Before reading, don’t forget to head to Part 1 to learn more about Quris’ founder Isaac Bentwich, why Quris was developed, and how the company is using its innovative bio-AI drug development platform to change drug development within the rare disease sphere.

Quris: Finding Solutions for Rare Diseases

As many people within the rare disease community know, there are many difficulties associated with clinical research and drug development. As Isaac explains:

The problem with rare diseases is that they represent a small market. In more common diseases, the regular process – which is already ineffective – still works to some extent and can be justified by the fact that there’s a huge market for it. With rare diseases, it makes it virtually impossible to develop drugs because to do so, the process has to be more efficient, more nimble, and more effective – but it’s still incredibly expensive. Quris decided to focus on rare diseases so that we can work to overcome these obstacles.

Right now, the first drug in the Quris pipeline is being developed and evaluated for those with Fragile X syndrome (FXS). When asked why the company was starting with Fragile X syndrome, Isaac shares:

It’s first and foremost a humane effort. We’ve met with families of people with this disease and we see how deep the desire is for a cure. There’s no treatment for Fragile X and so that is also compelling. But it also happens thatthere is no mouse model for Fragile X. What do we do for diseases with no mouse models? A platform like Quris is needed to take the drug from the discovery phase and develop it safely before testing it on people.

Additionally, while there is no mice model for FXS, there is a stem cell-based disease model. Quris approached a world leader of stem cell models in Jerusalem and was able to utilize the stem cell model for FXS. This means that Quris can use patient stem cells to develop a miniaturized organ and test potential therapies on that – a safer and more efficient process.

FXS also presents an opportunity for socially-driven drug development. In Israel and through the Fragile X Society in the US, Quris has been able to connect to patients and families to really understand their needs. With new technologies, families can become a part of the drug development process through crowdfunding, pooling resources, donating blood samples, or establishing stem cells. By offering a platform through which families can work, Quris can help translate drug development through a more patient-centric approach.

What is Fragile X Syndrome (FXS)?

Fragile X syndrome (FXS) is a rare inherited disorder which can cause developmental and cognitive delays. FMR1 gene mutations on the X chromosome cause FXS. This mutation prevents the gene from making fragile X mental retardation 1 protein. Normally, this protein plays an important role in nervous system function. However, in Fragile X syndrome, a protein shortage causes the resulting symptoms and characteristics. While both males and females can have FXS, males seem to be affected more frequently and more severely. Symptoms and characteristics vary, but often present themselves by age 2. These can (but do not always) include:

• Development delays
• Protruding ears, forehead, and chin
• Hypotonia (low muscle tone)
• Flat feet
• An elongated face
• Strabismus (crossed eyes)
• Stuttering
• Frequent ear infections
• Learning or intellectual disabilities
• Speech and language difficulties
• Sensory processing challenges
• Behavioral problems, such as anxiety, depression, or hyperactivity
• Seizures

A Potential Drug for Fragile X Syndrome

Currently, there are no cures for FXS – and limited therapeutic options. There have been attempts by Novartis and Roche to develop therapies within this realm, but unfortunately, these have been unsuccessful. However, shares Isaac:

In FXS, the single gene is inhibited during embryogenesis in an epigenetic mechanism. Using our AI,Quris has discovered a drug combination that undoes this inhibition and provides the missing FMRP protein. This drug has the potential to ‘cure’ the root cause of FXS, not just treat the symptoms.

This drug will enter into clinical testing within the coming year. If successful, it offers the potential to fill a huge unmet need within this patient community.

In the future, Quris is looking to expand into multiple other disease states – including different variants of autism, major diseases, and other rare diseases. Isaac believes that the Quris business model will help them not only address rare diseases, but to broaden drug discovery to the other, less rare but related disease entities.