Saniona ended 2023 by selecting SAN2355 as the first clinical candidate from its Kv7 epilepsy program. Having successfully passed critical candidate selection steps and secured a favourable opinion from the European Patent Office, Saniona will now advance SAN2355 into preclinical development. BioStock talked to Saniona’s CEO Thomas Feldthus to learn more about this milestone.

Saniona is focusing on the discovery and development of medicines modulating ion channels. The company’s epilepsy pipeline includes the phase II ready asset SAN711, the preclinical development compound SAN2219 and now also SAN2355 from the Kv7-program.

A new generation of epilepsy treatments

In the pursuit of advancing epilepsy treatments, Saniona and other pharmaceutical companies such as Xenon Pharmaceuticals and Biohaven, are increasingly focusing on Kv7 channels in the brain. Saniona is developing a novel group of compounds designed to surpass limitations of prior treatments with improved stability, selectivity, and mechanism-of-action for enhanced effectiveness and tolerance. Notably, SAN2355 addresses concerns like urinary retention, a potentially life-threatening side effect, and CNS side effects associated with non-selective Kv7 activators. Read more here.

Milestone reached with SAN2355

In November 2023, Saniona announced that it had initiated the candidate selection program with a subtype-selective frontrunner from the Kv7 lead optimization program. Last week, Saniona communicated that the new epilepsy candidate SAN2355 had completed all critical steps in this process and is now ready for preclinical development.

Comments from the CEO

BioStock contacted Saniona’s CEO Thomas Feldthus to learn more about SAN2355 and what he sees as the future for the candidate.

How does SAN2355’s subtype selectivity among Kv7 channels set it apart, and what advantages does it offer in terms of efficacy and tolerability for treating epilepsy compared to non-selective activators?

– The Kv7 channels comprise a family of five members, Kv7.1-Kv7.5.

– SAN2355 is a selective activator of the Kv7.2 and Kv7.3 channels which are localized in the brain and comprise the targets for treatment of epilepsy. We believe that Saniona is the first company, which has been able to produce a compound with this unique profile. We expect that SAN2355 will be more effective than competing pipeline programs because it can be given in higher doses, and we expect that patients will experience less side effects on comparable dose levels.

– All competing pipeline programs appear to be unselective activators of four Kv7 channels, Kv7.2 – Kv7.5, which results in dose limiting side effects and considerable dropouts from the clinical studies. Kv7.4 channels are expressed in various cells in the body including the bladder so activating Kv7.4 may result 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 competing programs in development.

Can you elaborate on the critical steps SAN2355 has successfully passed in the candidate selection process, and what factors contribute to its readiness for preclinical development?

– The candidate selection process comprises a battery of test and analysis, which is designed to de-risk the program and ensure that the lead candidate has drug-like characteristics before initiating expensive preclinical IND/CTA enabling studies. SAN2355 has now successfully passed all these tests which can be divided into:

• In vivo pharmacology (efficacy)
• Drug metabolism, distribution, pharmacokinetics and elimination including human dose estimation
• Safety pharmacology and toxicology (such as AMES test (carcinogenic risk) and hERG screens (negative cardiac effects), off-target screen (other side effect risk) and MTD studies (maximum tolerated dose)
• Preliminary establishment of large-scale manufacture of drug substance and formulation (CMC activities)

– Based on our candidate selection process, we have concluded that SAN2355 represents a clinical candidate with a differentiated pharmacology profile, which potentially offers better seizure control and improved tolerability than competing nonselective Kv7 pipeline programs.

Considering the commercial interest in the Kv7 program, what aspects of SAN2355 will increase its attractiveness, and how do you foresee its potential impact on the epilepsy treatment landscape?

– We see SAN2355 as a second generation of Kv7 activators which may have a significant impact on the treatment modality for patients with resistant focal and generalized seizures as well as paediatric patients with seizures caused by genetic mutations in the Kv7 channels.

Given the withdrawal of the non-selective Kv7 activator retigabine from the market, how does SAN2355 address or mitigate the side effects that led to the withdrawal?

– Retigabine is a non-selective Kv7 activator, which has been withdrawn from the market due to discolouring of the retina and certain other tissues due to unstable and reactive chemistry (aniline-moiety). SAN2355 is a selective Kv7 activator based on novel chemistry without the safety liabilities associated with the aniline-moiety of retigabine and XEN1101, the leading competing pipeline program from Xenon.

What patient populations do you anticipate benefiting most from this new candidate, both in terms of adult and childhood epilepsies?

– Kv7 is a validated target for treatment of adult patients with resistant focal onset seizures. It is a very large market. There are around 1.2 million patients with resistant focal onset seizures in the U.S. and Europe combined. There are no Kv7 drugs on the market today. But there are at least two promising Kv7 candidates in clinical development, which most likely will reach the market several years before the launch of SAN2355. Both compounds are expected to be highly efficacious and obtain peak sales of more than 1 BUSD. However, these drugs are non-selective Kv7 activators.

– A large fraction of patients may stop treatment due to side effects and/or not obtain seizure freedom due to dose limiting toxicity. These patients may be the initial target for SAN2355. In the long term SAN2355 may gain market share in the entire resistant patient population due to better efficacy and improved tolerability.

– Kv7 is also a very relevant target for treatment of many paediatric patients since genetic mutations in the Kv7.2/Kv7.3 channels are among the most common reasons for childhood epilepsy. This market could be wide open for SAN2355. Thus, previous small studies with retigabine in paediatric patients indicate that children are much more sensitive to activation of the Kv7.4 channels than adults leading to severe urinary retention, which was one of the known adverse effects caused by treatment with the unselective drug retigabine in adults. It should be noted that Xenon has recently discontinued development of retigabine for paediatric patients – although for undisclosed reasons.

Finally, what future potential do you see in SAN2355?

– SAN2355 has a clear differentiation to competing pipeline programs and represents a new generation of Kv7 activators for the treatment of resistant adult patients and pediatric patients with genetic mutations in the Kv7 channels. Each market segment represents a billion-dollar market opportunity.

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