Alumis Announces Positive Phase 1 Data for CNS Penetrant TYK2 Inhibitor, A-005
Alumis (NASDAQ: ALMS) announced positive Phase 1 clinical trial results for A-005, their CNS penetrant TYK2 inhibitor. The trial demonstrated that A-005 successfully crosses the blood-brain barrier and achieves maximal TYK2 inhibition with favorable pharmacokinetics in both CNS and peripheral systems.
Key findings include: no serious adverse events reported, significant and prolonged exposure in cerebral spinal fluid, dose-proportional drug exposure, peak drug concentration with half-lives up to 12 hours, and established PK/PD relationship showing sustained TYK2 inhibition. The company plans to advance to Phase 2 clinical trials for multiple sclerosis in the second half of 2025.
Alumis (NASDAQ: ALMS) ha annunciato risultati positivi della fase 1 della sperimentazione clinica per A-005, il loro inibitore TYK2 penetrante nel sistema nervoso centrale. La sperimentazione ha dimostrato che A-005 riesce a attraversare con successo la barriera emato-encefalica e raggiunge un'inibizione massimale di TYK2 con una farmacocinetica favorevole sia nel sistema nervoso centrale che in quello periferico.
I risultati chiave includono: nessun evento avverso grave segnalato, esposizione significativa e prolungata nel liquor cerebrospinale, esposizione al farmaco proporzionale alla dose, concentrazione massima del farmaco con emivite fino a 12 ore, e una relazione PK/PD stabilita che mostra un'inibizione sostenuta di TYK2. L'azienda prevede di passare alla fase 2 della sperimentazione clinica per la sclerosi multipla nella seconda metà del 2025.
Alumis (NASDAQ: ALMS) anunció resultados positivos del ensayo clínico de fase 1 para A-005, su inhibidor de TYK2 que penetra en el sistema nervioso central. El ensayo demostró que A-005 cruza con éxito la barrera hematoencefálica y logra una inhibición máxima de TYK2 con una farmacocinética favorable tanto en el sistema nervioso central como en los sistemas periféricos.
Los hallazgos clave incluyen: sin eventos adversos graves reportados, exposición significativa y prolongada en el líquido cefalorraquídeo, exposición al fármaco proporcional a la dosis, concentración máxima del fármaco con semividas de hasta 12 horas, y una relación PK/PD establecida que muestra una inhibición sostenida de TYK2. La compañía planea avanzar a ensayos clínicos de fase 2 para la esclerosis múltiple en la segunda mitad de 2025.
알루미스 (NASDAQ: ALMS)는 CNS 침투 TYK2 억제제인 A-005에 대한 1상 임상 시험의 긍정적인 결과를 발표했습니다. 시험 결과 A-005가 혈액-뇌 장벽을 성공적으로 통과하고 CNS와 말초 시스템 모두에서 유리한 약리학적 작용을 하면서 최대 TYK2 억제를 달성함을 보여주었습니다.
주요 발견 사항으로는: 심각한 부작용이 보고되지 않았고, 뇌척수액에서 유의미하고 지속적인 노출, 용량 비례 약물 노출, 최대 약물 농도와 최대 12시간의 반감기, 지속적인 TYK2 억제를 보여주는 PK/PD 관계가 설정되었습니다. 이 회사는 2025년 하반기에 다발성 경화증에 대한 2상 임상 시험으로 나아갈 계획입니다.
Alumis (NASDAQ: ALMS) a annoncé des résultats positifs des essais cliniques de phase 1 pour A-005, leur inhibiteur TYK2 pénétrant le SNC. L'essai a démontré qu'A-005 traverse avec succès la barrière hémato-encéphalique et atteint une inhibition maximale de TYK2 avec une pharmacocinétique favorable dans les systèmes SNC et périphériques.
Les résultats clés incluent : aucun événement indésirable grave signalé, exposition significative et prolongée dans le liquide céphalorachidien, exposition médicamenteuse proportionnelle à la dose, concentration maximale du médicament avec des demi-vies allant jusqu'à 12 heures, et une relation PK/PD établie montrant une inhibition soutenue de TYK2. L'entreprise prévoit de passer aux essais cliniques de phase 2 pour la sclérose en plaques dans la deuxième moitié de 2025.
Alumis (NASDAQ: ALMS) hat positive Ergebnisse der Phase-1-Studie für A-005, ihren TYK2-Hemmer mit ZNS-Penetration, bekannt gegeben. Die Studie zeigte, dass A-005 erfolgreich die Blut-Hirn-Schranke überwindet und eine maximale TYK2-Hemmung mit günstiger Pharmakokinetik sowohl im ZNS als auch in den peripheren Systemen erreicht.
Zu den wichtigsten Ergebnissen gehören: keine schweren unerwünschten Ereignisse berichtet, signifikante und verlängerte Exposition in der Rückenmarksflüssigkeit, dosisproportionale Arzneimittel-Exposition, maximale Arzneimittelkonzentration mit Halbwertszeiten von bis zu 12 Stunden und eine etablierte PK/PD-Beziehung, die eine anhaltende TYK2-Hemmung zeigt. Das Unternehmen plant, in der zweiten Hälfte des Jahres 2025 in die Phase-2-Studien für Multiple Sklerose überzugehen.
- Successfully demonstrated blood-brain barrier penetration
- No serious adverse events reported in Phase 1 trial
- Achieved maximal TYK2 inhibition with favorable pharmacokinetics
- Drug levels in CSF comparable to or exceeded plasma levels
- Clear pathway to Phase 2 trials in multiple sclerosis
- Phase 2 trials not starting until 2H 2025, indicating extended timeline to market
- Clinical efficacy in multiple sclerosis patients yet to be demonstrated
Insights
The Phase 1 data for A-005 represents a significant breakthrough in TYK2 inhibitor development. The drug's ability to cross the blood-brain barrier while maintaining potent TYK2 inhibition is particularly noteworthy, as this has been a major challenge in developing CNS treatments. The pharmacokinetic profile showing drug levels in CSF comparable to or exceeding plasma levels suggests optimal CNS penetration.
The 12-hour half-life and dose-proportional exposure indicate favorable drug properties that could support once-daily dosing. Maximal TYK2 inhibition in the periphery, confirmed through STAT protein phosphorylation, demonstrates strong target engagement. The clean safety profile with no serious adverse events is encouraging for future development.
Simple explanation: Think of the blood-brain barrier as a strict security checkpoint. Most drugs can't get through this checkpoint to reach the brain. A-005 has shown it can pass this checkpoint effectively, potentially making it a powerful tool against brain inflammation in multiple sclerosis.
The Phase 1 results establish critical benchmarks for A-005's development pathway. The demonstration of maximal TYK2 inhibition parallels the successful strategy seen with ESK-001 in psoriasis, suggesting a potentially predictive correlation between target engagement and clinical efficacy. The planned progression to Phase 2 in 2H 2025 is well-timed, allowing for thorough data analysis and trial design optimization.
The IC90 achievement in CSF is particularly important as it indicates the drug reaches therapeutic concentrations in the target tissue. This data package provides strong justification for advancing to Phase 2 in MS patients.
Simple explanation: Imagine testing a key in a lock before making copies. This Phase 1 trial shows the "key" (A-005) fits perfectly in its "lock" (TYK2) and reaches the right places in the brain, giving confidence to test it in patients with MS.
– A-005 was well tolerated and demonstrated ability to cross blood-brain barrier –
– Maximal TYK2 inhibition achieved with favorable pharmacokinetic profile in CNS and periphery –
– Data support advancement to Phase 2 clinical trial in multiple sclerosis, anticipated in 2H 2025 –
SOUTH SAN FRANCISCO, Calif., Dec. 19, 2024 (GLOBE NEWSWIRE) -- Alumis Inc. (Nasdaq: ALMS), a clinical stage biopharmaceutical company developing oral therapies using a precision approach to optimize clinical outcomes and significantly improve the lives of patients with immune-mediated diseases, today announced positive data from a Phase 1 clinical trial evaluating the safety, tolerability, and pharmacokinetics (PK) of single- and multiple-ascending doses of A-005, a potent, selective, central nervous system (CNS) penetrant TYK2 inhibitor, in healthy participants.
“A-005 is the first reported allosteric TYK2 inhibitor that has demonstrated the ability to cross the human blood-brain barrier to address inflammation within the central nervous system (CNS). Based on these data, we expect to begin a Phase 2 clinical trial in patients with multiple sclerosis (MS) in the second half of 2025,” said Jörn Drappa, M.D., Alumis’ Chief Medical Officer. “Our Phase 2 clinical trial of ESK-001 in psoriasis demonstrated that maximal TYK2 inhibition was critical for increased clinical responses. Similarly, we hope to demonstrate that potent and selective target engagement of A-005 in the CNS leads to clinical benefit in MS, our first indication, and potentially in other neuroinflammatory and neurodegenerative conditions in the future.”
In the clinical trial, A-005 was well tolerated with no serious adverse events reported. A-005 demonstrated the ability to penetrate into the CNS with significant and prolonged exposure in the cerebral spinal fluid (CSF). A-005 levels in the CSF were comparable to or exceeded the free drug exposure in plasma and exceeded IC90 levels in cell-based assays. In the single-ascending dose cohorts, drug exposures generally increased in a dose proportional manner, rapidly reaching peak drug concentration (Tmax) and half-lives of up to 12 hours. A PK/PD relationship was established showing prolonged and maximal TYK2 inhibition in the periphery, as assessed by levels of phosphorylated STAT proteins.
Alumis plans to present data from the Phase 1 clinical trial at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2025 taking place February 27- March 1, 2025, in West Palm Beach, Florida.
About the Phase 1 Clinical Trial
The Phase 1 clinical trial evaluated the safety, tolerability, and pharmacokinetics (PK) of single- and multiple-ascending doses of A-005 in 135 healthy participants. The trial included a single-ascending dose (SAD) portion which evaluated ten dose cohorts, a 14-day multiple-ascending (MAD) dose portion which evaluated five dose cohorts (n=8, 6 active, 2 placebo) and a single dose cohort which included a lumbar puncture to assess A-005 concentrations in the CSF. For the SAD and MAD portions of the study, pharmacodynamic (PD) markers (including pSTAT levels) were measured to establish a PK/PD relationship.
About A-005
A-005 is a potential first-in-class CNS penetrant allosteric tyrosine kinase 2 (TYK2) inhibitor being developed for the treatment of neuroinflammatory and neurodegenerative diseases such as multiple sclerosis and Parkinson’s Disease. A-005 is designed to achieve maximal TYK2 inhibition and to cross the blood brain barrier for localized treatment both within the CNS and in the periphery, supporting its potential across multiple TYK2-mediated indications. TYK2 is a protein that plays a role in mediating signaling responses to key proinflammatory cytokines, including interleukin (IL)-23, IL-12 and interferon-alpha (IFNα). TYK2 inhibition has been clinically validated in autoimmune conditions, and Alumis’ data analytics support a genetic rationale for TYK2 inhibition as a novel approach in diseases of the central nervous system.
About Alumis
Alumis is a clinical-stage biopharmaceutical company developing oral therapies using a precision approach to optimize clinical outcomes and significantly improve the lives of patients with immune-mediated diseases. Leveraging its proprietary precision data analytics platform, Alumis is building a pipeline of molecules with the potential to address a broad range of immune-mediated diseases as monotherapy or combination therapies. Alumis’ most advanced product candidate, ESK-001, is an oral, highly selective, small molecule, allosteric inhibitor of tyrosine kinase 2 that is currently being evaluated for the treatment of patients with moderate-to-severe plaque psoriasis and systemic lupus erythematosus. Alumis is also developing A-005, a CNS-penetrant, allosteric TYK2 inhibitor for the treatment of neuroinflammatory and neurodegenerative diseases, with multiple sclerosis (MS) as its initial indication. With two clinical-stage TYK2 inhibitors that have the ability to achieve maximal target inhibition, Alumis’ TYK2 franchise enables the company to pursue the broad range of immune-mediated diseases identified by TYK2 genetics in a strategically thoughtful way. Beyond TYK2, Alumis’ proprietary precision data analytics platform and drug discovery expertise have led to the identification of additional preclinical programs that exemplify its precision approach. Incubated by Foresite Labs and led by a team of industry veterans experienced in small-molecule compound drug development for immune-mediated diseases, Alumis is pioneering a precision approach to drug development to potentially produce the next generation of treatment to address immune dysfunction. For more information, visit https://www.alumis.com.
Forward-Looking Statements
This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as "aims," "anticipates," "believes," "could," "estimates," "expects," "forecasts," "goal," "intends," "may," "plans," "possible," "potential," "seeks," "will" and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. These forward-looking statements include, without limitation, statements regarding Alumis’ future plans and prospects, the cost and timing of its product candidate development activities and current and future clinical trials and studies, including its strategy in pursuing immune-mediated diseases, trial design and commencement, any expectations regarding the safety, efficacy, or tolerability of A-005, and the ability of A-005 to treat MS and other neuroinflammatory and neurodegenerative diseases, and Alumis’ participation at upcoming conferences. Any forward-looking statements in this press release are based on Alumis’ current expectations, estimates and projections only as of the date of this release 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. Readers are cautioned that actual results, levels of activity, safety, efficacy, performance or events and circumstances could differ materially from those expressed or implied in Alumis’ forward-looking statements due to a variety of risks and uncertainties, which include, without limitation, risks and uncertainties related to Alumis’ ability to advance ESK-001 and A-005 and to obtain regulatory approval of and ultimately commercialize Alumis’ clinical candidates, the timing and results of preclinical and clinical trials, Alumis’ ability to fund development activities and achieve development goals, Alumis’ ability to protect its intellectual property and other risks and uncertainties described in Alumis’ filings with the Securities and Exchange Commission (SEC), including any future reports Alumis may file with the SEC from time to time. Alumis explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.
FAQ
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