Combating Neurodegenerative and Age-related Diseases

We recently spoke to Karoly Nikolich, chairman and chief executive officer of Alkahest, a clinical-stage biotechnology company, to learn more about their approach to developing therapeutics for both neurodegenerative and age-related diseases. Karoly touches on the company's mission and highlights the development of GRF6021, which is currently being investigated for the treatment of cognitive impairment and dementia in patients with Parkinson's disease.

Laura Lansdowne (LL): Could you tell us more about Alkahest, the company history, mission and goals?

Karoly Nikolich (KN): Alkahest is a clinical-stage biopharmaceutical company dedicated to combating neurodegenerative and age-related diseases by developing transformative therapies that counteract the aging plasma proteome. Our pipeline includes both proprietary plasma fractions and protein-targeted interventions that reverse cognitive deficits caused by detrimental biological processes of aging to increase cognitive lifespan.

Our mission is to enrich the health and vitality of our aging population by developing disease-modifying therapies for age-related diseases. We hope to fill this large unmet need by addressing the complex pathology of age-related diseases.   

LL: Could you tell us about the processes that your interventions target?

KN: Alkahest is advancing a clinical stage pipeline targeting the complex biology of the aging plasma proteome underlying age-related disorders. Alkahest’s decoding of the plasma proteome has led to the assembly of a technology platform designed to identify new targets and develop new therapies.

Building on science from Stanford, Alkahest mapped the change in plasma proteins that occur with age.  Proteins that significantly increase or decrease with age or in diseases of aging, we call “chronokines”. We have leveraged this finding to develop therapeutic targets that either inhibit or slow the impact of “age-promoting” factors or enhance beneficial “restorative” factors. This approach is designed to target a multitude of biological functions that underlie aging, or conversely, promote biological functions that underlie preservation of health.  These chronokines have been shown to have an impact in animal models of Alzheimer’s disease, Parkinson’s disease, age-related macular degeneration and more. We currently have Phase 2 trials underway in these indications, with more planned.

Alkahest recently announced dosing of the first subject in a Phase 2 clinical trial of GRF6021.

LL: What is GRF6021 and what indications is it being investigated for?

KN: GRF6021 is a proprietary human plasma fraction in clinical trials being investigated for the treatment of cognitive impairment and dementia in Parkinson’s disease. GRF6021 is being developed with Alkahest partner, Grifols, a leading producer of plasma therapeutics.

LL: Could you describe GRF6021’s mechanism of action?

KN: GRF6021 is designed to replenish factors in the plasma proteome that promote neuroregeneration to counteract the detrimental processes of aging. It has been shown to enhance neurogenesis, improve learning and memory, and slow cognitive decline in animal models.

LL: Could you tell us more about the design of the Phase II study?

KN: GRF6021 entered into a phase 2 clinical trial in 2018. It is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability and potential effects on cognition of GRF6021 administered as an IV infusion to individuals with Parkinson’s disease and cognitive impairment. Alkahest intends to enrol approximately 90 subjects who will receive GRF6021 or placebo for five consecutive days at week one and week 13 over a seven-month duration.  More details about this study are available on clinicaltrials.gov.

LL: What other drug candidates are currently in the pipeline, and what indications are they being investigated for?

KN: GRF6019 is another human plasma fraction that is currently being studied in a phase 2 trial for the treatment of mild to moderate Alzheimer’s disease. GRF6019 also works by replenishing restorative factors in plasma. We are also developing AKST4290 to treat wet age-related macular degeneration (AMD). AKST4290 has recently completed enrolment in two phase 2a clinical trials in naïve and refractory wet AMD patients. AKST4290 inhibits the action of eotaxin, a detrimental chronokine that leads to inflammation and is associated with the poor visual outcomes in wet AMD. AKST1210 is in development for dialysis-related cognitive impairment, and other novel factors in the pipeline are in the discovery phase.

Karoly Nikolich, Ph.D was speaking to Laura Elizabeth Lansdowne, Science Writer for Technology Networks.