On November 14, 2022 Alpine Immune Sciences, Inc. (NASDAQ: ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for autoimmune and inflammatory diseases, reported financial results for the third quarter ended September 30, 2022 (Press release, Alpine Immune Sciences, NOV 14, 2022, View Source [SID1234623970]).

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"During our inaugural R&D Day and throughout subsequent scientific meetings this fall, we have shared promising nonclinical and clinical data that supports the best-in-class potential for our lead program ALPN-303 in multiple autoimmune and inflammatory indications. In particular, recent data from healthy volunteers presented at ASN’s Kidney Week demonstrated dose-dependent reductions in Gd-IgA1, a key effector molecule and clinical biomarker of disease progress in IgAN, and the first clinical disease-related biomarker data with ALPN-303," said Mitchell H. Gold, MD, Executive Chairman and Chief Executive Officer of Alpine. "To further accelerate development of this promising program in multiple indications, we completed a successful $113 million follow-on offering with top-tier investors in October, extending our cash runway through the end of 2025. We now look forward to beginning a broad development plan for ALPN-303, including a phase 2 study in systemic lupus erythematosus (SLE). In addition, we are particularly excited to begin open-label basket studies in glomerulonephritis and autoimmune cytopenias as they should provide a rapid assessment in multiple diseases and may potentially enable multiple accelerated development paths."

Gold continued, "As previously announced, we have voluntarily terminated enrollment in the davoceticept (ALPN-202) clinical studies. We would like to thank the patients and investigators who participated in the NEON studies. We remain focused on using our resources to further advance ALPN-303, as well as acazicolcept (ALPN-101) in SLE in collaboration with AbbVie."

Third Quarter 2022 and Recent Pipeline and Corporate Updates

ALPN-303

During the September R&D Day, the Company shared updated preliminary data from the phase 1 study (RUBY-1) of ALPN-303 in healthy volunteers and presented a broad development plan, including a proof-of-concept phase 2 study in SLE and basket studies in renal and hematologic autoimmune diseases, with initial clinical data from the basket studies expected in late 2023. (View Release)
At the American Society of Nephrology: Kidney Week Meeting, updated clinical data were presented in a poster titled, "Phase 1 Study in Healthy Adults of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALPN-303, a Dual BAFF/APRIL Antagonist for the Treatment of Autoimmune Glomerulonephritides (GN)". (View Release)
The data demonstrate that ALPN-303 continues to be well tolerated as single intravenous or subcutaneous doses of up to 960 mg and exhibits dose-related pharmacokinetic and on-target pharmacodynamic effects.
ALPN-303 maintains target coverage of free APRIL for 2-3 and ≥4 weeks with 80 and 240 mg, respectively, corresponding to reductions in serum Ig and antibody-secreting cells (CD38hi plasmablasts/plasma cells).
ALPN-303 dose-dependently reduces serum galactose-deficient IgA1 (Gd-IgA1), a critical molecule implicated in the pathogenesis of IgA nephropathy (IgAN).
These data support dose regimens of 80-240 mg SC every 4 weeks in future GN studies.
The Company also presented clinical data from the RUBY-1 study of healthy vs at the recent American College of Rheumatology in a poster titled, "A Randomized Placebo-Controlled Phase 1 Study in Healthy Adult Volunteers of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALPN-303, a Potent Dual BAFF/APRIL Antagonist for the Treatment of Systemic Lupus Erythematosus and Other Autoantibody-Associated Diseases". (View Poster)
Additional updates will be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Conference in December. (View Release)
Corporate

The Company ended the third quarter with $277.1 million in cash, cash equivalents, restricted cash, and investments, following the successful completion of a $100.0 million underwritten public offering where we sold 13.6 million shares of our common stock with net proceeds of approximately $93.5 million, after deducting underwriting commissions and estimated offering expenses.
An additional 1.9 million shares of our common stock were sold pursuant to the underwriters’ partial exercise of their over-allotment option, with net proceeds of $13.1 million received upon closing on October 4, 2022.
The financing brings our pro-forma cash and investments balance to $290.2 million as of September 30, 2022, which should be sufficient to fund our planned operations through 2025.
On October 24, the Company announced that it had voluntarily terminated enrollment in the NEON studies of davoceticept as a monotherapy and in combination with pembrolizumab. (View Release)
Third Quarter 2022 Financial Results

As of September 30, 2022, Alpine’s cash, cash equivalents, restricted cash, and investments totaled $277.1 million. The Company recorded net losses of $13.3 million and $13.5 million for the quarters ended September 30, 2022, and 2021, respectively.

Collaboration revenue for the third quarter ended September 30, 2022, was $8.4 million compared to $8.5 million for the third quarter ended September 30, 2021. The 2022 amounts were primarily attributable to revenue recognized under the Company’s AbbVie and Horizon collaborations, while 2021 revenue recognized solely related to the AbbVie collaboration.

Research and development expenses for the third quarter ended September 30, 2022, were $17.6 million compared to $18.3 million for the third quarter ended September 30, 2021. The decrease was primarily attributable to decreased clinical development activities offset by higher personnel-related expenses due to increased headcount.

General and administrative expenses for the third quarter ended September 30, 2022, were $4.6 million compared to $3.5 million for the third quarter ended September 30, 2021. The increase was primarily attributable to increases in personnel costs.

About ALPN-303 and the RUBY-1 Study

ALPN-303 is a dual antagonist of the BAFF (B cell activating factor) and APRIL (a proliferation inducing ligand) cytokines, which play key roles in the activation and survival of B cells. Based upon an engineered TACI (transmembrane activator and CAML interactor) domain, ALPN-303 exhibits greater potency in preclinical studies versus wild-type TACI-based comparators, as well as other inhibitors of BAFF and/or APRIL alone. ALPN-303 is in development for multiple B cell and/or autoantibody-related diseases, such as systemic lupus erythematosus, glomerulonephritides, and autoimmune cytopenias.

RUBY-1 (NCT05034484) is a phase 1, randomized, placebo-controlled study in healthy adult volunteers designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of intravenously and subcutaneously administered ALPN-303. Initial data show ALPN-303 to be well tolerated up to 960 mg with dose-dependent pharmacokinetics and reductions in circulating immunoglobulins and antibody-secreting cells, supporting the use of a once every four-week dose regimen for subsequent studies.