The main focus of this series is to highlight the progress being made in ion channel clinical drug development, which is a key validation parameter for target selection along with other considerations such as human genetic data, cryo-EM structures for drug design, availability of relevant animal and iPSC models, and medical and commercial drivers in each therapeutic indication. I’d like these discussions to help overcome perceptions that ion channels are ‘difficult’ drug discovery targets, and the tendency for historical failures to get blamed on the target class rather than the discovery process itself. We all know that drug discovery is a tortuous and expensive journey regardless of target or modality, so it is important to recognise the successes (and learn from the pitfalls) of ion channel modulators reaching clinical trials.

It was another relatively quiet but largely positive quarter of news in Q1 2026 for ion channel clinical drug discovery, with a slew of promising updates from a diverse set of peripheral and CNS programs, and numerous moderate licensing deals and company funding rounds.

The strong commercial news continues in Q1 2026 for neuroscience ion channel programs in pain, epilepsy and depression. In the CNS arena there were two hugely successful public share offerings for Xenon ($747.5 million) and Praxis Precision Medicines ($575 million) to help progress their headline epilepsy and other neuropsychiatry programs. Other CNS financial news included Rapport signing a Chinese licensing deal for their anti-convulsant RAP-219, and Angelini Pharma (EU) opting into the Nav1.x ASO expertise of US biotech Quiver Bioscience to develop novel DEE anti-epileptics. In Japan Shionogi paid $100 million to take back complete control of P2X3 antagonist sivopixant, previously tested in chronic cough but which is now being developed for sleep apnea. EU pharma Newron raised €38 million to help progress their global Ph III trials of evenamide in schizophrenia, and US company Gilgamesh Pharma raised $60 million for neuropsychiatric programs including NMDA-R modulator blixeprodil in Ph III trials for depression, and French biotech Sensorion raised €60 million to support their portfolio of hearing loss gene therapies and 5-HT3 small molecule modulator SENS-401. There were also smaller MJFF Parkinson’s grants to Casma Therapeutics for their lysosomal TRPML1 CSM-101 program and Lario Therapeutics who are developing modulators for Cav1.3 and Cav2.3 channels. In the peripheral ion channel field new Aussie biotech xCystence Bio announced pre-seed funding for a chronic kidney disease project targeting TRPP channels, and Welsh biotech Antiverse closed a small Series A round that includes support for work on CFTR respiratory channels. Dogwood Therapeutics (ex-Wex Pharma) announced a moderate  investment of $12.5 million primarily to support mid-stage clinical studies of non-opioid analgesic candidate Halneuron (injectable TTX formulation to block Nav1.x channels including Nav1.7) currently in a Ph IIb trial for CIPN, and lastly there also additional $93 million Series B extension funding for Nocion to support their ongoing Ph II trial of NOC-110 (taplucainium) for chronic cough.

In the peripheral disease indication section there are generally positive updates on a range of cardiac, respiratory, renal and pain ion channel programs. Two slowly progressing cardiac programs shared updates in Q1 2026, with Aussie biotech Infensa Bio finally starting Ph I dosing of their ASIC1a peptide IB409 designed to treat ischemia and stroke, and Danish biotech Acesion Pharma starting Ph II dosing of their follow-up SK blocker AP31969 for atrial fibrillation. In contrast Danish company NMD Pharma had to weather mixed topline news from a Ph IIa trial of muscle CLC-1 blocker NMD670 in patients with Charcot-Marie-Tooth disease type 1/2, which missed its primary endpoint but improved secondary measures. There was also mixed news for CFTR respiratory gene therapy programs in Q1 2026, with Krystal Bio and SpliSense both reporting positive results for their mid-stage gene replacement and RNAi ligands, respectively, but Boehringer Ingelheim halted work after disappointing early efficacy data in a Ph I/II trial of their lentivirus CFTR gene replacement therapy BI 3720931. Two good and one bad also for several kidney disease ion channel programs this quarter. Boehringer Ingelheim had Ph II success for follow-up TRPC6 inhibitor BI 764198 (apecotrep) in patients with FSGS, triggering a Ph III campaign alongside ongoing Ph II trials in other forms of proteinuric kidney disease. I mentioned Maze Therapeutics in my last blog, and this quarter they announced promising topline results from a small Ph IIa trial of APOL1 channel inhibitor MZE829 in patients with genetically-defined chronic kidney disease, with highest responder rates in those with FSGS. In contrast a Ph II study of ICrac inhibitor Auxora by US biotech CalciMedica in patients with acute kidney disease was halted early due to lack of any therapeutic index and some safety signals. Better news for German biotech Acousia Therapeutics who finally completed enrolment of a Ph IIa trial of Kv7.4 activator ACOU085 that first opened in Q1 2024, targeting young male testicular cancer patients at risk of cisplatin ototoxic hearing loss. Finally, just two updates in the pain field, with Grunenthal starting a Ph Ib trial of their new Nav1.8 inhibitor in a catch-up with more advanced players like Vertex, Latigo and Eli Lilly/SiteOne, and AlzeCure Pharma gaining another rare disease indication for TRPV1 antagonist ACD440, a topical gel targeting neuropathic pain patients and those with erythromelalgia.

This was a relatively quiet but overwhelmingly positive quarter for news from CNS players working on epilepsy, depression, neurodegeneration and other neuropsychiatric indications. The repeat entrants working on ion channel modulators for epilepsy made an appearance again, with Praxis receiving a PDUFA date of Sept 27th 2026 for FDA review of Nav1.x inhibitor Relutrigine (PRAX-562) in DEE, Encoded Tx receiving breakthrough therapy status for their Ph II Nav1.1 gene therapy ETX101 in Dravet epilepsy, and Stoke Tx also making progress in Dravet with their Nav1.1 ASO Zorevunersen starting a Ph III study after publication of very promising Ph II results in the NEJM this quarter.  Both clinical epilepsy Kv7.x programs also progressed this quarter, as Xenon released positive topline Ph III data on Azetukalner in focal onset seizure patients, and while Biohaven slowed down work on Opakalim (BHV-7000) in generalised epilepsy they committed  resources to finishing a Ph II/III study in focal onset seizures. Gilgamesh Pharma also released generally positive topline results for NMDA-R antagonist GM-1020 (Blixeprodil) being tested in a Ph IIa trial for major depression, and the 1st of many lysosomal ion channel modulators designed to treat Parkinson’s disease is on the verge of reaching the clinic with Lysoway Tx gaining approval for TRPML1 agonist LW-1017 in Ph I testing in Australia. Also starting Ph I trials are Ovid Tx who advanced their KCC2 transporter activator OV4071 into clinical testing for dementia-related psychosis, while UK biotech Monument Tx started a Ph II trial of nAChR ligand MT1988 for schizophrenia-linked psychosis. More advanced are GRIN Tx who started Ph III dosing of NMDA NAM Radiprodil in young patients with GRIN 2B gene-related neurodevelopmental disorders. Finally, Praxis received a PDUFA date of January 29th 2027 for Cav3.x blocker Ulixacaltamide (PRAX-944) which eventually aced Ph III trials in Essential Tremor after a few years of rocky progress, potentially becoming the company’s 2nd approved ion channel drug.

1.      Peripheral disease indications

a.     Cardiac and skeletal muscle

I’ve been waiting for this news from Aussie biotech Infensa Bioscience for some time, and they have finally completed preclinical development, CMC work and regulatory requirements and started the first-in-man Ph I clinical trial of their optimised ASIC1 channel toxin peptide IB409. The original toxin hit Hi1a was discovered in the venom of a funnel web spider from K’gari (Fraser Island) off the coast of Queensland and several more drug-like peptide analogues have been designed over recent years. Rather than being developed for pain, this program was targeted against (acid) activation of ASIC1 channels in cardiac ischemia & stroke to reduce the acute tissue damage and chronic remodelling of heart attacks.

Also making good but slow progress in cardiac ion channel drug discovery are Danish biotech Acesion Pharma, who announced the start of a Ph II trial of their latest SK blocker AP31969 for atrial fibrillation (AF). The company started off several years ago with an i.v. formulation of an earlier analogue AP30663 for acute AF cardioversion, which aced a Ph II trial back in 2023 showing equivalent efficacy to electrical or less specific chemical conversion, but also slowing ECG QTc as it exhibited some inhibition of hERG channels. The follow-on program developed more selective analogues suitable for oral administration, culminating in a successful Ph I trial in 2025 with little sign of QTC effects. The new Ph II trial will enrol 200 patients in the EU and is designed to monitor reductions in AF burden without increases in ventricular pro-arrythmia, and is expected to complete by Q1 2027.

In contrast, there was mixed topline news for NMD Pharma from a short exploratory Ph IIa study of the muscle Cl- channel inhibitor NMD670 (now called ignaseclant) in a small cohort of patients with type 1 or 2 Charcot-Marie-Tooth disease. While the company highlighted ‘consistent and clinically meaningful improvements’ in secondary endpoints of muscle strength, motor function and patient outcomes that occurred rapidly and lasted beyond dosing, industry writers noted that it missed the primary endpoint (walk test). Overall the results are promising enough over a short-term dosing period to warrant further Ph II studies with more prolonged dosing, alongside ongoing mid-stage trials of NMD670 in myasthenia gravis and SMA that I covered previously in 2024 and 2025.

b. Respiratory disease

There were two good and one bad program update in the field of CFTR gene therapy drug discovery this quarter. Starting with the positive, Krystal Biotech revealed positive results from their early efficacy Ph Ib study of CFTR gene replacement therapy KB407, which is mutation-agnostic and designed to treat many different types of CF patients regardless of their genotype (i.e. many who are ineligible for Vertex CFTR corrector and potentiator drug combos). The inhalable and re-dosable drug uses a modified herpes virus to deliver full-length native CFTR gene direct to the lung, with the highest dose producing 30-40% protein expression in lung tissue biopsies after a single day of repeat dosing. The company is taking this data to the FDA for discussions on finalising a registrational Ph III repeat dosing trial design, with hopes it can start enrolling patients in Q2 2026. Good news for Israeli biotech SpliSense as well whose own CFTR gene therapy was granted e-PRIME designation by the EMEA which will facilitate their plans for a global Ph IIb testing campaign in the EU and US later this year. SPL84 is an inhalable RNAi antisense oligonucleotide designed to correct splicing defects in the CFTR gene found in CF patients with the 3849+10Kb C>T mutation. Their Q3 2025 Ph II results showed marked and clinically meaningful lung function improvements in ~70% of CF patients.

Not such great news in contrast for Boehringer Ingelheim who decided to stop work on their one-and done CFTR gene therapy drug candidate BI 3720931 after a disappointing small Ph I/II trial. The inhaled lentivirus DNA vector was designed to deliver a full length copy of the CFTR gene directly into lung airway epithelial cells, but a small study carried out in the UK during 2025 failed to show sufficient efficacy (lung ejection volume) after 8 weeks at any of three dosing levels to warrant further development. The Fierce Biotech article noted similar setbacks for other CFTR mRNA gene therapies in 2025, including a failed Ph II trial for Arcturus Therapeutics and pausing of a Ph I/II trial of VX-522 (Vertex asset partnered from Moderna), although other doses in the MAD study will be completed and results are expected in 2H 2026.  However, there are still plenty of new drug options on the horizon for CF patients in addition to the positive gene therapy programs discussed above, including small molecule CFTR correctors and potentiators from Sionna Therapeutics that I covered previously, and recent news that the small molecule ENaC modulator from Enterprise Therapeutics had delivered positive results in a Ph II CF trial (more on that in my Q2 2026 update).

c. Other peripheral indications

It’s been awhile since I mentioned German biotech Acousia Therapeutics as it has taken them a long time to progress their early stage Kv7.4 activator for hearing loss, but this quarter they finally completed enrolment in the crucial Ph IIa trial. The Ph II process started way back in Q1 2024 (after a Ph I completed in Q4 2022), looking to enrol young male patients with metastatic testicular cancer who are undergoing cisplatin-based chemotherapy as this can result in ototoxic hearing loss which the company hopes can be reduced or prevented by ACOU085 (now called Bimokalner). Topline data is expected by the end of Q1 2026, but there is no update on the company website as I write this in Q2…

Now we switch to mixed news from several kidney ion channel clinical drug discovery programs. I recently reviewed the role of various renal ion channels in human disease for my preclinical blog series for Nanion Technologies, and mid-stage programs for some of those targets were in the news this quarter. Upregulation of TRPC6 and gain-of-function mutations linked to kidney disease has prompted keen industry interest over the last 15 years (GSK, Sanofi-Aventis, Novartis, Goldfinch Bio), but the last remaining active TRPC6 renal program seems to be at Boehringer Ingelheim who published on a potent and selective inhibitor BI 749327 in 2019, and this quarter revealed positive results from a Ph II study of the next generation antagonist BI 764198. Now called Apecotrep, the drug candidate reduced proteinuria by up to 40% in a 12 week trial in patients with primary focal segmental glomerulosclerosis (FSGS), but rather paradoxically there was an inverse dose-response with the 20 mg dose producing the best results. The overall efficacy (e.g. %responders vs placebo) and tolerability have convinced the company to start a Ph III trial in ~300 FSGS patients which is expected to conclude in late 2029, but the dose(s) in this study have not yet been revealed. The company is also advancing Apecotrep into additional Ph II studies this quarter, testing it in patients with other proteinuric kidney diseases such as secondary FSGS and Alport syndrome. While there is no approved treatment yet for FSGS despite it leading to chronic kidney disease requiring dialysis or organ transplant, the therapeutic space is quite busy and several of the previous TRPC6 players mentioned above are pursuing mid- and late-stage trials of agents targeting different disease proteins and pathways.

The other renal ion channel showing success in the clinic is APOL1, with Vertex’s Inaxaplin (VX-147) now in Ph II/III studies as I covered in my Q2 204 blog. Following close behind are Maze Therapeutics, who this quarter announced that their small molecule drug candidate MZE829 had also shown promising results in a Ph II trial in patients with genetically-defined APOL1-mediated kidney disease (AMKD), reducing proteinuria by 36%. Despite this result beating the company’s efficacy expectations, the response from industry experts and investors was decidedly mixed, perhaps as the average value fell below the 40-48% reduction in proteinuria seen with Apecotrep (TRPC6) and Inaxaplin (APOL1) in their recent mid-stage trials. The Ph IIa open label study was also very small with only with 12 patients enrolled, but interestingly there was a marked difference in efficacy across phenotypes, with a much larger 62% reduction in proteinuria in the handful of patients with FSGS (also tested in studies by Boehringer and Vertex) compared to those with diabetic nephropathy. Full results from the ongoing Ph IIa study will be released later this year, which should hopefully firm up its prospects (and selected patient populations) for late stage testing.

More concerning was the early termination of a Ph II acute kidney disease trial being run by CalciMedica for their ICrac ligand Auxora (CM4620), over safety concerns. ICrac channels (Orai/Stim subunit complex) are classically linked to store-operated Ca2+ entry (SOCE) and have been a target for auto-immunity drug discovery programs as they control the function and proliferation of T-cells and other immune cell types, something that CalciMedica had been working on last decade. The company had also been looking at the role of ICrac channel modulation by Auxora in Covid-19 pneumonia and pancreatitis, but this work in kidney disease was news to me. Other ICrac modulators (CM5480, CM6336) are in preclinical studies for pulmonary arterial hypertension, rheumatoid arthritis, ulcerative colitis and allergic asthma. This is a lot of ongoing work for a company seemingly running on fumes, as their Q3 2025 financial results showed only $14 million in the bank and a predicted cash runway to 2H 2026, so I hope they can salvage something positive from their long-running work on this target.

d.      Pain

A surprisingly short section this quarter on analgesia clinical programs, starting with news that Grunenthal have finally brought a Nav1.8 compound to the clinic by starting a Ph Ib trial. This will be a relatively large 70 patient SAD and MAD study, with analgesia assayed through  application of a cold-pressor test (as Nav1.8 channels are notably more active than other isoforms at lower temperatures). The company has been filing patents on their Nav1.8 program over the last few years, and also published a preclinical discovery paper on a urea-derived scaffold in early Q2 2026 (here) that looks quite promising in terms of selectivity, PK and drug-like properties, but you can never be certain if such public disclosures mean the program is now dead or might in fact be progressing into the clinic, so great to see it was the latter.

I’ll finish with a quick update on a TRPV1 program, which might surprise some people as this target definitely fell out of favour in the 2010s as systemic small molecule dosing produced serious on-target side-effects that stalled a lot of clinical analgesia programs. There are still a handful of companies working on various TRPV1 ligands (small molecule inhibitors, desensitising agonists, topicals and injectables) designed to avoid systemic exposure, including AlzeCure Pharma who are developing an old antagonist ACD440 as a topical treatment for neuropathic pain. After positive Ph II results in 2023 the company has pursued a number of rare disease indications, and this quarter received EMA Orphan Drug Designation for treating erythromelalgia, after receiving a similar designation from the FDA in 2025.

2.      CNS disease indications

a.     Epilepsy

A little less news this quarter from the usual players on the epilepsy Nav1.x and Kv7.x ion channel front, but all generally very positive. Indeed, as I predicted in Q4 2025 one of Praxis Precision Medicine’s Nav1.x blockers, namely Relutrigine, has received a PDUFA date from the FDA of Sept 27th 2026 so could be their first ever approved drug (chapeau Praxons!), and one of several new ion channel modulators that may get approved this year if all goes well. Relutrigine (PRAX-562) is a non-selective Nav1.x inhibitor with a preference to block persistent currents which aced a Ph II study in genetically-screened patients with Developmental and Epileptic Encephalopathies (DEEs) who carry mutations in Nav1,2 or Nav1.6 channels and is still being tested in another Ph II study of a broader DEE population that is expected to report topline data by the end of 2026, which could pave the way for another NDA submission to the FDA in 2027.

Encoded Therapeutics are also accelerating their clinical development timelines on the back of the FDA granting Breakthrough Therapy status to their Nav1.1 AAV gene therapy ETX101 for rare Dravet Syndrome epilepsy. Ongoing discussions with the FDA are firming up plans for a small but pivotal Ph II study in young patients with loss-of-function variants in the SCN1A gene, alongside expansion of an ongoing Ph I/II open label study in older patients, which will hopefully enable a Biological License Application (BLA). The Ph II study is now underway, recruiting up to 30 infants <4 years old to receive a single one-and-done dose of ETX101 or placebo followed by monitoring of seizure frequency and cognition for up to 52 weeks.

Similarly, Stoke Therapeutics are accelerating the clinical development timelines for their Nav1.1 Dravet epilepsy ASO program after publishing positive data from a Ph I/II open label extension study in the NEJM this quarter. Zorevunersen produced an astounding reduction in seizures in young patients (2-18 years) by up to 91% after repeat dosing every 2-4 months over 2 years. A Ph III study is now enrolling in the US and Japan aiming to recruit up to 150 patients by Q2 2026 and initial data readout in mid-2027 (similar to the timelines for Encoded Tx), which will enable an NDA to the FDA next year. These are definitely exciting times for Dravet epilepsy ion channel clinical development, as detailed in this nice background article from Fierce Biotech.

Xenon also continue to make good progress with their Kv7.x activator Azetukalner anti-convulsant (XEN1101), releasing positive topline data from a Ph III trial in patients with focal onset seizures (FOS) in March. The top dose of 25 mg produced a highly significant 53% reduction in seizure frequency after 12 weeks that exceeded the 35% reduction seen in the Ph II trial, compared to placebo response rates of ~10% in both studies. However, there was also a dose-dependent increase in side-effects with 15% of patients withdrawing from the top dose group, so focus is now on the lower dose of 15 mg which still produced a decent 35% reduction in seizure frequency vs a 4.5% withdrawal rate. This exceeds the company and investor expectation of a 30% reduction in seizures, so plans are being made to submit an NDA to the FDA in Q3 2026, which like Praxis’s Relutrigine would be the company’s 1st approved drug, and another ion channel drug success story in epilepsy. Additional Ph III studies of Azetukalner in FOS (for registration outside of the USA, especially Japan) and in primary generalized tonic-clonic seizures are well underway and continue to recruit patients.

Following close behind Xenon are Biohaven with their own Kv7.2/3 activator Opakalim (BHV-7000) which is also currently in Ph III trials for generalised and focal epilepsy, with both companies also testing their ligands in depression (and both seeing setbacks on that front in 2025). More peculiar was the news this quarter that Biohaven are seemingly moving away from their CNS focus on the back of the FDA rejection of troriluzole in spinocerebellar ataxia, and making high profile announcements of a pivot towards the red-hot area of obesity (driven by the 2022 acquisition of the myostatin-targeting protein BMS-986089/BHV-2000 from BMS). I was concerned about the prospects for Opakalim, and indeed the company stated that they were going to ‘pare down’ the Ph II/III study in generalised epilepsy (does this mean early termination or reduced patient enrolment?), but will thankfully maintain R&D support for a similar study in adult focal onset epilepsy that is expected to provide a quicker readout before the end of 2026.

b.     Depression

Also just one short item in this section for Q1 2026, with news that Gilgamesh Pharma have released positive topline data from a Ph IIa trial of their NMDA antagonist GM-1020 in major depressive disorder (MDD). Now called Blixeprodil, the small molecule ligand produced rapid (within 24 hours of a single oral dose), robust and long-lasting (beyond 28 days after treatment ceased) reductions in depression scores (significant 6 point reduction compared to placebo, which is pretty good by all accounts). The drug is dosed twice weekly and was safe and well tolerated, although there appears to be some residual effect of the initial dose so analysis of later time points was not statistically significant, and there was no difference between doses of 140 or 210 mg. Follow-on late stage studies will need to sort out this dosing issue, but the combination of rapid and safe long-lasting effect positions it as an at-home oral competitor to psychedelic anti-depressant treatments that may require injection and medical oversight. And speaking of psychedelics, it is important to note that the new company is a ‘spin-out’ of various assets from Gilgamesh Pharmaceutical after their clinical psilocybin analogue Bretisilocin was bought by AbbVie for $1.2 billion in 2025.

c.     Neurodegeneration

Just one item this quarter but it is a significant one: In the face of numerous preclinical and some IND-stage neurodegeneration drug discovery programs focused on lysosomal TMEM175 and TRPML1 ion channels, one company has now brought a ligand to clinical trials. Cambridge (US) biotech Lysoway Therapeutics announced in January that they are ready to start Ph I testing of their TRPML1 agonist LW-1017, with a trial approved in Australia that will start in May. The company has moved quickly and leanly since founding in 2020 and raising $22 million in a Series A round in 2022, beating several other companies to the clinical trial start line, such as early leader Libra Therapeutics who presented preclinical data on their TRPML1 program back in Feb 2024 at the Biophysics conference satellite meeting, and Genentech who did the same this year on their TMEM175 program.

d.     Other CNS indications

Four items in the ‘mixed bag’ category this quarter and all are positive, so once again things are looking good for CNS drug discovery when it comes to ion channels.

First up are GRIN Therapeutics who announced the start of Ph III dosing of the repurposed NMDA NAM radiprodil in young patients with GRIN-related neurodevelopmental disorder. Radiprodil maintains efficacy to inhibit excessive glutamatergic neurotransmission in patients with gain-of-function of the GluN 2B subunit of excitatory NMDA-Rs  produced by missense mutations in the GRIN2B gene. Radiprodil was originally discovered at Gedeon Richter in Hungary and developed as a clinical analgesic with Forest Labs in the 2000’s but development stalled due to lack of efficacy, before preclinical and early stage clinical trials in specific forms of epilepsy and infantile spasms that eventually lead to work in neurodevelopmental genetic disorders. GRIN Tx took over this work with a Ph Ib trial in GRIN-NDD patients in 2023; the drug is also being tested in Ph Ib/II trials in tuberous sclerosis complex and focal cortical dysplasia type II which started in Oct 2024. GRIN Tx is the first subsidiary company spun-out by the Neurvati Neuroscience investment and portfolio company. Created in 2021, the company is very well funded, with a recent Series D round raising $140 million in May 2025 that included $65 million from Angelini Pharma for non-US rights to radiprodil.

UK biotech Monument Therapeutics continues to make good progress with MT1988, a mixture of nAChR and 5-HT3 ionotropic receptor ligands Varenicline and Tropisetron, starting a Ph II trial in patients with a clinical risk of psychosis, such as those with schizophrenia. The ligand was selected for this clinical trial as part of a competition being run by the Accelerating Medicines Partnership-Schizophrenia program, which is a public-private partnership between NIH and FDA in the US and EMA in Europe, as well as pharma and life science companies, non-profits and other organizations. I covered MT1988 previously, notably it’s positive results in previous Ph II trials to improve cognition in patients with ADHD and schizophrenia.

New York biotech Ovid Therapeutics make their first entry into this blog series after they get approval to start a Ph I trial of the oral KCC2 activator OV4071, slated for Q2 in Australia. KCC2 is a neuronal K-Cl co-transporter that helps regulate Cl- ion distribution and membrane excitability, and OV4071 is initially being tested in psychosis associated with Parkinson’s disease and Lewy body dementia, but may have utility for other neuropsychiatric indications. The company also tested an i.v. formulation of a KCC2 modulator OV350, which reported positive Ph Ib results in Dec 2025 that included EEG biomarker data showing target engagement and modulation of GABAergic inhibitory tone in the brain, which might be useful for hospital treatment of seizures and psychosis.

Role of KCC2 K+-Cl- co-transporter in setting neuronal Cl- ion concentration and excitability Schematic taken from Ovid Tx website (https://ovidrx.com/our-science/programs/ov4071/)

The company also announced a $54 million private sale of shares and Series A warrants after the approval of Ph I testing of OV4071, further extending the company’s cash runway into 2029. Their website includes a lot of scientific publications, including a 2023 Cell article notable for the number of authors from AstraZeneca, so I dug a bit deeper and discovered that Ovid had signed a ‘strategic licensing and collaboration partnership’ with AZ in late 2021 that allowed exclusive access to a library of small molecule KCC2 modulators that had been discovered in a screen carried out by AZ and Tufts University researchers (but which were languishing when the pharma pivoted away from neuroscience). Financial terms were moderate, with AZ being paid $5 million upfront and receiving $7.5 million in Ovid stock to create the deal, and due $8 million in development and $45 million in regulatory milestones and ultimately up to $150 million in commercial payments plus sales royalties if a drug gets to market. Ovid are responsible all development and commercialization activities, and seem to be making good progress in getting a follow-up compound into Ph I trials within 5 years of signing the initial deal for some HTS hits.

Finally, a brief update on the Cav3.x blocker Ulixacaltamide (PRAX-944) which Praxis Precision Medicines have been assiduously developing as a novel treatment for Essential Tremor. I recently covered the eventual success of this long-running drug saga when two Ph III trials eventually completed with positive outcomes in Q4 2025, and now Fierce Pharma has a nice backgrounder article on this story (#7). Two things of note, the first being that following granting of Breakthrough Therapy for Essential Tremor by the FDA at the end of 2025 that the company filed an NDA in Q1 2026, which has now been accepted by the FDA. I was surprised and a little disappointed to see that the PDUFA date is Jan 29th 2027, as I had expected that Ulixacaltamide might be one of several ion channel neurology drugs approved from Praxis this year – and Fierce thought the same as they tipped it as a ‘Top 10’ potential drug approval for 2026 early in Q1 before the final FDA notice was published.  Annual sales are projected to reach $1 billion or more in coming years as there are around 10 million potential patients in the US alone, and only beta blockers are approved to treat Essential Tremor.

3.      Ion channel company financial news (funding, M&A, licensing deals, collaborations)

Following on from the strong commercial news in Q4 2025 for a number of neuroscience ion channel programs in pain, epilepsy and depression, the same trend continues in Q1 2026 to include funding and licensing deals for Cav (Lario) and AMPA modulators (Rapport) and other CNS ion channel targets for epilepsy, depression, neurodegeneration, neuropsychiatry and sleep disorders (Newron, Gilgamesh, Angelini, Casma, Shionogi). There were also two hugely successful public share offerings for major CNS players Xenon and Praxis in this quarter. In the peripheral ion channel field an Aussie biotech announced pre-seed funding for a chronic kidney disease project targeting TRPP channels, and a Welsh biotech closed a small Series A round that includes support for work on CFTR respiratory channels. There was also additional funding for Nav1.x pain and cough assets (Dogwood and Nocion).

Focusing first on the numerous neuroscience commercial news items, we can start in the periphery with Dogwood Therapeutics (ex-Wex Pharma) who announced a moderate  investment of $12.5 million, primarily to support mid-stage clinical studies of their non-opioid analgesic candidate Halneuron (injectable TTX formulation to block Nav1.x channels including Nav1.7). It is currently in a Ph IIb trial for chemotherapy-induced peripheral neuropathy (CIPN) and yielded positive interim results in late 2025, with full results expected in Q3 2026. Nocion are also working on non-selective Nav1.x channel inhibitors, and while there is potential for these as novel analgesics the company has initially focused on chronic cough (partly due to coming online during the covid-19 pandemic). A large Ph II trial of NOC-110 (taplucainium) is still ongoing, and many perhaps don’t realise just how big and drawn-out this exercise is to recruit and treat ~450 participants across multiple international sites; topline data is expected in August 2026. All this has taken time and expended considerable resources, so it was good news when the company announced a decent Series B extension funding round of $93 million in Q1 2026 to support all of this work.

Not to throw any shade on the news items above, but I should probably lead off the CNS section with the two big funding rounds in Q1 2026. Xenon has been active in ion channel drug development over the last 20 years, and are now finally on the cusp of getting their first drug approved given the excellent progress of their Kv7.x opener Azetukalner in Ph III trials for focal onset epilepsy. The company announced the public share offering in March with a guide value of $650 million but the upsized offering eventually closed with $747.5 million in the bank, which will be used for their many preclinical and clinical ion channel programs in pain and neuropsychiatry. Similarly, Praxis Precision Medicines announced a follow-on public share offering in January valued at $575 million in Q1, to bankroll their many mid- and late-stage and advanced preclinical small molecule and genetic therapies for both rare and more common CNS ailments such as DEE and epilepsy, two of which are lining up for possible FDA approval in late 2026 (Nav1.2/1.6 blocker PRAX-562/Relutrigine for DEE) and early 2027 (Cav3.x blocker PRAX-944/Ulixacaltamide in Essential Tremor).

Also working on epilepsy are Rapport Therapeutics, whose AMPA Tarp-binding NAM RAP-219 showed promising efficacy in a Ph IIa trial back in Q4 2025. The company announced this quarter that they had signed a licensing deal with Tenacia Biotechnology for exclusive commercial rights to the drug in China for focal onset and primary generalized tonic-clonic seizures, in a deal including $20 million upfront and up to $308 million in development and commercial milestones, with additional sales royalties once approved and on sale. Ph III trials of RAP-219 in focal onset seizures are planned for later in 2026 which will include sites in both the US and China.

A less specific epilepsy licensing deal was also signed this quarter between Quiver Bioscience in the US (previously Q-State Bioscience) and Angelini Pharma in Italy. Quiver have been utilising an optical neuronal electrophysiology platform to develop Nav1.7 and Nav1.8 blockers (ASOs and small molecules) for pain, but this technology is presumably amenable to studying CNS disease processes and Angelini have signed up for exclusive rights to drug targets for genetically-defined epilepsies (e.g. DEE). One might imagine these could be the same Nav1.2 and Nav1.6 channels that Praxis are working on in DEE, but could also include ionotropic receptors that Angelini are more familiar with from their work with GABA-A anti-convulsant Cenobamate (Xcopri in US, Ontozry in EU). The upfront payment was not disclosed but Quiver will receive ongoing R&D support and downstream preclinical success milestones, as well as being eligible for additional milestones payments up to $120 million, as well as additional royalties after selection of specific drug targets identified during the collaboration.

I’ve covered the previous Ph II and ongoing and very extensive global Ph III trials that Newron Pharma are carrying out with their mixed Nav-GluR modulator Evenamide in schizophrenia, which is no doubt proving very expensive. So it was positive to read that the company had received €38 million in new funding in a share offering to existing and new investors in February; this includes €15 million upfront followed by the possibility of another €11 million in clinical development milestones, and a final €12 million if the 12 week Ph III trial is successful (readout expected in late 2026).

Another neuropsychiatric ion channel player also announced funding in Q1 2026, with Gilgamesh Pharma raising $60 million in a Series A round to help develop their NMDA-R  antagonist blixeprodil (GM-1020) which aced a Ph II trial in depression in 2025, along with other CNS programs. The company spun-out and renamed itself after Abbvie acquired their 5-HT psychedelic clinical program (bretisilocin) for $1.2 billion in August 2025, which I covered previously.

French biotech Sensorion also announced new funding of €60 million, which includes €20 million from French pharma Sanofi and the remainder from existing investors. The company is on my list of ion channel players as they are testing an ionotropic 5-HT3 modulator SENS-401 for sensorineural hearing loss, with a Ph II readout in cisplatin-induced ototoxicity expected at the end of Q1 2026 (but no update on their website as I write this in early May). They are also working on two gene therapy hearing loss programs, a clinical stage Ph I/II project targeting otoferlin (SENS-501) and an IND-stage program targeting connexin-26 (GJB2) which in some regards could also be regarded as a transmembrane ion channel.

Next up are 2 financial news items in the neurodegeneration ion channel space. First up are US biotech Casma Therapeutics who received $7.6 million in grant funding from the Michael J Fox Foundation (MJFF), specifically to progress their lysosomal TRPML1 program for Parkinson’s Disease. The funds will primarily be used to advance the small molecule activator CSM-101 through final preclinical and IND studies and generate translational biomarker data on target engagement, dosing and study design required for clinical trial approval. Similarly, UK company Lario Therapeutics raised $2.4 million for several Cav channel CNS programs, including a $1.5 million grant from the MJFF to support development of a Cav1.3 program in Parkinson’s Disease. There is some genetic, preclinical and epidemiological evidence linking this neuronal L-type Cav channel to neurodegeneration, and the MJFF has listed it as a promising target for de-risking with further R&D. Also, following on from Lario’s work on Cav2.3 in cdkl5 genetic DEE and a 2024 grant of $6 million from the MJFF to study its role in Parkinson’s, the company received $900k from Wellcome to validate it as target in post-traumatic stress disorder (PTSD), based in part on recent human genetic data (GWAS meta analysis and transcriptome data published in 2024 in Nature) identifying CACNA1E as a risk factor. Some may be interested to hear that other ion channel genes were also identified in this paper, including GRIA1 AMPA and CHRNA7 a7 nACh ionotropic receptors (pursued by Bionomics for PTSD), ANO10 CaCl channel and Cav a2d subunits.

The final entry in the CNS section is news that Shionogi has negotiated a deal to take control of sleep disorder assets that were part of a JV with Apnimed, including a P2X3 blocker (Sivopixant) that was previously tested in chronic cough. There was an upfront payment of $100 million for the remaining 50% stake of the JV company SASS which was set-up in 2023, and a $50 million milestone payment linked to a 2nd ligand project (SASS-002 is a formulation of carbonic anhydrase inhibitor sulthiame). SASS-001 is a mixture of the P2X3 blocker Sivopixant and another CA inhibitor acetazolamide and a mysterious 3rd ligand, which is currently in a Ph IIa trial for sleep apnea that started last year.

I’ll finish up with two brief pieces of funding news on new companies (to me) who are beginning work on peripheral ion channels. Starting close to home, Welsh biotech Antiverse (spin-out from Cardiff University) raised $9.3 million in their recent Series A with funds from existing and new investors, bringing their total funding to over $20 million. The company utilises AI to enable de novo design of antibodies targeting transmembrane ion channels and GPCRs and signed a collaboration with UK company Nxera Pharma (previously Sosei-Heptares) in 2024, and this work seems to be at an early preclinical stage with the funds being earmarked for in vivo translational and PoC studies. The ion channel angle seems to involve CFTR respiratory channel proteins, as the company also announced a R&D agreement with the Cystic Fibrosis Foundation at the same time.

With homesick tears in my eyes I can wrap this blog up with news that Aussie spinout xCystence Bio has launched with pre-seed funding of A$2.5 million for their work on chronic kidney disease. Their approach exemplifies the quandary I sometimes find myself in categorising ion channel programs when the discovery target/mechanism is a protein that regulates ion channels (e.g. the developing story around TDP43 regulating Kv7.x channels and neuronal excitability in ALS). In this case Monash Uni scientists (in Melbourne, for those lacking a map or down-under geographic knowledge) have identified aurora kinase A as a regulator of TRPP2 cation channels (aka PKC or PKD proteins) present in the cilium of kidney proximal tubule cells where they help control salt and water excretion, and mutations are linked to polycystic kidney disease. Also intriguing is the fact that the company is taking a targeted protein degradation (TPD) approach, similar to PROTACs and molecular glues, to control the levels of aurora kinase A and it’s interactions with TRPP2 channels. I will write a review on the growing field of ion channel TPD in my next preclinical blog on the Nanion website  in Q3 (here), as this new modality holds significant promise to regulate ion channel expression and function in a different fashion to small molecule modulators.

© Dr. Marc Rogers, Cambridge (UK)

aka The Channelogist