afuresertib (LAE002) / Laekna Therap - LARVOL DELTA

Expected upcoming milestones in second half of 2025 (Laekna Press Release) - "To complete subject enrollment of AFFIRM-205 Phase III China trial."

Enrollment status • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

AKT inhibitors in gynecologic oncology: past, present and future. (PubMed, Front Oncol) - "Currently, multiple classes of AKT inhibitors-PH domain competitors (perifosine), allosteric inhibitors (MK-2206), and ATP-competitive agents (AZD5363, GSK2110183, GSK2141795, and GDC-0068) are under development, with several agents in phase II/III trials. This study systematically reviews recent AKTi research in gynecological cancers, aiming to provide a theoretical foundation for identifying potential biomarkers, overcoming drug resistance, and developing prognostic models. These insights may further facilitate the clinical translation of key therapeutic agents."

Journal • Review • Gynecologic Cancers • Oncology

Analysis of immune cell infiltration in the tumor microenvironment of cervical cancer and its impact on immunotherapy. (PubMed, Front Oncol) - "Drug sensitivity analysis indicated increased responsiveness of high-risk patients to agents such as Afuresertib and Venetoclax. The findings contribute to a more comprehensive understanding of the disease and provide a foundation for future clinical applications. Nevertheless, further large-scale validation is required to confirm these findings and enhance their clinical utility."

Biomarker • IO biomarker • Journal • Tumor mutational burden • Cervical Cancer • Oncology • Solid Tumor • BIRC5 • CD34 • CXCL12 • PCNA • TMB

Integrative multi-omic analysis of NLRP3 inflammasome dysregulation and subtyping for personalized treatment in acute myeloid leukemia. (PubMed, Discov Oncol) - "We revealed a positive correlation between the Nscore and macrophage M1, suggesting potential drug response mechanisms. Based on the identified AML subtypes and their distinct mutational landscapes, we predicted potential treatment options, with Paclitaxel, Afuresertib, and Mitoxantrone emerging as potential therapeutic agents for the AML subtypes."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CASP1 • COL2A1 • ITGB2 • NFKB2 • NLRP3 • PYCARD

CD52 PROMOTER METHYLATION PREDICTS RESPONSE TO AKT-TARGETING DRUGS IN ACUTE MYELOID LEUKEMIA (EHA 2025) - "Sensitivity to Akt inhibitors (Uprosertib/Afuresertib) was tested in ten wild-type (WT) cell lines and SET-2 shRNA model via MTT. CD52, an indicator of poor prognosis in AML, is associated with Akt expression in cell lines and patients. This seems to contribute to an aggressive phenotype characterized by enhanced cell proliferation and viability, resulting in a reduced survival rate in AML patients. This finding underlines the potential of targeting Akt in AML depending on the CD52 methylation profile, based on the favorable results obtained in vitro."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • CD52

Predictive Oncology Reports First Quarter 2025 Financial Results and Provides Corporate Update (GlobeNewswire) - "Announced that, using publicly available datasets on drugs that have either been abandoned or discontinued by large pharmaceutical companies, Predictive has developed a registry of promising candidates that can potentially be repurposed for additional or alternative indications. Predictive’s initial screening approach on a small, curated cohort of abandoned drugs identified three compounds that warrant further exploration in new colon and breast tumor indications. Specifically, Afuresertib (breast), Alisertib (colon) and Entinosta (colon) demonstrated the highest proportion of hits within those two tumor types." "

Clinical • Breast Cancer • Colon Cancer • Colorectal Cancer

Prognostic and immunological role of RHEBL1 in pan-cancer: a target for survival and immunotherapy. (PubMed, Discov Oncol) - "Pan-cancer samples suggested that high RHEBL1 expression facilitates TAM infiltration and is correlated with tumour immunosuppressive status (TCGA). High expression of RHEBL1 may benefit from the therapy of 5-FU, ABT737, Afuresertib, AGI-5198, AGI-6780, and Alisertib."

IO biomarker • Journal • Pan tumor • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor • CD8 • RHEB

CanSeer: a translational methodology for developing personalized cancer models and therapeutics. (PubMed, Sci Rep) - "To exemplify, three use cases involving paired samples, unpaired samples, and cancer samples only, of lung squamous cell carcinoma (LUSC) patients are provided. CanSeer reveals the effectiveness of repositioned drugs along with the identification of several novel LUSC treatment combinations including Afuresertib + Palbociclib, Dinaciclib + Trametinib, Afatinib + Oxaliplatin, Ulixertinib + Olaparib, etc."

Journal • Preclinical • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma

An open-label randomized active-controlled phase II clinical study to assess the efficacy and safety of afuresertib plus paclitaxel versus paclitaxel in patients with platinum-resistant ovarian cancer (PROFECTA-II/GOG-3044). (PubMed, Gynecol Oncol) - P2 | "The addition of afuresertib to paclitaxel did not significantly improve PFS/OS in patients with PROC. However, exploratory biomarker findings suggest potential efficacy in phospho-AKT positive patients, warranting further investigation. The safety/tolerability profile of A + P was consistent with prior AKT-inhibitor studies."

Clinical • Journal • P2 data • Platinum resistant • Gastrointestinal Disorder • Oncology • Ovarian Cancer • Solid Tumor • BRCA1 • BRCA2 • PI3K • PROC • PTEN

Anillin interacts with RhoA to promote tumor progression in anaplastic thyroid cancer by activating the PI3K/AKT pathway. (PubMed, Endocrine) - "ANLN plays a crucial role in ATC progression by activating the RhoA/PI3K/AKT pathway, suggesting its potential as a therapeutic target in ATC."

Journal • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • ANLN • RHOA

Afuresertib Plus Paclitaxel Does Not Elicit Substantial Clinical Benefit in Platinum-Resistant Ovarian Cancer (OncLive) - P2 | N=150 | PROFECTA-II (NCT04374630) | Sponsor: Laekna Limited | "The addition of afuresertib to paclitaxel did not generate a significant survival advantage compared with paclitaxel monotherapy in patients with platinum-resistant ovarian cancer, although the combination was associated with a manageable toxicity profile, according to dara from the phase 2 PROFECTA-II/GOG-3044 trial (NCT04374630) presented at the 2025 SGO Annual Meeting on Women’s Cancer. At a data cutoff of October 31, 2023, the combination of afuresertib—an ATP-competitive pan-AKT inhibitor—plus paclitaxel elicited a median progression-free survival (PFS) of 4.3 months (95% CI, 3.58-5.62) vs 4.1 months (95% CI, 2.63-5.36) with paclitaxel alone in the intention-to-treat (ITT) population (HR, 0.7; 95% CI, 0.5-1.1; P = .139)."

P2 data • Ovarian Cancer

An Open-Label Randomized Active-Controlled Phase II Clinical Study to Assess the Efficacy and Safety of Afuresertib Plus Paclitaxel Versus Paclitaxel in Patients with Platinum-Resistant Ovarian Cancer (GOG 3044) (SGO 2025) - No abstract available

Clinical • P2 data • Oncology • Ovarian Cancer • Solid Tumor

C6TSEDRVAJZ, a combination of small-molecule compounds, induces differentiation of human placental fibroblasts into epithelioid cells in vitro (PubMed, Nan Fang Yi Ke Da Xue Xue Bao) - "The small-molecule compound combination C6TSEDRVAJZ is capable of inducing HPFs into ciEP-Ls under hypoxic conditions with a high induction efficiency."

Journal • Preclinical • CD34 • CDH1 • COL1A1 • GLI3 • KRT18 • KRT18 • KRT19 • PAX8 • S100A4 • SMAD3 • VIM • WT1

Combinatorial screen of targeted agents with the PI3K inhibitors inavolisib, alpelisib, duvelisib, and copanlisib in multi-cell type tumor spheroids. (PubMed, SLAS Discov) - "Additive and/or synergistic effects were observed with alpelisib or inavolisib or copanlisib in combination with a RAS/MEK/ERK pathway inhibitor, either selumetinib (MEK), ravoxertinib (ERK 1/2), or tovorafenib (DAY101, RAF). Combinations of each of these three PI3K inhibitors with the KRAS mutation specific inhibitors MTRX1133 (KRAS G12D) or sotorasib (KRAS G12C) had selective activity in cell lines harboring the corresponding target. Lastly, combination effects were observed from vertical inhibition of the PI3K/AKT/mTOR pathway with a PI3K inhibitor in combination with either the mTORC1/2 inhibitor sapanisertib or an AKT inhibitor, ipatasertib or afuresertib."

Journal • Oncology • KRAS

AMP-dependent protein kinase alpha 1 predicts cancer prognosis and immunotherapy response: from pan-cancer analysis to experimental validation. (PubMed, Am J Cancer Res) - "Treatment of cells with the AKT inhibitors MK2206 and GSK2110183 revealed that the PRKAA1 overexpression group was less sensitive to AKT inhibitors than the negative control group. Taken together, PRKAA1 can be used as a potential prognostic marker and new target for tumor immunotherapy."

IO biomarker • Journal • Pan tumor • Brain Cancer • CNS Tumor • Glioma • Hepatocellular Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • AMPK

A PHASE I/II DOSE-ESCALATION AND EFFICACY/SAFETY STUDY OF AFURESERTIB PLUS SINTILIMAB PLUS NAB-PACLITAXEL IN SOLID TUMORS PRIMARILY CERVICAL CANCER AND ENDOMETRIAL CANCER (IGCS 2024) - "Of 16 CC/EC subjects, the median prior line of systematic anti-tumor therapy was 1 (0-3), including chemotherapy, bevacizumab or ICIs. Up to Apr 10, 2024, 18 subjects were dosed. The most common≥ grade 3 AEs were white blood cell count decreased (27.8%), rash/ rash maculo-papular (27.8%) and anemia (22.2%). Most of the AEs are manageable and reversible."

Clinical • P1/2 data • Cervical Cancer • Endometrial Cancer • Oncology • Solid Tumor

Afuresertib +Sintilimab+Chemotherapy in Patients with Selected Solid Tumors That Resistance to Prior Anti-PD-1/PD-L1 (clinicaltrials.gov) - P1/2 | N=22 | Active, not recruiting | Sponsor: Laekna Limited | Recruiting ➔ Active, not recruiting | N=167 ➔ 22

Enrollment change • Enrollment closed • Cervical Cancer • Endometrial Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • HER-2 • KRAS • PI3K • PTEN

A phase Ib study to evaluate the efficacy and safety of afuresertib plus fulvestrant in subjects with locally advanced or metastatic HR+/HER2- breast cancer who failed standard of care therapies: A subgroup analysis of efficacy in PIK3CA/AKT1/PTEN-altered subjects (ESMO 2024) - P3 | "Afuresertib plus fulvestrant combination demonstrated a promising antitumor activity, especially in the population with PIK3CA/AKT1/PTEN pathway alteration. The safety profile of Afuresertib plus fulvestrant was well-tolerated. This regimen warrants further investigation in phase III study."

Clinical • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • ER • HER-2 • PIK3CA • PTEN

Dose-Escalation and Efficacy Study of LAE001/Prednisone Plus Afuresertib Patients With m-CRPC (clinicaltrials.gov) - P1/2 | N=49 | Completed | Sponsor: Laekna Limited | Active, not recruiting ➔ Completed | N=74 ➔ 49 | Trial completion date: Oct 2024 ➔ Mar 2024

Enrollment change • Metastases • Trial completion • Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA • PIK3CA • PTEN

PROFECTA-II: Study With Afuresertib and Paclitaxel in Platinum Resistant Ovarian (clinicaltrials.gov) - P2 | N=150 | Completed | Sponsor: Laekna Limited | Active, not recruiting ➔ Completed

Trial completion • Oncology • Ovarian Cancer • Solid Tumor • BRCA1 • BRCA2 • MUC16

Study Evaluating Efficacy & Safety of Afuresertib Plus Fulvestrant in Patients w/ Locally Advanced or Metastatic HR+/HER2- Breast Cancer (clinicaltrials.gov) - P3 | N=256 | Recruiting | Sponsor: Laekna Limited | Active, not recruiting ➔ Recruiting | Phase classification: P1 ➔ P3 | N=20 ➔ 256 | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Apr 2023 ➔ Oct 2026

Enrollment change • Enrollment open • Metastases • Phase classification • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • AKT1 • HER-2 • PIK3CA • PTEN

Laekna Announces FDA Approval for the Phase III Clinical Trial Protocol of LAE002 (Afuresertib) PLUS LAE001 for the Treatment of Prostate Cancer (PRNewswire) - "Laekna, Inc...announced that the company has received approval from the U.S. Food and Drugs Administration for the protocol of the phase III clinical trial of LAE002 (afuresertib, an AKT inhibitor) plus LAE001 (CYP17A1/CYP11B2 dual inhibitor) ('LAE201') in patients with metastatic castration-resistant prostate cancer (mCRPC) following standard of care (SOC) treatment."

New P3 trial • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Prostate Cancer

Phase I/II clinical trials of LAE005, afuresertib plus nab-paclitaxel in patients with advanced solid tumors, primarily in patients with triple-negative breast cancer (TNBC) (AACR 2024) - P1 | "The triplet regimen shows a manageable safety profile and encouraging preliminary activity in the drug resistant TNBC patients. This triplet regimen warrants further investigation."

Clinical • Metastases • P1/2 data • Breast Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

PROFECTA-II: Study With Afuresertib and Paclitaxel in Platinum Resistant Ovarian (clinicaltrials.gov) - P2 | N=141 | Active, not recruiting | Sponsor: Laekna Limited | Trial completion date: Nov 2024 ➔ Jun 2024

Trial completion date • Oncology • Ovarian Cancer • Solid Tumor • BRCA1 • BRCA2 • MUC16

Bulk and single-cell sequencing identified a prognostic model based on the macrophage and lipid metabolism related signatures for osteosarcoma patients. (PubMed, Heliyon) - "Finally, our meticulous drug sensitivity analysis identified a spectrum of potential therapeutic agents for OS, including AZD2014, Sapitinib, Buparlisib, Afuresertib, MIRA-1, and BIBR-1532. These findings significantly augment the therapeutic arsenal available to clinicians managing OS, presenting a promising avenue for elevating treatment outcomes."

Journal • Metabolic Disorders • Oncology • Osteosarcoma • Sarcoma • Solid Tumor