Saniona has announced that the company is on the cusp of advancing its Kv7 programme for epilepsy to lead optimisation, which is the final phase of drug discovery before a clinical candidate is selected. BioStock reached out to CEO Thomas Feldthus to learn more about this new programme.

With more than 50 million affected worldwide and with five million new diagnosed cases each year, epilepsy is one of the most severe neurological diseases.

Epilepsy can be hereditary, but it can also be caused by brain damage associated with birth, severe head injuries, stroke, infections of the brain or brain tumours.  However, in about half of the cases, the cause is unknown. Today’s symptom-relieving treatments often lead to side effects and completely curative treatments are still lacking. In addition, only about 30 per cent of patients respond satisfactory to treatment with conventional medicines, which means that there is a great medical need.

Saniona’s Kv7 epilepsy programme

Most current antiepileptic treatment principles rely on regulation of ion channel activity and Kv7 channels in particular are highly relevant targets. Kv7 ion channels are potassium channels that play a critical role in brain function by inhibiting the repetitive electrical signalling of neurons, something that can potentially lead to seizure activity. The special importance of Kv7 channels in epilepsy is illustrated by the increasing numbers of mutations in the subtypes Kv7.2 and Kv7.3 that are found to be associated with severe inherited forms of epilepsy.

Danish biotech Saniona has now progressed into the lead optimisation stage of drug development with a new family of compounds that circumvent the limitations of first-generation drug candidates. The central properties of the new Kv7 activators are improved chemical stability, as well as differentiated selectivity and mechanism of action, which, according to the company, among other benefits can limit or eliminate the relaxing effect on bladder tissue. This is important because Kv7 modulators for the treatment of epilepsy in other cases risk leading to urinary retention, that is, an inability to empty the bladder, which is a potentially life-threatening condition.

The area commands a high value

An interesting reference to Saniona’s focus on Kv7.2 and Kv7.3 is Valiant/GSK who commercialised ezogabine(retigabine) for epilepsy just over a decade ago, based on a demonstrated strong antiepileptic effect. However, the drug was subsequently withdrawn due to skin discoloration and urinary retention. A much more recent reference is Biohaven Pharmaceuticals, which, in February 2022, acquired Channel Bioscience’s preclinical stage Kv7 ion channel programme for the treatment of epilepsy. The agreement shows that Kv7.2 and Kv7.3 are still considered highly relevant targets for drug development in epilepsy, and that the area has a high value.

The agreement entails an upfront payment of 35 MUSD along with 65 MUSD in BioHaven shares, as well as 325 MUSD if the drug receives marketing authorisation in the US, EU and Japan. An additional 250 MUSD can be paid if the drug receives marketing authorisation in more countries and in more indications.

Now, Saniona’s goal with the lead optimisation programme, is to develop a second generation of Kv7 drugs that can avoid the limitations and tolerability problems that have hampered previous drug candidates so severely.

»You should expect a heavy news flow from Saniona over the next few months« — Thomas Feldthus, CEO Saniona

Comments from the CEO

BioStock reached out to Thomas Feldthus for a comment.

Thomas, what makes the field of epilepsy so interesting for drug development from Saniona’s perspective?

– Firstly, the commercial potential is extensive and so is the medical need. Judging by recently concluded agreements in the Kv7 area, we have identified an opportunity to bring a new innovative treatment to patients that can overcome the problems that characterise today’s treatment options. Based on the data we have accumulated during the years, we have seen that we have a potential solution in developing the next generation of drug candidates of this class. In summary, vi see a significant potential to develop a new ground-breaking epilepsy treatment.

– Saniona has over the past years established a strong network with national and international epilepsy centers of excellence where tremendous progress has been made to identify specific genetic links between mutations in ion channels and development of epilepsies. Our deep knowledge about ion channels and our track record in identifying and developing new drug candidates in this field puts Saniona in a unique position to exploit and develop new treatment principles in both genetic and other epilepsies with large unmet medical need.

Can you talk about the Kv7 approach?

– The antiepileptic concept of Kv7 activation has been validated as an effective clinical target, but still there are no drugs of this class on the market. A chemically stable compound that preserves the strong antiepileptic effect, avoids relaxation of the bladder and limits CNS side effects could make a real difference in the lives of these patients. Urinary retention due to strong bladder relaxation can be a life-threatening condition that we really want to avoid. In my opinion, an optimised candidate from our new Kv7 program has a good shot at meeting the medical needs in difficult-to-treat patients, even when it comes to treatment-resistant partial epilepsy and epilepsy in children conditioned by mutations in Kv7.

What will be the road forward in this programme?

– We have now narrowed down our chemical space of hundreds of compounds to a single specific chemical scaffold that we believe will be able to deliver a clinical candidate within the next 1–2 years. This Lead Optimization Phase of our Kv7 program will involve detailed characterization of each potential drug candidate to enable us to select the most feasible candidate drug to move forward towards the clinic.

Finally, what is on the agenda for Saniona during the rest of 2022?

– We have a strong focus on partnering programs both from our clinical pipeline as well as our early- stage pipeline. I strongly believe that we will be able to conclude our first deal within a few months.

So far, we have not informed the market much about the preclinical programs but over the next few months we intend to roll out more detailed information about these, as we reach important preclinical milestones on the programs.

– So, you should expect a heavy news flow from Saniona over the next few months.