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BEAM-302 Clinical Data at ERS Congress 2026 September 8, 2026 NASDAQ: BEAM
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Today’s agenda 2 AATD Overview and BEAM-302 Clinical Program Beam Overview Introduction Amy Simon, M.D. Chief Medical Officer John Evans Chief Executive Officer Holly Manning Vice President, Investor Relations & External Communications Q&A Mr. Evans, Dr. Simon, Dr. McElvaney & Dr. Ciaramella TOPIC PARTICIPANT Updated BEAM-302 Data at ERS Gerry McElvaney, M.D. RCSI Education & Research Centre, Beaumont Hospital Closing Remarks Giuseppe Ciaramella, Ph.D. President
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Cautionary note regarding forward-looking statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding: the therapeutic applications and potential of our technology, including with respect to AATD; our plans, and anticipated timing, to advance our programs, including risto-cel, BEAM-103, BEAM-301, BEAM-304 and BEAM-302; our plans and anticipated timing to present data from ongoing clinical trials; our anticipated regulatory interactions and filings; our current expectations and anticipated results of operations, including our expected use of capital; the sufficiency of our capital resources to fund operating expenses and capital expenditure requirements and the period in which such resources are expected to be available; and the therapeutic applications and potential of our technology, including our potential to develop lifelong, curative, precision genetic medicines for patients through base editing, including potential safety advantages, all of which are subject to known and unknown important risks, uncertainties and other factors that may cause our actual results, performance or achievements, market trends, or industry results to differ materially from those expressed or implied by such forward-looking statements. Therefore, any statements contained herein that are not statements of historical fact may be forward-looking statements and should be evaluated as such. Without limiting the foregoing, the words "anticipate," "expect," "suggest," "plan," "vision," “strategy,” “possibility,” “promise,” "believe," "intend," "project," "forecast," "estimates," "targets," "projections," "potential," "should," "could," "would," "may," "might," "will," and the negative thereof and similar words and expressions are intended to identify forward-looking statements. Each forward-looking statement is subject to important risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement, including, without limitation, risks and uncertainties related to: our ability to develop, obtain regulatory approval for, and commercialize our product candidates, which may take longer or cost more than planned; our ability to raise additional funding, which may not be available; our ability to obtain, maintain and enforce patent and other intellectual property protection for our product candidates; that preclinical testing of our product candidates and preliminary or interim data from preclinical studies and clinical trials may not be predictive of the results or success of ongoing or later clinical trials; that initiation and enrollment of our clinical trials may take longer than expected; that our product candidates or the delivery modalities we rely on to administer them may cause serious adverse events; the uncertainty that our product candidates will receive regulatory approval necessary to initiate or continue human clinical trials, that our product candidates may experience manufacturing or supply interruptions or failures; risks related to competitive products; and the other risks and uncertainties identified under the headings "Risk Factors Summary" and "Risk Factors" and elsewhere in our annual report on Form 10-K for the year ended December 31, 2025, our quarterly reports on Form 10-Q, and in any subsequent filings with the Securities and Exchange Commission (the "SEC") which are available on the SEC's website at www.sec.gov. Additional information will be made available by our annual and quarterly reports and other filings that we make from time to time with the SEC. These forward-looking statements speak only as of the date of this presentation. Factors or events that could cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We undertake no obligation to update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by applicable law. 3 .
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Our vision is to provide lifelong cures for patients suffering from serious diseases POTENTIAL FOR one-time, curative therapies PLATFORM FOR rapidly programmable precision medicines GENE EDITING FOR rare and common diseases 4
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LESS GENOTOXICITY than traditional gene editing DURABLE correction for one-time cures CONSISTENT gene sequence outcomes Predictable, Reproducible Outcomes for Patients Beam was founded on a simple concept with profound implications 5 BASE EDITING T E C H N O L O G Y
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PRECISION GENETIC MEDICINES PLATFORM Underpinned by a unified culture that operates with integrity and transparency The power of predictability: Beam is building a reliable model for advancing genetic medicine 6 Multiple growing, high-value franchises Active pipeline expansion Creative platform partnerships REUSABLE delivery technology CONSISTENT preclinical and clinical outcomes HIGHLY SCALABLE internal manufacturing FLEXIBLE emerging regulatory framework Easily ADAPTABLE to new targets
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Three high-value programs with blockbuster potential Differentiated development programs across hematology and liver-targeted genetic diseases addressing large, underserved U.S. patient populations 7 Sickle Cell Disease Alpha-1 Antitrypsin Deficiency (AATD) Phenylketonuria (PKU) U.S. addressable population estimates per Beam internal data and market research. RISTO -CEL ~10K-100K U.S. patients eligible for ex vivo treatment and in vivo treatment, respectively KEY DIFFERENTIATORS • Best-in-class clinical profile for risto-cel • Internal manufacturing • Poised to enter an established market with high patient demand • Next-wave in vivo approach making rapid progress BEAM -302 ~100K U.S. patients with severe (PiZZ) AATD KEY DIFFERENTIATORS • Potential first-in-class one-time in vivo therapy addressing liver and lung manifestations • Only genetic medicine in pivotal development for AATD • Converts patients ' disease risk to carrier-like status • Long-term leadership and commitment to AATD patients BEAM -304 ~20K U.S. patients with PKU KEY DIFFERENTIATORS • Potential first-in-class one-time in vivo treatment • Multi-mutation approach using novel regulatory pathways • Limited competition • Evidence of Beam’s growing metabolic expertise
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8 Rapidly advancing and growing a portfolio of liver-targeted in vivo programs for genetic diseases PROGRAM DISEASE DELIVERY EDITING APPROACH RESEARCH LEAD OPTIMIZATION IND ENABLING PHASE I/II PIVOTAL BEAM-302 Alpha-1 antitrypsin deficiency (AATD) In vivo LNP Correction of E342K mutation BEAM-301 Glycogen storage disease type Ia (GSDIa) In vivo LNP Correction of R83C mutation BEAM-304 Phenylketonuria (PKU) In vivo LNP Correction of multiple mutations Industry- leading LNP capabilities Platform synergies potentially enable use of novel regulatory pathways and established clinical footprint Potential best-in-class and first-in- class AATD program Strategic pipeline expansion into PKU LNP = lipid nanoparticle
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Updated data from BEAM-302 Phase 1/2 trial support potential asbest-in- class and first-in-class one-time treatment for AATD 9 CORRECTION OF ROOT CAUSE OF DISEASE BEAM-302 continues to demonstrate the potential to become the first one-time treatment to address both lung and liver manifestations of AATD through direct correction of the disease-causing mutation. TOTAL AAT ABOVE THERAPEUTIC THRESHOLD A single dose of 60 mg BEAM-302 demonstrated durable correction of AAT biology, with all patients achievingtotal AAT levels above the protective threshold. RESTORATION OF AAT FUNCTION BEAM-302 restored normal AAT physiology, including production of corrected M-AAT for the first time that is functional and under normal physiologic control in response to inflammation. REDUCTION OF MUTANT Z-AAT BEAM-302 led to substantial reductions in disease-driving mutant Z-AAT and circulating Z-polymers, supporting its potential to address key drivers of both liver and lung disease. CONSISTENT SAFETY PROFILE Safety profile remains consistent with prior findings and those seen with LNP-based therapies. PIVOTAL LEADERSHIP As the most advanced genetic medicine in AATD and the only genetic medicine in pivotal development, BEAM-302 is now dosing patients globally in its pivotal cohort. Data cutoff June 24, 2026
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Alpha-1 Antitrypsin Deficiency and BEAM-302 Overview Amy Simon, M.D., Chief Medical Officer 10
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Severe AATD (PiZZ genotype) impacts >100,000 individuals in the U.S. with limited treatment options 11 Single G to A point mutation in the SERPINA1 gene (Pi*Z or “Z” mutation) Routine COPD care IV augmentation therapy given weekly is only approved option Supportive care and liver transplant for advanced disease No approved treatments for liver disease Progressive liver disease with fibrosis and cirrhosis due to: • Aggregation and accumulation of mutant Z-AAT Progressive lung disease due to: • Low and poorly functioning systemic Z-AAT levels • Circulating Z-AAT aggregates, causes inflammation AAT, alpha-1 antitrypsin; AATD, alpha-1 antitrypsin disease. National Center for Biotechnology Information. NM_001127701.1(SERPINA1):c.1096G>A (p.Glu366Lys) AND alpha-1-antitrypsin deficiency. Updated February 2, 2025. Available from: https://www.ncbi.nlm.nih.gov/clinvar/RCV000148877.67/ (Accessed March 27, 2026); Dasí F. Med Clin (Barc) 2024; 162:336–342
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AAT protective threshold >11 µM informed by clinical genetics, translates into marked risk reduction for AATD lung and/or liver disease Micromolar (µM) Adapted from Franciosi et al, ERJ 2022 and Vidal et al, Arch Bronconeumol 2006; Brode et al, CMAJ 2012; Fromme et al. 2022 AAT Levels Across Genotypes Disease in MZ and SZ individuals requires presence of additional risk factor, e.g., smoking or obesity 35.2 1.6 1.6 1.0 0 10 20 30 40 ZZ SZ MZ MM Emphysema Risk Liver Fibrosis / Cirrhosis Risk < 11 μM 0% 0% 40% 100% 31.0 1.6 1.6 1.0 0 10 20 30 40 ZZ SZ MZ MM ZZ SZ MZ MM 21.7 3.1 1.7 1.0 0 10 20 30 ZZ SZ MZ MM 12 Genotype Lifetime Risk Lifetime Risk
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BEAM-302 is a potential one-time therapy that uses base editing to directly correct the E342K mutation causing AATD CRISPR Protein Deaminase Guide RNA Corrected SERPINA1 gene PiM E342K mutation PiZ BEAM-302 BASE EDITOR 13
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BEAM-302 has the potential to be first, one-time treatment to address full spectrum of disease manifestations of AATD 14 Durable, single- course treatment Address both lung and liver manifestations • Liver produces M-AAT for the first time • Significantly reduces Z-AAT • Total AAT above 11 µM protective threshold • Increased total AAT is functional • AAT increases when needed with acute inflammation Correction at root cause of disease Restore physiologic control of AAT GOALS OF BEAM -302 TREATMENT
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Beam intends to pursue accelerated approval pathway for BEAM-302 based on FDA feedback to date 15 • Alignment reached with FDA on potential accelerated approval pathway for BEAM-302 in AATD • Primary endpoint based on AAT biomarkers evaluated over 12 months • Plan to enroll 50 additional patients in expansion of global, open-label Phase 1/2 trial • Ongoing FDA dialogue on confirmatory trial design • Accepted to FDA CMC Development and Readiness Pilot (CDRP) program Clinical proof of concept U.S. IND clearance INTEREST RMAT Designation Orphan Drug Designation FDA alignmentQ2 2025Q1 2025 Q4 2025 IND = investigational new drug; RMAT Designation = Regenerative Medicine Advanced Therapy Designation
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Robust and flexible Phase 1/2 trial design supported rapid advancement to pivotal development 16 PART A: AATD-associated Lung Disease PART B: AATD-associated Liver Disease with or without Lung Disease • Dosing initiated in global pivotal cohort • Significant site and patient interest • Utilizing existing extensive global site network: 14+ sites in 6 countries • Multiple U.S. sites activated with more planned PART C: PIVOTAL COHORT AATD-associated Lung Disease with or without Liver Disease DOSE ESCALATION & EXPANSION DOSE ESCALATION • Data reported at ERS from 21 patients treated with single-dose BEAM-302 in dose escalation • 3 patients treated in multi -dose cohort • 6 patients treated in 60 mg expansion • Data reported at ERS from 8 patients treated with single-dose BEAM-302 in dose escalation
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First-in-human in vivo gene editing for severe alpha-1 antitrypsin deficiency (AATD): initial data from the Phase 1/2 study of BEAM -302 John R Hurst , E mily FA van’ t Wo ut, Tho ma s Ash down, Ma tthew C onron , N. Ger ry McElvaney, Je ffrey Ga rrett, Ed Gan e, An drew A Wilson, Joe Kaserman, Ch arl ie Strange, J. Mic hael Wells, Catheri na L Chan g, Mar k Holmes, Ai shath Fazl een, Mark O’Carroll, Ul rike Lorc h, Jan Stolk , Amir Majid , Reem Al luhibi, Nicolas Cu rrier, Katy Hayes, Beatric e Ch iang, Gary L iu, James Maie r, Ar thur Lo, Karen Cao, Ba hru Hab temaria m, Pr iya S Choc kalin gam, John J Ko, Su nita Goyal, Amy Simon, Al ice Turn er
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Aims AATD, alpha-1 antitrypsin deficiency We present results from the BEAM-302 clinical study (NCT06389877) a Phase 1/2, multicenter, open-label, dose-exploration and dose-expansion study evaluating safety and efficacy of BEAM-302 in adults with PiZZ-AATD–associated lung disease and/or liver disease
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BEAM-302 clinical study enrolled patients with both AATD-associated lung and liver disease Data cutoff June 24, 2026. *Blood AAT was measured by turbidimetry. AAT, alpha-1 antitrypsin; AATD, alpha-1 antitrypsin deficiency; ppFEV1, percent predicted forced expiratory volume in 1 second; HNE, human neutrophil elastase; METAVIR, meta-analysis of histological data in viral hepatitis; TEAE, treatment-emergent adverse event AATD-associated lung disease 60 mg N=6 30 mg N=3 15 mg N=3 AATD-associated liver disease with or without lung disease 75 mg N=9 • Select key endpoints: – Rates of TEAEs – Blood levels of total AAT, Z-AAT and M-AAT, and functional AAT – HNE activity in blood – Z-polymer levels in blood • Baseline characteristics: – Age range 35–69 years; homozygous for PiZZ mutation; mean post-bronchodilator ppFEV1: 62.0% (range 38.8–101.5%) – Mean blood AAT level: 4.8 µM* (range 2.4–8.4 μM), with clinical diagnosis of emphysema; no evidence of liver disease (Part A only) – Clinical diagnosis of AATD-related liver disease (Part B only); METAVIR fibrosis stage F1 (n=4) and F2 (n=4) 60 mg N=5 30 mg N=3 PART A: PART B: NCT06389877 on ClinicalTrials.gov for full study design
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Initial safety data suggest that BEAM-302 safety profile is consistent with that of LNP-based therapies Part A (N=21) Part B (N=8) n (%) 15 mg (N=3) 30 mg (N=3) 60 mg (N=6) 75 mg (N=9) 30 mg (N=3) 60mg (N=5) Any TEAEs 3 (100) 3 (100) 6 (100) 8 (88.9) 3 (100) 5 (100) Related to BEAM-302 2 (66.7) 0 3 (50.0) 5 (55.6) 1 (33.3) 3 (60.0) Any TEAEs Grade ≥3 0 0 0 0 0 1 (20.0)* Related to BEAM-302 0 0 0 0 0 1 (20.0)* Serious TEAEs 0 0 0 0 0 1 (20.0)† Related to BEAM-302 0 0 0 0 0 0 IRRs 2 (66.7) 0 3 (50.0) 5 (55.6) 1 (33.3) 1 (20.0) Grade 1 2 (66.7) 0 1 (16.7) 1 (11.1) 0 1 (20.0) Grade 2‡ 0 0 2 (33.3) 4 (44.4) 1 (33.3) 0 AL T/AST elevations§ 3 (100) 1 (33.3) 6 (100) 7 (77.8) 2 (66.7) 3 (60.0) Grade 1 3 (100) 1 (33.3) 6 (100) 7 (77.8) 2 (66.7) 2 (40.0) Grade 2 0 0 0 0 0 0 Grade 3 0 0 0 0 0 1 (20.0)* Data cutoff June 24, 2026. *ALT/AST elevation above baseline began on Day 14 and reached Grade 3 on Day 25; bilirubin remained normal and resolved without intervention; †shortness of breath, assessed as unrelated to BEAM-302 and related to underlying disease; ‡Grade 2 IRRs required treatment intervention and/or infusion interruption; §ALT/AST elevations were identified from laboratory data during the dose- limiting toxicity monitoring period and graded per CTCAE v5.0. ALT, alanine aminotransferase; AST, aspartate aminotransferase; IRR, infusion-related reaction; LNP, lipid nanoparticle; TEAE, treatment-emergent adverse event
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Part A single-dose cohorts: BEAM-302 (60 mg) led to sustained increases in total AAT levels to above the 11 μM protective threshold Data cutoff June 24, 2026. Total blood AAT was measured by turbidimetry. *Protective serum AAT concentration above which protease-mediated lung damage is reduced, and which serves as a therapeutic target; †baseline for each patient is defined as the average of all assessments conducted within the 84-day screening period prior to BEAM-302 infusion; ‡steady state is defined as the period beginning on a patient’s Day 28 visit through their last available visit. AAT, alpha-1 antitrypsin; SEM, standard error of the mean. 1. Franciosi AN, et al. Eur Resp J 2022;59:2101410 Total AAT (μM) 15 mg (N=3) 30 mg (N=3) 60 mg (N=6) 75 mg (N=9) Baseline, † mean (SEM) 4.4 (0.2) 5.3 (0.3) 5.0 (0.3) 4.7 (0.6) Steady state, ‡ mean (SEM) Median (min, max) 7.5 (0.2) 7.6 (7.2, 7.8) 9.0 (1.5) 8.5 (6.7, 11.8) 14.4 (0.9) 15.2 (11.0, 16.4) 12.8 (0.8) 12.6 (9.0, 16.3) Time since BEAM -302 infusion 0 2 4 6 8 10 12 14 16 18Blood total AAT ( μM) Part A 15 mg Part A 30 mg Part A 60 mg Part A 75 mg 6 9 3 3 6 9 3 3 6 9 3 3 6 9 3 3 6 9 3 3 6 9 3 3 6 9 3 3 6 9 3 3 6 6 3 3 5 3 3 3 3 3 N= 11 μM protective threshold1*
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Part B cohorts: Post-treatment total AAT levels consistent with Part A Data cutoff June 24, 2026. Total blood AAT was measured by turbidimetry. *Protective serum AAT concentration above which protease-mediated lung damage is reduced, and which serves as a therapeutic target; †baseline for each patient is defined as the average of all assessments conducted within the 84-day screening period prior to BEAM-302 infusion; ‡steady state is defined as the period beginning on a patient’s Day 28 visit through their last available visit. AAT, alpha-1 antitrypsin; SEM, standard error of the mean. 1. Franciosi AN, et al. Eur Resp J 2022;59:2101410 Total AAT (μM) 30 mg (N=3) 60 mg (N=5) Baseline, † mean (SEM) 5.1 (0.5) 4.7 (0.5) Steady state, ‡ mean (SEM) Median (min, max) 11.7 (1.0) 11.4 (10.2, 13.5) 13.5 (0.9) 13.8 (11.1, 15.4) 0 2 4 6 8 10 12 14 16Blood total AAT ( μM) Part B 60 mg Part B 30 mg 5 3 5 3 5 3 3 3 3 3 3 33 3 N= Time since BEAM -302 infusion 11 μM protective threshold1*
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Functional AAT increased and human neutrophil elastase activity levels decreased with BEAM-302 at 60 mg dose Data cutoff June 24, 2026; functional AAT irreversibly binds and inhibits HNE; therefore, reduced NE levels indicate functional AAT activity. *n=5 for Part A HNE concentration at Day 28; †values below the LLOQ of 87.78 ng/mL were set to LLOQ/2 for analysis. AAT, alpha-1 antitrypsin; HNE, human neutrophil elastase; LLOQ, lower limit of quantification • Following a 60 mg dose, functional AAT levels increased and >80% of participants in Part A had at least one human neutrophil elastase (HNE) activity measurement below lower limit of quantification of 87.8 ng/mL; in Part B, functional AA T also increased and HNE activity decreased 0 100 200 300 400 500 600 0 2 4 6 8 10 12 14 16 HNE activity (ng/mL) Functional AAT (μM) Part A fAAT Part B fAAT Part A HNE Part B HNEPart A fAAT Part B fAATPart A HNE Part B HNE 6 5 6 5 6 3 6 3 6 6 66* 5 Time since BEAM -302 infusion LLOQ†
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Single dose BEAM-302 (60 mg) led to 84% reduction in circulating Z-AAT in Part A and Part B Data cutoff June 24, 2026; Z-AAT was measured by liquid chromatography-mass spectrometry; bold typeface indicates N numbers for 60 mg doses; *Measured at steady state, defined as the period beginning on a patient’s Day 28 visit through their last available visit. AAT, alpha-1 antitrypsin -120 -100 -80 -60 -40 -20 0 20 Change from baseline (%) Time since BEAM-302 infusion 3 3 6 5 3 3 6 5 3 3 6 5 3 3 6 3 3 3 6 3 3 3 6 3 3 6 3 3 6 3 3 6 3 5 3 Part A 60 mg Part B 60 mgPart A 30 mg Part B 30 mg Blood Z-AAT (%) Part A: 60 mg (N=6) Part B: 60 mg (N=5) Percentage change from baseline,* mean (SEM) −83.9 (2.6) −83.5 (2.7)
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BEAM-302 treatment led to a significant decrease in circulating Z-AAT protein aggregates, referred to as Z-polymers Data cutoff June 24, 2026; plasma Z-polymer was measured by enzyme-linked immunosorbent assay; patient numbers by visit: Part A 30 mg 1: 3, 3, 3, 3, 3, 3, 3 (Baseline–Month 18); Part A 60 mg: 6, 6, 5, 6, 6, 5 (Baseline–Month 12); Part B 30 mg: 3, 3, 3, 3, 3 (Baseline–Month 6); Part B 60 mg 2: 5, 5, 5, 3 (Baseline–Month 3) 1. Núñez et al. Respir Res; 2021;22:244 0 10 20 30 40 50 60 70 80 Plasma Z-polymer (μg/mL) Time since BEAM-302 infusion Part A 60 mg Part B 60 mgPart A 30 mg Part B 30 mg MZ reference1
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BEAM-302 (60 mg) treatment achieved sustained circulating M-AAT levels of 93% in Part A and Part B Data cutoff June 24, 2026. M-AAT/Z-AAT was measured by liquid chromatography mass spectrometry. %M-AAT=M- AAT/(M-AAT+Z-AAT)×100. Total AAT was measured by turbidimetry. *Steady state is defined as the period beginning on a patient’s Day 28 visit through their last available visit. AAT, alpha-1 antitrypsin; SEM, standard error of the mean. 1. Donato LJ, et al. Respir Res 2015;16:96 BEAM-302 restored predominant production of the M -AAT isoform M-AAT Z-AAT Proportion of total AAT (%) 0% 20% 40% 60% 80% 100% 120% 30 mg 60 mg 30 mg 60 mg Part A Part B Time since BEAM -302 infusion Time since BEAM -302 infusion • Proportion of M-AAT of >90% post-BEAM-302 at 60 mg dose is greater than MZ genotype (80%)1 M-AAT, as a proportion of total AAT Part A: 60 mg (N=6) Part B: 60 mg (N=5) Baseline,* mean (SEM) 0 (0) 0 (0) Steady state,† mean (SEM) 93.6 (1.1) 93.3 (1.5)
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0 5 10 15 20 25 30 Baseline Steady state mean, Day 28 –Month 6 Unscheduled visit for respiratory infection, ~Month 8 Month 9 Month 12 New AAT baseline after treatment with BEAM-302 Increased AAT level during upper respiratory tract infection 94% M-AAT 95% M-AAT 95% M-AAT 6μM 14 μM 23 μM 19 μM Total AAT (μM) 0% M-AAT 14 μM 95% M-AAT BEAM-302 restored normal physiologic control of AAT protein production Data cutoff June 24, 2026; total AAT was measured by turbidimetry *Data from a single patient treated with 60 mg BEAM-302 AAT, alpha-1 antitrypsin BEAM-302 resulted in normal AAT regulation during inflammation, while maintaining a beneficial M/Z ratio *
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Well tolerated at 60 mg, with mainly transient Grade 1 transaminase elevations and mild-to-moderate IRRs BEAM-302 is the first therapy in pivotal development to correct a disease-causing mutation 60 mg dose led to: increased total and functional AAT above the protective threshold, the majority of which was M-AAT, decreased Z-AAT, and increased circulating AAT during inflammation BEAM-302 offers the potential for a one-time therapy to correct the mutant Z allele in the SERPINA1 gene and restore AAT function AAT, alpha-1 antitrypsin; AATD, alpha-1 antitrypsin deficiency; IRR, infusion-related reaction; LNP, lipid nanoparticle Durable restoration of AAT function Safety profile is consistent with LNP-based therapies Correct DNA mutation – the root cause of disease The Phase 2 pivotal cohort of patients with AATD-associated lung disease with or without liver disease (Part C of this study) is currently dosing patients globally using the 60 mg dose of BEAM -302 Please see accompanying ePoster (5575) for additional information
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0 5 10 15 20 25 30 Steady state Inflammation What does the ideal AATD treatment look like? Adapted from Franciosi et al, ERJ 2022 and from Vidal et al, Arch Bronconeumol 2006; Brode et al, CMAJ 2012; Donato LJ, et al. Respir Res 2015;16:96; Mahadeva, Ravi et al. The American journal of pathology vol. 166,2 (2005): 377-86; Mulgrew, Alan T et al. Chest vol. 125,5 (2004): 1952-7. No Disease No Disease Unless Other Risk Factor Present Disease Genotype MM MZ SZ ZZ AAT < 11 µM 0% 0% ~40% 100% Emphysema risk None Low Low High Liver disease risk None Low Low High Total AAT above protective threshold eliminates risk unless second risk factor Total AAT aboveprotective threshold of 11 µM Increase in total AAT maintains composition with high M -AAT to protect lungs M-AAT increases with acute phase reaction Total AAT (μM) Lower Z-AAT and Z-polymer associated with decrease in liver and lung manifestations AAT composition with higher M- AAT and lower Z-AAT 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% MM ZZ MZ BEAM-302 Treated (60 mg)M-AAT Z-AAT 95% M-AAT 95% M-AAT 80% M-AAT 93% M-AAT
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Acknowledgments REFERENCES CITED IN THIS PRESENTATION: National Center for Biotechnology Information. NM_001127701.1(SERPINA1):c.1096G>A (p.Glu366Lys) AND alpha-1-antitrypsin deficiency. Updated February 7, 2026. Available from: https://www.ncbi.nlm.nih.gov/clinvar/RCV000148877.67/ (Accessed March 27, 2026); Dasí F. Med Clin (Barc) 2024; 162:336–342; Beam Therapeutics Inc. Data on file. Protocol no. BTX-302-001; Franciosi AN, et al. Eur Resp J 2022;59:2101410; Donato LJ, et al. Respir Res 2015;16:96 Thank you to the study participants, their families, and their caregivers for their participation, and the study investigators, study sites, Alpha-1 Foundation, and patient advocacy groups for their contributions This clinical study is sponsored by Beam Therapeutics Please see accompanying ePoster (5575) for additional information Boston University and Boston Medical Center, Boston, Massachusetts Medical University of South Carolina (MUSC), Charleston, South Carolina University of Alabama at Birmingham (UAB), Alabama University of Florida, Gainesville, Florida University Hospital Southampton NHS Foundation Trust, Southampton Richmond Pharmacology Ltd, London Royal Free London NHS Foundation Trust, London Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust Royal Adelaide Hospital, Adelaide St Vincents Hospital Melbourne, Fitzroy, Melbourne Beaumont Hospital, Dublin, Ireland Waikato Hospital, Hamilton New Zealand Clinical Research (NZCR), Auckland Aotearoa Clinical Trials (Middlemore Clinical Trials), Auckland Leiden University Medical Center, Leiden US UK AUS Ireland NZ The Netherlands
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Closing Remarks Giuseppe Ciaramella, Ph.D., President 31
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BEAM-302, the first genetic medicine in pivotal development, has the potential to be the first one-time treatment forboth lung and liver manifestations of AATD Correct DNA mutation – the root cause of disease Increase secreted AAT to prevent lung damage Decrease mutant Z-AAT to prevent liver & lung damage Restore physiologic control of AAT during inflammation Durable, one- time treatment without chronic administration BEAM-302 has potential to address critical aspects of AATD 32
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Beam’s long-term commitment to leading innovation for the AATD community 33 • Internal Beam lifecycle management through ongoing R&D efforts • Member of C-Path's Critical Path for AATD (CPA-1) consortium in collaboration with FDA to accelerate AATD research by identifying clinical efficacy endpoints • Collaboration with Alpha-1 Foundation and Alpha-1 Europe Allianceto educate about gene editing and obtain critical input on clinical trial design and patient experience • Inaugural industry sponsor of AlphaDetect, a nonprofit powered and funded by the Alpha-1 Foundation, to further strengthen efforts to accelerate route targeted detection of AATD
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34 Beam is well positioned to realize the power of predictability in 2026 through key anticipated milestones • BEAM-302 pivotal cohort ongoing • Plan to submit risto-cel BLA as early as YE 2026 • Study start-up activities ongoing for BEAM-304 Phase 1/2 clinical trial • Report initial BEAM-301 data by YE 2026 • Advance in vivo HSC editing program • $1.2 billion in cash as of June 30, 2026* • Expected runway into mid-2029 through anticipated risto-cel launch, execution of BEAM-302 pivotal development plan and clinical proof of concept for BEAM-304** Pursue Path to Approval for Lead Programs Maintain Financial Strength Advance and Expand Pipeline *Inclusive of cash, cash equivalents, and marketable securities. **Inclusive of potential additional $200 million from Sixth Street facility.
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35 THANK YOU Kyle LIVING WITH SICKLE CELL DISEASE Dan LIVING WITH ALPHA-1 ANTITRYPSIN DEFICIENCY Alyssa and Gayle LIVING WITH GLYCOGEN STORAGE DISEASE TYPE IA