SNAP25

Researchers have uncovered a strikingly similar suite of changes in gene activity in brain tissue from people with schizophrenia and from older adults. These changes suggest a common biological basis for the cognitive impairment often seen in people with schizophrenia and in the elderly. Researchers from the Broad Institute of MIT and Harvard, Harvard Medical School, and McLean Hospital have uncovered a strikingly similar suite of changes in gene activity in brain tissue from people with schizophrenia and from older adults. These changes suggest a common biological basis for the cognitive impairment often seen in people with schizophrenia and in the elderly. In a study published in Nature, the team describes how they analyzed gene expression in more than a million individual cells from postmortem brain tissue from 191 people. They found that in individuals with schizophrenia and in older adults without schizophrenia, two brain cell types called astrocytes and neurons reduced their expression of genes that support the junctions between neurons called synapses, compared to healthy or younger people. They also discovered tightly synchronized gene expression changes in the two cell types: when neurons decreased the expression of certain genes related to synapses, astrocytes similarly changed expression of a distinct set of genes that support synapses. The team called this coordinated set of changes the Synaptic Neuron and Astrocyte Program (SNAP). Even in healthy, young people, the expression of the SNAP genes always increased or decreased in a coordinated way in their neurons and astrocytes. "Science often focuses on what genes each cell type expresses on its own," said Steve McCarroll, a co-senior author on the study and an institute member at the Broad Institute. "But brain tissue from many people, and machine-learning analyses of those data, helped us recognize a larger system. These cell types are not acting as independent entities, but have really close coordination. The strength of those relationships took our breath away." Schizophrenia is well-known for causing hallucinations and delusion, which can be at least partly treated with medications. But it also causes debilitating cognitive decline, which has no effective treatments and is common in aging as well. The new findings suggest that the cognitive changes in both conditions might involve similar cellular and molecular alterations in the brain. "To detect coordination between astrocytes and neurons in schizophrenia and aging, we needed to study tissue samples from a very large number of individuals," said Sabina Berretta, a co-senior author of the study, an associate professor at Harvard Medical School, and a researcher in the field of psychiatric disorders. "Our gratitude goes to all donors who chose to donate their brain to research to help others suffering from brain disorders and to whom we'd like to dedicate this work." McCarroll is also director of genomic neurobiology for the Broad's Stanley Center for Psychiatric Research and a professor at Harvard Medical School. Berretta also directs the Harvard Brain Tissue Resource Center (HBTRC), which provided tissue for the study. Emi Ling, a postdoctoral researcher in McCarroll's lab, was the study's first author. SNAP insights The brain works in large part because neurons connect with other neurons at synapses, where they pass signals to one another. The brain constantly forms new synapses and prunes old ones. Scientists think new synapses help our brains stay flexible, and studies -- including previous efforts by scientists in McCarroll's lab and international consortia -- have shown that many genetic factors linked to schizophrenia involve genes that contribute to the function of synapses. In the new study, McCarroll, Berretta, and colleagues used single-nucleus RNA sequencing, which measures gene expression in individual cells, to better understand how the brain naturally varies across individuals. They analyzed 1.2 million cells from94 people with schizophrenia and 97 without. They found that when neurons boosted expression of genes that encode parts of synapses, astrocytes increased the expression of a distinct set of genes involved in synaptic function. These genes, which make up the SNAP program, included many previously identified risk factors for schizophrenia. The team's analyses indicated that both neurons and astrocytes shape genetic vulnerability for the condition. "Science has long known that neurons and synapses are important in risk for schizophrenia, but by framing the question a different way -- asking what genes each cell type regulates dynamically -- we found that astrocytes too are likely involved," said Ling. To their surprise, the researchers also found that SNAP varied greatly even among people without schizophrenia, suggesting that SNAP could be involved in cognitive differences in healthy humans. Much of this variation was explained by age; SNAP declined substantially in many -- but not all -- older individuals, including both people with and without schizophrenia. With better understanding of SNAP, McCarroll says he hopes it might be possible to identify life factors that positively influence SNAP, and develop medicines that help stimulate SNAP, as a way to treat the cognitive impairments of schizophrenia or help people maintain their cognitive flexibility as they age. In the meantime, McCarroll, Berretta, and their team are working to understand if these changes are present in other conditions such as bipolar disorder and depression. They also aim to uncover the extent to which SNAP appears in other brain areas, and how SNAP affects learning and cognitive flexibility. Funding: This work was supported by the Stanley Family Foundation, the Simons Collaboration on Plasticity and the Aging Brain, and the National Institute of Mental Health and the National Human Genome Research Institute at the National Institutes of Health.

– Open label extension (OLE) Phase 2 data show peak efficacy for all ABP-450 doses and cycles in treating cervical dystonia (CD) occurred early, within 4 weeks; durability of effect was demonstrated 12 to 16 weeks post treatment – – Early-phase, original research illustrated successful implementation of image-guided Stellate Ganglion Block (SGB) using ABP-450 both as monotherapy and in conjunction with lidocaine as a preclinical model for treating PTSD – IRVINE, Calif., Jan. 18, 2024 (GLOBE NEWSWIRE) -- AEON Biopharma, Inc. (“AEON” or the “Company”) (NYSE: AEON, AEON WS), a clinical-stage biopharmaceutical company focused on developing a proprietary botulinum toxin complex for the treatment of multiple debilitating medical conditions, today presented new clinical and pre-clinical data for ABP-450 in treating cervical dystonia (CD) and posttraumatic stress disorder (PTSD) at TOXINS 2024, a leading conference held by the International Neurotoxin Association (INA) from January 17th - 20th at the Estrel Berlin in Berlin, Germany. Cervical Dystonia OLE Phase 2 Data A poster titled, “Efficacy and Safety of ABP-450 (prabotulinumtoxinA) in Adults with Cervical Dystonia: Results From the Open-label Extension of a Phase 2 Trial,” was presented by Chad Oh, M.D., the Company’s Chief Medical Officer. Topline data from the recently completed open-label extension (OLE) of the Phase 2 trial demonstrate that ABP-450 was generally safe and well tolerated in CD patients for up to 4 treatment cycles during the 52-week duration of the study. ABP-450 did not appear to increase treatment-related TEAEs at any dose in the study. Peak efficacy for all ABP-450 doses and cycles occurred early, within 4 weeks, and durability of effect was demonstrated from 12 to 16 weeks post treatment. These results support further investigation of ABP-450 as a treatment option for patients with CD and other movement disorders. The OLE was a 52-week study of ABP-450 in adults with moderate to severe CD, a chronic and debilitating neurologic condition affecting the muscles of the neck, who participated in the placebo-controlled, double-blind Phase 2 (DBP) study and for whom ≥8 weeks had elapsed between their single DBP treatment and first OLE treatment. Patients who showed a lack or loss of efficacy at DBP Week 4 or later could transition to the OLE (after 8 weeks had elapsed for patients transitioning prior to Week 8); otherwise, patients entered the OLE at Week 20, providing they met the entry criteria. Patients received up to 4 treatments of ABP-450 during the OLE; patients received a dose range of 115 to 350 units as determined by and at the discretion of the investigator. After the first OLE treatment, patients were eligible for retreatment when their Toronto Western Spasmodic Torticollis rating scale total score (TWSTRS-T) returned to ≥20 and ≥10 weeks had passed since their last dose of ABP-450. “We are excited to announce positive data from the 52-week OLE portion of the Phase 2 study of ABP-450 for CD. We believe these results warrant further investigation of ABP-450 as a treatment option for patients with CD and other movement disorders and support advancing our CD program for ABP-450 into a proposed Phase 3 study,” commented Marc Forth, AEON’s President and Chief Executive Officer. “We look forward to meeting with the FDA to discuss the CD data generated to date, including from the OLE, and solidify the design of a Phase 3 study of ABP-450 to treat CD.” Pre-Clinical PTSD Data Utilizing Stellate Ganglion Block During TOXINS 2024 conference, Dr. Chad Oh also presented a poster titled, “New Investigations of Stellate Ganglion Block (SGB) with ABP-450 (PrabotulinumtoxinA) in Rats.” This poster reports new data from three pre-clinical studies showing right or left SGB, ABP-450 appeared to be safe and well tolerated, with no significant signs of toxicity observed. “We are excited to present new pre-clinical data supporting our ongoing post-traumatic stress disorder (PTSD) program. We utilize a proprietary injection paradigm in a novel part of the anatomy designed to provide safety and efficacy data to support an IND filing of the PTSD study. This innovative approach has the potential for use of ABP-450 to treat a broad neuropsychiatry portfolio, including PTSD. These early data clearly demonstrate AEON’s pioneering role in botulinum toxin research and look forward to keeping you apprised of our progress in advancing this program,” continued Dr. Chad Oh. The stellate ganglion (SG) is formed by the fusion of the sympathetic ganglia in the upper thorax and provides most of the sympathetic innervation to the head and body. The three pre-clinical studies utilized SGB to injected rats with ABP-450 (0.5 or 3 units) both individually and in conjunction with lidocaine (1%-2%) using an ultrasound-guided technique over a duration of 1 to 2 hours. For the SGB procedure, baseline recordings of physiological parameters were assessed (i.e., heart rate, eye appearance, and pupil size) and then the linear ultrasound transducer (FUJIFILM Vevo 3100 micro-ultrasound imaging system) was placed in a short axis view proximal to the clavicle. After identifying the lateral side of the cephalic brachial vein, a 27-gauge needle connected to an insulin syringe (0.5 mL) was advanced from the lateral to medial stellate ganglion (SG) to deliver lidocaine and/or ABP-450. Both lidocaine and ABP-450 were mixed with Chicago blue dye to confirm SGB targeting. Based on the results of this study, an appropriate dose for ABP-450 injected into the rat SG appears to be between 1 and 10 U/kg. The primary indicator for SGB (ptosis as a manifestation of the Horner’s syndrome) was clearly established and verified parenteral delivery of lidocaine to both the left and right SG, suggesting that left side and/or bilateral dosing is an option for future experiments. This early-phase, original research in a limited dataset illustrated the successful implementation of an imaging-guided SGB model using lidocaine. These results provided pilot data confirming the accurate delivery of combination doses of lidocaine and ABP-450, with evidence of appropriate SGB targeting without significant signs of toxicity, which supports future studies of ABP-450 as a potential treatment of PTSD. The posters presented by AEON at the TOXINS 2024 conference can be accessed on the Events and Presentations page of the Company’s corporate website. (click here). About ABP-450 (prabotulinumtoxinA) Injection ABP-450 contains a 900 kDa botulinum toxin type-A complex produced by the bacterium Clostridium botulinum. The active part of the botulinum toxin is the 150 kDa component, and the remaining 750 kDa of the complex is made up of accessory proteins that the Company believes help with the function of the active portion of the botulinum toxin. When injected at therapeutic levels, ABP-450 blocks peripheral acetylcholine release at presynaptic cholinergic nerve terminals by cleaving SNAP-25, a protein integral to the successful docking and release of acetylcholine from vesicles situated within the nerve endings leading to denervation and relaxation of the muscle. About AEON Biopharma AEON is a clinical stage biopharmaceutical company focused on developing its proprietary botulinum toxin complex, ABP-450 (prabotulinumtoxinA) injection, or ABP-450, for debilitating medical conditions, with an initial focus on the neurosciences market. AEON recently completed a Phase 2 study of ABP-450 for the treatment of cervical dystonia, released topline data from its Phase 2 study of ABP-450 for the preventive treatment of episodic migraine, and has an ongoing Phase 2 study of ABP-450 for the preventive treatment of chronic migraine. ABP-450 is the same botulinum toxin complex that is currently approved and marketed for cosmetic indications by Evolus under the name Jeuveau. ABP-450 is manufactured by Daewoong in compliance with current Good Manufacturing Practice, or cGMP, in a facility that has been approved by the U.S. Food and Drug Administration, or the FDA, Health Canada and European Medicines Agency, or EMA. AEON has exclusive development and distribution rights for therapeutic indications of ABP-450 in the United States, Canada, the European Union, the United Kingdom, and certain other international territories. The Company has built a highly experienced management team with specific experience in biopharmaceutical and botulinum toxin development and commercialization. To learn more about AEON and the development of its uniquely positioned therapeutic neurotoxin, visit . Forward-Looking Statements Certain statements in this press release may be considered forward-looking statements. Forward-looking statements generally relate to future events or AEON’s future financial or operating performance. For example, statements regarding continued listing on NYSE American, the anticipated timing of clinical results, the impact of current financing arrangements, the competitive environment in which AEON operates, AEON’s expected capital resources and liquidity needs and the expected future operating and financial performance and market opportunities of AEON are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as "pro forma", "may", "should", "could", "might", "plan", "possible", "project", "strive", "budget", "forecast", "expect", "intend", "will", "estimate", "anticipate", "believe", "predict", "potential" or "continue", or the negatives of these terms or variations of them or similar terminology. Such forward-looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward-looking statements. These forward-looking statements are based upon estimates and assumptions that, while considered reasonable by AEON and its management, are inherently uncertain. Factors that may cause actual results to differ materially from current expectations include, but are not limited to: (i) the outcome of any legal proceedings that may be instituted against AEON or others; (ii) AEON’s future capital requirements, including with respect to potential obligations pursuant to the forward purchase agreements; (iii) AEON’s ability to raise financing in the future; (iv) AEON’s ability to continue to meet continued stock exchange listing standards; (v) costs related to being a public company; (vi) changes in applicable laws or regulations; (vii) the possibility that AEON may be adversely affected by other economic, business, regulatory, and/or competitive factors; (viii) AEON’s estimates of expenses and profitability; (ix) the evolution of the markets in which AEON competes; (x) the ability of AEON to implement its strategic initiatives, including the continued development of ABP-450; (xi) the ability of AEON to defend its intellectual property; (xii) the ability of AEON to satisfy regulatory requirements; (xiii) the impact of adverse geopolitical and macroeconomic developments, such as the COVID-19 pandemic, the Israel-Hamas conflict, the Ukraine-Russia conflict and related sanctions, actual and anticipated changes in interest rates, economic inflation and the responses by central banking authorities to control such inflation on AEON’s business; and (xiv) other risks and uncertainties set forth in the section entitled “Risk Factors” and “Cautionary Note Regarding Forward-Looking Statements” in the Company’s filings with the Securities and Exchange Commission (the "SEC"), which are available on the SEC’s website at . Nothing in this press release should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements, which speak only as of the date they are made. AEON does not undertake any duty to update these forward-looking statements. Contacts Investor Contact: Corey Davis, Ph.D. LifeSci Advisors +1 212 915 2577 cdavis@lifesciadvisors.com Source: AEON Biopharma

– Expect to announce topline data in Q3 2024 – – Company plans in Q1 2024 an end-of-phase 2 meeting with the FDA to discuss the Phase 3 program in episodic migraine – – Anticipate shortening the open label extension (OLE) study to 2 treatment cycles – IRVINE, Calif., Dec. 12, 2023 (GLOBE NEWSWIRE) -- AEON Biopharma, Inc. (“AEON” or the “Company”) (NYSE: AEON, AEON WS), a clinical-stage biopharmaceutical company focused on developing a proprietary botulinum toxin complex for the treatment of multiple debilitating medical conditions, announced today completion of enrollment with the last patient first visit in the Phase 2 study of ABP-450 for the preventive treatment of chronic migraine. The Company expects to announce topline data in the third quarter of 2024. “We are excited to continue to successfully execute our clinical strategy with the completion of enrollment in the Phase 2 study of ABP-450 for chronic migraine. With the last patient enrolled in the study, we are narrowing our guidance for topline data from the study to the third quarter of 2024, which we had previously targeted for the second half of 2024. Compared to the episodic cohort, which enrolled approximately 70% of patients that appeared to be treatment naïve, the screening requirements in the chronic cohort will likely result in more treatment-experienced patients, which we believe should lower the placebo effect,” commented Marc Forth, AEON’s President and Chief Executive Officer. “We look forward to announcing the data from the chronic migraine cohort and advancing our chronic and episodic migraine programs into pivotal trials.” The Phase 2 randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of ABP-450 for the prevention of chronic migraine in adults who suffer from 15 or more headache days per month and at least 8 migraine days per month. The study has enrolled a total of 492 patients across approximately 50 sites in the United States, Canada and Australia. Patients have at least a one-year history of migraine (with or without aura) according to the ICHD-3 (2018) definition and diagnostic criteria. Study subjects were randomized evenly across a low dose group receiving 150 units of ABP-450, a high dose group receiving 195 units of ABP-450, and a placebo group. All patients will receive two treatment cycles utilizing the Company’s patented treatment paradigm (U.S. Patent No. 11,826,405) involving fewer injections than the current botulinum toxin treatment option for migraine. For the primary efficacy endpoint, the Company now plans to evaluate the change in mean monthly migraine days, or MMD, across the entire second injection cycle (weeks 13-24) relative to the four-week baseline period, as compared to placebo. This change to the evaluation period, which will also flow through to the secondary endpoints, is based on prior discussions with the U.S. Food and Drug Administration (“FDA”) and the observed effect from the Phase 2 episodic migraine cohort. The study’s other endpoints remain essentially unchanged, which include the primary safety endpoint showing the incidence of treatment-emergent adverse events (“TEAEs”), as compared to placebo, and secondary outcome measures that include the evaluation of patients with at least a 50% reduction in monthly migraine days and the number of rescue medication days per month. The only other planned change to the study endpoints is to remove as a secondary endpoint the evaluation of patients with a 100% reduction in MMD, as the measure is not expected to be a meaningful indicator of efficacy. The Company has also been in discussions with the FDA regarding adjusting the open label extension (OLE) study period from 48 weeks to 24 weeks to cover 2 treatment cycles instead of the current 4 treatment cycles. The Company is exploring this change with the hope that some of the patients who would have otherwise been enrolled in the OLE study will be available to participate in the Company’s planned Phase 3 migraine study. To date, there have been 421 patients enrolled in the OLE study across the episodic and chronic migraine Phase 2 cohorts. Participating patients who have already received 2 or 3 treatment cycles in the study will be informed of this update and will not receive additional cycles. Chronic Migraine Program Next Steps - The Company expects to announce topline data from the study in the third quarter of 2024. Episodic Migraine Program Next Steps – The Company plans to discuss the protocol and study design for a Phase 3 study at an end-of-phase 2 meeting with the FDA expected to take place in Q1 2024. The Company is evaluating multiple parameters for the Phase 3 trial that are expected to increase the statistical power and may reduce the observed higher placebo responses reported in the topline results of the Phase 2 study in episodic migraine. About Migraine Migraine is a complex neurological disease characterized by recurrent episodes of headaches that affects approximately 40 million people in the United States and approximately a billion people worldwide, making migraine the third most prevalent illness in the world. Patients who live with migraine experience symptoms that include recurring throbbing headache pain, nausea, vomiting, and sensitivity to light, sound, touch and smell. Migraine can be categorized as episodic migraine or chronic migraine. AEON projects that approximately 4 million Americans live with chronic migraine, which is characterized by 15 or more headache days per month and at least 8 migraine days per month. About ABP-450 (prabotulinumtoxinA) Injection ABP-450 contains a 900 kDa botulinum toxin type-A complex produced by the bacterium Clostridium botulinum. The active part of the botulinum toxin is the 150 kDa component, and the remaining 750 kDa of the complex is made up of accessory proteins that the Company believes help with the function of the active portion of the botulinum toxin. When injected at therapeutic levels, ABP-450 blocks peripheral acetylcholine release at presynaptic cholinergic nerve terminals by cleaving SNAP-25, a protein integral to the successful docking and release of acetylcholine from vesicles situated within the nerve endings leading to denervation and relaxation of the muscle. About AEON Biopharma AEON is a clinical stage biopharmaceutical company focused on developing its proprietary botulinum toxin complex, ABP-450 (prabotulinumtoxinA) injection, or ABP-450, for debilitating medical conditions, with an initial focus on the neurosciences market. AEON recently completed a Phase 2 study of ABP-450 for the treatment of cervical dystonia, released topline data from its Phase 2 study of ABP-450 for the preventive treatment of episodic migraine, and has an ongoing Phase 2 study of ABP-450 for the preventive treatment of chronic migraine. ABP-450 is the same botulinum toxin complex that is currently approved and marketed for cosmetic indications by Evolus under the name Jeuveau. ABP-450 is manufactured by Daewoong in compliance with current Good Manufacturing Practice, or cGMP, in a facility that has been approved by the U.S. Food and Drug Administration, or the FDA, Health Canada and European Medicines Agency, or EMA. AEON has exclusive development and distribution rights for therapeutic indications of ABP-450 in the United States, Canada, the European Union, the United Kingdom, and certain other international territories. The Company has built a highly experienced management team with specific experience in biopharmaceutical and botulinum toxin development and commercialization. To learn more about AEON and the development of its uniquely positioned therapeutic neurotoxin, visit www.aeonbiopharma.com. Forward-Looking Statements Certain statements in this press release may be considered forward-looking statements. Forward-looking statements generally relate to future events or AEON’s future financial or operating performance. For example, statements regarding continued listing on NYSE American, the anticipated timing of clinical results, the impact of current financing arrangements, the competitive environment in which AEON operates, AEON’s expected capital resources and liquidity needs and the expected future operating and financial performance and market opportunities of AEON are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as "pro forma", "may", "should", "could", "might", "plan", "possible", "project", "strive", "budget", "forecast", "expect", "intend", "will", "estimate", "anticipate", "believe", "predict", "potential" or "continue", or the negatives of these terms or variations of them or similar terminology. Such forward-looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward-looking statements. These forward-looking statements are based upon estimates and assumptions that, while considered reasonable by AEON and its management, are inherently uncertain. Factors that may cause actual results to differ materially from current expectations include, but are not limited to: (i) the outcome of any legal proceedings that may be instituted against AEON or others; (ii) AEON’s future capital requirements, including with respect to potential obligations pursuant to the forward purchase agreements; (iii) AEON’s ability to raise financing in the future; (iv) AEON’s ability to continue to meet continued stock exchange listing standards; (v) costs related to being a public company; (vi) changes in applicable laws or regulations; (vii) the possibility that AEON may be adversely affected by other economic, business, regulatory, and/or competitive factors; (viii) AEON’s estimates of expenses and profitability; (ix) the evolution of the markets in which AEON competes; (x) the ability of AEON to implement its strategic initiatives, including the continued development of ABP-450; (xi) the ability of AEON to defend its intellectual property; (xii) the ability of AEON to satisfy regulatory requirements; (xiii) the impact of adverse geopolitical and macroeconomic developments, such as the COVID-19 pandemic, the Israel-Hamas conflict, the Ukraine-Russia conflict and related sanctions, actual and anticipated changes in interest rates, economic inflation and the responses by central banking authorities to control such inflation on AEON’s business; and (xiv) other risks and uncertainties set forth in the section entitled “Risk Factors” and “Cautionary Note Regarding Forward-Looking Statements” in the Company’s filings with the Securities and Exchange Commission (the "SEC"), which are available on the SEC’s website at www.sec.gov. Nothing in this press release should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements, which speak only as of the date they are made. AEON does not undertake any duty to update these forward-looking statements. Contacts Investor Contact: Corey Davis, Ph.D. LifeSci Advisors +1 212 915 2577 cdavis@lifesciadvisors.com Source: AEON Biopharma