Elraglusib (9-ING-41): A Comprehensive Profile of a Clinically Promising Agent with a Contested Mechanism

Section 1: Executive Summary

Elraglusib (9-ING-41) is an investigational, first-in-class, small-molecule therapeutic developed by Actuate Therapeutics, Inc..[1] Originally conceived and advanced into clinical trials as a potent inhibitor of Glycogen Synthase Kinase-3 Beta (GSK-3β), a key enzyme implicated in numerous oncogenic signaling pathways, Elraglusib has demonstrated a compelling clinical profile, particularly in cancers with high unmet medical needs.[2] The most significant clinical achievement to date is from the randomized, controlled Phase 2 Actuate-1801 trial, where the addition of Elraglusib to standard-of-care chemotherapy resulted in a statistically significant and clinically meaningful improvement in overall survival for patients with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC).[3] This pivotal result has positioned Elraglusib as a potential paradigm-shifting treatment in one of oncology's most challenging indications.

However, the scientific foundation of Elraglusib is undergoing a significant re-evaluation. A growing body of rigorous, independent research presents a compelling alternative to its designated mechanism of action. Evidence published in peer-reviewed journals, such as Cancer Research Communications, strongly suggests that Elraglusib's primary cytotoxic effects are not mediated by GSK-3β inhibition but rather by direct microtubule destabilization, inducing mitotic arrest and subsequent apoptosis.[2] This mechanistic discrepancy is central to the Elraglusib story, as its clinical success may have been achieved through a pathway different from the one originally hypothesized. The drug's clinical efficacy was established under a development program predicated on GSK-3β as the primary target, yet the concentrations at which it demonstrates cytotoxicity in vitro and in vivo align more closely with those required to disrupt microtubule dynamics. This suggests the successful Phase 2 trial in mPDAC may have inadvertently identified a patient population responsive to a novel microtubule-targeting agent. This presents both a considerable opportunity to reposition the asset based on its true biological activity and a significant risk, as the lack of a clear, mechanistically-driven biomarker strategy could complicate late-stage development and regulatory review.

Beyond pancreatic cancer, Elraglusib has demonstrated promising activity in other difficult-to-treat malignancies, including pediatric Ewing Sarcoma, where early clinical data have shown durable complete responses.[7] This broad potential is underscored by multiple special regulatory designations from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), including Orphan Drug Designations for pancreatic cancer and soft tissue sarcomas, as well as a Rare Pediatric Disease Designation for Ewing Sarcoma.[7]

Strategically, Elraglusib is at a critical inflection point. The company is preparing for pivotal regulatory interactions with the FDA and EMA to define the path to commercialization in mPDAC.[10] The future trajectory of this promising therapeutic will depend on successfully navigating these discussions, reconciling the robust clinical data with the evolving understanding of its mechanism of action, and designing a confirmatory Phase 3 program that maximizes its potential for success.

Section 2: Chemical Identity and Pharmacological Profile

2.1. Chemical Structure and Physicochemical Properties

Elraglusib is a synthetic organic compound belonging to the maleimide class of molecules.[12] It is a small molecule drug under investigation for various oncologic indications.[14]

• Chemical Name and Synonyms: The International Union of Pure and Applied Chemistry (IUPAC) name for the compound is 3-(5-fluoro-1-benzofuran-3-yl)-4-(5-methyl-dioxolo[4,5-f]indol-7-yl)pyrrole-2,5-dione.[12] It is also known by several synonyms, including its formal chemical name, 3-(5-fluoro-3-benzofuranyl)-4-(5-methyl-5H-1,3-dioxolo[4,5-f]indol-7-yl)-1H-pyrrole-2,5-dione, and its development code name, 9-ING-41.[14]
• Key Identifiers: Elraglusib is uniquely identified by its CAS (Chemical Abstracts Service) Registry Number, 1034895-42-5, and its DrugBank Accession Number, DB16047 [User Query].
• Molecular Formula and Weight: The chemical formula of Elraglusib is $C_{22}H_{13}FN_{2}O_{5}$.[14] This corresponds to an average molecular weight of 404.353 g/mol and a monoisotopic mass of 404.08084969 g/mol.[14]
• Physicochemical and Drug-Likeness Properties: Elraglusib's properties have been computationally predicted to assess its drug-like characteristics. Notably, it has very low predicted water solubility, with values of 0.0352 mg/mL and a logS of -4.1, and is reported as insoluble in aqueous buffers like PBS.[14] This poor aqueous solubility necessitates an intravenous formulation for clinical administration to ensure adequate bioavailability. The compound adheres to Lipinski's Rule of Five and the Ghose Filter, common heuristics used to evaluate the potential of a chemical compound to be an orally active drug in humans.[14] However, it fails Veber's Rule, which relates to the number of rotatable bonds and polar surface area, suggesting potential limitations in oral bioavailability.[14] A summary of its key properties is presented in Table 1.

Property	Value	Source
Water Solubility	0.0352 mg/mL	ALOGPS 14
logP	3.57	ALOGPS 14
pKa (Strongest Acidic)	9.86	Chemaxon 14
pKa (Strongest Basic)	-3	Chemaxon 14
Hydrogen Acceptor Count	4	Chemaxon 14
Hydrogen Donor Count	1	Chemaxon 14
Polar Surface Area	82.7 $Å^{2}$	Chemaxon 14
Number of Rings	6	Chemaxon 14
Rule of Five	Yes	Chemaxon 14
Ghose Filter	Yes	Chemaxon 14
Veber's Rule	No	Chemaxon 14

2.2. Pharmacokinetics and Bioavailability

The pharmacokinetic (PK) profile of Elraglusib has been characterized in the Phase 1 portion of the Actuate-1801 clinical trial, which studied the drug in patients with advanced malignancies.[16] As an intravenously administered agent, bioavailability is 100%.

The PK data from this study are critical for contextualizing the drug's mechanism of action. The trial established that clinically relevant doses of Elraglusib result in significant and sustained plasma concentrations. Specifically, following intravenous infusion, Elraglusib achieves a peak plasma concentration ($C_{max}$) in the range of 17 to 20 µM.[18] Furthermore, the plasma concentration remains above 1 µM for a full 24 hours post-infusion.[18] This sustained exposure above the 1 µM threshold is a pivotal finding, as it directly correlates with the concentrations required to elicit the biological effects observed in preclinical mechanistic studies, particularly those related to microtubule disruption. While the provided materials highlight these concentration ranges, they do not contain detailed public data on other key PK parameters such as clearance rate, volume of distribution, or elimination half-life.[16]

The clinical dosing regimen for Elraglusib has evolved through its development. The initial recommended phase II dose (RP2D) was established at 15 mg/kg administered intravenously twice weekly.[16] This dose was determined not by the observation of dose-limiting toxicities (DLTs), but rather by practical limitations related to the large fluid volumes required for administration at higher doses.[19] Subsequently, the RP2D was amended to 9.3 mg/kg. This reduction was implemented to mitigate a specific administrative complication: an increased incidence of blockages in central and peripheral vascular access catheters observed at the higher dose.[16] For the pivotal randomized Phase 2 trial in mPDAC, the dosing schedule was further refined to 9.3 mg/kg administered once weekly, on Day 1 of each 28-day cycle.[3] This evolution demonstrates a pragmatic approach to optimizing the drug's administration for patient convenience and safety, independent of systemic toxicity concerns.

Section 3: The Evolving Understanding of Elraglusib's Mechanism of Action

The biological mechanism by which Elraglusib exerts its anticancer effects is a subject of significant scientific debate. While the drug was rationally designed and developed as a targeted inhibitor of GSK-3β, a compelling body of recent evidence indicates that its primary cytotoxic activity stems from an entirely different mechanism: the direct destabilization of microtubules. This evolving understanding has profound implications for the drug's future development, biomarker strategy, and clinical positioning.

3.1. The Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibition Hypothesis

The original scientific rationale for Elraglusib is rooted in the inhibition of Glycogen Synthase Kinase-3 Beta (GSK-3β). GSK-3β is a constitutively active serine/threonine protein kinase that functions as a critical regulatory node in a multitude of cellular processes, including metabolism, proliferation, and survival.[13] In many cancers, GSK-3β is aberrantly overexpressed or hyperactive, where it contributes to oncogenesis by phosphorylating and modulating the activity of proteins involved in tumor progression and resistance to therapy.[23]

Elraglusib was designed as a potent, ATP-competitive small-molecule inhibitor of GSK-3β, with a reported half-maximal inhibitory concentration ($IC_{50}$) of 0.71 µM.[2] The central tenet of this hypothesis is that by blocking GSK-3β activity, Elraglusib disrupts key pro-survival signaling cascades within cancer cells. The most frequently cited downstream pathway is the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway.[13] Inhibition of GSK-3β is proposed to lead to the downregulation of NF-κB activity and, consequently, the decreased expression of its target genes, which include critical anti-apoptotic and cell cycle-promoting proteins such as cyclin D1, B-cell lymphoma 2 (Bcl-2), and the X-linked inhibitor of apoptosis protein (XIAP).[13] This mechanism was first proposed in the foundational discovery paper by Gaisina et al., which demonstrated that treatment of pancreatic cancer cells with "compound 26" (Elraglusib) suppressed GSK-3β activity, reduced XIAP expression, and induced significant apoptosis.[28]

Based on this rationale, the drug's developer, Actuate Therapeutics, has described Elraglusib as having a multi-pronged mechanism of action centered on GSK-3β inhibition. This includes direct inhibition of tumor growth pathways, modulation of systemic and local cytokines, and significant immunomodulatory effects, such as enhancing anti-tumor immune responses.[23]

3.2. Emergent Evidence: Elraglusib as a Direct Microtubule Destabilizer

Despite the well-articulated GSK-3β hypothesis, recent independent research has fundamentally challenged this narrative. A 2024 study published in Cancer Research Communications provides conclusive evidence that the primary mechanism responsible for Elraglusib's cytotoxicity is the direct destabilization of microtubules (MTs), a process that occurs independently of GSK-3β inhibition.[2]

This conclusion is supported by several key lines of evidence. First, the cytotoxic effects of Elraglusib could not be replicated by other structurally distinct, potent GSK-3β inhibitors. In lymphoma cell lines, inhibitors such as CT99021, SB216763, and LY2090314 failed to reduce cell proliferation or viability, even when used at concentrations that produced robust and measurable inhibition of GSK-3β (e.g., stabilization of its substrate, β-catenin).[6] Second, the cytotoxic effect of Elraglusib is independent of the presence of its purported target. In lymphoma cells where both isoforms of GSK-3 (GSK3A and GSK3B) were depleted using shRNA, Elraglusib retained its ability to induce cell cycle arrest and apoptosis, demonstrating that GSK-3 is not required for its activity.[6]

In contrast, the evidence for a direct effect on microtubules is compelling. Treatment of cancer cells with Elraglusib was shown to cause profound defects in the formation of the mitotic spindle, the microtubule-based apparatus responsible for chromosome segregation during cell division. These defects were phenotypically similar to those caused by nocodazole, a well-characterized microtubule-depolymerizing agent.[6] This was confirmed biochemically through tubulin fractionation experiments, which directly measured the equilibrium between soluble (depolymerized) and insoluble (polymerized) tubulin. Elraglusib treatment led to a dose-dependent increase in soluble tubulin and a corresponding decrease in polymerized tubulin, a classic signature of a microtubule-destabilizing agent.[6] Crucially, this effect was confirmed in a cell-free system using purified tubulin. In these in vitro microtubule growth assays, Elraglusib directly impaired the polymerization of tubulin and increased the frequency of "catastrophe" events (the rapid depolymerization of a microtubule), proving that its action is directly on the microtubule structure itself and does not require any other cellular proteins.[6]

The downstream consequence of this microtubule destabilization is a potent anti-cancer effect. By preventing the proper attachment of chromosomes to the mitotic spindle via their kinetochores, Elraglusib triggers the mitotic checkpoint, causing a prolonged arrest in the M-phase of the cell cycle.[2] Cells that remain arrested in mitosis for an extended period eventually undergo one of two fates: direct apoptotic cell death in mitosis, or an aberrant exit from mitosis without dividing, a process known as "mitotic slippage." This slippage leads to the formation of aneuploid cells with gross chromosomal missegregation, which triggers catastrophic DNA damage and subsequent apoptosis.[2] This cascade of mitotic arrest, mitotic slippage, DNA damage, and apoptosis provides a complete and coherent explanation for the potent cytotoxicity observed with Elraglusib across numerous cancer types.

The clinical relevance of this mechanism is strongly supported by the pharmacokinetic data. The in vitro studies show that Elraglusib begins to affect microtubule stability and induce mitotic arrest at concentrations at or above 1 µM.[6] As noted previously, Phase 1 clinical data confirm that intravenous administration of Elraglusib achieves sustained plasma concentrations well above this 1 µM threshold for at least 24 hours.[18] This direct correlation between the clinically achievable drug concentration and the concentration required for microtubule destabilization strongly implies that this is the primary, clinically relevant mechanism of action.

3.3. Immunomodulatory Effects: A Bridge Between Mechanisms?

A significant aspect of Elraglusib's biological profile is its ability to modulate the anti-tumor immune response. Preclinical and clinical data have consistently shown that Elraglusib exerts powerful immunomodulatory effects. It has been demonstrated to reduce the expression of multiple immune checkpoint molecules on T cells, including Programmed cell death protein 1 (PD-1), T cell immunoreceptor with Ig and ITIM domains (TIGIT), and Lymphocyte-activation gene 3 (LAG-3).[22] This reduction in inhibitory signals is coupled with an enhancement of immune effector functions. Elraglusib promotes the killing of tumor cells by immune cells, augments the cytolytic activity of CD8+ T cells, and increases the secretion of key effector cytokines such as interferon-gamma (IFN-γ), granzyme B, and tumor necrosis factor-alpha (TNF-α).[5]

This immunomodulatory activity provides a strong rationale for combining Elraglusib with immune checkpoint inhibitors. Preclinical studies have shown a synergistic anti-tumor effect when Elraglusib is combined with anti-PD-1 or anti-PD-L1 antibodies. Notably, the greatest benefit was observed when the therapies were administered sequentially, with checkpoint inhibition preceding Elraglusib treatment, suggesting that priming the immune system first allows Elraglusib to subsequently unleash a more potent effector response.[22]

These immune effects can be rationalized under both mechanistic hypotheses, but the microtubule destabilization model may offer a more comprehensive explanation. The GSK-3β inhibition hypothesis connects these effects to the known role of GSK-3β as a negative regulator of T-cell activation; thus, inhibiting GSK-3β would be expected to directly enhance T-cell function.[22] However, the paradigm of immunogenic cell death (ICD) provides a powerful alternative explanation. Many cytotoxic drugs that target microtubules, such as taxanes, are known to be potent inducers of ICD. By causing catastrophic cell death through mitotic arrest, these agents trigger the release of damage-associated molecular patterns (DAMPs) from dying tumor cells. These DAMPs act as potent "danger signals" that recruit and activate dendritic cells, leading to the priming and activation of a robust, tumor-specific T-cell response. The observation of increased CD8+ and granzyme B-positive T cells infiltrating tumors in Elraglusib-treated patients is a classic hallmark of such an ICD-driven immune response.[5] Therefore, Elraglusib's immunomodulatory properties may be less of a direct, targeted effect on T-cells and more of a powerful downstream consequence of its primary cytotoxic mechanism, re-framing it as a novel cytotoxic agent that effectively converts the tumor into an in situ vaccine.

3.4. Downstream Signaling: Induction of Apoptosis, Cell Cycle Arrest, and NF-κB Pathway Modulation

Regardless of the primary upstream target, the terminal downstream effects of Elraglusib consistently converge on the induction of apoptosis and cell cycle arrest.[25] The microtubule destabilization mechanism provides a more precise definition for this cell cycle effect, identifying it as a specific arrest in the M-phase (mitosis) due to the activation of the mitotic checkpoint.[2]

The modulation of the NF-κB pathway remains a key feature of Elraglusib's activity. The GSK-3β hypothesis posits this is a direct consequence of inhibiting the kinase.[13] However, it is also plausible that the profound cellular stress, DNA damage, and metabolic disruption caused by mitotic catastrophe could secondarily lead to the downregulation of pro-survival pathways like NF-κB. Thus, while the effect on NF-κB is well-documented, its position as a direct versus indirect consequence of the drug's primary action remains open to interpretation in light of the new mechanistic data.

Section 4: Clinical Development and Efficacy Analysis

Elraglusib has undergone a broad clinical development program, investigating its potential across a range of hematologic and solid tumors, both as a monotherapy and in combination with various cytotoxic agents. This strategy of wide exploration has successfully identified mPDAC as a landmark indication where the drug demonstrates significant clinical benefit, leading to a more focused late-stage development plan.

Trial ID	Title / Phase	Indication(s)	Intervention	Status	Key Findings / Purpose
NCT03678883	Actuate-1801 / Phase 1/2	Advanced Refractory Cancers; mPDAC	Elraglusib mono; Elraglusib + various chemo; Elraglusib + GnP	Ongoing	Established RP2D; Landmark randomized data in 1L mPDAC showing significant OS benefit.
NCT04239092	Actuate-1902 / Phase 1/2	Pediatric Relapsed/Refractory Malignancies (incl. Ewing Sarcoma)	Elraglusib mono & combo	Ongoing	Promising early signals of activity, including durable complete responses in Ewing Sarcoma.
NCT04218071	Actuate 1901 / Phase 2	Myelofibrosis	Elraglusib mono; Elraglusib + Ruxolitinib	Completed	To evaluate efficacy in advanced myelofibrosis; results not publicly reported.
NCT04832438	9-ING-41 Plus Carboplatin / Phase 2	Advanced Salivary Gland Carcinoma	Elraglusib + Carboplatin	Withdrawn	To evaluate efficacy in advanced salivary gland carcinoma; reason for withdrawal not specified.

4.1. Phase 1 Foundation: Safety, Tolerability, and Dose Determination (Actuate-1801 Parts 1 & 2)

The foundation of Elraglusib's clinical program is the multi-part Phase 1/2 study, NCT03678883, known as Actuate-1801.[39] The initial dose-escalation phases of this trial were designed to establish the safety, tolerability, and RP2D of Elraglusib. Part 1 evaluated Elraglusib as a monotherapy in 67 patients, while Part 2 evaluated it in combination with eight different standard-of-care chemotherapy regimens in 171 patients with a variety of advanced, refractory malignancies.[16]

The safety profile established in this study was generally manageable. The most common adverse events (AEs) attributed to Elraglusib were transient, reversible visual disturbances and fatigue.[16] These visual events, which resolved shortly after infusion, are considered a likely class effect of GSK-3β inhibitors.[26] Grade ≥3 treatment-emergent AEs (TEAEs) were observed in 55.2% of patients receiving monotherapy and 71.3% of patients in the combination arms, a rate consistent with heavily pre-treated patient populations receiving chemotherapy.[16] As previously noted, the RP2D was ultimately established at 9.3 mg/kg, a decision driven by administrative considerations rather than systemic toxicity.[16]

Despite the refractory nature of the patient population, early signals of clinical activity were observed. In the monotherapy arm, notable responses included one patient with melanoma who achieved a complete response and one patient with adult T-cell leukemia/lymphoma who had a partial response (PR). In the combination therapy arms, seven PRs were observed across various tumor types.[16] These encouraging early results provided the rationale to advance Elraglusib into indication-specific Phase 2 expansion cohorts.

4.2. Landmark Indication: Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC)

The most significant clinical success for Elraglusib has been in the first-line treatment of mPDAC, an area of profound unmet medical need where therapeutic advances have been stagnant for over a decade.[3]

4.2.1. Actuate-1801 Part 3β: Trial Design and Efficacy Outcomes

Part 3β of the Actuate-1801 study was a randomized, controlled, open-label Phase 2 trial that enrolled 286 patients with previously untreated mPDAC.[3] Patients were randomized in a 2:1 ratio to receive either Elraglusib (at the 9.3 mg/kg weekly dose) in combination with standard-of-care gemcitabine and nab-paclitaxel (GnP), or GnP alone.[3] The primary endpoint of the study was overall survival (OS).[3]

Topline results, announced in May 2025 and presented at the ASCO 2025 Annual Meeting, showed that the trial successfully met its primary endpoint.[3] The addition of Elraglusib to GnP resulted in a statistically significant and clinically meaningful improvement in OS. The median OS for patients in the combination arm was 10.1 months, compared to 7.2 months for patients in the GnP control arm. This represents a 37% reduction in the risk of death, with a hazard ratio (HR) of 0.63 and a p-value of 0.01.[5]

The survival benefit was particularly pronounced at later time points. The 1-year survival rate was doubled in the Elraglusib arm, with 44.1% of patients alive at one year compared to 22.3% in the control arm.[5] This survival advantage was sustained, with 18-month and 24-month survival rates of 19.7% vs 4.4% and 13.8% vs 0%, respectively, for the combination versus control arms.[5] The combination also resulted in numerically improved secondary endpoints, including a higher overall response rate (ORR) of 29.0% vs 21.8% and a longer median progression-free survival (PFS) of 5.6 months vs 5.1 months.[5] These robust results from a randomized trial represent a significant potential advance for the first-line treatment of mPDAC.

Efficacy Endpoint	Elraglusib + GnP	GnP Alone	Hazard Ratio (95% CI) / p-value
Median Overall Survival (mOS)	10.1 months	7.2 months	HR = 0.63; p = 0.01
12-Month Survival Rate	44.1%	22.3%	-
18-Month Survival Rate	19.7%	4.4%	-
Median Progression-Free Survival (mPFS)	5.6 months	5.1 months	-
Overall Response Rate (ORR)	29.0%	21.8%	-

4.2.2. Safety and Tolerability in Combination with Gemcitabine/Nab-Paclitaxel

A critical component of the success in the mPDAC trial was the manageable safety profile of the Elraglusib-GnP combination. The study reported a "favorable risk-benefit profile," with the overall incidence of TEAEs and Serious Adverse Events (SAEs) in the combination arm being similar to that observed in the GnP control arm.[4] This suggests that Elraglusib adds significant efficacy without a commensurate increase in overall toxicity.

The most frequent AEs related to Elraglusib itself were the previously identified transient visual impairments, which were mostly Grade 1-2 in severity, reversible, and non-progressive.[5] Importantly, while Grade 3 or higher neutropenia is a known and significant toxicity of the GnP backbone, the rates of the most severe complications, febrile neutropenia and sepsis, were similar between the two treatment arms.[5] This finding is crucial, as it indicates that Elraglusib does not substantially exacerbate the life-threatening myelosuppressive effects of the chemotherapy backbone.

This favorable profile at the 9.3 mg/kg dose stands in contrast to the experience with the higher 15 mg/kg dose used in the initial single-arm portion of the study. In that earlier phase, the 15 mg/kg dose was associated with a "modest exacerbation of GnP-related toxicities," including higher rates of Grade ≥3 neutropenia (52.4%) and leukopenia (42.9%), which prompted the dose reduction for the randomized trial.[2] The successful outcome of the randomized trial validates this decision, demonstrating that the lower 9.3 mg/kg dose retains robust efficacy while offering an improved safety margin.

Key Grade ≥3 TEAEs (ITT Population, N=42, 15 mg/kg dose)	Any Grade (%)	Grade ≥3 (%)
Neutropenia / Neutrophil count decreased	59.5	52.4
Leukopenia / White blood cell count decreased	50.0	42.9
Fatigue	69.0	21.4
Visual Impairment	83.3	4.8

4.3. Pediatric Oncology: Ewing Sarcoma and the Actuate-1902 Trial

Elraglusib is also being investigated in pediatric populations through the Actuate-1902 trial (NCT04239092), an ongoing Phase 1/2 study in children and young adults with relapsed or refractory malignancies.[7] A key focus of this trial is Ewing Sarcoma, a rare and aggressive bone cancer.

Early data from this study have been highly promising. As of November 2024, objective tumor responses have been observed, including two ongoing and durable complete responses among the first six Ewing Sarcoma patients treated on the trial.[7] The study employs a flexible design, evaluating Elraglusib both as a monotherapy and in combination with standard pediatric chemotherapy regimens, including irinotecan plus temozolomide and cyclophosphamide plus topotecan, at a dose of 9.3 mg/kg twice weekly.[7] These encouraging early results, coupled with the FDA's granting of Rare Pediatric Disease Designation, highlight Elraglusib's potential to address a critical unmet need in this vulnerable patient population. Topline data from the Phase 1 portion of the study are anticipated in the second half of 2025.[7]

4.4. Exploration in Other Malignancies: Myelofibrosis and Lymphoma

Elraglusib's development program has included explorations in other cancer types. A Phase 2 trial in myelofibrosis (NCT04218071, Actuate 1901) has been completed.[44] This study evaluated Elraglusib as a single agent and in combination with the JAK inhibitor ruxolitinib in patients with advanced myelofibrosis.[45] Despite the trial's completion, the results have not been made publicly available in the provided documentation, representing a notable gap in the drug's clinical story.[45]

In lymphoma, strong preclinical data supported clinical investigation.[24] This translated into a clinical signal in the Phase 1 study, where a patient with refractory adult T-cell leukemia/lymphoma achieved a partial response to Elraglusib monotherapy.[16] It was also in lymphoma models that the mechanistic questions regarding GSK-3β as the true target were first rigorously investigated and challenged.[24]

4.5. Discontinued Investigations: The Case of Salivary Gland Carcinoma (NCT04832438)

Not all avenues of investigation have proven fruitful. A Phase 2 clinical trial designed to evaluate Elraglusib in combination with carboplatin for patients with advanced, metastatic salivary gland carcinoma (NCT04832438) was officially withdrawn before completion.[47] The provided source materials do not specify the reason for this withdrawal.[47] Such an action could be due to a variety of factors, including insufficient efficacy, unexpected toxicity, slow patient accrual, or a strategic decision by the sponsor to reallocate resources to more promising programs, such as the mPDAC and Ewing Sarcoma trials. This disciplined approach of focusing resources on the most promising assets is a rational development strategy, but the lack of a stated reason for the withdrawal remains a point for due diligence.

Section 5: Regulatory and Commercial Landscape

The development of Elraglusib has progressed from an academic discovery to a late-stage clinical asset backed by significant regulatory support and public financing, positioning it for potential commercialization in key oncology markets.

5.1. Development History: From Academic Discovery to Actuate Therapeutics

The origins of Elraglusib trace back to academic research focused on developing novel inhibitors of GSK-3β. The molecule, initially identified as "compound 26," was discovered and synthesized through a research collaboration between the University of Illinois Chicago (UIC) and Northwestern University (NU).[1] The foundational work, led by Gaisina and colleagues, was published in the Journal of Medicinal Chemistry in 2009 and described the identification of potent benzofuran-3-yl-(indol-3-yl)maleimides, including compound 26, derived from a natural product lead.[12]

Actuate Therapeutics, Inc. was subsequently formed as a clinical-stage biopharmaceutical company with the specific goal of advancing this technology into clinical development. The company acquired the exclusive license to the portfolio of GSK-3β inhibitors, including Elraglusib, from the collaborating universities.[1] Under Actuate's stewardship, Elraglusib has been advanced through a comprehensive clinical program, culminating in the successful randomized Phase 2 trial in mPDAC.

5.2. Key Regulatory Designations

Elraglusib has received multiple special designations from global regulatory authorities, recognizing its potential to treat rare and serious diseases with high unmet medical needs. These designations provide significant benefits, including potential for expedited review, extended market exclusivity, and financial incentives.

• Pancreatic Cancer:
• FDA Orphan Drug Designation: Granted in August 2023 for the treatment of pancreatic cancer.[8]
• EMA Orphan Medicinal Product Designation: Granted in January 2025 for the treatment of advanced pancreatic ductal adenocarcinoma.[8]
• Soft Tissue Sarcomas:
• FDA Orphan Drug Designation: Granted in September 2024.[9]
• Ewing Sarcoma:
• FDA Rare Pediatric Disease Designation: Granted in November 2024.[7] This designation may entitle the sponsor to a Priority Review Voucher upon approval, which can be used to obtain expedited review for a different product.

5.3. Intellectual Property and Patent Status

The intellectual property (IP) portfolio protecting Elraglusib is a critical component of its commercial value. The original composition of matter patent, which protects the molecular structure of Elraglusib itself, is cited as U.S. Patent Number 8,207,216.[48] Given that this patent would likely claim priority from filings made around the time of the 2009 discovery, its 20-year term is expected to expire in the late 2020s.

Recognizing the timeline of the primary patent, the IP strategy appears to have evolved to protect novel methods of using Elraglusib, thereby extending its period of market exclusivity. Recent patent applications, such as WO2024159185A1 filed by Brown University, do not focus on the molecule itself but on its application in combination therapies, specifically with immune checkpoint inhibitors, to enhance anti-tumor immune responses.[52] This strategy directly reflects the emerging scientific understanding of Elraglusib's potent immunomodulatory effects and aims to build a new IP estate around this novel application. This is a common and effective life-cycle management strategy for pharmaceutical assets.

To fund its late-stage development and pre-commercialization activities, Actuate Therapeutics successfully completed an initial public offering (IPO) in August 2024, and its stock is now listed on the Nasdaq Global Market under the symbol "ACTU".[1] This financing provides the necessary capital to advance the mPDAC program through pivotal regulatory interactions and prepare for a potential Phase 3 trial.[54]

Section 6: Expert Synthesis and Future Outlook

Elraglusib stands as a compelling late-stage oncology asset, distinguished by robust clinical data in a high-value indication. However, its future trajectory will be shaped by the need to reconcile its clinical success with a fundamental and evolving understanding of its biological mechanism, a challenge that will be central to its regulatory review and ultimate commercial potential.

6.1. Reconciling the Mechanism: Implications of the GSK-3β vs. Microtubule Target Debate

The central strategic issue facing Elraglusib is the discrepancy between its designated target (GSK-3β) and its evidence-based cytotoxic mechanism (microtubule destabilization). While the company's narrative remains focused on GSK-3β inhibition, the weight of the independent scientific evidence strongly supports the conclusion that microtubule disruption is the primary driver of the cytotoxicity observed at clinically relevant concentrations. The failure of other potent GSK-3β inhibitors to replicate Elraglusib's effects, combined with the direct, measurable impact of Elraglusib on tubulin polymerization in vitro, makes a compelling case for reclassifying the drug's primary mechanism.

This is not merely an academic distinction; it has profound strategic implications. First, it reframes the competitive landscape. Elraglusib should be benchmarked not against other investigational GSK-3β inhibitors, but against established and emerging microtubule-targeting agents like taxanes, vinca alkaloids, and eribulin. Its unique chemical structure and potential for a differentiated safety and efficacy profile within this class become the key points of value. Second, it must urgently inform the biomarker development strategy. A strategy based on measuring GSK-3β expression or pathway activity is likely to fail. Instead, future clinical trials should prioritize the development of biomarkers related to mitotic stress, mitotic checkpoint integrity, or genomic signatures that confer sensitivity to microtubule poisons. The company's current efforts to use machine learning to identify predictive cytokine signatures are a pragmatic step, but a mechanistically-grounded biomarker would be far more powerful for patient selection in a pivotal Phase 3 trial.[55] Finally, regulators at the FDA and EMA will almost certainly require a clear and evidence-based discussion of the drug's mechanism of action in any New Drug Application (NDA). Successfully navigating this discussion will be critical for approval.

6.2. Assessment of Clinical Potential in Pancreatic Cancer and Beyond

The clinical potential of Elraglusib in mPDAC is unambiguous and significant. The results of the randomized Actuate-1801 Part 3β trial—demonstrating a nearly three-month improvement in median OS and a doubling of the 1-year survival rate with a manageable safety profile—represent one of the most promising advances in this disease in years.[5] Pending a successful confirmatory Phase 3 trial, Elraglusib in combination with GnP has the potential to become a new global standard of care for the first-line treatment of mPDAC.

The potential in Ewing Sarcoma is also exceptionally high. The observation of durable complete responses in early-phase pediatric trials is a powerful signal of activity.[7] Given the high unmet need and the Rare Pediatric Disease Designation, this indication could offer an accelerated path to market, potentially providing the first approval for the drug.

The broader potential in other solid tumors remains to be defined but is considerable. A rational future development strategy would focus on tumor types known to be sensitive to microtubule-targeting agents (e.g., certain breast, lung, and ovarian cancers) and on rational combinations where Elraglusib's potent immunomodulatory effects can be leveraged.

6.3. Future Directions: Combination Strategies, Biomarkers, and Potential Hurdles

The future of Elraglusib will be defined by three key areas:

• Combination Strategies: Elraglusib's profile as a potent inducer of immunogenic cell death makes it an ideal partner for immune checkpoint inhibitors. Ongoing and future trials exploring these combinations are highly rational and could unlock its potential in "immunologically cold" tumors that are typically unresponsive to immunotherapy.[49] Furthermore, because mitotic catastrophe induced by microtubule agents leads to significant DNA damage, combinations with DNA Damage Response (DDR) inhibitors, such as PARP inhibitors, are also a highly synergistic and logical avenue for exploration.
• Biomarker Development: As noted, the identification of a predictive biomarker is the most critical next step to de-risk a large and expensive Phase 3 trial. Research should focus on identifying genetic or proteomic markers of sensitivity to microtubule disruption or mitotic checkpoint vulnerability.
• Execution and Hurdles: The primary hurdle for Actuate Therapeutics is execution. This includes designing and successfully running a global Phase 3 trial in mPDAC, which will require significant capital and operational expertise. The company must also secure regulatory alignment from the FDA and EMA on both the clinical data package and the mechanistic narrative.[11] Finally, the long-term commercial success will depend on the strength of its evolving intellectual property portfolio and its ability to compete in a crowded oncology market.

In conclusion, Elraglusib is a clinically validated therapeutic agent with the potential to make a significant impact on patients with pancreatic cancer, Ewing Sarcoma, and potentially other malignancies. Its journey is a fascinating case study in drug development, where clinical success has outpaced and even challenged the initial scientific hypothesis. The key to unlocking its full value will be to embrace the evolving science and align the future clinical and regulatory strategy with its true, potent mechanism of action as a novel microtubule destabilizer.

Works cited

1. tm247121-39_424b4 - none - 29.8907432s - SEC.gov, accessed October 17, 2025, https://www.sec.gov/Archives/edgar/data/1652935/000110465924088877/tm247121-39_424b4.htm
2. Elraglusib - Drug Targets, Indications, Patents - Patsnap Synapse, accessed October 17, 2025, https://synapse.patsnap.com/drug/0037b10f3d9340f389b0192c25f75224
3. Actuate Therapeutics Announces Statistically Significant Topline Results from Global Phase 2 Trial of Elraglusib in First-Line Treatment of Metastatic Pancreatic Cancer, accessed October 17, 2025, https://actuatetherapeutics.com/press_releases/actuate-therapeutics-announces-statistically-significant-topline-results-from-global-phase-2-trial-of-elraglusib-in-first-line-treatment-of-metastatic-pancreatic-cancer/
4. First-Line Elraglusib Plus Chemo Improves Survival in Metastatic Pancreatic Cancer, accessed October 17, 2025, https://www.onclive.com/view/first-line-elraglusib-plus-chemo-improves-survival-in-metastatic-pancreatic-cancer
5. Actuate Therapeutics Presents Topline Elraglusib Phase 2 Data at ASCO 2025 Annual Meeting: Trial Meets Primary Endpoint of Median Overall Survival and Doubles 1-Year Survival in First-Line Treatment of Metastatic Pancreatic Cancer, accessed October 17, 2025, https://actuatetherapeutics.com/press_releases/actuate-therapeutics-presents-topline-elraglusib-phase-2-data-at-asco-2025-annual-meeting-trial-meets-primary-endpoint-of-median-overall-survival-and-doubles-1-year-survival-in-first-line-treatment-o/
6. Elraglusib Induces Cytotoxicity via Direct Microtubule Destabilization ..., accessed October 17, 2025, https://aacrjournals.org/cancerrescommun/article/4/11/3013/750322/Elraglusib-Induces-Cytotoxicity-via-Direct
7. Elraglusib Earns FDA Rare Pediatric Disease Designation for Ewing ..., accessed October 17, 2025, https://www.onclive.com/view/elraglusib-earns-fda-rare-pediatric-disease-designation-for-ewing-sarcoma
8. EMA Grants Orphan Medical Product Designation to Elraglusib in ..., accessed October 17, 2025, https://www.onclive.com/view/ema-grants-orphan-medical-product-designation-to-elraglusib-in-advanced-pdac
9. Actuate Receives FDA Orphan Drug Designation for Elraglusib for ..., accessed October 17, 2025, https://actuatetherapeutics.com/press_releases/actuate-receives-fda-orphan-drug-designation-for-elraglusib-for-treatment-of-soft-tissue-sarcomas/
10. www.pharmanow.live, accessed October 17, 2025, https://www.pharmanow.live/latest-news/actuate-elraglusib-pancreatic-cancer#:~:text=Actuate%20Therapeutics%20Submits%20Updated%20Clinical,EMA%20submissions%20in%202025%E2%80%932026.
11. Actuate Sends New Elraglusib Data to FDA, EMA Talks Ahead, accessed October 17, 2025, https://www.pharmanow.live/latest-news/actuate-elraglusib-pancreatic-cancer
12. elraglusib | Ligand page - IUPHAR/BPS Guide to PHARMACOLOGY, accessed October 17, 2025, https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=11412
13. Definition of elraglusib - NCI Drug Dictionary, accessed October 17, 2025, https://www.cancer.gov/publications/dictionaries/cancer-drug/def/elraglusib
14. Elraglusib: Uses, Interactions, Mechanism of Action | DrugBank Online, accessed October 17, 2025, https://go.drugbank.com/drugs/DB16047
15. 9-ING-41 (Elraglusib, CAS Number: 1034895-42-5) | Cayman Chemical, accessed October 17, 2025, https://www.caymanchem.com/product/36629/9-ing-41
16. Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase ..., accessed October 17, 2025, https://pubmed.ncbi.nlm.nih.gov/37982822/
17. Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3b Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies - Northwestern Scholars, accessed October 17, 2025, https://www.scholars.northwestern.edu/en/publications/phase-i-study-of-elraglusib-9-ing-41-a-glycogen-synthase-kinase-3
18. Elraglusib Induces Cytotoxicity via Direct Microtubule Destabilization Independently of GSK3 Inhibition - PMC, accessed October 17, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11586712/
19. Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3b Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies - Mayo Clinic, accessed October 17, 2025, https://mayoclinic.elsevierpure.com/en/publications/phase-i-study-of-elraglusib-9-ing-41-a-glycogen-synthase-kinase-3
20. Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3β Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies - ResearchGate, accessed October 17, 2025, https://www.researchgate.net/publication/375771767_Phase_1_study_of_Elraglusib_9-ING-41_a_glycogen_synthase_kinase-3b_inhibitor_as_monotherapy_or_combined_with_chemotherapy_in_patients_with_advanced_malignancies
21. Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3b Inhibitor, as Monotherapy or Combined with Chemotherapy in - Actuate Therapeutics, accessed October 17, 2025, https://actuatetherapeutics.com/wp-content/uploads/2024/09/Carneiro-Publication-Multiple-types-of-cancer-2024.pdf
22. Elraglusib (9-ING-41), a selective small-molecule inhibitor of ..., accessed October 17, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9472445/
23. Targeting GSK-3β to Treat Cancer - Actuate Therapeutics, accessed October 17, 2025, https://actuatetherapeutics.com/our-science/
24. Elraglusib (formerly 9-ING-41) possesses potent anti-lymphoma ..., accessed October 17, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10265916/
25. 9-ING-41 (Elraglusib) | GSK-3β Inhibitor - MedchemExpress.com, accessed October 17, 2025, https://www.medchemexpress.com/9-ing-41.html
26. Phase II study of elraglusib (9-ING-41), a GSK-3β inhibitor, in combination with gemcitabine plus nab-paclitaxel in previously untreated metastatic pancreatic cancer - PMC, accessed October 17, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC12148735/
27. ascopubs.org, accessed October 17, 2025, https://ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.e22015#:~:text=The%20GSK%2D3%CE%B2%20inhibitor%20Elraglusib,in%20combination%20with%20cytotoxic%20chemotherapy.
28. From a natural product lead to the identification of potent and ..., accessed October 17, 2025, https://pubmed.ncbi.nlm.nih.gov/19338355/
29. From a Natural Product Lead to the Identification of Potent and Selective Benzofuran3-yl-(indol-3-yl)maleimides as Glycogen Synthase Kinase 3β Inhibitors That Suppress Proliferation and Survival of Pancreatic Cancer Cells - ResearchGate, accessed October 17, 2025, https://www.researchgate.net/publication/244451013_From_a_Natural_Product_Lead_to_the_Identification_of_Potent_and_Selective_Benzofuran3-yl-indol-3-ylmaleimides_as_Glycogen_Synthase_Kinase_3b_Inhibitors_That_Suppress_Proliferation_and_Survival_of_Panc
30. Actuate Therapeutics Provides FDA with Updated Clinical Data Package to Support Planned Regulatory Interactions with FDA and EMA Over the Coming Months, accessed October 17, 2025, https://actuatetherapeutics.com/press_releases/actuate-therapeutics-provides-fda-with-updated-clinical-data-package-to-support-planned-regulatory-interactions-with-fda-and-ema-over-the-coming-months/
31. Elraglusib Induces Cytotoxicity via Direct Microtubule Destabilization Independently of GSK3 Inhibition - AACR Journals, accessed October 17, 2025, http://aacrjournals.org/cancerrescommun/article-pdf/4/11/3013/3522063/crc-24-0408.pdf
32. Elraglusib (formerly 9-ING-41) possesses potent anti-lymphoma properties which cannot be attributed to GSK3 inhibition - PubMed, accessed October 17, 2025, https://pubmed.ncbi.nlm.nih.gov/37316860/
33. (PDF) Elraglusib Induces Cytotoxicity via Direct Microtubule Destabilization Independently of GSK3 Inhibition - ResearchGate, accessed October 17, 2025, https://www.researchgate.net/publication/385355303_Elraglusib_induces_cytotoxicity_via_direct_microtubule_destabilization_independently_of_GSK3_inhibition
34. Elraglusib (9-ING-41), a selective small-molecule inhibitor of glycogen synthase kinase-3 beta, reduces expression of immune checkpoint molecules PD-1, TIGIT and LAG-3 and enhances CD8+ T cell cytolytic killing of melanoma cells - Actuate Therapeutics, accessed October 17, 2025, https://actuatetherapeutics.com/publications/elraglusib-9-ing-41-a-selective-small-molecule-inhibitor-of-glycogen-synthase-kinase-3-beta-reduces-expression-of-immune-checkpoint-molecules-pd-1-tigit-and-lag-3-and-enhances-cd8-t-cell-cy/
35. GSK-3 inhibitor elraglusib enhances tumor-infiltrating immune cell activation in tumor biopsies and synergizes with anti-PD-L1 in a murine model of colorectal cancer - PMC, accessed October 17, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9934544/
36. GSK-3 Inhibitor Elraglusib Enhances Tumor-Infiltrating Immune Cell Activation in Tumor Biopsies and Synergizes with Anti-PD-L1 in a Murine Model of Colorectal Cancer - MDPI, accessed October 17, 2025, https://www.mdpi.com/1422-0067/24/13/10870
37. Elraglusib | GSK-3 inhibitor | Mechanism | Concentration - Selleck Chemicals, accessed October 17, 2025, https://www.selleckchem.com/products/9-ing-41.html
38. Elraglusib (9-ING-41) | CAS 1034895-42-5 | AbMole BioScience, accessed October 17, 2025, https://www.abmole.com/products/9-ing-41.html
39. Study Details | NCT03678883 | 9-ING-41 in Patients with Advanced Cancers - Clinical Trials, accessed October 17, 2025, https://clinicaltrials.gov/study/NCT03678883
40. Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3b Inhibitor, as Monotherapy or Combined with Chemotherapy in - AACR Journals, accessed October 17, 2025, https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-23-1916/3391824/ccr-23-1916.pdf
41. Elraglusib Combo Demonstrates OS Benefit in Metastatic Pancreatic Cancer, accessed October 17, 2025, https://www.cancernetwork.com/view/elraglusib-combo-demonstrates-os-benefit-in-metastatic-pancreatic-cancer
42. Phase 2 study of elraglusib (9-ING-41), a glycogen synthase kinase-3b inhibitor, in combination with gemcitabine plus nab-paclitaxel (GnP) in patients with previously untreated advanced pancreatic ductal adenocarcinoma (PDAC). - ASCO, accessed October 17, 2025, https://www.asco.org/abstracts-presentations/ABSTRACT418974
43. Phase 2 study of elraglusib (9-ING-41), a glycogen synthase kinase ..., accessed October 17, 2025, https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e16289
44. Elraglusib Completed Phase 2 Trials for Myelofibrosis Treatment | DrugBank Online, accessed October 17, 2025, https://go.drugbank.com/drugs/DB16047/clinical_trials?conditions=DBCOND0007071&phase=2&purpose=treatment&status=completed
45. Study Details | NCT04218071 | Actuate 1901: 9-ING-41 in ..., accessed October 17, 2025, https://clinicaltrials.gov/study/NCT04218071
46. Elraglusib | MedPath, accessed October 17, 2025, https://trial.medpath.com/drug/548641a0f353f8be/elraglusib?page=1&tab=news
47. Elraglusib Withdrawn Phase 2 Trials for Adenoid Cystic Carcinoma / Malignant Neoplasm of Salivary Gland / Salivary Gland Neoplasms / Salivary Gland Carcinomas Treatment - DrugBank, accessed October 17, 2025, https://go.drugbank.com/drugs/DB16047/clinical_trials?conditions=DBCOND0039494%2CDBCOND0141910%2CDBCOND0138298%2CDBCOND0038356&phase=2&purpose=treatment&status=withdrawn
48. ELRAGLUSIB - New Drug Approvals, accessed October 17, 2025, https://newdrugapprovals.org/2022/09/30/elraglusib/
49. Elraglusib Receives FDA Orphan Drug Designation in Pancreatic Cancer | CancerNetwork, accessed October 17, 2025, https://www.cancernetwork.com/view/elraglusib-receives-fda-orphan-drug-designation-in-pancreatic-cancer
50. ACTUATE THERAPEUTICS RECEIVES FDA ORPHAN DRUG DESIGNATION FOR ELRAGLUSIB FOR TREATMENT OF PANCREATIC CANCER, accessed October 17, 2025, https://actuatetherapeutics.com/press_releases/actuate-therapeutics-receives-fda-orphan-drug-designation-for-elraglusib-for-treatment-of-pancreatic-cancer/
51. FDA Grants Elraglusib Orphan Drug Designation in Soft Tissue Sarcoma | Targeted Oncology - Immunotherapy, Biomarkers, and Cancer Pathways, accessed October 17, 2025, https://www.targetedonc.com/view/fda-grants-elraglusib-orphan-drug-designation-in-soft-tissue-sarcoma
52. WO2024159185A1 - Gsk-3 inhibitor elraglusib (9-ing-41) modifies protein expression in the tumor microenvironment to enhance tumor-infiltrating immune cell activation in clinical tumor biopsies - Google Patents, accessed October 17, 2025, https://patents.google.com/patent/WO2024159185A1/en
53. Actuate Therapeutics - Corporate Overview, accessed October 17, 2025, https://actuatetherapeutics.com/wp-content/uploads/2024/08/Actuate_Therapeutics-Corporate_Deck-0824.pdf
54. Actuate Therapeutics Reports Positive Progress on Elraglusib as Backbone Therapy for Pancreatic Cancer Amid Ongoing Clinical Trials and Financing Milestone - Quiver Quantitative, accessed October 17, 2025, https://www.quiverquant.com/news/Actuate+Therapeutics+Reports+Positive+Progress+on+Elraglusib+as+Backbone+Therapy+for+Pancreatic+Cancer+Amid+Ongoing+Clinical+Trials+and+Financing+Milestone
55. Actuate Therapeutics Reports Positive Biomarker and Machine Learning Data from Phase 2 Elraglusib Trial in First-Line Treatment of Metastatic Pancreatic Cancer at ASCO - BioSpace, accessed October 17, 2025, https://www.biospace.com/press-releases/actuate-therapeutics-reports-positive-biomarker-and-machine-learning-data-from-phase-2-elraglusib-trial-in-first-line-treatment-of-metastatic-pancreatic-cancer-at-asco
56. Actuate Announces Scientific Reports Publication on Elraglusib's Novel Immunomodulatory Mechanism of Action as a GSK-3β Inhibitor - FirstWord Pharma, accessed October 17, 2025, https://firstwordpharma.com/story/5898398