PLA2R

-- First clinical data with povetacicept presented at American Society of Nephrology Kidney Week support best-in-class potential and broad pipeline opportunity – -- Company closed an oversubscribed $150 million equity offering to accelerate multiple development activities – -- Multiple catalysts with povetacicept targeted in 2024 including initiation of pivotal IgAN and phase 2 lupus clinical trials -- 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 reported financial results and company highlights for the third quarter ended September 30, 2023. “The first presentation of clinical data in patients for povetacicept during a late-breaking session at the American Society of Nephrology (ASN) Kidney Week Meeting marked an important milestone in Alpine’s history. Based on continued strong support from investigators and key opinion leaders, we plan to advance povetacicept into a pivotal study in IgA nephropathy (IgAN) and a phase 2 study in systemic lupus erythematosus (SLE) in the second half of 2024,” said Mitchell Gold, MD, Executive Chairman and Chief Executive Officer of Alpine. “Following our data presentation, we executed a follow-on equity offering of $150 million to bolster our balance sheet. The additional capital enables us to further accelerate development activities, including povetacicept, across multiple autoantibody-related diseases.” Dr. Gold continued, “These initial data and the subsequent follow-on offering set the stage for an active, catalyst-heavy 2024, with additional data expected in IgAN that will include longer term follow-up from our low-dose cohort and initial data from our high-dose cohort. In addition, we look forward to sharing initial data from povetacicept in autoimmune cytopenias. We believe povetacicept, which is a wholly-owned program, represents a unique, potentially best-in-class molecule and look forward to using our strong balance sheet to support a broad development plan across multiple indications.” Third Quarter 2023 Highlights & Recent Updates Highlights From Data Presented at the American Society of Nephrology (ASN) Kidney Week In IgAN, treatment with low-dose povetacicept, 80 mg subcutaneously (SC) every four weeks was associated with clinically meaningful improvements in proteinuria, with a 53.5% reduction from baseline in urine protein to creatinine ratio (UPCR; n=5) at 24 weeks. In addition, at 24 weeks, 4/5 (80%) had achieved remission, as defined as UPCR < 0.5 g/g and ≥ 50% reduction in UPCR from baseline with stable renal function (£ 25% reduction in eGFR from baseline). In IgAN, treatment with low-dose povetacicept was also associated with a >60% reduction in the key disease-related biomarker galactose-deficient IgA1 (Gd-IgA1), as well as stable renal function as assessed by estimated glomerular filtration rate (eGFR) (+7.1% from baseline at 24 weeks; n=5). The first participant with primary membranous nephropathy (pMN), also treated with povetacicept 80 mg subcutaneously (SC) every four weeks, achieved an immunological remission, defined as a reduction in the highly disease-relevant biomarker anti-PLA2R1 to an undetectable level, from a baseline of 209 to < 2 RU/mL by 22 weeks. Povetacicept has been well tolerated, with no reported administration-associated reactions, no instances of IgG < 3 g/L, and no severe infections. A higher dose of povetacicept, 240 mg SC every four weeks, continues to enroll, with initial data expected in first half of 2024. Link to the ASN poster: Highlights From Data Presented at the American Association of Neuromuscular & Electrodiagnostic (AANEM) Medicine Meeting In a model of murine experimental autoimmune myasthenia gravis (EAMG), povetacicept improved disease activity, with clinical scores superior to treatment with either the FcRn inhibitor efgartigimod or an anti-CD20 depleting antibody. It also reduced anti-AChR IgG autoantibodies and serum Ig isotypes, including IgM and IgA, superior to both comparator treatments. Link to the AANEM poster: Highlights From Data Presented at the American College of Rheumatology (ACR) Meeting In SLE patients, BAFF- and APRIL-related genes (i.e., BAFF, APRIL, TACI, and BCMA) were increased in myeloid lineage cells and B cells compared to healthy adults. Povetacicept, as compared to single BAFF or APRIL pathway inhibitors, more potently downregulated genes associated with activation in B cells. Povetacicept significantly reduced multiple disease parameters in a mouse model of lupus, more effectively than wild-type TACI-Fc or conventional B cell depletion. Link to povetacicept poster: Third Quarter 2023 Financial Results Cash Position and Runway: As of September 30, 2023, Alpine’s cash and investments totaled $227.2 million compared to $273.4 million as of December 31, 2022. The Company anticipates its current cash and investments, together with the $140.5 million in net proceeds after deducting discounts, commissions and estimated costs from the subsequently completed stock offering, are sufficient to fund planned operations into 2026. Collaboration Revenue: For the three and nine months ended September 30, 2023, collaboration revenue was $10.0 million and $28.0 million, respectively, compared to $8.4 million and $27.3 million for the same periods in 2022. The increase in collaboration revenue over the three-month period relates primarily to increases of $3.5 million in Horizon revenue, largely as the result of our two ongoing Research Programs nearing completion during the 2023 period, whereas the lower revenue during the 2022 period resulted from services rendered in connection with only the first Research Program. These increases were offset by decreases in AbbVie revenue of $1.4 million primarily due to lower contributed employee hours. The increase in collaboration revenue for the nine months ended September 30, 2023, as compared to the prior year, primarily relates to increases in AbbVie revenue as the related clinical trial continues patient enrollment, and Horizon revenue for services rendered in connection with our two ongoing Research programs, whereas the lower Horizon revenue in the 2022 period was primarily the result of the completion of the Existing Program, followed by the commencement of the first additional research program. Research and Development Expenses: For the three and nine months ended September 30, 2023, research and development expenses, inclusive of non-cash expenses, were $19.2 million and $58.0 million, respectively, compared to $17.6 million and $51.5 million for the same periods in 2022. The respective increases of $1.6 million and $6.5 million were primarily attributable to process development, manufacturing, higher clinical trial costs, as well as increases in personnel costs. General and Administrative Expenses: For the three and nine months ended September 30, 2023, general and administrative expenses, inclusive of non-cash expenses, were $5.4 million and $15.8 million, respectively, compared to $4.6 million and $13.6 million for the same periods in 2022. The respective increases of $0.8 million and $2.3 million were primarily attributable to increases in personnel and legal costs. Net Loss: Net loss for the three and nine months ended September 30, 2023, was $11.7 million and $38.1 million, respectively, compared to net losses of $13.3 million and $38.9 million for the same periods in 2022. Alpine Immune Sciences, Inc. Selected Condensed Consolidated Balance Sheet Data (In thousands) September 30, 2023 December 31, 2022 (unaudited) Cash and cash equivalents $ 18,981 $ 13,376 Short-term investments 174,472 224,265 Total current assets 197,415 240,993 Long-term investments 33,502 35,481 Total assets 240,547 286,686 Total current liabilities 51,818 57,996 Total stockholders’ equity 161,631 179,420 Total liabilities and stockholders’ equity 240,547 286,686 Condensed Consolidated Statement of Operations and Comprehensive Income (Loss) Data (In thousands, except share and per share amounts) Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 (unaudited) Collaboration revenue $ 10,043 $ 8,367 $ 28,023 $ 27,288 Operating expenses: Research and development 19,150 17,589 57,972 51,487 General and administrative 5,443 4,610 15,848 13,579 Total operating expenses 24,593 22,199 73,820 65,066 Loss from operations (14,550 ) (13,832 ) (45,797 ) (37,778 ) Other income (expense): Interest income 2,891 664 7,837 1,123 Interest expense — (105 ) (98 ) (389 ) Other, net (63 ) — (86 ) (72 ) Loss before taxes (11,722 ) (13,273 ) (38,144 ) (37,116 ) Income tax expense — — — (1,782 ) Net loss $ (11,722 ) $ (13,273 ) $ (38,144 ) $ (38,898 ) Comprehensive income (loss): Unrealized gain (loss) on investments 170 (307 ) 677 (1,385 ) Unrealized (loss) gain on foreign currency translation (60 ) 7 (96 ) (11 ) Comprehensive loss $ (11,612 ) $ (13,573 ) $ (37,563 ) $ (40,294 ) Weighted-average shares used to compute basic and diluted net loss per share 49,222,344 31,574,358 48,286,203 31,559,886 Basic and diluted net loss per share $ (0.24 ) $ (0.42 ) $ (0.79 ) $ (1.23 ) 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. 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/2a study of povetacicept in autoimmune glomerulonephritis, where povetacicept is being administered subcutaneously for up to 48 weeks. Key endpoints include proteinuria, eGFR, renal response, and disease-related autoantibodies. About RUBY-4 RUBY-4 (NCT05757570) is a multi-cohort, open label, phase 1b study of povetacicept in 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, including durable responses, as well as disease-related autoantibodies. 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 . 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, 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 Food and Drug Administration; 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. The RUBY and Alpine logos are registered trademarks of Alpine Immune Sciences, Inc. in various jurisdictions.

-- Low-dose povetacicept (80 mg administered once every four weeks) was well tolerated during subcutaneous administration and reduced UPCR by greater than 50% in IgA nephropathy -- -- Higher dose povetacicept (240 mg) administered once every four weeks currently being explored -- -- Based on this data Alpine will now seek to begin a pivotal phase 3 IgAN study in the second half of 2024 -- -- Company to host virtual investor call and webcast today at 4:30 pm ET with James Tumlin, M.D. and Jonathan Barratt, Ph.D., FRCP -- 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, announced that the Company today presented the first clinical data of povetacicept in autoimmune glomerulonephritis during a late-breaking poster session at the American Society of Nephrology (ASN) Kidney Week in Philadelphia, Pennsylvania. In addition, the Company plans to host an investor event today at 4:30 pm ET. This press release features multimedia. View the full release here: Figure 1. Clinically Meaningful Improvements in Proteinuria, Suggesting Remission (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, where povetacicept is administered subcutaneously (SC) once every four weeks for up to 48 weeks. Key Highlights from the Late-Breaking ASN Poster Include: As of October 25th, 20 participants with IgA nephropathy (IgAN) have been enrolled, 12 at the 80 mg dose level, of whom 5 have UPCR data available at 24 weeks. In IgAN, treatment with low-dose povetacicept, 80 mg SC every four weeks was associated with clinically meaningful improvements in proteinuria, with a 53.5% reduction from baseline in urine protein to creatinine ratio (UPCR; n=5) at 24 weeks. In addition, at 24 weeks, 4/5 (80%) had achieved remission, as defined as UPCR < 0.5 g/g and ≥50% reduction in UPCR from baseline with stable renal function (≤ 25% reduction in eGFR from baseline). (Fig. 1) In IgAN, treatment with low-dose povetacicept was also associated with a >60% reduction in the key disease-related biomarker galactose-deficient IgA1 (Gd-IgA1), as well as stable renal function as assessed by estimated glomerular filtration rate (eGFR) (+7.1% from baseline at 24 weeks; n=5). The first participant with primary membranous nephropathy (pMN), also treated with povetacicept 80 mg SC every four weeks, achieved an immunological remission, defined as a reduction in the highly disease-relevant biomarker anti-PLA2R1 to an undetectable level, from a baseline of 209 to < 2 RU/mL by 22 weeks. Povetacicept has been well tolerated, with no reported administration-associated reactions, no instances of IgG < 3 g/L, and no severe infections. A higher dose of povetacicept, 240 mg SC every four weeks, continues to enroll, with initial data expected in 1H 2024. “In this initial experience, low-dose povetacicept at 80 mg has been well tolerated and demonstrates highly encouraging improvements in UPCR and disease biomarkers in IgA nephropathy, with early evidence suggesting remission," noted James Tumlin, M.D., Professor of Medicine at Emory University School of Medicine, Founder and Chief Executive Officer of NephroNet Clinical Trials Consortium. “These findings suggest a highly compelling development pro povetacicept based upon a rapid reduction in the key pathogenic biomarker Gd-IgA1, marked and clinically meaningful reductions in UPCR, and a once-a-month dosing regimen. A higher dose of povetacicept 240 mg every four weeks is currently being explored and will be of great interest. Further clinical development of povetacicept in glomerulonephritis, particularly IgAN, is therefore strongly supported.” Dr. Tumlin continued, “There remains a significant unmet need for well-tolerated, convenient, and efficacious therapies in autoimmune kidney diseases, and dual BAFF/APRIL inhibition has the potential to be an important disease-modifying mechanism, especially if considered early in the treatment paradigm.” “Even at this low 80 mg dose level of povetacicept, the improvements in proteinuria, accompanied by analogous changes in Gd-IgA1, are impressive and support its potential to be an important therapy for IgAN,” remarked Jonathan Barratt, PhD, FRCP, Mayer Professor of Renal Medicine at the University of Leicester. “Based on this data, advancement of povetacicept to a pivotal trial in IgA nephropathy, where it has already accumulated a reasonably sized clinical experience, seems urgently warranted. The initial findings in primary membranous nephropathy, a disease with no approved therapies, are equally encouraging. Further study is clearly warranted and confirmation of the results in additional pMN patients, along with correlation with renal outcomes, may facilitate a rapid development path.” “These results are the first of what will hopefully be several data readouts over the next 12-18 months that will help validate the potential activity of povetacicept across multiple autoimmune diseases,” noted Stanford Peng, MD, PhD, President and Head of Research and Development at Alpine. “We eagerly await the initial data from the next 240 mg dose level in the first half of 2024. In the meantime, these data support our plan to advance povetacicept rapidly to a pivotal trial in IgAN, pending regulatory agreement, in the second half of next year. In addition, we plan to initiate RUBY-2, a phase 2 study of povetacicept in systemic lupus erythematosus.” American Society of Nephrology – Kidney Week 2023 Date/Time: Thursday, November 2, 2023, 10:00am – 12:00pm ET Poster Title: Povetacicept, an Enhanced Dual BAFF/APRIL Antagonist, in Autoantibody-Associated Glomerulonephritis (GN) Poster Board Number: TH-PO1125 Session Name: Late-Breaking Posters Location: Exhibit Hall, Pennsylvania Convention Center, Philadelphia Presenter: James Tumlin, M.D., Professor of Medicine at Emory University School of Medicine, Founder and Chief Executive Officer of NephroNet Clinical Trials Consortium Investor Conference Call and Webcast Information Date/Time: Thursday, November 2, 2023, at 4:30 pm – 5:30 pm ET Alpine will host a conference call and webcast to discuss the data update from ASN as well as provide a corporate update. Members of the Alpine executive team will be joined by James Tumlin, M.D., Professor of Medicine at Emory University School of Medicine, Founder and Chief Executive Officer of NephroNet Clinical Trials Consortium, and Jonathan Barratt, Ph.D., FRCP, the Mayer Professor of Renal Medicine at the University of Leicester. The link to the webcast is available in the investor relations section of the Company’s website at 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. 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/2a study of povetacicept in autoimmune glomerulonephritis, where povetacicept is being administered subcutaneously for up to 48 weeks. Key endpoints include proteinuria, eGFR, renal response, and disease-related autoantibodies. 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 . 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 progress and potential of our development programs and product candidates; 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; 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; 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 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. Source: Alpine Immune Sciences, Inc.

FDA granted Breakthrough Therapy Designation for felzartamab in PMN upon positive clinical data from M-PLACE, a Phase 2 study led by I-Mab partner HI-Bio I-Mab has full development and commercialization rights of felzartamab in Greater China for all indications, with Phase 3 multiple myeloma data expected in 2024, followed by a planned BLA submission ROCKVILLE, Md. and SHANGHAI, Nov. 2, 2023 /PRNewswire/ -- I-Mab (Nasdaq: IMAB) (the "Company"), a global biotechnology company focused on bringing highly differentiated medicines to patients around the world through the discovery, development, and commercialization of novel immunotherapies and biologics, and HI-Bio, a clinical-stage biotechnology company developing targeted therapies for patients with severe immune-mediated diseases (IMDs), today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for felzartamab, an investigational CD38 antibody, for the treatment of primary membranous nephropathy (PMN). "The FDA's decision to grant felzartamab Breakthrough Therapy designation is recognition of the promising data we have collected to date, as well as an acknowledgement of the need for major advances over available therapies in the treatment of patients with PMN," said Dr. Uptal Patel, Chief Medical Officer of HI-Bio. "We believe that the cellular depletion strategy with felzartamab in PMN is applicable to many more immune-mediated diseases driven by antibodies produced in CD38+ plasma cells. For that reason, we are currently developing felzartamab in multiple diseases including PMN, IgA nephropathy, antibody-mediated rejection and lupus nephritis." The FDA selectively grants Breakthrough Therapy Designation to expedite the development and review of drugs that are intended to treat a serious or life-threatening condition, and preliminary clinical evidence indicates the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s). The designation for felzartamab was based on clinical data submitted to the FDA, including results from M-PLACE, a Phase 1b/2a proof-of-concept, open-label study. The final analysis of the M-PLACE study has been accepted as an oral presentation at the American Society of Nephrology (ASN) Kidney Week 2023 Annual Meeting (Abstract TH-OR27), taking place November 1–5, 2023, by Brad Rovin, M.D., Director of the Division of Nephrology at Ohio State University. I-Mab has the full rights to develop and commercialize felzartamab for all indications in Greater China which encompasses Mainland China, Hong Kong, Macau, and Taiwan. I-Mab is evaluating felzartamab in oncology and autoimmune diseases. I-Mab is currently conducting a Phase 3 registrational study of felzartamab in combination with lenalidomide and dexamethasone as a second-line treatment for multiple myeloma (MM) in China with progression-free survival (PFS) as the primary endpoint, with a projected read-out in 2024, followed by a planned BLA submission. "We are excited about the potential therapeutic benefit of felzartamab through this Breakthrough Therapy Designation by the FDA, following the Orphan Drug Designation received in May," said Dr. Andrew Zhu, President of I-Mab. "This designation represents an important milestone for I-Mab, our partner HI-Bio, and the PMN community as we continue to evaluate felzartamab as an innovative immunotherapy for multiple indications, including cancers and autoimmune diseases." About Primary Membranous Nephropathy (PMN) PMN is a rare autoantibody-mediated autoimmune kidney disease and a leading cause of nephrotic syndrome (NS) in adults worldwide. Disease onset and diagnosis typically occurs between 40 and 50 years of age, with 80% of patients presenting with nephrotic syndrome (i.e., edema, >3.5 g/day proteinuria, hypoalbuminemia). PMN is characterized by a thickening of the glomerular basement membrane (GBM) due to the formation and deposition of immune complexes in this space between podocytes and the glomerular endothelium of the kidney. Approximately 80% of PMN cases arise due to autoantibodies that recognize the phospholipase A2 receptor (PLA2R) antigen expressed on podocytes. Anti-PLA2R is both a diagnostic and prognostic biomarker, and total aPLA2R antibody level has been shown to be a biomarker for prognosis of outcome in patients with PMN. Other autoantibodies have been identified in patients with PMN including anti-THSD7A, NELL-1 and Sema3B, further supporting the role of antibody-secreting plasma cells in the pathophysiology of PMN. CD38+ long-lived plasma cells and plasmablasts are a main source of autoantibodies. There are no approved therapies for PMN. The current standard of care comprises off-label use of supportive care measures (e.g., angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, statins, and diuretics), conventional immunosuppressive treatments (ISTs) (e.g. cyclophosphamide combined with steroids and calcineurin inhibitors) or B-cell depleting agents (e.g. anti-CD20 antibodies). However, these treatments are not effective in all patients, with a significant proportion of patients not achieving remission or relapsing. In addition, conventional immunosuppressive treatments are associated with a high risk of toxicity. About Felzartamab Felzartamab is an investigational therapeutic human monoclonal antibody directed against CD38, a protein expressed on mature plasma cells. The antibody is directed against CD38 on the surface of multiple myeloma cells, which has been characterized as one of the most strongly and uniformly expressed antigens on the surface of malignant plasma cells. According to its suggested mode of action, the antibody recruits cells of the body's immune system to kill the tumor through antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). The antibody does not involve complement dependent cytotoxicity, or CDC, an additional immune mechanism involved in tumor cell killing. Scientific research suggests that an anti-CD38 antibody may have therapeutic potential also in other cancers as well as autoimmune diseases. Based on a licensing agreement between MorphoSys and I-Mab signed in November 2017, I-Mab owns the exclusive rights for development and commercialization of felzartamab for all indications in Greater China, which encompasses Mainland China, Hong Kong, Macao, and Taiwan. HI-Bio in-licensed felzartamab from MorphoSys in June 2022, and holds exclusive worldwide rights for felzartamab with the exception of Greater China. About I-Mab I-Mab (Nasdaq: IMAB) is a global biotechnology company focused on bringing highly differentiated medicines to patients around the world through the discovery, development, and commercialization of novel immunotherapies and biologics. I-Mab's innovative pipeline is driven by internal R&D's Fast-to-Proof-of-Concept, Fast-to-Market development strategies, and through global partnerships. For more information, please visit and follow us on LinkedIn, Twitter, and WeChat. I-Mab Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding data from clinical studies of felzartamab, the potential implications of clinical data for patients, and I-Mab's advancement of, and anticipated clinical development, regulatory milestones, and commercialization of felzartmab. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including but not limited to I-Mab's ability to demonstrate the safety and efficacy of its drug candidates; the clinical results for its drug candidates, which may not support further development or NDA/BLA approval; the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approval of I-Mab's drug candidates; I-Mab's ability to achieve commercial success for its drug candidates, if approved; I-Mab's ability to obtain and maintain protection of intellectual property for its technology and drugs; I-Mab's reliance on third parties to conduct drug development, manufacturing and other services; I-Mab's limited operating history and I-Mab's ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates; and the impact of the COVID-19 pandemic on the Company's clinical development, commercial and other operations, as well as those risks more fully discussed in the "Risk Factors" section in I-Mab's most recent annual report on Form 20-F, as well as discussions of potential risks, uncertainties, and other important factors in I-Mab's subsequent filings with the US Securities and Exchange Commission. All forward-looking statements are based on information currently available to I-Mab, and I-Mab undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law. I-Mab Contacts View original content to download multimedia: SOURCE I-Mab Company Codes: NASDAQ-NMS:IMAB