SOM Webcast: Expert insights on Huntington’s Disease and SOM3355

www.SOMBiotech.com Expert insights on Huntington’s Disease and SOM3355 Webinar December 10, 2025 D R U G D I S C O V E R Y & D E V E L O P M E N T p o w e r e d b y S O M A I P R O , a p r o p r i e t a r y p l a t f o r m Webinar Structure Segment 1 – Huntington’s Disease and the patient journey Segment 2 – Treatment options and medical need Q&A Segment 3 – SOM3355 as a potential game changer in the treatment landscape Segment 4 – Phase 3 pivotal study Q&A Closing Remarks SOM3355, a potential game changer in the treatment of Huntington Disease KoLs Webinar, December 10, 2025 2 Welcome and Introduction Silvia Panigone, PhD, MBA SOM CEO and Chair of the Board Rossella Medori MD, PhD SOM Chief Medical Officer Daniel Claassen, MD, MS • Professor of Neurology at Vanderbilt University Medical Center, Nashville, TN (US) • CEO at Huntington Study Group (HSG) Victor Sung. MD • Professor of Neurology,UAB School of Medicine, University of Alabama (US) Dr. Claassen and Dr. Sung, participated to almost all clinical trials in Huntington disease with symptomatic and disease-modifying treatments. 3 SOM3355, a potential game changer in the treatment of Huntington Disease KoLs Webinar, December 10, 2025 Segment 1 Huntington’s Disease and the patient journey 4 Huntington’s Disease Huntington’s Disease and epidemiology Cause and age of onset Diagnosis Based on family/personal history, neurological examination of movement disorders (chorea, dystonia, UHDRS), psychiatric examination, genetic positive DNA test An autosomal dominant mutation in the Huntingtin gene (HTT) Age of onset - generally around 35-40 years A rare genetic progressive neurodegenerative disease characterized by motor, behavioral and psychiatric symptoms, and cognitive decline evolving until loss of autonomy. Under-estimated reported prevalence is 5-15 cases per 100’000 and over 250’000 in North America at risk 5 Most often reported HD-related indications per disease group in adult subjects Source: Feleus 2024 Data from the largest observational HD study, ENROLL -HD Huntington’s Complex Symptomatology Across the Disease Stages 0.2 5.8 2.7 0.1 10.2 0.2 0.1 14.5 0.2 4.2 1.1 8.3 2.4 1.4 0.2 15.1 0.5 0.2 14.8 0.2 5.5 5.9 11.3 6.7 33.9 1.3 28.2 1.5 0.2 2.2 0.8 15.6 0.3 12.4 8.9 16.1 11.0 46.4 2.5 39.1 2.6 0.5 4.6 2.0 18.8 0.8 17.6 12.9 17.6 15.7 60.9 3.2 44.2 3.9 1.2 9.8 3.6 19.4 0.6 21.8 16.8 16.5 30.3 57.6 2.5 38.7 3.4 3.1 13.7 2.5 19.9 2.0 23.8 22.7 24.5 51.8 45.2 33.6 2.7 5.5 18.2 2.7 25.5 6.4 14.5 0.0 10.0 20.0 30.0 40.0 50.0 60.0% medication users Controls Premanifest HD Stage 1 HD Stage 2 HD Stage 3 HD Stage 4 HD Stage 5 6 Disease Progression and Patient Journey HD PATIENT TIMELINE AT-RISK PRODROMAL MOTOR MANIFEST ADVANCED-HD Psychosocial morbidity Psychiatric Symptoms | Cognitive decline Chorea, Motor changes Swallowing, Weight loss, Increased care • All patients require coordinated multidisciplinary care throughout the course of disease • Patients Referral: - 30-40% are self referred to CoE; remain at their primary doctor for long time. - when come to CoE, patients often believe to be early symptomatic while they are already at moderate stage 7 SOM3355, a potential game changer in the treatment of Huntington Disease KoLs Webinar, December 10, 2025 Segment 2 Treatment options and medical need 8 Currently Approved Treatments Approved Therapies • FDA approved therapies are solely for chorea • Approved therapies are VMAT2 Inhibitors, dopamine depleting agents: - Tetrabenazine - Deutetrabenazine (Austedo®) - Valbenazine (Ingrezza®) • Antipsychotics are used off-label to treat the behavior and neuropsychiatric symptoms Limitations • Side effects cannot be distinguished from disease progression (akatasia, depression, parkinsonism, somnolence) • All approved drugs have Black Box Warning for suicidality and depression • Titration to adjust the dose • No approved treatments for behavior and neuropsychiatric symptomatology or cognitive decline 9 * Sources: 1) Longitudinal Treatment Patterns of Chorea in North American Patients with Huntington’s Disease: Data from Enroll‐HD; Stimming; Neuro Ther Dec 2024 2) Alira Health Analysis – Primary Market Research (KOL N=5, PAG N=2, Payer N=5) committed by SOM In the US, only 20-30%* HD patients are under pharmacological treatments The US Situation - Patient Distribution Across Current Treatments 10 Center of Excellence Rarely used due to AEs Used only when required as step therapy 1- 2% Off-label neuroleptics 60- 96% 3- 15% 20- 30% 5- 15% Mono- therapy Dual therapyPerceived better safety profile Effective patients support program by Teva Not preferred due to higher sedation rates and limited dosing flexibility Consistent across both settings generic retain 25-30% the total HD Private Practice Neurologist Mostly used as step therapy or due to cost concerns for patients unable to afford co-pays for branded products Off-label neuroleptics Mono- therapy Dual therapyUsed slightly less than Ingrezza due to the perception of complicated titration Increased use due to simpler titration regimen, despite lack of flexibility compared with Austedo 40% 35- 45% 25- 60% 20- 30% 5- 15% Consistent across both settings generic treat 70-75% the total HD (1) Alira Health Analysis – Primary Market Research (KOL N=5, PAG N=2, Payer N=5) committed by SOM VMAT2 are the first line when chorea symptoms occur first Viceversa neuroleptics are the first line when neuro-psychiatric symptomatology occurs first Out of the 20-30% patients treated Under Development Therapies and Unmet need for HD Treatment • Under development gene therapy & disease modifying approaches: - Slowing down disease progression, prolonging patients’ life - Pre-symptomatic and early symptomatic patients • Still a massive need for a chronic treatment of symptoms, even more if disease slows down its progression • Emerging trends and increased interest for: - non-dopamine depletion agents - replacement of antipsychotics 11 SOM3355, a potential game changer in the treatment of Huntington Disease KoLs Webinar, December 10, 2025 Q&A Daniel Claassen, MD, MS • Professor of Neurology at Vanderbilt University Medical Center, Nashville, TN (US) • CEO at Huntington Study Group (HSG) Victor Sung. MD • Professor of Neurology,UAB School of Medicine, University of Alabama (US) Dr. Claassen and Dr. Sung, participated to almost all clinical trials in Huntington disease with symptomatic and disease-modifying treatments. Segment 1 and Segment 2: Huntington’s Disease and Unmet Medical Need 12 SOM3355, a potential game changer in the treatment of Huntington Disease KoLs Webinar, December 10, 2025 Segment 3 SOM3355 as a potential game changer in the treatment landscape 13 • SOM3355 is a specific beta-blocker used safely as a mild anti-hypertensive for 40 years, currently on the market only in Japan, South Korea and China. • SOM discovered its multimodal MoA: selective beta1-blocker,VMAT1 and VMAT2 inhibitormaking it a different class of molecule for the symptomatic treatment of Huntington’s Disease (HD). • It has achieved positive results in both proof-of-concept and phase 2b clinical studies in Huntington’s patientsand showed efficacy and tolerability for the treatment of symptoms behond chorea including behavioural and neuropsychiatricones, with a very safe profile. • Received positive feedback from both EMA and FDA corroborating the positioning as symptomatic treatment of Huntington’s disease beyond chorea. • SOM is committed to move forward with a Phase 3 pivotal study. SOM3355 Molecule - Highlights 14 SOM3355: a Unique Novel Mechanism of Action - Differentiation Thesis VMAT1 InhibitionVMAT2 Inhibition With Dopamine Modulation • Binding to VMAT2 in a different binding side then tetrabenazine (TBZ) with similar inhibition potency of TBZ • 10-fold less potent than TBZ in inhibiting serotonin (5HT) uptake Lack of the side effects (eg depression, parkinsonism, fatigue) caused by dopamine depletion • Bind to VMAT1 with same potency as VMAT2 • Located in the CNS, in other regions of VMAT2 • Linked to the emotional brain circuits. A few antipsychotics inhibit VMAT1 (eg. Ziprasidone) Possible antipsychotic and antianxiety effects and limitation of dopamin depletion side effects Lack of the side effects caused by dopamine depletion (depression, parkinsonism, fatigue) Beta Adrenergic Properties • β-1-adrenergic blockers used to treat akathisia and anxiety • Long-term use of β-Blocker in HD reported to delay onset and progression of Huntington • SOM3355 unique action among β-Blocker Positive impact on akathisia and anxiety; potentially contributing to delay progression of HD 15 SOM3355 Clinical Profile in Huntington-s Disease – Efficacy 16 • In the Phase 2b double blinded, 12-weeks, placebo-controlled study, 140 pts with 2 doses, SOM3355 300mg BID (the highest dose) showed statistically significant reduction in the TMC scores compared to placebo (p=0.04) at endpoint with reductions from baseline that reached -4.73, similar to changes reported by marketed drugs • The Clinician and Patient global impressions of change (CGI-C and PGI-C) showed significantly higher percentage of patients improved for SOM3355 300mg BID compared to placebo • Improvement was also seen in Anxiety, Apathy, Compulsive, Disruptive and Irritable behaviors and Perseverative Thinking by Problem Behaviors Assessment (PBA-s) in HD patients who had these disturbances, although mild, at baseline while some of them showed mild worsening on placebo Efficacy SOM3355 Clinical Profile in Huntington-s Disease – Safety Scales (SAF Population) 17 • At Beck Depression Inventory (BDI) - No case of worsening of depression. Depressive symptoms improved in the 300mg BID SOM3355 group with mild depression at baseline • No increased suicidality at Columbia-Suicide Severity Rating Scale (C-SSRS) on Drug . Of 21 patients with history of suicidality at screening or baseline, only three patients reported suicidality during the study and they were all in the placebo group • No somnolence according to the Epworth Sleepiness scale (ESS) was reported, on the contrary, improvement in the daytime sleepiness was observed in some cases • No akathisia according to Barnes Akathisia Scale was reported in all treatment groups • No changes in cognitive function according to MoCA • No fatigue or falls compared to placebo Safety SOM3355 Clinical Profile in Huntington-s Disease – Summary Of Adverse Events of Specific Interest (SAF Population) 18 Related Treatment Emergent Adverse Events of special interest (related and possibly related) • Bradycardia : 2 cases in 200 mg BID and 6 cases in 300 mg BID group • Syncope : 1 case in each of the 3 treatment groups • Hypotension : 1 case in 200mg BID and 1 in 300mg BID group • Suicidal ideation : 1 case in Placebo group (SAE) • Delusion worsening requiring neuroleptic: 1 case in 300mg BID assessed as not related by the investigator Heart rate - expected, dose-related decrease in heart rate within the normal range and return to baseline after discontinuation. More importantly, a plateau effect was reached with 200 mg BID. No effect on QT prolongation No dose adjustment needed Safety and Cardiovascular Safety Experts Opinion – SOM3355 as a Potential Game Changer in the Treatment Landscape • What is catching your attention on SOM3355? • For which patients would you use it, if the profile is confirmed in Phase 3? 19 Daniel Claassen, MD, MS • Professor of Neurology at Vanderbilt University Medical Center, Nashville, TN (US) • CEO at Huntington Study Group (HSG) Victor Sung. MD • Professor of Neurology,UAB School of Medicine, University of Alabama (US) Dr. Claassen and Dr. Sung, participated to almost all clinical trials in Huntington disease with symptomatic and disease-modifying treatments. SOM3355, a potential game changer in the treatment of Huntington Disease KoLs Webinar, December 10, 2025 Segment 4 Phase 3 Pivotal Study 20 21Confidential Phase 3 Pivotal Study • End-of-Phase 2 meeting with FDA defined a clear registrational path • One pivotal study • 12-weeks placebo controlled, one dose (300mg BID), double blinded with less than 120 evaluable patients to drive to approval • Followed by Open Label Extension up to 9 months 21 • Protocol under final drafting: - replication of endpoints to confirm Phase 2 safety & efficacy data - incorporation of additional efficacy endpoints, as recommended by regulators, to more characterize the drug’s clinical potential • Planned to start by end 2026 Experts Opinion – Phase 3 Pivotal Study • Given what we just reviewed as the potential final protocol, which endpoints - if demonstrated – would most strengthen your belief that SOM3355 could be considered the drug of choice for the symptomatic treatment of Huntington patients? • How comfortable are you with this study design in terms of recruitment and study completion? 22 Daniel Claassen, MD, MS • Professor of Neurology at Vanderbilt University Medical Center, Nashville, TN (US) • CEO at Huntington Study Group (HSG) Victor Sung. MD • Professor of Neurology,UAB School of Medicine, University of Alabama (US) Dr. Claassen and Dr. Sung, participated to almost all clinical trials in Huntington disease with symptomatic and disease-modifying treatments. SOM3355, a potential game changer in the treatment of Huntington Disease KoLs Webinar, December 10, 2025 Q&A Daniel Claassen, MD, MS • Professor of Neurology at Vanderbilt University Medical Center, Nashville, TN (US) • CEO at Huntington Study Group (HSG) Victor Sung. MD • Professor of Neurology,UAB School of Medicine, University of Alabama (US) Dr. Claassen and Dr. Sung, participated to almost all clinical trials in Huntington disease with symptomatic and disease-modifying treatments. Segment 3 and Segment 4: SOM3355 as a Potential Game Changer 23 SOM3355, a potential game changer in the treatment of Huntington Disease KoLs Webinar, December 10, 2025 Thank you for your attendance www.SOMBiotech.com Investor Relations [email protected] 24

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