Entrada Therapeutics : Corporate Presentation

Corporate Presentation

March 2024

Disclaimer

This presentation 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 presentation include, but are not limited to, statements about our product development activities and clinical trials, our regulatory filings and approvals, statements related to our ability to continue to recruit for and complete its healthy volunteer trial, ENTR-601-44-101, in the United Kingdom, expectations regarding the timing of data from our Phase 1 trial for ENTR-601-44 in the second half of 2024, the ability to resolve the clinical hold for ENTR-601-44 and subsequent activities, expectations regarding the timing or content of any update regarding our regulatory filings, expectations regarding the safety and therapeutic benefits of ENTR- 601-44, our ability to develop and advance our current and future product candidates and discovery programs, expectations regarding the results of preclinical studies predicting the results of later preclinical studies or any clinical trials of our therapeutic candidates, our ability to establish and maintain collaborations or strategic relationships, our ability to raise additional funding, the rate and degree of market acceptance and clinical utility of our product candidates, the potential of our EEV product candidates and EEV platform, the ability and willingness of our third-party collaborators to continue research and development activities relating to our product candidates, including our Vertex partnership for ENTR-701, expectations regarding the expected timing, progress and success of our collaboration with Vertex, including any future payments we may receive under our collaboration and license agreements, our collaborators' ability to protect our intellectual property for our products, expectations regarding the timing of preclinical data results and planned CTA/IND submissions for ENTR-601-45 and ENTR-601-50, the continued development and advancement of ENTR-601-44,ENTR-601-45 and ENTR-601-50 for the treatment of DMD, and ENTR-701 for the treatment of DM1, and the sufficiency of our cash resources through the second quarter of 2026. By their nature, these statements are subject to numerous risks and uncertainties, including factors beyond our control, that could cause actual results, performance or achievement to differ materially and adversely from those anticipated or implied in the statements. You should not rely upon forward-looking statements as predictions of future events. Although our management believes that the expectations reflected in our statements are reasonable, we cannot guarantee that the future results, performance or events and circumstances described in the forward-looking statements will be achieved or occur. Recipients 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.

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 our own internal estimates and research. While we believe these third-party studies, publications, surveys and other data to be reliable as of the date of this presentation, it has not independently verified, and makes no representations as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of our internal estimates or research and no reliance should be made on any information or statements made in this presentation relating to or based on such internal estimates and research.

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March 2024

Our Mission

To Treat Devastating Diseases with Intracellular Therapeutics

An Expanding Pipeline of Intracellular Therapeutics

Entrada is leveraging its Endosomal Escape Vehicle platform (EEV ) to create a diverse and

expanding development portfolio of RNA-, antibody- and enzyme-based therapeutics

• Advancing new therapeutic options for people living with Duchenne muscular dystrophy (DMD)
• • ENTR-601-44completed dosing of a third cohort in its Phase 1 trial with data expected in H2 2024; Regulatory applications expected in Q4 2024 for global Phase 2 clinical trial
  • ENTR-601-45regulatory applications expected in Q4 2024 for global Phase 2 clinical trial
  • ENTR-601-50regulatory applications expected in 2025 for global Phase 2 clinical trial
• Transformative Vertex partnership for the development of myotonic dystrophy type 1 (DM1)
• • VX-670(ENTR-701) Phase 1/2 clinical trial initiated
  • $224M upfront payment and $26M equity investment; Up to $485M for the achievement of certain milestones, plus royalties; Four-year global research collaboration
• Extending the pipeline with novel intracellular therapeutic candidates by leveraging new moieties and targeting additional therapeutic areas
• Strong financial position with cash runway through the second quarter of 2026*

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*Assumes $352 million cash, cash equivalents and marketable securities as of December 31, 2023, together with Vertex collaboration ongoing research support and achievement of certain milestones.

A Differentiated and Expanding Pipeline

Entrada's pipeline includes a diverse array of high potential and high value assets;

Each disease has a substantial patient population with a significant unmet medical need

Disease/Condition

DMD

Neuromuscular

DM1

POMPE

Beyond

Neuromuscular

Platform

Expansion

Discovery

Lead Optimization

ENTR-601-44

ENTR-601-45

ENTR-601-50

Exon 51

VX-670 (formerly ENTR-701)

ERT/Oligonucleotide

Immunology

Ocular Gene editing mRNA delivery Antibody/Protein

IND Enabling

Clinical

Phase 1 data expected in H2 2024 and Phase 2 regulatory filings expected in Q4 2024

Phase 2 regulatory filings expected in Q4 2024

Phase 2 regulatory filings expected in 2025

Phase 1/2 trial initiated

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March 2024

Endosomal Escape

Vehicle (EEV )

Therapeutics

• Unique chemistry results in improved uptake and endosomal escape
• Cyclic structure designed to extend half life and increase stability
• Phospholipid binding potentially enables broad biodistribution to
  all cells
• Mechanism of internalization conserved across species

Entrada seeks to solve a fundamental

problem: a lack of efficient cellular uptake and escape from the endosome; Both are critical to intracellular target engagement and therapeutic benefit

1	High Intracellular Uptake	3	Prolonged Duration of Effect
(~90% Uptake)	(Intracellular Depot)

2	Efficient Endosomal Escape
	(~50% Escape v. 2% Standard)

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.

Functional Delivery for Target Tissues

EEV-therapeutic candidates can be designed to enhance functional delivery to target tissues

Discovery Engine for Intracellular Therapeutics

Functional Delivery in the EGFP-654 Transgenic Mice

EEV	Therapeutic modality

• High-throughput EEV library screening in vitro
• Functional validation of lead EEVs with PMO therapeutic modality in vitro and in vivo
• EEV optimized for the functional delivery to target tissues in vivo

EGFP Protein (a.u.)

200				PMO654
	138.6
				EEV-PMO654
150
	103.6
100		69.3
50				33.3
			27.1
6.6			14.6
4.0	4.1	2.9
0
Triceps Diaphragm	Tibialis	Kidney	Liver
		Anterior

Target Tissues

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PMO, phosphorodiamidate morpholino oligomer; EGFP-654 transgenic mouse model contains an EGFP gene interrupted by human beta-globin intron 2 with mutated nt654 (Sazani, P. et al. Nature Biotech. 2002); PMO654, splicing switching PMO targeting nt654; shown as mean ± standard deviation.

Translation from Update to Outcomes

Murine Example

EEV-therapeutic candidates have demonstrated favorable pharmacological properties: efficient intracellular delivery, significant uptake in target tissues and potent pharmacodynamic outcomes

Tissue Uptake in Muscle		Intracellular Delivery
✓	Skeletal muscle	+	✓	Endosomal escape	=
✓	Cardiac muscle	✓	Nuclear localization

Pharmacodynamic Outcome

• Rapid, dose-dependent response
• Duration of at least 12 weeks

	10000				3
(ng/g)Conc.Tissue				ConcentrationNuclear cells)(pmol/1e6
1000
					2
	100
	10				1
	1				0
	10	20	40	80
		Dose (mg/kg)

IV, hDMD mice, 5-day post injection

3 µM PMO

3 µM EEV-PMO

24-hour incubation

	120
(%)	100
80
Skipping
60
Exon	40
20
	0

10	20	40	80
	Dose (mg/kg)

IV, hDMD mice, 5-day post injection

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March 2024

hDMD mice express full-length human dystrophin gene.

Duchenne Muscular Dystrophy (DMD)

DMD: Significant Unmet Need

Heart

Respiratory muscles

Skeletal muscle

44

7.6%

45

9%

3.8% 50

14%

51

Duchenne is caused by

mutations in the DMD gene, which lead to a lack of functional dystrophin, causing progressive loss of

muscle function throughout the body

~40,000

people in the U.S. and Europe have Duchenne1

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1Parent Project Muscular Dystrophy: About Duchenne. 2Europeans Medicines Agency: Orphan designation for the treatment of Duchenne muscular dystrophy. 3Bladen, C.L. et al HUMAN MUTATION, 2015.