UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

 

FORM 8-K

 

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): January 13, 2020

 

ORCHARD THERAPEUTICS PLC

(Exact name of Registrant as Specified in Its Charter)

 

 

Registrant’s Telephone Number, Including Area Code: +44 (0) 203 808 8286

Not Applicable

(Former Name or Former Address, if Changed Since Last Report)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

Securities registered pursuant to Section 12(b) of the Act:

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

 

---

Item 2.02 Results of Operations and Financial Condition.

On January 13, 2020, Orchard Therapeutics plc (the “Company”) issued a press release announcing a preliminary unaudited estimate of its cash and investments as of December 31, 2019 (the “Financial Information”).  A copy of the press release is attached as Exhibit 99.1 to this current report on Form 8-K (the “Report”). The Financial Information is unaudited and does not present all information necessary for an understanding of the Company’s financial condition as of December 31, 2019 and its results of operations for the three or twelve months ended December 31, 2019.

The Financial Information contained in Item 2.02 of this Report and Exhibit 99.1 attached hereto shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended (the “Securities Act”), or the Exchange Act, except as expressly set forth by specific reference in such filing.

Item 7.01Regulation FD Disclosure.

The Company intends to participate in the 38th Annual J.P. Morgan Healthcare Conference during the week of January 13, 2020, including holding various investor and analyst meetings and presenting on January 14, 2020 at 11:30 a.m. Pacific Time.  A copy of the Company’s slide presentation is attached as Exhibit 99.2 to this Report. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.2.

The information contained in Item 7.01 of this Report and Exhibit 99.2 attached hereto shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act or the Exchange Act, except as expressly set forth by specific reference in such filing.

Item 8.01Other Events.

On January 13, 2020, the Company issued a press release announcing its 2020 strategic priorities.

A copy of the press release is attached as Exhibit 99.1 to this Report and is incorporated herein by reference.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits.

 

 

 

---

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

 

Exhibit 99.1

 

 

 

Orchard Therapeutics Highlights 2020 Strategic Priorities

 

Commercial Preparations on Track for Potential 2020 EU Launch of OTL-200

for Metachromatic Leukodystrophy (MLD) with U.S. Regulatory Filing Expected Late 2020 / Early 2021 

 

Initiation of Rolling U.S. Regulatory Filing for OTL-101 (ADA-SCID) Planned for 1H 2020;

U.S. and EU Regulatory Filings of OTL-103 (WAS) Expected in 2021

 

MPS-I and MPS-IIIA Proof-of-Concept Clinical Trials Ongoing with Additional Data Expected in 2020

 

New Research and Discovery Initiatives Expand Portfolio’s Potential into Larger Neurodegenerative Diseases

 

$325M in Cash and Investments to Support Execution on Strategic Priorities in 2020 and Beyond

 

BOSTON and LONDON, January 13, 2020 (GLOBE NEWSWIRE) – Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today outlined the company’s strategic priorities and recent progress in conjunction with its attendance at the 38^th Annual J.P. Morgan Healthcare Conference in San Francisco.

 

Mark Rothera, Orchard’s president and chief executive officer, will present a business overview on Tuesday, January 14, 2020 at 11:30 a.m. PT that will be webcast live at ir.orchard-tx.com. He will summarize the company’s strong fundamentals and differentiated approach to gene therapy utilizing gene-corrected hematopoietic stem cells (HSCs), with a special focus on the launch strategy for OTL-200 in metachromatic leukodystrophy (MLD) and newly announced research and discovery initiatives.   

 

“2020 has the potential to be a watershed year for Orchard as we work to bring the benefits of our gene therapy approach and expertise to patients,” Rothera said. “We are preparing diligently for the anticipated EU regulatory approval of OTL-200 for MLD while building the commercial team and executing our go-to-market strategy that will help ensure broad patient access. At the same time, we are readying our first regulatory filings in the U.S. and advancing multiple clinical-stage programs through important milestones, while also exploring the potential for gene-corrected HSCs in a broader range of severe disorders, including non-rare indications. With an unrelenting focus on execution, our organization is highly motivated to bring these investigational therapies to patients around the world.”

 

2020 Corporate Priorities

Orchard has outlined the following three high-level corporate goals for 2020:

 

---

Exhibit 99.1

 

Obtain Approval for and Launch OTL-200 for MLD in Europe

In preparation for a potential European approval in the second half of 2020, Orchard plans to establish the global infrastructure needed to support awareness and adoption of OTL-200. Orchard is putting in place a focused commercial team to serve as the backbone for the potential launch of OTL-200, as well as future product launches. A BLA filing for OTL-200 in the U.S. is planned for late 2020 or early 2021.  

 

 

Advance Two Registrational Programs Toward Upcoming Regulatory Filings

In support of its lead primary immune deficiency programs:

 

 

Investigate the Potential of ex vivo HSC Gene Therapy in Additional Neurodegenerative Diseases and New Therapeutic Areas

Orchard has entered into an agreement with Dr. Alessandra Biffi, a leading expert in gene therapy, chair of the pediatric hematology, oncology and stem cell transplant division at Padua University and co-director of the gene therapy program at Dana Farber/Boston Children’s Cancer and Blood Disorders Center, to support the expansion of its portfolio into additional areas of critical need for patients, including new programs for rare and non-rare neurodegenerative diseases. The company has also initiated in-house discovery programs to explore the application of ex vivo HSC gene therapy in other therapeutic areas.

 

Dr. Biffi commented, “Developing gene therapies for diseases with central nervous system involvement, such as neurometabolic and other neurodegenerative diseases, has been a challenge in the field. I am thrilled to partner with Orchard to continue development of this innovative gene therapy technology and, together, look forward to advancing potentially transformative treatments for these devastating diseases.”

 

As part of the agreement, Dr. Biffi will serve as senior scientific advisor of neurometabolic diseases at Orchard. Dr. Biffi’s previous role at the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) included the discovery and initiation of the OTL-200 program for MLD and the OTL-203 program for MPS-I.

---

Exhibit 99.1

 

 

In addition, Orchard plans to continue to advance the following clinical-stage neurometabolic programs currently underway in MPS-I and MPS-IIIA:

 

 

Key 2019 Achievements

Orchard achieved each of its 2019 corporate milestones, with key achievements highlighted below.

 

 

Cash Guidance

The company ended 2019 with approximately $325 million of cash and investments. The company expects that its cash, cash equivalents and marketable securities as of December 31, 2019 will enable the company to fund its currently anticipated operating expenses and capital expenditure requirements into the second half of 2021, which includes the capital investment required to build-out a new manufacturing facility operated by Orchard in Fremont, CA.

 

Presentation at 38th Annual J.P. Morgan Healthcare Conference

Orchard will webcast its corporate presentation from the 38th Annual J.P. Morgan Healthcare Conference in San Francisco on Tuesday, January 14, 2020 at 11:30 a.m. PT. A live webcast of the presentation will be available under “News & Events” in the Investors & Media section of the company's website at orchard-tx.com. A replay of the webcast will be archived on the Orchard website following the presentation.

 

About Orchard

---

Exhibit 99.1

Orchard Therapeutics is a global gene therapy leader dedicated to transforming the lives of people affected by rare diseases through innovative, potentially curative gene therapies. Our ex vivo autologous gene therapy approach harnesses the power of genetically-modified blood stem cells and seeks to permanently correct the underlying cause of disease in a single administration. The company has one of the deepest gene therapy pipelines in the industry and is advancing seven clinical-stage programs across multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist, including inherited neurometabolic disorders, primary immune deficiencies and blood disorders.

 

Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit www.orchard-tx.com, 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 (www.orchard-tx.com), the investor relations website (ir.orchard-tx.com), and on social media (twitter.com/orchard_tx and www.linkedin.com/company/10276396), 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 certain forward-looking statements about Orchard’s strategy, future plans and prospects, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements may be identified by words such as “anticipates,” “believes,” “expects,” “plans,” “intends,” “projects,” and “future” or similar expressions that are intended to identify forward-looking statements.  Forward-looking statements include express or implied statements relating to, among other things, the company’s business strategy and goals, the therapeutic potential of Orchard’s product candidates, including the product candidate or candidates referred to in this release, Orchard’s expectations regarding the timing of regulatory submissions for approval of its product candidates, including the product candidate or candidates referred to in this release, the timing of interactions with regulators and regulatory submissions related to ongoing and new clinical trials for its product candidates, the timing of announcement of clinical data for its product candidates and the likelihood that such data will be positive and support further clinical development and regulatory approval of these product candidates, the likelihood of approval of such product candidates by the applicable regulatory authorities, and the company’s financial condition and cash runway into the second half of 2021. 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, the risks and uncertainties include, without limitation: the risk that any one or more of Orchard’s product candidates, including the product candidate or candidates referred to in this release, will not be approved, successfully developed or commercialized, the risk of cessation or delay of any of Orchard’s ongoing or planned clinical trials, the risk that prior results, such as signals of safety, activity or

---

Exhibit 99.1

durability of effect, observed from preclinical studies or clinical trials will not be replicated or will not continue in ongoing or future studies or trials involving Orchard’s product candidates, the delay of any of Orchard’s regulatory submissions, the failure to obtain marketing approval from the applicable regulatory authorities for any of Orchard’s product candidates, the receipt of restricted marketing approvals, and the risk of delays in Orchard’s ability to commercialize its product candidates, if approved.  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 annual report on Form 20-F for the year ended December 31, 2018, as filed with the U.S. Securities and Exchange Commission (SEC) on March 22, 2019, 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
Director, Investor Relations
+1 862-242-0764
Renee.Leck@orchard-tx.com

Media
Molly Cameron
Manager, Corporate Communications
+1 978-339-3378
media@orchard-tx.com

 

Dedicated to Transforming the Lives of Patients Through Innovative Gene Therapies January 13 - 15, 2020 Exhibit 99.2

Forward Looking Statements | Certain information set forth in this presentation and in statements made orally during this presentation contains “forward-looking statements”. Except for statements of historical fact, information contained herein constitutes forward-looking statements and includes, but is not limited to, the Company’s expectations regarding: (I) the safety and efficacy of its product candidates; (II) the expected development of the Company’s business and product candidates; (III) the timing of regulatory submissions for approval of its product candidates; (IV) the timing of interactions with regulators and regulatory submissions related to ongoing and new clinical trials for its product candidates; (V) the timing of announcement of clinical data for its product candidates and the likelihood that such data will be positive and support further clinical development and regulatory approval of these product candidates; (VI) the likelihood of approval of such product candidates by the applicable regulatory authorities; (VII) execution of the Company’s vision and growth strategy, including with respect to global growth; and (VIII) projected financial performance and financial condition, including the sufficiency of the Company’s cash and cash equivalents to fund operations in future periods and future liquidity, working capital and capital requirements. The words “may,” “should,” “expects,” “intends,” “plans,” “anticipates,” “believes,” “estimates,” “predicts," “potential,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements are provided to allow investors the opportunity to understand management’s beliefs and opinions in respect of the future so that they may use such beliefs and opinions as one factor in evaluating an investment. These statements are neither promises nor guarantees of future performance. Such forward-looking statements necessarily involve known and unknown risks and uncertainties, which may cause actual performance and financial results in future periods to differ materially from any projections of future performance or result expressed or implied by such forward-looking statements. You are cautioned not to place undue reliance on forward-looking statements. These statements are subject to a variety of risks and uncertainties, many of which are beyond the Company’s control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. For additional disclosure regarding these and other risks faced by the Company, see the disclosure contained in the Company’s public filings with the U.S. Securities and Exchange Commission (the “SEC”), including in the Company’s annual report on Form 20-F filed with the SEC on March 22, 2019, as well as subsequent filings and reports filed with the SEC. These forward-looking statements speak only as of the date of this presentation. The Company undertakes no 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.

Global gene therapy company Dedicated to transforming the lives of patients with rare diseases Focused today on ex-vivo autologous HSC gene therapy | Confidential Orchard Therapeutics

| THE ORCHARD THERAPEUTICS STORY Strong Momentum – Transformative Year Ahead 1 Strong Fundamentals 2 Powerful Platform Approach 3 Commercial Ready 4 Our Future

Compelling Fundamentals Driving Near and Long-term Growth | Highly leverageable platform approach to gene therapy; potential to address numerous rare diseases Strong balance sheet (~$325M as of YE 2019) to fund the business into the second half of 2021 1Based on target label and pricing of recent gene therapy analogs, see slide 7-8 for additional detail Fully Integrated demonstrated R&D, manufacturing and commercial capabilities 1x to potentially cure a range of rare genetic diseases Treatment deep HSC gene therapy pipeline with therapeutic focus Clinical development candidates 7 1st regulatory submission (MLD) under EMA review U.S. / EU regulatory filings by 2021 5 lead 3 programs alone Annual addressable market opportunity1 >$1.5B

One of the Deepest Pipelines in Gene Therapy MAA decision BLA late 2020 / early 2021 Initiate rolling BLA 1H 2020 MAA & BLA submissions 2021 Interim POC data - 2020 Interim POC data - 2020 |

Building a Scalable Business in Rare Diseases | 1Based on target label and pricing of recent gene therapy analogs Incidence / prevalence figure estimates based on available literature, population data and in-house estimates, in countries where rare disease therapies are typically reimbursed. Higher incidence rates have been observed in certain populations with higher rates of consanguinity. Epidemiology incidence references: MLD: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027970/; SEG: https://ghr.nlm.nih.gov/condition/metachromatic-leukodystrophy ADA-SCID; https://ghr.nlm.nih.gov/condition/adenosine-deaminase-deficiency#statistics SEG: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911483/; WAS: ASM. Annals of Saudi Medicine. Wiskott-Aldrich Syndrome; NIH Genetics Home Reference https://ghr.nlm.nih.gov/condition/wiskott-aldrich-syndrome. Lead 3 Programs Represent Annual Incidence Opportunity of >$1.5B1 Annual Incidence 80% 80% 80% Prevalence 3,000 – 5,000 (total patients) 1,000 – 2,000 (total patients) 2,000 – 3,000 (total patients) WAS ADA-SCID MLD 20% 30% 55% 500 – 800 (total patients) 100 – 200 (total patients) 100 – 300 (total patients)

Annual Incidence 80% 80% 80% | 1Based on target label and pricing of recent gene therapy analogs Incidence / prevalence figure estimates based on available literature, population data and in-house estimates, in countries where rare disease therapies are typically reimbursed. Higher incidence rates have been observed in certain populations with higher rates of consanguinity. Epidemiology incidence references: MLD: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027970/; SEG: https://ghr.nlm.nih.gov/condition/metachromatic-leukodystrophy ADA-SCID; https://ghr.nlm.nih.gov/condition/adenosine-deaminase-deficiency#statistics SEG: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911483/; WAS: ASM. Annals of Saudi Medicine. Wiskott-Aldrich Syndrome; NIH Genetics Home Reference https://ghr.nlm.nih.gov/condition/wiskott-aldrich-syndrome. Prevalence 3,000 – 5,000 (total patients) 1,000 – 2,000 (total patients) 2,000 – 3,000 (total patients) WAS ADA-SCID MLD 20% 30% 55% 500 – 800 (total patients) 100 – 200 (total patients) 100 – 300 (total patients) 55% 100% Potential label expansion (adults) Target label (infantile & juvenile) Initial Target Label Focusing on Pediatric MLD Potential label expansion opportunity in adult MLD - Juvenile Adult

| THE ORCHARD THERAPEUTICS STORY Strong Momentum – Transformative Year Ahead 1 Strong Fundamentals 2 Powerful Platform Approach 3 Commercial Ready 4 Our Future

HSC Gene Therapy Offers a Highly Differentiated Approach | Integration Self-renewal One-time administration Monocyte / Macrophage / Microglia T cells B cells NK cells Megakaryocyte Erythrocyte Granulocyte Potential for permanent disease correction Differentiates into multiple cell types

Potential to Correct Multiple Cell Types Addresses Many Rare Diseases | Immune System MLD MPS-I MPS-IIIA MPS-IIIB ADA-SCID WAS X-CGD WAS TDT Monocyte / Macrophage / Microglia T cells B cells NK cells Megakaryocyte Erythrocyte Granulocyte Central Nervous System Immune System Blood Cell and Platelet Lineage

Durability of Response Out to 18+ Years with > 170 Patients Treated | Patients treated in the development phase, including in clinical trials and under pre-approval access (defined as any form of pre-approval treatment outside of a company-sponsored clinical trial, including, but not limited to, compassionate use, early access, hospital exemption or special license). Patient with longest Strimvelis® follow-up enrolled in registry study, with data available up to 19 years. Data based on in-house data as of December 2019. Data include all patients treated with CD34+ hematopoietic stem cells transduced ex vivo with vector of interest.

| THE ORCHARD THERAPEUTICS STORY Strong Momentum – Transformative Year Ahead 1 Strong Fundamentals 2 Powerful Platform Approach 3 Commercial Ready 4 Our Future

Metachromatic Leukodystrophy is a Devastating, Rapidly Progressive Disease | Disease Snapshot Fatal genetic CNS disorder Relentless loss of physical and cognitive function Presents on a spectrum with different ages of onset Age 5, pre-diagnosis Age 9, advanced disease

Significantly Superior Motor and Cognitive Function Demonstrated vs. Natural History | Both LI and EJ patients achieved a statistically significant difference on the co-primary endpoint of improvement of >10% of the total GMFM score in treated subjects when compared to the Natural History cohort at Year 2, and these were maintained through Year 3. Note: vertical error bars are SE of the adjusted mean; P-values are from a two-sided 5% hypothesis test with null hypothesis of ≤ 10% difference ;CI, confidence interval; EJ, early juvenile; GMFM, gross motor function measurement; LI, late infantile; MLD, metachromatic leukodystrophy. Cognitive Age-Equivalent at each visit has been derived as follows: For WPPSI and WISC: (DQp x Chronological Age)/100. For Bayley III: Cognitive Raw Scores have been compared to the tabulated values in the Bayley III manual to calculate Cognitive Age-Equivalent. For Bayley II: Cognitive Age-Equivalent is based on Mental Development Age as reported on the CRF. The Psychological Corporation. 2006.Bayley N. Bayley scales of infant and Toddler Development. Third Edition. San Antonio. Late Infantile Late Infantile Early Juvenile YEAR 3 78.7% 74.3% 2.8% 72.9% 16.3% LI MLD treated with OTL-200 (n=10) LI MLD untreated natural history (n=12) EJ MLD treated with OTL-200 (n=10) EJ MLD untreated natural history (n=12) Treatment difference = 71.5% (95% CI 50.3, 92.7) P<0.001 Treatment difference = 56.7% (95% CI 33.7, 79.6) P<0.001 Integrated analysis presented September 4 2019 at SSIEM annual meeting

Implementing Commercial Strategy to Launch OTL-200 Globally | Market Access 4 Multi-stakeholder engagement Gene therapy value determination Option for flexible payment models Patient ID and Diagnostics 1 Disease awareness and diagnostic testing Extensive newborn screening pilot testing efforts in EU and U.S. Geographic Footprint 2 Teams in place in key EU markets and U.S. Expansion to Middle East, Turkey, LatAm and Asia over time Qualifying leading centers with transplant and disease area experience Global Supply Network 3 Manufacturing hub to ship cryopreserved product globally Inventory, capacity and logistics of supply for launch

Multi-Pronged Approach to Identifying MLD Patients Confidential | Disease and Diagnostic Education Diagnostic Initiatives Newborn Screening Patient Identification Identify first symptoms and drive early suspicion KOL engagement and education of general pediatricians Peer to peer education Assay developed EU and U.S. pilots planned to initiate in 2020 Advocacy efforts at state / country level Sponsor diagnostic tests in academic centers and targeted centers of care Goal to test within 14 days of early suspicion

Establish Commercial and Operational Model: Building Teams and Infrastructure to Serve Patients Worldwide | Middle East includes GCC countries and Israel Phase 1 - 2019 / 2020 EU, Middle East 25 commercial FTEs 4 - 6 treatment centers planned Newborn screening pilots initiating (EU & U.S.) Penetration and reimbursement varies by market

Establish Commercial and Operational Model: Building Teams and Infrastructure to Serve Patients Worldwide | Middle East includes GCC countries and Israel Phase 2 - 2020 / 2021 U.S. Penetration and reimbursement varies by market

Establish Commercial and Operational Model: Building Teams and Infrastructure to Serve Patients Worldwide | Middle East includes GCC countries and Israel Phase 3 - 2021 / 2022 LatAm, ROW Penetration and reimbursement varies by market

Manufacturing in Place to Support Commercialization | MolMed producing drug product and vector Sufficient inventory being produced to meet expected launch demand Leveraging commercial process experience from Strimvelis CMO Infrastructure Established for Initial MLD Launch NEAR TERM Continue partnerships with CMOs Orchard facility in Fremont, CA Design complete Construction planned to initiate in 2020 Goal to be operational by 2021 Invest in Own Manufacturing Facilities MID - LONG TERM

Drive Global Access: Our Pricing Commitments | Shared value Ensure patients, society and industry share in human and economic benefits of innovation – now and in the future Shared risk Stand behind therapeutic outcomes and be willing to tie payment to outcomes Informed pricing Use demonstrable, objective measures of value and the best available evidence to inform price System-wide evolution Support healthcare system to adapt to emergence of one-time, potential cures

| THE ORCHARD THERAPEUTICS STORY Strong Momentum – Transformative Year Ahead 1 Strong Fundamentals 2 Powerful Platform Approach 3 Commercial Ready 4 Our Future

Investment to Scale and Innovate Across Our Business | PRODUCT PROCESS Transduction enhancers Non-toxic conditioning HSC subsets Stable cell line Closed automated systems Manufacturing facility (expected operational in 2021) Research and discovery for new indications in 2020 Technology innovations In-house capabilities

Gene-corrected HSCs and Macrophage Progeny Can Address Brain and Other Organ System Disorders | Other rare indications Potential non-rare (longer-term) Other Organ Systems Brain Macrophage High area of focus Potential future exploration Literature references: Alessia Capotondo, Rita Milazzo, Letterio Salvatore Politi, Angelo Quattrini, Alessio Palini, Tiziana Plati, Stefania Merella, Alessandro Nonis, Clelia di Serio, Eugenio Montini, Luigi Naldini, and Alessandra Biffi, PNAS September 11, 2012 109 (37) 15018-15023; https://doi.org/10.1073/pnas.1205858109; Tissue macrophages: heterogeneity and functions, Siamon Gordon and Annette Plüddemann, BMC Biology 2017 15:53, 29 June 2017

Building on our Strength in Neurometabolic Disorders | MPS-IIIB Preclinical MPS-I MPS-IIIA Interim POC data in 2020 MLD Pre-commercial / filed with EMA Multiple new neurodegenerative disorders Potential applications in larger / non-rare conditions Brain Research Undisclosed External collaboration Dr. Alessandra Biffi

Corporate Priorities & Expected Key Milestones | ADA-SCID Initiate a rolling BLA in the U.S. for OTL-101 in 1H 2020 with completion within 12 months MLD Submit a BLA filing in late 2020 or early 2021 Obtain approval and launch OTL-200 for MLD in Europe in 2H 2020 MPS-I Release interim data from POC study in 2020 Manufacturing Initiate construction of in-house manufacturing facility in 2020 Submit BLA and MAA filings for OTL-103 in 2021 WAS Enroll 5 patients in POC study, release interim data in 2020 MPS-IIIA