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

 •  4/19/2024 Letter Continued (Full PDF)
 •  4/21/2023 BEAM Stockholder Letter
 •  More "Biotechnology" Category Stockholder Letters
 •  BEAM Benford's Law Stock Score = 71

BEAM Shareholder/Stockholder Letter Transcript:

Dear Fellow Shareholders,
Beam was built from the beginning to push the gene editing field forward. We are pioneering a
cutting-edge, next-generation technology called base editing designed to make more precise and
predictable edits in genes without needing to make damaging, double-stranded cuts in the DNA.
We hypothesized that this breakthrough could provide a superior way to modify genes and open
up entirely new applications in gene editing.
Today, we are closer than ever to making this vision a reality. We have established and
integrated capabilities across our base editing platform, from research to manufacturing to
development. This year, we anticipate having four base editing programs in clinical development
for both ex vivo and in vivo applications, and we also expect to report our first in-human data
from multiple base editing programs this year. We have a high degree of focus and strategic
clarity across the organization, strong momentum in execution and significant financial strength.
Some of our notable achievements in 2023 and early 2024 include:
x We initiated patient dosing in two of our clinical studies for BEAM-101 and BEAM-201.
x We commenced good manufacturing practices (GMP) operations at our North Carolina
manufacturing facility, where capabilities include both CD34 cell manufacturing and
lipid nanoparticle (LNP) production, with additional capabilities expected to be added in
the future.
x We filed a clinical trial application for BEAM-302, which has now been approved for
Phase 1 development in the UK, and BEAM-301 has completed IND-enabling studies,
with a U.S. IND filing expected in coming months.
x We sold our opt-in rights to Verve   s base editing cardiovascular programs to Lilly for up
to $600 million in combined upfront payment, equity investment and potential future
development-stage payments.
x We prioritized our portfolio to focus on our rapidly growing hematology and liver genetic
disease franchises, led by the sickle cell disease and alpha-1 antitrypsin deficiency
(AATD) programs, respectively.
Our innovative efforts with base editing are also building on the foundation of a strong and
rapidly growing gene editing field. In 2023, Vertex received the first approval from the U.S.
Food and Drug Administration (FDA) of a CRISPR therapy, Verve Therapeutics achieved
positive editing proof of concept for patients treated with an in vivo base editor, and we
witnessed continued improvements in the regulatory environment for genetic medicines in both
the U.S. and EU. Collectively, these events establish meaningful clinical, regulatory and
commercial groundwork for both our in vivo and ex vivo programs and support the continued
advancement of our next-generation genetic medicines to patients.
Looking ahead, we believe Beam is well positioned to achieve the following goals:
1. Establish base editing as the best-in-class gene editing technology
2. Determine if our lead programs can become transformative one-time therapies for
patients

3. Establish a path to commercial viability and significant value creation for Beam, focusing
particularly on our two core franchises in hematology and genetic disease, each of which
feature potentially highly differentiated programs for large and underserved patient
populations
HEMATOLOGY FRANCHISE
Our hematology franchise is anchored by a long-term, staged development strategy for sickle cell
disease. We are advancing three    waves    of innovation, each of which builds on the last, with
the goal of progressively expanding the utility of our base editing approach to broader subsets of
patients and eventually deliver a one-time therapy to all patients around the world. This strategy
starts with our ex vivo gene editing therapy candidate, BEAM-101, which has best-in-class
potential and a validated regulatory pathway, followed by novel approaches that aim to eliminate
the challenging conditioning regimes of today   s gene therapies. Furthermore, as we establish this
expanding suite of technologies to better serve the sickle cell disease patient community, we
believe we will also unlock the ability to address many other hematologic conditions in an
expanding portfolio.
Wave 1: BEAM-101 is an autologous investigational cell therapy designed to efficiently and
uniformly increase fetal hemoglobin (HbF) in red blood cells without relying on double stranded
breaks, offering a potentially best-in-class profile. Preclinical models suggest base editing could
lead to higher and more uniform editing, improved HbF induction, and lower residual diseasecausing hemoglobin S compared to existing gene therapy options, all in a robust cell product that
benefits from the avoidance of double-stranded breaks in the DNA.
The first patient was dosed in the fourth quarter of 2023 and successfully achieved engraftment
in the BEACON Phase 1/2 clinical trial, an open-label, single-arm, multicenter study evaluating
the safety and efficacy of BEAM-101 in adult patients with severe sickle cell disease. Treatment
with BEAM-101, in which the edited cell product is delivered in an autologous bone marrow
transplant, is occurring on a sequential basis for the first three patients treated in the trial, and
then will be given in parallel for all subsequent patients. We   ve made significant progress on
enrollment and are on track to initiate dosing in patients in the expansion cohort in the first half
of 2024. In addition, we anticipate reporting initial data on multiple patients with long-term
follow-up from the BEACON trial in the second half of 2024.
Wave 2: We continue to advance and invest in our novel Engineered Stem Cell Antibody Paired
Evasion (ESCAPE) conditioning platform and anticipate initiating Phase 1-enabling preclinical
studies for the program in 2024. ESCAPE aims to avoid the toxicities associated with currently
available conditioning regimens that patients with sickle cell disease are required to undergo
prior to autologous transplant.
Wave 3: Finally, we are also exploring the potential for in vivo base editing programs for sickle
cell disease, in which the base editor would be delivered to the patient through intravenous
infusion of LNPs targeted to hematopoietic stem cells, eliminating the need for transplantation
altogether. This research is currently being conducted in rodent and monkey in vivo studies.

GENETIC DISEASE FRANCHISE
Our second major pipeline effort aims to treat genetic diseases using single course gene editing
therapies delivered through intravenous infusion of LNPs, which are a clinically validated
technology for delivery of nucleic acid payloads to the liver. BEAM-302 is our highest priority
genetic disease program that has the potential to demonstrate rapid proof-of-concept, followed
by BEAM-301. Together, they represent the first clinical programs in the gene editing field to
directly correct a genetic mutation back to a normal functional gene sequence.
BEAM-302: BEAM-302 is a potential treatment for AATD, which is characterized by early
onset emphysema, liver disease, and increased all-cause mortality compared to the general
population. There is a large unmet need for novel therapies that can treat patients with AATDassociated lung and liver disease. BEAM-302 is a potentially best-in-class liver-targeting LNP
formulation of base editing reagents designed to correct the PiZ allele, the most common gene
variant associated with severe AATD. Approximately 100,000 patients in the U.S. are estimated
to carry the PiZZ genotype.
Preclinical data to date demonstrated that treatment with BEAM-302 led to significantly
increased levels of corrected and functional alpha-1 antitrypsin (AAT) and reduced mutant PiZ
AAT in multiple in vivo rodent disease models at clinically relevant doses. These findings
support the potential of BEAM-302 to efficiently correct the disease-causal PiZ mutation after a
single dose and potentially address both the liver and lung disease associated with AATD. In
March, we announced clearance of the clinical trial authorisation (CTA) application in the U.K.
This is an important step in the advancement of our global Phase 1/2 clinical study of BEAM302, which is expected to initiate in the first half of 2024.
BEAM-301: In addition, we are advancing BEAM-301 for the potential treatment of glycogen
storage disease type 1a (GSD1a), an autosomal recessive disorder caused by mutations in the
G6PC gene that disrupt a key enzyme, glucose-6-phosphatase, involved in maintaining glucose
homeostasis. BEAM-301 is a liver-targeting LNP formulation of base editing reagents designed
to correct the R83C mutation, the most common disease-causing mutation that results in the most
severe form of GSD1a.
Preclinical data have shown that a single administration of BEAM-301 directly and durably
corrected the R83C mutation in vivo, with an ongoing significant survival benefit one year after
the initial dosing. We are focusing initial development of BEAM-301 in the U.S. and expect to
submit an investigational new drug (IND) application in the first half of 2024.
In both of these key franchises and beyond, we continue to build a sustainable portfolio for the
future, benefitting increasingly from having large parts of our technology stack    reduced to
practice    and from a world-class team with growing experience advancing novel base editors.
The programmable nature of base editing allows us to rapidly generate novel programs with high
efficiency and increased probability of success.

As we look to deliver on meaningful catalysts across our portfolio this year, a key factor in our
success lies in the continued dedication and passion of the Beam Team. Our culture and
comradery as well as the rigor and technical excellence of the team are what make Beam a great
place to work and will position us to continue to deliver for all stakeholders, especially the
patients who are counting on us.
Collectively, we believe base editing has an opportunity to offer highly differentiated, one-time
treatments with life-long impacts for a range of diseases     ultimately, changing the trajectory of
many people   s lives     and can significantly expand the scope and reach of gene editing. As we
near the critical phase of delivering first-in-human data from our core portfolio of lead base
editing programs, we wish to thank each of our shareholders for sharing our mission and for
taking this journey with us.
Sincerely,
John Evans, CEO, Beam Therapeutics
Cautionary Note Regarding Forward-Looking Statements
This letter contains forward-looking statements within the meaning of the Private Securities
Litigation Reform Act of 1995 relating to, among other things, future operating performance,
product development, market position and business strategy. The reader is cautioned not to rely
on these statements, which are based on current expectations of future events. For important
information about these statements, including the important risks, uncertainties and other factors
that could cause actual results to differ materially from the assumptions, expectations and
projections expressed in any forward-looking statements, the reader should review the enclosed
Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including the
sections captioned    Risk Factors Summary    and    Item 1A. Risk Factors.    Beam Therapeutics
Inc. does not undertake to update any forward-looking statement as a result of new information,
future events or developments or otherwise, except as may be required by applicable law.



 4/19/2024 Letter Continued (Full PDF)