Passage BIO, Inc 8-K, filed May 18, 2022
Passage BIO, Inc. (PASG)
About this 8-K
Passage BIO, Inc filed this 8-K on May 18, 2022.
Items reported
- Item 7.01: Regulation FD disclosure
- Item 8.01: Other events
- Item 9.01: Financial statements and exhibits
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Item 7.01 Regulation FD Disclosure.
On May 18, 2022, Passage Bio, Inc. (the “Company”) will present a scientific presentation (the “ASGCT Presentation”) at the 25th Annual American Society of Gene & Cell Therapy Conference 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”).
The Company also issued a press release on May 18, 2022, related to the ASGCT Presentation.
A copy of the press release and ASGCT 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:
| ● | Longer-term follow-up showed continued developmental improvement for both patients in assessments by study investigators and caregivers. Through the 12-month assessments following PBGM01 administration, improvement from baseline was observed and documented across all developmental areas for patient 1, with notable progression in motor and language domains. Improvement across multiple developmental domains was also observed and documented for patient 2, despite this patient having severe developmental delay at baseline and a prior history of regression. |
| ● | Interim safety data at thirteen and seven months from patients in Cohort 1 of the Imagine-1 clinical trial showed the low dose of PBGM01 was well tolerated and had a favorable safety profile. No serious adverse events, complications related to intra-cisterna magna administration or evidence of dorsal root ganglion toxicity were observed in either patient. |
| ● | Cerebral spinal fluid beta-galactosidase activity for both patients increased above levels measured in natural history study (“NHS”) samples following dosing and were sustained at the upper limit of NHS values. Serum beta-galactosidase activity also increased following administration of PBGM01 for both patients, with patient 1 levels above NHS values at 12-months post-treatment and patient 2 levels normalizing to NHS values at 6-months post-treatment. |
| ● | Volumetric MRI showed increases in brain volume at 12 months compared to baseline for patient 1 in multiple brain regions. Patient 2, who had severe developmental delay at baseline and was 31 months of age at gene transfer, showed a slight decline in brain volume from baseline at six months. |
| ● | The global Phase 1/2 study continues to enroll patients, with interim safety and biomarker data from Cohorts 2 and 3 expected in second half of 2022. |
2
Item 9.01Financial Statements and Exhibits.
(d) Exhibits
Exhibit No. |
| Description |
99.1 | | |
99.2 | | |
104 | | Cover Page Interactive Data File (formatted as Inline XBRL). |
3
Exhibit 99.1
Passage Bio Presents New Interim Clinical and Biomarker
Data for Patients with GM1 Gangliosidosis in Imagine-1
Study at ASGCT 25th Annual Meeting
| ● | Longer-term follow-up showed continued developmental improvement for both patients in assessments by study investigators and caregivers |
| ● | Interim safety data at 13 and seven months from patients in Cohort 1 of the Imagine-1 clinical trial showed low dose of PBGM01 was well tolerated and had a favorable safety profile |
| ● | Global Phase 1/2 study continues to enroll patients, with interim safety and biomarker data from Cohorts 2 and 3 expected in 2H22 |
PHILADELPHIA, May 18, 2022 – Passage Bio, Inc. (Nasdaq: PASG), a clinical-stage genetic medicines company focused on developing transformative therapies for central nervous system (CNS) disorders, today announced the presentation of longer-term clinical and biomarker data from Cohort 1 in Imagine-1, a Phase 1/2 study of PBGM01, a gene therapy for GM1 gangliosidosis (GM1). David Weinstein, M.D. M.M.Sc., senior vice president, Clinical Development, Passage Bio, will present the data at 8:30 a.m. ET during a late-breaker oral presentation at the American Society of Gene and Cell Therapy (ASGCT) 25th Annual Meeting, being held in Washington, D.C. and virtually.
“We continue to be encouraged by the interim data from the first cohort in our Imagine-1 trial and the potential promise if offers for patients. These data show that the low dose of PBGM01 is well-tolerated, has a favorable safety profile and exerts a biological effect that appears to translate to improvement in developmental milestones for these children,” said Mark Forman, M.D., Ph.D., chief medical officer, Passage Bio. “We look forward to continuing to advance the Imagine-1 study through additional cohorts and are excited to gather more data to see the impact of earlier intervention, which we believe may be important based on the initial clinical findings presented to date. The life expectancy for children with GM1 ranges from two to 10 years, so we are eager to pursue the opportunity to potentially offer the first disease-modifying treatment for this disease as quickly as possible.”
Key Highlights from Late-Breaker Presentation at ASGCT Include:
| ● | Low dose PBGM01 was well-tolerated and had a favorable safety profile with patient 1 data through 13 months and patient 2 data through seven months: No serious adverse events, complications related to ICM administration or evidence of dorsal root ganglion (DRG) toxicity were observed in either patient. |
| ● | Both patients showed continued improvement across developmental areas on the Vineland-II (caregiver-assed) and Bayley-III (investigator-assed) scales: Through the 12-month assessments following PBGM01 administration, improvement from baseline was observed and documented across all developmental areas for patient 1, with notable progression in motor and language domains. Improvement across multiple |
developmental domains was also observed and documented for patient 2, despite this patient having severe developmental delay at baseline and a prior history of regression.
| ● | Volumetric MRI data showed meaningful growth in brain volume for patient 1, who was 15 months of age at gene transfer: Volumetric MRI showed increases in brain volume at 12 months compared to baseline for patient 1 in multiple brain regions. Patient 2, who had severe developmental delay at baseline and was 31 months of age at gene transfer, showed a slight decline in brain volume from baseline at six months. |
| ● | Longer-term biomarker data for Beta-galactosidase enzyme activity in CSF and serum showed functional transgene expression: CSF beta-galactosidase activity for both patients increased above levels measured in natural history study (NHS) samples following dosing and were sustained at the upper limit of NHS values. Serum beta-galactosidase activity also increased following administration of PBGM01 for both patients, with patient 1 levels above NHS values at 12-months post-treatment and patient 2 levels normalizing to NHS values at 6-months post-treatment. |
The Imagine-1 study continues to advance. The first patient in Cohort 2, high dose, late infantile, and both patients in Cohort 3, low dose, early infantile, have been dosed. Interim safety and biomarker data from both cohorts are expected in the second half of 2022.
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
Passage Bio (Nasdaq: PASG) is a clinical-stage genetic medicines company on a mission to provide life-transforming therapies for patients with CNS diseases with limited or no approved treatment options. Our portfolio spans pediatric and adult CNS indications, and we are currently advancing three clinical programs in GM1 gangliosidosis, Krabbe disease and frontotemporal dementia with several additional programs in preclinical development. Based in Philadelphia, PA, our company has established a strategic collaboration and licensing agreement with the renowned University of Pennsylvania’s Gene Therapy Program to conduct our discovery and IND-enabling preclinical work. Through this collaboration, we have 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. 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:
Mike Beyer
Sam Brown Inc. Healthcare Communications
312-961-2502
MikeBeyer@sambrown.com
| Interim Safety, Biomarker, and Efficacy Data from Imagine - 1: A Phase 1/2 Open - Label, Multicenter Study to Assess the Safety, Tolerability, and Efficacy of a Single Dose, ICM Administration of PBGM01 in Subjects with Type I (Early Onset) and Type IIa (Late Onset) Infantile GM1 Gangliosidosis (GM1) David Weinstein, MD, MMSc SVP, Clinical Development and Clinical Lead, Imagine - 1, Passage Bio, Inc. ICM= intra - cisterna magna .. American Society of Gene & Cell Therapy (ASGCT) 25 th Annual Meeting Wednesday, May 18, 2022 |
| 2 Notice • This presentation is about a research study aimed at assessing the safety and efficacy of an investigational treatment called PBGM01. ▪ Use of PBGM01 is not approved by any of the regulatory agencies for the treatment of GM1. ▪ The safety and efficacy of PBGM01 for the treatment of GM1 has not been established in humans. ▪ For additional information about the study, go to www.clinicaltrials.gov/ct2/show/NCT04713475. GM1=GM1 gangliosidosis. |
| 3 GM1 Gangliosidosis • GLB1 gene mutation results in deficient β - Gal enzyme activity leading to intracellular ganglioside accumulation 1 • GM1 gangliosidosis is characterized by progressive neurological deterioration, progressive brain atrophy, cardiac and skeletal abnormalities 2 • Estimated incidence of 1 in 100,000 - 200,000 live births worldwide 1 • Currently, no effective medical treatment is available for the underlying GM1 gangliosidosis 3,4 Cooper GM1 patient Jaxson GM1 patient b - Gal= b - galactosidase; GM1=GM1 gangliosidosis. 1. Brunetti - Pierri N., Scaglia F. Mol Genet Metab. 2008;94(4):391 - 396. 2. Caciotti A., et al. Biochim Biophys Acta .. 2011;1812(7):782 - 790. 3. King KE, et al .. Mol Genet Meta Rep. 2020;25:100676. 4. Nicoli E - R, et al. Front. Genet. 2021; 12:734878. |
| 4 Clinical Course of Infantile GM1 GM1 Gangliosidosis is a Continuum Disease Severity Residual Enzyme Activity 1,3 - 6 Imagine - 1 Trial will include Type I (Early Infantile) and Type IIa (Late Infantile) patients 7 Negligible ~1 - 5% ~3 – 10% Type I (Early Infantile) 1 • Onset <6 months 1 - 5 • Hypotonia 1 - 3 • Neurodegeneration 1,4,6 • Developmental regression 2 - 4,6 • Seizures 2 - 4,6 • Skeletal dysplasia 1,3,4 • Survival: <2 years 1 Type IIa (Late - Infantile) 3 • Onset 6 - 24 months 3,4 • Developmental plateau, followed by regression 2,3,5,6 • Impaired ambulation 2,4 - 5 • Impaired cognition 2,4 • Seizures 2 - 5 • Survival: 5 to 10 years 2,5 Type IIb (Juvenile) 3 • Onset 2 - 3 years 3,4 • Impaired ambulation 4,5 • Dysarthria 4,6 • Variable skeletal disease 4 - 6 • Decreased cognition 4,6 • Survival into 2nd decade 5 Type I/Early Infantile • No new developmental milestones reached after 3 - 6 months 5.8 Type IIa/Late - infantile • No new developmental milestone reached after 12 - 15 months 8 1. Brunetti - Pierri N., Scaglia F. Mol Genet Metab. 2008;94(4):391 - 396. 2. Jarnes JR, et al. Mol Genet Metab .. 2017;121(2):170 - 179. 3. Lang FM, et al. Mol Genet Metab. 2020;129(3):228 - 235. 4. Regier DS, et al. Am J Med Genet Part A .. 2016;170(3):634 - 644. 5. King KE, et al .. Mol Genet Meta Rep. 2020;25:100676. 6. Regier DS, Tifft CJ. Rothermel CE. GLB1 - related disorders. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews® [Internet]. University of Washington, Seattle; 2019:1993 - 2022. https://www.n cbi.nlm.nih.gov/books/NBK164500/ October 17, 2013. Updated April 22, 2021. Accessed March 7, 2022. 7. Study of Safety, Tolerability and Efficacy of PBGM01 in Pediatric Subjects Wi th GM1 Gangliosidosis (Imagine - 1). ClinicalTrials.gov website https://www.clinicaltrials.gov/ct2/show/NCT04713475?term=passage+bio&draw=2&rank=3. January 19, 2021. Updated March 7, 2022. Acc essed March 7, 2022. 8. Nicoli E - R, et al. Front. Genet. 2021;12:734878. |
| 5 Imagine - 1: Global Phase 1/2 Trial with PBGM01 Initial safety and biomarker data from Cohorts 2 & 3 expected in 2H 2022 Trial Design Phase 1/2, multi - center , open - label, dose escalation and confirmatory study Route of Administration Intra - cisterna magna (ICM) Vector AAVhu68 Duration Two years, with rollover into a separate long - term follow - up study Primary Endpoints • Safety and tolerability • Efficacy (confirmatory cohort) Regulatory Clearances and Designations • Received multiple global regulatory clearances • Received Orphan Drug, Rare Pediatric Disease and Fast Track designations by FDA and Orphan designation by EC COHORT 4 Early Infantile n = 2 D OSE 2 (1.1e11 GC/g)* D O S E 1 (3.3e10 GC/g)* Expansion Cohort Early Infantile n = 6 Expansion Cohort Late Infantile n = 6 COHORT 2 Late Infantile n = 2 COHORT 3 Early Infantile n = 2 COHORT 1 Late Infantile n = 2 60 days between subject enrollment IDMC review Recruiting Dosing complete * Genome copies per gram of estimated brain weight |
| 6 Cohort 1: Baseline Patient Characteristics Patient 1 Patient 2 Diagnosis Late Onset Late Onset Dosing Cohort Low dose Low dose Gender Male Male Age at onset of symptoms (months) 14 12 Age at diagnosis (months) 2 30 Age at gene transfer (months) 15 31 DBS β - Gal activity * (nmol/mL/h) 0.0 0.2 Genotype p.R201C p.R201C p.R201C p.L578R Pre - existing vector nAbs – CSF † Negative Negative Pre - existing vector nAbs – Serum Positive Negative Developmental age on Bayley - III at baseline (months) 11 7 b - Gal= b - galactosidase; CSF=cerebrospinal fluid; DBS=dried blood spot; LLN=lower limit of normal; nAbs=neutralizing antibodies. * LLN: <5.0 nmol/mL/h. † Assay threshold titer value of 5. |
| 7 Cohort 1 Safety & Tolerability No SAEs have occurred in either patient Reported AEs were mild - to - moderate; all moderate AEs resolved without intervention and were deemed non - treatment related No complications related to ICM administration were reported No changes in ALT or GGT occurred in either patient following vector administration No evidence of DRG toxicity clinically or on nerve conduction studies in either patient PBGM01 had a positive safety profile and was well tolerated at the interim analysis* *Patient 1 follow - up: 13 months; Patient 2 follow - up: 7 months. AEs=adverse events; ALT=alanine transaminase; DRG=dorsal root ganglion; gamma - glutamyl transferase; ICM= intra - cisterna magna; SAEs=serious adverse events. |
| 8 Patient 1: Vineland - II Sustained improvement documented in all developmental areas through 12 - month assessments Parameter Baseline 3 months 6 months 9 months 12 months Patient Age 14 17 20 24 26 Motor Gross motor 13 14 21 22 21 Fine motor 12 14 16 19 22 Language Receptive language 12 14 25 34 32 Expressive language 8 12 16 19 18 Social Personal living skills 11 14 17 17 19 Interpersonal relationships 8 14 17 22 22 Play and leisure time 17 18 27 26 26 Overall Developmental Age (months) 12 16 21 23 24 8 13 18 23 28 33 38 13 15 17 19 21 23 25 27 Developmental Age (months) Chronological Age (months) Normal Fine motor Gross motor Receptive language Expressive language Personal living skills Interpersonal relationships Play and leisure time Overall T he Vineland - II is caretaker - assessed. |
| 9 Developmental Gains for Patient 1 (Vineland - II) Baseline 12 - month Visit Gross motor Taking a few steps without support Observed jumping Balancing on 1 foot Climbing Stairs Fine motor Sometimes able to squeeze toy Opening door and locks Pours liquid without spilling Stacking 4 blocks Receptive language Never points to named body parts Never points to named objects in book Rarely follows 1 step command Follows 2 - step instructions Follows instructions heard 5 minutes before Points to items in book and body parts Expressive language Never uses “mama/dada” No words with meaning Uses names to address siblings Uses combination of words Creating simple sentences T he Vineland - II is caretaker - assessed. |
| 10 Patient 1: Bayley - III Sustained improvement also directly observed in all developmental areas Parameter Baseline 3 months 6 months 12 months Patient Age 14 17 20 26 Motor Gross motor 13 14 15 15 Fine motor 11 16 16 17 Language Receptive language 10 16 16 18 Expressive language 10 14 15 19 Cognitive Cognition 13 16 19 19 Overall Developmental Age (months) 11.6 15.3 16.6 18 10 12 14 16 18 20 22 24 26 13 15 17 19 21 23 25 27 Developmental Age (months) Chronological Age (months) Normal Gross motor Fine motor Receptive language Expressive language Cognition Overall Patient 1 was subsequently found to have unrelated visual impairment that could have impacted the Bayley - III. ( Patient 1 recently began wearing glasses.) The Bayley scoring is based on direct observation by a neurodevelopmental specialist. |
| 11 Patient 2: Vineland - II Continued improvement despite having severe developmental delay at baseline and prior history of regression Parameter Baseline 3 months 6 months Patient Age 31.6 34.5 37.6 Motor Gross motor 11 12 13 Fine motor 11 12 12 Language Receptive language 14 13 20 Expressive language 8 12 12 Social Personal living skills 16 16 17 Interpersonal relationships 13 21 21 Play and leisure time 12 12 23 Overall Developmental Age (months) 13 16 19 7 10 13 16 19 22 31 33 35 37 Developmental Age (months) Chronological Age (months) Normal Fine motor Gross motor Receptive language Expressive language Personal living skills Interpersonal relationships Play and leisure time Overall * *Not shown on graph because values are too high. T he Vineland - II is caretaker - assessed. |
| 12 Developmental Gains for Patient 2 (Vineland - II) Baseline 6 - month Visit Gross motor Stand with support for 5 seconds Pulls to standing position Standing without support for 1 - 3 minutes Walks without support 2 - 3 steps Throws ball Fine motor Sometimes able to squeeze toy Transfers object from one hand to other Puts objects in container Removes objects in container Picks up small object with finger/thumb Receptive language Smiles upon hearing “yes” Stops when hearing no/stop Rarely follows 1 step command Follows 1 step command Points to 3 major body parts Expressive language Never uses “mama/dada” No words with meaning Pre - speech sounds Says mama/dada Waves goodbye Uses single words T he Vineland - II is caretaker - assessed. |
| 13 Patient 2: Bayley - III Overall improvement observed for motor, language, and cognitive domains Parameter Baseline 3 months 6 months Patient Age 31.6 35 37.6 Motor Gross motor 10 12 11 Fine motor 7 9 7 Language Receptive language 4 9 11 Expressive language 7 7 6 Cognitive Cognition 8 9 13 Overall Developmental Age (months) 7.3 9.1 10.1 0 3 6 9 12 15 31 33 35 37 Developmental Age (months) Chronological Age (months) Normal Gross motor Fine motor Receptive language Expressive language Cognition Overall * *Not shown on graph due to the severe developmental delay. The Bayley scoring is based on direct observation by a neurodevelopmental specialist. |
| 14 0 200 400 600 800 1000 Whole brain Cerebral cortex Cerebral white matter Cerebellum cortex Cerebellar white matter Baseline Month 6 Month 12 ↑ 15% ↑ 15% Patient 1: Change from Baseline at Month 12 (Age at gene transfer: 15 months) Patient 2: Change from Baseline at Month 6 (Age at gene transfer: 31 months) 35% inc 0 200 400 600 800 1000 Whole brain Cerebral cortex Cerebral white matter Cerebellum cortex Cerebellar white matter Baseline Month 6 ↑1% ↓~4% ↓~3% ↓~10% No change Cubic centimeters ↑27% ↓12% ↑35% 0 200 400 600 800 1000 Whole brain Cerebral cortex Cerebral white matter Cerebellum cortex Cerebellar white matter Baseline Month 6 Month 12 ↑ 15% ↑ 15% Cubic centimeters ↑27% ↓12% ↑35% Cohort 1 Volumetric MRI Data |
| 15 Cohort 1 Interim Biomarker Data *Baseline reflects the average of two samples collected within 48 - hours of dosing. † Based on preliminary data from University of Pennsylvania’s ODC NHS study (NCT04041102). b - Gal= b - galactosidase; CSF=cerebrospinal fluid; NHS=natural history study. NHS patient value range 2.25 - 10 nmol/mL/3hr† NHS patient value range 0.30 - 1.81 nmol/mL/3hr† • CSF β - gal activity increased above levels seen in NHS following dosing and sustained at upper limit of NHS • Serum β - gal activity increased in both patients; however, over time, post - treatment β - gal activity for Patient 1 was above NHS patient values, while Patient 2 normalized to NHS patient values • CSF GM1 gangliosi des increased in Patient 1 but subsequently stabilized; data for Patient 2 fluctuated • Whole blood GM1 gangliosides in Patients 1 and 2 increased slightly thru ~50 d post - treatment, then trended downward slightly over time * Patient 1 Patient 2 |
| 16 Key Takeaways from Cohort 1 Interim Data Low dose PBGM01 was well - tolerated with demonstration of functional transgene expression and developmental improvement AEs =adverse events; ICM= intra - cisterna magna .. SAFETY Positive safety profile and well - tolerated with no serious AEs and no complications related to ICM injection CLINICAL STATUS Sustained and continual improvement across developmental areas on both the Vineland and Bayley scal es ADDITIONAL STUDIES Are needed to determine if biomarkers can predict outcomes and if treating early is critical to maximize the response |
| 17 Acknowledgements Thank you to the patients, families, caregivers for their participation in this study. Thank you to the coordinators and site study staff who are instrumental in making this work happen. Co - authors Caroline A Hastings, UCSF Benioff Children’s Hospital Debra - Lynn Day - Salvatore, Saint Peter’s University Hospital Can Ficicioglu, Children’s Hospital of Philadelphia Chester B Whitley, University of Minnesota Michal Inbar - Feigenberg, The Hospital for Sick Children Geneviève Bernard, McGill University; McGill University Health Center Roberto Giugliani, Federal University of Rio Grande do Sul Julien Baruteau, Great Ormond Street Hospital for Children Fatih S Ezgü, Gazi University Sylvia Stockler, BC Children’s Hospital Jeanine R Jarnes, University of Minnesota Yan G. Ni, Pruthvi Nagilla, Victoria L Ballard, Thomas F Haws, Mark S. Forman, Passage Bio Michael H Gelb, University of Washington Michelle Miller, University of Pennsylvania Gene Therapy Program Vector is technology of The University of Pennsylvania (Gene Therapy Program). Imagine - 1 is funded by Passage Bio More information on the Imagine - 1 trial (NCT04713475) can be found at www.clinicaltrials.gov. |
