Beam Therapeutics Inc. Common Stock Study result

Thank you, operator. Good morning, everyone, and welcome to Beam's conference call to review initial clinical data from the phase I/II study of BEAM-301 in patients with glycogen storage disease type 1A presented at the ESGCT Annual Congress. You can access slides for today's call by going to the investor section of our website, beamtx.com. With me on the call today with prepared remarks are John Evans, our Chief Executive Officer, Dr. Amy Simon, our Chief Medical Officer, and Dr. Giuseppe Pino Ciaramella, our President. Before we get started, I would like to remind everyone that some of the statements we make on this call will include forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995.

Actual events and results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties and other factors, including those set forth in the Risk Factors section of our most recent annual report on Form 10-K, and any other filings that we may make with the SEC. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. Except as required by law, Beam specifically disclaims any obligation to update or revise any forward-looking statements, even if our views change. With that, I will turn the call over to John.

Thanks, Holly. When Beam was founded nearly a decade ago, it was driven by a bold belief that a new generation of genetic medicines could transform the treatment of serious genetic diseases. This opportunity is much bigger than one treatment, one disease, or even a handful of diseases. We believe this is the start of a new era of medicine, one in which we address disease at its genetic source with one-time therapies that potentially prevent a lifetime of disease progression. These medicines can free patients from the burdens of chronic treatment, and in so doing, they can also lower lifetime costs for the healthcare system. We know patients and their families want to move on from their disease. Physicians and payers want a treatment that prevents further decline and reduces the expense of chronic disease management.

Regulators want to enable these therapies to reach the people who need them. At Beam, we saw this coming and have positioned our company to lead this new era of medicine. Underpinning this vision is base editing, designed to make precise changes to DNA without creating double-strand breaks. This precision is capable of producing consistent gene sequence outcomes and durable correction following a single treatment. The promise of base editing treatment is profound. By fixing genetic disease at its root cause, we have the potential to deliver transformative disease modification or even functional cures for patients with highly predictable outcomes. Today, our vision for base editing is becoming a reality. Over the last several years, base editing has moved from an emerging scientific concept to a potential new class of medicines being administered to clinical trial patients across a growing range of serious genetic diseases.

Just three years ago, we treated the first clinical trial patient in our sickle cell disease program with the goal of enabling a life free from the constant burden of pain crises and organ damage that is sickle cell disease. That program is now progressing toward a potential regulatory submission. Last year, we made history by demonstrating for the first time genetic correction of a disease-causing mutation in a patient and establishing clinical proof of concept for our first in vivo liver-targeted therapy for alpha-1 antitrypsin deficiency, or AATD. That program is now in pivotal development. That same year, Baby KJ became the first person in the world to receive a personalized, on-demand base editing treatment designed specifically for a unique genetic mutation through the incredible work led by the team at the University of Pennsylvania and Children's Hospital of Philadelphia.

Today, we mark another important milestone with initial clinical data for BEAM-301, showing what targeted genetic correction could mean for people living with glycogen storage disease type 1A. Individually, each of these is a remarkable milestone in the history of medicine. Collectively, they showcase the coming era of genetic medicine in which we have the potential to correct the root cause of disease once and for all in a huge range of conditions, from people living with more common genetic diseases like sickle cell disease and AATD, to those with ultra-rare conditions that until now were not commercially viable, and ultimately, even a single child. To put this transformation into context, I'd like to share a little more about the life of a person living with glycogen storage disease type 1A.

Because their bodies cannot maintain normal glucose levels during fasting, people with GSD1a must take carefully timed doses of cornstarch throughout the day and night to maintain blood sugar levels. Since their glucose levels are constantly dropping, missing even a single dose can result in severe hypoglycemia with the potential for seizures, coma, or death. That means daily life is organized around constant vigilance. Patients and caregivers monitor glucose levels, manage repeated dietary dosing, and set their alarms to go off every few hours all through the night to prevent a potentially life-threatening event. One parent of a GSD1a patient told me she hasn't slept through the night once since her child was born because like so many GSD1a parents, she is part of the first line of defense to make sure her child gets through each night safely.

By correcting the underlying mutation, our goal is to restore the body's ability to produce glucose on its own. For patients and families, that could mean freedom from around-the-clock cornstarch dosing, more stable glucose levels, and the ability to sleep through the night without the disease dictating every decision. That is the potential of treating genetic disease at its source. Amy Simon will share some of the promising data from the BEAM-301 clinical trial in patients with GSD1a later in this presentation. For the past decade, we have built the core capabilities needed to bring these potentially transformative medical outcomes to patients at scale. Our editing and delivery technologies are highly adaptable and reusable, and they are delivering consistent preclinical and clinical results. In fact, across 4 of 4 distinct programs, we have now translated our preclinical findings into clinical proof of concept.

Each success strengthens the platform by generating translational and clinical experience and by establishing technical foundations that can be applied to the next program. Now that this flywheel is running at speed, each new program has the potential to be faster, more efficient, and more likely to succeed. In addition to the breakthrough science and technology underpinning our platform, two other factors are essential to expanding our impact across more diseases and patients, our internal manufacturing infrastructure and an increasingly flexible regulatory environment. I'd like to take a deeper dive into each of these now. First, we recognized early that the traditional model for developing and manufacturing genetic medicines would not support the scale of our ambition or the potential of this technology. Gene editing is a highly complex therapeutic modality with many critical components that must be precisely engineered.

That is why we made the decision in 2020 to begin building out fully integrated internal production capabilities for CRISPR medicines, spanning editor design, automation, computational biology, process development, manufacturing, and quality release. The silicon chip industry famously relies on fabs, highly specialized manufacturing facilities that fabricate the complex silicon chips underpinning the computer, internet, and AI revolutions. Our vision is to create a fab for CRISPR genetic medicines. Today, those capabilities allow us to move from the design of a new editor through the production of clinical and potentially soon commercial material within one vertically integrated organization. Just as important, the assays, procedures, and manufacturing experience established through one program can be cross-referenced and reused across all the programs that follow, helping us avoid redundant investment and serve even more patient populations in need of therapies. These capabilities are already paying off in our two most advanced programs.

Both are now in pivotal development and target large patient populations. In sickle cell disease, risto-cel has the potential to be a highly differentiated one-time therapy and Beam's first commercial launch. Because we create customized base edited cell products using each patient's cells, owning the manufacturing process has been critical to shaping the patient experience and improving manufacturing outcomes, as seen in the BEACON trial. It also let us design for commercial scale from the start, and we've already expanded capacity to meet potential demand. The same facility now manufactures our investigational base editing therapy, BEAM-302, a new kind of treatment designed to directly correct the exact DNA misspelling that causes disease in most patients with AATD. BEAM-302 has the potential to become the first one-time therapy addressing both the lung and liver manifestations of AATD.

Through these programs, we also have built a substantial base of validated assays, manufacturing processes, and quality systems designed to support late-stage development and potential commercialization. This foundation can be cross-referenced, adapted, and extended as we advance the next generation of programs through our platform. With all the momentum for base editing in the clinic, our focus now shifts to reaching as many patients as possible with this technology. While sickle cell disease and AATD are large enough to follow standard regulatory paths, the traditional regulatory model doesn't work for many genetic diseases. Some, like GSD1a, affect relatively small populations, while others, like PKU, are caused by many different mutations within the same gene. Luckily, the FDA has been closely following this new technology as well, and in recent years, they have advanced multiple new frameworks with potential to accelerate our ability to treat more patients with base editing medicines.

Some of these approaches enable us to cross-reference platform information across programs, avoiding needless duplication of effort and vastly simplifying the path to clinic for new editors. Other guidance frameworks, such as the plausible mechanism pathway, allow us to treat populations of patients who may have different mutations with different base editors but still combine them into a single efficient clinical program. Together, these new approaches at FDA represent a paradigm shift in drug development, away from evaluating each product in isolation and toward recognizing the cumulative evidence generated across the common components in a validated platform. And what Beam has been building for the last decade positions us perfectly for this potentially dramatic expansion in the reach of genetic medicines.