Kv7.3 x Kv7.2

Saniona (OMX: SANION), a clinical-stage biopharmaceutical company, today announces significant progress in the preclinical development of SAN2355, a new generation Kv7.2/Kv7.3 activator aimed at treating focal onset seizures. The company has identified a stable solid form of the compound and completed synthesis optimization, enabling a robust, scalable manufacturing process. As a result, Saniona has successfully produced 4 kg of SAN2355 for GLP toxicology studies. “We are delighted to have completed the analytical development, synthesis optimization, and production of the GLP toxicology batch. We expect the remaining preclinical work to take about nine months, which means that SAN2355 could enter Phase 1 clinical trials by Q3 2025,” said Janus Schreiber Larsen, Chief Development Officer at Saniona. “SAN2355 is a key asset in our epilepsy portfolio. Kv7 activators have previously been clinically and commercially validated for treating refractory focal onset epilepsy, but no products are currently available on the market. SAN2355 stands out due to its unique selectivity profile and has the potential to become best in class, addressing significant unmet needs in the epilepsy market,” added Thomas Feldthus, CEO of Saniona. The GLP toxicology batch was produced with assistance from the Danish firm Niels Clauson-Kaas, and the project is now ready for preclinical toxicity and safety studies, in compliance with GLP standards. About Kv7 Channels and Epilepsy Epilepsy is a neurological disorder characterized by recurrent seizures, affecting millions globally. Around 30% of patients do not respond to existing treatments, highlighting a critical unmet need. Kv7 channels are crucial for regulating potassium ion transport across neuronal membranes, helping to prevent uncontrolled nerve impulses. Kv7.2 and Kv7.3 subunits, primarily expressed in the brain, play a key role in dampening overactive neurons, thus preventing seizures. While the non-selective Kv7 activator retigabine demonstrated proof-of-concept for treating resistant focal onset seizures, it was withdrawn from the market due to side effects unrelated to its target. About SanionaSaniona (OMX: SANION) is a clinical-stage biopharmaceutical company leading the way in ion channel modulation for the treatment of epilepsy and other neurological disorders. Saniona’s epilepsy pipeline features SAN711, a Phase 2-ready candidate drug targeting absence seizures, SAN2219 for acute repetitive seizures, and SAN2355, addressing refractory focal onset seizures. Beyond epilepsy, Saniona oversees four clinical programs poised for collaboration. Tesofensine, Saniona’s most advanced candidate, is progressing towards regulatory approval for obesity in Mexico through a partnership with Medix. Tesomet™ is ready for Phase 2b, targeting rare eating disorders, while SAN903 is ready for Phase 1 for inflammatory bowel disease and SAN2465 is set for preclinical development for major depressive disorder. Saniona has esteemed partners, including Boehringer Ingelheim GmbH, Productos Medix, S.A de S.V, AstronauTx Limited, and Cephagenix ApS. Saniona is based in Copenhagen and listed on Nasdaq Stockholm Main Market.For more information, please visit www.saniona.com.

Biohaven reported full results from the BHV-7000 Phase 1 study examining doses up to 120 mg daily, demonstrating BHV-7000 was well-tolerated at all doses studied without the typical central nervous system (CNS) adverse effects associated with other anti-seizure medications (ASMs), such as somnolence and cognitive/mood disturbances. In a Phase 1 electroencephalogram (EEG) biomarker study, BHV-7000 demonstrated dose-dependent target engagement in the brain as measured by changes in EEG spectral power across all brain regions. Additional poster presentations at the American Epilepsy Society Annual Meeting will include: BHV-7000 preclinical data, health-related quality of life in patients with focal epilepsy, and functional impairments in patients with KCNQ2‐associated developmental and epileptic encephalopathy (KCNQ2-DEE). NEW HAVEN, Conn., Dec. 1, 2023 /PRNewswire/ -- Biohaven Ltd. (NYSE: BHVN) announced today that it is presenting expanded EEG and safety data for BHV-7000 at the 2023 American Epilepsy Society (AES) Annual Meeting, taking place December 1-5, 2023, in Orlando, Florida. The presentations include results from the BHV-7000 Phase 1 EEG biomarker study and additional BHV-7000 safety and tolerability data from Phase 1 single ascending dose (SAD) / multiple ascending dose (MAD) studies. Additional posters showcase BHV-7000's preclinical data, findings from a systematic literature review on health-related quality of life (HRQoL) in patients with focal epilepsy, and results from a cross-sectional survey assessing functional impairments in patients with KCNQ2-DEE. Jason Lerner, M.D., Medical Director and Epilepsy Clinical Lead at Biohaven, commented "Selective Kv7 activators are one of the most exciting new drug targets for the treatment of epilepsy, and BHV-7000 has shown a favorable and differentiated profile in preliminary Phase 1 studies to date. We are pleased to see favorable safety and tolerability with BHV-7000 dosed up to 120 mg daily for 15 days, without the CNS adverse effects typically associated with other ASMs, such as somnolence. Together with the preclinical data showing BHV-7000 is a selective Kv7.2/7.3 channel opener lacking GABAA activation and the results from our Phase 1 EEG study confirming target engagement, we are excited to advance BHV-7000 into late-stage development in epilepsy patients." Dr. Lerner added, "The robust BHV-7000 data presentations at the AES meeting underscore Biohaven's progress and commitment to developing novel, efficacious and well-tolerated therapies for people living with epilepsy." In addition, both the systematic literature review and parental survey illustrated the importance of Health-Related Quality of Life issues among patients with focal epilepsy and developmental manifestations of KCNQ2-DEE that are relevant to parents, such as communication, eating abilities, and motor impairments. Presentation Highlights: Poster 2.510: Novel, Selective Kv7.2/7.3 Potassium Channel Activator, BHV-7000, Demonstrates Dose-Dependent Pharmacodynamic Effects on EEG Parameters in Healthy Adults In this Phase 1 study, pharmacodynamic activity of BHV-7000 in the brain of healthy adults was demonstrated by dose-dependent increases in EEG spectral power. Unlike prior reports where EEG effects of a Kv7.2/7.3 activator showed the greatest power increase in the delta frequency band (Biondi et al. 2022), the highest spectral power increases with BHV-7000 were seen in alpha, beta, and gamma frequency bands. While changes in spectral power were observed across all frequency bands with BHV-7000, the minimal impact on slower frequencies (i.e., delta) is consistent with the low incidence of CNS adverse events, in particular somnolence, seen in the BHV-7000 Phase 1 SAD/MAD studies. EEG delta activity is associated with somnolence, an undesirable CNS adverse event often seen with other ASMs. Poster 3.265: A First in Human Phase 1 Study Evaluating the Safety and Tolerability of BHV-7000, a Novel, Selective Kv7.2/7.3 Potassium Channel Activator, in Healthy Adults BHV-7000 was safe and well-tolerated at single doses up to 100 mg and multiple doses up to 120 mg daily for 15 days No serious adverse events or severe treatment emergent adverse events were reported Adverse events typically associated with other ASMs, such as somnolence and cognitive/mood disturbances, were not reported Poster 2.249: Characterization of BHV-7000: A Novel Kv7.2/7.3 Activator for the Treatment of Seizures BHV-7000 is a potent activator of Kv7.2/7.3 channels, impacting both deactivation kinetics and voltage dependence of activation BHV-7000 requires the Kv7.2 W236 residue for channel activity No significant activation of the GABAA receptor with BHV-7000 BHV-7000 is potent in the maximal electroshock seizure (MES) test without impact on neurobehavior or motor (rotorod) behavior Poster 1.487: Determinants of Health-Related Quality of Life of Patients with Focal Epilepsy: A Systematic Literature Review This systematic literature review identified multiple factors associated with lower HRQoL in patients with focal epilepsy Depression and anxiety were among the most significant and frequent determinants of HRQoL change Other relevant and frequent determinants of HRQoL change included cognition, ASM adverse events, seizure freedom, and employment A comprehensive understanding of the modifiable determinants of HRQoL is relevant to patient health and well-being and can inform clinical practice and observational/interventional studies Poster 2.451: Functional Impairments in Patients with KCNQ2-DEE: Associations Among Key Clinical Features Data obtained from a cross-sectional survey (2018-2020) of parents of children aged ≥2 years with KCNQ2-DEE was analyzed Among individuals with KCNQ2-DEE, there is a hierarchy of impairments wherein communication is the most sensitive domain and is often affected in isolation from others Gross and fine motor skill impairments tend to be correlated Hand use impairment is closely correlated with multiple other functional impairments Full posters will be available on the Posters and Presentations page at: . Reference Biondi A, et al. Sci Rep. 2022 Feb 4;12(1):1919. About BHV-7000 BHV-7000, the lead asset from Biohaven's Kv7 platform, is a novel and selective activator of Kv7.2/Kv7.3, a key ion channel involved in neuronal signaling and in regulating the hyperexcitable state, that Biohaven is developing for the treatment of epilepsy and mood disorders. BHV-7000 was rationally developed as a potent activator of heteromeric Kv7.2/7.3 potassium channels, the molecular substrate that underlies the M-current (IKM). BHV-7000 is highly differentiated from ezogabine (known as retigabine in Europe), a Kv7 activator that was previously approved for adjunctive treatment of partial-onset seizures in adults. In comparison with ezogabine, BHV-7000 belongs to a significantly different structural class and differentiates from ezogabine in key properties, including pharmacology, plasma stability and stability to photooxidation. In addition, BHV-7000 does not exhibit GABAA receptor positive allosteric molecular activity as seen with ezogabine and similar compounds, which may contribute to the poor tolerability of ezogabine. This lack of GABAA receptor activity potentially gives BHV-7000 a wide therapeutic window which, based on dose-dependent clinical responses seen in other ASM clinical trials, should translate to improved efficacy without the typical dose dependent side effect profile often seen in patients receiving ezogabine and other anti-seizure medications. About Biohaven Biohaven is a global clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of life-changing therapies to treat a broad range of rare and common diseases. Biohaven's experienced management team brings with it a track record of delivering new drug approvals for products for diseases such as migraine, depression, bipolar and schizophrenia. The company is advancing a pipeline of therapies for diseases, many of which have limited or no treatment options, leveraging its proven drug development capabilities and proprietary platforms, including Kv7 ion channel modulation for epilepsy and neuronal hyperexcitability, glutamate modulation for obsessive-compulsive disorder and spinocerebellar ataxia, myostatin inhibition for neuromuscular diseases and metabolic disorders, and brain-penetrant TYK2/JAK1 inhibition for neuroinflammatory disorders. Biohaven's portfolio of early- and late-stage product candidates also includes discovery research programs focused on TRPM3 channel activation for neuropathic pain, CD-38 antibody recruiting, bispecific molecules for multiple myeloma, antibody drug conjugates (ADCs), and targeted extracellular protein degradation platform technology (MoDE™) with potential application in neurological disorders, cancer, and autoimmune diseases. Forward-looking Statements This news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The use of certain words, including "continue", "plan", "will", "believe", "may", "expect", "anticipate" and similar expressions, is intended to identify forward-looking statements. Investors are cautioned that any forward-looking statements, including statements regarding the future development, timing and potential marketing approval and commercialization of development candidates, are not guarantees of future performance or results and involve substantial risks and uncertainties. Actual results, developments and events may differ materially from those in the forward-looking statements as a result of various factors including: the expected timing, commencement and outcomes of Biohaven's planned and ongoing clinical trials; the timing of planned interactions and filings with the FDA; the timing and outcome of expected regulatory filings; complying with applicable U.S. regulatory requirements; the potential commercialization of Biohaven's product candidates; the potential for Biohaven's product candidates to be first in class therapies; and the effectiveness and safety of Biohaven's product candidates. Additional important factors to be considered in connection with forward-looking statements are described in Biohaven's filings with the Securities and Exchange Commission, including within the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations". The forward-looking statements are made as of the date of this news release, and Biohaven does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. MoDEs is a trademark of Biohaven Therapeutics Ltd. Investor Contact: Jennifer Porcelli Vice President, Investor Relations [email protected] 201-248-0741 Media Contact: Mike Beyer Sam Brown Inc. [email protected] 312-961-2502 SOURCE Biohaven Ltd.

Examination of EEG in healthy subjects administered single doses of BHV-7000 confirmed central nervous system (CNS) activity consistent with effects observed with other antiseizure medications. EEG results demonstrated dose-dependent and time-dependent effects of BHV-7000 on CNS target engagement in study subjects: At the lowest dose studied of 10 mg, subjects with targeted drug concentrations ≥EC50 showed a mean increase in EEG spectral power in beta and gamma bands while there were no meaningful changes in spectral power in subjects with drug concentrations