On Tuesday morning Saniona was able to announce advancements in its Kv7-programme. The company has now concluded the lead optimisation phase and the programme moves into the candidate selection phase. Comparable programmes have put peer companies’ valuations in the billions. BioStock contacted CEO Thomas Feldthus to find out more about the news and the programme.
After one year in the lead optimisation phase, Saniona can now progress its Kv7-programme. This means that the company has initiated the candidate selection phase with a proprietary subtype selective frontrunner molecule from the programme, where the aim is to develop a new treatment for epilepsy.
Sees great potential in epilepsy
Tuesday’s news is yet another step forward for a programme where Saniona sees great potential within the epilepsy area. Epilepsy represents an area of great medical need. Not only is it the most common chronic brain disease in the world, affecting more than 50 million people. There are also no completely curative treatments and today’s symptom-relieving treatments are associated with side effects. Furthermore, only about 30 per cent of patients respond satisfactorily to treatments, meaning that there is a significant group that would benefit from new treatments. Saniona’s aim within the Kv7-programme is to develop just such a treatment.
According to Saniona, the commercial potential of Kv7 epilepsy drugs is illustrated by the fact that peer companies Xenon and Biohaven both working within the Kv7 field, have market capitalisations of around 2 bUSD, to a large extent based on their Kv7 development programmes.
Aiming to develop a new generation of epilepsy treatments
In their quest to improve treatments for epilepsy, scientists are turning their attention to a specific set of channels in the brain called Kv7 channels. These channels regulate the electrical signalling in neurons, preventing the repetitive patterns that can trigger seizures.
Saniona works with a new group of compounds designed to overcome the limitations of previous epilepsy treatments. The company believes that its compound can represent a new generation of effective and well-tolerated epilepsy medicine. What sets these Kv7 activators apart is their enhanced chemical stability and selectivity and mechanism of action. According to the company, these features offer several advantages, including avoiding undesirable effects on bladder tissue that some earlier drugs caused. This is potentially an important breakthrough because traditional Kv7 modulators, while effective against epilepsy, sometimes pose risks of urinary retention. This is a condition that could become life-threatening due to the inability to empty the bladder.
Competitors within Kv7 channels
In the competitive landscape of treating epilepsy through Kv7 channels, Xenon has positioned itself with the acquisition of the compound XEN1101 from 1st Order Pharmaceuticals, advancing 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, completing a phase I study and expressing intentions to initiate a pivotal study.
The importance of Kv7 channels in controlling nerve cell activity underscores their potential significance in addressing epilepsy. The acquisitions within this area also reflect the interest and desire to explore the area further for this indication.
“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” – Thomas Feldthus, CEO Saniona
BioStock contacted Saniona’s CEO Thomas Feldthus for more information about the latest advancement in the programme.
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 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 programme?
– There are about 600,000 patients with focal onset seizures in the U.S. 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 programme. 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.The content of BioStock’s news and analyses is independent but the work of BioStock is to a certain degree financed by life science companies. The above article concerns a company from which BioStock has received financing.