Acepodia: linking antitumor antibodies to immune cells

Acepodia is using its antibody-cell conjugation platform to generate cell therapies for cancer

Acepodia is using its antibody-cell conjugation platform to link tumor-targeting antibodies to the surface of cell therapies while avoiding genetic engineering. The platform, which has the potential for cost savings compared with CAR T therapy, led JW Therapeutics to partner with the company for commercialization of its lead program Tuesday.

Acepodia Inc. gained global rights to components of the ACC technology from Carolyn Bertozzi’s lab at the University of California Berkeley, where co-founder, President and CEO Sonny Hsiao was a graduate student.

Unlike CAR-based cell therapies that require genetic engineering, Acepodia’s platform adds complementary single-stranded DNA to cells and antibodies that can be combined to create therapies targeted to a specific tumor antigen. The company is focused on applying the platform to off-the-shelf therapies.

“Without complicated genetic engineering and the virus transduction, we can lower the cost of our product,” said Hsiao. The company projects its manufacturing costs to be two to three orders of magnitude lower than that of autologous CAR T therapies.

The technology also allows for rapid testing of multiple antibodies, said Hsiao, who noted that it is difficult to test a variety of antibodies in traditional CAR-based therapies because CAR constructs would need to be engineered for each antibody.

The company’s platform activates cell therapies through different mechanisms than CAR-based approaches. By screening a library of linkers that preferentially bias which surface proteins the antibodies bind, Acepodia can select candidates that activate a variety of receptors, including CD16 and NKp44.

“Those are very strong NK cell activation receptors,” said Hsiao, adding that CAR constructs commonly incorporate CD3 and CD28 signaling domains. “Bringing in different types of receptors allows us to trigger better efficacy.”

Lead candidate ACE1702 comprises NK cells conjugated with the anti-HER2 antibody trastuzumab and is in a U.S. Phase I trial to treat HER2-expressing solid tumors. The company uses an NK cell line selected for its antitumor cytotoxicity.

Unpublished data showed ACE1702 had greater cytotoxicity in human breast and ovarian cancer cell lines than Herceptin trastuzumab or the trastuzumab antibody-drug conjugate Kadcyla from the Genentech Inc. unit of Roche (SIX:ROG; OTCQX:RHHBY), and “superior efficacy” to Herceptin in mice with solid tumors, said Hsiao.

He added that in preclinical solid tumor models, antibody-conjugated NK cells maintained tumor engagement in spite of immunosuppression, an improvement upon conventional CAR T therapies, which have struggled to maintain efficacy in the immunosuppressive microenvironment of solid tumors.

Under Tuesday’s licensing agreement, Acepodia granted JW Therapeutics (Shanghai) Co. Ltd. development and commercialization rights to ACE1702 and ACE1655, an anti-CD20 antibody conjugate for hematological malignancies, in Hong Kong, Macau and mainland China in return for undisclosed upfront and milestone payments plus royalties.

ACE1708, Acepodia’s second therapy slated for the clinic, is an anti-PD-L1 antibody conjugate in preclinical testing for PD-L1-expressing tumors including Hodgkin lymphoma, head and neck, lung and liver cancers. The company plans to move ACE1708 to the clinic this year or next.

After validating its technology in patients, Acepodia plans to partner with companies and research labs seeking to convert their antibody assets into cell therapies, said Hsiao.

ACC can also be a used to complement CAR technology, especially against solid tumors.

“Acepodia is also working on dual-targeting NK cells made by both ACC and CAR technologies,” said Hsiao.

The company’s pipeline includes two γδ T cell therapies for various solid and blood cancers. While both NK cells and γδ T cells can be administered off the shelf, they are activated through distinct mechanisms, show preferential trafficking to different tissues and cell types, said Hsiao, who added that γδ T cells may be suited for lung and blood cancers.

According to Hsiao, Acepodia is the only company developing ACCs, though alternative enzymatic methods of antibody-cell conjugation are being developed at Scripps Research by Associate Professor Peng Wu, another alumni of the Bertozzi lab.

The company has raised about $20 million in venture funding, which will support completion of its Phase I trial.

COMPANY PROFILE

Acepodia Inc.

Burlingame, California and Taipei, Taiwan

Technology: Antibody-conjugated off-the-shelf NK and γδ T cell therapies

Origin of technology: University of California Berkeley, in-house

Disease focus: Cancer

Clinical status: Phase I

Founded: 2016 by Patrick Yang and Sonny Hsiao

University collaborators: University of California Berkeley

Corporate partners: BioMab Inc., JW Therapeutics (Shanghai) Co. Ltd.

Number of employees: 20

Funds raised: $20 million

Investors: DEFTA Partners, Center Ventures, Top Taiwan Venture Capital, CIDC, other undisclosed investors

CEO: Sonny Hsiao

Patents: 4 issued, covering ACC technology and its applications and off-the-shelf NK cell technology

Targets

CD3

CD16 (FCGR3) - Fc γ receptor III

CD28

HER2 (EGFR2; ErbB2; neu) - Epidermal growth factor receptor 2

PD-L1 (B7-H1; CD274) - Programmed cell death 1 ligand 1

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