Aligos Therapeutics Announces Positive Topline Results from the Phase 2a HERALD Study of ALG-055009 for the Treatment of MASH
Aligos Therapeutics (Nasdaq: ALGS) announced positive topline results from the Phase 2a HERALD study of ALG-055009, a thyroid hormone receptor beta agonist, for treating metabolic-dysfunction associated steatohepatitis (MASH). The study met its primary endpoint with statistically significant reductions in liver fat at Week 12, measured by MRI-PDFF. Key findings include:
1. Placebo-adjusted median relative reductions in liver fat up to 46.2% with a clear dose response
2. ALG-055009 was well-tolerated with no serious adverse events
3. Significant reductions in atherogenic lipids, including LDL-C, lipoprotein (a), and apolipoprotein B
4. Up to 70% of subjects achieved ≥30% relative reduction in liver fat compared to baseline
The company is evaluating options for further development, including potential partnerships.
Aligos Therapeutics (Nasdaq: ALGS) ha annunciato risultati positivi preliminari dallo studio di Fase 2a HERALD su ALG-055009, un agonista del recettore degli ormoni tiroidei beta, per il trattamento della steatoepatite associata a disfunzione metabolica (MASH). Lo studio ha raggiunto il suo obiettivo primario con riduzioni statisticamente significative del grasso epatico alla Settimana 12, misurate tramite MRI-PDFF. I risultati chiave includono:
1. Riduzioni medie relative del grasso epatico, corrette per il placebo, fino al 46,2% con una chiara risposta alla dose
2. ALG-055009 è stato ben tollerato senza eventi avversi gravi
3. Riduzioni significative nei lipidi aterogeni, inclusi LDL-C, lipoproteina (a) e apolipoproteina B
4. Fino al 70% dei soggetti ha raggiunto una riduzione relativa del grasso epatico ≥30% rispetto al valore basale
La società sta valutando le opzioni per ulteriori sviluppi, inclusi potenziali partenariati.
Aligos Therapeutics (Nasdaq: ALGS) anunció resultados positivos preliminares del estudio de Fase 2a HERALD con ALG-055009, un agonista del receptor de hormonas tiroideas beta, para el tratamiento de esteatohepatitis asociada a disfunción metabólica (MASH). El estudio alcanzó su objetivo principal con reducciones estadísticamente significativas de grasa hepática a la Semana 12, medidas por MRI-PDFF. Los hallazgos clave incluyen:
1. Reducciones relativas medianas de grasa hepática ajustadas por placebo de hasta 46.2% con una clara respuesta a la dosis
2. ALG-055009 fue bien tolerado sin eventos adversos graves
3. Reducciones significativas en lípidos aterogénicos, incluyendo LDL-C, lipoproteína (a) y apolipoproteína B
4. Hasta el 70% de los sujetos logró una reducción relativa de grasa hepática ≥30% en comparación con la línea base
La empresa está evaluando opciones para el desarrollo futuro, incluyendo posibles asociaciones.
Aligos Therapeutics (Nasdaq: ALGS)는 ALG-055009, 갑상선 호르몬 수용체 베타 작용제에 대한 2a상 HERALD 연구에서 긍정적인 초기 결과를 발표했습니다. 이는 대사 기능 장애와 관련된 지방간염 (MASH) 치료를 위해 실시되었습니다. 이 연구는 MRI-PDFF로 측정된 12주차에 간 지방의 통계적으로 유의미한 감소라는 주요 목표를 달성했습니다. 주요 발견 사항은 다음과 같습니다:
1. 플라세보 조정 후, 간 지방의 중앙 상대 감소가 46.2%까지 이뤄졌으며, 분명한 용량 반응이 있었습니다.
2. ALG-055009는 잘 견디어냈으며 심각한 부작용이 없었습니다.
3. LDL-C, 지단백질 (a), 아포지단백질 B를 포함한 Atherogenic지질에서 유의미한 감소가 나타났습니다.
4. 최대 70%의 피험자들이 기준선 대비 간 지방 ≥30% 상대 감소를 달성했습니다.
회사는 잠재적인 파트너십을 포함하여 추가 개발을 위한 옵션을 평가하고 있습니다.
Aligos Therapeutics (Nasdaq: ALGS) a annoncé des résultats préliminaires positifs de l'étude de Phase 2a HERALD concernant ALG-055009, un agoniste des récepteurs des hormones thyroïdiennes beta, pour le traitement de la stéatohépatite associée à une dysfonction métabolique (MASH). L'étude a atteint son objectif principal avec des réductions statistiquement significatives de la graisse hépatique à la semaine 12, mesurées par MRI-PDFF. Les conclusions clés comprennent :
1. Réductions relatives médianes de la graisse hépatique ajustées par rapport au placebo allant jusqu'à 46,2% avec une réponse à la dose claire
2. ALG-055009 a été bien toléré sans événements indésirables graves
3. Réductions significatives des lipides athérogènes, y compris LDL-C, lipoprotéine (a) et apolipoprotéine B
4. Jusqu'à 70% des sujets ont atteint une réduction relative de la graisse hépatique ≥30% par rapport à la ligne de base
L'entreprise évalue les options pour un développement ultérieur, y compris des partenariats potentiels.
Aligos Therapeutics (Nasdaq: ALGS) gab positive Ergebnisse der Zwischenanalyse der Phase 2a HERALD-Studie zu ALG-055009, einem Agonisten des Beta-Thyroxins, zur Behandlung der metabolisch assoziierten Steatohepatitis (MASH), bekannt. Die Studie erreichte ihren primären Endpunkt mit statistisch signifikanten Reduktionen des Lebergfettes in Woche 12, gemessen mit MRI-PDFF. Zu den wichtigen Ergebnissen gehören:
1. Placebo-korrigierte mediane relative Reduktionen des Lebergfettes von bis zu 46,2% mit einer klaren Dosis-Wirkungs-Beziehung
2. ALG-055009 wurde gut vertragen und es traten keine schweren Nebenwirkungen auf
3. Signifikante Reduktionen von atherogenen Lipiden, einschließlich LDL-C, Lipoprotein (a) und Apolipoprotein B
4. Bis zu 70% der Probanden erreichten eine relative Reduktion des Lebergfettes von ≥30% im Vergleich zum Ausgangswert
Das Unternehmen prüft Optionen für die weitere Entwicklung, einschließlich möglicher Partnerschaften.
- ALG-055009 met primary endpoint with statistically significant liver fat reductions up to 46.2%
- Up to 70% of subjects achieved ≥30% relative reduction in liver fat
- Favorable tolerability profile with no serious adverse events
- Significant reductions in atherogenic lipids (LDL-C, lipoprotein (a), apolipoprotein B)
- Lower incidence of diarrhea compared to placebo
- One discontinuation due to worsening insomnia in a subject with pre-existing insomnia
- Further funding required for continued development and Phase 2b study
Insights
The Phase 2a HERALD study results for ALG-055009 in MASH patients are highly encouraging. The primary endpoint was met with statistically significant reductions in liver fat of up to
Notably, ALG-055009 showed a favorable safety profile with no serious adverse events and a lower incidence of diarrhea compared to placebo. This is important for chronic conditions like MASH, where long-term treatment adherence is essential. The significant reductions in atherogenic lipids (LDL-C, lipoprotein(a) and apolipoprotein B) also suggest potential cardiovascular benefits, which is a major concern in MASH patients.
These results position ALG-055009 as a promising candidate in the competitive MASH treatment landscape, potentially offering a best-in-class profile among THR-β agonists. However, longer-term studies are needed to confirm sustained efficacy and safety.
Aligos Therapeutics' positive Phase 2a results for ALG-055009 represent a significant milestone for the company. The data suggests a potential best-in-class profile in the highly competitive MASH market, which could translate into substantial market share if approved.
The company's stock is likely to see a positive reaction due to these results. However, investors should note that Aligos is exploring partnership opportunities and funding options for further development, indicating potential dilution or strategic changes ahead. The timeline for completing activities required for a Phase 2b study by mid-2025 provides a clear near-term catalyst for the stock.
While the results are promising, it's important to consider that MASH drug development is a crowded field with several late-stage competitors. Aligos will need to differentiate ALG-055009 further and secure funding for larger trials to maintain its competitive position. The company's ability to execute on these fronts will be important for long-term value creation.
- ALG-055009 dose groups met the primary endpoint with statistically significant reductions in liver fat at Week 12 as measured by MRI-PDFF
- Placebo-adjusted median relative reductions in liver fat were up to
46.2% with a clear dose response - ALG-055009 was well-tolerated with no serious adverse events or dose reductions. Importantly, ALG-055009 dose groups had a similar incidence of gastrointestinal-related adverse events with less diarrhea compared to placebo
- Significant reductions in atherogenic lipids, including LDL-C, lipoprotein (a), and apolipoprotein B were observed
- Conference call scheduled for 8:30am ET/5:30am PT today
SOUTH SAN FRANCISCO, Calif., Sept. 19, 2024 (GLOBE NEWSWIRE) -- Aligos Therapeutics, Inc. (Nasdaq: ALGS) a clinical stage biopharmaceutical company focused on improving patient outcomes through best-in-class therapies for liver and viral diseases, today announced positive topline results from the Phase 2a HERALD study of ALG-055009, a thyroid hormone receptor beta (THR-β) agonist, in metabolic-dysfunction associated steatohepatitis (MASH) subjects.
HERALD (NCT06342947) is a randomized, double-blind, placebo-controlled trial that enrolled 102 subjects with presumed MASH and stage 1-3 liver fibrosis (F1-F3). Subjects were randomized to receive one of four doses (0.3, 0.5, 0.7, 0.9 mg) of ALG-055009 or placebo (~20 subjects/arm) given orally once daily for 12 weeks. Only subjects weighing >85 kg were enrolled in the 0.9 mg dose group, with no body weight restrictions implemented in the other dose groups. Key endpoints assessed were safety, tolerability, pharmacokinetics, relative change in liver fat content by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF), and other non-invasive biomarkers/tests.
Doses of 0.5 mg to 0.9 mg ALG-055009 demonstrated statistically significant reductions in liver fat at Week 12, with placebo-adjusted median relative reductions up to
The MRI-PDFF results are summarized in the figure below.
“The robust improvements in liver fat and other clinically relevant biomarkers, such as lipoprotein (a), demonstrate why potency and PK are pertinent when designing molecules aimed at improving patient outcomes,” said Rohit Loomba, MD, MHSc, Chief, Division of Gastroenterology and Hepatology, University of California, San Diego. “This has been an exciting year for the MASH space, which continues with this excellent data from Aligos’ ALG-055009, which has the potential for not only improvement in resolution of MASH, but also fibrosis improvement. In addition, it has potential to improve cardiovascular risk if the non-invasive tests (NIT) data are confirmed in future trials. I look forward to continuing to work with the Aligos team to further develop this program.”
ALG-055009 demonstrated a favorable tolerability profile with no serious adverse events (SAEs), or clinical hyper/hypothyroidism. The majority of treatment emergent adverse events (TEAEs) were mild to moderate, with one discontinuation due to worsening insomnia in a subject with pre-existing insomnia. No clinically meaningful findings in laboratory tests, electrocardiograms, vital signs, or physical examinations were observed. Incidence of gastrointestinal-related TEAEs were similar in ALG-055009 dose groups compared to placebo. Specifically, a non-dose-related, lower incidence of diarrhea was observed in ALG-055009 dose groups compared to placebo.
Treatment with ALG-055009 resulted in significant reductions in atherogenic lipids, including LDL-C, lipoprotein (a) (LpA), and apolipoprotein B (ApoB). In addition, dose dependent increases in sex hormone binding globulin (SHBG), a marker of THR-β target engagement in the liver, were observed.
“When designing ALG-055009, our goal was to create a potential best-in-class THR-β agonist through enhanced potency and a superior PK profile,” stated Lawrence Blatt, Ph.D., MBA, Chairman, President, and Chief Executive Officer at Aligos Therapeutics. “Today’s data demonstrates that these enhanced pharmacologic properties did indeed translate into robust improvements in liver fat reduction. In addition, ALG-055009 demonstrated a favorable tolerability profile, which is important given that MASH medications will likely be administered for prolonged periods of time. We believe ALG-055009 has the potential to help patients better adhere to MASH treatment. These results indicate that ALG-055009 warrants further development. We are currently in early discussions with potential partners and evaluating a variety of options to fund the continued development. We plan to complete the activities required for a Phase 2b study by the middle of 2025 and are assessing potential Phase 2b clinical trial designs.”
The company plans to present additional results and analyses at a future scientific meeting later this year.
Conference Call & Webcast Details
The company will host a conference call and webcast with a slide presentation today at 8:30am ET/5:30am PT. To access the live webcast with slides, please visit the Presentation & Events page on the Aligos website at www.aligos.com. Please register ten minutes prior to its start. Following the live webcast, a replay will be available on the company’s website for 90 days.
About MASH
One of the effects of improper diet and insufficient exercise is the accumulation of fatty deposits in the liver, referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), which was estimated to occur in approximately
About the HERALD Study
HERALD (NCT06342947) is a randomized, double-blind, placebo-controlled trial that enrolled 102 subjects with presumed MASH and stage 1-3 liver fibrosis (F1-F3). Subjects were randomized to receive one of four doses (0.3, 0.5, 0.7, 0.9 mg) of ALG-055009 or placebo (~20 subjects/arm) given orally once daily for 12 weeks. The primary endpoint was relative change in liver fat content by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) at Week 12. Safety, pharmacokinetics (PK) and other non-invasive biomarkers/tests previously shown to be impacted by treatment with thyroid hormone receptor beta (THR-β) agonists were also evaluated.
About ALG-055009
ALG-055009 was designed to be a potential best-in-class thyroid hormone receptor beta (THR-β) agonist discovered by Aligos for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). Recent topline data from the Phase 2a HERALD study demonstrated a favorable tolerability profile with significant reductions in liver fat as measured by MRI-PDFF following once a day, low oral dose.
About Aligos
Aligos Therapeutics, Inc. (NASDAQ: ALGS) is a clinical stage biopharmaceutical company founded with the mission to improve patient outcomes by developing best-in-class therapies for the treatment of liver and viral diseases. Aligos applies its science driven approach and deep R&D expertise to advance its purpose-built pipeline of therapeutics for metabolic dysfunction-associated steatohepatitis (MASH) and viruses with high unmet medical need such as hepatitis B and coronaviruses.
For more information, please visit www.aligos.com or follow us on LinkedIn or X.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Any statements in this press release that are not historical facts may be considered “forward-looking statements,” including without limitation, statements regarding Aligos’ research and development activities, including Aligos’ goals in designing ALG-055009, MASH medications being administered for prolonged periods of time, ALG-055009’s potential for greater patient adherence, ALG-055009’s results indicating that ALG-055009 warrants future development, Aligos’ discussions with potential partners and evaluation of options to fund the continued development of ALG-055009, Aligos’ plans to complete the activities required for a Phase 2b study and Aligos’ assessment of potential Phase 2b clinical trial designs. Such forward looking statements are subject to substantial risks and uncertainties that could cause our development programs, future results, performance, or achievements to differ materially from those anticipated in the forward-looking statements. Such risks and uncertainties include, without limitation, risks and uncertainties inherent in the drug development process, including Aligos’ clinical stage of development, the process of designing and conducting clinical trials, the regulatory approval processes, and other matters that could affect the sufficiency of Aligos’ capital resources to fund operations. For a further description of the risks and uncertainties that could cause actual results to differ from those anticipated in these forward-looking statements, as well as risks relating to the business of Aligos in general, see Aligos’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on August 6, 2024 and its future periodic reports to be filed or submitted with the Securities and Exchange Commission. Except as required by law, Aligos undertakes no obligation to update any forward-looking statements to reflect new information, events or circumstances, or to reflect the occurrence of unanticipated events.
Investor Contact
Aligos Therapeutics, Inc.
Jordyn Tarazi
Vice President, Investor Relations & Corporate Communications
+1 (650) 910-0427
jtarazi@aligos.com
Media Contact
Inizio Evoke
Jake Robison
Vice President
Jake.Robison@inzioevoke.com
A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/f305238a-fd16-4b0d-85d9-5bc31c7dacc2
FAQ
What were the main results of Aligos Therapeutics' Phase 2a HERALD study for ALG-055009?
How did ALG-055009 perform in terms of liver fat reduction in the HERALD study?
What were the safety outcomes for ALG-055009 in the Phase 2a HERALD study?
What are Aligos Therapeutics' (ALGS) next steps for ALG-055009 after the Phase 2a results?
