Generate:Biomedicines Raises Largest Biotech Series C of 2023
When Molly Gibson, PhD, joined Flagship Pioneering in 2017, she had been mulling over the question of what the main drivers of biology were for rethinking…
When Molly Gibson, PhD, left her position as Kaleido Biosciences’ leader of computational biology and joined Flagship Pioneering in 2017, she had been mulling over the question of what the main drivers of biology were for rethinking the drug development process.
Molly Gibson, PhD, co-founder & chief strategy and chief innovation officer of Generate:Biomedicines and a senior principal at Flagship Pioneering.
“If you could look at the millions of protein sequences to learn nature’s rules for conferring functionality and then generate novel proteins for specific functions, you could almost reimagine the entire drug discovery process and change the economies of scale, the number of programs any individual company could go after, and ultimately the outcome and the success rate of those medicines, which the field and the industry as a whole are in desperate need of,” said Gibson, who is chief strategy and innovation officer at Generate:Biomedicines and senior principal at Flagship Pioneering, in an interview with GEN Edge last December.
“The mission is being able to reimagine the productivity challenge in drug discovery and using machine learning (ML) to make the process reproducible where we can program molecules versus relying on this process of discovery and this bespoke trial and error process.”
At the time, biophysics dominated the field of protein sciences. It was the only way to understand and design new proteins. However, Gibson, whose doctoral training was in computational and systems biology, said that this approach has a lot of problems with scalability and brittleness.
So, in 2018, together with Gevorg Grigoryan, Gibson founded Generate:Biomedicines to develop a generalizable data-driven approach to understanding the relationship between protein sequence and function, with the end goal of developing proteins that had never been seen before.
“We did some early experiments to show that on toy systems like GFP, we could create things that are 50 times better, but also on really important problems, showing that we could optimize antibody properties, which underlie some of the most impactful therapeutics on the market, to create entirely novel therapeutics,” said Gibson. “Once we were able to show that data-driven approaches to proteins were possible, we could start thinking about generating entirely new molecules. So if you understood those rules, you could learn from them, and then you could use the rules and apply them in generative ways.”
There are two core components to Generate:Biomedicines’ technology. One is based on de novo protein generation, in which a computer suggests sequences with binding specificity without previous knowledge of binding on a target of interest instead of being limited to what the immune system produces. The second piece is around optimizing. Computationally thinking up a protein is one thing, but making it a viable therapeutic, which requires mastery of affinity, immunogenicity, and manufacturability, is another. To address this, Generate:Biomedicines has created an optimization suite that allows them to take raw native proteins and make them into viable therapeutics for desired targets.
Gibson’s vision goes beyond this initial drug discovery process and says they are innovating across the entire drug development pipeline. She said they have built out the company to develop drugs end-to-end and constantly think about how our technology impacts every part of that drug discovery process.
“We weren’t going just to reimagine how proteins are generated,” said Gibson. “In that initial process, we felt it was important to reimagine the whole paradigm, from therapeutic hypotheses all the way to when a patient is first dosed to when you have an approved drug.”
Fast forward to today, and Generate:Biomedicines has announced the largest Series C for a biotech company in 2023 at $273 million, bringing their total equity financing since 2020 to nearly $700 million and eclipsing the $226.5 million raised by Apollo Therapeutics just weeks earlier.
Behind their $370 million series B, the five-year-old company seems to have been able to put some of their money where their mouth is, as they also announced their first-in-human clinical trial for GB-0669, a monoclonal antibody targeting a highly conserved region of the spike protein in SARS-CoV-2. Also, Generate:Biomedicines expects to file a Clinical Trial Application by early Q4 2023 for its anti-TSLP monoclonal antibody in asthma, which is expected to enter clinical trials shortly thereafter.
The Series C haul will support Generate:Biomedicines in advancing their entire pipeline of 17 existing programs, largely focused on three different therapeutic areas: immunology, infectious disease, and oncology.
In addition to company founder Flagship Pioneering, all of Generate:Biomedicine’s existing series B investors participated in this round, including a wholly owned subsidiary of the Abu Dhabi Investment Authority (ADIA); Fidelity Management & Research Company; funds and accounts advised by T. Rowe Price Associates; ARCH Venture Partners; and March Capital. Additionally, This financing round attracted many new investors, including Amgen; NVentures, NVIDIA’s venture capital arm; MAPS Capital (Mirae Asset Group); and Pictet Alternative Advisors.
From idea to IND
In March 2021, Merck executive Mike Nally joined Generate:Biomedicines as CEO, and it didn’t take long for him to have the Kool-Aid coursing through his veins.
Mike Nally, CEO of Generate:Biomedicines and a CEO-Partner at Flagship Pioneering.
“One of the things that became quickly apparent was that the early lessons that the technology was starting to suggest, if true, would transform the way drugs are made,” Nally told GEN Edge. “We’d migrate from the artisanal approaches of immunizing a humanized mouse or llama and move toward a paradigm of increasing programmability. If we could master the programming of proteins, we could drive biology in new, unique, and desired ways.”
So, over the last two years, Nally has worked with the rest of the leadership team to build up the company from Gibson’s and Grigoryan’s initial ideas and advancements, and they have demonstrated the ability to de novo generate an antibody and made the manufacturing pipeline reproducible and robust.
When I spoke to Gibson nine months ago, she said they expected two INDs in 2023, which looks like it will happen.
The first-in-human lead program is an antibody with pan-SARS-CoV-2 specificity, which allows them to maintain efficacy with new variants, which Gibson hopes will allow Generate:Biomedicines to demonstrate that their AI-generated molecules are safe and effective in humans. This is a relatively newer program that, under Nally, was taken from an idea to their first-in-human lead candidate, intended for specific immunocompromised populations (about 2% of the global population), in a speedy 16 months.
Of the IND expected to be filed in the next few weeks, which is for asthma, Gibson said back in 2022 that it demonstrates the potential to create optimal therapeutics where they’ve taken a molecule that had picomolar binding down to femtomolar binding.
“[Experimentally], this is incredibly challenging because it’s almost impossible even to measure that type of binding—you can do it computationally and then validate at a lower throughput,” said Gibson. “We completely changed the dosing paradigm of this molecule for patients because we have a tighter affinity.”
Since Nally was brought on, there have been several important strategic partnerships for the company—one with Amgen that happened around 18 months ago and another with MD Anderson Cancer Center that was signed this spring—and the pipeline has matured to the point that the company anticipates adding 10 programs annually.
(Not) lost in space
Generate:Biomedicines is just at the very onset of applying their technology, which is modality-agnostic. According to Nally, they’ve used it across antibodies, T-cell engagers, cell therapy, antibody-drug conjugates (ADCs), enzymes, peptides, and growth hormones. But Nally has kept Generate:Biomedicines focused.
They’ve invested in people, scaling up from about 30 to 60 at the time of Series B, and today there are about 280 people. They’re also trying to spend their money smartly, not reinventing every cog in the drug development wheel. For example, their first two programs are antibodies, so Nally said that they have opted to go with tried and true CDMO partners available for manufacturing, allowing Generate:Biomedicines to deploy their capital where they can add distinctive value on the molecular generation side of things or to advancing candidates.
“As we move things toward and into the clinic, our dollars will go to the toxicity studies, scaling up and manufacturing, getting IND readiness, and then running those clinical trials,” said Nally. “The runway on that will be multiple years. We think over the next 12 to 24 months, we should have four to six clinical assets and four to six well-characterized molecules that sit right behind those ready to move toward the clinic.”
While Generate:Biomedicines plugs in their AI technology wherever possible, they also have a reverence for experimental biology. They’ve got just as many, if not more, scientists in the wet lab as in the dry one.
In June of this year, Generate:Biomedicines announced they were expanding beyond their initial location in Somerville, investing in a cryogenic electron microscopy (cryoEM) laboratory in Andover, MA. It is among the largest privately owned cryoEM laboratories in the United States at 70,000 square feet and houses four industry-leading cryoEM setups, a full end-to-end wet lab, and data processing capabilities enabled by machine learning.
“Why cryoEM is so important to us is that, if you think about the protein-protein interaction data, each one of those points is an X, Y, and Z coordinate,” said Nally. “Feeding in the amount of data you gather from just one image of a protein-protein interaction that gets fed back into the learning loop of the machine learning aspect of this is enormously powerful.”
One thing I always hear when talking to AI-driven drug development companies is some idiom—typically “scratching the surface” or “tip of the iceberg”—communicating how big of a space has just been unlocked and how little has been investigated.
All of this idiomatic repetition has made me consider if there is a better way to describe the potential of this new approach to drug development. Perhaps more fitting is to think of AI-driven drug discovery as only having escaped the Earth’s atmosphere and making it past lunar orbit, but there’s a long way to go before leaving out the solar system, galaxy, and the undefined edges of the unimaginably vast universe. Many of these pioneers are aware of the possibility of being lost in space, so I’d expect the number of AI-driven companies and the amount of money thrown at them to continue to grow if they can stick to their focused slice of the heavens.
Airlines operate in a market that's dictated by supply and demand: If more people want to fly a specific route than there are available seats, then tickets on those flights cost more.
That makes scheduling and predicting demand a huge part of maximizing revenue for airlines. There are, however, numerous factors that go into how airlines decide which flights to put on the schedule.
Every airport has only a certain number of gates, flight slots and runway capacity, limiting carriers' flexibility. That's why during times of high demand — like flights to Las Vegas during Super Bowl week — do not usually translate to airlines sending more planes to and from that destination.
Airlines generally do try to add capacity every year. That's become challenging as Boeing has struggled to keep up with demand for new airplanes. If you can't add airplanes, you can't grow your business. That's caused problems for the entire industry.
Every airline retires planes each year. In general, those get replaced by newer, better models that offer more efficiency and, in most cases, better passenger amenities.
If an airline can't get the planes it had hoped to add to its fleet in a given year, it can face capacity problems. And it's a problem that both Southwest Airlines (LUV) and United Airlines have addressed in a way that's inevitable but bad for passengers.
Southwest Airlines has not been able to get the airplanes it had hoped to.
Image source: Kevin Dietsch/Getty Images
Southwest slows down its pilot hiring
In 2023, Southwest made a huge push to hire pilots. The airline lost thousands of pilots to retirement during the covid pandemic and it needed to replace them in order to build back to its 2019 capacity.
The airline successfully did that but will not continue that trend in 2024.
"Southwest plans to hire approximately 350 pilots this year, and no new-hire classes are scheduled after this month," Travel Weekly reported. "Last year, Southwest hired 1,916 pilots, according to pilot recruitment advisory firm Future & Active Pilot Advisors. The airline hired 1,140 pilots in 2022."
The slowdown in hiring directly relates to the airline expecting to grow capacity only in the low-single-digits percent in 2024.
"Moving into 2024, there is continued uncertainty around the timing of expected Boeing deliveries and the certification of the Max 7 aircraft. Our fleet plans remain nimble and currently differs from our contractual order book with Boeing," Southwest Airlines Chief Financial Officer Tammy Romo said during the airline's fourth-quarter-earnings call.
"We are planning for 79 aircraft deliveries this year and expect to retire roughly 45 700 and 4 800, resulting in a net expected increase of 30 aircraft this year."
That's very modest growth, which should not be enough of an increase in capacity to lower prices in any significant way.
United Airlines pauses pilot hiring
Boeing's (BA) struggles have had wide impact across the industry. United Airlines has also said it was going to pause hiring new pilots through the end of May.
United (UAL) Fight Operations Vice President Marc Champion explained the situation in a memo to the airline's staff.
"As you know, United has hundreds of new planes on order, and while we remain on path to be the fastest-growing airline in the industry, we just won't grow as fast as we thought we would in 2024 due to continued delays at Boeing," he said.
"For example, we had contractual deliveries for 80 Max 10s this year alone, but those aircraft aren't even certified yet, and it's impossible to know when they will arrive."
That's another blow to consumers hoping that multiple major carriers would grow capacity, putting pressure on fares. Until Boeing can get back on track, it's unlikely that competition between the large airlines will lead to lower fares.
In fact, it's possible that consumer demand will grow more than airline capacity which could push prices higher.
Simple blood test could predict risk of long-term COVID-19 lung problems
UVA Health researchers have discovered a potential way to predict which patients with severe COVID-19 are likely to recover well and which are likely to…
UVA Health researchers have discovered a potential way to predict which patients with severe COVID-19 are likely to recover well and which are likely to suffer “long-haul” lung problems. That finding could help doctors better personalize treatments for individual patients.
Credit: UVA Health
UVA Health researchers have discovered a potential way to predict which patients with severe COVID-19 are likely to recover well and which are likely to suffer “long-haul” lung problems. That finding could help doctors better personalize treatments for individual patients.
UVA’s new research also alleviates concerns that severe COVID-19 could trigger relentless, ongoing lung scarring akin to the chronic lung disease known as idiopathic pulmonary fibrosis, the researchers report. That type of continuing lung damage would mean that patients’ ability to breathe would continue to worsen over time.
“We are excited to find that people with long-haul COVID have an immune system that is totally different from people who have lung scarring that doesn’t stop,” said researcher Catherine A. Bonham, MD, a pulmonary and critical care expert who serves as scientific director of UVA Health’s Interstitial Lung Disease Program. “This offers hope that even patients with the worst COVID do not have progressive scarring of the lung that leads to death.”
Long-Haul COVID-19
Up to 30% of patients hospitalized with severe COVID-19 continue to suffer persistent symptoms months after recovering from the virus. Many of these patients develop lung scarring – some early on in their hospitalization, and others within six months of their initial illness, prior research has found. Bonham and her collaborators wanted to better understand why this scarring occurs, to determine if it is similar to progressive pulmonary fibrosis and to see if there is a way to identify patients at risk.
To do this, the researchers followed 16 UVA Health patients who had survived severe COVID-19. Fourteen had been hospitalized and placed on a ventilator. All continued to have trouble breathing and suffered fatigue and abnormal lung function at their first outpatient checkup.
After six months, the researchers found that the patients could be divided into two groups: One group’s lung health improved, prompting the researchers to label them “early resolvers,” while the other group, dubbed “late resolvers,” continued to suffer lung problems and pulmonary fibrosis.
Looking at blood samples taken before the patients’ recovery began to diverge, the UVA team found that the late resolvers had significantly fewer immune cells known as monocytes circulating in their blood. These white blood cells play a critical role in our ability to fend off disease, and the cells were abnormally depleted in patients who continued to suffer lung problems compared both to those who recovered and healthy control subjects.
Further, the decrease in monocytes correlated with the severity of the patients’ ongoing symptoms. That suggests that doctors may be able to use a simple blood test to identify patients likely to become long-haulers — and to improve their care.
“About half of the patients we examined still had lingering, bothersome symptoms and abnormal tests after six months,” Bonham said. “We were able to detect differences in their blood from the first visit, with fewer blood monocytes mapping to lower lung function.”
The researchers also wanted to determine if severe COVID-19 could cause progressive lung scarring as in idiopathic pulmonary fibrosis. They found that the two conditions had very different effects on immune cells, suggesting that even when the symptoms were similar, the underlying causes were very different. This held true even in patients with the most persistent long-haul COVID-19 symptoms. “Idiopathic pulmonary fibrosis is progressive and kills patients within three to five years,” Bonham said. “It was a relief to see that all our COVID patients, even those with long-haul symptoms, were not similar.”
Because of the small numbers of participants in UVA’s study, and because they were mostly male (for easier comparison with IPF, a disease that strikes mostly men), the researchers say larger, multi-center studies are needed to bear out the findings. But they are hopeful that their new discovery will provide doctors a useful tool to identify COVID-19 patients at risk for long-haul lung problems and help guide them to recovery.
“We are only beginning to understand the biology of how the immune system impacts pulmonary fibrosis,” Bonham said. “My team and I were humbled and grateful to work with the outstanding patients who made this study possible.”
Findings Published
The researchers have published their findings in the scientific journal Frontiers in Immunology. The research team consisted of Grace C. Bingham, Lyndsey M. Muehling, Chaofan Li, Yong Huang, Shwu-Fan Ma, Daniel Abebayehu, Imre Noth, Jie Sun, Judith A. Woodfolk, Thomas H. Barker and Bonham. Noth disclosed that he has received personal fees from Boehringer Ingelheim, Genentech and Confo unrelated to the research project. In addition, he has a patent pending related to idiopathic pulmonary fibrosis. Bonham and all other members of the research team had no financial conflicts to disclose.
The UVA research was supported by the National Institutes of Health, grants R21 AI160334 and U01 AI125056; NIH’s National Heart, Lung and Blood Institute, grants 5K23HL143135-04 and UG3HL145266; UVA’s Engineering in Medicine Seed Fund; the UVA Global Infectious Diseases Institute’s COVID-19 Rapid Response; a UVA Robert R. Wagner Fellowship; and a Sture G. Olsson Fellowship in Engineering.
To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog at http://makingofmedicine.virginia.edu.
These are the themes that emerged when I invited nine Black women to chronicle their professional experiences and relationships with colleagues as they earned their Ph.D.s at a public university in the Midwest. I featured their writings in the dissertation I wrote to get my Ph.D. in curriculum and instruction.
“It’s not just the beating me down that is hard,” one participant told me about constantly having her intelligence questioned. “It is the fact that it feels like I’m villainized and made out to be the problem for trying to advocate for myself.”
The women told me they did not feel like they belonged. They spoke of routinely being isolated by peers and potential mentors.
One participant told me she felt that peer community, faculty mentorship and cultural affinity spaces were lacking.
Participants also discussed the ways they felt they were duped into taking on more than their fair share of work.
“I realized I had been tricked into handling a two- to four-person job entirely by myself,” one participant said of her paid graduate position. “This happened just about a month before the pandemic occurred so it very quickly got swept under the rug.”
Why it matters
The hostility that Black women face in higher education can be hazardous to their health. The women in my study told me they were struggling with depression, had thought about suicide and felt physically ill when they had to go to campus.
Other studies have found similar outcomes. For instance, a 2020 study of 220 U.S. Black college women ages 18-48 found that even though being seen as a strong Black woman came with its benefits – such as being thought of as resilient, hardworking, independent and nurturing – it also came at a cost to their mental and physical health.
Several anthologies examine the negative experiences that Black women experience in academia. They include education scholars Venus Evans-Winters and Bettina Love’s edited volume, “Black Feminism in Education,” which examines how Black women navigate what it means to be a scholar in a “white supremacist patriarchal society.” Gender and sexuality studies scholar Stephanie Evans analyzes the barriers that Black women faced in accessing higher education from 1850 to 1954. In “Black Women, Ivory Tower,” African American studies professor Jasmine Harris recounts her own traumatic experiences in the world of higher education.
What’s next
In addition to publishing the findings of my research study, I plan to continue exploring the depths of Black women’s experiences in academia, expanding my research to include undergraduate students, as well as faculty and staff.
I believe this research will strengthen this field of study and enable people who work in higher education to develop and implement more comprehensive solutions.
The Research Brief is a short take on interesting academic work.
Ebony Aya received funding from the Black Collective Foundation in 2022 to support the work of the Aya Collective.
We use cookies on our website to give you the most relevant experience by remembering your preferences and repeat visits. By clicking “Accept”, you consent to the use of ALL the cookies.
This website uses cookies to improve your experience while you navigate through the website. Out of these, the cookies that are categorized as necessary are stored on your browser as they are essential for the working of basic functionalities of the website. We also use third-party cookies that help us analyze and understand how you use this website. These cookies will be stored in your browser only with your consent. You also have the option to opt-out of these cookies. But opting out of some of these cookies may affect your browsing experience.
Necessary cookies are absolutely essential for the website to function properly. These cookies ensure basic functionalities and security features of the website, anonymously.
Cookie
Duration
Description
cookielawinfo-checbox-analytics
11 months
This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Analytics".
cookielawinfo-checbox-functional
11 months
The cookie is set by GDPR cookie consent to record the user consent for the cookies in the category "Functional".
cookielawinfo-checbox-others
11 months
This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Other.
cookielawinfo-checkbox-necessary
11 months
This cookie is set by GDPR Cookie Consent plugin. The cookies is used to store the user consent for the cookies in the category "Necessary".
cookielawinfo-checkbox-performance
11 months
This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Performance".
viewed_cookie_policy
11 months
The cookie is set by the GDPR Cookie Consent plugin and is used to store whether or not user has consented to the use of cookies. It does not store any personal data.
Functional cookies help to perform certain functionalities like sharing the content of the website on social media platforms, collect feedbacks, and other third-party features.
Performance cookies are used to understand and analyze the key performance indexes of the website which helps in delivering a better user experience for the visitors.
Analytical cookies are used to understand how visitors interact with the website. These cookies help provide information on metrics the number of visitors, bounce rate, traffic source, etc.
Advertisement cookies are used to provide visitors with relevant ads and marketing campaigns. These cookies track visitors across websites and collect information to provide customized ads.
