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Item 1. Business

2026-03-18 compared with 2024-09-27 · 1050 added, 1632 removed, 331 unchanged (89% of the section changed)

are a clinical-stage biopharmaceutical company developing T-cell therapies with the capacity to address treatment challenges for patients

with cancers and autoimmune diseases.

The Company was originally incorporated as Estrella Biopharma, Inc.

in the State of Delaware on

March 30, 2022, by Eureka Therapeutics, Inc.

(“Eureka”), which was established in California in February 2006 and reincorporated

in Delaware in March 2018.

On June 28, 2022, Estrella entered into a Contribution Agreement with Eureka, under which Eureka contributed

certain assets related to T-cell therapies targeting CD19 and CD22 proteins in exchange for 105,000,000 shares of Estrella’s Series

AA Preferred Stock (the “Separation”).

This Separation included Estrella entering into a License Agreement with Eureka and

Eureka Therapeutics (Cayman) Ltd., granting Estrella an exclusive license to develop CD19 and CD22 targeted T-cell therapies using Eureka’s

ARTEMIS® platform.

Additionally, Estrella assumed the Collaboration Agreement between Eureka and Imugene Limited, which covers the

development of solid tumor treatments using Imugene’s CF33-CD19t in conjunction with Estrella’s EB103 therapy.

September 29, 2023, Estrella consummated a business combination (the “Business Combination”) with TradeUP Acquisition

(“UPTD”), a blank-check company, pursuant to the Agreement and Plan of Merger dated September 30, 2022 (the

“Merger Agreement”).

Under the terms of the Merger Agreement, Tradeup Merger Sub Inc., a wholly-owned subsidiary of

UPTD, merged with and into Estrella, resulting in Estrella becoming a wholly-owned subsidiary of UPTD.

Following the closing of the

business combination, UPTD was renamed Estrella Immunopharma, Inc.

On June 26, 2024, Estrella Immunopharma, Inc.

filed a Certificate

of Ownership and Merger with the Delaware Secretary of State to effect a merger with its wholly-owned subsidiary, Estrella

Biopharma, Inc.

under Section 253 of the Delaware General Corporation Law.

This merger, effective at 11:59 PM Eastern Time on June

30, 2024, was approved by the unanimous written consent of the Company’s board of directors.

As a result of the merger, the

separate existence of Estrella ceased, and Estrella Immunopharma, Inc.

became the surviving corporation, assuming all assets,

liabilities, and obligations of Estrella.

believe T-cell therapy continues to represent a revolutionary step towards providing a potential solution for many forms of cancer, including

cancers poorly addressed by current approaches.

Existing chimeric antigen receptor T-cell, or CAR-T, therapies, the initial class of

T-cell therapies, have demonstrated remarkable efficacy and significant survival benefit in certain CD19-positive blood cancers like

lymphomas and leukemias.

CD19 is a protein expressed on the surface of almost all B-cell leukemias and lymphomas.

Current CAR-T cell

therapies, however, have limitations that may preclude broad adoption, including potentially life-threatening side effects like the hypersecretion

of inflammatory cytokines known as Cytokine Release Syndrome (“CRS”) and immune effector cell-associated neurotoxicity syndrome

This side effect, however, is considered addressable with other treatment if the net effect is to target and kill

cancer cells in the body.

Additionally, CAR-T therapies target and kill all cells expressing CD19 (including healthy B-cells).

side effects have limited currently approved CAR-T therapies to specialized cancer centers and later lines of treatment for patients

that have undergone other types of treatment unsuccessfully.

mission is to harness the evolutionary power of the human immune system to transform the lives of patients fighting cancer and autoimmune

disease with safe, effective therapies.

To accomplish this mission, our lead product candidate, EB103, which is a T-cell therapy we also

call “CD19-Redirected ARTEMIS ® T-Cell Therapy,” utilizes Eureka’s ARTEMIS ® technology

to target CD19.

Unlike a traditional CAR-T cell, the unique design of an ARTEMIS ® T-Cell, like EB103 T-cells, allows it

to be activated and regulated upon engagement with cancer targets that use a cellular mechanism more closely resembling the one from

the endogenous T-cell receptor (TCR).

EB103 is currently undergoing a Phase I/II clinical trial (STARLIGHT-1) to assess safety and determine

the Recommended Phase II Dose (RP2D) in patients with relapsed/refractory B-cell Non-Hodgkin’s Lymphomas.

As of September 2024,

two patients have been treated in the STARLIGHT-1 clinical trial.

are also developing EB104, a T-cell therapy we also call “CD19/22 Dual-Targeting ARTEMIS ® T-Cell Therapy.”

Like EB103, EB104 utilizes Eureka’s ARTEMIS ® technology to target not only CD19, but also CD22, a protein that,

like CD19, is expressed on the surface of most B-cell malignancies.

EB104’s dual-targeting strategy has the potential to more effectively

treat patients with lower surface CD19 density or a greater prevalence of CD22, and reduce relapse due to CD19 antigen loss.

tumors represent approximately 90% of all cancers.

To date, T-cell therapy such as CAR-T has demonstrated limited success treating solid

One major barrier limiting the potential of T-cell therapy is the lack of tumor-specific targets.

We believe that, in collaboration

with Imugene and Imugene’s product candidate, CF33-CD19t, an oncolytic virus, EB103 T-cells have the potential to overcome this

barrier using a “mark and kill” strategy.

This “mark and kill” strategy entails using CF33-CD19t, to induce solid

tumor cells into expressing the CD19 protein on the cell surface.

Our EB103 T-cells can then pursue and kill the now CD19-expressing

solid tumor cells, offering a potential treatment to cancers that lack solid tumor-specific targets.

Hematological

cancers, or blood cancers, are cancers that begin in blood-forming tissue, such as the bone marrow, or in the cells of the body’s

immune system.

Examples of hematologic cancers are leukemia, lymphoma, and multiple myeloma.

Leukemia is a broad term for cancers of

the blood cells.

The type of leukemia depends on the type of blood cell that becomes cancer and whether it grows quickly or slowly.

occurs most often in adults older than 55, but it is also the most common cancer in children younger than 15.

We are a clinical-stage biopharmaceutical

company developing T-cell therapies to address treatment challenges for patients with cancers and autoimmune diseases.

Our strategy is

to harness the evolutionary power of the human immune system to provide patients with potentially safer, more efficacious T-cell therapies

compared to traditional CAR-T therapies.

Leveraging cutting-edge cellular engineering technologies, we aim to overcome the limitations

of current CAR-T therapies, such as high toxicity and prohibitive costs, so that T-cell therapy treatments can be accessible to a larger

patient population.

Lead Program Status

Our innovative ARTEMIS ®

T Cell Receptor Platform uniquely designs T cells that, unlike a traditional CAR-T cell, are activated and regulated upon engagement with

cancer targets using cellular mechanisms more resembling those from the endogenous T-cell receptor (TCR).

Our lead product candidate,

EB103, is a CD19-directed ARTEMIS T-cell therapy designed to address the unmet medical needs of patients with relapsed or refractory B-cell

malignancies, especially those who are not eligible for currently approved T-cell therapies.

EB103 is currently in the dose expansion

portion of a Phase I/II clinical trial (STARLIGHT-1) in patients with relapsed/refractory B-cell Non-Hodgkin’s Lymphomas.

December 2025, we have completed the second dose cohort in the Phase I dose-escalation portion of our STARLIGHT-1 Phase I/II clinical

trial of EB103, and an independent Data Safety Monitoring Board (DSMB) has completed its review of safety data from the Phase I dose-escalation

phase (n=9) and recommended advancing the trial into the Phase II expansion phase at the recommended Phase II dose (RP2D).

I dose-escalation phase, no treatment-related serious adverse events were reported, and the high-dose cohort achieved a 100% complete

response rate at Month 1 in all evaluable patients, a majority of whom were considered high-risk and ineligible for currently available

commercial CD19 products.

Additional Product Candidates

We are also developing EB104,

which are T-cells that utilize ARTEMIS ® technology to target not only CD19, but also CD22.

Like CD19, CD22 is expressed

on the surface of most B-cell malignancies.

EB104’s dual-targeting strategy has the potential to more effectively treat patients

with lower surface CD19 density or a greater prevalence of CD22, thus potentially reducing relapse due to CD19 antigen loss.

Solid tumors represent approximately

90% of all cancers.

To date, T-cell therapy such as CAR-T has demonstrated limited success in treating solid tumors.

One major barrier

limiting the potential of T-cell therapy is the lack of tumor-specific targets.

We believe that, in collaboration with Imugene and Imugene’s

product candidate, CF33-CD19t, an oncolytic virus, EB103 T-cells have the potential to overcome this barrier using a “mark and kill”

This “mark and kill” strategy entails using CF33-CD19t, to induce solid tumor cells into expressing the CD19 protein

on the cell surface.

Our EB103 T-cells can then pursue and kill the solid tumor cells expressing exogenous CD19, offering a potential

treatment to cancers that lack solid tumor-specific targets.

Corporate History

On June 28, 2022, pursuant to a Contribution Agreement between Estrella and Eureka, Eureka contributed certain

assets related to T-cell therapies targeting CD19 and CD22 in exchange for 105,000,000 shares of Estrella’s Series AA Preferred

Stock (“Separation”),

On September 29, 2023, Estrella

completed a business combination (the “Business Combination”) with TradeUP Acquisition Corp.

(“UPTD”), a blank-check

company, under the terms of the Agreement and Plan of Merger dated September 30, 2022.

Following the merger, Estrella became a wholly

owned subsidiary of UPTD, and UPTD was renamed Estrella Immunopharma, Inc.

On June 26, 2024, Estrella

Immunopharma, Inc.

merged with its wholly owned subsidiary, Estrella Biopharma, Inc., under Section 253 of the Delaware General Corporation

The merger, effective on June 30, 2024, was approved by the Board of Directors and resulted in Estrella Immunopharma, Inc.

all assets, liabilities, and obligations of Estrella Biopharma, Inc.

On November 27, 2024, the Company established a wholly owned

subsidiary in Hong Kong.

Key elements of our business

strategy include:

Effectively progress EB103, our lead product candidate, through clinical development.

We believe our autologous T-cell therapies have the potential to overcome major limitations of currently approved CAR-T cells with superior safety and efficacy, allowing access to significantly more patients.

As of December 2025, we have completed the dosing of nine patients in the Phase I dose escalation phase of STARLIGHT-1 and have initiated Phase II dose expansion phase at the RP2D.

We anticipate completing the Phase II portion of the STARLIGHT-1 clinical trial in 1H2027.

Total Addressable Market (TAM) in CD19-positive cancers through the demonstration of safety and efficacy of ARTEMIS T-cell in clinical

settings for patients not eligible for currently approved T-cell therapies:

EB103’s safety profile positions it for potential

use in earlier-line treatments, broader adoption in community hospital settings rather than being restricted to specialized medical centers,

and the ability to treat high-risk patient groups, thereby increasing market penetration and patient accessibility.

our second product candidate, EB104, into clinical development.

We are compiling

an Investigational New Drug (IND) filing for EB104 for the treatment of relapsed/refractory

and high-risk B cell malignancies.

Phase I trials may not commence until the FDA has approved

the Investigational New Drug (“IND”) Application for EB104.

the use of EB103 in conjunction with CF33-CD19t for multiple indications of solid tumors through clinical development.

Phase I/II Starlight-1 Clinical Trial is successful, we plan to submit an IND filing for the use of EB103 in conjunction with CF33-CD19t

in the future.

At this time, we have not determined the solid tumor indications to target or an exact timeframe for filing our IND application.

to innovate to develop and advance a novel T-cell therapy pipeline.

We are committed to developing more disruptive therapies

that have the potential to be adopted in earlier lines of treatment and to be delivered in community outpatient settings, as well as

treat patients in diverse indications beyond cancer, such as autoimmune diseases.

Our Pipeline of Clinical Programs

We intend to initially focus

on advancing our CD19-Redirected ARTEMIS T Cell programs in relapsed/refractory and high-risk blood cancers.

Meanwhile, we are advancing

a robust pipeline for other hematologic malignancies, solid tumor and autoimmune disease.

Our commitment to safety, accessibility, and

cost-effectiveness positions us to redefine the T-cell therapy paradigm and deliver transformative solutions to more patients.

The following

chart summarizes our clinical programs:

Our Therapeutic Focus

Our primary focus is on developing

innovative therapies for CD19-positive cancers, a significant subset of hematologic malignancies with high unmet medical needs.

approved therapies, such as Kymriah® (Novartis) and Yescarta® (Kite Pharma), have demonstrated efficacy in relapsed or refractory

B-cell malignancies but face limitations due to:

High rates of Cytokine Release Syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), often

requiring hospitalization and intensive management.

Complex and individualized manufacturing processes that result in significant financial burdens.

Limited availability in specialized tertiary care centers.

EB103 aims to address these challenges by enhancing safety, scalability, and accessibility.

Its excellent safety

profile allows for broader patient eligibility, including individuals with comorbidities or advanced age and potentially expands

treatment access to community settings.

Our streamlined production process also enables us to lower the cost of manufacturing.

Opportunities for Increasing Total Accessible

Market (TAM) for Blood Cancers with a Best-in-Class CD19 T-cell Therapy

Hematological Cancers

Hematological cancers, or

blood cancers, are cancers that begin in blood-forming tissues, such as the bone marrow, or in the body’s immune cells.

of hematologic cancers are leukemia, lymphoma, and multiple myeloma.

Leukemia is a broad term for cancers of the blood cells.

of leukemia depends on the type of blood cell that becomes cancerous and whether it grows quickly or slowly.

The National Cancer Institute

estimates that there will be over 60,000 new cases of leukemia in the United States in 2022, representing approximately 3.2% of all new

cancer cases.

(NCI) estimates 66,890 new cases of leukemia in the United States in 2025, representing approximately 3.3% of

all new cancer cases.

B-cell lymphoma is a type of cancer that forms in B-cells (a type of immune system cell).

B-cell lymphomas may be either

indolent (slow-growing) or aggressive (fast-growing).

Non-Hodgkin lymphoma (NHL) has an incidence rate of 19.0 per 100,000 per year and

B-cell lymphomas may be

either indolent (slow-growing) or aggressive (fast-growing).

NCI estimates 80,350 new cases of non-Hodgkin lymphoma (NHL) in 2025, and

B-cell lymphomas make up most (about 85%) of NHL in the United States.

2 unchanged sentences

(DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL).

field of immunotherapy has evolved rapidly over the past few decades, and we believe that we are positioned to build upon previous research

to harness the potential of immunotherapy to drive significant advances in cancer treatment.

T-cells are white blood cells in the body’s

immune system that fight infections and tumor cells.

T-cells also act to signal other immune cells to respond to threats.

ideally suited for immuno-oncology applications based on several characteristics.

T-cells recognize their targets because they are created

in a way that allows them to specifically recognize foreign antigens on the surface of other cells.

T-cells are extremely specific, able

to recognize a cancer cell and kill it, while ignoring an almost identical healthy cell.

However, tumor cells sometimes evolve to escape

killing by T-cells by activating a number of pathways that suppress T-cell function.

The goal with T-cell immunotherapy is to reprogram

a patient’s own T-cells so that the T-cells can seek out and destroy cancer cells wherever they are hiding in the body, despite

normal tumor suppressive mechanisms.

T-cell therapy is also referred to as T-cell transfer therapy, adoptive cell therapy, adoptive immunotherapy

and immune cell therapy.

therapies involve collecting a patient’s own T-cells, growing large numbers of these T-cells in a lab, and then giving the cells

back to the patient through a needle in the patient’s vein.

During the process of growing a patient’s T-cells in a lab environment,

a patient may have treatment with chemotherapy and, maybe, radiation therapy to eliminate other immune cells, as reducing the patient’s

immune cells can help the transferred T-cells to be more effective.

type of T-cell therapy for treating cancer, CAR-T cell therapy, uses T-cells reprogrammed to express chimeric antigen receptors (CAR)

directed at a certain target (“CAR-T cells”), allowing the CAR-T cells to attach to specific proteins on the surface of cancer

cells, improving their ability to attack the cancer cells.

THERAPY PROCESS

and Development of T-cell Therapies

the past 20 years, using T-cells to treat cancer has moved from a radical ideal to clinical reality, with the first major successes occurring

around 2010, when small clinical trials produced dramatically positive results in fighting aggressive blood cancers.

The first T-cell

trials were conducted in the mid-1990s targeting HIV CAR-T cells — the initial class of T-cell therapy.

The effects of these first

trials to fight HIV were mild, but the effort ended with the creation of successful HIV drug cocktails and, importantly, revealed that

CAR-T-cells survived for more than 17 years in patients following treatment.

In the mid-2000s, clinical trials using CAR-T-cells to treat

solid tumors were largely unsuccessful.

A few years later, trials for CAR-T-cells that targeted a surface protein called CD19, which

is found only on the immune system’s B cells and mutate to cause certain types of leukemia and lymphoma, showed positive results

in three patients with leukemia.

Those trials, however, also had the unexpected result of triggering CRS, in which the reengineered T-cells

trigger the release of inflammatory signaling molecules called cytokines, causing severe fever, nausea, fatigue and body aches that can

be life-threatening.

Over the past decade, clinicians developed strategies to treat the side effects of T-cell therapies.

Still, because

of risks associated with CRS and ICANS, nearly all T-cell therapies to treat cancer must be administered at dedicated cancer centers.

data that accumulated in the mid-2010s from trials by pharmaceutical companies Novartis and Kite Pharma was compelling, and in 2017,

the FDA approved Novartis’ Kymriah™ for adult patients with relapsed or refractory follicular lymphoma after two or more

lines of systemic therapy and Kite Pharma’s Yescarta™ for patients with large-B-cell lymphomas whose cancer had progressed

after receiving at least two prior treatment regimens.

Since 2017, four additional CAR-T therapies have been approved by the FDA.

on T-cell Therapies

approvals of CAR-T therapies over the past five years demonstrate the viability of T-cell therapies as a new class of cancer immunotherapies.

Analogous to the advent of monoclonal antibodies, we believe that T-cell therapies have the potential to become some of the most impactful

cancer immunotherapy products over the next decade, but will first need to overcome certain limitations that have constrained widespread

use over the past five years.

In particular, we believe the existing classes of commercially approved T-cell therapies may be unable

to realize their full potential due to the following limitations:

Limitations of Currently Approved T-cell

The approvals of CAR-T therapies

over the recent years demonstrate the viability of T-cell therapies as a new class of cancer immunotherapies.

Analogous to the advent

of monoclonal antibodies, we believe that T-cell therapies have the potential to become some of the most impactful cancer immunotherapy

products over the next decade, but will first need to overcome certain limitations that have constrained widespread use:

● Hyperactivation

of T-Cells Resulting in Severe Toxicities.

The uncontrolled activation of T-cells

can lead to CRS.

Currently marketed CAR-T therapies include a boxed warning citing fatal

or life-threatening risks of CRS and ICANS.

We believe these severe toxicity risks will likely

limit the incorporation of these therapies into earlier lines of therapy and their adoption

in community outpatient settings.

The uncontrolled activation of T-cells can lead to CRS.

Currently marketed CAR-T therapies

include a boxed warning citing fatal or life-threatening risks of CRS and ICANS.

We believe these severe toxicity risks will likely limit

the incorporation of these therapies into earlier lines of therapy and their adoption in community outpatient settings.

Costs and Consequences of Toxicities.

CRS and ICANS are very costly side effects

The risk of these occurrences results in standard treatment protocols that can

add significant indirect costs on top of direct reimbursement costs and are burdensome to

patients and the healthcare system overall.

Experimental clinical strategies aimed at mitigating

these risks include utilization of restrictive enrollment screening criteria to reduce the

potential for CAR-T related toxicities.

Such screening tactics would decrease the number

of patients eligible for these therapies and could also increase the overall burden and cost

of treatment.

CRS and ICANS are very costly side effects to manage.

The risk of these occurrences results

in standard treatment protocols that can add significant indirect costs on top of direct reimbursement costs and are burdensome to patients

and the healthcare system overall.

Currently, the average cost of standard CAR-T cell treatment plans is approximately $400,000.

in the Treatment of Solid Tumor Cancers.

Due to its ability to target cancer-specific

intracellular antigens, the currently preferred T-cell therapy platform to target solid tumors

is engineered T-Cell Receptor T-cells, or TCR-T.

Due to its ability to target cancer-specific intracellular antigens, the currently preferred

T-cell therapy platform to target solid tumors is engineered T-Cell Receptor T-cells, or TCR-T.

However, TCR-T therapies face the following

(i) T-cell receptors, or TCRs, have a suboptimal affinity for their target antigens;

(ii) enhancing TCRs’ affinity for therapeutic purposes can introduce off-target toxicity;

(ii) enhancing TCRs’ affinity

for therapeutic purposes can introduce off-target toxicity;

and (iii) engineered TCRs can mis-pair with endogenous TCRs, leading to cross-reactivity

with unknown consequences.

believe that EB103 and EB104 have the potential to overcome these limitations through providing a more selective immune response, limiting

According to Grand View Research,

the global CAR T-cell therapy market size was estimated at $5.82 billion in 2025 and is projected to reach $22.36 billion by 2033, growing

at a compounded annual growth rate of 18.06% from 2026 to 2033.

However, currently only about 20% of eligible patients are treated by

current CAR-T therapies, due to their various limitations described above.

We believe that EB103 and EB104 programs have the potential to

overcome these limitations and capture the vast majority of untapped TAM through providing a more selective immune response, limiting

tertiary costs associated with side effects of treatment, and attacking solid tumors with a “mark and kill” strategy.

opportunities in expanding the curative capacity of T-cell therapy to autoimmune diseases

diseases occur when the immune system, which normally defends the body against harmful invaders, mistakenly attacks healthy tissues.

These diseases can affect various organs, leading to chronic inflammation, tissue damage, and in some cases, life-threatening complications.

Common examples include systemic lupus erythematosus (SLE), rheumatoid arthritis, and multiple sclerosis.

The cause is often an overactive

immune response, particularly involving autoreactive B cells that produce antibodies targeting the body’s own tissues.

treatments for autoimmune diseases have focused on controlling symptoms and slowing disease progression.

B-cell depletion therapies,

such as CD20-targeting antibodies (e.g., Rituximab, Ocrelizumab) and BAFF inhibitors (e.g., Belimumab), have provided some relief for

conditions like lupus and multiple sclerosis.

Emerging opportunities in expanding the

curative capacity of T-cell therapy to autoimmune diseases

Autoimmune diseases occur

when the immune system, which normally defends the body against harmful invaders, mistakenly attacks healthy tissues.

These diseases can

affect various organs, leading to chronic inflammation, tissue damage, and in some cases, life-threatening complications.

Common examples

include systemic lupus erythematosus (SLE), rheumatoid arthritis, and multiple sclerosis.

The cause is often an overactive immune response,

particularly involving autoreactive B cells that produce antibodies targeting the body’s own tissues.

Traditional treatments for

autoimmune diseases have focused on controlling symptoms and slowing disease progression.

B-cell depletion therapies, such as CD20-targeting

antibodies (e.g., Rituximab, Ocrelizumab) and BAFF inhibitors (e.g., Belimumab), have provided some relief for conditions like lupus and

multiple sclerosis.

These therapies aim to reduce the number of autoreactive B cells.

However, they have limitations.

Most existing treatments only manage symptoms and are rarely curative.

Long-term administration is often required, and patients may experience

serious side effects, while the underlying disease continues to progress or return.

believe CD19-redirected T-cell therapy offers a promising new approach to treating autoimmune diseases.

In recent clinical studies, CD19-redirected

CAR T-cell therapy has shown the potential to go beyond symptom management by depleting the entire population of autoreactive B cells,

leading to rapid and durable disease remission.

A notable study in lupus patients demonstrated that a single dose of CD19-targeting CAR

T-cells resulted in significant improvements, with most patients entering remission and experiencing long-lasting benefits.

are expanding our clinical investigation of our CD19-redirected ARTEMIS T-cell therapy into autoimmune diseases.

Our EB201 program, in

preclinical development, is being explored as a potential therapeutic approach targeting Systemic Lupus Erythematosus (SLE).

Cell Receptor Platform

has granted us an exclusive license relating to targeted T-cell therapies, which we are developing, in the Licensed Territory.

using Eureka’s ARTEMIS ® ( A ntibody R edirected T -Cells with E ndogenous M odular

I mmune S ignaling) platform technology to develop such targeted T-cell therapies.

The ARTEMIS ® platform builds

on successes of current CAR-T therapies by using T-cells engineered to use a cellular mechanism more closely resembling one from an endogenous

T-cell receptor, producing a more natural and restrained immune response.

key units of ARTEMIS ® T-cells comprise of an antibody-T-cell-receptor (AbTCR) and a co-stimulatory molecule.

serves as the core component featuring a target-binding domain derived from an antibody fragment antigen-binding (Fab) region and an

effector domain derived from portions of a human gamma/delta (γδ) TCR.

Given that the AbTCR includes portions of a human

TCR, the AbTCR by its nature associates with the endogenous CD3 complex.

This enables the AbTCR to use the same activation and regulatory

pathways employed by natural TCRs.

The co-stimulatory molecule is an additional key component featuring a target-binding domain derived

from a single-chain variable fragment (scFv) and co-stimulatory domain derived from portions of a human co-stimulatory receptor.

preclinical data from Eureka’s 2018 paper published in Cell Discovery (the “2018 Paper”), ARTEMIS ®

T-cells expressing an AbTCR construct targeting CD19 functionally matched the potency of CAR-T cells, but released lower levels

of cytokines upon the killing of target-positive cells in both in vitro and tumor xenograft mouse models.

The 2018 Paper explored ARTEMIS ®

T-cells expressing only the AbTCR receptor, as the co-stimulatory molecule was added (and the current form of EB103 was created)

in late 2018.

conducted the study at Children’s Hospital of Philadelphia (CHOP) and Lumigenics (Richmond, CA) using female NSG mice aged eight

to ten weeks.

To compare the phenotypes between AbTCR-T cells and CAR-T cells, Eureka engineered a single-chain variable fragment and

fused it with a widely-used CAR T-cell (also called a “second generation” CAR T-cell).

This allowed Eureka to evaluate AbTCR-T

cells in comparison to an existing CAR-T platform that is widely used clinically.

T-cell manufacturing, AbTCR-T cells expanded with similar growth kinetics as the CAR T-cells and yielded T-cell populations with similar

transduction efficiencies and the composition of CD4+ T-cells and CD8+ T-cells, which are subsets of T-cells, which is a well-accepted

metric for evaluating the subsets of manufactured T-cells.

and CAR T- were cultured and the number of cells determined at the indicated time points.

(b) Proportions

of CD4/CD8 within receptor+ cells.

Retrospective

analysis from published CAR-T clinical studies have found that T-cells that are more naive, less differentiated, and less exhausted correlate

with improved efficacy.

After T-cell “expansion”, where T-cells proliferate multiple times during an immune reaction to fight

disease, but before antigen engagement, AbTCR-T cells in the study displayed a more naive and stem cell memory T-cell phenotype compared

to the CAR T-cells.

of naïve (CCR7+ CD45RA+), central memory (CM;

CCR7+ CD45RA−), effector memory

CCR7- CD45RA-) and effector (E;

CCR7- CD45RA+) T cells within CD8+ receptor+ cells.

(d) Frequency

of stem cell memory (SCM;

CCR7+ CD45RO- CD95+ CD122+) T cells within CD8+ receptor+ cells.

together with the shifts in increased CD28, which is a protein expressed on T-cells that provides co-stimulatory signals required for

T-cell activation, and lower granzyme B, which is a biomarker of immune cell activation, on CD8+ AbTCR-T cells, the increased CCR7 (a

biomarker for naïve and stem cell memory T-cells) expression indicates that T-cells engineered with AbTCR are less differentiated.

Furthermore, expression of programmed cell death-1 (“PD-1”) and T-cell immunoglobulin mucin-3 (“TIM-3”), which

are both markers of T-cell exhaustion, and TIM-3 were lower on AbTCR-T cells than in CAR-T cells.

(e) Expression

of T cell differentiation markers CD28, CCR7, and granzyme B.

(f) Expression

of T cell exhaustion markers PD-1, LAG-3, and TIM-3.

next characterized the T-cell phenotypes resulting from activation through the AbTCR.

Eureka co-incubated the CAR T-cells with Raji cells,

which are from a human B lymphoblastoid cell line originally derived from a patient with Burkitt Lymphoma.

The Raji cells were either

CD19-positive (“CD19+”) cells or cells in which CD19 was not present, or “knocked out” (“CD19ko”)

using CRISPR technology, which allows for genetic material to be added, removed, or altered.

Upon engagement with CD19+ cells, the AbTCR

T-cells expressed activation markers CD69 and CD25, demonstrating the ability of the ET190L1-AbTCR to trigger T-cell activation in an

antigen-dependent manner.

accumulation of CD107a, a marker for T-cell degranulation following stimulation, was determined as a measure of cellular degranulation,

a prerequisite for T-cell-mediated bursting of tumor cells, or cytolysis.

T-cells degranulated when the AbTCR was stimulated with CD19+

addition, when AbTCR-T cells were co-incubated with CD19+ cells, the analysis with intracellular flow cytometry showed that cytokines,

such as TNFα, IL-2, and IFNγ, are induced in response to CD19 antigen.

Importantly, no cytokines were produced when the AbTCR-T

cells were co-cultured with CD19ko cells.

These data demonstrate the ability of the AbTCR to trigger T-cell activation in an antigen-dependent

better characterize the activities of AbTCR-T cells, Eureka set up experiments to directly compare phenotypes of the AbTCR-T cells with

the CAR-T cells.

The percentage of AbTCR-positive and CAR-positive T cells were matched by dilutions with un-transduced mock T-cells

and co-cultured with multiple tumor cell lines.

were incubated with target cells for 16 hours at an effector to target ratio of 2:1.

Cytotoxicity was measured by lactate dehydrogenase

release assay (n = 3 technical replicates).

lysis, or disintegration, of only CD19+ tumor lines confirmed the antigen specificity of both the AbTCR-T cells and CAR-T cells while

demonstrating comparable cellular cytotoxicity and degranulation.

In addition, specific lysis across a range of effector to target (“E:T”)

ratios, or ratios of AbTCR T-cells versus tumor cells, also showed comparable T-cell killing at low E:T ratios, further demonstrating

the cytotoxic potential of using the AbTCR.

capacity of therapeutic T-cell in leukemia patients has been reported to be a key predictive biomarker for clinical efficacy.

used a fluorescent dye-based (or CFSE-based) assay to assess in vitro T-cell proliferation upon antigen stimulation.

As shown in the

graphic below, AbTCR-T cells divided in response to antigen with kinetics comparable to that observed with CAR-T cells.

a slight increase in the expression of CD69 and CD25 activation markers, which show T-cell activation levels, on tumor stimulated AbTCR-T

cells compared to CAR-T cells, AbTCR CD4+ T-cells expressed lower levels of the PD-1 exhaustion marker, than CAR-T CD4+ cells, and, in

both CD4+ and CD8+ AbTCR-T cells, lymphocyte-activation gene 3, or LAG-3, which is an immune checkpoint receptor protein found on the

cell surface of T-cells that has been found to inhibit the activation of T-cells and suppress immune response, was lower.

while AbTCR-T cells have comparable cytotoxicity and proliferative potential compared to existing CAR-T cells, the AbTCR-T cells released

lower levels of inflammatory cytokines, including TNF-α, IL-2, IFN-γ, and GM-CSF, after a 16 hour in vitro killing test.

between TCR-T and CAR-T cells have previously shown that activation through the TCR can comparatively reduce cytokine release while simultaneously

increasing antigen sensitivity.

Although the CAR construct incorporates a covalently-linked CD28 costimulatory domain, Raji cells express

CD80 and CD86 and thus provide CD28 costimulation to both CAR-T cells and AbTCR-T cells.

The study suggests that the cytokine secretion

and exhaustion differences between AbTCR and CAR-T cells stem from the utilization of endogenous signaling pathways by the γδTCR

effector domain of the AbTCR receptor.

the potential of AbTCR-T cells to reduce the secretion of several inflammatory cytokines has exciting clinical possibilities, the discovery

that tocilizumab, an anti-IL6R antibody, alleviates CRS pathology, singles out interleukin 6 receptors (IL6R) with particular clinical

significance.

Because the majority of IL-6 is produced by antigen-presenting cells, including monocytes, macrophages, and dendritic cells,

Eureka performed a co-culture assay to measure IL-6 concentrations.

The experiment separated T-cells and tumor cells from monocyte-lineage

Next, the AbTCR-T cells were compared to one of the anti-CD19 CAR-T cells that had been extensively studied and FDA-approved (CTL019,

a research grade version of Kymriah™).

In addition, CTL019 uses CD137 (4-1BB), a costimulatory receptor, for costimulation, thus

offering an opportunity to compare the AbTCR to a CD137-based CAR-T cell.

to the observed differences in cytokine release between the AbTCR-T cells and CAR-T cells, the AbTCR-T cells released lower levels of

TNF-α, IL-2, IFN-γ, GM-CSF compared to CTL019-T cells.

In the figure below, the purple bar indicates CTL019 targeting NALM-6

(B cell precursor leukemia) plus APCs (monocyte-lineage cells).

The green bar indicates AbTCR T cells targeting NALM-6 plus APCs.

blue bar indicates plain T cells (without engineering) targeting NALM-6 plus APCs.

study found that AbTCR-T cells induced monocyte-lineage cells to release substantially less IL-6 than CTL019-T cells.

To test if the

reduced cytokine release had an effect on in vivo anti-tumor activity, Eureka used AbTCR-T cells to treat a patient-derived xenograft

(PDX) mouse model of primary B-ALL (CHP105R1, which has fewer cytokines due to lack of CD28 ligand for co-stimulation) and observed similar

tumor inhibition between mice treated with the AbTCR and CTL019-T cells.

consistent with the in vitro studies described above, the study concluded that T-cells engineered with AbTCR reduced cytokine release

without a loss of anti-tumor activity in a PDX tumor model that lacked CD80 and CD86 costimulation.

study next tested the in vivo anti-tumor activity of the AbTCR-T cells in an established human CD19+ Raji B-cell lymphoma xenograft model.

As shown in the figures below, the study found that both the AbTCR and ET190L1 T-cell treatments resulted in tumor regression and long-lasting

tumor rejection.

At the time when mice treated with mock T-cells had to be euthanized, tumor burden was on average approximately 1000-fold

less in mice treated with ET190L1 T-cells than in the mock-treated mice and on average approximately 5300-fold less in mice treated with

AbTCR-T cells than in the mock arm in the experiment.

The figure below shows bioluminescent images (left) and total flux (right) over

time of three groups of six to eight Raji-implanted mice intravenously administered with 5 × 10 6 (1) un-transduced donor-matched

T-cells (“Mock”), (2) ET190L1-CAR-T cells (“CAR”), or (3) AbTCR-T cells (“AbTCR”).

Doses were based

on number of receptor-positive cells.

ability of persisting AbTCR-T cells to prevent growth of “newly-introduced” tumor cells was tested by re-injecting mice with

tumor cells weeks after the T-cells had cleared the initial tumor burden.

While tumors grew rapidly in control mice, two to three mice

in each of the six groups treated previously with either AbTCR-T cells or CAR-T cells were resistant to Raji lymphoma re-challenge (left).

Furthermore, a set of two to three mice in each of the six groups were re-challenged with NALM-6 cancer cells (right), which is CD80

and CD86 negative.

The resistance of tumor growth showed that AbTCR T-cells can be used for tumor types which do not express CD28 relevant

study found that in vivo cytokine release and exhaustion markers on T-cells recapitulated in vitro findings.

Whereas ET190L1 T-cell treatment

caused marked elevation of inflammatory cytokines, including IL-2, IL-10, IFN-γ, and TNF-α, lower levels of these cytokines

were released following AbTCR treatment.

Serum cytokine levels were collected and measured from six to eight Raji-bearing mice 24 hours

after T-cell dosing.

collected from peripheral blood nine days and 15 days post-T-cell dosing also revealed that AbTCR-T cells expressed lower levels of PD-1

than CAR-T cells.

PD-1 expression levels (measured by mean fluorescent intensity) are shown below on the CAR-T cells and AbTCR T-cells

at select times from six to eight Raji-bearing mice after T-cell infusion.

Collectively,

the data from the study suggested that AbTCR T-cells exhibited potent in vitro and in vivo anti-tumor activity, yet released lower levels

of inflammatory cytokines and expressed lower levels of exhaustion markers than CAR-T cells.

the study, to further augment AbTCR signaling, Eureka subsequently optimized the ARTEMIS ® cell receptor platform to include

the co-stimulatory molecule.

Importantly, the co-stimulatory molecule is provided as a separate molecule and not directly fused to the

This is in contrast to conventional CARs, which include the direct fusion of the target-binding domain to the co-stimulatory and

CD3ζ domains, which drives sustained T-cell activation and, often, subsequent release of large amounts of inflammatory cytokines.

Thus, unlike the linear CAR design of traditional CAR-T cell platforms, the configuration of the ARTEMIS ® cell receptor

platform resembles the endogenous TCR/co-stimulatory receptor architecture in which co-stimulation is provided through separate receptors

and acts as a potent synergistic signal that is naturally regulated by the body.

the manufacturing process, our EB103 T-cells are engineered to express ARTEMIS ® cell receptors (i.e., the AbTCR and co-stimulatory

molecule) on their cell surfaces.

Both the AbTCR and co-stimulatory molecule of EB103 are designed to recognize and bind the CD19 antigen.

The resulting EB103 T-cells are expanded and then cryopreserved for delivery into the patient.

Once infused, EB103 T-cells engage CD19-positive

cancer cells.

The AbTCR expressed on the EB103 T-cell by its nature associates, via its effector domain (γδ TCR chains),

with the endogenous CD3 complex.

When the AbTCR binds to its target, CD19, expressed on the cancer cell, AbTCR/CD3 complex-mediated signal

transduction within the EB103 T-cell is initiated.

This signal transduction process ultimately leads to the activation of the EB103 T-cell.

A second “enhancement” signal is generated when the co-stimulatory molecule expressed on the EB103 T-cells binds to its target,

CD19, expressed on the cancer cell.

The main function of the co-stimulatory molecule is to “boost” AbTCR signaling, resulting

in increased expansion and survival of EB103 T-cells inside the body.

The co-stimulatory molecule has also been optimized to provide

EB103 T-cells with enhanced T-cell activation.

In summary, EB103 T-cells seek out CD19-positive cancer cells, bind to these cells, and

destroy them.

Clinical Studies

Affiliated Investigator-Initiated Study

November 2018 to April 2021, the First Affiliated Hospital of Xi’an Jiaotong University (“First Affiliated”) conducted

an exploratory, single-arm, open-label, non-randomized early investigator-initiated study (“IIS”) to assess the safety and

feasibility of administering EB103 T-cells to patients with CD19-positive relapsed/refractory(r/r) B-cell lymphoma.

Unlike studies conducted

by pharmaceutical companies, IISs are clinical studies initiated and managed by nonpharmaceutical company researchers who could be an

individual investigator, an institution, or a group of institutions, a collaborative study group, or a cooperative group.

this case, IIS studies are exploratory in nature.

Generally, IISs are reviewed and approved by review boards or ethics committees at

First Affiliated sponsored the IIS study in collaboration with Eureka and conducted the study at First Affiliated.

provided EB103-related information to support the IIS study application and gave comments to the investigator on the IIS study design

and clinical protocol.

The Ethics Committee of First Affiliated reviewed preclinical data and approved the clinical protocol.

was registered at www.clinicaltrials.gov as #NCT03642496.All participants in the study provided written informed consent.

study results were published in 2022 in the Journal of Cancer Research and Clinical Oncology.

were eligible for the study if they had histologically confirmed CD19-positive r/r B-cell lymphoma.

Previous therapy must have included

at least one cycle of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or a similar R-CHOP, like chemotherapy.

Eligibility also required measurable disease as defined by at least one measurable node of which the longest diameter (LDi) is greater

than 1.5 cm or at least one measurable extra nodal lesion of which the LDi is greater than 1.0 cm.

In addition, an Eastern Cooperative

Oncology Group (ECOG) performance status, which is used by doctors and researchers to assess how a patient’s disease is progressing,

how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis, of less than or

equal to two was required.

primary endpoints included the tolerability of EB103 T-cell therapy and the cellular kinetics (i.e., expansion and persistence, which

refers to the number of T-cells and continuous presence of T-cells in vivo after infusion) of EB103 T-cells after infusion.

endpoints and other terms used in the study are explained below:

Response (CR):

The disappearance of all signs of cancer in response to treatment.

also called complete remission.

For tumor assessments after EB103 treatment, a CR indicated

the disappearance of measurable disease via computerized tomography (CT) scan or residual

masses that are positron emission tomography (PET)-negative.

Response (PR):

A decrease in the size of a tumor, or in the extent of cancer in the body,

in response to treatment.

It is also called partial remission.

For tumor assessments after

EB103 treatment, a PR indicates at least 50% decrease in tumor burden with ongoing PET avidity.

Response Rate (ORR):

The proportion of patients with a complete response (CR) or partial

response (PR) to treatment.

of Response (DoR):

the length of time that a tumor continues to respond to treatment without

the cancer growing or spreading.

For tumor assessment after EB103 treatment, DoR is the time

from the first documented disease response (CR or PR) to the date of first documented progression

A decrease in or

disappearance of signs and symptoms of cancer.

In partial remission, some, but not all, signs and symptoms of cancer have

In complete remission, all signs and symptoms of cancer have disappeared, although cancer still may be in the

Cancer that is neither decreasing nor increasing in extent or severity.

● Progressive

Cancer that is growing, spreading, or getting worse.

assessments were conducted at one, two, three, six, nine, 12, 18, and 24 months after initial infusion and response to treatment was

assessed by the principal investigator and radiologist according to the Lugano Classification 2014 (“Lugano Criteria”), which

is the most recent guideline to assess the presence of lymphoma, measure response to therapeutics intervention, and evaluate imaging

and clinical data.

By the Lugano Criteria, a CR indicates the disappearance of measurable disease via computerized tomography (CT) scan

or residual masses that are positron emission tomography (PET)-negative.

PR indicates at least a 50% decrease in tumor burden via PET

November 2018, and April 2021, 16 patients were enrolled, and a total of 12 patients received EB103 T-cells.

Four patients did not receive

an infusion because of an inability to manufacture T-cells as a result of the patient’s poor T-cell activation (one patient), high

tumor burden (one patient), or active infection (two patients).

As of the data cutoff date in April 2021, the median duration of follow-up

was 128 days (range:

34 to 728 days).

Of the 12 patients treated, six patients (50%) achieved a CR, and four (33%) achieved a PR, with

a best ORR of 83%.

CRs were durable, including two patients with ongoing CRs for over 22 months.

was well-tolerated by patients in the IIS study.

No patients experienced severe (grade > 3, based on the standards set by the

American Society for Transplantation and Cellular Therapy) CRS, and only one patient experienced ICANS of any grade.

In addition, heightened

elevations of cytokine levels were not seen, even in patients with a marked expansion of EB103 T-cells.

For the small patient population

size, a P-value is not available.

additional studies are required to confirm the results of this small, exploratory IIS study, the findings are consistent with the design

of the ARTEMIS ® platform as a potential alternative to other engineered T-cell therapies, such as CAR T-cell therapies.

The results from this early IIS study were disclosed to the FDA as supplementary supporting information for the IND application of EB103

in malignant B-cell lymphoma treatment.

Responses to EB103

(a) Treatment

response and duration of response after initial infusion of EB103 T-cells.

Black arrows indicate

ongoing remission and follow-up.

(b) Best response for the 12 patients.

Best response was

defined as the best response (i.e., CR > PR > SD > PD) the patient achieved at any

time after receiving EB103.

CR — complete response, PR — partial response, SD

— stable disease, PD — progressive disease.

of two responders (BH05-P10 and BH05-P19) at baseline and the indicated time points after

Red or yellow arrows mark the tumor lesions.

Full body images are PET-CT scans.

Cross-sectional

images are PET scans (top rows) and CT scans (bottom rows).

black, 20 cm;

of cytokines and serum inflammatory markers after EB103 T-cell infusion

(b) Serum c-reactive protein (CRP) and ferritin levels in patients during the first

month of EB103.

Horizontal lines denote median values.

Patients’ best responses are

denoted by color of the symbols:

CR (red), PR (blue), SD (green), and PD (black).

Hospital Clinical Study

July 2019 to August 2022, Union Hospital affiliated to Huazhong University of Science and Technology in Wuhan, China (“Union Hospital”),

in collaboration with Eureka, conducted the first-in-human, single-center investigator-initiated study designed to evaluate the safety

and efficacy of EB103 T-cells in patients with CD19 malignancies.

Eight patients with relapsed or refractory diffuse large B-cell lymphoma

(RR DLBCL) were reported in the study.

The Medical Ethics Committee of Union Hospital approved the study.

The study was performed at

Union Hospital in Wuhan, China.

The study was registered at www.clinicaltrials.gov as #NCT04014894.

The study results were published

on January 21, 2023 in the Journal of Hematology & Oncology.

collaborated with Union Hospital to support the study.

The fully human anti-CD19 antibody was selected from Eureka Therapeutics E-ALPHA ®

phage display library.

Cheng Liu, Eureka’s President, CEO and Chairman, and Qi Chang, an employee of Eureka, supervised

EB103 production and conducted the preclinical research.

Cheng Liu and Qi Chang are two of the twenty-one listed authors of the report,

and each’s employment by Eureka was disclosed as a competing interest.

No other competing interests were declared.

and Exclusion Criteria

inclusion criteria for the study were as follows:

(i) patient or his or her legal guardian voluntarily participates in and signs an informed

consent form;

(ii) male or female, aged 18 to 75 years;

(iii) pathologically confirmed CD19+ B-cell malignancies, and patients met the

following criteria for refractory or relapsed B-cell malignancies:

(a) refractory/relapsed B-cell lymphoblastic leukemia (meeting one

of the following):

(1) recurrence within six months after first remission;

(2) primary refractory disease which cannot achieve complete

remission after two cycles of standardized chemotherapy regimen;

(3) failure to achieve complete remission or relapse after one line

or multiple lines of salvage chemotherapy;

or (4) not suitable for hematopoietic stem cell transplantation (HSCT), abandonment of HSCT

due to various restrictions, or relapse after HSCT;

or (b) refractory/relapsed B-cell lymphoma (meeting one of the following three items

plus item four):

(1) tumor shrinkage less than 50% or disease progression after four cycles of standard chemotherapy or (2) achieved

complete remission after standard chemotherapy, but relapsed within six months or (3) two or more relapses after complete remission plus

(4) subjects must have received adequate treatment in the past, including anti-CD20 monoclonal antibody and combination chemotherapy

with anthracyclines;

(iv) having a measurable or evaluable lesion:

(a) patients with lymphoma require a single lesion greater than or

equal to 15 mm or two or more lesions greater than or equal to 10mm or (b) patients with leukemia require persistent positive or positive

relapse of bone marrow MRD;

(v) patient’s main organs functioning well:

(a) liver function:

ALT/AST less than or equal to 3 times

the upper limit of normal (ULN) and total bilirubin less than two times ULN;

(b) renal function:

creatinine less than 220μmol/L;

pulmonary function:

indoor oxygen saturation greater than or equal to 95% and (d) cardiac function:

left ventricular ejection fraction

(LVEF) greater than or equal to 50%;

(vi) greater than or equal to two weeks since prior therapy at the time of enrollment, and the toxicity

related to previous treatments returned to less than grade 1 (except for low grade toxicity such as alopecia);

(vii) ECOG score less

than or equal to two;

and (viii) estimated survival time greater than or equal to three months.

exclusion criteria for the study were as follows:

(i) women who are pregnant or breastfeeding;

(ii) women of child-bearing potential

and all male participants can’t use effective methods of contraception for at least 12 months following infusion;

(iii) patients

fail to collect enough PBMC;

(iv) patients with other uncontrolled diseases, such as active infection;

(v) active hepatitis B or active

(vi) known HIV positive patients;

(vii) patients with active autoimmune diseases requiring systemic immunosuppressive therapy;

(viii) participants with other active malignancies (except non-melanoma skin cancer and cervical cancer) within three years;

(ix) patients

with severe mental disorder or disorders of consciousness;

(x) patients who need immediate treatment to control tumor progression or

relieve tumor burden;

(xi) patients participated in other clinical treatments within six weeks;

(xii) patients with drug addiction;

(xiii) patients with poor treatment compliance.

primary objectives were incidence of adverse events (AEs) and ORR.

CRS and ICANS were graded using the American Society for Transplantation

and Cellular Therapy consensus grading.

All other AEs were graded according to the Common Terminology Criteria for Adverse Events.

Dose-limiting

toxicities (DLTs) were defined as EB103-related AEs within 30 days after infusion and included ≥ grade 3 cardiac, hepatic, pulmonary,

and renal toxicities, and ≥ grade 3 CRS and ICANS that lasted over 72 hours after treatment.

Exceptions to this definition were not

counted as a DLT.

Response was assessed using the Lugano Criteria.

secondary objectives included Duration of Response (DoR), progression-free survival (PFS), overall survival (OS), and expansion and persistence

of EB103 T-cells, and serum cytokines in the peripheral blood (PB) after infusion.

PB refers to the blood circulating in the body’s

blood vessels.

DoR, PFS, and OS were defined per the revised response criteria for malignant lymphoma.

Under the criteria, DoR is defined

as from the time when criteria for response (CR or PR) are met, for which the event is the first documentation of relapse or progression.

PFS is defined as the time from entry into a study until lymphoma progression or death as a result of any cause.

OS is defined as the

time from entry onto the clinical trial until death as a result of any cause.

Only the first infusion was included in the main analyses

of safety and efficacy.

Exploratory endpoints included the safety and efficacy among patients retreated with EB103 T-cells.

and pathological examination

F-fluorodeoxyglucose

positron emission tomography-computed tomography (PET-CT), computed tomography (CT), magnetic resonance imaging (MRI), cerebrospinal

fluid (CSF) assessment, and biopsies were performed on the patients following the Lugano Criteria.

The assessments of tumor tissue were

conducted and reviewed by two independent pathologists.

eight patients who received the infusion were included in the analyses.

Descriptive statistics include means with 95% confidence interval

(CI) or medians with minimum and maximum (range) for continuous variables and counts and percentages for categorical variables.

data were not imputed.

Continuous variables were compared using paired t-test when the data were normally distributed.

Otherwise, the

Wilcoxon test was used.

DoR, PFS, OS, and associated 95% CI were determined by the Kaplan — Meier methods and compared with the

log-rank test between subgroups.

Analysis was performed using Graphpad Prism version 8.0.

P values less than 0.05 (two-tailed) were considered

eight patients experienced adverse events (AEs) of grade 3 or higher.

Three patients (37.5%) experienced grade 1 CRS that resolved spontaneously,

with a median onset of four days (range:

two to nine days) and a median duration of three days (range:

one to eight days).

developed grade 3 ICANS after CRS, which manifested as confusion, barylalia, tremor, and agitation, but Patient Two responded to treatment

with corticosteroids.

ICANS occurred on the ninth day following infusion and lasted for nine days;

thus, it was judged as a DLT.

from Patient Two, DLTs were not observed in the patient cohort.

Patient Eight had a pulmonary infection on day 15 that lasted for four

days after antibiotic treatment.

Other infectious complications were not observed within one month due to the administration of antiviral

and antifungal preventative medicines in these patients.

Patient Four had lymphoma involvement in the intestinal tract and suffered an

acute intestinal perforation, resulting in emergency surgery 16 days after infusion.

Ultimately, all acute AEs were reversible with supportive

an anti-IL6R antibody, which can alleviate CRS.

Was not administered.

The increase in inflammatory cytokines from baseline to peak were

modest, except for the elevation of IL6R levels in Patients Two, Four, and Eight, which were greater than tenfold the baseline value.

This elevation generally coincided with serum C-reactive protein levels and was concurrent with the onset of CRS and ICANS in Patient

Two, intestinal perforation in Patient Four, and pulmonary infection in Patient Eight.

Therefore, the study concluded that there might

be alternative causes for the elevated inflammatory markers in these three patients other than the EB103 treatment.

toxicities were the most common AEs, including low levels of white blood cells (neutropenia) and low levels of platelets of grade 3 or

4 in seven (87.5%), six (75%), and two (25%) patients after EB103 infusion, respectively.

Severe anemia was not observed.

The preconditioning

regimens exhibited significant adverse effects on leucocytes, lymphocytes, monocytes (all types of blood cells), and hemoglobin levels,

but not on platelets and neutrophils (a type of white blood cell).

The median time from infusion to recovery of ≤ grade 2 neutropenia

and leukopenia (low levels of leukocytes) was 13 days (range, four to 26) days and 13 (range, four to 26) days, respectively.

recovery from severe thrombocytopenia (platelet deficiency) was observed in Patient Two for over two months.

aplasia, defined as CD19+ B-cells representing less than three percent of lymphocytes in peripheral blood (PB), was observed in all patients

The preconditioning chemotherapy exhibited significant inhibition on T cells and NK cells (another type of immune cell)

in the PB, and EB103 cells showed effects on T cells.

CD4+ T cells and CD8+ T cells decreased significantly after the preconditioning

chemotherapy and expanded on day 14 after EB103 infusion.

Three patients (37.5%) had preexisting hypogammaglobulinemia, a disorder caused

by low serum immunoglobulin (a type of antibody) levels, defined as serum IgG less than 800 mg/dL, IgM less than 50 mg/dL, and IgA less

than 100 mg/dL.

Serum IgG, IgM, and IgA are all types of antibodies.

The reduction of serum IgG, IgA, and IgM after EB103 infusion was

observed in seven (87.5%), eight (100%), and six (75%) patients, respectively.

The recovery of serum IgG, IgA, and IgM to their normal

levels during follow-up was observed in three (42.8%), two (25%), and four (66.7%) patients respectively.

One experienced two treatable long-term AEs:

viral encephalitis at month 18 and MOG + encephalomyelitis at month 30.

At the time of these

AEs, EB103 cells were undetectable in the patient.

As such, the authors of the study believed that these delayed AEs were not directly

caused by EB103 cells.

the clinical study, clinical responses were achieved by 87.5% of patients, with 75% achieving CR and 62.5% having ongoing CR.

The Kaplan-Meier

estimated OS at 12-36 months was 75.0% (95% CI:

The Kaplan-Meier estimated progression-free survival (PFS) at 12-36 months

was 62.5% (95% CI:

22.9-86.1), with a DoR at 12-36 months of 71.4% (95% CI:25.8-92.0).

One with primary central nervous system lymphoma had been refractory to eight previous lines of therapies.

She experienced a continuing

CR for over three years after EB103 infusion.

Numerous EB103 cells were detectable in both the PB and CSF after infusion (See Figure

4B below), indicating that EB103 cells could sufficiently traffic from the periphery to the central nervous system.

Patient Two had extensive

lesions and attained a quick PR at month one, but the diseases progressed at month two.

A second tissue biopsy demonstrated DLBCL.

patient received a second infusion with poor expansion, and the diseases progressed on day 14;

consequently, the patient withdrew from

the study for other salvage therapy.

Patient Three had two major lesions in the right eyeball and the pelvic cavity, and she attained

a PR on day 14 and an ongoing CR for over two years.

Patient Four achieved a CR at month two and kept CR for over two years.

Five’s EB103 cells exhibited rapid clearance and durable control of a bulky tumor.

Patient Six, with lymphoma mainly in the abdominal

cavity, did not respond to EB103 treatment and withdrew from the study at month two.

Patient Seven had extensive lesions mainly in the

lung and the abdominal cavity and attained a CR at month five.

However, new lesions appeared at month nine, and a second infusion failed.

Patient Eight had two lymph node lesions in the left heart diaphragm angle and retroperitoneal space, and obtained a CR on day 24, and

kept durable CR at month 24.

Two, Five and Seven received a second infusion.

Patients Two and Seven received a second infusion as salvage therapy after disease progression

but did not respond.

Patient Five maintained CR according to the Lugano Criteria at month six, but PET-CT scans showed minimal residual

lesions in the hepatogastric space-pancreatic head.

Despite low levels of EB103 cells in peripheral blood, Patient Five received a repeated

infusion without preconditioning chemotherapy and experienced self-limiting severe neutropenia, leukopenia, and thrombocytopenia.

from hematologic toxicities observed in Patients Two and Five, no other adverse events were reported.

and persistence of EB103

being infused into a patient, EB103 cells showed maximum expansion between nine and 21 days.

At their peak, these cells reached a median

count of 318 cells per milliliter (mL) of PB, with a range of 32 to 4,308,109 cells/mL.

The number of EB103 cells in PB was determined

through flow cytometry, which is a technique used to measure the characteristics of cells.

Additionally, quantitative polymerase chain

reaction (qPCR) measurements showed a median count of 76,897 copies per microgram (µg) of genomic DNA with a range of 21,278 to

273,032 copies/µg.

qPCR is a method used to measure the amount of specific DNA sequences in a sample.

The median area under the

curve from day 0 to day 28 post-infusion was calculated to be 585,493.5 copies/µg × days.

This value represents the total

amount of EB103 cells present in the patient over time.

At the end of the first year following infusion, EB103 cells were still detectable

in PB in half of the patients.

However, expansion was poor during second infusions.

authors of the study concluded that the data suggest that EB103 T-cells represent a novel and potentially potent therapeutic option for

the patient population being studied.

However, the authors noted that the findings were limited by the small sample size, and a recommended

phase 2 dose was not identified.

The authors also stated that larger and multi-center trials are needed to verify the long-term safety

and efficacy of CD19-specific T cells in RR DLBCL.

are four figures from the clinical study report related to the findings described above.

in serum inflammatory markers within 1 month after EB103 infusion

Fold changes of inflammatory cytokines from baseline to peak (n = 10).

Patient Five received the repeated infusions in the outpatient

department and data were not available.

(B-I) Changes in the serum interleukin (IL)-6, C-reactive protein (CRP), IL-2, IL-4, IL-10, interferon-γ

(IFN-γ), tumor necrosis factor-α (TNF-α) and ferritin in individuals.

(J) Changes in serum IL-6, CRP, and EB103 counts

and copies in peripheral blood (PB) of Patients Two, Four, and Eight.

plot and long-term outcomes of the treated patients

Swimmer’s plot of the eight treated patients.

(B-D) Kaplan — Meier estimates of the OS, PFS and DoR.

responses of EB103 cells

Changes in cranial MRI scans of Patient One.

(B) EB103 copies per microgram (µg) of genomic DNA in PB and CSF and body temperature

changes in Patient One within one month after infusion.

(D) Changes in ocular enhanced MRI

and abdominal-enhanced CT of Patient Three.

(E) Changes in PET-CT scans of Patient Seven.

vivo kinetics of EB103 cells

EB103 expansion and persistence were measured as copies per microgram (µg) of the genomic DNA by qPCR in the eight treated patients

within one year.

The detectable threshold was 100 copies per µg of the genomic DNA.

The black arrow indicates the second infusion.

(B) The violin plot of peak EB103 cells per milliliter of PB (cells/mL PB) as measured by flow cytometry, peak copies per µg of

genomic DNA (copies/µg DNA) as measured by qPCR and area under the curve from 0 to 28 days after infusion (AUC 0 – 28d ).

However, most existing treatments only manage symptoms

and are rarely curative.

Long-term administration is often required, and patients may experience serious side effects, while the underlying

disease continues to progress or return.

We believe CD19-redirected

T-cell therapy offers a promising new approach to treating autoimmune diseases.

In recent clinical studies, CD19-redirected CAR T-cell

therapy has demonstrated the potential to go beyond symptom management by depleting the entire population of autoreactive B cells, leading

to rapid and durable disease remission.

A notable study in lupus patients demonstrated that a single dose of CD19-targeting CAR T-cells

resulted in significant improvements, with most patients entering remission and experiencing long-lasting benefits.

We plan to expand our clinical

investigation of our CD19-redirected ARTEMIS T-cell therapy into autoimmune diseases.

Our EB201 program, in preclinical development, is

being explored as a potential therapeutic approach targeting Systemic Lupus Erythematosus (SLE).

Our Technology Platform:

The ARTEMIS® T-Cell Receptor System

We hold an exclusive license from Eureka Therapeutics

(“Eureka”) to utilize the proprietary ARTEMIS® Cell Receptor platform to develop and commercialize T-cell therapies targeting

CD19 and CD22 for the treatment of hematologic malignancies.

Under our License Agreement, we hold exclusive rights to develop and commercialize

ARTEMIS-based products targeting CD19 and CD22 in all territories worldwide, excluding Greater China and Association of Southeast Asian

Nations (ASEAN) countries, which are retained by Eureka.

The ARTEMIS platform utilizes

an Antibody-T Cell Receptor (AbTCR) architecture designed to potentially overcome limitations associated with conventional chimeric antigen

receptor (CAR) T-cell therapies, such as toxicity and exhaustion.

Unlike conventional second-generation CAR-T therapies, which rely on

synthetic fusion proteins that can drive chronic hyperactivation (tonic signaling) and premature T-cell exhaustion, the ARTEMIS AbTCR

is designed to mimic the natural regulation of native T-cells by recruiting endogenous CD3 complex to initiate T-cell activation.

differentiating feature of our platform is that the co-stimulatory molecule is provided as a separate protein rather than being covalently

linked to the activation domain.

By separating these signals, the ARTEMIS platform is designed to mimic the body’s natural immune

regulation, potentially limiting T-cell hyperactivation.

Based on Eureka’s internal

and published studies in Cell Discovery 1 (with CHOP/UPenn) and Cell Reports Medicine 2 (with NCI),

we believe the ARTEMIS platform offers distinct advantages over conventional CAR-T constructs:

● Improved Safety Profile and Economic Potential :

head-to-head comparisons with market-standard CAR-T constructs, ARTEMIS T-cells demonstrated comparable or superior antitumor potency

with significantly reduced release of inflammatory cytokines, such as IL-6, which are drivers of cytokine release syndrome (CRS) and

neurotoxicity.

We believe this improved safety profile has the potential to allow for the administration of our therapies in outpatient

settings rather than dedicated cancer centers, thereby decreasing the costs associated with patient monitoring and hospital stays.

Discovery 4, 62 (2018):

doi:10.1038/s41421-018-0066-6

Reports Medicine 6, 102378 (2025) doi:

10.1016/j.xcrm.2025.102378.

● Efficacy in Low-Antigen Density Tumors :

CAR-T therapies often fail when tumor cells express low levels of target antigen, leading to tumor escape.

The NCI studies from 2025

(conducted with the ARTEMIS platform targeting GPC2 in solid tumors) demonstrated that ARTEMIS T-cells maintain cytotoxic function at

antigen densities below the threshold required to activate conventional CAR-T cells.

The ability for ARTEMIS T-cells to function at a

lower antigen level can potentially expand the addressable patient population and reduce the risk of relapse.

● Superior T cell Phenotype :

Preclinical data indicates

that the ARTEMIS architecture promotes the expansion of stem-like memory T-cells (T SCM ) and reduces exhaustion markers compared

to standard CAR-T constructs.

The T SCM subset of T cells have been reported to be associated with long-term persistence and

durability of clinical response.

US Phase I/II Clinical Trial of EB103

EB103 is our lead CD19-targeted

ARTEMIS® T-cell therapy product candidate designed to address high unmet medical needs in patients with relapsed or refractory aggressive

B-cell non-Hodgkin lymphoma (r/r B-NHL).

We are currently evaluating EB103 in an open-label, dose escalation, multi-center, Phase I/II

clinical trial in the U.S.

(STARLIGHT-1, NCT06343311) in adult subjects (≥ 18 years of age) with relapsed/refractory (R/R) B-cell NHL.

The study includes a dose escalation phase followed by an expansion phase.

A traditional dose escalation model was used to determine the

The trial began enrolling patients in 2024, with UC Davis Comprehensive Cancer Center as the first clinical site.

A second site

(Baylor Scott and White Research Institute in Texas) was activated in April 2025.

As of December 2025, the

Phase I dose escalation phase has been completed.

The enrolled patient population (n=9) was heavily pretreated, with a median of three

prior lines of therapy.

Approximately 80% of the enrolled patients were considered high-risk, including patients with primary refractory

disease, high-grade B-cell lymphoma, and primary CNS lymphoma.

Notably, 33% of patients had undergone prior autologous stem cell transplantation,

and 89% had received two or more prior regimens.

Two dose levels were evaluated in Phase I:

Dose Level 1 (DL1, n=3) at 2.5 million receptor-positive

T cells/kg, and Dose Level 2 (DL2, n=6) at 5 million receptor-positive T-cells/kg.

Among the 9 patients in Phase I, no treatment-related

serious adverse events were reported, and the high-dose cohort achieved a 100% complete response rate at Month 1 in all 5 evaluable patients.

Safety and tolerability

EB103 has a favorable and

manageable safety profile in the nine patients treated in Phase I.

While Cytokine Release Syndrome (CRS) was observed in all treated patients,

all CRS events were low grade (Grade 1 or 2) and managed with standard of care.

There were no instances of Grade 3 or higher CRS observed

at either dose level.

A majority of patients also experienced transient low grade ICANS, though the clinical symptoms were easily managed

and the median duration of the events was only two days

Clinical Efficacy

In the Phase I study the

high-dose cohort (DL2) achieved a 100% (n=5/5) complete response rate at Month 1 in all evaluable patients.

One patient in the DL2 cohort

experienced Grade 5 sepsis on Day 18;

this event was determined by the investigator to be unrelated to the EB103 therapy.

Consequently,

this patient was not evaluable for efficacy response.

Responses for all evaluable patients have been durable to date, with all patients

remaining in remission as of the data cutoff date on January 28, 2026.

Pharmacokinetics

Analysis of peripheral blood

samples confirmed robust cellular expansion of EB103.

Pharmacokinetic data determined by quantification of the EB103 transgene vector

copy number showed a median C max of 77,693 copies/ug gDNA with a median T max of 8 days.

Development Plan

In December 2025, an independent

Data Safety Monitoring Board (DSMB) completed its review of safety data from the Phase I dose-escalation phase (n=9) and recommended advancing

the trial into the Phase II expansion phase at the recommended Phase II dose (RP2D).

Patient dosing for Phase II has commenced in January

2026 to further evaluate EB103 at RP2D in a larger patient cohort to confirm the Phase I results.

Manufacturing

to the Services Agreement and Statement of Work #001, among other services, Eureka agreed to provide Estrella with access to Eureka’s

Pursuant to the

Services Agreement and Statement of Work #001, among other services, Eureka agreed to provide Estrella with access to Eureka’s

T-cell manufacturing and lentiviral vector (LVV) processes in connection with the IND application and clinical trials for EB103.

“— Materia l Agreements — Services Agreement and Statement of Work #001 ” below for additional information

regarding the terms of the agreements.

and Advantages

developed the ARTEMIS ® platform in response to significant tolerability issues, including potentially fatal side effects

CRS and ICANS, observed after CAR-T-cell infusions in patients with hematological cancers.

We believe that the ARTEMIS ®

platform and our EB103 T-cell Therapy are superior to current T-cell therapy technologies based on three key features:

Antibody-based target recognition

The ability to achieve

high specificity and binding affinity to intended cancer target when compared to TCRs.

AbTCR includes portions of a human

The AbTCR associates

with the endogenous CD3 complex enabling the AbTCR to use the same activation and regulatory signaling pathways employed by natural

This feature may lead to a decreased risk of side effects in patients.

Co-stimulation provided as a separate

The AbTCR construct

does not include an intracellular signaling domain covalently-linked to a co-stimulatory domain, and thus has the potential to eliminate

T-cell hyperactivation and consequently, lower the risk of CRS and ICANS commonly observed with CAR-T therapy.

addition to the advantages provided above, we believe that the decreased risks of side effects of our EB103 T-cells have the potential

to allow for patients to receive treatments in locations other than dedicated cancer centers.

This would allow for more patients to be

able to receive EB103 T-cells and would ultimately decrease the costs associated with monitoring for side effects following treatment,

hospital stays, and other miscellaneous expenses associated with current treatments.

to Vision Research Reports, the cancer immunotherapy market size is expected to grow at a CAGR of 10.6% during the forecasted period

of 2022 to 2030 and is expected to grow to $130.6 billion in 2030 compared to $60.1 billion in 2020.

Generally, T-cell treatments for

blood cancers is covered by insurance, and each treatment costs an average of $400,000.

T-cells are engineered to express ARTEMIS ® cell receptors (i.e., the AbTCR and co-stimulatory molecule) on their cell

surfaces in a manner similar to EB103.

Like EB103, both the AbTCR and co-stimulatory molecule of EB104 are designed to recognize and

bind the CD19 antigen.

In addition, the AbTCR in EB104 T-cells recognizes and binds the CD22 antigen as well.

Once infused, EB104 T-cells

are able to engage CD19- and CD22-positive cancer cells.

The AbTCR expressed on the EB104 T-cell by its nature associates, via its effector

domain (γδ TCR chains), with the endogenous CD3 complex.

When the AbTCR binds to its target, CD19 or CD22, expressed on the

cancer cell, AbTCR/CD3 complex-mediated signal transduction within the EB104 T-cell is initiated.

This signal transduction process ultimately

leads to the activation of the EB104 T-cell.

A second “enhancement” signal is generated when the co-stimulatory molecule

expressed on the EB104 T-cells binds to its target, CD19, expressed on the cancer cell.

Although the co-stimulatory molecule expressed

on EB104 T-cells cannot bind to CD22, EB104 T-cells are able to engage CD19 or CD22 (with the AbTCR) while the co-stimulatory molecule

binds to CD19.

Like EB103, the main function of the co-stimulatory molecule is to “boost” AbTCR signaling, resulting in increased

expansion and survival of EB104 T-cells inside the body, and the co-stimulatory molecule has also been optimized to provide EB104 T-cells

with enhanced T-cell activation.

In summary, EB104 T-cells seek out CD19 and CD22-positive cancer cells, bind to these cells, and destroy

impressive outcomes of CAR-T cell treatments over the past five years, more than 50% of patients treated with CD19-targeted CAR-T cell

therapy experience progressive disease.

In addition, many patients treated with CD19-target CAR-T cell therapies subsequently show absent

Further, disease progression associated with loss of cell surface CD19 has been reported in 30 – 95% of relapses after

CD19-targeted CAR-T therapy in B-cell acute lymphoblastic leukemia.

We believe that this obstacle can be addressed by dual-targeting

both CD19 and CD22 with EB104.

For patients that may exhibit lower CD19 surface density, EB104 has the potential to bind to both CD19

and CD22 to increase the odds of effective T-cell therapy.

Preclinical Data

test the anti-tumor activity of EB104 towards low or no CD19 surface expression cancer cells, in 2019, Eureka constructed a Nalm-6-CD19ko

cell line, which is a B-cell precursor leukemia cell line, with the “knockout” of CD19 gene expression.

“ Material Agreements - Services Agreement and Statement of Work #001 ” below for additional information regarding

the terms of the agreements.

EB104 T-cells

EB104 T-cells are engineered

to express ARTEMIS ® cell receptors (i.e., the AbTCR and co-stimulatory molecule) on their cell surfaces in a manner similar

Like EB103, both the AbTCR and co-stimulatory molecule of EB104 are designed to recognize and bind the CD19 antigen.

the AbTCR in EB104 T-cells recognizes and binds the CD22 antigen as well.

Once infused, EB104 T-cells are able to engage CD19- and CD22-positive

cancer cells.

The AbTCR expressed on the EB104 T-cell by its nature associates, via its effector domain (γδ TCR chains), with

the endogenous CD3 complex.

When the AbTCR binds to its target, CD19 or CD22, expressed on the cancer cell, AbTCR/CD3 complex-mediated

signal transduction within the EB104 T-cell is initiated.

This signal transduction process ultimately leads to the activation of the EB104

A second “enhancement” signal is generated when the co-stimulatory molecule expressed on the EB104 T-cells binds to

its target, CD19, expressed on the cancer cell.

Although the co-stimulatory molecule expressed on EB104 T-cells cannot bind to CD22, EB104

T-cells are able to engage CD19 or CD22 (with the AbTCR) while the co-stimulatory molecule binds to CD19.

Like EB103, the main function

of the co-stimulatory molecule is to “boost” AbTCR signaling, resulting in increased expansion and survival of EB104 T-cells

inside the body, and the co-stimulatory molecule has also been optimized to provide EB104 T-cells with enhanced T-cell activation.

summary, EB104 T-cells seek out CD19 and CD22-positive cancer cells, bind to these cells, and destroy them.

Despite impressive outcomes

of CAR-T cell treatments over the past five years, more than 50% of patients treated with CD19-targeted CAR-T cell therapy experience

progressive disease.

In addition, many patients treated with CD19-target CAR-T cell therapies subsequently show absent or low CD19.

disease progression associated with loss of cell surface CD19 has been reported in 30 – 95% of relapses after CD19-targeted CAR-T

therapy in B-cell acute lymphoblastic leukemia.

We believe that this obstacle can be addressed by dual-targeting both CD19 and CD22 with

For patients that may exhibit lower CD19 surface density, EB104 has the potential to bind to both CD19 and CD22 to increase the

odds of effective T-cell therapy.

EB104 Preclinical Data

To test the anti-tumor

activity of EB104 towards low or no CD19 surface expression cancer cells, in 2019, Eureka constructed a Nalm-6-CD19ko cell line,

which is a B-cell precursor leukemia cell line, with the “knockout” of CD19 gene expression.

This cell line mimics

patients’ diminished CD19 surface expression after CD19-directed immunotherapies.

To confirm if EB104 T-cells have the potential

to overcome CD19 antigen loss in cancer cells, Eureka tested the activity of EB104 as well as EB103 cells in mice using NSG™ xenograft

models (which are highly immunodeficient mice) of leukemia with Nalm-6 and Nalm-6-CD19ko cells with a bioluminescence reporter.

flux from the bioluminescence reporter measured the tumor growth.

In the experiments shown below, Eureka tested EB104, EB103, and mock

T-cells head-to-head, against the NSG™ xenograft model, with six mice for each treatment group, respectively.

Four days before

the T-cells were infused, 0.5x106 leukemia cells Nalm-6 (expressing both CD19 and CD22) with bioluminescence reporter were injected into

Four days later, the mice were infused with a total of T-cells containing EB103 or EB104, or mock T cells, using the mock T-cells

as the control group.

The infusion of EB103 and EB104 showed tumor control until day 21, while the control group showed rapid tumor growth.

EB104 showed potentially better tumor control compared to EB103.

At day 21, Nalm-6 cells with 1% Nalm-6-CD19ko (expressing CD22, but

not CD19) cells were injected into mice that were previously treated by EB103 or EB104 as re-challenge.

This re-challenge experiment

mimicked the tumor relapse in patients due to CD19 antigen escape.

Mice treated with EB104 showed “durable” tumor control,

meaning that the tumor continued to respond to treatment without the cancer growing or spreading, and “clearance” of tumors,

which refers to the complete killing of tumor cells, for a total of more than 60 days or 40 days after the re-challenge.

However, mice

treated with EB103 showed rapid tumor growth after the re-challenge.

pre-clinical results showed that EB104 T-cells have the potential to eradicate Nalm-6 Primary Tumors and Nalm-6-CD19ko re-challenge tumors

in the xenograft model, suggesting that EB104 T-cells have the potential to control the growth of tumor cells that do not express CD19.

Collaboration with Imugene and CF33-CD19t

major challenge for current T-cell therapies is the identification of antigens that are expressed only on tumors and not in healthy tissue.

In the absence of such restricted expression, CAR-T cell therapy poses considerable safety concerns and potentially narrows therapeutic

window for their application against solid tumors.

CD19 has been an ideal target for CAR-T cells against hematological malignancies for

several reasons, including its highly restricted expression on B cells and acceptable off-tumor and on-target properties.

to the shared expression of solid tumor antigens on normal tissue, most of these antigens also have heterogeneous and nonuniform expression

patterns in tumors, limiting the potential for effective and durable antitumor responses.

Many solid tumors, including triple-negative

breast cancers and liver cancers, lack amenable tumor antigens for CAR-T cell development.

To potentially address the issue of the lack

of solid tumor-specific targets, we are collaborating with Imugene and its product candidate, CF33-CD19t, to research the use of EB103

in conjunction with CF33-CD19t to treat solid tumors using a “mark and kill” strategy.

“mark and kill” strategy entails first using CF33-CD19t to infect solid tumor cells which induces them to express the CD19

protein on the cell surface, thereby labeling the tumor cell as a target for EB103 T-Cells.

The EB103 T-cells are then infused into the

patient where they would target and kill the now CD19-positive solid tumor cells.

Collaboration

October 29, 2021, Eureka entered into a collaboration agreement (the “Collaboration Agreement”) with Imugene, a clinical

stage immuno-oncology company, to evaluate the use of CF33-CD19t in conjunction with Eureka’s CD19 ARTEMIS T-cell therapy for the

treatment of solid tumors.

July 28, 2022, as part of the Separation, Eureka contributed and assigned the Collaboration Agreement to Estrella.

To confirm if EB104 T-cells have the

potential to overcome CD19 antigen loss in cancer cells, Eureka tested the activity of EB104 as well as EB103 cells in mice using

NSG™ xenograft models (which are highly immunodeficient mice) of leukemia with Nalm-6 and Nalm-6-CD19ko cells with a

bioluminescence reporter.

The total flux from the bioluminescence reporter measured the tumor growth.

In the experiments shown

below, Eureka tested EB104, EB103, and mock T-cells head-to-head, against the NSG™ xenograft model, with six mice for each

treatment group, respectively.

Four days before the T-cells were infused, 0.5x106 leukemia cells Nalm-6 (expressing both CD19 and

CD22) with bioluminescence reporter were injected into mice.

Four days later, the mice were infused with a total of T-cells

containing EB103 or EB104, or mock T cells, using the mock T-cells as the control group.

The infusion of EB103 and EB104 showed

tumor control until day 21, while the control group showed rapid tumor growth.

Furthermore, EB104 showed

potentially better tumor control compared to EB103.

At day 21, Nalm-6 cells with 1% Nalm-6-CD19ko (expressing CD22, but not CD19) cells

were injected into mice that were previously treated by EB103 or EB104 as re-challenge.

This re-challenge experiment mimicked the tumor

relapse in patients due to CD19 antigen escape.

Mice treated with EB104 showed “durable” tumor control, meaning that the tumor

continued to respond to treatment without the cancer growing or spreading, and “clearance” of tumors, which refers to the

complete killing of tumor cells, for a total of more than 60 days, or 40 days after the re-challenge.

However, mice treated with EB103

showed rapid tumor growth after the re-challenge.

These pre-clinical results

showed that EB104 T-cells have the potential to eradicate Nalm-6 Primary Tumors and Nalm-6-CD19ko re-challenge tumors in the xenograft

model, suggesting that EB104 T-cells have the potential to control the growth of tumor cells that do not express CD19.

Our Collaboration with Imugene and CF33-CD19t

CF33-CD19t and EB103

A major challenge for current

T-cell therapies is the identification of antigens that are expressed only on tumors and not in healthy tissue.

In the absence of such

restricted expression, CAR-T cell therapy poses considerable safety concerns and potentially narrows therapeutic window for their application

against solid tumors.

CD19 has been an ideal target for CAR-T cells against hematological malignancies for several reasons, including

its highly restricted expression on B cells and acceptable off-tumor and on-target properties.

In addition to the shared expression of

solid tumor antigens on normal tissue, most of these antigens also have heterogeneous and nonuniform expression patterns in tumors, limiting

the potential for effective and durable antitumor responses.

Many solid tumors, including triple-negative breast cancers and liver cancers,

lack amenable tumor antigens for CAR-T cell development.

To potentially address the issue of the lack of solid tumor-specific targets,

we are collaborating with Imugene and its product candidate, CF33-CD19t, to research the use of EB103 in conjunction with CF33-CD19t to

treat solid tumors using a “mark and kill” strategy.

This “mark and kill”

strategy entails first using CF33-CD19t to infect solid tumor cells which induces them to express the CD19 protein on the cell surface,

thereby labeling the tumor cell as a target for EB103 T-Cells.

The EB103 T-cells are then infused into the patient where they would target

and kill the now CD19-positive solid tumor cells.

Collaboration Agreement

On October 29, 2021, Eureka

entered into a collaboration agreement (the “Collaboration Agreement”) with Imugene, a clinical stage immuno-oncology company,

to evaluate the use of CF33-CD19t in conjunction with Eureka’s CD19 ARTEMIS T-cell therapy for the treatment of solid tumors.

On July 28, 2022, as

part of the Separation, Eureka contributed and assigned the Collaboration Agreement to Estrella.

Pursuant to the Collaboration

Agreement, Estrella and Imugene have each granted to the other a royalty free, non-exclusive, worldwide license, with the right to grant

and authorize sublicenses, to their respective technologies to conduct the research activities each is responsible for performing under

the research plan set forth in the Collaboration Agreement.

The research plan is required to be reviewed no less frequently than every

six to eight months by a joint steering committee comprised of participants from each of Estrella and Imugene.

the completion of the research activities performed under the research plan in accordance with the Collaboration Agreement, Estrella

and Imugene will be required to discuss whether they want to jointly develop or commercialize the construct that is the subject of the

research plan (and all products that include such construct).

Notwithstanding the foregoing, neither Estrella nor Imugene will be required

to enter into any joint development agreement concerning such construct or any results, records, or reports that are generated by or

on behalf of either Estrella or Imugene while performing such research activities.

Additionally,

while Estrella and Imugene each retain their intellectual property rights with respect to their respective technologies and any improvements

that relate solely to their respective technologies, in the event that new intellectual property is generated from the collaboration

(each a “Joint Collaboration Patent Right”), Estrella and Imugene are required to jointly decide the strategy, and with respect

to any Joint Collaboration Patent Rights, the preparation, filing, prosecution, and maintenance of all Joint Collaboration Patent Rights

throughout the world.

Estrella and Imugene are required to share equally in the costs and expenses incurred in preparing, filing, prosecuting,

and maintaining such Joint Collaboration Patent Rights.

If only one of Estrella or Imugene wishes to file a patent on any Joint Collaboration

Patent Rights, then such party will assume all of the costs related to such patent, and the other party will assign all rights to such

patent to the prosecuting party as if they were an improvement of that party’s technology, and the other party may only use such

patent rights for internal research purposes.

Collaboration Agreement will continue to be in full force and effect as long as there are research activities being performed under the

research plan set forth therein, unless further extended by written consent of Estrella and Imugene, or unless earlier terminated as

(i) by written agreement of each of Estrella and Imugene;

(ii) from and after October 29, 2022 (or the termination of all research

under the research plan set forth therein, whichever occurs first), by either Estrella or Imugene effective upon 60 days’ prior

written notice to the other party;

or (iii) by either Estrella or Imugene, if the other party materially breaches the Collaboration Agreement

and fails to cure such breach within 60 days after receiving written notice thereof.

Uses and Expansion/Market

tumors represent approximately 1,600,000 new cancer cases, or 90% of total cancer diagnoses in the United States, each year.

time, there are no FDA-approved CAR or TCR-T cell therapies approved for the treatment of solid tumors.

Accordingly, it is currently

difficult to estimate specific market projections and the potential for our “mark and kill” strategy.

elements of our strategy include:

our lead product candidate, EB103, through clinical development.

On March 2, 2023,

the FDA cleared our IND for EB103, allowing us to initiate the Phase I/II Starlight-1 Clinical

Trial, which dosed its first patient in July 2024.

our second product candidate, EB104, for clinical development.

We are compiling an

IND filing for EB104 for the treatment of relapsed/refractory and high-risk blood cancers.

Phase I trials may not commence until the FDA has approved the IND for EB104.

researching the use of EB103 in conjunction with CF33-CD19t for multiple indications of solid

tumors through clinical development.

The FDA cleared our IND for EB103 on March 2,

2023, and the Starlight Phase I/II clinical trial for EB103 dosed its first patient in July

If the Phase I/II Starlight-1 Clinical Trial is successful, we plan to submit an IND

filing for the use of EB103 in conjunction with CF33-CD19t in the future.

At this time, we

have not determined the specific indications of solid tumors to be researched or an exact

timeframe for filing our IND application.

to develop a pipeline of T-cell therapies.

To address certain of the tolerability

shortcomings of currently approved CAR-T therapies, we intend to continue pursue development

of therapies that may be able to be adopted in earlier lines of treatment and to be delivered

in community outpatient settings.

Pipeline of Clinical Programs

approach is to advance our CD19-Redirected ARTEMIS T Cell programs in relapsed/refractory and high-risk blood cancers first.

we are also developing multiple pipeline candidates against solid tumor and autoimmune disease.

The following chart summarizes our clinical

Team and Investors

to the Services Agreement, we are supported by Eureka’s scientific team, which is comprised of leaders in the biopharmaceutical,

oncology, and T-cell cancer immunotherapy areas.

We have leveraged their expertise to analyze preclinical data and design and implement

our clinical trials.

Our CEO and President, Dr.

Cheng Liu, and members of our scientific advisory board are pioneers in their respective

fields, each having spent their careers advancing next-generation technologies and providing treatments in these areas.

our Chief Financial Officer, Peter Xu, brings years of executive experience and investment management abilities.

Board includes experienced industry leaders and investors who have been involved with many early-stage companies.

Furthermore, we are

supported by investors who share our belief that the world needs smarter medical treatments and our long-term vision that T-cell therapies

have the potential to transform the way we fight cancer.

biotechnology and pharmaceutical industries are characterized by rapid, unpredictable technological advancement and significant competition.

These industries dedicate significant resources to developing novel and proprietary therapies for the treatment of cancer, which often

incorporate innovative technologies and incorporate valuable intellectual property.

We compete with companies in the cell therapy and

immunotherapy space, as well as with companies developing other novel targeted therapies for cancer.

If approved, our product candidates

will compete with commercially available and development-stage innovative products in the fields of cell and immunotherapy, as well as

against existing products generally accepted as the standard-of-care for indications in which we plan to seek marketing approval.

anticipate that we will face intense and increasing competition from many different sources, including new and established biotechnology

and pharmaceutical companies, academic research institutions, governmental agencies, and public and private research institutions.

product candidates cover both hematological malignancies and solid tumors, and we expect to face direct competition in both areas from

companies focused on CAR-T and other cell-based therapies.

There are currently eight total FDA-approved drugs or therapies targeting

CD19, four of which are CD19-targeting T-cell therapies:

FIRST APPROVED

Acute lymphocytic

diffuse large B-cell lymphoma;

follicular lymphoma

US, EU, UK, Japan,

Australia, Canada, South Korea

Agreement, Estrella and Imugene have each granted to the other a royalty free, non-exclusive, worldwide license, with the right to

grant and authorize sublicenses, to their respective technologies to conduct the research activities each is responsible for

performing under the research plan set forth in the Collaboration Agreement.

The research plan under the Collaboration Agreement was

completed as of August 30, 2023.

Potential Uses and Expansion/Market

Solid tumors represent approximately

1,600,000 new cancer cases, or 90% of total cancer diagnoses in the United States, each year.

At this time, there are no FDA-approved

CAR or TCR-T cell therapies approved for the treatment of solid tumors.

Accordingly, it is currently difficult to estimate specific market

projections and the potential for our “mark and kill” strategy.

Our Team and Investors

Pursuant to the

Services Agreement entered into on June 28, 2022 and Statement of Work entered into on March 4, 2024, we are supported by

Eureka’s scientific team, which is comprised of leaders in the biopharmaceutical, oncology, and T-cell cancer immunotherapy

We have leveraged their expertise to analyze preclinical data and design and implement our clinical trials.

President, Dr.

Cheng Liu, and members of our scientific advisory board are pioneers in their respective fields, each having spent

their careers advancing next-generation technologies and providing treatments in these areas.

Our Chief Financial Officer, Peter Xu,

brings years of executive experience and investment management abilities.

In August 2024 we welcomed Ms.

Hong Zhang as our

Chairperson of the Board.

Zhang is a highly accomplished executive with over 25 years of experience in financial and corporate

We believe the addition of Ms.

Zhang to our Board will bring new opportunities to the company’s fundraising

Our Board includes experienced

industry leaders and investors who have been involved with many early-stage companies.

Furthermore, we are supported by investors who

share our belief that the world needs smarter medical treatments and our long-term vision that T-cell therapies have the potential to

transform the way we fight cancer.

The biotechnology and pharmaceutical

industries are characterized by rapid, unpredictable technological advancement and significant competition.

These industries dedicate

significant resources to developing novel and proprietary therapies for the treatment of cancer, which often incorporate innovative technologies

and incorporate valuable intellectual property.

We compete with companies in the cell therapy and immunotherapy space, as well as with

companies developing other novel targeted therapies for cancer.

If approved, our product candidates will compete with commercially available

and development-stage innovative products in the fields of cell and immunotherapy, as well as against existing products generally accepted

as the standard-of-care for indications in which we plan to seek marketing approval.

We anticipate that we will face intense and increasing

competition from many different sources, including new and established biotechnology and pharmaceutical companies, academic research institutions,

governmental agencies, and public and private research institutions.

Our product candidates cover both hematological malignancies and solid

tumors, and we expect to face direct competition in both areas from companies focused on CAR-T and other cell-based therapies.

currently ten total FDA-approved drugs or therapies targeting CD19, five of which are CD19-targeting T-cell therapies:

Pediatric/Young Adult B-ALL;

R/R Follicular Lymphoma

Kite Pharma (Gilead)

Diffuse large B-cell

non-Hodgkin’s lymphoma;

follicular lymphoma

US, EU, UK, Japan,

Canada, China

R/R Large B-cell Lymphoma;

R/R Follicular Lymphoma;

R/R Primary CNS Lymphoma

Kite Pharma (Gilead)

Mantel cell lymphoma;

acute lymphocytic leukemia

R/R Mantle Cell Lymphoma (MCL);

Juno (Bristol Myers Squibb)

Diffuse large B-cell

Follicular Lymphoma;

US, Japan, EU, UK,

competitors operating in the T-cell therapy space include, but are not limited to:

Yescarta and Tecartus)

Mantle Cell Lymphoma;

Marginal Zone Lymphoma

Adult Relapsed/Refractory B-cell precursor Acute Lymphoblastic Leukemia (ALL)

Our competitors operating

in the T-cell therapy space include, but are not limited to:

Kite Pharma, Inc.

Yescarta, Tecartus, KITE-753 and KITE-363)

Therapeutics Inc.

2 unchanged sentences

Carteyva/Relma-cel)

● Adaptimmune

Therapeutics PLC (Product Candidate:

ADP-A2M4CD8 SPEAR)

Therapeutics (Product Candidate:

Therapeutics (Product Candidates:

P-BCMA-ALLO1, P-MUC1C-ALLO1, and P-PSMA-ALLO1)

Allogene Therapeutics (Product:

Mustang Bio (Product:

Poseida Therapeutics (Product Candidates:

P-MUC1C-ALLO1, and P-CD19CD20-ALLO1)

Therapeutics PLC (Product Candidates:

obe-cel and Auto1/22)

competitors pursuing CD19 targeted drugs outside of the T-cell therapy space include, but are not limited to:

Therapeutics plc (Product:

Our competitors pursuing

CD19 targeted drugs outside of the T-cell therapy space include, but are not limited to:

● Amgen, Inc.

Blincyto and Uplizna)

AG (Novartis) (Product:

Therapeutics SA (Product:

and research institutes have been a proven new technology source in the field as well.

We also face competition from treatments in the

field of immunotherapy which are being developed and/or commercialized by several biotechnology companies as well as by large pharmaceutical

Such companies, whose immuno-oncology programs focus on the same indications or antigen targets as our current pipeline.

known types of immunotherapy, including but not limited to checkpoint inhibition and cancer vaccines, are not currently direct competitors

to T-cell-based therapeutics.

However, we cannot predict whether these other types of immunotherapy may eventually show efficacy in the

indications for which we may seek marketing approval, and it is possible that we may face direct and substantial competition from such

sources in the future.

of our current or potential competitors, either alone or with a strategic partner, have significantly greater financial, technical, and

human resources, as well as more expertise in research and development, manufacturing, preclinical testing, conducting clinical studies

and trials and commercializing and marketing approved products.

Competitors may compete with us in hiring scientific and management personnel,

establishing clinical study sites, registering patients for clinical studies and acquiring technologies complementary to, or necessary

for, our programs.

Mergers and acquisitions in the biotechnology and pharmaceutical industries may result in even more resources being

concentrated among a smaller number of competitors.

Smaller or early-stage companies may also prove to be significant competitors, particularly

through collaborative arrangements with large and established companies.

own certain unregistered intellectual property rights that we use in connection with our business, including a common law trademark for

We also own certain plasmids, cell lines, and materials related to CD19 and CD22 in connection with the ARTEMIS ®

platform, and trade secrets and other intellectual property rights related thereto.

A material portion of the intellectual property

we use in our business is in-licensed from Eureka, as described below.

We are also party to the Collaboration Agreement with Imugene,

as described above, to conduct certain preclinical research projects to investigate the use of EB103 in conjunction with CF33-CD19t for

efficacy in solid tumors.

Agreement with Eureka

June 28, 2022, we entered into the License Agreement with Eureka and Eureka Therapeutics (Cayman), Inc.

to license certain functions

related to any T-cell products that incorporate (a) the ARTEMIS ® platform and (b)(i) the CD19 binder and/or (ii) the CD22

binder identified in the License Agreement (the “Licensed Product”).

The License Agreement provides that, during the term,

Eureka grants Estrella an exclusive license, with the right to grant sublicenses through multiple tiers to (a) make, import, use, sell

or offer to sell the Licensed Products, (b) develop the Licensed Products solely for the purpose of obtaining regulatory approval of

such Licensed Products, (c) commercialize such Licensed products and (d) manufacture the Licensed Products solely for the purposes of

developing the Licensed Products for purposed of obtaining regulatory approval of such Licensed Products and for commercializing such

Licensed Products.

to the terms of the License Agreement, in partial consideration of Eureka’s grant of the rights and licenses to Estrella, Estrella

agreed to pay Eureka a one-time, non-refundable, non-creditable payment of $1,000,000.

As of October 2023, $1,000,000 has been paid to

is eligible to receive up to five one-time development milestone payments from Estrella in the aggregate amount of $60,150,000 if all

five development milestones are achieved.

Effective as of March 1, 2023, the parties further amended the License Agreement to provide

that if any development milestone is achieved prior to the Closing of the Business Combination, the corresponding development milestone

payment will not be due to Eureka until the Closing of the Business Combination.

On January 30, 2023, one development milestone payment

in the amount of $50,000 related to the submission of EB103 to the FDA was earned by Eureka under the Agreement, which became due and

payable to Eureka upon the Closing of the Business Combination.

is also eligible to receive up to four one-time sales milestone payments from Estrella based on the aggregate net sales of all Licensed

Products by or on behalf of Estrella or any of its affiliates or sublicensees in the Licensed Territory during any consecutive 12-month

period in the aggregate amount of $225,000,000 if all four sales milestones are achieved.

Each sales milestone payment will only be paid

once, regardless of the number of Licensed Products or the number of times a given sales milestone has been achieved.

Estrella is also

responsible (with input from Eureka) for the preparation, filing, prosecution, and maintenance of the patent rights, including all associated

addition, during the applicable royalty term, Estrella will be required to pay to Eureka royalties in the amount of a single digit percentage

of the aggregate Net Sales of all Licensed Products sold by or on behalf of Estrella or its affiliates or sublicensees in the Licensed

Territory during a calendar year.

Such amount is subject to certain reductions (not to exceed 50% of the amount otherwise payable) due

to the expiration of valid claims of a licensed patent right in a given country in the Licensed Territory or due to 50% or greater declines

in sales as a result of generic product competition in a given country in the Licensed Territory.

The royalty term begins upon the first

commercial sale of a Licensed Product in a country in the Licensed Territory and continues until the later of (a) the date on which such

Licensed Product is no longer covered by a valid claim within Eureka’s licensed patent rights in such country, (b) the expiration

of all exclusive marketing rights or data protection or other exclusivity rights (other than patent rights) conferred by any regulatory

authority with respect to a product in a country or jurisdiction that prohibits the commercialization of a generic product, including

orphan drug exclusivity or pediatric exclusivity for such licensed product in such country, and (c) 12 years after the first commercial

sale of such licensed product in such country.

License Agreement will remain in effect on a licensed product-by-licensed product and country-by-country basis, until the expiration

of the royalty term for a licensed product in a country and will finally expire upon expiration of the royalty term for the final Licensed

Estrella may terminate the License Agreement for any reason or no reason upon 120 days’ prior written notice to Eureka.

Either party has the right to terminate the License Agreement upon material breach of the other party that is not cured within 90 days

after the breaching party receives written notice of such breach from the non-breaching party.

of June 30, 2024, we have fully paid the $1,000,000 license fee to Eureka.

January 30, 2023, one development milestone payment in the amount of $50,000 related to the submission of EB103 to the FDA was earned

by Eureka under the Agreement, which was paid on October 10, 2023.

No other development milestone, sales milestone, or royalty payment

has been earned as of June 30, 2024, as we do not have any product candidates approved for sale and have not generated any revenue from

product sales.

With the dosing of the first patient in July 2024 in the STARLIGHT-1 clinical trial, the development milestone pursuant

to Section 8.2.1 (First Patient Dosed in the First Clinical Trial of a Licensed Product) in the Licensing Agreement with Eureka was met.

As a result, Estrella made a payment of $50,000 to Eureka for reaching this milestone.

As of September 2024, two patients have been dosed

in the STARLIGHT-1 clinical trial.

Patent Information

table below sets forth patents owned by Eureka relating to EB103 and EB104.

The expiration date for each patent is October 21, 2036.

OF PATENT PROT.

CANDIDATES COVERED

Antibody/T-cell