Estrella Immunopharma Submits IPO Prospectus Highlighting 100% Complete Response Rate of Novel CD19 CAR-T Therapy EB103 in High-Risk, Heavily Pretreated NHL Patients
In June, “easing regulatory oversight of early-stage clinical trials for cell and gene therapy (CGT)” emerged as a central topic at the FDA’s CGT Roundtable Meeting. In the same month, the FDA announced the removal of the Risk Evaluation and Mitigation Strategy (REMS) requirement for autologous CAR-T therapies, covering the six currently approved BCMA- and CD19-targeted CAR-T products.
Ensuring the safety and efficacy of CAR-T immunotherapy without REMS is interpreted as regulatory recognition of the maturing safety management system, indicating that the industry is ready for scalable expansion. With the removal of burdensome certification and risk warning requirements, geographical and institutional barriers to CAR-T diagnosis and treatment will be further lowered, particularly enabling community hospitals to provide these services more conveniently, thereby ushering in an era of “broad-coverage healthcare systems.”
Against this backdrop, CD19 CAR-T therapies still in the clinical stage need to chart a new course. ““The only path to breakthrough is to achieve a generational leap in therapeutic efficacy, rather than incremental optimization, while ensuring safety.”In the interview, Dr. Liu Cheng, Founder and CEO of Estrella, pointed out that highlighting safety and demonstrating excellent efficacy are both indispensable, as they are directly linked to clinical acceptance and patient accessibility.
Estrella’s strategy is to leverage a fully innovative CAR-T technology, aiming to achieve superior efficacy and safety profiles that distinguish it from existing commercially available CAR-T therapies. From achieving high infiltration in solid tumors to delivering a “dimensionality-reduction strike” in the treatment of hematologic malignancies, Estrella employs ARTEMIS®Delivering a Novel Solution for CAR-T Therapy.
Dr. Liu Cheng is the Chief Executive Officer and a Director of Estrella, and also serves asJuno Therapeutics (WuXi)Chairman of the Board of Directors of (HKEX Stock Code: 2126), alsoEureka TherapeuticsFounder, Chief Executive Officer, and Director of (a company focused on innovative cell-based cancer immunotherapies). Prior to founding UroCare, Dr. Liu had served atChiron Corporation (now acquired by Novartis)Serving as the Chief Scientist for antibody drug development, Dr. Liu Cheng has dedicated over two decades to the field, holding more than 300 patents and published patent applications. He ranks among the top globally in CAR-T patents and holds a prominent position in the CAR-T therapy sector. According to statistics from Nature Biotechnology (Volume 38, 2020), he is ranked 14th among inventors worldwide.
1Hematologic Malignancies: No SAEs, 100% Complete Response Rate, Pioneering the High-Risk Population Market
According to data from the American Cancer Society and the Global Cancer Observatory (GCO), since 2022, there have been 806,202 new cases of non-Hodgkin lymphoma (NHL) globally, with the cumulative number of cases exceeding 5.53 million. However, a 2024 report by Datamonitor indicated that only approximately 5,850 patients received CAR-T therapy.Treatment coverage is less than 1%, which meansOver 99% of NHL patients have not yet received CAR-T therapy。
From a technical perspective, safety concerns have significantly hindered clinical adoption and promotion. Previously, mandatory Risk Evaluation and Mitigation Strategy (REMS) measures imposed by regulators required that commercial CAR-T therapies be administered exclusively at large medical institutions with monitoring and emergency rescue capabilities, such as specialized cell and gene therapy centers and Grade A tertiary hospitals. Although regulators have since rescinded the REMS requirements, the inpatient treatment nature of CAR-T products still needs to be gradually relaxed.
The root cause lies in safety considerations from both regulators and end-users, which is directly reflected in the clinical acceptance by frontline physicians.Dr. Liu Cheng remarked, “The feedback from physicians has been very direct. Doctors at the Estrella clinical sites stated, ‘After administering your CAR-T product, we feel less psychologically burdened and can sleep soundly at night.’”
High Efficacy, High Safety, and High Clinical Acceptance Are ARTEMIS®Key Features of the CAR-T Platform.Presented at EB103 In the STARLIGHT-1 Phase I/II clinical data:
During the dose-escalation phase, the second dose cohort enrolled patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) who had received multiple prior lines of therapy. All evaluable patients achieved complete response (CR) by the first month of treatment, resulting in a 100% complete response rate.
No treatment-related serious adverse events (SAEs) occurred in any of the evaluable patients.
In the second dose cohort, all enrolled patients were high-risk individuals ineligible for treatment with commercially available CD19-directed products, including one patient with central nervous system (CNS) lymphoma.
In fact, this group of high-risk patients isHigh-risk populations that previous CD19 CAR-T therapies failed to address or treat represent a vast potential patient market with currently no available therapeutic options.“The favorable safety profile observed in high-risk populations validates EB103’s potential as a safe and effective therapeutic option for a broader patient population,” further explained Dr. Liu Cheng. He noted that its high safety margin encourages physicians to prescribe EB103 to more high-risk patients, many of whom have exhausted other treatment options.
Meanwhile, exceptional safetyGreatly expands the flexibility of clinical applications. It is worth noting that currently commercialized CD19 CAR-T therapies, due to their complex manufacturing processes and higher risks, are administered as a single infusion in clinical practice. In contrast, EB103 leverages its technological and safety advantages to produce multiple therapeutic doses from a single manufacturing run.Theoretically supports a multiple-infusion strategyThis design not only holds promise for enhancing efficacy and sustaining long-term complete remission, but may also pave new avenues for greater flexibility in CAR-T therapy. Dr. Liu Cheng stated that multiple infusions will be considered as a potential option in the design of subsequent clinical trials.
Currently, EB103 has entered the Phase II registration clinical trial stage.
2Solid Tumors: Head-to-Head Trials Show Significant Superiority Over Traditional CAR-T
To understand why EB103 offers a superior safety and efficacy profile compared to conventional CAR-T therapies, thereby benefiting a broader population of lymphoma patients, it is essential to examine its underlying ARTEMIS technology platform.®。
ARTEMIS®Platform, also known asAntibody T Cell Receptor (AbTCR), originating from Eureka Therapeutics, the parent company of Estrella. In terms of mechanism of action, ARTEMIS®Innovatively combines the antibody-antigen recognition mechanism with the native CD3 complex—which consists of three dimers—through interactions with the intracellular domains of the γ/δ chains. This mechanism of action resembles endogenous TCR signaling, distinguishing it from conventional CAR-T cells that rely on artificial activation domains.
In particular, ARTEMIS®The Unique Design and Superior Efficacy of T Cells Have Been Validated in the Field of Solid Tumors——In a head-to-head study of preclinical neuroblastoma models published in Cell Reports Medicine, ARTEMIS®T cells demonstrated significantly superior performance compared to conventional CAR-T therapy, with clear advantages in efficacy, tumor infiltration, and persistence:
ARTEMIS®T cells accounted for 54% of the T-cell population within the tumor, whereas conventional CAR-T cells constituted only 3%. Meanwhile, ARTEMIS®T cells upregulate T-cell signaling pathways, enabling more effective activation of tumor-associated antigens (NFAT) compared to traditional CAR T cells, thereby initiating endogenous TCR signaling pathways.
ARTEMIS in a Subcutaneous Mouse Model of High-GPC2 Neuroblastoma®T cells reduced tumor volume by 96.31%, with an overall survival rate of 100%; in the conventional CAR-T cell group, only two mice exhibited 69.36% tumor regression, and the overall survival rate was merely 50%.
In a neuroblastoma mouse model with low antigen GPC2 expression, ARTEMIS®T cells achieved complete tumor regression and a 100% survival rate by week 7. Conventional CAR-T cells using the same antigen achieved only a 50% survival rate.
ARTEMIS®T cells exhibit persistence, with a higher proportion of stem cell-like memory characteristics, enhanced activity, and reduced exhaustion, thereby promoting their anti-tumor activity, durability, and prolonged anti-tumor effects.
ARTEMIS®T cells maintain their activity and function in immunosuppressive, low-antigen environments, whereas conventional CAR-T cells typically lose efficacy in such settings.
In short, ARTEMIS®T cells areStronger TCR signaling, greater memory T cell expansion, and higher CD8+ T cell infiltration,Addressing the penetration issue in solid tumor therapy, overcoming therapeutic bottlenecks such as low antigen expression and immunosuppressive microenvironments, and demonstrating consistent result trends across multiple tumor models.
It is reported that this preclinical study wasThird-Party Independent Research Led by the U.S. National Cancer Institute (NCI), Eureka as ARTEMIS®The platform provider offers technical support, and the relevant patents are jointly held by both parties.
3From “Controlled Cytotoxicity” to “Dimensional-Reduction Strike”: EB103 Emerges as a Differentiated Competitor in CD19 CAR-T Therapy for Hematologic Malignancies
NCI’s head-to-head study, also known as ARTEMIS®First head-to-head comparison with conventional CAR-T in the field of solid tumors,First Demonstration That Restoring Native T Cell Signaling Can Overcome Barriers in Solid Tumor TherapyFurther, the valid evidence for solid tumors is ARTEMIS®The platform provides critical support, thereby conferring a “dimensionality-reduction strike”-style advantage in the treatment of hematologic malignancies.
“My phone has been ringing off the hook.”Following the completion of Phase I clinical trials, Estrella experienced a surge in capital inflow, andTwo rounds of private investment in public equity (PIPE) financing were completed in June and September this year.。
Liu Cheng stated, “The Phase II clinical trial of EB103 will rapidly expand its sample size to verify safety and efficacy in humans. Our goal is to maintain an excellent safety profile and achieve a complete response rate of 90%–100%, thereby establishing a competitive advantage in the CD19 CAR-T market.”
He further emphasized that Estrella remains committed to an open and collaborative approach, warmly inviting global pharmaceutical companies and investment institutions to join forces in unlocking the vast potential of the ARTEMIS® platform technology in the fields of solid tumors and hematologic malignancies.
Envisioning the future of Estrella and Eureka, Liu Cheng believes that EB103 will follow a path similar to that of Humira (adalimumab)—Surpassing competitors in the same category through superior safety and clinical acceptance, thereby deeply tapping into the market's clinical potential.
This will be a compelling narrative for innovative drugs.
As more high-risk and even outpatient patients gain access to ARTEMIS®At that time, its market boundaries will far exceed those of existing CAR-T products, ultimately achieving a “Best-in-class” commercial legend and clinical value.
About Estrella
Estrella Immunopharma, Inc. (Nasdaq: ESLA) is a clinical-stage biopharmaceutical company dedicated to developing ARTEMIS targeting CD19 and CD22®T-cell therapy for the treatment of cancer and autoimmune diseases.
In 2022, Estrella was established as a holding subsidiary of Eureka, focusing on the development of ARTEMIS for hematologic malignancies.®T-cell therapy, with a core pipeline including EB103 targeting CD19 and EB104 simultaneously targeting CD19/CD22. In September 2023, Estrella was listed on the NASDAQ.