UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
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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
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Item 2.01 Results of Operations and Financial Condition.
On January 9, 2023, Orchard Therapeutics plc (the “Company”) issued a press release announcing a preliminary unaudited estimate of its cash and investments as of December 31, 2022 (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, 2022 and its results of operations for the three or twelve months ended December 31, 2022.
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 7.01 Regulation FD Disclosure.
On January 9, 2023, the Company updated its corporate presentation for use in meetings with investors, analysts and others. A copy of the 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 9.01 Financial Statements and Exhibits.
(d) Exhibits.
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104 |
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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.
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ORCHARD THERAPEUTICS PLC |
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Date: January 9, 2023 |
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By: |
/s/ Frank E. Thomas |
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Frank E. Thomas |
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President and Chief Operating Officer |
Exhibit 99.1
Orchard Therapeutics Highlights Recent Progress Across HSC Gene Therapy Portfolio and Outlines Key 2023 Milestones
Libmeldy® revenue totaled $5.8M in Q4 2022 and $18.8M for the full year with commercial expansion activities continuing in Europe
Clinical Type B meeting with U.S. FDA to take place in early 2023 prior to OTL-200 (MLD) BLA submission
Ended 2022 with approximately $144M in cash and investments and reduced burn rate to support operations into Q2 2024
OTL-203 (MPS-IH) IND application cleared by U.S. FDA with global registrational trial to initiate in the second half of 2023
Preclinical proof-of-concept data for OTL-104 (NOD2-Crohn’s disease) expected in the first half of 2023; initiating IND-enabling activities ahead of 2024 filing
BOSTON and LONDON, January 9, 2023 (GLOBE NEWSWIRE) – Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced recent commercial and regulatory accomplishments and outlined key 2023 milestones, highlighting the strong potential of its hematopoietic stem cell (HSC) gene therapy platform to drive value for patients, providers and shareholders.
As a leader in the development, manufacturing and commercialization of HSC gene therapies, Orchard is well-positioned to leverage its expertise to provide potentially curative treatments to people suffering from a broad range of severe diseases with a single administration. To date, over 170 patients have been treated with Orchard’s current and former HSC gene therapy programs across seven different diseases, reflecting the broad clinical applicability of the company’s approach.
“Orchard’s accomplishments in 2022 showcase the depth and strength of our neurometabolic portfolio,” said Bobby Gaspar, M.D., Ph.D., chief executive officer. “We right sized our workforce and narrowed the focus of our HSC gene therapy portfolio to concentrate on severe neurometabolic diseases and research programs where alternative treatment options are limited or do not exist. At the same time, we continued to advance our commercialization and access strategy for Libmeldy. From securing reimbursement and treating the first eligible MLD patients commercially in Europe, to constructive engagement with the FDA to finalize the design of our OTL-203 global registrational trial for MPS-IH and presenting the first neurocognitive results from the OTL-201 program in MPS-IIIA, we are well-positioned to end the devastation caused by genetic and other severe diseases for patients and their families.”
Gaspar continued, “Looking ahead to the first half of 2023, we will maintain our disciplined strategy and stewardship of capital as we focus on execution and achieving our regulatory and clinical milestones while remaining open to partnership opportunities that could accelerate growth and value creation. We expect our upcoming clinical Type B meeting for OTL-200 for MLD with the FDA to provide further clarity on our anticipated BLA submission. Given the broad potential for our technology, we have a number of exciting prospects in our pipeline, including larger indications such as the NOD2 form of Crohn’s disease, and will advance the development of our portfolio prudently as we progress through anticipated near-term milestones.”
Key 2023 Priorities
Orchard has outlined the following key milestones expected for 2023:
Preliminary Financial Information (unaudited)
Preliminary estimated revenue from product sales of Libmeldy was $5.8 million for the three months ended December 31, 2022, and $18.8 million for the full year ended December 31, 2022.
The company ended 2022 with approximately $144 million of cash and investments. The burn rate was $2.9 million for the fourth quarter of 2022. Excluding offsets from one-time receipts of tax credits and real estate escrow funds, the burn rate would have been $23.4 million for the quarter. Moving forward, the company expects its burn rate in 2023 to continue declining as compared to 2022 due to an anticipated increase in revenue from Libmeldy product sales, continued savings realized by the March 2022 corporate restructuring, and ongoing management of operating expenses.
The company expects that its cash, cash equivalents and investments as of December 31, 2022 will support its currently anticipated operating and capital expenditure requirements into the second quarter of 2024.
Key 2022 Accomplishments
Business Operations
Technical Operations Platform
Libmeldy® (atidarsagene autotemcel)
Regulatory and Clinical Achievements for Investigational Therapies
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.
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 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
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,” and “expects,” or similar expressions, which are intended to identify forward-looking statements. Forward-looking statements include express or implied statements relating to, among other things, Orchard’s business strategy and goals, the therapeutic potential of Orchard’s products and product candidates, including the products and product candidates referred to in this release, Orchard’s expectations regarding the timing of regulatory submissions for approval of its product candidates, including the product 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, including the anticipated timing of a Type B meeting with the FDA regarding OTL-200 and an anticipated BLA submission for OTL-200, the timing of a potential registrational study for OTL-203 for MPS-IH, the timing of announcement of clinical data for its product candidates, 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 2024. 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 Orchard will not realize the anticipated benefits of its strategic plan or the expected cash savings from its restructuring; 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 or maintain marketing approval from the applicable regulatory authorities for any of Orchard’s product candidates or the receipt of restricted marketing approvals; the risk of delays in Orchard’s ability to commercialize its product candidates, if approved; the risk that the ongoing and evolving COVID-19 pandemic, or global macroeconomic and geopolitical developments, could affect the company's business; and the risk that the market opportunity for Libmeldy and its product candidates may be lower than estimated or that Orchard may be unable to identify patients for its products on a consistent basis. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements.
The estimates of revenue and expenses for the three and twelve months ended December 31, 2022 and of cash and investments as of December 31, 2022 are preliminary in nature and unaudited and do not present all information necessary for an understanding of Orchard’s financial condition as of December 31, 2022 and its results of operations for the three or twelve months ended December 31, 2022.
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
We aspire to end the devastation caused by genetic and other severe diseases through the curative potential of HSC gene therapy.
Forward-looking Statements Certain information set forth in this presentation and in statements made orally during this presentation contain “forward-looking statements”. Such forward-looking statements may be identified by words such as “anticipates,” “believes,” and “expects,” or similar expressions, which are intended to identify forward-looking statements. Forward-looking statements include express or implied statements relating to, among other things, Orchard’s business strategy and goals, the therapeutic potential of Orchard’s products and product candidates, including the products and product candidates referred to in this release, Orchard’s expectations regarding the timing of regulatory submissions for approval of its product candidates, including the product 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, including the anticipated timing of a Type B meeting with the FDA regarding OTL-200 and an anticipated BLA submission for OTL-200, the timing of a potential registrational study for OTL-203 for MPS-IH, the timing of announcement of clinical data for its product candidates, 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, the expected savings to Orchard’s business as a result of organizational updates, and the company’s financial condition and cash runway into 2024. 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 Orchard will not realize the anticipated benefits of its strategic plan; 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 or maintain marketing approval from the applicable regulatory authorities for any of Orchard’s product candidates or the receipt of restricted marketing approvals; the risk of delays in Orchard’s ability to commercialize its product candidates, if approved; the risk that the ongoing COVID-19 pandemic, or global macroeconomic and geopolitical developments, could affect the company's business; and the risk that the market opportunity for Libmeldy and its product candidates may be lower than estimated or that Orchard may be unable to identify patients for its products on a consistent basis. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements. The estimates of revenue and expenses for the three and twelve months ended December 31, 2022 and of cash and investments as of December 31, 2022 are preliminary in nature and unaudited and do not present all information necessary for an understanding of Orchard’s financial condition as of December 31, 2022 and its results of operations for the three or twelve months ended December 31, 2022. 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 presentation and in statements made orally during this presentation 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.
Compelling Fundamentals Driving Near and Long-term Growth Leveraging HSC Gene Therapy Approach 1x treatment – HSC gene therapy approach offers curative potential Strong clinical track record – over 170 patients treated 100% success rate – manufacturing & releasing drug product from 80+ patients Proven and effective technology platform Clinical validation in rare diseases increases confidence for larger indications Scalable, repeatable model with broad potential 1. 2. 12+ years of follow-up in first patients treated with MLD
Strong financial profile with revenue generating commercial assets 3. Estimated $144M in cash as of YE 2022 and runway expected into Q2 2024 Treating commercial early-onset MLD patients in the EU Opportunities to access additional capital and drive entry into new markets through strategic partnerships and licensing agreements Compelling Fundamentals Driving Near and Long-term Growth Disciplined Stewards of Capital 4.
NBS= newborn screening * Cumulative figure referencing patients treated at CDMO Summary of 2022 Accomplishments Constructive clinical / CMC discussions; response to information and data requests Treatment of patients in the U.S. on compassionate use basis with EU CDMO manufacturing OTL-200 Regulatory $18.8M in product sales in 2022 Reimbursement agreements with UK, Italy, Germany; renewal of early access program in France Patients treated via treatment abroad and cross border pathways First confirmed case of MLD identified via NBS Libmeldy Commercial IND clearance for upcoming OTL-203 MPS-IH registrational study Encouraging preliminary data from ongoing OTL-201 MPS-IIIA PoC trial MPS Development 80+ patients treated* with 100% success rate manufacturing and releasing drug product Libmeldy average manufacturing and product release time of 44 days Advancement of LVV suspension process Technical Platform Business Operations Refined portfolio focus Headcount reduction UK office consolidation Reduced burn rate
Focused Set of Corporate Goals for 2023 to Drive Strategy Libmeldy revenue growth and commercial expansion BLA submission for OTL-200 (MLD) in the U.S. Initiate registrational study for OTL-203 (MPS-IH) Initiate IND-enabling activities for OTL-104 (NOD2-Crohn’s) Prudent deployment of capital to create value and enable partnerships
Other Organ Systems Areas for potential future expansion Monocyte / Macrophage T cells B cells NK cells Megakaryocyte Erythrocyte Granulocyte Brain High area of focus GI Integration Self-renewal 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 Therapeutic gene HSC Gene Therapy Offers a Highly Differentiated Approach
Focusing Where We Believe HSC Gene Therapy is Scientifically and Clinically Differentiated
TIME VALUE Execute and deliver on rare disease portfolio Continue to build out capabilities in HSC gene therapy across regulatory, manufacturing, commercialization and access Expand on HSC gene therapy approach for larger indications and enabling technologies Seek partnership opportunities in areas where there is a compelling clinical and scientific rationale Mid-long term Near-mid term Strategic Long-term Growth and Value Creation with Expansion into Larger Indications
Libmeldy is approved in the European Union, UK, Iceland, Liechtenstein and Norway. Strong Momentum for Libmeldy Access - Reimbursement - Patient Identification - Newborn Screening U.S. & ROW European Expansion EU Launch
Fatal genetic CNS disorder Rapid and irreversible loss of motor and cognitive function In its most severe form, most children pass away within five years of symptom onset1 Age 5, pre-diagnosis Age 9, advanced disease Disease Snapshot 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.å Cognitive Age-Equivalent Performance (Years) Chronological Age (Years) Natural History (n = 14) OTL-200 (n = 16) Age-Equivalent 2 years Post GT (+/- 1 Normal SD) 0 1 2 5 6 8 0 1 2 3 4 5 6 7 8 10 9 4 3 7 11 12 13 14 15 16 Late Infantile MLD OTL:200 (MLD): Potential Significant Clinical Benefit for a Devastating Genetic Disease
Access Reimbursement Secured for all eligible MLD children Germany Italy UK KEY Treatment Center (current) Treatment Center (planned) France: Reimbursed early access program secured Treatment abroad: patient from Middle East Cross border (S2) pathway: via Eastern European country Libmeldy Commercial Launch Momentum Continuing to Grow Secure reimbursed treatment in at least 2 additional European markets in 2023 Saudi Arabia Spain Sweden
Implementing Newborn Screening for MLD KEY NBS Pilot/Study Location Some countries have more than one NBS site Newborn Screening Pilot Studies First confirmed case of MLD identified ~85,000 babies screened to date Expanding newborn screening activities throughout Europe, U.S. and the Middle East in 2023
OTL-200 (MLD): U.S. Regulatory Discussions Progressing Active, ongoing dialogue around final elements of clinical + CMC packages Constructive clinical and CMC discussions Response to information / data requests Treatment of patients in the U.S. on compassionate use basis (with EU CDMO manufacturing) Complete ongoing CMC interactions Hold type B clinical meeting in early 2023 in advance of an anticipated BLA submission
Significant Libmeldy Platform Synergies with Potential to be Leveraged Across Neurometabolic Pipeline MPS-IH MPS-IIIA MPS-IH MPS-IIIA Research programs in larger indications & discovery pipeline MLD Treatment Sites & Referral Network Regulatory Learnings Manufacturing, Distribution, Supply Chain
SD = Standard Deviation; IQ(C) = Intelligence Quotient (Cognition); Engl J Med 2021; 385:1929-1940 DOI: 10.1056/NEJMoa2106596 OTL-203 (MPS-IH): Interim Proof-of-concept Study Results 16 | 1:100,000 live births; NBS established in some geographies, incl. U.S. Current SOC: HSCT and/or ERT as a bridging or chronic therapy MPS-IH Neuropsychological Tests over Time Cognitive Age-Equivalent Score (Overall) Before Gene Therapy 1.5Y after Gene Therapy
OTL-203 MPS-IH Phase 3 Pivotal Trial Design Screening 1:1 Randomization Baseline Cell Harvest Conditioning OTL-203 Infusion Treatment OTL-203 20 patients HSCT 20 patients Baseline Treatment Conditioning Allogenic HSCT Follow-up Follow-up Primary Analysis at 2 Years Complication free survival (composite endpoint) Secondary endpoint analysis Day -15 Day -2 Day -5 Day 1 Year 2 Post Treatment Year 5 Post Treatment Up to 6 U.S. / European sites
Data presented at 2022 ASH Annual Meeting First Clinical Outcomes from OTL-201 POC Study in MPS-IIIA 4 / 5 patients are demonstrating gain of cognitive skills in line with development in healthy children Demonstration of developmental skill acquisition and behavioral phenotype not typically seen in untreated MPS-IIIA patients Acquisition of speech, continence and complex play requiring concentration engaged Longer follow-up is needed to further assess these outcomes and is ongoing Developmental Age Equivalent Chronological Age (Months) Cognitive Age Equivalent (Months)
Developmental Age Equivalent OTL-201 POC Study Patient 003: Marked Improvement Compared to Disease Natural History Patient 003 reached the ceiling of the Bayley scale and progressed onto the Kaufman assessment – first MPS-IIIA patient with rapidly progressive phenotype at Manchester that has completed the Kaufman assessment Pre-treatment with GT Post GT Treatment Chronological Age (Months) Cognitive Age Equivalent (Months) *Exceeded Bayley at 18 month visit– 24+ month visit not shown
Research Pipeline Maturing the science to fuel sustainable mid- and long-term growth
The Power of HSC Gene Therapy: Differentiation & Migration Alveolar macrophages Microglia Kupffer Cells Intestinal macrophages NOD2 Crohn’s FTD LUNG INTESTINE BRAIN LIVER Macrophage / Microglia T cells / B cells (regulatory T cells)
Research Spotlight: OTL-104 for NOD2 Crohn’s Disease 1,2 CD prevalence estimates: Centers for Disease Control and Prevention; European Crohn’s and Colitis Organisation (ECCO) 3 NOD2: Ashton, James J et al. Clin Transl Gastroenterol. 2020 Feb Program Highlights NOD2 mutations associated with Crohn’s disease severity Up to 200,000 estimated patients with two mutated NOD2 alleles (7-10% of all Crohn’s disease) in the U.S. and EU1,2,3 Restoration of NOD2 protein expression in murine and human stem cells can rescue a defective myeloid immune response to microbial peptides Preclinical Data Summary Preclinical PoC expected in first half 2023 and submit IND in 2024 Correction of NOD2 defective inflammatory functions achievable by LV-mediated NOD2 gene transfer in HSCs Functional reconstitution of NOD2 activity in a NOD2-ko murine disease model and in NOD2-Crohn’s patient-derived cells is in progress
Our Platform Provides Multiple Opportunities for Business Development Immunological Diseases Oncology Neuro-degenerative Diseases Robust pipeline provides potential for additional capital, as well as expanded research capabilities, disease state knowledge, geographic footprint, commercial infrastructure, and indications Partnerships in specific diseases OTL-105 for HAE partnered with Pharming Leveraging ongoing programs in CNS (FTD) 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
The Journey Ahead Our path to becoming the global HSC gene therapy leader
Prudent Capital Deployment Strategy Quarterly burn rate expected to continue declining in 2023 vs. 2022 Anticipated increase in Libmeldy product sales Continued savings realized from 2022 restructuring Ongoing management of operating expenses Disciplined stewards of capital prioritizing commercialization and development of pipeline to generate value and enable partnerships $144M in cash as of YE 2022 and runway into the second quarter of 2024
Executing Toward Regulatory, Clinical and Commercial Milestones Cash Position Supports Runway into Q2 2024 OTL-200: Clinical Type B meeting w/ FDA for MLD (early 2023) OTL-200: BLA submission / acceptance Regulatory Secure reimbursed treatment in at least two additional European markets Establish QTCs in Sweden, Spain & Saudi Arabia Pursue additional launch expansion opportunities Libmeldy - Commercial OTL-201: Report additional biochemical / clinical data from ongoing MPS-IIIA POC study OTL-203: Initiate global registrational trial for MPS-IH in 2H 2023 Development OTL-104: Report preclinical POC data for NOD2-CD (1H 2023) OTL-104: Initiate IND-enabling activities ahead of 2024 filing Pre-clinical $144M cash & investments (estimated as of YE’22) / expected runway into Q2 2024* Advance preclinical pipeline (OTL-105 for HAE, OTL-204 for GRN-FTD & Tregs) *assumes certain level of Libmeldy revenue
Strategic Anchors Represent Opportunities for Leadership in Gene Therapy All based on a de-risked HSC GT scientific and clinical platform Future Potential Regulatory Approvals Leverage success in rare disease Diagnostics and Newborn Screening Develop markets Commercial Model Establish scalable business and growth Manufacturing and Distribution Implement a sustainable platform Other Applications Advance scientific platform