Amylyx Pharmaceuticals Announces First Participant Dosed in Phase 1, Multiple Ascending Dose LUMINA Trial of AMX0114 in People Living with Amyotrophic Lateral Sclerosis
Amylyx Pharmaceuticals (NASDAQ: AMLX) has initiated the LUMINA Phase 1 trial for AMX0114, dosing its first participant. This multinational, randomized, double-blind, placebo-controlled study will evaluate AMX0114, an antisense oligonucleotide targeting calpain-2, in people with Amyotrophic Lateral Sclerosis (ALS).
The trial will enroll approximately 48 participants across North America, randomized 3:1 to receive AMX0114 or placebo via intrathecal administration once every four weeks for up to 4 doses. The study aims to assess safety, tolerability, pharmacokinetics, and pharmacodynamics, including changes in neurofilament light chain (NfL) levels.
Early cohort data from LUMINA is expected in 2025. Preclinical studies have shown improved neuronal survival and reduced extracellular NfL levels across multiple disease models. The drug targets calpain-2, a calcium-activated protease believed to be a key contributor to axonal degeneration in ALS.
Amylyx Pharmaceuticals (NASDAQ: AMLX) ha avviato il trial di fase 1 LUMINA per AMX0114, somministrando il trattamento al suo primo partecipante. Questo studio multinazionale, randomizzato, in doppio cieco e controllato con placebo valuterà AMX0114, un oligonucleotide antisenso che mira alla calpain-2, in persone affette da sclerosi laterale amiotrofica (SLA).
Il trial recluterà circa 48 partecipanti in Nord America, randomizzati in un rapporto di 3:1 per ricevere AMX0114 o placebo tramite somministrazione intratecale ogni quattro settimane per un massimo di 4 dosi. Lo studio mira a valutare sicurezza, tollerabilità, farmacocinetica e farmacodinamica, inclusi i cambiamenti nei livelli della catena leggera della neurofilamento (NfL).
I dati preliminari del gruppo di LUMINA sono attesi nel 2025. Studi preclinici hanno mostrato un miglioramento della sopravvivenza neuronale e una riduzione dei livelli extracellulari di NfL in diversi modelli di malattia. Il farmaco mira alla calpain-2, una proteasi attivata dal calcio che si ritiene sia un contributore chiave alla degenerazione assonale nella SLA.
Amylyx Pharmaceuticals (NASDAQ: AMLX) ha iniciado el ensayo de fase 1 LUMINA para AMX0114, administrando la primera dosis a su primer participante. Este estudio multinacional, aleatorizado, doble ciego y controlado con placebo evaluará AMX0114, un oligonucleótido antisentido dirigido a la calpain-2, en personas con .
El ensayo inscribirá aproximadamente 48 participantes en América del Norte, aleatorizados en una proporción de 3:1 para recibir AMX0114 o placebo mediante administración intratecal cada cuatro semanas hasta un máximo de 4 dosis. El estudio tiene como objetivo evaluar la seguridad, la tolerabilidad, la farmacocinética y la farmacodinamia, incluidos los cambios en los niveles de la cadena ligera de neurofilamento (NfL).
Se esperan datos preliminares del grupo de LUMINA para 2025. Los estudios preclínicos han mostrado una mejora en la supervivencia neuronal y una reducción de los niveles extracelulares de NfL en múltiples modelos de enfermedad. El fármaco tiene como objetivo la calpain-2, una proteasa activada por calcio que se cree que es un contribuyente clave a la degeneración axonal en la ELA.
아밀릭스 제약(Amylyx Pharmaceuticals) (NASDAQ: AMLX)는 AMX0114에 대한 LUMINA 1상 시험을 시작하며 첫 번째 참가자에게 투여했습니다. 이 다국적, 무작위, 이중 맹검, 위약 대조 연구는 근위축성 측삭 경화증(ALS) 환자에서 칼페인-2를 표적으로 하는 항센스 올리고뉴클레오타이드인 AMX0114를 평가할 것입니다.
이 시험은 북미에서 약 48명의 참가자를 모집하며, AMX0114 또는 위약을 4주마다 한 번씩 최대 4회 투여받기 위해 3:1의 비율로 무작위 배정됩니다. 이 연구는 안전성, 내약성, 약물동태학 및 약물역학을 평가하는 것을 목표로 하며, 여기에는 신경필라멘트 경량 사슬(NfL) 수준의 변화가 포함됩니다.
LUMINA의 초기 집단 데이터는 2025년으로 예상됩니다. 전임상 연구에서는 여러 질병 모델에서 신경 생존율이 개선되고 NfL의 세포외 수준이 감소했음을 보여주었습니다. 이 약물은 ALS의 축삭 퇴화에 주요 기여자로 여겨지는 칼페인-2를 표적으로 합니다.
Amylyx Pharmaceuticals (NASDAQ: AMLX) a lancé l'
L'essai recrutera environ 48 participants en Amérique du Nord, randomisés dans un rapport de 3:1 pour recevoir AMX0114 ou un placebo par administration intrathécale toutes les quatre semaines pour un maximum de 4 doses. L'étude vise à évaluer la sécurité, la tolérance, la pharmacocinétique et la pharmacodynamie, y compris les changements des niveaux de la chaîne légère des neurofilaments (NfL).
Les données préliminaires du groupe LUMINA sont attendues en 2025. Des études précliniques ont montré une amélioration de la survie neuronale et une réduction des niveaux de NfL extracellulaire dans plusieurs modèles de maladies. Le médicament cible la calpaïne-2, une protéase activée par le calcium, considérée comme un contributeur clé à la dégénérescence axonale dans la SLA.
Amylyx Pharmaceuticals (NASDAQ: AMLX) hat die LUMINA Phase 1 Studie für AMX0114 initiiert und die erste Teilnehmerin behandelt. Diese multinationale, randomisierte, doppelblinde, placebo-kontrollierte Studie wird AMX0114, ein Antisense-Oligonukleotid, das auf Calpain-2 abzielt, bei Menschen mit amyotropher Lateralsklerose (ALS) evaluieren.
Die Studie wird voraussichtlich etwa 48 Teilnehmer in Nordamerika einschließen, die im Verhältnis 3:1 randomisiert werden, um AMX0114 oder ein Placebo alle vier Wochen bis zu 4 Dosen intrathekal zu erhalten. Ziel der Studie ist es, Sicherheit, Verträglichkeit, Pharmakokinetik und Pharmakodynamik zu bewerten, einschließlich der Veränderungen der Neurofilament-Leichtkette (NfL) Werte.
Frühe Kohortendaten aus LUMINA werden für 2025 erwartet. Vorklinische Studien haben eine verbesserte neuronale Überlebensfähigkeit und reduzierte extrazelluläre NfL-Werte in mehreren Krankheitsmodellen gezeigt. Das Medikament zielt auf Calpain-2 ab, ein calciumaktiviertes Enzym, das als wichtiger Faktor für die axonale Degeneration bei ALS gilt.
- Successful initiation of Phase 1 LUMINA trial with first patient dosed
- Preclinical studies showed improved neuronal survival and reduced NfL levels
- Novel therapeutic approach targeting a fundamental disease mechanism
- Early-stage Phase 1 trial with results not expected until 2025
- Small trial size of only 48 participants
Insights
Amylyx's dosing of the first participant in the Phase 1 LUMINA trial represents a meaningful pipeline advancement for this small-cap biotech. This clinical milestone for AMX0114, an antisense oligonucleotide targeting calpain-2, diversifies their neurodegenerative disease portfolio beyond their existing ALS treatment.
The trial's design is scientifically robust - multinational, randomized, double-blind, placebo-controlled with multiple ascending doses evaluating standard Phase 1 endpoints plus biomarkers like neurofilament light chain (NfL). With 48 participants across North America, this is a reasonably sized early-stage study for a rare disease like ALS.
What's particularly notable is AMX0114's mechanistic approach. By targeting calpain-2, a calcium-activated protease implicated in axonal degeneration, Amylyx is pursuing a pathway with significant scientific rationale and preclinical evidence. The inclusion of NfL as a biomarker is strategically important as it may provide early signals of biological activity.
For a company with a market cap around $321M, advancing a second clinical candidate with a differentiated mechanism represents a positive development, though early-stage clinical trials carry substantial failure risk. Expected early cohort data later this year could provide important directional insights on safety and potentially early biomarker signals.
The initiation of this Phase 1 LUMINA trial for AMX0114 represents a scientifically sound approach to ALS treatment development. Targeting calpain-2 addresses a fundamental mechanism in axonal degeneration, which is crucial in ALS pathophysiology.
Calpain-2 inhibition is a well-researched but clinically untapped approach. This calcium-activated protease contributes to the structural breakdown of axons - the critical communication channels between neurons and muscles that progressively degenerate in ALS. The intrathecal delivery method ensures the antisense oligonucleotide reaches the central nervous system directly.
The inclusion of neurofilament light chain (NfL) measurements is particularly valuable. NfL serves as a quantifiable marker of axonal damage, potentially enabling researchers to detect biological signals of efficacy before clinical symptoms show measurable change. This could accelerate development decision-making.
While Phase 1 trials primarily assess safety, the multiple ascending dose design may provide preliminary insights into biological activity. The participation of the Sean M. Healey & AMG Center for ALS and NEALS consortium involvement suggests high-quality trial execution. Though still very early-stage, this approach represents a mechanistically distinct addition to treatment options for this devastating neurodegenerative disease.
- Amylyx expects early cohort data from LUMINA this year
- AMX0114 is an Amylyx-developed antisense oligonucleotide designed to target calpain-2, a key contributor to the axonal degeneration pathway in ALS
The LUMINA trial (NCT06665165) will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMX0114 in people living with ALS. LUMINA will also assess broadly researched ALS biomarkers, including change from baseline in neurofilament light chain (NfL) levels. LUMINA is anticipated to enroll approximately 48 people living with ALS across
“AMX0114 targets calpain-2, which has been found to be an important contributor to axonal degeneration and studied over decades of research as a potential target for the treatment of ALS and other neurodegenerative diseases. In preclinical studies, AMX0114 showed improved neuronal survival and reductions in extracellular NfL levels across multiple disease models. We are excited to progress AMX0114 into the clinic for people with ALS as we work to advance a potential therapy for this relentlessly progressive, fatal disease,” said Camille L. Bedrosian, MD, Chief Medical Officer at Amylyx.
Amylyx designed AMX0114 to target calpain-2, a calcium-activated protease. Peer-reviewed research has demonstrated that overactive calpain-2 activity may be an important driver of disease progression in ALS and other neurodegenerative diseases by executing the degeneration of axons, the long tubular neuronal segments which carry signals from neurons to the muscle or other neurons. Preclinical studies in ALS models suggest that the inhibition of calpain-2 may improve neuron survival and mitigate axonal degeneration.
“ALS is a devastating and fatal neurodegenerative disease with limited treatment options, underscoring the urgent need for new therapeutic approaches that target the underlying mechanisms driving ALS progression. AMX0114 represents a potential therapeutic approach to inhibiting one of the fundamental drivers of axonal degeneration,” said Sabrina Paganoni, MD, PhD, principal investigator of the LUMINA trial, investigator at the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital, and member of the Scientific Advisory Board of the Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS). “Dosing the first participant in LUMINA is a step toward a potential treatment option for people living with ALS and their loved ones.”
More information about the LUMINA clinical trial can be found at www.clinicaltrials.gov, NCT06665165.
About AMX0114
AMX0114 is an investigational antisense oligonucleotide (ASO) targeting calpain-2 (CAPN2) for the potential treatment of ALS. In preclinical studies, treatment with AMX0114 resulted in potent, dose-dependent, and durable reduction in CAPN2 mRNA and calpain-2 protein levels in disease-relevant cell models of axonal degeneration. This translated to improved neuronal survival, including in a model of TDP-43 ALS, and reductions in extracellular neurofilament light (NfL) levels across multiple disease models and paradigms of neuronal injury. AMX0114 was well-tolerated in in vivo preclinical safety studies.
About LUMINA
The Phase 1 LUMINA clinical trial (NCT06665165) is a multinational, randomized, double-blind, placebo-controlled, multiple ascending dose trial evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMX0114 in people living with ALS. LUMINA is anticipated to enroll approximately 48 adult participants. LUMINA will also assess change from baseline in calpain-2 levels, neurofilament light (NfL) levels, and other pharmacodynamic biomarkers of ALS.
About ALS
Amyotrophic lateral sclerosis (ALS, also known as motor neuron disease) is a relentlessly progressive and fatal neurodegenerative disorder caused by motor neuron death in the brain and spinal cord. Motor neuron loss in ALS leads to deteriorating muscle function, the inability to move and speak, respiratory paralysis, and eventually, death. More than
About Amylyx Pharmaceuticals
At Amylyx, our mission is to usher in a new era of treating diseases with high unmet needs. Where others see challenges, we see opportunities that we pursue with urgency, rigorous science, and unwavering commitment to the communities we serve. We are currently focused on three investigational therapies across several neurodegenerative and endocrine diseases in which we believe they can make the greatest impact. For more information, visit amylyx.com and follow us on LinkedIn and X. For investors, please visit investors.amylyx.com.
Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, Amylyx’ expectations regarding: the potential for AMX0114 as a treatment for ALS and the expected timeline for data readout. Any forward-looking statements in this press release and related comments in the Company's earnings conference call are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: the success, cost, and timing of Amylyx’ program development activities; Amylyx’ ability to execute on its regulatory development plans and expectations regarding the timing of results from its planned data announcements and initiation of clinical studies; the risk that early-stage results may not reflect later-stage results; Amylyx’ ability to fund operations, and the impact that global macroeconomic uncertainty, geopolitical instability, and public health events will have on Amylyx’ operations, as well as the risks and uncertainties set forth in Amylyx’ United States Securities and Exchange Commission (SEC) filings, including Amylyx’ Annual Report on Form 10-K for the year ended December 31, 2024, and subsequent filings with the SEC. All forward-looking statements contained in this press release and related comments in our earnings conference call speak only as of the date on which they were made. Amylyx undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.
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Source: Amylyx Pharmaceuticals, Inc.
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