MECP2

Data from first adult patient in REVEAL Phase 1/2 trial showed TSHA-102 (low dose, 5.7x1014 total vg) was well-tolerated with no treatment-emergent SAEs as of 35-week assessment, with sustained improvement across key efficacy measures at decreased steroid levels and new improvement in RSBQ at month six Data from second adult patient showed TSHA-102 (low dose, 5.7x1014 total vg) was well-tolerated with no treatment-emergent SAEs as of 19-week assessment, with sustained improvement across key efficacy measures, significantly reduced seizure events and new improvement in R-MBA at week 12 Principal Investigator observed sustained and new improvements across multiple clinical domains following completion of steroid taper for patient one through 35-weeks post-treatment and for patient two through 19-weeks post-treatment at decreased steroid levels Received Independent Data Monitoring Committee approval of Company’s request to proceed to early advancement to cohort two (high dose, 1x1015 total vg) in REVEAL adolescent and adult trial, and approval to dose second pediatric patient in cohort one (low dose, 5.7x1014 total vg) in REVEAL pediatric trial Initial data from cohort one (low dose, 5.7x1014 total vg) in REVEAL pediatric trial expected mid-2024; initial data from cohort two (high dose, 1x1015 total vg) in both trials (adolescent/adult and pediatric) expected in 2H 2024 Conference call and live webcast today at 4:30 PM Eastern Time DALLAS, March 19, 2024 (GLOBE NEWSWIRE) -- Taysha Gene Therapies, Inc. (Nasdaq: TSHA) (Taysha or the Company), a clinical-stage gene therapy company focused on developing and commercializing AAV-based gene therapies for the treatment of severe monogenic diseases of the central nervous system (CNS), today reported financial results for the full-year ended December 31, 2023, and provided corporate and clinical updates. “We are highly encouraged by the safety profile and durable response reported in the longer-term data from the low dose cohort in our REVEAL adolescent and adult trial. Importantly, following completion of the steroid taper for the first patient and at decreased steroid levels for the second patient, both patients showed sustained improvements across multiple clinical domains, as well as new improvements compared to earlier post-treatment assessments, which supports the transformative potential of TSHA-102,” said Sean P. Nolan, Chairman and Chief Executive Officer of Taysha. “These continued improvements in both adult patients with advanced stage four Rett syndrome and the initial clinical data from the first pediatric patient were reviewed by the Independent Data Monitoring Committee (IDMC) and enabled us to proceed to earlier dose escalation in the adolescent and adult trial, which will expedite and further inform our clinical development and regulatory strategy for the dose expansion portion of the studies. With this progress, we believe we are well-positioned to focus on generating clinical data in a broad range of ages and stages of patients with Rett syndrome across multiple geographies this year.” Dr. Elsa Rossignol, M.D., FRCP, FAAP, Associate Professor in Neuroscience and Pediatrics at the Université de Montréal, and Principal Investigator of the REVEAL trial at the CHU Sainte-Justine added, “Both adult patients treated with TSHA-102 showed sustained and new improvements across key areas of disease impacting activities of daily living, including multiple aspects of autonomic function, social communication, motor skills, and experienced stabilized or significantly reduced seizures. The first patient sustained improvements at week 35 post-treatment after the completion of her steroid taper, with restored movement in her legs, the gained ability to sit unassisted for the first time in over a decade and gained function in her non-dominant hand. She has also sustained improvements in breathing dysrhythmia and sleep quality and duration, including the gained ability to sleep through the night for the first time in 20 years. Notably, she has vastly increased interest in social communication and activities at week 35 compared to earlier post-treatment assessments. She is more alert and socially interactive, with increased vocalizations and enhanced ability to use an eye-driven communication device. The second patient showed sustained improvements at decreased steroid levels at week 19 post-treatment, including reduced hand stereotypies for the first time since regression at age three, and sustained improvements in breathing dysrhythmia, including hyperventilation and reduced apneic spells. As of week 19 post-treatment, she’s experienced a significant reduction in seizures at a lower dose of anti-seizure medication. Collectively, these continued improvements in both adult patients with different genetic mutation severity and phenotypic expression are encouraging and support the potential of TSHA-102 to bring meaningful change to the lives of patients and their caregivers.” Data Summary from Cohort One (Low Dose, 5.7x1014 total vg) of the REVEAL Phase 1/2 Adolescent and Adult Trial TSHA-102 in Rett syndrome: a self-complementary intrathecally delivered AAV9 gene transfer therapy in clinical evaluation for Rett syndrome, a rare genetic neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene. TSHA-102 utilizes a novel miRARE technology designed to mediate levels of MECP2 in the CNS on a cell-by-cell basis without risk of overexpression. The safety and preliminary efficacy of TSHA-102 are being evaluated in female patients aged 12-years and older with Rett syndrome due to MECP2 loss-of-function mutation in the REVEAL Phase 1/2 adolescent and adult trial, a first-in-human, open-label, randomized, dose-escalation and dose-expansion study taking place in Canada and the United States (U.S.). Dose escalation will evaluate two dose levels of TSHA-102 sequentially. The maximum tolerated dose (MTD) or maximum administered dose (MAD) established in Part A will then be administered during dose expansion in Part B of the study. Results from the first patient (large MECP2 deletion; associated with severe phenotype) and second patient (missense MECP2 mutation; associated with milder phenotype) with late motor deterioration stage four Rett syndrome dosed with TSHA-102 in the low dose cohort (5.7x1014 total vg): Generally well-tolerated with no treatment-emergent serious adverse events (SAEs) as of 35-week assessment post-treatment for patient one and 19-week assessment post-treatment for patient twoSustained and new improvements observed across multiple clinical domains, as of 35-weeks post-treatment for patient one following completion of steroid taper at week 33, and 19-weeks post-treatment for patient two at decreased steroid levels (taper began at week 17), based on clinical observations by the Principal Investigator (PI), including: Autonomic function: improved breathing patterns, sleep quality/duration and circulation (patient one), and improved breathing patterns and circulation (patient two)Socialization/Communication: improved social interest, vocalization and ability to use eye-driven communication device (patient one), and improved social interest (patient two)Motor skills: improved hand function and gained ability to sit unassisted and move legs (patient one), and improved hand stereotypies (patient two)Seizures: stable seizure events (patient one), and significantly reduced seizure events (patient two) Seizure Diary showed stable seizure events at lower levels of anti-seizure medication relative to baseline through 35-weeks post-treatment in patient one, and significantly reduced seizure events with lower levels of anti-seizure medication relative to baseline through 19-weeks post-treatment in patient two, based on caregiver-reported medical history Clinical improvements seen across key efficacy measures in both patients include: Patient one at six-month assessment: Sustained improvement in Clinical Global Impression–Improvement (CGI-I), Clinical Global Impression–Severity (CGI-S), Parental Global Impressions–Improvement (PGI-I), Revised Motor Behavior Assessment (R-MBA), Rett Syndrome Hand Function Scale (RSHFS) and Seizure Diaries, at decreased steroid levels, with new improvement in Rett Syndrome Behavior Questionnaire (RSBQ)Patient two at 12-week assessment: Sustained improvement in CGI-I, PGI-I and RSBQ, with new improvement in R-MBA and Seizure Diaries Figure accompanying this announcement is available here. Recent Corporate and Program Highlights Strengthened clinical and regulatory leadership with the promotion of Meredith Schultz, M.D., M.S., to Chief Medical Officer and Rumana Haque-Ahmed to Chief Regulatory Officer, reporting to Sukumar Nagendran, M.D., President and Head of R&D. Dr. Schultz is a board-certified, licensed pediatric neurologist experienced in treating patients with Rett syndrome and leading gene therapy clinical trials. She brings more than 17 years of clinical experience and will lead the Company’s clinical development, clinical operations, medical affairs and safety activities. Rumana Haque-Ahmed brings nearly 30 years of experience in regulatory strategy and product development in the biopharmaceutical space. She will continue to lead the Company’s regulatory affairs department and initiatives. REVEAL Phase 1/2 Adolescent and Adult Trial (Canada and U.S.): Completed dosing in cohort one (low dose, n=2) of 5.7x1014 total vg.Received IDMC approval of the Company’s request to dose escalate immediately, enabling early advancement to cohort two (high dose, n=3) of 1x1015 total vg.Announced expansion of ongoing trial in Canada into the U.S. and initiated site activation. REVEAL Phase 1/2 Pediatric Trial (U.S. and United Kingdom (U.K.)): Received IDMC approval to dose the second pediatric patient in cohort one (low dose, n=3) of 5.7x1014 total vg following review of initial clinical data from the six-week post-treatment assessment.Received authorization from U.K. Medicines and Healthcare Products Regulatory Agency (MHRA) of Clinical Trial Application (CTA) for TSHA-102, enabling expansion of ongoing trial in U.S. into the U.K.Received Innovative Licensing and Access Pathway (ILAP) designation for TSHA-102 from U.K. MHRA. The ILAP aims to facilitate patient access to novel treatments by accelerating time to market through opportunities for enhanced engagements with U.K. regulatory authorities and other stakeholders. Anticipated 2024 Milestones REVEAL Adolescent and Adult Trial Dosing of the first patient in cohort two (high dose, n=3) of 1x1015 total vg expected in the second quarter of 2024.Initial safety and efficacy data from cohort two expected in the second half of 2024. REVEAL Pediatric Trial Dosing of the second patient in cohort one (low dose, n=3) of 5.7x1014 total vg expected in the first quarter of 2024.Initial safety and efficacy data from cohort one expected in mid-2024.Initial safety and efficacy data from cohort two (high dose, n=3) of 1x1015 total vg expected in the second half of 2024. Full-Year 2023 Financial Highlights Revenue: Revenue for the full year ended December 31, 2023, was $15.5 million compared to $2.5 million for the full year ended December 31, 2022, as revenue was derived entirely from the Company’s Option Agreement with Audentes Therapeutics, Inc. (d/b/a Astellas Gene Therapies). The increase in revenue is primarily a result of Rett syndrome research and development activities performed in 2023. Research and Development Expenses: Research and development expenses were $56.8 million for the full year ended December 31, 2023, compared to $91.2 million for the full year ended December 31, 2022. The decrease was due to reduced research and development headcount, lower research and development manufacturing expenses and a reduction in third-party research and development consulting fees, mainly related to pre-clinical studies and IND-enabling toxicology studies. General and Administrative Expenses: General and administrative expenses were $30.0 million for the full year ended December 31, 2023, compared to $37.4 million for the full year ended December 31, 2022. The decrease was primarily attributable to a reduction in compensation expenses as a result of lower headcount and reduced corporate insurance and consulting expenses. Net loss: Net loss for the full year ended December 31, 2023, was $111.6 million, or $0.96 per share, as compared to a net loss of $166.0 million, or $3.78 per share, for the full year ended December 31, 2022. The net loss includes a non-recurring and non-cash expense of $34.5 million related to the change in fair value from the pre-funded warrants as a result of the August 2023 private placement financing. Cash and cash equivalents: As of December 31, 2023, Taysha had $143.9 million in cash and cash equivalents. The Company continues to expect that its current cash resources will support planned operating expenses and capital requirements into 2026. Conference Call and Webcast InformationTaysha management will hold a conference call and webcast today at 4:30 p.m. ET to review its financial and operating results and to provide corporate and clinical updates. The dial-in number for the conference call is 877-407-0792 (U.S./Canada) or 201-689-8263 (international). The conference ID for all callers is 13744574. The live webcast and replay may be accessed by visiting Taysha’s website at https://ir.tayshagtx.com/news-events/events-presentations. An archived version of the webcast will be available on the website for 30 days. About TSHA-102TSHA-102 is a self-complementary intrathecally delivered AAV9 investigational gene transfer therapy in clinical evaluation for Rett syndrome. Designed as a one-time treatment, TSHA-102 aims to address the genetic root cause of the disease by delivering a functional form of MECP2 to cells in the CNS. TSHA-102 utilizes a novel miRNA-Responsive Auto-Regulatory Element (miRARE) technology designed to mediate levels of MECP2 in the CNS on a cell-by-cell basis without risk of overexpression. TSHA-102 has received Fast Track designation and Orphan Drug and Rare Pediatric Disease designations from the FDA and has been granted Orphan Drug designation from the European Commission. TSHA-102 has also received Innovative Licensing and Access Pathway designation from the U.K. Medicines and Healthcare Products Regulatory Agency. About Rett SyndromeRett syndrome is a rare neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene encoding methyl CpG-binding protein 2 (MeCP2), which is essential for regulating neuronal and synaptic function in the brain. The disorder is characterized by loss of communication and hand function, slowing and/or regression of development, motor and respiratory impairment, seizures, intellectual disabilities and shortened life expectancy. Rett syndrome progression is divided into four key stages, beginning with early onset stagnation at 6 to 18 months of age followed by rapid regression, plateau and late motor deterioration. Rett syndrome primarily occurs in females and is one of the most common genetic causes of severe intellectual disability. Currently, there are no approved disease-modifying therapies that treat the genetic root cause of the disease. Rett syndrome caused by a pathogenic/likely pathogenic MECP2 mutation is estimated to affect between 15,000 and 20,000 patients in the U.S., EU, and U.K. About Taysha Gene TherapiesTaysha Gene Therapies (Nasdaq: TSHA) is a clinical-stage biotechnology company focused on advancing adeno-associated virus (AAV)-based gene therapies for severe monogenic diseases of the central nervous system. Its lead clinical program TSHA-102 is in development for Rett syndrome, a rare neurodevelopmental disorder with no approved disease-modifying therapies that address the genetic root cause of the disease. With a singular focus on developing transformative medicines, Taysha aims to address severe unmet medical needs and dramatically improve the lives of patients and their caregivers. The Company’s management team has proven experience in gene therapy development and commercialization. Taysha leverages this experience, its manufacturing process and a clinically and commercially proven AAV9 capsid in an effort to rapidly translate treatments from bench to bedside. For more information, please visit www.tayshagtx.com. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “anticipates,” “believes,” “expects,” “intends,” “projects,” “plans,” and “future” or similar expressions are intended to identify forward-looking statements. Forward-looking statements include statements concerning the potential of TSHA-102, including the reproducibility and durability of any favorable results initially seen in patient dosed to date in clinical trials, and our other product candidates, to positively impact quality of life and alter the course of disease in the patients we seek to treat, our research, development and regulatory plans for our product candidates, including the timing of initiating additional trials and reporting data from our clinical trials, the potential for these product candidates to receive regulatory approval from the FDA or equivalent foreign regulatory agencies, and our current cash resources supporting our planned operating expenses and capital requirements into 2026. Forward-looking statements are based on management’s current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. Risks regarding our business are described in detail in our Securities and Exchange Commission (“SEC”) filings, including in our Annual Report on Form 10-K for the full-year ended December 31, 2023, which is available on the SEC’s website at www.sec.gov. Additional information will be made available in other filings that we make from time to time with the SEC. These forward-looking statements speak only as of the date hereof, and we disclaim any obligation to update these statements except as may be required by law. Taysha Gene Therapies, Inc.Condensed Consolidated Statements of Operations(in thousands, except share and per share data) For the YearEnded December 31, 2023 2022 Revenue$15,451 $2,502 Operating expenses: Research and development 56,778 91,169 General and administrative 30,047 37,360 Impairment of long-lived assets 1,065 36,420 Total operating expenses 87,890 164,949 Loss from operations (72,439) (162,447)Other income (expense): Change in fair value of warrant liability (34,718) — Loss on debt extinguishment (1,398) — Change in fair value of term loan (1,538) — Interest income 3,572 249 Interest expense (4,998) (3,798)Other expense (47) (18)Total other expense, net (39,127) (3,567)Net loss$ (111,566) $ (166,014)Net loss per common share, basic and diluted$(0.96) $(3.78)Weighted average common shares outstanding, basic and diluted 116,121,482 43,952,015 Taysha Gene Therapies, Inc.Condensed Consolidated Balance Sheet Data(in thousands, except share and per share data) December 31,2023 December 31,2022ASSETS Current assets: Cash and cash equivalents$143,940 $87,880 Restricted cash 449 — Prepaid expenses and other current assets 3,479 8,537 Assets held for sale 2,000 — Total current assets 149,868 96,417 Restricted cash 2,151 2,637 Property, plant and equipment, net 10,826 14,963 Operating lease right-of-use assets 9,582 10,943 Other non-current assets 304 1,316 Total assets$ 172,731 $ 126,276 LIABILITIES AND STOCKHOLDERS' EQUITY Current liabilities: Accounts payable$6,366 $10,946 Accrued expenses and other current liabilities 12,284 18,287 Deferred revenue 18,106 33,557 Total current liabilities 36,756 62,790 Term loan, net 40,508 37,967 Operating lease liability, net of current portion 18,953 20,440 Other non-current liabilities 1,577 4,130 Total liabilities 97,794 125,327 Stockholders' equity Preferred stock, $0.00001 par value per share; 10,000,000 shares authorized and no shares issued and outstanding as of December 31, 2023 and December 31, 2022 — — Common stock, $0.00001 par value per share; 400,000,000 shares authorized and 186,960,193 issued and outstanding as of December 31, 2023, and 200,000,000 shares authorized and 63,207,507 issued and outstanding as of December 31, 2022 2 1 Additional paid-in capital 587,942 402,389 Accumulated deficit (513,007) (401,441)Total stockholders’ equity 74,937 949 Total liabilities and stockholders' equity$ 172,731 $ 126,276 Company Contact:Hayleigh Collins Director, Head of Corporate Communications and Investor RelationsTaysha Gene Therapies, Inc.hcollins@tayshagtx.com Media Contact:Carolyn HawleyInizio EvokeCarolyn.hawley@inizioevoke.com A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/466835b0-a81c-400a-af61-1395051604ec

FARMINGDALE, N.Y., March 19, 2024 (GLOBE NEWSWIRE) -- Depymed, Inc. (“DepYmed” or the “Company”) is a clinical-stage pharmaceutical company focused on developing transformative medicines for many poorly treated diseases that may benefit significantly by targeting the protein tyrosine phosphatase (PTP) family of enzymes. Today, DepYmed announces it has received clearance from the U.S. Food and Drug Administration to initiate its phase 1 clinical trial for DPM-1003 for the treatment of Rett Syndrome. “This is a foundational achievement for DepYmed. It allows us to transition into a clinical-stage company with a transformational new drug candidate that has the possibility to provide significant benefit for patients,” said Andreas Grill, DepYmed’s President and CEO. “As an IND for the first drug of its kind, we believe this milestone opens a pathway to the development of important new treatments for a wide range of diseases where inhibiting PTP enzymes holds promise. This includes Rett Syndrome, cancer, metabolic disease and obesity, and Alzheimer’s Disease. We look forward to beginning to assess the safety and tolerability of DPM-1003 and continue our development of this compound for Rett Syndrome and our other ongoing programs.” About DPM-1003 Protein tyrosine phosphatases are major players in the control of cell signaling pathways that are disrupted in many diseases, yet to date no drug modulators of these enzymes have been successfully developed. DepYmed is the first company to develop a new class of orally bioavailable drug candidates that act by inhibiting PTP1B, one of the most important PTP drug targets. One of its lead compounds has shown promising efficacy in preclinical models of Rett syndrome, and the Company hopes to initiate a phase 1 clinical trial in 2024. DPM-1003 has been granted Orphan Drug designation by the U.S. Food and Drug Administration and conditionally designated under the FDA’s Rare Pediatric Disease program. About Rett Syndrome Rett syndrome is a progressive neurodevelopmental disorder that almost exclusively affects females. Infants with Rett syndrome generally develop normally for 6 to 18 months after birth. At this point, they lose previously acquired skills (developmental regression) such as purposeful hand movements and the ability to communicate. Affected children often develop autistic-like behaviors, breathing irregularities, feeding and swallowing difficulties, growth retardation, and seizures. Most Rett syndrome cases are caused by mutations of the MECP2 gene on the X chromosome and can present with a wide range of disability ranging from mild to severe. The expression of PTP1B, DepYmed’s target in Rett syndrome, is regulated by MECP2; in turn, PTP1B controls important cell functions that are disrupted in the disease. About DepYmed, Inc. DepYmed, Inc. is a New York-based rare disease and cancer therapeutic development company that was founded to capitalize on the scientific discoveries of the Tonks lab at Cold Spring Harbor Laboratory in the physiological function of PTP1B and ways to modulate its role in various human diseases. DepYmed is currently developing a new class of potent, orally bioavailable small molecule inhibitors of the enzyme PTP1B as novel therapeutics for Rett Syndrome, different types of cancer, metabolic diseases, obesity, and Alzheimer’s Disease where the PTP1B target has shown promise. In addition, DepYmed has also discovered a novel class of small molecules with copper chelating properties that it is developing as potential therapeutic agents for diseases such as Wilson disease and various cancers. The company is actively developing a deep pipeline of new compounds with broad therapeutic potential in these emerging drug classes in collaboration with Cold Spring Harbor Laboratory. For more information, please visit the Company’s website at: . For Media Inquiries please contact: Jules Abraham JQA Partners, Inc. jabraham@jqapartners.com 917-885-7378 DepYmed: info@depymedinc.com

Expanded Phase 1/2 gene therapy trial for Rett syndrome to inform future registrational study design; Company remains on track to share interim clinical data in 4Q:24 Strong financial position with runway into 2H:26 following reverse merger and private financing in December 2023 NEW YORK--(BUSINESS WIRE)-- Neurogene Inc. (Nasdaq: NGNE), a clinical-stage company founded to bring life-changing genetic medicines to patients and families affected by rare neurological diseases, today announced fourth quarter and full year 2023 financial results and highlighted recent corporate updates. “We started the year with strong execution in our Phase 1/2 NGN-401 gene therapy trial for female pediatric patients with Rett syndrome, meeting our goal to expand the trial and add a high-dose cohort. We believe this expanded dataset will support future regulatory discussions to align on the design of a potential registrational study,” said Rachel McMinn, Ph.D., Chief Executive Officer and Founder of Neurogene. “NGN-401 has the potential to be a best-in-class treatment option with a targeted route of administration to deliver full-length, functional copies of the MECP2 gene. We are pleased that NGN-401 has been well-tolerated in all three patients dosed, with no signs of overexpression-related toxicity, demonstrating the potential of our EXACT transgene regulation technology to constrain MECP2 levels within a narrow and therapeutically relevant range. As we look ahead, we remain on track for interim clinical data from the NGN-401 trial in the fourth quarter of this year.” Continued Dr. McMinn, “Our decision to execute a reverse merger, along with the concurrent private financing, provides us with cash runway into the second half of 2026, beyond key inflection points in our NGN-401 program and our NGN-101 program for CLN5 Batten disease. We look forward to sharing data from both programs later this year and continuing to advance our pipeline to enable an additional development candidate using EXACT in 2025.” Fourth Quarter 2023 and Recent Highlights, and Anticipated Milestones Phase 1/2 Trial of NGN-401 Gene Therapy for Treatment of Rett Syndrome As previously planned, amended the protocol, expanding the trial to include more patients in low-dose Cohort 1 and added a high-dose Cohort 2; these updates are expected to provide a robust dataset and inform the design of a future registrational study Remains on track to report interim clinical data from Cohort 1 in the fourth quarter of 2024; additional interim data, including from Cohort 2, are expected in the second half of 2025 Dosed the third patient early in the first quarter of 2024; removed the dosing stagger in Cohort 1, enabling the remaining patients in the cohort to be dosed in parallel Plans to complete enrollment in Cohort 1 in the second half of 2024; enrollment in Cohort 2 is expected to begin in the second quarter of 2024 Reported that NGN-401 has been generally well-tolerated and there have been no treatment-emergent or procedure-related serious adverse events or signs of overexpression-related toxicity observed in any patient Received NGN-401 clinical trial application approval from the United Kingdom (“UK”) Medicines and Healthcare products Regulatory Agency and working to on-board clinical sites in the UK Phase 1/2 Trial of NGN-101 Gene Therapy for Treatment of CLN5 Batten Disease Continuing enrollment in high-dose Cohort 3, and expects to provide interim clinical data and regulatory update in the second half of 2024 Additional Corporate Updates Expanded the leadership team with appointment of Julie Jordan, M.D., as Chief Medical Officer; Dr. Jordan brings more than 20 years of experience to Neurogene, including design and execution of clinical trials for central nervous system disorders and gene therapies Completed reverse merger and concurrent private placement of $95 million, and began trading on the Nasdaq Global Market under “NGNE” in mid-December 2023 Continues to expect to advance one additional product candidate, using EXACT technology, from the discovery stage into the clinic in 2025 Fourth Quarter and Full Year 2023 Financial Results Cash and Cash Equivalents: Cash, cash equivalents and investments as of December 31, 2023 were $197.2 million. Research & Development (“R&D”) Expenses: R&D expenses were $12.2 million and $44.4 million for the three and twelve months ended December 31, 2023, respectively, compared to $11.0 million and $47.5 million for the three and twelve months ended December 31, 2022, respectively. The decrease in R&D expenses for the twelve months ended December 31, 2023 was primarily driven by a decrease in manufacturing and development and pre-clinical costs offset by increased clinical trial costs. General & Administrative (“G&A”) Expenses: G&A expenses were $2.5 million and $11.2 million for the three and twelve months ended December 31, 2023, respectively, compared to $2.0 million and $9.0 million for the three and twelve months ended December 31, 2022, respectively. The increase in G&A expenses for the twelve months ended December 31, 2023 was primarily driven by an increase in personnel costs, increased professional and consulting fees related to the reverse merger, and increased insurance and information technology costs. Due to the timing of the closing of the reverse merger in mid-December 2023, additional transaction-related expenses are expected to be recognized in the first quarter of 2024. Net Income and Net Loss: Net income was $2.4 million and net loss was $36.3 million for the three and twelve months ended December 31, 2023, respectively, compared to net loss of $12.3 million and $55.2 million for the three and twelve months ended December 31, 2022, respectively. Net income for the three months ended December 31, 2023 included a one-time $16.4 million bargain purchase gain related to the reverse merger. Upcoming Events Stifel 2024 Virtual CNS Days: Management will participate in a fireside chat on Wednesday, March 20 at 9:30 a.m. ET About Neurogene The mission of Neurogene is to treat devastating neurological diseases to improve the lives of patients and families impacted by these rare diseases. Neurogene is developing novel approaches and treatments to address the limitations of conventional gene therapy in central nervous system disorders. This includes selecting a delivery approach to maximize distribution to target tissues and designing products to maximize potency and purity for an optimized efficacy and safety profile. The Company’s novel and proprietary EXACT transgene regulation platform technology allows for the delivery of therapeutic levels while limiting transgene toxicity associated with conventional gene therapy. Neurogene has constructed a state-of-the-art gene therapy manufacturing facility in Houston, Texas. CGMP production of NGN-401 was conducted in this facility and will support pivotal clinical development activities. For more information, visit . Cautionary Note Regarding Forward-Looking Statements Statements in this press release which are not historical in nature are intended to be, and hereby are identified as, forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may discuss goals, intentions and expectations as to future plans, trends, events, results of operations or financial condition, or otherwise, based on current expectations and beliefs of the management of Neurogene, as well as assumptions made by, and information currently available to, management of Neurogene, including, but not limited to, statements regarding: the therapeutic potential and utility, efficacy and clinical benefits of NGN-401; the safety and tolerability pro NGN-401; trial designs, clinical development plans and timing for NGN-401, including anticipated timing of enrollment in and clinical trial results from the Company’s NGN-401 Phase 1/2 trial for Rett syndrome; effects of the removal of staggered dosing in Cohort 1; initiation of new clinical sites for NGN-401 in the UK; expected interactions with the FDA regarding NGN-101; nomination of additional preclinical product candidates; and our expected cash resources and liquidity. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as “may,” “will,” “should,” “would,” “expect,” “anticipate,” “plan,” “likely,” “believe,” “estimate,” “project,” “intend,” “on track,” and other similar expressions or the negative or plural of these words, or other similar expressions that are predictions or indicate future events or prospects, although not all forward-looking statements contain these words. Forward-looking statements are based on current beliefs and assumptions that are subject to risks, uncertainties and assumptions that are difficult to predict with regard to timing, extent, likelihood, and degree of occurrence, which could cause actual results to differ materially from anticipated results and many of which are outside of Neurogene’s control. Such risks, uncertainties and assumptions include, among other things: risks related to the timing and success of enrolling patients in the expanded cohort of our Phase 1/2 clinical trial of NGN-401 for the treatment of Rett syndrome; the expected timing and results of dosing of patients in our clinical trials, including NGN-401; the potential that we may not be able to expand our Phase 1/2 clinical trial of NGN-401 for the treatment of Rett syndrome into the UK based on a variety of factors, including but not limited to any decisions of regulatory authorities, costs of expanding the trial in the UK, the availability of suitable clinical test sites, and the ability to enroll patients in the UK or other reasons; the potential for negative impacts to patients resulting from using a higher dose of NGN-401 in Cohort 2 of the Phase 1/2 clinical trial for the treatment of Rett syndrome; the risk that we may not be able to report our data on the predicted timeline; our limited operating history; the risk that we may not be able to raise adequate additional capital to finance our operations, complete our clinical trials and commercialize our products; risks related to our ability to obtain regulatory approval for, and ultimately commercialize, our product candidates, including NGN-401; risks related to the outcome of non-clinical testing and early clinical trials for our product candidates, including the ability of those trials to satisfy relevant governmental or regulatory requirements; risks related to our limited experience in designing clinical trials and lack of experience in conducting clinical trials; and other risks and uncertainties identified under the heading "Risk Factors" included in our Annual Report on Form 10-K for the year ended December 31, 2023, filed with the Securities and Exchange Commission (“SEC”) on March 18, 2024, and other filings that the Company has made and may make with the SEC in the future. Nothing in this communication should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that the contemplated results of any such forward-looking statements will be achieved. Forward-looking statements in this communication speak only as of the day they are made and are qualified in their entirety by reference to the cautionary statements herein. Except as required by applicable law, Neurogene undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. This communication contains hyperlinks to information that is not deemed to be incorporated by reference into this communication. - Financial Tables Follow - Neurogene Inc. Condensed Consolidated Balance Sheet Data (In thousands of U.S. dollars) December 31, 2023 December 31, 2022 Assets Cash and cash equivalents $ 148,210 $ 82,021 Other current assets 52,138 2,698 Non-current assets 22,225 24,546 Total assets $ 222,573 $ 109,265 Liabilities Current liabilities $ 22,973 $ 6,651 Non-current liabilities 13,576 3,987 Total liabilities 36,549 10,638 Total convertible preferred stock — 244,366 Stockholders' equity (deficit) 186,024 (145,739) Total liabilities, convertible preferred stock and stockholders' equity (deficit) $ 222,573 $ 109,265 Neurogene Inc. Condensed Consolidated Statements of Operations (In thousands of U.S. dollars, except share information) Year Ended December 31, 2023 2022 Operating expenses: Research and development $ 44,394 $ 47,505 General and administrative 11,189 9,012 Total operating expenses 55,583 56,517 Loss from operations (55,583) (56,517) Other income, net 2,911 1,328 Bargain purchase gain 16,355 — Net loss $ (36,317) $ (55,189) Pre-Merger Post- Merger Pre-Merger Per share information (1): (a) (b) (c) (a) (b) Net income (loss) per share, basic $ (117.28) $ — $ 27.76 $ (139.88) $ — Weighted-average shares outstanding used in computing net income (loss) per share, basic 426,097 — 491,867 394,533 — Net income (loss) per share, diluted $ (117.28) $ — $ 2.93 $ (139.88) $ — Weighted-average shares outstanding used in computing net income (loss) per share, diluted 426,097 — 4,656,947 394,533 — (1) On December 18, 2023, the Company completed its reverse merger, which among other things, resulted in Neurogene OpCo merging with and into a wholly owned subsidiary of Neoleukin Therapeutics, Inc. As the earnings per share information for the pre-merger period is not comparable to the earnings per share information for the post-merger period, the earnings per share information is being presented separately for these periods. See Note 3, Net Income (Loss) Per share, for additional information. (a) Presents information for the pre-merger period for Class A common stock. The pre-merger period is January 1, 2023 through December 17, 2023 for the year ended December 31, 2023 and the full fiscal year ended December 31, 2022. (b) Presents information for the pre-merger period for Class B common stock. The pre-merger period is January 1, 2023 through December 17, 2023 for the year ended December 31, 2023 and the full fiscal year ended December 31, 2022. (c) Presents information for the post-merger period for common stock. The post-merger period is December 18, 2023 through December 31, 2023.