Home Blog

The 100 Million Cell Challenge Announces Winning Projects

When Giovanna Prout, president and CEO of Scale Bio, thinks about single cell technology, she thinks big. (Meaning, a lot of cells.) And she wants researchers to think big with her. To that end, a few months ago, she developed a plan that would inspire researchers to submit proposals for experiments that they have always wanted to do, but couldn’t because of cost or logistics. Not only that, but she created a way to support those proposals, as well.

Together with her team at Scale Bio, she established the 100 Million Cell Challenge. But Scale Bio couldn’t do it alone; they needed collaborators. Soon after the idea was born, the Chan Zuckerberg Initiative (CZI; funding), Ultima Genomics (sequencing), NVIDIA (compute power), and Bioturing (access to their advanced analysis platform, BBrowserX) joined the initiative to collaborate and subsidize costs of the projects.

They solicited proposals and, recently, at the ASHG meeting in Denver, CO, the team announced the 14 winners; the projects span across diverse applications, addressing critical challenges in global health—from childhood respiratory diseases to cancer disparities.

The initiative ended up drawing 147 different proposals, totaling nearly one billion cells, from researchers in 27 countries. The project, Prout said, is showcasing that there is a demand “for these really large-scale initiatives.”

The number of submissions “blew her away,” Prout told GEN. At first, she expected that they would get somewhere in the range of 30 projects. So, when more than 140 came in, “it was really exciting to see the demand.” There were submissions from established single cell researchers limited by their current technology. There were also proposals from researchers new to single cell—scientists who wanted to try single cell, but it has been too expensive or too intimidating to get started.

Scale Bio, located in San Diego, CA, has developed a massively parallelized single cell barcoding technology. The large-scale projects will utilize the company’s newest technologies, QuantumScale, a single cell RNA sequencing technology, and ScalePlex, a multiplexing technology that enables seamless sample pooling. Together, these technologies enable researchers to multiplex samples and prepare up to two million cells in parallel.

Scale plans to go to the researchers’ labs to help them fix and prepare their cells, which will be shipped to Scale Bio. Scale will then process them and send the libraries to Ultima Genomics, in Fremont, CA, for sequencing. The data will then be sent back to the researchers.

The winning projects will be fully subsidized by the CZI where Jonah Cool, PhD, cell science senior program officer, led the initiative. The remaining proposals have been offered subsidized projects, for their willingness to submit an application. “We didn’t want to leave them hanging,” noted Prout. “At the end of the day, this is really all about their science and trying to enable them as much as possible.”

Data from the winning projects will be made openly available on CZ CELL by GENE Discover and will accelerate modeling efforts including CZI’s commitment to build AI-powered virtual cell models, capable of predicting the behavior of healthy and diseased cells.

“The scale of these single cell omics projects will enhance Chan Zuckerberg CELL by GENE Discover—a platform CZI built where scientists can explore curated cellular data and discover new information—making it an even more powerful resource for the global research community,” said Cool. “Each cell analyzed brings us closer to understanding diverse populations, complex diseases, and how to develop more effective treatments.”

The selected projects span a remarkable range of applications, from expanding the first global atlas of pediatric health to investigating population-specific differences in cancer outcomes. Collectively, they demonstrate how increased scale in single cell analysis can transform our understanding of human biology and disease.

Prout says that they focused on a few areas: studying diversity and different populations that may be underrepresented: finishing biology by studying systems or tissue types that have been underrepresented (for example in the Human Cell Atlas) to interrogate healthy tissues to a level that other tissues have been interrogated: and drug screening projects to showcase high numbers of conditions across many cells and build foundation models off of that.

“When researchers can analyze millions of cells instead of thousands,” said Prout, “we unlock entirely new possibilities for understanding human health and disease.”

For more updates on the project, please check here.

The winners:

Winning projects were selected to reflect four key priorities in biomedical research:

  1. Global Health Equity: Studies spanning multiple continents and diverse populations across age and ancestry
  2. Disease Characterization: Looking at many patients and tissues temporally to fully understand disease-specific mechanisms
  3. Cancer Biology: New approaches to understanding treatment responses
  4. Therapeutic Innovation: Novel platforms for disease perturbations and drug development

The projects selected for full subsidy include:

  • Federico Gaiti, University Health Network, Elucidating Molecular Dependencies of Glioblastoma Cells Engaged in Neuronal Crosstalk
  • Caleb Webber, UK Dementia Research Institute, Zebrafish Whole Brain Disease Modeling
  • Sophia George, University of Miami, African Caribbean Single Cell NetwRork
  • Kevin Matthew Byrd, Virginia Commonwealth University, Mapping the Pediatric Inhalation Interface at Single Cell Resolution
  • David van Heel, Genes & Health/Queen Mary University of London, Genes & Health, Multiomics
  • Tom Taghon, Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Molecular Drivers of Human T Cell Development
  • Drew Neavin, Garvan Institute of Medical Research, Identifying Patients at Risk of Drug-Induced Cardiotoxicity
  • Luis Barreiro, University of Chicago, Unveiling Immune Variation Across Diverse Human Populations
  • Barbara Treutlein, ETH Zurich, Predictive Modeling of Cell State-Specific Responses to Small Molecule Perturbations in Human Organoids
  • Zack Lewis, Allen Institute for Brain Science, Sympathetic Nervous System Atlas
  • John Tsang, Yale University/Chan Zuckerberg Biohub New York, Deciphering the Immune Health of Global Populations
  • Constantine Tzouanas, MIT, Protein Platform Perturbing Human PBMCs with Transcriptomic Readout
  • Christine Disteche, University of Washington, Single Cell Transcriptome Analyses of Sex Differences in Normal Human Development and in Genetic Conditions with an Abnormal Number of Sex Chromosomes
  • April Foster, Wellcome Sanger Institute, Signalling Perturbations to Understand Human Development

Seer Showcases Deep Proteomics Capabilities, Announces Co-Marketing Deal with Thermo Fisher Scientific

0

At ASHG, Seer showcased its Proteograph product suite which it claims delivers proteomic insights that complement and strengthen other forms of omics data. Through various sessions at the meeting, the company highlighted applications of the technology in the context of neurodegenerative disease, cancer, and metabolic disease. Seer also announced a co-marketing and sales agreement with Thermo Fisher Scientific to jointly promote Proteograph alongside Thermo Scientific Orbitrap Astral™ mass spectrometers to provide customers of the Orbitral Astral an integrated solution for unbiased proteomic analysis. 

The list of presentations at ASHG, which was held in Denver, CO, included one from healthcare company PrognomiQ focused on lung cancer. Philip Ma, PhD, CEO and founder of PrognomiQ, a spin-out from Seer, and his team are exploring a multi-omics biomarker test that uses proteomics, transcriptomics, and metabolomics to detect early-stage lung cancer.  

Earlier this year, the company shared results from a study in a medRxiv pre-print that highlighted data generated from a 2,513-subject case-control study using their multi-omics classifier. For that study, they analyzed molecular differences between the peripheral blood plasma of lung cancer subjects and noncancer controls, including those at high risk for lung cancer. The research demonstrated 89% overall sensitivity and 89% specificity in the validation cohort to detect lung cancer, including 80% sensitivity to detect stage one lung cancer.

A separate presentation at ASHG, this time from the Satchidananda Panda Lab at the Salk Institute for Biological Studies, focused on Relative Energy Deficiency in Sport (REDs), a condition associated with insufficient energy intake and excessive energy expenditure that can result in systemic neuroendocrine and metabolic abnormalities in athletes. Mouse studies of the condition have shown wide-ranging effects including significant shrinkage of vital organs like the kidney and reproductive organs, deterioration of bone quality, and negative psychological consequences.

Salk scientists are using Seer’s technology to analyze data from animal models of REDs in order to identify protein signatures of the disease. “A multi-omics approach, including unbiased proteomics, is arguably even more important for a condition like REDs for which little is known about its diagnosis, effects, or potential treatments,” said Satchidananda Panda, PhD, director, Wu-Tsai Human Performance Alliance at Salk Institute. “Seer’s technology allows our team to understand REDs on a cellular and molecular level, which in turn could lead to diagnostic tests and therapies to halt, reverse, or prevent it entirely.”

Pairing deep proteomics with mass spectrometry

Seer’s collaboration with Thermo Fisher builds on an existing relationship between both companies. Under the terms of this new nonexclusive agreement, Thermo Fisher’s global sales force will be able to quote and sell the Proteograph product suite, which includes an automation instrument, proprietary engineered nanoparticles, and software analysis suite. The partners will also conduct joint marketing activities, including conference promotions, seminars, and webinars, to showcase the combined power of their proteomic platforms.

The integration is set to commence in early 2025. When it does, it will further expand the commercial reach of Seer’s platform, Omid Farokhzad, MD, PhD, CEO and chair of Seer told GEN in an interview during the meeting. The companies will work together to improve workflows, creating a seamless sample-to-data experience. Seer and Thermo Fisher also plan to collaborate on research studies that demonstrate the comprehensive capabilities of their combined platforms.  

Farokhzad described the Orbirtrap as the gold-standard for mass spectrometry. Pairing it with the Proteograph will help researchers extract even more information. To date, Seer has invested well over $250 million in developing its platform to ensure that scientists get the most from their data. “If you take a plasma sample and digest it and inject it in the Astral, you will see about 750 proteins. But if you take the same plasma sample, and run it on the Proteograph and then run it on the Astral, you would get to about 6,000 proteins,” he said. Now “if you do a study of let’s say 40 or 50 or a hundred or a thousand samples… you may get to 8, 9, or 10,000 proteins across the study. So truly remarkable numbers.” 

Seer’s team will be on hand to support Orbitrap customers who purchase Proteograph including providing consumables and other support services. Customers for the combined solutions will likely fall into a few buckets, Farokhzad said. A key demographic is customers who are processing complex samples such as plasma or serum. 

Access to the Proteograph suite could also be helpful for customers of the Orbitrap who are working with a large number of single cells. With the Proteograph, these customers could automate their workflows with improved reproducibility. The other is customers focused on single cells. For these customers, “you can get pretty deep on a mass spec without the Proteograph” but “you’ll see more with [it].” He anticipates that as much as half of the Orbitrap customers would benefit from the insights provided by Proteograph.

The solutions from both companies already work together seamlessly, according to Farokhzad. Customers can simply transfer the peptide output from the Proteograph into their Orbitrap. However, the partners plan to work on workflows for specific use cases and applications. 

“Both Thermo and Seer are interested in larger studies. When you combine the two, suddenly you have the tools to do population scale, deep proteomic study, something that previously was completely impossible to even imagine,” Farokhzad said. “To be able to exemplify to the customer and to the scientific community the powerful biological insights that can emerge when you do very large scale studies at [a] different speed that was previously not possible … at a cost point that makes it feasible.”

The response to Proteograph from attendees at ASHG was very positive. Serafim Batzoglou, PhD, Seer’s chief data officer, told GEN at the meeting that the company’s conversations with scientists indicated that many were surprised at how quickly proteomics is advancing. For a long time, some scientists’ impressions of proteomics was that while the information was useful, it was a “really difficult” data type to get access to.

“Before our technology, doing mass spectrometry on plasma involved a considerable amount of time [to] first of all process the samples depleted of the common proteins and then mass spectrometry acquisition,” he explained. Advances in mass spectrometry technology as well as the launch of Proteograph have now made it possible to routinely run tens of samples per day using a single instrument at a much lower price point. Moving forward, “I think that things are picking up [and] hopefully it’s going to speed up over the next year or two. And this data type will become more and more ubiquitous.”

Reaching the clinic

So far Proteograph is designated for research use only. However, Seer has secured certifications that allow it to move the instrument towards use in clinical testing. In line with those efforts, Seer spun out PrognomiQ in September 2020. The company’s proprietary approach combines the information provided by the Proteograph product suite with genotype and phenotype data including cell-free DNA, RNA, metabolites, and lipids to identify important biomarkers. 

PrognomiQ recently announced a series D financing round in which the company raised $34 million. The round was led by Seer with participation from a new strategic investor in the diagnostics segment as well as from existing investors, including Catalio Capital Management, aMoon, Invus, and Bruker. The company has raised more than $135 million in total since its founding four years ago. Isaac Ro, a partner with Catalio Capital Management, has joined PrognomiQ’s Board as an independent director. 

PrognomiQ is using that funding to develop a laboratory-developed test for lung cancer as well as an in vitro diagnostic test for the disease. PrognomiQ was recently granted a Clinical Laboratory Improvement Amendment license to support the development of the LDT product, and it is currently enrolling a prospective 15,000-subject study in lung cancer that was initiated in 2023 to support registration of the IVD product.

StockWatch: Wall Street Weighs Trump Effect on Biopharma, from Vaccines to M&A

A trio of stock analysts this week examined the likely impacts on biopharma from Donald Trump’s election victory and forthcoming return to the White House in January, with insightful results that portend dramatic shifts not only in federal policy, but in how the industry is likely to act in response.

Jefferies analysts Michael J. Yee and Akash Tewari, and Leerink Partners analyst David Risinger, all pinpointed the most dramatic effect on biopharma coming from the presence of Robert F. Kennedy, Jr., in a yet-to-be-defined role in healthcare.

“He’s going to help make America healthy again,” Trump said of Kennedy while declaring victory Wednesday morning, using his slogan designed to describe his administration’s public health and biopharma agenda. “He’s a great guy and he really means that he wants to do some things, and we’re going to let him go to it.”

Trump all but announced a dramatic role for Kennedy in late October by stating publicly that would allow RFK Jr. to “go wild on health.” Kennedy’s role is expected to be far-reaching and extend into reshaping how vaccines are regulated, since he has emerged in recent years as a sharp critic of the COVID-19 vaccines, quoted as calling it “criminal medical malpractice to give a child one of these.” Trump catalyzed the development of the COVID-19 vaccines through his first administration’s Operation Warp Speed effort.

“We need to see who Trump advances into key power positions,” Risinger cautioned Wednesday in a research note. “Nominations for HHS Secretary and FDA Commissioner will be important perception drivers ahead; we will need to see if there is disruption to FDA’s ability to execute and retain staff.”

Speaking on NPR the day after Election Day, Kennedy insisted: “Of course, we’re not going to take vaccines away from anybody,” adding: “We are going to make sure that Americans have good information about vaccines and vaccine safety.”

“Pack your bags”

Kennedy has targeted the FDA for drastic changes on a host of biopharma and broader healthcare concerns that Risinger said suggest equally drastic changes in FDA leadership.

Late last month, ABC News reported based on unnamed sources that Kennedy recommended Florida Surgeon General Joseph Ladapo to Trump’s transition team as a candidate for secretary of HHS, which oversees the FDA.

Ladapo opposed mandatory closings and mask mandates for Florida schools while publishing data showing that the mRNA-based COVID-19 vaccines increased the risk to younger men of cardiac-related deaths—though Ladapo was faulted for not submitting the data to peer review by Peter Hotez, MD, co-director of Texas Children’s Hospital Center for Vaccine Development and dean of the National School of Tropical Medicine at Baylor College of Medicine.

The ABC report quoted Kennedy as saying: “The president has asked me to clean corruption out of the agencies, to return them to doing the kind of gold-standard, evidence-based science that they were famous for when I was a kid, and to end the chronic disease epidemic. And he’s asked that I get measurable results in reducing chronic disease in children within two years.”

In an October 25 post on X (formerly Twitter), Kennedy warned current FDA officials: “If you work for the FDA and are part of this corrupt system, I have two messages for you: 1. Preserve your records, and 2. Pack your bags.”

“FDA’s war on public health is about to end,” Kennedy declared. “This includes its aggressive suppression of psychedelics, peptides, stem cells, raw milk, hyperbaric therapies, chelating compounds, ivermectin, hydroxychloroquine, vitamins, clean foods, sunshine, exercise, nutraceuticals, and anything else that advances human health and can’t be patented by Pharma.”

Based on these and numerous other public statements and comments, Yee of Jefferies wrote Wednesday, “RFK’s pot’l neg[ative] impact on vaccines and related developers is most ‘new’ or intriguing to biotech investors.

“Investors are bracing for a realization of consistent Trump RFK comments (even as recently as again [Wednesday morning] in the victory speech) and promises to give RFK a role or some power over healthcare strategy and policy will put some form of a cloud on vaccine stocks (and pot’l neg headwind on future outer year sales at least on branded vaccines—such as COVID-19, flu, etc.),” Yee added.

While Yee cited speculation that some members of a second Trump administration may try to temper anti-vaccine sentiment, he countered: “We expect a more hostile environment for vaccine makers (“whittle down the # of recommended vaccines”) and “(-) [negative] impact for vaccine and/or mRNA makers.” [emphasis in original]

Yee cited by name Moderna (NASDAQ: MRNA) as an example of a vaccine developer hurt by declining sentiment around vaccination as the number of COVID-19 cases retreats from spikes earlier this year.

Gathering clouds

Proverbially speaking, gathering clouds if not gray skies were evident Thursday when Moderna (MRNA) reported its third-quarter earnings. Even though the company surprised analysts by reporting net income of $13 million (up from a $3.63 billion net loss in Q3 2023) and higher-than-expected sales of its COVID-19 vaccine Spikevax® ($1.8 billion), Moderna shares have fallen nearly 3% since Wednesday, from $51.81 to $50.28 Thursday, then down another nearly 7% to $46.84 Friday as of 2:02 p.m. ET.

Investors connected Moderna’s profit to earlier vaccine sales compared with a year earlier (Q3 vs. Q4), and to the cost-cutting it announced in September, when the company said it will chop between $1 billion and $1.2 billion in expenses by shrinking its R&D budget by about 20%, going from the $4.8 billion it anticipated spending this year to between $3.6 billion to $3.8 billion by 2027. Moderna also pushed back its profitability forecast two years, to 2028—a forecast it achieved years ahead of schedule.

Another Leerink analyst, Mani Foroohar, noted that Moderna did not change its full-year product sales guidance to investors ranging from $3 billion to $3.5 billion, even with the Q3 sales spike.

“Our COVID-19 projections are largely unchanged, as declining vaccination rates and competitive pressures continue to weigh on revenue,” Foroohar wrote Thursday.

He estimates COVID-19 vaccine sales next year will fall to ~$2.0B, lower than the $2.6 billion predicted by a consensus of other Wall Street analysts cited by Foroohar. Based on that plus a lower 2025 product sales estimate than the company’s investor guidance of $2.5B–$3.5B, Foroohar lowered Leerink’s 12-month price target on Moderna shares 17%, from $46 to $38.

Addressing analysts on Moderna’s quarterly earnings call, CEO Stéphane Bancel noted that Moderna was among companies that had cooperated with Trump and Operation Warp Speed more than four years ago. In August 2020, for example, Moderna agreed to manufacture and deliver 100 million doses of its COVID-19 vaccine for the U.S. Department of Health and Human Services (HHS) and Department of Defense (DoD), with the federal government owning the doses.

“We worked very collaboratively with President Trump during his first term and so we’re going to continue to do that,” Bancel said. “Our mission is to make sure we help people and increase people’s health, which is [also] what the administration is going to work on.”

When it comes to pharma and biotech giants, Risinger and Leerink concluded, “We view the Trump win as mixed for large-cap biopharma since it creates potential uncertainty regarding FDA independence.”

Friendlier FTC for smaller biotechs

Smaller biotechs can expect to fare better under Trump, Risinger added, because the returning president is expected to name a U.S. Federal Trade Commission (FTC) chair who would be friendlier to mergers and acquisitions (M&A) in biopharma and other industries than the chair who took office during President Biden’s administration, Lina M. Khan.

Under Khan, the FTC opposed Illumina’s (NASDAQ: ILMN) acquisition of cancer blood test developer GRAIL (NASDAQ: GRAL), which the sequencing giant spun out in June after ending the deal last December. However, the FTC ultimately allowed Amgen (NASDAQ:AMGN) to proceed with its $27.8 billion acquisition of Horizon Therapeutics after the companies signed a consent order whose terms included barring Amgen from bundling one of its products with either of two Horizon treatments, Tepezza® or Krystexxa®, indicated for thyroid eye disease and chronic refractory gout, respectively. The FTC also allowed Pfizer (NYSE:PFE) to acquire Seagen for $43 billion, nine months after the deal was announced.

“FTC changes should lead to a more favorable M&A environment which is (+),” Yee wrote.

Yee observed that the Amgen and Pfizer reviews “put mega or large size deals (>$5B) on the sidelines given Khan’s other actions across other sectors,” citing among examples the FTC’s lawsuit against Facebook parent Meta Platforms (NASDAQL META), alleging that the company was illegally maintaining a personal social networking monopoly; Meta has denied wrongdoing.

“While we don’t nec expect any specific biopharma mega mergers, we do expect more smidcap (small- to mid-capitalization) deals with valuations higher than under the Khan administration if replaced (her term ends in Sept.),” Yee added.

A key opinion leader tapped by Jefferies analyst Tewari—Desh Peramunetilleke, the firm’s head of quantitative strategy—said small-cap biotechs will react positively enough to Trump’s triumph for two weeks to a month, which should lift electronic transfer funds (ETFs) specializing in shares of such companies, citing specifically the SPDR S&P Biotech ETF (XBI), the largest biotechnology ETF with total assets of $7.446 billion, as tracked by VettaFi.

Over the past year, the XBI has grown 44%, to $103.01 as of Thursday’s close, from $71.52 a year earlier. Since Election Day, the XBI has risen 2.4% from $100.62.

“Post-initial reaction, the XBI would flatten out,” Peramunetilleke predicted. But the XBI could instead continue to perform well if interest rates become extremely low or if the “yield curve”—a comparison between interest rates of long-term and short-term bonds closely watched by investors—steepens due to broad-based small- to mid-cap recovery, a scenario that he views as unlikely.

Another key opinion leader cited by Tewari—John Brooks, a former staffer at HHS and the Centers for Medicare and Medicaid Services—similarly opined that Trump’s second administration “will be more friendly toward M&A + more similar to what we saw prior to Lina Khan’s tenure but not completely revert back to those days, since the current framework has a chilling effect on economic activity and is not sustainable in the long term.”

Leaders and laggards

  • Tango Therapeutics (NASDAQ: TNGX) shares plummeted 37% from $5.18 to $3.24 Wednesday, after the company said in its Q3 earnings release that it would halt enrollment in trials of TNG908 after data from a Phase I/II trial (NCT05275478) showed the MTA-cooperative brain-penetrant PRMT5 inhibitor did not show activity in glioblastoma in 23 patients at active doses, “likely because CNS exposure did not meet the required exposure threshold for clinical efficacy.” Tango said it would shift resources to developing TNG462 as a potential best-in-class molecule in MTAP-deleted non-CNS tumors, citing the 24-weeks-and-increasing time on treatment seen for TNG462 vs. 16 weeks for TNG908, plus ‘462’s superior target coverage, and safety and tolerability profile.
  • Verrica Pharmaceuticals (NASDAQ: VRCA) shares nosedived 44% from $1.43 to 80 cents Tuesday, after the company reported it was exploring cost-cutting strategies following its third-quarter net loss of $22.86 million (vs. $24.802 million net loss in Q3 2023) based in part on negative net revenue of $1.865 million, vs. positive net revenue of $2.792 million a year earlier as the company set aside $1.7 million more in its reserve for estimated returns from certain distributors of expired product. Verrica also appointed Jayson Rieger, PhD, as president and CEO effective November 1, succeeding Ted White, and John Kirby as interim CFO effective Tuesday, succeeding Terry Kohler, now CFO of Optinose (NASDAQ: OPTN). Gregory Renza, MD, director and senior analyst of Biotechnology Equity Research at RBC Capital Markets, downgraded Verrica to “Sector Perform” from “Outperform,” and slashed the firm’s 12-month target price 82%, from $11 to $2.

Gut Microbiome Changes May Serve as Risk Factors for Rheumatoid Arthritis

A study headed by researchers at the University of Leeds has found that changes in the makeup of the gut microbiome are linked to the onset of clinically evident rheumatoid arthritis (RA) in those at risk of the disease because of genetic, environmental, or immunological factors. The cross-sectional and longitudinal observational study found alterations to the abundance of Prevotellaceae bacteria in the gut before individuals developed clinical rheumatoid arthritis.

The study initially took data from 124 individuals with high levels of CCP+, an antibody that attacks healthy cells in the blood, indicating risk of developing rheumatoid arthritis. The researchers compared their samples to 22 healthy individuals and seven individuals with a new rheumatoid arthritis diagnosis.

The findings from this larger group showed that the gut microbiome was less diverse in the at-risk group, compared to the healthy control group. The longitudinal study, which took samples from 19 patients over 15 months, revealed the changes in bacteria at ten months before progression to rheumatoid arthritis.

While previous research has linked rheumatoid arthritis to the gut microbiome, the newly reported study could point to a potential intervention point. While the researchers noted that it’s not clear if this instability is a cause or consequence of disease development, the findings might help identify those at risk and pave the way for preventive and personalized treatment strategies, they suggest.

Lead researcher Christopher Rooney, PhD, NIHR academic clinical lecturer at the University of Leeds and Leeds Teaching Hospitals NHS Trust, said: “Patients at risk of rheumatoid arthritis are already experiencing symptoms such as fatigue and joint pain, and they may know someone in their family who has developed the disease. As there is no known cure, at-risk patients often feel a sense of hopelessness, or even avoid getting tested. This new research might give us a major opportunity to act sooner to prevent rheumatoid arthritis.”

Rooney and colleagues reported on their study findings in Annals of the Rheumatic Diseases, in a paper titled, “Dynamics of the gut microbiome in individuals at risk of rheumatoid arthritis: a cross-sectional and longitudinal observational study.” The research was carried out in collaboration with the National Institute for Health Research Leeds Biomedical Research Centre, under the research themes of antimicrobial resistance and infection and musculoskeletal disease. Leeds Teaching Hospitals NHS Trust, Versus Arthritis, and Leeds Hospitals Charity were also partners on the project.

Affecting more than half a million people in the U.K., rheumatoid arthritis is a chronic disease that causes swelling, pain, and stiffness in the joints because the immune system is mistakenly attacking the body’s healthy cells. “Understanding the RA disease spectrum with recognition of at-risk individuals has propelled RA research into prevention strategies,” the authors wrote.

Previously published research consistently shows an unfavorable imbalance in the gut microbiomes of those at risk as well as those diagnosed with rheumatoid arthritis compared with the gut microbiomes of those without the disease. But it’s not clear exactly which microbes might be involved. “… there remains little consensus on the bacterial constituent members of an RA-related dysbiosis,” the team continued. “Subsequently, a variety of gut bacteria have been implicated as a potential impetus in the development of RA, none more so than Prevotella copri.” Prevotellaceae, and particularly Prevotella copri, have been inconsistently associated with RA development, the investigators pointed out, but while early studies showed an overabundance, there have been more recent studies that question these observations. “This work aimed to resolve the conflicting reports on Prevotellaceae abundance in the development of rheumatoid arthritis (RA) and to observe structural, functional, and temporal changes in the gut microbiome in RA progressors versus non-progressors.”

For their study, the team tracked changes in the gut microbiome profiles of 124 people at risk of developing rheumatoid arthritis, in seven people with newly diagnosed people (new onset RA; NORA) and in 22 healthy people over a period of 15 months, by assessing their stool and blood samples at five different time points.

Those at risk were identified by the presence of precursor anti-cyclic citrullinated protein (anti-CCP) antibodies, which attack healthy cells and are specific for rheumatoid arthritis, and by the experience of joint pain in the preceding three months.

During the study period, 30 of the 124 individuals in the at-risk group progressed to rheumatoid arthritis, and their microbial diversity was notably reduced compared with that of the healthy comparison group, particularly within specific areas—known as alpha diversity.

Alpha diversity was also reduced in both those who progressed and those who didn’t, and linked to anti-CCP antibody levels. In those with low anti-CCP antibody levels, microbial diversity was comparable with that of the healthy comparison group.

Recognized genetic, blood, and imaging risk factors for arthritis development were also significantly linked to lower microbial diversity, as was steroid use.

A specific strain of Prevotellaceae sp.—(ASV2058) most likely P. copri—was abundant in the microbiomes of those who progressed as well as in those of the newly diagnosed, but not in the microbiomes of those in the healthy comparison group. Another strain (ASV1867) of P. copri was also increased at the start of the study in those who progressed, possibly suggesting that different strains of P. copri might have different roles in rheumatoid arthritis progression, the investigators suggested.

Further analysis indicated that both enrichment (three) and depletion (five) of Prevotellaceae-specific strains were associated with progression. “Strain-specific phenomena are noted with both enrichment (three strains) and depletion (five strains) of Prevotellaceae-specific strains associated with progression,” the team wrote. “ASV2058 is included as one of those five depleted strains.”

While P. copri strains were most strongly associated with clinical risk factors for rheumatoid arthritis, other Prevotellaceae strains were also implicated, including Alloprevotella, Paraprevotella clara, Prevotella stercorea, Prevotellamassilia timonensis, and Prevotella shahii.

The authors acknowledged that as an observational study, the findings don’t allow any firm conclusions to be drawn about causal factors. They acknowledged various study limitations, including the small number of participants, the relatively short monitoring period, and the lack of direct one-on-one comparison between the at-risk and healthy participants.

Nevertheless, they stated, “Individuals at risk of RA harbor a distinctive gut microbial composition, including but not limited to an overabundance of Prevotellaceae species.” This microbial signature is consistent and correlates with traditional risk factors, they pointed out. “Longitudinal examination shows a dynamic microbial environment preceding RA onset. Further research into this late phase of disease development is merited, especially given the potential of the gut microbiome as a target for prevention, including in high-risk individuals with imminent arthritis.”

The Leeds research team will now carry out an analysis of treatments that have already been trialed, to inform future testing of treatments at this potential ten-month intervention point. Potential treatments that the researchers want to test at the ten-month window include changes to diet like eating more fiber, taking prebiotics or probiotics, and improving dental hygiene to keep harmful bacteria from periodontal disease away from the gut.

Targeting CD47 Could Be Critical Step in Attacking Colorectal Cancer

Researchers from the USC Norris Comprehensive Cancer Center and collaborators report that they have found evidence that targeting CD47, a protein that is part of the innate immune system, could be a key step in fighting colorectal cancer.

Their findings represent one of the first indications that targeting part of the innate immune system, combined with traditional immunotherapy drugs which work on the adaptive immune system, could be more effective in fighting colorectal cancer, according to the scientists, who published their work, “Role of CD47 gene expression in colorectal cancer: a comprehensive molecular profiling study” in the Journal for ImmunoTherapy of Cancer.

Until recently, immunotherapies only targeted the body’s learned immune response once cancer cells had already slipped by the body’s first line of defense against disease—the innate immune system—explain the researchers.

Novel approach

“Up until now, immune checkpoint inhibitors targeting the adaptive immune system have been the mainstream in immunotherapy,” said first author Hiroyuki Arai, MD, PhD, a former postdoctoral researcher at the USC Norris Comprehensive Cancer Center, part of the Keck School of Medicine of USC. “But in our current study, we focused on CD47, a checkpoint molecule in the innate immune system.”

The researchers knew colorectal cancer cells use the immune checkpoint CD47 to dodge macrophages (the innate immune cells that would otherwise target and destroy them). But how exactly do cancer cells manipulate CD47, and what could this mean when it comes to treating colon cancer?

In the present study, funded in part by the National Institutes of Health, researchers analyzed DNA and RNA from 14,287 colorectal cancer tumors to answer those questions. They compared tumors with higher levels of CD47 expression to those with lower levels, finding that higher levels were linked to more aggressive tumors, more activated cancer pathways, and more immune cells inside the tumor.

“In CD47-high tumors, the proportion of consensus molecular subtypes 1 and 4 was significantly higher than in CD47-low tumors. The expression levels of damage-associated molecular pattern-related genes showed a positive correlation with CD47 expression levels,” the investigators wrote.

“Major oncogenic pathways, such as mitogen-activated protein kinase, phosphoinositide 3-kinase, angiogenesis, and transforming growth factor beta, were significantly activated in CD47-high tumors. Additionally, the expression levels of a panel of adaptive immune checkpoint genes and estimates of immune cells constituting the tumor microenvironment (TME) were significantly higher in CD47-high tumors.

CD47 expression in CRC was associated with the activation of several oncogenic pathways and an immune-engaged TME. Our findings may provide valuable information for considering new therapeutic strategies targeting innate immune checkpoints in CRC.”

Key takeaway

Those findings suggest that developing an immune checkpoint inhibitor drug that can block the activity of CD47 could improve outcomes for colon cancer patients, many of whom are not well served by existing immunotherapy drugs.

“The most important takeaway is this data suggests that CD47 is an attractive target for drug development,” said senior author Heinz-Josef Lenz, MD, deputy director for research programs and co-director for the Rosalie and Harold Rae Brown Center for Cancer Drug Development at the USC Norris Cancer Center.

“The key is to develop an antibody or an engineered immune cell that can inhibit CD47 signaling, but it has to be used in combination with other drugs. The right combination is not clear yet, so more research is needed,” continued Lenz, who is also a professor of medicine and preventive medicine at the Keck School of Medicine.

Lenz and the rest of the team are also studying other methods of shrinking colorectal cancer tumors, including with compounds that stimulate macrophages to attack cancer cells.

Also participating in the research were scientists from Caris Life Sciences, University of Cincinnati Medicine, West Virginia University Cancer Institute, Fox Chase Cancer Center, University of Arizona Cancer Center, GI Medical Oncology Levine Cancer Institute, University of Minnesota, Georgetown University Medical Center, and the Rutgers Cancer Institute of New Jersey.

Genomics in Snowy Denver: A Video Update from ASHG

Julianna LeMieux, PhD, GEN’s Deputy Editor-in-Chief took a minute away from the talks, posters, and expo hall to join Uduak Thomas, Senior Editor at GEN, who is also in Denver, to talk about the meeting, the sessions they attended, and the trends that they are noticing. Some of the highlights were an interview with Jacob Thaysen, Illumina’s new CEO, a single cell initiative, how proteomics is trying to change Alzheimer’s detection, and the launch of PacBio’s new instrument—the Vega—complete with a review of the OneRepublic concert.

Cancer-Fighting Zeal Regained by Tired T Cells Deprived of Lactic Acid

As cancer cells grow, they pump out metabolic byproducts such as lactic acid into the tumor microenvironment. Newly reported research by scientists at the University of Pittsburgh and UPMC Hillman Cancer Center suggests that exhausted T cells—which have lost their cancer-fighting vigor—consume this lactic acid, which further saps their energy. When the researchers blocked the solute carrier (SLC) protein MCT11, which imports lactic acid into cells, the exhausted T cells gained a new lease on life. Antibody blockade of MCT11 led to improved tumor control in mouse models of cancer when used as monotherapy, and also when combined with anti-PD1 immunotherapy.

“Blocking access to inhibitory metabolites is a completely new take on how we can reinvigorate the immune system,” said Greg Delgoffe, PhD, professor of immunology at Pitt and director of the Tumor Microenvironment Center at UPMC Hillman. “We often think of exhausted T cells being useless, but this study shows that we can actually get juice out of these cells by blocking negative effects of the tumor microenvironment.”

Delgoffe is senior author of the team’s published paper in Nature Immunology, titled “Dysfunction of exhausted T cells is enforced by MCT11-mediated lactate metabolism,” in which they concluded “… this study suggests SLCs can be targeted on immune cells for therapeutic benefit.”

CD8+ T cells have a “crucial role” in orchestrating immune responses against pathogens and tumors, the authors wrote. However, when continually exposed to tumors, T cells progressively become less effective due to expression of coinhibitory receptors that act like brakes. Progenitor exhausted T cells, which still retain some cancer-killing function, can deteriorate further to a terminally exhausted state. “CD8+ T cells are critical mediators of antitumor immunity but differentiate into a dysfunctional state, known as T cell exhaustion, after persistent T cell receptor stimulation in the tumor microenvironment (TME),” the team continued. “Exhausted T (Tex) cells are characterized by upregulation of coinhibitory molecules and reduced polyfunctionality.”

Most immunotherapies, including the checkpoint inhibitor drugs anti-PD1 and anti-CTLA4, attempt to release these brakes by blocking coinhibitory receptors. “Checkpoint inhibitors, which are the main weapons in our immunotherapy arsenal, have been incredibly successful for some patients with certain cancers, but there have also been a lot of failures, and they haven’t been the gamechangers we expected in many cancers,” said Delgoffe. “There’s only so much you can do by taking your foot off the brake.”

On the hunt for new ways to jumpstart tired T cells, Delgoffe and first author Ronal Peralta, PhD, postdoctoral fellow in Delgoffe’s lab, started by looking at the solute carrier family of proteins, which transport nutrients into cells.

“Exhausted T cells have been studied extensively in terms of what they can no longer do,” said Peralta. “But what do exhausted T cells do? What do they eat? What nutrients do they have access to? These questions were the starting point of our study.”

Greg Delgoffe, Ph.D. professor of immunology at the University of Pittsburgh and director of the Tumor Microenvironment Center at UPMC Hillman Cancer Center [Tiffany Cooper]
Greg Delgoffe, PhD, professor of immunology at the University of Pittsburgh and director of the Tumor Microenvironment Center at UPMC Hillman Cancer Center [Tiffany Cooper]
The researchers found that a solute carrier called MCT11, which imports lactic acid, was dramatically increased in terminally exhausted T cells compared to their progenitor versions, suggesting that lactic acid contributes to loss of function.

When the investigators then deleted the gene encoding MCT11 in mice or blocked the protein with a monoclonal antibody, T cells ingested less lactic acid and showed improved functionality and tumor control in mouse models of melanoma, colorectal carcinoma and head and neck cancer.” Conditional deletion of MCT11 in T cells reduced lactic acid uptake by Tex cells and improved their effector function,” the researchers reported. “Targeting MCT11 with an antibody reduced lactate uptake specifically in Tex cells, which, when used therapeutically in tumor-bearing mice, resulted in reduced tumor growth.”

The researchers found that the MCT11 antibody promoted clearance of tumors in mice when given alone, but in some mouse models was even more effective when combined with the checkpoint inhibitor anti-PD1. “MCT11 antibody blockade has an effect as a monotherapy, leading to complete responses in MC38 and MEER models and also as a combination therapy, doubling the CRs in mice bearing MC38 tumors in combination with αPD1,” they wrote.

If coinhibitory receptors that lead to T cell exhaustion are the brakes on a car, lactic acid is like poor quality gas contaminated with dirt and particulates that hinders the vehicle’s performance. By blocking access to the gas station that sells this subpar fuel, the car accesses better gas that improves its performance—just like blocking MCT11 stops T cells from accessing lactic acid that impedes their function. “When we get rid of MCT11, there’s no difference in the expression of coinhibitory receptors on T cells,” explained Delgoffe. “They’re still technically exhausted, but they behave as functional T cells because we cut off the tap of this bad metabolite, lactic acid.”

In their paper the authors concluded, “By modulating nutrient transporters, such as in the case of MCT11, terminally differentiated T cells can be rendered insensitive to metabolites such as lactic acid, driving tumor eradication and therapeutic response.” Through their new spinout company, Delgoffe and Peralta are now working to optimize the MCT antibody for effectiveness in human T cells, with the goal of testing it in future clinical trials.

According to Peralta, MCT11 is an attractive therapeutic target because it is almost exclusively expressed in exhausted T cells, which are concentrated in tumors. This means that drugs targeting MCT11 could have fewer side effects than traditional immunotherapies such as anti-PD-1, which act on T cells throughout the body. Reporting on their collective findings, the team suggested, “Short-term targeting of MCT11 in patients with cancer could, thus, limit the possibilities of potential toxicities and adverse autoimmune reactions.”

Peralta added, “This research is really exciting because it’s proof-of-concept that targeting how T cells interact with metabolites in their environment can promote better outcomes in cancer. It opens the door for exploring how we can go after other targets in immune cells for treating cancer and many other diseases.”

Supplier-Turned-Partner: Twist Joins Absci in AI Antibody Collaboration

As it builds a pipeline of artificial intelligence (AI)-designed treatments, Absci has reached out to its preferred supplier of DNA for its latest collaboration—one of three partnerships that the AI drug developer has either launched or advanced in recent weeks.

Twist Bioscience says the potential for developing an AI-based drug is great enough to depart from its usual business model as it joins Absci in designing a novel therapeutic using generative AI.

The companies have agreed to apply Twist’s silicon-based high-throughput gene synthesis platform and Absci’s Integrated Drug Creation™ platform toward their combined drug discovery effort, which is designed to accelerate the design and preclinical development of an antibody therapeutic for an undisclosed set of diseases.

The undisclosed disease set is expected to be one of Absci’s three therapeutic areas—inflammatory bowel disease (IBD), dermatology, and immuno-oncology, Absci founder and CEO Sean McClain told GEN Edge.

“We do see this falling within those broader I&I and oncology therapeutic areas of focus,” McClain said.

Emily M. Leproust, PhD, Twist’s CEO and co-founder, told GEN Edge the collaboration with Absci marks a departure from her company’s traditional fee-for-service business model.

Emily M. Leproust, PhD, Twist Bioscience CEO and co-founder

“I call this partnership the cherry on top of the cake,” Leproust said, “because our usual measure of success for us is revenue ramp, gross margin improvement, getting to profitability. Our day-in, day-out focus of what we do is usually to sell a service or sell a product: Someone gives us a sequence, we give them a tube, they pay us.”

For the Absci-Twist collaboration, she explained, both companies have agreed to fund their own costs and share the resulting asset.

Creating value

“Hopefully it will create an asset that will be valuable, and we’ll share in that value creation,” Leproust said. “It’s an opportunity for us to participate in the value creation of a new asset, as well as show to the world how the new technology that we’ve developed is particularly suited for AI developed antibody discovery.”

The companies will test and validate antibody candidates designed using Absci’s AI de novo design capabilities, combining that technology with Twist’s silicon-based synthesis platform. Twist’s platform includes its Multiplexed Gene Fragments, double stranded gene fragment sequences of up to 500 base pairs in length with no limit on sequence number, delivered as a pool instead of one fragment per well matrix. Twist says the pooled format of fragments enables high-throughput screening applications such as prime editing, ultra-complex CRISPR-based functional screening, peptide and protein engineering.

“With 500 base pairs, you can synthesize a full heavy chain or a full light chain of an antibody. In the past, when you thought antibody, you were always thinking, I either have to restrict myself to a portion of a heavy chain, light chain, or I have to assemble. The first part is not ideal, and the second part takes time,” Leproust said.

“Now that we have those multiplexed gene fragments, because we can do the full heavy chain or full light chain, you get the full antibody and you get speed. That accelerates the design-build-test cycle,” she added.

Customers who furnish Twist with an antibody sequence can receive an antibody tube completed in as little as 13 days, compared with as much as six weeks using the previous fragments of up to 300 base pairs long. Twist says its platform enables it to produce high quality gene fragments starting at starting at 7 cents per base pair (bp) and next-generation sequencing (NGS)-verified sequence perfect clonal genes starting at 9 cents per bp.

Twist launched its Multiplexed Gene Fragments in May. Three months later, it expanded its DNA synthesis offering by launching Gene Fragments with increased lengths ranging from 1.8 kb to 5.0 kb.

While the value of the collaboration has not been disclosed, Twist says the collaboration is the company’s first with an AI drug developer.

“A little bit of a risk”

“We’re both taking a little bit of a risk,” Leproust added. “Frankly, this collaboration is not something we can do too many of because our business model is to ramp revenue and be paid. But we’re very happy to do it with Absci because I think they have a great platform.”

“If it works great, maybe we’ll do more.”

Absci founder and CEO Sean McClain

For Absci, McClain said, the partnership is the first with a partner that does not involve a biopharma company or a research institution: “This is a unique partnership for us, and I think something from which we see a lot of potential for value creation.”

“One of the things that we’re seeing is that there are a lot of exciting targets that can be prosecuted on,” McClain explained. “We don’t have the ability to prosecute on all of these ourselves. And so being able to co-develop these allows us to essentially prosecute on more assets ourselves than we could do on our own

As the partnership progresses, Absci and Twist plan to seek a partner for human clinical development and commercialization.

“Once we have some of that initial preclinical data, especially around a drug candidate, I think that’ll be the time we take this data to a big biotech or large pharma,” McClain said.

Also in recent weeks, Absci disclosed that it had successfully completed the first milestone in its nearly year-old drug discovery collaboration with AstraZeneca—namely, successfully delivering AI de novo designed antibody sequences to the pharma giant.

“They have acknowledged the successful completion of the milestone and have elected to move forward” with advancing the antibody sequences into AI-lead optimization, McClain said.

As a result of achieving that milestone, Absci received an undisclosed payment from AstraZeneca. The companies “The agreement was structured to have technical milestone payments in there, along with the other traditional clinical and development milestones as well,” McClain added.

The companies agreed in December 2023 to partner on accelerating the discovery of a potential new cancer treatment candidate, with AstraZeneca agreeing to pay Absci an upfront payment, R&D funding, payments tied to achieving milestones, plus royalties on product sales—all of which were undisclosed.

The collaboration was designed to combine Absci’s platform with AstraZeneca’s oncology expertise. Oncology is one of AstraZeneca’s five therapeutic areas of focus, along with cardiovascular, renal, and metabolism; respiratory and immunology; vaccines and immune therapies; and rare diseases.

Work on the partnership started early this year.

Generating binders

“Within six months, we were able to use our de novo AI model to generate binders to this oncology target of interest. And this was designing all six CDRs [antibody complementarity-determining regions] from scratch; there were no known binders,” McClain explained.

“We’ve obviously applied this to our own internal pipeline, but applying it successfully to a partner program is something we see as a huge achievement as well as a very strong validation of the model and the platform,” McClain added. “We’re planning on moving forward into the next stage of the partnership. We’re really excited.”

Numerous leads toward the target have been generated, from which only one candidate will be selected to advance toward the clinic. The companies have yet to finalize a timeframe for clinical study, McClain said.

Absci’s all-preclinical pipeline is led by ABS-101, which is designed to treat IBD by targeting tumor necrosis factor-like cytokine 1A (TL1A). The company remains on track for an early 2025 launch of a first-in-human Phase I trial of ABS-101, McClain said.

Also in Absci’s pipeline:

  • ABS-201, which is being developed for an undisclosed dermatological indication that according to the company has significant unmet need.
  • ABS-301, a fully human antibody that is designed to bind to a novel target discovered through Absci’s Reverse Immunology platform.

In August, Absci broadened its cancer pipeline by agreeing to partner with Memorial Sloan Kettering Cancer Center (MSK) on using generative AI to discover and develop up to six cancer therapies, through a collaboration intended to marry Absci’s platform with MSK’s research and clinical expertise in oncology.

Absci and MSK have not disclosed the value of their collaboration or the types of cancer for which they plan to develop new treatments.

“As a leading cancer research institute, MSK has a lot of exciting new novel oncology targets to prosecute. We’re going to take that novel biology and cancer expertise along with our generative AI models and be able to develop some potential first-in-class therapeutics together,” McClain said. “It’s another really strong validation of the platform.”

Absci is the first AI-based drug developer with which MSK has partnered. The partners have offered no public updates since announcing their collaboration, though McClain said that will change when Absci holds its R&D Day on December 12.

MSK and Twist are two of four planned partnerships Absci planned to announce during the second half of this year. Absci still plans to reveal the other two by year’s end.

Inscripta Reports Successful Scaleup of an Anti-Aging Skincare Ingredient

Officials at Inscripta say they successfully completed scale-up runs and are moving into commercial manufacturing of an anti-aging skincare ingredient.

Commercial biomanufacturing addresses serious challenges in sourcing plant-based ingredients, according to a company spokesperson, including the environmental footprint associated with current extractive sourcing and the limited depth and consistency of supply chains, which can negatively impact availability and affordability. Biomanufacturing also eliminates sensitizing impurities native to plant-based extracts, notes the spokesperson.

Inscripta reportedly is engaged with commercial partners to deliver “an ingredient product with demonstrated efficacy, superior quality, and consistency that will benefit branded manufacturers and their customers.”

“There is an incredible opportunity for the bioeconomy to meet global consumer demands, not just in personal care, but well beyond by improving sustainability, stabilizing supply chains, and reducing time to market,” said Sri Kosaraju, president and CEO, Inscripta. “We not only develop robust and productive strains, but we also create scalable manufacturing supply chains that deliver sought-after materials to market.”

Inscripta’s development program leveraged its GenoScaler technology, a novel and proprietary ultra-high-throughput, CRISPR-enabled platform designed to rapidly optimize microbial strains for biomanufacturing, explained Kosaraju, and pointed out that this two-year effort yielded engineered strains with commercially relevant productivities and consistent performance across four orders of magnitude in bioreactor scale.

PacBio Launches Vega Benchtop, Hopes People Get “Hooked on HiFi”

If ASHG attendees can count on one thing, it’s PacBio creating a buzz (and throwing a great party). The company has developed a reputation for launching its products with flair, typically accompanied by a concert with a band that is not too old (but not too new, either) like Maroon 5 and Flo Rida. This year was no exception. When PacBio launched their latest instrument, Vega, on Wednesday night, One Republic was on site to help them do it.

PacBio
Vega [PacBio]
The new instrument was introduced by Christian Henry, PacBio’s CEO, before the band took the stage. And the Vega draws attention, even without One Republic’s help. First of all, it’s pink. Part of PacBio’s new look, introduced two years ago with the launch of the Revio, was a commitment to the color pink that could rival Barbie’s.

Vega is a true benchtop (measuring 2 feet by 2 feet) with a list price of $169,000 and a run time of 24 hours (the same as a Revio run). Vega’s one 25M SMRT cell offers a throughput of 600 full-length RNA samples per year or 200 human genomes. The company is now accepting orders for Vega systems, which it plans to begin shipping in the first quarter of 2025.

Rolling the Vega out now is part of PacBio’s larger strategy to build a portfolio of sequencers, both long and short read. Why? Because PacBio needs to “meet customers where they are.” Revio was introduced to break the $1000 genome, for the people who want high throughput sequencing. But Revio is big, high throughput, and costly. Many people cannot afford it and don’t do enough sequencing to make it count.

Henry told GEN that they want to make HiFi technology more accessible. “Because if we can do that,” said Henry, “these customers will get hooked on HiFi. Over time their projects will scale and they’ll scale into Revio, and then maybe over time they’ll scale into what comes after Revio.”

Creating a SPRQ

The Vega launch comes on the heels of an announcement made last week of a new chemistry (called SPRQ) for the Revio. Henry said that the new chemistry “does two or three fundamental things that give researchers new capability and give us a great opportunity to grow.” Perhaps the most important advance, he said, is that it reduces DNA input down from 2 μg to 500 ng, allowing access to samples that couldn’t be used before, such as blood spots and saliva. More sample types mean a broader market for PacBio.

One Republic
One Republic playing at PacBio’s ASHG party [Julianna LeMieux]
Henry also explained that they have learned how DNA gets into the Zero-mode waveguides (ZMWs) on their semiconductor chips. Knowing that has allowed them to optimize their chemistry to make the process more efficient. Getting more of the single molecules into the wells results in 33% more throughput per SMRT cell and takes the cost of a HiFi genome from the current price of $995 to $500. Lastly, PacBio has improved the methylation calling software and has introduced methylation A calling,  enabling the Fiber-seq assay which analyzes chromatin fingerprinting and nucleosome positioning on genetic regulation. Existing Revios can use the new chemistry—which will be available in December—with a change in reagents and updated software. In contrast, the Vega does not use the new SPRQ chemistry.

Engaging the community 

A benchtop machine is not unique; there are now multiple options available to users. Notably, just a few weeks ago, Illumina launched a new version of its decade-old benchtop standby, the MiSeq. And there are thousands of customers already doing sequencing on benchtop sequencers.

PacBio hopes to reach those customers based on HiFi’s advantages and also because they are “catching up to [short reads] on the economic front.” The reason to launch the Vega right now is to “engage the entire genomics community” and to “enable people to adopt the power of long read sequencing.” Then, when people are hooked on their smaller VEGAs, they can grow into a Revio (and whatever other platforms Henry has up his sleeve).

PacBio has seen ups and downs this year (the downs coming from the stock market). Given that, can Henry justify a big party, with a rock band, at the conference? “Oh my God. Yeah!,” he answered. “We are trying to stand out!”

The event works to galvanize groups of people, he explained. They launched the Revio with a Maroon 5 concert two years ago and sold 76 units in eight weeks. Did Adam Levine’s tattoos have an effect? Maybe. Henry asserts that there is “a direct correlation between the scale of the event and the sales.”

Because PacBio is “the small kid on the block”, they have to be leaders of the community, Henry noted. The band is fun and cool, but it will also bring 1500 people in the same space at the same time, all ready to engage with PacBio, and learn about Vega. It’s priceless, noted Henry.

“We do not want to be just a life science company,” he added. “They are boring. We want to be changing the world and enabling the power of genomics to improve human health. That’s bigger than just a life science company at a genetics company. That’s our dream.”

 

To receive more ASHG news from GEN, including on-the-ground reporting, register for our newsletter here.

96 well plate
The 100 Million Cell Challenge, a collaboration between Scale Bio, CZI, Ultima Genomics, NVIDIA, and Bioturing, drew 147 different proposals from researchers. At ASHG, they announced the winning projects across diverse applications, from global health initiatives to therapeutic discovery.
PPIs
At ASHG, Seer highlighted how its deep proteomics technology helps scientists gain insights into neurodegenerative conditions, cancer, and metabolic conditions. The company also has a deal to pair its Proteograph product with Thermo’s Orbitrap Astral mass spectrometers.
Robert F. Kennedy and Donald Trump
Jefferies analysts Michael J. Yee and Akash Tewari, and Leerink Partners analyst David Risinger, CFA, all pinpointed the most dramatic effect on biopharma coming from the presence of Robert F. Kennedy, Jr., in a yet-to-be-defined role in healthcare.
Microbiota of the human intestine, illustration
Researchers identified changes in the make-up of the gut microbiome prior to onset of clinically evident rheumatoid arthritis in those at risk of the disease, which could feasibly offer up opportunities for preventive and personalized treatment strategies.
colon cancer
The researchers knew colorectal cancer cells use the immune checkpoint CD47 to dodge macrophages. But how do cancer cells manipulate CD47, and what could this mean when it comes to treating colon cancer?
Denver
GEN editors Julianna LeMieux, PhD, and Uduak Thomas take a break at ASHG to discuss some of what they have learned and the trends that they have noticed.
T cells attacking cancer cells
Researchers showed how blocking a solute carrier protein can reinvigorate exhausted T cells, which in mouse models of cancer led to improved tumor control, both when used as monotherapy, and also when combined with immunotherapy.
Absci researchers at work in the company's lab.
The companies have agreed to apply Twist’s silicon-based high-throughput gene synthesis platform and Absci’s Integrated Drug Creation™ platform, aiming to accelerate the design and preclinical development of an antibody therapeutic for an undisclosed set of diseases.
bioreactors
Commercial biomanufacturing addresses serious challenges in sourcing plant-based ingredients, according to a spokesperson at Inscripta, including the environmental footprint associated with current extractive sourcing and the limited depth and consistency of supply chains.
PacBio
One thing ASHG attendees have grown to count on is PacBio creating a buzz. And this year is no exception. The company launched its latest instrument with a party and concert by One Republic on Wednesday evening.