NEW YORK – Following a successful $3 million seed funding round earlier this month, University of California, San Diego spinout Micronoma is commercializing a blood-based diagnostic assay that identifies a patient's organ microbiome signature to potentially detect early-stage cancers.
The firm anticipates completing construction of a CLIA-certified, CAP-accredited lab within the next 12 to 18 months and later launching a laboratory-developed test (LDT) for early-stage lung cancers, including lung adenocarcinoma, squamous cell lung carcinoma, and small-cell lung carcinomas.
After filing for IP based on a machine-learning data analysis platform at UCSD with the US Patent and Trademark Office in late 2018, UCSD scientists Rob Knight and Gregory Poore launched Micronoma to commercialize the technology with CEO Sandrine Miller-Montgomery, former head of the university's Center for Microbiome Innovation, in June 2019.
Initially publishing a proof-of-concept study on the platform earlier this year in Nature, Miller-Montgomery, Knight, Poore, and their colleagues demonstrated that microbial signatures were not only unique within and between most cancer types, but that they also remained predictive when used on patients with stage Ia to IIC cancer and cancer that did not have any genomic alterations.
In addition, the study authors found that blood-based microbial DNA (mbDNA) could help discriminate between several cancer types, regardless of the algorithm and database used to classify the disease.
Miller-Montgomery explained that the commercial assay's workflow will begin by extracting cell-free DNA (cfDNA) from 250 microliters of plasma from a patient's blood sample. After performing proprietary targeted amplification and library prep steps, the team then sequences the enriched sample.
While the study applied whole-genome shotgun sequencing, Miller-Montgomery noted that her team plans to use targeted sequencing on patient blood samples in the commercial assay to identify microbes because the method minimizes sample waste and is more cost-effective per sample. She explained that the problem with shotgun sequencing is that most of a human blood sample (97 percent) contains human DNA, while the team mainly focuses on the microbial DNA (3 percent). She therefore believes the method is not a financially sensitive approach for a commercialized version of the assay.
Micronoma will then run a proprietary algorithm to discriminate between samples from healthy, cancer-free individuals and patients with one or more types of cancer.
In order to determine whether a patient has a specific cancer type, Micronoma's algorithm detects pieces of nucleic acids — what Miller-Montgomery describes as "features"— from several different species or strains of bacteria or viruses in the patient's bloodstream. The Micronoma algorithm's microbial "feature" profile will be compared to those of specific cancer samples that have been previously been analyzed in Micronoma's data repository, including patient features in the the Nature study.
Miller-Montgomery also noted that the number of features that are important can also vary based on the cancer type.
"We are looking at pieces of nucleic acids that can [can overlap] between certain strains or species," Miller-Montgomery said. "The test is sensitive and specific even in early-stage cancers because we're not looking at just one gene with 10 alterations in the genome, but instead looking at a combination of about 20 to 100 features, which gives us more granularity in the calls we can make."
In the study, the researchers found that in a prospective cohort of 25 lung cancer samples, the platform had a clinical sensitivity of 88 percent and specificity of 93 percent. Miller-Montgomery said Micronoma will use the study's clinical sensitivity and specificity as a baseline for the commercial lung cancer assay's clinical sensitivity and specificity.
Miller-Montgomery highlighted that one of the platform's distinguishing factors is that while the method "uses" liquid biopsy, it places a bigger emphasis on the microbial impact than the patient's or tumor DNA in a blood sample.
"That's not to say that microbes are the only focus, as we're not only producing data only on microbes," Miller-Montgomery said. "But it's an important piece of the puzzle that has been ignored and that many people are missing by only looking at the patient's or tumor's genome."
However, Miller-Montgomery acknowledged that her team will need to perform validation studies to improve the test's clinical sensitivity and specificity. While Micronoma is finalizing its validation study design, the firm expects to collect hundreds of blood and tissue samples to run on the platform.
"We don't know yet if the microbial signal we find in the plasma might be 'leaking out' of the tumor, or if it is caused by the host sending the microbes to protect itself against the tumor," Miller-Montgomery said. "We're only taking a snapshot of the blood, but we know it's linked to a specific cancer."
Miller-Montgomery noted that Micronoma holds the exclusive worldwide rights to develop assays based on the technology the firm is licensing from UCSD. While the platform performed well in discriminating between multiple tumors in the study, the firm is initially targeting early-stage lung cancer detection — including adenocarcinoma, squamous cell carcinoma, and small cell lung carcinomas — because it sees the space as an underserved market.
"There are other wonderful companies like Guardant Health that are looking at later-stage cancer detection, recurrence, and other applications," Miller-Montgomery said. "We went in and wanted to see where we could make a major difference in a very underserved market."
At the same time, Miller-Montgomery acknowledged that Micronoma's platform is "pretty out there" as a potential early-stage diagnostic assay. While the US market is slowly acknowledging liquid biopsy's potential for cancer detection, she noted that trying to convince the market to think about using microbes as a liquid biopsy marker may initially appear strange to customers.
"Therefore, we want to focus on lung cancer, because we want to make everyone comfortable with the method, and we will do that by targeting one cancer at a time," Miller-Montgomery explained. "Because lung cancer is one cancer that is extremely predominant, deadly, and underserved in terms of early-stage detection, we want to target this community to [potentially help] start treatment earlier."
As part of the push for commercialization, Micronoma is using the $3 million from the seed funding round to build a CLIA-certified, CAP-accredited lab in San Diego while simultaneously performing the lung cancer validation study.
As part of the envisioned clinical workflow, oncologists will send a tube of patient's blood to the firm's CLIA-CAP lab, where Miller-Montgomery noted the team will be able to produce diagnostic results using the data analysis platform within a week.
"The longest amount of time needed will be for the algorithm to compute the data analysis," Miller-Montgomery said. "That's one of the reasons we want to apply targeted sequencing, as the method would speed up the overall workflow."
However, Miller-Montgomery said that her team may deal with several challenges as it commercializes the lung cancer test as an early-stage diagnostic. For example, the targeted assay that the firm is currently developing may potentially become more difficult to design and finalize.
"While we don't expect that to happen, the solution would be to brute force it by shotgun sequencing, which is a shame cost-wise, but we know it works," Miller-Montgomery said. "What we have in mind is to use [a method] that drives us to the results, so even if it's not sexy and elegant, it's a path we will take."
In addition, Miller-Montgomery said that Micronoma may encounter potential challenges gathering enough clinical samples to validate the platform, especially with the global COVID-19 pandemic. Aiming to overcome this potential issue, the firm is collaborating with the Moores Cancer Center at UCSD Health and other undisclosed academic partners to increase lung cancer sample collection.
Micronoma is also discussing potential collaborations with undisclosed biotech firms to potentially expansion of their assays beyond the lung cancer space.
"Our goal is to ensure that we can put this new type of detection method in the hands of as many clinicians and their patients as possible in the most timely manner," Miller-Montgomery said in an email. "We are really looking to build some synergies with groups [that] may have better access and expertise in specific cancers or for [that] our technology would be a complement to their current solutions."