Introduction: The Urgency of Multivariate Companion Markers in Precision Medicine
In the pursuit of personalized medicine, multivariate companion markers (MCMs) represent a critical frontier. MCMs can harness complex proteomic data to accurately distinguish patient subgroups, paving the way for highly targeted treatments that could transform personalized medicine and improve therapeutic outcomes.
However, the path to clinical adoption is fraught with challenges—ranging from regulatory complexities, technological hurdles, acceptance by stakeholders, to commercialization barriers.
Recognizing the need for cross-disciplinary insights, we convened an exclusive dinner with leaders in proteomics, clinical practice, biotech, biopharma, venture capital, and regulatory affairs. Our goal: to examine the current state of the field, envision success, and identify steps to accelerate MCMs’ journey to the clinic.
Held at Boston’s iconic Sonsie Wine Room, the dinner fostered a dynamic exchange around the “What,” “So What,” and “Now What” of MCMs, setting the foundation for a roadmap to clinical impact. This blog post aims to capture the evening’s key discussions.
And first - icebreakers!
The evening started with a lighthearted icebreaker, asking each guest to share two things: their childhood nickname and first paid job. From running research at a zoo, to wedding photography, and selling ice cream, these reflections on humble beginnings highlighted the journey to becoming Key Opinion Leaders. This shared moment created a relaxed and open atmosphere, laying the groundwork for dynamic and candid conversations.
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From left to right: Harris Bell-Temin, Jen Burgess, Pamela Groen, Paula Burton, Undisclosed Attendee, Andrew Webb, Undisclosed Attendee, Hanno Steen and Daniel Franke. Absent from photo: Iris Grossman
“What” – Current Landscape of MCM: Identifying the Barriers
Fragmented Pathways to Clinical Adoption
The discussion opened with insights into the fragmented nature of MCM applications in clinical settings. It was agreed that while mass spectrometry (MS)-based proteomics offers unmatched measurement precision, the field could accelerate with improvements in sample preparation, standardized protocols, and data interpretation.
With regulation in mind, it was noted that a primary hurdle lies in achieving "proof of compliance" required for securing CPT coding and reimbursement. A guest explained that in the U.S., to be adopted into the market, Centers for Medicare & Medicaid Services (CMS) approval for reimbursement is key to broad adoption, yet the lack of clear frameworks stalls MCM adoption. However, upstream barriers were also suggested, such as the validation processes in proteomics, as well as the unique challenges —such as isoform variability— demanded robust evidence of clinical utility before clinicians and payers will fully support MCMs.
Standardization and Industrialization: A Call for Transparent Protocols
Lack of standardization emerged as a prominent theme, with guests emphasizing the need for transparent and reproducible sample preparation methods. While some academic labs keep their preparation protocols proprietary, others like Dana-Farber’s core lab, have published their protocols to promote reproducibility.
One guest highlighted the importance of unifying MCMs’ protocols outputs to make proteomics data accessible to clinicians,suggesting a “Turbotax for labs”—to streamline data management and make MCM outputs more comprehensible to non-specialists.
Establishing Clinical Value: The “Numbers Game”
Another critical challenge discussed was the necessity of demonstrating MCMs’ clinical value. For MCM to gain traction, it must provide streamlined solutions to a relevant clinical question current technologies (used in routine diagnostics) cannot address. The consensus: evidence of cost-effectiveness and improved outcomes is crucial for MCMs’ place in clinical settings.
“So What” – Defining Success: What Could MCMs Bring to Medicine?
A Vision for Patient-Centric Precision Medicine
Envisioning success, guests saw a future where MCMs enable personalized, data-driven therapies that elevate patient outcomes. If current barriers are overcome, MCMs could transform diagnostics, making early detection and treatment personalization more effective and accessible. As one guest framed it, this is the "holy grail" of diagnostics, empowering MCMs to support diagnosis, monitoring, and therapeutic decisions across disease areas.
Another guest added that MCMs could surpass the “black-and-white” diagnostic approaches of genomics by offering proteomic “phenotypic fingerprints,” that enable clinicians to stratify patients based on unique biological profiles, thereby tailoring treatments more precisely.
Simplifying and Securing Data for Clinical Use
Simplifying MCMs’ data for clinical accessibility. As one guest suggested, the goal should be to distill proteomic data into “signatures” that clearly indicate patient response profiles. Security and privacy were also highlighted, especially as MCMs’ data becomes integrated with patient histories. Proteomics data, while not inherently linked to PHI, would require robust frameworks as it enters clinical workflows.
In summary, success for MCMs could mean creating a simplified, standardized diagnostic tool that seamlessly integrates into clinical workflows, enhances therapeutic precision, and maintains data integrity.
“Now What” – Action Steps: Building a Pathway Forward for MCMs
Engaging Early Advocates to Drive Familiarity and Acceptance
As the discussion moved to action, several guests emphasized the importance of engaging clinicians as advocates for MCMs’ technology. Familiarity with MCM’s technology and data will be key to adoption, and building relationships with clinicians can facilitate smoother integration into clinical practice.
Leveraging Commercial Investment for Standardization
From a commercialization standpoint, the consensus was clear: standardized MCM assays are essential for market success, and commercial backing could help make this a reality. One guest noted investment would be more forthcoming if MCMs could be standardized and monetized effectively, suggesting that partnerships between industry and proteomics experts could fuel the development of robust, repeatable MCM assays.
Navigating Regulatory Pathways
On the regulatory side, a guest noted that clear pathways already exist; the challenge being to ensure that the pathways are known to the relevant parties, accessible and adhered to. For MCM developers, this means embracing prescribed protocols early to facilitate the journey through regulatory channels.
Reflections and Future Perspectives
As the evening concluded, guests reflected on the future of MCMs in clinical practice. Using the prompt “As a ___, what I wish for is ___”, many expressed hopes of seeing proteomics integrated into clinical workflows within the next five years. A common shared theme was the need for collaborative forums where diverse perspectives can converge to address MCMs’ unique challenges. Several guests wished for greater diagnostic funding and more capital to unlock MCMs’ potential impact on healthcare.
Next Steps: Planning the Next Roundtable
Looking ahead, guests agreed that ongoing dialogue (like this blog post) is essential for advancing MCMs. The next roundtable should involve additional expertise to address specific topics identified as critical during the dinner. These include:
- Intellectual Property (IP) Experts: To discuss protections and IP strategies for proprietary MCM assays.
- Small Biotech Representatives: To provide valuable perspectives on early-stage innovation and commercialization strategies.
- KOLs in Commercials and Pricing: To explore the cost of goods (COGs) and pricing strategies essential to make MCMs a viable product in clinical practice.
- Regulatory Success Stories: To discuss what tools and services are currently available in the market such as Business of Science and to learn from companies that have successfully navigated regulatory pathways with simplified assays, such as Somalogic and others, and to provide practical insights into overcoming approval barriers.
Future sessions will also focus on the semantic nuances within the field, ensuring consistent terminology around “mass spectrometry” and “proteomics” that aligns with stakeholders across disciplines. Such clarity, along with the broader actions outlined, is crucial to translate the insights from these roundtables into meaningful, real-world progress.
Conclusion
The evening underscored the transformative potential of MCMs and the collaborative commitment required to bring this vision to life. All participants affirmed that MCMs offer unparalleled insights into patient biology, yet the journey to clinical impact demands standardization, simplification, and secure, accessible data frameworks. Bringing these advanced diagnostics to patients will require clear regulatory pathways, strategic commercial investments, and sustained clinical advocacy. With momentum and collaboration across sectors, MCMs could soon stand as a cornerstone of personalized medicine, bridging the gap between sophisticated measurement and real-world impact.
We extend our sincere thanks to each guest for dedicating two hours to this pivotal conversation. Their perspectives enriched our collective understanding of the complex challenges and opportunities surrounding MCMs, reinforcing the power of cross-disciplinary collaboration.
Conversations like these, integrating regulatory, technological, commercial, and clinical insights, are critical for advancing MCMs toward clinical use. We look forward to continuing this dialogue and translating these ideas into actionable steps that bring the transformative potential of MCMs closer to patients. If you’re interested in contributing to future discussions or becoming involved in this effort, please reach out—we welcome new perspectives in this important journey.
This blog post was produced using a combination of original notes from discussions and insights. Final compilation was completed with assistance from ChatGPT. Any errors or omissions are unintentional, and the content is provided for informational purposes only.
