BT-02: A First-in-Class ITPRIPL1-Targeting Monoclonal Antibody for Advanced Solid Tumors

1. Executive Summary

BT-02 is an investigational, first-in-class monoclonal antibody developed by Shanghai BioTroy Therapeutics Co., Ltd. (also known as Shanghai Baiquan Biotechnology Co., Ltd.). It is designed to treat advanced solid tumors by targeting Inositol 1,4,5-trisphosphate receptor-interacting protein-like 1 (ITPRIPL1), a novel immune checkpoint. ITPRIPL1 has been identified as a ligand for CD3ε, a critical component of the T-cell receptor complex. By binding to CD3ε, ITPRIPL1 impedes T-cell activation, thereby enabling tumor immune evasion. BT-02, by neutralizing ITPRIPL1, aims to restore T-cell anti-tumor activity.

Preclinical studies have demonstrated promising efficacy and a good safety profile for BT-02, leading to Investigational New Drug (IND) application approvals from both the U.S. Food and Drug Administration (FDA) in September 2023 and the China National Medical Products Administration (NMPA) in January 2024. BioTroy Therapeutics, in collaboration with Fudan University, has established a robust global intellectual property portfolio around this novel target and its therapeutic modulation.

Currently, BT-02 is being evaluated in parallel Phase 1/2 clinical trials in both the United States (NCT06404905) and China (CTR20240083) for patients with advanced solid tumors. These open-label studies are assessing the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary anti-tumor activity of BT-02. The development of BT-02 represents a significant "from 0 to 1" innovation, focusing on a novel mechanism that may address tumors unresponsive to existing PD-1/PD-L1 inhibitors. The successful clinical development of BT-02 could offer a new therapeutic paradigm in cancer immunotherapy.

2. Introduction to BT-02

BT-02 is an investigational anti-tumor agent positioned as a globally pioneering, first-in-class drug candidate.[1] It is a monoclonal antibody injection under development for the treatment of advanced solid tumors.[1] The nomenclature for this agent also includes BT 02 and BT02.[2] The development of BT-02 is characterized by an original "from 0 to 1" research and development model, signifying a departure from incremental drug development and an emphasis on foundational target discovery to create a novel therapeutic approach.[1]

Developer: Shanghai Baiquan Biotechnology Co., Ltd. / BioTroy Therapeutics

BT-02 is self-developed by Shanghai BioTroy Therapeutics Co., Ltd., which is also referred to as Shanghai Baiquan Biotechnology Co., Ltd..1 BioTroy Therapeutics, established in Shanghai in 2020, is a biopharmaceutical company focused on the research and development of new tumor treatment targets and drugs. The company particularly emphasizes the creation of "first-in-class" agents derived from original target discovery and supported by a global intellectual property strategy.1 BioTroy Therapeutics has successfully completed financing rounds totaling over 150 million RMB to support its research and development endeavors.1

Therapeutic Modality

BT-02 is classified as a monoclonal antibody.1 Its intended route of administration is via injection, with clinical trial designs implying intravenous administration.1

The consistent emphasis on BT-02 being "first-in-class" and originating from "original target discovery" is particularly noteworthy in the pharmaceutical industry.[1] A "first-in-class" designation suggests that BT-02 operates via a novel mechanism of action, distinct from existing therapeutic options. This novelty holds the potential to address significant unmet medical needs, particularly for patients whose diseases do not respond to, or have developed resistance to, current standard-of-care treatments. The "original target discovery" aspect underscores the innovative nature of BioTroy's research, moving beyond the development of "me-too" drugs. While this path inherently carries higher developmental risks, the potential rewards, in terms of clinical impact and market differentiation, are also substantially greater if the drug proves successful. The scientific underpinning for BT-02's development is strengthened by the discovery of its target, ITPRIPL1, and its role as a ligand for CD3ε, which is implicated in tumor immune evasion, as detailed in a publication in the journal Cell.[6] This combination of originality in target and mechanism, coupled with a proactive global intellectual property strategy from an early stage, positions BioTroy Therapeutics for a potentially unique standing in the market should BT-02 demonstrate safety and efficacy. Consequently, BT-02 is not merely an incremental advancement but represents a potentially disruptive technology in the field of cancer immunotherapy, targeting a novel immune checkpoint. This pioneering approach, while promising, also entails the significant developmental challenges typically associated with first-in-class therapeutics.

Table 1: BT-02 - Key Drug Characteristics

Characteristic	Details	Snippet Citations
Name	BT-02	User Query
Alternative Names	BT 02, BT02	2
Developer	Shanghai Baiquan Biotechnology Co., Ltd. / BioTroy Therapeutics	1
Modality	Monoclonal Antibody	1
Target	ITPRIPL1 (Inositol 1,4,5-trisphosphate receptor-interacting protein-like 1)	2
Mechanism of Action	ITPRIPL1 Inhibitor	2
Primary Therapeutic Area	Oncology (Advanced Solid Tumors)	1
Current Highest Development Phase	Phase 1/2	2
Route of Administration	Injection (Intravenous implied)	1

3. Mechanism of Action and Scientific Rationale

The therapeutic strategy of BT-02 revolves around the novel target, Inositol 1,4,5-trisphosphate receptor-interacting protein-like 1 (ITPRIPL1).

Target Identification: ITPRIPL1

BT-02 is specifically designed to target ITPRIPL1.2 ITPRIPL1 is also known by the alias ITPRIP like 1.2

• Function of ITPRIPL1 in Immune Regulation: The primary function of ITPRIPL1 relevant to BT-02's mechanism is its role as an inhibitory ligand of CD3ε (epsilon), a crucial subunit of the CD3 complex found on T-lymphocytes.[6] The CD3 complex is an integral part of the T-cell receptor (TCR) and is essential for initiating T-cell activation upon antigen recognition. The binding of the extracellular domain of ITPRIPL1 to CD3ε on T-cells directly impedes the initial stages of T-cell activation. This interference is achieved by significantly reducing intracellular calcium influx and inhibiting the phosphorylation of ZAP70 (Zeta-chain-associated protein kinase 70), both of which are critical downstream signaling events following TCR engagement.[6] By disrupting these early signaling steps, ITPRIPL1 effectively inhibits the TCR-CD3 complex signaling cascade, preventing full T-cell activation.[7] This mechanism is characterized as impeding T-cell activation during the critical "signal one" phase of the immune response, which is the primary antigen-specific signal required for T-cell priming.[6]
• Role of ITPRIPL1 in Tumor Immune Evasion: Cancer cells can exploit the ITPRIPL1-CD3ε interaction as a mechanism to evade immune surveillance and thereby promote tumor growth. The upregulation of ITPRIPL1 expression by tumor cells leads to the inhibition of T-cells within the tumor microenvironment (TME).[6] This positions ITPRIPL1 as a novel immune checkpoint, similar in concept to established checkpoints like PD-1/PD-L1, but operating through a distinct molecular interaction and at a potentially earlier stage of T-cell response.
• Expression and Significance of ITPRIPL1 in Cancer: Studies have indicated that ITPRIPL1 is widely overexpressed in Non-Small Cell Lung Cancer (NSCLC), where its levels positively correlate with tumor stage. Furthermore, in NSCLC, ITPRIPL1 expression is negatively correlated with the infiltration of CD8+ T-cells, suggesting that higher ITPRIPL1 levels are associated with poorer immune cell presence in the tumor and, consequently, a worse clinical prognosis.[11] In Low-Grade Glioma (LGG), high expression of ITPRIPL1 has been identified as a risk factor associated with poor overall survival and relapse-free survival, further underscoring its prognostic significance.[9] Methylation studies have also implicated ITPRIPL1 in breast cancer, suggesting its potential utility as a diagnostic biomarker in this malignancy.[9] Data from The Human Protein Atlas indicates that while the RNA expression of ITPRIPL1 shows low cancer specificity overall, it is nonetheless detected in various cancer types, including colorectal, breast, prostate, and lung cancer.[12] This broad detection across multiple cancer types suggests a potentially wide applicability for therapeutic strategies targeting ITPRIPL1.

BT-02: An ITPRIPL1 Inhibitor

BT-02 is a neutralizing monoclonal antibody developed to specifically target and inhibit ITPRIPL1.2

• Hypothesized Therapeutic Effect: The therapeutic hypothesis for BT-02 is that by binding to and neutralizing ITPRIPL1, the antibody will prevent ITPRIPL1 from interacting with CD3ε on T-cells. This blockade is expected to disinhibit T-cells, thereby restoring or enhancing their activation and cytotoxic capabilities against tumor cells. The anticipated outcomes of this restored immune function are the restraint of tumor growth and an increased infiltration of activated T-cells into the tumor microenvironment.[6]

The discovery of the ITPRIPL1-CD3ε axis represents a significant advancement in understanding tumor immune evasion, particularly as it introduces a checkpoint mechanism distinct from the well-characterized PD-1/PD-L1 pathway. Research indicates that the effectiveness of current cancer immunotherapies varies among patients, suggesting the existence of alternative immune evasion strategies employed by tumors.[6] ITPRIPL1's interaction with CD3ε, a fundamental component of the T-cell receptor complex essential for the primary activation signal ("signal one"), constitutes a different mode of immune suppression compared to the PD-1/PD-L1 pathway, which typically modulates co-stimulatory or co-inhibitory signals influencing later phases of T-cell response or sustained activity. BioTroy Therapeutics has explicitly stated that its primary pipeline focus is on developing treatments for tumors that are unresponsive to PD-1/PD-L1 inhibitors.[1] Therefore, by targeting the ITPRIPL1-CD3ε axis, BT-02 has the potential to address a critical unmet medical need in cancer immunotherapy. It may offer a novel therapeutic avenue for patients whose tumors do not respond to, or have acquired resistance to, existing checkpoint inhibitors. This distinct mechanism also raises the possibility, though not explicitly detailed in the available information, for future exploration of BT-02 in combination therapies with current immunotherapies to achieve synergistic anti-tumor effects.

Table 2: ITPRIPL1 - Function and Role in Cancer Immunotherapy

Aspect	Details	Snippet Citations
Gene/Protein Name	ITPRIPL1 (Inositol 1,4,5-trisphosphate receptor-interacting protein-like 1)	2
Known Aliases	ITPRIP like 1, KIAA1754L, D1B	2
Molecular Function	Enables receptor ligand activity; functions as a ligand of CD3E.	7
Biological Process	Involved in negative regulation of T cell receptor signaling pathway.	7
Interaction Partner	CD3ε (epsilon subunit of the CD3 complex on T-cells). Patent literature also mentions NRP2.	6
Role in T-cell Activation	Inhibits TCR-CD3 complex signaling by binding to CD3ε, leading to decreased calcium influx and ZAP70 phosphorylation, thereby impeding initial T-cell activation (Signal 1).	7
Expression Pattern in Tumors	Upregulated in various cancer cells, including NSCLC (correlates with stage), LGG (prognostic marker), and implicated in breast cancer. Detected in colorectal, breast, prostate, and lung cancer tissues.	9
Implication in Tumor Immune Evasion	Upregulation by cancer cells inhibits T-cells in the tumor microenvironment, allowing tumors to evade immune surveillance and promote growth. Acts as a novel immune checkpoint.	6
Therapeutic Implication of Inhibition	Neutralizing ITPRIPL1 (e.g., with BT-02) is expected to restore T-cell activation, promote T-cell infiltration into tumors, and restrain tumor growth. May be effective in tumors unresponsive to PD-1/PD-L1 inhibitors.	1

4. Preclinical Development

The preclinical development of BT-02 has yielded significant findings regarding its efficacy and safety, forming a strong basis for its progression into clinical trials.

Summary of Preclinical Efficacy Findings

BioTroy Therapeutics has reported that BT-02 demonstrated "outstanding preclinical efficacy against various hard-to-treat advanced solid tumors".1 This efficacy was further substantiated in studies where a neutralizing antibody against ITPRIPL1, serving as a proxy for BT-02, effectively restrained tumor growth and promoted the infiltration of T-cells into the tumor microenvironment in mouse models across diverse solid tumor types.6 Adding to the translational relevance of these findings, an antibody targeting the canine ortholog of ITPRIPL1 exhibited "notable therapeutic efficacy against naturally occurring tumors in pet clinics".6 This observation in a larger animal model with spontaneous tumors often provides a more predictive insight into potential human efficacy compared to traditional induced tumor models in mice.

Preclinical Safety Profile

The preclinical safety assessment of BT-02 has been positive, with studies indicating "good safety through detailed data".1 While specific details of toxicology studies were not provided in the available information, this general assertion supports the progression to human trials.

Supporting Evidence for Clinical Translation

The quality and comprehensiveness of the preclinical research for BT-02 have been recognized by major regulatory bodies. The drug received Investigational New Drug (IND) application approvals from both the United States Food and Drug Administration (FDA) and the China National Medical Products Administration (NMPA), with the company noting that this reflected "high recognition" of their preclinical work.1 This dual approval from stringent regulatory agencies is a critical validation point for a first-in-class molecule. BioTroy Therapeutics emphasizes that its research is grounded in "solid scientific research data and cutting-edge translational medicine concepts".1 Further bolstering the scientific validation of the underlying mechanism and target, the discovery of ITPRIPL1's role in immune evasion and the development of antibodies against it (conceptual basis for BT-02) was published in the high-impact journal Cell in April 2024.6

The preclinical data package for BT-02 appears robust and compelling. The consistent reports of "outstanding preclinical efficacy" and "good safety" [1], while standard for company communications, are significantly reinforced by the subsequent IND approvals from both the US FDA and China's NMPA.[1] These regulatory green lights indicate that the preclinical data met rigorous standards for safety and rationale for human testing, a particularly important hurdle for a first-in-class therapeutic targeting a novel pathway. The reported efficacy in "various hard-to-treat advanced solid tumors" and across "various solid tumor types" in murine models [1], combined with the positive results in naturally occurring canine tumors [6], offers a broader and more compelling preclinical evidence base than studies limited to a single tumor model. The canine tumor data, in particular, is valuable as it involves a more complex, immunologically diverse, and heterogeneous tumor environment that often better reflects human cancer. Finally, the publication of the foundational science in a prestigious, peer-reviewed journal like Cell [6] lends significant credibility to the scientific rigor and novelty of the ITPRIPL1 target and the therapeutic approach. This confluence of positive preclinical efficacy across multiple models, favorable safety data, dual regulatory acceptances for clinical investigation, and high-level scientific publication strongly supports the continued development of BT-02.

5. Clinical Development Program

Following a robust preclinical program, BT-02 has advanced into clinical development, marked by key regulatory approvals and the initiation of Phase 1/2 studies.

Regulatory Milestones

BioTroy Therapeutics successfully obtained IND approvals from two major global regulatory agencies:

• U.S. Food and Drug Administration (FDA): IND approval was granted in September 2023, allowing for the commencement of clinical trials in the United States.[1]
• China National Medical Products Administration (NMPA): IND approval (approval number: CXSL2300740) was announced in January 2024, permitting clinical investigation in China.[1]

Overview of Clinical Trials

Three clinical trials have been identified for BT-02:

• NCT06404905: This is a first-in-human, open-label, Phase 1/2 study designed to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary anti-tumor activity of BT02 in patients with advanced solid tumors. The trial is currently recruiting participants.[2]
• CTR20240083 (ChiCTR): Registered with the Chinese Clinical Trial Registry, this is an open-label Phase 1/2 study with objectives closely mirroring NCT06404905: evaluating the safety, tolerability, PK, immunogenicity, and preliminary anti-tumor activity of BT02 in patients with advanced solid tumors. This trial is also recruiting, with an estimated primary completion date of December 31, 2024.[2]
• ChiCTR2300075191: This was an earlier Phase 1 open dose-exploration study intended to evaluate the safety, tolerability, PK characteristics, and anti-tumor efficacy of BT02 in patients with advanced solid tumors. According to the latest available information, the status of this trial is suspended.[2] The reasons for suspension are not detailed in the provided information.

Detailed Review of Active Phase 1/2 Trials (NCT06404905 and CTR20240083)

The two currently active trials, NCT06404905 (US-based) and CTR20240083 (China-based), represent the spearhead of BT-02's clinical evaluation.

• Study Design and Phase: Both are structured as open-label, Phase 1/2 studies.[2] The Phase 1 portion typically involves dose escalation cohorts to determine the maximum tolerated dose (MTD) and identify dose-limiting toxicities (DLTs). The Phase 2 portion usually consists of expansion cohorts at the recommended Phase 2 dose (RP2D) to further assess safety and gather preliminary evidence of efficacy in specific tumor types or patient populations.
• Primary Objectives: The primary goals for both trials are consistently stated as the evaluation of the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary anti-tumor activity of BT-02.[2]
• Secondary Objectives: While not explicitly detailed in the provided materials, secondary objectives in such trials typically include assessments of Objective Response Rate (ORR) based on criteria like RECIST, Duration of Response (DOR), Progression-Free Survival (PFS), Overall Survival (OS), and further exploratory biomarker analyses to understand the drug's effects and identify potential predictors of response.
• Key Inclusion/Exclusion Criteria: The target population for these trials consists of patients with advanced solid tumors.[2] More specific inclusion or exclusion criteria, such as prior lines of therapy, performance status, or specific tumor types for expansion cohorts, are not available in the provided snippets.
• Dosage and Administration: BT-02 is administered as a monoclonal antibody injection [1], presumably intravenously, consistent with typical antibody administration routes in oncology. Specifics regarding the dosing regimens, schedules for dose escalation, or the doses to be explored are not detailed.
• Current Recruitment Status and Timelines:
• NCT06404905 is actively recruiting participants.[2] No specific primary completion or overall study completion dates are provided in the snippets for this trial.
• CTR20240083 is also actively recruiting participants, with an estimated primary completion date of December 31, 2024.[2]

Preliminary Clinical Data

As of the latest information available in the research snippets (Ozmosi update May 8, 2024, noted as a "Clinical Trial Update" 3), no specific preliminary clinical data, such as observed response rates, detailed safety events from human participants, or pharmacokinetic profiles in patients, have been publicly disclosed.

The initiation of parallel clinical trials in the United States and China signifies a deliberate global development strategy by BioTroy Therapeutics. The near-simultaneous IND approvals from the FDA (September 2023) and NMPA (January 2024) [1], followed by the launch of Phase 1/2 studies (NCT06404905 and CTR20240083) with virtually identical core objectives [2], points towards a concerted effort to gather clinical data from diverse patient populations concurrently. This approach can potentially accelerate the overall global development timeline for BT-02 and facilitate broader market access in the future if the drug proves successful. Such a strategy, especially for a company of BioTroy's stage, reflects significant confidence in the drug candidate and a forward-thinking approach to navigating the complex landscape of international drug development and regulatory pathways. While this parallel development can expedite data generation, it also introduces increased logistical and regulatory coordination challenges. The suspension of the earlier Chinese trial, ChiCTR2300075191 [2], might suggest a strategic consolidation of early-phase efforts into the more recently initiated CTR20240083, or it could be due to other unspecified factors requiring further clarification as development progresses.

Table 3: Overview of Clinical Trials for BT-02

Trial Identifier	Phase	Title/Brief Description	Study Status	Indication(s)	Key Objectives	Sponsor	Est. Primary Completion	IND Approval Details
NCT06404905	Phase 1/2	A First-in-Human, Open Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Antitumor Activity of BT02 in Patients With Advanced Solid Tumors	Recruiting	Advanced Solid Tumors	Safety, Tolerability, PK, Immunogenicity, Preliminary Anti-tumor Activity	Shanghai Baiquan Biotechnology Co., Ltd.	Not Specified	US FDA (Sept 2023) 1
CTR20240083	Phase 1/2	An open-label study evaluating the safety, tolerability, pharmacokinetics, immunogenicity and preliminary anti-tumor activity of BT02 in patients with advanced solid tumors	Recruiting	Advanced Solid Tumors	Safety, Tolerability, PK, Immunogenicity, Preliminary Anti-tumor Activity	Shanghai Baiquan Biotechnology Co., Ltd.	Dec 31, 2024 3	NMPA (CXSL2300740, Jan 2024) 1
ChiCTR2300075191	Phase 1	A phase I open dose exploration study to evaluate the safety, tolerability, pharmacokinetic characteristics and anti-tumor efficacy of BT02 in patients with advanced solid tumors	Suspended	Advanced Solid Tumors	Safety, Tolerability, PK, Anti-tumor Efficacy	Shanghai Baiquan Biotechnology Co., Ltd.	Not Specified	Implied NMPA, prior to CTR20240083

6. Developer Profile: BioTroy Therapeutics

BioTroy Therapeutics (officially Shanghai Baiquan Biotechnology Co., Ltd.) is a biopharmaceutical company founded in Shanghai in 2020.[1] The company is dedicated to the research and development of first-in-class therapies, primarily targeting cancer and immunological disorders. A core tenet of BioTroy's philosophy is the pursuit of "from 0 to 1" original target discovery, aiming to develop truly novel medicines rather than incremental improvements on existing therapies.[1] A significant focus of their pipeline is on tumors that have shown unresponsiveness to current PD-1/PD-L1 checkpoint inhibitors, addressing a major unmet need in oncology.[1] To fuel its ambitious research programs, BioTroy Therapeutics has successfully completed financing rounds amounting to over 150 million RMB.[1] The company is committed to establishing a global intellectual property footprint and advancing its drug candidates based on robust scientific evidence and cutting-edge translational medicine concepts.[1]

Key Personnel

Dr. Jie Xu is the founder of BioTroy Therapeutics and is recognized as a leading talent in national science and technology innovation in China.1 He is a senior researcher with extensive experience in translational oncology and oncoimmunotherapy.17 Dr. Xu's research group has been credited with discovering regulatory mechanisms of immune checkpoint pathways and identifying novel mechanisms involved in cancer immune evasion, which has led to the development of promising first-in-class therapeutic antibodies, including BT-02.17 His contributions to the field also include authoring and editing a book titled "Regulation of Cancer Immune Checkpoints" and serving as an associate editor for several prominent journals in immunology and oncology.17 In interviews, Dr. Xu has emphasized the company's dedication to novel target discovery, acknowledging the inherent challenges but also the profound importance of this approach for making significant advances in cancer treatment, particularly within the Chinese biopharmaceutical landscape.18

Research Platforms and Capabilities

BioTroy Therapeutics has established a comprehensive suite of research platforms, collectively referred to as the "BioTroy Engine." This integrated system supports various stages of drug discovery and development, including tumor multi-omics analysis, receptor-ligand discovery, research into target signal transduction pathways, antibody discovery and engineering, in vivo pharmacodynamics studies, translational medicine in large animal models, and biomarker development.1 A landmark achievement stemming from these capabilities is the discovery of ITPRIPL1 as the first identified ligand of CD3ε, functioning as a novel target for cancer immunotherapy. This foundational research was published in the prestigious scientific journal Cell, highlighting the caliber of the company's scientific output.5

Pipeline

BioTroy Therapeutics' pipeline reflects its focus on innovative oncology drugs:

• BT-02: An ITPRIPL1-inhibiting monoclonal antibody, currently the lead candidate, is in Phase 1/2 clinical development for advanced solid neoplasms.[2]
• BT-01: A SEMG2 (semenogelin 2) antagonist intended for solid tumors, currently in preclinical development.[16]
• BT04 and BT03: These are earlier-stage projects targeting neoplasms, currently in the discovery phase.[16]
• A patent (CN116688125) related to SEMA3G (semaphorin 3G) for neoplasms is also listed as part of their discovery-phase projects.[16]

The strategic direction of BioTroy Therapeutics is clearly centered on high-risk, high-reward innovation. The company's consistent narrative underscores its commitment to developing "first-in-class" drugs based on "original target discovery," following a "from 0 to 1" model.[1] Dr. Jie Xu, the founder, has explicitly stated that the company's primary mission was to unearth "entirely new targets from scratch".[18] This ambition is further evidenced by their strategic focus on tumors that are unresponsive to existing PD-1/PD-L1 inhibitors, a domain where novel therapeutic mechanisms are urgently needed.[1] This approach markedly contrasts with a "fast-follow" or "me-too" drug development strategy, indicating a greater appetite for pioneering research. Such a strategy, while inherently carrying higher risks and longer development timelines, also holds the promise of significant breakthroughs and substantial market differentiation if successful. The considerable early-stage funding of over 150 million RMB [1] provides the necessary resources to pursue this ambitious and innovative agenda. The success of BT-02 would not only bring a new therapeutic option to patients but also serve as a crucial validation of BioTroy's discovery platform and its overarching innovation-driven strategy, potentially paving the way for further novel candidates from its pipeline.

7. Intellectual Property

BioTroy Therapeutics has proactively established a global patent layout to protect its innovations related to BT-02, encompassing the antibody itself, its specific epitopes, and the novel target, ITPRIPL1.[1]

Specific Patent Information

A key piece of intellectual property is detailed in patent application AU2021371709A1, titled "Use of regulator of itpripl1 in preparation of drug that regulates immune responses or fights tumors".19 This patent application was jointly filed by BioTroy Therapeutics and Fudan University, underscoring the collaborative nature of the foundational research. The scope of this patent is broad, covering:

• The use of regulators that can either increase or decrease the expression or function of the ITPRIPL1 gene or protein for therapeutic purposes in immune responses or cancer.
• Pharmaceutical compositions comprising such ITPRIPL1 regulators.
• Isolated ITPRIPL1 recombinant protein.
• Antibodies that recognize and bind to ITPRIPL1.

The claims are based on the principle that the ITPRIPL1 protein binds to CD3ε and also Neuropilin-2 (NRP2) receptors to regulate the functions of different immune cells, thereby participating in the regulation of immune responses and the process of tumor immune evasion.[19]

The international patent application PCT/CN2021/127234, which is related to AU2021371709A1, currently has pending status in numerous key jurisdictions, including China (CN), the United States (US), Canada (CA), Australia (AU), South Korea (KR), Europe (EP), and Japan (JP).[19] The priority for this patent family dates back to Chinese applications CN202011191447.3A (filed in October 2020) and CN202110566040.2A (filed in May 2021).[19]

The intellectual property strategy for BT-02 and its target ITPRIPL1 appears to be both proactive and comprehensive, which is critical for a first-in-class therapeutic. The explicit mention of a "global patent layout" covering "antibodies, epitopes, and targets" [1] is a standard yet vital assertion for protecting such innovations. The details available from patent application AU2021371709A1 [19] reveal a multifaceted IP approach. This strategy extends beyond protecting the specific antibody (BT-02) to encompass the broader concept of modulating ITPRIPL1 activity for therapeutic benefit, methods of use for treating diseases, and potentially the ITPRIPL1 protein and its variants for diagnostic or research applications. The joint inventorship and filing with Fudan University [19] indicates a strong academic-industry partnership, likely originating from the fundamental scientific discoveries regarding ITPRIPL1's function. Securing patent rights across multiple major pharmaceutical markets (US, Europe, Japan, China, etc.) [19] is an essential step for future commercialization, attracting investment, and forming strategic partnerships. This robust IP position is fundamental for safeguarding BioTroy's innovation in the competitive global biopharmaceutical landscape. Notably, the patent literature's mention of NRP2 as another potential binding partner for ITPRIPL1 [19], although not a focal point in the abstract of the Cell publication concerning CD3ε [6], hints at potentially broader biological roles for ITPRIPL1. These roles might be explored in future research and could lead to further therapeutic applications or refinements of the current understanding of ITPRIPL1's mechanism.

8. Discussion and Future Outlook

BT-02 emerges as a drug candidate with considerable potential in the evolving landscape of cancer immunotherapy, primarily due to its novel mechanism of action and its development by a company focused on original target discovery.

Potential Significance of BT-02 in Oncology

As a first-in-class monoclonal antibody targeting ITPRIPL1, BT-02 represents a novel immunotherapeutic strategy.1 ITPRIPL1 has been identified as a new immune checkpoint that, when expressed by tumor cells, binds to CD3ε on T-cells, thereby dampening T-cell activation and facilitating tumor immune escape.6 By inhibiting this interaction, BT-02 aims to unleash the anti-tumor activity of T-cells. This mechanism, focused on enhancing T-cell activation at a fundamental level (Signal 1), holds promise for efficacy in a variety of solid tumors. Its most significant potential may lie in treating patients whose tumors are resistant to or have relapsed after treatment with existing immunotherapies, such as PD-1/PD-L1 inhibitors.1

Unmet Needs Addressed

A key area of unmet need that BT-02 aims to address is the treatment of tumors that do not respond to current PD-1/PD-L1 checkpoint inhibitors, a specific focus of BioTroy Therapeutics.1 The variability in patient responses to existing cancer immunotherapies highlights the necessity for alternative therapeutic targets and pathways, such as the ITPRIPL1-CD3ε axis.6 If successful, BT-02 could provide a new option for a patient population with limited effective treatments.

Future Research Directions (Inferred)

The progression of BT-02 will likely involve several key research avenues. Firstly, the identification of predictive biomarkers will be crucial for patient selection and maximizing therapeutic benefit. Understanding which patients are most likely to respond to ITPRIPL1 inhibition could involve assessing ITPRIPL1 expression levels in tumors, the status of CD3ε on T-cells, or other immune microenvironment characteristics. Secondly, the exploration of BT-02 in combination therapies is a logical next step. Given its distinct mechanism, combining BT-02 with existing checkpoint inhibitors (e.g., anti-PD-1/PD-L1), chemotherapy, or other targeted therapies could lead to synergistic anti-tumor effects and overcome resistance mechanisms. Thirdly, further investigation into the role and expression of ITPRIPL1 across a broader spectrum of cancer types, beyond those already suggested by preclinical data and expression atlases, will be important. The mention of NRP2 as a potential interaction partner for ITPRIPL1 in patent literature also opens avenues for deeper mechanistic studies.19 Finally, upon successful completion of the ongoing Phase 1/2 trials, advancement to later-phase clinical studies, including larger Phase 2 efficacy trials in specific tumor types and pivotal Phase 3 trials, will be necessary for regulatory approval.

Potential Challenges (Inferred)

The development of a first-in-class agent like BT-02 is not without significant challenges. Establishing a favorable safety profile in larger and more diverse patient populations will be paramount. While preclinical safety was reported as good 1, unforeseen on-target or off-target toxicities can emerge in human trials. Demonstrating a clear and significant clinical benefit, either as a monotherapy or in combination, over or in addition to the current standard of care, will be a high bar. The complexities of developing a novel agent include establishing optimal dosing regimens, refining patient selection strategies based on emerging biomarker data, and thoroughly understanding and managing any unique adverse event profiles. Furthermore, the field of cancer immunotherapy is highly competitive, with numerous novel agents and combination strategies under investigation.

The development trajectory of BT-02 exemplifies the challenging yet potentially transformative journey from "bench-to-bedside-to-market" for a drug targeting a completely novel biological pathway. BioTroy Therapeutics' commitment to the "0 to 1" model, starting from original target discovery (the elucidation of ITPRIPL1's role in immune evasion) [1], through rigorous preclinical validation (evidenced by efficacy in multiple models and strong scientific publication) [1], and culminating in early-phase clinical trials [2], is a testament to this approach. Key milestones, such as the high-impact Cell publication validating the science [6], the establishment of a comprehensive intellectual property portfolio [1], and the dual IND approvals from both the FDA and NMPA [1], have significantly de-risked this pioneering endeavor to a certain extent. Dr. Xu's commentary acknowledging the inherent difficulties in new target discovery alongside the necessity for robust scientific backing underscores the company's realistic yet ambitious perspective.[18] The progression from identifying ITPRIPL1's function to engineering a therapeutic antibody and advancing it into human testing illustrates a pathway fraught with uncertainty but one that offers the prospect of a paradigm shift in treatment if the preclinical promise translates into clinical success. The company's early adoption of a global strategy, evident in its IP filings, regulatory approvals, and parallel clinical trials, suggests a clear ambition to position BT-02 as a significant therapeutic option worldwide, should the ongoing and future clinical data support its efficacy and safety.

9. Conclusion

BT-02 is a promising, first-in-class monoclonal antibody developed by Shanghai BioTroy Therapeutics, targeting the novel immune checkpoint ITPRIPL1. Its mechanism of action, which involves inhibiting the ITPRIPL1-CD3ε interaction to restore T-cell activation, offers a new approach to cancer immunotherapy. Preclinical data have been encouraging, leading to regulatory approvals for clinical trials in both the United States and China.

The potential of BT-02 lies in its ability to address unmet medical needs, particularly for patients with advanced solid tumors that are unresponsive or resistant to existing treatments, including PD-1/PD-L1 inhibitors. The commitment of BioTroy Therapeutics to "from 0 to 1" innovation, backed by strong scientific research including a publication in Cell, and a comprehensive global intellectual property strategy, positions BT-02 as a significant candidate in the oncology pipeline.

Currently, BT-02 is undergoing Phase 1/2 clinical evaluation to determine its safety, tolerability, pharmacokinetics, and preliminary efficacy. The outcomes of these ongoing trials will be critical in defining the future therapeutic role of BT-02 and validating ITPRIPL1 as a clinically relevant target in cancer treatment. Success in these early phases could pave the way for broader clinical development and potentially offer a new therapeutic option for patients with challenging cancers.

Works cited

1. China's IND Approved! BioTroy Therapeutics' Globally Pioneering Anti-Tumor Drug Receives NMPA Approval to Enter Clinical Phase, accessed June 11, 2025, https://www.biotroy.com/News-m.html?article_id=99
2. Global Drug Intelligence Database - Patsnap Synapse, accessed June 11, 2025, https://synapse.patsnap.com/drug/dd4a0e058f1b45c5ad6629fc2d0041ce
3. BT-02 Drug Profile - Ozmosi, accessed June 11, 2025, https://pryzm.ozmosi.com/product/32855
4. BioTroy Therapeutics' globally pioneering anti-tumor drug receives approval for clinical research in the United States, accessed June 11, 2025, http://www.biotroytherapeutics.com/News-m.html?article_id=97
5. BioTroy, accessed June 11, 2025, https://www.biotroy.com/
6. ITPRIPL1 binds CD3ε to impede T cell activation and enable tumor immune evasion, accessed June 11, 2025, https://pubmed.ncbi.nlm.nih.gov/38614099/
7. ITPRIPL1 Gene - GeneCards | IPIL1 Protein | IPIL1 Antibody, accessed June 11, 2025, https://www.genecards.org/cgi-bin/carddisp.pl?gene=ITPRIPL1
8. pubmed.ncbi.nlm.nih.gov, accessed June 11, 2025, https://pubmed.ncbi.nlm.nih.gov/38614099/#:~:text=tumor%20immune%20evasion-,ITPRIPL1%20binds%20CD3%CE%B5%20to%20impede%20T%20cell%20activation%20and%20enable,Cell.
9. ITPRIPL1 - Drugs, Indications, Patents - Patsnap Synapse, accessed June 11, 2025, https://synapse.patsnap.com/target/68fe2dd6c6cb401b9eeb88c4246402ef
10. Itpripl1 - Inositol 1,4,5-trisphosphate receptor-interacting protein-like 1 - Mus musculus (Mouse) | UniProtKB | UniProt, accessed June 11, 2025, https://www.uniprot.org/uniprotkb/A2ASA8/entry
11. Development of a monoclonal antibody to ITPRIPL1 for immunohistochemical diagnosis of non-small cell lung cancers: accuracy and correlation with CD8+ T cell infiltration - PubMed Central, accessed June 11, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10770237/
12. Expression of ITPRIPL1 in cancer - Summary - The Human Protein Atlas, accessed June 11, 2025, https://www.proteinatlas.org/ENSG00000198885-ITPRIPL1/cancer
13. News - BioTroy, accessed June 11, 2025, https://www.biotroy.com/News.html
14. BioTroy Therapeutics' globally pioneering anti-tumor drug receives approval for clinical research in the United States, accessed June 11, 2025, https://www.biotroy.com/News-m.html?article_id=97
15. BT-02 - MedPath, accessed June 11, 2025, https://trial.medpath.com/drug/124a9f0f8cd0aa41/bt-02
16. BioTroy Therapeutics - Drug pipelines, Patents, Clinical trials - Patsnap Synapse, accessed June 11, 2025, https://synapse.patsnap.com/organization/0fadad10ea8ac81572b4a2547c84ec5a
17. About us - BioTroy, accessed June 11, 2025, https://www.biotroy.com/About-us.html
18. Dr. Xu Jie, Founder of BioTroy Therapeutics, Accepts Media Interview, Expressing Unique Insights into Target Discovery, accessed June 11, 2025, https://www.biotroy.com/News-m.html?article_id=94
19. AU2021371709A1 - Use of regulator of itpripl1 in preparation of drug that regulates immune responses or fights tumors - Google Patents, accessed June 11, 2025, https://patents.google.com/patent/AU2021371709A1/en
20. Huanbin Wang's research works | Fudan University and other places - ResearchGate, accessed June 11, 2025, https://www.researchgate.net/scientific-contributions/Huanbin-Wang-2098813573