BG1805: A Comprehensive Clinical and Scientific Profile of an Investigational Anti-CLL1 CAR-T Cell Therapy for Acute Myeloid Leukemia

Executive Summary

This report provides a comprehensive analysis of BG1805, an investigational, autologous Chimeric Antigen Receptor (CAR) T-cell therapy developed by Guangzhou Bio-gene Technology Co., Ltd., for the treatment of acute myeloid leukemia (AML).[1] As a biotech therapeutic, BG1805 represents a significant advancement in the application of cell and gene therapy to myeloid malignancies, a field that has historically faced challenges due to a lack of suitable tumor-specific antigens.

The core therapeutic strategy of BG1805 is centered on the targeting of C-type lectin-like molecule-1 (CLL1), also known as CLEC12A. The selection of this target is highly strategic, as CLL1 is preferentially expressed on AML blasts and, critically, on leukemic stem cells (LSCs) which are responsible for disease relapse.[3] Concurrently, CLL1 demonstrates low or absent expression on normal hematopoietic stem cells (HSCs), offering a potential therapeutic window to eradicate the leukemia while preserving the patient's capacity for hematopoietic reconstitution.[3] This selective expression profile forms the fundamental basis for the therapy's anticipated efficacy and favorable safety profile.

Currently, BG1805 is in Phase I clinical development, with Investigational New Drug (IND) approvals from China's National Medical Products Administration (NMPA) to conduct trials in both adult and pediatric patients with relapsed or refractory (r/r) AML.[1] The program's advancement into formal clinical trials was significantly de-risked by promising early data from Investigator-Initiated Trials (IITs), which demonstrated notable efficacy signals in both adult and pediatric populations.[6] Further validation comes from a published interim analysis of a multi-center pediatric trial, which reported that 75% of patients achieved at least a complete remission with incomplete hematologic recovery (CRi) or a morphologic leukemia-free state (MLFS), with a manageable safety profile characterized by low-grade cytokine release syndrome (CRS) and no lethal events.[8]

The clinical and commercial potential of BG1805 has been recognized by major global regulatory bodies. The therapy has received Orphan Drug Designation (ODD) from both the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA), a key milestone that provides significant developmental incentives and validates the high unmet medical need in r/r AML.[3] This positions BG1805 as a promising candidate in the global oncology landscape, with a strong scientific rationale, encouraging early clinical data, and a clear regulatory pathway.

Drug Profile and Scientific Rationale

Disambiguation of the 'BG1805' Identifier

A critical point of clarification is necessary when reviewing the available literature concerning the identifier "BG1805." This designation has been applied to two fundamentally different and unrelated entities. The first, and the subject of this report, is the clinical-stage therapeutic agent: an anti-CLL1 CAR-T cell therapy developed for oncological indications.[9] The second is a laboratory tool: a yeast Open Reading Frame (ORF) expression vector used for protein expression and purification in molecular biology research.[12] This vector, derived from pRSAB1234, features components such as a GAL1 promoter, a URA3 selectable marker, and various C-terminal fusion tags (e.g., 6xHis, HA, Protein A) for affinity purification.[12] All information pertaining to this yeast expression system is irrelevant to the clinical therapeutic and is therefore excluded from the subsequent analysis in this report. This distinction is paramount for an accurate assessment of the drug's profile.

Identification and Classification

• Generic Name: BG1805 [11]
• Synonyms: autologous anti-CLL-1-CAR T lymphocytes BG1805, BG 1805, BG-1805 [15]
• DrugBank ID: DB18667 [11]
• Type/Modality: BG1805 is classified as a biotech therapeutic. More specifically, it is an autologous cell transplant therapy, a form of adoptive cell transfer, and is also considered a gene therapy product due to the genetic modification of the patient's T-cells.[11]
• Status: The therapy is currently in the investigational stage of development and is not approved for commercial use.[9]

The Molecular Target: C-type Lectin-like Molecule-1 (CLL1 / CLEC12A)

The therapeutic potential of BG1805 is intrinsically linked to the biological characteristics of its molecular target, C-type lectin-like molecule-1 (CLL1).

Biological Function and Structure

CLL1, also known by the designations CLEC12A, DCAL-2, MICL, and CD371, is a type II transmembrane protein belonging to the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily.[7] The protein is composed of 265 amino acids and features an extracellular C-type lectin-like domain, a single transmembrane segment, and a cytoplasmic tail.[18] This cytoplasmic domain contains an Immunoreceptor Tyrosine-based Inhibition Motif (ITIM), which, upon phosphorylation, can recruit phosphatases such as SHP-1 and SHP-2 to negatively regulate the activation of myeloid cells like granulocytes and monocytes.[17]

Expression Profile and Therapeutic Rationale

The selection of CLL1 as a target for AML therapy is a deliberate and scientifically grounded strategy. The ideal target for a potent immunotherapy like CAR-T is one that is highly and consistently expressed on malignant cells while being absent from essential healthy tissues, thereby creating a wide therapeutic window. In the context of AML, sparing the normal hematopoietic stem cell (HSC) compartment is of paramount importance to avoid inducing irreversible, life-threatening bone marrow failure.

The expression profile of CLL1 aligns remarkably well with these ideal characteristics. It is highly expressed on the vast majority of AML blasts and, critically, on the leukemic stem cells (LSCs) that are believed to drive disease persistence and relapse.[3] This stable and high-level expression makes it an excellent candidate for therapeutic targeting. The most crucial aspect of its profile, however, is its low or absent expression on normal, healthy HSCs (defined by markers such as CD34+/CD38−) and mature lymphocytes.[3]

This differential expression pattern is the scientific cornerstone of the BG1805 program. It presents the opportunity to eliminate the bulk of the leukemia as well as its self-renewing source (the LSCs), while leaving the healthy HSC pool intact. This allows for the potential reconstitution of a normal hematopoietic system post-treatment, theoretically avoiding the profound and long-term myelosuppression that would result from targeting an antigen co-expressed on HSCs. This favorable profile suggests that BG1805 could achieve potent anti-leukemic activity with a significantly reduced risk of severe on-target, off-leukemia toxicity, a primary obstacle that has hindered the development of other myeloid-directed CAR-T therapies.

Mechanism of Action and CAR Construct

BG1805 functions based on the principles of CAR-T cell therapy, a revolutionary approach that reprograms a patient's own immune cells to fight cancer. The process involves leukapheresis to collect a patient's T-lymphocytes, which are then genetically engineered ex vivo using a viral vector (typically lentiviral) to express a synthetic CAR. This CAR redirects the T-cells to recognize a specific antigen on tumor cells. The engineered cells are expanded to therapeutic doses and then infused back into the patient, where they function as "living drugs," seeking out and destroying cancer cells.[21]

The BG1805 CAR construct is engineered with specific features to optimize its function:

• Antigen Binding Domain: The extracellular portion of the CAR contains a single-chain variable fragment (scFv), which is derived from the variable regions of an antibody's heavy and light chains. This scFv is designed to specifically recognize and bind to the CLL1 protein on the surface of AML cells.[15]
• Antibody Engineering: The antibody from which the scFv is derived has undergone a deliberate engineering process, including affinity screening to ensure high-specificity binding and humanization.[3] The process of humanization involves modifying the murine (mouse) antibody framework regions to more closely resemble human antibody sequences. This is a critical design choice intended to reduce the immunogenicity of the CAR construct. The human immune system can recognize non-human protein sequences as foreign, potentially mounting an immune response against the CAR-T cells themselves. Such a response can lead to their rapid clearance, limiting their persistence and, consequently, their long-term therapeutic efficacy. By utilizing a humanized scFv, BG1805 is designed for enhanced persistence in vivo, which is directly correlated with the potential for more durable clinical responses and a reduced risk of immunogenicity-related adverse events.
• Therapeutic Action: Upon infusion, the autologous anti-CLL-1-CAR T lymphocytes BG1805 circulate throughout the body. When they encounter CLL-1-expressing AML cells, the CAR's scFv binds to the target antigen. This binding event triggers the CAR's intracellular signaling domains, activating the T-cell to execute its effector functions. This results in the targeted and selective killing of the CLL-1-positive tumor cells through mechanisms such as the release of cytotoxic granules (perforin and granzymes) and the secretion of pro-inflammatory cytokines.[15]

Preclinical and Investigator-Initiated Trial (IIT) Evidence

Preclinical Development

While specific, detailed preclinical study reports for BG1805 are not publicly available within the provided materials, statements from Guangzhou Bio-gene Technology consistently refer to a robust preclinical data package that supported the therapy's transition into human trials. The company's Chief Technology Officer, Dr. Min Luo, has publicly expressed excitement about the "preclinical profile of BG1805," indicating that this foundational research was highly encouraging.[2]

To contextualize the likely nature of these studies, data from a similar allogeneic anti-CLL-1 CAR-T therapy (CB-012) can serve as a proxy. Preclinical evaluation of CB-012 demonstrated potent and specific antigen-dependent cytotoxic activity against human AML cell lines in co-culture experiments.[20] Furthermore, in AML xenograft mouse models, a single administration of the anti-CLL-1 CAR-T cells resulted in robust tumor control and a significant prolongation of survival.[20] It is highly probable that BG1805 demonstrated similarly compelling results in analogous in vitro cytotoxicity assays and in vivo animal models to justify its advancement into formal clinical development.

Role and Impact of Investigator-Initiated Trials (IITs)

Before initiating formal, company-sponsored clinical trials, BG1805 was evaluated in Investigator-Initiated Trials (IITs). Company communications repeatedly highlight that these early studies "demonstrated significant efficacy in both adults and children".[6] The use of IITs appears to be a core component of Guangzhou Bio-gene's broader R&D strategy, with the company having six autologous and two allogeneic CAR-T candidates in IITs alongside its formal clinical programs.[23]

This approach serves as a highly effective strategic tool for de-risking and accelerating development. Formal IND-based trials are resource-intensive, requiring significant capital investment and adherence to stringent regulatory protocols. By collaborating with academic medical centers on IITs, a biotechnology company can generate initial human proof-of-concept data in a more agile and cost-effective manner. The "significant efficacy" observed in the BG1805 IITs likely provided the critical validation and human safety data necessary to build confidence among investors, internal stakeholders, and regulatory bodies like the NMPA. This allowed the company to commit to the more substantial investment required for the formal Phase I program with a higher degree of certainty, effectively de-risking the asset before major capital deployment.

Interim Multi-Center Analysis in Pediatric R/R-AML

The most concrete public evidence of BG1805's clinical performance comes from a published interim analysis of a Phase 1/2 multi-center trial in pediatric patients with r/r-AML.[8] The study, which lists Guangzhou Bio-gene Technology as a collaborator, enrolled eight children who received a single dose of autologous anti-CLL1 CAR-T cells after lymphodepletion conditioning.[8]

Efficacy Results

The preliminary efficacy from this cohort of heavily pre-treated pediatric patients was highly encouraging [8]:

• High Response Rates: A total of 6 out of 8 patients (75%) achieved a meaningful clinical response, defined as either a morphologic leukemia-free state (MLFS) or complete remission with incomplete hematologic recovery (CRi).
• Deep Responses: Of the responders, 4 of the 8 total patients (50%) achieved a deep response, characterized by both MLFS and negativity for minimal residual disease (MRD), which is a key predictor of long-term remission.
• Partial and Stable Disease: One patient achieved a partial remission (PR), and one patient remained with stable disease (SD) but demonstrated clearance of CLL1-positive AML blasts, indicating on-target biological activity even in the absence of a formal response.[8]

Safety Results

The safety profile observed in this initial pediatric cohort was manageable and supportive of further development [8]:

• All treated patients experienced cytokine release syndrome (CRS), a common on-target toxicity of CAR-T therapy. However, all cases were low-grade (Grade 1-2).
• Crucially, no lethal events or higher-grade CRS were reported.

These early clinical findings represent the first human validation of the therapeutic hypothesis behind BG1805, suggesting that it can be a well-tolerated and effective option for children with r/r-AML.

Formal Clinical Development Program

Overview of Clinical Strategy

Following the promising results from IITs, Guangzhou Bio-gene initiated a formal clinical development program for BG1805. The program is structured around a standard first-in-human design for cell therapies: a Phase I, single-arm, open-label study architecture incorporating both dose-escalation and dose-expansion phases.[1] The initial dose-escalation phase is designed to determine the safety and tolerability of increasing doses of BG1805 to identify the maximum tolerated dose (MTD) or the recommended Phase 2 dose (RP2D). Subsequently, the dose-expansion phase will enroll additional patients at the RP2D to further characterize the therapy's safety profile and gather more extensive preliminary efficacy data.[1]

Analysis of Key Clinical Trials

The clinical program for BG1805 comprises several registered trials targeting both adult and pediatric populations, primarily conducted in China. The key trials are summarized in Table 1.

Table 1: Summary of Key BG1805 Clinical Trials

Trial Identifier	Phase	Title / Brief Description	Patient Population	Status	Estimated Primary Completion	Primary Objectives
NCT06118788	Phase I	A Single-arm, Dose-escalation and Dose-expansion Phase I Clinical Study to Evaluate the Tolerability, Safety and Preliminary Efficacy of BG1805 Injection in the Treatment of Relapsed or Refractory Acute Myeloid Leukemia [1]	Adults (18-70 years) with r/r AML [1]	Recruiting [1]	March 2027 [1]	Safety, Tolerability, RP2D determination [2]
NCT06347458	Phase I	A Single-arm, Dose-escalation and Dose-expansion Phase I Clinical Study...in the Treatment of Relapsed or Refractory Acute Myeloid Leukemia in Children 5	Children (3-18 years) with r/r AML 5	Not yet recruiting [16]	April 2027 5	Determine highest safe dose, assess preliminary efficacy [26]
ChiCTR2200060127	Phase I	A single-arm, dose-escalation and dose-expansion phase I clinical study to evaluate the tolerability, safety and preliminary efficacy of BG1805 injection... 25	Patients with r/r AML 25	Prospective registration 25	Not Applicable	Safety, Tolerability 25

Primary and Secondary Objectives

The clinical trials share a consistent set of objectives aimed at establishing the foundational safety and activity profile of BG1805.

• Primary Objectives: The foremost goals across all Phase I studies are to assess the safety and tolerability of the BG1805 infusion.[7] This includes monitoring for treatment-emergent adverse events and dose-limiting toxicities (DLTs). A key outcome of this phase is the identification of the RP2D and the optimal lymphodepletion chemotherapy regimen to be used in subsequent studies.[2]
• Secondary Objectives: Secondary endpoints are designed to provide an initial characterization of the therapy's clinical activity and behavior. These include evaluating the pharmacokinetic (PK) profile of BG1805 (i.e., the expansion and persistence of CAR-T cells in vivo), assessing preliminary efficacy through metrics like overall response rate (ORR), and measuring the immunogenicity of the therapy.[25]
• Exploratory Objectives: The studies also include exploratory endpoints to deepen the biological understanding of the therapy's effects, such as analyzing pharmacodynamic (PD) markers and quantifying the change in the proportion of CLL1-positive tumor cells in patients after receiving the infusion.[25]

Patient Population and Eligibility Criteria

The trials define specific patient populations through rigorous inclusion and exclusion criteria, which are compared for the adult and pediatric studies in Table 2.

Table 2: Comparative Analysis of Patient Eligibility Criteria (Adult vs. Pediatric Trials)

Criteria Category	NCT06118788 (Adults)	NCT06347458 (Pediatric)
Age	18-70 years (inclusive) [1]	3-18 years (inclusive) 5
Weight	Not specified	≥10 kg 5
Diagnosis	Confirmed r/r AML per 2016 WHO and 2017 Chinese guidelines [27]	Confirmed r/r AML per 2016 WHO and 2017 Chinese guidelines 5
Biomarker	Not explicitly specified in summary	Flow cytometry confirmed AML Blast CLL-1 expression ≥50% 5
Performance Status	Not specified in summary (ECOG 0-1 in ChiCTR trial 25)	ECOG performance status of 0-1 5
Organ Function	Adequate organ function (e.g., LVEF ≥45%, CrCl ≥60 mL/min) [1]	Adequate organ function (e.g., LVEF ≥45%, CrCl ≥60 mL/min) 5
Key Exclusions	Acute promyelocytic leukemia, active CNS involvement, active HBV/HCV/HIV, prior organ transplant (non-HSCT), active GVHD, prior CAR-T therapy 25	Same as adult trial 25

A notable distinction in the eligibility criteria is the explicit biomarker requirement for the pediatric trial (NCT06347458), which mandates that at least 50% of a patient's AML blasts must express CLL-1 as confirmed by flow cytometry.[5] This reflects a sophisticated, precision-medicine approach to clinical trial design. By pre-selecting patients whose tumors highly express the target antigen, the sponsor significantly increases the statistical probability of observing a clinical response. This biomarker-driven enrichment strategy is a causal factor that can lead to clearer and stronger efficacy signals in early-phase trials, providing a more definitive assessment of the drug's potential and a more straightforward path toward regulatory discussions compared to an "all-comers" trial design that includes patients with low or no target expression.

Safety and Tolerability Profile

Anticipated CAR-T Class-Related Toxicities

As with all CAR-T cell immunotherapies, BG1805 is associated with a risk of unique and potentially severe toxicities stemming from profound immune activation. The two most significant and well-characterized complications are Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).[28]

• CRS: This systemic inflammatory response is caused by the massive release of cytokines from activated CAR-T cells and other immune cells. Manifestations can range from mild, flu-like symptoms (fever, fatigue) to severe, life-threatening conditions involving high fever, hypotension, hypoxia, and organ dysfunction.[28]
• ICANS: This neurological toxicity can present with a wide range of symptoms, including confusion, aphasia, delirium, seizures, and cerebral edema. The pathophysiology is not fully understood but is related to endothelial activation and blood-brain barrier disruption.28 Other potential serious adverse reactions include tumor lysis syndrome (TLS), prolonged cytopenias, and on-target, off-tumor toxicity, where CAR-T cells attack healthy tissues that express the target antigen.28

BG1805-Specific Safety Rationale

The central safety hypothesis for BG1805 is built upon the selective expression profile of its target, CLL1. A major safety concern for any therapy targeting myeloid lineage antigens is the potential for on-target, off-leukemia toxicity against healthy hematopoietic cells. The destruction of normal HSCs and myeloid progenitors can lead to aplastic anemia, a catastrophic and potentially fatal outcome. The rationale for BG1805 is that since CLL1 is absent or expressed at very low levels on normal HSCs, the therapy should be able to eradicate CLL1-positive leukemia cells while largely sparing the essential stem cell pool required for long-term blood production.[3] This selective targeting is designed to mitigate the risk of severe and irreversible myelotoxicity, representing a key potential safety advantage over therapies directed at less specific myeloid antigens.

Observed Clinical Safety Data

The most direct evidence for the safety profile of BG1805 comes from the interim analysis of the multi-center pediatric trial.[8] In this study of eight children with r/r-AML, the observed safety profile was highly encouraging:

• Patients developed Grade 1-2 CRS, which is considered a manageable level of this toxicity.
• No instances of severe (Grade 3 or higher) CRS were reported.
• No lethal events occurred.[8]

These early clinical results provide the first piece of human evidence to support the preclinical safety hypothesis. The observation of a manageable safety profile, particularly the absence of severe toxicities, in the first patient cohort is a critical de-risking event for the program. It suggests that the selective targeting of CLL1 may indeed translate into a favorable therapeutic window in patients. If this safety profile is maintained as more patients are treated in the ongoing Phase I trials, it will constitute a primary competitive advantage for BG1805, as safety and tolerability are often the limiting factors for the broad application of potent cancer therapies.

Corporate and Regulatory Landscape

Developer Profile: Guangzhou Bio-gene Technology Co., Ltd.

BG1805 is being developed by Guangzhou Bio-gene Technology Co., Ltd., a biotechnology company based in Guangzhou, China.[1] The company is focused on the discovery, development, and delivery of novel cell therapies for the treatment of hematological malignancies, solid tumors, and autoimmune diseases.[3]

Guangzhou Bio-gene has established comprehensive, end-to-end capabilities, including a full R&D platform that spans from initial antibody screening and engineering to in-house, GMP-compliant manufacturing of lentiviral vectors and CAR-T cell products to support its clinical trials.[23] BG1805 is a landmark asset for the company, representing its first cell therapy candidate to advance into formal, IND-based clinical development.[2] The company's broader pipeline demonstrates a deep commitment to the cell therapy space, with additional autologous CAR-T programs targeting CD7, GPRC5D, B7H3, and Claudin18.2, as well as allogeneic platforms under development.[3] This positions Guangzhou Bio-gene as a significant and emerging player in the highly competitive Chinese cell therapy ecosystem.

Regulatory Milestones and Designations

BG1805 has achieved several key regulatory milestones that validate its therapeutic potential and facilitate its global development pathway.

• Orphan Drug Designation (ODD): The therapy has been granted ODD by both the U.S. FDA and the European Medicines Agency (EMA).[3] Securing these dual designations is a major strategic achievement. It provides external validation from the world's two most influential regulatory bodies that BG1805 targets a serious and life-threatening condition with a high unmet medical need. Furthermore, ODD unlocks significant financial and procedural incentives that are crucial for development. These benefits include seven to ten years of market exclusivity upon approval, waivers or reductions of substantial application fees, and access to specialized regulatory guidance, such as protocol assistance from the EMA.[30] For Guangzhou Bio-gene, these advantages substantially lower the financial and regulatory hurdles for potential entry into the lucrative U.S. and European markets.
• Investigational New Drug (IND) Approvals: The company has received two separate IND approvals from China's NMPA, authorizing the initiation of clinical trials for BG1805 in both adult and pediatric patient populations with r/r AML.[3]

Intellectual Property

Guangzhou Bio-gene has established a robust intellectual property portfolio surrounding its CLL1-targeted technology.

• Core Patent: The company's foundational invention patent, titled "Targeted CLL1 Chimeric Antigen Receptor and Its Application," was awarded the 25th China Patent Excellence Award.[33] This prestigious national award, co-established by China's National Intellectual Property Administration (NIPA) and the World Intellectual Property Organization (WIPO), is a significant honor. It signifies that the core technology underlying the BG1805 CAR construct is not merely novel enough to be patentable, but is recognized by national experts as a high-quality and significant invention. This external validation strengthens the company's IP position and signals a high degree of technological innovation.
• Patent Filings: The company is the assignee on multiple patents and patent applications covering the key components of the therapy. These include filings for an "Anti-CLL1 antibody and use thereof" and a "Chimeric antigen receptor targeting CLL1".[17] For instance, U.S. Patent #12,358,990, issued to the company, describes an anti-CLL1 antibody with high affinity and its potential applications in the diagnosis and treatment of tumors.[17] This comprehensive patent strategy aims to protect the novel antibody, the CAR construct, and their therapeutic applications.

Synthesis and Forward-Looking Analysis

Consolidated Assessment

BG1805 emerges from this analysis as a scientifically compelling and strategically well-managed investigational CAR-T cell therapy. Its primary strength lies in its foundational science: the selection of CLL1 as a target offers a highly rational approach to treating AML by potentially eradicating both leukemic blasts and the underlying LSCs while sparing the healthy hematopoietic system. This strong target rationale is now supported by encouraging early clinical evidence from IITs and a formal pediatric interim analysis, which have demonstrated high response rates and a manageable safety profile.

The program is further bolstered by a strong regulatory and intellectual property foundation. The dual Orphan Drug Designations from the FDA and EMA provide a clear and incentivized path for global development, while the award-winning patent portfolio signals a high degree of technological novelty. The developer, Guangzhou Bio-gene Technology, has demonstrated a savvy development strategy, using IITs to de-risk the program before committing to formal trials, and has built the in-house capabilities necessary to advance its pipeline.

The primary risks are those inherent to any early-stage therapeutic. The promising clinical data, while highly encouraging, are derived from a small number of patients. The safety and efficacy profile must be confirmed in larger patient cohorts in the ongoing and future trials. Furthermore, as an autologous cell therapy, BG1805 will face the complex manufacturing, logistical, and cost challenges common to all personalized cell therapies.

Future Development Trajectory

The immediate path forward for BG1805 is clear. The primary objective is the successful completion of the dose-escalation portions of the ongoing Phase I trials (NCT06118788 and NCT06347458) to formally establish the RP2D. Following this, the dose-expansion cohorts will be crucial for generating a more robust dataset on safety and efficacy, which will inform the design of potential pivotal Phase II studies.

Looking further ahead, the competitive landscape for AML therapies is dynamic. While BG1805 is a leading autologous anti-CLL1 CAR-T, other approaches are also in development. Notably, Caribou Biosciences is advancing CB-012, an allogeneic (off-the-shelf) anti-CLL-1 CAR-T therapy.[35] Allogeneic therapies, derived from healthy donor cells, offer potential advantages in terms of manufacturing scalability and immediate availability, and will represent a key competitive modality in the future. The long-term success of BG1805 will depend on its ability to demonstrate a superior or differentiated profile in terms of efficacy, durability of response, and safety compared to these emerging competitors.

Concluding Remarks

In conclusion, BG1805 is a promising investigational therapy that addresses a profound unmet medical need in relapsed and refractory acute myeloid leukemia. It is built on a strong scientific foundation, supported by encouraging early clinical data, and guided by a sound development and regulatory strategy. The program's ultimate success will hinge on the ability to translate these early signals into durable clinical benefit in larger, well-controlled studies. If the favorable therapeutic window afforded by the selective targeting of CLL1 is confirmed, BG1805 has the clear potential to become a transformative new treatment option for patients battling this devastating disease.

Works cited

1. Study Details | NCT06118788 | Phase I Clinical Study: BG1805 ..., accessed October 30, 2025, https://clinicaltrials.gov/study/NCT06118788
2. Guangzhou Bio-gene Technologies Announces Initiation of Phase I Clinical Trial for BG1805, a CAR-T Targeting CLL-1 - FirstWord Pharma, accessed October 30, 2025, https://firstwordpharma.com/story/5852769
3. Guangzhou Bio-gene Technology Co., Ltd, accessed October 30, 2025, https://gzbiogene.com/en/index.aspx
4. Pipeline - Guangzhou Bio-gene Technology Co., Ltd, accessed October 30, 2025, https://gzbiogene.com/en/development/list.aspx
5. Study Details | NCT06347458 | BG1805 Injection in the Treatment of ..., accessed October 30, 2025, https://www.clinicaltrials.gov/study/NCT06347458
6. Guangzhou Bio-gene Technologies Announces Initiation of Phase I Clinical Trial for BG1805, a CAR-T Targeting CLL-1 - GlobeNewswire, accessed October 30, 2025, https://www.globenewswire.com/news-release/2024/05/02/2874092/0/en/Guangzhou-Bio-gene-Technologies-Announces-Initiation-of-Phase-I-Clinical-Trial-for-BG1805-a-CAR-T-Targeting-CLL-1.html
7. Guangzhou Bio-gene Technologies Announces Initiation of Phase I Clinical Trial for BG1805, a CAR-T Targeting CLL-1 - BioSpace, accessed October 30, 2025, https://www.biospace.com/guangzhou-bio-gene-technologies-announces-initiation-of-phase-i-clinical-trial-for-bg1805-a-car-t-targeting-cll-1
8. Characteristics of anti-CLL1 based CAR-T therapy for children with ..., accessed October 30, 2025, https://pubmed.ncbi.nlm.nih.gov/36151140/
9. Advanced Filter - DrugBank, accessed October 30, 2025, https://go.drugbank.com/unearth/q?c=_score&d=up&page=237&query=topisulfa+g+lis&searcher=drugs
10. xuxuxuxuxu/Pharmacology-QA · Datasets at Hugging Face, accessed October 30, 2025, https://huggingface.co/datasets/xuxuxuxuxu/Pharmacology-QA/viewer/default/train?p=2
11. BG1805: Uses, Interactions, Mechanism of Action | DrugBank Online, accessed October 30, 2025, https://go.drugbank.com/drugs/DB18667
12. Yeast ORF collection - Horizon Discovery, accessed October 30, 2025, https://horizondiscovery.com/-/media/Files/Horizon/resources/Technical-manuals/yeast-orf-collection-manual.pdf
13. THE MOLECULAR PHARMACOLOGY OF PATEAMINE A, accessed October 30, 2025, https://s3-ap-southeast-2.amazonaws.com/pstorage-wellington-7594921145/31430635/thesis_access.pdf?X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Credential=AKIA3OGA3B5WBO5PUAXV/20250903/ap-southeast-2/s3/aws4_request&X-Amz-Date=20250903T141835Z&X-Amz-Expires=86400&X-Amz-SignedHeaders=host&X-Amz-Signature=c5a1e8c7fc040fc2af146da59de4538bbe0099f0083c507dcb7763bd6455b6c3
14. pBG1805 vector map and sequence - NovoPro Bioscience Inc., accessed October 30, 2025, https://www.novoprolabs.com/vector/Vgmztmmy
15. Definition of autologous anti-CLL-1-CAR T lymphocytes BG1805 - NCI Drug Dictionary, accessed October 30, 2025, https://www.cancer.gov/publications/dictionaries/cancer-drug/def/autologous-anti-cll-1-car-t-lymphocytes-bg1805
16. Autologous Anti-CLL-1 Chimeric Antigen Receptor T cells (Guangzhou Bio-Gene) - Drug Targets, Indications, Patents - Patsnap Synapse, accessed October 30, 2025, https://synapse.patsnap.com/drug/918d477439ae428e973f9c5c2a6e9ce0
17. Anti-CLL1 antibody and use thereof - Justia Patents, accessed October 30, 2025, https://patents.justia.com/patent/12358990
18. Unveiling the potential of CLL-1: a promising target for AML therapy, accessed October 30, 2025, https://d-nb.info/1364582325/34
19. Successful Anti-CLL1 CAR T-Cell Therapy in Secondary Acute Myeloid Leukemia - Frontiers, accessed October 30, 2025, https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.00685/full
20. CLL-1-Targeted Allogeneic CAR-T Cells Exhibit High on-Target Specificity and Potent Cytotoxicity in Preclinical Models of Acute Myeloid Leukemia | Request PDF - ResearchGate, accessed October 30, 2025, https://www.researchgate.net/publication/376150376_CLL-1-Targeted_Allogeneic_CAR-T_Cells_Exhibit_High_on-Target_Specificity_and_Potent_Cytotoxicity_in_Preclinical_Models_of_Acute_Myeloid_Leukemia
21. Recent advances of CAR-T cells in acute myeloid leukemia - PMC - PubMed Central, accessed October 30, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11938459/
22. Engineering CAR-T cells - PMC - NIH, accessed October 30, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC5482931/
23. Guangzhou Bio-gene Technology Co., Ltd. - Drug pipelines, Patents, Clinical trials - Patsnap Synapse, accessed October 30, 2025, https://synapse.patsnap.com/organization/3de5ca2a6e265a383c4b248d2aaca193
24. Guangzhou Bio-gene Starts Phase I Trial for CLL-1 CAR-T BG1805 - Patsnap Synapse, accessed October 30, 2025, https://synapse.patsnap.com/article/guangzhou-bio-gene-starts-phase-i-trial-for-cll-1-car-t-bg1805
25. Chinese Clinical Trial Register (ChiCTR) - The world health organization international clinical trials registered organization registered platform, accessed October 30, 2025, https://www.chictr.org.cn/showprojEN.html?proj=169846
26. BG1805 Injection in the Treatment of Relapsed or Refractory Acute Myeloid Leukemia in Children | TrialScreen, accessed October 30, 2025, https://app.trialscreen.org/trials/phase-1-bg1805-injection-treatment-relapsed-or-refractory-acute-myeloid-trial-nct06347458
27. The journey of CAR-T therapy in hematological malignancies - PMC - PubMed Central - NIH, accessed October 30, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9547409/
28. Company Profile - Guangzhou Bio-gene Technology Co., Ltd, accessed October 30, 2025, https://gzbiogene.com/en/company/index.aspx
29. Special FDA designations for drug development: orphan, fast track, accelerated approval, priority review, and breakthrough therapy - PMC - PubMed Central, accessed October 30, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11283430/
30. Orphan designation: Overview | European Medicines Agency (EMA), accessed October 30, 2025, https://www.ema.europa.eu/en/human-regulatory-overview/orphan-designation-overview
31. Neurogene Announces EMA Grants Orphan Drug Designation to CLN5 Batten Disease Gene Therapy - Business Wire, accessed October 30, 2025, https://www.businesswire.com/news/home/20210629005392/en/Neurogene-Announces-EMA-Grants-Orphan-Drug-Designation-to-CLN5-Batten-Disease-Gene-Therapy
32. [Glorious Moment!] Guangzhou BioGenius Wins China Patent ..., accessed October 30, 2025, https://gzbiogene.com/en/CompanyNews/info.aspx?itemid=135
33. Guangchao LI Inventions, Patents and Patent Applications, accessed October 30, 2025, https://patents.justia.com/inventor/guangchao-li
34. Study Details | NCT06128044 | CRISPR-Edited Allogeneic Anti-CLL-1 CAR-T Cell Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia | ClinicalTrials.gov, accessed October 30, 2025, https://clinicaltrials.gov/study/NCT06128044
35. A phase 1, multicenter, open-label study of cb-012, a CRISPR-edited allogeneic anti-cll-1 CAR-T cell therapy in patients with relapsed/refractory acute myeloid leukemia (amplify) - MD Anderson Cancer Center, accessed October 30, 2025, https://www.mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2023-0930.html
36. A first-in-human phase 1, multicenter, open-label study of CB-012, a next-generation CRISPR-edited allogeneic anti-CLL-1 CAR-T cell therapy for adults with relapsed/refractory acute myeloid leukemia (AMpLify). - ASCO Publications, accessed October 30, 2025, https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS6586