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CURRENT REPORT
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On January 5, 2024, Vor Biopharma Inc. (the “Company”) updated its investor presentation (the “Corporate Presentation”). The Corporate Presentation is available on the Company’s website and is filed as Exhibit 99.1 hereto and incorporated herein by reference.
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| 99.1 | Corporate Presentation, dated January 5, 2024 | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |
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 hereunto duly authorized.
| Vor Biopharma Inc. | ||||||
| By: | /s/ Robert Ang | |||||
| Robert Ang | ||||||
| Chief Executive Officer | ||||||
| Date: January 5, 2024 | ||||||
January 2024 Ambition: Curing blood cancers through cell and genome engineering Exhibit 99.1
This presentation (the “Presentation”) contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 about Vor Biopharma Inc. (“Vor,” “Vor Bio” or the “Company”). The words “aim,” “anticipate,” “believe,” “can,” “could,” “design,” “enable” “estimate,” “expect,” “intend,” “may,” “ongoing,” “plan,” “potential,” “project,” “should,” “target,” “towards,” “will,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements in this Presentation include those regarding the feasibility of a trem-cel (formerly VOR33) transplant to be successfully manufactured, to engraft normally, to maintain blood counts following treatment with Mylotarg following allogeneic hematopoietic cell transplant and to be well tolerated, the potential of VCAR33ALLO in combination with trem-cel as a Treatment System, the potential of trem-cel to enable targeted therapies in the post-transplant setting including Mylotarg and CD33-targeted CAR-Ts, the potential of Vor Bio’s platform, Vor Bio’s plans, strategies, expectations and anticipated milestones for its preclinical and clinical programs, the availability and timing of results from preclinical studies and clinical trials, the timing of regulatory filings, the expected safety profile of Vor Bio’s product candidates, cash runway and expected capital requirements, and its plans and expectations related to the Company’s manufacturing and facilities. Vor Bio may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: uncertainties inherent in the initiation, completion of, and availability and timing of results from, preclinical studies and clinical trials and clinical development of Vor Bio’s product candidates; whether preclinical data or interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials; the uncertainty of regulatory approvals to conduct trials or to market products; the success of Vor Bio’s in-house manufacturing capabilities and efforts; and availability of funding sufficient for its foreseeable and unforeseeable operating expenses and capital expenditure requirements. The interim data for trem-cel presented in this Presentation is based on five patients and future results for these patients or additional patients may not produce the same or consistent results. These and other risks are described in greater detail under the caption “Risk Factors” included in Vor Bio’s most recent annual or quarterly report and in other reports it has filed or may file with the Securities and Exchange Commission. Any forward-looking statements contained in this Presentation speak only as of the date of this Presentation, and Vor Bio expressly disclaims any obligation to update any forward-looking statements, whether because of new information, future events or otherwise, except as may be required by law. Certain information contained in this Presentation relates to or is based on studies, publications, surveys and other data obtained from third party sources and Vor Bio’s own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this Presentation, we have not independently verified, and make no representation as to the adequacy, fairness, accuracy or completeness of any information obtained from third party sources. In addition, there can be no guarantee as to the accuracy or reliability of any assumptions or limitations that may be included in such third-party information. While we believe our own internal research is reliable, such research has not been verified by any independent source. Disclaimer
Our Vision: Cure Blood Cancers Through Cell and Genome Engineering Unique approach Positive clinical proof of concept VCAR33ALLO as of Sept. 30, 2023 Cash runway into 2H 2025 $160M In-house GMP manufacturing facility *tremtelectogene empogeditemcel, formerly VOR33 $160M in cash, cash equivalents and marketable securities as of September 30, 2023. Fully owned CD33-directed transplant donor CAR-T Multiple sites activated Four modular clean rooms for clinical supply shielded stem cell transplants enabling targeted therapy demonstrated in AML with CD33-deleted trem-cel* transplants
Current AML Disease State and Standard of Care Conditioning Mobilize and collect stem cells from matched healthy donor Transplant Remission (MRD-) 2 0.8 Years Since HSCT Active disease Remission (MRD+) 0.0 0.2 0.4 0.6 0 Cumulative Incidence of Relapse 1 Status at Time of Transplant1 Despite transplantation, relapse is still common in AML patients 1 MRD: measurable residual disease; SOC: standard of care; HSCT: Hematopoietic Stem Cell Transplant 1 Araki et al, JCO 2016 4 Watchful Waiting 3 2 3 3 Standard of Care: Replace Diseased Bone Marrow with Transplanted Healthy Donor Cells Toxic therapies to kill existing bone marrow Harvest Infuse stem cells into patient to restore the blood system Monitor for relapse; any follow-up treatment will damage the transplant
Clear Unmet Need in AML ~200K Post-transplant relapse, with <20% two-year survival3,4 50% Increase in # of AML transplants over the last 10 years2 ~20,000 People in the U.S. diagnosed with AML annually1 AML Transplants per year (U.S.)2 ~4,000 ~40% ~40% 1 American Cancer Society 2023 2 Current use and outcome of hematopoietic stem cell transplantation: CIBMTR summary slides 2022 3 Araki et al, JCO 2016 4 Schmid et al, Blood 2012
Changing the Thinking on Tumor Targeting Cancer antigens also expressed on healthy cells Biology: Overlapping Targets Limits treatment opportunities leading to poor outcomes Problem: On-target Toxicity Shielded transplants allowing therapies to be cancer-specific Solution: Shielded Transplants
The Vision: eHSC + CAR-T Treatment Systems CD33-directed antibody-drug conjugate CD33-directed transplant donor CAR-T therapy Clinical proof of concept Engraftment Heme protection VCAR33ALLO Healthy donor source, stemlike phenotype Tolerized to new marrow VCAR33AUTO Phase 1/2 NMDP-sponsored trial Addresses tumor heterogeneity and potential escape mechanisms Next-gen shielded HSC transplant Mylotarg Multi-targeted CAR-T therapy Trem-cel Trem-cel VCAR33 Multiplex-edited HSCs Multi-specific CAR-Ts Shielded CD33-deleted HSC transplant Shielded CD33-deleted HSC transplant
Description Preclinical Clinical Program / Trial Modality Indication Discovery/ Validation IND- Enabling Phase 1/2 Phase 2/3 Trem-cel + Mylotarg / VBP101 Shielded CD33-deleted transplant + CD33-directed ADC AML MDS, MPN MDS, MPN VCAR33ALLO (allogeneic) / VBP301 CD33-directed transplant donor CAR-T AML Post-transplant VCAR33AUTO (autologous) CD33-directed autologous CAR-T AML Bridge-to-transplant Trem-cel + VCAR33 Treatment System Shielded CD33-deleted transplant + CD33-directed transplant donor CAR-T AML CD33-CLL1 Treatment System Multiplex-edited HSCs + Multi-specific CAR-T AML Expanding Pipeline Driven by Innovative Platform AML: acute myeloid leukemia; HSCs: hematopoietic stem cells; MDS: myelodysplastic syndrome; MPN: myeloproliferative neoplasm * The VCAR33 construct is being studied in a Phase 1/2 clinical trial sponsored by the National Marrow Donor Program (“NMDP”), and the timing of data release is dependent on the investigators conducting the trial. NMDP-sponsored trial* Discovery Platform Leveraging our proprietary Vor Bio platform, we are exploring additional surface targets such as CD123, EMR2, and CD5 including multiplex genome engineering approaches where multiple surface targets are removed. We are conducting ongoing discovery efforts in commonly transplanted hematologic malignancies.
Proprietary Dual Cell Product Potential Trem-cel Starting Material Apheresis Product from Healthy Matched Donor Trem-cel: CD33-deleted Shielded HSC Product VCAR33ALLO: CD33-targeted Transplant Donor CAR-T Therapy Cell selection Lentivirus transduction T cells CAR-T VCAR33ALLO Material preparation Cell selection CRISPR/Cas9 engineering Engineered Hematopoietic Stem Cells (eHSCs) Treatment System uses non-stem cell fraction to make CAR-T from the same matched donor Unique In-house Manufacturing: Multi-product GMP facility in Cambridge, MA Four independent clean rooms and on-site QA/QC Rapid manufacturing and release process fits into standard transplant procedure
Trem-cel + Mylotarg CD33-directed antibody-drug conjugate CD33-directed Transplant Donor CAR-T therapy Clinical proof of concept Engraftment Heme protection VCAR33ALLO Healthy donor source, stemlike phenotype Tolerized to new marrow VCAR33AUTO Phase 1/2 NMDP-sponsored trial Addresses tumor heterogeneity and potential escape mechanisms Next-gen shielded HSC transplant Mylotarg Multi-targeted CAR-T therapy Trem-cel Trem-cel VCAR33 Multiplex-edited HSCs Multi-specific CAR-Ts Shielded CD33-deleted HSC transplant Shielded CD33-deleted HSC transplant
VBP101: Trem-cel + Mylotarg Phase 1/2a Clinical Trial Transplant Decision Infusion Donor Journey Related Unrelated Maintenance Mylotarg Manufacturing vein-to-vein 7-10 days Unedited back-up graft Transplant-eligible AML patients at high risk of relapse Trem-cel Manufacturing ~7-day process Engraftment No delay in typical patient transplant process If relapse occurs: Induction-course Mylotarg VCAR33ALLO (VBP301) Alternative treatments Starting ~day 60 up to 4 cycles dose escalation 0.5-2 mg/m2 Conditioning Consolidation/Salvage Stem Cell Mobilization, Collection Screening Relapse-free survival Heme protection from Mylotarg Trem-cel engraftment Key Endpoints 01 02 03 Patient Journey
Patient Characteristics Pt Age/ Sex Disease and Genetics Weight Donor, Dose, CD33 gene-editing efficiency 1 64/F AML-MRC Highly complex cytogenetics; CR2; TP53 mutation MRD: 1.8% 69.9 kg 10/10 HLA MUD 7.6 × 106 CD34 cells/kg, 88% CD33 gene editing 2 32/M AML after myeloid sarcoma resected from abdomen Inv 16 and +22, t(3;3) 120.7 kg 10/10 HLA MUD 3.2 × 106 CD34 cells/kg, 87% CD33 gene editing 3 55/F AML-MRC DNMT3A, IDH2 and SMC1A mutations 114.1 kg 10/10 HLA MUD 2.6 × 106 CD34 cells/kg, 80% CD33 gene editing 4 68/M AML-MRC Complex cytogenetics; active disease; NRAS, ZRSR2, TET2 mutations MRD: 16% 72.4 kg 10/10 HLA MSD 5.8 × 106 CD34 cells/kg, 89% CD33 gene editing 5 66/M Secondary AML KIT D816V, CBL, SRSF2, RUNX1/2, BCORL1 mutations 102.1 kg 10/10 HLA MUD 4.6 × 106 CD34 cells/kg, 85% CD33 gene editing 6 63/F AML-MRC Highly complex cytogenetics; TP53, NRAS, WT1 mutations 66.2 kg 10/10 HLA MUD 5.7 × 106 CD34 cells/kg, 91% CD33 gene editing 7 67/M AML with recurrent abnormalities CR2; NPM1, TET2, EZH2, SETBP1, PIGA mutations 72.8 kg 10/10 HLA MUD 9.4 × 106 CD34 cells/kg, 87% CD33 gene editing 8 57/M AML (myelomonocytic) with nml karyotype CR2 (CRi/CRp) 68.9kg 10/10 HLA MUD 9.5 × 106 CD34 cells/kg, 91% CD33 gene editing MRC = myelodysplasia-related changes, MRD = Measurable Residual Disease, MUD = Matched Unrelated Donor, MSD = Matched Sibling Donor All patients received myeloablative conditioning with busulfan/melphalan/fludarabine/rabbit anti-thymocyte globulin (ATG), with exception for patient #3, who received equine ATG. Data Cutoff: 4 Dec 2023. Presented data from EDC and site/PI communication; pending full source verification
Patient Clinical Timelines (Patients 1-8) Patients Ineligible for Mylotarg: Patient 2 Secondary graft failure in context of prior sepsis, TMP-SMZ/possible DRESS and persistent hKU1 coronavirus infection. Graft failure resolved after back-up graft given. Patient 3 Immune thrombocytopenia. Resolving after treatment with IVIg, steroids, rituximab, CD34 boost. Patient 4 CNS and systemic relapse prior to Mylotarg dosing. Days Post Transplant With Trem-cel Neutrophil engraftment Mylotarg infusion Discontinued Back-up graft Relapse CD34 boost intended to overcome immune thrombocytopenia 0 30 60 90 120 180 210 240 150 270 300 (CD33+ relapse) Pt 3 Pt 5 Pt 2 Pt 4 Pt 1 Pt 6 Pt 7 Pt 8
Highly Efficient Removal of CD33 from Donor HSCs Proof of Concept: Successful Engraftment of CD33-Deleted HSCs CD33 editing efficiency (%) Arrows indicated day of individual patient neutrophil engraftment Neutrophil engraftment = 3 days ≥ 500 cells/L *Luznik L. et al. J Clin Oncol 2022;40(4):356–368 Timely Post-transplant Neutrophil Engraftment Donor Chimerism (Day 28) 100% 100% 100% 100% 100% 100% 100% Median engraftment unmodified CD34+ graft* 100%
Mylotarg Causes Deep Cytopenias Across Various Regimens Fostvedt et al. Clin Pharm Thera 2019;106(5):1006-1017 Platelet counts (cells/µL) 1000 10000 100000 10000 1000 100 10 Neutrophil counts (cells/µL)
Evidence of Protective Effect from Mylotarg at 0.5 mg/m2 Mylotarg C1 Start: Pt 1 D+68; Pt 5 D+74; Pt 6 D+66 post-HCT Day from first Mylotarg dosing Mylotarg dose
Enrichment of CD33-negative Cells following Mylotarg Myeloid Cells (Peripheral Blood) Days from first Mylotarg dosing Mylotarg dose
Patients 1, 5, 6: PK after 1st Dose of Maintenance Mylotarg Pharmacokinetics VBP101 Relapsed/Refractory AML Population (Mylotarg Phase 1 Study 0903A1-101-US)1 Parameter Mean +/- SD 0.5 mg/m2 0.25 mg/m2 0.5 mg/m2 1 mg/m2 2 mg/m2 4 mg/m2 5 mg/m2 Cmax (ng/mL) 236 (+/- 151) 15 28 50 411 611 1,325 AUCinf (Hr*ng/mL) 10,890 (+/- 13958) 82 468 943 11,110 10,970 29,980 1Mylotarg ODAC 2017 Relationship Between Mylotarg Cmax and Veno-occlusive Disease in Prior Transplant1 Probability of Veno-occlusive Disease (%) Cmax after first dose of Mylotarg (ng/mL) 2,000 4,000 6,000 8,000 10,000 0 95% CI Geometric mean (R/R AML) Mean VBP101 Cmax
VCAR33 CD33-directed antibody-drug conjugate CD33-directed Transplant Donor CAR-T therapy Clinical proof of concept Engraftment Heme protection VCAR33ALLO Healthy donor source, stemlike phenotype Tolerized to new marrow VCAR33AUTO Phase 1/2 NMDP-sponsored trial Addresses tumor heterogeneity and potential escape mechanisms Next-gen shielded HSC transplant Mylotarg Multi-targeted CAR-T therapy Trem-cel Trem-cel VCAR33 Multiplex-edited HSCs Multi-specific CAR-Ts Shielded CD33-deleted HSC transplant Shielded CD33-deleted HSC transplant
A New Way of Generating CAR-T Therapy T cells exactly matched to patient’s new immune system, more likely to persist Stem-like, CAR-T cells more likely to expand and less prone to exhaustion Poor expansion and persistence Poorer clinical durability Exhausted, depleted T cells High manufacturing failure Traditional Approaches Vor Bio Approach Autologous cells (derived from patient) Allogeneic cells (off-the-shelf) Transplant Donor Cells
VBP301: VCAR33ALLO Phase 1/2 Clinical Trial* Enroll VCAR33ALLO Infusion Prior Transplant Donor MRD+ or relapsed AML following SOC transplant or trem-cel transplant VCAR33ALLO Manufacturing ~7-day process Day 28 Follow-up Consent Collect 2nd transplant if required Arm B: MRD+ Arm A: Blasts ≥ 5% 3x3 dose escalation starting at 1 x 106 CAR+ cells/kg *Multiple active clinical sites that overlap with VBP101 trem-cel Phase 1/2a clinical study Lymphodepletion Disease control/response Expansion, persistence Safety Key Endpoints 01 02 03 Patient Journey
VCAR33AUTO Shows Signs of Activity; VCAR33ALLO Potentially More Active Autologous starting material 6-site IST Young adults and children (median 16 y, range 1-35) Academic manufacturing process Accepted for oral presentation at ASH N=24 enrolled, 19 infused Manageable tox (n=4 with CRS ≥ Grade 3) Transplant donor starting material IND cleared in June, multiple sites opened Targeting ~12 sites Streamlined manufacturing process with objective of stem like cell phenotype Allows trem-cel patients to enroll Starting dose 1 x 106 CAR+ cells/kg VCAR33AUTO (NCI CD33CART) VCAR33ALLO Dose (CAR+ cells/kg) Total 3 x 105 1 x 106 3 x 106 1 x 107 # infused 19 3 3 7 6 (resp assess in 5) # with CR, (%) 2 (11%) 0 (0%) 0 (0%) 0 (0%) 2 (40%) Data from ASH 2023 Abstract: https://ash.confex.com/ash/2023/webprogram/Paper179667.html
Moving Beyond Proof of Concept to Pivotal Targeting Short Registrational Pathway R/R AML Single Arm Pivotal Trials Fast Track granted on basis of trem-cel heme protection Exploring heme protection endpoints with agency Agent Indication # pts Endpoint Ivosidenib IDH1, Agios R/R AML 174 CR 25% CRh 8%1 Enasidenib IDH2, Agios R/R AML 199 CR 19% CRh 4%2 Gilteritinib FLT3, Astellas R/R AML 138 CR 12% CRh 9%3 Revumenib KMT2Ar, Syndax R/R AML 57 CR 18% CRh 5%4 Mylotarg ADC, Pfizer R/R AML 57 CR 26%5 High unmet need in AML Precedence for single-arm pivotal trials CR and CR/CRh are approvable endpoints Norsworthy KJ, et. al. FDA Approval Summary: Ivosidenib for Relapsed or Refractory Acute Myeloid Leukemia with an Isocitrate Dehydrogenase-1 Mutation. Clin Cancer Res. 2019 Jun 1;25(11):3205-3209. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-granted-regular-approval-enasidenib-treatment-relapsed-or-refractory-aml Pulte ED, et. al. FDA Approval Summary: Gilteritinib for Relapsed or Refractory Acute Myeloid Leukemia with a FLT3 Mutation. Clin Cancer Res. 2021 Jul 1;27(13):3515-3521. https://cms.syndax.com/wp-content/uploads/2023/12/Aldoss-2023-AUGMENT-101-3.pdf. Per company, NDA initiated with FDA under RTOR program. https://labeling.pfizer.com/showlabeling.aspx?id=9548 CR: Complete Remission CRh: Complete remission with partial hematologic recovery
Trem-cel and VCAR33: Defining Success in 2024 Based on discussions with KOLs and our clinical investigators, even a single patient with clinical activity and heme protection may provide validation of the approach Expect clinical validation in 2024 Opportunity Activity Benchmark Evidence of clinical activity Trem-cel transplant Relapse or MRD+ Mylotarg induction course (D1, 4, 7) VCAR33ALLO Evidence of heme protection
Mylotarg dosing escalated to next dose level of 1.0 mg/m2 Multiple therapeutic options enabled for patients who relapse following trem-cel transplant: Induction-course Mylotarg VCAR33ALLO Upcoming Milestones Significant Clinical Progress and Upcoming Milestones Trem-cel Potentially superior transplant donor cell source IND cleared; multiple sites active Trem-cel patients are eligible to enroll VCAR33AUTO (CD33CART) showed activity at highest dose level and manageable safety in NCI study1 Trem-cel can be reliably manufactured with efficient CD33 deletion (87% average) CD33 appears biologically dispensable in regard to engraftment (8/8) Trem-cel provides hematologic protection from acute Mylotarg toxicity (3/3) Progress to Date Preliminary VCAR33ALLO safety and efficacy data VCAR33 1ASH 2023 Abstract: https://ash.confex.com/ash/2023/webprogram/Paper179667.htm
Next-generation Approaches CD33-directed antibody-drug conjugate CD33-directed Transplant Donor CAR-T therapy Clinical proof of concept Engraftment Heme protection VCAR33ALLO Healthy donor source, stemlike phenotype Tolerized to new marrow VCAR33AUTO Phase 1/2 NMDP-sponsored trial Addresses tumor heterogeneity and potential escape mechanisms Next-gen shielded HSC transplant Mylotarg Multi-targeted CAR-T therapy Trem-cel Trem-cel VCAR33 Multiplex-edited HSCs Multi-specific CAR-Ts Shielded CD33-deleted HSC transplant Shielded CD33-deleted HSC transplant
In Vitro Proof of Concept for Multi KO Target Cell + Multi-Specific CAR-T CD33 and CLL-1 Dual-CAR-T Active Against Wild Type and Single Knock-out Target Cells 0 40 80 100 20 60 % of Viable Cells Tandem CAR-T Untransduced T Cells Tandem CAR-T Untransduced T Cells Tandem CAR-T Untransduced T Cells Tandem CAR-T Untransduced T Cells Unmodified AML cell line AML cell line CD33KO AML cell line CLL-1KO AML cell line CD33KOCLL-1KO n=1 biological replicaten=3 technical replicatesEffector: Target ratio 1:1 Denotes individual experiment
Multiplex Editing: Proprietary Capabilities Minimize Translocations and Protects from CAR-T Effector : Target = 1:1 Target Cell Survival (%) Wild Type CD33Del 0 40 60 80 20 CLL-1Del CD33DelCLL-1Del Translocation (%) Simultaneous Cas9 0.3 0.4 0.2 0.1 0 Sequential Cas9 Sequential Cas + Inhibitor Base Editing Genome Engineering Strategies Minimized Translocation Rate Cell Protection from CAR-T Killing
Our Vision: Cure Blood Cancers Through Cell and Genome Engineering Unique approach Positive clinical proof of concept VCAR33ALLO as of Sept. 30, 2023 Cash runway into 2H 2025 $160M In-house GMP manufacturing facility *tremtelectogene empogeditemcel, formerly VOR33 $160M in cash, cash equivalents and marketable securities as of September 30, 2023. Fully owned CD33-directed transplant donor CAR-T Multiple sites activated Four modular clean rooms for clinical supply shielded stem cell transplants enabling targeted therapy demonstrated in AML with CD33-deleted trem-cel* transplants
Experienced and Passionate Leadership Team Deep Cell & Gene Therapy Expertise Robert Ang, MBBS, MBA President and CEO Tirtha Chakraborty, PhD Chief Scientific Officer Eyal Attar, MD Chief Medical Officer Tania Philipp Chief People Officer John King, MBA Chief Commercial Officer & Head of Business Development Nathan Jorgensen, PhD MBA Chief Financial Officer Robert Pietrusko, PharmD Chief Regulatory & Quality Officer David Phillips, MBA Senior Vice President, Head of Quality Samir Vattompadam, MS Senior Vice President, Portfolio Strategy and Program Management
Data from 3.0 mg/m2 mean (+/- ci) data digitized from simulations presented in Hibma et al, 2019 VBP101 R/R AML Mylotarg at 0.5 mg/m2 Equivalent to ~3 mg/m2 in the Context of CD33-negative Hematopoiesis Mylotarg Plasma Concentration (ng/mL) Time (h)
Safety Events Reported as Possibly Related to Either Trem-cel or Mylotarg (AE ≥ Grade 3 or any Grade SAE) Adverse Event Max Grade Related to Trem-cel (# of events) Related to Mylotarg (# of events) SAE (# of events) Anemia 3 1 — — Neutropenia 3 1 — — Thrombocytopenia 3 2 — — Graft Failure 4 1 — 1 Platelet count decreased 3 — 1 — Platelet count decreased, worsening 3 1 1 — Worsening maculopapular rash of whole body 2 1 — 1 For Mylotarg dosing: No dose-limiting toxicity criteria met No increase in liver function tests above upper limit of normal No observed sinusoidal obstruction syndrome / veno-occlusive disease Data as of Oct. 31, 2023, presented at HSCT2
Potential Reimbursement Pathways MS-DRG 014 applies to allogeneic bone marrow transplants Section 108 (2020) provides new cost-based reimbursement for 100% of stem cell acquisition and processing Omisirge® (recently FDA-approved HSC product) priced at $338,000 Shielded Stem Cell Transplants As of 2020, new MS-DRG 018 created for CAR-T therapy with base reimbursement rate of $247,939 CAR-T Therapies
High Editing Frequency for Next-Generation Targets CD34+ Editing Frequency CD5 0 40 80 100 20 60 Editing Frequency (%) Control guide T Cell Target n=9 CD123 0 40 80 100 20 60 Editing Frequency (%) Control guide Myeloid Targets n=19 n=21 n=6 CLL-1 EMR2
Multiplex Editing Strategies Achieve Highly Efficient Double Knock-out CLL1 CD33 CLL-1 CD33 CD33-CLL-1- Double KO 79.5% CD33+CLL-1+ Double Pos 82.6% Sequential Cas9 Editing Base Editing Mock Mock Edited Edited CD33+CLL-1+ Double Pos 99.4% CD33-CLL-1- Double KO 84.3%