Leanna Stokes had gotten into the habit of asking her oncologist what might be next for her treatment, and for good reason. Stokes, a 36-year-old gymnastics manager from New Rochelle, New York, had received one of the most difficult diagnoses in oncology: metastatic pancreatic cancer. Her oncologist kept mentioning two syllables, KAY-ras, referring to her cancer’s mutation on the KRAS gene. Mutations in this gene can make cancers more aggressive. But for Stokes, it was a possible key to extending her life.

“She always mentioned this — KRAS, KRAS, KRAS,” Stokes said of her oncologist. As Stokes proceeded to receive line after line of chemotherapy, she would remind herself, “It’s there. It’s there. It’s there. Then finally, it was my turn.”

Just a few years ago, such a refrain might have sounded odd to pancreatic cancer experts. For most of the nearly 50 years since KRAS was first discovered, scientists struggled to effectively drug the cancer protein. When Kevan Shokat, a biochemist at University of California, San Francisco, finally discovered how to drug a rare subset of KRAS mutant cancers, the first-generation drugs were a clinical disappointment. For the roughly 1% of pancreatic cancer patients who could receive them, the drugs improved outcomes only marginally, with resistance forming rapidly.

“We did not have a home run on the first effort,” said Channing Der, a pancreatic cancer researcher at the University of North Carolina, Chapel Hill. “It’s fair to say we’ve been disappointed by the durability of the responses.”

But once Shokat had shown it could be done at all, more and more companies jumped into developing drugs for KRAS, with new agents now regularly moving into clinical trials. The company leading the field has been Revolution Medicines, with the drug daraxonrasib, which targets KRAS and related proteins.

This was the drug that Stokes got on her clinical trial. It transformed her life, she said, enabling her to live far longer than most patients with her diagnosis. It’s also generating immense excitement among oncologists and drug developers, who say it heralds a new era for pancreatic cancer medicine and could bring new treatments for other cancer types with KRAS mutations including lung, colorectal, endometrial, and more. Beyond Revolution Medicines, dozens of other companies are also testing promising KRAS inhibitors in the clinic.

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The genomics community’s long wait for 10x Genomics’ highly anticipated news is finally over. On Saturday night, at the Hard Rock Café Hotel in San Diego—across the street from the American Association for Cancer Research (AACR) conference—the company hosted the “Impossible” party to announce its new spatial instrument—the Atera.

Serge Saxonov, PhD, CEO of 10x Genomics, walking onto the stage to thunderous applause, noted that there is “a gap between what we need to see and what we have been able to measure.” The Atera, which enables whole-transcriptome spatial biology at scale, “obliterates the typical trade offs” that come with existing spatial tools, he said.

“This is the biggest launch in our history. I am the most excited I’ve ever been about any product, or any product category, across the board,” Saxonov told GEN. “It has been a long time in development, and it is what we have known the world needs for a long time. I think it will fundamentally change how we measure and understand biology, and it really puts research on a new trajectory. It is really exciting to be at a place now where we can deliver it to the world.”

Nuts and bolts

Atera offers more plex, throughput, and sensitivity than 10x Genomics’ Xenium—enabling whole-transcriptome at scale. More specifically, when compared to Xenium, Atera has four times the throughput, six times higher plex capacity for targeted assays, 3.6x higher plex, and 2–3x sensitivity for whole transcriptome assays.

The price for Atera is $495,000, and the instrument measures roughly 53” x 36” x 64” or (4.42 ft × 3 ft × 5.33 ft). Orders are currently being taken, and the instrument will be available in the second half of this year.

The instrument can run up to 800 1 cm² whole transcriptome samples (FFPE and fresh frozen) per year, with flexible run configurations, and a greater than 5 cm² imageable area per slide (for greater than 2,000 mm² total tissue per run when using all four slides.)

There are 18,000-genes on the Atera WTA (whole transcriptome) with stackable customization of 1,000-gene Atera Select panels available now, and optional stacking of up to three 1,000-gene panels coming in the future.

“Spatial genomics with whole-transcriptome profiling capabilities is the ultimate approach to measure single cells in their tissue context,” Holger Heyn, PhD, ICREA professor at the Centro Nacional de Análisis Genómico (CNAG) and member of the Human Cell Atlas, added. “All other lower-plexity approaches have been just a warm-up phase leading to this application.”

Jasmine Plummer, PhD, associate member of the St. Jude Faculty and director of the Center for Spatial OMICs points out that the whole transcriptome, while exciting, can bring a big “sticker shock” for many researchers because it will require a lot more probes in contrast to a sequencing-based platform, where a library accesses all of the genes.

The instrument uses standard glass microscopy slides, which is exciting to Plummer. In the past, she said, slides have posed a challenge when coordinating with other researchers, and using regular slides will be more “pathology friendly.”

An end to tradeoffs? 

Existing spatial technologies, which are still relatively nascent in genomics, have been constrained by tradeoffs between plex, resolution, and throughput. Researchers have had to make choices and prioritize.

“In general, with the landscape as it is today, there is a tradeoff,” Nick Banovich, PhD, VP of scientific development at TGen, and professor of bioinnovation and genome sciences division and director of the Center for Spatial Multi-Omics (COSMO), told GEN. “The closer you walk toward whole transcriptome, the lower the per gene sensitivity.”

“The most exciting thing [about Atara],” he continued, “is that there is still quite good sensitivity with whole transcriptome breadth. That’s the huge advantage of this system; there is no tradeoff anymore.”

However, this launch comes just over three years after Xenium’s launch. Purchasing a new instrument so soon may pose a challenge. Plummer notes: “In this economy, with the uncertainty of scientific funding, it is concerning to ask customers—many of whom just landed a machine—to spend another several hundred thousand dollars.”

Why AACR?

Oncology is one of the most exciting, most promising applications of spatial, especially in the near term, noted Saxonov. This is, in large part, because the work exists across the spectrum—from basic discovery to translation to clinical applications. Spatial is unambiguously important, he asserted.

Unveiling at AACR “just made a lot of sense.”

In addition to the party, the company will host a digital launch event on Tuesday, April 21. Within the AACR program, a presentation from the German Cancer Research Center (DKFZ) will include data generated on the platform, highlighting Atera’s ability to uncover cancer biology not accessible with legacy approaches. Researchers distinguished multiple malignant and stem cell states across disease stages, within a single colorectal tumor sample, and mapped how these populations interact with the surrounding immune microenvironment. The data reveal a more complex immune landscape that could inform future therapeutic strategies and drug development. In addition, two posters (#7116, #6216) will include data from Atera.

The future

10x Genomics said that Atera will play a role in advancing large data studies. For example, the company noted that Atera will enable the goal of the Human Cell Atlas (HCA) as it continues its mission to map every cell type in the human body.

“With the Human Cell Atlas entering its next phase of generating spatially resolved atlases, whole-transcriptome approaches will be the workhorse for data generation,” Heyn told GEN.

“I am excited to see the Atara platform being launched now,” he added. “It is very timely as we ramp up production for the Human Cell Atlas 2.0 phase.”

Atera’s future

The company presented a roadmap with future plans at the AACR event, highlighting spatial proteomics, automation, base by base sequencing (a de novo sequencing assay) and software improvements.

Atera, Saxonov told GEN, is a fundamental platform that the company will continue enabling. It lays the groundwork for the next decade of research and work. This point in time, he said, feels similar to the early days of next generation sequencing (NGS). And although the company will continue to develop its other platforms and product lines, Atera has “massive amounts of headroom to keep building on top of it. It is the convergence of all these different technology stacks and different fields onto one.”

“What the platform can do right out of the gate is exciting. And all the things that it can do in the future will be really, really exciting,” he asserted.

The post 10x Genomics Unveils Atera Spatial Platform at AACR Meeting appeared first on GEN – Genetic Engineering and Biotechnology News.

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