Alpha1H shows favorable safety, efficacy in phase 2 NMIBC trial

A phase 2 trial of Alpha1H (EUCT, 2024-514628-17-00) has met all primary and secondary end points, demonstrating the efficacy and favorable safety of the agent in patients with non–muscle invasive bladder cancer (NMIBC), Hamlet BioPharma reported in a news release.¹

Alpha1H is a novel biologic anti-cancer drug. The agent currently has fast track designation, which was awarded by the FDA in November 2023 for the treatment of NMIBC.² With this designation, the development process for Alpha1H can benefit from more frequent engagement with the FDA and eligibility for accelerated approval and priority review.

"The final clinical report's consistent efficacy outcomes and favorable safety profile are highly encouraging,” said Catharina Svanborg, MD, PhD, CEO of Hamlet BioPharma, in the news release from the company.¹ “The strength of the data provides compelling evidence of Alpha1H's potential to become a much-needed proactive treatment option, and we look forward to advancing it in our regulatory discussions.”

In total, the study enrolled approximately 60 patients with NMIBC who were randomly assigned to receive Alpha1H or placebo standard of care. Treatment was administered prior to surgery for about 1 month.

The primary end points in the study were adverse events (AEs), characteristics of papillary tumors, and the quantification of cell shedding in urine. Secondary end points included induction of apoptosis, histopathology scoring, tumor response to Alpha1H by gene expression analysis, and proteomic analysis of immune markers in urine.

Overall, efficacy of the agent was confirmed with 80% of tumors responding to treatment with Alpha1H. The average reduction in tumor size following treatment was 59% in the high-dose group. The efficacy of Alpha1H was also maintained with repeat dosing—the company reported that patients who received a second round of instillations continued to show tumor cell death and reduction.

On the trial’s secondary end points, Hamlet BioPharma reported, “Alpha1H reaches tumor tissue, triggers tumor cell apoptosis, and causes rapid shedding of tumor cells into the urine.”

Cytokine profiling also showed that Alpha1H elicits BCG-like immune activation, but the agent triggers this response more rapidly and without lasting AEs compared with BCG. Advanced RNA sequencing also revealed that Alpha1H downregulated over 700 of approximately 800 cancer-related genes. This included RAS and GJA1, which the company says, “provides a mechanistic explanation for its unique tumor-killing profile.”

Notably, treatment with Alpha1H was well-tolerated, with no drug-related serious AEs reported. AEs were generally mild and comparable to those seen in the placebo arm. No

systemic AEs were observed, which Hamlet BioPharma noted is consistent with the agent’s local mechanism of action.

According to Hamlet BioPharma, these data have been submitted to the FDA, and the company is engaged in discussions with the agency surrounding the initiation of a phase 3 trial of Alpha1H. In July 2025, the company reported that they remained on track to initiate the pivotal study.³

REFERENCES

1. Hamlet BioPharma announces the completion of the Alpha1H phase II study in non-muscle invasive bladder cancer. News release. Hamlet BioPharma AB (publ). August 21, 2025. Accessed August 21, 2025. https://hamletbiopharma.com/hamlet-biopharma-announces-the-completion-of-the-alpha1h-phase-ii-study-in-non-muscle-invasive-bladder-cancer/

2. Hamlet BioPharma receives U.S. FDA Fast Track designation for Alpha 1H for the treatment of non-muscle invasive bladder cancer. News release. Hamlet BioPharma. November 29, 2023. Accessed August 21, 2025. https://hamletbiopharma.com/hamlet-biopharma-receives-u-s-fda-fast-track-designation-for-alpha-1h-for-the-treatment-of-non-muscle-invasive-bladder-cancer/

3. Hamlet BioPharma holds successful in person meeting with US FDA. News release. Hamlet BioPharma. June 25, 2025. Accessed August 21, 2025. https://hamletbiopharma.com/hamlet-biopharma-holds-successful-in-person-meeting-with-us-fda/