abequolixron (RGX-104) / Inspirna - LARVOL DELTA

Abequolixron (RGX-104) and Durvalumab in Lung Cancer (clinicaltrials.gov) - P1 | N=1 | Active, not recruiting | Sponsor: UNC Lineberger Comprehensive Cancer Center | Recruiting ➔ Active, not recruiting | N=24 ➔ 1 | Trial completion date: Dec 2026 ➔ Feb 2029 | Trial primary completion date: Dec 2025 ➔ Sep 2024

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of RGX-104 in Patients With Advanced Lung & Endometrial Cancer (clinicaltrials.gov) - P1 | N=146 | Completed | Sponsor: Inspirna, Inc. | Active, not recruiting ➔ Completed

Trial completion • Endometrial Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • ALK • APOE • CTLA4 • EGFR

Abequolixron (RGX-104) and Durvalumab in Lung Cancer (clinicaltrials.gov) - P1 | N=1 | Terminated | Sponsor: UNC Lineberger Comprehensive Cancer Center | Trial completion date: Feb 2029 ➔ Feb 2025 | Active, not recruiting ➔ Terminated; Sponsor is closing the trial.

Trial completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Abequolixron (RGX-104), a first-in-class oral immunotherapy targeting the liver-X receptor (LXR), in combination with docetaxel in recurrent advanced/metastatic non-small cell lung cancer (NSCLC) (SITC 2024) - P1 | "Conclusions The combination of abequolixron and docetaxel was well tolerated and resulted in promising preliminary efficacy in second/third-line NSCLC. A Phase 2 randomized trial in subjects with recurrent advanced/metastatic NSCLC with disease progression after CPI and platinum-based therapy is planned."

Combination therapy • IO biomarker • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • APOE • CD8

A Study of RGX-104 in Patients With Advanced Lung & Endometrial Cancer (clinicaltrials.gov) - P1 | N=146 | Active, not recruiting | Sponsor: Inspirna, Inc. | Trial completion date: Sep 2024 ➔ Dec 2024 | Trial primary completion date: Sep 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date • Endometrial Cancer • Gastrointestinal Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • ALK • APOE • CTLA4 • EGFR

Abequolixron (RGX-104) and Durvalumab in Lung Cancer (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: UNC Lineberger Comprehensive Cancer Center | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Combination therapy • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of RGX-104 in Patients With Advanced Lung & Endometrial Cancer (clinicaltrials.gov) - P1 | N=146 | Active, not recruiting | Sponsor: Inspirna, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: May 2024 ➔ Sep 2024 | Trial primary completion date: Dec 2023 ➔ Sep 2024

Combination therapy • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Endometrial Cancer • Gastrointestinal Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • ALK • APOE • CTLA4 • EGFR

Abequolixron (RGX-104) and Durvalumab in Lung Cancer (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: UNC Lineberger Comprehensive Cancer Center | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Pilot Study of Abequolixron (RGX-104) and Durvalumab in Lung Cancer (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: UNC Lineberger Comprehensive Cancer Center | Initiation date: Nov 2023 ➔ Mar 2024

Combination therapy • Trial initiation date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Reversing cancer immunoediting phases with a tumor-activated and optically reinforced immunoscaffold. (PubMed, Bioact Mater) - "Upon response to tumoral reactive oxygen species, TURN will first release RGX-104 to attenuate excessive immunosuppressive cells and cytokines, and thus immunosuppression falls and immunogenicity rises...TURN achieves over 90 % tumor growth inhibition in both primary and secondary tumor lesions, induces potent systemic immune responses, and triggers superior long-term immune memory in vivo. Taken together, TURN provides a prospective sight for ISV from the perspective of immunoediting phases."

Journal • Oncology

A Study of RGX-104 in Patients With Advanced Lung & Endometrial Cancer (clinicaltrials.gov) - P1 | N=150 | Recruiting | Sponsor: Inspirna, Inc.

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Endometrial Cancer • Gastrointestinal Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • ALK • APOE • CTLA4 • EGFR

Pilot Study of Abequolixron (RGX-104) and Durvalumab in Lung Cancer (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: UNC Lineberger Comprehensive Cancer Center

Combination therapy • New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Abequolixron Plus Docetaxel Shows Promising Efficacy in NSCLC and SCLC (Targeted Oncology) - P1/2 | N=17 | NCT02922764 | Sponsor: Inspirna, Inc. | "'The data thus far demonstrate that abequolixron is well tolerated in combination with full-dose docetaxel, while showing encouraging clinical activity suggesting that this drug candidate could be a valuable addition to a current standard-of-care chemotherapy in heavily-pretreated patients with lung cancer,' Hossein Borghaei, DO, MS...principal investigator on the study, said in a statement."

Media quote • P2 data

Abequolixron Plus Docetaxel Elicits Responses in Relapsed/Refractory Lung Cancer (OncLive) - P1b/2 | N=NA | NCT02922764 | Sponsor: Inspirna, Inc. | "'The data thus far demonstrate that abequolixron is well tolerated in combination with full-dose docetaxel, while showing encouraging clinical activity suggesting that this drug candidate could be a valuable addition to a current standard of care chemotherapy in heavily-pretreated patients with lung cancer,' Hossein Borghaei...study, stated in a press release. 'I am very encouraged by the ORR, DCR, and time to progression so far seen in the study, and I look forward to further evaluation of this unique compound as the clinical trial progresses.'"

Media quote • P1/2 data

Inspirna Announces Interim Data from Phase 1b/2 Study of Abequolixron (RGX-104) in Relapsed or Refractory Lung Cancer (Businesswire) - P1b/2 | N=150 | NCT02922764 | Sponsor: Inspirna, Inc. | "Inspirna, Inc...announced today interim data from its ongoing Phase 1b/2 clinical trial of abequolixron in patients with non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC)....The ORR across all evaluable patients was 38% (n=13), with a disease control rate (DCR) of 77%, including five patients who achieved partial response (PR); In the 2/3L NSCLC cohort, of five evaluable patients, four patients achieved PRs with two patients achieving confirmed partial responses....In the 2L SCLC cohort, of eight evaluable patients, one patient achieved a PR and five patients had a best overall response (BoR) of stable disease (SD). Four patients (50%) were on study drug progression free for > 24 weeks....The expansion stage of the study is ongoing and continues to enroll patients with 2/3L NSCLC."

P1/2 data • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer

Immunomodulatory-Photodynamic Nano-Stimulators for Invoking Pyroptosis to Augment Tumor Immunotherapy. (PubMed, Adv Healthc Mater) - "Herein, acidic tumor micro-environment (TME) evoked MRC nanoparticles (MRC NPs) co-delivering immune agonist RGX-104 and photosensitizer chlorine e6 (Ce6) is reported for pyroptosis-mediated precise immunotherapy...MRC-elicited pyroptosis in combination with anti-PD-1 blockade therapy boosts immune response in solid tumors, successfully arresting invasive metastasis and extending survival based on its remarkable antitumor immunity. MRC may initiate a new window for immuno-photo pyroptosis stimulators augmenting pyroptosis-based immunotherapy."

Journal • Immune Modulation • Inflammation • Oncology • Solid Tumor • APOE • GSDME

A Study of RGX-104 in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - P1 | N=150 | Recruiting | Sponsor: Inspirna, Inc. | Trial completion date: Mar 2022 ➔ May 2024 | Trial primary completion date: Dec 2021 ➔ Dec 2023

Combination therapy • Trial completion date • Trial primary completion date • Endometrial Cancer • Gastrointestinal Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • ALK • APOE • CTLA4 • EGFR

[VIRTUAL] Correlative analysis of pharmacokinetics and pharmacodynamics of RGX-104, a first-in-class Liver-X-Receptor (LXR) agonist, and clinical outcomes in patients with advanced solid tumors (AACR-II 2020) - "The study entailed multiple escalation arms with RGX-104 as monotherapy and in combination with nivolumab, ipilimumab, or docetaxel. Low baseline levels of tumoral ApoE were associated with greater clinical benefit, with almost all patients with stable disease or partial response exhibiting ApoE tumor positive score of ≤20%; these patients also exhibited low/negative PD-L1 (<1%) staining, revealing a target specific tumor biomarker and PD-L1 subset that could support prospective patient selection. These and additional markers will be tracked in expansion cohorts of RGX-104 in combination with pembrolizumab and carboplatin/pemetrexed for 1st line treatment of patients with metastatic non-small cell lung cancer (PD-L1 <1%) and in combination with docetaxel for 2nd line treatment of patients with small cell lung cancer."

Clinical • Clinical data • IO biomarker • Late-breaking abstract • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer • APOE • CD8 • PD-L1

Inspirna Announces Clinical Collaboration with Bristol Myers Squibb to Study RGX-104 in Combination with Yervoy (ipilimumab) for Treatment of Metastatic Endometrial Cancer (Businesswire) - "Inspirna, Inc...announced a collaboration with Bristol Myers Squibb on a clinical trial of a combination therapy using RGX-104 (abequolixron), the Company’s small molecule agonist of the Liver X Receptor/Apolipoprotein E ('LXR/APOE') pathway, and Yervoy® (ipilimumab), Bristol Myers Squibb’s Cytotoxic T-Lymphocyte Associated protein 4 (CTLA-4) inhibitor. Under the terms of the agreement, Bristol Myers Squibb will provide ipilimumab for a Phase 1b/2 expansion study investigating the combination therapy for the 2nd and 3rd line treatment of patients with metastatic endometrial cancer whose genomes possess the E2 or E4 APOE genetic biomarker, including those patients who have progressed on prior checkpoint inhibitor therapy. Inspirna will sponsor the study and be responsible for study costs."

Licensing / partnership • Endometrial Cancer • Gynecologic Cancers • Oncology

Pharmacodynamic and clinical activity of RGX-104, a first-in-class immunotherapy targeting the liver-X nuclear hormone receptor (LXR), in patients with refractory malignancies. (ASCO 2018) - P1; "Proof of principle has been demonstrated for immunologic and anti-tumor activity of the first-in-class LXR-agonist RGX-104 in advanced cancer patients. RGX-104 was well tolerated at doses up to 160mg BID and demonstrated robust PD effects on ApoE expression and relevant immune cell populations. Dose escalation with a PD-1 inhibitor has begun with plans to study RGX-104 both as monotherapy and in combination with a PD-1 inhibitor in select malignancies."

Clinical • IO biomarker • PD(L)-1 Biomarker • PK/PD data • Hepatocellular Cancer • Neuroendocrine Tumor

[VIRTUAL] RGX-104, a first-in-class immunotherapy targeting the liver-X receptor (LXR): Initial results from the phase 1b RGX-104 plus docetaxel combination dose escalation cohorts (AACR-I 2020) - "The safety profile and marked pharmacodynamic and clinical activity of the RGX-104/docetaxel combination in CPI-refractory patients supports further development of this regimen. Consequently, the RGX-104/docetaxel regimen will be evaluated in a Phase 1b/2 expansion cohort in patients with relapsed/refractory ES-SCLC/high grade-neuroendocrine tumors."

IO Biomarker • P1 data • Head and Neck Cancer • Lung Cancer • Melanoma • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • APOE • CD8 • IFNG • LAG3

A Study of RGX-104 in Patients With Advanced Solid Malignancies and Lymphoma (clinicaltrials.gov) - P1; N=135; Recruiting; Sponsor: Rgenix, Inc.; Trial primary completion date: Mar 2020 ➔ Dec 2020

Clinical • Combination therapy • Trial primary completion date • Gastrointestinal Cancer • Hematological Malignancies • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CTLA4 • EGFR • PD-L1

A Study of RGX-104 in Patients With Advanced Solid Malignancies and Lymphoma (clinicaltrials.gov) - P1; N=135; Recruiting; Sponsor: Rgenix, Inc.; Trial completion date: Oct 2019 ➔ Mar 2021; Trial primary completion date: Jun 2019 ➔ Mar 2020

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hematological Malignancies • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Oncology • ALK • CTLA4 • EGFR • PD-L1

A Study of RGX-104 in Patients With Advanced Solid Malignancies and Lymphoma (clinicaltrials.gov) - P1; N=130; Recruiting; Sponsor: Rgenix, Inc.; N=80 ➔ 130; Trial primary completion date: Oct 2017 ➔ Jun 2018

Clinical • Combination therapy • Enrollment change • IO biomarker • Trial primary completion date • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Non Small Cell Lung Cancer • ALK • CTLA4 • EGFR • PD-L1

A Study of RGX-104 in Patients With Advanced Solid Malignancies and Lymphoma (clinicaltrials.gov) - P1; N=80; Not yet recruiting; Sponsor: Rgenix, Inc.

Clinical • Combination therapy • IO biomarker • New P1 trial • Gastrointestinal Cancer • Hematological Malignancies • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Oncology • ALK • CTLA4 • EGFR • PD-L1