BACKGROUND

The range of technologies that enable multiplex tissue analysis (MTA) and digital pathology (DigPath) are rapidly growing and entering the clinical research space, providing new means of characterizing the tumor micro-environment and driving the field of spatial-omics forward. In the following analysis, we aim to take the ‘pulse’ of how MTA and DigPath are emerging as clinical tests and companion diagnostics (CDx) by analyzing conference abstracts presented at the ASCO 2021 annual meeting.

We analyzed the ~4,500 abstracts presented at this year’s ASCO congress to identify the subset that mention keywords relevant to MTA and / or DigPath (e.g. mIHC, spatial-transcriptomics, automated image analysis, digital pathology) for further review. In total, ~58 abstracts were relevant for this study, the analysis of which is summarized below.

AUTHORSHIP & MOST ACTIVE PLAYERS

Table 1. MTA and DigPath related abstracts authored by industry stakeholders who appear in >1 relevant publication at the ASCO 2021 annual meeting; this represents 17/58 total MTA-DigPath abstracts identified this year.

Pharma is not yet driving much research – Pharma companies were authors in only ~15% of the MTA/DigPath abstracts presented this year, and even among these studies, research was generally translational / retrospective, rather than prospective for patient stratification in trials. ~60% of studies were fully academic-led, but we can expect greater biopharma presence in these publications as CDx utility becomes more established.

Table 1 outlines all abstracts with >1 commercial author (diagnostic or biopharma). AstraZeneca and Roche/Genentech were the only biopharma companies that authored multiple relevant abstracts this year. Notably, both companies co-published with PathAI, and in additional abstracts, both explored H&E signatures that may help predict checkpoint-inhibitor (CPI) response. The widespread global access to H&E is expected to be attractive to many biopharma developers as the first generation of spatial-omic, image-analysis based CDx tests.

DigPath authors were notably present; specific MTA technology mentions were not – While several ML/AI based DigPath companies had multiple publications this year (notably Lunit, PathAI, and 4D Path), most of the top MTA platform / kit developers were not authors at this year’s congress (e.g. 10X, Ultivue, Akoya, Roche Dx). Additionally, ~60% of abstracts mentioned mIHC/mIF as the supporting technology (Figure 1), but only a small fraction actually named the associated technologies, even though the aforementioned MTA developers are still likely closely involved with this research. During future congresses, there is a key opportunity for MTA and DigPath developers to raise their visibility by both publishing and having their technologies named in clinical conference abstracts, especially those co-authored by biopharma companies.

TECHNOLOGY AND PLEX

Figure 1. ASCO2021 MTA/DigPath abstract distribution by referenced technology.

Figure 2. – ASCO2021 MTA/DigPath abstract count by plex-level / panel size.

mIHC/mIF most studied; spatial-RNA is notably absent  – Among technologies mentioned in MTA/DigPath abstracts, multiplex-antibody based methods are by far the most common at ~60% of mentions (Figure 1). Conversely, spatial RNA mentions such as DSP are only included in ~3 abstracts (~5%), which given the significant excitement that has surrounded platforms like the NanoString GeoMx or 10X Visium over the past year was lower than one might expect. However, even though spatial-proteomics were on display this year, spatial-transcriptomics are much newer technologies with less clinical maturity, so we certainly expect a boost in RNA-based clinical data as soon as next year.

Despite access to high-plex tools, clinical research plex remains low – Among IHC/IF technologies (mono and multiplex), the average plex level explored in abstracts this year was 4-5 (Figure 2), and only two studies had panels >10 plex.

We generally believe 4-5 plex mIHC/mIF tests will enter clinical use after H&E and monoplex automated scoring assays (i.e. automated PD-L1). Our ongoing hypothesis is that early clinical MTA research will use high plex technologies at first then deplex for the clinic. Given that routine clinical mIHC/mIF signatures are still likely >3 years away, we expect to start seeing more trial-linked, high plex studies soon that will lay the groundwork to identify clinically actionable subsets of <5 markers.

ANALYZED CELL TYPES AND MTA / DIGPATH PURPOSE

Figure 3. ASCO2021 MTA/DigPath abstract distribution by primary cell types analyzed in the studies.

Figure 4. ASCO2021 MTA/DigPath abstract distribution by application being pursued with spatial-omics technologies in each study.

Immune cells are central to MTA and DigPath analysis –~85% of abstracts include immune cells, either directly measured via immune-specific antibodies (i.e. CD8, CD3, FOXP3) or through morphological assessment of H&E images. This immune-centric analysis is reinforced by the fact that >55% of studies discussed the use of MTA/DigPath for immuno-oncology (I/O) therapies.

The small subset (~15%) of studies that did not directly involve immune cells focused on applications like automated HER2 scoring, tumor grading, and pathological response monitoring due to tumor shrinkage. When it comes to novel CDx applications involving H&E or antibody-based technologies, holistic views of the TME that capture tumor + immune cells are expected to yield the most data, and signatures that interrogate both are likely to be preferred across technologies.

This space is not just exploratory; CDx utility and automated scoring are well under development – Evaluating the purpose for which novel / emerging technologies are used in publications is a key measure of overall tech maturity; tests / techs that are only used for exploratory purposes may need further refinement before they are ready to serve as diagnostic tools. According to ASCO abstracts this year, only ~20% of studies included MTA/DigPath for exploratory purposes (Figure 4), while ~40% pursued predictive/prognostic applications. Monitoring applications contributed another ~20%.

The fact that the majority of studies are already exploring MTA and DigPath for clinical applications is a strong signal of their demonstrated utility and hints that we could see prospective studies enrolling patients with these tools in 1-3 years.

CONCLUSION

MTA and DigPath technologies are not only highly present in the I/O clinical research space today, they are well on their way to emerging as clinically enabling companion diagnostics. There are still many hurdles that must be overcome for the clinical potential of these tools to be fully realized, chief among them is global scalability, reimbursable deployment of an algorithm-based diagnostic, and the refinement of clinically actionable signatures. MTA and DigPath are poised to grow together, starting with widely available H&E and monoplex staining supported by automated scoring algorithms. However, the infrastructure for multiplex technologies (especially mIF) is rapidly growing, and when coupled with AI/ML, 4-5 plex signatures could be revolutionary to guiding I/O treatments and expanding our knowledge of other immune implicated diseases

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