Financial Data and Key Metrics Changes - As of June 30, 2025, the company reported cash, cash equivalents, and investments totaling $302.6 million, extending its cash runway into 2027 [22] - The net loss for the second quarter was $50.9 million, or $0.23 per share, which included non-cash stock-based compensation expenses of $8.7 million and non-cash impairment of long-lived asset expenses of $2.4 million [22] Business Line Data and Key Metrics Changes - The ALPHA-three study has been streamlined into a two-arm randomized trial comparing treatment with semisel following a standard lymphodepletion regimen to observation [6][7] - ALLO-three 16, targeting renal cell carcinoma, presented promising Phase I data at ASCO 2025, indicating robust CAR T cell expansion and durable clinical responses [8][16] - The Resolution study, focusing on autoimmune diseases, has opened enrollment, aiming to simplify or eliminate lymphodepletion altogether [10][19] Market Data and Key Metrics Changes - More than 50 sites are now activated across the U.S. and Canada for the ALPHA-three study, with additional international expansion underway [7] - The company is actively exploring partnership opportunities to advance the ALLO-three 16 program [8][17] Company Strategy and Development Direction - The company aims to redefine CAR T therapy by prioritizing patient accessibility and safety in every stage of development [7][10] - The focus is on making allogeneic CAR T the standard of care, with near-term milestones viewed as value-driving catalysts [13][21] - The company emphasizes the importance of scientific excellence, rigorous decision-making, and thoughtful execution in advancing its clinical pipeline [6][12] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing clinical trials and the potential for transformative breakthroughs in cell therapy [11][20] - The company acknowledges the complexities of clinical development but remains committed to navigating these challenges effectively [12][20] Other Important Information - The company expects a cash burn of approximately $150 million for 2025 and full-year GAAP operating expenses of about $230 million, excluding potential business development activities [22] - The ALPHA-three study's futility analysis is planned for 2026, with expectations to share MRD conversion rates at that time [16][22] Q&A Session Summary Question: What does good look like for MRD conversion rates? - Management indicated that a 30% delta in MRD conversion rates would be meaningful, referencing historical data from Yescarta and BRYANZI studies [27][29] Question: How should we expect similar EFS benefits with a 30% delta on MRD conversion? - Management confirmed that equating MRD conversion to complete remission is a fair assumption, suggesting potential similar EFS benefits [32] Question: How is enrollment progressing for ALPHA-three? - Management reported positive momentum in enrollment, with investigators expressing satisfaction with the simplified treatment regimen [38][39] Question: Will the timing of capturing MRD positive patients impact conversion rates? - Management stated that the timing of MRD testing is aligned with standard practices and should not significantly impact conversion rates [44][46] Question: What are the criteria for the interim analysis? - Management clarified that the MRD assessment is conducted at a specific time point, and the data collected will be analyzed accordingly [92] Question: How does the company view the impact of recent adverse events on enrollment? - Management believes that the overall risk profile remains acceptable, and the consensus among stakeholders supports continuing enrollment [78][80] Question: What proof of concept data is needed for ALLO-three 29? - Management indicated that B cell depletion and the phenotype of returning B cells will be critical indicators for moving the program forward [100][101]

[PART I: FINANCIAL INFORMATION](index=3&type=section&id=PART%20I%3A%20FINANCIAL%20INFORMATION) [Financial Statements](index=3&type=section&id=Item%201.%20Financial%20Statements) The company's unaudited financials show declining assets and ongoing net losses driven by significant R&D spending [Condensed Consolidated Balance Sheets](index=3&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) Total assets decreased to $470.6 million as of June 30, 2025, reflecting a growing accumulated deficit Condensed Consolidated Balance Sheet Data (in thousands) | Account | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $52,332 | $75,218 | | Total current assets | $282,655 | $303,386 | | Total assets | $470,593 | $548,710 | | **Liabilities & Stockholders' Equity** | | | | Total current liabilities | $31,675 | $35,523 | | Total liabilities | $126,032 | $126,531 | | Accumulated deficit | $(1,930,499) | $(1,819,823) | | Total stockholders' equity | $344,561 | $422,179 | | Total liabilities and stockholders' equity | $470,593 | $548,710 | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=4&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) The company reported a reduced net loss of $110.7 million for H1 2025 due to lower operating expenses Statement of Operations Highlights (in thousands, except per share data) | Metric | Q2 2025 | Q2 2024 | H1 2025 | H1 2024 | | :--- | :--- | :--- | :--- | :--- | | Research and development | $40,156 | $50,355 | $90,356 | $102,614 | | General and administrative | $14,281 | $16,087 | $29,272 | $33,354 | | Loss from operations | $(56,819) | $(71,431) | $(122,010) | $(140,935) | | Net loss | $(50,943) | $(66,358) | $(110,676) | $(131,358) | | Net loss per share, basic and diluted | $(0.23) | $(0.35) | $(0.51) | $(0.73) | [Condensed Consolidated Statements of Cash Flows](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operations improved to $92.0 million in H1 2025, offset by cash from investing and financing Cash Flow Summary for Six Months Ended June 30 (in thousands) | Activity | 2025 | 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(91,959) | $(119,487) | | Net cash provided by investing activities | $50,011 | $96,746 | | Net cash provided by financing activities | $19,062 | $110,253 | | **Net change in cash, cash equivalents and restricted cash** | **$(22,886)** | **$87,512** | [Notes to Condensed Consolidated Financial Statements](index=8&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) Notes detail accounting policies, a workforce reduction, and a significant clinical trial modification due to an adverse event - The company is a clinical-stage immuno-oncology firm developing 'off-the-shelf' allogeneic T cell product candidates for cancer and autoimmune diseases[20](index=20&type=chunk) - Management expects that its **cash, cash equivalents, and investments of $302.6 million** as of June 30, 2025, will be sufficient to fund operations for at least the next 12 months[24](index=24&type=chunk)[25](index=25&type=chunk) - In May 2025, the company initiated a **28% workforce reduction**, recording charges of **$4.7 million** in Q2 2025[45](index=45&type=chunk)[46](index=46&type=chunk) - In May 2024, the agreement with Servier was amended, expanding the licensed territory for CD19 products and modifying future milestone and royalty payments[58](index=58&type=chunk)[59](index=59&type=chunk) - Subsequent to the quarter end, the company **closed the FCA arm (FC plus ALLO-647) of its ALPHA3 study** to enrollment due to a **Grade 5 adverse event** attributed to ALLO-647[110](index=110&type=chunk)[111](index=111&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=23&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses clinical program priorities, a key trial modification, and an extended cash runway into H2 2027 [Overview](index=23&type=section&id=Overview) The company is advancing its CAR T pipeline, highlighted by a pivotal trial modification and a workforce reduction - The company's strategic focus is on three core clinical programs: **ALPHA3 (cema-cel), RESOLUTION (ALLO-329), and TRAVERSE (ALLO-316)**[118](index=118&type=chunk) - On August 1, 2025, the company closed the arm testing FC plus ALLO-647 (FCA) in the ALPHA3 trial due to a **Grade 5 adverse event attributed to ALLO-647**[121](index=121&type=chunk)[122](index=122&type=chunk) - In May 2025, a **workforce reduction of approximately 28%** was initiated to reprioritize resources towards clinical programs[133](index=133&type=chunk) - As of June 30, 2025, the company had **$302.6 million in cash, cash equivalents, and investments**, with an expected cash runway into the second half of 2027[134](index=134&type=chunk) [Results of Operations](index=29&type=section&id=Results%20of%20Operations) Operating expenses decreased 13% in H1 2025, driven by lower R&D and G&A costs, resulting in a reduced net loss Comparison of Operating Results (in thousands) | Line Item | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | Change (%) | | :--- | :--- | :--- | :--- | | Research and development | $90,356 | $102,614 | (12)% | | General and administrative | $29,272 | $33,354 | (12)% | | Impairment of long-lived assets | $2,382 | $4,989 | (52)% | | **Total operating expenses** | **$122,010** | **$140,957** | **(13)%** | | **Net Loss** | **$(110,676)** | **$(131,358)** | **(16)%** | - The **$12.3 million decrease in H1 2025 R&D expenses** was driven by a $7.1 million reduction in external development and manufacturing costs and a $2.7 million decrease in personnel-related costs[177](index=177&type=chunk) [Liquidity and Capital Resources](index=32&type=section&id=Liquidity%20and%20Capital%20Resources) With $302.6 million in cash and investments, the company has sufficient liquidity for at least the next 12 months - The company had **$302.6 million in cash, cash equivalents, and investments** as of June 30, 2025, and believes this is sufficient to fund operations for at least the next 12 months[184](index=184&type=chunk) - In May 2024, a registered offering generated **net proceeds of $105.2 million**, and during H1 2025, ATM offerings resulted in **net proceeds of $11.5 million**[185](index=185&type=chunk) Cash Flow Summary for Six Months Ended June 30 (in thousands) | Activity | 2025 | 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(91,959) | $(119,487) | | Net cash provided by investing activities | $50,011 | $96,746 | | Net cash provided by financing activities | $19,062 | $110,253 | [Quantitative and Qualitative Disclosures About Market Risk](index=35&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company's primary market risks relate to interest rate fluctuations on its investment portfolio and foreign exchange - The company's main market risks are interest rate fluctuations on its **$302.6 million cash and investment portfolio** and foreign exchange risk from Euro-denominated payments[206](index=206&type=chunk)[207](index=207&type=chunk) - As of June 30, 2025, the company had **$23.5 million in an escrow deposit** and minimal current liabilities denominated in foreign currency, primarily related to the Servier agreement[208](index=208&type=chunk) [Controls and Procedures](index=35&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of the end of the reporting period - Management concluded that as of June 30, 2025, the company's **disclosure controls and procedures were effective**[209](index=209&type=chunk) - There were **no changes in internal control over financial reporting** during the quarter ended June 30, 2025, that materially affected, or are reasonably likely to materially affect, internal controls[210](index=210&type=chunk) [PART II: OTHER INFORMATION](index=36&type=section&id=PART%20II%3A%20OTHER%20INFORMATION) [Legal Proceedings](index=36&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently involved in any material legal proceedings - Management believes there are **currently no pending claims or actions** that could have a material adverse effect on the company[212](index=212&type=chunk) [Risk Factors](index=36&type=section&id=Item%201A.%20Risk%20Factors) Key risks include a history of losses, financing needs, clinical trial uncertainties, and reliance on third parties - The company has a history of net losses (**$1.9 billion accumulated deficit** as of June 30, 2025) and will require substantial additional financing to continue development[225](index=225&type=chunk) - The business is **highly dependent on the success of its lead product candidates** (cema-cel, ALLO-316, ALLO-329), and failure of any could significantly harm the company[217](index=217&type=chunk)[248](index=248&type=chunk) - A **Grade 5 serious adverse event (SAE)** in the ALPHA3 trial's FCA arm led to its discontinuation, creating risks of regulatory action, negative perception, and potential liability[217](index=217&type=chunk)[263](index=263&type=chunk) - There is **uncertainty whether the FC lymphodepletion regimen alone** (without ALLO-647) will be sufficient for cema-cel's efficacy in the ALPHA3 trial[223](index=223&type=chunk)[366](index=366&type=chunk) - The company is **heavily reliant on partners** like Cellectis for TALEN gene-editing technology and Foresight Diagnostics for the MRD assay essential for the ALPHA3 trial[223](index=223&type=chunk)[367](index=367&type=chunk)[370](index=370&type=chunk) - **Reduced manufacturing operations** following the May 2025 workforce reduction may limit the ability to support development programs and require a costly ramp-up in the future[217](index=217&type=chunk)[302](index=302&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=84&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company reports no unregistered sales of equity securities during the period [Exhibits](index=85&type=section&id=Item%206.%20Exhibits) This section lists all exhibits filed with the report, including corporate governance and certification documents [Signatures](index=86&type=section&id=Signatures) The report is duly signed by the Chief Executive Officer and Chief Financial Officer on August 13, 2025

[Corporate Updates & Highlights](index=1&type=section&id=Corporate%20Updates%20%26%20Highlights) Allogene reported significant progress in Q2 2025, advancing the pivotal ALPHA3 trial for cema-cel, initiating the RESOLUTION trial for ALLO-329 in autoimmune diseases, and aligning with the FDA on a pivotal path for ALLO-316 in solid tumors, ending the quarter with a strong cash position extending its runway into the second half of 2027 - Key strategic advancements include streamlining the ALPHA3 trial, initiating clinical enrollment for ALLO-329 in autoimmune indications, and aligning with the FDA on a pivotal path for ALLO-316 in solid tumors[3](index=3&type=chunk) - The company ended Q2 2025 with **$302.6 million** in cash, cash equivalents, and investments, with a projected cash runway into the **second half of 2027**[8](index=8&type=chunk)[10](index=10&type=chunk) [Program Updates](index=1&type=section&id=Program%20Updates) The company provided updates on its key clinical programs, including the pivotal Phase 2 ALPHA3 trial for cema-cel, the initiated Phase 1 RESOLUTION trial for ALLO-329 in autoimmune diseases, and the aligned pivotal trial design for ALLO-316 with the FDA [Cema-Cel: Pivotal Phase 2 ALPHA3 Trial in LBCL](index=1&type=section&id=Cema-Cel%3A%20Pivotal%20Phase%202%20ALPHA3%201L%20Consolidation%20Trial%20in%20LBCL) The ALPHA3 trial for cema-cel in Large B-Cell Lymphoma (LBCL) will now proceed as a two-arm randomized study, comparing cema-cel with standard fludarabine and cyclophosphamide (FC) lymphodepletion against observation, supported by early safety and biomarker data, with a futility analysis scheduled for the first half of 2026 and over 50 clinical sites activated - The ALPHA3 trial is now a randomized two-arm study comparing cema-cel with standard fludarabine and cyclophosphamide (FC) lymphodepletion to observation, the current standard of care[4](index=4&type=chunk) - The selection of the FC regimen is based on encouraging preliminary safety, MRD conversion rates, and operational benefits for community cancer centers[5](index=5&type=chunk) - A futility analysis comparing MRD conversion rates between the two arms is expected in **1H 2026**[6](index=6&type=chunk)[8](index=8&type=chunk) - **Over 50** clinical sites are activated across the U.S. and Canada, with international expansion underway[6](index=6&type=chunk)[8](index=8&type=chunk) [ALLO-329: Phase 1 RESOLUTION Trial in Autoimmune Disease (AID)](index=1&type=section&id=ALLO-329%3A%20Phase%201%20RESOLUTION%20Trial%20in%20Autoimmune%20Disease%20%28AID%29) The Phase 1 RESOLUTION basket trial for ALLO-329 was initiated in Q2 2025 for rheumatology indications like lupus and systemic sclerosis, featuring a first-in-class dual CAR T product incorporating Dagger® technology with initial proof-of-concept data expected in the first half of 2026 - The Phase 1 RESOLUTION basket trial was launched in **Q2 2025** for rheumatology, including conditions such as systemic lupus erythematosus, idiopathic inflammatory myopathies, and systemic sclerosis[7](index=7&type=chunk) - The trial features two lymphodepletion arms: one with cyclophosphamide alone and one with no lymphodepletion[7](index=7&type=chunk) - ALLO-329 is a first-in-class allogeneic CD19/CD70 dual CAR T product incorporating Dagger® technology to potentially reduce the need for lymphodepletion[9](index=9&type=chunk) - First clinical update with biomarker and proof-of-concept data is expected in **1H 2026**[7](index=7&type=chunk)[8](index=8&type=chunk) [ALLO-316: TRAVERSE Trial in RCC](index=1&type=section&id=ALLO-316%3A%20TRAVERSE%20Trial%20in%20RCC) Enrollment in the Phase 1b cohort for ALLO-316 in advanced Renal Cell Carcinoma (RCC) is complete, with updated data presented at ASCO 2025 showing clinical responses and robust cell expansion, leading to alignment with the FDA on a pivotal trial design that supports potential partnership discussions - Enrollment is complete for the Phase 1b cohort evaluating ALLO-316 in heavily pretreated advanced or metastatic Renal Cell Carcinoma (RCC)[9](index=9&type=chunk) - Updated Phase 1b results presented at **ASCO 2025** highlighted clinical responses and the potential of Dagger® technology[8](index=8&type=chunk)[9](index=9&type=chunk) - The company has aligned with the FDA on a pivotal trial design, setting the stage for potential partnership discussions[3](index=3&type=chunk)[8](index=8&type=chunk)[9](index=9&type=chunk) [Financial Results Summary](index=2&type=section&id=2025%20Second%20Quarter%20Financial%20Results) For the second quarter of 2025, Allogene reported a net loss of $50.9 million, ending the quarter with $302.6 million in cash, cash equivalents, and investments, with a projected cash runway into the second half of 2027 and full-year 2025 GAAP operating expenses expected to be approximately $230 million Key Financial Metrics for Q2 2025 | Metric | Value (USD) | | :--- | :--- | | Cash, Cash Equivalents, and Investments (as of June 30, 2025) | $302.6 million | | Research and Development Expenses | $40.2 million | | General and Administrative Expenses | $14.3 million | | Net Loss | $50.9 million | | Net Loss per Share | $0.23 | - Cash runway is expected to extend into the **second half of 2027**[10](index=10&type=chunk) - 2025 guidance includes an expected decrease in cash of approximately **$150 million** and GAAP Operating Expenses of approximately **$230 million**, including about **$45 million** in non-cash stock-based compensation[10](index=10&type=chunk) [Selected Financial Data](index=4&type=section&id=SELECTED%20FINANCIAL%20DATA) The detailed financial tables show a year-over-year decrease in operating expenses and net loss for Q2 2025, with the balance sheet reflecting a reduction in cash and total assets since the end of 2024, consistent with the company's operational spending [Statements of Operations](index=4&type=section&id=STATEMENTS%20OF%20OPERATIONS) For the three months ended June 30, 2025, Allogene reported total operating expenses of $56.8 million, a decrease from $71.4 million in the same period of 2024, resulting in a net loss of $50.9 million, or $0.23 per share, compared to a net loss of $66.4 million, or $0.35 per share, in Q2 2024 Consolidated Statements of Operations (Unaudited) | | Three Months Ended June 30, 2025 (in thousands) | Three Months Ended June 30, 2024 (in thousands) | | :--- | :--- | :--- | | Research and development | $40,156 | $50,355 | | General and administrative | $14,281 | $16,087 | | Total operating expenses | $56,819 | $71,431 | | Loss from operations | $(56,819) | $(71,431) | | Net loss | $(50,943) | $(66,358) | | Net loss per share, basic and diluted | $(0.23) | $(0.35) | [Selected Balance Sheet Data](index=4&type=section&id=SELECTED%20BALANCE%20SHEET%20DATA) As of June 30, 2025, Allogene had $302.6 million in cash, cash equivalents, and investments, a decrease from $373.1 million at the end of 2024, with total assets at $470.6 million and total stockholders' equity at $344.6 million Selected Balance Sheet Data (Unaudited) | | As of June 30, 2025 (in thousands) | As of December 31, 2024 (in thousands) | | :--- | :--- | :--- | | Cash, cash equivalents and investments | $302,630 | $373,149 | | Total assets | $470,593 | $548,710 | | Total liabilities | $126,032 | $126,531 | | Total stockholders' equity | $344,561 | $422,179 |

Core Insights - Allogene Therapeutics is advancing its clinical programs, particularly the ALPHA3 trial for cema-cel and the ALLO-329 trial for autoimmune diseases, indicating a focused strategy for value creation in cell therapies [2][3][4] Program Updates - The ALPHA3 trial has been amended to a randomized study comparing cema-cel after standard fludarabine and cyclophosphamide (FC) lymphodepletion to observation, with over 50 clinical sites activated across the U.S. and Canada [3][5][7] - Early data from the ALPHA3 trial shows promising minimal residual disease (MRD) conversion rates and a favorable safety profile for cema-cel following standard FC lymphodepletion [4][5] - The ALLO-329 trial, targeting autoimmune diseases, has launched a Phase 1 RESOLUTION basket trial, with the first clinical update expected in the first half of 2026 [6][8] Financial Results - As of June 30, 2025, the company reported a net loss of $50.9 million, or $0.23 per share, with total operating expenses of $56.8 million [15][21] - The company ended the second quarter with $302.6 million in cash, cash equivalents, and investments, projecting a cash runway into the second half of 2027 [11][15][23]

Company Overview - Allogene Therapeutics is a clinical-stage biotechnology company focused on developing allogeneic CAR T (AlloCAR T™) products for cancer and autoimmune diseases [4] - The company aims to provide "off-the-shelf" CAR T cell product candidates that are readily available, reliable, and scalable for patient treatment [4] Upcoming Events - Allogene Therapeutics will report its second quarter 2025 financial results and provide a business update on August 13, 2025, after market close [1] - A live audio webcast and conference call will follow the announcement at 2:00 p.m. PT/5:00 p.m. ET [1] Webcast Information - The listen-only webcast will be available on the company's website under the Investors tab in the News and Events section, with a replay accessible for approximately 30 days [2] - Registration is required for those who wish to ask questions during the conference call, and participants will receive a personal PIN upon registration [3]

Summary of Allogene Therapeutics Conference Call Company Overview - **Company**: Allogene Therapeutics - **Focus**: Update on the ALPHA-three trial for Semacell in first-line consolidation for large B-cell lymphoma Key Points Industry and Company Updates - Allogene provided an update on the ALPHA-three trial, focusing on patient safety and clinical development efficiency [4][7] - The trial will now proceed with standard fludarabine and cyclophosphamide as the sole lymphodepletion regimen, closing the FCA arm that included ALLO-six 47 [7][9] - The decision to close the FCA arm was influenced by a grade five adverse event involving a patient who developed fatal adenoviral hepatitis [8][13] Clinical Trial Adjustments - The ALPHA-three study will now have a streamlined two-arm trial design comparing Semacell F to standard Fc lymphodepletion versus observation [9][10] - The planned futility analysis is still on track for 2026, with the trial expected to answer pivotal clinical questions regarding CAR T therapy for high-risk LBCL patients [15][16] - The retirement of ALLO-six 47 is seen as a strategic decision to enhance safety and simplify the trial design [10][17] Safety and Efficacy Insights - An unplanned review of safety and biomarker data indicated encouraging MRD conversion rates and a supportive safety profile in the standard Fc arm [9][14] - The trial aims to minimize or eliminate the need for standard lymphodepletion, which is crucial for broader access to CAR T therapies [11][17] - The patient who experienced the adverse event was treated at a community cancer center, and the event is not seen as related to the treatment setting [49] Regulatory Engagement - Allogene has had productive and timely discussions with the FDA regarding the trial adjustments, with no outstanding issues reported [51][54] - The company is confident that there is no risk of a formal clinical hold from the FDA at this time [82] Recruitment and Screening - Screening activity for the trial remains high, with over 90% of invited patients undergoing MRD screening tests [22][60] - There has been no evidence of a decline in recruitment or screening interest following the adverse event [60] Future Outlook - Allogene is optimistic about the potential of the FC regimen to meet the efficacy expectations set for the trial, with no changes to the overall statistical design or patient enrollment targets [40][71] - The company aims to lead allogeneic CAR T therapies into everyday cancer care beyond academic settings [18][17] Additional Important Insights - The decision to streamline the trial is expected to enhance operational strength and real-world relevance [15][16] - The focus on patient safety and simplifying treatment regimens aligns with current clinical practices, potentially redefining care delivery in the first-line setting [16][17] - The company is committed to advancing the ALPHA-three trial and transforming access to CAR T therapy for patients in need [89]

Core Insights - Allogene Therapeutics has selected standard fludarabine and cyclophosphamide (FC) as the lymphodepletion regimen for its ALPHA3 study evaluating cemacabtagene ansegedleucel (cema-cel) in first-line consolidation for large B-cell lymphoma (LBCL) [1][6] - The ALPHA3 trial has shifted to a randomized study design comparing cema-cel after standard FC lymphodepletion to observation, with a futility analysis expected in the first half of 2026 [4][6] Company Developments - The decision to close the arm testing FC plus ALLO-647 was made due to a Grade 5 adverse event attributed to ALLO-647, leading to a review of trial data and a shift in clinical strategy [2][3] - Allogene is advancing next-generation AlloCAR T product candidates using the proprietary Dagger® Platform Technology, which aims to minimize or eliminate the need for standard lymphodepletion [3][6] Clinical Trial Details - The ALPHA3 study is designed to treat over 60,000 patients annually for LBCL in the US, EU, and UK, with cema-cel positioned as a potential standard "7th cycle" treatment following initial chemotherapy [8] - The trial has over 50 clinical sites activated across the US and Canada, including community cancer centers and major academic institutions [4][6] Product Information - Cemacabtagene ansegedleucel (cema-cel) is an investigational anti-CD19 AlloCAR T™ product for LBCL, with oncology rights held by Allogene in the US, EU, and UK, and options for rights in China and Japan [7][9]

Core Insights - Allogene Therapeutics has selected standard fludarabine and cyclophosphamide (FC) as the lymphodepletion regimen for its ALPHA3 study evaluating cemacabtagene ansegedleucel (cema-cel) in first-line consolidation for large B-cell lymphoma (LBCL) [1][6] - The trial's design has shifted to a randomized study comparing cema-cel after standard FC lymphodepletion to observation, with a futility analysis expected in the first half of 2026 [4][6] Company Developments - The arm testing FC plus ALLO-647 has been closed due to a Grade 5 adverse event attributed to ALLO-647, leading to a strategic shift in the company's clinical approach [2][3] - Allogene is advancing next-generation AlloCAR T product candidates using the proprietary Dagger Platform Technology, which aims to minimize or eliminate the need for standard lymphodepletion [3][6] Clinical Trial Information - The ALPHA3 trial is now a two-arm randomized study, with over 50 clinical sites activated across the U.S. and Canada [4][6] - The pivotal Phase 2 ALPHA3 study launched in June 2024 aims to treat LBCL patients who may relapse after first-line treatment [7][8] Market Context - Approximately 60,000 patients are expected to be treated for LBCL annually in the U.S., EU, and UK, with about 30% of those initially responding to treatment likely to relapse [8]

Industry Overview - The global cancer treatment market is experiencing rapid growth due to rising cancer incidence, an aging population, and increasing demand for safer, more effective therapies, with over 2 million new cancer cases and 618,000 related deaths projected in the U.S. for 2025 [1] - Breakthroughs in immunotherapy, targeted treatments, and personalized cancer vaccines are reshaping the oncology landscape, offering greater precision and improved outcomes [2] - The oncology market is poised for robust, long-term growth, presenting compelling opportunities for investors [4] Major Companies and Developments - Major pharmaceutical companies such as Novartis, AstraZeneca, Johnson & Johnson, Pfizer, AbbVie, Bristol Myers Squibb, and Eli Lilly are heavily investing in advanced approaches like antibody-drug conjugates and immuno-oncology agents, while smaller biotechs are driving innovation and becoming attractive acquisition targets [3] - Johnson & Johnson's oncology segment accounts for approximately 27% of its total revenues, with oncology sales rising 22.3% to $6.3 billion in Q2 2025, driven by strong market growth and key product share gains [6] - Johnson & Johnson expects its oncology sales to reach $50 billion by the end of the decade, citing strong growth in marketed cancer drugs and the potential of upcoming launches [7] - Novartis has a diverse oncology portfolio, with significant contributions from drugs like Kisqali, which recorded sales of $1.1 billion in Q2 2025, up 64% year over year [9][10] - Novartis' oncology sales rose 20% in constant currency terms to $4.3 billion in Q2 2025, bolstered by new drug approvals and acquisitions [10] Emerging Companies and Innovations - Allogene Therapeutics is focused on developing allogeneic CAR T therapies for cancer treatment, particularly in hematologic indications with high unmet needs [11] - Allogene Therapeutics has multiple clinical-stage pipeline candidates, including cema-cel for large B-cell lymphoma and ALLO-316 for advanced renal cell carcinoma, showing promising early anti-tumor activity [12][13]

Cema-cel & ALPHA3 Trial - The ALPHA3 trial is designed to predict and intervene BEFORE relapse in LBCL patients, using cema-cel as a 1L consolidation treatment for MRD+ patients[16] - Phase 1 data showed cema-cel achieved a 100% CR rate in patients with low disease burden, paving the way for ALPHA3[19] - The ALPHA3 trial aims to enroll ~240 LBCL patients in CR/PR at the end of 1L therapy with MRD across ~50 US cancer centers and additional international sites[41] - The ALPHA3 addressable population creates a ~$5 billion potential market opportunity in the US and EU5[44, 92] ALLO-329 - Phase 1 Rheumatology Basket Trial for ALLO-329 was IND cleared in Jan 2025, with trial initiation expected in mid-2025 and potential clinical and biomarker PoC data in 1H 2026[52] - ALLO-329 is a dual CD19/CD70 allogeneic CAR T with Dagger® technology, designed to maximize CAR T expansion and potentially eliminate the need for lymphodepletion[54] - The RESOLUTION basket study will address four large diseases: Lupus (SLE) with an estimated US diagnosed prevalence of 330,000, Lupus Nephritis with 90,000, Systemic Sclerosis with 100,000 and Myositis with 70,000[63] ALLO-316 - The TRAVERSE Ph1 trial supports the potential of ALLO-316 in CD70+ RCC, with encouraging activity in solid tumors and FDA RMAT designation[64] - ASCO 2025 will feature the next Ph1b data update for ALLO-316[65] - The TRAVERSE addressable population creates a >$3.5 billion global market opportunity[65, 97] Financial Position - Allogene has a strong financial position with $335.5 million in cash, cash equivalents, and investments at the end of Q1 2025, projecting runway into 2H 2027[78]