Sonnet BioTherapeutics has completed the discovery phase for its cytokine-based immunotherapy platform and begun a tech transfer to CDMO Oncobiologics.

New Jersey-based biopharma firm Sonnet has announced it is planning to move its preclinical candidates towards the clinic, and has begun CMC development for up to four immuno-oncology candidates with a contract development and manufacturing organization (CDMO).

John Cini, co-founder and chief scientific office of Sonnet, told BioProcess Insider the CDMO is fellow New Jersey-based firm Oncobiologics, which will manufacture the candidates at a 200 L scale using single use bioreactors.

“At this stage, Sonnet does not have manufacturing capabilities and believes it would be cost-prohibitive to develop such capability, especially given the availability of high quality CDMO capabilities,” Cini said.

Putting on the Brakes

The delivery of cytokines is believed to be an excellent strategy for stimulating an immune response against tumor tissue, the firm said. Sonnet is looking at the improved delivery of cytokines along with current checkpoint inhibitors, which potentially could enhance response rates and survivability.

In layman’s terms, the immune system includes ‘brakes’ and ‘accelerators,’ Cini explained.

“Cancer cleverly tricks the body into applying the brakes when the immune system tries to attack tumor tissue. Checkpoint inhibitors can turn off these brakes, allowing the immune system to eradicate tumor tissue.

“Once the brakes are turned off, a robust immune response is needed to attack the cancer, and the introduction of increased cytokine levels should help achieve this immune response.”

Albumin Binding Domain

The Sonnet platform contains an Albumin Binding Domain (ABD), which, he continued, seeks out and attaches to albumin in the bloodstream when injected into a patient.

“Albumin naturally gathers around inflamed tissue in the body including tumor tissue, so the Sonnet product ‘hitch-hikes’ on the albumin so that it is delivered efficiently to the tumor. Without this ABD, the product would circulate around the body, with only a small portion arriving at tumor sites.”

The platform also allows the attachment of 1-2 different cytokines (interleukins) or other molecules. “Thus the platform becomes a targeted delivery vehicle for the two different cytokine and/or other molecule as one therapeutic molecule.”

And furthermore, Cini continued, because molecules such as interleukins are very small, they quickly pass through the kidneys and are eliminated from the body.

“As a result, when interleukins are used in traditional settings, they must be delivered repeatedly and in high doses in order to deliver sufficient quantities to tumor tissue. The high dose results in harmful side-effects which require very careful and close monitoring.

“With the Sonnet platform, a smaller amount of interleukin material can be administered, because a much higher percentage of it is delivered to the tumor site. This allows for greater impact of the interleukin while also dramatically reducing the risk of side-effects.”