Legend Biotech (NASDAQ: LEGN) unveils promising first-in-human LB2501 in vivo CAR-T results
Rhea-AI Filing Summary
Legend Biotech reported first-in-human proof-of-concept data for LB2501, an in vivo CD19/CD20 dual-targeting CAR-T therapy, in relapsed or refractory B-cell non-Hodgkin lymphoma. In an ongoing Phase 1 trial, a single infusion at the higher dose level achieved a 100% objective response rate and an 83.3% complete response rate, with all responses ongoing at data cutoff. Across 12 patients treated at two dose levels, overall objective response was 50.0% and complete response was 41.7% in a heavily pretreated population. LB2501 generated dose-dependent in vivo CAR-T expansion without lymphodepletion and showed a favorable safety profile, with no dose-limiting toxicities, serious adverse events, ICANS, or deaths, and only Grade 1–2 infusion reactions and cytokine release syndrome. Pharmacokinetic and translational data showed rapid vector clearance, T-cell–specific transduction, highly polyclonal integration, and persistent CAR-T detection, supporting clinical proof-of-concept for Legend’s in vivo TaVec platform.
Positive
- LB2501 shows strong early efficacy at higher dose: In relapsed/refractory B-cell non-Hodgkin lymphoma, dose level 2 achieved a 100% objective response rate and 83.3% complete response rate after a single infusion, with all responses ongoing at data cutoff.
Negative
- None.
Insights
Early LB2501 data show strong activity and clean safety in a small Phase 1 study.
Legend Biotech presented first-in-human LB2501 results in relapsed or refractory B-cell non-Hodgkin lymphoma. At the higher dose level, a single infusion produced a 100% objective response rate and 83.3% complete response rate in six patients, without lymphodepletion.
The safety profile appears favorable: no dose-limiting toxicities, serious adverse events, ICANS, or deaths were reported. Cytokine release syndrome and infusion-related reactions were all Grade 1–2 and managed without glucocorticoids for CRS, which is notable for a first-in-human CAR-T–like approach.
Pharmacokinetic and integration analyses showed dose-dependent CAR-T expansion, persistent detection, rapid vector clearance, and polyclonal lentiviral integration, supporting the mechanistic rationale for the in vivo TaVec platform. While the dataset is small and early, these results strengthen the case for further LB2501 and platform development.
Key Figures
Key Terms
in vivo CAR-T medical
cytokine release syndrome medical
immune effector cell-associated neurotoxicity syndrome (ICANS) medical
objective response rate financial
lentiviral vector technical
dose-limiting toxicities medical
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
Form 6-K
REPORT OF FOREIGN PRIVATE ISSUER PURSUANT TO RULE 13a-16 OR 15d-16 UNDER THE SECURITIES EXCHANGE ACT OF 1934
Date of Report: June 15, 2026
Commission File Number: 001-39307
Legend Biotech Corporation
(Translation of registrant's name into English)
2101 Cottontail Lane
Somerset, New Jersey 08873
(Address of principal executive office)
Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.
Form 20-F [ X ] Form 40-F [ ]
Legend Biotech Presents First-in-Human LB2501 In Vivo CAR-T Data at EHA 2026
On June 14, 2026, Legend Biotech Corporation (“Legend Biotech”) issued a press release announcing first clinical proof-of-concept data for LB2501, its investigational in vivo CD19/CD20 dual-targeting CAR-T cell therapy, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL)(the “Proof-of-Concept Data”). The press release is attached to this Form 6-K as Exhibit 99.1.
The Company has also made available an investor presentation regarding the Proof-of-Concept Data, a copy of which is attached to this Form 6-K as Exhibit 99.2 and may be viewed on the Company’s website at https://investors.legendbiotech.com/events-and-presentations.
This report on Form 6-K, including Exhibit 99.1 and Exhibit 99.2, is hereby incorporated herein by reference in the registration statements of Legend Biotech on Form F-3 (Nos. 333-278050, 333-272222, and 333-257625) and Form S-8 (No. 333-239478 and 333-283217), to the extent not superseded by documents or reports subsequently filed.
EXHIBIT INDEX
| Exhibit | Title | |||
| 99.1 | Press Release, dated June 15, 2026 | |||
| 99.2 | EHA 2026 Investor Presentation |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
| Legend Biotech Corporation | ||
| (Registrant) | ||
| Date: June 15, 2026 | /s/ Ying Huang | |
| Ying Huang, Ph.D. | ||
| Chief Executive Officer | ||
EXHIBIT 99.1
Legend Biotech Establishes Clinical Proof-of-Concept for LB2501, a Potential First-in-Class In Vivo CD19/CD20 Dual-Targeting CAR-T, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma
- Achieved 100% ORR and 83.3% CR rate at dose level 2 following a single infusion in patients with relapsed/refractory B-NHL in an ongoing Phase 1 study
- Single infusion of LB2501 generated dose-dependent in vivo CAR-T expansion without lymphodepletion
- No dose-limiting toxicities, serious adverse events, ICANS, or deaths were reported; infusion-related reactions and CRS were Grade 1–2, and none required glucocorticoids for CRS management
- Additional translational data showed rapid vector clearance, polyclonal vector integration, and no evidence of non-specific transduction
- Proof-of-concept progress demonstrates leadership in next-generation cell therapies, with results presented in a late-breaking session at EHA 2026
BRIDGEWATER, N.J., June 15, 2026 (GLOBE NEWSWIRE) -- Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global leader in cell therapy, today announced first clinical proof-of-concept data for LB2501, its investigational in vivo CD19/CD20 dual-targeting CAR-T cell therapy, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL). The results are being presented today in a late-breaking session at the European Hematology Association (EHA) 2026 Congress (Abstract #LB5006).
In the ongoing Phase 1 study, a single infusion of LB2501 generated dose-dependent in vivo CAR-T expansion without lymphodepletion. At the higher dose level (DL2), LB2501 achieved a 100% objective response rate (ORR) (6/6) and an 83.3% complete response rate (CR) (5/6), with all responses ongoing at the time of data cutoff. LB2501 also showed a favorable safety profile, with no dose-limiting toxicities (DLTs), serious adverse events (SAEs), immune effector cell-associated neurotoxicity syndrome (ICANS), or deaths reported.
“In vivo CAR-T represents a compelling frontier in cell therapy, enabling the generation of CAR-T cells directly within the patient, with the potential to simplify treatment and expand access over time,” said Ying Huang, Ph.D., Chief Executive Officer of Legend Biotech. “LB2501 is our step toward realizing that vision and reflects further progress toward our goal of leading the future of cell therapy. Backed by the commercial and scientific foundation we have built with CARVYKTI, we are well-positioned to advance this next generation of CAR-T delivery. These early data, with deep responses from a single infusion across patients, give us confidence in the path ahead.”
LB2501 Demonstrates In Vivo CAR-T Generation and Early Clinical Activity
In an ongoing Phase 1 study, 12 patients with R/R B-NHL received LB2501 across two dose levels, DL1 (n=6) and DL2 (n=6). Patients had received a median of three prior lines of therapy, and 58.3% were refractory to their most recent treatment. The open-label, multi-center, dose-escalation study is evaluating safety, recommended Phase 2 dose, pharmacokinetics, and preliminary efficacy in adults with R/R B-NHL. The study was conducted without lymphodepletion.
At DL2, LB2501 achieved a 100% ORR (6/6) and an 83.3% CR rate (5/6), with responses observed across patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL). Across both dose levels, the ORR was 50.0% (6/12), and the CR rate was 41.7% (5/12). At the time of data cutoff, all responses at DL2 were ongoing.
LB2501 showed a favorable safety profile. No DLTs, SAEs, ICANS, or deaths were reported. Infusion-related reactions (IRR) and cytokine release syndrome (CRS) were the most common adverse events of special interest and were all Grade 1–2. Infusion-related reactions occurred in 75.0% (9/12) of patients overall, with a median onset of 1.4 hours after infusion and a median recovery time of 18.6 hours. CRS occurred in 66.7% (8/12) of patients overall, with a median onset at Day 11 and a median duration of 4.5 days. IRR and CRS were all Grade 1–2, no patients required glucocorticoids for CRS management. Four patients received tocilizumab.
Pharmacokinetic analyses showed dose-dependent in vivo CAR-T expansion in 100% (6/6) of patients at DL2 and 83% (5/6) of patients at DL1. CAR-T cells remained detectable in peripheral blood for up to 116 days. Viral copy number in peripheral blood peaked immediately after infusion and decreased to undetectable concentrations within 24 hours.
Additional translational analyses further characterized the in vivo profile of LB2501. No evidence of non-specific transduction was detected in NK cells or other non-T/B/NK lymphocyte populations. Vector integrations were highly polyclonal and diverse. These findings support proof-of-concept for in vivo T-cell engineering, with polyclonal vector integration and rapid vector clearance.
“These early clinical findings are encouraging in a heavily pretreated relapsed or refractory B-cell non-Hodgkin lymphoma population,” said Lei Fan, M.D., Ph.D., Professor, Doctoral Supervisor, and Administrative Director, Hematology Department, Jiangsu Province Hospital, Nanjing, China. “The responses observed at the higher dose level achieved a 100% objective response rate, together with a favorable safety profile and the absence of lymphodepletion, support further investigation of LB2501 as a novel in vivo CAR-T approach. The additional pharmacokinetic and translational findings presented at EHA further support the feasibility of generating CAR-T cells directly within the patient.” ‡
ABOUT LB2501
LB2501 is an investigational, potential first-in-class CD19/CD20 dual-targeting in vivo CAR-T therapy designed to generate CAR-T cells directly within the patient following a single intravenous infusion. It is being evaluated in an ongoing Phase 1, open-label study (NCT07002112) in patients with relapsed/refractory B-cell malignanciesi to assess safety, tolerability, and preliminary efficacy.[i]
ABOUT B-CELL NON-HODGKIN LYMPHOMA
Non-Hodgkin lymphoma (NHL) is a group of cancers that originate in lymphocytes, a type of white blood cell that plays a key role in the body’s immune system.ii B-cell lymphomas account for approximately 85% of NHL cases and arise from abnormal growth of B lymphocytes (B cells), which are responsible for producing antibodies. These malignancies include a range of subtypes that vary in aggressiveness, from slow-growing to highly aggressive disease.iii
While treatment advances have improved outcomes for some patients, those with relapsed or refractory B-cell NHL, particularly after multiple lines of therapy, often face limited options.
ABOUT LEGEND BIOTECH
With over 3,000 employees, Legend Biotech is the largest standalone cell therapy company and a pioneer in treatments that change cancer care forever. Legend Biotech is at the forefront of the CAR-T cell therapy revolution with CARVYKTI®, a one-time treatment for relapsed or refractory multiple myeloma, which it develops and markets with collaborator Johnson & Johnson. Centered in the United States, Legend Biotech is building an end-to-end cell therapy company by expanding its leadership to maximize CARVYKTI’s patient access and therapeutic potential. From this platform, Legend Biotech plans to drive future innovation across its pipeline of cutting-edge cell therapy modalities.
Learn more at https://legendbiotech.com and follow us on X, Instagram, and LinkedIn.
CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS
Statements in this press release about future expectations, plans, and prospects, as well as any other statements regarding matters that are not historical facts, constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to Legend Biotech’s strategies and objectives, the Phase 1 clinical trial of LB2501, and the potential benefits of LB2501, including the reproducibility and durability of any favorable results initially seen in patients dosed to date in clinical trials, and LB2501’s potential to be first-in-class. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors. Legend Biotech’s expectations could be affected by, among other things, uncertainties involved in the development of new pharmaceutical products; unexpected clinical trial results, including as a result of additional analysis of existing clinical data or unexpected new clinical data; unexpected regulatory actions or delays, including requests for additional safety and/or efficacy data or analysis of data, or government regulation generally; unexpected delays as a result of actions undertaken, or failures to act, by Legend Biotech’s third-party partners; uncertainties arising from challenges to Legend Biotech’s patent or other proprietary intellectual property protection, including the uncertainties involved in the U.S. litigation process; government, industry, and general product pricing and other political pressures; as well as the other factors discussed in the “Risk Factors” section of Legend Biotech’s Annual Report on Form 20-F filed with the Securities and Exchange Commission on March 10, 2026. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described in this press release as anticipated, believed, estimated, or expected. Any forward-looking statements contained in this press release speak only as of the date of this press release. Legend Biotech specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events, or otherwise.
‡ Lei Fan, M.D., Ph.D., Professor, Doctoral Supervisor, and Administrative Director, Hematology Department, Jiangsu Province Hospital, Nanjing, China, has provided consulting and advisory services to Legend Biotech; he has not been paid for any media work.
INVESTOR CONTACT:
Jessie Yeung
Tel: (732) 956-8271
investor@legendbiotech.com
PRESS CONTACT:
Kim Fox
Tel: (848) 388-8445
media@legendbiotech.com
______________________________
i ClinicalTrials.Gov. The CD19/ CD20 Dual-Target in Vivo CAR-T Lentiviral Product in the Treatment of Relapsed/Refractory B-cell Malignancies. https://clinicaltrials.gov/study/NCT07002112. Accessed May 2026
ii American Cancer Society. “What Is Non-Hodgkin Lymphoma?”. Available at: https://www.cancer.org/cancer/types/non-hodgkin-lymphoma/about/what-is-non-hodgkin-lymphoma.html.Accessed May 2026.
iii American Cancer Society. “Types of B-cell Lymphoma”. Available at: https://www.cancer.org/cancer/types/non-hodgkin-lymphoma/about/b-cell-lymphoma.html. Accessed May 2026.
Exhibit 99.2
EHA 2026 Recap June 2026 © 2026 Legend Biotech. All rights reserved.
Forward Looking Statements 2 This presentation has been prepared by Legend Biotech Corporation (“Legend Biotech” or the “Company”) solely for information purpose and does not contain all relevant information relating to the Company. The safety and efficacy of the agents and/or uses under investigation discussed in this presentation have not been established, except to the extent specifically provided by marketing authorizations previously received from relevant health authorities. Further, for investigational agents and/or uses, the Company cannot guarantee health authority approval or that such agents and/or uses will become commercially available in any country. Certain information contained in this presentation and statements made orally during this presentation relate to or are based on studies, publications, surveys and other data obtained from third - party sources and Legend Biotech's own internal estimates and research. While Legend Biotech believes these third - party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third - party sources. While Legend Biotech believes its internal research is reliable, such research has not been verified by any independent source. Statements in this presentation about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, constitute “forward - looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to Legend Biotech’s strategies and objectives; the ongoing Phase 1 clinical trial of LB2501; the potential benefits of LB2501, including the reproducibility and durability of any favorable results initially seen in patients dosed to date in clinical trials; LB2501's potential to be first - in - class; the progress of submissions with the FDA, the EMA and other regulatory authorities; expected results and timing of clinical trials; Legend Biotech’s expectations on advancing its pipeline and product portfolio, including TaVec and LB2501; and the potential benefits of Legend Biotech’s product candidates and its in vivo platform. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward - looking statements, although not all forward - looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward - looking statements as a result of various important factors. Legend Biotech’s expectations could be affected by, among other things, uncertainties involved in the development of new pharmaceutical products; unexpected clinical trial results, including as a result of additional analysis of existing clinical data or unexpected new clinical data; unexpected regulatory actions or delays, including requests for additional safety and/or efficacy data or analysis of data, or government regulation generally; unexpected delays as a result of actions undertaken, or failures to act, by our third party partners; uncertainties arising from challenges to Legend Biotech’s patent or other proprietary intellectual property protection, including the uncertainties involved in the U.S. litigation process; competition in general; government, industry, and general product pricing and other political pressures; as well as the other factors discussed in the “Risk Factors” section of Legend Biotech’s Annual Report on Form 20 - F for the year ended December 31, 2025, filed with the Securities and Exchange Commission (SEC) on March 10, 2026 and Legend Biotech’s other filings with the SEC. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described in this presentation as anticipated, believed, estimated or expected. Any forward - looking statements contained in this presentation speak only as of the date of this presentation. Legend Biotech specifically disclaims any obligation to update any forward - looking statement, whether as a result of new information, future events or otherwise. .
3 Agenda In Vivo Platform Overview 1 Recap of LB2501 Data from EHA 2026 2 Next Steps 3 Q&A 4
4
5 In Vivo Delivery A next generation approach to off - the - shelf CAR - T 1 • Better CAR - T cell fitness • Off - the - shelf therapy • No lymphodepletion necessary • Scalable manufacturing Ex vivo CAR - T In vivo CAR - T non - targeted virus engineered cell is drug product engineered virus is drug product In Vivo CAR - T Therapy Reprogramming immune cells directly in the body through direct infusion, eliminating the need for ex vivo cell engineering and manufacturing 1. Chimeric Antigen Receptor T - cell
6 Leveraging Stand - Alone Cell Therapy Leadership In Vivo TaVec (T - Cell Activation Vector) Design and Mechanism of Action TARGET • Oncology and autoimmune indications Mechanism of Action/Scientific Rationale • Cocal glycoprotein in TaVec platform • Provide T cell specificity, activation and safety • Mutations in glycoprotein to block transduction of non - T cells T cell engager 1 1. Low - Density Lipoprotein Receptor .
7
8 LB2501: Engineered LVV for In Vivo CD19/CD20 CAR - T Generation • A third - generation, replication - incompetent lentiviral vector (LVV) with CD3 binder and T - cell targeting design on surface • Proprietary CD19/CD20 dual - target CAR design to broaden antigen coverage • LB2501 generates CAR - T cells and controls tumor dose - dependently in human PBMC - reconstituted NSG mouse model 1 1. Transducing Units. CD19/CD20: Cluster of Differentiation 19 / Cluster of Differentiation 20: PBMC: Peripheral Blood Mononucle ar Cell; NSG: NOD scid gamma; CD3; Cluster of Differentiation 3; COVGmut : Cocal virus glycoprotein mutation; TM: Transmembrane
9 *Disease that did not respond to, or progressed within 12 months after completion of first - line therapy. DL: Dose Level; 1. ECOG PS Eastern Cooperative Oncology Group Performance Status ; 2. LBCL: large B - cell lymphoma; 3. iNHL : indolent lymphoma; 4. MCL: mantle cell lymphoma; 5. CLL: chronic lymphoblastic leukemia; TCE: T - cells engager; Study Design An open - label, multi - center, dose - escalation Phase I study to evaluate the safety and efficacy of in vivo CD19/CD20 dual - target CAR - T lentivirus therapy in Adults with Relapsed/Refractory B - Cell NHL Primary endpoint s : • Safety • Recommended Phase 2 D ose (R2PD) • Pharmacokinetics (PK) of Lentiviral Vector (LVV) and CAR - T Secondary endpoints: • Efficacy : Objective Response Rate ( ORR), time to response (TTR), duration of response (DOR), progression - free survival (PFS), and overall survival (OS) • Immunogenicity: anti - LVV and anti - CAR - T Key Eligibility Criteria: • Age ≥ 18 years; ECOG PS 1 0 - 1; • Histologically confirmed LBCL 2 (including transformed iNHL ) 3 , iNHL , MCL 4 , and confirmed CLL 5 ; • ≥ 2 prior lines or refractory to 1st line* systemic therapy; • Previous CD19 - autologous CAR - T and T - Cell Engager (TCE) therapy were allowed. Dose escalation (N max = 30) DL1 1 × 10 8 ~5 × 10 8 TU DL2 8 × 10 8 ~1.5 × 10 9 TU DL3 2 × 10 9 ~4 × 10 9 TU 3+3 with back - fill Clinical Study Flowchart screening ( 28 days) Bridging therapy if applicable In vivo CART infusion (D1) Follow up （ Q30D × 6, then Q90D ） No Lympho - depletion P rophylactic Medicines: NAIDS+ antihistamine Steroid not required Median follow - up time was 4.0 months (range, 2.0~7.9 months) at data cutoff date of Apr 1, 2026
10 *Both TCE therapies are CD20 × CD3. DL, dose level; 1. DLBCL, diffuse large B - Cell lymphoma; 2. FL, follicular lymphoma; 3. MCL, mantle cell lymphoma; PMBL, primary mediastinal large B - cell lymphoma; 4. SPD, sum of the product of the diameters. Demographics and Baseline Characteristics Total ʤ N=12 ʥ DL2 㸦 N=6 㸧 DL1 㸦 N=6 㸧 n (%) 58.5 (36, 73) 62.5(36, 73) 50.0(43, 63) Age, median (range) 2 (16.7) 2 (33.3) 0 ≥ 65 years, n (%) 5 (41.7) 1 (16.7) 4 (66.7) Male, n (%) 6 (50.0)/6 (50.0) 1 (16.7)/5 (83.3) 5 (83.3)/1 (16.7) ECOG PS 0/1, n (%) Histology, n (%) 6 (50.0) 3 (50.0) 3 (50.0) DLBCL 1 3 (25.0) 2 (33.3) 1 (16.7) FL 2 2 (16.7) 1 (16.7) 1 (16.7) MCL 3 1 ( 8.3) 0 1 (16.7) Primary mediastinal large B - cell lymphoma 8 (66.7) 5 (83.3) 3 (50.0) Ann Arbor staging III - IV, n (%) 1.03 (0.58, 1.44) 0.77 (0.58, 1.44) 1.21 (0.93, 1.40) Absolute Lymphocyte Count (ALC), median (range), ̩ 10 9 /L 557 (311, 1713) 425 (311, 676) 808 (453, 1713) CD3+, median (range), cells/ μL 3.0 (1, 7) 3.5 (1, 7) 2.5 (2, 6) No. prior lines of treatment, median (range) Disease status to last line of prior therapy 5 (41.7) 2 (33.3) 3 (50.0) Relapse, n (%) 7 (58.3) 4 (66.7) 3 (50.0) Refractory, n (%) 921.4 (144, 2540) 1444.1 (440, 2540) 852.6 (144, 1041) SPD 4 (mm2), median(range) 1 (8.3) 0 1 (16.7) Prior CD19 CAR - T cell therapy 2 (16.7) 1 (16.7) 1 (16.7) Prior T - cell engager* therapy • As of April 1, 2026: • 12 patients dosed with LB2501 • 6 patients in DL1 (4 at 2 × 10 8 TU and 2 at 5 × 10 8 TU ) • 6 patients in DL2 (all at 1 × 10 9 TU). • No patients received bridging - therapy before infusion of LB2501 • The median time from consent to infusion was 17.5 days
11 • The median follow - up for DL2 was 2.3 months (range, 2.0 to 4.5). • At the data cutoff date, all responses were ongoing • In DL2 across DLBCL, MCL, and FL: • (6/6) ORR • (5/6) CR High Objective Response Rate and Complete Response in DL2 Duration of Responses in Patients (DL2) Total (N=12) DL2 (N=6) Response Rate 6 (50.0) [21.1 - 78.9] 6 (100) [54.1 - 100] ORR 1 , n (%) [95% CI] 5 (41.7) [15.2 - 72.3] 5 (83.3) [35.9 - 99.6] CR 2 , n (%) [95% CI] 0 1 2 3 4 Pt 7: FL Pt 8: FL Pt 9: DLBCL Pt 10: DLBCL Pt 12: MCL Pt 11: DLBCL Pt 8 had prior TCE with washout of 2.7 months Months since infusion 1. Objective Response Rate; 2. Complete Response.
12 Large Target Lesion Reductions from Baseline Across DL2 The Lugano 2014 criteria were used to assess the response at each prespecified time point in patients with NHL Percent C hange from B aseline in SPD for B est R esponse (DL2) -100 -80 -60 -40 -20 0 20 40 Change in target lesions from baseline (%) CR CR CR CR CR PR Pt 10 DLBCL Pt 11 DLBCL Pt 8 FL Pt 12 MCL Pt 7 FL Pt 9 DLBCL
13 LB2501: Pharmacokinetics Total (N=12) DL2 (N=6) DL1 (N=6) 11 6 5 N Patients with CAR - T expansion 87,899.0 ( 51, 137,457 ) 109,117.5 ( 32,497, 137,457 ) 1,068.0 (51, 113,350) Median (Min, Max) C max 1 (copies/ug gDNA) 17.0 ( 13, 30 ) 15.0 ( 13, 18 ) 17.0 ( 14, 30 ) Median (Min, Max) T max 2 (day) Total (N=12) DL2 (N=6) DL1 (N=6) 79,905.0 (1,167, 421,549) 160,124.0 ( 36,755, 421,549 ) 22,540.5 ( 1,167, 83,666 ) Median (Min, Max) C max (copies/mL) 0.050 ( 0.02, 0.08 ) 0.050 ( 0.02, 0.07 ) 0.050 ( 0.02, 0.08 ) Median (Min, Max) T max (hours) LVV PK In vivo CAR - T PK *Lines represent median values over time *Lines represent median values over time 1. Maximum observed CAR - T copy number; 2. Time to reach Cmax .
14 Confirmed Expansion and Persistent PK • Viral copy number in peripheral blood peaked immediately after infusion and decreased to undetectable concentrations within 24 hours • In vivo CAR - T expansion was detected by qPCR 1 in 5/6 patients (83%) at DL1 and all patients (6/6, 100%) at DL2 in a dose - dependent manner . At the time of data cutoff, patients exhibited persistent PK • In DL2: • 109,117.5 copies/ μ g DNA • 15 days 1. Quantitative Polymerase Chain Reaction.
15 Lentiviral integration analysis demonstrated a safe transgene profile • Vector integrations were highly polyclonal and diverse with no indication of dominant clonal expansion • Integration patterns were concordant with established public HIV and LVV datasets 1,2 at both chromosomal and genomic functional region levels • Average vector copy number (VCN) of ≈1 per patient, indicating controlled transgene integration • No evidence of non - specific transduction was detected in NK 3 cells or other non - T/B/NK 4 lymphocyte populations. No CAR transduction detected in non - T lymphocytes. ( A) NK cells and (B) CD19−CD56−CD3−CD5−lymphocytes 1. Citu C, et al. Sci Data . 2026;13(1):695. 2. Yan KK, et al. Sci Adv . 2023;9(40):eadg9959. HIV: Human Immunodeficiency Virus. 3. Natural Killer cells. 4. T lymphocytes / B lymphocytes / Natural Killer cells.
16 DL, dose level; DLBCL, diffuse large B - Cell lymphoma; ECOG, Eastern Cooperative Oncology Group; FL, follicular lymphoma; MCL, ma ntle cell lymphoma; PMBL, primary mediastinal large B - cell lymphoma; SPD, sum of the product of the diameters. TEAE: Treatment - emergent adverse event; DTL, dose - limiting toxi city. SAE, severe adverse event. IRR, infusion - related reaction. CRS, cytokine release syndrome. ICANS, immune effector cell - associated neurotoxicity syndrome. LVV, lentiviral vector. AESI, adverse event of special interest. * The relationship assessment was based on investigator decision. Safety Summary • LB2501 was well tolerated with no DLTs, SAEs, and no deaths • Most common AESIs were IRR and CRS, all Grade 1 - 2. No ICANS Total (N=12) DL2 ʤ N=6 ʥ DL1 (N=6 ʥ Treatment - Emergent Adverse Events (TEAEs), n (%) Grade ≥ 3 Any Grade Grade ≥ 3 Any Grade Grade ≥ 3 Any Grade 11 (91.7) 12 (100.0) 6 (100.0) 6 (100.0) 5 (83.3) 6 (100.0) Number of Subjects with TEAE 6 (50.0) 12 (100.0) 4 (66.7) 6 (100.0) 2 (33.3) 6 (100.0) Related to LB2501 LVV* 7 (58.3) 9 (75.0) 5 (83.3) 6 (100.0) 2 (33.3) 3 (50.0) Related to generated CAR - T* 0 0 0 0 0 0 SAE 0 0 0 0 0 0 DLT Adverse event of special interest (AESI) 0 9 (75.0) 0 6 (100.0) 0 3 (50.0) IRR related to LB2501 LVV infusion 0 8 (66.7) 0 6 (100.0) 0 2 (33.3) CRS 0 0 0 0 0 0 ICANS 0 0 0 0 0 0 Non - ICANS Neurotoxicity 0 0 0 0 0 0 Second primary malignancy
17 LB2501 LVV Infusion - Related TEAEs (≥ 30%) • IRR occurred in 50% (DL1) and 100% (DL2) of patients • All Grades 1 – 2 and manageable, with a median onset of 1.4 hours after infusion and a median recovery time of 18.6 hours • No steroid prophylaxis. No IRR required tocilizumab or glucocorticoids for treatment • Transient Grade ≥3 cytopenias resolved within a few days -100 -50 0 50 100 66.7% 66.7% 50.0% 33.3% 33.3% 33.3% 33.3% 33.3% 33.3% 33.3% 33.3% 50.0% 50.0% 50.0% 33.3% 66.7% 16.7% 16.7% 100% 83.3% CRP increased Lymphocyte count decreased Infusion - related reaction White blood cell count decreased Anemia Platelet count decreased Neutrophil count decreased Serum ferritin increased Hypoalbuminemia Patients (%) DL2 (N=6) DL1 (N=6) Grade 1 - 2 Grade ≥3
18 LB2501 Generated CAR - T Related TEAEs (≥30%) • CRS occurred in 33.3% (DL1) and 100% (DL2) of patients. • All Grades 1 – 2 and manageable, with a median onset at Day 11 and a median duration of 4.5 days. • Tocilizumab given to 4 patients (DL1: 1, DL2: 3); no glucocorticoids for CRS • Grade ≥3 cytopenias were observed, manageable, and recovered -100 -50 0 50 100 33.3% 33.3% 33.3% 16.7% 33.3% 16.7% 16.7% 66.7% 16.7% 50.0% 100% CRS White blood cell count decreased Lymphocyte count increase Lymphocyte count decreased Serum ferritin increased Platelet count decreased C - reactive protein increased Fibrin D dimer increased Neutrophil count decreased DL2 (N=6) DL1 (N=6) Grade 1 - 2 Grade ≥3 Interleukin level increased Anemia Blood LDH increased 33.3% 16.7% 16.7% 16.7% 16.7% 50.0% 16.7% 66.7% 83.3% 83.3% 83.3% 83.3% 66.7% 66.7% 66.7% 33.3%
19 Conclusions • In this First - In - Human Phase 1 study in R/R B - NHL, LB2501 showed a favorable safety profile and promising efficacy results: • LB2501 was well tolerated: no DLT, no SAE, no ICANS, and no deaths • IRR and CRS were all Grade 1 – 2, no glucocorticoid treatment • At DL2, 100% ORR and 83.3% CR achieved across DLBCL, MCL and FL • Dose - dependent expansion was observed, with consistent expansion at DL2 • LB2501 establishes a proof - of - concept for TaVec in vivo CAR - T platform in clinic; it showed T - cell specific transduction and robust CAR - T expansion, polyclonal random integration, and rapid vector clearance Legend believes t hese findings support further development of LB2501 as potential first - in class off - the - shelf, single - infusion, outpatient use, in vivo CD19/CD20 dual - target CAR - T therapy in R/R B - NHL
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Leveraging Stand - Alone Cell Therapy Leadership In Vivo State - of - the - art R&D facility in Philadelphia, Pennsylvania 21 Current Status Phase I Pre - Clinical Indication Target Program In Vivo Therapies Enrolling Relapsed/Refractory B - cell Non - Hodgkin Lymphoma (2) CD19 x CD20 LB2501 Enrolling Relapsed/Refractory Multiple Myeloma (2) GPRC5D LB2503 Initiating Relapsed/Refractory Autoimmune Diseases (2) BCMA LB2505 Clinical Development Goals • File U.S. IND for LB2501 • File additional INDs based on in vivo data in the future
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