Intervenn Biosciences said it has identified stark differences in the glycoproteomic profile of COVID-19 patients who became very sick and people infected with the SARS-CoV-2 virus who were either asymptomatic or experienced only minimal effects. The contrast could help clinicians better understand the biological mechanisms of the disease and triage patients at risk of responding detrimentally to early treatments and more intensive care.

The South San Francisco-based startup analyzed nearly 100 blood samples of individuals who became seriously ill after contracting COVID-19 and another group of people who tested positive for the virus but were asymptomatic. When they looked at the glycoproteins of these two groups, “they were as different as night and day,” said Klaus Lindpaintner, Intervenn’s chief scientific and medical officer.

Understanding how the body reacts

Klaus Lindpaintner, Intervenn’s chief scientific and medical officer

The company is in the process of running additional controls “to understand better what it means with regard to how the body reacts to COVID if someone gets really sick versus someone who doesn’t get sick, or to what extent the type of protein signatures or biomarkers that we see would identify someone who is prone to getting sick rather than not getting very symptomatic,” Lindpaintner told BioWorld.

The latter could enable doctors to take proactive steps to “deter ahead of time” a worst-case scenario, he added, and to safely send home patients who are at low risk of complications, increasing the availability of intensive care beds during future waves of the pandemic.

Aldo Carrascoso, Intervenn’s CEO

Once more data has been collected, Intervenn plans to provide the information to public health authorities and the scientific community. It also is looking at devising a test that could be used in the clinical setting to guide triage and treatment decisions.

“For us, the next steps are really to partner and to find other collaborators that we may be able to expedite their own clinical trials or their own assay development projects” using proteomic signatures, said Aldo Carrascoso, Intervenn’s CEO.

Empowering mass spec with AI

Intervenn’s technology platform applies artificial intelligence (AI)-powered analytics of mass spectrometry to the emerging field of proteomics and glycomics to push beyond understanding genetics to how the body is functioning based on specific genomic information. With glycoproteomics, scientists attempt to look at human biology on a day-to-day, hour-by-hour, dynamic protein level and at the modifications that are occurring when sugar molecules attach to those proteins, changing how they look and function.

But to glean insights that could reach beyond the research lab, automated analysis was needed.

“What we have done at Intervenn is create an ecosystem … that marries some very, very powerful wet lab technologies based on mass spectrometry, which has this amazing resolution of getting down to the molecular level, but also has the problem with creating so much data that people are just overwhelmed with it and really couldn’t use it,” Lindpaintner explained. “And we marry that to our core competence in [AI], machine learning, neural networks such as we can process things that used to take months in literally minutes.”

The COVID-19 findings expand the set of indications Intervenn’s platform can be used to address.

Over the past year, the company has found strong signatures for several different cancers and is in the process of advancing some of those to a commercial product.

“We believe that there really isn’t anyone out there that can do it and certainly not as well as we can do it and as scalable and high-throughput,” Lindpaintner said. “And if you’re trying to get to patients, you need to not just run one or two patients, but 20, 30, 40 or 50 ... to get some reliable information.”

Focus on cancer

Last fall, Intervenn reported interim results showing its Vocal liquid biopsy test significantly exceeds the state-of-the-art ovarian cancer test CA-125 both in specificity and sensitivity. The test consistently differentiated between malignant and benign tumors using only a blood test.

Despite the challenges caused by the pandemic, the trial is now more than halfway completed, Lindpaintner said. “We expect to have probably a soft endpoint somewhere at the end of this year or early next year and then move forward toward commercialization.”

In March, the company added a colorectal cancer/advanced adenoma diagnostic panel to its proprietary glycoproteomic analysis platform. The company has additional indications in its pipeline, Carrascoso said.

When it comes to oncology, which is Intervenn’s primary focus, the company believes its approach offers advantages over other pan-cancer tests. Rather than having a single signature to recognize multiple cancers, Intervenn has a panel of markers that, when subsegmented into separate subpanels of markers, provides greater sensitivity and specificity to recognize any one individual cancer, such as kidney or prostate cancer, Lindpaintner explained.

“It’s the holy grail, if you will, to have a test that finds as many cancers as possible. We just think that you need to be a bit more sophisticated and a bit more differentiated and not necessarily rely on a single test that can find all cancers,” he said.

Two-pronged business strategy

Intervenn sees opportunities in two main product groups: partnership solutions and clinical solutions.

“There is an overabundance of companies that are looking at genomic-based solutions, and we seem to be the only company offering the glycoproteomic solutions,” Carrascoso said. “There’s a tremendous amount of benefit for other partners to use that.”

Use cases like the COVID-19 findings also offer partnership opportunities, he added, noting the company will announce a third offering for partnerships soon in the area of targets and molecules.

The clinical products are geared toward physicians, and Intervenn plans to take a number of assays into the clinic in the future for a variety of cancers.

Meanwhile, the company also is honing its AI platform to more quickly comb the glycome and identify new biomarkers, which it will assign neural networks to interrogate to provide new insights into disease states.

Given Intervenn’s focus on cancer, the company was unprepared for the striking results in COVID-19.

“It just goes to show how ubiquitously important and impactful glycoproteomics and glycoprotein biomarkers are across the health care universe, Lindpaintner said. “We’ve obviously seen indications beyond oncology … but the fact that such a small pilot study in coronavirus shows us such tremendously positive results – it literally blew me away. And I was a believer to begin with.”

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