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Preclinical proof-of-concept data show the therapeutic potential of OTL-104 for NOD2 Crohn’s disease, a severe and treatment-refractory form of the disease In vivo data demonstrate the development of CAR-Treg cells from genetically engineered HSCs as a potential one-time treatment for autoimmune disorders Company to host conference call and webcast Tuesday, May 23 at 8:00 a.m. EDT BOSTON and LONDON, May 18, 2023 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today presented new data from the company’s hematopoietic stem cell (HSC) gene therapy research pipeline targeting larger indications at the ongoing 26th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) in Los Angeles. Presentations include preclinical proof-of-concept data from OTL-104, the company’s investigational HSC gene therapy for the treatment of nucleotide-binding oligomerization domain containing protein 2 (NOD2) Crohn’s disease, as well as in vivo preclinical data demonstrating the development of functional CAR-Treg cells from genetically engineered HSCs. Both programs were designed and developed in Orchard’s own research laboratories utilizing the company’s proprietary HSC gene therapy platform. “These data continue to demonstrate the power of our HSC gene therapy platform and its applicability beyond our rare neurometabolic franchise into diseases with larger patient populations,” said Fulvio Mavilio, Ph.D., chief scientific officer of Orchard Therapeutics. “Due to their unique ability to self-renew and differentiate into multiple cell types that migrate to tissues and organs often inaccessible to other therapeutic modalities, HSC-based gene therapies have immense therapeutic and collaborative potential. We look forward to advancing IND-enabling activities for our research program in NOD2 Crohn’s disease and further developing the HSC-derived CAR-Treg cell technology.” OTL-104 (NOD2 Crohn’s Disease) Preclinical Data Summary Using established in vitro and in vivo models of NOD2 deficiency, including NOD2 knockout mice and HSC-derived macrophages from Crohn’s patients with biallelic NOD2 mutations, Orchard researchers evaluated the safety and efficacy of HSC gene therapy in restoring NOD2-dependent immune responses. The chimeric promoter used in OTL-104 was originally developed and clinically tested in patients with X-linked chronic granulomatous disease (X-CGD), where enhanced expression of gp91-Phox in myeloid and monocyte lineages was demonstrated. In a poster session tomorrow, the first preclinical proof-of-concept data will highlight the therapeutic potential of this approach, including: OTL-104, a lentiviral vector expressing NOD2 under the control of a myeloid-directed chimeric promoter, fully restores NOD2-dependent immune responses in macrophages derived from HSCs obtained from Crohn’s patients carrying biallelic NOD2 mutations to within the range of healthy donor cells. Transplantation of OTL-104 in NOD2 knockout mice reconstitutes NOD2 expression in intestinal tissue resident cells and broadly restores NOD2-dependent innate immune cell functions. Taken together, these results confirm the negative impact of NOD2 deficiency in primary immune activation and support the therapeutic potential of HSC gene therapy to provide long-term correction of NOD2 Crohn’s disease. Work to evaluate OTL-104’s ability to correct an induced NOD2 knockout mouse model of ileitis is currently ongoing. The company expects to commence IND- and CTA-enabling studies in the second half of 2023, with a potential filing now anticipated in the first half of 2025. HSC CAR-Treg cell Technology Preclinical Data Summary Yesterday’s poster session demonstrates the feasibility of utilizing HSC gene therapy to provide stable and targeted immunotherapy, through the ability of HSCs to differentiate into T regulatory (Treg) cells engineered to express chimeric antigen-specific receptors (CAR). This approach combines the proven durability of HSC gene therapy with the specific suppressive activity of CAR-Treg cells, providing an alternative to current treatments which fail to effectively control chronic autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis and Type 1 diabetes. Data from transplanted mice show that the preferential expression of CAR in HSC-derived regulatory T cells in vivo does not significantly alter the development, phenotype or function of these suppressive immune cells. Also, the functionality of the CAR receptor is demonstrated when HSC-derived CAR-Tregs can be activated ex vivo by exposure to a CAR-specific ligand, producing the immunosuppressive cytokine IL-10. The company will continue to advance its preclinical research activities aimed at further demonstrating the feasibility and applicability of its HSC CAR-Treg cell technology. Conference Call and Webcast A live webcast to recap the data will be available under "News & Events" in the Investors & Media section of the company's website at on Tuesday May 23, 2023, at 8:00 a.m. EDT. A replay of the webcast will be archived on the Orchard website following the presentation. About OTL-104 and NOD2 Crohn’s Disease Crohn’s disease is a form of Inflammatory Bowel Disease (IBD), a condition affecting the gastrointestinal tract. Mutations in a number of genes are known to confer susceptibility to the risk of Crohn’s, and among these the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene is the most common genetic factor. NOD2 deficiency results in an impaired detection and clearance of bacteria penetrating the gut during gastrointestinal infection. This leads to a form of Crohn’s disease more severe and refractory to existing therapies, with manifestations including chronic abdominal pain, diarrhea, weight loss, fatigue, malnutrition and for some patients, more severe intestinal damage requiring surgical resection. Epidemiological studies suggest NOD2 genetic variants causing functional defects are associated with 7 to 10% of all cases of Crohn’s, with up to 200,000 patients in the U.S. and Europe with two NOD2 mutated alleles. There is currently no cure for Crohn's disease, and long-term, effective treatment options are limited. Current clinical management for Crohn’s disease includes use of immune-suppressive medications, biological agents such as anti-TNF, steroids and surgical resection. OTL-104 is an investigational HSC gene therapy in development for the potential treatment of patients with NOD2 Crohn’s disease. As the pathogenesis of NOD2 Crohn’s disease is associated with the function of cells of the hematopoietic system, OTL-104 may therefore be used to restore NOD2 function to immune cells such as tissue resident macrophages within the gastrointestinal tract. OTL-104 is designed to introduce the NOD2 gene into cells of the hematopoietic system by lentiviral transduction of a patient’s own HSCs, and the gene-modified cells can then be infused back into the patient. About Orchard’s Proprietary HSC T-reg Cell Technology HSC gene therapy is well-suited to address severe autoimmune disorders due to the ability of HSCs to differentiate into regulatory T-cells (Tregs) which are a specialized subset of T-cells that can suppress inflammation and be harnessed as a cell therapy with an approach similar to that used to create chimeric antigen receptor T-cells (CAR-Ts). Orchard’s approach aims to combine the demonstrated durability of HSC gene therapy in genetic diseases with the specific suppressive potential of Tregs. Orchard has established a proprietary position covering the concept, therapeutic application and specifics of HSC-antigen-specific Treg therapy. About Orchard Therapeutics At Orchard Therapeutics, our vision is to end the devastation caused by genetic and other severe diseases. We aim to do this by discovering, developing and commercializing new treatments that tap into the curative potential of hematopoietic stem cell (HSC) gene therapy. In this approach, a patient’s own blood stem cells are genetically modified outside of the body and then reinserted, with the goal of correcting the underlying cause of disease in a single treatment. In 2018, the company acquired GSK’s rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy. Today, Orchard is advancing a pipeline spanning preclinical, clinical and commercial stage HSC gene therapies designed to address serious diseases where the burden is immense for patients, families and society and current treatment options are limited or do not exist. Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit , and follow us on Twitter and LinkedIn. Availability of Other Information About Orchard Investors and others should note that Orchard communicates with its investors and the public using the company website ( ), the investor relations website (ir.orchard-tx.com), and on social media (Twitter and LinkedIn), including but not limited to investor presentations and investor fact sheets, U.S. Securities and Exchange Commission filings, press releases, public conference calls and webcasts. The information that Orchard posts on these channels and websites could be deemed to be material information. As a result, Orchard encourages investors, the media, and others interested in Orchard to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Orchard’s investor relations website and may include additional social media channels. The contents of Orchard’s website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933. Forward-looking Statements This press release contains forward-looking statements, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Forward-looking statements include express or implied statements relating to, among other things, Orchard’s business and product development strategy and goals, including the therapeutic potential of the programs mentioned in this press release, Orchard’s expectations with respect to regulatory submissions for its product candidates, and Orchard’s expectations regarding its ongoing preclinical and clinical trials, including the timing of enrollment for clinical trials and release of additional preclinical and clinical data, and the likelihood that data from clinical trials will be positive and support further clinical development and regulatory approval of Orchard's product candidates. These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchard’s control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, these risks and uncertainties include, without limitation: the risk that prior results, such as signals of safety, activity or durability of effect, observed from clinical trials will not continue or be repeated in Orchard’s ongoing or planned clinical trials, will be insufficient to support regulatory submissions or support or maintain marketing approval in the US or European Union, or that long-term adverse safety findings may be discovered; and the risk that any one or more of Orchard’s product candidates will not be approved, successfully developed or commercialized. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements. Other risks and uncertainties faced by Orchard include those identified under the heading "Risk Factors" in Orchard’s most recent annual or quarterly report filed with the U.S. Securities and Exchange Commission (SEC), as well as subsequent filings and reports filed with the SEC. The forward-looking statements contained in this press release reflect Orchard’s views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law. Contacts Investors Renee Leck Senior Director, Investor Relations +1 862-242-0764 Renee.Leck@orchard-tx.com Media Benjamin Navon Director, Corporate Communications +1 857-248-9454 Benjamin.Navon@orchard-tx.com

TOTUM•854 protects human cells of the vascular wall, particularly against inflammation and oxidative stress, which is key to preventing worsening of high blood pressure. TOTUM•854 also reduces angiotensin I-converting enzyme (ACE1) activity, one of the main modes of action known to reduce blood pressure. The bioavailability study also confirms the presence of 10 metabolites of interest in human serum after oral administration of 3.7 g of TOTUM•854, the daily clinical dose used in the Phase II/III INSIGHT clinical study. In line with the preclinical data, these very strong results confirm the potential of TOTUM•854 against mild to moderate high blood pressure in humans and provide strong prospects for late clinical development. With a view to marketing TOTUM•854, Valbiotis is targeting the signature of international partnerships and will market directly on the French market; the market for mild to moderate high blood pressure currently includes 123 million adults in the United States and Europe1. LA ROCHELLE, France--(BUSINESS WIRE)-- Regulatory News: Valbiotis (FR0013254851 – ALVAL, PEA / SME eligible) (Paris:ALVAL), a commercially oriented Research and Development company, with a commercial purpose, committed to scientific innovation for preventing and combating metabolic and cardiovascular diseases, announces positive results in the bioavailability and mode of action clinical study conducted on TOTUM•854 against high blood pressure, the number one cardiovascular risk factor worldwide. The mode of action results demonstrate a protective effect of TOTUM•854 on vascular wall cells and a reduction in angiotensin I-converting enzyme (ACE1) activity in humans. These robust data confirm the potential of TOTUM•854 to reduce blood pressure at the earliest stages of arterial hypertension, which affect 123 million people in the US and Europe1. They hold great promise for the late-stage clinical development of TOTUM•854. Pascal SIRVENT, Director of Discovery and Preclinical and Translational Research, member of the Executive Committee, comments: "These innovative bioavailability and mode of action studies once again demonstrate their scientific value for the development of our plant-based active substances. In line with our preclinical work, we can now confirm that TOTUM•854 preserves the integrity of the cells of the blood vessel wall, more specifically of its endothelium. Damage to the vascular wall is a major mechanism in the progression of high blood pressure. Moreover, we also discovered that this active substance acts on the angiotensin pathway, a well-known target of anti-hypertensive strategies. This first-in-human evidence confirms the relevance of TOTUM•854's positioning in the early stages of the disease and bodes well for the ongoing Phase II/III clinical efficacy studies in high blood pressure." TOTUM•854, a patented active substance based on a combination of plant extracts, is developed to reduce blood pressure in people with mild to moderate hypertension, a risk factor for cardiovascular disease. Mild to moderate arterial hypertension now affects 123 million adults in the United States and the 5 major European countries1. No non-drug product has strong clinical evidence or a specific health claim. TOTUM•854 is currently in the final phase of clinical development before being marketed. Valbiotis aims to sign one or more international commercial partnerships while it will market this active substance in France itself, in accordance with the strategy announced on October 7, 2022 (press release of October 7, 2022). TOTUM•854 will be marketed in two stages. The first step will be based on the recommendation by healthcare professionals, thanks to the Phase II/III results. In a second step, obtaining a proprietary health claim will strengthen the medical positioning of TOTUM•854, especially with patients/consumers. Enrollment in the first Phase II/III clinical trial (INSIGHT study) is expected to be completed by half-year 2023. Results of the bioavailability and mode of action clinical study on TOTUM•854 The TOTUM•854 bioavailability and mode of action clinical study, conducted in 10 healthy volunteers, first confirmed the presence of 10 metabolites of interest2, mainly polyphenolic compounds, in volunteers' serum3. These analyses were performed after taking 3.7 g of TOTUM•854 orally, the daily clinical dose also used in the Phase II/III INSIGHT clinical study. Ex vivo mode of action analyses then demonstrated a triple protective effect of these metabolites on human blood vessel wall cells (endothelial cells): increased resistance and viability of these cells to stress induced by excess lipids; strong protection against inflammatory processes, with a significant decrease in the production of pro-inflammatory agents such as interleukin 1-ß (IL1-ß) and in the expression of MCP-1 and VCAM-2 markers; protection against oxidative stress with a decrease in the concentration of free radicals and a reduced expression of the Nox2 enzyme. Mode of action tests also revealed a reduction in angiotensin I-converting enzyme (ACE1) activity, an enzyme well known in the pathophysiology of high blood pressure. This protective effect on the vascular wall in humans confirms the data already obtained in preclinical studies and presented at the annual meetings of the American Heart Association (AHA), the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) in 2022. Above all, it confirms the preventive positioning of TOTUM•854 in the early stages of high blood pressure. In the initial phases of the disease, when blood pressure rises, the vascular wall undergoes damage involving inflammation and oxidative stress. Ultimately, these changes lead to the narrowing of blood vessels: hypertension worsens, becomes chronic and requires long-term pharmacological treatment. Protection of the vascular wall is therefore a major challenge in the management of early high blood pressure, in order to prevent the progression of the condition. The innovative protocol of the TOTUM•854 bioavailability and mode of action clinical study The study was conducted on 10 healthy volunteers in an open-label setting and followed a protocol combining metabolomics and mode of action. Prof. Gisèle PICKERING, coordinator of the Clinical Investigation Center at Clermont-Ferrand University Hospital, was the principal investigator4. Metabolomic analysis consists of characterizing the metabolites of an active substance in serum, i.e., the molecules derived from this active substance after their intestinal absorption and their passage into the blood. After a single oral intake of 3.7 g of TOTUM•854, the daily clinical dose also used in the INSIGHT Phase II/III clinical study, analysis of the volunteers' serum confirmed the presence of 10 metabolites of interest, polyphenolic compounds mostly known to exert biological activity on metabolism. Kinetic measurements confirmed good bioavailability of these metabolites in serum within three hours after oral administration of TOTUM•854. In a second step, serum from volunteers was collected after oral intake of 3.7 g TOTUM•854. This serum rich in active metabolites was used to conduct in vitro mode of action tests on human umbilical vein endothelial cells (HUVECs), exposed to massive lipid intake, or lipotoxic stress, generating inflammation and oxidative stress. About Valbiotis Valbiotis is a commercially oriented Research & Development company, committed to scientific innovation for preventing and combating metabolic and cardiovascular diseases in response to unmet medical needs. Valbiotis has adopted an innovative approach, aiming to revolutionize healthcare by developing a new class of health nutrition products designed to reduce the risk of major metabolic diseases, relying on a multi-target strategy enabled by the use of plant-based terrestrial and marine resources. Internationally, its products are intended to be the subject of licensing or distribution agreements with global and regional health and nutrition players. In France, Valbiotis will be responsible for marketing its own products. Created at the beginning of 2014 in La Rochelle, the Company has forged numerous partnerships with leading academic centers. The Company has established three sites in France – Périgny, La Rochelle (17) and Riom (63) – and a subsidiary in Quebec City (Canada). Valbiotis is a member of the "BPI Excellence" network and has been recognized as an "Innovative Company" by the BPI label. Valbiotis has also been awarded "Young Innovative Company" status and has received major financial support from the European Union for its research programs via the European Regional Development Fund (ERDF). Valbiotis is a PEA-SME eligible company. For more information about Valbiotis, please visit: Name: Valbiotis ISIN code: FR0013254851 Ticker symbol: ALVAL EnterNext© PEA-PME 150 This press release contains forward-looking statements about Valbiotis’ objectives. Valbiotis considers that these projections are based on rational hypotheses and the information available to Valbiotis at the present time. However, in no way does this constitute a guarantee of future performance, and these projections may be affected by changes in economic conditions and financial markets, as well as certain risks and uncertainties, including those described in the Valbiotis Universal Registration Document filed to the French Financial Markets Regulator (AMF) on May 19, 2022, and completed by an amendment on November 8, 2022. This document is available on the Company’s website ( ). This press release and the information it contains do not constitute an offer to sell or subscribe, or a solicitation to purchase or subscribe to Valbiotis’ shares or financial securities in any country. 1Elevated LDL, pre-HTA and NAFL preliminary market estimation, AEC Partners, 2020. 2Molecules from TOTUM•854, after they have been absorbed from the intestine and passed into the bloodstream. 3The fraction of blood remaining after all blood cells (red blood cells, leukocytes, platelets) and fibrinogen (a protein involved in coagulation) have been removed. 4ID-RCB: 2021-A02695-36

– Proceeds to advance lead program into clinical development– – Financing Led by Perceptive Xontogeny Venture Fund– PHILADELPHIA--(BUSINESS WIRE)-- Peroxitech Inc., an emerging biopharmaceutical company developing a novel peptide for treating acute lung injury (ALI), announced the successful completion of a Series A financing round of $25 million led by the Perceptive Xontogeny Venture Fund (“PXV Fund”). The company will use the proceeds to build upon the preclinical work conducted through collaborative partnership and seed investment with the Xontogeny development team to advance the lead candidate, PIP-2, through IND-enabling studies and into clinical development. “The data generated to date for PIP-2 represents a potential breakthrough in the prevention and treatment of ALI” stated Thomas Han, Chief Executive Officer and Co-Founder of Peroxitech. “We are pleased with the progress we have made through the Xontogeny seed investment and to expand upon our close partnership through this PXV Fund Series A approval so that we can bring this compelling program forward to patients as expeditiously as possible.” Peroxitech’s lead asset mechanism leverages the discovery of a novel signaling pathway, NOX2, related to the oxidative injury cascade, which has demonstrated broad protection and rescue in several preclinical models. The Company’s novel peptide shows it can protect cells from injury and enables injured ones to recover to near normal levels. These product characteristics could provide significant benefits in ALI and may have applications in other diseases. “Peroxitech is well positioned with this unique mechanism, strong preclinical data, and a clear path forward to address the unmet needs in ALI/ARDs and become a transformative treatment option for patients,” said Chris Garabedian, Portfolio Manager of the PXV Funds, Chief Executive Officer of Xontogeny. “Perceptive Advisors is excited to announce this investment to extend our support for Peroxitech as they progress through IND-enabling studies to accelerate the path to clinical development. We are confident in the program design and strategic pathway developed to provide meaningful clinical data in patients.” Peroxitech was seeded and incubated at Xontogeny in 2021 to advance the program through confirmatory preclinical efficacy studies and further optimize the CMC development. In addition to the lead program, the company has also secured additional grants from the National Institutes of Health (NIH) for follow-on indications and further pipeline development. Peroxitech is led by Thomas Han and co-founded by Sheldon Feinstein, Ph.D. and Aron Fisher, M.D. Chris Garabedian and Ben Askew, Ph.D., Xontogeny Chief Executive Officer and Xontogeny Partner, Research and Development, respectively, serve on the Board of Directors. About Peroxitech Peroxitech Inc. is a privately held biopharmaceutical company focused on the development and commercialization of a novel therapeutic for treatment of acute lung injury. The company was launched the University of Pennsylvania’s Penn Center for Innovation (PCI) Ventures and was seeded at Xontogeny. In addition to the first clinical indication, Peroxitech is also evaluating our lead compound for several high unmet need areas where oxidative injury signaling pathways are a major contributor to disease progression. Please visit our website for further information, About Perceptive Xontogeny Venture Fund The Perceptive Xontogeny Venture (PXV) Fund is Perceptive Advisors' investment vehicle focused purely on early-stage, private venture investments in life sciences companies. Primary investments for the Fund include companies that are seeking a lead investor for Series A financings, which include both companies that are seeded and incubated at Xontogeny and companies that are seeded and incubated by other organizations, accelerators and investors. The PXV Fund is also open to participating in syndicated Series A financings as a co-lead or passive investor with other venture capital firms. For more information, visit . About Xontogeny, LLC Based in Boston, MA, Xontogeny seeks to accelerate the development of life science technologies by providing entrepreneurs with funding options as well as the leadership, strategic guidance and operational support necessary to increase the probability of success in early drug and technology development. Through a differentiated approach, the Xontogeny team partners with founding scientists and entrepreneurs to support their vision while allowing a more efficient development model that benefits company founders and early equity holders. For more information visit .