The adoption of spatial biology in research labs around the world continues to gain momentum. Among a seemingly endless variety of applications, scientists are defining immunotherapy response mechanisms and the roles of immune cell subpopulations on clinical outcomes with greater precision, and applying the technology to bio banked tissue samples to fuel reverse translational research studies.
The primary aim of these multiplex immunofluorescence studies in oncology is to identify biomarkers that can select patients likely to benefit from advanced immunotherapies. Despite the potential of these therapies, their efficacy is limited to a small subset of patients, exposing others to unnecessary adverse effects. In the case of experimental medicines that are in clinical trials, the inability to properly stratify patient cohorts means that some promising drugs never make it to the finish line.
In a discussion with Pascal Bamford, PhD, Akoya’s Senior Vice President of R&D and Laboratory Operations, we explored the progression of spatial biology from research to clinical application and highlight our collaborations with leading biotech and diagnostics companies. Q: How does Akoya view the continuum from discovery research to clinical application?
PB: Akoya offers a seamless transition from high-plex biomarker discovery on the PhenoCycler®-Fusion, all the way through biomarker validation to a globally deployed clinical in vitro diagnostics (IVD) on the PhenoImager® HT system, while maintaining consistent chemistries and optics. This streamlined workflow supports Akoya’s unique position in facilitating the entire process from the lab bench to the clinical setting.
In discovery and translational phases, you want access to every bit and byte of information. You want to cut the data in a million different ways. You want to look at every single detail, and process a lot of samples, with a lot of data that you then have to crunch and manipulate.
In contrast, the clinical phase emphasizes, operational reliability. We want a room full of instruments that work flawlessly every time, and simply requires a technician to push some buttons. Ultimately the product on the clinical side is a piece of paper – a patient report that says either the tissue sample is positive, and the drug will work or it’s negative and other options need to be considered. It’s a completely different process than the discovery environment.
Q: What makes multiplexed immunofluorescence such a powerful approach for biopharmaceutical companies?
PB: The fundamentals of multiplex immunofluorescence make this approach the right modality when you need to be able to look at multiple targets on the same tissue biopsy and have them co-localized or have them interact with each other. Immunofluorescence is really the only technology that will work to answer clinical questions. This is crucial for applications like antibody drug conjugates, where you want to be able to look at multiple targets on the patient tissue. Many of these are co-localized, which means that the same small area might have multiple biomarkers that need to be assessed simultaneously.
Imagine having a seven-biomarker test like NeraCare’s to predict the risk of melanoma relapse. Preparing, staining, and analyzing seven separate tissue sections from a biopsy isn’t practical in a clinical setting with traditional immunohistochemistry techniques. However, by adapting this test for multiplex immunofluorescence not only conserves valuable biopsy samples, but can be automated, which is crucial for an in vitro diagnostic (IVD). (Read more about NeraCare and our clinical collaborations below).
Q: What does Akoya offer in terms of expertise in the regulatory pathways to take spatial biology-based assays into the clinical setting?
Fundamentally, you must be able to take any patient slide or any patient biopsy and be able to put that into any lab around the world on any day and get exactly the same result. At Akoya, we have a very rigorous, risk-based approach to this, aligning with both FDA guidelines and ISO-13485 standards.
The reliability of the assays extends beyond clinical data, which can be demonstrated in couple of controlled sites with meticulous attention to detail. The goal is to create a system so robust and compatible with existing laboratory infrastructure that the risk of errors or issues is minimized, ensuring that any patient, anywhere in the world, receives the same accurate results. Behind the scenes, there’s a complex system in place. We anticipate all possible ways things could go wrong and then design multiple safeguards to prevent those failures.
There’s hardware, software, and reagent components and the systems are developed under good manufacturing processes (GMP). Each component is thoroughly characterized to ensure it performs as expected. The workflow software is designed to be user-friendly and minimize potential errors, both human and automated.
We ensure that each individual component functions as intended, then verify that groups of these components work correctly together on a modular basis. We then test the entire system by varying key factors, such as who runs the assay, the reagent lots, the instrument used, and the laboratory setting. Throughout these tests, we consistently confirm that the results remain highly concordant.
By adopting the same discipline and rigor to developing IVDs as the major companies in the industry, and leveraging expertise from seasoned professionals, Akoya maintains a reduced-risk approach through development, regulatory approval, and commercialization process of bringing a spatial biology-based assays to the clinical market.
Q: What is the significant benefit of using a multiplexed immunofluorescence companion diagnostic for biopharmaceutical companies?
PB: We refer to these assays as a selection device. They help identify which patients will gain the most benefit from a particular therapy. Traditionally, the industry has conducted clinical studies where all patients receive the drug, but only 5% to 10% respond exceptionally well, forming the basis for drug approval. However, this approach means that 90% of patients are treated with little to no benefit. Clinical trials often fail because of this broad approach.
So that’s the example with Acrivon – a company we consider to be a true pioneer in the industry. Acrivon is advancing a compound initially developed by Eli Lilly that failed to meet primary endpoints in earlier trials because overall survival and response rate of the patients was below the threshold that they needed to be able to drug everyone. So, having a selection device allows for precise identification of the subset of patients who will respond to the therapy (Read more about Acrivon and our clinical collaborations below).
Since drug development pipelines are not limitless, it’s crucial to bring these drugs to market efficiently. That’s where we come in. We are the only company capable of guiding you from high-plex discovery all the way to the clinical assay, helping to ensure that these drugs reach the right patients.
Read more about some of our clinical collaborations.
Acrivon Therapeutics
Acrivon and Akoya are partnering on the ongoing clinical development and future commercial use of the ACR-368 OncoSignature Assay, the first-of-its-kind spatial signature companion diagnostic assay to identify patients for a targeted oncology agent. The test is being used to screen patient to determine clinical treatment in Acrivon’s registrational intent Phase 2 trial of ACR-368 in patients with ovarian or endometrial cancers.
At the company’s recent R&D event, Acrivon shared the following initial ACR-368 clinical data in patients with ovarian or endometrial cancers (n=26; 10 OncoSignature-positive and 16 OncoSignature-negative) in the ongoing registrational-intent Phase 2b trial are being presented (data cut as of April 1, 2024):
At the company’s recent R&D event, Acrivon shared the following initial ACR-368 clinical data in patients with ovarian or endometrial cancers (n=26; 10 OncoSignature-positive and 16 OncoSignature-negative) in the ongoing registrational-intent Phase 2b trial are being presented (data cut as of April 1, 2024):
- A confirmed ORR (per RECIST 1.1) of 50% was observed in the prospective cohort of OncoSignature-positive patients who were efficacy-evaluable. All confirmed responders continue to be on treatment, median duration of response (DoR) has not yet been reached. Notably, endometrial cancer is a new tumor type with significant unmet medical need that was identified and predicted to be sensitive to ACR-368 by AP3 indication screening.
- Initial, prospective validation of the AP3-based ACR-368 OncoSignature assay demonstrated its ability to identify ovarian and endometrial patients sensitive to ACR-368 monotherapy in the ongoing clinical trial, with clear segregation of RECIST responders in the OncoSignature-positive (50% confirmed ORR in 10 patients) versus OncoSignature-negative (0% ORR in 16 patients) arms (p-value=0.0038).
NeraCare
In June 2024, NeraCare published data demonstrating the clinical validation of a prognostic 7-biomarker multiplex Immunoprint® assay for prediction of relapse in patients with early-stage cutaneous melanoma. Currently, adjuvant therapy is only approved for stages IIB-IV resectable cutaneous melanoma (c. 15-20% of patients), however, earlier-stage patients contribute a significant share of overall melanoma mortality but cannot be identified with current staging methods.
Robust clinical performance in identifying early-stage melanoma patients at high risk of relapse and death was demonstrated:
- The biomarker assay identified 98% of relapses and 100% of cutaneous melanoma-related deaths in stage IB/IIA patients
- Patients with stage IB/IIA melanoma identified as high-risk had a relapse rate comparable to later-stage patients for whom adjuvant therapy is already approved
The prognostic assay may be useful in selecting early-stage melanoma patients for adjuvant trials and is currently being transferred to the Akoya Biosciences’ PhenoImager® HT multiplex platform to enable automation and tissue preservation.
KR Gene
Akoya and Shanghai KR Pharmtech, a leading company providing molecular diagnostic solutions in China, have co-developed KR-HT5, a high-throughput platform based on PhenoImager HT technology, to provide clinicians with the ability to perform multiplex biomarker workflows. The platform recently received premarket approval from China’s National Medical Products Administration (NMPA) to support next generation pathology clinical workflows.
Other resources:
- Partner with our Advanced Biopharma Solutions (ABS) team and get expert help developing your assay
- Learn more about clinical applications of spatial proteomics
