SULT1A1

Geneva, Switzerland, January 16th, 2024 – Stalicla SA, a clinical-stage biopharmaceutical company advancing precision medicine pipelines for neuropsychiatric and neurological disorders, announces the successful completion of the first closing of its Series B financing round, securing $17.4 million. Led by SPRIM Global Investments Pte, Ltd, with key participation from core investors, this funding includes a $3.8 million credit facility. The proceeds will be utilized for: (i) preparation of Stalicla’s pioneering precision Autism Spectrum Disorder (ASD) Phase 2 trial – STP1; (ii) the establishment of its STP7 mGluR5 Negative Allosteric Modulator (mGluR5 NAM) platform, including the launch a Phase III study in Substance Use Disorders (SUDs) slated for 2025, fully supported by the NIH /National Institute on Drug Abuse; (iii) the ramp up of its ongoing biosampling/ patient identification trial STA-B-001 currently enrolling in sites in the USA, Spain and Australia. Alongside these key developments, Stalicla will further strengthen the package supporting its second precision ASD asset, STP2. Lynn Durham, CEO of Stalicla commented: “This financial backing underscores Stalicla's role as a trailblazer in the neuro precision space with first applications in precision psychiatry. Additionally, our STP7 mGluR5 NAM platform is offering multifaceted advanced clinical development opportunities in the wider neurology space in a timely period of recent clinical progress & increased transaction activity level in the neurology and neuropsychiatry space. There has never been a more promising time to advance transformative treatment options for millions of patients with brain diseases and Stalicla is determined to play a key role in this progress.” To support these advancements, Stalicla will strengthen its Management Team and Board of Directors, reinforcing the foundation for the exciting journey ahead. About STALICLA SASTALICLA is a precision molecular neuroscience clinical stage company, advancing through its DEPI precision neuro platform 2 precision autism assets: STP1 and STP2. Following the in-licensing of mavoglurant from Novartis in 2023, STALICLA has also established an advanced mGLuR5 NAM platform with multi-faceted late-stage clinical development opportunities.For further information, please visit: https://stalicla.com/ Contact:Stalicla SALynn Durham, Founder & CEOLynn.durham@stalicla.com Attachment Press Release 2024-01-SeriesB_final

STALICLA and Firefly Neuroscience enterPartnership Agreement for the Development of Electroencephalogram (EEG) asa Biomarker for Subgroups of Patients with ASD The combination of STALICLA and FireflyNeurosciences’s machine learning platforms and know-how will further strengthen the development of precision medicine for these patients Geneva, Switzerland – 27March2023, STALICLA S.A. and Firefly Neuroscience today announced a partnership to further validate EEG-based biomarkers in biologically enriched subgroups of patients with Autism Spectrum Disorder (ASD). This follows the successful completion of STALICLA’s Phase 1b clinical trial for its lead asset STP1 where EEG measurement was shown to be a powerful predictor of efficacy. STALICLA and Firefly Neuroscience will leverage their technological platforms including the Databased Endophenotyping Patient Identification (DEPI) platform and the FDA-cleared Brain Network Analytics (BNA™) platform respectively to further advance EEG validation in two upcoming Phase 2 clinical trials, sponsored by STALICLA. Applying BNA™ to the DEPI-driven biologically enriched subgroups of patients with ASD is expected to establish and expand EEG as a biomarker in the field of ASD. EEG measurements will reinforce the DEPI stratification capacity and prediction of treatment response in patients with a behavioral diagnosis of ASD. STP1 is a tailored treatment candidate for ASD-Phenotype 1, the first DEPI-enriched subgroup of patients. STP1 positive target engagement was demonstrated by specific EEG signal modulation in brain areas of interest. Lynn Durham, STALICLA’s CEO & Founder, commented:“STALICLA is thrilled to partner with Firefly Neuroscience to advance an EEG-based treatment response marker in the NDD population. STALICLA will leverage its DEPI platform and Firefly Neuroscience’s technology to reinforce its leadership in precision medicine for neurodevelopmental disorders with rapid implementation of precision EEG in our upcoming two phase 2 programs in Autism Spectrum Disorder.” Jon Olsen, Firefly Neuroscience’s CEO, commented:“Firefly Neuroscience is excited to partner with STALICLA on the advancement of treatment for people with ASD. Using BNA™ to target sub-groups of patients for precision medicine treatment in the CNS space is a core focus for the company. The fact that BNA™ is FDA cleared and used by clinicians in the United States to support therapy decisions for people with mental disorders puts us in a very strong position to build a referral network in support of the commercialization of novel drugs and therapies for the treatment of NDD diseases.” STALICLA has developed and validated a machine learning platform, DEPI, allowing ASD subgroup identification and precision medicine treatment candidate selection. With multiple clinical proof of concepts, DEPI has allowed for the identification of two distinct subgroups of patients with ASD and their tailored treatments STP1 and STP2. Both STP1 and STP2 are planned to enter Phase 2 clinical trials in 2023. Firefly Neuroscience’s BNA™ platform is a patented technology that provides an objective, quantified assessment of cognition (brain function). It measures brain function and compares it to an FDA-cleared, normative, age-matched database using proprietary AI and advanced signal processing technology. Firefly Neuroscience’s AI platform (‘Fly-AI’) will help develop future biomarkers and companion diagnostics allowing for the expansion of existing pharma collaborations and partnerships to make the development of new CNS drugs more efficient. About STALICLA STALICLA is a precision molecular neuroscience clinical stage biotech company, advancing the first precision medicine platform (DEPI) for patients with neurodevelopmental disorders (NDDs), and neuropsychiatric disorders. STALICLA’s unique approach is addressing the poor construct validity of behaviourally defined disorders through its unique platform integrating molecular data with human genetic information to create testable clinical hypotheses in psychiatry and neuroscience. With multiple clinical proof of concepts, DEPI has allowed for the identification of two distinct subgroups of patients with Autism Spectrum Disorder (ASD) and their tailored treatments STP1 and STP2, both of which are planned to enter Phase 2 clinical trials in 2023. STP1 and STP2 hold a multi-billion market potential. The DEPI platform has been validated in a clinical setting showing high specificity, sensitivity and positive predictive value in prospectively designed trials recalling ‘high’ responder patients to previously failed drug candidates. STALICLA is currently preparing its next stage of growth to advance its pipelines and scale its platform. For further information, please visit: About Firefly Neuroscience Firefly Neuroscience leverages technical advances in computing and AI to deconstruct, analyze, and compare electroencephalograms (EEG), making them clinically useful for front-line clinicians to objectively measure, monitor, and manage brain function. Building on over a decade of research, the product has received FDA clearance and is commercially used in American clinics since mid-2022. With BNA™, clinicians and their patients can now make informed, objective therapy and disease management decisions, track changes over time and improve therapy compliance. It takes the guesswork and subjectivity out of managing mental illnesses and cognitive disorders- as one can only effectively manage what can accurately be measured. Firefly Neuroscience’s AI platform (‘Fly-AI’) has been built to develop future biomarkers and companion diagnostics (pharma) allowing for the expansion of existing pharma collaborations to bring new drugs to market. It has been used with leading companies such as Novartis, Takeda, and Purdue and is poised to revolutionize the required objective measurement for effective CNS drug development. For further information, please visit: Contacts STALICLA SA Lynn Durham, Founder & CEO Lynn.durham@stalicla.com Firefly Neuroscience Jon Olsen, CEO Jon.olsen@fireflyneuro.com Media inquiries Consilium Strategic Communications stalicla@consilium-comms.com

Scientists at the National Institutes of Health and Massachusetts General Hospital in Boston have uncovered a potential new approach against liver cancer that could lead to the development of a new class of anticancer drugs. In a series of experiments in cells and mice, researchers found that an enzyme produced in liver cancer cells could convert a group of compounds into anticancer drugs, killing cells and reducing disease in animals. The researchers suggest that this enzyme could become a potential target for the development of new drugs against liver cancers, and perhaps other cancers and diseases as well. "We found a molecule that kills cells in a rare liver cancer in a unique way," said translational scientist Matthew Hall, Ph.D., one of the leaders of the work at NIH's National Center for Advancing Translational Sciences (NCATS). "It emerged from a screening to find molecules that selectively kill human liver cancer cells. It took a lot of work to figure out that the molecule is converted by an enzyme in these liver cancer cells, creating a toxic, anticancer drug." Hall, Nabeel Bardeesy, Ph.D., a liver cancer specialist at Massachusetts General Hospital and their colleagues reported their results March 13 in Nature Cancer. The finding stems from a collaboration between Massachusetts General Hospital and NCATS researchers. Bardeesy was originally studying cholangiocarcinoma, a type of liver cancer that affects the bile duct. The cancer is characterized by mutations in the IDH1 enzyme. Bardeesy's team wanted to find compounds and drugs that might be effective against the IDH1 mutation. Through a collaboration with NCATS, Hall and other NCATS scientists rapidly tested thousands of approved drugs and experimental cancer agents for their effectiveness in killing cholangiocarcinoma cells, with IDH1 as a target. They found several molecules, including one called YC-1, could kill the cancer cells. Yet, when they looked to see how YC-1 was working, they discovered the compound wasn't affecting the IDH1 mutation. The Massachusetts researchers showed that the liver cancer cells made an enzyme, SULT1A1. The enzyme activated the YC-1 compound, making it toxic to tumor cells in cancer cell cultures and mouse models of liver cancers. In the animal models treated with YC-1, the liver tumors either had reduced growth or shrank. Conversely, the researchers found no changes in tumors treated with YC-1 in animals with cancer cells lacking the enzyme. The researchers examined other databases of drug screening results in compound and drug libraries to match drug activity with SULT1A1 activity. They also looked at a large National Cancer Institute database of anticancer compounds for additional possibilities to test for their activity with the enzyme. They identified several classes of compounds that relied on SULT1A1 for their tumor-killing activity. Using computational methods, they predicted other compounds that also likely were dependent on SULT1A1. "Once we found SULT1A1 activated YC-1, it led us to ask, 'What other compounds are active and can kill cells by the same mechanism?'" Hall said. "Can we identify other compounds that were being developed and demonstrate that they were also active because of SULT1A1 activation? The answer was yes. We found other compounds with the same mechanism of action as YC-1." The scientists suggest these findings have broader implications for developing new anticancer drugs. "We think these molecules have the potential to be an untapped class of anticancer drugs that depend on SULT1A1 for their activity against tumors," Bardeesy said. The researchers see YC-1 and similar molecules as prototypes for developing compounds that could be effective against important proteins on cells. Modifying different parts of these molecules could make them more specific for such proteins. The researchers point to the creation of a "toolkit of SULT1A1-activated molecules" that could affect many different targets. Such a toolkit is comprised of hundreds of known molecules. In theory, the toolkit covers many types of enzymes, called sulfotransferases, that are active in different tissues in the body. For example, in addition to SULT1A1, the human sulfotransferase SULT4A1 is active in the brain. It can activate a subset of the molecules in the toolkit. This might be useful in developing drugs specific for brain cancers. "We knew SULT1A1-dependent drugs had already been identified," Bardeesy said. "Our results suggest there could be other SULT1A1-dependent compounds with ranges of different targets. Identifying such compounds and targets on cells could have potential implications for developing other types of small molecules and drugs, not just limited to these cancers. This might become a new approach for some diseases." This work was supported by the MGH Fund for Medical Discovery Award; the Cholangiocarcinoma Foundation Christopher J. Wilke Memorial Research Fellowship; NCI 1K99CA245194-01, the V Foundation for Cancer Research, the Department of Defense Translational Team Science Award W81XWH-17-1-0491; NCI SPORE P50 CA127003; the Gallagher Chair in Gastrointestinal Cancer Research and Target Cancer Foundation; and the MGH Excellence Award. Shi L, Shen W, Davis MI, Kong K, Vu P, Saha SK, Adil R, Kreuzer J, Egan R, Lee TD, Greninger P, Shrimp JH, Zhao W, Wei TY, Zhou M, Eccleston J, Sussman J, Manocha U, Weerasekara V, Kondo H, Vijay V, Wu MJ, Kearney SE, Ho J, McClanaghan J, Murchie E, Crowther GS, Patnaik S, Boxer MB, Shen M, Ting DT, Kim WY, Stanger BZ, Deshpande V, Ferrone CR, Benes CH, Haas W, Hall MD, Bardeesy N. SULT1A1-dependent sulfonation of alkylators is a lineage-dependent vulnerability of liver cancers. Nat Cancer. 2023 Mar 13. doi: 10.1038/s43018-023-00523-0