Fuchs' Endothelial Dystrophy

ALISO VIEJO, Calif.--( BUSINESS WIRE )--Glaukos Corporation (NYSE: GKOS), an ophthalmic medical technology and pharmaceutical company focused on novel therapies for the treatment of glaucoma, corneal disorders and retinal diseases, announced today the U.S. Food and Drug Administration (FDA) approved its New Drug Application (NDA) for a single administration per eye of iDose ® TR (travoprost intracameral implant) 75 mcg, a prostaglandin analog indicated for the reduction of intraocular pressure (IOP) in patients with ocular hypertension (OHT) or open-angle glaucoma (OAG). iDose TR is a first-of-its-kind, long-duration, intracameral procedural pharmaceutical therapy designed to continuously deliver 24/7 therapeutic levels of a proprietary formulation of travoprost inside the eye for extended periods of time. iDose TR is intended to improve the standard of care by addressing the ubiquitous patient non-compliance issues and chronic side effects associated with topical glaucoma medications. “The FDA approval of iDose TR represents a significant milestone for Glaukos following an extensive pioneering journey since the inception of the original idea nearly 15 years ago. Today’s approval ushers in a new era of interventional glaucoma therapy by enabling a more proactive and reliable approach for patients in need,” said Thomas Burns, Glaukos chairman and chief executive officer. “We believe iDose TR can be a transformative, novel technology able to fundamentally improve the treatment paradigm for patients with open-angle glaucoma or ocular hypertension. We are grateful to the clinical investigators and study participants in the clinical trials for their instrumental roles in helping us reach this important advancement for glaucoma patient care. At Glaukos, we are relentlessly focused on delivering novel therapies for chronic eye diseases and now iDose TR has the potential to redefine the standard of care for patients in the U.S. affected by open-angle glaucoma and ocular hypertension.” “With the next generation of procedural pharmaceutical solutions for glaucoma such as iDose TR , we now have a new tool that will confront the standard legacy practice of relying on topical drops, which are known to cause uncomfortable side effects and present a myriad of challenges such as treatment adherence, complex dosing regimens, and difficulty with self-administration,” said John Berdahl, MD, clinician and researcher at Vance Thompson Vision. “The clinical data suggest that iDose TR is not only effective with a favorable safety profile, but it has potential to relieve patients from the burdens of prescription eye drops for an extended period of time. I look forward to adding this novel therapy into my treatment toolbox for the benefit of my patients.” The FDA approval is based on results from two prospective, randomized, multicenter, double-masked, Phase 3 pivotal trials (GC-010 and GC-012) designed to compare the safety and efficacy of a single administration of one of two iDose TR models with different travoprost release rates (referred to as the fast- and slow-release iDose TR models, respectively) to topical timolol ophthalmic solution, 0.5% BID (twice a day), in reducing IOP in subjects with open-angle glaucoma or ocular hypertension. In total, the Phase 3 trials randomized 1,150 subjects across 89 clinical sites. The FDA approval and Phase 3 data referenced below is for the slow-release iDose TR model, consistent with the company’s NDA submission and commercialization plans. Both Phase 3 trials successfully achieved the pre-specified primary efficacy endpoints through 3 months and demonstrated a favorable tolerability and safety profile through 12 months. IOP reductions from baseline over the first 3 months were 6.6-8.4 mmHg in the iDose TR arm, versus 6.5-7.7 mmHg in the timolol control arm (mmHg range represents IOP reduction means across the six U.S. FDA pre-specified timepoints of 8 a.m. and 10 a.m. at Day 10, Week 6 and Month 3). Based on these outcomes, the FDA concluded in the prescribing information that iDose TR demonstrated non-inferiority to timolol ophthalmic solution in IOP reduction during the first 3 months. The FDA also noted that subsequently iDose TR did not demonstrate non-inferiority over the next 9 months. At 12 months, 81% of iDose TR subjects were completely free of IOP-lowering topical medications across both trials. In both trials, iDose TR demonstrated excellent tolerability and subject retention with 98% of iDose TR subjects continuing in the trial at 12 months, versus 95% of timolol control subjects. In controlled studies, the most common ocular adverse reactions reported in 2% to 6% of iDose TR patients were increases in intraocular pressure, iritis, dry eye, and visual field defects, most of which were mild and transient in nature. iDose TR is also supported by positive results from a Phase 2b clinical trial, which were recently highlighted in a peer-reviewed publication in Drugs ( link here ). The study authors concluded, “The travoprost intraocular implant demonstrated robust IOP-lowering and substantially reduced topical IOP-lowering medication burden for up to 36 months following a single administration, while maintaining a favorable safety profile.” Glaukos intends to commence initial commercial launch activities for iDose TR in the latter part of the first quarter of 2024. Glaukos has established a wholesale acquisition cost for iDose TR of $13,950, per dose (or implant). Alongside the iDose TR approval announcement, Glaukos is proud to introduce the iDose Your Dose Initiative. For every iDose TR sold, Glaukos pledges to make available an equal number of iDose TR units for qualifying charitable donation requests in the U.S. and around the globe for recipients that satisfy independent eligibility requirements. For more information about iDose TR and Full Prescribing Information, please visit www.iDoseTRhcp.com . 2023 and 2024 Revenue Guidance The company reaffirms its 2023 net sales range of $307 million to $310 million and introduces preliminary 2024 net sales guidance range of $350 million to $360 million. Webcast & Conference Call The company will host a conference call and simultaneous webcast on December 14, 2023, at 8:30 a.m. ET (5:30 a.m. PT) to discuss the FDA approval of iDose TR . A link to the webcast is available on the company’s website at http://investors.glaukos.com . To participate in the conference call, please dial 888-210-2212 (U.S.) or 646-960-0390 (international) and enter Conference ID 7935742. A replay of the webcast will be archived on the company’s website following completion of the call. About iDose TR iDose TR (travoprost intracameral implant) is a long duration prostaglandin analog approved for a single administration and indicated for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Made from medical-grade titanium, iDose TR is implanted through the trabecular meshwork and back wall of Schlemm's canal, directly into scleral tissue. Once implanted, 75 mcg of a novel, preservative-free, proprietary formulation of travoprost continuously elutes into the anterior chamber via membrane-controlled diffusion, allowing for 24/7 release of medication. About Glaukos Glaukos ( www.glaukos.com ) is an ophthalmic medical technology and pharmaceutical company focused on developing and commercializing novel therapies for the treatment of glaucoma, corneal disorders and retinal diseases. Glaukos first developed Micro-Invasive Glaucoma Surgery (MIGS) as an alternative to the traditional glaucoma treatment paradigm, launching its first MIGS device commercially in 2012, and continues to develop a portfolio of technologically distinct and leverageable platforms to support ongoing pharmaceutical and medical device innovations. Products or product candidates for each of these platforms are designed to advance the standard of care through better treatment options across the areas of glaucoma, corneal disorders and retinal diseases. iDose TR Indication and Important Safety Information INDICATIONS AND USAGE iDose TR (travoprost intracameral implant) is indicated for the reduction of intraocular pressure (IOP) in patients with open angle glaucoma (OAG) or ocular hypertension (OHT). Dosage and Administration For ophthalmic intracameral administration. The intracameral administration should be carried out under standard aseptic conditions. Contraindications iDose TR is contraindicated in patients with active or suspected ocular or periocular infections, patients with corneal endothelial cell dystrophy (e.g., Fuch’s Dystrophy, corneal guttatae), patients with prior corneal transplantation, or endothelial cell transplants (e.g., Descemet’s Stripping Automated Endothelial Keratoplasty [DSAEK]), patients with hypersensitivity to travoprost or to any other components of the product. Warnings and Precautions iDose TR should be used with caution in patients with narrow angles or other angle abnormalities. Monitor patients routinely to confirm the location of the iDose TR at the site of administration. Increased pigmentation of the iris can occur. Iris pigmentation is likely to be permanent. Adverse Reactions In controlled studies, the most common ocular adverse reactions reported in 2% to 6% of patients were increases in intraocular pressure, iritis, dry eye, visual field defects, eye pain, ocular hyperaemia, and reduced visual acuity. Forward-Looking Statements All statements other than statements of historical facts included in this press release that address activities, events or developments that we expect, believe or anticipate will or may occur in the future are forward-looking statements. Although we believe that we have a reasonable basis for forward-looking statements contained herein, we caution you that they are based on current expectations about future events affecting us and are subject to risks, uncertainties and factors relating to our operations and business environment, all of which are difficult to predict and many of which are beyond our control, that may cause our actual results to differ materially from those expressed or implied by forward-looking statements in this press release. These potential risks and uncertainties include, without limitation, the timing and extent to which we are able to obtain regulatory approval for investigational products, our ability to successfully commercialize and generate sales of our products, the ability to obtain and maintain adequate financial coverage and reimbursement for our products, our ability to properly train, and gain acceptance and trust from, ophthalmic surgeons in the use of our products, our ability to compete successfully in the pharmaceutical industry, which is highly competitive and rapidly changing, our compliance with federal and state laws and regulations for the approval, sale and marketing of our products and our manufacturing processes, the lengthy and expensive clinical trial process and the uncertainty of timing and outcomes from any particular clinical trial or regulatory approval processes, and the continued efficacy and safety profile of our products as reported in the pivotal trials and other clinical studies. These and other risks, uncertainties and factors related to Glaukos, and our business are described in detail under the caption “Risk Factors” and elsewhere in our Quarterly Report on Form 10-Q for the quarter ended September 30, 2023, which was filed with the Securities and Exchange Commission (SEC) on November 1, 2023. Our filings with the SEC are available in the Investor Section of our website at www.glaukos.com or at www.sec.gov . In addition, information about the risks and benefits of our products is available on our website at www.glaukos.com . All forward-looking statements included in this press release are expressly qualified in their entirety by the foregoing cautionary statements. You are cautioned not to place undue reliance on the forward-looking statements in this press release, which speak only as of the date hereof. We do not undertake any obligation to update, amend or clarify these forward-looking statements whether as a result of new information, future events or otherwise, except as may be required under applicable securities law.

Seasoned Biotech Executive Pratik Shah Appointed as Chief Executive Officer to Lead Company Turnaround Current Cash and Securities of ~$290M Support Extended Five-Year Operating Runway Through 2028 Revised Corporate Strategy with Realignment Towards Long-Term Growth to be Presented in Early 2024; Additional Details to Follow CARLSBAD, Calif., Nov. 13, 2023 (GLOBE NEWSWIRE) -- Design Therapeutics, Inc. (Nasdaq: DSGN), a biotechnology company developing treatments for serious degenerative genetic diseases, today reported third quarter 2023 financial results. A strategic realignment was initiated to prioritize long-term growth, focus capital resources on program spend and implement cost savings. As a result, Design now expects its cash, cash equivalents and marketable securities to fund its planned operating expenses through at least the next five years. Additionally, Design announced plans to provide an update on its corporate strategy and priorities, and outline anticipated milestones across its business and clinical- and research-stage pipeline of novel GeneTAC™ small molecules in early 2024. “When we started Design just five years ago, we were looking to address the problem of genetic diseases differently by working alongside a person’s genome. Our solution, GeneTAC™ small molecules, are thoughtfully designed to dial up or down the expression of specific genes, addressing the root cause of disease without permanently modifying their genome. We believe this technology has the potential to transform the treatment landscape for many patients suffering from devastating degenerative diseases,” said Pratik Shah, Ph.D., chairperson and chief executive officer of Design Therapeutics. “The recently reported data from our observational biomarker study and multiple-ascending dose Phase 1 trial in patients with Friedreich ataxia (FA) provided us with important proof-of-concept for our GeneTAC™ platform, with the first human in history with FA experiencing a restoration of mRNA to carrier levels without the need for an irreversible genetic modification. Additionally, the initial clinical results provided important learnings on the behavior and tolerability of our lead GeneTAC™ molecule, DT-216, in patients, leading to our efforts to further optimize the formulation of DT-216 containing excipients with improved injection site tolerability, to enable the long-term treatment of patients with FA.” Dr. Shah continued, “We believe that GeneTAC™ molecules can be transformative therapies for patient populations with urgent unmet medical needs, including FA, Fuchs endothelial corneal dystrophy and myotonic dystrophy type-1. To maximize our future potential, we are undertaking a close review of our business to build on the progress already made and determine the optimal paths forward and development timelines for each of our programs. Already, we have sharpened our focus to prioritize our long-term growth, allowing us to strategically deploy our capital for pipeline investment that extends our operating plans through at least the next five years. We look forward to sharing more on our near- and long-term strategic priorities as part of a comprehensive update in early 2024. This is an important time for Design, and it’s an honor to lead this incredible team as we work to translate the proof-of-concept established for our platform into meaningful treatments for patients and the treating communities.” Third Quarter 2023 Financial Results R&D Expenses: Research and development (R&D) expenses were $13.3 million for the quarter ended September 30, 2023.G&A Expenses: General and administrative (G&A) expenses were $5.6 million for the quarter ended September 30, 2023.Net Loss: Net loss was $15.8 million for the quarter ended September 30, 2023.Cash Position and Operating Runway: Cash, cash equivalents and marketable securities were $290.9 million as of September 30, 2023. As a result of a strategic realignment to prioritize long-term growth, focus capital resources on program spend and implement cost savings, Design now expects its cash, cash equivalents and marketable securities as of September 30, 2023, to fund its planned operating expenses through at least the next five years. About Design Therapeutics Design Therapeutics is a biotechnology company developing a new class of therapies based on its platform of GeneTAC™ gene targeted chimera small molecules. The company’s GeneTAC™ molecules are designed to either dial up or dial down the expression of a specific disease-causing gene to address the underlying cause of disease. In addition to its lead GeneTAC™ small molecule, DT-216, in development for patients with Friedreich ataxia, the company is advancing programs in Fuchs endothelial corneal dystrophy and myotonic dystrophy type-1. Discovery efforts for multiple other serious degenerative disorders caused by nucleotide repeat expansions are also underway, including for fragile X syndrome, spinocerebellar ataxias, Huntington disease, spinobulbar muscular atrophy, and C9orf72-amyotrophic lateral sclerosis/frontotemporal dementia. For more information, please visit designtx.com. Forward-Looking Statements Statements in this press release that are not purely historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to projections from early-stage programs, nonclinical data and early-stage clinical data; the ability of an improved formulation of DT-216 to improve injection site tolerability to enable the long-term treatment of patients with FA; Design’s ability to advance the GeneTAC™ platform; the potential of GeneTAC™ molecules to be transformative therapies for patient populations with urgent unmet medical needs, including FA, Fuchs endothelial corneal dystrophy and myotonic dystrophy type-1; Design’s estimated financial runway and the sufficiency of its resources to support its planned operations; and the capabilities and potential advantages of Design’s pipeline of GeneTAC™ molecules. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “believes,” “designed to,” “anticipates,” “aims,” “plans to,” “expects,” “estimate,” “intends,” “will,” “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Design’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks associated with the acceptance of INDs by the FDA for the conduct of planned clinical trials of our product candidates and our proposed design of future clinical trials; risks associated with designing and implementing investigational drug product formulation improvements; risks associated with conducting a clinical trial and patient enrollment, which is affected by many factors, and any difficulties or delays encountered with such clinical trial or patient enrollment may delay or otherwise adversely affect Design’s clinical development plans; the process of discovering and developing therapies that are safe and effective for use as human therapeutics and operating as a development stage company; the risk that undesirable side effects or other properties could cause Design or regulatory authorities to suspend or discontinue clinical trials which could delay or prevent Design’s product candidates’ development or regulatory approval; Design’s ability to develop, initiate or complete nonclinical studies and clinical trials for its product candidates; the risk that promising early research or clinical trials do not demonstrate safety and/or efficacy in later nonclinical studies or clinical trials; changes in Design’s plans to develop its product candidates; uncertainties associated with performing clinical trials, regulatory filings and applications; risks associated with reliance on third parties to successfully conduct clinical trials and nonclinical studies; Design’s reliance on key third parties, including contract manufacturers and contract research organizations; Design’s ability to raise any additional funding it will need to continue to pursue its business and product development plans; regulatory developments in the United States and foreign countries; Design’s ability to obtain and maintain intellectual property protection for its product candidates; Design’s ability to recruit and retain key scientific or management personnel; competition in the industry in which Design operates, which may result in others discovering, developing or commercializing competitive products before or more successfully than Design; and market conditions. For a more detailed discussion of these and other factors, please refer to Design’s filings with the Securities and Exchange Commission (“SEC”), including under the “Risk Factors” heading of Design’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2023, as filed with the SEC on August 14, 2023, and under the “Risk Factors” heading of Design’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023, being filed with the SEC later today. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and Design undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof, except as required by law. Contacts:Investors:Chelcie ListerTHRUST Strategic Communicationschelcie@thrustsc.com Media:Amanda SellersVerge Scientific Communicationsasellers@vergescientific.com DESIGN THERAPEUTICS, INC.CONDENSED STATEMENTS OF OPERATIONS(in thousands, except share and per share data) Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 (unaudited) Operating expenses: Research and development $13,257 $14,304 $46,051 $34,358 General and administrative 5,565 4,888 17,018 13,843 Total operating expenses 18,822 19,192 63,069 48,201 Loss from operations (18,822) (19,192) (63,069) (48,201)Other income, net 3,033 1,488 8,049 2,233 Net loss $(15,789) $(17,704) $(55,020) $(45,968) Net loss per share, basic and diluted $(0.28) $(0.32) $(0.98) $(0.83)Weighted-average shares of common stock outstanding, basic and diluted 55,988,691 55,782,329 55,948,867 55,654,490 DESIGN THERAPEUTICS, INC.CONDENSED BALANCE SHEETS(in thousands) September 30, December 31, 2023 2022 (unaudited) Assets Current assets: Cash, cash equivalents and investment securities $290,940 $330,387 Prepaid expenses and other current assets 3,603 4,732 Total current assets 294,543 335,119 Property and equipment, net 1,778 1,947 Right-of-use asset, related party 3,111 3,612 Other assets 437 459 Total assets $299,869 $341,137 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable $2,207 $3,025 Accrued expenses and other current liabilities 10,183 7,751 Total current liabilities 12,390 10,776 Operating lease liability, net, related party 2,522 3,051 Total liabilities 14,912 13,827 Total stockholders’ equity 284,957 327,310 Total liabilities and stockholders’ equity $299,869 $341,137

Pictured: Hand changing blocks from Plan A to B/iStock, BrianAJackson Design Therapeutics faces clinical delays for its Phase I Friedreich’s ataxia drug due to injection site reactions. The biopharma announced plans to reformulate its only clinical asset on Monday in its second-quarter earnings report. On the news, the company’s stock dropped more than 70% in Tuesday morning trading. The company’s lead GeneTAC small molecule, DT-216, was showing early promise in a Phase I trial for Friedreich’s ataxia (FA), a genetic disorder that causes progressive damage to the nervous system. Initial results demonstrated a significant and dose-related increase in frataxin mRNA levels in skeletal muscles, confirming clinical activity. However, injection site thrombophlebitis—blood clot formation in veins—occurred in five patients across the dose cohorts, according to Design. Four were considered mild with one moderate. The company announced Monday that a redesign of the drug to alleviate the side effects should allow for higher dosage and chronic IV administration. The new formulation will cause significant delays for the asset. A multiple dose Phase I trial is now expected to begin in the second half of 2024. With initial data readouts in 2025, that’s a substantial setback from Design’s previous guidance that projected a Phase II study start later this year. In February 2023, the FDA approved the first treatment for FA. In clinical studies, patients on Reata Pharmaceuticals’ Skyclarys performed better on the modified Friedreich’s Ataxia Rating Scale, which measures disease progression. The treatment will be priced at $370,000 a year. Five months later, Biogen announced plans to drop $7.3 billion to acquire Reata, bolstering its neuro and rare disease business. Nevertheless, FA continues to be a challenging indication. In May, PTC Therapeutics’ Phase III candidate for FA missed its primary endpoint. While cutting other programs, PTC held on to the FA asset despite the flop and planned to open talks with the FDA about a path to approval for the drug. Design CEO João Siffert in a statement Monday said that “the totality of the data” from its Phase I program “supports the continued development” of DT-216 for FA and the company is now conducting bridging nonclinical studies to resume clinical development. DT-216 is Design’s only asset currently in clinical studies. An IND filing is anticipated for its GeneTAC eye drop for Fuchs Endothelial Corneal Dystrophy, a genetic eye disease. Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.