Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $169 per year, you reward quality independent biotech reporting, and encourage more.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $169 per year, you reward quality independent biotech reporting, and encourage more.
Today’s guest on The Long Run is Jo Viney.
She is the CEO of Watertown, Mass.-based Seismic Therapeutic. Seismic is working to discover biologic drugs for autoimmune disease. It aims to speed up the process by using machine learning on key aspects – starting with structural biology and including engineering of the protein drugs themselves.
Jo Viney, co-founder, president and CEO, Seismic Therapeutic
Jo has a long track record in this field. She was previously chief scientific officer of Pandion Therapeutics, a startup acquired by Merck for $1.85 billion in February 2021. Before that, she worked at Biogen, Amgen, Immunex and Genentech.
In this conversation, Jo talks about immigrating from the UK, how she found a career path in industry, and some key insights on how she thinks about building a startup with a creative culture.
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
For Bensalem Township in Pennsylvania, going a step beyond meant taking the word ‘serial’ out of crime, thanks to DNA analysis technology. Before the introduction of this technology, processing the sample of a suspect took 18 months. But with the dedicated efforts of Director Fred Harran and Thermo Fisher Scientific’s RapidHIT ID analysis system, it now takes only 90 minutes – meaning offenders can be caught and put behind bars before they have a chance to become repeat offenders. It’s also helped prove the innocence of 16 people in the last five years.
To watch Director Harran’s story, visit www.thermofisher.com/bensalem-DNA-analysis
Now, please join me and Jo Viney on The Long Run.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $169 per year, you reward quality independent biotech reporting, and encourage more.
Today’s guest on The Long Run is Ivan Liachko.
Ivan the founder and CEO of Seattle-based Phase Genomics.
Ivan Liachko, founder and CEO, Phase Genomics
First off, Ivan is originally from Kiev, Ukraine. He came with his family to the US at the age of 11, around the time of the fall of the old Soviet Union. When Russia invaded Ukraine back in February, he spoke up and mobilized his team and members of the biotech community to stand with the people of Ukraine.
That was interesting. But it turns out the work at Phase Genomics is also quite interesting.
Phase Genomics is helping scientists assemble difficult to put-together genomes, and metagenomes. That’s an extra tricky form of assembly of the DNA jigsaw puzzle that comes when you have a whole bunch of microorganisms co-existing in the messiness of life you find in something like a slab of dirt. One interesting application is now being supported by the Bill & Melinda Gates Foundation and the National Institute for Allergy and Infectious Diseases. The company is creating a repository of phage – bacteria interactions – a so-called interactome – that could be used to help identify precise phage therapies that could be used to fend off scourges from drug-resistant bacteria.
Talking with Ivan reminds me of the magic that comes when the right person lands in the right place at the right time. He and I come from very different backgrounds, but we both appreciate what’s special about Seattle as a community, and the long tradition of the United States as a leader in research and entrepreneurship. He is an immigrant who has had some success, and might have quite a bit more, partly because of his own skills and initiative, but also in large part because of the surrounding community, research culture, and business traditions.
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
What does going a step beyond mean? For Gideon, a young boy fighting leukaemia, it meant getting a second shot at life. Through an innovative new treatment called CAR T cell therapy, Thermo Fisher Scientific supported our customers and the healthcare community to help Gideon reach full remission. Today, he is a healthy, happy eleven-year-old playing basketball and enjoying time with his family, thanks to our customers going a step beyond every single day to make a difference in the world. To watch Gideon’s story, visit www.thermofisher.com/Gideon.
Now, please join me and Ivan on The Long Run.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $169 per year, you reward quality independent biotech reporting, and encourage more.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $169 per year, you reward quality independent biotech reporting, and encourage more.
David Shaywitz
The implementation of emerging technologies requires front-line users to figure out what to do with the technology – how to adapt the technology to the problems users are actively trying to solve.
The most impactful use cases often are not immediately obvious – for example, Edison envisioned the phonograph would be predominantly used to record wills.
Moreover, effective adoption typically requires more than simply substituting new technology into processes built around legacy technology. For example, when factories first started using electric generators to replace steam power, there was minimal impact on productivity. It was only when the design of the factory was reimagined by entrepreneurs like Henry Ford (a redesign enabled by electricity) that the promised gains were realized.
It’s also important to consider what success looks like. PCR, an approach to amplifying often tiny amounts of DNA, was developed by Kary Mullis, who received the 1993 Nobel Prize in Chemistry for his efforts. Adopted relatively quickly, PCR enabled advances from disease detection (eg for COVID) to molecular engineering.
Yet if you look around medical labs today, you won’t find a “Department of PCR” or a “PCR Center of Excellence.” In a sense, the lack of such exceptionalism is a measure of PCR’s success and impact. Today, PCR is organically incorporated into the way science is done. It’s a tool, like the telescope and the microscope, that can be used to enhance our exploration of nature.
Today, medical researchers are actively exploring how to utilize AI. Rather than investing the methodology with spiritual or magical properties, it is increasingly recognized as a tool — a powerful tool if applied thoughtfully — that scientists are incorporating into their study of nature.
Alphafold, for example, is a deep learning tool that offers powerful predictions of 3D chemical structures based on the underlying amino acid sequence. It is already routinely, and appreciatively, utilized by structural biologists. It’s become a powerful new addition to the armamentarium.
Now that AI in healthcare has hopefully transitioned past both the peak of inflated (and truly extravagant) expectations as well as the trough of despair, we seem to have at last arrived at the point where savvy scientists are using AI as another technique to pursue their questions.
For these researchers, AI (like PCR, like microscopy) is a valuable means, a tool used to solve a meaningful problem; AI is not (like in too many breathless early publications) an exalted end, where the use of AI is celebrated, rather than any result it enabled, the “dancing bear” phenomenon I’ve described.
A recent paper, called to my attention by my long-time colleague Dr. Anthony Philippakis, a thoughtful physician-scientist and the chief data officer at the Broad Institute, offers an inspiring example of where AI in medicine may be headed.
The research he describes (and of which he’s a co-author) was led by MGH cardiologist Dr. Patrick Ellinor, who I first met when he was a cardiology and electrophysiology fellow at MGH, during the start of my medical training.
Patrick Ellinor
Ellinor and his colleagues were interested in understanding the basis of aortic aneurysms, dilations of the large blood vessel that can lead to sudden death. The identification of genes associated with aortic dilation could potentially guide the development of future medicines, while also enabling the identification of patients at risk.
Previous work had identified several extremely rare alleles that, if present, unquestionably contribute to the development of aneurysms. Yet most patients who develop aneurysms don’t have any of these alleles.
Other researchers conducted a genome-wide association study (GWAS) to identify genetic variations (single nucleotide polymorphisms, or SNPs) associated with aortic abnormalities based on data meticulously measured and recorded by echocardiography technicians; a dozen or so SNPs that could potentially contribute to disease were identified.
A talented member of Ellinor’s group, Dr. James Pirruccello, had another approach in mind. Pirruccello wanted to leverage the UK BioBank, a massive collection of deep genetic and extensive phenotypic data available to researchers for analysis. For example, cardiac MRI studies were available for about 40,000 subjects. This treasure trove of phenotypic data could be paired with the genetic data associated with participants in the U.K. database.
The elegance of Pirruccello’s approach was how he extracted the data he required from the MRI images. Manual annotation of 40,000 cMRI studies (each containing about 100 images) would be prohibitively demanding and expensive. Instead, Pirruccello trained an AI algorithm to assess aortic diameter, and, amazingly, he did so using a relatively small number of manually annotated images – 116 (92 in the initial training set, 24 in the validation set).
This approach was feasible because algorithms had previously been trained to do similar tasks. While millions of labeled images are required to train the algorithm initially, you need comparatively few to adapt an established AI algorithm to perform a similar task. This is the principle of “transfer learning.”
With the algorithm in place, Pirruccello was then able to turn it loose on the 40,000 or so cMRI images. The team was essentially converting a binary variable (aortic aneurysm: yes/no) into a continuous variable (aortic diameter). That enabled a more sensitive GWAS. Indeed, just focusing on the ascending aorta, Ellinor’s team identified 82 independent genetic regions (loci) of interest, 75 of these were novel. These loci could potentially shed light on the pathophysiology of aortic aneurysm.
These SNPs were then used to generate a “polygenic risk score”– an approach that seeks to integrate the risk contributed by a number of different SNPs, as I’ve discussed here; see also here). In turn, this measurement was used to analyze nearly 400,000 UK BioBank participants to see if it might help predict aortic aneurysms.
Remarkably, subjects with a genetic risk score in the top 10% were found to be twice as likely to develop aortic aneurysms as participants in the other 90% of the population. This type of approach, in theory, could be used to identify patients at higher risk of aortic aneurysm, and presumably help guide prevention strategies, as well as help select patients for future clinical studies. The genetic data might also help identify promising therapeutic targets.
There are many lessons from this approach, including the value of large integrated genetic/phenotypic databases, the power of GWAS analyses and its potential in target identification, and the promise of polygenic risk score assessments.
But the most exciting lessons here involve the intelligent incorporation of deep learning to “parameterize phenotype,” as Philippakis explains. The idea is to elicit an important continuous variable from a collection of images.
Significantly, Ellinor’s critical GWAS analysis, integrating genetics and phenotype, didn’t involve deep learning – just comparatively staid analytics that geneticists have been doing for two decades; the approach is at this point relatively routine.
Similarly, the polygenic risk score calculation didn’t involve deep learning.
And the research certainly didn’t involve someone asking Watson, Jeopardy-style, to think hard and come up with genes involved in aortic aneurysms.
What was clever was how the researchers leveraged AI to generate the input phenotype used in the GWAS analysis.
I hope and expect we’ll see more of these types of “organic applications” of AI as the approach becomes both less exotic and more accessible, and establishes itself as a powerful enabling tool for thoughtful medical scientists.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $169 per year, you reward quality independent biotech reporting, and encourage more.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $169 per year, you reward quality independent biotech reporting, and encourage more.
Vikas Goyal, former SVP, business development, Pandion Therapeutics (now part of Merck)
James Mutamba is the chief business officer of Waltham, Mass.-based Arrakis Therapeutics. It’s a biotech developing small molecules against RNA targets.
Arrakis struck its first major pharma partnership in 2020 with Roche. During the JP Morgan Healthcare Conference this past January, Arrakis announced another multi-target collaboration with Amgen to discover and develop small molecule RNA degraders, a new drug class which Arrakis calls nucleic acid targeting chimeras (NUTACs).
Arrakis’ and Amgen’s research teams are now working together to jointly design and characterize these novel NUTAC bifunctional compounds. For Arrakis, the partnership provided $75 million of upfront working capital, and expanded its platform capability for making small molecules against RNA. Amgen is getting the right to nominate a set of five initial targets and it has the option to nominate more. The deal is part of a pattern for Amgen, as it underscores the priority it has placed on drugs that specifically inhibit more than one target implicated in disease biology.
James Mutamba, chief business officer, Arrakis Therapeutics
Mutamba joined Arrakis on Dec. 6, 2021. Arrakis received the first draft of the agreement from Amgen that week. The deal was signed before Christmas Eve and announced two weeks later at the biggest healthcare investment and dealmaking event of the year.
Mutamba spoke with me recently about what it took to close such a broad and high-impact collaboration so quickly.
Why do partners come to Arrakis for access to your RNA platform?
Arrakis is building a broad platform that, given any RNA target, can figure out the structure of that RNA and develop a small molecule compound against that RNA. Building this kind of platform necessitates a lot of external resources, expertise, and insights. So as we build our platform, we are also out talking about our work. As folks hear about what we are doing, some have come to us and said, “Hey, we have a problem that Arrakis might be able to help with.” That is really what precipitated our collaboration with Amgen, as well as our earlier collaboration with Roche.
Arrakis is developing small molecules that bind to RNA. One way to leverage this is to target RNA’s intrinsic functions, and this is the focus of our partnership with Roche. This means inhibiting translation, changing splicing, modifying RNA stability, or other aspects of the RNA function. Another way is to look at extrinsic properties – can we use a binding event to force a function? One ‘extrinsic’ approach we are pursuing is our NUTAC platform for targeted RNA degradation. NUTACs are hetero-bifunctional small molecules – one side targets and binds RNA, the other side recruits a nuclease or other factor to eliminate the disease-causing RNA.
Why did Arrakis and Amgen want to work together?
We had done some early concepting and could keep working on NUTACs on our own. But, just like our partnership with Roche, we saw the potential to have a landmark NUTAC partnership to supercharge our efforts and more rapidly provide a foundation for us to build our capabilities. There is no better group to work with in the multispecific space than Amgen. They have deep expertise in both targeted degradation and induced-proximity degradation, as well as vast capabilities and competencies in the multispecific small molecule space. In addition to their technical expertise, they also have strategic goals and commitment to multispecific small molecules. And that’s an important piece in choosing the right partner. Is your partner committed to finding a way to make the collaboration and science work? Are they willing to work through any hardships?
We recognized that Amgen has a strong interest in proximity-induced drug approaches. Our NUTAC concept is akin to a PROTAC – an area in which by the way Ray Deshaies, SVP of Global Research at Amgen, is a leading expert. There’s a media interview Ray did on our deal where he explained that Amgen was looking across the RNA space seeking technologies to enable this kind of RNA degradation approach. They kicked the tires of a bunch of players in the space, and ultimately concluded that we were the right group to go with. My supposition is, again, that their decision to work with us is a testament to the breadth of our platform. At Arrakis, our proposition is ‘give us any RNA target and we’re able to tell you what structures are targetable and we can build binders.’ Amgen was bringing the drug function with the effector piece of the hetero-bifunctional molecule. So I suspect for them the focus was on which partner could best figure out the RNA binding.
How did your discussions with Amgen start and grow into this collaboration?
While we had a goal to ultimately find a good partner on NUTACs, we were not yet actively reaching out to potential partners. This collaboration started with an informal discussion between Ray Deshaies and Arrakis’ CEO Mike Gilman. Mike and Ray are both UC Berkeley alumni and were on campus together for a reunion. They started to talk and there was an alignment of vision that ultimately opened the door to this collaboration. And because of the strategic decisions we made early on to go after any RNA target, Arrakis was uniquely positioned to work on RNA degradation strategies compared to some of our peer RNA companies.
It was about a year from that initial discussion between Mike and Ray to when we executed the deal. Things really got serious when we came up with, what I like to call, our “peanut butter and jelly sandwich” concept. Arrakis is bringing the RNA binder to the table, and Amgen is bringing the effector molecule to recruit the degradation factor, and we will work together to develop those into hetero-bifunctional medicines.
Once that bifunctional concept came into view, we started putting the agreement together, including the workplan of who was responsible for which research efforts, and the budgets. We really know how to build the RNA binding piece. Amgen has the demonstrated expertise and interest in building hetero-bifunctional molecules. So a lot of the discussion was about how, working together, we and Amgen could do things sooner or faster or better than what we would have been able to do by ourselves.
This all went really quickly because we had alignment and a shared vision. From the first agreement draft to execution was three weeks. It is the fastest deal that I have ever worked on. Everyone was aligned on who would be doing what, and what was of interest to each party. There were snags here and there, which is true for most deals, but we quickly got over those because people had a very clear view of what success looked like. And we just pushed towards that.
How did you figure out the economics of the collaboration? Did you have any precedent deals or templates you could use as a starting point?
I would say there were more proxy deals we could look at, such as partnerships in the degrader space where one party brought the ubiquitination bait portion and another brought the targeting side. There were some macro guiding principles from those that we could learn from.
In parallel to working through who was going to do what part of the research plan, we also discussed how we each viewed the economics, and how we wanted to share and apportion downstream value upon successfully developing medicines.
Some of these discussions did have the risk to blow up the deal. There were 11th-hour issues that that needed to be worked through. But this is often the case during negotiations, right? Our teams at Arrakis and Amgen just had to step back and ask, “What is our larger goal here? Can we work around this issue?” And on some of the negotiation issues, both sides had to just prioritize what we actually needed to figure out how to get the technical work started and defer other issues that could be worked out in the future.
Going into your collaboration discussions with Amgen, how well did the two companies understand each other?
Both Arrakis and Amgen have done a really good job of telling the external world what we’re interested in and what our expertise areas are. From Arrakis’s side, we have rigorous publications speaking to the scientific community, for example on our PEARL-seq tool. There are also informal things we do. We post about our culture on social media and our website. Our CEO has a huge Twitter following and talks about everything from his guitars to our company. Our success at getting the word out has really been through utilizing a mix of the technical and informal channels available to us.
Of course, Amgen spent time under the hood to confirm we were the best partner with RNA binders. The main effort was on making sure both we and Amgen were thinking about the NUTAC application in the same way. I remember a technical discussion where both we and Amgen were presenting our proposed workplans – there were a lot of nodding heads and people bouncing ideas off of each other. And it became clear that our working together would be complementary. For our team, I think that meeting really cemented for us that Amgen was the right partner.
How did you approach your role in this BD process?
I joined Arrakis the first week of December 2021. Just a few days later, we received Amgen’s first draft of the agreement. This was a high priority for Amgen. They wanted to announce the deal at JPM 2022. Both teams were aligned that we did not want to work over Christmas. So the deal was actually executed on Christmas Eve at 6 pm.
The pressure was on to get the deal done fast. We needed a quarterback to manage the deal timeline. I stepped into this role to coordinate our discussions – which conversations needed to happen, who needed to be in the room, did it get scheduled, did our people actually have the bandwidth to work on it, can I make this process more frictionless? And then ultimately making sure what we discussed made its way back to Amgen and into the contract. We were parallel processing discussions across the overall agreement, the IP terms, the technical work plan and the program management team. There was a lot to coordinate.
There were also strategic things coming up. If Amgen asked for something, I was taking the lead on analyzing how that issue might affect our interests. And as things zigged and zagged, I was keeping an eye on what we were trying to achieve overall and making sure we were landing in an optimal place.
And I was definitely the hub of the discussions with Amgen. Formally, I was the one facilitating all the communications that were happening. Informally, I was also doing the work to understand what Amgen really wanted. For example, some term would appear in a draft which, as written, might have been problematic. I was the person able to go to the lead contact at Amgen and just say, “Hey, what’s the real ask? OK could we solve it like this instead?” And then I was able to come to the next drafting session with a real solution. Having those one-on-one conversations in a low-pressure way helped us get the deal over the finish line, and de-escalate issues that sometimes initially seemed like a hornet’s nest. Of course, there were also some issues that we had to escalate, but we tried to keep them to a minimum.
My counterpart was Chester Wong. who led the transaction from the Amgen side. Chester and I didn’t know each other before this deal and actually never met face-to-face, negotiating the entire deal by video. When we started, it felt like we were across the table from each other. By the end, after spending many late nights together, our relationship got much tighter. Discussions would veer off the deal to what we were watching on Netflix . . .
[laughs]
By the end we were all around the same table trying to figure out how to make the deal work. I remember one late night call with the IP folks from both teams, and in real time, we started writing the agreement together. There was none of the usual posturing you often get.
This was an all-hands-on-deck effort with Amgen. How did that impact everything else happening at Arrakis?
One thing is to just brutally triage what is and isn’t important. Amgen was right at the top of the list of priorities. Mike and everyone on the operational side was on board with that. Plus, we didn’t need to disrupt the entire organization over this. There were specific people from our senior research team who needed to weigh in with Amgen, and we just activated people from our side as and when needed. So we could keep running the business as usual. But sometimes I needed to get an hour of the research team’s time to get their input on the Amgen negotiation, and the team just had to pause whatever they were doing.
I had just been through a similarly complex, time-gated IPO process, so I quickly intuited the role I needed to play on this deal. I also had people around me who wanted and supported me to play that role. When I joined Arrakis, the team was very welcoming and gave me leeway to get the deal done.
Who were all the people around the table during these discussions to hammer out all the aspects of the deal?
We had multiple sub-groups who were parallel processing the discussions. The Arrakis team was literally exchanging notes at the end of every day to keep track of what was changing.
Our overarching BD team working on the actual agreement included me, our CEO Michael Gilman, and our Head of Legal, Erik Spek. Erik has a great IP background, as well, so he was really weighing in those considerations.
On the technical side, it was our CSO Jacques Dumas and our Chief Innovation Officer Jen Petter. They were taking the lead on reviewing the targets Amgen wanted to work on, even doing some early research to validate the ideas. Amgen also had a technical lead on their BD team, Duncan Huston-Paterson who was working closely with Ryan Potts, Executive Director and Head of Amgen’s Induced Proximity Platform.
And we also had our program management team, led by our SVP & Head of Operations, Heather Lounsbury. Heather’s team was instrumental in putting together the budgets and the timelines for the collaboration, and really mapping out what was required to bring this science over the finish line. One of Arrakis’ lessons from the Roche collaboration process was the value for coordination between the scientific and business discussions, so we also built this into the Amgen deal process.
All in all, it was an effort of working through all these facets of the collaboration and integrating all of them.
Now that you are in the collaboration, can you describe how it’s helping accelerate the NUTAC approach?
One way I think Amgen might help us is by learning the requirements for hetero-bifunctional small molecules. For example, how to consider the exit vectors from the RNA piece and therefore what the linker needs to look like. Amgen has also worked on the nuclease targeting side, which should enable us to put together that “peanut butter and jelly sandwich” much faster. So now we can work in parallel on the RNA binding piece, the linker piece, and the bait molecules.
Amgen is also nominating the targets for the collaboration. They know the biologies, likely have the assays in place, and know what success on those targets looks like.
And from a resource perspective, the funding Amgen is providing helps to finance the work and hire people to do our work even faster.
Ultimately, what’s also important is having a mature, seasoned, experienced partner help shape how we develop these NUTACs. We experienced this with Roche, as well. Where we are today, as a function of that partnership, is an order of magnitude difference. For example, with Roche we’ve industrialized our screening methods and run more than 40 high throughput screens and matured our approach to building RNA targeting molecules. So similarly with NUTACs, I think Amgen has the potential to help us mature how we think about hetero-bifunctional medicines.
How does this create more value for Arrakis?
Our collaboration with Amgen is initially focused on five targets. There’s undoubtedly more than five RNA targets one would want to degrade. All of that is open to us. That goes full circle back to our strategy to have landmark partnerships that helps us mature the platform. Yes, we give up value to a well circumscribed number of targets in the space, but then everything else is available to us. So we can work beyond the Amgen collaboration to build our capabilities and still retain value that we can build on.
The collaboration also definitely brought a new visibility to Arrakis. This deal made a splash at JPM, which is exciting for a preclinical deal. People across the biotech investor and business spectrum got interested and reached out to us. We were one of the few preclinical companies to present at the JPM conference this year
Shifting gears a bit, what have you learned about BD working on deals for so long now?
First is just my disposition, in any deal, to take nothing for granted. Until the money is in the bank, anything can go wrong. So foremost is just get stuff done, keep the trains running, be aggressive on the timelines, and just keep slogging away to get the deal done.
Second is to root out any sensitivities that might exist but aren’t being stated explicitly. It’s always navigating people. It’s what’s not being said that, in some cases, is more important.
What was surprising with Amgen was how fast we did it, and also what it takes to get it done that fast. I was blocking off whole portions of my days to do calls with Amgen, and also doing these calls at weird times. In some ways it was helpful to have the West Coast, East Coast time differential. We tried to set up cycle times where one group was working while the other was sleeping.
And we also built a really good relationship with Amgen’s deal team. I think that was because they were so strategically aligned with what we are trying to do and there was buy-in across the whole organization on their side. During meetings, we didn’t come into the room and pontificate or grandstand. Everything was solutions focused. We were very quickly just being transparent if something really was unacceptable. All in all, none of these are all that unusual. But when you bring all these pieces together, that’s the surprise. And I think because of our strategic alignment and the relationship we built, we were able to get over a lot of contract issues and other snags that otherwise could have become showstoppers.
What did I forget to ask you?
Maybe a few parting thoughts on the road ahead. At Arrakis, we have the opportunity to replicate all of the novel modalities and progress that has happened on the protein side, except with RNA. Historically small molecules bind to a protein’s active site to change the behavior of that protein. That’s what our intrinsic partnership with Roche represents. The NUTAC partnership is a play on PROTACs. We’re now looking at irreversible inhibition or irreversible binders to RNA, which is similar to some of the covalent protein modifiers. Arrakis is sitting at the precipice of this large opportunity space, and there continues to be a desire at Arrakis to work with other partners to broaden our knowledge and enhance our scope and speed of developing new medicines. We are interested in doing more partnerships. I wouldn’t be doing my job if I didn’t put that plug in.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $169 per year, you reward quality independent biotech reporting, and encourage more.
Today’s guest on The Long Run is Dr. Sanduk Ruit.
He is an ophthalmologist and the founder and executive director of the Tilganga Institute of Ophthalmology. The institute is in Kathmandu, Nepal.
Dr. Sanduk Ruit, founder, Tilganga Institute of Ophthalmology
Dr. Ruit has restored the eyesight of more than 130,000 people in Asia and Africa. He’s the pioneer of a small-incision form of cataract surgery. Not only was that a medical triumph, but he’s found a way to make the treatment accessible to many very poor people in Nepal and beyond. His institute has developed a way to manufacture its own intraocular lenses to insert in the eyes of patients, with the same quality of Western suppliers, and at a tiny fraction of the cost.
Dr. Ruit comes from a very poor and remote region of Nepal. He’s an inspiration in his home country, and has won more than 40 awards from governments and other institutions around the world. There’s a book about him called “The Barefoot Surgeon.”
I was fortunate to meet Dr. Ruit in Nepal this past spring. I was there with my team of 18 biotech executives for a trek to Everest Base Camp, in which we raised $1.3 million for research at the Fred Hutch Cancer Center.
While in Kathmandu, one of the trekkers, Jeff Huber, the former CEO of Grail, introduced me to Dr. Ruit and his amazing story. Jeff and I invited him to speak to our broader group. I’m glad, because Dr. Ruit’s work shows what a difference a talented and driven scientific entrepreneur can make. We were thinking a lot about how to make an impact for people in need, and Dr. Ruit really shows the way.
When he and his trainees do these eye surgeries, they are giving people their lives back, and relieving a major burden from whole families.
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 Dr. Ruit on The Long Run.
David Shaywitz
Living in innovative domains like biomedical research requires an appreciation for the exceptional, the outlier. You might even argue that the goal of innovators – at least those who hope to see their ideas gain acceptance, or their inventions adopted – is to institutionalize the exceptional and make it routine.
In the Perez model of technology adoption, this is the basic difference between the “Installation Phase,” and the “Deployment Phase.” In the Installation Phase, the world tries to make sense of a new technology, and considers many possible expressions of it (rejecting most). In the Deployment Phase, the technology is widely adopted, becoming domesticated and routine.
Surviving and thriving in an innovation-oriented realm requires a distinctive mindset: the persistence and patience to search constantly for the exception..
At one level, of course, we understand the challenge: we know that most drug candidates don’t reach the market, that most startups fail, that most creative endeavors – music, literature, film – never leave an imprint on large numbers of people.
It’s also why many rational people prefer the comfort of more predictable domains, where consistency is both expected and prized.
The difference between exception-driven domains, ruled by the power law, and more predictable domains, governed by gaussian distributions, was also a central theme of Nassim Taleb’s The Black Swan – see here. Taleb termed these two worlds “Extremistan” and “Mediocristan.”
For those opting for innovation, for Extremistan, it’s easy to get discouraged and distracted by the median – especially after you’ve been pitched by the umpteenth unmoored AI startup or the latest vendor overpromising comprehensive distributed clinical trial capabilities, or forced yourself to remain awake through yet another dismal corporate visioning activity or ideation session.
Yet it’s critical to recall, as Stephen J. Gould famously explained, “the median isn’t the message.” Gould was diagnosed with a rare form of cancer, associated with a median survival time of eight months. While initially “stunned,” and “not, of course, overjoyed,” he was nevertheless able to recognize the possibility and promise of life on the far extreme of the distribution. Thanks to a deliberately positive attitude, exquisite medical care, and a lot of luck (not necessarily in that order), he lived another 20 years.
Colleagues who have thrived in innovative spaces seem to share Gould’s ability to locate the exception. Dr. Amy Abernethy, now at Verily, has long impressed me with her ability to identify the most hopeful outliers – ideas, people, organizations – however rare they might be.
The mindset is not to be confused with toxic positivity, which asserts that everything is just great; Abernethy, from what I can tell, has little trouble recognizing abundant mediocrity – but it doesn’t prevent her from also identifying and cultivating hints of unusual brilliance, wherever she might find it.
Similarly, I’ve always found myself involuntary drawn to the exceptional, and the most interesting. In organizations where most people are highly competent but just seeking to get their jobs done, I’ve consistently found the outliers, those with a slightly different perspective, and a more ambitious personal mission. The experience of connecting with an exceptional, perhaps overlooked innovator can turn a day of tedious, predictable meetings into one of discovery and promise.
Without question, in innovative spaces, it’s easy to get disillusioned. The hype is constant, and most innovation doesn’t pan out.
Nevertheless, to paraphrase Miracle Max from The Princess Bride (a movie that, as my friend and fellow Timmerman Report contributor Lisa Suennen has pointed out, may be the fount of all entrepreneurial wisdom), “there’s a big difference between ‘mostly crap’ and ‘all crap.’ ‘Mostly crap’ is slightly promising.”
And it’s this promise, however slight and elusive, that we need to celebrate, nurture, and relentlessly pursue.
As you wish.
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Shehnaaz Suliman, CEO, ReCode Therapeutics
[Editor’s Note: this letter was drafted by female biotech leaders in response to the Supreme Court’s Dobbs decision. It was co-signed by more than 65 female biotech executives as of July 1. They’re listed at the end.]
Friends and colleagues, legislators and elected officials
We join the resounding millions in chorus to express our profound dismay and disappointment at the United States Supreme Court’s decision to strike down and ignore our fundamental rights as women to make personal reproductive health choices and for clinicians to practice evidence-based medicine without fear of reprisal.
Julia Owens, CEO, Ananke Therapeutics
It is a tragic moment in our history to see this blatant disregard for stare decisis and the repudiation of the will of the majority of the populace by the court’s conservative bloc. It negates the ability of medical practitioners that are best suited to provide care to vulnerable, pregnant women. It flagrantly ignores the physical, mental and financial consequences of carrying an unwanted pregnancy to term.
It is notable and discouraging that the decision comes at a time when our democracy bends under the heavy strain of partisanship.
Sheila Gujrathi, former CEO Gossamer Bio; board chair Ventyx Biosciences, ImmPACT Bio, ADARx Pharmaceuticals
By making such a cataclysmic decision, the Court demonstrated that America has become a country focused on special interests of the few rather than the interests of the majority. Whilst our nation was once conceived as a beacon of liberty for all, and an inclusive democracy and protector of fundamental human rights, this Court’s decision forces us to recognize the jolting reality that not all Americans are seen as equal.
Our right to be pregnant or unpregnant is a fundamental personal choice and civil liberty that should be safeguarded constitutionally. We believe in freedom of choice over our own bodies for all – but especially for women, underrepresented minorities, and LGBTQIA+ communities.
Abortion is reproductive healthcare. As doctors, scientists, innovators, caregivers, leaders and allies who are at the forefront of innovation in science and medicine for the benefit of patients and women around the world – we decry and denounce the decision by the Court.
We will not stand by silently. Our voices rise. We strongly dissent.
Shehnaaz Suliman, MD, MBA, M.Phil.
CEO ReCode Therapeutics
Julia Owens, PhD
CEO Ananke Therapeutics
Sheila Gujrathi, MD
Former CEO Gossamer Bio
Board Chair Ventyx Biosciences, ImmPACT Bio, ADARx Pharmaceuticals
Amy Burroughs
CEO Cleave Therapeutics
Wendye Robbins, MD
CEO Blade Therapeutics
Rene Russo
CEO Xilio Therapeutics
Hilary M Malone, PhD
CEO Certego Therapeutics
Leslie J Williams
CEO hC Bioscience
Rosana Kapeller MD, PhD
CEO ROME Therapeutics
Rekha Hemrajani
CEO Jiya Acquisition Corp.
Julie Anne Smith
ESCAPE Bio, Inc.
Aetna Wun Trombley, Ph.D.
CEO Lycia Therapeutics
Grace E. Colón, Ph.D.
CEO InCarda Therapeutics
Elizabeth Jeffords
CEO Iolyx Therapeutics
Alice Zhang
CEO, Verge Genomics
Angie You, PhD
Former CEO Amunix Pharmaceuticals, Board director Oric Pharmaceuticals and RayzeBio
Joanne D Kotz, PhD
CEO Jnana Therapeutics
Sabrina Martucci Johnson
CEO Daré Bioscience
Nancy Whiting, PharmD
CEO Recludix Pharma
June Lee, MD
Former CEO, Esker Therapeutics
Board Director at Tenaya Therapeutics, GenEdit, Cincor Pharma, Eledon Therapeutics
Kristen Fortney, PhD
CEO BioAge Labs
Yael Weiss MD PhD
CEO, Mahzi Therapeutics
Sevgi Gurkan, MD
Venture Partner, Orbimed
Sarah Boyce
CEO, Avidity Biosciences
Emily Drabant Conley, PhD
CEO Federation Bio
Board Director at Nuvalent, Medrio, and TMRW
Maria Soloveychik, PhD
CEO SyntheX
Kristine Ball
CEO Soteria Biotherapeutics
Samantha Truex
CEO, Upstream Bio
Kate Haviland
CEO Blueprint Medicines
Victoria Richon
Former CEO of Ribon Therapeutics
Ramani Varanasi
Former CEO, X-Biotix Therapeutics
Managing Director, ReVive
Daphne Koller, Ph.D.
CEO and Founder, insitro
Co-founder and former co-CEO, Coursera
Diala Ezzeddine, PhD
Former CEO, Xios Therapeutics
Ivana Liebisch
CEO Vigil Neuroscience
Catherine Stehman-Breen
CEO, Chroma Medicine
Alicia Levey, PhD
COO, Pionyr Immunotherapeutics
Mary Rozenman
CFO/CBO, Insitro
Susan B. Dillon
CEO Aro Biotherapeutics
JeenJoo Kang
CEO Appia Bio
Barbara Troupin, MD
Board Director, Equillium
Lisa Bowers
Former CEO, Rhia Ventures
CCO, Day One Bio
Charlene Liao, PhD
CEO Immune-Onc Therapeutics, Inc.
Sophia Yen, MD, MPH
CEO/Co-Founder
Pandia Health
Melita Sun Jung
Chief Business Officer, ShouTi
Siobhan Nolan Mangini
President & CFO, NGM Bio
Caryn McDowell
Chief Legal Officer, Cortexyme, Inc.
Lucinda Y. Quan
EVP, CBO & General Counsel, Aligos Therapeutics, Inc.
Suha Jhaveri
CBO and CCO, Leyden Labs
Christy Oliger
Board Director, Sierra Oncology, Reata, Replimune, Karyopharm
Yvonne Linney, PhD
COO Artificial Inc.
Christine O’ Brien
CEO, Tizona Therapeutics
Gisela A. Paulsen
COO, Oncocyte Corporation
Lori Lyons-Williams
CEO, a stealth biotech company
Karen LaRochelle
Venture Capital Advent Life Sci
Artax Biopharma CBO
Jodie Morrison
Venture Partner, Atlas Venture
Katherine Vega Stultz
President and CEO, Ocelot Bio
Katherine Bowdish
CEO , PIC Therapeutics
Patrice Milos
Board Director at 54gene, SeqLL, ProThera Bio
Sylvia McBrinn
Former CEO, Axerion Therapeutics
Director, BioAtla
Sarah Kurz
EVP, Partner Therapeutics
Lisa Iadicicco
Executive Director – WIB
Rosamond Deegan
CEO OMass Therapeutics
Linda Blackerby
CDIO, Informa PLC
Jennifer Petter
Founder and Chief Innovation Officer, Arrakis Therapeutics
Nerissa Kreher MD
CMO Entrada Therapeutics
Laura Lande-Diner
CBO Satellite Bio
Donna Higgins
CEO, The Higgins Group
Gail Maderis
CEO Antiva Biosciences
Rhonda Farnum
CBO, Theravance Biopharma
Clarissa Shen,
COO and Board Director, Q Bio
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $169 per year, you reward quality independent biotech reporting, and encourage more.
Lisa Suennen
Matt Wilsey, CEO of Grace Science, once said, “You may have a plan set out for your career and your family, but life doesn’t always turn out that way…you have to make the most of it…turn the lemons into lemonade.”
It is a fitting description for a person who has made several shifts on a quest to cure a rare disease.
Matt started his career in politics. He then moved to Silicon Valley, and co-founded several tech companies, including Zazzle and CardSpring.
In 2013, he was on the precipice of selling the latter company to Twitter when his daughter, Grace, was diagnosed with NGLY1 Deficiency. She was three.
NGLY1 deficiency is a complex neurological syndrome in which the patient lacks an enzyme known as N-glycanase 1 (NGLY1). NGLY1 helps the body degrade mis-folded, malfunctioning proteins, a process essential for cell homeostasis. People with NGLY1 deficiency experience many physical challenges and tend to have relatively short life spans. There is no known cure.
Matt Wilsey, co-founder and CEO, Grace Science
Matt and his wife Kristen struggled to understand how to best care for Grace and to learn all they could about the disease. The body of evidence was thin. Only five people in the world were known to have NGLY1 Deficiency at that time. Things looked grim, but Matt and Kristen didn’t give in to despair. Rather, they scoured the world for knowledge that could help them understand what could be done for Grace and others like her.
Matt made a sharp turn in his career, moving from tech to medicine. He taught himself as much as he could about the genetic disorder and related diagnostic and treatment options and sought out scientists who could help him learn about rare genetic diseases. One thing he learned early on – there was a lot for scientists to learn about the biology of NGLY1, and that new knowledge offered some new hope for patients.
With a bias towards action, Matt and Kristen poured their heart and resources into the founding of the Grace Science Foundation, a non-profit focused on funding medical research that could facilitate a cure for NGLY1, and Matt volunteered as President of the organization. While they feared they would be too late to help Grace, they wanted to ensure that other families would not experience what their family was going through.
As Matt and Kristen sought funding for the Foundation, a key challenge was convincing donors that the organization could operate at the highest level of scientific validity given the backgrounds of the founders. Many asked Matt and Kristen, who had no formal scientific training, how they could possibly drive the kind of quality medical discovery that would be necessary.
They answered those questions and successfully raised donations to support the Foundation. They spent a relatively small portion of it to find as many of the people on earth that they could who also had the condition that Grace has. By 2022, they had identified 100 individuals around the world who were living with NGLY1 Deficiency.
In 2017, when approximately 40 affected families had been identified, the Grace Science Foundation brought 21 of the families together for a conference in Palo Alto, Calif. They commiserated, shared their day-to-day experiences of living with NGLY1, and took genetic tests that could be used to the benefit of all. This was the beginning of a tight-knit rare disease community, and a valuable resource on which to build knowledge about NGLY1 Deficiency.
Many of these patients and families had never been on an airplane or left their countries or states of origin, much less interacted with others who lived with the same condition.
As the research progressed, it became clear to Matt and Kristen that the Foundation needed to partner with a biotech company to get the science translated into a treatment.
An entrepreneur by heart, Matt wanted to start his own company. He set that idea aside for a while, as he suspected that an existing for-profit enterprise would be able to develop a drug faster. He tried to convince one of the rare disease companies to collaborate but was told that the disease was too rare and that a cure was too much of a long shot. Having been denied, the team at Grace Science Foundation set their sights on starting their own company.
Along the way, Matt reached out to Carolyn Bertozzi, Professor of Chemistry and Professor of Chemical & Systems Biology and Radiology at Stanford University. Bertozzi is also an entrepreneur, having co-founded Lycia Therapeutics and Palleon Pharmaceuticals among others. The Foundation funded a few projects in her lab and she and Matt had become friendly. When she heard about the biobank he had built and met Grace, she offered up some of her post-doctoral students to help.
Carolyn Bertozzi
When Matt suggested that a more targeted approach would be to start a company together, Bertozzi got excited. Through the collaboration with Grace Science Foundation, Bertozzi had already shown in her lab that it was possible to shut down or turn off the proteasome as a means of treating cancers such as multiple myeloma.
To advance the new enterprise, incorporated in 2017 and named Grace Science, LLC, the team realized they had to open the aperture of the work to attract a broader slate of investors who had an interest in both the social mission and financial returns, not just in helping Grace and those like her.
To date, the company has raised $54 million, mostly from high-net-worth individuals and family offices who are patient; these investors are focused not just on returns, but also on the ability to make a societal impact.
Having secured the capital they needed, the company hired and partnered with an experienced team of scientists and drug development experts. They started focusing on churning out lemonade.
It wasn’t easy. Gene therapy was still a nascent approach. But it seemed the best path for their work after realizing that gene therapy had the potential advantage of addressing the missing gene and restoring function in key tissues. Small molecule development would probably take longer, and likely had too many off-target effects. So, they set off down the path of developing a gene therapy for NGLY1 deficiency.
This particular shift was especially challenging, as an entirely new animal model had to be developed to test their lead drug candidates. They found a partner in Takeda Pharmaceuticals, which helped them establish a new rat model. After Grace Science tested 39 different gene therapy constructs in human cell lines and advanced the top two candidates through preclinical tests, the company was able to demonstrate that their lead candidate was safe and effective in rats.
Grace Science now has a lead drug candidate for NGLY1 Deficiency in the GMP manufacturing process and is hopeful the FDA will soon provide a “green light” to start a clinical trial.
While this was happening, another shift was in the works – Grace Science began expanding its orientation towards becoming a multi-product company. Because the science had potential value for treating cancer, consistent with Bertozzi’s earlier work, the company is now developing a small molecule drug for cancers that that can be treated through NGLY1 inhibition. So far, they have identified eight potential malignancies that are dependent on NGLY1. Grace Science is ramping up fast on these initiatives, securing lab space, hiring a dedicated team and speaking with potential partners.
Along the way, Matt says, he learned three critical things.
First, it’s essential for a company like his to have “more than one line in the water…as many as the budget will allow.” This raises the chances of success.
He also learned the importance of finding balance between micro and macro managing. He works hard to stay close to what’s important, giving his employees autonomy to do their work, but without over-delegating. For instance, he said, he and Kristen used to speak regularly to every family in the NGLY1 community but as the numbers grew, he realized it wasn’t sustainable. They now have a genetic counseling team that helps keep in touch with their patient community. But Matt and Kristen continue to find ways to stay personally connected with the families with whom they share so much hope.
Matt says that his third key learning has been the importance of hiring people who are truly excellent and empathetic. “It’s not just A+ operators that you need, it’s A+ people,” he said.
Considering the short timeline – just eight years from starting the nonprofit foundation – a lot has happened. The foundation raised money and built a patient and scientific network. That work gave rise to a company. The drug development enterprise now has a novel product candidate on track to enter a Phase I trial in early 2023. The company knows it still has much evolution and lemonade-making ahead, but the family’s optimism for Grace and those like her grows by the day.
Academia has a tradition of doing nothing, or next to nothing, to educate and encourage young people to learn about entrepreneurship.
But whether academia wants it or not, it’s coming. Young scientists are taking matters into their own hands, organizing themselves in many major research hubs.
Nucleate, the nonprofit providing free resources to empower a new generation of biotech entrepreneurs, is announcing today it is roughly doubling its network of regional chapters from 9 to 17. The new nodes will organize young scientists in some major US research centers – Ann Arbor, Atlanta, Boulder, Chicago, Seattle and Texas. The group is also expanding internationally to the UK and Switzerland.
Soufiane Aboulhouda, PhD student, Church Lab at the Wyss Institute of Harvard University; co-founder and co-president, Nucleate
“Nucleate has created a mechanism for connecting us all together,” said Soufiane Aboulhouda, a PhD student in the George Church Lab at the Wyss Institute of Harvard University. “We’re no longer limited to the Harvard or MIT peer network. Now I interact with people from all around the world.”
What the trainees want to learn about, and interact over, is all the stuff they don’t get from the lab, or from class. How to put together a business plan to build on the science. How to start a company. How to think about IP. How to find the right service providers. How to make a pitch to raise money. How to build a network of people with complementary skills to turn an idea into a reality.
“They want to learn, and they want to learn by doing,” says Oliver Dodd, a co-founder and co-president of Nucleate. He’s also a PhD student in the Church Lab, long known for its entrepreneurial bent.
The current crop of young leaders at Nucleate have assembled educational resources online for what it takes to start a company. They’ve tracked down skilled industry mentors like Peter Barrett of Atlas Venture, former Alnylam CEO John Maraganore, Mira Chaurushiya of Westlake Village Biopartners, Cami Samuels of Venrock and Peter Kolchinsky of RA Capital. Well-known scientific entrepreneurs like George Church at Harvard, Steve Quake at Stanford and Pam Silver at Harvard are also among the advisors.
During the pandemic times, they’ve poured their energy into community organizing of students across the country, which would not have been possible before Slack and Zoom and social media. The resources they put online for their members, like so much else online, are free. Even a long-anticipated two-day in-person summit in Boston Aug. 29-30 is free to members.
About 560 grad students and postdocs are active organizers, Aboulhouda said.
Campus culture usually says to keep your head down in the science, work hard, and maybe someday you can become a principal investigator.
That’s not realistic for most people, and hasn’t been for a long time.
Mira Chaurushiya, senior partner at Westlake Village Biopartners, said the Nucleate model reminds her of Biotech Connection Bay Area – a student-led group that’s been focused more on preparing students for careers in consulting. She’s been impressed with the combination of talent, drive, and humility from the founding Nucleate crew.
Mira Chaurushiya, senior partner, Westlake Village Biopartners
“I love it when PhD students and postdocs self-organize in a way that’s productive for the whole community,” Chaurushiya said. “Unsurprisingly, they are incredibly high achieving people. To go from a standing start to what they’ve achieved today is really impressive. I’ve found them very thoughtful and humble. There’s a sense of ‘we know what we don’t know.’”
John Maraganore added: “Nucleate is a remarkable organization of students and young entrepreneurs keen to advance new frontiers of medicine. I’m amazed with how this group has grown over the years, and I’m awed by their passion and energy. There’s so much potential for this group to continue to expand as a nexus for future leaders in our industry.”
One of the key challenges will be sustainability. Student-led groups naturally have high turnover as people graduate and get jobs. Part of the challenge will be to institutionalize some of Nucleate’s processes, and develop leadership succession plans at each chapter to keep the momentum going, Aboulhouda and Dodd said.
Diversity as a value is almost a given. Half of the active members are women or gender non-binary, one in four members are from underrepresented minority groups, and members come from 44 countries around the world. Increasing diversity is “one of our primary goals,” the organization says.
There is so much interest, Nucleate turned away a few local chapters that expressed interest in joining the model this time. The group had inquiries from students at about 30-40 campuses around the world for this round of expansion that ultimately included 9 new chapters. Nucleate wants to make sure it expands its donor base to support thoughtful expansion.
The group has hired its first full-time employee, a finance person, Aboulhouda said. The vision longer-term is to have a small professional staff that can do a lot of the day-to-day work of managing the organization, with volunteer students remaining in leadership. That way, Nucleate will maintain its street cred as a group run by students, for students. It’s important to keep a finger on the pulse, to stay close to what the students need, Dodd and Aboulhouda said.
Michael Retchin, PhD student, Memorial Sloan Kettering Cancer Center; EVP of strategy, Nucleate
Dodd and Aboulhouda both say they’ve been influenced by the experience in building Nucleate, and their “Plan A” is to work at a startup after getting their PhDs.
Michael Retchin, a PhD student at Memorial Sloan Kettering Cancer Center in New York and EVP of strategy for Nucleate, said something about the group’s influence that stuck with me for days.
The community that’s been created is providing something deep, something needed, and something missing from traditional graduate school experience. It’s both a supportive fellowship for entrepreneurs, and an outlet for personal growth.
“It’s like going from being blind to being able to see things,” Retchin said. “I can see possibilities for my own career that I didn’t see before. And no longer do I think of my career as being solely for myself. Now my career is something collective. It’s about how do we work together, how do we advance the science together in the next generation. It makes me thrilled to work on this.”
Roger Longman, chairman, Real Endpoints
More than 14,000 people attended the annual #BIO22 meeting in San Diego, meaning there are at least 14,000 versions of what happened. But unless you have the emotional intelligence of a rock, you felt the unease, if not outright panic, of an industry with a fast-evaporating cash runway.
No one really knows what to do about it. If they say they do, they’re lying.
The biotechnology industry depends on two major financing sources: investors and acquirers. The former, in general, invest in companies they hope will sooner or later be acquired; the latter in companies that create medicines of significant medical and commercial value.
One problem: whereas acquirers were willing to pay significant premiums for drugs which had proven their value in clinical trials, the acquirers apparently now want their targets to do more to prove commercial value too, often by launching and selling their drugs.
It’s a recent change. A good example: the difference between Novartis in 2019 being willing to pay $9.7 billion for The Medicines Co. and its almost-approved PCSK9 inhibitor inclisiran (now marketed as Leqvio) and Pfizer, two years later, paying $11.6 billion for BioHaven only after it had successfully launched the migraine medicine rimegepant (Nurtec). It’s why, I increasingly believe, we see more biotechs launching, or about to launch, their own drugs.
The implication for investors: they’ll have to wait longer for most of their exits; capital costs will increase; returns in too many cases will decrease. The implication for biotech C-suites: they’ll now have to get smart about something most really haven’t had to worry much about — actually selling drugs.
Earlier stage companies will need to show investors they recognize the hurdles in front of them, commercially speaking. They’ll need to show they have a sophisticated understanding of payer strategies, distribution, pricing and contracting analogs, and patient support services. Moreover, they will need to be able to crisply articulate why they will succeed in a market chockablock with competitors, whether that competition is direct or for overall budget dollars.
Later-stage companies will need management who have successfully brought products to market – and actually want to do it again. Those people aren’t common and they’re not cheap. And both early- and late-stage companies will need board members who have an intimate and contemporary — not decades-old — understanding of the commercial and reimbursement challenges products face today.
A few CEOs we met at BIO think they just need to sit tight. Trim their costs, sure – but no need to re-set the goalposts. The investment cycle, as it has before, will roll on, they believe, and valuations will rise to pre-crash levels. They may be right about valuations — though that’s not a bet I’d be willing to stake my company on. And it doesn’t mean that the valuation endpoints will be the same.
We firmly believe that the biotech industry has delivered – and will continue to deliver – extraordinary value to both society and investors. The science continues to astound. But the valuation markers have moved. While clinical and regulatory proof is still a must-have, there’s now a second hurdle: quarterly sales.
The question is how quickly, and how well, biotechs can prepare themselves to meet that challenge.
