Business Overview and History

CRISPR Therapeutics AG (CRSP) is a leading biopharmaceutical company at the forefront of the gene editing revolution, leveraging its proprietary CRISPR-Cas9 technology to develop transformative gene-based medicines for serious diseases. With a diverse pipeline of product candidates spanning multiple therapeutic areas, CRISPR Therapeutics is poised to make a significant impact on the lives of patients worldwide.

CRISPR Therapeutics was incorporated in October 2013 in Basel, Switzerland, with the mission of translating the revolutionary CRISPR-Cas9 genome editing technology into novel gene-based treatments. The company's origins can be traced back to the groundbreaking work of Dr. Emmanuelle Charpentier, one of CRISPR Therapeutics' scientific founders, who co-invented the CRISPR-Cas9 system and was awarded the Nobel Prize in Chemistry in 2020 for her pioneering contributions.

In April 2014, CRISPR Therapeutics secured an exclusive license to the foundational CRISPR-Cas9 intellectual property, laying the foundation for the company's therapeutic development efforts. In its early years, CRISPR devoted substantially all of its efforts to product research and development activities, initial market development, and raising capital. The company has financed its operations through a series of preferred share and convertible loan issuances, proceeds from its initial public offering, subsequent public offerings of its common shares, at-the-market offerings, as well as upfront fees and milestones received under its collaboration and license arrangements.

CRISPR faced several challenges in its early stages as a research-stage company, including the need to advance its CRISPR-Cas9 technology from discovery to an approved medicine. The company had to navigate the complex regulatory landscape for gene editing therapies, as the FDA, EMA, and other regulatory authorities demonstrated caution in their oversight of this new technology. CRISPR also had to build internal manufacturing capabilities and establish partnerships to complement its expertise.

Despite these challenges, CRISPR made significant progress in developing its portfolio of gene editing therapeutic programs. The company established strategic collaborations, including a partnership with Vertex Pharmaceuticals starting in 2015 focused on hemoglobinopathies and cystic fibrosis. In 2017, Vertex exercised its option to co-develop and co-commercialize the hemoglobinopathies program, leading to the joint development and commercialization of CRISPR's lead program, CASGEVY.

Over the past decade, CRISPR Therapeutics has built a robust portfolio of product candidates targeting a wide range of serious diseases, including hemoglobinopathies, oncology, autoimmune disorders, and type 1 diabetes. One of the company's most significant achievements to date is the landmark 2023 approval of CASGEVY, the first-ever CRISPR-based gene therapy, for the treatment of eligible patients with severe sickle cell disease and transfusion-dependent beta-thalassemia. This groundbreaking approval has positioned CRISPR Therapeutics as a leader in the field of gene editing therapies.

Financial Snapshot

As of December 31, 2024, CRISPR Therapeutics reported $1.9 billion in cash, cash equivalents, and marketable securities, providing the company with ample resources to continue advancing its robust pipeline of product candidates. The company's full-year 2024 financial results included:

• Total revenue of $37.3 million, primarily driven by collaboration revenue and grant income.

• Research and development expenses of $320.7 million, reflecting the company's ongoing investments in its diverse pipeline.
• Net loss of $366.3 million, as the company continues to prioritize the development of its transformative gene-based therapies.
• Operating cash outflow of $142.8 million, with the company's strong cash position supporting its long-term growth initiatives.

It's important to note that CRISPR Therapeutics' financial performance has been significantly impacted by its strategic collaborations, particularly the partnership with Vertex for the development and commercialization of CASGEVY. The company's financial results can fluctuate based on the timing of milestone payments and the allocation of expenses related to these collaborative efforts.

In the most recent quarter (Q4 2024), CRISPR Therapeutics reported revenue of $35.7 million and a net loss of $37.3 million. The company experienced a significant year-over-year revenue decline of 82% compared to Q4 2023, primarily due to the inclusion of a $200 million milestone payment related to the approval of CASGEVY in the prior year period.

Liquidity

CRISPR Therapeutics maintains a strong liquidity position, with $1.9 billion in cash, cash equivalents, and marketable securities as of December 31, 2024. This robust cash reserve provides the company with the financial flexibility to fund its ongoing research and development activities, advance its clinical programs, and support potential future commercialization efforts. The company's strategic collaborations, particularly with Vertex Pharmaceuticals, also contribute to its liquidity through milestone payments and shared development costs.

Additional liquidity metrics as of December 31, 2024 include:

• Debt/Equity Ratio: 0.12

• Current Ratio: 22.07
• Quick Ratio: 22.07

These strong liquidity ratios underscore CRISPR Therapeutics' solid financial footing and ability to meet its short-term obligations. The company expects its current cash position to fund its operating plan for at least the next 24 months.

Pipeline and Key Developments

CRISPR Therapeutics operates in one reportable segment, focusing on discovering, developing, and commercializing therapies derived from or incorporating genome-editing technology. The company's diversified pipeline encompasses a range of product candidates across its core franchises, including hemoglobinopathies, CAR-T cell therapies, in vivo gene editing approaches, and type 1 diabetes treatments. The company's progress in these areas has been marked by several key developments:

Hemoglobinopathies

• CASGEVY, the company's landmark CRISPR-based gene therapy for sickle cell disease and beta-thalassemia, has continued to gain momentum since its initial approval in 2023. As of the end of 2024, more than 50 authorized treatment centers had been activated globally, and more than 50 patients had undergone cell collection procedures across all regions.

• CASGEVY is a non-viral, ex vivo CRISPR-Cas9 gene-edited cell therapy that edits the erythroid-specific enhancer region of the BCL11A gene, resulting in the production of high levels of fetal hemoglobin to compensate for defective adult hemoglobin in patients with sickle cell disease (SCD) and transfusion-dependent beta-thalassemia (TDT).

• CASGEVY has been approved in the United States, European Union, Great Britain, Canada, Switzerland, Kingdom of Saudi Arabia, Kingdom of Bahrain, and the United Arab Emirates for the treatment of eligible patients 12 years and older with SCD or TDT.

• The company and its partner Vertex continue to investigate CASGEVY, including three clinical trials assessing the safety and efficacy in patients aged 12 to 35 with severe SCD and TDT, two trials in patients aged 5 to 11, and long-term follow-up trials.

• The safety data for CASGEVY has been generally consistent with an autologous stem cell transplant, and the efficacy data supports its potential as a one-time functional cure for severe SCD and TDT.

• The company is advancing additional hemoglobinopathy programs, including its targeted conditioning and in vivo hematopoietic stem cell editing approaches, which have the potential to further expand the addressable patient population for these devastating genetic disorders.

CAR-T Cell Therapies

• CRISPR Therapeutics is making significant strides in its next-generation allogeneic CAR-T programs, with CTX112 (targeting CD19) and CTX131 (targeting CD70) currently in clinical trials. These product candidates incorporate multiple gene edits designed to enhance potency, reduce exhaustion, and evade the immune system, potentially offering improved efficacy and safety profiles compared to existing CAR-T therapies.

• The company's CRISPR-Cas9 platform has enabled the continuous innovation of its CAR-T pipeline, with plans to provide updates on CTX112 in oncology and autoimmune diseases, as well as CTX131 in solid tumors and hematological malignancies, throughout 2025.

• Early data from these trials suggest the novel potency-enhancing edits lead to significantly higher CAR T cell expansion and functional persistence compared to first-generation candidates.

• The company's internal GMP manufacturing facility in Framingham, Massachusetts produces these next-generation CAR T candidates for clinical trials.

In Vivo Gene Editing

• CRISPR Therapeutics is rapidly advancing its in vivo gene editing portfolio, with a focus on addressing severe monogenic diseases and common diseases through gene disruption and whole gene correction. The company's lead in vivo programs, CTX310 (targeting ANGPTL3) and CTX320 (targeting Lpa), are currently in clinical trials for the treatment of cardiovascular diseases.

• CTX310 aims to disrupt the ANGPTL3 gene to treat cardiovascular disease, while CTX320 targets the LPA gene encoding apolipoprotein(a) to lower Lp(a) levels, which are independently associated with increased cardiovascular risk. Both programs are currently in Phase 1 clinical trials.

• The company's proprietary lipid nanoparticle (LNP) delivery platform has been instrumental in supporting the development of its in vivo gene editing initiatives, which have the potential to transform the treatment landscape for a wide range of genetic disorders.

• CRISPR is also progressing earlier stage in vivo programs for rare and common diseases, as well as programs focused on gene correction in the liver.

Type 1 Diabetes

• CRISPR Therapeutics is leveraging its gene editing expertise to develop innovative stem cell-derived therapies for the treatment of type 1 diabetes. The company's lead program, CTX211, is an allogeneic, gene-edited, hypoimmune stem cell-derived product candidate that is currently in a Phase 1 clinical trial.

• CTX211 is designed to produce insulin in a glucose-dependent manner and is being evaluated as a potential durable beta-cell replacement option without the need for long-term immunosuppression.

• The company's parallel efforts in this area, including its deviceless beta cell replacement approach (CTX213) and its non-exclusive license agreement with Vertex, underscore its commitment to addressing the significant unmet need in type 1 diabetes.

Risks and Challenges

While CRISPR Therapeutics has made remarkable progress in advancing its gene-based therapies, the company faces several risks and challenges that investors should be aware of:

1. Regulatory Hurdles: As a pioneer in the gene editing field, CRISPR Therapeutics must navigate a complex and evolving regulatory landscape, both in the United States and globally. Delays or setbacks in the regulatory approval process could significantly impact the company's ability to bring its product candidates to market.

2. Clinical Development Risks: The development of gene-based therapies, including those based on CRISPR-Cas9 technology, carries inherent risks, such as potential safety issues, unexpected side effects, and challenges in demonstrating robust efficacy in clinical trials. Failures or delays in the company's clinical programs could adversely affect its financial performance and future growth prospects.

3. Manufacturing and Supply Chain Complexities: The production of gene-based therapies, including cell and gene therapies, requires specialized manufacturing capabilities and a reliable supply chain. Any disruptions or challenges in this area could impede CRISPR Therapeutics' ability to meet demand and commercialize its products effectively.

4. Intense Competition: CRISPR Therapeutics operates in a highly competitive landscape, with other biotechnology and pharmaceutical companies, as well as emerging gene editing platforms, vying for a share of the rapidly evolving gene-based medicine market. The company's ability to maintain its competitive edge and market position will be crucial to its long-term success.

5. Intellectual Property Challenges: The CRISPR-Cas9 technology underlying CRISPR Therapeutics' platform is the subject of ongoing intellectual property disputes, which could potentially impact the company's freedom to operate and the commercialization of its product candidates.

Despite these risks, CRISPR Therapeutics has demonstrated its resilience and adaptability in navigating the challenges of the gene editing field. The company's strong cash position, diverse pipeline, and continued innovation provide a solid foundation for its long-term growth and success.

Human Capital Management

As of December 31, 2024, CRISPR Therapeutics AG had 393 full-time employees. The majority of employees were based in Boston, Massachusetts, with additional employees in Framingham, Massachusetts, Mission Bay, California, and Switzerland. The company's workforce is highly skilled, with 68 employees holding Ph.D., Pharm. D., or M.D. degrees. A significant portion of the workforce, 342 employees, is engaged primarily in research and development or technical operations, underscoring the company's commitment to advancing its innovative pipeline.

CRISPR Therapeutics considers its employee relations to be good and is committed to building a diverse and inclusive workplace. The company recognizes that its human capital is a key asset in driving innovation and success in the competitive field of gene editing and cell therapy.

Industry Trends

The gene editing and cell therapy market is experiencing rapid growth and is expected to continue expanding at a compound annual growth rate (CAGR) of approximately 20-25% over the next five years. This growth is primarily driven by the continued development and commercialization of transformative therapies like those being developed by CRISPR Therapeutics.

Key factors contributing to this growth include:

1. Increasing prevalence of genetic disorders and cancer
2. Advancements in gene editing technologies, particularly CRISPR-Cas9
3. Growing investment in research and development by biotechnology and pharmaceutical companies
4. Favorable regulatory environment for cell and gene therapies
5. Rising patient awareness and acceptance of gene-based treatments

As a leader in the field, CRISPR Therapeutics is well-positioned to capitalize on these industry trends and contribute to the ongoing revolution in gene-based medicines.

Outlook and Conclusion

As CRISPR Therapeutics enters 2025, the company is poised for a catalyst-rich year, with multiple upcoming milestones and data readouts across its diverse pipeline of gene-based therapies. The ongoing launch of CASGEVY is expected to gain further momentum, with the company anticipating a significant increase in new cell patient collection initiations throughout the year.

Moreover, CRISPR Therapeutics is making steady progress in its next-generation CAR-T programs, with mid-2025 updates planned for CTX112 in oncology and autoimmune diseases, as well as CTX131 in solid tumors and hematological malignancies. The company's in vivo gene editing initiatives, including CTX310 and CTX320, are also expected to generate important data in 2025, further expanding the potential of its CRISPR-Cas9 platform.

CRISPR Therapeutics' comprehensive approach to gene-based medicine, coupled with its innovative R&D efforts and strategic partnerships, positions the company as a leader in the rapidly evolving field of gene editing. The company's strong financial position, with $1.9 billion in cash, cash equivalents, and marketable securities, provides a solid foundation to support its ongoing research and development activities and potential commercialization efforts.

As CRISPR Therapeutics continues to advance its diverse pipeline and navigate the regulatory landscape, investors will closely monitor the company's ability to deliver on its transformative vision and create lasting value for patients and shareholders alike. The company's progress in translating its groundbreaking CRISPR-Cas9 technology into approved therapies, as exemplified by CASGEVY, demonstrates its potential to revolutionize the treatment of serious genetic disorders and other diseases.

While challenges remain, including regulatory hurdles, clinical development risks, and intense competition, CRISPR Therapeutics' strong scientific foundation, strategic collaborations, and robust pipeline position it well for future growth and success in the dynamic field of gene-based medicines.