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On November 7, Arkuda Therapeutics announced the completion of a $44 million Series A round of financing, led by Atlas Venture and Pfizer Ventures, and Tekla Capital Management and BioInnovation Capital. The company will use the funds to promote its treatment of frontotemporal dementia (FTD) drugs through Phase I safety testing, and then through Phase Ib studies to assess the drug’s ability to alter granule protein precursor (PGRN) levels in patients with GRN mutations.

Arkuda Therapeutics, a Massachusetts-based biotechnology company, and CEO and co-founder Dr. Gerhard Koenig brings to Arkuda his previous experience in neuroscience drug development. Koenig was the chief scientific officer of Forum Pharmaceuticals, a Massachusetts-based biotech company that closed in 2016 for the failure to develop drugs for Alzheimer’s and schizophrenia. However, he said that despite the failure, the neuroscience research at Forum paved the way for his current work.

Dr. Gerhard Koenig, CEO and co-founder of Arkuda Therapeutics

Koenig said in a statement: “We believe that the challenge of treating neurodegenerative diseases stems from the fact that drug development often targets the pathology of the disease rather than the root causes such as lysosomal dysfunction, but also because serious damage has occurred. The treatment of the patient is too late.”


Arkuda Therapeutics is trying to change this situation. A drug developed by the company can address the underlying causes of the GRD mutation-related FTD (FTD-GRN) and potentially prevent the disease from occurring.


FTD refers to a group of brain diseases characterized by atrophy of the frontal lobe and temporal lobe. Patients with dementia syndrome with personality changes, speech disorders, and behavioral abnormalities appear slowly, and some of them have hereditary GRN mutations. Specifically, the GRN gene directs the encoding of the PGRN protein, which plays a key role in lysosomal function and innate immunity in the brain. When a copy mutation in the GRN gene that produces the PGRN instruction is provided, the patient will not be able to produce sufficient PGRN, thereby affecting the production of granule proteins in the lysosomes of the neurons, causing progressive neuronal degeneration and eventual death.

PGRN is a protein produced by various cells of the body, including cells of the central nervous system. Inside the lysosome, PGRN is processed into granule proteins, which is the key to maintaining protein homeostasis in cells.


The Arkuda Therapeutics drug targets the remaining healthy copies of the GRN gene, prompting it to produce more PGRN. Koenig said that the production of more PGRN is expected to solve the problem of low lysosomal function. However, for reasons of competition, he could not disclose the specific target of the company’s experimental drugs and its specific mechanism of action.

Arkuda’s initial focus was on developing a drug that increased endogenous PGRN levels in asymptomatic FTD-GRN patients, thereby increasing lysosomal granule protein levels, maintaining protein homeostasis, and restoring disordered immune regulation.


Of course, in addition to Arkuda Therapeutics, other companies are trying to treat neuropathy by increasing PGRN levels. Alector, a clinical-based biopharmaceutical company based in South San Francisco, aims to prevent the decline of PGRN levels with a drug called AL001, which blocks the cell’s breakdown of PGRN. In July, the company reported that Phase Ib data showed that its drugs increased PGRN levels in blood and cerebrospinal fluid in healthy volunteers. In addition, a phase II study of patients with FTD began in September.


On the R&D track, Arkuda Therapeutics also caught up. The company has now identified highly effective and selective small molecules that meet the expected drug development goals. Animal experiments have shown that their drugs can raise PGRN to levels that are beneficial to humans, and they are looking forward to clinical trials.


Koenig said that the first human trial may begin in 2021. In addition, he pointed out that more and more studies have shown that PGRN is very important for resisting diseases, and that lysosomal function and resulting protein homeostasis are associated with a series of neurodegenerative diseases (including Alzheimer’s disease, Parkinson’s disease). Disease, amyotrophic lateral sclerosis and frontotemporal dementia are related. But the company will wait until the clinical data of FTD is available before developing drugs for other diseases.

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