On January 13, 2025 Exelixis, Inc. (Nasdaq: EXEL) reported its preliminary unaudited financial results for the fiscal year 2024, provided financial guidance for fiscal year 2025 and delivered an update on its business (Press release, Exelixis, JAN 13, 2025, View Source [SID1234649653]). Exelixis anticipates 2025 will be a year of clinical and regulatory execution and continued growth for its cabozantinib franchise, as well as multiple data readouts for zanzalintinib and across its diversified pipeline of small molecules and biotherapeutics with the potential to improve standards of care for patients with cancer.

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Preliminary Fiscal Year 2024 Financial Results & 2025 Financial Guidance
Exelixis is providing the following preliminary unaudited 2024 financial results and financial guidance for 2025. Net product and total revenues guidance do not currently reflect any revenues resulting from a potential U.S. regulatory approval and commercial launch of CABOMETYX (cabozantinib) for the treatment of patients with previously treated advanced neuroendocrine tumors (NET). The U.S. Food and Drug Administration (FDA) is currently reviewing Exelixis’ supplemental New Drug Application (sNDA) for this proposed indication, with a Prescription Drug User Fee Act (PDUFA) target action date of April 3, 2025.
Fiscal Year 2024
Fiscal Year 2025 Guidance
Total revenues
~ $2.165 billion
$2.15 billion – $2.25 billion
Net product revenues
~ $1.805 billion
$1.95 billion – $2.05 billion(1)
Cost of goods sold ~ 4.2% 4% – 5% of net product revenues
Research and development expenses
~ $910 million(2)
$925 million – $975 million(3)
Selling, general and administrative expenses
~ $495 million(4)
$475 million – $525 million(5)
Effective tax rate
n/a(6)
21% – 23%
Ending cash and marketable securities(7)
~ $1.75 billion n/p

___________________
(1) Exelixis’ 2025 net product revenues guidance range includes impact of a U.S. wholesale acquisition cost increase of 2.8% for CABOMETYX effective Jan. 1, 2025.
(2) Includes $30.7 million of non-cash stock-based compensation expense.
(3) Includes $40.0 million of non-cash stock-based compensation expense.
(4) Includes $63.2 million of non-cash stock-based compensation expense.
(5) Includes $60.0 million of non-cash stock-based compensation expense.
(6) Preliminary results not yet available.
(7) Cash and marketable securities are composed of cash, cash equivalents and marketable securities. Fiscal year 2025 guidance not provided (n/p).
The preliminary 2024 financial information presented in this press release has not been audited and is subject to change. The complete Exelixis Fourth Quarter and Fiscal Year 2024 Financial Results are planned for release after market on Tuesday, February 11, 2025.
"Entering 2025, Exelixis stands at an inflection point as we work toward our goal of building a multi-product, multi-franchise oncology business," said Michael M. Morrissey, Ph.D., President & CEO, Exelixis. "Exelixis had a very successful 2024 highlighted by strong commercial and financial performance, the favorable ruling on our cabozantinib patent litigation, accelerating progress with the zanzalintinib pivotal trial program and establishing our zanzalintinib clinical development collaboration with Merck. We’re carrying that momentum into the new year as we seek to grow cabozantinib franchise revenues, accelerate and expand our zanzalintinib pivotal development program, and advance our diversified therapeutic pipeline of small molecules and biotherapeutics."
Dr. Morrissey continued: "We expect 2025 to be a year of regulatory, clinical and commercial execution as we work toward a potential regulatory approval and launch for cabozantinib in neuroendocrine tumors and prepare for multiple zanzalintinib and pipeline data readouts throughout the year. As cabozantinib’s commercial success drives the business forward in the near-term, we’re excited by zanzalintinib’s potential to surpass cabozantinib’s scope and scale in the coming years and to become an important component of our mid- and long-term revenue growth. We’re also optimizing our earlier stage pipeline, rapidly profiling compounds and advancing only those with the highest probability of success into full development. We look forward to providing more detailed updates on our pipeline progress at an R&D Day later this year. Finally, we’ll maintain our balanced approach to capital allocation, leveraging our strong balance sheet to execute on business development opportunities within the GU and GI oncology space, while using free cash flows to fund our stock repurchase program and return capital to shareholders."
Corporate Updates
Stock Repurchase Program Update. In August 2024, Exelixis announced that the company’s Board of Directors authorized the repurchase of up to $500 million of the company’s common stock through the end of 2025, the third stock repurchase program undertaken by Exelixis since March 2023. Under this program, as of the end of fiscal year 2024, Exelixis has repurchased $205.6 million of the company’s common stock, at an average price of $33.62 per share.

Anticipated Cabozantinib Milestones

Potential Label Expansion and Commercial Launch into NET. Exelixis is preparing for the potential commercial launch of CABOMETYX for the treatment of patients with previously treated advanced NET following the FDA’s acceptance of its sNDA and assignment of a PDUFA target action date of April 3, 2025. In January 2025, the FDA notified Exelixis that its sNDA will no longer be the subject of discussion at an Oncologic Drugs Advisory Committee meeting. The regulatory filing was based on positive results from the phase 3 CABINET pivotal trial sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and led by the NCI-funded Alliance for Clinical Trials in Oncology. CABINET met its primary endpoint, demonstrating statistically significant and clinically meaningful improvements in progression-free survival (PFS) for patients treated with cabozantinib as compared to placebo in both its pancreatic NET (pNET) and extra-pancreatic NET (epNET) cohorts. Final results from the trial were subsequently presented at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and published in The New England Journal of Medicine. In January 2025, the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for NET were updated to include cabozantinib as category 1 for certain types of NET following specific treatments, and as a category 2A preferred regimen for several other forms of advanced NET, depending on site of origin and grade. A subgroup analysis from CABINET detailing the experience of patients with advanced gastrointestinal (GI) NET will also be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) GI Cancers Symposium (ASCO GI 2025) later this month. Exelixis’ partner Ipsen anticipates a decision from the European Medicines Agency on its Marketing Authorization Application for its own proposed NET label expansion in the EU for cabozantinib in 2025. While Exelixis prioritizes supporting the FDA’s ongoing review of its proposed NET indication, the company will continue to evaluate the timing of its potential regulatory filing for cabozantinib in metastatic castration-resistant prostate cancer based on the phase 3 CONTACT-02 pivotal study.

Anticipated Development Milestones

Expansion and Acceleration of the Zanzalintinib Pivotal Trial Program. Zanzalintinib is a third-generation tyrosine kinase inhibitor (TKI) that Exelixis believes can become the vascular endothelial growth factor receptor TKI of choice as the solid tumor therapeutic landscapes continue to evolve. The zanzalintinib pivotal development program currently consists of six ongoing or planned pivotal trials, with additional studies to be announced in 2025 and beyond:
•STELLAR-303 is evaluating zanzalintinib in combination with atezolizumab compared with regorafenib in patients with metastatic, refractory non-microsatellite instability-high or non-mismatch repair-deficient colorectal cancer (CRC). The primary endpoint in the study is overall survival (OS) in the patients without liver metastases (NLM). If OS is positive in the NLM population, the study will evaluate OS in the intent-to-treat population that includes patients with and without liver metastases. The study completed enrollment in the third quarter of 2024, and preliminary results are expected in the second half of 2025, dependent on study event rates.
•STELLAR-304 is evaluating zanzalintinib in combination with nivolumab versus sunitinib in previously untreated patients with advanced non-clear cell renal cell carcinoma. The primary endpoints in the trial are PFS and objective response rate. Based on current enrollment status in the trial, the primary endpoint of PFS is expected to be available in the second half of 2025, dependent on study event rates.
•STELLAR-305 is evaluating zanzalintinib in combination with pembrolizumab versus pembrolizumab alone in patients with previously untreated PD-L1-positive recurrent or metastatic squamous cell carcinoma of the head and neck. The study was designed to enroll approximately 250 eligible patients in the phase 2 portion of the trial to be randomly assigned to zanzalintinib in combination with pembrolizumab or pembrolizumab alone to evaluate the activity of the combination therapy. Data from the phase 2 portion are expected be available in the second half of 2025, which would inform whether the data support expansion into the phase 3 portion of the trial, during which an additional 350 patients would be randomized for a total of 600 patients. The primary endpoints in the study are PFS and OS.
•Exelixis also expects to initiate STELLAR-311, a phase 3 pivotal trial evaluating zanzalintinib compared with everolimus as a first oral therapy in patients with advanced NET, regardless of site of origin, in the first half of 2025.
•Additionally, as part of Exelixis’ clinical development collaboration with Merck, two pivotal renal cell carcinoma (RCC) studies are planned for 2025. The companies will provide further details on these trials closer to their initiation.

Earlier Stage Zanzalintinib Data Readouts Expected This Year. Exelixis anticipates initial clinical data readouts from zanzalintinib’s phase 1b/2 STELLAR-001 and STELLAR-002 clinical studies in the first half of 2025, including data from CRC and RCC cohorts. STELLAR-001 and -002 are evaluating zanzalintinib as a monotherapy and in potentially best-in-class combination regimens across various tumor types. In the nearest term, at ASCO (Free ASCO Whitepaper) GI 2025 later this month, investigators will present preliminary results from a randomized expansion cohort of STELLAR-001 designed to assess the contribution of atezolizumab to zanzalintinib in patients with previously treated metastatic CRC.
Advance XL309 Phase 1 Program in PARP Inhibitor Refractory Setting and Beyond. XL309, Exelixis’ potentially best-in-class small molecule inhibitor of USP1, is currently being evaluated in a phase 1 study as a single agent and in combination with olaparib, a PARP1/2 inhibitor, in patients with advanced solid tumors. Enrollment in the dose escalation cohorts for XL309 monotherapy and olaparib combination are ongoing. The mechanism of action of XL309 and its potential to combine with PARP-inhibitors (PARPi)provide optionality for a robust development program in a variety of solid tumors. Exelixis’ clinical development plans for XL309 include its development as a potential therapy for tumors that have become refractory to PARPi therapy, including forms of ovarian, breast and prostate cancers, pursuing potential PARPi combinations, and moving beyond the PARPi market into new areas. Exelixis plans to present data from the XL309 program at a scientific meeting in 2025.
Progress of Phase 1 Clinical Trials for XB010 and XL495. Exelixis initiated clinical development of its XB010 and XL495 pipeline programs in 2024. The company plans to rapidly profile each compound to determine if early clinical data support further advancement toward full development. XB010 is an antibody-drug conjugate (ADC) consisting of a monomethyl auristatin E payload conjugated to a monoclonal antibody targeting the tumor antigen 5T4 and is the first custom ADC generated through Exelixis’ biotherapeutics collaboration network. The first-in-human, global phase 1 trial of XB010 is evaluating the compound in patients with locally advanced or metastatic solid tumors. The dose-escalation stage of the study is evaluating XB010 as a single agent and in combination with pembrolizumab to inform the cohort-expansion stage. The expansion cohorts are designed to further assess the tolerability and activity of monotherapy and of the combination in specific indications. XL495 is a novel, potent, small molecule inhibitor of PKMYT1. The first-in-human phase 1 clinical trial of XL495 is evaluating the compound in patients with advanced solid tumors; the dose-escalation stage of the study is designed to determine the maximum tolerated dose of XL495. The expansion cohorts are designed to further assess the tolerability and activity of XL495 both as monotherapy and in combination with select cytotoxic agents in tumor-specific indications. Exelixis plans to present preclinical data from the XL495 program at a scientific meeting in 2025.
Anticipated Discovery Milestones
Three Potential Investigational New Drug (IND) Applications in 2025. Exelixis anticipates advancing three biotherapeutics programs into clinical development this year, including the XB628 PD-L1-NKG2A bispecific antibody, XB064 ILT-2 monoclonal antibody and XB371 TF-topoisomerase I inhibitor ADC. The company expects to file the IND applications for these compounds in 2025 if preclinical data continue to be supportive. Exelixis plans to present preclinical data from one or more of these programs at a scientific meeting in 2025.
Presentation and Webcast
Exelixis President and Chief Executive Officer Michael M. Morrissey, Ph.D., will provide a corporate overview and discuss the company’s preliminary fiscal year 2024 financial results, 2025 financial guidance and key priorities and milestones for 2025 during the company’s presentation at the 43rd Annual J.P. Morgan Healthcare Conference beginning at 5:15 p.m. PT / 8:15 p.m. ET on Monday, January 13, 2025.
To access the webcast link, log onto www.exelixis.com and proceed to the Event Calendar page under the Investors & News heading. A replay will also be available at the same location for at least 30 days.

On January 13, 2025 Eli Lilly and Company (NYSE: LLY) and Scorpion Therapeutics, Inc. ("Scorpion"), a private biotechnology company developing small molecule precision oncology therapies, reported a definitive agreement for Lilly to acquire Scorpion’s PI3Kα inhibitor program STX-478 (Press release, Eli Lilly, JAN 13, 2025, View Source [SID1234649652]). STX-478 is a once-daily oral, mutant-selective PI3Kα inhibitor currently being evaluated in a Phase 1/2 clinical trial for breast cancer and other advanced solid tumors.

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STX-478 could represent the next generation of PI3Kα targeting agents by selectively targeting the pathway in cancerous but not healthy cells, thus overcoming a key limitation of currently available medicines that target the PI3Kα pathway. This approach could potentially offer better disease control through deeper pathway inhibition, as well as improved tolerability.

"PI3Kα mutations occur in a meaningful proportion of hormone-positive breast cancers, and there is significant unmet need for new treatment options that effectively and safely target this pathway," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. "The selectivity profile of STX-478 has led to a differentiated clinical profile, enabling use in combinations with standard-of-care therapies to potentially deliver meaningful impact in earlier treatment settings when there is the best opportunity to improve outcomes for patients. We look forward to leveraging the great work of the Scorpion team to date, along with Lilly’s deep expertise in breast cancer, to further advance STX-478 with speed and focus."

Under the terms of the agreement, Lilly will acquire Scorpion and Scorpion shareholders could receive up to $2.5 billion in cash, inclusive of an upfront payment and subsequent payments upon achievement of certain regulatory and sales milestones. Additionally, as part of the transaction, Scorpion will spin out a new entity to hold its employees and non-PI3Kα pipeline assets. The new, independent company would be owned by Scorpion’s current shareholders with Lilly holding a minority equity interest. The new company will be led by Dr. Friedman and members of the current Scorpion management team and will focus on discovering and delivering a portfolio of precision medicines to patients, accelerated by Scorpion’s discovery capabilities and non-PI3Kα pipeline of medicines.

"Lilly has advanced scientific breakthroughs for some of the most difficult-to-treat cancers," said Adam Friedman, M.D., Ph.D., president and chief executive officer of Scorpion. "We believe Lilly’s global capabilities and strategic commitment to patients with breast cancer will accelerate our goal of developing STX-478 to improve outcomes for the many patients with solid tumors driven by PI3Kα mutations. This acquisition is a testament to the expertise of the Scorpion team and our drug discovery capabilities, which will become the foundation of our new company."

The transaction is subject to customary closing conditions. Lilly will determine the accounting treatment of this transaction in accordance with Generally Accepted Accounting Principles (GAAP) upon closing. This transaction will thereafter be reflected in Lilly’s financial results and financial guidance.

For Lilly, Citi is acting as exclusive financial advisor and Ropes & Gray LLP is acting as legal counsel. For Scorpion, Centerview Partners LLC is acting as lead financial advisor with additional financial advisory from Morgan Stanley, and Kirkland & Ellis LLP is acting as legal counsel.

On January 13, 2025 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, reported program updates and upcoming milestones (Press release, Elevation Oncology, JAN 13, 2025, View Source;utm_medium=rss&utm_campaign=elevation-oncology-provides-updates-on-differentiated-adc-programs-and-upcoming-milestones [SID1234649651]).

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"We are rapidly advancing EO-3021 to address significant unmet needs in treating earlier lines of advanced gastric/GEJ cancer, where we believe we have a unique ability to improve on the standard of care," said Joseph Ferra, President and Chief Executive Officer of Elevation Oncology. "As we enter 2025, we are honing our focus, leveraging the competitive anti-tumor activity and differentiated safety profile of EO-3021 to explore combination approaches in the first- and second-line settings. With our Phase 1 clinical trial ongoing and now enrolling both monotherapy and combination cohorts, we are in a leading position to explore the compelling potential of EO-3021, our differentiated Claudin 18.2 ADC, to improve outcomes for people living with advanced gastric/GEJ cancer."

Mr. Ferra continued, "We look forward to sharing additional data from our Phase 1 dose escalation and expansion study of EO-3021 in the first half of 2025. With this readout, we aim to build on the promising initial data reported in August 2024, reinforcing EO-3021’s robust anti-tumor activity and potential better combinability, while garnering additional insights to inform our go-forward clinical development efforts. We are enthusiastic about the potential of EO-3021 in addressing meaningful market opportunities and look forward to a transformative 2025."

Program Updates and Upcoming Milestones

EO-3021: Elevation Oncology is developing EO-3021, a differentiated, potentially best-in-class antibody drug conjugate (ADC) for the treatment of patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2, including gastric/GEJ cancer.

In August 2024, Elevation Oncology reported promising initial monotherapy data from the dose escalation portion of its ongoing Phase 1 clinical trial of EO-3021, demonstrating competitive efficacy, with a 42.8% confirmed overall response rate (ORR) in a biomarker-enriched population, and a differentiated safety profile, including minimal hematological toxicity and hepatotoxicity, and no peripheral neuropathy/hypoesthesia.

Based on these data, Elevation Oncology is focusing the clinical development of EO-3021 on the first- and second-line treatment of advanced gastric/GEJ cancer, where EO-3021’s key attributes can potentially provide differentiated benefits and address unmet needs in both patient outcomes and safety.

Monotherapy:

The dose expansion portion of Elevation Oncology’s Phase 1 clinical trial of monotherapy EO-3021 is ongoing. As of January 2025, Elevation Oncology has implemented prospective Claudin 18.2 expression testing as part of the patient screening process, focusing enrollment on patients with ≥25% of tumor cells at IHC 1+/2+/3+. Elevation Oncology expects to report additional safety and efficacy data from the dose escalation and expansion portions of the study in the first half of 2025.

Combination:

Patient dosing is ongoing in the combination portion of Elevation Oncology’s Phase 1 clinical trial of EO-3021. The combination cohorts are evaluating EO-3021 in combination with dostarlimab, a PD-1 inhibitor, in the first line setting and with ramucirumab, a VEGFR2 inhibitor, in the second line setting.

By combining EO-3021 and dostarlimab, an immune checkpoint inhibitor, Elevation Oncology aims to deliver synergistic benefit, potentially offering patients improved outcomes beyond those seen with the existing combination of immunotherapy and chemotherapy. The combination of an immunotherapy and chemotherapy agent is the standard of care for the treatment of gastric/GEJ cancer in the front-line setting.

With the EO-3021 and ramucirumab combination, Elevation Oncology aims to deliver improved tolerability and synergistic anti-tumor activity compared to the approved combination of ramucirumab and paclitaxel. The combination of ramucirumab and paclitaxel is the standard of care for the treatment of second-line gastric/GEJ cancer.

Elevation Oncology expects to report initial data from the combination cohorts in the fourth quarter of 2025 or the first quarter of 2026.

EO-1022: Elevation Oncology is developing EO-1022, a differentiated HER3 ADC for the treatment of patients with HER3-expressing solid tumors, including breast cancer, EGFR-mutant non-small cell lung cancer, and pancreatic cancer. EO-1022 combines seribantumab, a fully human anti-HER3 monoclonal antibody, and a monomethyl auristatin E (MMAE) payload with site-specific conjugation to glycan. It is designed to leverage seribantumab’s desirable internalization capability and the latest site-specific ADC technology to deliver a safe, effective option for patients living with solid tumors that express HER3.

Elevation Oncology expects to present preclinical data for EO-1022 in the first half of 2025 and to file an IND application in 2026.

Financial Guidance

Elevation Oncology expects that its cash, cash equivalents and marketable securities as of September 30, 2024, will be sufficient to fund its current operations into 2026.

On January 13, 2025 Delcath Systems, Inc. (Nasdaq: DCTH) ("Delcath" or the "Company"), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, reported preliminary financial results for the fourth quarter and year-ended December 31, 2024 (Press release, Delcath Systems, JAN 13, 2025, View Source [SID1234649650]).

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Preliminary Fourth Quarter and Full-Year 2024 Financial Results (unaudited)

Total fourth quarter and full year revenue expected to be approximately $15.1 million and $37.2 million, respectively
HEPZATO KIT fourth quarter and full year revenue expected to be approximately $13.7 million and $32.3 million, respectively
CHEMOSAT fourth quarter and full year revenue expected to be approximately $1.4 million and $4.9 million, respectively
Gross margins expected to be in the 80%-85% range
As of December 31, 2024, the Company had approximately $53.2 million of cash, cash equivalents and short-term investments and no debt
Final financial results for the fourth quarter and full year 2024 and a detailed business update will be provided during Delcath’s annual financial results release and investor call scheduled for March 6, 2025.

On January 13, 2025 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported its strategic priorities and anticipated 2025 milestones (Press release, CRISPR Therapeutics, JAN 13, 2025, View Source [SID1234649648]).

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"As we look ahead to 2025, we are in a privileged position with an approved commercial product, a rich pipeline, a strong balance sheet and an organizational foundation to drive our pipeline forward," said Samarth Kulkarni, Ph.D., Chairman and Chief Executive Officer of CRISPR Therapeutics. "Building on the success of CASGEVY’s launch, we continue to broaden our portfolio across oncology, autoimmune and cardiometabolic indications. 2025 promises to be a milestone-rich year, with clinical data updates across several programs spanning a range of indications. In parallel, we are continuously innovating on our platform with next-generation gene editing and delivery technologies, which have the potential to broaden our ability to address additional diseases with curative treatments."

Strategic Priorities and Recent Advancements
2025 is an important inflection year for CRISPR Therapeutics as we establish CASGEVY and advance our pipeline candidates to human proof-of-concept and beyond.

Key Priorities:

Ongoing launch of CASGEVY, driven by strong patient demand and robust payer and system support.
Continue advancing our pipeline candidates, with several key updates in 2025, including CTX112 in oncology and autoimmune diseases, as well as CTX310 and CTX320 in cardiovascular indications, alongside the potential for further updates across our pipeline.
Continue advancing our next-generation gene editing and lipid nanoparticle (LNP) delivery platform for the liver, hematopoietic stem cells (HSCs), and other target organs.
Hemoglobinopathies and CASGEVY (exagamglogene autotemcel [exa-cel]):
2024 served as a foundational year for the launch of CASGEVY. In its first year, CASGEVY has seen strong global patient demand, and our partner, Vertex, has made significant progress in activating authorized treatment centers (ATCs) and securing payer access.

Rapid pace of global approvals underscores high unmet need and transformative potential of CASGEVY. On December 31, 2024, CASGEVY received regulatory approval in the United Arab Emirates (UAE) for the treatment of both sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT).
Progress in cell collections has been strong, with high demand across all regions and indications. As of the end of 2024, more than 50 patients have initiated cell collection.
Significant progress has been made in activating ATCs, with more than 50 ATCs globally.
Strong payer support has been established in regions where CASGEVY is approved, through major payer contracts and early access programs. In the U.S., Vertex recently negotiated a first-of-its-kind, voluntary agreement with the Centers for Medicare & Medicaid Services (CMS), which will provide a single outcomes-based arrangement for CASGEVY, available to all state Medicaid programs to ensure broad and equitable access for patients.
Additionally, CRISPR Therapeutics continues to advance its internally developed targeted conditioning program as well as in vivo approaches utilizing LNP-mediated delivery through preclinical studies. Both initiatives could significantly expand the addressable patient populations for SCD and TDT.
Immuno-Oncology and Autoimmune Disease (AID):
CRISPR Therapeutics is developing CTX112 for both hematologic malignancies and autoimmune indications, with an emerging best-in-class profile.

CRISPR presented positive data from its ongoing Phase 1/2 trial of CTX112 in relapsed or refractory CD19+ B-cell malignancies at the 2024 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual meeting, demonstrating strong efficacy comparable to autologous therapies, a tolerable safety profile and robust cell expansion.
CTX112 was awarded regenerative medicine advanced therapy (RMAT) designation by the FDA based on these strong preliminary data.
The most recent data with CTX112 demonstrate responses in patients who have received prior T-cell engager-based therapies (TCEs), with responses observed in all 6 patients, including 3 large B-cell lymphoma (LBCL) patients, who either relapsed post-TCE treatment or were refractory to TCEs.
CRISPR Therapeutics plans to engage with regulatory authorities to align on the path forward for CTX112 in B-cell malignancies, with an update expected in mid-2025.
Preliminary safety, pharmacokinetic, and pharmacodynamic data in oncology highlight the potential of CTX112 in autoimmune indications. Based on favorable oncology data, CRISPR Therapeutics is expanding the trial for CTX112 in system lupus erythematosus to include patients with systemic sclerosis and inflammatory myositis patients in a basket study, with updates expected in mid-2025.
Clinical trials are on-going for CTX131 in both solid tumors and hematologic malignancies, with updates expected in 2025. Additionally, we are advancing an autologous, gene-edited CAR T therapy targeting glypican-3 (GPC3) for the potential treatment of solid tumors and expect to initiate a clinical trial in the first half of 2025.
In Vivo Cardiovascular:
CRISPR Therapeutics continues to make significant progress in advancing its proprietary LNP delivery technologies for gene editing in the liver, with ongoing development in both clinical and preclinical stages.

Dose escalation for CTX310, directed towards angiopoietin-related protein 3 (ANGPTL3), and CTX320, directed towards LPA, the gene encoding apolipoprotein(a) (apo(a)), a major component of lipoprotein(a) [Lp(a)]), is ongoing, with updates expected in the first half of 2025.
CTX310 is being developed for patients with homozygous or heterozygous familial hypercholesterolemia, severe hypertriglyceridemia, or mixed dyslipidemias, and has the potential for approval based on validated biomarkers, pending regulatory discussions.
CTX320 is being developed for patients with high Lp(a), a genetically determined cardiovascular risk factor affecting millions worldwide.
Rapid preclinical progress is being made with CTX340, targeting angiotensinogen (AGT) for refractory hypertension, as well as CTX450, targeting 5’-aminolevulinate synthase 1 (ALAS1) for acute hepatic porphyria.
Regenerative Medicine:
Progress continues in regenerative medicine, with ongoing efforts to develop innovative therapies, including the clinical trial for CTX211 in Type 1 diabetes (T1D) and subsequent next generation programs.

These programs focus on allogeneic, gene-edited, stem cell-derived beta islet cell precursors for the treatment of T1D, which have the potential to render patients insulin-independent without the need for chronic immunosuppression. The Company anticipates providing an update in 2025.
Anticipated Key Milestones
CRISPR Therapeutics anticipates several key milestones in 2025 across its development portfolio.

Quarterly updates on CASGEVY launch progress.
Updates for CTX310 and CTX320 in the first half of 2025.
A broad update with CTX112 in oncology and autoimmune disease in mid-2025.
Update for CTX131 in 2025.
Update in regenerative medicine in 2025.
About CASGEVY (exagamglogene autotemcel [exa-cel])
CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible patients with SCD or TDT, in which a patient’s own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene. This edit results in the production of high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. CASGEVY has been shown to reduce or eliminate recurrent vaso-occlusive crises (VOCs) for patients with SCD and transfusion requirements for patients with TDT. CASGEVY is approved for certain indications in multiple jurisdictions for eligible patients.

About the CRISPR Collaboration and Vertex
CRISPR Therapeutics and Vertex entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. CASGEVY represents the first potential treatment to emerge from the joint research program. Under an amended collaboration agreement, Vertex now leads global development, manufacturing, and commercialization of CASGEVY and splits program costs and profits worldwide 60/40 with CRISPR Therapeutics. Vertex is the manufacturer and exclusive license holder of CASGEVY.

About CTX112
CTX112 is being developed for both oncology and autoimmune indications. CTX112 is a next-generation, wholly-owned, allogeneic CAR T product candidate targeting Cluster of Differentiation 19, or CD19, which incorporates edits designed to evade the immune system, enhance CAR T potency, and reduce CAR T exhaustion. CTX112 is being investigated in an ongoing clinical trial designed to assess safety and efficacy of the product candidate in adult patients with relapsed or refractory CD19-positive B-cell malignancies who have received at least two prior lines of therapy. In addition, CTX112 is being investigated in an ongoing clinical trial designed to assess the safety and efficacy of the product candidate in adult patients with systemic lupus erythematosus, systemic sclerosis, and inflammatory myositis.

About CTX131
CTX131 is being developed for both solid tumors and hematologic malignancies, including T cell lymphomas (TCL). CTX131 is a next-generation, wholly-owned, allogeneic CAR T product candidate targeting Cluster of Differentiation 70, or CD70, an antigen expressed on various solid tumors and hematologic malignancies. CTX131 incorporates edits designed to evade the immune system, prevent fratricide, enhance CAR T potency, and reduce CAR T exhaustion. CTX131 is being investigated in ongoing clinical trials designed to assess the safety and efficacy of the product candidate in adult patients with relapsed or refractory solid tumors and hematologic malignancies, including TCL.

About In Vivo Programs
CRISPR Therapeutics has established a proprietary lipid nanoparticle (LNP) platform for the delivery of CRISPR/Cas9 to the liver. The Company’s in vivo portfolio includes its lead investigational programs, CTX310 (directed towards angiopoietin-related protein 3 (ANGPTL3)) and CTX320 (directed towards LPA, the gene encoding apolipoprotein(a) (apo(a)), a major component of lipoprotein(a) [Lp(a)]). Both are validated therapeutic targets for cardiovascular disease. CTX310 and CTX320 are in ongoing clinical trials in patients with heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, mixed dyslipidemias, or severe hypertriglyceridemia, and in patients with elevated lipoprotein(a), respectively. In addition, the Company’s research and preclinical development candidates include CTX340 and CTX450, targeting angiotensinogen (AGT) for refractory hypertension and 5’-aminolevulinate synthase 1 (ALAS1) for acute hepatic porphyria (AHP), respectively.

About CTX211
CTX211 is an allogeneic, gene-edited, stem cell-derived investigational therapy for the treatment of type 1 diabetes (T1D), which incorporates gene edits that aim to make cells hypoimmune and enhance cell fitness. This immune-evasive cell replacement therapy is designed to enable patients to produce their own insulin in response to glucose. A Phase 1 clinical trial for CTX211 for the treatment of T1D is ongoing.