Aulos Bioscience is now recruiting cancer patients in Australian medical centers for a trial of the world’s first antibody drug designed by a computer.
The computationally designed antibody, known as AU-007, was planned by the artificial intelligence platform of Israeli biotech company Biolojic Design from Rehovot, in a way that would target a protein in the human body known as interleukin-2 (IL-2).
The goal is for the IL-2 pathway to activate the body’s immune system and attack the tumors.
The clinical trial will be conducted on patients with final stage solid tumors and will last about a year – but the company hopes to present interim results during 2022. The trial has raised great hopes because if it is successful, it will pave the way for the development of a new type of drug using computational biology and “big data.”
Aulos presented pre-clinical data from a study on 19 mice – and they all responded positively to the treatment. In the 17-day trial period of the study, the antibody led to the complete elimination of the tumors in 10 of the mice – and to a significant delay in the development of the tumors in the other nine mice.
Aulos was founded in Boston as a spin-off of Biolojic and venture capital firm Apple Tree Partners, which invested $40 million in the company to advance the antibody project and prove its clinical feasibility.
Computers, not mice
Drugs based on antibodies are considered to be one of the greatest hopes for anti-cancer solutions. Among the best-known in the field are Keytruda, mostly used to treat melanomas and lung cancer; and Herceptin for breast cancer. But the antibodies given today to cancer patients are created by a method that also has disadvantages – most are produced by the immune system in mice, and then are replicated to enable mass production.
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These mice are immunized with a protein involved in cancer, and then develop the antibody as an immune response. But the murine immunological system does not make a great effort to neutralize the foreign protein the mice were injected with to treat the cancer – but only acts to prevent the infection. The result is that sometimes, even though the mouse manages to produce the antibody that attacks the target protein, this process cannot be controlled and it could also cause serious negative side effects. For example, IL-2 – the protein molecule chosen by Biolojic, can also inhibit the immune system and cause severe toxicity in the patient’s body.
Instead, in the case of Biolojic Design, the antibody is not the product of a living and uncontrolled creature, but it is designed by the computer – and the antibody is planned based on the large amount of scientific knowledge accumulated about the action of IL-2. Prof. Yanay Ofran, the founder and CEO of Biolojic, said the company programmed is antibody to capture to IL-2 manufactured in the human body – and to harness it so that it works against the growth, but at the same time it will prevent it from inhibiting the immune system or causing toxicity – “so that the endogenous IL-2 cannot inhibit the immune system or cause its notorious toxicity of blood vessel leakage and pulmonary edema". None of that could be accomplished using mice, said Ofran.
Biolojic’s AI platform mimics the human immunological system, and teaches the computers to design antibodies based on models. In simple terms, an antibody is like a glove that needs to be tailored to the molecule we want to attack, said Ofran. “We showed the computer a million gloves and a million hands appropriate for them. Eventually, we showed a hand we don’t have a glove for, and asked the algorithm to create a precise glove for it,” he added.
The company has been developing its technology for a decade, and has been working on the specific antibody being used in the trial for three years. Because Biolojic also provides services to pharmaceutical companies, it already has significant revenues and has needed to raise relatively little venture capital, less than $30 million, since it was founded.
Ofran is a computational biophysicist and a biotech entrepreneur. He received his Ph.D. in molecular biophysics and biomedical informatics with distinction from Columbia University. He is a professor of bioinformatics and biophysics at Bar Ilan University, and the author of over 100 scientific papers and patents.
"Out of over 200 anti-cancer drugs that have come into use in recent years, only two significantly improved the patients’ survival rate – in other words, they extended their lives by more than six months", said Ofran. “We have finally reached a stage that enables us to assess the performance of the computationally designed antibody on real patients.”