Alpine Immune Sciences, Inc. (NASDAQ:ALPN) is a clinical-stage biopharmaceutical company dedicated to discovering and developing innovative, protein-based immunotherapies to treat autoimmune and inflammatory diseases. The company's lead product candidate, povetacicept, is a dual antagonist of the B cell activating factor (BAFF) and a proliferation inducing ligand (APRIL) cytokines, which play key roles in the pathogenesis of multiple autoimmune diseases.

Financials

In 2023, Alpine reported annual revenue of $58.9 million, up from $30.1 million in the prior year, driven primarily by a $24.9 million increase in revenue from its collaboration with AbbVie and a $4.5 million increase from its collaboration with Amgen. However, the company incurred a net loss of $32.2 million for the year, compared to a net loss of $57.8 million in 2022. Alpine's annual operating cash flow was -$79.0 million, and its annual free cash flow was -$79.5 million.

For the first quarter of 2024, Alpine reported collaboration revenue of $7.0 million, down from $9.4 million in the same period of 2023. The company's net loss for the quarter was $17.9 million, compared to a net loss of $13.3 million in the prior-year period. Alpine's operating cash flow was -$27.7 million, and its free cash flow was -$27.7 million in the first quarter of 2024.

Povetacicept: A Potentially Best-in-Class Dual BAFF/APRIL Inhibitor

The highlight of Alpine's pipeline is povetacicept, a dual antagonist of the BAFF and APRIL cytokines, which play key roles in the pathogenesis of multiple autoimmune diseases. Povetacicept was discovered using Alpine's proprietary directed evolution platform and has exhibited greater potency in preclinical studies compared to wild-type TACI-based comparators, as well as other inhibitors of BAFF and/or APRIL alone and B cell depletion.

In November 2023, Alpine presented positive initial data from its RUBY-3 clinical trial of povetacicept in adult patients with autoimmune glomerulonephritis, including IgA nephropathy (IgAN). The data showed that both the 80 mg and 240 mg monthly doses of povetacicept were well-tolerated and demonstrated highly encouraging improvements in urine protein-creatinine ratio (UPCR) and disease biomarkers, with early evidence suggesting potential for disease remission.

Based on these results, Alpine plans to initiate RAINIER, a pivotal Phase 3 study of povetacicept in IgAN, in the second half of 2024. The company also plans to initiate DENALI, a Phase 2 study of povetacicept in systemic lupus erythematosus (SLE), during the same timeframe.

Broad Potential of Povetacicept Across Multiple Autoimmune Indications

In addition to IgAN and SLE, Alpine believes povetacicept has the potential to be a best-in-class treatment for a broad range of autoimmune and inflammatory diseases, including other autoimmune kidney diseases, autoimmune cytopenias, and potentially neurological and allergic conditions.

The company is currently evaluating povetacicept in the RUBY-3 basket study, which is enrolling patients with autoimmune glomerulonephritis, including lupus nephritis, renal ANCA-associated vasculitis, and primary membranous nephropathy, as well as the RUBY-4 basket study in autoimmune cytopenias, including immune thrombocytopenia, warm autoimmune hemolytic anemia, and cold agglutinin disease.

Preclinical data presented by Alpine suggest that povetacicept may also have potential applications in neurological conditions, such as myasthenia gravis and autoimmune encephalitis, as well as in IgE-mediated allergic diseases, due to its observed effects on reducing IgE levels in IgAN patients.

Robust Financial Position to Advance Povetacicept and Pipeline

As of December 31, 2023, Alpine had cash, cash equivalents, and investments totaling $368.2 million, which the company believes will be sufficient to fund its planned operations into 2026. This strong financial position was bolstered by a $150 million equity offering completed in 2023, which the company plans to use to accelerate the development of povetacicept and its broader pipeline.

In addition to its work on povetacicept, Alpine continues to invest in its proprietary directed evolution platform, which has generated a pipeline of novel protein-based immunotherapies targeting autoimmune and inflammatory diseases. The company's platform has the potential to produce differentiated, multi-targeted therapeutics designed to modulate the immune system in a variety of disease settings.

Risks and Challenges

While Alpine's progress with povetacicept is encouraging, the company faces several risks and challenges common to the biopharmaceutical industry. These include the inherent uncertainties of clinical development, the potential for regulatory setbacks, competition from other therapies, and the need to successfully navigate complex commercial and reimbursement landscapes.

Additionally, as a clinical-stage company, Alpine is subject to the risks associated with its limited operating history, reliance on collaborations and partnerships, and the need to continue raising capital to fund its ongoing operations and development activities.

Outlook

Alpine Immune Sciences is well-positioned to advance povetacicept, its potentially best-in-class dual BAFF/APRIL inhibitor, across multiple autoimmune and inflammatory indications. The company's strong financial position, coupled with the promising data generated to date, supports its plans to initiate pivotal trials in IgAN and SLE in the second half of 2024.

Conclusion

Beyond povetacicept, Alpine's proprietary directed evolution platform continues to generate novel drug candidates that may address unmet needs in autoimmune and inflammatory diseases. As the company executes on its robust clinical development plan and explores the broader potential of its pipeline, Alpine Immune Sciences remains an intriguing player in the rapidly evolving immunotherapy landscape.