Long-term Extension of a Phase 3, Multicenter, Randomized, Double-Blind, Placebo- Controlled Study of the Efficacy, Safety, and Biomarker Effects of ALZ-801 in Subjects With Early Alzheimer's Disease and APOE4/4 Genotype

This study is being conducted to evaluate the long-term safety and efficacy of ALZ-801 in Early Alzheimer's disease (AD) subjects with the APOE4/4 genotype. This is an open-label trial of treatment with ALZ-801.

Start Date02 Apr 2024

Sponsor / Collaborator

Alzheon, Inc.

NCT04770220

/ CompletedPhase 3

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Efficacy, Safety and Biomarker Effects of ALZ-801 in Subjects With Early Alzheimer's Disease and APOE4/4 Genotype

This study is being conducted to evaluate the safety and efficacy of ALZ-801 in Early Alzheimer's disease (AD) subjects with the APOE4/4 genotype. This is a double-blind, randomized trial with one dose of ALZ-801 compared to placebo.

Start Date19 May 2021

Sponsor / Collaborator

Alzheon, Inc.

[+1]

NCT04693520

/ Active, not recruitingPhase 2

A Phase 2, Single-arm Study of the Biomarker Effects of ALZ-801 in Subjects With Early Alzheimer's Disease Who Are Carriers of the ε4 Variant of the Apolipoprotein E Gene (APOE4/4 or APOE3/4)

The study will investigate the effects of oral ALZ-801, in subjects with Early AD who have the APOE4/4 or APOE3/4 genotype, on the biomarkers of core AD pathology. The objectives of this study include determining the efficacy and safety/tolerability of ALZ-801. In addition, the study will evaluate the extended PK profile over 8 hours in 16 subjects after 65 weeks of treatment.

Start Date30 Sep 2020

Sponsor / Collaborator

Alzheon, Inc.

100 Clinical Results associated with Valiltramiprosate

100 Translational Medicine associated with Valiltramiprosate

100 Patents (Medical) associated with Valiltramiprosate

Literatures (Medical) associated with Valiltramiprosate

01 Jul 2024·Alzheimers & Dementia-Translational Research & Clinical Interventions

APOLLOE4 Phase 3 study of oral ALZ‐801/valiltramiprosate in APOE ε4/ε4 homozygotes with early Alzheimer's disease: Trial design and baseline characteristics

Article

Author: Abushakra, Susan ; Porsteinsson, Anton P. ; Tolar, Martin ; Watson, David ; Liang, Earvin ; Sabbagh, Marwan ; McLaine, Rosalind ; Power, Aidan ; Kesslak, J. Patrick ; Boada, Merce ; Hey, John A. ; MacSweeney, Emer ; Flint, Susan

Abstract:

INTRODUCTION:

The approved amyloid antibodies for early Alzheimer's disease (AD) carry a boxed warning about the risk of amyloid‐related imaging abnormalities (ARIAs) that are highest in apolipoprotein E (APOE) ε4/ε4 homozygotes. ALZ‐801/valiltramiprosate, an oral brain‐penetrant amyloid beta oligomer inhibitor is being evaluated in APOE ε4/ε4 homozygotes with early AD.

METHODS:

This Phase 3 randomized, double‐blind, placebo‐controlled, 78‐week study of ALZ‐801 administered as 265 mg twice per day tablets, enrolled 50‐ to 80‐year‐old homozygotes with Mini‐Mental State Examination (MMSE) ≥ 22 and Clinical Dementia Rating–Global Score 0.5 or 1.0. The study is powered to detect a 2.0 to 2.5 drug–placebo difference on the Alzheimer's Disease Assessment Scale 13‐item Cognitive subscale primary outcome with 150 subjects/arm. The key secondary outcomes are Clinical Dementia Rating–Sum of Boxes and Instrumental Activities of Daily Living; volumetric magnetic resonance imaging and fluid biomarkers are additional outcomes.

RESULTS:

The APOLLOE4 Phase 3 trial enrolled 325 subjects with a mean age of 69 years, 51% female, MMSE 25.6, and 65% mild cognitive impairment. Topline results are expected in 2024.

DISCUSSION:

APOLLOE4 is the first disease‐modification AD trial focused on APOE ε4/ε4 homozygotes. Oral ALZ‐801 has the potential to be the first effective and safe anti‐amyloid treatment for the high‐risk APOE ε4/ε4 population.

Highlights:

The APOLLOE4 Phase 3, placebo‐controlled, 78‐week study is designed to evaluate the efficacy and safety of ALZ‐801 265 mg twice per day in early Alzheimer's disease (AD) subjects with the apolipoprotein E (APOE) ε4/ε4 genotype.The enrolled early AD population (N = 325) has 51% females, a mean age = 69 years, and a mean Mini‐Mental State Examination = 25.6, with the majority being mild cognitive impairment subjects, a similar disease stage to the lecanemab Phase 3 AD trial (Clarity AD).The primary outcome is the cognitive Alzheimer's Disease Assessment Scale 13‐item Cognitive subscale, with two functional measures as key secondary outcomes (Clinical Dementia Rating–Sum of Boxes, Amsterdam‐Instrumental Activities of Daily Living), and with hippocampal volume and fluid biomarkers as additional outcomes.The study is unique in allowing a large number of microhemorrhages or siderosis at baseline magnetic resonance imaging, lesions that indicate concomitant cerebral amyloid angiopathy (CAA).At baseline, 32% of the enrolled population had at least 1 microhemorrhage, 24% had 1 to 4, and 8% had > 4 microhemorrhages; 10% had at least 1 siderosis lesion; with more males than females having microhemorrhages (63% vs. 37%) and siderosis (68% vs. 32%).Study results will become available in the second half of 2024 and, if positive, ALZ‐801 may become the first oral drug to demonstrate a favorable benefit/risk profile in APOE ε4/ε4 AD subjects.

01 Jul 2024·DRUGS

Analysis of Cerebrospinal Fluid, Plasma β-Amyloid Biomarkers, and Cognition from a 2-Year Phase 2 Trial Evaluating Oral ALZ-801/Valiltramiprosate in APOE4 Carriers with Early Alzheimer’s Disease Using Quantitative Systems Pharmacology Model

Article

Author: Schaefer, Jean F ; Power, Aidan ; Abushakra, Susan ; Kesslak, Patrick ; Hey, John A ; Tolar, Martin ; Yu, Jeremy Y

INTRODUCTION:

ALZ-801/valiltramiprosate is an oral, small-molecule inhibitor of beta-amyloid (Aβ) aggregation and oligomer formation in late-stage development as a disease-modifying therapy for early Alzheimer's disease (AD). The present investigation provides a quantitative systems pharmacology (QSP) analysis of amyloid fluid biomarkers and cognitive results from a 2-year ALZ-801 Phase 2 trial in APOE4 carriers with early AD.

METHODS:

The single-arm, open-label phase 2 study evaluated effects of ALZ-801 265 mg two times daily (BID) on cerebrospinal fluid (CSF) and plasma amyloid fluid biomarkers over 104 weeks in APOE4 carriers with early AD [Mini-Mental State Examination (MMSE) ≥ 22]. Subjects with positive CSF biomarkers for amyloid (Aβ₄₂/Aβ₄₀) and tau pathology (p-tau₁₈₁) were enrolled, with serial CSF and plasma levels of Aβ₄₂ and Aβ₄₀ measured over 104 weeks. Longitudinal changes of CSF Aβ₄₂, plasma Aβ₄₂/Aβ₄₀ ratio, and cognitive Rey Auditory Verbal Learning Test (RAVLT) were compared with the established natural disease trajectories in AD using a QSP approach. The natural disease trajectory data for amyloid biomarkers and RAVLT were extracted from a QSP model and an Alzheimer's disease neuroimaging initiative population model, respectively. Analyses were stratified by disease severity and sex.

RESULTS:

A total of 84 subjects were enrolled. Excluding one subject who withdrew at the early stage of the trial, data from 83 subjects were used for this analysis. The ALZ-801 treatment arrested the progressive decline in CSF Aβ₄₂ level and plasma Aβ₄₂/Aβ₄₀ ratio, and stabilized RAVLT over 104 weeks. Both sexes showed comparable responses to ALZ-801, whereas mild cognitive impairment (MCI) subjects (MMSE ≥ 27) exhibited a larger biomarker response compared with more advanced mild AD subjects (MMSE 22-26).

CONCLUSIONS:

In this genetically defined and biomarker-enriched early AD population, the QSP analysis demonstrated a positive therapeutic effect of oral ALZ-801 265 mg BID by arresting the natural decline of monomeric CSF and plasma amyloid biomarkers, consistent with the target engagement to prevent their aggregation into soluble neurotoxic oligomers and subsequently into insoluble fibrils and plaques over 104 weeks. Accompanying the amyloid biomarker changes, ALZ-801 also stabilized the natural trajectory decline of the RAVLT memory test, suggesting that the clinical benefits are consistent with its mechanism of action. This sequential effect arresting the disease progression on biomarkers and cognitive decline was more pronounced in the earlier symptomatic stages of AD. The QSP analysis provides fluid biomarker and clinical evidence for ALZ-801 as a first-in-class, oral small-molecule anti-Aβ oligomer agent with disease modification potential in AD.

TRIAL REGISTRY:

https://clinicaltrials.gov/study/NCT04693520.

01 Jul 2024·DRUGS

Effects of Oral ALZ-801/Valiltramiprosate on Plasma Biomarkers, Brain Hippocampal Volume, and Cognition: Results of 2-Year Single-Arm, Open-Label, Phase 2 Trial in APOE4 Carriers with Early Alzheimer’s Disease

Article

Author: Abushakra, Susan ; Hey, John A ; Kesslak, Patrick ; Power, Aidan ; Tolar, Martin ; Hort, Jakub ; Albayrak, Adem ; Paul, Jijo ; Blennow, Kaj ; Schaefer, Jean F ; Prins, Niels D ; Reiman, Eric M ; Shen, Larry ; Zhu, Xinyi ; Sheardova, Katerina

INTRODUCTION:

ALZ-801/valiltramiprosate is a small-molecule oral inhibitor of beta amyloid (Aβ) aggregation and oligomer formation being studied in a phase 2 trial in APOE4 carriers with early Alzheimer's disease (AD) to evaluate treatment effects on fluid and imaging biomarkers and cognitive assessments.

METHODS:

The single-arm, open-label phase 2 trial was designed to evaluate the effects of the ALZ-801 265 mg tablet taken twice daily (after 2 weeks once daily) on plasma fluid AD biomarkers, hippocampal volume (HV), and cognition over 104 weeks in APOE4 carriers. The study enrolled subjects aged 50-80 years, with early AD [Mini-Mental State Examination (MMSE) ≥ 22, Clinical Dementia Rating-Global (CDR-G) 0.5 or 1], apolipoprotein E4 (APOE4) genotypes including APOE4/4 and APOE3/4 genotypes, and positive cerebrospinal fluid (CSF) AD biomarkers or prior amyloid scans. The primary outcome was plasma p-tau₁₈₁, HV evaluated by magnetic resonance imaging (MRI) was the key secondary outcome, and plasma Aβ42 and Aβ40 were the secondary biomarker outcomes. The cognitive outcomes were the Rey Auditory Verbal Learning Test and the Digit Symbol Substitution Test. Safety and tolerability evaluations included treatment-emergent adverse events and amyloid-related imaging abnormalities (ARIA). The study was designed and powered to detect 15% reduction from baseline in plasma p-tau₁₈₁ at the 104-week endpoint. A sample size of 80 subjects provided adequate power to detect this difference at a significance level of 0.05 using a two-sided paired t-test.

RESULTS:

The enrolled population of 84 subjects (31 homozygotes and 53 heterozygotes) was 52% females, mean age 69 years, MMSE 25.7 [70% mild cognitive impairment (MCI), 30% mild AD] with 55% on cholinesterase inhibitors. Plasma p-tau₁₈₁ reduction from baseline was significant (31%, p = 0.045) at 104 weeks and all prior visits; HV atrophy was significantly reduced (p = 0.0014) compared with matched external controls from an observational Early AD study. Memory scores showed minimal decline from baseline over 104 weeks and correlated significantly with decreased HV atrophy (Spearman's 0.44, p = 0.002). Common adverse events were COVID infection and mild nausea, and no drug-related serious adverse events were reported. Of 14 early terminations, 6 were due to nonserious treatment-emergent adverse events and 1 death due to COVID. There was no vasogenic brain edema observed on MRI over 104 weeks.

CONCLUSIONS:

The effect of ALZ-801 on reducing plasma p-tau₁₈₁ over 2 years demonstrates target engagement and supports its anti-Aβ oligomer action that leads to a robust decrease in amyloid-induced brain neurodegeneration. The significant correlation between reduced HV atrophy and cognitive stability over 2 years suggests a disease-modifying effect of ALZ-801 treatment in patients with early AD. Together with the favorable safety profile with no events of vasogenic brain edema, these results support further evaluation of ALZ-801 in a broader population of APOE4 carriers, who represent two-thirds of patients with AD.

TRIAL REGISTRATION:

https://clinicaltrials.gov/study/NCT04693520 .

News (Medical) associated with Valiltramiprosate

11 Apr 2025

·www.biopharmadive.com

Amgen says Imdelltra extended survival; Parker Institute adds new leaders

Today, a brief rundown of news involving Amgen and the Parker Institute, as well as updates from J&J, Alzheon and Amylyx Pharmaceuticals that you may have missed.Amgens bispecific cancer antibody Imdelltra helped people with previously treated small cell lung cancer live longer than those who received chemotherapy, the company said Friday. The conclusion was made at an interim analysis of the Phase 3 DeLLphi-304 trial, which enrolled 500 people around the world and randomized half to receive Imdelltra and half to receive standard-of-care chemotherapy. Amgen didnt disclose specific data, but said treatment with Imdelltra led to a statistically significant and clinically meaningful improvement in survival. The data, if confirmed, could help it convert Imdelltras conditional U.S. approval into a full clearance. Jonathan GardnerThe Parker Institute for Cancer Immunotherapy has appointed two well-known researchers to its leadership in recent weeks. In March, the institute announced its new CEO would be Karen Knudsen, who recently served as the CEO of the American Cancer Society and its Cancer Action Network. And on Thursday the Parker Institute appointed Ira Mellman as its president of research. A Genentech veteran, Mellman played a major role in the development of new cancer medicines such as anti-TIGIT antibodies, patient-specific neo-antigen mRNA and DNA vaccines and the immunotherapy Tecentriq, which has been on the market for years. Delilah AlvaradoJohnson & Johnsons experimental autoimmune drug icotrokinra helped 84% of adolescents with psoriasis achieve clear or nearly clear skin after 16 weeks, compared with 27% of those receiving a placebo, the company said Thursday. The data came from an analysis presented at the World Congress of Pediatric Dermatology of the ICONIC-LEAD trial, which enrolled adolescents aged 12 and older along with adults to test the oral peptide drug. Icotrokinra targets IL-23, and if approved, would offer an oral alternative to injectable drugs like AbbVies Skyrizi and J&Js own Tremfya in the skin condition. J&J is developing the drug as part of a collaboration with Protagonist Therapeutics. Jonathan GardnerAlzehons experimental Alzheimers disease drug valiltramiprosate failed to delay cognitive decline in a trial of people with genetic mutations that lead to early onset of the disease, the company said Thursday. The Phase 3 trial enrolled 325 early Alzheimers patients with two copies of the 4 allele of the apolipoprotein E gene and randomized them to take valiltramiprosate or placebo. Researchers found no difference between people given the drug versus those on placebo when examining a measure called ADAS-Cog13, nor on any of the studys secondary endpoints. Trial investigators identified a nominal benefit on ADAS-Cog13 and two other measures among participants who were categorized as having mild cognitive impairment. That difference didnt meet pre-specified statistical analysis goals, however, and would likely need to be confirmed by additional trials before regulators would review valiltramiprosate. Jonathan GardnerAmylyx Pharmaceuticals on Wednesday said it dosed the first participant in a Phase 1 trial of a new treatment for ALS. The company, which previously pulled the ALS drug Relyvrio from market and switched its R&D focus, is looking again to target the neurodegenerative condition. Known as Lumina, the trial will evaluate the tolerability, safety, pharmacokinetics, and pharmacodynamics of Amylyxs new experimental drug, an antisense oligonucleotide targeting the protease calpain-2. The trial will enroll 48 individuals with ALS in the U.S. who will be randomized 3-to-1 to receive either placebo or Amylyxs drug. Early data from the trial is expected this year. Delilah Alvarado '

Phase 3Clinical ResultExecutive ChangeOligonucleotidePhase 1

10 Apr 2025

·www.fiercebiotech.com

Alzheon Alzheimer\'s drug knocked down in pivotal APOLLOE4 bout

Alzheon saw signs of efficacy in patients with the earliest symptomatic stage of the disease. \n Sixteen years after tramiprosate flunked a phase 3 trial, Alzheon’s prodrug form of the molecule has joined the lengthy list of pivotal Alzheimer’s disease failures.The biotech picked tramiprosate off the scrap heap after identifying shortcomings with the failed phase 3 study and seeing signs of efficacy in patients with copies of the APOE4 gene. After public investors rebuffed its IPO plans twice in nine months, Alzheon rounded up $150 million across two private rounds and started a phase 3 trial of its valiltramiprosate prodrug formulation.Valiltramiprosate was no better than placebo at slowing cognitive decline, as assessed by ADAS-Cog13, in the latest phase 3 trial, causing the study of 325 people with early Alzheimer’s to miss its primary endpoint. The result favored valiltramiprosate numerically, but the difference fell short of statistical significance. That story repeated across the secondary endpoints. The study drug was numerically but not statistically better than placebo on cognition and function scale CDR-SB, cognitive impairment test MMSE and disability scale DAD. Scores on the daily living scale A-IADL favored placebo. Following an age-old playbook for failed Alzheimer’s trials, Alzheon looked to a subgroup of patients with the earliest symptomatic stage of the disease for signs of efficacy. The prespecified analysis revealed a nominally statistically significant improvement in cognition versus placebo, as measured by ADAS-Cog13. Valiltramiprosate’s numeric advantage over placebo on other measures widened in the subgroup. Alzheon saw the signs of efficacy in a subpopulation of patients who are poorly served by existing drugs. The study enrolled people with two copies of the APOE4 gene. People with the genes are more likely to develop amyloid-related imaging abnormalities than other patients when taking drugs such as Eisai and Biogen’s Leqembi and Eli Lilly’s Kisunla, a fact the FDA communicated in boxed warnings.Susan Abushakra, M.D., chief medical officer of Alzheon, said in a statement that “a precision medicine approach is key to addressing the needs of Alzheimer’s patients who have the APOE4/4 genotype, and we are committed to this patient population.”

$Alzheon Alzheimer\'s drug knocked down in pivotal APOLLOE4 bout$

Phase 3Clinical ResultIPO

10 Apr 2025

·endpts.com

Alzheon’s amyloid-targeting pill fails another Phase 3 study in Alzheimer’s

Alzheon’s controversial, decade-long bet that a failed Alzheimer’s drug could offer bigger benefits to a subset of patients at the highest risk for the disease has ended in another disappointment. On Thursday, the Framingham, MA-based startup announced that its daily pill valiltramiprosate, also known as ALZ-801, failed to slow cognitive decline, the Phase 3 study’s primary endpoint. Valiltramiprosate is a reformulated version of tramiprosate, a molecule Alzheon licensed from Canadian drugmaker Bellus Health (formerly Neurochem) in 2013. Tramiprosate failed a major study in 2007, but Alzheon’s founders were convinced by a post-hoc analysis that the drug moved the needle for Alzheimer’s patients who carry two copies of the dreaded APOE4 gene, which dramatically increases the chance of developing Alzheimer’s. The new study enrolled 325 people with early Alzheimer’s and who had two copies of APOE4. According to the company’s press release, valiltramiprosate slowed cognitive decline by 11% on one scale (ADAS-Cog13, p=0.607) and 23% on another common scale (CDR-SB, p=0.309) compared with placebo. But both results were far from statistically significant. The results looked more promising in a prespecified subset of 125 people with mild cognitive impairment — the earliest symptomatic form of Alzheimer’s. Alzheon said the drug slowed cognitive decline in these patients by 52% on one scale (ADAS-Cog13, p=0.041) and appeared to practically stop decline on another scale (CDR-SB, p=0.053). But the first result was barely statistically significant and the second was insignificant. Alzheon had previously said that it expected to share the results and file for approval in 2024. And according to clinicaltrials.gov , the company finished the study in July 2024. That same month, the company raised a $100 million Series E financing to support regulatory filings and potential commercialization in 2025. Alzheon tried to go public twice but scrapped plans in 2018 and 2019 for an IPO . A lifeline came from a $47 million five-year grant from the National Institutes of Health in 2020, which expanded to more than $51 million by 2024 for its recently completed clinical trial. The company didn’t immediately respond to questions about its next steps, its plans for valiltramiprosate and its financial status. In the past few years, Alzheon had pitched its pill as a potentially safer alternative to antibody infusions developed by Biogen, Eisai and Lilly, whose trials have shown slow cognitive decline by about 30%. Those antibodies remove amyloid plaques from the brain, but in doing so can cause potentially lethal side effects of brain bleeding and swelling known as ARIA. The risk of ARIA is heightened for people with one copy of the APOE4 gene and dramatically enhanced for people with two copies of the gene. Alzheon’s pill, had it worked, would have provided a much-needed alternative for these patients. Alzheon says its small molecule blocks the misfolding and aggregation of amyloid monomers, potentially preventing or stalling the buildup of plaques. By avoiding direct plaque removal, it hoped the approach would be safer. That theory bore out in the study, with no increased risk of ARIA among drug recipients. The most common side effects were decreased appetite, loss of weight, nausea and vomiting. But the safety benefits were mooted by the lack of efficacy. The study may add fuel to an ongoing debate among neurologists about whether plaque removal is necessary for efficacy, and whether it is possible to disentangle the serious risks of amyloid-removing drugs from their benefits.

Phase 3Clinical Result

100 Deals associated with Valiltramiprosate

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Phase 3	United States	Alzheon, Inc.	19 May 2021
Alzheimer Disease	Phase 3	Canada	Alzheon, Inc.	19 May 2021
Alzheimer Disease	Phase 3	Czechia	Alzheon, Inc.	19 May 2021
Alzheimer Disease	Phase 3	France	Alzheon, Inc.	19 May 2021
Alzheimer Disease	Phase 3	Germany	Alzheon, Inc.	19 May 2021
Alzheimer Disease	Phase 3	Iceland	Alzheon, Inc.	19 May 2021
Alzheimer Disease	Phase 3	Netherlands	Alzheon, Inc.	19 May 2021
Alzheimer Disease	Phase 3	Spain	Alzheon, Inc.	19 May 2021
Alzheimer Disease	Phase 3	United Kingdom	Alzheon, Inc.	19 May 2021
Down Syndrome	Clinical	United States	Alzheon, Inc.	11 Jun 2022

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04770220 (Company_Website) Manual	Phase 3	Alzheimer Disease APOE4/4 homozygotes	325	valiltramiprosate	jcpvxqidez(egmiwtaspr): Difference (LS Mean) = -0.504, P-Value = 0.607 Not Met View more	Negative	10 Apr 2025
NCT04770220 (Company_Website) Manual	Phase 3	Alzheimer Disease APOE4/4 homozygotes	325	Placebo		Negative	10 Apr 2025
NCT04693520 (Biospace) Manual	Phase 2	Alzheimer Disease	84	ALZ-801/Valiltramiprosate 265 mg	mmygyxxrkk(nvgrjgkkde) = statistically significant and clinically relevant reduction in plasma biomarkers of neurodegeneration, preservation of brain volume, and positive cognitive effects in Early AD patients who are carriers of apolipoprotein ε4 allele (APOE4) following 24 months of treatment with investigational oral agent ALZ-801/valiltramiprosate. vboiptwdpy (nxvtyrxyvl )	Positive	25 Jun 2024
NCT04693520 (phase 2, Pubmed)	Phase 2	Alzheimer Disease plasma Aβ42	84	ALZ-801 265 mg tablet	fqofdunmge(hynqnruidb) = ngugfkwhol ashdejnzvz (wmtxgeocek )	Positive	20 Jun 2024
NCT04693520 (Corporate Publications) Manual	Phase 2	Alzheimer Disease	75	Valiltramiprosate	yrgvvzvegk(mjfctntzym) = skrnhjhhhv jyjymbsdla (objhqghpoq ) View more	Positive	20 Sep 2022
AAIC2019	Not Applicable	Alzheimer Disease	-	ALZ-801/tramiprosate	infknedfyq(bbhdnwwkau) = mwmimfkqta wygsjgvutn (vcpojixfwb )	-	01 Jul 2019

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