A Phase 1, Safety, Tolerability, Single-ascending Dose, Multiple-ascending Dose, Food Effect, and Pharmacokinetic Study of TML-6 in Healthy Volunteers

The purpose of this study is to evaluate the safety, tolerability, single-ascending dose (SAD), multiple-ascending dose (MAD), food effect, and pharmacokinetic (PK) Study of TML-6.

Start Date11 Jul 2024

Sponsor / Collaborator

Merry Life Biomedical Co Ltd.

100 Clinical Results associated with Merry Life Biomedical Co Ltd.

0 Patents (Medical) associated with Merry Life Biomedical Co Ltd.

Literatures (Medical) associated with Merry Life Biomedical Co Ltd.

01 Dec 2024·Alzheimer's & Dementia

Design of A Phase 1 Trial for Safety, Tolerability, Single‐ascending Dose, Multiple‐ascending Dose, Food Effect, and Pharmacokinetic Study of TML‐6, A Novel Oral Multi‐Target Drug, in Healthy Volunteers

Author: Lin, Chien Hong ; Wang, Hui‐Chen ; Yu Hsu, Chia‐ ; Chen, Shang Hung ; Su, Ih‐Jen

AbstractBackgroundAlzheimer’s disease (AD) is complex in pathogenesis and related to aging biology, especially in late‐onset AD. We identified a novel synthetic curcumin analog TML‐6 through the platform of 6 biomarkers of anti‐aging, anti‐inflammation, and anti‐Aβ as the potential AD drug candidate. TML‐6 exhibits multi‐target effects on AD pathogenesis, including the activation of NrF‐2, the regulation of autophagic machinery through mTOR, the inhibition of APP synthesis and reduction of Aβ, the upregulation of ApoE, and the inhibition of microglial activation. In the past years, we conducted series of preclinical studies on TML‐6 which showed satisfactory bioavailability and sufficient safety. US pre‐IND consultation has been completed, and IND/ phase I trial is expected to be approved on February, 2024.MethodPhase 1 trial was designed into 5 parts containing 8 cohorts on 72 healthy subjects, including single ascending doses and multiple ascending doses. The food effect, the elderly subjects, the plasma pK analysis, and the CSF pK analysis were studied.ResultThe final phase I trial protocol was shown in the flow chart. The phase 1 trial will be conducted by CRO in Glendale Adventist Medical Center, LA, USA. According to pre‐clinical data, we anticipate good tolerability and safety of phase 1 trial through TML‐6 oral administration in healthy adults. The pK data will be analyzed for the design of dosing regimens in phase 2.ConclusionTML‐6 exhibits a multi‐target action mechanism meeting the new era strategy to develop AD drug. The combined data of phase 1 trial and 9‐month chronic toxicology in dogs will be applied to US FDA for global phase 2a trial, with integration of blood biomarkers. We look forward to the success of TML‐6 in clinical trials that will provide an ideal therapy, with potential of combining with anti‐amyloid drug, for Alzheimer’s disease.Key Words: TML‐6; curcumin analogue; Alzheimer’s disease; amyloid‐beta; aging biology

01 Dec 2023·Alzheimer's & Dementia

TML‐6 is a novel anti‐aging and Aβ‐lowering drug candidate with potential for anti‐Aβ antibody drug combination therapy

Author: Lin, Tzu‐Han ; Shie, Feng‐Shiun ; Hou, Ting‐Yi ; Wang, Hui‐Chen ; Yu Hsu, Chia‐ ; Su, Ih‐Jen ; Hsueh, Jung‐Tsung ; Wu, Chiu‐Chu

AbstractBackgroundThese suggest that TML‐6’s ability to enter the brain parenchyma and possibly interact with and reduce Aβ, while possessing anti‐aging and anti‐inflammatory properties contributes to its effects on alleviating AD‐like pathology and behavioral deficit in APP/PS1 mice. Importantly, TML‐6 is safe and has promising drug bioavailability and exposure in pre‐clinical development. Taken together, TML‐6 exhibits promising druggability and meets the current strategy to develop as a first‐in‐class oral therapeutic drug for AD.MethodTML‐6 was applied to investigate the binding with Aβ peptide (1‐40 or 1‐42), hERG, and safety panel screening assay in vitro. Further, the effects of TML‐6 treatment on reducing AD‐like pathology, TML‐6 concentration in plasma‐to‐brain ratio, and inflammaging biomarkers in APP/PS1 mice were evaluated. Lastly, pharmacokinetic and toxicology studies in rats and dogs were performed.ResultData from pre‐clinical development showed that TML‐6 bound Aβ1‐40 and Aβ1‐42 in vitro and improved behavioral deficits with reduced inflammaging in AD model mice (e.g., TNF‐α, IL‐1β, & IL‐6). The TML‐6 levels in the plasm and brain tended to dose‐dependently increase in AD mice, which inversely correlated with behavioral deficits and AD‐like pathologies. TML‐6 was well tolerated in toxicology in rats and dogs and had no off‐target safety pharmacology issue by hERG & safety panel screening. Most importantly, formulation optimization of TML‐6 exerted satisfactory drug bioavailability and exposure.ConclusionThese suggest that TML‐6’s ability to enter the brain parenchyma and possibly interact with and reduce Aβ, while possessing anti‐aging and anti‐inflammatory properties contributes to its effects on alleviating AD‐like pathology and behavioral deficit in APP/PS1 mice. Importantly, TML‐6 is safe and has promising drug bioavailability and exposure in pre‐clinical development. Taken together, TML‐6 exhibits promising druggability and meets the current strategy to develop as a first‐in‐class oral therapeutic drug for AD.

International Journal of Molecular SciencesQ2 · BIOLOGY

The Beneficial Effects of Combining Anti-Aβ Antibody NP106 and Curcumin Analog TML-6 on the Treatment of Alzheimer’s Disease in APP/PS1 Mice

Q2 · BIOLOGY

ArticleOA

Author: Liang, Jia-Jun ; Hsu, Ying-Ting ; Su, Ih-Jen ; Shie, Feng-Shiun ; Hsu, Chia-Yu ; Hsu, John Tsu-An ; Shen, Santai ; Hsueh, Jung-Tsung ; Chao, Po-Kuan

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a multifactorial etiology. A multitarget treatment that modulates multifaceted biological functions might be more effective than a single-target approach. Here, the therapeutic efficacy of combination treatment using anti-Aβ antibody NP106 and curcumin analog TML-6 versus monotherapy was investigated in an APP/PS1 mouse model of AD. Our data demonstrate that both combination treatment and monotherapy attenuated brain Aβ and improved the nesting behavioral deficit to varying degrees. Importantly, the combination treatment group had the lowest Aβ levels, and insoluble forms of Aβ were reduced most effectively. The nesting performance of APP/PS1 mice receiving combination treatment was better than that of other APP/PS1 groups. Further findings indicate that enhanced microglial Aβ phagocytosis and lower levels of proinflammatory cytokines were concurrent with the aforementioned effects of NP106 in combination with TML-6. Intriguingly, combination treatment also normalized the gut microbiota of APP/PS1 mice to levels resembling the wild-type control. Taken together, combination treatment outperformed NP106 or TML-6 monotherapy in ameliorating Aβ pathology and the nesting behavioral deficit in APP/PS1 mice. The superior effect might result from a more potent modulation of microglial function, cerebral inflammation, and the gut microbiota. This innovative treatment paradigm confers a new avenue to develop more efficacious AD treatments.

News (Medical) associated with Merry Life Biomedical Co Ltd.

07 Jun 2024

·www.prnewswire.com

MLB Announces IND Approval by US FDA to Initiate Phase 1 Trial of TML-6, a New Era Multi-Target Drug for the Treatment of Alzheimer's Disease

TAINAN, June 7, 2024 /PRNewswire/ -- MLB (Merry Life Biomedical Company, Ltd., Taiwan: ), a biomedical company, announced that the U.S. Food and Drug Administration (FDA) has approved IND application for TML-6, an novel drug to treat Alzheimer's disease (AD), enabling a Phase 1 clinical trial to be initiated this July. Advancing TML-6 into clinical trial is a critical milestone for MLB to develop a new era multi-target drug for AD since 2018. About TML-6 Continue Reading TML-6 is a novel synthetic curcumin analog. Professor Ih-Jen Su at Southern Taiwan University used a platform of 6 aging and AD biomarkers to screen the 12 compounds from Androscience (San Diego, USA) for AD candidate. Preclinical studies showed that TML-6 (ASC-6) exhibits a multi-target action mechanism for AD, including anti-aging, activation of autophagy (mTOR inhibitor), reducing amyloid accumulation, and anti-inflammation (Figure 1), the efficacy confirmed by 2 AD animal models. TML-6 has a high bioavailability through formulation and then completed preclinical toxicology and safety studies. TML-6 should be potentially a novel drug to improve or reverse the progression of early-stage AD. The Design and Future Plan of TML-6 for AD Clinical Trial s TML-6 is developed as an oral drug and will conduct a SAD/MAD phase 1 clinical trial at Glendale Adventist Medical Center, LA, USA in 2024 Q3. Elderly cohort and CSF pharmacokinetics (PK) studies were specifically designed. For a global multi-site phase 2a clinical trial, several distinguished global AD experts provided consultation. Blood biomarkers will be included in the phase 2a trial as the surrogate endpoint of efficacy. Furthermore, TML-6 is considering to combine with the current anti-amyloid drugs in phase 2 trial. The drug combination could not only exhibit synergistic effects to improve AD behavior, reducing amyloid accumulation and ant-inflammation, but can also reduce antibody dosing to only 10% and avoid the adverse events (ARIAs) of anti-body drugs. MLB has successfully raised funds to conduct this global phase 2a clinical trial, scheduled to be conducted on 2025 Q3. Contact: Chien Hong Lin, PhD Email: [email protected] SOURCE Merry Life Biomedical Company, Ltd.

Phase 2INDPhase 1

100 Deals associated with Merry Life Biomedical Co Ltd.

100 Translational Medicine associated with Merry Life Biomedical Co Ltd.

Corporation Tree

Boost your research with our corporation tree data.

view full example data

Pipeline

Pipeline Snapshot as of 05 Feb 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Phase 1 Clinical

Other

Current Projects

Drug(Targets)	Indications	Global Highest Phase

TML-6 ( APOE x APP x NF-κB x mTOR )	Alzheimer Disease More	Phase 1
NP-106 ( APP )	Alzheimer Disease More	Pending

Deal

Boost your decision using our deal data.

view full example data

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Profit

Explore the financial positions of over 360K organizations with Synapse.

view full example data

Grant & Funding(NIH)

Access more than 2 million grant and funding information to elevate your research journey.

view full example data

Investment

Gain insights on the latest company investments from start-ups to established corporations.

view full example data

Financing

Unearth financing trends to validate and advance investment opportunities.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis