After a year in the lead optimization phase, Saniona can now move forward with its Kv7 program. This means that the company has entered the candidate selection phase with a proprietary subtype-selective frontrunner molecule from the program, with the goal of developing a new treatment for epilepsy.
Sees high potential in epilepsy
Tuesday's news is another step forward for a program where Saniona sees great potential in the field of epilepsy. Epilepsy is an area with great medical need. It is not only the most common chronic brain disease in the world and which affects more than 50 million people. There are also no completely curative treatments and today's symptom-relieving treatments are associated with side effects. In addition, only about 30 percent of patients respond satisfactorily to today's treatments, which means that there is a significant group that would benefit from new treatments. Saniona's goal with the Kv7 program is to develop just such a treatment.
According to Saniona, the commercial potential of Kv7 epilepsy drugs is illustrated by the fact that companies Xenon and Biohaven, both of which operate in the Q7 space, have a market capitalization of approximately $2 billion, largely based on their Q7 development programs.
Aiming to develop a new generation of epilepsy treatments
In their quest to improve the treatment of epilepsy, researchers are focusing their attention on a specific set of channels in the brain called Kv7 channels. These regulate electrical signaling in nerve cells and prevent the repetitive patterns that can trigger seizures.
Saniona is working on a new group of compounds designed to overcome the limitations of previous epilepsy treatments. The company believes that its compounds could represent a new generation of effective and well-tolerated epilepsy drugs. What sets these Kv7 activators apart from others is their improved chemical stability and selectivity and mechanism of action.
According to the company, these features offer several benefits, including avoiding the unwanted effects on bladder tissue caused by some previous drugs. This is potentially an important breakthrough because traditional Kv7 modulators, while effective against epilepsy, sometimes pose a risk of urinary retention. This is a condition that can become life-threatening due to the inability to empty the bladder.
Competitors in Q7 channels
Regarding the current situation for the treatment of epilepsy through Kv7 channels, Xenon has positioned itself through the acquisition of the substance XEN1101 from 1st Order Pharmaceuticals and moved on to phase III after a successful Phase II study. Biohaven, on the other hand, acquired a preclinical Kv7 program from Knopp for USD 100 million in 2022, and completed a Phase I study and expressed the intention to initiate a pivotal study.
The importance of Kv7 channels in controlling neuronal activity underscores their potential importance in treating epilepsy. The acquisitions in this area also reflect the interest and willingness to explore the area further for this indication.
“We have been working on this goal for more than two decades in collaboration with partners and internally to achieve this profile. Now we know how to do it. So these are exciting times” – Thomas Feldthus, CEO Saniona
Comments from the CEO
BioStock contacted Saniona's CEO Thomas Feldthus to get more information about the latest progress in the program.
Thomas, can you elaborate on your reasoning behind the choice of compound?
- The Kv7 channel is a commercially and clinically validated target by GSK's retigabine, which was launched in 2011 and proved to be very effective for the treatment of patients with resistant focal onset seizures. However, retigabine was withdrawn from the market in 2017 because of unstable chemistry which led to mis-coloring of the retina and other tissue. It is a unique situation where there is a commercially validated target without a drug on the market.
– The Kv7 channels comprise a family of five members, Kv7.1 – Kv7.5. Apart from the mis-coloring, retigabine has other problems as it activates four Kv7 members, Kv7.2 – Kv7.5 channels.
- The Kv7.2 and Kv7.3 channels are the targets for the treatment of epilepsy. Activating the others may lead to severe side effects. Kv7.4 channels are expressed in various cells in the body including the bladder resulting in life threatening urinary retention in some patients. Kv7.5 channels are also expressed in the brain and are likely contributing to the dose limiting CNS side effects of retigabine and competing programs in development.
Could your compound potentially avoid these side effects?
- Yes, we believe that Saniona is the first company which has been able to make a compound that is truly selective for Kv7.2 and Kv7.3, without activating the other subtypes thereby avoiding many of the side effects seen with retigabine and competing programs. As some of these side effects appear to be dose limiting, we have an asset which may be more effective and with fewer side effects than competing programs.
- The compound is of cause based on stable chemistry without the risk of mis-coloring. It is very potent, and it appears to be highly druggable. We are now pressure testing this compound and have several back-ups. It is hard to obtain this selectivity. We have worked on this target for more than two decades in collaboration with partners and internally to achieve this profile. We now know how to do it. So, it is exciting times.
Moving forward, what are the next steps in the Kv7 programme?
- We hope to select this compound for pre-clinical development and will in parallel work on identifying additional back-up compounds. If selected as a candidate, it will need to go through the IND/CTA enabling pre-clinical studies before we can start phase I.
What does the timeline look like for the selection phase?
- The candidate selection phase usually takes 6 months. We have produced the first batch and made some of the critical studies, so we may do it faster than that.
How does Saniona assess the market potential for this program?
- There are about 600,000 patients with focal onset seizures in the US who are not well treated with existing drugs. There is a similar number of patients in Europe. In addition, the product may be used for the treatment of pediatric epilepsy caused by mutation in the Kv7 channel genes. So, the market is significant.
Can you discuss the competitive landscape and elaborate on the factors that set your program apart from others?
- As you concluded above, it is a competitive field. Xenon is in the lead with XEN1101 (phase III) followed by Biohaven with BHV-7000 (completed phase I). These are valuable assets. Both companies have a market cap of about USD 2 billion and these assets take a fair share of that.
- We know that XEN1101 has the same selectivity profile as retigabine and we have reasons to believe that this is also the case for BHV-7000. Some companies claim to have selective Kv7.2/7.3 compounds. What they mean is that their compounds don't activate Kv7.1, which would be a no-go as it controls the heart rhythm. As mentioned, we believe that we are the first company that has been able to make compounds which are selective towards Kv7.2 and Kv7.3 only. So, without a doubt, this type of selectivity will be a cornerstone of future epilepsy treatments.
In the press release, you mention that you have experienced great commercial interest in your program. Can you tell us more about the interest you have seen?
- Kv7 is an interesting target for epilepsy, MDD and bipolar disorders. Several companies recognize the potential advantages of our selective profile and can see the upside.
You also mention potential within other brain disorders. Is this something that you plan to explore further?
- We are focusing our internal development on epilepsy but are a CNS company when it comes to partnering.