The Future of Gene Editing: Turning DNA Dreams Into Dollars.

Recent advancements in gene editing technology

Recent advancements in gene editing technology include chemically modified guide RNAs for lipid nanoparticle-mediated in vivo gene editing, superior base editing technology, new platform advancements by Intellia, and the efficacy and safety of KASgevy for sickle cell beta thalassemia. Additionally, next-generation delivery technologies are being evaluated.

"So as you know, base editing is our core technology and we're bringing that forward to patients with a wide variety of diseases with what we think will be a best in class and superior technology offering to those patients than what has been possible to date in gene editing." --- (BEAM, conference, 2024/05/15)

""Today's data showcase an exciting new platform advancement for Intellia and the field of gene editing." --- (NTLA, press release, 2024/06/25)

"Yes. So, obviously, the foundation of our approach is that the gene editing with KASgevy has demonstrated both high rates of efficacy in the current approach for both sickle cell beta thal as well as safety and tolerability profile consistent with the bone marrow transplant. And so the goal is now to be able to get improved patient" --- (VRTX, conference, 2024/06/11)

"Additionally, we're evaluating next generation delivery technology. Second, our in vivo capabilities with the potential to be used in developing transformative in vivo gene editing medicines are demonstrated by the preclinical data we are presenting at the American Society of Gene and Cell Therapy or ASGCT Annual Meeting in three presentations taking place on Thursday and Friday of this week." --- (EDIT, earning call, 2024/Q1)

Applications of gene editing in healthcare

Gene editing in healthcare is advancing with treatments targeting tissues beyond the liver, one-time therapies for hemophilia B, and innovative approaches for acute myeloid leukemia. These developments highlight the potential for gene editing to revolutionize disease treatment and improve patient outcomes.

"By leveraging Regeneron's expertise in AAV and antibody engineering and Mammoth's expertise in ultracompact gene editing systems, the teams will endeavor to create disease-modifying medicines that can be delivered to tissues beyond the liver, to which most gene editing treatments are currently limited." --- (REGN, press release, 2024/04/25)

"For eligible patients living with hemophilia B, the goal of this gene therapy is to enable them to produce FIX themselves via this one-time treatment rather than having to receive frequent infusions of FIX, as is the current standard of care.1,2,4 It is currently approved in the U.S. for the treatment of adults with moderate to severe hemophilia B (congenital factor IX deficiency) who: Currently use factor IX prophylaxis therapy, or" --- (PFE, press release, 2024/04/26)

"We are eager to continue to study this combination and generate additional data that could support advancing into clinical studies of Actimab-A with menin inhibitors. Menin inhibitors are a class of drug candidates being developed for patients with AML that have a rearrangement of the KMT2A gene, previously known as the mixed-lineage leukemia (MLL) or mutation of the NPM1 gene." --- (JNJ, press release, 2024/06/17)

"Founded by CRISPR pioneer and Nobel laureate Jennifer Doudna and Trevor Martin, Janice Chen, and Lucas Harrington, the company's ultracompact systems are designed to be more specific and enable in vivo gene editing in difficult to reach tissues utilizing both nuclease applications and new editing modalities beyond double stranded breaks, including base editing, reverse transcriptase editing, and epigenetic editing." --- (REGN, press release, 2024/04/25)

"Today @US_FDA approved @Pfizer’s gene therapy that could enable adults with hemophilia B to produce FIX themselves via a one-time treatment, the latest step in Pfizer’s 40+ year effort to advance the standard of care for people living with hemophilia: https://t.co/z6UImvvBw2" --- (PFE, Twitter, 2024/04/26)

Regulatory landscape and its impact on gene editing

Companies are focusing on rare, severe diseases to enhance regulatory success and commercial viability. Anticipation for regulatory approval is high, as seen with the excitement surrounding upcoming Phase 3 trials, highlighting the critical role of regulatory landscapes in advancing gene editing technologies.

"Those are other ways that we would actually select to maximize the probability of technical success, you know, focusing on rare, severe diseases where it can maximize the size of the signal and to maximize the probability of regulatory success and ultimately by truly differentiating maximize the probability of commercial success." --- (EDIT, conference, 2024/05/15)

"Based on the landmark findings published in the New England Journal of Medicine, we are already seeing grassroots excitement about 2,002 and the upcoming Phase 3 trial. We look forward to discussing the trial design in more detail once we have regulatory approval." --- (NTLA, event transcript, 2024/06/03)

Key players and competitive landscape

Vertex Pharmaceuticals is proactively engaging with key decision-makers and stakeholders, while Beam Therapeutics is positioning its therapy within the evolving competitive landscape. Vertex's acquisition of Alpine further strengthens its strategic positioning in gene editing.

"We are already engaging with key decision-makers across the formulary and access landscape." --- (VRTX, earning call, 2024/Q1)

"We are already engaging with key decision-makers across the formulary and access landscape, including pharmacists, PBMs, payers, IDNs and GPOs." --- (VRTX, earning call, 2024/Q1)

"In Alpine, we see extraordinary strength across all of these dimensions. Specifically, and as Reshma will discuss in greater detail, the key elements that lead to our enthusiasm and our conviction to acquire Alpine are first, Phase 3 ready class potential in IgAN.2nd, pipeline in a product potential in multiple serious immune renal diseases and cytopenias." --- (VRTX, event transcript, 2024/04/10)

Investment opportunities in gene editing

Intellia and Editas Medicine present promising investment opportunities in gene editing, driven by their focus on commercialization and robust treatment pipelines. However, potential investors should be aware of financial risks and the need for additional funding, which could impact product development and market introduction.

""We are very pleased to welcome Brian to our board of directors. Brian's extensive global commercialization experience, coupled with his track record of success leading rare disease product launches, will be invaluable to Intellia as we commercialize our first CRISPR-based gene editing therapies for people with life-threatening diseases," said Intellia President and Chief Executive Officer John Leonard, M.D." --- (NTLA, press release, 2024/06/14)

"About Editas MedicineAs a clinical-stage gene editing company, Editas Medicine is focused on translating the power and potential of the CRISPR/Cas12a and CRISPR/Cas9 genome editing systems into a robust pipeline of treatments for people living with serious diseases around the world." --- (EDIT, press release, 2024/05/08)

"If we are unable to raise additional funds through equity financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves. Outlook" --- (NTLA, sec filing, 2024/Q1)

"Our forecast of the period of time through which our existing cash and cash equivalents and investments will be adequate to support our operations is a forward-looking statement and involves significant risks and uncertainties." --- (EDIT, sec filing, 2024/Q1)

"If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce, or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves." --- (EDIT, sec filing, 2024/Q1)

Challenges and risks in gene editing

Gene editing faces significant challenges, including the risk of bystander editing, ensuring targeted delivery to specific organs like the liver and lungs, and achieving consistent biological responses. Continuous monitoring and evaluation of product development are crucial to balance these risks with potential benefits.

"And also, is there any risk of bystander editing there? If I recall it correctly, you have an A that is in kind of close proximity to the A that you were trying to target." --- (BEAM, conference, 2024/05/15)

"I'm talking about gene edited risk for gene edited products, which is where you have essentially a response rate of a 100%, biological response rate a 100% and almost a 100% clinically." --- (EDIT, conference, 2024/05/15)

"Our investments in product candidates are subject to considerable risks. We closely monitor the results of our discovery, research, clinical trials and nonclinical studies and frequently evaluate our product development programs in light of new data and scientific, business and commercial insights, with the objective of balancing risk and potential." --- (VRTX, sec filing, 2024/Q1)

"What we've learned is that the degree of editing is really quite independent of body weight within a given dose. So a simple way of thinking about this is really what you're treating is the liver as opposed to exposure to the rest of the body." --- (NTLA, study update, 2024/06/03)

"It's not restoring it. Obviously, not getting into the lungs. Obviously, not restoring the natural increases and decreases as you have an infection because that gene therapy is different." --- (BEAM, conference, 2024/06/06)