GRF6019 / Grifols - LARVOL DELTA

Nowhere to run, nowhere to hide - targeting the immune system in AD with multimodal plasma therapeutics (AAIC 2023) - "Here we discuss insights from deep plasma proteomics profiling in patients from the GRF6019 and AMBAR clinical trials in which multi-modal plasma therapeutics were used and limited cognitive decline was observed... AD has multifaceted nature and plasma therapeutics have proven safety, efficacy, and versatility. The proteomics results from these trials shed the light on the underlying mode of action of multi-modal plasma-derived therapies and demonstrate that they can modulate multiple pathways relevant to AD, with a strong effect on the immune and inflammatory responses which may contribute to slowing down AD progression."

Alzheimer's Disease • CNS Disorders • Inflammation

Network propagation unveils molecular mechanisms modulated in Alzheimer’s Disease patients treated by the complex plasma fraction GRF6019 (AAIC 2023) - "Network propagation procedure highlights the importance of interactome-based analysis in understanding complex plasma proteomics signals. These results suggest that the treatment of AD patients with a complex plasma fraction modulates AD-related biological pathways."

Clinical • Age-related Macular Degeneration • Alzheimer's Disease • Cardiovascular • CNS Disorders • Ischemic stroke

Interactome-guided machine learning modeling reveals information embedded in blood plasma protein-protein interactions in Alzheimer’s Disease patients treated by the complex plasma fraction GRF6019 (AAIC 2023) - "Complex biological functions can be mapped into pathways which are composed of and regulated by PPIs. Biological functionality can be encoded in concentrations of individual proteins, also in relative concentrations of interacting proteins. Our results indicate that the latter aspect may contain a significant amount of complementary information, not accessible with traditional approaches analyzing proteins as independent entities."

Clinical • Machine learning • Alzheimer's Disease • CNS Disorders • Targeted Protein Degradation

Deep plasma proteomics reveal age-related molecular pathways modulated by GRF6019 treatment in Alzheimer’s disease patients (AAIC 2022) - No abstract available

Clinical • Alzheimer's Disease • CNS Disorders

DEEP PLASMA PROTEOMICS REVEAL AGE-RELATED MOLECULAR PATHWAYS MODULATED BY GRF6019 TREATMENT IN ALZHEIMER’S DISEASE PATIENTS (ADPD 2022) - "Conclusions Altogether, our results suggest that the treatment of AD patients with a complex plasma fraction modulates biological pathways that are relevant to aging and AD. Our results establish deep proteomics as a powerful tool to study human response to treatment in clinical trials."

Clinical • Alzheimer's Disease • CNS Disorders

[VIRTUAL] The Plasma Fraction GRF6019 Slows Brain Atrophy in Mild-to-Moderate Alzheimer’s Disease (AAIC 2021) - "In mild-to-moderate AD, the plasma fraction GRF6019 slowed hippocampal atrophy and lateral ventricle enlargement compared to matched individuals with AD in ADNI. The MRI data are consistent with the lack of cognitive worsening observed in these trial participants and supports continued clinical development of GRF6019 in AD."

Alzheimer's Disease • CNS Disorders • Immunology • AGER • MRI

Safety and Tolerability of GRF6019 Infusions in Severe Alzheimer's Disease: A Phase II Double-Blind Placebo-Controlled Trial. (PubMed, J Alzheimers Dis) - "GRF6019 demonstrated excellent safety, feasibility, and tolerability. Future trials designed to characterize the potential functional benefits of GRF6019 and related plasma fractions in severe AD are warranted."

Clinical • Journal • P2 data • Alzheimer's Disease • CNS Disorders • Dementia • Hypertension • Hypotension • Immunology • Inflammation

[VIRTUAL] EFFICACY OF A NOVEL HUMAN PLASMA THERAPEUTIC IN A MOUSE MODEL OF ALZHEIMER’S DISEASE (ADPD 2021) - "We have developed two therapeutic plasma fractions derived from healthy human donors, GRF6019 and GRF6021, that show beneficial effects on symptoms of aging. Treatment of P301S mice with a human plasma fraction ameliorates multiple AD-related symptoms, including deficits in cognition and neuronal activity, microgliosis, and tau pathology. These results demonstrate the potential of plasma fractions to transform approaches and support the advancement of GRF6021 to clinical testing for AD."

Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Immunology • Inflammation

Alkahest Announces Peer-Reviewed Publication Demonstrating Safety and Tolerability of GRF6019 in Patients with Mild-to-Moderate Alzheimer’s Disease (GlobeNewswire) - P2a, N=47; NCT03520998; Sponsor: Alkahest, Inc.; "Alkahest, Inc....announced the publication of a peer-reviewed article...The publication...describes Alkahest’s Phase 2 clinical trial...The trial met its primary endpoint, demonstrating that both dose levels were safe and well tolerated, with no clear difference in adverse events between the 100 and the 250 milliliter dose arms. Patients treated with GRF6019 showed a lack of cognitive decline and limited functional decline over the 24-week study period....Alkahest plans to advance GRF6019 to further study its efficacy in these patient populations."

P2a data • Alzheimer's Disease • CNS Disorders

Safety and tolerability of GRF6019 in mild-to-moderate Alzheimer's disease dementia. (PubMed, Alzheimers Dement (N Y)) - "GRF6019 was safe and well tolerated, and patients experienced no cognitive decline and minimal functional decline. These results support further development of GRF6019."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Psychiatry

[VIRTUAL] PLASMA FRACTIONS IN ALZHEIMER’S DISEASE: BIOMARKER ANALYSIS IN THE ALK6019-201 AND ALK6019-202 TRIALS (CTAD 2020) - "Pharmacodynamic changes observed in the plasma proteome are indicative of acute downstream effects on pathways of relevance for systemic function. Although limited datasets, the lack of decline indicated by CSF biomarkers and MRI imaging correlate with the lack of decline observed in clinical endpoints. These data are supportive of continued development of Plasma Protein Fractions for AD and related disorders."

Biomarker • Alzheimer's Disease • CNS Disorders • MRI

[VIRTUAL] A Randomized, Placebo-Controlled, Double-Blind Trial of the Plasma Fraction GRF6019 in Severe Alzheimer Disease (ANA 2020) - P2 | "This trial demonstrated that daily infusions of 250 mL GRF6019 for 5 consecutive days is safe, welltolerated and feasible in individuals with severe AD. The excellent safety profile supports continued development of plasma fractions for the treatment of AD."

Clinical • Alzheimer's Disease • CNS Disorders • Psychiatry

Grifols Moves Deeper Into Proteome R&D With $146M Deal for Alkahest (Xconomy) - "Alkahest, a company that analyzes blood proteins to develop therapies that address neurological disorders including Alzheimer’s disease, is set to be acquired by partner Grifols in a $146 million deal.....Alkahest drug candidates, GRF-6019 and GRF-6021, are intended to enhance the growth and development of nerve tissue, improve the deficits in learning and memory that come with aging, and reduce neuroinflammation....The other Alkahest lead compound, GRF-6021, is being evaluated in separate a Phase 2 study in Parkinson’s disease. The company’s pipeline also includes AKST4290, in mid-stage tests for the wet form of age-related macular degeneration as well as Parkinson’s..."

M&A • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

A Study to Assess the Safety of GRF6019 Infusions in Subjects With Severe Alzheimer's Disease (clinicaltrials.gov) - P2; N=26; Completed; Sponsor: Alkahest, Inc.; Active, not recruiting ➔ Completed; N=20 ➔ 26

Clinical • Enrollment change • Trial completion • Alzheimer's Disease • CNS Disorders • Reperfusion Injury

[VIRTUAL] EFFICACY OF A NOVEL HUMAN PLASMA THERAPEUTIC IN A MOUSE MODEL OF ALZHEIMER’S DISEASE (AAT-ADPD 2020) - "We have developed two therapeutic plasma fractions derived from healthy human donors, GRF6019 and GRF6021, that show beneficial effects on symptoms of aging. Treatment of P301S mice with a human plasma fraction ameliorates multiple AD-related symptoms, including deficits in cognition and neuronal activity, microgliosis, and tau pathology. These results demonstrate the potential of plasma fractions to transform approaches and support the advancement of GRF6021 to clinical testing for AD."

Preclinical

[VIRTUAL] RESULTS FROM THE PHASE 2 TRIAL OF THE PLASMA FRACTION GRF6019 IN MILD-TO-MODERATE ALZHEIMER’S DISEASE (AAT-ADPD 2020) - P2 | "Over the course of 6 months, there was no significant decline in clinical or MRI endpoints. Conclusions The clinical and biomarker data from this Phase 2 trial in AD are consistent with GRF6019 treatment appearing to slow clinical progression."

P2 data • APOE • MRI

[VIRTUAL] EFFICACY OF A NOVEL HUMAN PLASMA THERAPEUTIC IN A MOUSE MODEL OF ALZHEIMER’S DISEASE (AAT-ADPD 2020) - "We have developed two therapeutic plasma fractions derived from healthy human donors, GRF6019 and GRF6021, that show beneficial effects on symptoms of aging. Treatment of P301S mice with a human plasma fraction ameliorates multiple AD-related symptoms, including deficits in cognition and neuronal activity, microgliosis, and tau pathology. These results demonstrate the potential of plasma fractions to transform approaches and support the advancement of GRF6021 to clinical testing for AD."

Preclinical

A Study to Assess the Safety of GRF6019 Infusions in Subjects With Severe Alzheimer's Disease (clinicaltrials.gov) - P2; N=20; Active, not recruiting; Sponsor: Alkahest, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

A PHASE 2 TRIAL OF GRF6019 IN MILD-TO- MODERATE ALZHEIMER’S DISEASE. (CTAD 2019) - P2; "The main exclusion criteria were: any neurological disorder other than AD; > 2 lacunar strokes on Magnetic Resonance Imaging (MRI); change in the dose of cholinesterase inhibitor or memantine in the last 3 months. This Phase 2 trial in AD demonstrates that daily infusions with up to 250 mL of the plasma protein fraction GRF6019 for 5 consecutive days is safe and well-tolerated in this population. Furthermore, progression of disease in GRF6019- treated subjects was slower than what would be expected in this population. Based on these data, the benefit-risk of continued clinical development of plasma protein fractions in AD is favorable, and a placebo-controlled Phase 2b trial is currently being planned."

P2 data • MRI

Alkahest presents data from phase 2a study in mild-to-moderate Alzheimer’s disease (GlobeNewswire) - P2a, N=40, AKST6019-201 (NCT03520998), Sponsor: Alkahest, Inc; "Alkahest Inc...presented data this weekend from its phase 2a study, AKST6019-201, in mild-to-moderate Alzheimer’s Disease (AD). The study met its primary endpoint of safety and tolerability and key secondary endpoints measuring cognitive and functional performance indicated limited-to-no declines over the six-month treatment period. The clinical results were presented in a podium presentation Saturday, December 7th at the 12th Annual Clinical Trials on Alzheimer’s Disease (CTAD) meeting, in San Diego, California."

P2 data

Alkahest to Present New Data from Phase 2a Study in Mild-to-Moderate Alzheimer’s Disease at the Clinical Trials in Alzheimer’s Disease (CTAD) Conference (GlobeNewswire, Alkahest, Inc.) - P2a, N=40; ALK6019-201 (NCT03520998); Sponsor: Alkahest; "Alkahest Inc....today announced an oral presentation of data from its phase 2a study ALK6019-201 in mild-to-moderate Alzheimer’s Disease at the 12th Clinical Trials on Alzheimer’s Disease from December 4 – 7, 2019 in San Diego. Title: A Phase 2 trial of GRF6019 in mild-to-moderate Alzheimer’s Disease."

P2a data

A transformational plasma-based approach to Alzheimer's disease therapeutics (Neuroscience 2019) - "Deep analysis of the plasma proteome in both healthy aging and in the progression of Alzheimer’s disease suggest that proteins in the plasma proteome can contribute to disease progression and that the modulation of the plasma proteome via infusion of plasma fractions can confer benefits. The therapeutic potential of this approach is being translated to human clinical testing with evaluation of the human plasma protein fraction GRF6019 in mild-moderate AD patients."

Alkahest Announces Positive Top-line Data from Phase 2 Study in Mild to Moderate Alzheimer’s Disease (GlobeNewswire, Alkahest, Inc.) - SAN CARLOS, Calif., Aug 05, 2019 (GLOBE NEWSWIRE) -- Alkahest, Inc, a clinical-stage biotechnology company focused on developing transformative therapies to treat age-related diseases, today announced top-line data from its phase 2 clinical trial of its candidate GRF6019 in mild-to-moderate Alzheimer’s disease dementia (AD). The study was designed to evaluate the safety, tolerability, and potential therapeutic effects of multiple doses of GRF6019 in patients with mild-to-moderate AD over six months.

Clinical • Clinical data

Malleability of Aging Processes Via Plasma Based Therapeutics (AAIC 2019) - "A plasma fraction has been identified that has the ability to modulate multiple underlying mechanisms of relevance in age-related disorders including Alzheimer’s disease. These fractions are being advanced into clinical testing to understand potential as transformative therapeutics for patients."

A Randomized Study to Assess the Safety of GRF6019 Infusions in Subjects With Mild to Moderate Alzheimer's Disease (clinicaltrials.gov) - P2; N=40; Completed; Sponsor: Alkahest, Inc.; Active, not recruiting ➔ Completed; Trial completion date: Nov 2019 ➔ May 2019; Trial primary completion date: Nov 2019 ➔ May 2019

Clinical • Trial completion • Trial completion date • Trial primary completion date