Acepodia Presents Positive Interim Phase 1 Feasibility Data for Antibody Cell Effector Therapy, ACE1702, in Advanced HER2-Positive Tumors

Source: Acepodia USA

Interim results from ongoing Phase 1 dose-escalation study demonstrate safety and tolerability of repeat dosing with ACE1702, a novel, off-the-shelf natural killer cell therapy

Initial results show potential for anti-tumor activity

Dose escalation is continuing up to 15 billion cells per cycle to determine the recommended starting dose to further evaluate the effectiveness of ACE1702

Acepodia, a clinical-stage biotechnology company developing first-in-class cell therapies with its unique Antibody-Cell Conjugation (ACC) platform technology to address gaps in cancer care, today reported new interim data from an ongoing Phase 1 dose escalation study demonstrating feasibility with ACE1702, the company’s most advanced investigational antibody effector cell therapy (ACE), in development for patients with advanced HER2-positive tumors. Initial results from this first-in-human study show that repeat dosing of ACE1702 was safe and well-tolerated across the first four dose levels, comprising 9 billion cells per cycle at dose level four (DL4). No clinical signs of dose limiting toxicity (DLT), such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) or graft versus host disease (GvHD) have been reported so far.

These data are available to view in an on-demand e-Poster (presentation number 1006P) as part of the European Society of Medical Oncology (ESMO) 2021 Virtual Congress starting today, Thursday, September 16, 2021.

“Current cell therapies hold promise for a range of diseases, but many remain limited in use due to toxicities associated with high or repeat therapeutic dosing,” said principal investigator Sarina A. Piha-Paul, M.D., associate professor, Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center. “The initial feasibility and safety findings from the ACE1702 study are encouraging as they suggest that this approach to cell therapy may enable more treatment options in the future for difficult-to-treat diseases, including lower-expressing HER2-positive tumors. As the study advances, we will work to determine optimal dosing for this investigational drug and continue to explore its therapeutic potential.”

These initial data were presented based on eight subjects who received escalating doses of ACE1702 in the range of 0.3 to 9 billion cells per cycle (DL1 and DL4, respectively) over the course of 14 days following a standard low dose lymphodepletion (LD) regimen. Enrolled patients have HER2-expressing tumors with an immunohistochemistry (IHC) score of 2+ or higher and may or may not have received prior treatment with a HER2-specific targeted therapy.

Additional study findings include:

  • One patient with an IHC score of 2+ achieved a partial response at DL3 (3 billion cells per cycle) based on RECIST criteria with no signs of CRS. The patient showed increased serum levels of interferon gamma (IFNγ) (18-fold increase on day 21) and IL-10 (2.6 fold increase on day 14).
  • The most frequent adverse events (AEs) were hematological toxicities attributed to the LD regimen prior to infusion with ACE1702.
  • There were no severe adverse events (SAE) related to ACE1702. One patient experienced two unrelated SAEs of pulmonary embolism and death due to progressive disease.

“We believe that ACE1702 has the potential to serve as a powerful, next-generation cell therapy candidate based on Acepodia’s unique conjugation process, which combines proven monoclonal antibodies, such as trastuzumab, and our proprietary oNK cell line, which has high expression of multiple NK activation and signaling receptors with limited expression of inhibitory receptors,” said Dr. Thorsten Graef, M.D., Ph.D, chief medical officer of Acepodia. “These promising interim data build on the recently published preclinical findings of ACE1702, which demonstrated in vitro and in vivo potency in HER2-expressing solid tumors, and provide ongoing validation of our overall ACC platform technology. We look forward to continuing to evaluate the safety and clinical activity of ACE1702 at higher doses in order to unlock its full treatment potential as we also continue to explore our ACC technology across other strategic disease indications.”

This ongoing Phase 1 open-label, dose escalation study (NCT04319757) is designed to evaluate the safety and tolerability of ACE1702 over the course of a six-week dosing schedule and determine the starting dose for a subsequent follow-on study of this differentiated cell therapy. The study will continue to enroll up to 36 patients with dose escalation continuing up to 15 billion cells per cycle.

Acepodia’s first-of-its-kind ACC platform technology can link more than 100,000 tumor-targeting antibodies to a variety of different activating and signaling receptors expressed on individual immune effector cells. The ACC platform, combined with Acepodia’s proprietary immune effector cells, increases binding strength against tumors that express low levels of tumor antigens to prevent tumor cell escape. This novel technology enables the company to develop ACE therapies, such as ACE1702, which are potent and targeted, next-generation off-the-shelf cell therapies with the potential to treat a variety of solid tumors and hematologic cancers.

About ACE1702
ACE1702 is an investigational next-generation cell therapy developed with Acepodia’s antibody-cell conjugation (ACC) platform, which conjugates the company’s proprietary off-the-shelf natural killer (oNK) cells with trastuzumab – a clinically-validated antibody that binds to HER2 – using complementary DNA linkers. The antibody cell effector (ACE) therapy, ACE1702, expresses high levels of multiple natural killer (NK) cell activation and signaling receptors, including CD16, with limited expression of inhibitory receptors. These features enhance the innate ability of NK cells to target and destroy tumors. In preclinical studies, ACE1702 showed excellent in vitro and in vivo potency against HER2-expressing cancers. In additional preclinical studies, ACE1702 was effective in targeting a broad range of HER2-expressing cancers, including those unaffected by current anti-HER2 therapies, and has also demonstrated an ability to overcome the immunosuppressive tumor microenvironment.

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