Developing Cell Therapies for Solid Tumors and Hematologic Malignancies

Sonny Hsiao, PhD, chief executive officer, president and cofounder, Acepodia, discussed the company’s cell therapy technologies.

Acepodia is focused on targeting solid tumors and hematologic malignancies with the use of their off-the-shelf cell therapies and novel development platforms. Among these technologies are amplified natural killer cells, supercharged cell therapies, and γδ T cells developed using the company's antibody cell-conjugation platform.

ACE1702, an allogeneic, amplified natural killer cell therapy, is the company’s lead program and is currently being evaluated in a phase 1 study (NCT04319757) for HER2-positive solid tumors. Positive efficacy and safety data were presented at the European Society of Medical Oncology 2021 Annual Congress, September 16-21, 2021.

GeneTherapyLive spoke with Sonny Hsiao, president, cofounder, and chief executive officer, Acepodia, to learn more about the company’s cell therapy technologies. He also discussed ACE1702.

GeneTherapyLive: Tell me about Acepodia and your focus on off-the-shelf cell therapies.

Sonny Hsiao, PhD: Decades ago, cures for cancer were virtually unheard of and early development of cell therapies were highly experimental. Since then, cell therapies have evolved and emerged as a powerful tool to treat cancer and other diseases, yet challenges remain with manufacturing, cost, time from diagnosis to treatment, and access.

The speed and success of medical innovation in this space raised questions for me: Why can’t we cure cancer? Could cell therapies have that power? As a graduate student fifteen years ago in the labs of Dr. Carolyn Bertozzi and Dr. Matthew Francis at the University of California, Berkeley, my team and I discovered what would become the foundational technology for a new company: antibody-cell conjugation (ACC). ACC acts like “Velcro” between a variety of antibodies and cell types, giving rise to a new class of cellular therapies called antibody-cell conjugation effectors (ACE). Unlike chimeric antigen receptor (CAR)-based cell therapies that require genetic engineering, ACC can link hundreds of thousands of antibodies to a single effector cell using a proprietary DNA linker, effectively combining the precision of tumor-targeting antibodies and cancer-killing potential of the body’s own immune cells into a potent cell therapy with the potential to improve the lives of countless cancer patients.

Today, Acepodia is now a clinical-stage biotechnology company developing first-in-class cell therapies with its unique ACC platform technology, to address important needs for patients and physicians in cancer care. Our seasoned leadership and scientific experts are dedicated to advancing our robust pipeline of off-the-shelf ACE therapies with the potential to bring effective and affordable cell therapies to a broad population of patients, across a variety of solid tumors and hematologic cancers.

Can you tell me about the company’s cell therapy technologies and their advantages in treating cancers?

Today, Acepodia is developing potent and targeted off-the-shelf cell therapies to treat solid tumor and hematologic cancers with validated targets. Our ACE therapies essentially combine the precision of tumor-targeting antibodies and cancer-killing potential of the body’s own immune cells into a potent cell therapy.

Our first programs link tumor-targeting antibodies with cells of the innate immune system, namely off-the-shelf natural killer (oNK) cells derived from a proprietary screening process and gamma-delta T cells derived from healthy donors. oNK cells are distinct in that they have elevated levels of activating receptors (such as CD16) and low levels of inhibitory receptors, ensuring that they are primed and ready to engage cancer cells. Meanwhile, gamma-delta T cells can directly recognize and attack cancerous cells as well as coordinate a broad antitumor immune response by recruiting and activating other immune factors and cells to the site of disease. Compared with the cell types used in traditional cell therapies, these cells have several key advantages including low risk of graft versus host disease, cytokine release syndrome and neurotoxicity. Acepodia’s proprietary enhanced effector cells have enhanced potency, stable receptor profile expression and retain potency even after cryopreservation.

Tell me about ACE1702, its phase 1 study, and the preclinical data.

Acepodia’s lead product candidate is ACE1702, an allogeneic, trastuzumab-conjugated oNK cell therapy targeting HER2-positive solid tumors. Recent preclinical data published in the journal Cancers demonstrated that ACE1702 has the ability to kill HER2-expressing solid tumor cells. Furthermore, irradiated and cryopreserved ACE1702 retained HER2-specific potency with no tumorigenic potential, suggesting it can be frozen and shipped to clinical sites, allowing for an ‘on-the-shelf’ product that can be stored on-site with immediate availability. Because it has the potential to target and kill tumors that express a low level of HER2, this approach holds promise for attacking tumors that may otherwise evade immune cells.

Acepodia recently presented interim data from our ongoing Phase 1 study evaluating ACE1702 at the European Society of Medical Oncology 2021 Annual Congress. The preliminary data from this first-in-human study showed early clinical activity and that repeat dosing of ACE1702 was safe and well-tolerated across the first four dose levels. No clinical signs of dose limiting toxicity, such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome or graft versus host disease have been reported so far. The trial will continue to enroll patients with advanced HER2-expressing tumors. Dose escalation is continuing with updated clinical data to be provided.

Transcript edited for clarity.