Biologic drugs are well established treatments for a wide range of disorders, and many of these medicines have become blockbuster products. But currently available biologics still have limitations, says Avak Kahvejian, CEO co-founder of startup Abiologics. These large molecules are made for injectable, not oral dosing. Those injections are frequent. Furthermore, biologics come with the risk of dangerous immune responses.
Cambridge, Massachusetts-based Abiologics is working to improve on biologic drugs by starting with the way they are designed. The Flagship Pioneering-founded startup emerged from stealth Tuesday with details about its science and its ambitions for developing novel medicines for use in immunology and oncology.
The biologic drugs on the market today are made from the 20 standard amino acids found in nature. Abiologics works with a different set of building blocks called non-standard amino acids. The company, which has been incubating within Flagship for the past three years, has developed a technology platform that has a digital component and an automated wet lab. Using artificial intelligence, the company learns the rules of a protein’s structure and the ways to bind to a protein. Computers then apply those rules to non-standard amino acids to design new proteins. Abiologics calls its synthetic proteins Synteins.
“It’s been very difficult to do that, to incorporate non-natural or artificial building blocks because these building blocks are not compatible with our systems,” Kahvejian said. “It’s been difficult until the advent of computational chemistry. What we’re doing is designing synthetic proteins with these non-canonical building blocks.”
Abiologic designs its Synteins with desirable pharmacological properties, such as the ability to bind to a particular target while also evading the body’s immune system. These drugs also offer greater stability, enabling them to persist in the body for a longer period of time. Those properties could be helpful in cancer, offering the potential for a Syntein drug to reside in the tumor longer, which could bring these treatments to the solid tumors that have eluded biologic drugs and cell therapies so far.
Another example of a potential application of Synteins is metabolic disease. Kahvejian points to GLP-1 drugs, which are administered as injections. An oral GLP-1 drug developed with natural amino acids would last only minutes in the gastrointestinal tract. By contrast, a Syntein GLP-1 drug could persist, available to offer its effect in the gut, he said.
GLP-1 may or may not be one of the targets Abiologics is pursuing. The startup is not disclosing specific disease targets for now. But within immunology and oncology, Kahvejian said Abiologics is exploring a range of targets. In some cases, a Syntein go after well-established targets but with advantages over currently available biologic medicines. In other cases, the Abiologics technology could readily design a Syntein to reach an elusive target.
Abiologics has successfully tested its Synteins in animal models. Kahvejian said the startup is revealing itself now to advance an internal drug pipeline and also look for biopharmaceutical industry partners that could leverage the technology platform for their own research interests. Abiologics is backed by the customary $50 million in financing that Flagship provides its startups at launch. Now that the company is out of stealth, it can work toward securing additional investment as well, Kahvejian said.
There are other companies applying AI to biologic drug design, including another Flagship startup, Generate Biomedicines. But Kahvejian said Generate and its AI technology were trained on the amino acid building blocks found in nature. He contends that what sets Abiologics apart is its creation of new tools and technologies that work with non-standard amino acids. Non-standard amino acids are the basis of protein drugs from GRO Biosciences, a Cambridge-based startup based on research from Harvard. GRObio’s lead program is proceeding toward clinical testing as a treatment for refractory gout.
The idea and the technology behind Abiologics was developed entirely within Flagship, Kahvejian said. Brad Pentelute, an MIT professor of chemistry, is an academic co-founder of the startup. Kahvejian said Pentelute partnered with Flagship to develop the Abiologics platform, bringing his expertise designing protein drugs that go beyond the standard 20 amino acids. Similar to drug discovery efforts at other companies, Abiologics picks a target, and then sees how and where to engage that target. Using its technology, the startup designs a Syntein to hit that target.
“This was not possible before,” Kahvejian said. “We’re so excited because we’ve made it possible. It’s like being at the dawn of the antibody era or the DNA or the mRNA era. Synteins are going to be a new class that people will use for a broad range of things now that we’ve made this a possibility.”
Photo by Abiologics
