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| Item 7.01 | Regulation FD Disclosure. |
On October 2, 2024, Vera Therapeutics, Inc. (the “Company”) announced an expanded atacicept development program in multiple autoimmune kidney diseases through the initiation of two new studies – ORIGIN Extend and PIONEER. A copy of the press release is furnished as Exhibit 99.1. In connection with the press release, the Company compiled a presentation entitled “R&D Day” (the “R&D Day Presentation”) that includes a discussion of the study design and purpose of ORIGIN Extend and PIONEER. A copy of the R&D Day Presentation is furnished as Exhibit 99.2. For important information about forward-looking statements, see the slide titled “Forward-Looking Statements” in Exhibit 99.2 attached hereto.
The information in this Item 7.01 of this Current Report on Form 8-K, including Exhibits 99.1 and 99.2, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended. The information contained in this Item 7.01, including Exhibits 99.1 and 99.2, shall not be incorporated by reference into any filing with the U.S. Securities and Exchange Commission (“SEC”) made by the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.
| Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits.
| Exhibit |
Description | |
| 99.1 | Press Release of Vera Therapeutics, Inc., dated October 2, 2024. | |
| 99.2 | Slide presentation entitled “R&D Day”. | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Vera Therapeutics, Inc. | ||||||
| Dated: October 2, 2024 | ||||||
| By: | /s/ Marshall Fordyce, M.D. | |||||
| Marshall Fordyce, M.D. | ||||||
| Chief Executive Officer | ||||||
Exhibit 99.1
Vera Therapeutics Announces Expanded Atacicept Development Program In Multiple Autoimmune Kidney Diseases
| • | PIONEER study expands the investigation of atacicept into a broad definition of IgA nephropathy and into multiple autoimmune glomerular diseases, supported by the disease-modifying potential of BAFF/APRIL dual inhibition; |
| • | Multiple regulatory and clinical milestones expected over the next 18 months; |
| • | Announcements made at Vera’s R&D Day in New York, where the company’s management team was joined by academic leaders Jonathan Barratt, Richard Lafayette, and Brad Rovin |
BRISBANE, Calif., October 2, 2024 (GLOBE NEWSWIRE) — Vera Therapeutics, Inc. (Nasdaq: VERA), a late clinical-stage biotechnology company focused on developing and commercializing transformative treatments for patients with serious immunological diseases, today announced expansion of its development pipeline for its lead asset, atacicept. This program is expected to build on the positive data reported to date from the ongoing ORIGIN Phase 2b and 3 clinical program developing atacicept to treat patients with IgAN, by extending into a broader population of IgAN and other autoimmune kidney indications.
“Based on the positive clinical data announced over the past year, we have a greater understanding of atacicept’s disease-modifying mechanism of action and potential to be a best-in-class treatment option for patients with IgAN. We’re committed to providing long-term access to atacicept for all ORIGIN participants, and the PIONEER study will expand that opportunity to a significantly greater number of patients with IgAN,” said Marshall Fordyce, M.D., Founder and CEO of Vera Therapeutics. “We believe that B cell modulation through BAFF/APRIL dual inhibition has the potential to transform the treatment landscape for other autoimmune diseases, including autoimmune forms of primary membranous nephropathy, focal segmental glomerulosclerosis, and minimal change disease.”
“We view this expansion of our pipeline as highly complementary to our lead program in IgAN. As such, we remain focused on completing the pivotal clinical program for atacicept in IgAN. We look forward to keeping everyone apprised of our progress, as we have a number of significant milestones planned across our pipeline,” concluded Dr. Fordyce.
| • | ORIGIN Extend – The company plans to initiate a study in Q4 2024 that will provide ORIGIN participants with extended access to atacicept prior to commercial availability in their region, as well as an opportunity to capture longer-term data. |
| • | PIONEER Study – In 2025, the company plans to initiate a study evaluating the efficacy and safety of atacicept in: |
| • | Expanded IgAN populations – The first set of cohorts will include adults with low kidney function (eGFR 20 to <30 mL/min/1.73 m2), low (UPCR <1.0 g/g) or high proteinuria (UPCR ≥5.0 g/g), or IgAN recurrence after kidney transplant; adolescents at high risk of progression (UPCR ≥0.3 g/g); as well as adolescents and adults with IgA vasculitis nephritis. |
| • | Anti-PLA2R and anti-nephrin podocytopathies – The PIONEER study will expand to additional autoimmune glomerular diseases characterized by the presence of antibodies to glomerular antigens, including primary membranous nephropathy (pMN), focal segmental glomerulosclerosis (FSGS), and minimal change disease (MCD). |
These new indications represent a significant potential opportunity for atacicept, with the combined peak prevalence of IgAN and autoimmune-driven PMN, FSGS, and MCD in the US estimated at ~230,000. The company believes atacicept may have therapeutic potential in additional rheumatologic and hematologic indications.
Vera’s management team was joined by Jonathan Barratt, MD, PhD, FRCP (University of Leicester), Richard Lafayette, MD, FACP (Stanford University Medical Center), and Brad Rovin, MD, FACP, FASN (Ohio State University Wexner Medical Center). A replay of the event is available on the Investor Calendar of the company’s website at https://ir.veratx.com or (click here).
The R&D event was held in advance of the anticipated 96-week data from the Phase 2b ORIGIN study of atacicept in immunoglobulin A nephropathy (IgAN), which will be presented as a Late Breaking Oral Presentation at the American Society of Nephrology Kidney Week 2024.
About Vera
Vera Therapeutics is a late clinical-stage biotechnology company focused on developing treatments for serious immunological diseases. Vera’s mission is to advance treatments that target the source of immunological diseases in order to change the standard of care for patients. Vera’s lead product candidate is atacicept, a fusion protein self-administered as a subcutaneous injection once weekly that blocks both B-cell Activating Factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL), which stimulate B cells and plasma cells to produce autoantibodies contributing to certain autoimmune diseases, including IgAN, also known as Berger’s disease, and lupus nephritis. In addition, Vera is evaluating additional diseases where the reduction of autoantibodies by atacicept may prove medically useful. Vera is also developing MAU868, a monoclonal antibody designed to neutralize infection with BK virus (BKV), a polyomavirus that can have devastating consequences in certain settings such as kidney transplant. Vera retains all global developmental and commercial rights to atacicept and MAU868. For more information, please visit www.veratx.com.
About Atacicept
Atacicept is an investigational recombinant fusion protein that contains the soluble transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) receptor that binds to the cytokines B-cell activating factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL). These cytokines are members of the tumor necrosis factor family that promote B-cell survival and autoantibody production associated with certain autoimmune diseases, including IgAN and lupus nephritis.
The Phase 2b ORIGIN clinical trial of atacicept in IgAN met its primary and key secondary endpoints, with statistically significant and clinically meaningful proteinuria reductions and stabilization of eGFR versus placebo through 36 weeks. The safety profile during the randomized period was comparable between atacicept and placebo. Through 72 weeks, atacicept demonstrated further reductions in Gd-IgA1, hematuria, and proteinuria, as well as stabilization of eGFR reflecting a profile consistent with that of the general population without IgAN.
Atacicept has received FDA Breakthrough Therapy Designation for the treatment of IgAN, which reflects the FDA’s determination that, based on an assessment of data from the Phase 2b ORIGIN clinical trial, atacicept may demonstrate substantial improvement on a clinically significant endpoint over available therapies for patients with IgAN. Vera believes atacicept is positioned for best-in-class potential, targeting B cells and plasma cells to reduce autoantibodies and having been administered to more than 1,500 patients in clinical studies across different indications.
Forward-looking Statements
Statements contained in this press release regarding matters, events or results that may occur in the future are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, Vera’s expectations regarding the expansion of its development pipeline for atacicept, atacicept’s potential to be a best-in-class treatment for patients with IgAN, Vera’s expectations regarding the potential for B cell modulation through BAFF/APRIL dual inhibition to transform the treatment landscape for certain autoimmune diseases, Vera’s plans to initiate a study in the fourth quarter of 2024 providing extended access to atacicept to ORIGIN participants, Vera’s plans to initiate the PIONEER study in 2025, Vera’s anticipated presentations of clinical trial data, and Vera’s product candidates, strategy, and regulatory matters. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “expanded,” “substantial,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Vera’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks related to the regulatory approval process, results of earlier clinical trials may not be obtained in later clinical trials, preliminary results may not be predictive of topline results, risks and uncertainties
associated with Vera’s business in general, the impact of macroeconomic and geopolitical events, and the other risks described in Vera’s filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. Vera undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.
For more information, please contact:
Investor Contact:
Joyce Allaire
LifeSci Advisors
212-915-2569
jallaire@lifesciadvisors.com
Media Contact:
Madelin Hawtin
LifeSci Communications
MHawtin@lifescicomms.com
Exhibit 99.2 R&D Day October 2, 2024 © 2024 VERA THERAPEUTICS, INC.
Forward-looking statements Disclaimer This material has been made available to you with the consent of Vera Therapeutics, Inc. ( we , us , our , or the Company ). Statements in this presentation that are not statements of historical fact are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include, without limitation, atacicept's potential to be a transformational treatment for patients with IgAN and a best-in-class and first-in-class therapy, the Company's expectations regarding the presentation of anticipated 96-week data from the Phase 2b ORIGIN trial at ASN Kidney Week, the Company's expectations regarding completing the pivotal Phase 3 ORIGIN 3 trial and initiating a Phase 2 extension study in participants who complete the Phase 2b or Phase 3 ORIGIN trials, atacicept's potential to be a transformational treatment for additional patient cohorts beyond those with IgAN, the Company's expectations regarding initiating clinical trials of atacicept for additional indications, the design and management of the Company's clinical trials, expectations regarding reporting results from such clinical trials and regulatory matters, including the timing and likelihood of success in obtaining drug approvals and atacicept's projected launch. Words such as “believe,” “anticipate,” “plan,” “expect,” “intend,” “will,” “may,” “goal,” “project,” “estimate,” “on track,” “potential” and similar expressions are intended to identify forward-looking statements, though not all forward-looking statements necessarily contain these identifying words. These forward-looking statements are based on the beliefs of the Company’s management as well as assumptions made by and information currently available to the Company. Such statements reflect the current views of the Company with respect to future events and are subject to known and unknown risks, including business, regulatory, economic and competitive risks, uncertainties, contingencies and assumptions about the Company, including, without limitation, risks related to the regulatory approval process, the potential that results of earlier clinical trials may not be obtained in later clinical trials, risks and uncertainties associated with the Company's business in general, the impact of macroeconomic and geopolitical events, including the COVID-19 pandemic, and the other risks described in the Company's filings with the Securities and Exchange Commission. In light of these risks and uncertainties, the events or circumstances referred to in the forward-looking statements may not occur. The actual results may vary from the anticipated results and the variations may be material. These forward-looking statements should not be taken as forecasts or promises nor should they be taken as implying any indication, assurance or guarantee that the assumptions on which such forward-looking statements have been made are correct or exhaustive or, in the case of the assumptions, fully stated in this presentation. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this presentation, and are based on management's assumptions and estimates as of such date. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. This presentation does not constitute an offer to sell or the solicitation of an offer to buy any securities, or a solicitation of any vote or approval, nor shall there be any sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction. Investment in any securities described herein has not been approved or disapproved by the Securities and Exchange Commission or any other regulatory authority nor has any authority passed upon or endorsed the merits of the offering or the accuracy or adequacy of the information contained herein. Any representation to the contrary is a criminal offense. This presentation discusses product candidates that are under clinical study and which have not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to the safety or effectiveness of these product candidates for the use for which such product candidates are being studied. The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products. 2 © 2024 VERA THERAPEUTICS, INC.
Agenda Marshall Fordyce, MD Opening Remarks Founder and CEO, Vera Therapeutics Robert Brenner, MD Vera Expansion Strategy Chief Medical Officer, Vera Therapeutics Q&A Panel Jonathan Barratt, MD, PhD, FRCP Mayer Professor of Renal Medicine, University of Leicester Richard Lafayette, MD, FACP Professor of Medicine (Nephrology), Stanford University Medical Center Director, Stanford Glomerular Disease Center Brad Rovin, MD, FACP, FASN Lee A. Herbert Professor of Nephrology Ohio State University Wexner Medical Center Marshall Fordyce, MD Closing Remarks Founder and CEO, Vera Therapeutics 3 © 2024 VERA THERAPEUTICS, INC.
Atacicept potentially best and first-in-class dual BAFF/APRIL B cell modulator in IgAN, with pipeline-in-a-product opportunity IgAN Potential Best-in-Class Indication Expansion Resourced for Potential Launch • eGFR normalization may suggest • B cell modulation represents a • Regulatory exclusivity expected functional cure treatment paradigm shift for through 2038 in US and 2037 in EU autoimmune diseases • Only program with 2-yr data in Phase 2 • Currently ~$384M cash, cash → potential for commercial • Atacicept clinical data to date supports equivalents and marketable securities differentiation, if approved potential for chronic administration as of June 30, 2024 • Only investigational drug with at home • Progressive expansion in addressable • Management focused on potential for self administration of 1 mL QW and patients: initial autoimmune kidney successful commercial launch >90% patient retention at 1.5 yr disease opportunity >200K • Phase 3 read out on track for Q2 2025; • Additional potential upside in if successful, anticipated PDUFA 2026 hematologic, rheumatologic, and other kidney indications BAFF = B cell activating factor; APRIL = A proliferation inducing ligand; eGFR = estimated glomerular filtration rate; IgAN = IgA nephropathy; SC = subcutaneous. 4 © 2024 VERA THERAPEUTICS, INC.
Cumulative Atacicept data offers best-in-class potential 1 2 3 Atacicept Sibeprenlimab Povetacicept Zigakibart Mechanism BAFF/APRIL inhibition APRIL inhibition only BAFF/APRIL inhibition APRIL inhibition only 25/75/150 mg SC QW (Ph2) 2/4/8 mg/kg IV (Ph2) 450 mg IV Q2W (Ph2) Dosing & 80/240 mg SC QM (Ph1b) 150 mg SC QW (Ph3) 400 mg SC QM (Ph3) 600 mg SC Q2W (Ph3) Administration 1xTBD mL injection 1x1 mL self-administered 1x2 mL in-clinic injection 2x2 mL in-clinic injection Development Stage Ph3 Ph3 Ph3 Ph3 Randomized ✓✓✗✗ Controlled Trial Data 64% at W36 ~60% at W52 No placebo No placebo Gd-IgA1 Reduction vs 7% placebo vs ~+20% placebo controlled data controlled data Reductions at W36 Hematuria 80% resolution at W36 Not reported Not reported (nonquantifiable) UPCR Reduction No placebo No placebo Δ 43% (p=0.003) at W36 Δ 43% at W36 vs Placebo controlled data controlled data 18 months, n=109 eGFR Duration Data 12 months, n=145 12 months, n=1 12 months, n=35 24 months coming soon* Projected 2026 2026 2027 2027 Commercial Launch *To be presented at ASN Kidney Week 2024. This data is based on a cross-trial comparison and not a head-to-head clinical trial; such data may not be directly comparable due to differences in study protocols, conditions and patient populations. Atacicept 150 mg data shown for urine protein-creatinine ratio (UPCR), galactose-deficient immunoglobulin A1 (Gd-IgA1), and hematuria. 1. Ph2 4 mg/kg IV Gd-IgA1 data from Mathur M, et al. NEJM 2023, Ph2 4 mg/kg IV hematuria data from Barratt J, et al. WCN 2024, WCN24-AB-1799, Ph2 pooled sibeprenlimab UPCR data from Kooienga ASN 2022, TH-PO991, and estimated glomerular filtration rate (eGFR) data from Barratt J, et al. ASN 2023, abstr TH-PO1124; 2. Ph1b 80 mg data from Tumlin J, et al. ASN 2023, TH-PO1125, and Tumlin J, et al. WCN 2024, WCN24-AB-762. 3. Barratt J, et al. ERA 2024, late breaking abstract. 5 © 2024 VERA THERAPEUTICS, INC.
Vera optionality to expand in autoimmune kidney disease & beyond US prevalence estimates ~230K Potential Future Indications 1-10 + ~70K Hematology ITP, AIHA, CAD, APS 1 ~160K Rheumatology Non-IgAN SLE, Sjogren’s, Long COVID autoimmune Neurology kidney disease MG pMN, FSGS, MCD and Metabolism Expanded IgAN DM Type 1 Atacicept Vera Therapeutics corporate estimates for peak year prevalence based on 1. ClearView Healthcare Partners Analysis; 2. US Census 2023; 3. McGrogan A. Nephrol Dial Transplant 2011; 4. Couser ASN 2017; 5. Beck LH. N Engl J Med 2009; 6. Filler G. Am J Kidney Dis 2003; 7. Troyanov S. J Am Soc Nephrol 2005. 8. Hommos MS. Mayo Clin Proc 2017; 9. Hengel FE. N Engl J Med 2024; 10. Vivarelli M. Clin J Am Soc Nephrol 2017. pMN = primary membranous nephropathy; FSGS = focal segmental glomerulosclerosis; MCD = minimal change disease; ITP = immune thrombocytopenia; AIHA = autoimmune hemolytic anemia; CAD = cold agglutinin disease; APS = antiphospholipid syndrome; SLE = systemic lupus erythematosus; MG = myasthenia gravis; COVID = Coronavirus disease 2019; DM = diabetes mellitus. 6 © 2024 VERA THERAPEUTICS, INC.
Vera financial position is strong ~$384M ~54.8M Cash, cash equivalents, Shares outstanding (as of 8.5.24) and marketable securities (as of 6.30.24) 7 © 2024 VERA THERAPEUTICS, INC.
Atacicept: previously shared projected catalysts Catalyst 2024 2025 2026 Phase 3 primary endpoint cohort full enrollment 3Q Phase 2b 96-week results 4Q Phase 3 top-line results 2Q (IgAN) BLA submission 2H Projected US launch Vera holds worldwide, exclusive rights to develop and commercialize atacicept Based on management’s current assumptions. 8 © 2024 VERA THERAPEUTICS, INC.
Atacicept: additional projected catalysts Catalyst 2024 2025 2026 Phase 3 primary endpoint cohort full enrollment 3Q Phase 2b 96-week results 4Q Phase 3 top-line results 2Q (IgAN) BLA submission 2H Projected US launch Initiation New clinical trial Initial data available Initiation New clinical trial Initial data available Vera holds worldwide, exclusive rights to develop and commercialize atacicept Based on management’s current assumptions. 9 © 2024 VERA THERAPEUTICS, INC.
Agenda Marshall Fordyce, MD Opening Remarks Founder and CEO, Vera Therapeutics Robert Brenner, MD Vera Expansion Strategy Chief Medical Officer, Vera Therapeutics Q&A Panel Jonathan Barratt, MD, PhD, FRCP Mayer Professor of Renal Medicine, University of Leicester Richard Lafayette, MD, FACP Professor of Medicine (Nephrology), Stanford University Medical Center Director, Stanford Glomerular Disease Center Brad Rovin, MD, FACP, FASN Lee A. Herbert Professor of Nephrology Ohio State University Wexner Medical Center Marshall Fordyce, MD Closing Remarks Founder and CEO, Vera Therapeutics 10 © 2024 VERA THERAPEUTICS, INC.
Atacicept has broad therapeutic potential in autoimmune disease Immunity in health BAFF Antibodies bind to foreign antigens B cell APRIL Autoimmune disease Autoantigens and autoantibodies mediate autoimmune disease BAFF Autoantibodies bind to autoantigens B cells are the source of autoantibodies → B target cell of interest for therapeutic intervention cell B cells are fueled by two (and only two) cytokines, BAFF and APRIL APRIL Atacicept: Rationally designed therapeutic of modern biotechnology that binds BAFF and APRIL with nanomolar potency offers the promise of precision modulation of B cells and autoantibodies 11 © 2024 VERA THERAPEUTICS, INC.
Lead indication: IgAN is a disease of B cell origin with kidney pathology B Cell Activation Formation of Circulating Immune Complexes Immune Complex Deposition Leading to Glomerulonephritis and Kidney Damage Autoantigen (Gd-IgA1) BAFF B cell Glomerulus APRIL Autoantibody (anti-Gd-IgA1) 1 2 3 4 6 BAFF and APRIL are Activated B cells produce …forming …which deposit in the …and progressive upregulated and autoantigen (Gd-IgA1) and immune mesangium, resulting in kidney injury with activate B cells via autoantibodies (anti-Gd-IgA1)… complexes… glomerular inflammation hematuria, proteinuria, the TACI receptor (nephritis)… and eGFR decline TACI = transmembrane activator and calcium-modulator and cyclophilin ligand. 12 © 2024 VERA THERAPEUTICS, INC.
Atacicept is an example of rational drug design Native TACI-Fc fusion: Soluble protein binds both BAFF and APRIL with nanomolar potency Atacicept BAFF APRIL BAFF APRIL 1 t =35 days 1/2 Kd Kd 2 2 1.45 nM 0.672 nM TACI TACI receptor receptor B cell B cell Fc domain of IgG1 Fc = fragment crystallizable. 1. Willen D, et al. Eur J Drug Metab Pharmacokinet 2020;45(1):27-40; 2. Vera data on file. 13 © 2024 VERA THERAPEUTICS, INC.
An ideal IgAN disease modifying therapy would be expected to… Reduce Reduce Reduce Convert eGFR profile to Gd-IgA1 hematuria proteinuria general population 14 © 2024 VERA THERAPEUTICS, INC.
ORIGIN Phase 2b 72-week results consistent with IgAN FDA Breakthrough disease modification Therapy Designation Including eGFR Profile consistent with the general population of -1 mL/min/year Reduction in Reduction in Reduction in eGFR profile consistent Gd-IgA1 hematuria proteinuria with general population 0 0 0 20 150 mg OLE 150 mg OLE 150 mg OLE 150 mg OLE -15 -20 -15 10 -30 -40 -30 0 -45 -60 -45 -10 -60 -80 -75 -100 -60 -20 0 12 24 36 48 60 72 0 12 24 36 48 60 72 0 12 24 36 48 60 72 0 12 24 36 48 60 72 Week Week Week Week Set the standard in IgAN Lafayette R, et al. ERA 2024, abstr 812. 1. Mean ± SE; 2. Change from baseline in percentage of participants with hematuria at each visit out of those with baseline hematuria. Data from participants originally randomized to any atacicept group in the double-blind period in the intent-to-treat analysis for Gd-IgA1, hematuria, UPCR and eGFR. OLE = open-label extension. 15 © 2024 VERA THERAPEUTICS, INC. 1 Gd-IgA1 % Change from Baseline 2 Change from Baseline in % Participants 1 UPCR % Change from Baseline 1 eGFR Change from Baseline, 2 mL/min/1.73m
Atacicept treated participants have an eGFR slope profile consistent with general population without kidney disease 4 All atacicept → 150 mg 0 Slope General population 1 ~ -1 estimate -4 1 mL/min/y IgAN natural history including supportive -8 2 CKD therapy Slope ~ -6 2 mL/min/y -12 0 4 12 24 36 48 60 72 82 96 Week This data is based on a cross-trial comparison and not a head-to-head clinical trial; such data may not be directly comparable due to differences in study protocols, conditions and patient populations. Projected eGFR trajectories for general population and IgAN natural history do not represent clinical data and assume a constant eGFR slope over time. CKD = chronic kidney disease. 1. Slope estimate from Baba M, et al. PLOS ONE 2015; 2. Average historical placebo slope from 7 clinical trials3-11; 3. Lafayette R, et al. Lancet 2023; 4. Rovin BH, et al. Lancet 2023; 5. Li PK-T, et al. Am J Kidney Dis 2006; 6. Manno C, et al. Nephrol Dial Transplant 2009; 7. Lv J, et al. JAMA 2017; 8. Wheeler DC, et al. Kidney Int 2021; 9. Lv J, et al. JAMA 2022; 10. Zhang H, et al. ASN Kidney Week 2023, poster TH-PO1123; 11. Mathur M, et al. N Engl J Med 2023. 16 © 2024 VERA THERAPEUTICS, INC. Mean Change from Baseline in 2 eGFR, mL/min/1.73m
2024 Draft KDIGO IgAN guidelines call for target eGFR slope ≤ -1 mL/min/year 1 % patients who will reach kidney failure 0 25 50 75 100 -0.1 0 0 2 2 1 1 -0.5 25 17 19 15 6 8 -1 56 40 38 40 23 16 -2 100 89 80 78 60 26 2 Filspari ~ -3 -3 100 100 100 91 85 46 3 4 SGLT2i , Tarpeyo ~ -4 -5 100 100 100 100 95 59 5 Generic CKD therapy ~ -6 0 – <18 18 – <30 30 – <40 40 – <50 50 – <60 60 – 75 Age group SGLT2i = sodium-glucose cotransporter-2 inhibitor. 1. Adapted from Pitcher D, et al. CJASN 2023; 2. Rovin BH, et al. Lancet 2023; 3. Wheeler DC, et al. Kidney Int 2021; 4. Lafayette R, et al. Lancet 2023; 5. Average historical placebo (including chronic kidney disease standard of care) data from 7 clinical trials: Li PK-T, et al. Am J Kidney Dis 2006; Manno C, et al. Nephrol Dial Transplant 2009; Lv J, et al. JAMA 2017; Wheeler DC, et al. Kidney Int 2021; Lv J, et al. JAMA 2022; Zhang H, et al. ASN Kidney Week 2023, poster TH-PO1123; Mathur M, et al. N Engl J Med 2023; Lafayette R, et al. Lancet 2023, Rovin BH, et al. Lancet 2023. 17 © 2024 VERA THERAPEUTICS, INC. 2 Annual eGFR slope, mL/min/1.73m
5-year mean mortality in ESKD comparable to cancer in US 80 72 60 59 40 36 20 9 0 Lung Cancer ESKD Colorectal Cancer Breast Cancer ESKD = end-stage kidney disease. 1. US CDC Cancer Statistics; 2. Thurlow JS, et al. Am J Nephrol 2021. 18 © 2024 VERA THERAPEUTICS, INC. 1,2 5-Year % Mortality in US
ORIGIN Phase 2b long-term data will be revealed in late breaking oral presentation during ASN Kidney Week Double-Blind Treatment Open-label Extension Placebo n=30 Atacicept 25 mg QW n=15 Atacicept 150 mg QW Atacicept 75 mg QW n=30 Atacicept 150 mg QW n=30 Week 0 24 36 72 96 1° Endpoint 2° Endpoint Interim Analysis Longest duration B cell modulator Inclusion Criteria Endpoints data to date • Participants ≥18 years old with IgAN on kidney • Primary efficacy: UPCR-24h at week 24 biopsy and high risk of disease progression • Key secondary: UPCR-24h at week 36 • Stable and optimized RAASi for ≥12 weeks • eGFR change up to week 96 • Use of SGLT2i allowed • Gd-IgA1 change • UPCR-24h >0.75 g/g or UP >0.75 g per 24h • Hematuria change 2 • eGFR ≥30 mL/min/1.73 m • Safety • Blood pressure ≤150/90 mmHg ET = end of treatment; RAASi = renin-angiotensin-aldosterone system inhibitor; UPCR = urine protein:creatinine ratio. 19 © 2024 VERA THERAPEUTICS, INC.
Consistency with ORIGIN 2b instills great confidence in ORIGIN 3 Double-Blind Treatment Open-label Extension Placebo Atacicept 150 mg QW Atacicept 150 mg QW 156 Week 0 36 104 Fully enrolled 2° Endpoint 1° Endpoint for 1° endpoint eGFR: n=376 UPCR: n=200 September 12, 2024 2Q 2025 Inclusion Criteria Endpoints • Patients ≥18 years old with IgAN on kidney • Primary efficacy: UPCR-24h at week 36 biopsy and high risk of disease progression to support potential accelerated approval • Stable and optimized RASi for ≥12 weeks, – >90% power at week 36 use of SGLT2i allowed • Key secondary: eGFR change up to week 104 • UPCR-24h ≥1.0 g/g or UP ≥1.0 g per 24h – 90% power for eGFR Δ 4 mL/min at week 104 2 • eGFR ≥30 mL/min/1.73 m • Safety • Blood pressure ≤150/90 mmHg • Operational efficiency leveraging similar study design and worldwide sites as ORIGIN 2b • Same self-administered SC formulation and dose as used in ORIGIN 2b 20 © 2024 VERA THERAPEUTICS, INC.
Atacicept expansion roadmap US prevalence estimates 1 ~160K and Expanded IgAN Atacicept 1. Vera Therapeutics corporate estimates for peak year prevalence based on ClearView Healthcare Partners Analysis. 21 © 2024 VERA THERAPEUTICS, INC.
ORIGIN Extend: Commitment to providing long-term access to atacicept for all ORIGIN participants Off treatment ORIGIN 2b Group 1 Atacicept 150 mg QW ORIGIN 3 Group 2 Week 0 156/Beyond • Phase 2 extension study in participants who complete ORIGIN 2b/3; initiating Q4 2024 • Objectives: 1. Provide patients with extended access to atacicept prior to commercial availability in their country/region 2. Capture longer-term data for research purposes 3. Document impact of withdrawal from therapy, followed by restart 22 © 2024 VERA THERAPEUTICS, INC.
Atacicept at home, self-administered QW dosing highly attractive; QM program begins in 2025 • Biologic therapies utilizing at home, self-administered, vs SC 1 mL QW dosing widely used and accepted t 1/2• This dosing paradigm has the potential to support atacicept as 1 35 days a foundational therapy for IgAN • Atacicept half life also supports evaluation of extended dosing • QM dose finding study in 2025 1. Willen D, et al. Eur J Drug Metab Pharmacokinet 2020;45(1):27-40. 23 © 2024 VERA THERAPEUTICS, INC.
PIONEER: Phase 2 basket study in expanded IgAN cohorts Patients ineligible for ORIGIN 3 will have an opportunity to enroll in PIONEER at same clinical sites Expanded IgAN populations, n ≤120 Atacicept 150 mg qwk 1 1 Adult IgAN with low kidney function , n ≤20 2 2 Adult IgAN with low proteinuria , n ≤50 3 36 Week 0 3 52 Adult IgAN with high proteinuria , n ≤20 1° Endpoint 2° Endpoint 4 5 4 Adolescent IgAN at high risk of progression , n ≤10 5 Adult recurrent IgAN post kidney transplant, n ≤10 Endpoints 4 6 Adolescent and adult IgAVN, n ≤10 • Primary: UPCR change at week 36 1 2 • Key secondary: eGFR change at weeks 36, 52 eGFR 20 to <30 mL/min/1.73 m 2 UPCR <1.0 g/g • Gd-IgA1 change at weeks 36, 52 3 UPCR ≥5.0 g/g 4 Age ≥15 years • Change in percentage of participants with hematuria 5 UPCR ≥0.3 g/g at weeks 36, 52 • Safety IgAVN = immunoglobulin A vasculitis nephritis (purpura nephritis). 24 © 2024 VERA THERAPEUTICS, INC.
Atacicept expansion roadmap US prevalence estimates ~230K 1-10 + ~70K 1 ~160K Non-IgAN autoimmune kidney disease pMN, FSGS, MCD and Expanded IgAN Atacicept Vera Therapeutics corporate estimates for peak year prevalence based on 1. ClearView Healthcare Partners Analysis; 2. US Census 2023; 3. McGrogan A. Nephrol Dial Transplant 2011; 4. Couser ASN 2017; 5. Beck LH. N Engl J Med 2009; 6. Filler G. Am J Kidney Dis 2003; 7. Troyanov S. J Am Soc Nephrol 2005. 8. Hommos MS. Mayo Clin Proc 2017; 9. Hengel FE. N Engl J Med 2024; 10. Vivarelli M. Clin J Am Soc Nephrol 2017. 25 © 2024 VERA THERAPEUTICS, INC.
Autoimmune glomerular disease: podocyte injury and cytoskeletal derangement drives proteinuria and progressive disease Healthy Podocyte Foot Processes Disrupted Podocyte Foot Processes Podocyte foot process Urinary Foot process effacement space Podocyte Protein Endothelial cell GBM Glomerulus Vascular space Mesangium Podocytes play a key role in Causes of podocyte injury: Resulting in clinically …leading to proteinuria preventing large molecules • Immune mediated injury relevant alterations in the including nephrotic (proteins) from being filtered • Secondary causes glomerular filtration barrier… syndrome and nephron loss into urine• Genetic predisposition • Environmental factors Kopp JB, et al. Nat Rev Dis Primer 2021. 26 © 2024 VERA THERAPEUTICS, INC.
Atacicept mechanism of action has broad potential in autoimmune glomerular disease including membranous nephropathy B Cell Activation Autoantibody Production Autoantibodies Bind to Glomerular Antigens, Driving Kidney Injury BAFF Anti-PLA2R antibodies PLA2R Cytoskeletal B dysregulation cell APRIL Podocyte Atacicept Anti-PLA2R podocytopathy pMN High anti-PLA2R antibody levels associated with treatment 1 response in patients with MN PLA2R = phospholipase A2 receptor. 1. Barbour SJ, et al. CJASN 2023. 27 © 2024 VERA THERAPEUTICS, INC.
Atacicept expansion roadmap US prevalence estimates ~195K 1-5 + ~35K 1 ~160K Anti-PLA2R podocytopathy pMN and Expanded IgAN Atacicept Vera Therapeutics corporate estimates for peak year prevalence based on 1. ClearView Healthcare Partners Analysis; 2. US Census 2023; 3. McGrogan A. Nephrol Dial Transplant 2011; 4. Couser ASN 2017; 5. Beck LH. N Engl J Med 2009. 28 © 2024 VERA THERAPEUTICS, INC.
PIONEER: Operationally efficient Phase 2 basket study in expanded IgAN and anti-PLA2R podocytopathy (PMN) Atacicept 150 mg qwk Population 1, n ≤120 Expanded IgAN populations Week 0 36 52 1° Endpoint 2° Endpoint Endpoints Population 2, n ≤20 • Primary: UPCR change at week 36 Anti-PLA2R podocytopathy • Key secondary: eGFR change at weeks 36, 52 (Membranous Nephropathy) • Exploratory: – Gd-IgA1 change at weeks 36, 52 – Change in percentage of participants with hematuria at weeks 36, 52 – Change in anti-PLA2R antibodies • Safety 29 © 2024 VERA THERAPEUTICS, INC.
Atacicept expansion roadmap US prevalence estimates ~230K 2,3,6-10 + ~35K ~195K 1-5 + ~35K 1 ~160K Anti-nephrin podocytopathy Anti-PLA2R FSGS, MCD podocytopathy and pMN Expanded IgAN Atacicept Vera Therapeutics corporate estimates for peak year prevalence based on 1. ClearView Healthcare Partners Analysis; 2. US Census 2023; 3. McGrogan A. Nephrol Dial Transplant 2011; 4. Couser ASN 2017; 5. Beck LH. N Engl J Med 2009; 6. Filler G. Am J Kidney Dis 2003; 7. Troyanov S. J Am Soc Nephrol 2005. 8. Hommos MS. Mayo Clin Proc 2017; 9. Hengel FE. N Engl J Med 2024; 10. Vivarelli M. Clin J Am Soc Nephrol 2017. 30 © 2024 VERA THERAPEUTICS, INC.
FSGS and MCD are histologic diagnoses with heterogeneous etiology; Autoimmunity, including anti-nephrin antibodies, is one driver of disease B Cell Activation Autoantibody Autoantibodies Bind to Glomerular Antigens, Production Leading to Kidney Injury FSGS MCD BAFF Fused foot processes Anti-nephrin antibodies Nephrin Cytoskeletal degradation B and reorganization Scarring cell Nephrin endocytosis APRIL Podocyte Anti-nephrin podocytopathy FSGS = focal segmental glomerulosclerosis; MCD = minimal change disease. Kopp JB, et al. Nat Rev Dis Primer 2021; Fogo AB. Nat Rev Nephrol 2015. 31 © 2024 VERA THERAPEUTICS, INC.
PIONEER: Operationally efficient Phase 2 basket study in expanded IgAN and anti-PLA2R & anti-nephrin podocytopathies Atacicept 150 mg qwk Population 1, n ≤120 Expanded IgAN populations Week 0 36 52 1° Endpoint 2° Endpoint Endpoints Population 2, n ≤20 • Primary: UPCR change at week 36 Anti-PLA2R podocytopathy • Key secondary: eGFR change at weeks 36, 52 (Membranous Nephropathy) • Exploratory: – Gd-IgA1 change at weeks 36, 52 – Change in percentage of participants with hematuria at weeks 36, 52 Population 3, n ≤20 – Change in anti-PLA2R antibodies Anti-nephrin podocytopathy – Change in anti-nephrin antibodies (Minimal Change Disease/FSGS) • Safety 32 © 2024 VERA THERAPEUTICS, INC.
Targeting B cell production of autoantibodies against glomerular antigens offers the promise of additional kidney indications B Cell Activation Autoantibody Production Immune Complex Deposition Leading to Glomerulonephritis and Kidney Damage BAFF Anti-Gd-IgA1 antibodies IgAN B cell Anti-PLA2R antibodies Anti-PLA2R podocytopathy APRIL Anti-nephrin antibodies Anti-nephrin podocytopathy Atacicept Antibodies associated with… Other autoimmune kidney diseases 33 © 2024 VERA THERAPEUTICS, INC.
Vision for an evolved approach to autoimmune glomerular disease Identification of autoantigen/autoantibody constructs that drive autoimmune glomerular diseases Gd-IgA1 & PLA2R & Nephrin & Future anti-Gd-IgA1 anti-PLA2R anti-nephrin autoantigen/autoantibody constructs identified 1 2 3 1999 2009 2022 Today Importantly, atacicept represents both a potential therapeutic agent and also a diagnostic tool: Characterize patients with proteinuric and Patients demonstrating a response nephritic conditions based on responsiveness have a B-cell modulatory responsive B autoimmune glomerular disease to a diagnostic trial of atacicept Does not require pre-existing elucidation of all autoantigen/autoantibody constructs Provides an opportunity for both future clinical investigation and long-term treatment 1. Tomana M, et al. J Clin Invest 1999. 2. Beck LH, et al. N Engl J Med 2009. 3. Watts AJ, et al. JASN 2022. 34 © 2024 VERA THERAPEUTICS, INC.
Vera optionality to expand in autoimmune kidney disease & beyond US prevalence estimates ~230K Potential Future Indications 1-10 + ~70K Hematology ITP, AIHA, CAD, APS 1 ~160K Rheumatology Non-IgAN SLE, Sjogren’s, Long COVID autoimmune Neurology kidney disease MG pMN, FSGS, MCD and Metabolism Expanded IgAN DM Type 1 Atacicept Vera Therapeutics corporate estimates for peak year prevalence based on 1. ClearView Healthcare Partners Analysis; 2. US Census 2023; 3. McGrogan A. Nephrol Dial Transplant 2011; 4. Couser ASN 2017; 5. Beck LH. N Engl J Med 2009; 6. Filler G. Am J Kidney Dis 2003; 7. Troyanov S. J Am Soc Nephrol 2005. 8. Hommos MS. Mayo Clin Proc 2017; 9. Hengel FE. N Engl J Med 2024; 10. Vivarelli M. Clin J Am Soc Nephrol 2017. pMN = primary membranous nephropathy; FSGS = focal segmental glomerulosclerosis; MCD = minimal change disease; ITP = immune thrombocytopenia; AIHA = autoimmune hemolytic anemia; CAD = cold agglutinin disease; APS = antiphospholipid syndrome; SLE = systemic lupus erythematosus; MG = myasthenia gravis; COVID = Coronavirus disease 2019; DM = diabetes mellitus. 35 © 2024 VERA THERAPEUTICS, INC.
Atacicept projected catalysts Catalyst 2024 2025 2026 Phase 3 primary endpoint cohort full enrollment 3Q Phase 2b 96-week results 4Q Phase 3 top-line results 2Q (IgAN) BLA submission 2H Projected US launch Initiation (IgAN) Initial data available Initiation (IgAN, PMN, Initial data available FSGS, MCD) Vera holds worldwide, exclusive rights to develop and commercialize atacicept Based on management’s current assumptions. 36 © 2024 VERA THERAPEUTICS, INC.
Agenda Marshall Fordyce, MD Opening Remarks Founder and CEO, Vera Therapeutics Robert Brenner, MD Vera Expansion Strategy Chief Medical Officer, Vera Therapeutics Q&A Panel Jonathan Barratt, MD, PhD, FRCP Mayer Professor of Renal Medicine, University of Leicester Richard Lafayette, MD, FACP Professor of Medicine (Nephrology), Stanford University Medical Center Director, Stanford Glomerular Disease Center Brad Rovin, MD, FACP, FASN Lee A. Herbert Professor of Nephrology Ohio State University Wexner Medical Center Marshall Fordyce, MD Closing Remarks Founder and CEO, Vera Therapeutics 37 © 2024 VERA THERAPEUTICS, INC.
Q&A Panel Jonathan Barratt Richard Lafayette Brad Rovin MD, PhD, FRCP MD, FACP MD, FACP, FASN Dr. Barratt leads the Renal Research Group within the Dr. Lafayette is a Professor of Medicine (Nephrology) and Dr. Brad H. Rovin is the Lee A. Hebert Professor of Nephrology. Dr. Rovin College of Life Sciences, University of Leicester. His Director of the Stanford Glomerular Disease Center at received his BS in Chemical Engineering from Northwestern University research is focused on a bench-to-bedside approach Stanford University Medical Center. Dr. Lafayette and his MD from the University of Illinois Medical School. He completed to improving our understanding of the pathogenesis completed his medical education at New York Medical a residency in Internal Medicine at Barnes Hospital in St. Louis, Missouri, of IgAN, a common global cause of kidney failure. College and went on to complete his residency at the Long and a Fellowship in Nephrology at Washington University School of Dr. Barratt is the IgAN Rare Disease Group lead for Island Jewish Medical Center, and his fellowship at Medicine, St. Louis. He joined the Ohio State University College of the UK National Registry of Rare Kidney Diseases Stanford University School of Medicine. Dr. Lafayette is Medicine Faculty in 1990, became Director of the Division of Nephrology (RaDaR), and a member of the steering committee board-certified in Internal Medicine and Nephrology. in 2004, and served as Vice Chairman of Medicine for Research from for the International IgAN Network. He works closely Dr. Lafayette served as the Associate Chair of the Stanford 2009-2019. In 2019 he became the Medical Director of the Ohio State with pharmaceutical companies interested in new University Department of Medicine from 2002–2007, the University Center for Clinical Research Management. treatments for IgAN, is Chief Investigator for a Clinical Chief of Nephrology at Stanford University from Dr. Rovin has had several leadership roles in the American Society of number of international randomized controlled 1999–2012, and currently serves as the Director of the Nephrology, including running the Glomerular Diseases Pre-Course and Phase 2 and 3 clinical trials in IgAN, and was a Stanford Glomerular Disease Center since 2010. Dr. Co-Editing NephSAP-Glomerular Diseases. Most recently, he was member of the U.S. Food and Drug Administration Lafayette was honored in America’s Top Doctors, Best appointed Deputy Editor of Kidney International,. He also is Co-Chair for and American Society of Nephrology Kidney Health Doctors from 2004–2018, and received America’s Top glomerular disease guideline development for the Kidney Disease Initiative: Identifying Surrogate Endpoints for Clinical Doctors Award, Castle Connolly Medical Ltd. from 2014– Improving Global Outcomes effort. Trials in IgAN Workgroup. 2022. Dr. Lafayette has been part of the following boards Dr. Rovin’s laboratory studies the immunopathogenesis of glomerular and professional organizations: Editorial Board, Kidney and autoimmune diseases. He is heavily involved in clinical trial News, American Society of Nephrology (2010–2021) development and design for investigator-initiated and industry- Member, Glomerular Disease Advisory Committee, sponsored trials. He is a founding member of NephroNet, a grass-roots American Society of Nephrology (2013–2017) Member (ex- nephrology clinical trial organization, and the Lupus Nephritis Clinical officio), Communications Committee, American Society of Trials Network. He is and has been the Principal Investigator on several Nephrology (2015–Present). trials of novel therapeutics for glomerular diseases. 38 © 2024 VERA THERAPEUTICS, INC.
Agenda Marshall Fordyce, MD Opening Remarks Founder and CEO, Vera Therapeutics Robert Brenner, MD Vera Expansion Strategy Chief Medical Officer, Vera Therapeutics Q&A Panel Jonathan Barratt, MD, PhD, FRCP Mayer Professor of Renal Medicine, University of Leicester Richard Lafayette, MD, FACP Professor of Medicine (Nephrology), Stanford University Medical Center Director, Stanford Glomerular Disease Center Brad Rovin, MD, FACP, FASN Lee A. Herbert Professor of Nephrology Ohio State University Wexner Medical Center Marshall Fordyce, MD Closing Remarks Founder and CEO, Vera Therapeutics 39 © 2024 VERA THERAPEUTICS, INC.
Atacicept projected catalysts Catalyst 2024 2025 2026 Phase 3 primary endpoint cohort full enrollment 3Q Phase 2b 96-week results 4Q Phase 3 top-line results 2Q (IgAN) BLA submission 2H Projected US launch Initiation (IgAN) Initial data available Initiation (IgAN, PMN, Initial data available FSGS, MCD) Vera holds worldwide, exclusive rights to develop and commercialize atacicept Based on management’s current assumptions. 40 © 2024 VERA THERAPEUTICS, INC.
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