Hansa to Advance HSNA-5487 in Chronic Autoimmune Diseases Following Robust IgG Reduction in First-in-Human Trial

Søren Tulstrup

Recently announced results from a 12-month follow-up analysis of the NICE-1 trial, a first-in-human study of HNSA-5487 (Hansa Biopharma), showed that treatment with the investigational agent resulted in highly robust reduction of immunoglobulin G (IgG) levels by more than 95% within a few hours post treatment. All told, these positive data open the possibilities for the company to advance the treatment in chronic autoimmune diseases like myelin glycoprotein antibody disease (MOGAD), neuromyelitis optica (NMO), and myasthenia gravis (MG).

NICE-1 was a double-blind, placebo-controlled trial that included 36 healthy adult participants to test the safety, tolerability, pharmacokinetics, and pharmacodynamics of HNSA-5487, a next-generation IgG-cleaving enzyme. In the study, treatment with single ascending doses of the investigational agent were considered safe and well tolerated, with no serious adverse events (AEs) observed. In addition, the therapy demonstrated lower pre-treatment anti-drug antibody (ADA) levels and significant reduced ADA responses when compared with imlifidase, Hansa’s first-generation IgG-cleaving enzyme.

"There is mounting clinical evidence that faster and more robust IgG reduction is directly linked to more successful therapeutic outcomes in autoimmune and other diseases. We are very encouraged by these results that demonstrate HNSA-5487 can robustly and very rapidly reduce IgG levels, has redosing potential, and a favorable safety and tolerability profile,” Søren Tulstrup, president and chief executive officer at Hansa, said in a statement.¹

"We believe HNSA-5487 has a highly differentiated profile compared to published data from studies with other IgG-targeted therapies," Tulstrup added. "These results underscore the transformational potential of HNSA-5487 to address significant unmet need across a spectrum of IgG driven diseases and conditions, including autoimmune where there is a clear need for better management of initial and repeat immune system attacks."

Following a significant reduction of IgG levels, a 12-month follow-up showed that these levels returned to normal range 6 months after initial dosing. Overall, the investigational agent revealed highly robust reduction in IgG levels with similar efficacy in nearly 100% of serum samples collected in the trial and analyzed at 6- and 12-months after the initial dose. All together, these data support the theory that HNSA-5487 can effectively reduce IgG levels, making it a potential candidate in certain autoimmune diseases that have misguided IgG antibodies.

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HNSA-5487 shows similar properties to imlifidase, an antibody-cleaving enzyme originating from Streptococcus pyrogenes that specifically targets and cleaves IgG antibodies and inhibits IgG-mediated immune response. Imlifidase, a therapy that is conditionally approved in Europe, is reserved for patients who are unlikely to be transplanted under the available kidney allocation system, including prioritization programs for highly sensitized patients.

The first reported positive data from NICE-1 was announced in October 2023, with results showing that the molecule was safe and well tolerated. It mirrored the newly announced findings, in that there was fast and complete depletion of IgG antibodies observed at increasing doses in all participants. Overall, pharmacokinetics was in line with expectations and pharmacodynamics showed a fast and complete cleavage of IgG to F(ab)2- and Fc-fragments with increasing doses.²

Based on the newly reported data, the belief is that HNSA-5487 may be able to help patients with various autoimmune disorders of the central nervous system. MOGAD, an inflammatory disorder characterized by attacks of immune-mediated demyelination, has currently no approved therapies for the disease. The treatment market for NMO and myasthenia gravis is much more robust, with several approved agents; however, current immunomodulatory treatments do not achieve sufficient improvement or resolution of symptoms.

REFERENCES
1. Hansa Biopharma's HNSA-5487 Achieved Rapid and Highly Robust IgG Reduction by More Than 95% and Clear Redosing Potential in First-in-Human Trial. News release. Hansa Biopharma. October 7, 2024. Accessed October 10, 2024. https://www.prnewswire.com/news-releases/hansa-biopharmas-hnsa-5487-achieved-rapid-and-highly-robust-igg-reduction-by-more-than-95-and-clear-redosing-potential-in-first-in-human-trial-302268672.html
2. Hansa Biopharma announces encouraging high-level results for first-in-human trial of HNSA-5487. October 9, 2023. Accessed October 10, 2024. https://www.hansabiopharma.com/media/press-releases/2023/hansa-biopharma-announces-encouraging-high-level-results-for-first-in-human-trial-of-hnsa-5487/