San Diego Business Journal

Dr. Jiwu Wang was thinking ahead when he purchased a plot of land in Fallbrook to raise llamas about 12 years ago.

The founder and CEO of Allele Biotechnology and Pharmaceuticals Inc. has worked with nanoantibodies created in llamas for over a decade and when Wang saw how the coronavirus was ravaging China in February, he figured “this is not going to come and go.”

Antigens from Llamas

So his team got to work looking for a solution using Allele’s core technology and SARS-CoV-2 viral antigens from llamas.

It is this kind of forward thinking that drives Allele Biotechnology to use nanoantibodies, or nanobodies, created in llamas in its search for therapies and treatments that aim to lessen the impact of COVID-19.

The University of California, San Francisco published research early in August that showed how nanoantibodies effectively blocked SARS-CoV-2 infection in a lab setting.

Researchers identified and isolated a library of nanoantibodies found in llamas that would bind to the protein spikes of the virus and neutralize it from infecting other cells.

While the UCSF research has not been peer-reviewed yet and the proposed antibody treatments still need to make it through animal testing and clinical trials, it points to another opportunity for innovation in the battle against COVID-19.

When UCSF released its preliminary research about llama nanoantibodies, Wang said he was “happy because his team had been hearing him babbling about it for months.”

Pack of Small Wolves

Wang, who has a Ph.D in molecular biology, used an animal metaphor to explain how nano antibodies block viruses from infecting cells. He likened the nanobodies to a pack of small wolves fighting one big lion, the SARS-CoV-2 infection.

“Imagine a wolf pack fighting a lion,” Wang said. “They [nano antibodies] are much smaller, but if they are fighting from all angles, they win. They can attack the virus from all angles and essentially seal it off.”

According to Wang, llama nanobodies are about one-tenth the size of antibodies found in humans. The UCSF preliminary research also revealed the lab-made nanobodies are cheap to replicate and stable enough to be converted to a dry powder to be aerosolized for a spray.

Allele is in pre-clinical trial stages, which includes collecting data from animal testing to study the effectiveness of a prophylactic, or protective, treatment for COVID-19.

If the treatment proves to be safe and effective, the goal is to make a prophylactic spray that could be produced cheaply and be administered at home as a nasal spray or inhaler before going to high risk areas, events or even school, Wang said.

Treatment More Transient

While many companies race to produce a vaccine -- which is supposed to build a long-term immune defense -- Wang said “this treatment would be more transient,” and administered more frequently.

Allele is not the only San Diego biotech company working on an antibody-based prophylactic nasal spray.

Diomics Corp. and Active Motif partnered to develop a prophylactic spray using human monoclonal antibodies derived from convalescent COVID-19 plasma, or blood taken from people who have recovered from the coronavirus.

According to Active Motif CEO, Ted DeFrank -- whose company is developing the antibodies for Diomics -- one advantage of using recombinant human COVID-19 cloned antibodies is that it can be produced on a large scale under cGMP conditions.

“There are many recombinant antibodies that have already been approved by the FDA for years, many in the field of cancer treatments,” DeFrank said.

Diomics CEO, Anthony Zolezzi, explained that nasal aerosol sprays are a popular method of drug delivery for the treatment of respiratory ailments and allergies.

The company’s prophylactic spray, Dioguard, is currently undergoing in vitro testing and Zolezzi hopes it will be “one part of a complete solution that will involve product innovations from a myriad of companies.”

No Single Silver Bullet

“Our perspective is that there is no single silver bullet that will, in a single stroke, wipe out this pandemic or the next,” Zolezzi wrote.

On a similar note, Wang said that while Allele might not be the front runner in developing an immunization treatment, because they are a small biotech, they will be there to fill the gaps in innovating a solution.

“We don’t want to be repeating what other companies are doing,” Wang said. “We wish everybody the best of luck, because it is not a competition in our minds.”

On Sept. 15, Allele announced that it made it to the semifinalist round of XPRIZE COVID Rapid Testing Competition with its llama antibodies and cell phone assay, to help people quickly and cost-effectively detect the virus.