Illumina has revealed plans to step up its cancer detection efforts by launching a new in vitro diagnostic (IVD) test and bolstering its oncology-focused companion diagnostic (CDx) collaborations—as well as plans to launch a new cloud-based bioinformatics data platform.
Addressing the virtual J.P. Morgan 39th Healthcare Conference, Illumina CEO Francis deSouza said Illumina will extend its TruSight™ Oncology product family by adding IVD test.
The tumor profiling assay will have similar chemistry and analytics to TruSight Oncology 500 (TSO 500). The IVD test is now undergoing regulatory review and is set to be launched in both the U.S. and Europe later this year.
TSO 500 is a “family” or set of three assays–the basic test, a high-throughput version allowing for processing batches of up to 192 samples at a time, and a circulating tumor DNA (ctDNA) blood-based version. The IVD test would be the fourth test in the family of TSO 500 products.
TSO 500 is a Research Use Only comprehensive pan-cancer assay designed to identify 523 known and emerging tumor biomarkers. TSO 500 uses both DNA and RNA from tumor samples to identify key somatic variants critical for cancer development and progression, such as small DNA variants, fusions, and splice variants.
“We believe that the way to do efficient cancer testing is really the CGP [comprehensive genomic profiling] approach,” Alex Aravanis, MD, PhD, Illumina Chief Technology Officer, told GEN.
CGP is a next-generation sequencing (NGS) approach that uses a single assay to assess relevant cancer biomarkers, as established in guidelines and clinical trials, for therapy guidance. Aravanis noted that CGP is covered for 230 million lives in the U.S., a majority of the population, through private payer or public payers for certain indications—not just users of TSO 500 but other providers of the technology, or companies that offer tests based on Illumina sequencing technology.
“Broaden the Access Further”
“There has been real pioneers in the field that we’ve worked with, customers of ours like Guardant [Health] or Foundation Medicine. We think it’s important to broaden the access further, both in the U.S. and outside the U.S. and that’s making distributed kits,” Aravanis added, “so that the labs that don’t have a significant R&D budget to develop their own tests and do complex, large clinical trials can also offer this comprehensive testing locally, in the community, at academic hospitals.”
Several companies are also pursuing CGP tests across cancer indications based on 500 or more genes, including Exact Sciences, QIAGEN, Roche, and Thermo Fisher Scientific. On the CDx side, Foundation Medicine and Guardant Health have also had success, having been granted eight and one FDA approvals, respectively, for indications tied to specific cancer drugs.
In addition to announcing the IVD test launch, Illumina said it will apply TSO 500 toward growing its focus on CDx for cancer treatments, by launching two new collaborations and expanding two of its existing alliances. Aravanis also noted that the number of oncology therapies that have molecular markers required for prescribing stood at 55 and growing.
“A comprehensive approach here is to do nearly all the genes implicated in cancer in a single test. Having one test that allows you to do all or a large number of them is really the way to get the most access for patients,” Aravanis said. “For many of these tests, it may only be 1% or 2% of lung cancer patients that are eligible. And then if that test isn’t done as an individual test, they may not get access to it. So we think there’s a tremendous efficiency to a comprehensive approach.”
Focus on Signatures
The CGP approach, he added, better enables testing for key signatures that require the testing of several genes, such as homologous recombination repair deficiency (HRD) and tumor mutational burden (TMB).
HRD figures in two of the four CDx partnerships announced by Illumina yesterday.
In one HRD partnership, launched with Myriad Genetics, Illumina agreed to leverage its sequencing instrument install base and knowledge from growing market adoption of its TSO 500 next-generation sequencing assay to develop and commercialize distributed kits globally for the assessment of HRD along with other proprietary biomarkers, while Myriad expands access and extends the reach of myChoice® CDx through Myriad’s services offering.
“It’s really about having much broader access by having a kit that any accredited lab can use, versus a smaller number of labs that innovate and develop their own products, which is fantastic and creates the market, and opens up the field, but there’s many, many cancer patients today who wouldn’t be able to get access that way without a true IVD,” Aravanis said.
Illumina and Myriad inked a time-limited exclusive agreement for Illumina to provide a kit-based version of Myriad’s myChoice CDx test for international markets.
“The agreement between Myriad and Illumina combines clinically validated companion diagnostics and next-generation sequencing to advance comprehensive genomic profiling of tumor samples and drive improved outcomes for oncology patients,” stated Paul J. Diaz, Myriad’s President and CEO.
In the other HRD alliance, Illumina and Merck agreed to conduct a study focused on an expanded TruSight Oncology HRD offering.
BMS, Kura Partnerships
Illumina also announced CDx partnerships with two additional cancer drug developers. Illumina and Bristol-Myers Squibb (BMS) expanded a 2018 collaboration as BMS agreed to develop a microsatellite instability (MSI) CDx as well as a diagnostic based on Illumina’s first liquid biopsy assay, TSO 500 ctDNA.
Illumina could have a second cancer blood test in its portfolio: GRAIL, the test developer Illumina plans to acquire for $8 billion later this year— confirmed it expects to introduce Galleri™, a multi-cancer early detection blood test, in the second quarter. By then, GRAIL expects to present initial results from PATHFINDER, a prospective, 6,600-participant multi-site study conducted under an FDA Investigational Device Exemption application to evaluate Galleri in clinical practice.
“By also developing some of these capabilities on blood and ultimately getting IVD claims on blood, that further opens up access,” Aravanis said. “You don’t need to do a biopsy or obtain a sample from a previous surgery. That again makes it more convenient and easier to access the molecular profile of their tumor and find the right therapy for them. [BMS is] excited about adding the MSI, and then also looking at both the previous CDx work that we did with them, and also in MSI, and bringing that not just to tissue samples but to blood samples.”
BMS plans to use both products with its portfolio of cancer therapeutics, anchored by the blockbuster checkpoint inhibitor immunotherapies Opdivo® (nivolumab) and Yervoy® (ipilimumab).
Illumina has also partnered with Kura Oncology to build a CDx claim for HRAS mutations in head and neck squamous cell carcinomas. Illumina agreed to develop and commercialize a CDx test to identify suitable patients with an HRAS mutation for use with one of Kura’s lead drug candidates, tipifarnib.
“[Kura] asked us, could we develop within TSO 500 a capability to detect these HRAS mutations in patients, and then ultimately, with success of their drug during their clinical trials, obtain IVD claims on it?” Aravanis said. “That’s what the partnership is about; it’s to add the capability to detect the HRAS mutations, which their drug is focused on, and then ultimately obtain IVD claims for that.”
deSouza also announced that later this month, Illumina plans to launch an integrated, private cloud-based bioinformatics solution designed to let customers manage, analyze, and explore large volumes of multi-omic data in a secure, scalable, and flexible environment.
The new data platform, Illumina Connected Analytics (ICA), combines technologies and services offered by Illumina through three companies it acquired in recent years, with the goal of building a cloud-based portfolio enabling customers to accelerate analysis and sharing of NGS data at scale.
“This software solution enables population initiatives to analyze, interpret, aggregate, explore and share multiomic data at scale, combining the technology from our Edico, Enancio and BlueBee acquisitions into a single, fully integrated solution,” deSouza said.
Illumina shelled out $100 million in 2018 to acquire Edico Genome, creator of what is now the Illumina DRAGEN Bio-IT Platform. DRAGEN—which stands for Dynamic Read Analysis for GENomics—is designed to provide accurate, ultra-rapid secondary analysis of sequencing data, processing an entire human genome at 30× coverage in about 25 minutes.
In June 2020, Illumina acquired BlueBee for an undisclosed price, adding to its portfolio genomic analysis solutions by the cloud-based, rapidly configurable omics data analysis platform developer. A month later, Illumina bought Enancio, a French developer of genomic compression software. Enancio’s loss-less compression technology is designed to reduce data storage costs by as much as 5x by compressing the output from Illumina’s sequencers from 50 GB to 10 GB.
Aravanis said ICA is intended to help customers as they scramble to manage the torrents of data they generate through sequencing and choose between local or cloud-based storage solutions.
“They need to process that data efficiently in well-controlled and validated pipelines. They need to store the results of that. They need to be able to report the results from those analyses. And then often do more complex analyses data science—for example, looking in a research context for new targets, or new discoveries,” Aravanis explained.
“Some customers have developed all of that capability themselves, but many have not, and it could be a barrier for them to use the technology,” he asserted. “[ICA] is that whole suite of capabilities.”
While ICA can reside on the cloud platforms of tech giants, Aravanis said Illumina’s solution offers advantages not available to customers who rely on Amazon Web Services (AWS), Microsoft Genomics, Google Cloud Life Sciences, or IBM Cloud.
“A common way to implement the ICA would be on top of AWS, for example. But AWS by itself does not have the native functionality to take data from our sequencers, to store it in the cloud. It certainly doesn’t have the DRAGEN capability, which is to do those specific analyses that customers want, to find mutations in a cancer genome, or the genomic data coming from a TruSight 500 assay,” Aravanis said. “It doesn’t have the additional analyses—for example, looking for new variants that were not previously appreciated in cancer. Nor does it have the data compression to reduce the cost of data storage.”
“You need all the software to do the data management, the particular genomic analysis, and the particular genomic data compression. ICA does all that, and then leverages in the background in AWS, but can also reside on Microsoft’s Azure or Google’s Cloud. So they’re very complementary, but distinct,” Aravans added.
ICA will serve as the flagship offering of Illumina’s cloud-based portfolio, which for years has been anchored by BaseSpace™, a website and suite of products designed for biologists and informaticians to easily store, analyze, and share genetic data. A key component of the BaseSpace Informatics Suite is the BaseSpace Sequence Hub, a software solution intended for sequencing run management and data sharing.
“BaseSpace today is still used by many customers for some of these analyses, and some of the capabilities are analogous,” Aravanis said. “Going forward in the future, ICA will be our main product and focus for these. But we’ll be very mindful about how we support customers if they wish to migrate from BaseSpace to ICA.”
Puneet Souda, managing director, life sciences tools at SVB Leerink, wrote in a research note that the new product and service introductions won’t likely elevate Illumina shares beyond their recent trading range: “We believe the shares could continue to remain range bound in a market that is valuing names that address massive TAMs [total addressable markets] and have a leading position in a high growth end-markets such as genomics.”
$100 Genome Update
During the “breakout” session following his formal presentation, deSouza said several technology breakthroughs will enable Illumina to eventually deliver on its long-expressed commitment to drive the cost of sequencing down to a $100 genome.
Illumina’s breakthroughs, he said, include 5x higher cluster density than NovaSeq version 1.5 kits; yielding 5x the data from the same flow cell area. The company has also developed a flow cell manufacturing process using 300-millimeter wafers, doubling its wafer yield. Combined, both innovations are projected to reduce flow cell cost by 90%.
deSouza said Illumina has also made fundamental improvements to its flagship sequencing-by-synthesis (SBS) technology, including new dies and blocking chemistries. The enhancements enable 3x higher accuracy, 2x faster cycle times and 2x longer reads.
“We certainly have now the technologies available and running in our labs,” deSouza said “We’ll think about what is the right form factor to bring it into the market. We haven’t announced that yet, whether it’s in addition to NovaSeq or a new instrument.”
Two years ago, deSouza told J.P. Morgan attendees that Illumina viewed the development of a $100 genome as a multi-year process combining engineering work—which he said was now in progress—with customer demand. deSouza’s predecessor Jay Flatley and Illumina electrified the 2014 J.P., Morgan conference by announcing the $1,000 genome.
deSouza’s presentation also included financial updates for 2020 and 2021:
- 2020 preliminary results: Illumina said it finished last year with about $3.24 billion in revenue, down 9% from 2019, including about $950 million in fourth-quarter revenue, about the same as Q4 2019 and well ahead of Wall Street forecasts for $876 million. The company said it will report fourth quarter and full-year 2019 results in February.
- 2021 guidance: Illumina is projecting 2021 revenues of between $3.79 billion and $3.86 billion, reflecting 17-20% year-over-year revenue growth. At the midpoint of that range, Illumina said, it expects about 20% sequencing growth and about 20% sequencing consumables growth. Illumina furnished a non-GAAP earnings per share (EPS) forecast for 2021 of between $5.10 and $5.35. Citing current Wall Street expectations for 2021 of $3.9 billion in revenue and an EPS of $6.17, “we believe Illumina should be able to post upside to these estimates given the amount of conservatism baked in – barring any setbacks in macro recovery,” SVB Leerink’s Souda observed.