walking meetings don’t work for every situation. Sensitive meetings, large group meetings, and board meetings that require consensus are best held elsewhere.

Zoom had its uses. Some 2-hour group brainstorm session helped bring his team out of an inventive lull. But walking became his preferred option for one-on-ones. People got the message over time that if you need to meet with Mostafa one-on-one, walking outside was the way to go.

David Shaywitz, the VP and Distinguished R&D fellow for data and digital at Takeda Pharmaceuticals in Cambridge, Mass., said he picked up the walking meeting habit years ago while at a Silicon Valley startup. The Boston biotech community doesn’t enjoy the same weather, but he’s found similar enthusiasm from East Coast walkers.

Quite a few senior leaders at Takeda like to walk and talk, including R&D president Andy Plump. “People have routes they use for 30-minute and 60-minute meetings. Love it,” Shaywitz says.

Amy Abernethy, the president of clinical studies platforms at Verily Life Sciences and former principal deputy commissioner of the FDA, is another biotech leader known for her walking meeting habit. She took it to a new level early in the pandemic. “I routinely walked 6 to 12 miles a day,” she said. Now she says she’s walking about half that much, and is back to a normal walking and exercise routine a few days a week.

Amy Abernethy

Generally, Abernethy said she tries to get outside for any meeting that doesn’t require her to be on video. “Walking allows me to focus on the conversation without getting distracted by things on my computer screen (emails, slacks, etc). I also find that I think better when I am moving,” Abernethy says.

She’s developed some habits to make it easy to get out the door on busy days. Tennis shoes and a weather-appropriate change of clothes are ready by the door, in case she needs to change between meetings. She even has practiced a 28-minute walking loop that’s the right distance for the typical 30-minute meeting.  

Some especially good ideas have emerged. The Evidence Accelerator run by Reagan Udall Foundation, in consultation with the FDA, was a byproduct of a walking meeting. In a short time at Verily, she said walking meetings have already produced new ideas for data partnerships and projects.

There are potential downsides. Abernethy shared one funny story.

With airpods in, absorbed in a conversation about efficient clinical research, she tried to tap contemporaneous notes on her phone.

Ideas were flowing. But she wasn’t watching her step.

“I heard a man yelling at me “Lady”, “Lady”, “Lady”. His voice was getting louder and louder. I turned to look at him – he was about 10 feet behind me pointing at the path and saying “LADY!!!”. He was pointing at a huge snake stretched across the whole path. I had managed to step over the snake and keep walking without even noticing.”

The moral of the story? Try not to get bit by a snake or hit by a car.

Seriously, though, walking meetings strike me as one of those old ideas whose time may have come. They are healthy. They foster creativity. They’re good for certain kinds of collaboration.

They just might be part of what could make the workplace a better place.

 

Data That Mattered

Netherlands-based Argenx said it passed a Phase III clinical trial with efgartigimod alfa-fcab (Vyvgart) for adults with Primary Immune Thrombocytopenia. The drug, a neonatal Fc receptor (FcRn) blocker, was able to help 22 percent of ITP patients boost their platelet counts, compared with 5 percent on placebo. The drug was initially approved by the FDA in December for myasthenia gravis.

AstraZeneca’s dapagliflozin (Farxiga), an SGLT2 inhibitor originally developed for diabetes, met the primary endpoint of a Phase III trial in heart failure patients. The drug was tested on a composite primary endpoint of cardiovascular death or worsening of heart failure. Data will be presented at an upcoming medical meeting.

Novartis reported that ribociclib (Kisqali), its CDK4/6 inhibitor for HER2-negative advanced breast cancer, delivered a median survival time of five and a half years (67.6 months), when given to newly diagnosed patients in combination with fulvestrant. The drug reduced the risk of dying by one-third (33 percent), when compared with patients who got the fulvestrant alone. Long-term follow up results were from the Monaleesa-3 study.

Regulatory Action

Hong Kong, Shanghai and Florham-Park NJ-based Hutchmed said it received a Complete Response Letter from the FDA. The company said it submitted an application to market surufatinib, which contained data from two positive studies from China for patients with neuroendocrine tumors, plus a bridging study from the US. The FDA responded that’s not enough. It wants to see a multi-regional clinical trial (a response in line with a new policy outlined by FDA cancer review boss Richard Pazdur).

Boston-based Vertex Pharmaceuticals said its VX-880 program, a pancreatic islet cell replacement therapy for type 1 diabetes, has been placed on Clinical Hold by the FDA because there’s not enough information to support dose escalation. The company said it was surprised.

Shanghai-based Junshi Biosciences and Coherus Biosciences of Redwood City, Calif. said they received a Complete Response Letter from the FDA. The companies are seeking to market toripalimab in combo with chemotherapy for nasopharyngeal carcinoma. The companies said in a statement that the agency is asking for a process change that they believed is “readily addressable.”

New York-based Axsome Therapeutics received a Complete Response Letter from the FDA for its application to market a treatment for acute migraine headaches. The agency is asking for more information on chemistry, manufacturing and controls. The company said it believes the questions are addressable.

Rockville, Maryland-based Supernus secured FDA clearance to market viloxazine extended-release capsules (Qelbree) for adults with attention-deficit hyperactivity disorder.

Florham Park, NJ-based Phathom Pharmaceuticals secured FDA approval for a pair of new antibiotics. One is vonoprazan, amoxicillin, clarithromycin (Voquezna Triple Pak), and the other is vonoprazan, amoxicillin (Voquezna Dual Pak) for the treatment of H. pylori infection in adults.

AstraZeneca and Daiichi Sankyo secured FDA approval to market fam-trastuzumab deruxtecan-nxki (Enhertu) as a treatment for metastatic HER2-positive breast cancer, in patients who got a prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy. This approval was based on some extraordinary clinical data, which showed Enhertu reduced the risk of disease worsening or death by 72 percent when compared head-to-head with Roche/Genentech’s TDM-1 (Kadcyla). The drug was first approved in 2019 based on a different study.

Deals

Gilead Sciences agreed to a collaboration with Waltham, Mass.-based Dragonfly Therapeutics to develop engineered NK cell engaging therapies for cancer and inflammatory diseases. Gilead is paying $300 million upfront to Dragonfly, and getting an exclusive worldwide license to Dragonfly’s 5T4-targeting investigational immunotherapy program, DF7001. Gilead is also getting options to license other drug candidates that use Dragonfly’s tri-specific NK cell engaging platform.

UK-based Amphista Therapeutics struck a partnership with Bristol Myers Squibb to develop targeted protein degrading therapies. Amphista is getting $30 million upfront. The statement didn’t mention other terms, like which therapeutic areas or indications BMS has in mind. Separately, Amphista announced a deal with Merck that brings in $44 million upfront. That deal pertains to targeted protein degraders for oncology and immunology indications.

Vancouver, BC and Seattle-based Zymeworks, the multi-functional antibody developer, confirmed the board has received an unsolicited takeover bid from All Blue Falcons for $10.50 a share. The company ended trading at $6.49 Thursday.

Burlingame, Calif.-based Genesis Therapeutics, an AI for drug discovery company, pocketed $20 million upfront through a partnership with Eli Lilly. The deal covers up to five targets across a variety of therapeutic indications.

Strategy

Illumina, the leading maker of DNA sequencing instruments, said it intends to branch into the drug discovery business. It’s through a five-year partnership with Deerfield Management. (STAT coverage).

SARS-CoV-2
  • See this study from the UK that says cognitive impairment for severe COVID patients equals roughly a 10 point drop in IQ, or about what normally occurs between the ages of 50 and 70. “Multivariate profile and acute-phase correlates of cognitive deficits in a COVID-19 hospitalised cohort.” eClinicalMedicine. May 2022. (Adam Hampshire, Doris Chatfield et al from Imperial College London and University of Cambridge) Summary in New Scientist.
  • “Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospitalized Patients During the First Year of the COVID-19 Pandemic.” Critical Care Explorations. Apr. 2022. (Anna Cervantes-Arslanian et al Boston University School of Medicine)
  • WHO Study Says SARS-CoV-2 Has Killed Nearly 15 Million People. New Scientist. May 5. (Michael Le Page et al)
  • You Were Right About COVID, and Then You Weren’t. Understanding when to abandon beliefs and when to recommit to them can help us ride out this pandemic and prepare for the next one. The Atlantic. May 3. (Olga Khazan)
  • It Ain’t Over Till It’s Over. Science. May 5. (Holden Thorp)
  • 2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection. BioRxiv. May 2. (Yunlong Cao et al Changping Laboratory, Beijing)
Science Policy

The White House issued a summary of work on pandemic preparedness through the new Center for Forecasting and Outbreak Analytics – sometimes likened to a National Weather Service for pandemics.

The President’s Conference on Hunger, Nutrition and Health is being scheduled for September. Food companies are obviously a big piece of the puzzle. But given the magnitude of the obesity public health crisis, I hope a few people from the biopharmaceutical industry are at the table – especially given there’s a new generation of potent weight loss drugs that could be another piece of the puzzle (see last week’s Frontpoints).

Three key FDA officials – Peter Marks, Janet Woodcock and new commissioner Robert Califf – summed up a few of the key considerations in COVID-19 vaccine reviews, with an eye toward preparing for a fall surge. See “COVID-19 Vaccination—Becoming Part of the New Normal” in the May 2 edition of JAMA. The FDA always has a hard job, but consider the current situation:

They’ll need to decide on the best vaccine formula for the variants in circulation in June.

That’s the advance time needed for manufacturers to make enough doses at scale to have them ready for October, when the seasonal surge is expected, like with flu.

Problem is, we might have a new variant in circulation then, rendering the new vaccine formulation a day late and a dollar short.

Notice they mentioned the vaccine advisory committee recently expressed a desire to push for uniformity on vaccine formulation from the vaccine makers. Why? One can surmise that we are bogged down in such a misinformation cesspool that these officials are afraid that run-of-the-mill competitive differentiation from manufacturers might confuse the public. That doesn’t worry anyone in ordinary times. But we know all too well that the antivax movement is ready to pounce at a minute’s notice. They could manufacture enough phony doubt to scuttle an entire national booster campaign, especially if there’s any legitimate ambiguity whatsoever about the new vaccine’s effectiveness against the variants.

It’s going to be a high-wire act at the FDA, and for the companies, in June.

 

Personnel File

Biogen said CEO Michel Vounatsos is heading out the door. The company has begun a search for his replacement, and he will stay until the new boss arrives. Vounatsos will remembered as the leader who drove the company into the ditch, overseeing the Aduhelm regulatory controversy and the commercial disaster that damaged the credibility of the company and the industry. His exit has seemed like an inevitable result for months. See previous TR coverage — “The Biogen Debacle Continues” from January, “Biogen’s Alzheimer’s Controversy” from June, and “Biogen’s Perilous Path” and “Biogen’s Bumbling Defense” from July).

Mary Klotman, a physician-scientist at Duke University with extensive experience in HIV, is being considered as the next director of the National Institutes of Health, according to the Washington Post. The story reads like a classic trial DC trial balloon. At least one other unnamed candidate is being considered, according to the Post.

Kathrin Jansen is planning to retire from her leadership role in Pfizer’s vaccine R&D organization. Mikael Dolsten, Pfizer’s chief scientific officer, announced the move on LinkedIn.

Cambridge, Mass.-based Spero Therapeutics, the antibiotic developer, is cutting 75 percent of its workforce. The company suffered a setback in a recent meeting with the FDA, which suggested its New Drug Application for tebipenem HBr isn’t likely to be approved with the existing data package. The company is cutting commercial efforts for the program and focusing its resources on a couple of other programs in earlier development. Spero had $146 million in cash at the start of the year.

An activist investor in Bothell, Wash.-based Athira Pharma, an Alzheimer’s drug developer, issued a statement calling for the board to replace CEO Mark Litton with his preferred candidate, former GSK chief medical officer Ronald Krall.

Cambridge, Mass.-based Codiak Biosciences hired David Mauro as chief medical officer.

Philadelphia and UK-based Adaptimmune, the developer of T cell therapies for cancer, said it promoted Joanna Brewer to chief scientific officer. She most recently served as Senior Vice President, Allogeneic Research.

Watertown, Mass.-based Seismic Therapeutic, the company using machine learning for immunology drug discovery, hired Maude Tessier as chief business officer. She was most recently with Ikena Oncology. (See TR coverage of Seismic, and Tessier’s comments in a recent BD Secrets column by Vikas Goyal).

San Francisco-based Xcell Biosciences, an automation and instrumentation company for cell therapies, hired Shannon Eaker as chief technology officer. He comes from Cytiva (formerly GE Healthcare) Cell and Gene Therapy.

Earnings Corner

Moderna generated $6.1 billion in first quarter revenue, and has signed purchase agreements worth $21 billion in revenue for 2022 for its COVID vaccine. The world eagerly awaits what kind of data it can deliver with bivalent vaccine candidates, which hopefully can be scaled up in time for the anticipated fall surge, and which will be more effective against the Omicron family of variants or whatever might be circulating then.

Pfizer reported $25.7 billion in first quarter revenue. The company forecasts $32 billion in 2022 revenue from its COVID-19 vaccine, and another $22 billion in 2022 revenue for Paxlovid, the most effective antiviral treatment on the market (which ordinary people are still, tragically, finding hard to access).

Science
  • A bivalent Epstein-Barr virus vaccine induces neutralizing antibodies that block infection and confer immunity in humanized mice. Science Translational Medicine. May 4. (Gary Nabel et al Sanofi, the National Institute of Allergy and Infectious Disease and ModeX Therapeutics)
  • An Old Drug, Finally With a Structure. In the Pipeline. May 5. (Derek Lowe)
Financings

Boston-based Hillevax closed its IPO with total proceeds of $230 million. It’s a vaccine developer working to prevent moderate-to-severe acute gastroenteritis caused by norovirus infection.

Waltham, Mass.-based Dianthus Therapeutics said it raised $100 million in a Series A financing to develop more convenient complement-directed therapies. 5AM Ventures, Avidity Partners and Fidelity led. (TR coverage)

Germany-based Tubulis raised $63 million in a Series B financing led by Andera Partners, and which included Evotec and Fund+. It’s developing antibody-drug conjugates against solid tumors.

Menlo Park, Calif.-based Patient Square Capital said it’s received a $300 million commitment to invest in Enavate Sciences. It’s an entity that will provide strategic growth capital to drug developers. It’s led by James Boylan, former president and head of investment banking at SVB Leerink.

Our Shared Humanity

This one caught my eye as a Wisconsin native who left for the West Coast 20 years ago. “Our region is rich in top-notch academic research, but we struggle to develop local businesses from it.” Milwaukee Journal Sentinel. Apr. 26. (Kathleen Gallagher)

A Failure to Invest

How are nonprofits hospitals doing on their legal responsibilities to provide charity care and community investment? Not good. Not good at all. See the Lown Institute Hospitals Index for a detailed look at 275 nonprofit hospital systems around the country – and the 227 of them who spend less on charity care and community investment than they get in the value from tax breaks. H/t @bijans

3
May
2022

Ram Aiyar on Finding Deal Alignment Internally and Externally

Vikas Goyal, former SVP, business development, Pandion Therapeutics (now part of Merck)

Ram Aiyar is currently the CEO of Cambridge, Mass.-based Korro Bio, a company using RNA editing to treat genetic diseases, including Alpha-1 Antitrypsin Deficiency.

Before he took that job, he was a founder and executive vice president of corporate and business development at Corvidia Therapeutics. That company was acquired by Novo Nordisk in August 2020 for $725 million upfront, and $2.1 billion total.

The deal gave Novo access to ziltivekimab, a fully human monoclonal antibody with half-life extension technology, targeting the IL-6 ligand. The drug was in a Phase 2b trial in chronic kidney disease at the time of the acquisition, with plans to proceed into a global cardiovascular outcomes Phase 3 study. The Phase 2b data that drove the acquisition was published in The Lancet in May 2021.

Novo saw a large commercial opportunity in cardiovascular disease in chronic kidney disease patients, which would build on their existing insulin and GLP-1 driven diabetes franchise.

Aiyar spoke with me recently about that deal and some of the lessons learned.

Ram Aiyar, CEO, Korro Bio

Why did your team and board believe it was the right time to partner? Why was Novo the right partner to work with?

The science behind our drug was validated. The question was ‘did we have the money to bring ziltivekimab through approval?’ This would have required running a large cardiovascular outcome study that might cost between $300-500 million – and not to mention the investments required to support the commercial piece after that.

When you think about the likelihood of success and the amount of capital required to fully develop, we wanted to find a group that was committed to running that outcome study, and running it in a way that we thought would have a high likelihood of success.

Let’s leave money aside for a second. There were a couple of parties around the table during our acquisition. When we thought about how these companies might develop the drug themselves, we were very aligned with Novo on how we were approaching the unmet need for patients, and on how we would execute the drug development plans towards approval (assuming the science continued to play out).

There were other potential partners that wanted to go into larger patient populations. We agreed those trials could be done, but also believed conducting those trials could delay the approval and launch of ziltivekimab for CKD patients, where the unmet need was very high and where ziltivekimab’s mechanism had a very good chance of success. For example, Novartis’ CANTOS study with Paul Ridker [evaluating the anti IL-1ꞵ mAb canakinumab in patients with atherosclerosis] showed really differentiated benefit in patients with CKD. In just 1,800 patients over two years they showed a 50% mortality benefit.

Philosophically, Novo was aligned with our approach. Case in point, Novo has stuck to the timelines that we had put together back in 2020. To see large pharma move with that pace is so encouraging. I really believe the drug is in the hands of the right folks.

What was your role in building the relationship with Novo and ultimately closing the collaboration?

This is a team sport! We built our relationship with Novo over the course of three years. Initially, they were interested in one of our earlier programs which was going after acute pancreatitis. Those interactions built up a lot of goodwill. Over that time, Novo had strategic changes with new people coming in and a new desire to expand into cardiovascular disease. Our interactions shifted to ziltivekimab. We became deeply engaged on the drug’s science, where the drug needed to go, and the evidence that would be required to support approval.

I was on the frontline to a certain extent to set up those relationships – and managing a lot of back channel discussions to keep our companies aligned – but all of us played a role. Our CMO Michael Davidson played a big part in convincing Novo’s leadership of ziltivekimab’s therapeutic potential. Matt Devalaraja, our CSO and head of R&D who was responsible for all of our nonclinical, translational and CMC development, was key to convincing Novo the safety benefits our drug brought due to the low-dose and that we were at commercial stage manufacturing and ready for Phase 3. And during the final stages of the transaction, it was our CEO Marc de Garidel who played a role with Novo’s CEO [Lars Fruergaard Jørgensen] to ensure all the pieces tied together, and to remind Novo’s leadership that ziltivekimab’s had the potential to completely change Novo’s revenue trajectory.

How far into this 3-yr relationship building did you realize how serious Novo’s interest was?

I remember it very well – it was at the 2019 European Socety of Cardiology Congress [in Paris]. I knew we needed to get the right folks within Novo Nordisk educated, interested and engaged on ziltivekimab. We did two things. First, to at least start the conversation, I asked an old colleague [Marian Nakada at JJDC] who had previously worked with Novo’s head of CV [Karin Conde-Knape] to make a personal connection. At the same time, Michael [Davidson] and I reached out to one of Novo’s KOLs, [Dr. John Kastelein]. So there was this independent and positive reinforcement with Novo around the ESC Congress. That’s where the engagement really started and they got interested to dig deeper.

Over the next year as we generated more clinical data, that interest level just grew. I think we were on the top of their list for a year or so before we transacted.

It started with a small group of people at ESC 2019, but it very rapidly progressed to high level discussions with Novo’s leadership. There were maybe 10 people from Novo involved – their CSO [Mads Krogsgaard], Head of R&D [Marcus Schindler] their CV team, and the corresponding business development people. Zaki Salanti in Novo’s Search and Evaluation group led the scientific discussions. On the transactions side it was John McDonald, Novo’s head of business development.

In addition to the clinical data, what else drove Novo’s interest in partnering with you?

We had a pre-filled syringe in commercial scale manufacturing.

I think sometimes, especially with manufacturing, if a potential transaction could occur, companies may defer the investments and take a “minimal” path. We did not do that.

We started on CMC even in our Series A and that paid dividends for us. If there is any question you haven’t asked yet, it is where would I advise companies to invest early. We made a conscious investment in CMC. We were ready to go whether we were doing the study or a partner was doing it. Because if we didn’t do that, Novo wouldn’t have been able to start the outcomes study so rapidly. It would have taken a year or so of CMC work. And that would have had an impact on the transaction.

We had checked a lot of boxes for them. What was surprising for Novo was that Corvidia was a 15-person company. I remember when we went through diligence and transfer of CMC – they had 50 people on their side and we had literally 5. It was amazing to them that a 5 person team could do everything.

So you’ve got this really big clinical opportunity already with CKD, but then this even much larger opportunity with broader cardiovascular disease – how do you keep people’s eyes on the ball?

The Novo team was very pragmatic – they wanted to get the drug approved, they wanted to follow the strongest scientific evidence, and they wanted to start generating revenues. And CKD was a natural extension of Novo’s existing product mix of insulin and GLP-1 drugs for diabetes.

Diabetics are patients who have kidney and cardiovascular complications. 60% of CKD patients are diabetics.

When you think about the cardiometabolic unmet need from an anti-inflammatory standpoint, CKD really jumps out. And CKD is a very large clinical opportunity – it’s 3 million patients! And we had done enough commercial legwork on how we’d go to market, including looking at potential pricing strategies, to know that CKD was a very attractive business opportunity compared to other potential new drug opportunities.

As a small company, we made a conscious effort to provide the best benefit and long-term value to patients. There were some parties who got the huge potential across other cardiovascular indications and were only focused on that. But we were always clear about where we thought the data was strongest and where we wanted to take ziltivekimab in CKD.

We were lucky with Novo.

One, we had multiple parties at the table, including other potential industry partners and also potential investors. Novo had to at least offer us par value.

Two, we found a partner who really wanted ziltivekimab and is moving the drug like it’s their own child.

At one point, the CEO and CSO of Novo said that if Novo believes in this asset Novo should go after it and get the deal done. And so now we have the confidence that they will treat the drug well, develop it well, and turn it into a product. Even more than a year after the transaction, Lars [Novo’s CEO] mentions ziltivekimab and Corvidia in investor calls.

There’s an interesting aside here on how we approached indication selection internally. At one point in Corvidia’s history, we had considered going after anemia. But the clinical data said the mechanism could have huge benefit in CKD. And both indications would have been similar heavy lifts in terms of development costs and timelines. We as a team made a change in strategy in mid to early-2019 to follow where the data led us and committed to pursuing the cardiovascular outcomes in CKD patients. As a biotech, this decision was not for the faint of the heart, and [we were] fortunate to have the support of our board of directors.

We were in our Phase 2 is when COVID-19 was hitting. At the time, Actemra was being used off-label to treat COVID cytokine storm [Actemra (tocilizumab) is another mAb working in the IL-6 pathway, is already approved for multiple rheumatological diseases, and received an EUA for use in hospitalized COVID patients in June 2021].

The Corvidia team saw there may be an opportunity for us to approve ziltivekimab in a very rapid fashion for COVID, an indication that would not require a $400 million clinical outcomes study. But there was also a lot of frenzy about COVID at the time, and the Pfizer and Moderna vaccines were coming together. And we didn’t want to jeopardize access to ziltivekimab for CKD patients.

By the way, we were very transparent with Novo about all of this.

What other deal structures were being discussed? Did your team ever consider a co-development / co-commercialization structure?

There were some parties at the table who wanted to partner with us in Europe. But Marc had a lot of commercial experience and wanted us to be wary of slicing up the drug to multiple parties whose commercial interests may or may not be aligned in the future.

And we were pretty confident that we could get started with the Phase 3 study on our own. We had financing term sheets from investors that would have let us do this . . .

. . . wait, so Novo was competing against you raising more money and going it alone?

OK, that’s where the money part comes in. At the end of the day, when you compare a $725 million upfront cash vs a hypothetical $300+ million follow-on financing, it’s hard to ignore the tangible return that amount of capital would give our shareholders today.

Even when you’ve got access to the amount of capital you need with a nice premium on the valuation, you still have to ask the question about time to return for shareholders. Our investors had been in the company for 3-4 years already; if we kept going, how much longer would it take from here?

But yes, we had options and could say no to less attractive partnership proposals.

Any advice on how to say “no” to partners? How do you do that in a way that makes them come back with an even better offer?

Haha, that’s a good one. The balancing act is to not say “no” in an aggressive manner, to have real alternative options, and to be able to share your business situation. Most folks on the other side understand this. They wouldn’t even engage in a conversation if there was no possibility of a transaction. I think that’s also part of why it took a year plus to get here with Novo. The Novo team was really feeling us out to see where to even start the business discussion.

All of us understood that if we had done a follow-on financing, Corvidia’s valuation would significantly change. And all of us understood that we weren’t just talking about an upfront acquisition payment, we were also talking about a several hundred million dollar subsequent investment to develop ziltivekimab.

We were also transparent about how we would do the development, sharing data to help guide what pricing could be, and sharing tangible data on the relevant patient population. And we laid out for partners what we thought our worst case and upside scenarios could be, effectively setting expectations.

None of our discussions ever started at a super low-ball range, but the first offers were not the best offers. And if we did get a “low” offer, I actually spent time with the other party to explain why it was not a fair offer and to walk them through Corvidia’s perspective of the potential. If you as a company are not fully committed to a path from a patient population perspective, or not fully committed to getting the data to really support that potential, then you’re in no man’s land negotiating on opinion. By the time we launched our Phase 2b, we had all of that buttoned up.

And how did your team work out your own reservation price? How did you know what was “good enough”?

That can be hard. When there’s an interested party at the table, there can already be expectations on size of exit. As a management team, we’re in the middle aligning the interests between investors, the Board, and external parties.

What I found helpful was just laying out opportunities and risks – not necessarily putting probabilities – but just laying out the binary things that could go well or could go wrong, and then discussing with the team that we would be fine with either of those outcomes. So when you lay out the pros and cons, the opportunities and the costs, that plays itself out in terms of level-setting for everybody. And the question is an easier one at that point.

There was also an older partnership process that went through some negotiation dynamics. It was an earlier potential transaction with a separate company about 18 months before all of this with Novo, and before we had started our Phase 2b study. Corvidia had a diverse investor base including European investors, US investors, small investors, big investors, and even single LP investors.

There were some investors who were OK with lower exit numbers. There were others who, given the potential of the company, wanted more. Through that historical process, there was some level-setting in terms of what the market thought was reasonable, how Corvidia should approach a transaction, our valuation expectations, as well as an understanding of our investors’ range of intentions. So coming into the Novo discussion, there was already Board alignment about how we would move forward with a potential acquisition.

Another consideration for us was that we needed access to significant capital to fund the next cardiovascular outcomes study. Everybody loved the science, the product, and the team. But there was financing risk that would need to be removed off the table.

Should we go public? Did we need a step before that to support the IPO? We started a financing process about a potential Series C, and ended up with $350-400 million in term sheets. The Board was involved in all of those investor discussions about capital availability and the risks of running the clinical outcomes study. Let’s just say the valuation proposals from new investors were a tad bit lower than what we ultimately got in the acquisition.

I will say one thing, Vikas, outside of investors and the market, a very key alignment is internal team alignment. I cannot stress enough that it is critical the management team first knows what it wants to do. And then we can align with the other parties around the table. If there are disparate voices within the team about what to do or not to do, no matter where you end up in a negotiation, there is uncertainty. That was a learning for us in that previous transaction discussion. Some folks at Corvidia wanted to do it, others didn’t want to do it, and still other folks wanted to do something different. That also got clarified over time. If there is trust around the team, I don’t think that is necessarily a challenge. In Corvidia’s case, I truly believe that the four of us [Marc, Michael, Matt, and Ram] were tied at the hip. Sure, we had disparate opinions, but all opinions were heard and discussed, and we disagreed and committed.

In those last stages with Novo, how did the process go?

Over the year or so of our process with Novo, the drama was really around data, and that really came to a head when we were close to executing. They wanted, all of us wanted, to see what our Phase 2b data looked like. Any deal and its terms were contingent on that data. And this was during COVID [which was straining many clinical trial timelines]. Luckily, our clinical team was fantastic and we recruited faster than anticipated and got our data early. We were sharing data with Novo and other parties as the database lock came through. We were very factual about what we saw and what the safety and efficacy profile looked like. And we were fortunate that the data came out as we anticipated.

As our Phase 2b data came out, multiple parties got excited and came to the table trying to move fast. We hired a banker at the very last minute, first to have a buffer so the same information was exchanged with all parties, and to also ensure we had the right relationships around the table. And then it went very, very fast. We executed in about a week and a half.

How did you create this situation with so many people ready for your data?

An important aspect there is that it takes 3 years to build competitive tension. You have to start with the relationship and then you’ve got to update people with everything going on along the way. There is no guarantee they are actually listening and interested. Strategies change any given moment in large pharmas. So a big part is keeping everyone informed – whether they like it or not. It seems like an obvious thing to just maintain relationships over time, but it’s under-appreciated in the industry.

As an aside, the data room is a great indicator of how many people are actually digging in and how interested they really are.

[laughs]

So now you’re CEO of Korro. What are the pro’s and con’s of being the BD person vs the CEO? What advice would you share?

One difference is the BD person is in a position to get overruled, no harm no foul. But the CEO, the buck 100% stops with them. At the end of the day, it’s the CEO’s judgment that the Board has to listen to or not.

Second, the BD person is in the middle between your team, the external party, and the Board. Because you’re just a conduit to ensure that everyone is aligned. That means you can do the market check – coming back and letting the team know what is going on outside. Usually, the BD person is alone in those market check discussions, so it gives you a buffer and room to play with business terms with the other side. And you can always be overruled and go back afterwards and play the “what do I know” card.

That said, some of the best interactions in my opinion were when you had both a scientific leader and a BD person together with the external party, to bridge those two topics. It’s also a good check for yourself, too. There were times where we would come back from meetings with different perspectives. There are things that my colleague caught, and there were things that I heard and they were different. It’s important to have that check.

Lot of times, folks internally may have drunk their own Kool-Aid. They’re so focused on doing the work. They don’t go out and see what’s happening externally. So the BD person will actually have to bring the scientific team members to the table to say “OK, here’s what others externally are doing and saying. Here’s the evidence to support their position. Should we do something different?” You’re not telling people what to do – you’re just opening up the window. Sometimes it’s an under-appreciated part of the BD job, but it is critical. Whether we like it or not, whether it’s on the science side or the finance side, the market is often right. We can go in a different direction than the market, but at least we need to know that perspective. You can’t just put your head down and do the work.

2
May
2022

Biopharmas: Digitizing, But Not Quite Digital

David Shaywitz

What a difference two years makes.

In January 2020, I left my role as a senior partner at a corporate life-science venture fund to pursue my interest in what I recognized as a captivating frontier: the intersection of biopharma with emerging digital and data technology.

I set up an independent consultancy, and advised senior R&D executives in both large and small pharmas.  The need to understand digital technologies profoundly intensified with the arrival of the pandemic – as my co-authors and I documented in this National Academy of Medicine-sponsored analysis published earlier this year.

Our family moved from the Bay Area back to Boston in the summer of 2021. After a decade developing infectious disease medicines at Gilead, my wife became CEO of Allovir, a Cambridge-based public biotech company – a profoundly exciting opportunity.  In autumn of 2021, our three daughters – entering grades 7, 9, and 11 – each started the academic year in a new school. 

And in March 2022, I returned to the pharma company I left two years prior, in what feels like a tailor-made role, VP-Distinguished R&D Fellow, Data and Digital. The ambition: “to realize the future of biopharma through the thoughtful and pragmatic integration of rigorous biomedical science and emerging digital and data technologies.”

It’s been…busy.

Returning to the same company (albeit a different location) after a two-year hiatus is providing an unusual before-and-after view into the organization and the industry more generally: a lot has happened, and so much is different.

Office life: the new normal

As so many of us have discovered, the office has radically changed.  Most work is hybrid, and teams show up to the office several times a week (or less if someone is truly remote).  Moreover, many organizations, including ours, have adopted a “hoteling” system meaning that you don’t have your own office, or even your own cubicle.  In the morning, you plunk your stuff down at an available desk in your team’s designated “neighborhood,” and then you haul it away at the end of each day.

I’m not a huge fan of this approach; I like the idea of having a designated work area, which I can personalize; in my pre-pandemic life, I enjoyed stopping by my colleagues’ desks, seeing pictures of the families, knowing where to find them if I had a quick question.  It contributed to my sense of belonging and the feeling of community.  In contrast, I’m finding the flash-mob approach to office life less congenial – although our dog appreciates the extra attention he receives on the days I’m working from home.

Digital progress

Other changes I’ve noticed are surely for the better. Digital and data strategy has moved from the periphery of the organization to the core, as part of a CEO-driven digital transformation effort that seems to have really taken hold. There’s a sense of pragmatic possibility among the folks working on digital and data, driven by the palpable progress they’ve seen in a number of areas (like finally moving most compute from on-premise to the cloud, for example). 

The organization has also recruited – and retained – exceptional talent, which seems especially encouraging given the demand for these skills.

These efforts occur in the context of an industry that (as I’ve written in this space in the context of Novartis, AstraZeneca, and Lilly) is clearly making efforts to embrace digital, while also coming to terms with the challenges.

At a high level, it seems like what’s happening across the industry is what Jeanne Ross and her co-authors of Designed for Digital describe as “digitization,” which they distinguish from the higher-order ambition to develop and deliver digital offerings. 

As Ross and colleagues write:

“We distinguish these two potential impacts of digital technologies as the difference between digitized and digital. Digitizing with digital technologies involves enhancing business processes and operations with SMACIT [social, mobile, analytics, cloud, internet of things] and related technologies. For example, Internet of Things technologies can automate support of distributed equipment or operations; mobile computing can create a seamless employee experience; artificial intelligence can help automate repetitive administrative processes. The applications of digital technology can certainly benefit a company, but they digitize a company; they do not make it digital.”

The authors continue, “digitization enhances operational excellence; digital enhances the customer value proposition.” Digitization “is a prerequisite to digital transformation,” they argue, not equivalent to it.

This description of digitization seems like a perfect summary of what the industry is currently (and unevenly) attempting, an effort to improve operational efficiencies by leveraging the digital resources now available and routine in other industries.

Digital and COVID-19

As described by Pfizer CEO Albert Bourla in his captivating new book Moonshot, Pfizer’s ability to deliver a COVID-19 vaccine with such speed is attributable, at least in part, to an effort initiated prior to the pandemic to digitize operations. In the context of COVID-19, Bourla seems to have imbued the organization with a palpable, urgent, must-do culture (grounded on the premise that “time = lives”). By affording a common and up-to-date window into progress and problems, the digital dashboards enabled this culture by allowing the entire organization to align and focus. 

(It should be noted that, as this insightful 2021 McKinsey analysis points out, most of the 10-fold acceleration in vaccine development observed during the pandemic likely reflects the combination of enhanced regulatory engagement and extraordinary at-risk investment. Even so, the operational efficiencies – enabled by digitization – were also important.)

It will be interesting to see the extent to which biopharma can build on this success to further digitize, and rationalize/organize the many data flows within companies. Established biopharmas are notoriously siloed, as well as stitched together from years of successive acquisitions. This has a tendency to lead to kludged-together data solutions (see figure) that may get the job done, MacGyver-style, but are inefficient and result in missed learning opportunities.

In theory, digitally-native companies, such as Moderna, should start with an enormous advantage.  The ability of Moderna – a young company that entered the pandemic a fraction the size of Pfizer – to develop and deliver a novel vaccine in record time speaks to promise of such a foundation, as Iansiti and Lakhani argue in Competing in the Age of AI

Of course, it’s also easy to rationalize that COVID-19 was a special case, and that Moderna just happened to be in exactly the right spot at the right time. 

Hence question one: can digitally-native biotechs consistently beat pharmas at their own game?  Phrased differently, will the apparent operational efficiencies, and improved access to data (which can serve as the basis for further learnings, including those enabled by AI) enjoyed by digitally-native biotech companies represent a meaningful competitive advantage, or will experienced pharma giants manage, through selective digitization, to capture enough of the benefits to avoid disruption?

Question two, of course, is whether digitally-native biotechs – particularly those intent on building digital platforms – can potentially win at a different game, similar to how the iPhone beat Nokia; more on this later.

Lakhani, for his part, asserts that “traditional incumbent organizations have no choice but to embrace [a digital future].  Either you’re going to be competing against the platform or you’re going to be part of a platform that is going to be AI-first.”

Follow this space…

I am following progress in three areas with particular interest:

Future of evidence generation. This is a broad area that generally seeks a more complete understanding of and relationship with patient/participants, involving enhanced breadth (longitudinal data) and depth (e.g. wearables). It prioritizes both ease of participation (eg distributed/hybrid trials) and equity (diverse representation). For a phenomenal overview of this area by one of its leading lights, see this recent presentation by Dr. Amy Abernethy of Verily.

Getting beyond operational efficiency. Digital efforts to date in our industry and others have been most successful in the context of structured, high-volume data and repeatable activities. But in the big picture, what we need more than anything in biopharma are improved translational models – a way of figuring out if a molecule we put into people will actually work, and work safely. The failure rate of clinical development remains abysmal. While AI approaches are constantly hyped, the available data, as Andreas Bender eloquently discusses here, and as Derek Lowe has written here, appears to represent a poor fit for AI solutions.

Escalating security and privacy concerns. The potential insights associated with participant data are accompanied by profound responsibility for ensuring these data are managed appropriately, and always in accordance with the participant’s wishes; thus data stewardship has emerged as a critical pilar of all digital efforts. Add to this the increasing concerns related to bad actors. As FBI Director Robert Mueller said in 2012, “I am convinced that there are only two types of companies: those that have been hacked and those that will be. And even they are converging into one category: companies that have been hacked and will be hacked again.”

To these I might add a fourth topic, which could be called service-oriented architecture, but really boils down to the central premise of both the Ross book and the Iansiti and Lakhani book: will any biopharma embrace the radical digital transformation both sets of authors advocate, as captured in this figure:

The authors of both books emphasize the power of what they describe as a digital platform, constructed as shown at the right of the figure. 

Here’s the basic idea: in traditional firms, as Iansiti and Lakhani write (slightly paraphrased), the

“organization, data, and technology evolve into silos, with disparate retail focus areas largely contained in separate, disconnected units. Connections between silos are haphazard and often unpredictable, motivated by meeting immediate needs and fighting fires.”

A better approach, the authors contend, is to adopt a “modular, distributed structure” based on “a common set of building blocks that could be deployed to drive scale and scope.” At the heart of this approach is a “central, standardized set of services” and the ability to easily communicate through interfaces known as APIs. 

Consequently, “one of the seminal documents in the digital transformation of business,” according to Iansiti and Lakhani, might be a memo Jeff Bezos issued in 2002, in the early days of Amazon, mandating the use of this API-based approach throughout the company. While challenging to adopt, this approach is what ultimately enabled Amazon to scale so fast and so well.

In an industry that seems to be struggling even to digitize the information in narrow silos, such a transformation seems like a nearly impossibly heavy lift for established organizations. As Brian Bergstein has written in Technology Review, “the most common uses of AI have involved business processes that are siloed but nonetheless have abundant data.” Most work is happening within silos, not across them.

Most folks in pharma would love to do their existing jobs better, and struggle less to find and manage the data they currently need; but the idea of transforming the entire enterprise in hopes of facilitating the development of novel digital solutions may prove a prohibitively difficult sell, especially when their current objective – developing impactful new medicines — seems intrinsically worthy and consequential.

Besides, as Bergstein points out, the reports from the AI front are mixed, as “people in a wide range of industries say the technology is tricky to deploy. It can be costly. And the initial payoff is often modest.”  While he notes that technologists may be most interested in “What can the technology do,” the key question for companies is “How much will we benefit from investing in it?”

Transformation visionaries like Ross, Lakhani and their co-authors might suggest another question: “How much will you lose by not investing in disruptive technologies?” And they might suggest we speak to the good folks who used to work at Kodak and Nokia for perspective.