Cold Agglutinin Disease

Pivotal Phase 3 Data for ANX005 in Guillain-Barré Syndrome (GBS) Expected in Second Quarter 2024 Initiation of Pivotal Phase 3 ANX007 ARCHER II Trial in Geographic Atrophy (GA) Expected in mid-2024, a Global Sham-Controlled Trial Using Vision Preservation as Primary Outcome Measure Clinical Proof-of-Concept Data with ANX1502 Oral Inhibitor of the Classical Pathway Expected in Second Half of 2024 Robust Balance Sheet with Cash, Cash Equivalents, and Short-term Investments of Approximately $260 Million as of December 31, 2023, and Anticipated Runway into mid-2026 BRISBANE, Calif., March 26, 2024 (GLOBE NEWSWIRE) -- Annexon, Inc. (Nasdaq: ANNX), a biopharmaceutical company advancing a late-stage clinical platform of novel therapies for people living with devastating classical complement-mediated neuroinflammatory diseases of the body, brain, and eye, today highlighted portfolio progress and reported fourth quarter and full year 2023 financial results. “Our strong execution in 2023 across our three priority programs successfully achieved key clinical and regulatory milestones and created a solid foundation from which to reach several important upcoming catalysts in 2024,” said Douglas Love, president and chief executive officer of Annexon. “Importantly, our approach in blocking C1q to stop classical complement-driven neuroinflammation in diseases of the body, brain and eye continues to show unique and consistent functional outcomes across our pipeline programs.” Mr. Love continued, “In the year ahead, we are excited by ANX005’s near-term potential to be the first targeted treatment for GBS, and we are on track to report topline data from our pivotal, placebo-controlled trial in the second quarter. For our global registrational program in GA, we plan to initiate two pivotal trials in 2024 to underscore the unique mechanism of action of ANX007 and its competitive differentiation in visual function. Finally, we anticipate clinical proof-of-concept data from our novel oral inhibitor ANX1502 later in the year. With our balance sheet strengthened and anticipated runway into mid-2026, we are poised to generate significant near- to mid-term value for patients and our shareholders.” Recent Corporate and Clinical Program Updates Successful $125 Million Financing: In December 2023, Annexon announced a $125 million financing and extension of operating runway into mid-2026. Flagship Programs ANX005 in GBS: First-in-class monoclonal antibody designed to block C1q and the entire classical complement pathway in both the body and the brain. Completed enrollment of randomized, double-blind, placebo-controlled, multi-center Phase 3 clinical trial (N=241) designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of ANX005 in patients with GBS. Initiated a real-world evidence (RWE) comparability protocol with International Guillain-Barré Syndrome Outcomes Study (IGOS), with initial RWE data expected in the first half of 2025 to support a planned Biologics License Application (BLA) submission. IGOS is a global, prospective, observational, multicenter cohort study that has enrolled ~2000 patients who were followed for one to three years. Granted Fast Track and orphan drug designations from the U.S. Food and Drug Administration (FDA). Granted orphan drug designation from the European Medicines Agency (EMA) based on a meta-analysis of past studies with ANX005 and intravenous immunoglobulin (IVIg) demonstrating notable, early improvement in muscle strength with ANX005 that translated into observable gains in health status, including a reduction in the need of mechanical ventilation. Hosted an R&D Day on the burden of disease, current treatment paradigm and market opportunity for GBS in March 2024. ANX007 in GA: First-in-class, non-pegylated antigen-binding fragment (Fab) designed to block C1q and activation of the classical complement cascade locally in the eye with an intravitreal formulation. Gained alignment with FDA on persistent best corrected visual acuity (BCVA) ≥ 15-letter loss as primary outcome measure and trial with comparison to an injection agent; no requirement to evaluate lesion growth, a surrogate anatomical endpoint for vision used previously for the approval of other GA programs. Pivotal primary endpoint alignment is based on the randomized, sham-controlled Phase 2 ARCHER trial demonstrating ANX007 is the first and only program reported to show statistically significant and consistent protection against vision loss in a broad population of patients with GA. Granted Fast Track designation from the FDA. Granted Priority Medicine (PRIME) designation by the EMA, the first and only therapeutic candidate for the treatment of GA to receive such a designation. ANX1502 in Cold Agglutinin Disease (CAD): First-in-class oral small molecule inhibitor of the classical complement pathway designed to target chronic autoimmune diseases. Announced Phase 1 single-ascending dose (SAD), and multiple-ascending dose (MAD) data from a clinical trial in healthy volunteers evaluating the safety, tolerability, pharmacokinetics, or PK, and pharmacodynamics. Key findings include: ANX1502 was generally well tolerated across cohorts with no serious adverse events. Target levels of active drug achieved in healthy volunteers with oral twice daily dosing. Supportive impact on pharmacodynamic biomarker of complement activity that supports clinical advancement. Next Wave Programs ANX005 in Amyotrophic Lateral Sclerosis (ALS): First-in-class monoclonal antibody designed to block C1q and the entire classical complement pathway. Completed a signal-finding open-label Phase 2a study evaluating the safety and tolerability of chronic dosing of ANX005 in patients with ALS. Key topline findings include: Study met all primary objectives, demonstrating ANX005 was generally well-tolerated, displayed rapid and sustained full C1q inhibition, and reduced downstream pharmacodynamic complement markers. Consistent with what has been shown in other neurodegenerative diseases, including Huntington’s disease, exploratory analyses indicated that patients with higher baseline classical complement activation who enrolled within 12 months of diagnosis achieved better outcomes, including less functional decline on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and stabilization of neurofilament light chain (NfL). These analyses support a precision medicine approach to identify patients most likely to respond to anti-C1q therapy in clinical trials with recently diagnosed patients with ALS who have elevated baseline levels of classical complement activity. Annexon plans to submit the Phase 2a data for presentation at an upcoming medical conference later this year. Key 2024 Anticipated Milestones for Flagship Programs ANX005 in GBS: Topline data from pivotal, randomized, placebo-controlled Phase 3 trial expected in the second quarter of 2024. Initial data from RWE comparability protocol with IGOS expected in first half 2025 to support a planned BLA submission. ANX007 in GA: Global pivotal Phase 3 ARCHER II trial vs. sham control expected to initiate in mid-2024. Pivotal Phase 3 head-to-head ARROW trial vs. SYFOVRE® (pegcetacoplan injection) planned to initiate in the second half of 2024. ANX1502 in CAD: Proof-of-concept (POC) trial evaluating the pharmacodynamics and efficacy of an oral tablet formulation in CAD anticipated to provide initial data in the second half of 2024, with plans for program expansion in autoimmune indications upon completion of clinical POC. Fourth Quarter and Full Year 2023 Financial Results Cash and operating runway: Cash and cash equivalents and short-term investments were $259.7 million as of December 31, 2023. Annexon continues to expect its cash, cash equivalents and marketable securities as of December 31, 2023, to be sufficient to fund the company’s planned operating expenses into mid-2026. Research and development (R&D) expenses: R&D expenses were $23.3 million for the quarter ended December 31, 2023, and $113.8 million for the year ended December 31, 2023, reflecting the advancement of the Company’s priority programs, including GBS, GA and ANX1502, compared to $28.5 million for the quarter ended December 31, 2022, and $112.5 million for the year ended December 31, 2022. General and administrative (G&A) expenses: G&A expenses were $6.7 million for the quarter ended December 31, 2023, and $30.0 million for the year ended December 31, 2023, compared to $8.2 million for the quarter ended December 31, 2022, and $33.1 million for the year ended December 31, 2022. Net loss: Net loss was $27.9 million for the quarter ended December 31, 2023, and $134.2 million for the year ended December 31, 2023, compared to $34.4 million for the quarter ended December 31, 2022, and $141.9 million for the year ended December 31, 2022. About Annexon Annexon Biosciences (Nasdaq: ANNX) is a biopharmaceutical company advancing a late-stage clinical platform of novel therapies for people living with devastating classical complement-mediated neuroinflammatory diseases of the body, brain, and eye. Annexon’s novel scientific approach targets upstream C1q to block the classical complement inflammatory cascade before it starts, and its therapeutic candidates are designed to provide meaningful benefits across multiple autoimmune, neurodegenerative and ophthalmic diseases. With proof-of concept data in Guillain-Barré syndrome, Huntington’s disease and geographic atrophy, Annexon is rigorously advancing its mid-to late-stage clinical trials to bring new potential treatments to patients as quickly as possible. To learn more visit annexonbio.com. Forward Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “target,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. All statements other than statements of historical facts contained in this press release are forward-looking statements. These forward-looking statements include, but are not limited to, statements about: the timing of completion of Phase 3 trial of ANX005 in patients with GBS; the potential therapeutic benefit of ANX005; potential benefit of ANX005, if approved, compared to existing therapies; anticipated timing of the completion of a RWE comparability study and BLA submission for ANX005; timing of initiation of the ARCHER II and ARROW trials; ANX007’s distinct potential neuroprotective mechanism of action and potential to provide protection from vision loss; timing of proof-of-concept data for ANX1502;; continued development of ANX007 and ANX1502;; anticipated cash runway into mid-2026; the potential benefits from treatment with anti-C1q therapy; and continuing advancement of the company’s portfolio. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, risks and uncertainties related to: the ongoing off-treatment follow-up portion of the ARCHER trial and final results from the ARCHER trial; the company’s history of net operating losses; the company’s ability to obtain necessary capital to fund its clinical programs; the early stages of clinical development of the company’s product candidates; the effects of public health crises on the company’s clinical programs and business operations; the company’s ability to obtain regulatory approval of and successfully commercialize its product candidates; any undesirable side effects or other properties of the company’s product candidates; the company’s reliance on third-party suppliers and manufacturers; the outcomes of any future collaboration agreements; and the company’s ability to adequately maintain intellectual property rights for its product candidates. These and other risks are described in greater detail under the section titled “Risk Factors” contained in the company’s Annual Report on Form 10-K and Quarterly Reports on Form 10-Q and the company’s other filings with the SEC. Any forward-looking statements that the company makes in this press release are made pursuant to the Private Securities Litigation Reform Act of 1995, as amended, and speak only as of the date of this press release. Except as required by law, the company undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise. Investor Contact: Joyce Allaire LifeSci Advisors jallaire@lifesciadvisors.com Media Contact: Sheryl Seapy Real Chemistry 949-903-4750 sseapy@realchemistry.com ANNEXON, INC. Condensed Consolidated Statements of Operations (in thousands, except share and per share amounts) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 (unaudited) Operating expenses: Research and development (1) $ 23,267 $ 28,535 $ 113,756 $ 112,501 General and administrative (1) 6,742 8,160 29,967 33,098 Total operating expenses 30,009 36,695 143,723 145,599 Loss from operations (30,009 ) (36,695 ) (143,723 ) (145,599 ) Interest and other income, net 2,118 2,312 9,486 3,652 Net loss $ (27,891 ) $ (34,383 ) $ (134,237 ) $ (141,947 ) Net loss per share, basic and diluted $ (0.36 ) $ (0.48 ) $ (1.77 ) $ (2.60 ) Weighted-average shares used in computing net loss per share, basic and diluted 78,217,945 72,368,539 75,673,081 54,673,572 ___________________ (1) Includes the following stock-based compensation expense: Research and development $ 2,077 $ 2,365 $ 8,878 $ 8,874 General and administrative $ 2,290 $ 2,468 $ 9,305 $ 9,642 ANNEXON, INC. Condensed Consolidated Balance Sheets (in thousands) December 31, 2023 2022 Assets Current assets: Cash and cash equivalents $ 225,110 $ 140,020 Short-term investments 34,606 102,637 Prepaid expenses and other current assets 4,144 5,441 Total current assets 263,860 248,098 Restricted cash 1,032 1,032 Property and equipment, net 14,773 16,838 Operating lease right-of-use assets 18,009 19,128 Total assets $ 297,674 $ 285,096 Liabilities and Stockholders' Equity Current liabilities: Accounts payable $ 5,487 $ 7,416 Accrued liabilities 10,235 13,448 Operating lease liabilities, current 2,165 1,316 Other current liabilities 41 180 Total current liabilities 17,928 22,360 Operating lease liabilities, non-current 29,190 31,542 Total liabilities 47,118 53,902 Stockholders’ equity: Common stock 78 48 Additional paid-in capital 823,029 669,780 Accumulated other comprehensive loss (52 ) (372 ) Accumulated deficit (572,499 ) (438,262 ) Total stockholders' equity 250,556 231,194 Total liabilities and stockholders’ equity $ 297,674 $ 285,096

-- Clinical data on povetacicept in IgA nephropathy will be updated at the upcoming WCN meeting, including follow up at 80 mg and initial data at 240 mg SC once every four-weeks -- -- Povetacicept advancing towards a pivotal phase 3 trial in IgA nephropathy and a phase 2 trial in systemic lupus erythematosus -- 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 full year 2023 financial results and company highlights for the fourth quarter ended December 31, 2023. “2023 was a transformational year for Alpine, with initial IgA nephropathy (IgAN) data presented at the American Society of Nephrology Kidney Week 2023 suggesting a best-in-class pro povetacicept, our next-generation dual BAFF/APRIL inhibitor. With our encouraging data set in IgAN, convenient once monthly dosing regimen, and strong balance sheet, we are rapidly advancing development of povetacicept as a potentially meaningful new therapeutic option for patients living with IgAN, systemic lupus erythematosus (SLE), and multiple other autoantibody-related diseases,” said Mitchell H. Gold, MD, Executive Chairman and Chief Executive Officer of Alpine. Dr. Gold continued, “Looking ahead, Alpine is well positioned for a year of meaningful catalysts, with multiple updates for povetacicept in IgAN and other indications, and the planned initiation of RAINIER, a pivotal phase 3 study of povetacicept in IgAN, and DENALI, a phase 2 study of povetacicept in SLE. In addition to updates on our clinical studies, we look forward to sharing translational data that further supports the best-in-class potential of povetacicept in multiple inflammatory diseases.” Fourth Quarter 2023 Corporate Updates Povetacicept (ALPN-303) First clinical data in IgAN demonstrate that povetacicept 80 mg administered once every four-weeks (Q4W) reduced proteinuria (as assessed by urine protein to creatinine ratio, UPCR) by greater than 50% and was associated with stable renal function (as assessed by estimated glomerular filtration rate, eGFR) at six months. In addition, povetacicept was well tolerated during subcutaneous administration, with no instances of IgG < 3 g/L, and no severe infections (2023 American Society of Nephrology Kidney Week). In a model of murine experimental autoimmune myasthenia gravis, povetacicept improved disease activity, with clinical scores superior to treatment with either the FcRn inhibitor efgartigimod or an anti-CD20 depleting antibody (2023 American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting). New translational data from povetacicept in systemic lupus erythematosus demonstrate that povetacicept, as compared to single BAFF or APRIL pathway inhibitors, more potently downregulates genes associated with activation in B cells and significantly reduces multiple disease parameters in a mouse model of lupus, more effectively than WT TACI-Fc or conventional B cell depletion (2023 American College of Rheumatology Convergence). Throughout 2023, the Company presented multiple oral and poster presentations on povetacicept at scientific conferences (Full List of Company Publications and Presentations). Corporate Updates The Company plans to present additional data on povetacicept in IgA nephropathy, including follow up data from the 80 mg Q4W and initial data from the IgAN 240 mg Q4W dose cohorts, during a Late Breaking Abstract session at the World Congress of Nephrology 2024 on Monday April 15th at 4:45 PM ET. The Company plans to present new preclinical data on povetacicept, demonstrating its greater distribution to disease-related end organs compared with WT TACI-Ig, at the 14th European Lupus Meeting. These findings correlate with povetacicept’s improved efficacy in multiple preclinical disease models. The Company intends to initiate RAINIER, a pivotal phase 3 study of povetacicept in IgA nephropathy and DENALI, a phase 2 study of povetacicept in systemic lupus erythematosus in the second half of 2024, pending regulatory agreement. The Company plans to share initial data from RUBY-4 in autoimmune cytopenias in the first half of 2024 at a relevant scientific congress. The Company amended its option and license agreement on acazicolcept with AbbVie, stopping enrollment in the phase 2 study in systemic lupus erythematosus (Synergy), and facilitating early assessment of data. The Company ended the year with $368.2 million in cash and investments as of December 31, 2023, which the Company anticipates should be sufficient to fund its planned operations into 2026. 2023 Financial Results Cash Position and Runway: As of December 31, 2023, Alpine’s cash and investments totaled $368.2 million compared to $273.4 million as of December 31, 2022. The Company anticipates its current cash and investments are sufficient to fund planned operations into 2026. Collaboration Revenue: For the year ended December 31, 2023, collaboration revenue was $58.9 million compared to $30.1 million for the same period in 2022. The increase in collaboration revenue relates primarily to a $24.9 million increase in AbbVie revenue, of which $20.4 million relates to a cumulative catch-up adjustment resulting from the completion of enrollment in Synergy per the amendment with AbbVie, and a $4.5 million increase in Amgen revenue, driven primarily by the expiration of Amgen’s option to select a third Research Program. These increases were partially offset by a $0.6 million decrease in Adaptimmune revenue as we completed our final deliverables under the agreement in June 2023. Research and Development Expense: For the year ended December 31, 2023, research and development expense, inclusive of non-cash expenses, were $80.9 million compared to $70.2 million for the same period in 2022. The increase of $10.7 million was driven by an $8.2 million increase in povetacicept costs, primarily related to higher clinical trial costs, process development, and manufacturing, a $1.3 million increase in acazicolcept costs, due primarily to process development and manufacturing costs, and a $7.7 million increase in personnel costs. General and Administrative Expenses: For the year ended December 31, 2023, general and administrative expenses, inclusive of non-cash expenses, were $22.2 million compared to $18.0 million for the same period in 2022. The increase of $4.3 million was primarily attributable to increases in personnel costs and professional services. Net Loss: Net loss for the year ended December 31, 2023, was $32.2 million compared to $57.8 million for the same period in 2022. Alpine Immune Sciences, Inc. Selected Consolidated Balance Sheet Data (In thousands) December 31, 2023 December 31, 2022 (unaudited) Cash and cash equivalents $ 43,921 $ 13,376 Short-term investments 283,491 224,265 Total current assets 330,034 240,993 Long-term investments 40,556 35,481 Total assets 379,852 286,686 Total current liabilities 41,980 57,996 Total stockholders’ equity 327,941 179,420 Total liabilities and stockholders’ equity 379,852 286,686 Consolidated Statement of Operations and Comprehensive Income (Loss) Data (In thousands, except share and per share amounts) Years Ended December 31, 2023 2022 (unaudited) Collaboration revenue $ 58,876 $ 30,064 Operating expenses: Research and development 80,904 70,243 General and administrative 22,222 17,968 Total operating expenses 103,126 88,211 Loss from operations (44,250 ) (58,147 ) Other income (expense): Interest income 11,852 3,288 Interest expense (98 ) (476 ) Other, net 415 (97 ) Loss before taxes (32,081 ) (55,432 ) Income tax (expense) benefit (103 ) (2,330 ) Net loss $ (32,184 ) $ (57,762 ) Comprehensive income (loss): Unrealized gain (loss) on investments 1,493 (901 ) Unrealized gain (loss) on foreign currency translation 25 53 Comprehensive loss $ (30,666 ) $ (58,610 ) Weighted-average shares used to compute basic and diluted net loss per share 50,000,339 33,435,280 Basic and diluted net loss per share $ (0.64 ) $ (1.73 ) 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, 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, 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, including cash equivalents and restricted cash, and investments 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 the second half of 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 the second half of 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.

Ongoing clinical trial has reached target enrollment of 109 patients across clinical sites in the United States and France Open-label dose optimization and proof of concept study of PT-112 monotherapy includes interim data results, with top-line read-out and conference presentations expected in late 2024 NEW YORK, March 8, 2024 /PRNewswire/ -- Promontory Therapeutics Inc., a clinical stage pharmaceutical company advancing immunogenic small molecule approaches in oncology, has completed enrollment of its Phase 2 clinical trial of lead therapeutic candidate, PT-112, reaching its target enrollment of 109 patients with late-line metastatic castration-resistant prostate cancer (mCRPC) (ClinicalTrials.gov Identifier: NCT02266745). The study is evaluating PT-112 in patients who have been treated with at least three prior life-prolonging therapies for mCRPC, and who exhibited radiographic evidence of disease progression at study entry. Patients with bone-only metastatic disease are also included in the study. These requirements create a representative treatment population following standard of care of androgen receptor signaling inhibitors, taxane chemotherapies, and any other drug approved by FDA on the basis of overall survival. The clinical trial enrolled patients across leading sites in the United States (23) and France (9). "This clinical trial is the largest study to date of PT-112 and will establish the optimal dose in line with the FDA's Project Optimus, as well as proof of concept in our late-line mCRPC patient population," said Promontory Therapeutics Chief Medical Officer Johan Baeck, MD. "Data from our earlier Phase 1/2 studies have shown that PT-112 is clinically safe and active, and promotes immunogenic cancer cell death induced by the inhibition of ribosomal biogenesis, which is a promising mechanism of action for late-stage patients with prostate cancer — an 'immune-cold' disease with no broadly approved and effective immunotherapy." Promontory Therapeutics plans for a Type C meeting with the FDA in the second half of 2024, followed by an End-of-Phase 2 meeting with FDA and further engagement with European regulatory authorities. In addition to safety and efficacy findings among late-stage metastatic patients, the study aims to generate meaningful supportive data via correlative research, including on immune activation by PT-112 monotherapy as evaluated by the propagation of new T cell populations, as well as reductions in circulating tumor cells and ctDNA. "Promontory is grateful to our clinical partners across the U.S. and France, including Gustave Roussy Paris, for completing enrollment of this critical Phase 2 study. We are confident in PT-112's potential as an effective treatment for patients with mCRPC who have progressed on androgen receptor directed therapy, chemotherapy or radioligand therapy and who lack any effective immunotherapy," said Promontory Therapeutics Chief Executive Officer Robert Fallon. "We look forward to presenting topline safety, efficacy, and correlative data at relevant research and medical conferences later this year." About PT-112 PT-112 is the first small-molecule conjugate of pyrophosphate in clinical development in oncology. PT-112 has numerous advantages — including its tolerability and inhibition of ribosomal biogenesis which leads to immunogenic cell death, through the release of damage associated molecular patterns that bind to dendritic cells and lead to downstream immune effector cell recruitment in the tumor microenvironment. PT-112 represents a highly potent inducer of this immunological form of cancer cell death. Further, PT-112 harbors a property known as osteotropism, or the propensity of the drug to reach its highest concentrations in certain areas of the bone, making it a candidate for treatment of patients with cancers that originate in, or metastasize to, the bone. The first in-human study of PT-112 demonstrated an attractive safety profile and evidence of long-lasting responses among heavily pre-treated patients and data were published in eClinicalMedicine, part of The Lancet. The combination Phase 1b dose escalation study of PT-112 with PD-L1 checkpoint inhibitor avelumab in solid tumors was reported in a mini-oral presentation at the ESMO 2020 Virtual Congress, and the Phase 2a dose confirmation cohort in non-small cell lung cancer patients was reported at ESMO I-O 2022. The Phase 1 study in patients with relapsed or refractory multiple myeloma presented at ASH 2020 is the third completed Phase 1 study of PT-112. Monotherapy Phase 2 development is ongoing in mCRPC, and includes the Phase 2 proof of concept study in thymic epithelial tumors under the company's formal CRADA with the NCI. Interim data from the NCI study were published at ASCO 2023. About Promontory Therapeutics Promontory Therapeutics Inc. is a privately held, clinical stage pharmaceutical company focused on small molecule immunotherapy, based in New York City. Clinical data generated across three Phase 1 studies have demonstrated single-agent and combination anti-cancer activity and an attractive tolerability profile, and two Phase 2 studies of PT-112 are underway. The company's research and development work has been conducted in the United States, Europe and Asia. The company sponsored the completed clinical study of PT-112 in combination with the PD-L1 inhibitor avelumab, and has an active Phase 2 trial under formal CRADA collaboration with the National Cancer Institute (NCI), utilizing PT-112 in thymic epithelial tumors, rare cancers with no FDA approved drug, where PT-112 has received Orphan Drug designation. Promontory Therapeutics is also a company member of the Paris-Saclay Cancer Cluster, Europe's emerging bio-cluster for oncology, and was a 2023 Nominee for Best Startup by the Prix Galien USA. To learn more about Promontory Therapeutics, visit the company's website here. CONTACTS: Promontory Therapeutics Brooke Raphael, MS VP, Strategy & Operations Tel: +1 (646) 974-6453 Email: [email protected] Investors: Stan Musial Tel: +1 (646) 222-6932 Email: [email protected] ICR Westwicke Media: Alexis Feinberg Tel: +1 (203) 939-2225 Email: [email protected] SOURCE Promontory Therapeutics Inc.