On this page of StockholderLetter.com we present the latest annual shareholder letter from Passage BIO, Inc. — ticker symbol PASG. Reading current and past PASG letters to shareholders can bring important insights into the investment thesis.

 •  4/9/2024 Letter Continued (Full PDF)
 •  4/14/2023 PASG Stockholder Letter
 •  More "Biotechnology" Category Stockholder Letters
 •  PASG Benford's Law Stock Score = 60

PASG Shareholder/Stockholder Letter Transcript:

2023 ANNUAL REPORT

OUR MISSION
To improve the lives of patients with
neurodegenerative diseases by delivering
genetic medicines that will permanently
redefine the course of their conditions
To Our Shareholders,
In 2023, Passage Bio made significant strides in our mission to
improve the lives of people with neurodegenerative diseases.
We are energized by our progress in advancing cutting-edge
genetic medicines as we continue to build momentum in 2024,
embarking on a path to best serve those who count on us.
In our bold pursuit to redefine the course of devastating
neurodegenerative conditions, every decision we make is guided
by our commitment to putting patients first. Their urgency for
life-changing solutions requires us to be agile as an organization,
realigning priorities and optimizing resources so that we can give
our gene therapy candidates the best chance to succeed. Mindful
of our purpose, Passage Bio responded in 2023 by taking steps to
sharpen our ongoing clinical focus and position our portfolio for
future success.
Validating the therapeutic potential of PBFT02
We are particularly excited about the growing body of evidence
demonstrating the best-in-class potential of our lead clinical
candidate, PBFT02, an adeno-associated virus (AAV)-delivery
gene therapy for the treatment of frontotemporal dementia (FTD)
caused by granulin mutations (GRN). FTD-GRN is a devastating
form of early-onset dementia that occurs due to a mutation in the
GRN gene and a resulting progranulin (PRGN) deficiency. Disease
progression is rapid and degenerative, including loss of speech and
expression, severe behavioral changes, and immobility.
As a one-time gene therapy delivered directly to the cerebrospinal
fluid (CSF) in the brain via intra-cisterna magna (ICM) injection,
PBFT02 aims to restore a functional GRN gene and address
progranulin deficiency, a key driver of neurodegeneration in
individuals with FTD-GRN. By elevating PRGN levels to restore
lysosomal function and slow disease progression, we believe
PBFT02 offers a therapeutic approach that could potentially
change the prognosis in FTD-GRN, which has no approved
disease-modifying therapies.
Compelling interim clinical data drives new strategic path
In December 2023, we reported initial data from our Phase 1/2
upliFT-D clinical trial in FTD-GRN, which showed the ability of
PBFT02 to increase CSF PRGN to levels greater than normally
found in the body. By consistently achieving high levels in CSF,
PBFT02 has the potential to improve neuronal function and
achieve meaningful clinical benefit for patients.
These encouraging results not only exceeded our expectations
for PBFT02 based on our preclinical models, but also provided
compelling evidence to drive an opportunistic shift in our R&D
roadmap. Based on preclinical evidence supporting progranulin   s
role in neurodegeneration, we plan to explore the therapeutic
potential of PBFT02 in multiple diseases. In tandem with our
continued clinical development of PBFT02 in the treatment of
FTD-GRN, we are targeting portfolio expansion in additional
adult neurodegenerative diseases where PBFT02 has the
potential to correct underlying pathology and modulate disease,
including FTD-C9orf72, amyotrophic lateral sclerosis (ALS), and
Alzheimer   s disease.
Acting with intention on behalf of patients
A gene therapy program is only as promising as its clinical data.
Our strategic priorities embody our intention to follow the science
as we aim to protect patients and their families against the lifethreatening consequences of neurodegenerative diseases.
As we continue to explore the potential of PBFT02, we also are
prioritizing advancement of our preclinical program in Huntington   s
disease through our existing partnership with the University of
Pennsylvania Gene Therapy Program. In addition, we are actively
pursuing out-licensing opportunities to advance our clinical-stage
pediatric programs in GM1 gangliosidosis, Krabbe disease and
metachromatic leukodystrophy (MLD).
Looking ahead
2024 will be an important year of continued progress for Passage
Bio. We look forward to achieving several key milestones, including
reporting new safety and biomarker data from cohort 1 patients
in our upliFT-D trial and initiating dosing in a second cohort of
patients. As we pursue pipeline expansion for PBFT02, we also
plan to engage regulatory authorities on the pathway to evaluate
PBFT02 for the treatment of FTD-C9orf72 and ALS.
With a strong cash position into the fourth quarter of 2025,
Passage Bio is well-positioned to execute against our goals.
Above all, we will lean on our deeply experienced team, who are
razor-focused on clinical execution and continue to demonstrate
unwavering dedication to the call of patients. I could not be
prouder to lead our company on the critical journey that lies ahead.
On behalf of all of us at Passage Bio, thank you for your
continued support.
Sincerely,
William Chou, M.D.
President and Chief Executive Officer



 4/9/2024 Letter Continued (Full PDF)