ADP

SAN DIEGO, CA, USA I November 27, 2023 I Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) today announced the initiation of a Phase 2 study evaluating the efficacy and safety of ACP-204 for the treatment of hallucinations and delusions associated with Alzheimer's disease psychosis (ADP). Of the more than 6.5 million people in the United States living with Alzheimer’s disease (AD), approximately 30% will experience psychosis, commonly consisting of hallucinations and delusions. 1-3 The Phase 2 study is part of a seamless Phase 2 / Phase 3 program that includes three studies: a single Phase 2 study and two Phase 3 studies which have almost identical design. The Phase 2 study is a global, multi-center, randomized, double-blind, placebo-controlled trial that will enroll approximately 318 patients and evaluate ACP-204 30 mg and 60 mg doses compared to placebo. The primary endpoint is change from Baseline in the Scale for the Assessment of Positive Symptoms–Hallucinations and Delusions subscales (SAPS-H+D) total score at Week 6. The clinical trial sites will enroll seamlessly from Phase 2 into Phase 3. Each of the planned Phase 3 studies will enroll approximately 378 patients with ADP. Patients who complete the study will have the option of participating in a long-term open-label extension (OLE) study. For more information about this study contact This email address is being protected from spambots. You need JavaScript enabled to view it. // About Alzheimer’s Disease Psychosis According to the Alzheimer’s Association, more than 6.5 million people in the United States are living with Alzheimer’s disease (AD). 1,2 Approximately 30% of patients with AD experience psychosis, commonly consisting of hallucinations and delusions. 3 These symptoms may be frequent and severe and may recur over time. 4 A hallucination is defined as a perception-like experience that occurs without an external stimulus and is sensory (seen, heard, felt, tasted, sensed, smelled) in nature. A delusion is defined as a false, fixed belief despite evidence to the contrary. Serious consequences have been associated with psychosis in patients with dementia, such as increased likelihood of nursing home placement, more severe dementia, and increased risk of morbidity and mortality. 5,6 There is no FDA-approved drug for the treatment of Alzheimer’s disease psychosis. About ACP-204 ACP-204 works primarily as an inverse agonist at the 5-HT 2A receptor. ACP-204 is currently being developed for the treatment of Alzheimer's disease psychosis, for which there is a large unmet medical need and no FDA-approved medication. About Acadia Pharmaceuticals Acadia is advancing breakthroughs in neuroscience to elevate life. For 30 years we have been working at the forefront of healthcare to bring vital solutions to people who need them most. We developed and commercialized the first and only approved therapies for hallucinations and delusions associated with Parkinson’s disease psychosis and for the treatment of Rett syndrome. Our clinical-stage development efforts are focused on treating the negative symptoms of schizophrenia, Prader-Willi syndrome, Alzheimer’s disease psychosis and neuropsychiatric symptoms in central nervous system disorders. For more information, visit us at www.acadia.com and follow us on LinkedIn and Twitter . References 1 Alzheimer’s Association. 2023 Alzheimer’s Disease Facts and Figures. Alzheimers Dement 2023;19(4). 2 Rajan KB et al. Population estimate of people with clinical Alzheimer’s disease and mild cognitive impairment in the United States (2020-2060). Alzheimer’s and Dementia . 2021: 1-10. 3 Cummings J et al. Criteria for Psychosis in Major and Mild Neurocognitive Disorders: International Psychogeriatric Associations (IPA) Consensus Clinical and Research Definition. Am J of Geriatric Psychiatry . 2020; 28(12): 1256-1269. 4 Ballard C et al. A prospective study of psychotic symptoms in dementia sufferers: psychosis in dementia. Int Psychogeriatr . 1997; 9(1): 57-64. 5 Scarmeas N et al. Delusions and hallucinations are associated with worse outcome in Alzheimer Disease. Arch Neurol . 2005; 62(10): 1601-1608. 6 Peters ME et al. Neuropsychiatric symptoms as predictors of progression to severe Alzheimer’s dementia and death: the Cache County Dementia Progression study. Am J Psychiatry . 2015; 172(5): 460-465. SOURCE: Acadia Pharmaceuticals

- Outlined strategy to build integrated cell therapy company and the Company’s “2-2-5-2” five-year core value drivers - - Reported compelling durable responses in patients with synovial sarcoma, and initial responses in lung, head and neck, liver, esophagogastric junction, and melanoma cancers confirming potential of SPEAR T-cells for solid tumors - - Completed enrollment of SPEARHEAD-1 clinical trial, to support planned BLA filing and commercialization in 2022 for ADP-A2M4 for people with synovial sarcoma - - Initiating Phase 2 trial (SURPASS-2) with ADP-A2M4CD8 in esophageal and esophagogastric junction cancers in 1H 2021 - - Demonstrated killing of cancer cells with T-cells derived from the Company’s allogeneic platform. MAGE-A4 and mesothelin to be first allogeneic programs into the clinic - - Financial guidance confirmed: funded into early 2023 - PHILADELPHIA and OXFORDSHIRE, United Kingdom, Feb. 25, 2021 (GLOBE NEWSWIRE) -- Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in cell therapy to treat cancer, today reported financial results for the fourth quarter and year ended December 31, 2020, and provided a business update. “We are building the cell therapy company of the future for people with cancer. With our ‘2-2-5-2’ by 2025 strategic plan, we will deliver value with marketed SPEAR T-cell products starting with ADP-A2M4 for people with synovial sarcoma,” said Adrian Rawcliffe, Adaptimmune’s Chief Executive Officer. “We completed enrollment in our SPEARHEAD-1 trial in approximately 12 months to support our first BLA, which is strong evidence of our ability to execute rapidly. We are focusing the SURPASS trial, using our next-generation ADP-A2M4CD8 product, on lung, gastroesophageal, head and neck, and bladder cancers to identify new indications to take forward to late-stage development.” Planned 2021 data updates1 SPEARHEAD-1 trial with ADP-A2M4 for people with synovial sarcoma June: preliminary data at American Society of Clinical Oncology (ASCO) November: full update at Connective Tissue Oncology Society (CTOS) SURPASS Phase 1 trial with ADP-A2M4CD8 (next-generation product targeting MAGE-A4) September: update at European Society for Medical Oncology (ESMO) Additional clinical updates September: update at International Liver Cancer Association (ILCA) conference for ADP-A2AFP Phase 1 trial for people with liver cancer October: update at American Society for Radiation Oncology (ASTRO) for radiation sub-study of the ADP-A2M4 Phase 1 trial 2 November: ADP-A2M4 translational data update at Society for Immunotherapy of Cancer (SITC) “2-2-5-2” by 2025 strategic plan At an Investor Day held in November 2020, the Company outlined its “2-2-5-2” by 2025 strategic plan encompassing: “2” - Two marketed products targeting MAGE-A4 Estimated potential addressable population in tumor types with significant MAGE-A4 expression, factored for HLA-A23, is ~39,000 patients per year in the US and EU Durable responses in synovial sarcoma – on track to file a Biologics License Application (BLA) for ADP-A2M4 in 2022 The first commercial opportunity for SPEAR T-cells targeting MAGE-A4 will be in synovial sarcoma with plans to file a BLA in the US in 2022 In 2020, the Company received positive endorsements from regulatory authorities with Regenerative Medicine Advanced Therapy (RMAT) designation and Orphan Drug Designation (ODD) in the US, and access to PRIority MEdicines (PRIME) regulatory support and ODD in the EU Data from the Phase 1 trial with ADP-A2M4 (presented at CTOS 2020) In 16 patients with synovial sarcoma, there was an Overall Response Rate of 44% and a Disease Control Rate of 94% Responses were durable with a median duration of response of 28 weeks with ongoing responses beyond 72 weeks in two patients (median overall survival had not been reached) These data are considerably superior 4 to response rates observed with available second line therapies in synovial sarcoma SURPASS-2 in esophageal and esophagogastric junction (EGJ) cancers in 1H 2021 The Company will initiate a Phase 2 trial, SURPASS-2, with ADP-A2M4CD8 (next-generation SPEAR T-cells targeting MAGE-A4 that co-express CD8α intended to increase potency) for patients with esophageal or EGJ cancers in 1H 2021 SURPASS-2 is supported by encouraging data from the Phase 1 SURPASS trial (presented at SITC 2020) with one confirmed partial response (PR) in a patient with EGJ cancer and tumor reductions in two additional patients (1 with esophageal and 1 with EGJ cancer) The trial will be conducted at multiple centers in North America and the EU, and is intended to enroll 45 people with esophageal or EGJ cancers to be treated with doses up to 10 billion SPEAR T-cells The Company also presented preclinical data at SITC 2020 indicating that AKT inhibition during the manufacture of SPEAR T-cells results in a more consistent expansion and phenotype of the final product. This process is currently being used for the Phase 1 SURPASS trial. “2” - Two additional BLAs for SPEAR T-cell products Adaptimmune’s Phase 1 SURPASS trial with ADP-A2M4CD8 continues to enroll patients, focusing on lung, gastroesophageal, head and neck, and bladder cancers – indications for which the Company has reported responses or signs of efficacy with its MAGE-A4 targeted products In 2020, Adaptimmune initiated SPEARHEAD-2 with its first-generation SPEAR T-cells targeting MAGE-A4 in combination with pembrolizumab for people with head and neck cancers The Phase 1 trial with ADP-A2AFP for people with liver cancer is ongoing. As presented at ILC 2020, nine patients were treated as of the data cut-off and best responses were: One patient with a complete response, one with stable disease (SD), and two with progressive disease (PD) among the four patients who received ~5 billion or more SPEAR T-cells Five patients with SD who received doses of 100 million and 1 billion SPEAR T-cells in the first two dose cohorts “5” - Five new autologous products in the clinic Adaptimmune has a deep preclinical pipeline from which it expects to bring five new products into the clinic. These include multiple possibilities for next-generation autologous SPEAR T-cells such as: ADP-A2AFP SPEAR T-cells co-expressing CD8α ADP-A2M4 SPEAR T-cells co-expressing IL-7, IL-15, dnTGFβ, and/ or PDE7 Enhancing SPEAR T-cells with IL-7 for proliferation and survival and CCL19 for migration into tumor in collaboration with Noile-Immune Biotech, Inc. Enhancing SPEAR T-cells using transmembrane and surface immunoregulatory mechanisms with Alpine Immune Sciences, Inc. The Company is also developing new products, including: Expanding into HLAs beyond HLA-A2 to increase the addressable patient population HLA-independent TCR (HiT) candidates for multiple targets including GPC3 A new program for next-generation TILs co-expressing IL-7 in melanoma in collaboration with leading TIL therapy center (CCIT, Denmark) “2” - Two allogeneic products in the clinic In January 2020, Adaptimmune announced it had entered into an agreement to co-develop and co-commercialize stem-cell derived allogeneic cell therapies with Astellas The first target nominated is a HiT targeting mesothelin At ASGCT 2020, Adaptimmune presented data with evidence of its allogeneic platform demonstrating differentiation of functional T-cells from human-induced pluripotent stem cells (hiPSCs) that can kill MAGE-A4 expressing target cells in vitro –targeted to become the Company’s first allogeneic product in the clinic Corporate updates from 2020 Despite the impact of the COVID-19 pandemic on the biotechnology industry, Adaptimmune continued to see improved enrollment in its clinical trials In Q1, the Company received an upfront payment of $50 million from Astellas. The Company is also entitled to receive research funding of up to $7.5 million per collaboration target per year Underwritten public offering in Q1 generated net proceeds of approximately $90 million Underwritten public offering in Q2 generated net proceeds of approximately $244 million Financial Results for the fourth quarter and year ended December 31, 2020 Cash / liquidity position: As of December 31, 2020, Adaptimmune had cash and cash equivalents of $56.9 million and Total Liquidity 5 of $368.2 million. As of December 31, 2020, Adaptimmune had cash and cash equivalents of $56.9 million and Total Liquidity of $368.2 million. Revenue: Revenue for the fourth quarter and year ended December 31, 2020 was $1.5 million and $4.0 million, respectively, compared to $0.7 million and $1.1 million for the same periods in 2019. The increase was due to revenue arising under the collaboration agreement with Astellas, which was entered into in January 2020. Revenue for the fourth quarter and year ended December 31, 2020 was $1.5 million and $4.0 million, respectively, compared to $0.7 million and $1.1 million for the same periods in 2019. The increase was due to revenue arising under the collaboration agreement with Astellas, which was entered into in January 2020. Research and development (R&D) expenses: R&D expenses for the fourth quarter and year ended December 31, 2020 were $25.8 million and $91.6 million, respectively, compared to $20.4 million and $97.5 million for the same periods in 2019. R&D expenses in the year ended December 31, 2019 included the accrual of a purchase commitment and higher costs for in-process research and development; excluding the impact of these, research and development expenses have increased as the Company progresses development of its cell therapies. R&D expenses for the fourth quarter and year ended December 31, 2020 were $25.8 million and $91.6 million, respectively, compared to $20.4 million and $97.5 million for the same periods in 2019. R&D expenses in the year ended December 31, 2019 included the accrual of a purchase commitment and higher costs for in-process research and development; excluding the impact of these, research and development expenses have increased as the Company progresses development of its cell therapies. General and administrative (G&A) expenses: G&A expenses for the fourth quarter and year ended December 31, 2020 were $13.2 million and $45.8 million, respectively, compared to $10.7 million and $43.4 million for the same periods in 2019. The increase in G&A expenses was due to an increase in general corporate costs, including professional fees and insurance. G&A expenses for the fourth quarter and year ended December 31, 2020 were $13.2 million and $45.8 million, respectively, compared to $10.7 million and $43.4 million for the same periods in 2019. The increase in G&A expenses was due to an increase in general corporate costs, including professional fees and insurance. Net loss: Net loss attributable to holders of the Company’s ordinary shares for the fourth quarter and year ended December 31, 2020 was $36.6 million and $130.1 million ($(0.15 per ordinary share), compared to $29.4 million and $137.2 million ($(0.22) per ordinary share) for the same periods in 2019. Financial Guidance The Company believes that its existing cash, cash equivalents and marketable securities will fund the Company’s current operations into early 2023, as further detailed in the Company’s Annual Report on Form 10-K for the year ended December 31, 2020, to be filed with the Securities and Exchange Commission following this earnings release. Conference Call Information The Company will host a live teleconference and webcast to provide additional details at 8:00 a.m. EST (1:00 p.m. GMT) today, February 25, 2021. The live webcast of the conference call will be available via the Events page of Adaptimmune’s corporate website at . An archive will be available after the call at the same address. To participate in the live conference call, if preferred, please dial (833) 652-5917 (US or Canada) or +1 (430) 775-1624 (International). After placing the call, please ask to be joined into the Adaptimmune conference call and provide the confirmation code (2099860). About Adaptimmune Adaptimmune is a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapy products for people with cancer. The Company’s unique SPEAR (Specific Peptide Enhanced Affinity Receptor) T-cell platform enables the engineering of T-cells to target and destroy cancer across multiple solid tumors. Forward-Looking Statements This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 (PSLRA). These forward-looking statements involve certain risks and uncertainties. Such risks and uncertainties could cause our actual results to differ materially from those indicated by such forward-looking statements, and include, without limitation: the success, cost and timing of our product development activities and clinical trials and our ability to successfully advance our TCR therapeutic candidates through the regulatory and commercialization processes. For a further description of the risks and uncertainties that could cause our actual results to differ materially from those expressed in these forward-looking statements, as well as risks relating to our business in general, we refer you to our Quarterly Report on Form 10-Q filed with the SEC on November 5, 2020, and our other SEC filings. The forward-looking statements contained in this press release speak only as of the date the statements were made and we do not undertake any obligation to update such forward-looking statements to reflect subsequent events or circumstances. Total Liquidity (a non-GAAP financial measure) Total Liquidity (a non-GAAP financial measure) is the total of cash and cash equivalents and marketable securities (available-for-sale debt securities). Each of these components appears separately in the consolidated balance sheet. The US GAAP financial measure most directly comparable to Total Liquidity is cash and cash equivalents as reported in the consolidated financial statements, which reconciles to Total Liquidity as follows (in millions): The Company believes that the presentation of Total Liquidity provides useful information to investors because management reviews Total Liquidity as part of its assessment of overall liquidity, financial flexibility, capital structure and leverage. Consolidated Statement of Operations (unaudited, in thousands, except per share data) Consolidated Balance Sheets (unaudited, in thousands, except share data) Consolidated Cash Flow Statement (unaudited, in thousands) Adaptimmune Contacts: Media Relations: Sébastien Desprez — VP, Communications and Investor Relations T: +44 1235 430 583 M: +44 7718 453 176 Sebastien.Desprez@adaptimmune.com Investor Relations: Juli P. Miller, Ph.D. — Senior Director, Investor Relations T: +1 215 825 9310 M: +1 215 460 8920 Juli.Miller@adaptimmune.com 1 All data updates subject to congress acceptance 2 The main portion of the ADP-A2M4 Phase 1 trial is closed for enrollment 3 Mortality figures based on American Cancer Society 2020 (US) and Global Can (EU) – synovial sarcoma data based on internal market research; MAGE-A4 expression ranges based on Adaptimmune samples and expression cut-off criteria of ≥30% tumor cells at ≥2+ intensity; HLA-A2 expression of 41% based on Adaptimmune samples (1,043 patient samples); serum AFP expression ranges based on internal samples (62 patients) and expression cut off >100ng/mL 4 Pollack S, et al. Cancer Medicine. 2020; 9:4593–4602; Seto T, et al Med. Sci. 2019, 7, 48; van der Graaf WT, et al. 2012, Lancet, 379(9829), 1879-1886 5 Total liquidity is a non-GAAP financial measure, which is explained and reconciled to the most directly comparable financial measures prepared in accordance with GAAP below.