polyinosinic:polycytidylic acid (BO-112) / Highlight Therap - LARVOL DELTA

Efficacy of intratumoral BO-112 with systemic pembrolizumab in patients with advanced melanoma refractory to anti-PD-1-based therapy: Final results of SPOTLIGHT203 phase 2 study (AACR 2022) - P1, P2 | "The primary efficacy endpoint has been met. Additionally, disease control (PR+CR+SD) is meaningful and durable in a population with no current standard treatment options. Very high LDH levels (LDH >3xULN) and acral mel could predict poor outcome."

Clinical • IO biomarker • P2 data • Melanoma • Oncology • Solid Tumor • BRAF • CD8

Neoadjuvant BO-112 and hypofractionated radiation therapy with or without nivolumab in soft tissue sarcoma: preclinical and phase 1 results. (PubMed, Cancer Discov) - "BO-112 and RT reprogrammed tumor-associated myeloid cells toward antigen-presenting states, promoted clonal replacement by less exhausted T cells, and enhanced malignant cell depletion compared to standard RT. These immunologic changes coincided with encouraging disease control in a small, high-risk cohort, supporting further clinical development."

Journal • P1 data • Preclinical • Cardiovascular • CNS Disorders • Immunology • Myasthenia Gravis • Myositis • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

BO-112 Plus Pembrolizumab for Patients With Anti-PD-1-Resistant Advanced Melanoma: Phase II Clinical Trial SPOTLIGHT-203. (PubMed, J Clin Oncol) - P2 | "The clinical trial has met its primary end point (ORR) making BO-112 with pembrolizumab a potential strategy to revert anti-PD-1 resistance in patients with MEL. PFS results are in line with other clinical trials in anti-PD-1-resistant scenario, with promising OS data."

Journal • P2 data • Melanoma • Oncology • Solid Tumor

Safety and tolerability of BO-112, a novel intralesional immuno-therapy, in patients with basal cell carcinoma (EADV 2026) - No abstract available

Clinical • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Intralesional BO-112 for high-risk basal cell carcinoma in cosmetically and functionally sensitive areas: first results from the phase 2b SPOTLIGHT-204 trial (EADV 2026) - No abstract available

P2b data • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

SPOTLIGHT 204: Clinical Trial to Evaluate BO-112 in Patients With Basal Cell Carcinoma (BCC) (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: Highlight Therapeutics | Trial primary completion date: Jun 2026 ➔ Dec 2026

Trial primary completion date • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Potential Abscopal Effect Following Intralesional BO-112 in Basal Cell Carcinoma: A Case Report (EADV 2026) - No abstract available

Case report • Clinical • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Predictors of clinical and pathological response in patients with basal cell carcinoma treated with BO-112, a novel intralesional treatment (EADO 2026) - "Other demographic and clinical covariates (age, gender, Fitzpatrick skin type, prior skin cancer and other medical history, and concomitant medication) did not show any correlation with clinical or pathological response.Conclusions BO-112 shows promising efficacy in BCC lesions, especially in cosmetically sensitive areas of head & neck. Early and substantial visual lesion shrinkage with >80% volume reduction strongly predicted complete pathological clearance, supporting BO-112's further clinical development as a potential non-surgical treatment option for patients with BCC."

Clinical • Basal Cell Carcinoma • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Skin Nodular Basal Cell Carcinoma

NCI-2019-08556: Nivolumab and BO-112 Before Surgery for the Treatment of Resectable Soft Tissue Sarcoma (clinicaltrials.gov) - P1 | N=14 | Active, not recruiting | Sponsor: Jonsson Comprehensive Cancer Center | Trial completion date: Jan 2027 ➔ Jan 2028 | Trial primary completion date: Jan 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Brain Cancer • Fibrosarcoma • Leiomyosarcoma • Liposarcoma • Neurofibrosarcoma • Oncology • Osteosarcoma • Retroperitoneal Sarcoma • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Spindle Cell Sarcoma • Synovial Sarcoma • Undifferentiated Pleomorphic Sarcoma

SPOTLIGHT 204: Clinical Trial to Evaluate BO-112 in Patients With Basal Cell Carcinoma (BCC) (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Highlight Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Nodular Basal Cell Carcinoma

KEYNOTE-B77: BO-112 With Pembrolizumab in Unresectable Malignant Melanoma (clinicaltrials.gov) - P2 | N=42 | Completed | Sponsor: Highlight Therapeutics | Active, not recruiting ➔ Completed

Trial completion • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • BRAF • CD4

Erratum: BO-112 Plus Pembrolizumab for Patients With Anti-PD-1-Resistant Advanced Melanoma: Phase II Clinical Trial SPOTLIGHT-203. (PubMed, J Clin Oncol) - No abstract available

Journal • P2 data • Melanoma • Oncology • Solid Tumor

NCI-2019-08556: Nivolumab and BO-112 Before Surgery for the Treatment of Resectable Soft Tissue Sarcoma (clinicaltrials.gov) - P1 | N=14 | Active, not recruiting | Sponsor: Jonsson Comprehensive Cancer Center | Trial completion date: Jan 2026 ➔ Jan 2027 | Trial primary completion date: Jan 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • Brain Cancer • Fibrosarcoma • Leiomyosarcoma • Liposarcoma • Neurofibrosarcoma • Oncology • Osteosarcoma • Retroperitoneal Sarcoma • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Spindle Cell Sarcoma • Synovial Sarcoma • Undifferentiated Pleomorphic Sarcoma

KEYNOTE-A06: Study of BO-112 With Pembrolizumab for Colorectal or Gastric/GEJ Cancer With Liver Metastasis (clinicaltrials.gov) - P2 | N=18 | Terminated | Sponsor: Highlight Therapeutics | Phase classification: P2a ➔ P2

Combination therapy • Phase classification • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Hepatology • Oncology • Solid Tumor

Targeting myeloid cells with BO-112 engages T cell immunity in combination with radiotherapy and checkpoint blockade in preclinical models and a phase 1 neoadjuvant clinical trial (SITC 2024) - P1 | "In a Phase I neoadjuvant trial, patients with STS received intratumoral BO-112, hypofractionated RT ± nivolumab followed by surgery. Targeting myeloid cells with BO-112 may be a complementary strategy to promoting T cell responses in STS. Ethics Approval Ethics approval was obtained for the Phase I clinical trial (NCT02828098 approved the UCLA Institutional Review Board #19-000419) and animal research (ARC-2017-088 approved by the UCLA Institutional Animal Care and Use Committee/Animal Research Committee (ARC)) Clinical trial participants gave informed consent before enrolling and participating in the trial."

Checkpoint block • Checkpoint inhibition • Combination therapy • IO biomarker • P1 data • Preclinical • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CD8 • IFNG • KRAS

PHASE 1 STUDY OF INTRATUMORAL BO-112 AND NIVOLUMAB IN RESECTABLE SOFT TISSUE SARCOMA UNDERGOING HYPOFRACTIONATED PREOPERATIVE RADIOTHERAPY (CTOS 2024) - No abstract available

P1 data • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

SPOTLIGHT204: Clinical Trial to Evaluate BO-112 in Patients With Basal Cell Carcinoma (BCC) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Highlight Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Nodular Basal Cell Carcinoma

SPOTLIGHT204: Clinical Trial to Evaluate Safety, Tolerability and Preliminary Efficacy of BO-112 in Patients With BCC (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Highlight Therapeutics

New P2 trial • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Nodular Basal Cell Carcinoma

Efficacy of LCMV-based cancer immunotherapies is unleashed by intratumoral injections of polyI:C. (PubMed, J Immunother Cancer) - "Intratumoral injection of poly(I:C) sensitizes MHClow tumors to the antitumor effects of artLCMV-E7E6, resulting in a potent therapeutic synergy."

IO biomarker • Journal • CNS Disorders • Infectious Disease • Oncology • BATF3 • CCL3 • CD8 • CXCL10 • IFNA1

NCI-2019-08556: Nivolumab and BO-112 Before Surgery for the Treatment of Resectable Soft Tissue Sarcoma (clinicaltrials.gov) - P1 | N=14 | Active, not recruiting | Sponsor: Jonsson Comprehensive Cancer Center | Trial completion date: Jan 2025 ➔ Jan 2026 | Trial primary completion date: Jan 2024 ➔ Jan 2025

Surgery • Trial completion date • Trial primary completion date • Brain Cancer • Fibrosarcoma • Leiomyosarcoma • Liposarcoma • Neurofibrosarcoma • Oncology • Osteosarcoma • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Spindle Cell Sarcoma • Synovial Sarcoma • Undifferentiated Pleomorphic Sarcoma

KEYNOTE-B77: BO-112 With Pembrolizumab in Unresectable Malignant Melanoma (clinicaltrials.gov) - P2 | N=42 | Active, not recruiting | Sponsor: Highlight Therapeutics | Trial completion date: Dec 2023 ➔ Aug 2024

Combination therapy • Trial completion date • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • BRAF • CD4

Exploratory Study of BO-112 in Adult Patients With Aggressive Solid Tumors (clinicaltrials.gov) - P1 | N=44 | Completed | Sponsor: Highlight Therapeutics | Terminated ➔ Completed

Combination therapy • Trial completion • Oncology • Solid Tumor

Intratumoral neoadjuvant immunotherapy based on the BO-112 viral RNA mimetic. (PubMed, Oncoimmunology) - "The anti-tumor efficacy of this neoadjuvant immunotherapy approach depended on the presence of antigen-specific effector CD8 T cells and cDC1 antigen-presenting cells. Since BO-112 has been successful in phase-two clinical trials for metastatic melanoma, these results provide a strong rationale for translating this pre-surgical strategy into clinical settings, especially in combination with standard-of-care checkpoint inhibitors."

Journal • Melanoma • Oncology • Solid Tumor

BO-112 and Pembrolizumab for the Treatment of PD-1/PD-L1 Refractory Liver Cancer (clinicaltrials.gov) - P1 | N=1 | Terminated | Sponsor: Jonsson Comprehensive Cancer Center | N=15 ➔ 1 | Trial completion date: Oct 2025 ➔ Mar 2023 | Suspended ➔ Terminated | Trial primary completion date: Oct 2024 ➔ Mar 2023; Withdrawn by sponsor

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Intratumoral BO-112 in combination with pembrolizumab in patients with melanoma and skin only metastases; subgroup analysis of BOT112-03 clinical trial (EADO 2022) - No abstract available

Clinical • Combination therapy • Melanoma • Oncology • Solid Tumor