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Alpine Immune Sciences Shares Updated Clinical Data from Povetacicept in IgA Nephropathy

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Alpine Immune Sciences, Inc. (ALPN) shares updated clinical data for povetacicept in IgA nephropathy, showing UPCR reductions of over 60% at 36 weeks, remission, resolution of hematuria, and stable renal function. Successful end of phase 2 meeting with FDA supports advancement to phase 3 study. Key biomarkers Gd-IgA1 and Gd-IgA1/C3 ratios significantly reduced. Monthly dosing well-tolerated with no severe infections.
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The recent announcement by Alpine Immune Sciences regarding the successful conclusion of a phase 2 meeting with the FDA for povetacicept in IgA nephropathy (IgAN) represents a significant milestone in the drug's clinical development. The progression to a phase 3 study is a pivotal step, indicating the treatment has shown sufficient promise in earlier trials to warrant a more extensive investigation into its efficacy and safety.

From an investment perspective, this transition from phase 2 to phase 3 can be a value inflection point for Alpine Immune Sciences, as it suggests a level of confidence from the regulatory body, which could positively influence investor sentiment. However, it is important to note that clinical trials are inherently risky and a successful phase 2 outcome does not guarantee phase 3 success or regulatory approval.

The reported data showing a reduction in UPCR of greater than 60% and stabilization of renal function are encouraging, as proteinuria is a key indicator of kidney damage in IgAN patients. The potential for povetacicept to become a front-line disease-modifying treatment, if approved, could disrupt the current treatment landscape and provide a new option for patients suffering from this chronic kidney disease. The long-term impact on Alpine's financials would depend on the drug's market uptake, pricing and competitive landscape at the time of potential approval.

The clinical improvements observed with povetacicept in IgAN patients, such as the significant reduction in proteinuria and the stabilization of renal function, are medically significant. Proteinuria is not only a marker of disease activity but also a prognostic indicator and its reduction is associated with better long-term kidney outcomes. The resolution of hematuria, another common symptom of IgAN, further indicates a positive response to the treatment.

As a nephrologist, the dual antagonism of BAFF and APRIL by povetacicept is noteworthy because these cytokines are implicated in the pathogenesis of IgAN. By targeting these pathways, povetacicept could address the underlying immune dysfunction in IgAN, which is not directly targeted by current standard-of-care treatments that primarily focus on controlling blood pressure and proteinuria. This novel mechanism of action could be revolutionary in the management of IgAN if the phase 3 trials confirm efficacy and safety.

Moreover, the monthly subcutaneous administration of povetacicept may offer a more convenient option for patients compared to current therapies, potentially improving adherence and outcomes. However, the long-term implications for kidney function and the impact on end-stage renal disease progression, a critical concern for IgAN patients, will need to be assessed in the forthcoming phase 3 studies.

The advancement of povetacicept into phase 3 trials could have a notable impact on Alpine Immune Sciences' market positioning. IgAN, being a rare disease with limited effective treatment options, represents a high unmet medical need and a potentially lucrative market niche for novel therapies like povetacicept. The biotech sector often sees increased volatility around key clinical trial milestones and this announcement could lead to heightened investor interest in Alpine's stock.

Market analysts will be closely monitoring the enrollment and progress of the phase 3 study, as well as any partnership or licensing deals that may arise as a result of these positive developments. The biotech industry values innovation, especially in areas of unmet need and Alpine's focus on autoimmune and inflammatory diseases places it in a high-growth potential market segment.

Investors will also be interested in the broader implications of povetacicept's mechanism of action. If successful in IgAN, there may be potential for its application in other autoimmune diseases, which could significantly expand the drug's market potential. The company's strategic planning and execution of subsequent studies will be critical in determining its future valuation and market share.

-- Povetacicept administered subcutaneously once every four weeks continues to be well tolerated in IgA nephropathy, with UPCR reductions of greater than 60% observed at 36 weeks, associated with remission, resolution of hematuria, and stable renal function (eGFR) --

-- Company reports successful end of phase 2 meeting with FDA, supporting advancement to a registrational, placebo-controlled phase 3 study of povetacicept in IgA nephropathy, targeted in 2H 2024 --

-- Company will host an investor call and webcast today at 5:15 pm ET --

SEATTLE--(BUSINESS WIRE)-- Alpine Immune Sciences, Inc. (NASDAQ: ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for autoimmune and inflammatory diseases, today shared updated clinical data for povetacicept in IgA nephropathy (IgAN) which will be presented as a late breaking poster at the World Congress of Nephrology (WCN) April 13-16, 2024 in Buenos Aires, Argentina.

Figure 1. Povetacicept is Associated with Clinically Meaningful UPCR Reductions, Stable eGFR in IgA Nephropathy, and Reductions in Gd-IgA1 and Gd-IgA1/C3 Ratio (Graphic: Business Wire)

Figure 1. Povetacicept is Associated with Clinically Meaningful UPCR Reductions, Stable eGFR in IgA Nephropathy, and Reductions in Gd-IgA1 and Gd-IgA1/C3 Ratio (Graphic: Business Wire)

Povetacicept is a potent dual antagonist of the BAFF (B cell activating factor) and APRIL (a proliferation inducing ligand) cytokines, which play key roles in pathogenesis of multiple autoimmune diseases via their roles in the activation, differentiation and/or survival of B cells, particularly antibody-secreting cells, as well as T cells and innate immune cells. RUBY-3 is a multiple ascending dose, multi-cohort, open label, phase 1b/2a study of povetacicept in autoimmune glomerulonephritis, including IgA nephropathy, where povetacicept is administered subcutaneously (SC) once every four weeks.

Key Highlights Include:

  • As of March 01, 2024, 41 patients with IgAN had received povetacicept 80 or 240 mg subcutaneously every 4 weeks. Treatment with povetacicept 80 mg SC Q4W has been associated with a clinically meaningful improvement in proteinuria, with a 64.1% reduction from baseline in urine protein to creatinine ratio (UPCR; n=6) at 36 weeks, associated with stable renal function as assessed by estimated glomerular filtration rate (eGFR). At this same time, 4/6 (67%) had achieved remission, as defined as UPCR < 0.5 g/g, ≥50% reduction in UPCR from baseline, and stable renal function (≤ 25% reduction in eGFR from baseline).
  • Resolution of hematuria, as defined as negative or trace/small hematuria in patients with non-negative/trace hematuria at baseline, was achieved in all (100%) patients with data available at 36 or more weeks (N=4).
  • Treatment with povetacicept 240 mg SC Q4W has been associated with similar improvements in proteinuria, stable renal function, and remission, based on initial data through 12 (13 patients) and 24 (2 patients) weeks.
  • Treatment with both doses was associated with significant reductions in the key disease-related biomarker Gd-IgA1, with the 80 mg dose achieving a 68.9% reduction at 40 weeks, and the 240 mg dose achieving a 78.6% reduction at 20 weeks. Both doses achieved reductions in IgA/C3 and Gd-IgA1/C3 ratios, which are additional severity and prognostic biomarkers in IgAN.
  • Both doses have been well tolerated in IgAN, with no instances of IgG < 3 g/L and no severe infections.

“These updated findings for povetacicept are highly promising and continue to support the potential for the program as an important new therapy in IgA nephropathy,” noted Jonathan Barratt, M.D., the Mayer Professor of Renal Medicine and Honorary Consultant Nephrologist and IgA Nephropathy Rare Disease Group Lead, University of Leicester. “The marked and clinically meaningful improvement in UPCR and stable eGFR observed with a monthly dosing regimen at 36 weeks are particularly impressive, as are the deep reductions in Gd-IgA1, a key disease-related biomarker, and resolution of hematuria in patients. The lack of serious adverse events with longer duration of treatment and higher dose is also notable and, together with povetacicept’s disease modifying potential and substantial patient experience, strongly supports the rapid advancement of povetacicept into a pivotal study for IgA nephropathy.”

“Despite advancements in IgA nephropathy, there remains an urgent need for safe and convenient therapies that effectively treat the underlying cause of the disease,” said James Tumlin, M.D., Professor of Medicine at Emory University School of Medicine, Founder and CEO of NephroNet Clinical Trials Consortium. “Dual APRIL/BAFF inhibition is a potent inhibitor of Galactose Deficient IgA1 (Gd-IgA1) production which is closely linked to the pathogenesis and progression of IgA nephropathy. Monthly administration of povetacicept has been shown to be well-tolerated at both the 80mg and 240 mg doses with clinical responses including Gd-IgA1, urine protein levels and eGFR stabilization within 3 months. These data strongly support the inhibition of APRIL/BAFF pathways by povetacicept and its efficacy in the treatment of IgAN as well as the need for further clinical development. If approved, povetacicept could be used a front-line disease modifying treatment in IgAN.”

“These data indeed continue to further our enthusiasm for the potential of povetacicept in IgAN and other autoimmune diseases,” remarked Stanford Peng, MD PhD, President and Head of Research and Development at Alpine. “We are pleased to have completed our successful end of phase 2 meeting with FDA, enabling advancement to a registrational trial in IgAN (RAINIER) later this year. In addition, we plan to continue to explore povetacicept’s potential in multiple other autoimmune diseases via the ongoing RUBY-3 and RUBY-4 studies, and via the initiation of a phase 2 study (DENALI) in systemic lupus erythematosus later this year.”

World Congress of Nephrology Late-Breaking Poster

Date/Time: Monday, April 15, 2024, 5:45 pm local time (GMT-3) /4:45 pm ET/1:45 pm PT
Poster Title: Updated Results from the RUBY-3 study of Povetacicept, an Enhanced Dual BAFF/APRIL Antagonist in IgA Nephropathy
Poster Number: MON-304
Session Name: Poster Session 3 (Late Breaking)
Location: Exhibition Hall and Main Foyer, Buenos Aires Convention Center, Buenos Aires, Argentina
Presenter: James Tumlin, M.D., Professor of Medicine at Emory University School of Medicine, Founder and CEO of NephroNet Clinical Trials Consortium

Alpine will host an investor call and webcast to discuss the data update as well as provide a corporate update.

The link to the webcast is available in the investor relations section of the Company’s website at https://ir.alpineimmunesciences.com/events and a replay will be available on the Company's website for 90 days following the live event.

About Povetacicept (ALPN-303)

Povetacicept (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 pathogenesis of multiple autoimmune diseases via their roles in the activation, differentiation and/or survival of B cells, particularly antibody-secreting cells, as well as T cells and innate immune cells. Based upon an engineered TACI (transmembrane activator and CAML interactor) domain, povetacicept has exhibited greater potency in preclinical studies versus other inhibitors of BAFF and/or APRIL alone and B cell depletion and has demonstrated initial activity in patients with IgA nephropathy. Povetacicept is in development for multiple autoimmune diseases, including IgA nephropathy and other autoimmune kidney diseases, systemic lupus erythematosus, and autoimmune cytopenias.

About RUBY-3

RUBY-3 (NCT05732402) is a multiple ascending dose, multi-cohort, open label, phase 1b/2 study of povetacicept in autoimmune glomerulonephritis, including IgA nephropathy, primary membranous nephropathy, lupus nephritis, and renal ANCA-associated vasculitis, where povetacicept is being administered subcutaneously for up to 104 weeks. Key endpoints include proteinuria, eGFR, renal response, and disease-related autoantibodies.

About RUBY-4

RUBY-4 (NCT05757570) is a multi-cohort, open label study of povetacicept in autoimmune cytopenias, including immune thrombocytopenia, autoimmune hemolytic anemia, and cold agglutinin disease, where povetacicept is being administered subcutaneously for up to 48 weeks. Key endpoints include respective blood cell counts, durable responses, as well as disease-related autoantibodies.

About RAINIER

RAINIER is an upcoming, randomized, double-blind, placebo-controlled, pivotal phase 3 study to evaluate the safety and efficacy of povetacicept in patients with IgA nephropathy at risk of progression to kidney failure.

About DENALI

DENALI is an upcoming, randomized, double-blind, placebo-controlled phase 2 study to evaluate the safety and efficacy of povetacicept in patients with active systemic lupus erythematosus.

About Alpine Immune Sciences

Alpine Immune Sciences is committed to leading a new wave of immune therapeutics. With world-class research and development capabilities, a highly productive scientific platform, and a proven management team, Alpine is seeking to create first- or best-in-class multifunctional immunotherapies via unique protein engineering technologies to improve patients’ lives. Alpine has entered into strategic collaborations with leading global biopharmaceutical companies and has a diverse pipeline of clinical and preclinical candidates in development. For more information, visit www.alpineimmunesciences.com. Follow @AlpineImmuneSci on X and LinkedIn.

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, including cash equivalents and restricted cash, and investments to fund our planned operations; 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 as well as a phase 2 study in systemic lupus erythematosus, 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; 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.

Additional Information about the Acquisition (the offer) of Alpine by Vertex Pharmaceuticals Incorporated (Vertex) and Where to Find It

The offer has not yet commenced. This press release is for informational purposes only, is not a recommendation and is neither an offer to purchase nor a solicitation of an offer to sell any securities, nor is it a substitute for the tender offer materials that Vertex and the Purchaser will file with the SEC upon commencement of the offer. A solicitation and offer to buy outstanding shares of Alpine will only be made pursuant to the tender offer materials that Vertex and the Purchaser intend to file with the SEC. At the time the offer is commenced, Vertex and the Purchaser will file with the SEC tender offer materials on Schedule TO, and Alpine will file with the SEC a Solicitation/Recommendation Statement on Schedule 14D-9 with respect to the offer.

THE TENDER OFFER MATERIALS (INCLUDING AN OFFER TO PURCHASE, A RELATED LETTER OF TRANSMITTAL AND CERTAIN OTHER TENDER OFFER DOCUMENTS) AND THE SOLICITATION/RECOMMENDATION STATEMENT WILL CONTAIN IMPORTANT INFORMATION ABOUT THE PROPOSED TRANSACTION AND THE PARTIES THERETO. INVESTORS AND STOCKHOLDERS OF ALPINE ARE URGED TO READ THESE DOCUMENTS CAREFULLY WHEN THEY BECOME AVAILABLE (AND EACH AS IT MAY BE AMENDED OR SUPPLEMENTED FROM TIME TO TIME), BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION THAT INVESTORS AND STOCKHOLDERS OF ALPINE SHOULD CONSIDER BEFORE MAKING ANY DECISION REGARDING TENDERING THEIR SHARES OF COMMON STOCK IN THE OFFER. The tender offer materials (including the Offer to Purchase and the related Letter of Transmittal) will be made available to all stockholders of Alpine at no expense to them under the “Investors” section of Vertex’s website at https://investors.vrtx.com/financial-information/sec-filings or by email at Investorinfo@VRTX.com, or by directing requests for such materials to the information agent for the offer, which will be named in the tender offer materials, and (once they become available) the tender offer materials as well as the Solicitation/Recommendation Statement will be mailed to the stockholders of Alpine free of charge. Copies of the documents filed with the SEC by Alpine will be available free of charge on Alpine’s website, ir.alpineimmunesciences.com, or by contacting Alpine’s investor relations department at ir@alpineimmunesciences.com. The information contained in, or that can be accessed through, Vertex’s website and Alpine’s website is not a part of or incorporated by reference herein. The tender offer materials (including the Offer to Purchase and the related Letter of Transmittal), as well as the Solicitation/Recommendation Statement, will also be made available for free on the SEC’s website at www.sec.gov. In addition to the Offer to Purchase, the related Letter of Transmittal and certain other tender offer documents, as well as the Solicitation/Recommendation Statement, Vertex and Alpine file annual, quarterly, and current reports, proxy statements, and other information with the SEC. You may read any reports, statements, or other information filed by Vertex and Alpine with the SEC for free on the SEC’s website at www.sec.gov.

Media and Investor Relations Contact:

Alpine Immune Sciences, Inc.

ir@alpineimmunesciences.com

media@alpineimmunesciences.com

Source: Alpine Immune Sciences, Inc.

FAQ

What is the clinical data shared by Alpine Immune Sciences, Inc. (ALPN) for povetacicept in IgA nephropathy?

Alpine Immune Sciences, Inc. (ALPN) shared updated clinical data for povetacicept in IgA nephropathy, including UPCR reductions of over 60% at 36 weeks, remission, resolution of hematuria, and stable renal function.

What supports the advancement of povetacicept to a phase 3 study according to the press release?

The successful end of phase 2 meeting with FDA supports the advancement of povetacicept to a registrational, placebo-controlled phase 3 study in IgA nephropathy targeted in the second half of 2024.

What key biomarkers were significantly reduced by povetacicept in IgA nephropathy?

Key biomarkers Gd-IgA1 and Gd-IgA1/C3 ratios were significantly reduced by povetacicept in IgA nephropathy.

How was the monthly dosing of povetacicept in IgA nephropathy described in the press release?

The monthly dosing of povetacicept in IgA nephropathy was well-tolerated with no instances of IgG < 3 g/L and no severe infections reported.

Alpine Immune Sciences, Inc.

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About ALPN

founded in 2015 by a team responsible for the fda's approval of the world's first cancer immunotherapy and experts in the field of recombinant protein based immunotherapies, alpine immune sciences was created to capitalize on our unique understanding of immunology, modifying the complexities of the immune synapse for the benefit of patients living with cancer, autoimmune disorders, and other diseases. traded on nasdaq under ticker alpn.