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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): February 11, 2022

PASSAGE BIO, INC.

(Exact name of registrant as specified in its charter)

Delaware

001-39231

82-2729751

(State or other jurisdiction
of incorporation)

(Commission
File Number)

(IRS Employer
Identification No.)

One Commerce Square
2005 Market Street, 39th Floor
Philadelphia, PA

19103

(Address of principal executive offices)

(Zip Code)

(267) 866-0311

(Registrant’s telephone number, including area code)

N/A

(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

Common Stock, $0.0001 Par Value Per Share

PASG

The Nasdaq Stock Market LLC
(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.

Item 7.01 Regulation FD Disclosure.

On February 11, 2022, Passage Bio, Inc. (the “Company”) will present a corporate presentation (the “Investor Presentation”) summarizing the data presented by the Company at the 18th Annual WORLDSymposium Conference (“WORLD”).

In addition to the Company’s Investor Presentation, the Company also issued a press release on February 11, 2022, regarding updates to the Company’s Imagine-1 clinical trial, a Phase 1/2 study of PBGM01, a gene therapy for the treatment of GM1 gangliosidosis (“Imagine-1”).

A copy of the press release and Investor Presentation are attached as Exhibits 99.1 and 99.2, respectively, to this Current Report on Form 8-K.

The information in this Item 7.01, including Exhibits 99.1 and 99.2 to this report, shall not be deemed to be “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act. The information contained in this Item 7.01 and in the accompanying Exhibits 99.1 and 99.2 shall not be incorporated by reference into any other filing under the Exchange Act or under the Securities Act, except as shall be expressly set forth by specific reference in such filing.

Item 8.01 Other Events.

PBGM01 Program Updates

The Company announced the following updates with respect to Imagine-1 for the treatment of early and late infantile GM1:

Both children with late infantile GM1 gangliosidosis in cohort 1 of the Imagine-1 clinical trial showed meaningful developmental improvement in assessments by trained healthcare providers and caregivers using the Bayley III assessment tool and the Vineland II scale.
Interim safety data at three and nine months in Imagine-1 showed low dose PBGM01 was well tolerated with no serious adverse events reported and no evidence of dorsal root ganglion toxicity.
One patient in each of cohort 2 (late infantile with high dose PBGM01) and cohort 3 (early infantile with low dose PBGM01) have been dosed. The Company anticipates reporting initial biomarker and safety data in the second half of 2022 for these cohorts 2 and 3.

Item 9.01Financial Statements and Exhibits.

(d) Exhibits

Exhibit No.

    

Description

99.1

Passage Bio, Inc. press release dated February 11, 2022.

99.2

Investor Presentation.

104

Cover Page Interactive Data File (formatted as Inline XBRL).

2

SIGNATURE

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.

PASSAGE BIO, INC.

Date: February 11, 2022

By:

/s/ Simona King

Simona King

Chief Financial Officer

3

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Passage Bio Presents New Interim Clinical Data for Patients with GM1 Gangliosidosis in Imagine-1 Study at 2022 WORLDSymposium

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Both children with late infantile GM1 gangliosidosis in Cohort 1 of the Imagine-1 clinical trial showed developmental improvement in assessments by study investigators and caregivers

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Interim safety data at three and nine months in Imagine-1 showed low dose PBGM01 well tolerated with no serious adverse events reported and no evidence of dorsal root ganglion toxicity

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First patients dosed in Cohort 2 (late infantile with high dose PBGM01) and Cohort 3 (early infantile with low dose PBGM01); anticipate reporting initial biomarker and safety data in 2H2022

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Management to host conference call and webcast on Friday, February 11 at 1 p.m. ET

PHILADELPHIA, February 11, 2022 – Passage Bio, Inc. (Nasdaq: PASG), a clinical-stage genetic medicines company focused on developing transformative therapies for central nervous system (CNS) disorders, today presented updated clinical data from Imagine-1, a Phase 1/2 study of PBGM01, a gene therapy for GM1 gangliosidosis (GM1). The platform presentation at the 18th Annual WORLDSymposium included clinical assessments of development milestones for Cohort 1 (two patients with late infantile GM1 who were administered a low dose of PBGM01). Additionally, the presentation reviewed safety and biomarker data first announced in December 2021.

Life expectancy for children with GM1, a rare lysosomal storage disorder caused by mutations in the GLB1 gene, ranges from 2 to 10 years. Currently there are no approved disease-modifying treatments for the disorder.

David Weinstein, M.D. M.M.Sc., senior vice president, Clinical Development, Passage Bio, presented interim data showing meaningful improvement in development milestones and no reported serious adverse events or complications related to intra-cisterna magna delivery. Development milestones were evaluated using two standardized, norm-referenced scales – the Bayley III, a formal assessment tool used by trained healthcare providers, and the Vineland II, a scale for parent or caregiver assessment.

“The interim biomarker and safety data reported in December for these first two patients were positive indicators that PBGM01 is exerting a biological effect, and it is also important to see improvement in developmental milestones for these children,” said Eliseo Salinas, M.D., MSc., chief research and development officer, Passage Bio. “We are very encouraged by the initial reports of clinical improvement. We look forward to further follow up and continuing with additional cohorts in the Imagine-1 study.”

Interim safety profile for low dose PBGM01 (patient 1 data through nine months and patient 2 data through three months)

·

Reported adverse events were mild to moderate in severity

·

No serious adverse events were reported for either patient

·

No evidence of dorsal root ganglion toxicity in either patient, as measured by nerve conduction studies


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Investigator assessments of development - Bayley III

The Bayley III is an extensive formal tool for the assessment of developmental delays in early childhood comprising physical, cognitive, social-emotional, linguistic, and behavioral milestones.

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Improvement in all developmental areas through the six-month assessments was observed for patient 1. Through the six months following administration of low dose PBGM01, overall development age tracked closely to chronologic age progressing from 12 months at baseline to 17 months at the six-month study visit. The nine-month Bayley III assessment by the study investigator was not conducted due to potential COVID-19 exposure.

·

At the three-month assessments for patient 2, improvement was observed for motor, receptive language, and cognitive domains. Despite a severe developmental delay at study start, the overall development age progressed during the three months following administration of PBGM01 from 7 months at baseline to 9 months. Also, at month four, following the three-month Vineland and Bayley assessments, patient 2 was clinically observed to have regained previously lost developmental milestones, such as the ability to walk and use expressive language.

Caregiver assessments of development - Vineland II

The Vineland II scale is a standardized tool for caregivers to assess four broad areas of development: communication, daily living skills, socialization, and motor skills.

·

Through the nine-month assessments following PBGM01 administration, improvement in all developmental areas was documented for patient 1, with notable progress in the domains of fine motor skills, receptive language, and interpersonal relationships. For example, patient 1 went from a baseline of taking a few steps to running without falling. He also achieved meaningful gains with expressive language never used before, now able to use 10 to 20 other words with specific meaning. Overall development age progressed from 12 months at study start to 23 months at the nine-month interim assessments, approaching the patient’s chronologic age of 24 months.

·

Meaningful improvements were observed through the three-month assessments for patient 2, notably in expressive language and interpersonal relationships. Caregiver/family reports of overall development age progressed through the period following administration of PBGM01, from 13 months at baseline to 16 months at the three-month assessments.

“After initially gaining early milestones, children with late onset GM1 typically plateau at 12-13 months of age developmentally before regressing. Seeing a child continuing to achieve new developmental milestones at 2 years of age is highly encouraging and atypical of this condition.” said Roberto Giugliani, M.D., Ph.D., Department of Genetics UFRGS and Medical Genetics Service HCPA, Porto Alegre, Brazil, and Imagine-1 principal investigator. “In 35 years of seeing GM1 patients, I have also never seen a child regain the ability to walk after losing this skill. While still relatively early, these results are exciting, and I look forward to the continuation of this trial.”

Bruce Goldsmith, Ph.D., chief executive officer and president, Passage Bio, said: “We are very pleased with the interim data from cohort 1 of the Imagine-1 trial and what it potentially means for patients. Our focus for each of our clinical programs is selecting in partnership with Penn’s Gene Therapy Program an optimal AAV capsid, expression cassette and ICM delivery method for our gene therapies. The effectiveness of this approach is being validated with our Imagine-1 trial and it reinforces our confidence as we advance our other two global clinical trials for Krabbe disease and frontotemporal dementia with granulin mutations. We are grateful to the children participating in Imagine-1 as well as their families and caregivers and the clinical trial investigators for their continued support of our study.”


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Following positive interim safety and biomarker data for Cohort 1, the Imagine-1 study has progressed to enroll additional cohorts: Cohort 2 with children with late infantile GM1 receiving a high dose of PBGM01; and Cohort 3 with children with early infantile GM1 receiving the same low dose of PBGM01 as Cohort 1. Thus far, one patient in each of the cohorts has been dosed. Interim data from these two cohorts is anticipated in 2H 2022.

Passage Bio continues to open Imagine-1 clinical trial sites across the world. Since December, the company has opened two sites in Canada and Brazil. Currently, six sites are open with plans to activate an additional four sites.

Conference Call Details

Passage Bio will host a conference call and webcast today at 1 p.m. ET to discuss the Imagine-1 data presented at the 2022 WORLDSymposium. To access the live conference call, please dial 833-528-0605 (domestic) or 830-221-9711 (international) and reference Conference ID number: 5635958. A live audio webcast of the event will be available on the Investors & News section of Passage Bio’s website at investors.passagebio.com. The archived webcast will be available on Passage Bio's website approximately two hours after the completion of the event and for 30 days following the call.

About Imagine-1

Imagine-1 is a Phase 1/2, global, open-label, dose-escalation study of PBGM01 administered by a single injection into the cisterna magna in pediatric subjects with early and late infantile GM1. The primary goal of the study is to first assess safety and tolerability and then efficacy of PBGM01 in patients. The U.S. Food and Drug Administration (FDA) has granted PBGM01 Fast Track, Orphan Drug, and Rare Pediatric Disease designations. PBGM01 has also received an Orphan designation from the European Commission.

To learn more about the clinical trial program, please visit ClinicalTrials.gov: NCT04713475.

About PBGM01

PBGM01 is an AAV-delivery gene therapy currently being developed for the treatment of infantile GM1, in which patients have mutations in the GLB1 gene causing little or no residual beta-galactosidase enzyme activity and subsequent neurodegeneration. PBGM01 utilizes a next-generation AAVhu68 capsid administered through the cisterna magna to deliver a functional GLB1 gene encoding beta-galactosidase to the brain and peripheral tissues. By increasing beta-galactosidase activity, PBGM01 has the potential to reduce accumulation of toxic GM1 gangliosides and reverse neuronal toxicity, thereby restoring developmental potential. In preclinical models, PBGM01 has demonstrated broad brain distribution and high levels of expression of the beta-galactosidase enzyme in both the CNS and critical peripheral organs, suggesting potential treatment for both the CNS and peripheral manifestations of GM1.

About GM1

GM1, a rare monogenic lysosomal storage disease, is caused by mutations in the GLB1 gene, which encodes the lysosomal enzyme beta-galactosidase (β-gal). Reduced β-gal activity results in the accumulation of toxic levels of GM1 gangliosides in neurons throughout the brain, causing rapidly progressive neurodegeneration. GM1 accumulation also results in progressive damage to other tissues including the heart, liver, and bones and manifests with hypotonia (reduced muscle tone), progressive CNS dysfunction, seizures, and rapid developmental regression. Life expectancy for infants with GM1 ranges from 2-10 years, and infantile GM1 represents approximately 60 percent of the global GM1 incidence of 0.5 to 1 in 100,000 live births.

About Passage Bio

At Passage Bio (Nasdaq: PASG), we are on a mission to provide life-transforming genetic medicines for patients with CNS diseases that replace their suffering with boundless possibility, all while building lasting relationships with the communities we serve. Based in Philadelphia, PA, our company has established a strategic collaboration and licensing agreement with the renowned University of Pennsylvania’s Gene Therapy


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Program to conduct our discovery and IND-enabling preclinical work. This provides our team with enhanced access to a broad portfolio of gene therapy candidates and future gene therapy innovations that we then pair with our deep clinical, regulatory, manufacturing and commercial expertise to rapidly advance our robust pipeline of optimized gene therapies into clinical testing. As we work with speed and tenacity, we are always mindful of patients who may be able to benefit from our therapies. More information is available at www.passagebio.com.

Forward-Looking Statements

This press release contains “forward-looking statements” within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectations about timing and execution of anticipated milestones, including subsequent events in our Imagine-1 trial; initiation of clinical trials and the availability of clinical data from such trials; our expectations about our collaborators’ and partners’ ability to execute key initiatives; our expectations about manufacturing plans and strategies;and the ability of our lead product candidates to treat their respective target CNS disorders. These forward-looking statements may be accompanied by such words as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “might,” “plan,” “potential,” “possible,” “will,” “would,” and other words and terms of similar meaning. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop and obtain regulatory approval for our product candidates; the timing and results of preclinical studies and clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; failure to protect and enforce our intellectual property, and other proprietary rights; our dependence on collaborators and other third parties for the development and manufacture of product candidates and other aspects of our business, which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; and the other risks and uncertainties that are described in the Risk Factors section in documents the company files from time to time with the Securities and Exchange Commission (SEC), and other reports as filed with the SEC. Passage Bio undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

For further information, please contact:

Passage Bio Investors:

Stuart Henderson

Passage Bio

267-866-0114

shenderson@passagebio.com

Passage Bio Media:

Gwen Fisher

Passage Bio

215-407-1548

gfisher@passagebio.com


Exhibit 99.2

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PBGM01 Study in Infantile GM1 GangliosidosisInterim Safety, Biomarker and Efficacy Results from Low Dose, Late Infantile Cohort of Ongoing Imagine-1 Clinical StudyFebruary 11, 2022

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2 Welcome & Agenda Eliseo Salinas, M.D.Chief R&D OfficerBruce Goldsmith, Ph.D.Chief Executive OfficerExecutive Summary & Overview of GM1 GangliosidosisBruce GoldsmithImagine-1 Clinical Study Overview & Review of Safety, Biomarker, and Preliminary Efficacy ResultsEliseo SalinasClosing RemarksBruce GoldsmithQ&AAll

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3 Forward-Looking StatementThis presentation includes “forward-looking statements” within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectation about timing and execution of anticipated milestones, including the timing of subsequent results from our Imagine-1 trial; our planned initiation of clinical trials and the availability of clinical data from such trials; our expectations about our collaborators’ and partners’ ability to execute key initiatives; the expected impact of the COVID-19 pandemic on our operations; and the ability of our lead product candidates to treat their respective target CNS disorders. These forward-looking statements may be accompanied by such words as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “might,” “plan,” “potential,” “possible,” “will,” “would,” and other words and terms of similar meaning. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop, obtain regulatory approval for and commercialize PBGM01, PBFT02, PBKR03 and future product candidates; the timing and results of preclinical studies and clinical trials; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; failure to protect and enforce our intellectual property, and other proprietary rights; failure to successfully execute or realize the anticipated benefits of our strategic and growth initiatives; risks relating to technology failures or breaches; our dependence on collaborators and other third parties for the development of product candidates and other aspects of our business,which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; risks associated with current and potential future healthcare reforms; risks relating to attracting and retaining key personnel; failure to comply with legal and regulatory requirements; risks relating to access to capital and credit markets; and the other risks and uncertainties that are described in the Risk Factors section of our most recent filings with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this presentation. We do not undertake any obligation to publicly update any forward-looking statements except as required by law. By attending or receiving this presentation you acknowledge that you are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date such statements are made; you will be solely responsible for your own assessment of the market and our market position; and that you will conduct your own analysis and be solely responsible for forming your own view of the potential future performance of Passage Bio.

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4 Executive Summary of Low Dose PBGM01Interim results from Cohort 1 in ongoing Imagine-1 clinical study Well tolerated and positive safety profile with no serious AEs and no complications related to ICM injection No evidence of DRG toxicity based on nerve conduction studies Substantial increases in β-gal enzyme activity observed in both CSF and serum after ICM delivery Meaningful improvement across developmental areas on both the Vineland and Bayley scales

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5 GM1 Gangliosidosis: A Devastating Pediatric Disease FATAL, PEDIATRIC NEUROLOGICAL LYSOSOMAL STORAGE DISORDER caused by GLB1gene mutations characterized by destruction of neurons in the brain and spinal cord.Characterized by rapidly progressive neurological decline resulting in reduced muscle tone, progressive CNS dysfunction, deafness, blindness, rigidity and skeletal dysplasia. RARE AND UNDERSERVEDpopulations with incidence of up to ~1 per 100,000 live births worldwide.No disease-modifying therapies are presently approved.Source: NIH, CHOP, American Journal of Neuroradiology

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6 GM1 Gangliosidosis Disease Continuum GM1 Gangliosidosis is a Continuum Disease SeverityResidual Enzyme Activity (Serum) Focus of Imagine-1 TrialNegligible to 5%~ 1–5%~ 3 –10% Type 1 (Early Infantile)•Onset <6 months•Hypotonia•Neurodegeneration•Developmental regression•Seizures•Skeletal dysplasia •Survival: <2 years without supportive careType 2a (Late Infantile)•Onset 6–24 months•Developmental plateau, followed by regression•Impaired ambulation•Impaired cognition•Seizures•Survival: 5 to 10 yearsType 2b (Juvenile)•Onset 2–5 years•Impaired ambulation•Dysarthria•Variable skeletal disease•Decreased cognition•Survival into 2nd decade Adapted from Regier DS, et al. 2016 GLB-1 Disorders, In Adam MP, et al. GeneReviews.Elevate β-gal activity to preserve neurological function and improve clinical outcomes

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7 Natural History of Late Infantile GM1•Type 2 late infantile GM1 generally characterized by plateau of motor and cognitive development followed by slow developmental regression•Declines in ambulation and expressive language are often the first and most prominent clinical features•Patients experience a slow, unremitting regression of milestones•Late infantile population distinguished by never walking independently or using more than single wordsCharacterized by developmental plateau and regression “After initially gaining early milestones, children with late onset GM1 typically plateau at 12-13 months of age developmentally before regressing.”Roberto Giugliani, M.D., Ph.D., Department of Genetics UFRGS and Medical Genetics Service HCPA, Porto Alegre, BrazilImagine-1 Principal Investigator

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8 Imagine-1: Global Phase 1/2 Trial with PBGM01Currently enrolling Cohort 2 and Cohort 3 COHORT 4Early Infantilen = 2DOSE 2 (1.1e11 GC/g)*DOSE 1 (3.3e10 GC/g)* Expansion CohortEarly Infantilen = 6 Expansion CohortLate Infantilen = 6 COHORT 2Late Infantilen = 2 COHORT 3Early Infantilen = 2 COHORT 1Late Infantilen = 2 60 days between subject enrollment IDMC review Recruiting Complete* Genome copies per gram of estimated brain weight Trial DesignPhase 1/2, multi-center, open-label, dose escalation and confirmatory study Route of AdministrationIntra-cisterna magna (ICM)VectorAAVhu68ImmunosuppressionLow dose steroids 4 weeks then taper DurationTwo years, with rollover into a separate long-term follow-up studyPrimary Endpoints•Safety and tolerability•Efficacy (confirmatory cohort)Biomarkers•β-gal activity (CSF & serum)•GM1 gangliosides (CSF)•Other exploratory biomarkers

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9 Imagine-1 Study: Baseline Patient CharacteristicsCohort 1 (n=2): Low dose (3.3e10 GC/g)*, Late Infantile (Type 2a) Patient 1Patient 2Gender MaleMaleAge at onset of symptoms (months)1412Age at gene transfer (months)1531DBS β-Gal activity(1)(nmol/ml/hr)0.00.2Pre-existing vector nAbs–CSF(2)NegativeNegativePre-existing vector nAbs–Serum(2)PositiveNegativeClinical status at baseline•Developmental delay, mostly on language domains•Developmental age: 11 months•Chronological age: 14 months•Developmental delay in all domains•Developmental age: 7 months•Chronological age: 31 monthsDose3.3e10 GC/g*GC administered3.3e13 GC3.6e13 GCDose administered(3)3.3e12 GC/kg body weight3.2e12 GC/kg body weightDBS, dry blood spot; nAbs, neutralizing antibodies * Genome copies per gram estimated brain weight(1) Lower limit of normal (LLN): <5.0 nmol/ml/hr(2)Assay threshold titer value of 5(3)Dose values in GC/kg are calculated based on patient body weight

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10 Imagine-1 Study: Cohort 1 Safety & Tolerability No serious adverse events (SAEs) in either patient Reported adverse events (AEs) were mild-to-moderate; all moderate AEs resolved without intervention and were deemed not treatment related No complications related to ICM administration No changes in liver function in either patient No evidence of DRG toxicity in either patient, as measured by nerve conduction studiesPBGM01 was well tolerated and had a positive safety profile at interim analysis** Patient 1 follow-up: 10 months; Patient 2 follow-up: 4 months

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11 Imagine-1 Study: Cohort 1 Adverse Events Adverse EventClinical SeverityTreatment RelatedDiaper RashMildUnrelatedThrombocytopeniaModerateUnrelatedHeadacheModerateProcedureBruise (1-2mm)MildProcedureConstipationMildUnrelatedBruiseMildUnrelatedFall at HomeMildUnrelatedCoughMildUnrelatedAbnormal Fluid during LPMildPossiblyLip BleedMildPre-doseSuspected PainMildPre-doseWheezingMildPre-doseCoughMildUnrelatedLeft Ventricular HypertrophyMildUnrelatedBack PainMildUnrelatedNasal StuffinessMildUnrelatedLip BleedMildUnrelated

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12 •CSF β-gal Activity increased in both patients•Post treatment β-gal activity above NHS patient values (Range 0.30–1.81 nmol/mL/3hr)2Cohort 1 Interim Biomarker Data 01 2 340306090120150180β - Gal Activity, CSF (nmol/mL/3hr) Time (Days)CSF β-gal+0.6+2.7 •Serum β-gal activity increased in both patients•Post treatment β-gal activity above NHS patient values (Range: 2.25–10 nmol/mL/3hr)2•CSF GM1 gangliosides decreased in patient with high β-gal expression•NHS data is needed to provide further context•Longer follow up is needed 02 4 6 8101214160306090120150180β - Gal Activity, Serum (nmol/mL/3hr) Time (Days)Serum β-gal1 020 40 60 801001201401600306090120150180nM*Time (Days)CSF GM1 Gangliosides+6.0+2.1+28-63Patient 2 Patient 1 * Apparent estimated concentration1. Baseline reflects the average of two samples collected within 48-hours of dosing. 2. Based on preliminary data from University of Pennsylvania’s ODC NHS study (NCT04041102) NHS patientvalue range NHS patient value range

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13 Measuring Developmental MilestonesVineland-II and Bayley-III scales Vineland-IIAssessed by CaregiverBayley-IIIAssessed by Trained ClinicianExample MeasurementsMotorGross MotorXXAbility to walk, run or balanceFine MotorXXAbility to squeeze toy or put piece in puzzleLanguage Receptive languageXXAbility to follow commandsExpressive languageXXUses simple words or words with meaningSocial Personal living skillsXDrinks from bottle/cupInterpersonal relationshipsXResponds to othersPlay and leisure timeXEngages in play activitiesCognitive CognitionXRecognizes caregiver; responds to novel surroundings

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14 Patient 1: Vineland-IIImprovement documented in all developmental areas through 9-month assessments 813182328 33381214161820222426Developmental Age (months)Chronological Age (months) Normal Fine motor Gross motor Receptive language Expressive language Personal living skills Interpersonal relationships Play and leisure time Overall (months)Baseline3 months6 months9 monthsPatient Age14172024MotorGross motor13142122Fine motor12141619Language Receptive language12142534Expressive language8121619Social Personal living skills11141717Interpersonal relationships8141722Play and leisure time17182726Overall developmental age12162123

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15 Patient 1: Bayley-IIIImprovement also directly observed in all developmental areas 81012 14 16 18 20 221315171921Developmental Age (months)Chronological Age (months) Normal Gross motor Fine motor Receptive language Expressive language Cognition Overall (months)Baseline3 months6 monthsPatient Age141720MotorGross motor131415Fine motor111616Language Receptive language101616Expressive language101415Cognitive Cognition131619Overall developmental age121517Note: 9-month Bayley III assessment was not conducted due to potential COVID-19 exposure.

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16 Patient 2: Vineland-IIImprovement documented despite severe developmental delay at baseline 81012 14 16 18 20 2230323436Developmental Age (months)Chronological Age (months) Fine motor Gross motor Receptive language Expressive language Personal living skills Interpersonal relationships Play and leisure time Overall (months)Baseline3 monthsPatient Age3134MotorGross motor1112Fine motor1112Language Receptive language1413Expressive language812Social Personal living skills1616Interpersonal relationships1321Play and leisure time1212Overall developmental age1316

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17 Patient 2: Bayley-IIIImprovement observed for motor, language, and cognitive domains 02 4 6 810 12 1430323436Developmental Age (months)Chronological Age (months) Gross motor Fine motor Receptive language Expressive language Cognition Overall (months)Baseline3 monthsPatient Age3134MotorGross motor1012Fine motor79Language Receptive language49Expressive language77Cognitive Cognition89Overall developmental age79

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18 Case Study: Patient 1 (Vineland-II)Meaningful gains in developmental milestones Baseline9-month AssessmentGross motorTaking a few steps without supportRunning without fallingAble to climb off bedAble to balance on one footAble to move up and down stairsFine motorSometimes able to squeeze toyAlways able to squeeze toyAble to put piece in puzzleAble to put coin in slotReceptive languageNever points to named body partsNever points to named objects in bookRarely follows 1 step commandAlways points to 3 named body partsAlways points to named objects in bookAlways follows 1 step commandExpressive languageNo words with meaningNames 10 familiar objects10-20 words with specific meaning

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19 Case Study: Patient 2•Patient 2 presented with advanced disease, showing significant developmental delays in all domains–Developmental age of 7 months vs. chronological age of 31 months•At month 4, following the 3-month Vineland and Bayley assessments, Patient 2 was clinically observed to have regained previously lost developmental milestones:–Motor: regained the ability to walk–Language: regained the ability to use specific wordsDocumented gain of previously lost developmental milestones

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20 Initial Patients Dosed in Both Cohort 2 and 3 Patient 3Patient 4DiagnosisEarly Onset (Type 1) Late Onset (Type 2a)Dosing Cohort*Low dose (3.3e10 GC/g)High dose (1.1e11 GC/g)Gender FemaleFemaleAge at onset of symptoms (months)511Age at gene transfer (months)1518DBS β-Gal activity(1)(nmol/ml/hr)0.00.0DBS, dry blood spot* Genome copies per gram estimated brain weight(1) Lower limit of normal (LLN): <5.0 nmol/ml/hr

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21 Key Takeaways from Interim Cohort 1 DataWell tolerated, demonstration of functional transgene expression, and meaningful developmental improvement BIOMARKERSPost treatment CSF and serum β-gal activity for both patients above natural history study (NHS) patient values•Increases in CSF and serum β-gal activity for Patient 1 were sustained at 6 months* SAFETYPBGM01 was well tolerated and had a positive safety profile•No serious adverse events (SAEs)•No complications related to ICM injection•No evidence of DRG toxicity CLINICAL STATUSMeaningful improvement across developmental areas on both the Vineland and Bayley scales including regaining of lost milestones* 6-month data from Patient 2 not yet available.

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22 Program Anticipated Next Steps •Leverage patient identification efforts to identify future study participants Continue to enroll Cohorts 2 and 3 •2 additional sites opened since December (Canada & Brazil)•6 sites currently open, 4 additional planned Continue to open additional trial sites in multiple countries •Additional biomarker and efficacy data from Cohort 1 as follow-up visits are completed•Initial safety and biomarker data from Cohorts 2 and 3 in 2H 2022 Expect to provide additional data updates throughout 2022

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Thank you to the patients, families, caregivers and investigators for their participation in this study.