Clinical Trial Updates - Data from the ASPEN-06 trial highlights CD47 expression as a key predictive biomarker, demonstrating a compelling clinical response of evorpacept activity in HER2+ gastric cancer[12] - The Phase 2 ASPEN-Breast evorpacept trial design was updated to enable a CD47 and HER2 biomarker-driven strategy in a single-arm study[12] - Dose escalation was completed in the Sanofi-sponsored trial of evorpacept with SARCLISA® and dexamethasone in previously treated multiple myeloma, with Sanofi moving into dose optimization[12] - The first patient is anticipated to be enrolled in August in the phase 1 clinical trial of the novel EGFR-targeted antibody-drug conjugate (ADC), ALX2004[12] Financial Strategy - Focus on evorpacept in ASPEN-Breast and ALX2004, while pausing ASPEN-CRC, results in cash runway extended into Q1 2027[12] - The company had cash, cash equivalents, and investments of $84 million as of June 30, 2025[100] Upcoming Milestones - ASPEN-06 CD47 expression data update is expected in Q4 2025[12] - Initial safety data for ALX2004 is anticipated in 1H 2026[12] - ASPEN-breast interim data readout is expected in Q3 2026[12] ASPEN-06 Trial Results - In the ITT population, Evorpacept + TRP showed a 41% ORR compared to 27% in the TRP control arm[42] - In patients with HER2-positivity confirmed by fresh biopsy or ctDNA, evorpacept demonstrated a 49% ORR compared to 245% in control[45] - In patients with HER2+ and CD47-high gastric cancer (n=43), evorpacept + TRP had a 65% ORR versus 26% ORR for TRP[53] ASPEN-Breast Trial - In breast cancer patients with confirmed HER2-positivity, evorpacept + zanidatamab had a 56% confirmed ORR[63]

PART I FINANCIAL INFORMATION [Item 1. Financial Statements (Unaudited)](index=5&type=section&id=Item%201%20Financial%20Statements%20%28Unaudited%29) The unaudited condensed consolidated financial statements for ALX Oncology Holdings Inc. as of June 30, 2025, show a decrease in total assets to $95.3 million from $147.8 million at year-end 2024, primarily due to a reduction in cash and investments [Condensed Consolidated Balance Sheets](index=5&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) As of June 30, 2025, the company had total assets of $95.3 million, a decrease from $147.8 million at December 31, 2024, driven by a reduction in cash, cash equivalents, and short-term investments Condensed Consolidated Balance Sheet Highlights (in thousands) | Balance Sheet Item | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $19,302 | $17,567 | | Short-term investments | $60,012 | $110,190 | | Total current assets | $85,257 | $134,352 | | **Total assets** | **$95,320** | **$147,775** | | **Liabilities & Equity** | | | | Total current liabilities | $18,848 | $18,500 | | **Total liabilities** | **$30,905** | **$34,157** | | **Total stockholders' equity** | **$64,415** | **$113,618** | [Condensed Consolidated Statements of Operations](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) For the three months ended June 30, 2025, the company reported a net loss of $25.9 million, an improvement from the $39.4 million loss in the same period of 2024, primarily due to lower research and development expenses Statement of Operations Summary (in thousands, except per share data) | Metric | Q2 2025 | Q2 2024 | Six Months 2025 | Six Months 2024 | | :--- | :--- | :--- | :--- | :--- | | Research and development | $18,022 | $34,653 | $41,910 | $66,370 | | General and administrative | $5,451 | $6,872 | $13,383 | $12,917 | | Impairment charge | $3,175 | $— | $3,175 | $— | | Total operating expenses | $26,648 | $41,525 | $58,468 | $79,287 | | Loss from operations | $(26,648) | $(41,525) | $(58,468) | $(79,287) | | **Net loss** | **$(25,949)** | **$(39,399)** | **$(56,703)** | **$(74,980)** | | Net loss per share | $(0.49) | $(0.76) | $(1.05) | $(1.47) | [Condensed Consolidated Statements of Cash Flows](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) For the six months ended June 30, 2025, net cash used in operating activities was $48.1 million, offset by $50.0 million provided by investing activities, resulting in a net increase in cash of $1.7 million Cash Flow Summary for Six Months Ended June 30 (in thousands) | Activity | 2025 | 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(48,069) | $(64,490) | | Net cash provided by investing activities | $49,961 | $27,380 | | Net cash (used in) provided by financing activities | $(157) | $30,238 | | **Net increase (decrease) in cash** | **$1,735** | **$(6,872)** | | Cash at end of period | $19,368 | $15,600 | [Notes to Condensed Consolidated Financial Statements](index=10&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) The notes detail the company's accounting policies, financial instruments, and operational structure, including its clinical-stage status, reliance on future financing, and an impairment charge related to a leased property - The company is a clinical-stage biotechnology firm with no product revenues and expects to incur additional losses, though management believes existing capital is sufficient to fund operations for at least the next twelve months[27](index=27&type=chunk)[29](index=29&type=chunk)[30](index=30&type=chunk) - In May 2025, the company decided to sublease its Palo Alto property, resulting in a pre-tax long-lived asset impairment charge of **$3.2 million** on the right-of-use asset and leasehold improvements[55](index=55&type=chunk)[140](index=140&type=chunk) - The company has a term loan agreement for up to **$100.0 million**, with **$10.0 million** drawn, and a **$25.0 million** tranche remained available at the lenders' sole discretion as of June 30, 2025, after the company opted not to draw down other available tranches[63](index=63&type=chunk)[156](index=156&type=chunk) - As of June 30, 2025, the company had non-cancellable commitments of approximately **$1.5 million** for manufacturing and services, primarily with KBI Biopharma and three other contract manufacturers[89](index=89&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=21&type=section&id=Item%202%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the company's clinical-stage pipeline, led by evorpacept and ALX2004, highlighting recent clinical trial results, strategic shifts to preserve capital, and financial performance showing a reduced net loss for Q2 2025 [Overview](index=21&type=section&id=Overview) ALX Oncology is a clinical-stage biotechnology company focused on cancer therapies, with lead product evorpacept showing promising results in gastric cancer but not qualifying for accelerated FDA approval, leading to a strategic focus on the ASPEN-Breast trial - Lead product evorpacept is a next-generation CD47 blocker designed to avoid hematologic toxicities of other CD47 approaches[94](index=94&type=chunk)[95](index=95&type=chunk) - In the ASPEN-06 trial for gastric cancer, evorpacept plus TRP showed a **65% ORR** in CD47-high patients, compared to **26%** with TRP alone, with full data to be presented in Q4 2025[103](index=103&type=chunk)[105](index=105&type=chunk) - The FDA advised that ASPEN-06 data is not eligible for accelerated approval, leading the company to not pursue a Phase 3 trial in gastric cancer and instead focus resources on the ASPEN-Breast trial[105](index=105&type=chunk) - The company's second candidate, ALX2004, an EGFR-targeted ADC, received IND clearance from the FDA in April 2025[115](index=115&type=chunk) - The company received a Nasdaq minimum bid price non-compliance notice on April 23, 2025, and has until October 20, 2025, to regain compliance[114](index=114&type=chunk)[117](index=117&type=chunk) [Results of Operations](index=28&type=section&id=Results%20of%20Operations) The company's net loss decreased to $25.9 million in Q2 2025 from $39.4 million in Q2 2024, primarily driven by a 48% decrease in R&D expenses and a 21% decrease in G&A expenses Comparison of Results of Operations (in thousands) | Item | Q2 2025 | Q2 2024 | Change ($) | Change (%) | | :--- | :--- | :--- | :--- | :--- | | Research and development | $18,022 | $34,653 | $(16,631) | -48% | | General and administrative | $5,451 | $6,872 | $(1,421) | -21% | | Impairment charge | $3,175 | $— | $3,175 | 100% | | **Loss from operations** | **$(26,648)** | **$(41,525)** | **$14,877** | **-36%** | | **Net loss** | **$(25,949)** | **$(39,399)** | **$13,450** | **-34%** | - R&D expenses for Q2 2025 decreased by **$16.6 million** year-over-year, mainly due to a decrease of **$8.5 million** in clinical and development costs (less manufacturing of clinical trial materials) and a **$4.1 million** decrease in stock-based compensation[135](index=135&type=chunk) - G&A expenses for Q2 2025 decreased by **$1.4 million** year-over-year, primarily due to a **$1.0 million** decrease in stock-based compensation and lower legal consulting costs[138](index=138&type=chunk) - A **$3.2 million** impairment charge was recorded in Q2 2025 after the company decided to sublease its Palo Alto property[140](index=140&type=chunk) [Liquidity and Capital Resources; Plan of Operations](index=29&type=section&id=Liquidity%20and%20Capital%20Resources%3B%20Plan%20of%20Operations) As of June 30, 2025, the company had $83.5 million in cash, cash equivalents, and investments, which management believes is sufficient to fund operations into the first quarter of 2027 - The company had cash, cash equivalents, and investments of **$83.5 million** as of June 30, 2025[144](index=144&type=chunk)[189](index=189&type=chunk) - Management estimates that existing cash will fund operating expenses and capital requirements into the **first quarter of 2027**[157](index=157&type=chunk)[189](index=189&type=chunk) Cash Flow Summary for Six Months Ended June 30 (in thousands) | Activity | 2025 | 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(48,069) | $(64,490) | | Net cash provided by investing activities | $49,961 | $27,380 | | Net cash (used in) provided by financing activities | $(157) | $30,238 | - The company decided not to draw down on a **$40.0 million** tranche of its loan agreement by the June 30, 2024 deadline, resulting in only a **$25.0 million** tranche remaining available at the lenders' sole discretion as of June 30, 2025[156](index=156&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=33&type=section&id=Item%203%20Quantitative%20and%20Qualitative%20Disclosures%20about%20Market%20Risk) The company's primary market risks are related to interest rate sensitivity on its $83.5 million in cash and investments and $10.0 million in floating-rate debt, and credit risk managed through highly-rated securities - The company is exposed to interest rate risk on its **$83.5 million** in cash, cash equivalents, and investments, and on its **$10.0 million** in floating-rate debt[171](index=171&type=chunk)[172](index=172&type=chunk) - Borrowings under the Loan Agreement bear interest at a floating rate equal to the greater of 1-month term SOFR or **2.33%**, plus **6.25%**[172](index=172&type=chunk) - Credit risk is concentrated in cash and investments, mitigated by investing in highly-rated securities, though deposits may exceed federally insured limits[173](index=173&type=chunk) [Item 4. Controls and Procedures](index=34&type=section&id=Item%204%20Controls%20and%20Procedures) Management, including the CEO and CFO, concluded that the company's disclosure controls and procedures were effective as of June 30, 2025, with no material changes in internal control over financial reporting during the quarter - The CEO and CFO concluded that the company's disclosure controls and procedures were effective as of June 30, 2025[178](index=178&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[180](index=180&type=chunk) PART II OTHER INFORMATION [Item 1. Legal Proceedings](index=35&type=section&id=Item%201%20Legal%20Proceedings) The company reports that it is not currently a party to any material legal proceedings, while acknowledging potential involvement in legal matters in the ordinary course of business - As of the filing date, the company is not a party to any material legal proceedings[182](index=182&type=chunk) [Item 1A. Risk Factors](index=35&type=section&id=Item%201A%20Risk%20Factors) This section details significant risks including a history of net losses, the need for substantial additional capital, dependence on evorpacept's success, clinical trial uncertainties, reliance on third-party manufacturers, competition, intellectual property challenges, potential Nasdaq delisting, and regulatory hurdles [Risks Related to Financial Position and Need for Additional Capital](index=36&type=section&id=Risks%20Related%20to%20Our%20Financial%20Position%20and%20Need%20for%20Additional%20Capital) The company has a history of significant net losses and expects them to continue, requiring substantial additional capital to fund operations, with existing cash projected to last into Q1 2027, subject to restrictive loan covenants - The company has incurred significant net losses since inception, with an accumulated deficit of **$677.8 million** as of June 30, 2025, and expects to continue incurring losses[186](index=186&type=chunk) - The company will require substantial additional capital, with existing cash of **$83.5 million** projected to fund operations into **Q1 2027**, though this estimate is subject to change[188](index=188&type=chunk)[189](index=189&type=chunk) - The company's Loan Agreement contains covenants that restrict its ability to, among other things, incur additional debt, make acquisitions, or pay dividends, and a default could lead to acceleration of obligations[197](index=197&type=chunk)[200](index=200&type=chunk)[201](index=201&type=chunk) [Risks Related to Product Discovery, Development, and Commercialization](index=39&type=section&id=Risks%20Related%20to%20the%20Discovery%2C%20Development%20and%20Commercialization%20of%20Our%20Product%20Candidates) The company's success is heavily dependent on its lead candidate, evorpacept, facing inherent risks in clinical development, potential adverse side effects, substantial competition, and reliance on third-party manufacturers for supply and quality - The business is substantially dependent on the success of its lead product candidate, evorpacept, which has not completed a pivotal trial[202](index=202&type=chunk) - Early clinical trial outcomes are not predictive of later success, as evidenced by the company's April 2025 announcement that Phase 2 trials for evorpacept in HNSCC (ASPEN-03 and ASPEN-04) did not meet their primary endpoints[203](index=203&type=chunk)[205](index=205&type=chunk) - The company relies on third-party contract manufacturers for its product candidates and has no manufacturing facilities of its own, creating risks related to supply, quality, and regulatory compliance[233](index=233&type=chunk) - The company faces substantial competition from major pharmaceutical and biotech companies, many of whom are also developing drugs targeting the CD47 pathway, including Pfizer and Gilead Sciences[220](index=220&type=chunk)[221](index=221&type=chunk) [Risks Related to Government Regulation](index=50&type=section&id=Risks%20Related%20to%20Government%20Regulation) The company is subject to extensive, costly, and unpredictable government regulation, including lengthy approval processes, post-marketing requirements, potential impacts from healthcare reform, and compliance with fraud, abuse, data privacy, and anti-corruption laws - The regulatory approval process is lengthy and unpredictable, and there is no guarantee of approval for any product candidate[271](index=271&type=chunk) - While the company has received Fast Track and Orphan Drug designations for evorpacept, these may not lead to a faster review or approval and do not increase the likelihood of receiving marketing approval[276](index=276&type=chunk)[278](index=278&type=chunk) - Current and future legislation, including the Inflation Reduction Act of 2022, may increase the difficulty and cost of commercialization and negatively affect drug pricing[280](index=280&type=chunk)[285](index=285&type=chunk) - The company is subject to complex data privacy laws like GDPR in Europe and CCPA/CPRA in California, which impose significant compliance costs and potential liabilities for non-compliance[303](index=303&type=chunk)[310](index=310&type=chunk)[311](index=311&type=chunk) [Risks Related to Intellectual Property](index=61&type=section&id=Risks%20Related%20to%20Intellectual%20Property) The company's success depends on its ability to obtain, maintain, and enforce patent protection, facing an uncertain and litigious patent landscape, global protection challenges, infringement claims from third parties, and difficulties in protecting trade secrets - The company's ability to protect its product candidates through patents is uncertain and may not prevent competitors from developing similar products[313](index=313&type=chunk)[315](index=315&type=chunk) - The company may not be able to protect its intellectual property rights globally, as laws in some foreign countries are less protective than in the U.S[318](index=318&type=chunk) - The company is aware of third-party patents, such as those owned by University Health Network (UHN) and licensed to Pfizer, that could potentially be construed to cover evorpacept and limit its ability to commercialize in certain indications and geographies[343](index=343&type=chunk) - The company relies on trade secrets and confidentiality agreements, but these may be breached, and enforcing claims of misappropriation is difficult and costly[334](index=334&type=chunk)[335](index=335&type=chunk) [Risks Related to Operations](index=69&type=section&id=Risks%20Related%20to%20Our%20Operations) The company faces operational risks including managing growth, hiring and retaining key personnel, potential adverse effects from a recent reduction in force, reliance on third parties for critical services, challenges with novel technology, and potential product liability claims - The company is highly dependent on key personnel and faces significant competition for talent, with a recently announced reduction in force (RIF) potentially harming morale and leading to loss of expertise[361](index=361&type=chunk) - The company relies on third parties for crucial services, including clinical trial management and manufacturing, and any failure by these parties could delay or terminate development programs[358](index=358&type=chunk) - The company's product candidates are based on novel technology, making it difficult to predict the time and cost of development[360](index=360&type=chunk) - The company may be exposed to costly product liability claims from clinical trials or commercial use, and its insurance may not be sufficient to cover all damages[371](index=371&type=chunk)[373](index=373&type=chunk) [Risks Related to Ownership of Our Common Stock](index=74&type=section&id=Risks%20Related%20to%20Ownership%20of%20Our%20Common%20Stock) Ownership of the company's common stock involves significant risk due to high price volatility, non-compliance with Nasdaq's minimum bid price requirement, potential dilution from future equity financings, significant insider control, and a history of material weaknesses in internal controls - The trading price of the company's common stock is highly volatile[389](index=389&type=chunk) - The company is not in compliance with the Nasdaq Global Select Market's minimum bid price requirement and faces a risk of delisting if it cannot regain compliance by October 20, 2025[394](index=394&type=chunk) - Future sales of common stock, including under the ATM facility or upon exercise of warrants, will cause dilution to stockholders[388](index=388&type=chunk)[414](index=414&type=chunk) - As of June 30, 2025, executive officers, directors, and affiliated 5% holders beneficially owned approximately **21.3%** of the stock, allowing them to exert significant control[410](index=410&type=chunk) - The company has identified and remediated material weaknesses in internal control over financial reporting in the past and may identify others in the future, which could harm investor confidence[422](index=422&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=83&type=section&id=Item%202%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company reports no material change in the planned use of proceeds from its initial public offering and no unregistered sales of equity securities during the period - There has been no material change in the planned use of proceeds from the company's initial public offering[438](index=438&type=chunk) - There were no unregistered sales of equity securities in the reported quarter[439](index=439&type=chunk) [Item 3. Defaults Upon Senior Securities](index=83&type=section&id=Item%203%20Defaults%20Upon%20Senior%20Securities) This item is not applicable as the company has not defaulted upon any senior securities - Not applicable[441](index=441&type=chunk) [Item 4. Mine Safety Disclosures](index=83&type=section&id=Item%204%20Mine%20Safety%20Disclosures) This item is not applicable to the company - Not applicable[442](index=442&type=chunk) [Item 5. Other Information](index=83&type=section&id=Item%205%20Other%20Information) The company reports that none of its officers or directors adopted or terminated a Rule 10b5-1 trading arrangement or a non-Rule 10b5-1 trading arrangement during the last fiscal quarter - No officers or directors adopted or terminated a Rule 10b5-1 trading arrangement during the last fiscal quarter[443](index=443&type=chunk) [Item 6. Exhibits](index=84&type=section&id=Item%206%20Exhibits) This section lists the exhibits filed with the Form 10-Q, including certifications by the Principal Executive Officer and Principal Financial Officer as required by the Sarbanes-Oxley Act, and XBRL data files - Exhibits filed include CEO and CFO certifications pursuant to Sarbanes-Oxley Sections 302 and 906, and Inline XBRL documents[445](index=445&type=chunk)

Core Insights - ALX Oncology is advancing its clinical programs, particularly focusing on evorpacept and ALX2004, with significant data expected in the coming years [1][3][4] Clinical Developments - The ASPEN-06 trial indicates that CD47 expression is a predictive biomarker for response to evorpacept in HER2+ gastric cancer, with a 65% objective response rate (ORR) in CD47-high patients compared to 26% with standard treatment [4] - The ASPEN-Breast trial design has been updated to a single-arm study to evaluate CD47 and HER2 biomarker-driven strategies, with interim data expected in Q3 2026 [1][4] - The Phase 1 clinical trial for ALX2004 is on track to enroll its first patient in August 2025, targeting EGFR-expressing solid tumors [1][4][6] Financial Overview - As of June 30, 2025, ALX Oncology reported cash, cash equivalents, and investments totaling $83.5 million, sufficient to fund operations into Q1 2027 [11][16] - Research and Development (R&D) expenses for Q2 2025 were $18.0 million, a decrease from $34.7 million in the prior year, attributed to reduced clinical trial material manufacturing and other cost-saving measures [11][14] - The net loss for Q2 2025 was $25.9 million, down from $39.4 million in Q2 2024, reflecting lower R&D expenses [11][14] Corporate Updates - Daniel Curran, M.D., has been appointed to the Board of Directors, bringing extensive experience in drug discovery and corporate strategy [2][3][5] - The company has extended its cash runway into Q1 2027, allowing for the achievement of multiple data milestones across its pipeline [1][4][11]

[Executive Summary](index=1&type=section&id=Executive%20Summary) ALX Oncology reported Q2 2025 financial results and corporate updates, highlighting significant progress in evorpacept and ALX2004 clinical programs, cash runway extension, and new board appointment - ASPEN-06 trial data indicates **CD47 expression** as a key predictive biomarker for better evorpacept response in HER2+ gastric cancer patients; updated data to be presented in Q4 2025[1](index=1&type=chunk) - The Phase 2 ASPEN-Breast evorpacept trial design is updated to a single-arm study with a CD47 and HER2 biomarker-driven strategy; interim data expected in Q3 2026[1](index=1&type=chunk) - The ALX2004 Phase 1 clinical trial is on track to enroll its first patient in August[1](index=1&type=chunk) - The company focuses on advancing ASPEN-Breast and ALX2004 data milestones within its cash runway, now extended to **Q1 2027**[1](index=1&type=chunk)[2](index=2&type=chunk) - Dr Daniel Curran appointed to the Board of Directors[1](index=1&type=chunk)[2](index=2&type=chunk) [Q2 2025 Highlights and Recent Developments](index=2&type=section&id=Q2%202025%20Highlights%20and%20Recent%20Developments) The company achieved significant clinical and strategic progress in Q2 2025, including positive evorpacept biomarker data, revised breast cancer trial design, ALX2004 IND approval, and strategic prioritization to extend financial runway [Evorpacept Clinical Program Updates](index=2&type=section&id=Evorpacept%20Clinical%20Program%20Updates) [ASPEN-06 Trial (HER2+ Gastric Cancer)](index=2&type=section&id=ASPEN-06%20Trial%20(HER2%2B%20Gastric%20Cancer)) - In a pre-planned exploratory analysis of the ASPEN-06 clinical trial, **CD47 overexpression** was identified as a key predictive biomarker for response and durable clinical benefit[3](index=3&type=chunk) ASPEN-06 Trial Results | Patient Group (n) | Combination Therapy | ORR | vs. TRP alone ORR | | :-------------------- | :------------------ | :-- | :---------------- | | HER2+, CD47-high (43) | Evorpacept + TRP | 65% | 26% | | HER2+, CD47-low (47) | Evorpacept + TRP | 39% | 25% | - In CD47-high expressing patients, evorpacept demonstrated significant benefits in **Duration of Response (DOR)**, **Progression-Free Survival (PFS)**, and **Overall Survival (OS)**[3](index=3&type=chunk) - The full dataset will be presented at an upcoming medical conference in **Q4 2025**[3](index=3&type=chunk) [ASPEN-Breast Trial (HER2+ Breast Cancer)](index=2&type=section&id=ASPEN-Breast%20Trial%20(HER2%2B%20Breast%20Cancer)) - Based on significant benefits in CD47-high expressing patients with HER2+ gastric cancer, the ASPEN-Breast study has been revised to a single-arm design evaluating evorpacept in all previously treated HER2-positive patients, assessed by CD47 expression[3](index=3&type=chunk) - The revised study design is expected to optimize enrollment and allow for an interim data readout in **Q3 2026**[3](index=3&type=chunk)[6](index=6&type=chunk) - The goal is for these study results to support a biomarker-driven registrational study in HER2-positive breast cancer[3](index=3&type=chunk) [UMBRELLA Study (Multiple Myeloma)](index=2&type=section&id=UMBRELLA%20Study%20(Multiple%20Myeloma)) - Sanofi and ALX Oncology announced the completion of the dose-escalation portion of the UMBRELLA randomized Phase 1/2 study, combining evorpacept with SARCLISA® (isatuximab-irfc) and dexamethasone in previously treated multiple myeloma patients[3](index=3&type=chunk) - Sanofi will initiate the dose-optimization portion of the study[3](index=3&type=chunk) [ALX2004 Clinical Program Update (EGFR-expressing Solid Tumors)](index=2&type=section&id=ALX2004%20Clinical%20Program%20Update%20(EGFR-expressing%20Solid%20Tumors)) - The company received FDA IND approval in April to advance ALX2004 for clinical evaluation in epidermal growth factor receptor (EGFR)-positive solid tumors, with the first patient in the Phase 1 clinical trial expected to be dosed in August[3](index=3&type=chunk) - The Phase 1 dose-escalation trial will include patients with relapsed/refractory EGFR-expressing solid tumors, including non-small cell lung cancer, colorectal cancer, head and neck squamous cell carcinoma, and esophageal squamous cell carcinoma[3](index=3&type=chunk) - Preliminary safety data from the Phase 1 trial are anticipated in **H1 2026**[3](index=3&type=chunk)[6](index=6&type=chunk) - ALX2004 utilizes a proprietary topoisomerase I inhibitor payload and linker-payload platform, designed to provide enhanced bystander effect and improved linker stability for targeted payload delivery[3](index=3&type=chunk) - Preclinical model results showed no EGFR-related skin toxicity or payload-related interstitial lung disease at clinically relevant doses, suggesting a potentially differentiated safety profile[3](index=3&type=chunk) [Strategic Prioritizations and Cash Runway Extension](index=2&type=section&id=Strategic%20Prioritizations%20and%20Cash%20Runway%20Extension) - The company prioritized evorpacept development, focusing on breast cancer and pausing the ASPEN-CRC study in colorectal cancer to extend its cash runway[3](index=3&type=chunk) - Through these strategic prioritizations, the company extended its cash runway into **Q1 2027**[2](index=2&type=chunk)[6](index=6&type=chunk) [Corporate and Leadership Changes](index=1&type=section&id=Corporate%20and%20Leadership%20Changes) - Dr Daniel Curran, a physician executive with extensive experience in business development, corporate strategy, drug discovery, and development, was appointed to the Board of Directors[1](index=1&type=chunk)[2](index=2&type=chunk)[6](index=6&type=chunk) - Dr Allison Dillon, previously Chief Business Officer, was appointed Chief Operating Officer, effective immediately[6](index=6&type=chunk) [Upcoming Clinical Milestones](index=3&type=section&id=Upcoming%20Clinical%20Milestones) Key upcoming clinical milestones include ASPEN-Breast patient dosing in Q4 2025 with interim data in Q3 2026, and ALX2004 patient dosing in August with preliminary safety data in H1 2026 - ASPEN-Breast cancer: Patient dosing expected to commence in **Q4 2025**; interim data from this trial are anticipated in **Q3 2026**[6](index=6&type=chunk) - ALX2004: Patient dosing expected to commence in **August**; preliminary safety data from the Phase 1 trial in EGFR-expressing solid tumors are anticipated in **H1 2026**[6](index=6&type=chunk) [Second Quarter 2025 Financial Results](index=3&type=section&id=Second%20Quarter%202025%20Financial%20Results) ALX Oncology reported a reduced net loss in Q2 2025, driven by lower R&D and G&A expenses, partially offset by an impairment charge, with cash sufficient to fund operations until Q1 2027 [Financial Summary and Cash Position](index=3&type=section&id=Financial%20Summary%20and%20Cash%20Position) Cash, Cash Equivalents and Investments | Metric | Amount (June 30, 2025) | | :----------------------------------- | :--------------------- | | Cash, cash equivalents and investments | **$83.5 million** | - The company believes its cash, cash equivalents, and investments are sufficient to support planned operations into **Q1 2027**[7](index=7&type=chunk) [Operating Expenses Analysis](index=3&type=section&id=Operating%20Expenses%20Analysis) [Research and Development (R&D) Expenses](index=3&type=section&id=Research%20and%20Development%20(R%26D)%20Expenses)) R&D Expenses Overview | Metric | Q2 2025 (Millions) | Q2 2024 (Millions) | Change (Millions) | | :----------- | :----------------- | :----------------- | :---------------- | | R&D Expenses | **$18.0** | **$34.7** | **$(16.6)** | - The decrease in R&D expenses was primarily due to a **$8.5 million reduction** in clinical and development costs (mainly from decreased clinical trial material manufacturing for evorpacept), a **$4.1 million decrease** in stock-based compensation, a **$2.1 million reduction** in personnel and related costs, and a **$1.7 million decrease** in preclinical costs due to pipeline prioritization[7](index=7&type=chunk)[8](index=8&type=chunk) [General and Administrative (G&A) Expenses](index=4&type=section&id=General%20and%20Administrative%20(G%26A)%20Expenses)) G&A Expenses Overview | Metric | Q2 2025 (Millions) | Q2 2024 (Millions) | Change (Millions) | | :----------- | :----------------- | :----------------- | :---------------- | | G&A Expenses | **$5.5** | **$6.9** | **$(1.4)** | - The decrease in G&A expenses was primarily attributable to a reduction in stock-based compensation expense[11](index=11&type=chunk) [Net Loss and Per Share Data](index=4&type=section&id=Net%20Loss%20and%20Per%20Share%20Data) Net Loss and Per Share Summary | Metric | Q2 2025 (Millions) | Q2 2024 (Millions) | Change (Millions) | | :---------------------- | :----------------- | :----------------- | :---------------- | | GAAP Net Loss | **$(25.9)** | **$(39.4)** | **$13.5** | | GAAP Net Loss per Share | **$(0.49)** | **$(0.76)** | **$0.27** | | Non-GAAP Net Loss | **$(23.7)** | **$(32.1)** | **$8.4** | - The decrease in net loss was primarily due to lower R&D expenses, partially offset by a **$3.2 million impairment charge** on long-lived assets recorded in Q2 2025, related to leased laboratory space following preclinical research staff reductions announced in March 2025[11](index=11&type=chunk) [Condensed Consolidated Financial Statements](index=5&type=section&id=Condensed%20Consolidated%20Financial%20Statements) This section presents unaudited condensed consolidated statements of operations, balance sheet data, and GAAP to non-GAAP reconciliation for the three and six months ended June 30, 2025 and 2024 [Condensed Consolidated Statements of Operations](index=5&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) Condensed Consolidated Statements of Operations (in thousands) | Metric (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------------------------------------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development | $18,022 | $34,653 | $41,910 | $66,370 | | General and administrative | $5,451 | $6,872 | $13,383 | $12,917 | | Impairment charge | $3,175 | — | $3,175 | — | | Total operating expenses | $26,648 | $41,525 | $58,468 | $79,287 | | Loss from operations | $(26,648) | $(41,525) | $(58,468) | $(79,287) | | Interest income | $1,106 | $2,563 | $2,589 | $5,185 | | Interest expense | $(405) | $(429) | $(811) | $(856) | | Other (expense) income, net | $(2) | $(8) | $(13) | $(22) | | Net loss | $(25,949) | $(39,399) | $(56,703) | $(74,980) | | Net loss per share, basic and diluted | $(0.49) | $(0.76) | $(1.05) | $(1.47) | | Weighted-average shares of common stock used to compute net loss per shares, basic and diluted | 53,445,631 | 51,831,157 | 54,031,176 | 50,969,089 | [Condensed Consolidated Balance Sheet Data](index=5&type=section&id=Condensed%20Consolidated%20Balance%20Sheet%20Data) Condensed Consolidated Balance Sheet Data (in thousands) | Metric (in thousands) | June 30, 2025 | December 31, 2024 | | :----------------------------- | :------------ | :---------------- | | Cash, cash equivalents and investments | $83,546 | $131,281 | | Total assets | $95,320 | $147,775 | | Total liabilities | $30,905 | $34,157 | | Accumulated deficit | $(677,825) | $(621,122) | | Total stockholders' equity | $64,415 | $113,618 | [GAAP to Non-GAAP Reconciliation](index=5&type=section&id=GAAP%20to%20Non-GAAP%20Reconciliation) GAAP to Non-GAAP Reconciliation (in thousands) | Metric (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------------------------------ | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | GAAP net loss, as reported | $(25,949) | $(39,399) | $(56,703) | $(74,980) | | Stock-based compensation expense | $2,136 | $7,252 | $7,352 | $14,283 | | Accretion of term loan discount and issuance costs | $69 | $66 | $136 | $130 | | Total adjustments | $2,205 | $7,318 | $7,488 | $14,413 | | Non-GAAP net loss | $(23,744) | $(32,081) | $(49,215) | $(60,567) | [Use of Non-GAAP Financial Measures](index=6&type=section&id=Use%20of%20Non-GAAP%20Financial%20Measures) This section explains that non-GAAP financial measures provide additional information for management's business assessment but are not GAAP compliant and should not be considered in isolation or as substitutes for GAAP results - Non-GAAP financial measures provide additional information reflecting the amounts and financial basis on which management assesses and operates the business[18](index=18&type=chunk) - These non-GAAP financial measures are not in accordance with GAAP and should not be viewed in isolation or as a substitute for reported GAAP net loss[18](index=18&type=chunk) - "Non-GAAP net loss" is GAAP net loss adjusted to exclude stock-based compensation expense and accretion of term loan discount and issuance costs[19](index=19&type=chunk) [About ALX Oncology](index=4&type=section&id=About%20ALX%20Oncology) ALX Oncology is a clinical-stage biotechnology company advancing a pipeline of novel therapies to treat cancer and extend patient lives, with evorpacept as its lead candidate and ALX2004 as its second pipeline candidate - ALX Oncology is a clinical-stage biotechnology company dedicated to advancing a pipeline of novel therapies designed to treat cancer and extend patient lives[9](index=9&type=chunk) - ALX Oncology's lead therapeutic candidate, evorpacept, has shown potential as a cornerstone immuno-oncology therapy and is being evaluated in multiple ongoing clinical trials across a broad range of cancer indications[9](index=9&type=chunk) - ALX Oncology's second pipeline candidate, ALX2004, is a novel EGFR-targeted antibody-drug conjugate with a differentiated mechanism of action, expected to enter Phase 1 trials in mid-2025[9](index=9&type=chunk) [Cautionary Note Regarding Forward-Looking Statements](index=4&type=section&id=Cautionary%20Note%20Regarding%20Forward-Looking%20Statements) This section warns that the press release contains forward-looking statements involving significant risks and uncertainties, where actual results may differ materially from those expressed or implied - This press release contains forward-looking statements involving significant risks and uncertainties[10](index=10&type=chunk) - Forward-looking statements are based on ALX Oncology's beliefs and assumptions and may involve known and unknown risks, uncertainties, and other factors that could cause ALX Oncology's actual results, performance, or achievements to differ materially from those expressed or implied[10](index=10&type=chunk) - Except as required by law, ALX Oncology undertakes no obligation to update such statements to reflect events or circumstances occurring after their publication date[10](index=10&type=chunk) [Investor and Media Contacts](index=6&type=section&id=Investor%20and%20Media%20Contacts) This section provides contact information for investor relations and media inquiries - Investor Relations Contact: Elhan Webb, CFA, IR Consultant, ewebb@alxoncology.com[20](index=20&type=chunk) - Media Contact: Audra Friis, Sam Brown LLC, audrafriis@sambrown.com, (917) 519-9577[20](index=20&type=chunk)

Core Viewpoint - ALX Oncology Holdings Inc. is set to report its second quarter 2025 financial results and provide a business update on August 12, 2025, after market close [1] Group 1: Financial Results Announcement - The company will host a teleconference in conjunction with its financial results press release [1] - The webcast for the financial results will take place on August 12, 2025, at 1:30 PM PT / 4:30 PM ET [2] - Access to the conference call can be made via phone or through a dedicated link for instant telephone access [3] Group 2: Company Overview - ALX Oncology is a clinical-stage biotechnology company focused on developing novel therapies for cancer treatment [4] - The lead therapeutic candidate, evorpacept, is being evaluated in multiple ongoing clinical trials across various cancer indications [4] - The second pipeline candidate, ALX2004, is an EGFR-targeted antibody-drug conjugate expected to enter Phase 1 trials in mid-2025 [4]

Summary of Conference Call Company and Industry - The conference call discusses ALX Oncology, focusing on their drug development programs, particularly in the oncology sector, including anti-CD47 antibodies and antibody-drug conjugates (ADCs) targeting EGFR. Core Points and Arguments 1. **Current Drug Development**: ALX Oncology is developing an anti-CD47 antibody, aboricept, which is unique due to its dead Fc mechanism, showing no on-target related issues that have affected similar drugs in the past [6][10][12]. 2. **Clinical Studies**: The company has five positive clinical studies supporting their initial hypothesis from 2015, with ongoing studies in breast and colorectal cancers [9][17]. 3. **New ADC Program**: ALX is working on a new ADC targeting EGFR, which is still in early stages but shows promise. The company aims to be first and best in class against this validated target [3][10]. 4. **Breast Cancer Study**: A randomized study is being launched for patients post-HER2 treatment, showing a 55% overall response rate (ORR) in previous studies. The study will compare the combination of vorprecept and Herceptin with chemotherapy [19][33]. 5. **Colorectal Cancer Study**: The company is initiating a study combining their drug with cetuximab in colorectal cancer, addressing a significant unmet need in this area [60][61]. 6. **EGFR ADC Development**: ALX is innovating in the ADC space by optimizing the payload, linker, and antibody to minimize on-target toxicity, particularly skin toxicity, which has plagued previous EGFR ADCs [82][84]. 7. **Preclinical Success**: In non-human primate studies, ALX has dosed up to 10 mg/kg without observing skin toxicity, indicating a potential therapeutic window for their ADC [86][102]. 8. **Financial Position**: The company reported approximately $100 million in cash at the end of Q1, with plans to manage expenses effectively while executing their studies [110][111]. Other Important Content 1. **Patient Selection**: The company emphasizes the importance of selecting HER2 positive patients for their studies, utilizing ctDNA as a surrogate marker for patient eligibility [51][53]. 2. **Market Strategy**: ALX is focused on executing their studies while exploring potential partnerships for their drugs, particularly after positive data presentations at ASCO [117][118]. 3. **Future Data Readouts**: Interim data for the breast cancer study is expected in the second half of 2026, while colorectal study data may be available in the first half of 2026 [80][115]. This summary encapsulates the key points discussed during the conference call, highlighting ALX Oncology's strategic focus on innovative cancer therapies and their clinical development pipeline.

Core Insights - ALX Oncology Holdings Inc. is a clinical-stage biotechnology company focused on developing novel therapies for cancer treatment and improving patient survival [2] Group 1: Company Overview - ALX Oncology's lead therapeutic candidate, evorpacept, shows promise as a foundational therapy for future immuno-oncology treatments and is currently undergoing multiple clinical trials across various cancer indications [2] - The second pipeline candidate, ALX2004, is an innovative EGFR-targeted antibody-drug conjugate with a unique mechanism of action, expected to enter Phase 1 trials in mid-2025 [2] Group 2: Upcoming Events - Management will participate in the Jefferies 2025 Global Healthcare Conference, scheduled for June 5, 2025, at 1:25 PM ET in New York, NY [1] - A live webcast of the event will be available on ALX Oncology's website, with a replay accessible for up to 90 days post-event [1]

ALX2004 Program Overview - ALX2004 is an EGFR-targeted ADC with a DAR of 8, utilizing a topoisomerase I inhibitor (Top1i) payload, with IND cleared in April 2025[13, 98] - ALX2004 is designed to maximize the therapeutic window and overcome toxicity challenges, with a focus on EGFR-expressing solid tumors[14, 99] - ALX2004's Phase 1a dose escalation trial is planned to start in mid-2025, targeting NSCLC, CRC, HNSCC, and ESCC[14, 99] ALX2004 Design and Preclinical Data - ALX2004's EGFR antibody binding epitope is selected to minimize off-tumor skin toxicities, and its affinity is tuned to maximize the therapeutic window[20] - The linker-payload is designed for lysosomal cleavage, similar to deruxtecan ADCs, with improved linker-antibody stability to minimize off-tumor payload release[20] - Preclinical data demonstrates dose-dependent activity across a range of tumors and EGFR expression levels, with a differentiated safety profile in NHP toxicity studies, showing no EGFR-related skin toxicity at clinically relevant doses[24] - In preclinical studies, ALX2004 demonstrated superior anti-tumor activity compared to DXd ADCs in CDX mouse models, showing improved bystander effect[47, 49] Clinical Development Plan - The Phase 1 trial is rationally designed around tumor types with established sensitivity to EGFR-directed therapies, including HNSCC, CRC, NSCLC, and ESCC, representing over 250,000 patient prevalence in the US[87] - The Phase 1 clinical development plan includes dose escalation (Phase 1a, up to 40 patients), dose exploration (up to 50 patients), and dose expansion (Phase 1b, up to 80 patients)[89, 90, 91] - ALX Oncology anticipates initial safety data for ALX2004 in EGFR-expressing solid tumors in the first half of 2026[101]

Summary of ALX Oncology Holdings (ALXO) Conference Call Company Overview - **Company**: ALX Oncology Holdings (ALXO) - **Focus**: Development of ALX2004, a differentiated antibody-drug conjugate (ADC) targeting EGFR Key Points and Arguments Industry and Product Development - **ADC Focus**: ALX2004 is designed to maximize therapeutic window and overcome historical toxicity challenges associated with EGFR-targeted ADCs [5][6][10] - **Clinical Pipeline**: The company is advancing its ADC in combination with anti-cancer antibodies, specifically targeting breast and colorectal cancers [4][5] - **IND Clearance**: ALX2004 has received Investigational New Drug (IND) clearance, with plans to launch a Phase I trial in mid-2025 [5][7] Scientific Rationale - **Payload and Linker Design**: ALX2004 utilizes a proprietary topoisomerase one inhibitor payload, designed to minimize off-target toxicity while maximizing tumor cell killing [17][20] - **Immunogenic Cell Death**: The payload triggers immunogenic cell death, potentially enhancing long-term tumor control through adaptive immune response [18][28] - **Optimized Antibody**: The antibody component is designed to block EGFR signaling and bind to a unique epitope, potentially overcoming resistance to existing therapies [30][32] Clinical Development Plans - **Phase I Study**: The study will focus on four tumor types: head and neck squamous cell carcinoma, colorectal cancer, non-small cell lung cancer, and esophageal squamous cell carcinoma, targeting patients with relapsed or refractory disease [40][41] - **Safety and Efficacy Goals**: Initial safety data is expected in the first half of 2026, with an emphasis on establishing a recommended dosing schema [42][43] Competitive Landscape - **Market Positioning**: ALX Oncology aims to be a leader in the ADC space targeting EGFR, which currently lacks an approved drug [43][85] - **Comparison with Competitors**: The company is aware of other ADCs in development, such as MRG003, but believes its optimized design gives it a competitive edge [85] Additional Important Insights - **Preclinical Data**: Robust preclinical data supports the efficacy and safety profile of ALX2004, with encouraging results in various tumor models [14][34] - **Toxicity Management**: The design aims to avoid common toxicities seen in previous EGFR-targeted ADCs, such as skin toxicity and interstitial lung disease [14][72] - **Funding and Capital Allocation**: The company has sufficient cash to fund its ongoing studies into 2024, with plans to explore additional capital options as needed [51][52] This summary encapsulates the critical aspects of ALX Oncology's conference call, highlighting the company's strategic focus on developing ALX2004 and its potential impact on the oncology market.

Core Insights - ALX Oncology is advancing ALX2004, a potential best- and first-in-class antibody-drug conjugate (ADC) targeting EGFR-expressing solid tumors, designed to maximize therapeutic efficacy while minimizing toxicity [1][2] - The U.S. FDA has cleared the IND application for ALX2004, with clinical studies set to begin in mid-2025 and initial safety data expected in the first half of 2026 [1][6] - The company plans to initiate trials for its lead therapy, evorpacept, in breast and colorectal cancers around the same time, with significant milestones anticipated in 2026 [1] ALX2004 Development Overview - ALX2004 is developed using a proprietary linker-payload platform, featuring an affinity-tuned EGFR antibody and a stable linker-Top1i payload, aimed at enhancing anti-tumor activity and reducing toxicity [3][4] - Preclinical data indicates that ALX2004 has superior stability and a favorable safety profile compared to other ADCs, showing dose-dependent activity across various tumors and EGFR expression levels [5] Clinical Trial Plans - The Phase 1 clinical trial for ALX2004 will target EGFR-expressing solid tumors, including non-small cell lung cancer and colorectal cancer, focusing on patients with relapsed or refractory cancers [6] - The trial is expected to begin in mid-2025, with initial safety data anticipated in the first half of 2026 [1][6]