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CURRENT REPORT
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Item 2.02 Results of Operations and Financial Condition.
On January 15, 2025, Entrada Therapeutics, Inc. (the “Company”) presented at the 43rd Annual J.P. Morgan Healthcare Conference, which presentation included certain preliminary financial results as of and for the fiscal year ended December 31, 2024. Specifically, the Company announced that its cash resources, which consist of cash, cash equivalents and marketable securities, were approximately $420.0 million as of December 31, 2024 and that it expects such cash resources to fund operations and capital expenditure requirements into the second quarter of 2027.
The information in this Item 2.02 is unaudited and preliminary, and it does not present all information necessary for an understanding of the Company’s results of operations for the fiscal year ended December 31, 2024, or financial condition as of December 31, 2024. The audit of the Company’s financial statements for the year ended December 31, 2024 is ongoing and could result in changes to the information in this Item 2.02.
The information in Item 2.02 of this Current Report on Form 8-K is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Item 8.01 Other Events.
A copy of the Company’s presentation for use by management in meetings with investors, analysts and others during the 43rd Annual J.P. Morgan Healthcare Conference is attached as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.
Forward Looking Statements
This Current Report on Form 8-K includes express and implied “forward-looking statements.” Forward looking statements include all statements that are not historical facts, and in some cases, can be identified by terms such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. Forward-looking statements contained in this Current Report on Form 8-K include, but are not limited to, statements about the Company’s preliminary and unaudited estimate of cash resources and the sufficiency of its cash resources through the second quarter of 2027. By their nature, these statements are subject to numerous risks and uncertainties, including factors beyond the Company’s control, that could cause actual results, performance or achievement to differ materially and adversely from those anticipated or implied in the statements. For further information regarding the risks, uncertainties and other factors that may cause differences between the Company’s expectations and actual results, you should review the “Risk Factors” in Item 1A of Part II of the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, as well as discussions of potential risks, uncertainties and other important factors in the Company’s subsequent filings. You should not rely upon forward-looking statements as predictions of future events. Although the Company’s management believes that the expectations reflected in the Company’s statements are reasonable, the Company cannot guarantee that the future results, performance or events and circumstances described in the forward-looking statements will be achieved or occur. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date such statements are made and should not be construed as statements of fact.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
| 99.1 | Corporate Presentation of Entrada Therapeutics, Inc. as of January 15, 2025. |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). |
SIGNATURE
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.
| Entrada Therapeutics, Inc. | ||
| Date: January 15, 2025 | By: | /s/ Dipal Doshi |
| Dipal Doshi | ||
| Chief Executive Officer |
Exhibit 99.1
2025 J.P. Morgan Healthcare Conference NASDAQ: TRDA
Disclaimer This presentation has been prepared by Entrada Therapeutics, Inc. (the “Company”) and shall not constitute an offer to sell o r a solicitation of an offer to buy securities or an invitation or inducement to engage in investment activity nor shall there be any sale of securities in any jurisdiction in which such of fer , solicitation or sale would be unlawful prior to registration or qualification of such securities under the securities law of any such jurisdiction. The Company has filed a shelf registra tio n statement (including a prospectus) with the Securities and Exchange Commission (the “SEC”) for the offering to which this presentation relates. Before you invest in any securities of t he Company, you should read the prospectus in that registration statement and any other documents the Company has filed with the SEC for more complete information about the Com pan y and the offering. You may get these documents for free by visiting EDGAR on the SEC website at www.sec.gov. This presentation contains forward - looking statements that involve substantial risks and uncertainties. All statements, other th an statements of historical facts, contained in this presentation, including statements regarding the Company's strategy, future operations, prospects and plans, objectives of ma nag ement, the validation and differentiation of Entrada’s approach and EEV platform and its ability to provide a potential treatment for patients, expectations regarding significant a ccu mulation of exon skipping and dystrophin production in patients, expectations regarding the importance of endosomal escape to therapeutic index optimization, the translatability of th e data from the Phase 1 clinical study for ENTR - 601 - 44 to future clinical studies for ENTR - 601 - 44, expectations regarding the ability of the Company’s preclinical studies and clinical studies to demonstrate safety and efficacy of its therapeutic candidates, and other positive results, expectations regarding the approvals and specific protocols for the Compa ny’ s planned Phase 1/2 clinical studies for ENTR - 601 - 44 and ENTR - 601 - 45, the timing of regulatory filings for the planned Phase 1/2 clinical studies for ENTR - 601 - 50 in 2025 and ENTR - 60 1 - 51 in 2026, the ability to recruit for and complete a global Phase 1/2 study for ENTR - 601 - 44, ENTR - 601 - 45, ENTR - 601 - 50 and ENTR - 601 - 51, the potential of its EEV product candidates and EEV platform, including the potential for ENTR - 601 - 44 to be a transformative treatment option, the continued development and advancement of ENTR - 601 - 44, ENTR - 601 - 45, ENTR - 601 - 50 and ENTR - 601 - 51 for the treatment of Duchenne and the partnered product VX - 670 for the treatment of myotonic dystrophy type 1, and the sufficiency of th e Company’s cash resources extending into 2027, constitute forward - looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words “ant icipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “objective,” “ongoing,” “plan,” “predict,” “project,” “potential,” “should,” or “would,” or the negative of these terms, or other comparable terminology are intended to identify forward - looking statements, although not all forward - looking statements contain these identifying words. Th e Company may not actually achieve the plans, intentions or expectations disclosed in these forward - looking statements, and you should not place undue reliance on these forwa rd - 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 vario us important factors, including: uncertainties inherent in the identification and development of product candidates, including the conduct of research activities and the initiation and co mpletion of preclinical studies and clinical studies; uncertainties as to the availability and timing of results from preclinical and clinical studies; timing of and expectations reg arding the Company’s ability to submit and obtain regulatory clearance and initiate clinical studies; whether results from preclinical studies will be predictive of the results of later pre clinical studies and clinical studies; whether earlier clinical data will be predictive of later clinical data; our ability to establish and maintain collaborations or strategic relationships; w het her the Company's cash resources will be sufficient to fund the Company's foreseeable and unforeseeable operating expenses and capital expenditure requirements; as well as the risks and unc ert ainties identified in the Company's filings with the SEC, including the Company's most recent Form 10 - K and in subsequent filings the Company may make with the SEC. In addition, the forward - looking statements included in this presentation represent the Company's views as of the date of this presentation. The Company anticipates that subsequent event s a nd developments will cause its views to change. However, while the Company may elect to update these forward - looking statements at some point in the future, it specifically dis claims any obligation to do so. These forward - looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date of this presen tat ion. January 2025 2
d Entrada is entering 2025 with momentum January 2025 3 Entrada enters 2025 with significant momentum January 2025 3 Entrada expects to have four Phase 1/2 MAD patient studies in DMD and DM1 by the end of 2025* Actively planning the initiation of two global Phase 1/2 MAD studies in H1 2025 and one in H2 2025 Ex - US clinical strategy designed to efficiently advance franchise Initiated MAD portion of VX - 670 global Phase 1/2 to evaluate safety and efficacy Partnership terms include milestone payments, plus royalties Generating preclinical data from programs outside of neuromuscular Includes new moieties Ended 2024 with ~$420M cash balance Cash runway extended into Q2 2027 Rapidly expanding DMD franchise Vertex accelerating DM1 program Advancing preclinical pipeline Bolstered financial position** *All references in this presentation regarding planned regulatory filings and clinical study designs are subject to ongoing d isc ussion with US and international regulatory authorities; **Based on current operating plans and ~$420M in preliminary unaudited cash, cash equivalents and marketable securities as of De cember 31, 2024; MAD: Multiple ascending dose; DMD: Duchenne muscular dystrophy; DM1: myotonic dystrophy type 1.
OUR MISSION: To Treat Devastating Diseases With Intracellular Therapeutics January 2025 4
Breakthrough approach to intracellular therapeutics January 2025 5 75% of disease - causing targets are located inside cells 1 Increasing cellular uptake and improving endosomal escape Potential for best - in - class therapeutics These targets are largely considered to be inaccessible and undruggable as only 2% of biological material will escape the endosome to reach an intracellular target 2 We are leveraging our Endosomal Escape Vehicles (EEV ) and other technologies to optimize intracellular target engagement and therapeutic benefit Initial focus on DMD and DM1, where we are working to develop safe and effective therapies that meet the significant needs of patients 1 Verdine GL, Walensky LD. The challenge of drugging undruggable targets in cancer: lessons learned from targeting BCL - 2 family members. Clin Cancer R es. 2007;13(24):7264 - 70; 2 Kilchrist KV, et al. Gal8 visualization of endosome disruption predicts carrier - mediated biologic drug intracellular bioavailabi lity. ACS Nano. 2019;13(2):1136 - 52.
Endosomal Escape Vehicle (EEV ) - based therapies January 2025 6 High Intracellular Uptake ~90% Uptake Efficient Endosomal Escape ~50% Escape vs. ~2% Standard Unique Budding Mechanism Conserves Endosomal Integrity Unique chemistry Improved uptake and endosomal escape Cyclic structure Extended half - life and increased stability Phospholipid binding Broad biodistribution to all cells Consistent and predictable pharmacokinetics Same EEV used across initial programs Qian, Z. et al. ACS Chem. Biol. 2013; Qian, Z. et al. Biochemistry 2014; Qian, Z. et al. Biochemistry 2016; Sahni, A. et al. ACS Chem. Biol. 2020; Pei, D. Acc. Chem. Res. 2022.
d Entrada’s pipeline includes a diverse array of high potential and high value assets Each target disease has a substantial patient population with a significant unmet medical need An Expanding Pipeline of Intracellular Therapeutics January 2025 7 DM1 DMD ENTR - 601 - 50 VX - 670 ENTR - 601 - 44 ENTR - 601 - 45 ENTR - 601 - 51 Immunology Ocular Discovery IND Enabling Lead Optimization Global Phase 1/2 MAD regulatory filings ongoing Global Phase 1/2 MAD regulatory filings expected H2 2025 Neuromuscular Platform Expansion Clinical Development Beyond Neuromuscular Global Phase 1/2 MAD regulatory discussions underway Antibody/Protein Gene editing mRNA delivery Global Phase 1/2 MAD regulatory filings expected 2026
EEV therapies have the potential for a best - in - class approach in neuromuscular diseases January 2025 8 Delivered positive Phase 1 data in DMD (ENTR - 601 - 44) • Robust clinical validation in healthy volunteers • No treatment - related AEs • Potential best - in - class target exposure and target engagement • Potential for minimum of 6 - week dosing intervals Strong, translational DMD data support franchise expansion • Leverages ENTR - 601 - 44’s positive Phase 1 results • Best - in - class potential for ENTR - 601 - 45, ENTR - 601 - 50 and ENTR - 601 - 51 • Pursuing efficient, direct - to - patient clinical strategy Vertex partnership further validates EEV potential (VX - 670) • Vertex completed SAD portion of VX - 670 global Phase 1/2 clinical study • Vertex initiated MAD portion of VX - 670 global Phase 1/2 to evaluate safety and efficacy in patients with DM1 Entrada expects to have four Phase 1/2 MAD patient studies in DMD and DM1 by the end of 2025
(n=6:2) (n=6:2) (n=6:2) (n=6:2) Positive ENTR - 601 - 44 Phase 1 data support the initiation of a Phase 1/2 MAD clinical study in patients January 2025 *Data presented at 2024 World Muscle Society conference; **One participant enrolled and randomized into Cohort 3 was removed pri or to dosing. 9 Cohort 1 0.75 mg/kg Cohort 2 1.5 mg/kg Cohort 3 3 mg/kg** Cohort 4 6 mg/kg 32 Adult Subjects Outcome Measures Key findings: Strong clinical safety up to 6 mg/kg, with the potential for best - in - class pharmacokinetics and pharmacodynamics in patients 6:2 randomization Single IV dose Total Active: Placebo = 24:8 • Safety and tolerability • Evaluation of PK and PD • Target engagement as measured via exon skipping ENTR - 601 - 44 - 101: Placebo - controlled single ascending dose (SAD) study in healthy volunteers*
ENTR - 601 - 44 - 101: Safety Safety and tolerability were assessed at each study visit following a single IV dose of ENTR - 601 - 44 or placebo. One participant enrolled and randomized into Cohort 3 was removed prior to dosing. Renal biomarkers assessed using FNIH and the C - Path . Kidney Safety CM Biomarker User’s Guide v1.1, 2019; AE: adverse event; SAE: serious adverse event; TEAE: treatment - emergent adverse event. January 2025 10 ENTR - 601 - 44 - 101: No treatment - related adverse events were reported in the ENTR - 601 - 44 - 101 study up to the highest dose of 6 mg/kg ENTR - 601 - 44 Pooled placebo (N=8) n (%) Total (N=25) 6.0 mg/kg (n=6) 3.0 mg/kg (n=7) 1.5 mg/kg (n=6) 0.75 mg/kg (n=6) 24 6 6 6 6 8 Dosed 24 6 6 6 6 8 Completed Study 13 3 3 2 5 1 Any TEAE 0 0 0 0 0 0 Treatment - related TEAE • No AEs related to study drug • Most common AE was headache (n=7; 5 mild and 2 moderate) • No clinically significant findings with lab values, ECG or vital signs • No adverse findings or clinically relevant changes to biomarkers of renal toxicity at highest dose of 6 mg/kg
Plasma Concentration of ENTR - 601 - 44 Dose - Dependent Increases In Urinary Excretion of Final PMO - 44 Metabolite ENTR - 601 - 44 Dose (mg/kg) Plasma ENTR - 601 - 44 AUC last ( hr *ng/mL) 0 3 0.75 1.5 6 0 20,000 40,000 60,000 11 For every doubling of dose, there is a more than doubling of metabolite excretion, implying the potential for increasing efficacy without a proportional risk of increasing toxicity High drug concentration s up p orts potential for efficacy at relatively low doses January 2025 (Left) Blood samples for PK assessment were collected at 2 hours pre - dose and post - end of infusion: 5 minutes, 1 hour, 4 hours, 8 hours, 16 hours, 24 hours, and every 24 hours after. Additional samples were taken at follow - up study visits; (Right) 24 - hour urine samples for PK assessment were collected the day prior to dosing and every 24 hours after. Additional samples were taken at follow - up study visits. Data shown as mean ± standard deviation; AUC last : area under the plasma concentration - time curve to the last measurable plasma concentration; PMO: phosphorodiamidate morpholino oligomer . ENTR - 601 - 44 - 101: Potential best - in - class dose - dependent pharmacokinetics ENTR - 601 - 44 - 101: Pharmacokinetics Increase (%) 100% 100% 100% 114% 130% 184% 0% 50% 100% 150% 200% 0.75 to 1.5 mg/kg 1.5 to 3 mg/kg 3 to 6 mg/kg ENTR-601-44 Dose Change (%) Metabolite Excretion Change (%)
Muscle concentrations and exon skipping were assessed using a needle muscle biopsy taken from biceps brachii 72 hours ( ± 4 hours) post - dose of ENTR - 601 - 44. Box and whisker plot illustration: the boxes represent the IQR and median. Whiskers show the smallest and largest values within 1.5 times the IQ R; ** p <0.005 vs. placebo using Mann - Whitney U test; IQR: interquartile range; LLOQ: lower level of quantification. 0 20 10 50 40 30 70 60 80 Concentration of final metabolite (ng/g) 6 mg/kg ENTR - 601 - 44 3 mg/kg ENTR - 601 - 44 LLOQ 0.4 0.2 0.0 0.8 0.6 1.0 Exon 44 skipping (%) 6 mg/kg ENTR - 601 - 44 ** Placebo LLOQ January 2025 12 Skeletal Muscle Concentration DMD Exon 44 Skipping Robust target engagement with statistically significant exon skipping observed versus placebo Dose - dependent skeletal muscle concentration was observed ENTR - 601 - 44 - 101: Favorable target exposure and engagement at 6 mg/kg ENTR - 601 - 44 - 101: Target Exposure and Engagement
Rapidly expanding DMD clinical programs January 2025 13 ENTR - 601 - 44’s Phase 1 results unlock DMD portfolio investment across multiple populations Regulatory Filings Under Review Accelerated Program Timelines ENTR - 601 - 44 ENTR - 601 - 45 ENTR - 601 - 51 IND Enabling ENTR - 601 - 50 IND Enabling • Discussions underway with several regulatory agencies • Global Phase 1/2 MAD preparedness ongoing Ex - US clinical strategy designed to efficiently advance franchise • Regulatory filings in additional geographies underway • Global Phase 1/2 MAD preparedness ongoing • On track to submit regulatory filings in H2 2025 • Global Phase 1/2 MAD initiation expected in Q4 2025 • Candidate selected in December 2024 • Global Phase 1/2 MAD regulatory filings expected 2026 1 Parent Project Muscular Dystrophy; 2 European Medicines Agency: orphan designation for treatment of Duchenne muscular dystrophy (EU/3/20/2375). ~41,000 people in the US 1 and Europe 2 have Duchenne 44 45 50 51 14% 9% 8% 4% ENTR - 601
Multiple Ascending Dose Clinical strategy is designed for efficient regulatory path January 2025 14 All ENTR - 601 - series programs will follow a similar clinical and regulatory approach Multiple Ascending Dose Phase 2b Accelerated Approval Regulatory Filings* Direct to Patient Studies Accelerated Approval Regulatory Filings* Accelerated Approval Regulatory Filings* Multiple Ascending Dose Phase 2b Phase 2b Collection of Safety and Biomarker Data Collection of Safety and Biomarker Data Collection of Safety and Biomarker Data Protocols pending regulatory feedback; *Accelerated Approval in the US, followed by confirmatory Phase 3 studies to obtain Fu ll Approval in the US and ex - US countries. Clinical Proof of Concept Clinical Proof of Concept Clinical Proof of Concept ENTR - 601 - 44 - 101 Phase 1
Robust preclinical data support global direct - to - patient Phase 1/2 MAD clinical studies across DMD franchise January 2025 15 ENTR - 601 - 50 ENTR - 601 - 45 • Robust dystrophin restoration in del44hDMD. mdx mouse model after just 3 doses, 6 weeks apart • Complete functional correction and maintenance of correction 6 weeks post - washout • Robust dose - dependent response and saturation of exon 50 skipping in hDMD mouse model after just 3 doses, 6 weeks apart • Preclinical data support potential for high and persistent dystrophin restoration in patients • Robust dose - dependent exon 51 pharmacodynamics in both del52hDMD. mdx and hDMD mouse models • Preclinical data support potential for high and persistent dystrophin restoration in patients ENTR - 601 - 51 R egulatory filings ongoing R egulatory filings expected H2 2025 R egulatory filings expected 2026 Global Phase 1/2 MAD Study Global Phase 1/2 MAD Study Global Phase 1/2 MAD Study
Gene Editing RNA Splicing RNA Editing RNA Silencing RNA Blocking Protein Replacement Protein Degradation Protein Inhibition Ongoing exploration of pipeline expansion opportunities Deliver CRISPR enzyme and repair gene function with guide RNA Deliver oligonucleotide therapeutics for RNA editing Modify RNA via exon/intron splicing to activate protein expression Block trinucleotide repeats in RNA to inhibit adverse binding Silence or knockdown RNA to prevent protein expression Replace proteins and enzymes Inhibit protein signaling pathways Degrade disease - causing proteins GOAL APPROACH January 2025 16 Entrada’s flexible approach to intracellular therapeutic s enables pipeline expansion by leveraging new moieties and by targeting additional therapeutic areas PROTEINS RNA TARGET DNA
Multiple near and long - term value drivers Cash runway extended into Q2 2027 January 2025 17 • ENTR - 601 - 44: Discussions underway with several regulatory agencies • ENTR - 601 - 45: Global Phase 1/2 MAD regulatory filings ongoing • ENTR - 601 - 50: Global Phase 1/2 MAD regulatory filings expected in H2 2025 • ENTR - 601 - 51: IND enabling studies ongoing • VX - 670: MAD portion of global Phase 1/2 ongoing • EEV platform is broadly applicable to intracellular targets and a wide range of diseases • Efficient development framework in place for advancing new therapeutic candidates • Preclinical data support potential for broad therapeutic index across multiple modalities • Initial focus on ocular and metabolic diseases Moving beyond neuromuscular Four clinical programs expected in 2025
Q&A
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Consistent and durable efficacy across species ~40 - fold higher ENTR - 601 - 44 Exon 44 Skipping in Healthy and Patient Myoblasts Exon 44 Skipping (%) Healthy Cells; n=4 cells/dose Patient Cells (DMDD45); n=4 cells/dose Exon 44 Skipping (%) W e e k 1 W e e k 2 W e e k 4 W e e k 8 W e e k 1 2 0 20 40 60 80 100 Exon 44 Skipping in hDMD Mouse • Post - IV infusion of single 35 mg/kg (PMO equivalent) dose, robust exon 44 skipping observed in biceps in the ENTR - 601 - 44 treated NHPs (n=3 per cohort) for at least 12 weeks P r e d o s e D a y 2 D a y 7 D a y 1 4 D a y 1 9 D a y 2 8 D a y 3 5 D a y 4 2 D a y 5 6 D a y 7 0 D a y 8 4 0 20 40 60 80 100 • Single 60 mg/kg (PMO equivalent) dose • Tibialis anterior Exon 44 Skipping in NHP Data presented at the 2022 MDA Clinical and Scientific Conference, TIDES 2022 and OPT 2024. January 2025 20 Cohort 1 Cohort 2 Exon 44 Skipping (%) ENTR - 601 - 44 Significant potential for patient benefit is supported by ENTR - 601 - 44 data in the mouse and the NHP at clinically relevant levels; in vitro data suggest much higher target engagement in patient cells
Dose - dependent exon skipping and dystrophin • Del45hDMD.mdx mice dosed with EEV - PMO - 44*** • n=4, gastrocnemius sample collection 2 weeks post - injection Dystrophin Restoration** 15 mg/kg 30 mg/kg 60 mg/kg 0 20 40 60 80 100 % D y s t r o p h i n R e s t o r a t i o n Dose Exon Skipping* 15 mg/kg 30 mg/kg 60 mg/kg 0 20 40 60 80 100 Dose % E x o n 4 4 S k i p p i n g Dose - dependent response at a minimally effective dose of 15 mg/kg is observed, with near saturation at a clinically relevant dose of 60 mg/kg implying a wide therapeutic index January 2025 21 * ddPCR : double drop PCR; **JESS: automated western blot system; ***EEV conjugated to an exon 44 skipping PMO; Data on file.
Preclinical data support potential for best - in - class clinical profile Data are shown as mean ± SD; *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001; 25 mg/kg correlates to ~5 mg/kg human equivalent dose (HED), 50 mg/kg correlates to ~10 mg/kg HED, 75 mg/kg correlates to ~15 mg/kg HED; JESS: automated western blot system; ddPCR : droplet digital PCR; Data p resented at the 2024 World Muscle Society conference. • Active and vehicle del44hDMD. mdx mice, n=5 per cohort, EEV - PMO - 45 ( Q6W x 3 doses) ; Control saline treated hDMD. mdx mice, n=10 ( Q6W x 3 doses) • Skipping ( ddPCR ) and dystrophin production (JESS) is significantly increased 6 weeks after the third dose of ENTR - 601 - 45 (gastrocnemius muscle shown) Dystrophin Restoration Exon Skipping Functional Correction Dose - dependent increase in exon skipping and dystrophin expression correlates to functional correction to wild type January 2025 22 ENTR - 601 - 45 0 20 40 60 80 100 % H u m a n E x o n 4 5 S k i p p i n g ** **** **** Dose in mg/kg 0 20 40 60 80 100 D y s t r o p h i n R e s t o r a t i o n ( % ) N o r m a l i z e d t o h D M D . m d x **** ** * Dose in mg/kg 0 20 40 60 80 100 % D y s t r o p h i n P o s i t i v e F i b e r s **** **** **** Dose in mg/kg 0 50 100 % F o r c e A f t e r 1 0 C o n t r a c t i o n s **** **** **** *** Dose in mg/kg
January 2025 23 del44hDMD. mdx mice were treated with three Q6W IV injections of ENTR - 601 - 45 or vehicle. ECC - induced muscle force loss generated by repeated ec centric force (ECC) contraction of the gastrocnemius muscle was assessed 5 weeks (left/center) or 4 and 8 weeks (right) after the third dose. Data (mean ± standard deviation) shown across 10 ECC contractions normalized into a percentage of the initial force before any ECC contrac ti ons and as the percentage of force retained after the 10th contraction. Vehicle - treated hDMD. mdx mice were used as a control group for normal muscle function. One - way ANOVA was used for statistical comparison to vehicle - treat ed del44hDMD. mdx mice; Q6W: every 6 weeks. **p < 0.01 , ***p < 0.001, *** *p < 0.0001 vs. vehicle; Data presented at the 2024 World Muscle Society conference.
ENTR - 601 - 50 in hDMD show high levels of durable exon skipping • Repeated doses administered via IV injection (Q6W x 3 doses) with 1 or 6 - week washout; Exon skipping assessed by ddPCR (tibialis anterior muscle shown) Data are shown as mean ± SD; **p ≤ 0.01, ****p ≤ 0.0001 vs vehicle. d dPCR , droplet digital PCR; Data on file. January 2025 24 ENTR - 601 - 50 Repeated doses of ENTR - 601 - 50 in hDMD mice leads to robust dose - responsive levels of exon 50 skipping that largely persists to 6 weeks, supporting the potential for persistent dystrophin production hDMD mouse 1 Week after Last Dose hDMD mouse 6 Weeks after Last Dose ENTR - 601 - 50 Vehicle Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4 0 20 40 60 80 100 % E x o n 5 0 S k i p p i n g **** **** **** ** ENTR - 601 - 50 Vehicle Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4 0 20 40 60 80 100 % E x o n 5 0 S k i p p i n g **** **** **
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