Introduction

Oncology has driven adoption of precision medicine, which in turn has resulted in dramatic improvements for patient outcomes in some indications. Nevertheless, prognosis is often still poor for many late-stage cancers (e.g., lung); survival worsen as time to diagnosis increases, and for patients at later disease stage (see Figure 1 below).

Figure 1: Average 5-year Survival Rate by Stage at Diagnosis

Detecting cancer earlier both minimizes mortality and improve quality of life for patients by decreasing the need for later stage treatment regimens that are often highly toxic, taxing to undergo, and can introduce significant side effects. Additionally, it has the potential to bring tangible changes to how cancer is diagnosed, treated, and managed (see Figure 2 below).

Figure 2: How might early detection shift the cancer care paradigm?

Many companies have dedicated time and resources towards creating a blood-based assay (or underlying differentiated technologies) that can diagnose cancer in the earliest stages. Exciting events in recent years hint towards a promising future for early detection, but the field is still nascent.Here we put together a timeline of events for 20 cancer early detection (EDx) companies focused on blood-based approaches*. (*Note: This is not a comprehensive list of all companies working in the early detection space)

Figure 3: Cancer Early Detection – Timeline of Select Key Events

Below are the 3 key takeaways from our observation of the early detection space and discussions with top industry stakeholders:

Takeaway 1
The EDx space is exploding with multiple smaller companies battling alongside the larger, high-profile NGS-focused players

The early detection space is flooded with many key players, both large and small. Large companies like Grail, Guardant, or Exact Sciences (through acquisition of Thrive Earlier Detection and Base Genomics) are some of the biggest names in blood-based cancer early detection and often make headlines. Other start-ups like Freenome and Singlera have attracted significant interest and funding (e.g., ~$500M for Freenome, ~$210M for Singlera). The most groundbreaking announcements and achievements from these players feature large-scale studies (with over tens of thousands of patients), pan-cancer detection tests, versatile machine learning / AI algorithms, and hundreds of millions to billions of dollars in total funding. These firms also display different competitive advantages (e.g., funding & sequencing expertise for GRAIL, testing for the entire patient journey for Guardant, primary care physician channels for Exact, and AI-prowess for Freenome).

Nevertheless, these big names are not the only competitive stakeholders in the space.  A long tail of smaller companies and startups exist, including Delfi Diagnostics, Adela, and Singlera Genomics are emerging with innovative technologies.  The battle is an ongoing arms race to develop the most sensitive assays through the most innovative technologies to detect various analytes whether by analyzing methylation, fragmentation, proteins, circulating tumor cells, among other analytes.  Company roadmaps follow a similar pattern: 1) launch product, 2) demonstrate utility through studies, and 3) secure approval / reimbursement, with a large number of competitors currently in the 2nd phase.  The space is currently crowded with many viable players, but we are looking forward to watching frontrunners gain traction and take the lead.

Our biggest questions are:

1. Which technologies will “win” and which analytes will they detect?
2. Is the best approach a pan-cancer detection assay or a “best-in-class,” indication specific assay?
3. How much will technological superiority (vs. other attributes such as time to market, reimbursement, channels) ensure commercial success?

Takeaway 2
Many EDx companies with promising technologies have headquarters, or key business operations, in China

In this global race to detect cancer earlier, eyes are turning to China. Currently, we have identified 13 early detection companies that have either headquarters or branches in China. This offers a key distinct advantage of access to large patient or study populations, numbers of samples, and databases. Some companies like Predicine and Singlera Genomics have CLIA / CAP certified labs and / or collaborations both in the U.S. and in China to access both Chinese and U.S. markets.

A few unanswered questions that we have for the integration of Chinese early detection assays into U.S. markets are:

1. Will physicians trust the test?
2. If the algorithm is “trained” with an all-Chinese cohort, how will the algorithms backed by machine learning translate to a non-Chinese population?
3. To be approved and reimbursed in the U.S., does the test need to be “trained” on a U.S. cohort?

We recently published a Forbes article that highlighted the importance of a cohort’s population diversity in order to optimize precision medicine technologies. In the context of EDx, training an assay on an all-Chinese population may increase the risk of missing critical mutations and signatures prevalent in other ethnic groups.  Nevertheless, despite hesitations surrounding a Chinese-based entrant into the U.S. early detection market, the powerhouses that back prominent Chinese competitors are undeniable.

Takeaway 3
Although significant financial and human resources are pouring into the space (>$3B in the past ~5 years), the field is still in early stages of development and has yet to reach its full potential

Mirroring excitement in the field, money and resources continue to pour into the space (see the “financial activity” row on the timeline above).  However, despite significant capital and activity, the space is still in its early days and pre-dates exciting, milestone achievements that inevitably will occur in the near- and mid-term.  In the near-term, many companies will continue with large scale studies to build and bulk large databases of samples to develop, validate, and enhance algorithms.  In the mid- to long-term, large prospective trials will be necessary to demonstrate the clinical utility of these assays, and therefore secure reimbursement. Betting on earlier detection, especially for pan-cancer approaches, is a long-term play but one that may yield significant ROI, with a potential total addressable market north of $100B worldwide.

Conclusion

A future-thinking belief in the possibility of earlier detection of cancer is grounded in promising, emerging technologies and in the continued investment of companies towards bolstering large databases that support machine learning.  A world where early detection blood-testing is part of routine lab work is increasingly taking shape, as seen with the recent launch of GRAIL’s Galleri test in June 2021.

In oncology diagnostics, time to market matters, as demonstrated by many tests / products. It is a landgrab; the first players tend to get entrenched unless alternatives with significant improvements (across multiple potential dimensions, including performance) reach the market with a clearly improved value proposition. We look forward to many exciting achievements that are sure to come, and for a world where these tests are routinely conducted. Early cancer detection is a key part of how we will win the war on cancer.

Disclaimer: Companies listed above may be DeciBio clients and/or customers

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