A developer of programmable medicines that combine generative artificial intelligence (AI) and high throughput chemical protein synthesis became Flagship Pioneering’s latest startup to emerge from stealth mode.
Abiologics made its public launch with Flagship Pioneering committing an initial $50 million in financing that is intended to advance the company’s platform and develop a pipeline of Synteins™, protein-like treatments created from artificial amino acids such as D-amino acids, mirror images of the L-amino acids from which conventional biologics are created.
“That simple flip can help create medicines that look like proteins, act like proteins, but don’t have the liabilities of proteins because our body’s defenses and normal degradation enzymes can’t destroy them, can’t cut them,” Avak Kahvejian, PhD, Abiologics’ co-founder and CEO, told GEN Edge. “Synteins are in some ways proteins. But they’re made with synthetic building blocks and therefore have the advantages of designability, and programmability that you could get with a biologic. But they don’t have the drawbacks of lack of stability, immunogenicity, and so on.”
Kahvejian, who is also a general partner at Flagship Pioneering, said he and colleagues at the venture capital giant created Abilogics three years ago by thinking about how to address the downsides associated with biologics and protein drugs that reduce their usability, route of administration, persistence, and tolerability—such as susceptibility to being degraded, being cleaved, and engendering an immune response.
“What we in the industry had started to appreciate was that if you maybe tweak some of the building blocks or replace some of the building blocks post facto after the drugs have been created or designed, you could mitigate some of these liabilities,” Kahvejian explained.
Yet drug developers have been hampered in generating antibodies, enzymes, peptides, and other biologics with these nonstandard building blocks through their reliance on recombinant technologies to discover, prototype, and manufacture their treatments: “Therefore, you’re beholden to natural building blocks. That’s been a bit of a tension or a roadblock in the industry.”
Freedom from recombinant technology
Applying Flagship’s strengths in generative AI and biology, Kahvejian and colleagues concluded that computational design for creating drugs would free them from having to rely on recombinant technology, enabling them to incorporate nonstandard building blocks in their drug creation process by chemically synthesizing designs that emerged through computation rapidly, with high accuracy and efficiency.
“We’re using the ribosome, tRNA, the translational machinery inside biological systems. But if you’re using nonstandard building blocks, that approach doesn’t work. These natural systems, whether they be bacteria, yeast, or phages, can’t tolerate non-natural building blocks. They weren’t evolved for that. So that’s why we have to move to chemical synthesis.”
Chemical synthesis has been advanced in part based on the research of an academic co-founder of Abiologics, Bradley L. Pentelute, PhD, a professor of chemistry at MIT, has carried out pioneering research in chemical synthesis of proteins and peptides. Pentelute’s lab has developed a series of highly efficient and selective chemistries that can selectively modify the amino acids cysteine and lysine within unprotected peptides and proteins, and has designed fully automated fast-flow machines to accelerate the chemical manufacture of sequence-defined biopolymers–activity that has informed the development of Abiologics’ own chemical synthesis platform.
“He developed faster, more efficient, more accurate, and more parallelized methods for making polymers with building blocks, whether they be L-amino acids, D-domain amino acids, or others. That has been another enabling capability because you can imagine things in a computer, but you also need to make them to test them and then to scale them,” Kahvejian explained. “That’s why both computation and chemical synthesis needed to come together to make Abiologics’ platform a reality and Synteins as a class, a possibility.”
“A lot of the computational tools in biology now are geared toward using natural building blocks, and they’ve been trained on natural building block proteins. So, we had to refashion them. We had to make them compatible with nonstandard, noncanonical building blocks,” Kahvejian continued. “But that’s what we’ve achieved. And so we can now paint with that broader palette, design things that a human couldn’t imagine or a biological system couldn’t imagine for us. And then we can use the chemical synthesis to in essence print them in the real world.”
Initial focus on immunology, oncology
Abiologics’ initial focus is the development of new treatments for indications in immunology and oncology. In the case of immunology, Kahvejian said, Abiologics is striving to create oral drugs since so many therapies in the space are injected or infused into patients.
“In the case of biologics that target solid tumors, there’s a challenge with respect to getting deep inside solid tumors or accessing metastases that are in hard to reach organs or tissues. Synteins may have an advantage there in terms of their format and stability, such that they can get into solid tumors or maybe cross the blood-brain barrier. And so that’s why we focused on a number of oncology applications that take advantage of those of those properties,” Kahvejian said.
Over time, Abiologics plans to expand its staff, which now stands at 20 people.
“A lot of their work was focused on platform development. We have a very strong and talented computational team and a very powerful chemistry and automation group, and then a preclinical group,” Kahvejian said. “The team is going to expand, indeed, with an expansion of our preclinical efforts and entry into the clinic, and with the enhancement of the management team.”
Joining Kahvejian in Abiologics’ founding team of executives are:
- Mike Hamill, PhD, chief innovation officer of Abiologics and senior principal at Flagship Pioneering
- Kala Subramanian, PhD, founding president of Abiologics and operating partner at Flagship Pioneering
- Jaclyn Dunphy, PhD, senior director of strategy and research operations at Abiologics
- Alicia Kaestli, PhD, senior associate at Flagship Pioneering.
Based in Cambridge, MA, Flagship Pioneering has built a primary portfolio of companies focused on life sciences or “human health” and sustainability, as well as on AI. The firm’s best-known companies that have grown from startups include Moderna, the messenger RNA (mRNA) vaccine giant that has brought several COVID-19 vaccines to approval, and Generate:Biomedicines, a developer of therapeutics based on de novo protein generation. Flagship was among investors who funded Generate:Biomedicines’ $273 million Series C financing completed last year, bringing its total equity financing since 2020 to nearly $700 million.
Earlier this month, Flagship Pioneering announced plans to deploy a combined $3.6 billion in new capital to support the creation and development of about 25 new startups—consisting of $2.6 billion raised into its eighth fund, Fund VIII, and side funds totaling $1 billion that include sector-specific strategic partnerships.
Noubar Afeyan, PhD, Flagship Pioneering’s founder and CEO, serves as co-founder and chairman of Abiologics’ Strategic Oversight Board.
“With the convergence of advancements in generative artificial intelligence, automated polymer synthesis, and chemical functionalization coupled with a vision to develop more powerful medicines with unprecedented diversity, we asked, what if we could design biologics entirely from new building blocks that could overcome the most critical limitations of today’s medicines?”
