PH-894 / Phio Pharma - LARVOL DELTA

SIlencing BRD4 to increase NK cell activity for adoptive cell therapy: a novel self-delivering RNAi approach (ITOC 2025) - "Current BET inhibitors such as JQ1 and molibresib target BRD4 but lack specificity, leading to off-target effects that limit their clinical application...Conclusions Incorporating PH-894 treatment into ex vivo NK cell expansion protocols prior to ACT represents a promising strategy for improving NK cell efficacy. These findings suggest that BRD4 may play an important role in regulating NK cell activity and that its silencing may modulate NK cell function, potentially enhancing their antitumor activity. This study provides a foundation for further exploration of BRD4 as a target for enhancing NK cell-based immunotherapies."

IO biomarker • Oncology • BRD4 • IL2RA • KLRD1 • NCAM1

Phio Announces Data Showcasing INTASYL’s Role in Helping Immune Cells Target and Kill Cancer Cells (Phio Pharma Press Release) - "Phio Pharmaceuticals Corp....today announced that it is presenting data about its proprietary INTASYL platform and INTASYL compounds....INTASYL compound PH-762 silences PD-1, improving therapeutic efficacy in vivo. The PH-894 compound precisely silences BRD4 to enhance tumor cell immunogenicity and induce apoptosis. Silencing TIGIT in NK cells, using compound PH-804, enhances their activation, cytokine release, and target cell killing. The PH-905 compound silences CBLB, increasing NK cell cytotoxicity and proliferation....The data is being presented on October 8th at the 20th Annual Oligonucleotide Therapeutics Society (OTS) Meeting in Montreal."

Preclinical • Oncology

Phio Pharmaceuticals Announces Upcoming Presentation at ASGCT’s 2024 Advancing Gene + Cell Therapies for Cancer Conference (Phio Pharma Press Release) - "Phio Pharmaceuticals Corp....today announced it is presenting data about its INTASYL compound PH-894 at the American Society of Gene & Cell Therapy’s (ASGCT’s) 2024 Advancing Gene + Cell Therapies for Cancer conference. The conference will take place October 16-17, 2024, virtually and at the Wyndham Hotel, Philadelphia Historic District, 400 Arch Street, Philadelphia, PA."

Preclinical • Oncology

Phio Pharmaceuticals Presents New Data for Targeting of BRD4 with its INTASYL Compound PH-894 (GlobeNewswire) - "Phio Pharmaceuticals Corp...announced the poster presentation of two key preclinical studies of its INTASYL compound PH-894 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, Massachusetts on October 11th -15th. The first study shows that melanoma cells treated with its PH-894 compound makes them more recognizable to the immune cells. Specifically, the treatment results in an increase in the tumor marker MART-1...allowing for better recognition and potentially increased killing by T cells....The second study demonstrates the effectiveness of PH-894 as an antitumor cytotoxic agent (directly killing tumor cells). The addition of PH-894 to cells in vitro elicited concentration-associated apoptosis of all human cancer cell lines tested, including head and neck squamous cell carcinoma (HNSCC), hepatocellular carcinoma (HCC), breast cancer, lung cancer, glioblastoma, melanoma, colon cancer, ovarian cancer, and cervical cancer."

Preclinical • Brain Cancer • Breast Cancer • Cervical Cancer • CNS Tumor • Gastrointestinal Cancer • Glioblastoma • Gynecologic Cancers • Head and Neck Cancer • Hepatocellular Cancer • Liver Cancer • Lung Cancer • Melanoma • Oncology • Ovarian Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

INTASYL™ PH-894 self-delivering RNAi targeting BRD4 enhances the antigenicity of melanoma cells through MART-1 upregulation. (AACR-NCI-EORTC 2023) - No abstract available

Melanoma • Oncology • Solid Tumor • BRD4

PH-894, an INTASYL self-delivering siRNA targeting BRD4, has dual functions to sensitize tumor cell killing and activate CD8 T cells (SITC 2022) - "Conclusions We demonstrate that PH-894 potently activates CD8 + T cells, and PH-894 pretreatment of tumor cells can sensitize tumor cell killing by CD8 + T cells. These data provide additional mechanistic insight and support further development and clinical investigation of PH-894 as a new class of antitumor therapeutic."

Melanoma • Oncology • Solid Tumor • BRD4 • CD8 • IFNG

Phio Pharmaceuticals Announces Study Results at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) on November 10th and 11th (PRNewswire) - 'Phio Pharmaceuticals...announced the results of several studies of its INTASYL™ compounds....The posters will be presented on November 10th and 11th at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), which is being held in Boston, MA from November 8 – 12, 2022."

P1 data • Preclinical • Breast Cancer • Melanoma • Oncology • Solid Tumor

Phio Pharmaceuticals Announces Upcoming Presentations at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (PRNewswire) - "Phio Pharmaceuticals...announced it is scheduled to provide an update on its programs at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), which will be held in Boston, MA from November 8 - 12, 2022. This will include an update on its first-in-human clinical trial with PH-762 in advanced melanoma; data demonstrating the potential of PH-762 to further enhance the function of tumor infiltrating lymphocytes (TILs) with its partner AgonOx, Inc.; and new preclinical data on relevant targets identified in cancer immunotherapy using our INTASYL compounds."

P1 data • Preclinical • Breast Cancer • Melanoma • Oncology • Skin Cancer • Solid Tumor

Phio Pharmaceuticals Reports Second Quarter 2022 Financial Results and Provides Business Update (PRNewswire) - "Upcoming Pipeline Milestones: (i) Plans to initiate a clinical trial evaluating the use of PH-762 and DP TILs in ACT during the fourth quarter of 2022 in partnership with AgonOx, Inc.; (ii) Expects to finalize IND-enabling studies for PH-894 in the second half of 2022; (iii) Expects to report top-line data from the first group of subjects with advanced melanoma in the clinical trial for PH-762 in the first quarter of 2023; (iv) Additional data publications on the Company's pipeline programs."

Clinical data • IND • New trial • Melanoma • Oncology • Skin Cancer • Solid Tumor

Self-Delivering RNAi Targeting BRD4 (PH-894) Improves the Phenotype of HER2-CAR-T Cells During Expansion (ASGCT 2022) - "These data provide proof-of-concept to suggest that silencing BRD4 with INTASYL PH-894 can be used to improve the phenotype of CAR-T during activation and expansion phases of their manufacturing process by reducing exhaustion, immunosuppression, and conferring a phenotype associated with cell persistence, thus serving to improve the quality of a final CAR-T cell product. Follow-up studies are ongoing on the use of PH-894 in T cell adoptive cell therapy."

CAR T-Cell Therapy • IO biomarker • Gene Therapies • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor • BRD4 • CCR7 • CD8 • FAS • HAVCR2 • HER-2 • IL10 • PD-1 • TIGIT

Phio Pharmaceuticals Presents New Data Demonstrating PH-894 Enhances Activity of HER2-CAR-T Cells at ASGCT 2022 (PRNewswire) - "Phio Pharmaceuticals...presented new preclinical data showing that silencing BRD4 with PH-894, a self-delivering RNAi INTASYL compound, can be used to improve the characteristics of CAR-T cell products during the activation and expansion phases of the cell manufacturing process. These new data will be presented at the American Society of Gene & Cell Therapy (ASGCT) 25th Annual Meeting, which is being held in Washington D.C., from May 16-19, 2022....Results showed that PH-894 reduced the expansion-associated production of BRD4 and BRD4-regulated genes and mitigated the production of inhibitory receptors and markers of T cell exhaustion, PD-1, TIGIT and TIM3."

Preclinical • Oncology • Solid Tumor

Phio Pharmaceuticals Announces Upcoming Presentation of PH-894 Data at ASGCT 25th Annual Meeting 2022 (PRNewswire) - "Phio Pharmaceuticals Corp....announced today that it will present new preclinical data on PH-894 for use in adoptive cell therapy (ACT) at the American Society for Gene and Cell Therapy (ASGCT) 25th Annual Meeting, which is being held May 16-19, 2022 in-person in Washington, D.C. and virtually."

Preclinical • Oncology

Local administration of BRD4-targeting self-delivering RNAi (PH-894) provides abscopal efficacy toward untreated distal tumors and potentiates the efficacy of systemic anti-PD-1 antibody therapy (AACR 2022) - "In addition, PH-894 silencing of BRD4 not only inhibited tumor growth at the local site of therapy, but also elicited an abscopal effect toward distal tumors, with efficacy similar to that provided by systemically administered anti-PD-1 mAb. These results indicate that IT PH-894 can potentiate the efficacy of systemic anti-PD-1 mAb, warranting further investigation of clinical applications in combination with anti-PD-1 mAbs toward improving patient outcomes."

Clinical • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • BRD4

Phio Pharmaceuticals Presents Positive New Data on PH-894 Demonstrating Antitumor Efficacy in Model of PD-1 Refractory Disease at the AACR Annual Meeting 2022 (PRNewswire) - "Data from in vivo studies demonstrated that PH-894 inhibits tumor growth in both PD-1 inhibition responsive, as well as PD-1 inhibition insensitive models. In both models, after local administration, strong antitumor efficacy was seen in directly treated as well as distal, untreated tumors. Additionally, intratumoral treatment with PH-894 enhanced the antitumor efficacy of systemic anti-PD-1 antibody therapy, not only for the PH-894 locally treated tumors, but for the PH-894 untreated distal tumors. In the PD-1 inhibition insensitive model, local PH-894 therapy was shown to be efficacious as a systemic anti-PD-1 antibody treatment, and enhanced the antitumor efficacy of anti-PD-1 treatment when used together."

Preclinical • Oncology • Solid Tumor

Phio Pharmaceuticals Announces Upcoming Presentation of PH-894 Data at the AACR Annual Meeting 2022 (PRNewswire) - "Phio Pharmaceuticals Corp...announced that it is scheduled to present new preclinical data on PH-894, Phio's self-delivering RNAi compound targeting the bromodomain-containing protein 4 (BRD4), in an in-person poster session at the AACR Annual Meeting 2022, which is being held in New Orleans, Louisiana, from April 8-13, 2022."

Preclinical • Oncology • Solid Tumor

Phio Pharmaceuticals Reports Third Quarter 2021 Financial Results and Provides Business Update (PRNewswire) - "Expect to initiate a first-in-human clinical study on the direct therapeutic use of PH-762 in patients with advanced melanoma in the first quarter of 2022. Expect to initiate a first-in-human clinical study on the use of PH-762 and tumor infiltrating lymphocytes (TILs) in adoptive cell therapy (ACT) in patients with advanced melanoma in the second quarter of 2022. Expect to file a clinical trial application for PH-894 in the second half of 2022."

IND • New trial • Melanoma • Oncology • Solid Tumor

Phio Pharmaceuticals Presents New BRD4 Data at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (PRNewswire) - “The data presented add to the growing body of evidence that BRD4 not only plays a role in tumor cells, but can also regulate T cell function and that PH-894 can reprogram T cells to provide enhanced immunotherapeutic activity….‘The data we presented today at the AACR-NCI-EORTC meeting demonstrates silencing BRD4 with our INTASYL compound PH-894 has a significant impact on T cell function and phenotype promoting T cell activation and immunosuppression in the tumor microenvironment...Our new data shows how BRD4 can regulate immune cells activity and therefore BRD4 silencing with PH-894 could become an important approach to treat cancer'"

Clinical data • Oncology