Estrella Biopharma’s CD19-Targeted T-cell Therapy for B-Cell Lymphomas Gets IND Clearance

Estrella Biopharma’s EB103, an investigational CD19-targeted T-cell therapy intended to treat B-cell lymphomas, has received clearance of its investigational new drug (IND) application from the FDA.¹

Estrella announced that it has designed a phase 1/2 clinical trial, called Starlight-1, which will evaluate the safety and preliminary efficacy of EB103, and determine the recommended phase 2 dose.¹ The trial will enroll patients with relapsed/refractory (r/r) non-Hodgkin lymphoma and has received clearance to include patients with HIV-associated lymphoma and primary and secondary central nervous system lymphoma. The company noted that it anticipates that UC Davis Health will serve as the initial site for the trial’s enrollment activities.

"We are thrilled to have received FDA clearance for our IND application for EB103, which will allow us to evaluate its safety and efficacy in a broader range of patients, including those who are typically excluded from other clinical trials, often due to cytokine release syndrome and neurotoxicity," Cheng Liu, PhD, president and chief executive officer at Estrella Biopharma, said in a statement regarding the news.¹ "Our goal is to develop a safe and effective therapy that can help address the unmet medical needs of patients with r/r B-cell malignancies, including those who are currently underserved by existing therapies. We hope to enroll our first patient in the second half of 2023."

EB103 incorporates a technology licensed from Eureka Therapeutics, referred to as ARTEMIS, that Estrella has utilized as part of its agreement between the companies. ARTEMIS T-cells are engineered with an antibody-T-cell receptor that functions by “recruiting the endogenous CD3 complex and utilizing the same activation and regulatory signaling pathways employed by natural TCRs, which enables both potent killing activity against CD19+ tumor cells and a superior safety profile.”²

In addition to the Starlight-1 trial, which will evaluate EB103 as a monotherapy, Estrella Biopharma is also conducting preclinical research evaluating EB103 in combination with its partner Imugene’s onCARlytics (CF33-CD19) oncolytic virus for the potential treatment of multiple solid tumor indications.^1,2 onCARlytics is intended to induce expression of a truncated CD19 antigen on tumor cells in order to allow them to be targeted by CD19-directed T-cell therapies.³

Data from that preclinical research were recently presented at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting, November 8-12, 2022, in Boston, Massachusetts. It was reported that EB103 in combination with onCARlytics showed greater efficacy in vitro in triple negative breast cancer cell line MDA-MB-468 and hepatocellular carcinoma cell lines HepG2 and Hep3B compared with onCARlytics alone. In addition, EB103 cocultured with onCARlytics showed a higher trend of IL-2 production and lower IFNγ production in comparison with City of Hope CD19-directed chimeric antigen receptor T-cells cocultured with onCARlytics.

"The data supports the potential benefit of the 'Mark-and-Kill' approach in addressing the lack of tumor-specific targets in treating solid tumors with T-cell therapies,” Liu said in a November 2022 statement.² "We look forward to continue working with Imugene to validate our combination approach as an effective treatment for cancer as quickly as possible.”

REFERENCES

1. Estrella Biopharma announces FDA clearance of IND application for phase I/II clinical trial (Starlight-1) of EB103, a CD19-targeted ARTEMIS® T cell therapy, to patients with B-cell lymphomas. News release. Estrella Biopharma, Inc. March 8, 2023. Accessed March 9, 2023. https://www.estrellabio.com/news/estrella-biopharma-announces-fda-clearance-of-ind-application-for-phase-i%2Fii-clinical-trial-(starlight-1)-of-eb103%2C-a-cd19-targeted-artemis%C2%AE-t-cell-therapy%2C-to-patients-with-b-cell-lymphomas

2. Imugene’s onCARlytics combination with Estrella’s CD19-Redirected ARTEMIS® T Cells presented at SITC Annual Meeting. News release. Estrella Biopharma, Inc. November 14, 2022. Accessed March 9, 2023. https://www.estrellabio.com/news/imugene%E2%80%99s-oncarlytics-combination-with-estrella%E2%80%99s-cd19-redirected-artemis%C2%AE-t-cells-presented-at-sitc-annual-meeting

3. Park AK, Monroy I, Cook C, et al. CF33-CD19t oncolytic virus (onCARlytics) targets hepatocellular carcinoma (HCC) and in combination with CD19-Redirected ARTEMIS® T cells results in significant tumor killing. Presented at: Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting November 8-12, 2022; Boston, Massachusetts.