Vitamin A

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today presented the most contemporary analysis of the HELIOS-B Phase 3 study of vutrisiran for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM) as a late-breaking abstract at the Heart Failure 2025 Congress, a scientific congress of the European Society of Cardiology, taking place May 17-20 in Belgrade, Serbia. The results demonstrate that vutrisiran, which rapidly knocks down transthyretin, reduces key cardiovascular (CV) events such as CV hospitalizations, and heart failure (HF) hospitalizations. Additionally, in the analysis, urgent HF visits were reduced by 46% (95% CI: 0.30, 0.98; p = 0.041) in the overall population during the double-blind period, compared to placebo. These CV events often precede all-cause mortality (ACM) and are key indicators of disease progression. Importantly, results from the November 2024 data cut, including further follow up through up to 42 months, reinforce the primary HELIOS-B analysis showing vutrisiran’s effect on ACM, and further demonstrate that vutrisiran reduces CV mortality. Through 42 months, the risk of ACM was reduced by 36% (95% CI: 0.46, 0.88; p = 0.007) and the risk of CV mortality was reduced by 33% (95% CI: 0.47, 0.96; p = 0.038) in the overall population, compared to placebo. For both the primary analysis and the current analysis, vital status through 42 months was ascertained for over 99% of all randomized patients from the HELIOS-B study, underscoring the robustness of the results. The study was conducted in a contemporary patient population with patients receiving robust background therapy, inclusive of treatment with a TTR stabilizer and SGLT2 inhibitors. The analysis of the HELIOS-B Phase 3 study, including mortality data through up to 42 months, was simultaneously published in JACC. “From the primary analysis of HELIOS-B, we know that AMVUTTRA profoundly impacts all-cause mortality, while preserving patients’ functional capacity and quality of life,” said Pushkal Garg, M.D., Chief Medical Officer of Alnylam. “These new data—including the impact on mortality, on cardiovascular events and on urgent heart failure visits, the latter of which was reduced by nearly half—add to the story of consistency and magnitude of benefit. I remain impressed by the HELIOS-B results, which are noteworthy given the substantial use of heart failure treatments in the study population, and I believe they continue to reinforce AMVUTTRA as a clinically differentiated, first-line option for patients with ATTR-CM.” The results from the analysis underscore the rapid and sustained benefits of vutrisiran in treating ATTR-CM across key endpoints: Impact of Vutrisiran Versus Placebo Overall Population N=654 Reduction in Urgent HF Visits through 36 Months 46% RR: 0.54 P = 0.041 Reduction in HF Hospitalizations through 36 Months 33% RR: 0.67 P = 0.002 Reduction in Risk of CV Events through 36 Months 27% RR: 0.73 P = 0.001 Reduction in CV Hospitalizations through 36 Months 25% RR: 0.75 P = 0.004 Reduction in Risk of ACM through 42 Months 36% HR: 0.64 P = 0.007 Reduction in CV Mortality through 42 Months 33% HR: 0.67 P = 0.038 In a separate presentation on Tuesday, May 20, Alnylam will share findings from a subgroup analysis of HELIOS-B evaluating the impact of vutrisiran on ACM and recurrent CV events among patients identified by investigators as having experienced disease progression while being treated with tafamidis. Also at the Heart Failure 2025 Congress, Alnylam will present the study design and rationale for TRITON-CM, a Phase 3, randomized, double-blind, study of nucresiran in patients with ATTR-CM. Nucresiran is an investigational next-generation RNAi therapeutic targeting TTR that has been shown to deliver rapid knockdown of TTR greater than 95% with twice-annual dosing in a Phase 1 study. TRITON-CM is an event-driven CV outcomes trial with a primary endpoint of composite ACM and CV events. The study is on track to initiate in the first half of 2025 and will enroll approximately 1,200 patients with wild-type or variant TTR and confirmed cardiomyopathy, including those receiving background stabilizer therapy. Additional details of the study’s secondary endpoints and key inclusion and exclusion criteria will be shared on Monday, May 19. AMVUTTRA® (vutrisiran) was approved by the U.S. Food and Drug Administration (FDA) and the Brazilian Health Regulatory Agency (ANVISA) for treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending the approval of vutrisiran for the same indication. A formal regulatory decision by the European Commission of the EMA is expected by the third quarter of 2025. Vutrisiran is currently under review for the treatment of ATTR-CM by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). Alnylam remains on track to proceed with additional global regulatory submissions for vutrisiran in 2025 and beyond. For additional information on Alnylam’s presentations at the Heart Failure 2025 Congress, please visit Capella. Indications and Important Safety Information Indications Approved by the U.S. FDA AMVUTTRA® (vutrisiran) is indicated for the treatment of the: cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits. polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. Important Safety Information Reduced Serum Vitamin A Levels and Recommended Supplementation AMVUTTRA treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking AMVUTTRA. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with AMVUTTRA, as serum vitamin A levels do not reflect the total vitamin A in the body. Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness). Adverse Reactions In a study of patients with hATTR-PN, the most common adverse reactions that occurred in patients treated with AMVUTTRA were pain in extremity (15%), arthralgia (11%), dyspnea (7%), and vitamin A decreased (7%). In a study of patients with ATTR-CM, no new safety issues were identified. For additional information about AMVUTTRA, please see the full U.S. Prescribing Information (revised March 2025) About AMVUTTRA® (vutrisiran) AMVUTTRA® (vutrisiran) is an RNAi therapeutic that delivers rapid knockdown of variant and wild-type transthyretin (TTR), addressing the underlying cause of transthyretin (ATTR) amyloidosis. Administered quarterly via subcutaneous injection, vutrisiran is approved and marketed in more than 15 countries for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. In Europe, it is administered as a subcutaneous injection once every three months, either by a healthcare professional, or self-administered by patients or their caregivers. Vutrisiran is also in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM), which encompasses both wild-type and hereditary forms of the disease. About ATTR Transthyretin amyloidosis (ATTR) is an underdiagnosed, rapidly progressive, debilitating and fatal disease caused by misfolded transthyretin (TTR) proteins, which accumulate as amyloid deposits in various parts of the body, including the nerves, heart and gastrointestinal tract. Patients may present with polyneuropathy, cardiomyopathy, or both manifestations of disease. There are two different forms of ATTR – hereditary ATTR (hATTR), which is caused by a TTR gene variant and affects approximately 50,000 people worldwide, and wild-type ATTR (wtATTR), which occurs without a TTR gene variant and impacts an estimated 200,000 – 300,000 people worldwide.1-4 About RNAi RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines known as RNAi therapeutics is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases. About Alnylam Pharmaceuticals Alnylam (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding in 2002, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “Alnylam P5x25” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. Alnylam Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than historical statements of fact regarding Alnylam’s expectations, beliefs, goals, plans or prospects including, without limitation, Alnylam’s expectations regarding the safety and efficacy of vutrisiran for the treatment of ATTR-CM, including the ability of vutrisiran to reduce mortality and cardiovascular events in ATTR-CM patients and to preserve patients’ functional capacity and quality of life; the potential for vutrisiran to become a first-line therapy for ATTR-CM; the timing of the initiation of the TRITON-CM study and the number of patients who will be enrolled in that study; the timing of additional global regulatory submissions for vutrisiran; the timing or receipt of any additional regulatory approvals for vutrisiran for ATTR-CM; Alnylam’s ability to execute on its “Alnylam P5x25” strategy and to deliver transformative medicines in both rare and common diseases benefit patients around the world through sustainable innovation and exceptional financial performance; and Alnylam’s ability to have a leading biotech profile should be considered forward-looking statements. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation, risks and uncertainties relating to Alnylam’s ability to successfully execute on its “Alnylam P5x25” strategy; Alnylam’s ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for Alnylam’s product candidates; actions or advice of regulatory agencies and Alnylam’s ability to obtain and maintain regulatory approval for its product candidates, as well as favorable pricing and reimbursement; successfully launching, marketing and selling Alnylam’s approved products globally; delays, interruptions or failures in the manufacture and supply of Alnylam’s product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial profile in the future; Alnylam’s ability to maintain strategic business collaborations; Alnylam’s dependence on third parties for the development and commercialization of certain products; the outcome of litigation; the potential risk of future government investigations; and unexpected expenditures; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam’s 2024 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as may be updated from time to time in Alnylam’s subsequent Quarterly Reports on Form 10-Q, and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing Alnylam’s views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements. 1 Hawkins PN, Ando Y, Dispenzeri A, et al. Ann Med. 2015;47(8):625-638. 2 Gertz MA. Am J Manag Care. 2017;23(7):S107-S112. 3 Conceicao I, Gonzalez-Duarte A, Obici L, et al. J Peripher Nerv Syst. 2016;21:5-9. 4 Ando Y, Coelho T, Berk JL, et al. Orphanet J Rare Dis. 2013;8:31.

Following a pre-specified interim analysis, an independent Data Safety Monitoring Board (DSMB) recommended the pivotal Phase 3 trial (DRAGON) of Tinlarebant in adolescent Stargardt disease (STGD1) patients proceed without any modification; trial completion expected Q4 2025 (including a three-month follow-up period)DSMB also recommended the Company submit the interim data for further regulatory review for drug approvalA pivotal global Phase 3 trial (PHOENIX) of Tinlarebant in geographic atrophy (GA) patients is ongoing with 464 of targeted 500 subjects enrolledRaised $15 million in gross proceeds in a registered direct offering on February 5, 2025Conference call and webcast on Wednesday, May 14, 2025, at 4:30 p.m. ET SAN DIEGO, May 13, 2025 (GLOBE NEWSWIRE) -- Belite Bio, Inc (NASDAQ: BLTE), a clinical-stage biopharmaceutical drug development company focused on advancing novel therapeutics targeting degenerative retinal diseases that have significant unmet medical needs, today announced its financial results for the first quarter ended March 31, 2025, and provided a business update. “We continue to advance the clinical development of Tinlarebant, reaching a major milestone with the favorable interim analysis of our Phase 3 DRAGON trial earlier this year,” said Dr. Tom Lin, Chairman and CEO of Belite Bio. “We are excited by the encouraging feedback from the DSMB on the safety and efficacy outcomes in DRAGON as we work toward trial completion by the end of 2025. We are focused on maintaining strong execution across our late-stage clinical programs as we aim to deliver new treatment options for people living with degenerative retinal diseases, where there is significant unmet need.” First Quarter 2025 Business Highlights and Upcoming Milestones: Clinical Highlights Tinlarebant is an oral, once-daily, potent retinol binding protein 4 (RBP4) antagonist that decreases RBP4 levels in the blood and reduces vitamin A (retinol) delivery to the eye without disrupting systemic retinol delivery to other tissues. Vitamin A is critical for normal vision but can accumulate as toxic byproducts (bisretinoids) in individuals affected with STGD1 and GA, the advanced form of dry age-related macular degeneration (AMD), leading to retinal cell death and loss of vision. Stargardt disease (STGD1): Accumulation of cytotoxic bisretinoids compounds has been implicated in the onset and progression of STGD1, for which there are no approved treatments. Tinlarebant has been granted Fast Track and Rare Pediatric Disease Designations in the U.S.; Orphan Drug Designation in the U.S., Europe, and Japan; and Sakigake (Pioneer Drug) Designation in Japan for the treatment of STGD1. DRAGON Trial: Ongoing, 24-month, randomized (2:1, active: placebo), double-masked, placebo-controlled, global, multi-center, pivotal Phase 3 trial in adolescent STGD1 patients Following a pre-specified interim analysis, an independent DSMB recommended trial continuation without modifications, maintaining a sample size of 104 subjectsIn addition, the DSMB recommended submitting the data for further regulatory review for drug approvalPrimary efficacy endpoint is the growth rate of atrophic lesions; safety and tolerability will also be assessedTrial completion expected by Q4 2025 (including a three-month follow-up period) DRAGON II Trial: Combination of a Phase 1b open-label trial to evaluate the pharmacokinetics and pharmacodynamics of Tinlarebant in adolescent Japanese STGD1 patients and a Phase 2/3, 24-month, randomized (1:1, active: placebo), double-masked, placebo-controlled, multicenter trial in adolescent STGD1 patients Enrolled 16 subjects in the Phase 2/3 trial, with a target enrollment of approximately 60 subjects, aged 12 to 20 years old, including approximately 10 Japanese subjects; data from the Japanese subjects is intended to facilitate a future new drug application in JapanPrimary efficacy endpoint is the growth rate of atrophic lesions; safety and tolerability will also be assessed Geographic Atrophy (GA): GA is a chronic degenerative disease of the retina that leads to blindness in the elderly. Accumulation of cytotoxic vitamin A byproducts (bisretinoids) has been implicated in the progression of GA. There are currently no FDA-approved, orally administered treatments for GA. PHOENIX Trial: Ongoing, 24-month, randomized (2:1, active: placebo), double-masked, placebo-controlled, global, multi-center, pivotal Phase 3 trial in GA patients 464 of the targeted 500 subjects have been enrolled to datePrimary efficacy endpoint is the growth rate of atrophic lesions; safety and tolerability will also be assessedCompany expects to conduct an interim analysis Corporate Highlights In February 2025, Belite completed a registered direct offering priced at the market, raising gross proceeds of $15 million, with the potential for additional proceeds of approximately $15 million from the exercise of five-year warrants issued in the offering. First Quarter 2025 Financial Results: Current Assets: As of March 31, 2025, the Company had $157.4 million in cash, liquidity funds, time deposits, and U.S treasury bills. R&D Expenses: For the three months ended March 31, 2025, research and development expenses were $9.4 million compared to $6.8 million for the same period in 2024. The increase in research and development expenses was primarily attributable to (i) share-based compensation granted in the third quarter of 2024 and first quarter of 2025, (ii) slightly higher clinical trial expenses related to the PHOENIX trial. G&A Expenses: For the three months ended March 31, 2025, general and administrative expenses were $6.1 million compared to $1.6 million for the same period in 2024. The increase resulted primarily from an increase in share-based compensation granted in the third quarter of 2024 and first quarter of 2025. Other Income: For the three months ended March 31, 2025, other income was $1.2 million compared to $0.5 million for the same period in 2024. The increase in other income was attributable to accrued interest from time deposits and U.S. treasury bills. Net Loss: For the three months ended March 31, 2025, the Company reported a net loss of $14.3 million, compared to a net loss of $7.9 million for the same period in 2024. Webcast Information Belite Bio will host a webcast on Wednesday, May 14, 2025, at 4:30 p.m. Eastern Time to discuss the Company’s financial results and provide a business update. To join the webcast, please visit https://events.q4inc.com/attendee/137642555. A replay will be available for approximately 90 days following the event at the Company’s Investor Relations website at https://investors.belitebio.com/presentations-events/events. About Belite Bio Belite Bio is a clinical-stage biopharmaceutical drug development company focused on advancing novel therapeutics targeting degenerative retinal diseases that have significant unmet medical need, such as Stargardt disease type 1 (STGD1) and Geographic Atrophy (GA) in advanced dry age-related macular degeneration (AMD), in addition to specific metabolic diseases. Belite’s lead candidate, Tinlarebant, an oral therapy intended to reduce the accumulation of toxins in the eye, is currently being evaluated in a Phase 3 study (DRAGON) and a Phase 2/3 study (DRAGON II) in adolescent STGD1 patients and a Phase 3 study (PHOENIX) in patients with GA. For more information, follow us on X, Instagram, LinkedIn, Facebook or visit us at www.belitebio.com. Important Cautions Regarding Forward Looking Statements This press release contains forward-looking statements about future expectations and plans, as well as other statements regarding matters that are not historical facts. These statements include but are not limited to statements regarding the potential implications of clinical data for patients, and Belite Bio’s advancement of, and anticipated preclinical activities, clinical development, regulatory milestones, and commercialization of its product candidates, and any other statements containing the words “expect”, “hope” and similar expressions. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including but not limited to Belite Bio’s ability to demonstrate the safety and efficacy of its drug candidates; the clinical results for its drug candidates, which may not support further development or regulatory approval; the timing to complete relevant clinical trials and/or to receive the interim/final data of such clinical trials; the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approval of Belite Bio’s drug candidates; the potential efficacy of Tinlarebant, as well as those risks more fully discussed in the “Risk Factors” section in Belite Bio’s filings with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Belite Bio, and Belite Bio undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law. BELITE BIO, INC UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (Amounts in thousands of US Dollars, except share and per share amounts) For the Three MonthsEnded March 31, 2024 2025 Expenses Research and development 6,765 9,396 General and administrative 1,563 6,121 Total operating expenses 8,328 15,517 Loss from operations (8,328) (15,517)Other income: Total other income, net 463 1,240 Loss before income tax (7,865) (14,277)Income tax expense 6 - Net loss (7,871) (14,277)Other comprehensive income (loss) Foreign currency translation adjustments, net of nil tax (96) 18 Total comprehensive loss (7,967) (14,259)Weighted average number of ordinary shares used in per share calculation: - Basic and Diluted 29,677,173 32,084,106 Net loss per ordinary share - Basic and Diluted $(0.27) $(0.45) BELITE BIO, INC UNAUDITED CONDENSED CONSOLIDATED BALANCE SHEETS (Amounts in thousands of US Dollars, except share amounts) December 31, March 31, 2024 2025 Current assets $147,073 $159,287 Other assets 5,059 4,914 TOTAL ASSETS $152,132 $164,201 TOTAL LIABILITIES $6,311 $6,131 TOTAL SHAREHOLDERS’ EQUITY 145,821 158,070 TOTAL LIABILITIES AND SHAREHOLDERS’ EQUITY $152,132 $164,201 Ordinary shares authorized 400,000,000 400,000,000 Ordinary shares issued 31,857,802 32,595,001 Ordinary shares outstanding 31,826,549 32,544,784 Media and Investor Relations Contact: Jennifer Wu ir@belitebio.com Julie Fallon belite@argotpartners.com