Visceral Myopathy Familial External Ophthalmoplegia

– Initiated a Phase 1 clinical trial of ENTR-601-44 for the potential treatment of Duchenne muscular dystrophy, marking Entrada’s transition to a clinical-stage company – – Expanded the Company’s Duchenne franchise with the selection of its third clinical candidate, ENTR-601-50, for the potential treatment of people living with Duchenne who are exon 50 skipping amenable – – Cash runway expected through 2025 with $354 million in cash, cash equivalents and marketable securities as of September 30, 2023 – BOSTON, Nov. 07, 2023 (GLOBE NEWSWIRE) -- Entrada Therapeutics, Inc. (Nasdaq: TRDA), a biopharmaceutical company aiming to transform the lives of patients by establishing intracellular Endosomal Escape Vehicle (EEV™)-therapeutics as a new class of medicines, today reported financial results for the third quarter ending September 30, 2023, and highlighted recent business updates. “The third quarter marked an important milestone for Entrada, as we transitioned into a clinical-stage company, with the initiation of the Phase 1 clinical trial in healthy volunteers for our lead Duchenne product candidate, ENTR-601-44. Duchenne muscular dystrophy is a relentlessly progressive neurodegenerative disease, and we are committed to bringing forward potential new therapeutic options for people living with Duchenne who have mutations that are amenable to particular exon skipping therapies,” said Dipal Doshi, President and Chief Executive Officer of Entrada Therapeutics. “We are well-positioned to embark upon our next phase of growth, as we further advance our Duchenne franchise and progress indications beyond neuromuscular diseases.” Recent Corporate Highlights In September 2023, Entrada dosed the first participant in its Phase 1 clinical trial evaluating ENTR-601-44 for the potential treatment of individuals with Duchenne muscular dystrophy (DMD) who are exon 44 skipping amenable. The primary objective of Entrada’s Phase 1 clinical trial, which is being conducted in the United Kingdom, is to evaluate the safety and tolerability of a single dose of ENTR-601-44 in healthy male volunteers, with a target enrollment of approximately 40 participants. The trial will also evaluate pharmacokinetics and target engagement, as measured by exon skipping in skeletal muscle. Entrada expects to report data from the Phase 1 clinical trial in the second half of 2024.The Company will provide an update on the clinical hold on its Investigational New Drug (IND) application for ENTR-601-44 with the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2023. Entrada announced the selection of a third clinical candidate within its Duchenne franchise, ENTR-601-50, for the potential treatment of people living with Duchenne who are exon 50 skipping amenable. The selection of ENTR-601-50 is based on in vivo preclinical data demonstrating robust exon 50 skipping and dystrophin production across cardiac and skeletal muscle groups. Entrada expects to present these preclinical data in the first half of 2024 and plans to submit a Clinical Trial Application (CTA)/IND submission to initiate clinical development for ENTR-601-50 in 2025. In October 2023, the Company achieved a milestone pursuant to the Vertex Agreement related to preclinical IND-enabling GLP toxicology studies of ENTR-701 that triggered a $17.5 million milestone payment, which the Company expects to receive in the fourth quarter of 2023. In July 2023, Entrada entered into a license agreement to advance the development of ENTR-501 with Pierrepont Therapeutics, Inc., a mitochondrial disease-focused company. ENTR-501 is an intracellular thymidine phosphorylase enzyme replacement therapy in development for the treatment of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). MNGIE is a slowly progressive and fatal, ultra rare disease for which there are no treatment options available. Third Quarter 2023 Financial Results Cash Position: Cash, cash equivalents and marketable securities were $353.6 million as of September 30, 2023, compared to $188.7 million as of December 31, 2022. Entrada anticipates that its cash, cash equivalents and marketable securities as of September 30, 2023, together with Vertex collaboration ongoing research support and the anticipated achievement of certain milestones, will be sufficient to fund the Company's operating expenses and capital expenditure requirements through 2025. Collaboration Revenue: Collaboration revenue was $43.7 million for the third quarter of 2023. There was no collaboration revenue in the third quarter of 2022. Research & Development (R&D) Expenses: R&D expenses were $22.2 million for the third quarter of 2023, compared to $19.0 million for the same period in 2022. This increase was primarily due to the initiation of the ENTR-601-44 Phase 1 clinical trial, additional investment in IND-enabling studies to support future clinical trials and higher personnel costs, including non-cash, stock-based compensation. General & Administrative (G&A) Expenses: G&A expenses were $7.5 million for the third quarter of 2023, compared to $7.0 million for the same period in 2022. This increase was primarily due to higher personnel costs, including non-cash, stock-based compensation, legal costs and other costs to support its ongoing clinical trial and continued research and development activities. Net Income (Loss): Net income was $35.5 million for the third quarter of 2023, compared to a net loss of $(25.1) million for the same period in 2022. About Entrada TherapeuticsEntrada Therapeutics is a clinical-stage biopharmaceutical company aiming to transform the lives of patients by establishing a new class of medicines, Endosomal Escape Vehicle (EEV™)-therapeutics, to engage intracellular targets that have long been considered inaccessible and undruggable. The Company’s EEV therapeutics are designed to enable the efficient intracellular delivery of a wide range of therapeutics into a variety of organs and tissues, resulting in an improved therapeutic index. Through its proprietary, highly versatile and modular EEV platform, Entrada is building a robust development portfolio of RNA-, antibody- and enzyme-based programs for the potential treatment of neuromuscular, immunological, ocular and metabolic diseases, among others. The Company’s lead oligonucleotide programs include ENTR-601-44, ENTR-601-45 and ENTR-601-50 for the potential treatment of people living with Duchenne who are exon 44, 45 and 50 skipping amenable, respectively, as well as our partnered candidate ENTR-701 for the potential treatment of myotonic dystrophy type 1 (DM1). For more information about Entrada, please visit our website, www.entradatx.com, and follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release, including statements regarding Entrada’s strategy, future operations, prospects and plans, objectives of management, Entrada’s ability to continue to recruit for and complete a healthy volunteer trial for ENTR-601-44 in the United Kingdom, expectations regarding the timing of data from its Phase 1 trial for ENTR-601-44 in the second half of 2024, express or implied statements regarding the clinical hold on the IND for ENTR-601-44, Entrada’s ability to address the FDA’s concerns regarding its IND for ENTR-601-44, expectations regarding the timing and content of any update expected in the fourth quarter of 2023 concerning the clinical hold on the IND for ENTR-601-44, expectations regarding the therapeutic benefits of ENTR-601-44, expectations regarding the timing of preclinical data results and planned CTA/IND submission for ENTR-601-50, the continued development and advancement of ENTR-601-44, ENTR-601-45 and ENTR-601-50 for the treatment of DMD, ENTR-501 for the treatment of MNGIE, and ENTR-701 for the treatment of DM1, including the IND-enabling studies, 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, the ability to develop additional therapeutic programs, including further exon skipping programs, the potential therapeutic benefits of its EEV candidates, statements regarding any future payments Entrada may receive under the Vertex Agreement, and the sufficiency of its cash resources through 2025, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words “anticipate,” “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. Entrada 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 important factors, including: uncertainties inherent in the identification and development of product candidates, including the conduct of research activities and the initiation and completion of preclinical studies and clinical trials; uncertainties as to the availability and timing of results from preclinical studies and clinical trials; the timing of and Entrada’s ability to submit and obtain regulatory clearance for IND or equivalent foreign applications and initiate or complete clinical trials; whether results from preclinical studies will be predictive of the results of later preclinical studies and clinical trials; whether Entrada’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 uncertainties identified in Entrada’s filings with the Securities and Exchange Commission (SEC), including the Company’s most recent Form 10-K and in subsequent filings Entrada may make with the SEC. In addition, the forward-looking statements included in this press release represent Entrada’s views as of the date of this press release. Entrada anticipates that subsequent events and developments will cause its views to change. However, while Entrada may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Entrada’s views as of any date subsequent to the date of this press release. ENTRADA THERAPEUTICS, INC.Condensed Consolidated Statements of Operations (Unaudited)(In thousands, except share and per share amounts) Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Collaboration revenue 43,735 — 87,165 — Operating expenses: Research and development 22,191 18,958 71,593 50,924 General and administrative 7,532 6,978 23,639 20,745 Total operating expenses 29,723 25,936 95,232 71,669 Income (loss) from operations 14,012 (25,936) (8,067) (71,669)Other income: Interest and other income 4,051 799 10,926 1,682 Total other income 4,051 799 10,926 1,682 Income (loss) before benefit from income taxes 18,063 (25,137) 2,859 (69,987)Benefit from income taxes 17,398 — — — Net income (loss) 35,461 (25,137) 2,859 (69,987)Net income (loss) per share, basic$1.07 $(0.80) $0.09 $(2.24)Net income (loss) per share, diluted$1.02 $(0.80) $0.08 $(2.24)Weighted‑average common shares outstanding, basic 33,281,287 31,298,052 32,942,958 31,273,612 Weighted‑average common shares outstanding, diluted 34,775,451 31,298,052 34,289,411 31,273,612 ENTRADA THERAPEUTICS, INC.Condensed Consolidated Balance Sheet Data (Unaudited)(In thousands) September 30,2023 December 31,2022 Cash, cash equivalents and marketable securities$353,578 $188,712Total assets 485,033 252,056Total liabilities 238,370 39,502Total stockholders’ equity 246,663 212,554 Investor and Media ContactKarla MacDonaldChief Corporate Affairs Officerkmacdonald@entradatx.com

It’s once again open season for biotech IPOs, as the summer drought has given way to an autumn flood. Five companies filed to go public on Friday, including four penciling in $100 million fundraises: Evotec, Entrada Therapeutics, Aura Biosciences and Vaxxinity. The fifth biotech, Blue Water Vaccines, is estimating a more modest $24 million. The combined industry raise surpassed $14 billion last week after two more biotechs priced, per the Endpoints News tally, and the sector remains on pace to eclipse last year’s record of $16.5 billion. It could come down to the wire, however, after a third quarter lull that saw the lowest levels of IPO numbers since the start of 2020. German biotech Evotec has racked up a veritable stable of biopharma partners, and now it’s taking its talents to Nasdaq. Evotec has made its name with its range of platform plays aimed at helping its collaborators develop drugs. The biotech has, over the last 25 years, built a suite of five different technologies that it utilizes in partnerships covering small molecules, omics, biologics, cell therapy and gene therapy. Some of Evotec’s more prominent recent deals come from Takeda, shooting for the first small molecule ligand for RNA in a March partnership, and Novo Nordisk, which plans to shell out nearly $180 million per kidney disease program. Additionally, Evotec has spent time building out its manufacturing capabilities, acquiring a former GlaxoSmithKline R&D site in Italy over the summer after buying a French plant in April. Novo Holdings and T. Rowe Price are the big winners from the IPO, holding 11% and 10% stakes in Evotec, respectively, according to the F-1 . Mubadala Investment Company, the UAE’s sovereign wealth fund that purchased $236 million worth of shares last October, also nets a 5.6% stake pre-offering. The biotech also says its pipeline contains more than 130 drug candidates. Most of the IPO funds will be directed toward continued manufacturing expansion. When Evotec starts trading, it will do so under the ticker $EVO . — Max Gelman Half a year after locking down a hefty $116 million crossover round , Entrada Therapeutics says it’s ready for its public debut. The Boston-based biotech filed its S-1 papers on Friday, penciling in a $100 million raise, which has become the standard for companies that often go on to raise much more. The platform, based on Dehua Pei’s lab research at Ohio State University, involves a new technology Entrada calls endosomal escape vehicles. EEVs are essentially cyclic peptides that trigger a process enabling cell membranes to take in biologic conjugates, CEO Dipal Doshi told Endpoints News back in March. Priority number one is neuromuscular diseases like Duchenne muscular dystrophy. In such diseases, patients have mutations that prevent the translation of RNA into proteins — in Duchenne’s case, dystrophin. Oligonucleotides connected to the EEVs force the cells to skip these mutations in their genetic code, Doshi said, allowing for the creation of dystrophin. Through this method, the dystrophin can then get into the appropriate muscles. Entrada’s lead candidate, ENTR-601-44, is expected to enter the clinic in DMD next year — and some of the IPO funds will be used to help get it there. Before pivoting to oligonucleotides, Entrada’s main focus was enzyme replacement therapies, with a primary target of the mitochondrial disease known as MNGIE. While the startup has completed IND-enabling studies, it’s now looking for another company to take the program into the clinic. “We continue to believe that the program will have an important role in the future treatment of patients with MNGIE,” the company said in the S-1 , noting that it’s still exploring potential partnerships. MPM Capital and 5AM Ventures, which have been around since the launch round, hold a considerable proportion of shares, with 20.74% and 19.94% pieces of the pie, respectively. Doshi, on the other hand, has a 5.14% stake, according to the S-1. The company plans to trade under the ticker $TRDA . — Nicole DeFeudis Aura Biosciences CEO Elisabet de los Pinos hinted at a forthcoming IPO after securing a Series E round back in March. That day has apparently come, as the company submitted its S-1 papers last Friday, penciling in a $100 million raise. Aura’s platform centers around virus-like particles, which can be conjugated with drugs or loaded with nucleic acids to create virus-like drug conjugates, or VDCs. The viral nanoparticles — modeled after the human papillomavirus — are light-activated, meaning they selectively destroy the membrane of cancer cells upon activation with an ophthalmic laser. AU-011, Aura’s first VDC candidate, is being developed for primary choroidal melanoma, an eye cancer for which no other drugs exist. The current approach to treatment is radioactivity, which can cause irreversible damage to the retina and lead to blindness. “The cytotoxic payload for the drug in the clinic is activated with light, so it’s very safe,” de los Pinos told Endpoints News in March. “And because of the cell activity of the virus-like particles, not binding to retina, it preserves vision.” Aura plans to present six- to 12-month data from a Phase II dose escalation trial in 2022, and if all goes well, launch a pivotal trial in the second half of 2022, according to the S-1 . There’s also an IND coming in the second half of 2022 for choroidal metastases, the company said. Matrix Capital Management and Medicxi, which led Aura’s Series E and D rounds, respectively, each hold 10.1% of the company’s shares. De los Pinos has a 3% stake. Aura will trade under the ticker $AURA . — Nicole DeFeudis Dallas vaccine biotech Vaxxinity, rebranded from the consolidation of COVAXX and United Neuroscience in April, is shooting for a quick IPO. The biotech centers its efforts around developing peptide-based vaccines for chronic diseases, arguing the current vaccine market struggles to ward off persistent conditions. Vaxxinity also believes this approach can capture some of the market share from monoclonal antibodies, saying its candidates can be manufactured more cheaply. As its former name implies, the company has a Covid-19 vaccine candidate in development and has secured $2.8 billion worth of advance purchase commitments with Brazil, Ecuador, Peru and other countries to deliver more than 140 million doses of its vaccine. There are also pipeline programs for Alzheimer’s and Parkinson’s diseases, as well as migraines. Most of the IPO funds will go toward clinical trials for the neurodegenerative indications, according to the S-1 . Vaxxinity did not spell out the stakes of its principal shareholders but said there had been investment from United Biomedical and Prime Movers Lab. When Vaxxinity goes public, it will trade under the ticker $VAXX . — Max Gelman Blue Water Vaccines is penciling in $24 million to take its flu shot programs public. Everything is preclinical so far, but the biotech is working on a universal flu vaccine as well as what it calls an “H1 pre-pandemic shot” that it hopes will provide long-lasting protection. Both programs are licensed from the University of Oxford. Preclinical proof of concept studies are slated to begin for the universal shot in the first half of next year, while the pre-pandemic shot will launch IND-enabling studies in the same time period. Blue Water also has two norovirus vaccine candidates under its belt, in addition to a vaccine program for the bacteria Streptococcus pneumoniae . When the offering is completed, the company will hire a new CEO in Joseph Hernandez, who pre-offering owns about 37% of shares. Cincinnati Cornerstone Investors owns the highest stake, however, at about 41%. Once Blue Water goes public, it will trade under the ticker $BWV . — Max Gelman

A little over two years since its last $59 million round, Entrada Therapeutics is making some more noise Wednesday with a nine-figure crossover. And they’ve got a new focus on neuromuscular diseases, led by Duchenne muscular dystrophy, as their research has broadened over the years. Entrada pulled in a $116 million Series B, with the funds primarily slated for getting its first Duchenne program into the clinic. The Boston-based biotech hopes to get past the IND acceptance phase for the lead candidate and then expand into other neuromuscular areas. The platform here, originally based on Dehua Pei’s lab research from Ohio State University, centers around what Entrada calls endosomal escape vehicles, or EEVs. At their core, EEVs are cyclic peptides that trigger a process enabling cell membranes to take in biologic conjugates, CEO Dipal Doshi told Endpoints News. Back in 2018 during the Series A fundraise, Entrada’s main efforts dealt with applying the EEVs to enzyme replacement therapies, with a primary target of the mitochondrial disease known as MNGIE. But last year, Doshi said, the company saw a “remarkable opportunity” in its oligonucleotide research and decided to pivot toward this area in earnest. Doshi now describes Entrada as being broken into three parts: enzyme replacement, oligonucleotides and protein degradation. As their sights have turned toward neuromuscular diseases with the oligonucleotides research, Entrada is now looking to partner out the MNGIE program. “We’ve been very explicit to say, look, we’re not going to be cute here, we want to find a home for this program,” Doshi told Endpoints. “We want to put it into a company that has the ability to recruit an ultra-rare clinical study in the immediate time frame.” Entrada doesn’t necessarily have a specific partnership model in mind, Doshi added, but they’re hoping to find a rare disease-focused pharma that can run the trial while teaming up on manufacturing. When it comes to applying the EEVs to oligonucleotides for Duchenne and its other neuromuscular programs, Entrada does so by targeting the RNA. In such diseases, patients have mutations that prevent the translation of RNA into proteins — in Duchenne’s case, the protein in question is dystrophin. The oligonucleotides connected to the EEVs force the cells to skip these mutations in their genetic code, Doshi says, allowing for the creation of dystrophin. And through this method, the dystrophin can then get into the appropriate muscles. In early research, Entrada believes it can differentiate itself from other Duchenne players due to the dystrophin uptake they’ve seen in animal models. Specifically, researchers have recorded significant uptake in the heart, which could validate the EEV technology for use in other neuromuscular diseases with similar pathologies, Doshi said. Entrada isn’t disclosing yet which exon it’s skipping in the lead program, but Doshi noted that they see a “basket opportunity” in going after exons 44, 45, 51 and 53 at around the same time. That would comprise about 40% of all DMD patients. With Wednesday’s financing now in hand, Entrada is looking to get the lead Duchenne candidate into the clinic sometime next year. Duchenne is an area that’s seen heavy investment but few successes in recent years. Last August, the FDA approved the third Duchenne drug on the market, but regulators continued to express concerns about the efficacy of the drug from NS Pharma. The other two drugs come from Sarepta, where in one case the FDA infamously flip-flopped from CRL to accelerated approval after just four months. The round was led by Wellington Management Company and joined by Redmile Group, TCG Crossover, Greenspring Associates, Point72, Qatar Investment Authority (“QIA”), Moore Strategic Ventures, Goldman Sachs, CureDuchenne Ventures and one undisclosed global investment firm. Existing investors 5AM Ventures, MPM Capital, Roche Venture Fund, MRL Ventures Fund and Agent Capital also participated in the Series B.