High Notes: Octave Biosciences’ Protein Panel Predicts MS Trajectory

As employee number one at Octave Biosciences, Farhan Qureshi has spent the last six years deriving clinical insights from multi-modal data to develop diagnostic laboratory tests for multiple sclerosis (MS) disease activity. 

“MS is a very complex heterogeneous disease—it’s chronic, lifelong, and heterogeneous between patients,” Qureshi, now senior vice president of biomarker R&D at Octave, told Inside Precision Medicine. “We know there are multiple cell types, pathways, and mechanisms that are important in an MS patient’s activity, progression, and severity of the disease.”

Instead of just looking at one marker like neurofilament light chain (NfL), Qureshi used proteomic analysis on patient serum to better understand what would happen with MS patients at any point in their case. Although serum NfL (sNfL) levels have been linked to neurodegeneration in MS and symptoms of the disease, this correlation is not very strong because it is not very sensitive or specific and, therefore, not a particularly good metric for making clinical decisions.

Qureshi’s team used data from two well-known MS clinical trials, EPIC from the University of California, San Francisco (UCSF) and CLIMB from Brigham and Women’s Hospital, to look for biomarkers linked to new disease activity in over 1,400 proteins found in 630 samples from three different groups of MS patients.

Octave’s research showed that the MS disease activity (MSDA) test, which is a custom proteomics panel of twenty sensitive biomarkers, can predict several important clinical and radiographic signs of disease activity in MS. Notably, their panel has exceptional predictive power without considering sNfL levels. Their work on the MSDA, the first and only clinically validated multivariate blood test that measures MS disease activity, was published in Nature Communications.

“The manuscript describes the process of a complex heterogeneous disease like MS or Parkinson’s disease and the utilization of proteomics to make sure you’re capturing that heterogeneity, giving you a dynamic measurement,” said Qureshi.

For the foreseeable future, Octave will run the MSDA test in its lab. Qureshi said that the test requires a relatively complex methodology and that Octave has spent much time on automation and other techniques to ensure high-quality results. In the future, there’s always the option that Octave might have more of a kit-based approach where a kit could be applied, but that’s further down on the roadmap. 

Goodbye guess and check treatment

While he’s only been at Octave for a bit over half a year, Octave CEO Doug Biehn has become well-versed in the data and pain points for MS patients. According to Biehn, MS is the most common neurodegenerative disease among young adults between 20 and 40—patients who are “in their prime.” However, the current standard of care is fairly antiquated in that there are no precision measurement tools to guide treatment.

“A lot of the treatment is trial and error, very qualitative—it’s like, try this drug, maybe it’ll work, come back to me in a year,” said Biehn. “The problem is, if you have an event or a relapse, it’s disabling. You lose your vision and mobility, and you can’t work. To simplify things, clinicians working with MS patients have about 25 different disease-modifying therapies to choose from. Octave designed the MSDA to empower clinicians with actionable data.” 

One major beneficial quality of the MSDA is that it doesn’t only have to be used at the onset of MS so patients can get started on the right treatment right away. The MSDA also provides information to empower a physician to switch a drug to extend the frequency of the drug, oftentimes even to discontinue the drug when the drug is causing more harm to the patient than good to the MS disease at that given time.

“What’s unique about this data is that it empowers the patient to have more confidence and peace of mind that they’re taking the right treatment course to improve their quality of life,” said Biehn. “It’s a win-win for the patient, provider, and payer because you could eliminate lots of drug waste, improve utilization, and hopefully reduce the downstream health care resource utilization that’s not necessary.” 

The MSDA is just one of several pillars of Octave’s Precision Care Solution. Octave has also developed an AI tool for analyzing MRI imaging for radiographic detection of lesions and a virtual care management tool that tracks and connects patients with MS-certified nurse care partners in real-time. Ten of the top 20 MS Centers of Excellence in the nation are already using Octave’s Precision Care Solution to guide treatment for their MS patients proactively and to really empower a more shared decision-making dynamic between the doctor and the patient to ensure they are on the right track at the right time.

Blood, skin, and tears

Biehn is fascinated by the potential for diagnostic techniques beyond multiple sclerosis. He sees the proteomic approach as applicable to neurodegenerative diseases. 

“The neurodegenerative space is compared to the cancer space 20 years ago—cancer has tons of genetics and diagnostic tools for prevention, early detection, and screening,” said Biehn. “But if you look at the neurodegenerative space, it’s vast and white. Our vision is to become the precision measurement platform for the neurodegenerative space.

Octave is applying its knowledge of developing the MSDA to other indications in neurodegenerative diseases. In November of last year, the Michael J. Fox Foundation for Parkinson’s Research (MJFF) awarded Octave a $10 million grant to work toward discovering, developing, and validating a new biomarker panel to measure Parkinson’s disease activity. 

“Investors really want to see what we’ve done in MS for Parkinson’s,” said Biehn. “It validates our vision around being a neurodegenerative precision medicine platform versus just MS, and so it’s absolutely where we’re going, and we’re well underway on Parkinson’s R&D.” 

Qureshi said that Octave is only in the early stages of developing a diagnostic for Parkinson’s disease. While the concept can be applied across indications, the clinical endpoints and data differ significantly across neurodegenerative diseases. Since Qureshi began working on the MSDA six years ago, proteomics technologies have advanced to enable the testing of many more analytes. 

“In Parkinson’s, we’re planning to measure up to 5,000 proteins and then iteratively whittle that down to the most meaningful selections for a custom assay panel that we intend to translate to the clinic and support pharma trials with,” said Qureshi. “It’s a great way to bridge the work that we’ve proven and that we’ve done in MS and that process is now being applied to Parkinson’s and hopefully other neurodegenerative diseases in the future as well.”

This approach will differ from many Parkinson’s diagnostics focusing solely on α-synuclein, a crowded space with all sorts of approaches, including using skin biopsies or even tear drops as samples.