A28 Therapeutics Founder Dr. Stanley Lewis Urges Industry To Close Gap On Aggressive Approaches In Cancer Treatments

Cancer treatment dates back centuries before modern medicines were developed. Ever since cancer was discovered, treatment has been a major challenge, because cancer cells are of human origin but mutate and grow rapidly in very harmful ways. When surgery is not an option or is unsuccessful in the removal of tumor cells, physicians turn to medications to treat the malignancy.

Over the past several decades, there have been various advancements in cancer treatment, the most common of which is chemotherapy. Initial treatment paradigms featured sequential monotherapy. However, the methods for treating cancer have evolved to favor combination therapy. If results are still unsatisfactory, physicians often proceed to other modalities such as radiation therapy, cryotherapy, and more recently, immunotherapy. Unfortunately, initial treatment with chemotherapies can be very toxic, killing both tumor cells and healthy cells. This often results in further depletion of the patient’s immune system. This immunosuppression works against subsequent treatments designed to strengthen the immune system, such as immunotherapy. 

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Although chemotherapy can be an effective way of treating cancer, some patients prefer to forgo treatment due to fear of toxic side effects, with some patients stating that the treatments are worse than the disease itself. 

Dr. Stanley Lewis, an Internal Medicine physician and founder of A28 Therapeutics, suggests that society's approach to cancer is backward. "Chemotherapy can be very toxic to the immune system; however we know that the immune system is very important in treating cancer," Dr. Lewis says. "The conventional approach to start with chemotherapy undermines future treatment with immunotherapies designed to enhance the body’s ability to fight cancer. Why would you kill all your soldiers before you go to war?"

He adds, "Perhaps a better way to treat cancer would be to start with immunotherapy and reserve more toxic chemotherapy for later if treatment is unsuccessful."  Dr. Lewis goes on to say that he is guided by three principles in developing new cancer treatments. These three principles are "First, do no harm" referring to the physicians calling from the ‘Hippocratic Oath'. Lewis insists that treatments should be safe and well tolerated. "If patients are choosing not to take medications that are toxic, that’s a problem," states Lewis. Secondly, nature will provide clues. "It's okay to create enhancements but in general, the closer a treatment mirrors or leverages nature, the better." Finally, simple is better than complex. "For some reason, medical approaches have trended towards increasing complexity. I favor the KISS principle ‘Keep It Simple Stupid,'" states Lewis.   

To implement these drug development principles, Dr. Lewis founded A28 Therapeutics, a privately held, clinical-stage biopharmaceutical company that develops medications to precisely identify and attack cancer cells. These medications are part of a targeted lytic peptide platform.

The company's flagship product is AT-101 which is in late-stage clinical development. AT-101 is a targeted molecule that binds to cancer cells and kills them on contact. It targets over-expressed or inappropriately expressed receptors on cancer cells. AT-101 also targets the negative electrical charge found on the surface of cancer cells that is absent in healthy cells, reducing the potential for toxicity and side effects compared to conventional treatments like chemotherapy. 

Driven by his safety first principle, Dr. Lewis is developing AT-101 to be well tolerated by the patient. He emphasizes the structure of AT-101 which combines a 10-amino acid hormone unit that binds to a specific receptor on the surface of cancer cells. This hormone unit is conjugated to an 18-amino acid lytic peptide unit that carries a positive electrical charge. The positively charged lytic peptide is attracted to the negatively charged cancer cell membrane, and this interaction results in the destruction of the cancer cell.

Dr. Lewis favors simple solutions over ‘sexy science'. He says, "At A28 Therapeutics we produce blue-collar cancer killers. Complexity just introduces more opportunities for things to go wrong."

The platform originates from an appreciation of how natural killer cells eliminate bacteria and malignant cells from the body. This forms the basis of AT-101's cytotoxic mechanism. If successful, Lewis believes this could be a blueprint for the future of cancer treatments. "We have the opportunity to change the paradigms of cancer care. The vision of A28 Therapeutics is a world where we no longer fear cancer or its treatments," states Dr. Lewis.

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