May 24, 2021

Eddie Sullivan was talking about COVID-19 variants back when few others were.

The CEO of Sioux Falls-based SAB Biotherapeutics said then and will get to show now that the company’s unique treatment for COVID-19 could be effective against not just the first strain of the novel coronavirus but subsequent ones.

“SAB’s technology is designed to deliver an immune response that is the natural way our bodies fight disease, and that is a polyclonal response,” Sullivan said.

“We have also designed (the therapeutic) SAB-185 specifically to deliver highly neutralizing and highly potent antibodies the natural way that our bodies fight disease. That way, these antibodies are helping the patient activate the rest of their immune system.”

Late last month, the company dosed the first patients in its phase two clinical trial. While a phase one trial is designed to prove a treatment is safe, a phase two trial is meant to show it is effective.

SAB already has completed phase one trials in healthy volunteers and in COVID-19 patients, including some at Sanford Health.

In phase two, there will a high and a low dose level tested in 110 patients each, as well as 110 patients who receive a placebo.

“This therapeutic is meant for patients that have risk of developing severe disease, and we know that COVID is a very difficult disease because it is affecting different people different ways,” Sullivan said.

“You don’t want to think about this in terms of a therapeutic that is going to save someone, necessarily, when they’ve gone into the ICU. What we’re trying to find out in this trial is are we preventing people from advancing into severe disease.”

SAB-185 was developed using the company’s genetically modified cows, which adaptively produce fully human polyclonal antibodies.

It’s part of the proprietary DiversitAb Rapid Response Antibody Program in collaboration with the U.S. government. The therapeutic was developed from a subunit of the Wuhan strain but has shown it neutralizes the Munich, Washington and other variant strains in preclinical studies.

“We are testing SAB-185 to the variants,” Sullivan said. “We have data that was put into bioRxiv on a study we did with Washington University showing SAB-185 is very effective to a lot of the variants we are seeing … and on top of that, our technology is also designed for being able to add activity to the product, and that’s something we’re working on as well.”

The current clinical trial is structured in a particularly unique way.

SAB is part of the ACTIV-2 master protocol from the National Institutes of Health. The Sioux Falls company is one of five with therapeutics being tested and the only one using polyclonal antibodies. The others use monoclonal antibodies or small molecule antivirals.

“SAB’s technology is unique among all of those,” Sullivan said.

The master protocol will allow all five participants to share the same group of patients receiving a placebo, helping accelerate the process. SAB’s therapeutic will be administered intravenously in patients with mild or moderate COVID-19 who are at risk for disease progression.

Multiple primary endpoints will be assessed, including the duration of COVID-19 symptoms and the quantification of viral load on multiple time points through day 28.

While the master protocol will be offered at more than 100 sites, it’s hard to say how long the trial will last, Sullivan said.

“When a patient comes in, they have to fit the criteria of the study, and they are randomized among the products being evaluated,” he said.

“So we have to be patient and wait for a patient to come in who is identified and consented to participate and randomized among the products being evaluated.”

Scaling up

SAB is positioning itself to meet potential demand for the COVID-19 therapeutic and beyond.

“Our scale-up process is pretty straightforward,” Sullivan said. “When we need more plasma, we put more animals on it, and we have scaled up our production herd significantly. There was a time we had 20 or 30, and now we have more than 200 animals and are continuing to produce more.”

From its Sioux Falls headquarters, the company has grown to more than 125 employees.

It added an office and warehouse in northeast Sioux Falls that’s within walking distance of Sanford Research, where part of the team continues to work.

“It has been quite a ride of rapid expansion of the company,” Sullivan said. “We have fantastic people. There’s always growing pains and finding space and increasing capacity, but it has been just marvelous, quite frankly, not only the quality and caliber of people but the way we have been able to continue to develop the organization and keep everybody pulling toward a common goal.”

Developing SAB-185 has been only part of the workload in the past year. SAB is working through clinical trials of a therapeutic for influenza and is building its capacity to be looking at other potential targets for its polyclonal antibodies. That could include everything from other infectious diseases to cancers and autoimmune disorders.

“For the first time, we can develop oncology immunotherapies that are polyclonal,” Sullivan said. “So SAB is really keen on looking at the full spectrum.”

The experience developing a therapeutic for COVID-19 will have long-term effects on the company, he added.

“I think it’s absolutely something that will help us in the future – relationships with the U.S. government, with the universities we’ve worked with, certainly those that are managing clinical trials. We’re very much focused on the idea that we are gaining as a company significant capacity and capabilities because of our response to COVID that will carry all our programs going forward.”