Oral small molecules for rare diseases

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About ALESTA Therapeutics

Pioneering Small Molecule Therapeutics 

Pioneering Small Molecule Therapeutics at Leiden

Based in Leiden, Netherlands, our company is leading the development of innovative small molecules for rare diseases. With advanced chemistry, our clinical candidates are backed by extensive pre-GLP toxicology and are gearing up for GLP toxicology studies.

We are supported by Droia Ventures, Thuja Capital, Praxis Biotech, and Casi Pharmaceuticals. 

Science

Small molecule to target hypophosphatasia

Hypophosphatasia (HPP) is a rare genetic disorder that severely affects the development of bones and teeth due to defective mineralization. HPP causes a further spectrum of symptoms:  ranging from neurological, to muscle, joints, gastric and kidney. HPP affects 1 in 300,000 newborns. Current treatments only target bone-related symptoms and have low tolerability.

We focus on oral therapy competitive with the existing proof of care. Our in vivo data indicate that we can achieve major improvement in the patient status, without irritating side effects.

Program

Advanced Therapeutic Programs in Focus

Our research programs leverage GCN2 inhibitors to address critical needs in oncology and neurology. In cancer treatment, these inhibitors exploit genetic deficiencies in amino acid processing to suppress tumor growth effectively, particularly enhancing outcomes in combination with immune therapies. In neurology, our focus is on Charcot-Marie-Tooth (CMT) disease, where GCN2 inhibitors have shown promise in genetically engineered mouse models, slowing disease progression and modulating key biological pathways.

 
As we prepare for our first-in-human (FIH) studies in early 2025, our efforts are informed by rigorous preclinical evaluations and collaborations with leading medical institutions. This approach ensures a solid foundation for potential clinical success and transformative patient outcomes.

Science

Targeting GCN2 to Combat Charcot-Marie-Tooth Disease

Charcot-Marie-Tooth (CMT) is a debilitating inherited neurological disorder that affects motor and sensory functions in the hands and feet, impacting approximately 126,000 people in the US and 2.6 million worldwide. Research has linked CMT to genetic alterations in tRNA synthetases, such as GARS, which are crucial for tRNA loading with amino acids. These alterations can lead to significant motor neuropathy, characterized by disabling muscle weakness and potential immobility.

Our focus on GCN2 inhibitors represents a groundbreaking approach to alleviate these symptoms. Studies in mouse models, which also exhibit similar motor dysfunction, utilize ‘latency to fall’ measurements to assess muscle strength and response to treatment. Our data indicates that pharmacological inhibition of GCN2 not only alleviates symptoms but mirrors the therapeutic effects seen in GCN2 knockout scenarios, offering a promising avenue for significantly improving the quality of life for those affected by CMT

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