8-K: Theriva Biologics' VCN-01 Shows Promising Safety and Efficacy in Refractory Retinoblastoma Phase 1 Study

Theriva Biologics announced positive Phase 1 clinical trial results for its oncolytic virus VCN-01 in refractory retinoblastoma patients, demonstrating good tolerability and promising antitumor activity, including eye preservation.

Summary

• Theriva Biologics, Inc. (TOVX) issued a press release on May 27, 2025, announcing results from an investigator-sponsored Phase 1 study of VCN-01 in refractory retinoblastoma patients.
• The results were presented by Dr. Jaume Catal-Mora at the 2025 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Illinois, from May 30 to June 3, 2025.
• The study concluded that VCN-01 was well tolerated after intravitreal administration at two dose levels (2E+9 vp/eye and 2E+10 vp/eye).
• The most frequently reported treatment-related adverse events were Grade 1 or 2 uveitis, with 44% of patients experiencing Grade 3 uveitis and 78% experiencing uveitis of any grade.
• VCN-01 did not cause retinal toxicity, and no dose-limiting toxicities or ocular/systemic toxicities equal to or greater than Grade 3 were observed during the evaluation period.
• Ocular inflammation and associated turbidity were observed but were managed by local and systemic anti-inflammatory drugs, leading to improved vitreous haze in some cases.
• VCN-01 demonstrated selective replication in retinoblastoma cells and was not observed in healthy tissue, nor did it appear to change retinal function.
• Intravitreal VCN-01 showed promising antitumor activity, with four patients exhibiting unequivocal improvement in vitreous seed density.
• Eye enucleation was avoided in 3 out of 9 patients to date, with one patient retaining their eye after 4 years of follow-up.
• The study defined 2 doses of VCN-01 at 2E+10 vp/eye as the Recommended Phase 2 Dose (RP2D).
• Five patients achieved a partial response, three had stable disease, and one had progressive disease; the eyes of 3 of the 5 patients with partial response were preserved with vision after eye-conservative therapy (12-49 months follow-up).

Sentiment

Score: 8

Explanation: The sentiment is highly positive given the promising safety and efficacy results from a Phase 1 study for a severe pediatric cancer. The drug was well-tolerated, showed tumor selectivity, and, most importantly, led to eye preservation in a significant portion of heavily pre-treated patients, which is a critical outcome in retinoblastoma.

Positives

• VCN-01 was well tolerated with no dose-limiting toxicities or severe ocular/systemic toxicities (Grade 3 or higher).
• The drug did not cause retinal toxicity and did not appear to change retinal function.
• Selective replication of VCN-01 was observed in retinoblastoma cells but not in healthy tissue, indicating tumor specificity.
• Promising antitumor activity was demonstrated, with four patients showing unequivocal improvement in vitreous seed density.
• Eye enucleation was avoided in 3 patients, with one patient retaining their eye after 4 years of follow-up, a significant outcome for retinoblastoma treatment.
• The Recommended Phase 2 Dose (RP2D) of 2E+10 vp/eye was established, paving the way for further clinical development.

Negatives

• Uveitis was the most common treatment-related adverse event, occurring in 78% of patients (Grade 1 or 2), with 44% experiencing Grade 3 uveitis.
• Ocular inflammation and turbidity were observed, requiring management with anti-inflammatory drugs.
• One patient with Grade 3 uveitis did not receive the second dose due to medical decision and also experienced glaucoma requiring treatment.
• One patient experienced progressive disease.

Risks

• Treatment-related uveitis (Grade 1 or 2, with 44% Grade 3) is a common adverse effect.
• Ocular inflammation and associated turbidity can occur post-injection.
• Potential for glaucoma, as observed in one patient with Grade 3 uveitis.
• Serious adverse events (SAEs) reported included retinal detachment, vitreous and anterior chamber hemorrhage, and enucleation, though these were deemed non-related to VCN-01 in the study.

Future Outlook

The successful completion of this Phase 1 study, including the determination of a Recommended Phase 2 Dose (RP2D) of 2E+10 vp/eye, sets the stage for further clinical development of VCN-01 in refractory retinoblastoma. The promising safety and efficacy signals suggest potential for VCN-01 as a novel treatment option.

Industry Context

Retinoblastoma is the most frequent intraocular malignancy in children, often leading to eye enucleation. Current treatments often involve chemotherapy, which carries risks of toxicity and subsequent malignant neoplasms. VCN-01, as an oncolytic adenovirus, represents a novel approach aiming for tumor selectivity and reduced toxicity, aligning with the industry's need for targeted therapies that minimize exposure to conventional chemotherapy and preserve vision.

Comparison to Industry Standards

• The study highlights the need for novel treatments that offer tumor selectivity, reduced toxicity in healthy eye tissues, and minimized exposure to chemotherapy to lower the risk of subsequent malignant neoplasms, which are common challenges with existing retinoblastoma therapies.
• VCN-01's demonstrated selective replication in retinoblastoma cells and absence of replication in normal retinas (preclinical) directly addresses the need for tumor selectivity, a key advantage over less targeted systemic chemotherapies.
• The observed lack of retinal toxicity and Grade 3 or higher ocular/systemic toxicities (excluding uveitis) positions VCN-01 favorably against treatments with more severe side effect profiles.
• The ability to avoid eye enucleation in 3 patients, with one eye preserved for 4 years, represents a significant improvement over outcomes where enucleation is often the only option for refractory cases, offering a potential vision-sparing alternative to current standards of care like intra-arterial or intravitreal chemotherapy (e.g., melphalan, topotecan, carboplatin) which patients in this study had previously failed.

Stakeholder Impact

• **Shareholders:** Positive impact due to promising clinical data for a key pipeline asset, potentially increasing company valuation and investor confidence.
• **Patients:** Significant positive impact, offering a novel, potentially eye-preserving treatment option for refractory retinoblastoma, a condition that often leads to enucleation.
• **Medical Community:** Provides new insights into oncolytic virus therapy for ocular cancers and a potential new therapeutic modality for retinoblastoma.
• **Employees:** Positive impact from successful clinical progress, potentially boosting morale and job security.

Next Steps

• Further clinical development of VCN-01, likely moving into Phase 2 studies, based on the established Recommended Phase 2 Dose (RP2D) of 2E+10 vp/eye.
• Continued monitoring of patients for long-term safety and efficacy outcomes, as some patients have follow-up extending to 4 years.

Key Dates

Recommendation

Keywords

Retinoblastoma, VCN-01, Oncolytic Virus, Phase 1 Clinical Trial, Ophthalmology, Pediatric Oncology, Eye Cancer, Antitumor Activity, Theriva Biologics, ASCO, Intravitreal Injection