Unveiling Pheast Therapeutics, an immuno-oncology company that is activating the immune system to Pheast on cancer

By Amira Barkal, MD, PhD, Principal Founder and Interim CEO

It is my sincere pleasure to announce today the launch of Pheast Therapeutics, an immuno-oncology company backed by Arch Ventures and Catalio Capital Management. Pheast is focused on developing treatments to unleash the full potential of macrophages in the fight against cancer. We are taking a novel approach to cancer immunotherapy and going after some of the most challenging-to-treat cancers. I’m thrilled to be able to share more about Pheast’s origin and our vision for the future of cancer treatment. We are also pleased to announce we’ve raised 76M in our Series A to make this a reality.

Pheast originated from a passion shared with my co-founders to shepherd scientific discoveries made in the lab to real patients who may benefit from them. This philosophy made the formation of Pheast a natural and necessary advancement of our research that first revealed the importance of the CD24 molecule in cancer. My co-founders and mentors, Irv Weissman and Ravi Majeti, have already demonstrated through their work developing CD47 molecule-targeting therapies that in order to maximize the success of a therapeutic program, the scientists who made the foundational discovery should be integrally involved in its clinical development. Pheast is led by the scientists who made the foundational discoveries. Our goal is to bring these advances in cancer immunotherapy directly to the patients who need them the most.

From left to right: Amira Barkal, MD, PhD; Irv Weissman, MD; Ravi Majeti, MD, PhD; Roy Maute, PhD

Pheast is activating the immune system to pheast on cancer

We are developing cancer immunotherapies that block “don’t eat me” signals in order to activate the patient’s own immune system to devour cancer cells.

Pheast takes a different approach to cancer immunotherapy by activating an important type of immune cell found in tumors, the macrophage. Macrophages — Greek for “Big Eaters” — are white blood cells that detect damaged cells, including cancer cells, and then engulf and destroy them in a process called “phagocytosis.” A macrophage is like a Pac-man that patrols all tissues in the body, gobbling up threatening cells and debris. In addition to phagocytosis, macrophages also coordinate immune responses with other cell types, help fight infection, and even contribute to wound healing. Pheast’s name alludes to the act of macrophages eating bodily intruders, a process known as phagocytosis.

Macrophages are present in high numbers in nearly all tumors. Why are these powerful defenders idle, or even counterproductive, when it comes to an immune attack on tumors? Cancer cells grow quickly and express proteins on their surfaces that act like shields of armor, blocking macrophages from detecting and killing them. These protein shields are referred to as “don’t eat me” signals, or macrophage checkpoints. By commandeering these “don’t eat me” signals, cancer cells are able to operate in “stealth mode” despite the high numbers of macrophages surrounding them within the tumor.

Harnessing the potential of macrophages for cancer immunotherapy

The prototypical “don’t eat me” signal is a protein molecule called CD47. Pheast co-founders Irv Weissman and Ravi Majeti were among the first scientists to recognize that blocking CD47 in cancer could allow macrophages to effectively recognize and destroy cancer cells. Therapies targeting CD47 are currently in late-stage clinical trials and have shown tremendous promise for the treatment of multiple cancers, especially cancers arising from blood cells such as leukemias and lymphomas.

When I joined Irv’s lab for my PhD, there was substantial excitement surrounding the discovery of CD47, the first known macrophage checkpoint. Before then macrophages had typically been thought of as “bad guys” in the fight against cancer, because some types of macrophages actually promote tumor growth and inhibit immune responses in tumors. The idea that macrophages could be redirected to eat cancer cells and to provide meaningful benefit for patients was unconventional, but Irv and the team of scientists working on CD47 were not deterred. This spirit of independent thinking and the persistence to go after medicine’s most complex problems are also cornerstones of our approach at Pheast.

Live cell microscopy image of human macrophages co-cultured with human cancer cells (green). Macrophages in the act of phagocytosis of cancer cells are marked by pH-sensitive dye (pink).

While studying various cancers in the lab, we soon discovered that there were more “don’t eat me” signals beyond CD47. Through my PhD research we uncovered a new, potent “don’t eat me” signal called CD24. CD24 is a protein that is highly expressed by many tumors, especially ovarian cancer and breast cancer..

When we blocked CD24 signaling, essentially neutralizing the shield of armor on the cancer cells, we saw that they were now readily recognized and killed by macrophages — even cancers for which CD47-blockade brought little to no response. We were particularly thrilled to see strong responses to CD24-blockade in preclinical models of ovarian cancer, as this disease is incredibly difficult to treat and has shown weak responses to existing immunotherapies. Pheast is developing therapies to target CD24 to unleash the potential of macrophages, with the goal of transforming the therapeutic landscape for these resistant tumors.

Pheast is not just a CD24 company, though. We intend to maximize the potential of macrophages in more tumor types, and for more patients. We know now that “don’t eat me” signals are redundant — many tumors express two or even more different signals. Each tumor type — and perhaps each individual tumor — likely has a sort of “don’t eat me” signal signature. Pheast’s goal is to leverage our innovative discovery platform to identify many such signals, then learn which “don’t eat me” signals are functional in each tumor. By advancing our pipeline of macrophage checkpoint inhibitors, we could therapeutically block the right combination of “don’t eat me” signals to eliminate each tumor type. This is Pheast’s vision: to bring about a Macrophage Revolution through precision cancer immunotherapy.

Join Pheast’s journey

Pheast is fortunate to have the support and leadership of our co-founders, scientific experts in the field of cancer immunotherapy, and our investors who share our vision. Pheast has an outstanding team of scientists, physicians, and engineers, all united under our goal of developing novel, transformative cancer immunotherapies and bringing them to patients who need them most. We look forward to welcoming new Pheasters to the team. If you are interested in joining us or learning more, please visit our website at Pheast.com or view our open job listings on Linkedin.

Amira Barkal, MD, PhD, Principal Founder and Interim CEO. Dr. Barkal is a Clinical Fellow in Medicine at Brigham and Women’s Hospital at Harvard Medical School. She earned her MD and PhD degrees from Stanford University School of Medicine in 2021 as part of the Medical Scientist Training Program, where she led the discovery of CD24 as a novel innate immune checkpoint in cancer. Dr. Barkal is an expert in cancer immune evasion pathways as well as regulators of macrophage function. She is a recipient of the Ruth L. Kirschstein Fellowship of the National Cancer Institute, the Harold M. Weintraub Award, and the Society of Immunotherapy of Cancer Young Investigator Award.

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