ALPINE IMMUNE SCIENCES, INC. Leading the Next Evolution of Immunotherapies
March 2024
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Notice: Forward Looking Statements
This release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. These forward-looking statements are not based on historical fact and include statements regarding our platform technology and potential therapies; the timing of and results from clinical trials and preclinical development activities; clinical and regulatory objectives and the timing thereof; expectations regarding the sufficiency of cash, cash equivalents, restricted cash, and investments, along with proceeds from our November 2023 follow-on equity offering, to fund our planned operations into 2026; our ability to achieve additional milestones in our collaborations and proprietary programs; the progress and potential of our development programs; future development plans and clinical and regulatory milestones and objectives, including the timing and achievement thereof; the efficacy of our clinical trial designs; anticipated enrollment in our clinical trials and the timing thereof; expectations regarding the anticipated reporting of data from our ongoing and planned clinical trials and potential publication of future clinical data; our ability to potentially advance povetacicept directly into a pivotal trial in 2024 as well as a phase 2 study in systemic lupus erythematosus, pending engagement with and approval of the FDA; and the potential efficacy, safety profile, addressable market, regulatory success and commercial or therapeutic potential of our product candidates. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions and include words such as "may," "will," "should," "would," "expect," "plan," "intend," and other similar expressions, among others. These forward-looking statements are based on current assumptions that involve risks, uncertainties, and other factors that may cause actual results, events, or developments to be materially different from those expressed or implied by such forward-looking statements. These risks and uncertainties, many of which are beyond our control, include, but are not limited to: clinical trials may not demonstrate safety and efficacy of any of our product candidates; our ongoing discovery and preclinical efforts may not yield additional product candidates; our discovery stage and preclinical programs may not advance into the clinic or result in approved products; any of our product candidates may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; we may not achieve additional milestones in our proprietary or partnered programs; the impact of competition; adverse conditions in the general domestic and global economic markets; we may be unable to advance povetacicept directly into a pivotal trial or a phase 2 study in systemic lupus erythematosus in 2024; the impact of pandemics, or other related health crises on our business, research and clinical development plans and timelines and results of operations, including the impact on our clinical trial sites, collaborators, and contractors who act for or on our behalf; as well as the other risks identified in our filings with the Securities and Exchange Commission. These forward- looking statements speak only as of the date hereof and we undertake no obligation to update forward-looking statements, and readers are cautioned not to place undue reliance on such forward-looking statements.
"RUBY" and the Alpine logo are registered trademarks or trademarks of Alpine Immune Sciences, Inc. in various jurisdictions.
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Unless otherwise indicated, all data presented herein has been derived from research conducted by Alpine Immune Sciences, Inc.
OUR MISSION
United to create and deliver transformative novel therapies for serious autoimmune and inflammatory diseases
OUR VISION
We will be recognized for our ingenious protein engineering, courageous passion for immunology, and trailblazing interrogation of critical immunological pathways, resulting in innovative medicines that revolutionize patient care
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DEVELOPING NOVEL THERAPIES FOR
AUTOIMMUNE AND INFLAMMATORY DISEASES
POVETACICEPT SUMMARY:
PoC data achieved in IgAN at 80 mg SC Q4W
- Best-in-classpotential with dual BAFF/APRIL blockade
- Convenient once every four-week dosing regimen
- Phase 3 in IgAN targeted to begin in 2H 20241
- Potential best-in-class profile enables broad development plan in multiple autoimmune diseases
- Regular cadence of catalysts anticipated throughout 2024
- Wholly-owned,internally discovered program with composition of matter IP to 20412
→ $368M cash and investments as of 12/31/2023 | 1 | Subject to engagement with and approval of regulatory authorities | 4 |
2 | Additional opportunity for patent term extension (PTE) | ||
Povetacicept (ALPN-303)
Dual B Cell Cytokine Antagonist
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Dual BAFF/APRIL Inhibition for Potentially Superior Clinical Outcomes
Improved Targeting of Pathogenic B Cells (Memory, Plasmablasts, Plasma Cells) and Autoantibodies
Centrocyte Memory | Plasmablast | Plasma cell | |||||||||
λ5 | IgM | IgM IgD | IgM | IgD | IgM, IgA, IgG, or IgE | ||||||
Large | |||||||||||
Small | |||||||||||
Pro-BPre-B | Pre-B-II | Immature | Transitional | Naïve | Centroblast | Pathogenic Autoantibodies |
Therapeutics Approved or in Development
CD20 | CD20-depleting mAbs |
Dual BAFF/APRIL | ||||
BAFF-R | BAFF only: | Anti-BAFF mAbs | Inhibitors in Development | |
Povetacicept | ||||
BCMA | ||||
BAFF + APRIL | Anti-APRIL mAbs | Atacicept (TACI-Ig) | ||
TACI | Telitacicept (TACI-Ig)* | |||
INCREASING DEVELOPMENT | |
*Granted conditional approval in China to treat SLE | 6 |
Adapted from Nat Rev Neurol 8:613, 2012 |
Povetacicept: BAFF/APRIL Inhibitor Enables Broad Development Plan Across Multiple Therapeutic Areas
APRIL
ACTIVATED | PLASMABLAST/ |
B CELL | SHORT-LIVED |
PLASMA CELL |
BAFF
Povetacicept
Neutralizes both
BAFF & APRIL
LONG-LIVED PATHOGENIC
PLASMA CELL ANTIBODY PRODUCTION
THERAPEUTIC AREAS
Autoimmune
Bullous Diseases
(e.g., pemphigus, pemphigoid)
Glomerulonephritis
(e.g., IgAN, pMN, LN, AAV) | Red Blood Cells | |
Platelets | ||
skin | ||
Autoimmune Cytopenias | ||
heart | (e.g., ITP, wAIHA, CAD) | |
kidneys | ||
Connective | blood | |
Tissue | muscles | |
Disease | joints | |
(e.g., SLE, Sjögren's, | ||
vasculitis)Autoimmune
Neurological Diseases (e.g., myasthenia gravis, autoimmune encephalitis, NMOSD)
IgAN IgA nephropathy
pMN Primary membranous nephropathy
LN Lupus nephritis | SLE | Systemic lupus erythematosus | wAIHA Warm autoimmune hemolytic anemia NMOSD Neuromyelitis optica spectrum disorder 7 |
AAV ANCA-associated vasculitis | ITP | Immune thrombocytopenia | CAD Cold agglutinin disease |
Povetacicept Demonstrates Best-In-Class Inhibitory Potential
Relative to Data From Comparator Molecules Targeting BAFF / APRIL Pathway
IC (nM)1 | |||||
50 | |||||
Reagent | APRIL | BAFF | APRIL + BAFF | ||
Povetacicept (ALPN-303) | 3.8 | 1.4 | 3.1 | ||
WT TACI-Fc2 | >200 | 20.8 | >200 | ||
Telitacicept3 (Tai'ai®) | 53.9 | 14.5 | >200 | ||
Anti-APRIL mAb4 | 21.9 | CNBD | >200 | ||
Anti-APRIL mAb5 | 5.1 | CNBD | CNBD | ||
Belimumab (Benlysta®) | CNBD | 4.8 | CNBD | ||
Belimumab + Anti-APRIL mAb4 | 18.9 | 4.8 | 10.8 | ||
TACI/Jurkat/NF-κB Functional Assay
APRIL BAFF
Extracellular TACI
Cytoplasm
NF-KB | Luciferase |
Activation |
NF-KB Nucleus
Luciferase
Reporter
1 TACI/Jurkat/NF-kB reporter assay prepared for preclinical evaluation purposes
2 WT TACI 30-110-Fc; generated by ALPN using published atacicept sequence (SEQ ID NO: 54 of US Patent 8,815,238 B2)
3 WT TACI 13-118-Fc, as identified in WHO Drug Information, Vol. 32, No. 4, 2018 and confirmed by mass spec/peptide sequencing on Tai'ai® 4 Generated by ALPN using published zigakibart (BION-1301) sequence (SEQ ID NO: 50 and 52 from US Patent Appl. US 2020/0079859)
5 Generated by ALPN using published sibeprenlimab (VIS649) sequence (https://www.imgt.org/3Dstructure-DB/cgi/details.cgi?pdbcode=11575) CNBD, could not be determined
Source: Arthritis Rheumatol 75:1187 (2023) and ALPN data on file
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Dual BAFF/APRIL Inhibition Provides Superior Preclinical Efficacy
NZB/W Murine Lupus and Murine Experimental Autoimmune Myasthenia Gravis (EAMG)
Autoimmune Hemolytic | ||||
Murine Experimental | ||||
Lupus Nephritis / GN | ||||
α | Anemia | Autoimmune Myasthenia Gravis | ||
IFN -Accelerated NZB/W F1 | IFNα-Accelerated NZB/W F1 | |||
Renal Histology
Lesions | 15 | |||
10 | ||||
Renal | 5 | |||
Total | 0 | |||
control | -mCD20 | |||
Telitaciceptanti | ||||
Fc | Povetacicept |
Hemoglobin
15
(g/dL) | |
Hemoglobin | 10 |
5
Povetacicept | ||
control | Telitaciceptanti | |
Fc | -mCD20 |
2.0 | Fc Control | |||
- 4) | Anti-CD20 | |||
Efgartigimod | ||||
1.5 | ||||
Povetacicept | ||||
1.0 | ||||
0.5 | ||||
ScoreClinical(0 MeanSE± | ||||
0.0 | ||||
30 | 45 | 60 | 75 | 90 |
Day After 1st Immunization
Blair et al. ACR 2023 | Blair et al. ACR 2023 | Source: Dillon et al. AANEM 2023 |
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Povetacicept Mediates On-Target Effects in Healthy Adults
Well-tolerated as Single 80-240 mg Subcutaneous Doses; Pharmacodynamics Support Q4W Dosing
Target Coverage
Mean Drug Free:TotalAPRIL (normalized % ofbaseline) | 1 | 80 mg SC |
240 mg SC | ||
0.1 | ||
0.01 | Free/Total APRIL | |
0 | 4 | |
Weeks Post-Dose
Mean Drug-Free:TotalBAFF (normalized % ofbaseline) | 1 | |
0.1 | ||
0.01 | ||
0.001 | Free/Total BAFF | |
0 | 4 | |
Weeks Post-Dose
Ig Reductions
% Change fromBaseline (Mean ± SD) | 0 | 80 mg SC |
240 mg SC | ||
-20 | ||
-40 | ||
-60 | IgA | |
0 | 4 |
Weeks Post-Dose
% Change fromBaseline (Mean ± SD) | 0 | |
-20 | ||
-40 | ||
-60 | IgM | |
0 | 4 |
Weeks Post-Dose
Gd-IgA1 Reduction
%Change from Baseline (Mean+SD) | 0 | 80 mg SC |
240 mg SC | ||
-20 | ||
-40 | ||
-60 | Gd-IgA1 | |
0 | 4 |
Weeks Post-Dose
Antibody Secreting Cell
Reduction
Change fromBaseline | -20 | 80 mg SC | |
(Mean+SD) | 240 mg SC | ||
-40 | |||
-60 | |||
-80 | ASCs | ||
% | -100 | ||
0 | 4 |
Weeks Post-Dose
Dillon et al,
IIgANN 2023
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Disclaimer
Alpine Immune Sciences Inc. published this content on 18 March 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 18 March 2024 20:26:05 UTC.
