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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 10, 2022

 

ORCHARD THERAPEUTICS PLC

(Exact name of Registrant as Specified in Its Charter)

 

 

England and Wales	001-38722	Not Applicable
(State or Other Jurisdiction of Incorporation)	(Commission File Number)	(IRS Employer Identification No.)
	108 Cannon Street London EC4N 6EU United Kingdom (Address of Principal Executive Offices; Zip Code)

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:

 

☐	Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
☐	Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
☐	Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
☐	Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

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

 

Title of each class		Trading Symbol(s)		Name of each exchange on which registered
American Depositary Shares, each representing one ordinary share, nominal value £0.10 per share		ORTX		The Nasdaq Global Select Market

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. ☐

 

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Item 2.02Results of Operations and Financial Condition.

On January 10, 2022, Orchard Therapeutics plc (the “Company”) issued a press release announcing a preliminary unaudited estimate of its cash and investments as of December 31, 2021 (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, 2021 and its results of operations for the three or twelve months ended December 31, 2021.

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 40th Annual J.P. Morgan Healthcare Conference during the week of January 10, 2022, including holding various investor and analyst meetings and presenting on January 13, 2022 at 9:00 a.m. Eastern time. A copy of the Company’s 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 10, 2022, the Company issued a press release announcing its 2022 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.

 

Exhibit Number		Description
99.1		Press release, dated January 10, 2022
99.2		Presentation of Orchard Therapeutics plc
104		Cover page interactive data file (embedded within the Inline XBRL document)

 

 

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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.

 

		ORCHARD THERAPEUTICS PLC
Date: January 10, 2022		By:	/s/ Frank E. Thomas
			Frank E. Thomas
			President and Chief Operating Officer

 

Exhibit 99.1

 

Orchard Therapeutics Announces Recent Commercial and Regulatory Progress for Late-stage HSC Gene Therapy Programs and Outlines Key 2022 Milestones

 

Launch Momentum Building for Libmeldy® in Europe with Health Technology Assessments Progressing Favorably and Treatment Underway for Multiple Commercial Patients

 

Initiating U.S. BLA Submission for OTL-200 as Early as Year End 2022; Constructive CMC Meeting with FDA Supports Timeline

 

EU MAA Submission for OTL-103 in Wiskott-Aldrich Syndrome Expected in Mid-2022 Following Productive Regulatory Interactions

 

Ended 2021 with approximately $220M in Cash and Investments to Support Operations into the First Half of 2023

 

BOSTON and LONDON, January 10, 2022 (GLOBE NEWSWIRE) – Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today outlined commercial and regulatory updates and key 2022 milestones in advance of its attendance at the virtual 40^th Annual J.P. Morgan Healthcare Conference. These activities and priorities support the company’s vision to end the devastation caused by genetic and other severe diseases through the curative potential of HSC gene therapy.

 

“Looking back at 2021 Orchard has accomplished much, from significant progress in the launch of Libmeldy in Europe, to receiving clarity from regulators on the potential path forward for our MLD, WAS and MPS-IH programs, as well as showcasing new discovery projects through our HAE collaboration with Pharming and at our latest R&D Day,” said Bobby Gaspar, M.D., Ph.D., chief executive officer. “There is still work to do, and we are starting 2022 with the same passion and commitment to continue building a company focused on changing the treatment paradigm for patients with severe genetic diseases.”

 

Libmeldy Commercial Updates in Europe

 

As part of Orchard’s objective to build a successful and sustainable commercial business in HSC gene therapy, the company is focused on three foundational pillars of the Libmeldy launch: market access, patient identification and treatment delivery.

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“As leaders in the field of HSC gene therapy, we are pioneering all aspects of our operations—including how we commercialize and deliver these potentially transformative medicines to the communities we serve,” said Braden Parker, chief commercial officer. The foundation and experience we are establishing for this launch will serve us well in 2022 and beyond as we expand geographically.”

 

Regulatory Progress and Upcoming Milestones for OTL-200 and OTL-103

 

OTL-200 for MLD (U.S.)

Orchard has completed the majority of the activities necessary in advance of a pre-Biologics License Application (BLA) meeting with U.S. Food and Drug Administration (FDA) for OTL-200. In December 2021, a Type B CMC meeting took place with the FDA, the feedback from which confirms a planned BLA submission timeline of late 2022 to early 2023.

 

OTL-103 for WAS (EU and U.S.)

Following productive regulatory interactions with the European Medicines Agency (EMA) and recent rapporteur and co-rapporteur meetings, Orchard is preparing for a Marketing Authorization Application (MAA) submission for OTL-103 in Europe in mid-2022. In the U.S., Orchard is planning to interact with FDA in early 2022 to discuss elements of a potential BLA filing package, including development work on a functional potency assay and the clinical dataset.

 

Orchard is utilizing the benefits provided under FDA’s regenerative medicine advanced therapy (RMAT) designation for both OTL-103 and OTL-200’s regulatory interactions in the U.S.

 

Additional 2022 Corporate Priorities

 

To lead the development of gene therapies for neurodegenerative disorders and investigate the potential of HSC gene therapy in future indications where there is a compelling scientific and clinical rationale, Orchard has outlined the remaining key milestones expected for 2022:

 

Key 2021 Achievements

Orchard’s key achievements from 2021 are highlighted below.

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Cash Guidance

The company ended 2021 with approximately $220 million of cash and investments. The company expects that its cash, cash equivalents and investments as of December 31, 2021 will support its currently anticipated operating and capital expenditure requirements into the first half of 2023. This cash runway excludes an additional $67 million that could become available under the company’s credit facility and any non-dilutive capital received from potential future partnerships or priority review vouchers granted by the FDA following future U.S. approvals.

 

About Libmeldy / OTL-200

Libmeldy (atidarsagene autotemcel), also known as OTL-200, has been approved by the European Commission for the treatment of MLD in eligible early-onset patients characterized by biallelic mutations in the ARSA gene leading to a reduction of the ARSA enzymatic activity in children with i) late infantile or early juvenile forms, without clinical manifestations of the disease, or ii) the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline. Libmeldy is the first therapy approved for eligible patients with early-onset MLD.

The most common adverse reaction attributed to treatment with Libmeldy was the occurrence of anti-ARSA antibodies. In addition to the risks associated with the gene therapy, treatment with Libmeldy is preceded by other medical interventions, namely bone marrow harvest or peripheral blood mobilization and apheresis, followed by myeloablative conditioning, which carry their own risks. During the clinical studies, the safety profiles of these interventions were consistent with their known safety and tolerability.

For more information about Libmeldy, please see the Summary of Product Characteristics (SmPC) available on the EMA website.

Libmeldy is approved in the European Union, UK, Iceland, Liechtenstein and Norway. OTL-200 is an investigational therapy in the US.

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Libmeldy was developed in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy.

About Orchard

 

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 GlaxoSmithKline (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 has a deep pipeline spanning pre-clinical, 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 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 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

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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. Forward-looking statements include express or implied statements relating to, among other things, Orchard’s business strategy and goals, including its plans and expectations for the commercialization of Libmeldy, the therapeutic potential of Libmeldy (OTL-200) and Orchard’s product candidates, including the product candidates referred to in this release, 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, the likelihood that data from clinical trials will be positive and support further clinical development and regulatory approval of Orchard's product candidates, and Orchard’s financial condition and cash runway into the first half of 2023. 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 of Libmeldy will not continue or be repeated in our ongoing or planned clinical trials of Libmeldy, will be insufficient to support regulatory submissions or marketing approval in the US or to maintain marketing approval in the EU, or that long-term adverse safety findings may be discovered; the risk that any one or more of Orchard’s product candidates, including the product 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 Orchard may not successfully recruit or enroll a sufficient number of patients for its clinical trials; the risk that prior results, such as signals of safety, activity or 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 or the receipt of restricted marketing approvals; the inability or risk of delays in Orchard’s ability to commercialize its product candidates, if approved, or Libmeldy, including the risk that Orchard may not secure adequate pricing or reimbursement to support continued development or commercialization of Libmeldy; the risk that the market opportunity for Libmeldy, or any of Orchard’s product candidates, may be lower than estimated; and the severity of the impact of the COVID-19 pandemic on Orchard’s business, including on clinical development, its supply chain and commercial programs. 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 quarterly report on Form 10-Q for the quarter ended September 30, 2021, as 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
Director, Investor Relations
+1 862-242-0764
Renee.Leck@orchard-tx.com

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Media
Benjamin Navon
Director, Corporate Communications
+1 857-248-9454
Benjamin.Navon@orchard-tx.com

Bobby Gaspar, M.D., Ph.D., chief executive officer 40th Annual J.P. Morgan Healthcare Conference January 13, 2022 Reaching New Heights, Looking to New Horizons Exhibit 99.2

2 | 40th Annual J.P. Morgan Healthcare Conference Photo courtesy of Great Ormond Street Hospital From Clinician to CEO: The Evolution of HSC Gene Therapy

We aspire to end the devastation caused by genetic and other severe diseases through the curative potential of HSC gene therapy.

4 | Libmeldy is approved in the European Union, UK, Iceland, Liechtenstein and Norway. OTL-200 is an investigational therapy in the US. 2021 Progress and Achievements Lays Strong Foundation for 2022

5 | Reaching New Heights Looking to New Horizons The Journey Ahead 2022: Reaching New Heights, Looking to New Horizons 40th Annual J.P. Morgan Healthcare Conference

Certain information set forth in this presentation and in statements made orally during this presentation contain “forward-looking statements”. Except for statements of historical fact, information contained herein constitute forward-looking statements and may include, but are not limited to, the Company’s expectations regarding: (i) the safety and efficacy of Libmeldy and its product candidates; (ii) the Company’s ability to establish the infrastructure necessary to enable the treatment of eligible MLD patients and the adequacy of the Company’s supply chain and ability to commercialize Libmeldy; (iii) the expected development of the Company’s business and product candidates; (iv) the timing of regulatory submissions for approval of its product candidates; (v) the timing of interactions with regulators and regulatory submissions related to ongoing and new clinical trials for its product candidates; (vi) the timing of announcement of preclinical data for its product candidates and the likelihood that such data will be positive and support further development and regulatory approval of these product candidates; (vii) the timing and likelihood of approval of such product candidates by the applicable regulatory authorities; (viii) the adequacy of the Company’s manufacturing capacity and plans for future investment and commercialization; (ix) execution of the Company’s vision and growth strategy, including with respect to global growth; (x) the size and value of potential markets for Libmeldy and the Company’s product candidates; and (xi) expected financial performance and financial condition. 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, 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. In particular, these risks and uncertainties include, without limitation, the risk that Libmeldy will not be successfully commercialized, including the risk that the Company may not secure adequate pricing or reimbursement to support continued development of Libmeldy or its product candidates, if approved; the risk that any one or more of Orchard’s product candidates, including OTL-200, will not be approved, successfully developed or commercialized; the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies or clinical trials of Orchard’s product candidates will not be repeated or continue in ongoing or future studies or trials involving its product candidates; the risk that the market opportunity for Libmeldy or its product candidates may be lower than estimated; and, the severity of the impact of the COVID-19 pandemic on Orchard’s business, including on preclinical and clinical development, its supply chain and commercial programs. You are cautioned not to place undue reliance on 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 quarterly report on Form 10-Q filed with the SEC on November 4, 2021, 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. 6 | 40th Annual J.P. Morgan Healthcare Conference Forward-looking Statements

7 | 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 HSC Gene Therapy Offers a Highly Differentiated Approach HSC Therapeutic gene

8 | 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). Data based on in-house data as of February 2021 and comprises all patients treated with CD34+ hematopoietic stem cells transduced ex vivo with vector of interest, inclusive of current and former programs. Durability of Response Demonstrated via Longest Patient Follow-up with Orchard’s HSC Gene Therapy

9 | 40th Annual J.P. Morgan Healthcare Conference Accelerating Long-term Growth and Value Creation By Expanding into Other Neurodegenerative and Immunological Diseases

Reaching New Heights Market Access and Reimbursement Patient Identification and Newborn Screening Treatment of Eligible Reimbursed Patients Libmeldy is approved in the European Union, UK, Iceland, Liechtenstein and Norway. OTL-200 is an investigational therapy in the US. Entering 2022 with Strong Momentum for Libmeldy/OTL-200 10 | Future Potential Regulatory Approvals

40th Annual J.P. Morgan Healthcare Conference 11 | European HTA and Reimbursement Discussions Progressing Well Broad Recognition of Libmeldy's Clinical Impact

40th Annual J.P. Morgan Healthcare Conference 12 | 2 eligible patients in process of reimbursed treatment 4 5 centers treatment ready Newborn screening (NBS) pilots/studies launched or planned Utilizing Our Commercial Infrastructure to Identify, Treat and Secure Reimbursement for Eligible Patients in Europe

40th Annual J.P. Morgan Healthcare Conference 13 | OTL-200 (MLD): Advancing U.S. Regulatory Discussions RMAT meeting with confirmation of expected clinical package Productive Type B CMC meeting Clarity on manufacturing facility FDA inspection readiness NEXT STEP: Pre-BLA submission meeting with U.S. FDA Provided OTL-200 for U.S. investigator-initiated compassionate use INDs; Successfully released investigational drug product shipped between U.S. treatment site and EU CDMO

14 | Meet the need in genetic and other severe diseases Looking to New Horizons 40th Annual J.P. Morgan Healthcare Conference Deliver on rare disease portfolio Expand HSC gene therapy approach

15 | 40th Annual J.P. Morgan Healthcare Conference Productive rapporteur / co-rapporteur interactions MAA filing planned for mid-2022 OTL-103 for WAS: Progressing Toward Regulatory Submissions in Europe and the U.S. Active IND / RMAT designation FDA interaction planned for early 2022

16 | Neuropsychological Tests over Time Cognitive Age-Equivalent Score (Overall) Conducted parallel scientific advice meeting with EMA and FDA Recent Program Achievements and Next Steps Note: SD = Standard Deviation; IQ(C) = Intelligence Quotient (Cognition); For Bayley III, the IQ(C) is the cognitive composite score as collected. For WPPSI, the IQ(C) is defined as the performance scales score. For Bayley II: Cognitive Age-Equivalent will be defined as the Mental developmental Age recorded on the CRF. For Bayley III: Cognitive Raw Scores will be compared to the tabulated values in the Bayley III manual to calculate the Cognitive Age-Equivalent. For WPPSI, Age-Equivalent = (IQ*Chronological Age)/100. 2021 MPS Symposium OTL-203 for MPS-IH: Stable Cognitive Function and Growth within the Normal Range in Proof-of-concept Study Proof-of-concept study results published in New England Journal of Medicine Obtain necessary regulatory clearance in mid-2022 to enable global registrational study Initiate global registrational trial by year end

17 | 40th Annual J.P. Morgan Healthcare Conference Rare Disease Portfolio Provides Clinical Proof-of-concept in More Prevalent Neurodegenerative and Immunological Diseases 40th Annual J.P. Morgan Healthcare Conference Proof-of-concept in rare neurometabolic disease

18 | 40th Annual J.P. Morgan Healthcare Conference Orchard’s Discovery and Early Research Program Highlights 40th Annual J.P. Morgan Healthcare Conference Future Applications for HSC Gene Therapy Neurodegenerative disorders Approach leverages success of Libmeldy in whole-brain secretion of ARSA from fully distributed microglial cells Targets include GRN-FTD, ALS and other indications Two key areas to expand HSC gene therapy platform: Vectorized antibody platform to deliver mAbs to specific tissues or sites HSC CAR-Treg platform as a durable therapy for autoimmune disorders Status: Tech. development and preclinical proof-of-concept models ongoing NOD2 Crohn’s disease Orchard is developing OTL-104, an HSC gene therapy product targeting NOD2 mutations associated with Crohn’s disease severity Early preclinical data shows potential Status: Preclinical proof-of-concept models ongoing Status: Exploratory research ongoing

19 | 40th Annual J.P. Morgan Healthcare Conference Combining the Proven Durability of HSC Gene Therapy with the Specific Suppressive Potential of CAR-Tregs

Pancreatic beta-cells Myelin sheath Synovial tissue 20 | Image credit: Biorender Potential Applications of the HSC CAR-Treg Technology

21 | Roadmap for a sustainable future 40th Annual J.P. Morgan Healthcare Conference Pursue partnership opportunities Potential for disease-specific or technology driven approaches The Journey Ahead Invest for growth Leverage HSC GT platform as engine for new indications Utilize global infrastructure and footprint for future potential approvals and launches Maintain strong balance sheet Multiple near-term value-creating milestones expected

22 40th Annual J.P. Morgan Healthcare Conference Research Platform Provides Multiple Opportunities for Business Development Partnerships in specific diseases OTL-105 for HAE partnered with Pharming Leveraging ongoing programs in CNS (FTD/ALS) and colitis (NOD2-Crohn’s) Partnerships built on specific technologies Antigen-specific Tregs for autoimmune diseases mAb vectorization technology to target specific tumors or other targets

23 Libmeldy: Reach reimbursement agreement with at least two countries in 1H’22 Libmeldy: Continue to broaden patient identification and newborn screening initiatives OTL-103: MAA filing in WAS in mid-2022; FDA interaction planned in early 2022 to discuss elements of a potential BLA filing package OTL-200: Planned BLA submission for MLD in late 2022 / early 2023 OTL-203: Initiate global registrational trial for MPS-IH by year end OTL-201: Present data from ongoing MPS-IIIA POC trial in 1H’22 Advance research programs in GRN-FTD (OTL-204), NOD2-CD (OTL-104), HAE (OTL-105) and HSC-generated antigen-specific Tregs Clinical Regulatory Commercial 40th Annual J.P. Morgan Healthcare Conference Anticipated 2022 Milestones: A Catalyst-Rich Year Spanning All Phases of Development and Commercialization

24 | 40th Annual J.P. Morgan Healthcare Conference Compelling Fundamentals Driving Near-term Value Creation and Long-term Growth

Thank you! 25