Comprehensive Report on BAY2862789 (Pasodacigib): An Investigational Diacylglycerol Kinase Alpha Inhibitor

I. Executive Summary

BAY2862789, also identified by the International Nonproprietary Name (INN) pasodacigib, is an orally bioavailable, small molecule investigational drug that selectively inhibits Diacylglycerol Kinase alpha (DGKα).[1] This agent is the product of a collaborative development effort between Bayer and the German Cancer Research Center (DKFZ).[1] Currently, BAY2862789 is undergoing Phase 1 first-in-human clinical evaluation (NCT05858164) primarily for the treatment of advanced solid tumors, with a specific focus that includes Non-Small Cell Lung Cancer (NSCLC).[1]

The mechanism of action of BAY2862789 is centered on the inhibition of DGKα, an enzyme that plays a critical regulatory role in T-cell receptor (TCR) signaling and is also implicated in cancer cell survival and proliferation.[1] By blocking DGKα, BAY2862789 prevents the phosphorylation of diacylglycerol (DAG) to phosphatidic acid (PA). This leads to an accumulation of DAG, which in turn enhances and sustains TCR-mediated signaling pathways in T-cells. The downstream consequences of this enhanced signaling include increased T-cell proliferation, restoration of T-cell effector functions, augmented cytokine production, and the activation of a more potent cytotoxic T-cell-mediated anti-tumor immune response.[3] Furthermore, because DGKα is often overexpressed in various cancer types where it contributes to cell survival and resistance to apoptosis, its inhibition by BAY2862789 may also exert direct anti-tumor effects by inducing apoptosis and suppressing the proliferation of malignant cells.[1]

Robust preclinical studies have provided substantial support for the clinical development of BAY2862789. These investigations have demonstrated its capacity to activate T-cells, effectively overcome tumor-induced immunosuppressive mechanisms, and mediate significant anti-tumor efficacy in diverse syngeneic mouse models.[8] A particularly promising aspect of the preclinical data is the observed synergistic potential when BAY2862789 is combined with other immunotherapeutic agents, such as PD-1/PD-L1 checkpoint inhibitors and anti-CCR8 antibodies targeting regulatory T-cells.[8]

The intellectual property portfolio for BAY2862789 includes key patents such as US11998539B2. This patent specifically identifies pasodacigib as Example 298 and reports a high in vitro potency for human DGKα inhibition, with a pIC₅₀ value of 9.3 (corresponding to an IC₅₀ of 0.5 nM).[2]

Collectively, BAY2862789 emerges as a novel immuno-oncology candidate characterized by a dual mechanism of action targeting both host immune responses and tumor cell intrinsic pathways. Its oral bioavailability, coupled with compelling preclinical efficacy and synergy data, positions it as a potentially valuable therapeutic agent, particularly in combination strategies for solid malignancies. The ongoing Phase 1 clinical trial (NCT05858164) will be critical in validating its safety, tolerability, pharmacokinetic profile, and preliminary efficacy in human subjects.

II. Introduction to BAY2862789 (Pasodacigib)

The landscape of cancer immunotherapy is continually evolving, with ongoing efforts to identify novel targets and therapeutic strategies that can overcome existing limitations and improve patient outcomes. Within this context, BAY2862789, also known by its International Nonproprietary Name (INN) pasodacigib, represents an innovative approach targeting the Diacylglycerol Kinase alpha (DGKα) enzyme.

Nomenclature and Identification

The primary development code for this investigational agent is BAY2862789, which is consistently utilized by its developers in scientific communications and clinical trial registries.[1] The INN pasodacigib has been assigned to a DGK inhibitor that structurally aligns with a compound (Example 298) detailed in Bayer's patent US11998539B2.[2] Given that BAY2862789 is the drug intervention listed in clinical trial NCT05858164, which is also linked to this patent, it is highly probable that BAY2862789 and pasodacigib refer to the same chemical entity, although definitive confirmation of the BAY2862789 structure's public disclosure is awaited.[2] Alternative identifiers found in various databases include DGKalpha Inh (BAY) and BAY-2862789.[1]

Chemical Nature and Formulation

BAY2862789 is classified as a small molecule drug, indicating it is a chemically synthesized compound rather than a biological product like a monoclonal antibody.[1] A significant characteristic of BAY2862789 is its oral route of administration; the ongoing Phase 1 clinical trial employs an oral solution formulation of the drug.[1] The development of an orally bioavailable agent offers considerable advantages in the oncological setting. Compared to intravenously administered therapies, oral drugs typically provide greater patient convenience, reduce the burden on healthcare facilities, and allow for more flexible and potentially chronic dosing regimens. This is particularly relevant for maintenance therapies or for treatments requiring long-term administration in patients with advanced cancers.

Developers and Collaborative Effort

The development of BAY2862789 is a collaborative effort spearheaded by Bayer (through its entities Bayer Healthcare Pharmaceuticals Inc., Bayer AG, and Bayer Pharma AG).[1] Bayer is primarily responsible for the extensive clinical development program, including the management and execution of the current first-in-human Phase 1 trial.[5] The German Cancer Research Center (DKFZ) is a key research collaborator in this endeavor.[1] This partnership between a major pharmaceutical corporation with global drug development expertise and a leading academic cancer research institution is a common and often highly effective model in drug discovery. Such collaborations typically leverage the strengths of both partners: the academic institution often contributes to target identification, validation, and early-stage discovery, while the pharmaceutical company provides the resources and expertise necessary for comprehensive preclinical development, navigating complex regulatory pathways, conducting large-scale clinical trials, and ultimately, commercialization. This synergistic approach can significantly accelerate the translation of novel scientific concepts into viable therapeutic options for patients.

Table 1: BAY2862789 (Pasodacigib) - Key Drug Characteristics

Characteristic	Details	Source Snippets
Official Name/Code	BAY2862789	1
International Nonproprietary Name (INN)	Pasodacigib (highly probable)	2
Synonyms	DGKalpha Inh (BAY), BAY-2862789	1
Developers	Bayer (Lead), German Cancer Research Center (DKFZ) (Collaborator)	1
Drug Class	Small Molecule, Diacylglycerol Kinase alpha (DGKα) Inhibitor	1
Molecular Target	Diacylglycerol Kinase alpha (DGKα)	1
General Mechanism of Action	Inhibition of DGKα leading to T-cell activation and potential direct anti-tumor effects	1
Route of Administration	Oral (solution in Phase 1)	1
Primary Therapeutic Areas (Investigational)	Advanced Solid Tumors, Non-Small Cell Lung Cancer (NSCLC)	1

This table provides a consolidated summary of the fundamental attributes of BAY2862789, serving as a quick reference to its identity, development background, and core pharmacological properties.

III. Mechanism of Action

The therapeutic strategy underpinning BAY2862789 (pasodacigib) revolves around the selective inhibition of Diacylglycerol Kinase alpha (DGKα), an enzyme with pivotal roles in both immune cell regulation and cancer cell biology.

Primary Molecular Target: Diacylglycerol Kinase alpha (DGKα)

BAY2862789 is designed as a selective inhibitor of DGKα (also denoted as DGKA), one of several isoenzymes within the diacylglycerol kinase family.[1] Physiologically, DGKα catalyzes the ATP-dependent phosphorylation of diacylglycerol (DAG) to produce phosphatidic acid (PA).[3] This enzymatic activity is critical because DAG is a key second messenger involved in a multitude of cellular signaling pathways, including those downstream of T-cell receptor (TCR) activation. By converting DAG to PA, DGKα effectively terminates DAG-mediated signals, thus acting as a negative regulator of these pathways.

Pharmacodynamics on T-lymphocytes

The primary immuno-oncology rationale for BAY2862789 lies in its ability to modulate T-cell function by targeting DGKα:

• Target Engagement and Biochemical Effect: Upon administration, BAY2862789 is intended to bind to and inhibit DGKα expressed within T-lymphocytes.[3] This blockade prevents the enzymatic conversion of DAG to PA, leading to an accumulation of intracellular DAG.
• Enhancement of TCR Signaling: DAG is essential for the optimal activation of several downstream effectors of TCR signaling, including Protein Kinase C (PKC) isoforms and Ras guanyl nucleotide-releasing proteins (RasGRPs). By increasing the concentration and prolonging the availability of DAG, BAY2862789 effectively amplifies and sustains TCR signaling.[3] DGKα normally functions as an intrinsic immune checkpoint, attenuating T-cell responses; its inhibition by BAY2862789 effectively "releases this brake."
• Cellular Consequences in T-cells: The enhanced TCR signaling translates into several beneficial cellular outcomes for anti-tumor immunity:
• Increased T-cell Activation and Proliferation: Inhibition of DGKα leads to more robust T-cell activation and promotes their proliferation, expanding the pool of tumor-reactive T-cells.[1]
• Enhanced Effector Functions: Activated T-cells exhibit improved effector functions, including increased production of key cytokines (e.g., IFN-γ, TNF-α) and enhanced cytotoxic capabilities against tumor cells.[3]
• Overcoming T-cell Anergy/Exhaustion: DGKα is often upregulated in T-cells within the tumor microenvironment, contributing to a state of anergy (unresponsiveness) or exhaustion, which limits their anti-tumor efficacy.[1] BAY2862789, by inhibiting DGKα, aims to reverse or prevent this dysfunctional state, thereby restoring the capacity of T-cells to effectively target and eliminate cancer cells. This is a critical aspect of its therapeutic potential, as T-cell exhaustion is a major hurdle for the success of many immunotherapies, including checkpoint blockade.

Potential Direct Anti-Tumor Effects

Beyond its effects on T-cells, the inhibition of DGKα by BAY2862789 may also exert direct anti-cancer activity:

• DGKα Expression and Role in Cancer Cells: DGKα is not only expressed in immune cells but is also found to be significantly expressed in various types of cancer cells. In this context, DGKα has been implicated in promoting cancer cell survival, enhancing proliferation, and inhibiting apoptosis.[1]
• Direct Cytotoxic Potential: Consequently, the inhibition of DGKα activity within cancer cells by BAY2862789 could potentially lead to direct anti-tumor effects, such as the induction of apoptosis and the suppression of tumor cell proliferation.[3] This dual mechanism—targeting both the immune system and the tumor cells directly—is a highly attractive feature. If clinically validated, it could offer a more comprehensive anti-cancer strategy compared to agents that act solely on either the tumor or the immune response. This "double-strike" approach could be particularly effective against tumors that are only moderately immunogenic or those that have developed intrinsic dependencies on DGKα signaling for their growth and survival.

Therapeutic Rationale in Oncology

The development of BAY2862789 as an oncology therapeutic is based on several key premises:

• Dual Mechanism of Action: The ability to simultaneously enhance anti-tumor immunity and potentially exert direct cytotoxic effects on cancer cells offers a multifaceted approach to cancer treatment.[1]
• Addressing Immune Evasion: By targeting DGKα, BAY2862789 aims to counteract T-cell exhaustion and anergy, which are critical mechanisms of immune evasion employed by tumors, particularly in advanced stages of disease.[1]
• Synergy with Other Immunotherapies: There is a strong rationale for combining BAY2862789 with other immuno-oncology agents, such as PD-1/PD-L1 checkpoint inhibitors. DGKα inhibition could potentially sensitize tumors to, or restore sensitivity in tumors resistant to, checkpoint blockade by improving the functional state of T-cells within the tumor microenvironment.[1]

IV. Therapeutic Indications and Potential

BAY2862789 (pasodacigib) is being investigated for its potential across a spectrum of oncological conditions, driven by its unique mechanism of action that targets fundamental pathways in both immune cells and cancer cells.

Primary Investigational Indications (Clinical Phase 1)

The initial clinical evaluation of BAY2862789, through the NCT05858164 study, is focused on patients with advanced solid tumors. This broad inclusion criterion is typical for first-in-human (FIH) Phase 1 trials, allowing for an initial assessment of safety, tolerability, and pharmacokinetics across a range of malignancies, and providing an opportunity to observe early signals of anti-tumor activity in different cancer types.[1]

Within this broad category, Non-Small Cell Lung Cancer (NSCLC) has been specifically highlighted as an active indication for Phase 1 development, with clinical trial sites planned or operational in the United States, China, and Japan.[1] The explicit focus on NSCLC suggests a potentially stronger preclinical rationale or a perceived higher unmet medical need for novel agents like BAY2862789 in this particular malignancy. NSCLC remains a leading cause of cancer-related mortality worldwide, and while immune checkpoint inhibitors have revolutionized treatment for a subset of patients, many individuals either do not respond or eventually develop resistance. An agent like BAY2862789, which could potentially overcome T-cell exhaustion or synergize with existing immunotherapies, would be of significant clinical interest in this setting.

Broader Therapeutic Potential and Rationale

The therapeutic potential of BAY2862789 extends beyond the initial indications being explored in the Phase 1 trial:

• Mechanism-Driven Applicability: Given that DGKα plays roles in T-cell regulation and can be expressed by various tumor types, BAY2862789 could theoretically benefit patients with a wide array of cancers where these mechanisms are relevant. Its utility may not be confined to specific histological subtypes but rather to tumors characterized by DGKα-mediated immune suppression or DGKα-dependent survival pathways.
• Overcoming Immunotherapy Resistance: A significant area of potential impact for BAY2862789 is in the context of resistance to existing immune checkpoint inhibitors (ICIs) such as anti-PD-1/PD-L1 antibodies. T-cell exhaustion and an immunosuppressive tumor microenvironment (TME) are key contributors to ICI resistance. By reactivating exhausted T-cells and potentially remodeling the TME, BAY2862789 might restore or enhance sensitivity to ICIs in patients who have previously failed such therapies.[1]
• Combination Therapy Cornerstone: The immune-enhancing properties of BAY2862789 make it an attractive candidate for combination therapies. Preclinical evidence strongly supports its synergy with other ICIs.[1] Beyond this, it could potentially be combined with targeted therapies, chemotherapies, or radiotherapies to create a more immunogenic tumor environment and improve overall treatment efficacy. The ability to modulate the host immune response could complement the direct cytotoxic effects of these other modalities.
• Biomarker-Guided Patient Selection: The future development and optimal utilization of BAY2862789 will likely benefit from the identification of predictive biomarkers. Potential biomarkers could include the expression levels of DGKα in tumor cells or tumor-infiltrating lymphocytes, the baseline status of T-cell exhaustion (e.g., expression of PD-1, TIM-3), or specific signatures of the TME (e.g., high levels of TGFβ or PGE2). Identifying such biomarkers through translational research integrated into clinical trials could allow for the selection of patient populations most likely to derive clinical benefit, thereby enhancing the therapeutic index of BAY2862789. This approach is fundamental to precision oncology and could guide its development into specific niches where it offers the greatest advantage.

V. Preclinical Research and Findings

The progression of BAY2862789 (pasodacigib) into clinical trials is supported by a body of preclinical research elucidating its mechanism of action, in vitro and in vivo efficacy, and potential for combination therapies.

In Vitro Pharmacology

Studies conducted in controlled laboratory settings have provided key insights into the cellular effects of DGKα inhibition:

• T-cell Receptor (TCR) Signaling and Activation: Inhibition of DGKα, for instance by BAY2862789, leads to an increase in intracellular diacylglycerol (DAG) levels. This accumulation of DAG, a critical second messenger, augments downstream TCR signaling pathways, resulting in enhanced T-cell activation, increased proliferation, and improved effector functions such as cytokine release and cytotoxic potential.[8]
• Overcoming Immunosuppression: The tumor microenvironment (TME) often contains various immunosuppressive factors that dampen T-cell activity. Preclinical studies have shown that DGK inhibitors, including those targeting DGKα, can help T-cells overcome the inhibitory effects of molecules like Transforming Growth Factor-beta (TGFβ), Prostaglandin E2 (PGE2), and adenosine.[8] This suggests that BAY2862789 could restore T-cell function even in hostile TMEs. This capability is particularly important because these immunosuppressive molecules are common barriers to effective anti-tumor immunity.
• Enhanced Cytolytic Activity: Selective inhibitors of DGKα (like BAY2862789) and DGKζ (like BAY2965501) have both demonstrated the ability to enhance T-cell mediated killing of tumor cells in vitro.[8]
• Direct Tumor Cell Effects: Beyond immune modulation, DGKα is expressed in many cancer cell types and contributes to their survival and proliferation.[1] Consequently, direct inhibition of DGKα by BAY2862789 is proposed to induce apoptosis and suppress the growth of these tumor cells.[3] This potential for a direct anti-proliferative effect on cancer cells distinguishes DGKα inhibition from strategies that solely target immune cells. It is noteworthy that the DGKζ-selective inhibitor BAY2965501 reportedly did not show direct anti-proliferative effects on human tumor cell lines in vitro [9], suggesting that the direct anti-tumor activity may be more specifically associated with the DGKα isoform. Confirmation of this dual action for BAY2862789 in various cancer cell lines will be important.

In Vivo Pharmacology (Animal Models)

Studies in animal models of cancer have further substantiated the therapeutic potential of DGKα inhibition:

• Monotherapy Anti-Tumor Efficacy: BAY2862789, when administered as a single agent, has demonstrated anti-tumor efficacy in various preclinical syngeneic mouse tumor models.[8]
• Combination Therapy Efficacy: The anti-tumor effects of DGKα inhibition are often significantly enhanced when combined with other therapeutic modalities:
• With DGKζ Inhibition: In some tumor models, such as the MC38 colon carcinoma model, the combination of BAY2862789 (DGKα inhibitor) with BAY2965501 (DGKζ inhibitor) resulted in greater anti-tumor activity than DGKζ inhibition alone, suggesting complementary roles for these isoforms in regulating anti-tumor immunity.[8]
• With Anti-CCR8 Antibodies: Combining DGK inhibitors (including BAY2862789) with antibodies targeting CCR8 (a receptor often expressed on immunosuppressive regulatory T-cells, or Tregs) led to significantly improved anti-tumor efficacy compared to either monotherapy. This combination was associated with increased activation and proliferation of tumor-infiltrating cytotoxic T-lymphocytes (CTLs) and enhanced infiltration of tumor-antigen-specific T-cells.[8] This suggests that simultaneously relieving T-cell intrinsic suppression (via DGKα inhibition) and depleting or neutralizing Tregs can create a more potent anti-tumor immune response.
• With PD-1/PD-L1 Blockade: DGKα inhibition has been shown to cooperate with PD-1/PD-L1 checkpoint blockade.[10] Preclinical data strongly support the combination of DGK inhibition (including BAY2862789) with anti-PD-L1 antibodies, potentially alongside anti-CCR8 therapy, to achieve maximal therapeutic benefit by concurrently targeting multiple immune escape pathways.[1]
• Modulation of T-cell Exhaustion: While much of the specific in vivo data on T-cell exhaustion markers comes from studies with the DGKζ inhibitor BAY2965501, the underlying principle of DGK involvement in T-cell anergy and exhaustion is relevant to DGKα. Inhibition of DGKζ was shown to reduce the expression of exhaustion markers like PD-1 and TIM-3 on T-cells and enhance T-cell responses in chronic viral infection models, which serve as a surrogate for T-cell exhaustion in cancer.[8]

Preclinical Pharmacokinetics/Pharmacodynamics (PK/PD)

• Oral Bioavailability: BAY2862789 is characterized as an orally bioavailable inhibitor, a key feature for its clinical development.[1]
• Exposure-Response Modeling: An important aspect of the preclinical development of Bayer's DGK inhibitors (including BAY2862789) has been the creation of an exposure-response model. This model, based on preclinical PK/PD data, was developed to predict T-cell activation resulting from various combinations of DGKα and DGKζ inhibition. The predictions generated by this model showed a high degree of correlation with in vivo efficacy endpoints observed in animal models.[8] Such robust in vitro to in vivo extrapolation (IVIVE) is highly valuable. It provides a more quantitative understanding of the drug concentrations required to achieve the desired pharmacological effect (i.e., T-cell activation) and how this relates to anti-tumor activity. This, in turn, informs rational dose selection and scheduling for early-phase human clinical trials, potentially increasing the likelihood of observing clinical benefit and optimizing the therapeutic window for both monotherapy and combination regimens.

Preclinical Toxicology

Specific, detailed preclinical toxicology findings for BAY2862789 are not extensively covered in the provided materials. However, the development of isoform-selective DGK inhibitors like BAY2862789 (for DGKα) and BAY2965501 (for DGKζ) allows for more targeted investigations into the pharmacology and toxicology associated with inhibiting each specific isoform.[8] For the related DGKζ inhibitor BAY2965501, preclinical toxicology studies reportedly showed only low-grade gastrointestinal effects, suggesting that DGK inhibition might have a manageable safety profile.[8] The comprehensive safety and tolerability profile of BAY2862789 in humans will be a primary focus of the ongoing Phase 1 clinical trial.

Table 3: Summary of Significant Preclinical Findings for BAY2862789 and Related DGK Inhibitors

Study Type/Model	Compound(s) Tested	Key Pharmacodynamic Effect / Efficacy Outcome	Reported Potency/Effect Detail	Source Snippets
In vitro T-cell assays	DGKα inhibitors (e.g., BAY2862789)	Enhanced TCR signaling, T-cell activation & proliferation	Elevation of DAG levels	8
In vitro T-cell assays	DGK inhibitors	Overcame immunosuppression by TGFβ, PGE2, adenosine	Restoration of T-cell function in presence of suppressors	8
In vitro co-culture	BAY2862789 (DGKα inh), BAY2965501 (DGKζ inh)	Enhanced T-cell mediated tumor cell killing	Increased cytolytic activity	8
In vivo syngeneic tumor models	BAY2862789 (monotherapy)	Anti-tumor efficacy	Tumor growth inhibition	8
In vivo MC38 tumor model	BAY2862789 + BAY2965501	Enhanced anti-tumor efficacy vs DGKζ inh alone	Additional tumor growth inhibition	8
In vivo tumor models	DGK inhibitors + anti-CCR8 Ab	Significantly enhanced anti-tumor efficacy	Greater CTL activation & infiltration	8
In vivo tumor models / Mechanistic studies	DGKα inhibition + anti-PD-1/PD-L1	Cooperative anti-tumor effects	Enhanced T-cell responses	8
In vivo chronic viral infection model (LCMV)	BAY2965501 (DGKζ inh)	Reduced T-cell exhaustion markers (PD-1, TIM-3)	Enhanced antiviral T-cell responses	8
Preclinical PK/PD Modeling	DGKα/ζ inhibitors	Exposure-response model developed	Predictions correlated with in vivo efficacy	8

This table highlights the breadth of preclinical evidence supporting the development of BAY2862789, particularly its immune-modulatory effects and its potential in combination therapies.

VI. Clinical Development Program: NCT05858164 (Bayer Study 22231)

The entry of BAY2862789 (pasodacigib) into human clinical trials marks a critical phase in its development. The primary study investigating this agent is registered under the ClinicalTrials.gov identifier NCT05858164, also known by Bayer's internal identifier 22231.

Trial Identification and General Information

• ClinicalTrials.gov Identifier: NCT05858164.[1]
• Sponsor Protocol Code Number: Bayer Identifier 22231.[1]
• Official Title: "An Open-label, Phase 1, First-in-human, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Maximum Tolerated or Administered Dose, Pharmacokinetics, Pharmacodynamics, and Tumor Response Profile of the Diacylglycerol Kinase Alpha Inhibitor (DGKαi) BAY 2862789 in Participants With Advanced Solid Tumors".[1]
• Phase: Phase 1.[1]
• Sponsor: Bayer Healthcare Pharmaceuticals Inc..[5]

Study Design and Objectives

This is a first-in-human, open-label, multicenter study involving a dose-escalation phase followed by a dose-expansion phase.[1] This design is standard for early clinical development of oncology drugs, allowing for careful safety assessment while gradually increasing the dose to identify an optimal level for further testing. The open-label nature facilitates close monitoring of participants for any adverse events.

• Primary Objectives:

1. To evaluate the safety and tolerability of BAY2862789 in participants with advanced solid tumors.[1]
2. To determine the Maximum Tolerated Dose (MTD) and/or the Recommended Dose for Expansion (RDE) of BAY2862789.[1]

• Secondary and Exploratory Objectives:

1. To characterize the pharmacokinetic (PK) profile of BAY2862789 after single and multiple oral doses.[1]
2. To evaluate the pharmacodynamic (PD) effects of BAY2862789, assessing how the drug affects biological pathways in the body, presumably including markers of T-cell activation consistent with its mechanism of action.[1]
3. To assess the preliminary anti-tumor activity of BAY2862789 across different advanced solid tumors.[1]

Patient Population

The study enrolls participants with advanced solid tumors for which standard curative or life-prolonging therapies are no longer effective or available.[1] While the dose-escalation phase may include a variety of tumor types, the dose-expansion phase might focus on specific cancers, such as Non-Small Cell Lung Cancer (NSCLC), where a stronger biological rationale or early signals of activity are observed.[1] Detailed inclusion and exclusion criteria, though not fully provided in the snippets, would typically involve parameters such as Eastern Cooperative Oncology Group (ECOG) performance status, adequate organ function, and potentially measurable disease for participants in the expansion cohorts.

Intervention Details

• Investigational Drug: BAY2862789.[1]
• Formulation and Route: Administered as an oral solution.[1]
• Dosing Strategy: The study employs a dose-escalation design where successive cohorts of participants receive increasing doses of BAY2862789 to identify the MTD/RDE. Once the RDE is determined, additional participants are enrolled into expansion cohorts at this dose level.[1]
• Treatment Duration: Participants continue treatment with BAY2862789 until evidence of disease progression, unacceptable toxicity, participant decision to withdraw, or termination of the study.[1]
• Cycle Length: The treatment is administered in 21-day cycles.[1]

Outcome Measures

• Primary Outcome Measures:
• The incidence, nature, and severity of Treatment-Emergent Adverse Events (TEAEs), graded according to standard criteria (e.g., CTCAE). This is assessed throughout the study and for up to 90 days following the last dose of BAY2862789.[1]
• The number of participants experiencing Dose-Limiting Toxicities (DLTs) at each dose level during the dose-escalation phase. DLTs are typically defined as specific types and grades of adverse events occurring within the first treatment cycle (e.g., up to 21 days post-first dose) that are considered unacceptable.[1]
• Determination of the RDE, based on a comprehensive evaluation of all safety, tolerability, PK, PD, and preliminary efficacy data, assessed for up to 2 years.[1]
• Secondary Pharmacokinetic Outcome Measures:
• Maximum observed plasma concentration (Cmax) of BAY2862789 following a single oral dose (typically on Cycle 1, Day 1, with sampling up to 24 hours post-dose).[1]
• Cmax of BAY2862789 following multiple oral doses (e.g., at steady-state, such as on Day 16 of Cycle 1, with sampling up to 24 hours post-dose).[1]
• Area Under the plasma concentration-time Curve (AUC) for BAY2862789 after a single dose (Cycle 1, Day 1, over a defined period, e.g., 0-24 hours).[1]
• Other standard PK parameters such as AUC after multiple doses (AUCtau), elimination half-life (t1/2), time to reach Cmax (Tmax), apparent clearance (CL/F), and apparent volume of distribution (Vz/F) are also expected to be characterized as part of understanding the drug's disposition ("how it moves into, through and out of the body").[1]
• Other Secondary/Exploratory Outcome Measures:
• Pharmacodynamic Effects: Assessment of biomarkers related to the mechanism of action of BAY2862789. This would likely include markers of T-cell activation (e.g., proliferation markers, cytokine levels in peripheral blood or tumor biopsies) and potentially markers of direct tumor cell effects if applicable.[1]
• Anti-Tumor Activity: Evaluation of tumor responses using standardized radiological criteria such as Response Evaluation Criteria in Solid Tumors (RECIST). Key efficacy endpoints would include Objective Response Rate (ORR), Duration of Response (DOR), Disease Control Rate (DCR), and Progression-Free Survival (PFS).[1]

Study Status and Logistics

• Enrollment Status: The trial is actively recruiting participants globally. News from June 2024 indicated clinical trial approvals for BAY2862789 in China, signifying ongoing global trial initiation efforts.[14] However, specific sites, such as AdventHealth in Florida, were reported as "not currently enrolling" at the time of their individual webpage updates, which is common as site activation and enrollment fluctuate.[5]
• Estimated Enrollment: The target enrollment for the study is approximately 69 participants.[1]
• Study Timeline: The study was estimated to start in August 2023, with an estimated primary completion date of July 2025.[1]
• Follow-up Procedures: Participants are monitored for health status and changes in their cancer at approximately 30 and 90 days after their last dose of BAY2862789, and then every 12 weeks thereafter.[1]
• Geographical Locations: This is a multi-national trial with sites planned or active in several key regions, including the United States (e.g., Celebration, Florida, with Dr. Guru Sonpavde as a Principal Investigator [5]), China, Japan, Australia, Israel, South Korea, and Spain.[1] The broad geographical scope reflects a coordinated global development strategy aimed at accelerating patient recruitment, gathering data from diverse populations, and facilitating potential future regulatory submissions in multiple major markets.

Reported Results or Updates

As of the information available in the provided research materials, no specific clinical efficacy, detailed safety, or human PK/PD data from the NCT05858164 trial have been publicly disclosed. The study is ongoing, and results will likely be presented at future scientific congresses or in publications upon completion of various study phases or interim analyses. The approval for clinical trials in new regions, such as China, confirms the active progression of the study's operational setup.[14]

Table 2: Overview of Phase 1 Clinical Trial NCT05858164 (BAY2862789)

Feature	Details	Source Snippets
Trial Identifier	NCT05858164 (ClinicalTrials.gov ID); 22231 (Bayer ID)	1
Phase	Phase 1	1
Official Title	An Open-label, Phase 1, First-in-human, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Maximum Tolerated or Administered Dose, Pharmacokinetics, Pharmacodynamics, and Tumor Response Profile of the Diacylglycerol Kinase Alpha Inhibitor (DGKαi) BAY 2862789 in Participants With Advanced Solid Tumors	1
Sponsor	Bayer Healthcare Pharmaceuticals Inc.	5
Key Collaborator	German Cancer Research Center (DKFZ) (in development of the compound)	1
Study Design	Open-label, multicenter, dose-escalation followed by dose-expansion	1
Primary Objectives	Assess safety and tolerability; Determine MTD and/or RDE	1
Key Secondary/Exploratory Objectives	Characterize PK profile; Evaluate PD effects; Assess preliminary anti-tumor activity	1
Patient Population	Participants with advanced solid tumors (including specific cohorts like NSCLC)	1
Intervention	BAY2862789, administered as an oral solution	1
Dosing Regimen	Dose escalation in 21-day cycles; Expansion at MTD/RDE	1
Current Status	Recruiting (globally)	1
Estimated Enrollment	Approximately 69 participants	1
Estimated Timelines	Start: August 2023; Primary Completion: July 2025	1
Key Geographical Regions	USA, China, Japan, Australia, Israel, South Korea, Spain	1

This table offers a structured summary of the pivotal first-in-human trial for BAY2862789, outlining its core design, objectives, and operational parameters.

VII. Intellectual Property

The development and potential commercialization of novel therapeutic agents like BAY2862789 (pasodacigib) are heavily reliant on robust intellectual property (IP) protection. Key patents and patent applications secure exclusivity for the compound, its synthesis, formulations, and methods of use.

Key Patents and Applications

• US11998539B2:
• Title: "Substituted aminoquinolones as DGKalpha inhibitors for immune activation".[2] This title clearly indicates the chemical class of compounds and their intended pharmacological effect and therapeutic application.
• Assignees: The patent is assigned to Bayer AG, Bayer Pharma AG, and the Deutsches Krebsforschungszentrum (DKFZ).[2] This joint assignment underscores the collaborative nature of the research and development leading to these compounds.
• Key Claim/Example - Pasodacigib (BAY2862789): The INN pasodacigib is explicitly identified as Example 298 within this patent.[2] This directly links the patented chemical matter to the investigational drug BAY2862789.
• Reported Biological Activity: Crucially, the patent discloses biological activity data for pasodacigib (Example 298). It reports a pIC₅₀ value of 9.3 for the inhibition of human DGKα.[2] This pIC₅₀ value translates to an IC₅₀ (half-maximal inhibitory concentration) of 0.5 nM, indicating that pasodacigib is a highly potent inhibitor of its target enzyme in vitro. Such high potency is a desirable characteristic for a drug candidate, as it suggests that therapeutic effects might be achievable at lower, potentially safer, doses.
• Relevant Dates: The patent has a priority date of November 30, 2022, and was published on June 4, 2024.[11] These dates are important for determining the patent term and the timeline of IP protection.
• WO2021105117A1:
• Title: "Substituted aminoquinolones as dgkalpha inhibitors for immune activation".[17] This is an international patent application filed under the Patent Cooperation Treaty (PCT).
• Content: This application likely covers the same or a very similar class of aminoquinolone compounds as detailed in US11998539B2, describing them as DGKα inhibitors for immune activation.[18]
• International Filing Strategy: The existence of a WO (PCT) application signifies Bayer and DKFZ's intent to seek patent protection in multiple countries/regions around the world. The application claims priority to earlier European patent applications (e.g., EP20808438.4A) and has led to subsequent national/regional phase entries in various jurisdictions, including Japan (JOP), China (CN), and Peru (PE), among others.[17] This broad filing strategy is standard practice for protecting valuable pharmaceutical inventions globally.

The strong in vitro potency (IC₅₀ = 0.5 nM) against DGKα disclosed in the patent for pasodacigib (BAY2862789) is a critical piece of data supporting its development. This level of potency suggests a high affinity of the drug for its target, which is often a prerequisite for achieving therapeutic efficacy at clinically relevant and tolerable doses. The comprehensive patent filings (US granted patent and international WO application with multiple national entries) provide a robust IP framework. This framework is essential for securing market exclusivity, thereby protecting the substantial investment required for the continued research, development, clinical trials, and eventual commercialization of an oncology drug.

Table 4: Key Intellectual Property for BAY2862789 (Pasodacigib)

Patent/Application ID	Title	Assignees	Key Relevance/Claims	Reported Biological Data (for Pasodacigib/Ex. 298)	Key Dates (Priority/Publication)	Source Snippets
US11998539B2	Substituted aminoquinolones as DGKalpha inhibitors for immune activation	Bayer AG, Bayer Pharma AG, Deutsches Krebsforschungszentrum (DKFZ)	Claims DGKα inhibitors; Pasodacigib is Example 298.	pIC₅₀ = 9.3 for human DGKα (IC₅₀ = 0.5 nM)	Priority: 30/11/2022; Publication: 04/06/2024	2
WO2021105117A1	Substituted aminoquinolones as dgkalpha inhibitors for immune activation	Bayer AG, Deutsches Krebsforschungszentrum (DKFZ)	International application covering aminoquinolone DGKα inhibitors.	(Implied to cover Example 298 / Pasodacigib)	Filing: 24/11/2020; Publication: 03/06/2021 (Priority to EP application)	17

This table summarizes the core patent protection identified for BAY2862789, linking the compound to specific patented chemical entities and associated high-potency biological data.

VIII. Discussion and Future Perspectives

BAY2862789 (pasodacigib) is emerging as a noteworthy investigational agent in the field of immuno-oncology, characterized by its novel mechanism of action, oral bioavailability, and promising preclinical profile. Its development addresses the ongoing need for new therapeutic strategies, particularly for advanced solid tumors where existing treatments have limitations.

Synthesis of Current Knowledge

BAY2862789 is a potent, selective, orally administered small molecule inhibitor of Diacylglycerol Kinase alpha (DGKα). It is currently in Phase 1 clinical development (NCT05858164) under the stewardship of Bayer and the German Cancer Research Center (DKFZ). The drug's proposed therapeutic effect is twofold: firstly, by inhibiting DGKα in T-cells, it enhances anti-tumor immune responses by promoting T-cell activation, proliferation, and effector functions, while counteracting T-cell anergy and exhaustion. Secondly, DGKα inhibition may directly induce apoptosis and suppress proliferation in cancer cells that overexpress this enzyme. This dual mechanism, supported by extensive preclinical in vitro and in vivo studies, forms the basis of its clinical investigation in advanced solid tumors, including NSCLC.

Therapeutic Potential and Significance

The potential of BAY2862789 lies in its ability to address several key challenges in cancer therapy:

• Novel Immunotherapeutic Target: DGKα represents a relatively new target in immuno-oncology. Its inhibition offers a distinct mechanism to modulate T-cell activity compared to established checkpoint inhibitors like anti-PD-1/L1 or anti-CTLA-4 antibodies. This novelty may provide therapeutic options for patients whose tumors do not respond to, or become resistant to, current immunotherapies.
• Overcoming T-cell Dysfunction: T-cell exhaustion and anergy within the tumor microenvironment are major barriers to effective anti-tumor immunity. BAY2862789's capacity to "release the brakes" on T-cell signaling by preventing DAG degradation directly addresses this issue.
• Oral Route of Administration: The oral formulation of BAY2862789 offers significant advantages in terms of patient convenience, potential for outpatient management, and flexibility in dosing schedules, which could be particularly beneficial for long-term treatment or maintenance strategies.
• High Potency: The sub-nanomolar IC₅₀ value against DGKα (0.5 nM, derived from pIC₅₀ of 9.3) [2] indicates a high degree of target engagement at potentially low drug concentrations, which is favorable for achieving therapeutic effects while minimizing off-target toxicities.
• Strong Rationale for Combination Therapies: The preclinical data compellingly suggest that the efficacy of BAY2862789 can be significantly enhanced when combined with other anti-cancer agents, particularly other immunotherapies like PD-1/L1 inhibitors or Treg-targeting agents (e.g., anti-CCR8 antibodies).[8] This positions BAY2862789 as a potentially valuable component of multi-pronged therapeutic strategies. The drug might "prime" the tumor microenvironment or re-invigorate T-cells, making them more responsive to subsequent or concurrent checkpoint blockade.

Challenges and Unanswered Questions

Despite its promise, the development of BAY2862789 faces several challenges inherent in oncology drug development:

• Clinical Safety and Tolerability: As a first-in-human agent targeting a kinase involved in widespread cellular signaling, the full safety and tolerability profile of BAY2862789 in humans remains to be established. Potential on-target, off-tumor effects resulting from systemic DGKα inhibition in normal tissues will require careful monitoring and management in the ongoing Phase 1 trial.
• Translation of Efficacy: While preclinical models provide a strong rationale, translating efficacy from these models (often inbred mice with transplanted tumors) to the complex and heterogeneous nature of human cancers is a significant hurdle.
• Biomarker Development: Currently, there are no validated predictive biomarkers to identify patients most likely to respond to DGKα inhibition. The identification of such biomarkers—potentially related to DGKα expression levels in tumors or immune cells, the baseline immune status of the patient, or specific TME characteristics—will be crucial for optimizing patient selection and maximizing clinical benefit in later-phase trials.
• Competitive Landscape: The field of immuno-oncology is dynamic, with numerous agents targeting various immune pathways under development. BAY2862789 will need to demonstrate a clear clinical benefit and a favorable risk-benefit profile to establish its place.
• Isoform Specificity and Redundancy: The DGK family comprises multiple isoforms (e.g., DGKα, DGKζ). While BAY2862789 is selective for DGKα, Bayer is also investigating a DGKζ-selective inhibitor (BAY2965501).[8] Preclinical data suggest that these isoforms may have distinct or complementary roles in immune regulation, with some tumor models showing enhanced benefit from combined DGKα/ζ inhibition.[8] A key unanswered question is whether selective DGKα inhibition alone will be optimally effective, or if broader DGK inhibition or specific combinations of isoform-selective inhibitors might offer a superior therapeutic index. The parallel clinical development of these agents will be instrumental in addressing this.

Future Research and Development Directions

The future development of BAY2862789 will likely focus on several key areas:

• Phase 1 Trial Completion: Successful completion of the NCT05858164 trial is the immediate priority, to establish the MTD/RDE, and to obtain initial human data on safety, PK, PD (confirming target engagement and T-cell modulation), and preliminary anti-tumor activity.
• Combination Studies: Based on the strong preclinical rationale, early-phase (Phase 1b/2a) clinical trials evaluating BAY2862789 in combination with standard-of-care agents, particularly PD-1/L1 inhibitors, are anticipated in selected tumor types (e.g., NSCLC, and others identified from Phase 1 expansion cohorts or biomarker analyses).
• Translational Research: Integrated translational studies, utilizing patient-derived samples (blood, tumor biopsies) from clinical trials, will be essential to confirm the mechanism of action in humans, explore pharmacodynamic effects, and identify potential predictive and pharmacodynamic biomarkers.
• Expansion into Specific Tumor Types: As efficacy signals emerge, development will likely focus on specific cancer indications where BAY2862789, either as monotherapy or in combination, shows the most promise.

IX. Conclusions

BAY2862789 (pasodacigib) is an orally bioavailable, highly potent, and selective small molecule inhibitor of Diacylglycerol Kinase alpha (DGKα), emerging from a collaborative effort between Bayer and the German Cancer Research Center. Its development is grounded in a compelling dual mechanism of action: the enhancement of anti-tumor T-cell immunity through modulation of TCR signaling, and the potential for direct anti-proliferative and pro-apoptotic effects on cancer cells overexpressing DGKα.

The extensive preclinical data package for BAY2862789 is encouraging, demonstrating its ability to activate T-cells, overcome key immunosuppressive pathways within the tumor microenvironment, and mediate anti-tumor efficacy both as a monotherapy and, notably, in synergistic combinations with other immunotherapeutic agents such as PD-1/L1 checkpoint inhibitors and anti-CCR8 antibodies. The development of sophisticated preclinical PK/PD models further supports a rational approach to its clinical translation.

The ongoing first-in-human Phase 1 clinical trial (NCT05858164) is a critical inflection point for BAY2862789. This study will provide the first human data on its safety, tolerability, pharmacokinetic profile, pharmacodynamic effects (confirming target engagement and immune modulation), and preliminary signals of anti-tumor activity. The results from this trial will be pivotal in guiding dose selection for subsequent studies and in identifying specific tumor types or patient populations where BAY2862789 may offer the most significant benefit.

Looking ahead, the trajectory of BAY2862789 will likely be heavily influenced by its performance in combination regimens, given the strong preclinical rationale. The identification of predictive biomarkers to guide patient selection will also be crucial for its successful development in a precision oncology landscape. While challenges inherent to oncology drug development remain, particularly regarding the translation of preclinical efficacy to human clinical benefit and the establishment of a favorable long-term safety profile, BAY2862789 represents a promising and innovative addition to the immuno-oncology pipeline. Its unique mode of action holds the potential to address unmet medical needs in patients with advanced solid tumors, particularly those who are refractory to or have relapsed after current standard-of-care immunotherapies.

X. References

1 Synapse Patsnap. (Date N/A). BAY-2862789 Drug Profile.

5 AdventHealth Research Institute. (Date N/A). Clinical Trial NCT05858164: An open-label, phase 1, first-in-human, dose escalation and expansion study to evaluate the safety... of BAY 2862789 in participants with advanced solid tumors.

19 Wikipedia. (Date N/A). Selinexor.

2 IUPHAR/BPS Guide to PHARMACOLOGY. (Date N/A). Pasodacigib Ligand Page.

6 Bayer Clinical Trials. (Date N/A). Study 22231: Advanced solid tumors, Non-small cell lung cancer.

3 National Cancer Institute. (Date N/A). Definition of DGKalpha inhibitor BAY 2862789 - NCI Drug Dictionary.

20 Dovatohcp.com. (2025, March 10). PASO DOBLE Trial Study Data.

21 IUPHAR/BPS Guide to MALARIA PHARMACOLOGY. (Date N/A). Pasodacigib Ligand Page. (Note: Link appears to be for malaria pharmacology but snippet refers to pasodacigib and DGK).

4 Larvol Delta. (2025, January 21). BAY 2862789 / Bayer, German Cancer Research Center.

7 Bayer US Medical Affairs. (2023, January). Oncology Pipeline in Clinical Development.

22 The ASCO Post. (2022, February 10). David Cescon, MD, PhD, Comments on the MONALEESA Analyses.

23 Oncology Resource Group. (2022, June 17). ESMO 2025.

3 National Cancer Institute. (Date N/A). Definition of DGKalpha inhibitor BAY 2862789..3

1 Synapse Patsnap. (Date N/A). BAY-2862789 - Drug Targets, Indications, Patents..1

8 ResearchGate. (2025, January 23). 729 Boosting anti-tumor immunity via triple combination of DGK, CCR8 and PD-L1 targeting agents.

24 Scribd. (Date N/A). Bayer Pharma RD Event 2023.

25 Bayer. (2024, November). Bayer Pharmaceuticals Handout.

26 Bayer. (2024, March 5). Bayer Capital Markets Day 2024.

27 American Association for Cancer Research. (2024). Abstracts | AACR Annual Meeting 2024.

28 American Association for Cancer Research. (2025, April 22). AACR Annual Meeting 2025 Regular Abstracts.

29 American Society of Clinical Oncology. (Date N/A). Abstracts & Presentations - Program Guide – ASCO Meeting Program Guide.

14 Synapse Patsnap. (Date N/A). DGK - Drugs, Indications, Patents.

30 European Society for Medical Oncology. (Date N/A). ESMO Congress 2025: Abstracts.

21 IUPHAR/BPS Guide to MALARIA PHARMACOLOGY. (Date N/A). Pasodacigib Ligand Page..21

31 IUPHAR/BPS Guide to PHARMACOLOGY. (Date N/A). Pasodacigib Ligand Page.

1 Synapse Patsnap. (Date N/A). BAY-2862789 - Drug Targets, Indications, Patents..1

32 IUPHAR/BPS Guide to IMMUNOPHARMACOLOGY. (Date N/A). Pasodacigib Ligand Page.

3 National Cancer Institute. (Date N/A). Definition of DGKalpha inhibitor BAY 2862789..3

33 ResearchGate. (2023, October 31). Small molecule inhibitors for cancer immunotherapy and associated biomarkers – the current status.

34 ResearchGate. (2023, November). Diacylglycerol kinases: A look into the future of immunotherapy.

35 European Medicines Agency. (2025, April 3). Clinical Trials Information System designated as WHO primary registry.

36 World Health Organization. (Date N/A). ICTRP Search Portal.

37 University of North Texas Libraries. (Date N/A). Google Patents Guide.

38 Google Patents. (Date N/A). Homepage.

39 Synapse Patsnap. (Date N/A). Target DGKA (Diacylglycerol kinase alpha).

40 Synapse Patsnap. (Date N/A). Target DGKZ (Diacylglycerol kinase zeta).

16 OncologyPipeline.com. (Date N/A). Xencor could face second challenge from former partner.

33 ResearchGate. (2023, October 31). Small molecule inhibitors for cancer immunotherapy and associated biomarkers – the current status..33

3 National Cancer Institute. (Date N/A). Definition of DGKalpha inhibitor BAY 2862789..3

2 IUPHAR/BPS Guide to IMMUNOPHARMACOLOGY. (Date N/A). Pasodacigib Ligand Page..32

5 AdventHealth Research Institute. (Date N/A). Clinical Trial 4364-22231 (BAY 2862789)..5

41 ClinTrialReferApp.com. (Date N/A). Trial Details: An Open-label, Phase 1...BAY 2862789.

42 United States Patent and Trademark Office. (Date N/A). Patent Public Search.

38 Google Patents. (Date N/A). Homepage..38

12 ResearchGate. (Date N/A). Detlef Stoeckigt Scientific Contributions. (Contains abstract on BAY2965501).

43 PubMed Central. (Date N/A). Small molecule inhibitors for cancer immunotherapy and associated biomarkers – the current status..33

16 OncologyPipeline.com. (Date N/A). Xencor could face second challenge from former partner..16

44 European Patent Office. (Date N/A). Espacenet - patent search.

39 Synapse Patsnap. (Date N/A). Target DGKA (Diacylglycerol kinase alpha)..39

45 CIMT. (2025, May 9). CIMT 2025 Book of Abstracts.

46 ResearchGate. (Date N/A). Dennis Kirchhoff Scientific Contributions..12

24 Scribd. (Date N/A). Bayer Pharma RD Event 2023..24

47 World Health Organization. (Date N/A). International Clinical Trials Registry Platform (ICTRP).

48 ISRCTN Registry. (Date N/A). Homepage.

17 Google Patents. (Date N/A). WO2021105117A1 - Substituted aminoquinolones as dgkalpha inhibitors for immune activation.

18 Google Patents. (Date N/A). WO2021105115A1 - Substituted aminoquinolones as dgkalpha inhibitors for immune activation. (Similar title, different WO number).

39 Synapse Patsnap. (Date N/A). Target DGKA (Diacylglycerol kinase alpha)..39

9 ResearchGate. (2023, October). 926 BAY 2965501, a highly selective DGK zeta inhibitor for cancer immunotherapy. (Abstract on DGKζ inhibitor).

14 Synapse Patsnap. (2024, June 27). Bayer's Novel Drugs...Receive Clinical Trial Approvals in China. (News on BAY2862789).

15 Synapse Patsnap. (2024, June 27). Bayer's Novel Drugs...Receive Clinical Trial Approvals in China..14

1 Synapse Patsnap. (Date N/A). BAY-2862789 - Drug Targets, Indications, Patents..1

45 CIMT. (2025, May 9). 2025 Abstract book..45

49 Google Patents. (Date N/A). WO2024165468A1 - Combination therapy for cancer. (Different patent, mentions DGKalpha inhibitor).

44 European Patent Office. (Date N/A). Espacenet - patent search..44

32 IUPHAR/BPS Guide to PHARMACOLOGY. (2025, February 20). References for Pasodacigib.

11 IUPHAR/BPS Guide to PHARMACOLOGY. (2025, May 4). Diacylglycerol kinases Family Page.

50 ResearchGate. (2023). Targeting DGKA therefore has the potential to combat cancer... (Excerpt from a publication).

10 ResearchGate. (Date N/A). Diacylglycerol kinase α inhibition cooperates with PD-1-targeted therapies to restore the T cell activation program.

44 European Patent Office. (Date N/A). Espacenet - patent search..44

51 European Patent Office. (Date N/A). Searching for patents.

1 Synapse Patsnap. (Date N/A). BAY2862789 clinical trials clinicaltrials.gov. (Consolidated information).

5 AdventHealth Research Institute. (Date N/A). BAY2862789 clinical trial information, NCT number...

2 IUPHAR/BPS Guide to IMMUNOPHARMACOLOGY. (Date N/A). Details on pasodacigib (BAY2862789)...

13 ClinicalTrials.gov. (Date N/A). Detailed information from clinical trial NCT05858164... (Meta-result from search).

8 ResearchGate. (2025, January 23). Preclinical data, T-cell activation...of BAY2862789...

11 IUPHAR/BPS Guide to PHARMACOLOGY. (2025, May 20). Pasodacigib (BAY2862789) DGKalpha inhibitor pIC50 9.3...

Works cited

1. BAY-2862789 - Drug Targets, Indications, Patents - PatSnap Synapse, accessed May 20, 2025, https://synapse.patsnap.com/drug/ad26b264a6734f46ad7a80cc6249021d
2. pasodacigib | Ligand page | IUPHAR/BPS Guide to IMMUNOPHARMACOLOGY, accessed May 20, 2025, https://www.guidetoimmunopharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=13751
3. Definition of DGKalpha inhibitor BAY 2862789 - NCI Drug Dictionary, accessed May 20, 2025, https://www.cancer.gov/publications/dictionaries/cancer-drug/def/dgkalpha-inhibitor-bay-2862789
4. BAY 2862789 / Bayer, German Cancer Research Center - LARVOL DELTA, accessed May 20, 2025, https://delta.larvol.com/Products/?ProductId=d6b28f7d-7c86-4ab9-af4f-f535512be64a
5. 22231 - An open-label, phase 1, first-in-human, dose escalation and ..., accessed May 20, 2025, https://www.adventhealth.com/institute/adventhealth-research-institute/clinical-cancer-research/clinical-trials/4364-22231-open-label-phase-1-first-human-dose-escalation-and-expansion-study-evaluate-safety
6. Advanced solid tumors || Non-small cell lung cancer | Study 22231 - Bayer Clinical Trials, accessed May 20, 2025, https://clinicaltrials.bayer.com/study/22231
7. Oncology Pipeline in Clinical Development - Bayer US Medical Affairs, accessed May 20, 2025, https://oncology.medicalaffairs.bayer.com/Bayer-Oncology-Pipeline-Brochure_January_2023.pdf
8. (PDF) 729 Boosting anti-tumor immunity via triple combination of ..., accessed May 20, 2025, https://www.researchgate.net/publication/385582515_729_Boosting_anti-tumor_immunity_via_triple_combination_of_DGK_CCR8_and_PD-L1_targeting_agents
9. 926 BAY 2965501: a highly selective DGK zeta inhibitor for cancer immunotherapy, accessed May 20, 2025, https://www.researchgate.net/publication/375130429_926_BAY_2965501_a_highly_selective_DGK_zeta_inhibitor_for_cancer_immunotherapy
10. Diacylglycerol kinase α inhibition cooperates with PD-1-targeted therapies to restore the T cell activation program | Request PDF - ResearchGate, accessed May 20, 2025, https://www.researchgate.net/publication/350791451_Diacylglycerol_kinase_a_inhibition_cooperates_with_PD-1-targeted_therapies_to_restore_the_T_cell_activation_program
11. Diacylglycerol kinases | Enzymes | IUPHAR/BPS Guide to ..., accessed May 20, 2025, https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1090
12. Detlef Stoeckigt's research works | Bayer and other places - ResearchGate, accessed May 20, 2025, https://www.researchgate.net/scientific-contributions/Detlef-Stoeckigt-2073995270
13. clinicaltrials.gov, accessed May 20, 2025, https://clinicaltrials.gov/study/NCT05858164
14. DGK - Drugs, Indications, Patents - Patsnap Synapse, accessed May 20, 2025, https://synapse.patsnap.com/target/285760e9f1093865a5f015a26f359585
15. DGKζ - Drugs, Indications, Patents - Patsnap Synapse, accessed May 20, 2025, https://synapse.patsnap.com/target/e2eeff87633e325e9b70c6bf11921c2a
16. Xencor could face second challenge from former partner | ApexOnco - Oncology Pipeline, accessed May 20, 2025, https://www.oncologypipeline.com/apexonco/xencor-could-face-second-challenge-former-partner
17. WO2021105117A1 - Substituted aminoquinolones as dgkalpha inhibitors for immune activation - Google Patents, accessed May 20, 2025, https://patents.google.com/patent/WO2021105117A1/he
18. WO2021105115A1 - Substituted aminoquinolones as dgkalpha inhibitors for immune activation - Google Patents, accessed May 20, 2025, https://patents.google.com/patent/WO2021105115A1/en
19. Selinexor - Wikipedia, accessed May 20, 2025, https://en.wikipedia.org/wiki/Selinexor
20. PASO DOBLE Trial Study Data | DOVATO (dolutegravir/lamivudine), accessed May 20, 2025, https://www.dovatohcp.com/efficacy-and-resistance/head-to-head/paso-doble/
21. pasodacigib | Ligand page | IUPHAR/BPS Guide to MALARIA PHARMACOLOGY, accessed May 20, 2025, https://www.guidetomalariapharmacology.org/GRAC/LigandDisplayForward?ligandId=13751
22. David Cescon, MD, PhD, Comments on the MONALEESA Analyses - The ASCO Post, accessed May 20, 2025, https://ascopost.com/issues/february-10-2022/epov-david-cescon/
23. ESMO 2025 - Oncology Resource Group, accessed May 20, 2025, https://onc-rg.com/conferences/esmo-2025/
24. Bayer Pharma RD Event 2023 | PDF | Personalized Medicine | Innovation - Scribd, accessed May 20, 2025, https://www.scribd.com/document/710702696/Bayer-Pharma-Rd-Event-2023
25. Bayer Pharmaceuticals Handout, accessed May 20, 2025, https://www.bayer.com/sites/default/files/bayer-pharmaceuticals-2024-november.pdf
26. Bayer Capital Markets Day 2024, accessed May 20, 2025, https://www.bayer.com/sites/default/files/2024-03/bayer-capital-markets-day-2024-pharmaceuticals-0_0.pdf
27. Abstracts | AACR Annual Meeting 2024, accessed May 20, 2025, https://www.aacr.org/meeting/aacr-annual-meeting-2024/abstracts/
28. AACR Annual Meeting 2025 Regular Abstracts, accessed May 20, 2025, https://www.aacr.org/wp-content/uploads/2025/04/AACR2025_Proceedings.pdf
29. Abstracts & Presentations - Program Guide – ASCO Meeting Program Guide, accessed May 20, 2025, https://www.asco.org/abstracts
30. ESMO Congress 2025: Abstracts, accessed May 20, 2025, https://www.esmo.org/meeting-calendar/esmo-congress-2025/abstracts
31. pasodacigib | Ligand page | IUPHAR/BPS Guide to PHARMACOLOGY, accessed May 20, 2025, https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=13751
32. pasodacigib | Ligand page | IUPHAR/BPS Guide to IMMUNOPHARMACOLOGY, accessed May 20, 2025, https://www.guidetoimmunopharmacology.org/GRAC/LigandDisplayForward?tab=refs&ligandId=13751
33. Small molecule inhibitors for cancer immunotherapy and associated biomarkers – the current status - ResearchGate, accessed May 20, 2025, https://www.researchgate.net/publication/375150806_Small_molecule_inhibitors_for_cancer_immunotherapy_and_associated_biomarkers_-_the_current_status
34. Diacylglycerol kinases: A look into the future of immunotherapy - ResearchGate, accessed May 20, 2025, https://www.researchgate.net/publication/375248504_Diacylglycerol_kinases_A_look_into_the_future_of_immunotherapy
35. Clinical Trials Information System designated as WHO primary registry | European Medicines Agency (EMA), accessed May 20, 2025, https://www.ema.europa.eu/en/news/clinical-trials-information-system-designated-who-primary-registry
36. ICTRP search portal - World Health Organization (WHO), accessed May 20, 2025, https://www.who.int/tools/clinical-trials-registry-platform/the-ictrp-search-portal
37. Google Patents - Google Guide - Guides at University of North Texas, accessed May 20, 2025, https://guides.library.unt.edu/google/patents
38. Google Patents, accessed May 20, 2025, https://patents.google.com/
39. DGKA - Drugs, Indications, Patents - Patsnap Synapse, accessed May 20, 2025, https://synapse.patsnap.com/target/bf992db699414c0694aa7456b1f66664
40. DGKζ - Drugs, Indications, Patents - PatSnap Synapse, accessed May 20, 2025, https://synapse.patsnap.com/target/c6869a843f2b4bf1aaf63dfeaed0d5f9
41. Back to List/Filter - ClinTrial Refer, accessed May 20, 2025, https://web.clintrialreferapp.com/SearchTrial/Details?trialId=21XrGV24IVc%3D
42. Patent Public Search - USPTO, accessed May 20, 2025, https://www.uspto.gov/patents/search/patent-public-search
43. Small molecule inhibitors for cancer immunotherapy and associated biomarkers – the current status - PMC - PubMed Central, accessed May 20, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10644399/
44. Espacenet - patent search | epo.org, accessed May 20, 2025, https://www.epo.org/en/searching-for-patents/technical/espacenet
45. 2025 Abstract book, accessed May 20, 2025, https://cdn.prod.website-files.com/614b2b26cfb8c9606f742911/681dcb667cc4d97204a57228_CIMT2025Book_of_Abstracts_250509.pdf
46. Dennis Kirchhoff's research works | Berlin-Chemie AG and other places - ResearchGate, accessed May 20, 2025, https://www.researchgate.net/scientific-contributions/Dennis-Kirchhoff-2159455790
47. International Clinical Trials Registry Platform (ICTRP) - World Health Organization (WHO), accessed May 20, 2025, https://www.who.int/tools/clinical-trials-registry-platform
48. ISRCTN Registry, accessed May 20, 2025, https://www.isrctn.com/
49. WO2024165468A1 - Combination of ccr8 antibodies with dgk inhibitors in the treatment of cancer - Google Patents, accessed May 20, 2025, https://patents.google.com/patent/WO2024165468A1/en
50. Oral administration of DGKAI suppressed liver tumor growth and improved... - ResearchGate, accessed May 20, 2025, https://www.researchgate.net/figure/Oral-administration-of-DGKAI-suppressed-liver-tumor-growth-and-improved-survival-of-model_fig2_354375842
51. Searching for patents | epo.org, accessed May 20, 2025, https://www.epo.org/en/searching-for-patents