On October 23, 2025 ALX Oncology Holdings Inc., ("ALX Oncology" or the "Company") (Nasdaq: ALXO), a clinical-stage biotechnology company advancing a pipeline of novel therapies designed to treat cancer and extend patients’ lives, reported preclinical data and the trial design for the ongoing Phase 1 clinical trial for its ADC candidate, ALX2004, in two poster presentations at the 2025 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), taking place October 22 – 26, 2025 in Boston, Massachusetts. ALX2004-01 is a first-in-human study to evaluate the safety, tolerability, and preliminary efficacy of ALX2004 in patients with advanced or metastatic solid tumors that are known to express EGFR.

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"Our preclinical findings have shown potent anti-tumor activity and a favorable toxicity profile supporting our advancement of ALX2004 into the clinic," said Jason Lettmann, Chief Executive Officer at ALX Oncology. "Given that toxicity challenges of earlier generation ADCs have limited the therapeutic window in the treatment of EGFR-expressing solid tumors; we are encouraged by our preclinical data that this unique molecule, ALX2004 could potentially overcome these limitations. Enrollment in this trial began in August and continues to be on track to allow us to deliver initial safety data in the first half of next year. We are pleased to present extensive preclinical data supporting ALX2004’s potential to break new ground in ADC innovation in the EGFR-targeting class at the AACR (Free AACR Whitepaper)-NCI-EORTC Conference."

The Company’s first ADC, ALX2004, is the result of a rigorous internal drug design process. Developed in house by ALX Oncology’s protein engineers utilizing the Company’s proprietary topoisomerase I inhibitor (Top1i) payload and linker payload platform, ALX2004 is designed to optimize all mechanisms of ADC cancer killing while maximizing the therapeutic window. ALX2004 uses a matuzumab-derived EGFR antibody selected to minimize off tumor skin toxicity and maximize therapeutic window, with a binding epitope distinct from U.S. Food and Drug Administration approved EGFR antibodies. Additionally, ALX2004 has a proprietary linker-payload and Top1i payload engineered to offer improved linker stability for on-target delivery of payload and enhanced bystander effect.

ALX2004 is currently being evaluated in a first-in-human, open-label multicenter study in participants with advanced or metastatic select EGFR-expressing solid tumors. The design of this Phase 1 clinical trial (NCT07085091) will also be presented at the meeting.

Details for ALX Oncology’s poster presentations are as follows:

Title: ALX2004, A Novel Anti-EGFR Topoisomerase I Inhibitor Antibody-Drug Conjugate for the Treatment of EGFR-Expressing Solid Tumors
Presenter: Marja Vrljic, Ph.D., Vice President, Antibody Technologies, ALX Oncology
Abstract: #A119
Date and Time: Thursday, October 23, 12:30-4:00 p.m. ET
Session: Poster Session A
Location: Hynes Convention Center, Level 2, Exhibit Hall D

Title: A Phase 1, First-in-Human, Open-Label Multicenter Study to Evaluate ALX2004, Antibody-Drug Conjugate Targeting EGFR, in Patients With Advanced or Metastatic Select Solid Tumors (ALX2004-01)
Abstract: LB-A004
Date and Time: Thursday, October 23, 12:30-4:00 p.m. ET
Session: Poster Session A
Location: Hynes Convention Center, Level 2, Exhibit Hall D

(Press release, ALX Oncology, OCT 23, 2025, View Source [SID1234656933])

On October 23, 2025 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) has granted priority review for two supplemental Biologics License Applications (sBLA) for KEYTRUDA (pembrolizumab) and KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa-pmph), each in combination with Padcev (enfortumab vedotin-ejfv), for the treatment of patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy. The FDA set a Prescription Drug User Fee Act (PDUFA), or target action, date of April 7, 2026, marking the first concurrent review of both KEYTRUDA and KEYTRUDA QLEX for the same novel indication.

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"New options for muscle-invasive bladder cancer are vital — patients who are ineligible for chemotherapy have not seen a treatment advance beyond surgery in decades," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "With the FDA’s priority review, we are one step closer to offering KEYTRUDA or KEYTRUDA QLEX plus Padcev as a potential treatment option to these patients with MIBC who are ineligible for cisplatin-containing chemotherapy and have such high unmet medical need."

The sBLAs are based on data from the Phase 3 KEYNOTE-905 trial (also known as EV-303), which was conducted in collaboration with Pfizer and Astellas. Results, which were presented at the recent European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, showed that after a median follow-up of 25.6 months, KEYTRUDA plus Padcev, as perioperative treatment, demonstrated a statistically significant and clinically meaningful improvement in event-free survival (EFS), the trial’s primary endpoint, reducing the risk of EFS events by 60% (HR=0.40 [95% CI, 0.28-0.57]; p<0.0001) versus surgery (radical cystectomy) alone in patients with MIBC who are not eligible for or declined cisplatin-based chemotherapy. Median EFS was not reached [NR] (95% CI, 37.3-NR) for the KEYTRUDA plus Padcev regimen versus 15.7 months (95% CI, 10.3-20.5) for surgery alone.

KEYTRUDA plus Padcev also demonstrated a statistically significant and clinically meaningful improvement in key secondary endpoints of overall survival (OS) and pathologic complete response (pCR) rate. KEYTRUDA plus Padcev reduced the risk of death by 50% (HR=0.50 [95% CI, 0.33-0.74]; p=0.0002) versus surgery. The pCR rate increased from 8.6% in patients treated with surgery alone (n=15/174) to 57.1% in patients treated with perioperative KEYTRUDA plus Padcev (n=97/170), an estimated increase of 48.3 percentage points (95% CI, 39.5-56.5; p<0.000001).

KEYTRUDA plus Padcev is currently approved for the treatment of adult patients with locally advanced or metastatic urothelial cancer (la/mUC) in the U.S., the European Union (EU), Japan and several other countries around the world based on results from the Phase 3 KEYNOTE-A39 trial, also known as EV-302. KEYTRUDA as a monotherapy is also approved in the U.S., EU, Japan and other countries for the treatment of certain patients with la/mUC or a type of non-muscle-invasive bladder cancer (NMIBC).

Four additional Phase 3 studies are currently evaluating KEYTRUDA across all stages of bladder cancer, including non-muscle-invasive, muscle-invasive and metastatic disease. Three of these studies are in MIBC including KEYNOTE-B15 (NCT04700124), which is also known as EV-304 and is being conducted in collaboration with Pfizer and Astellas, KEYNOTE-866 (NCT03924856) and KEYNOTE-992 (NCT04241185). KEYTRUDA is also being evaluated in combination with Bacillus Calmette-Guerin (BCG) in patients with NMIBC in the Phase 3 KEYNOTE-676 (NCT03711032) trial.

About KEYNOTE-905/EV-303
KEYNOTE-905, also known as EV-303, is an open-label, randomized, multi-arm, controlled Phase 3 trial (ClinicalTrials.gov, NCT03924895) evaluating perioperative KEYTRUDA, with or without Padcev, versus surgery alone in patients with MIBC who are either not eligible for or declined cisplatin-based chemotherapy. The trial enrolled 595 patients who were randomized to receive either:

Arm A: Three cycles of neoadjuvant KEYTRUDA, followed by surgery to remove the bladder (radical cystectomy), followed by 14 cycles of adjuvant KEYTRUDA;
Arm B: Surgery alone;
Arm C: Three cycles of neoadjuvant KEYTRUDA plus enfortumab vedotin, followed by surgery to remove the bladder (radical cystectomy), followed adjuvantly by six cycles of KEYTRUDA plus enfortumab vedotin and then eight cycles of KEYTRUDA alone.
The primary objective of this trial is to compare EFS between arm C and arm B, defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes RC surgery or failure to undergo RC surgery in participants with residual disease, gross residual disease left behind at the time of surgery, local or distant recurrence as assessed by imaging and/or biopsy or death due to any cause. The key secondary objectives are to compare OS and the difference in pCR rate between arm C and arm B, as well as EFS, OS and the difference in pCR rate between arm A and arm B. The study remains ongoing to test hypotheses between arm A and arm B.

About bladder cancer
Bladder cancer is the ninth most common cancer worldwide, diagnosed in more than 614,000 patients each year globally. Muscle-invasive bladder cancer represents approximately 30% of all bladder cancer cases. The standard of care for patients with MIBC has been neoadjuvant cisplatin-based chemotherapy followed by surgery, which is shown to prolong survival. However, up to half of patients with MIBC are not eligible to receive cisplatin and face limited treatment options, typically undergoing surgery alone.

(Press release, Merck & Co, OCT 23, 2025, View Source [SID1234656949])

On October 23, 2025 CDR-Life, Inc., a biotechnology company developing highly selective T cell engagers (TCEs) to treat cancer and autoimmune diseases, reported the first clinical data showing that CDR404, the company’s lead M-gager TCE, achieved all four canonical pharmacodynamic (PD) hallmarks of TCE activity in patients with MAGE-A4+ solid tumors. The data, presented at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), in Boston, Massachusetts, highlights CDR404’s robust immune activation and early signals of clinical activity, including tumor stabilization and biomarker improvements in patients with ovarian cancers and synovial sarcomas.

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CDR404 is an antibody-based TCE designed to target intracellular tumor antigens presented on HLA molecules. It engages MAGE-A4 peptides displayed by HLA-A*02:01 on cancer cells and redirects CD3+ T cells for targeted tumor cell killing. The ongoing Phase 1 CDR404 trial (NCT06402201) is being conducted at leading cancer centers across the United States and Europe. Unlike conventional approaches utilizing T cell receptors, the proprietary M-gager platform leverages antibody-derived binding domains that combine exceptional specificity with strong potency, excellent developability and ease of manufacturing.

At initial dose levels of 100–200 μg, CDR404 triggered the full cascade of immune activation associated with effective TCE therapy, including CD8+ T cell activation and expansion, reprogramming to a memory phenotype and recruitment of lymphocytes into tumors. Notably, repeated dosing did not induce PD-1–mediated T cell exhaustion, suggesting sustained biological activity. In one patient, a transient tumor flare followed by stabilization was observed, which is consistent with tumor infiltration by cytotoxic T cells.

"These early data demonstrate that our M-gager platform can extend the precision and power of antibody-based T cell engagers to intracellular antigens, an area long thought to be accessible only to TCR-based modalities," said Christian Leisner, PhD, Chief Executive Officer of CDR-Life. "Seeing all four pharmacodynamic hallmarks of activity in patients even at low doses underscores the potential of this approach to redefine how we target solid tumors."

The study’s first-in-human dose was guided by quantitative systems pharmacology modeling, enabling detection of pharmacodynamic effects more quickly than traditional approaches. Based on these encouraging signals, the trial will begin to focus on patients with MAGE-A4–positive ovarian cancers, a population with high unmet need.

Additional analyses, including integrated pharmacokinetic-pharmacodynamic and circulating tumor DNA (ctDNA) data, are ongoing.

Presentation Details:
Title:

Hallmarks of pharmacodynamic activity of CDR404, a new antibody-derived T cell engager (TCE) targeted against MAGE-A4+ solid tumors in HLA-A02:01+ patients

Presenter:

Melissa Vrohlings, Head of Translational Science, CDR-Life

Date and Time:

October 23, 2025 | 12:30 – 4 pm ET

Location:

Poster Session A

Level 2, Exhibit Hall D

In addition to the poster presentation on CDR404, CDR-Life is also presenting a poster on CDR609, the company’s newest T cell engager clinical candidate that targets LGR5, a highly cancer-specific cell surface antigen widely expressed on common solid tumors.

Presentation Details:

Title:

CDR609: A First-in-Class LGR5-targeted T Cell Engager for treatment of Colorectal Cancer and other solid tumors

Presenter:

Sophie Barsin, Project Leader, CDR-Life

Date and Time:

October 23, 2025 | 12:30 – 4 pm ET

Location:

Poster Session A

Level 2, Exhibit Hall D

(Press release, CDR-Life, OCT 23, 2025, View Source [SID1234656966])

On October 23, 2025 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a late-stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat cancers and viral infections, reported it is working with Atlantic Health on an investigator-initiated Phase 1B/2 single-arm study evaluating Annamycin for third-line ("3L") treatment of advanced pancreatic cancer.

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Pancreatic cancer continues to present significant treatment challenges, being the cancer with the highest mortality rate globally and the seventh leading cause of cancer death. However, recent preclinical studies indicate that Annamycin may target critical factors associated with this disease, showcasing its potential as a novel therapeutic option.

Walter Klemp, Chairman and CEO of Moleculin, commented, "We are excited to work with Atlantic Health to advance the development of Annamycin for the treatment of pancreatic cancer. Their interest in funding and conducting this study stems from the compelling preclinical data presented at several American Association for Cancer Research (AACR) (Free AACR Whitepaper) conferences showing a high level of activity by Annamycin against pancreatic cancer and associated liver metastases in preclinical studies. We believe this may be related to Annamycin’s demonstrated high affinity for and ability to concentrate in the pancreas, especially considering the well-documented challenge of achieving adequate drug uptake to the pancreas with existing therapies. In addition, recent published data1 now reveal that the upregulation of topoisomerase II, the primary target of Annamycin, is highly correlated with poor survival in pancreatic cancer patients, so we have a highly validated target with pancreatic cancer. Coupled with Annamycin’s demonstrated lack of cardiotoxicity, which could enable, for the first time ever, the use of an anthracycline in chronic or maintenance therapies, we believe pancreatic cancer could be an important additional opportunity for Annamycin. Such maintenance therapy demonstrated promising results in a recently concluded clinical study with Annamycin for the treatment of soft tissue sarcoma metastasized to the lungs (MB-107)."

"This study further bolsters our efforts to advance and develop Annamycin through multiple investigator-initiated studies to unlock its potential as a treatment option for many other types of cancers," Mr. Klemp continued. "We continue to be encouraged by the preliminary preclinical data seen to date and believe Annamycin is a highly promising candidate for patients where there remains significant unmet need, such as pancreatic cancer."

"Pancreatic cancer remains one of the most devastating and difficult-to-treat malignancies, with limited options once patients progress beyond first- and second-line therapy," commented Dr. Angela Alistar, MD, Atlantic Health, the study’s principal investigator. "In particular, for the treatment options in the third-line setting, where survival rates are poor, no approved standard of care exists. We are committed to driving innovation in this space and based on the consistent safety and efficacy data, both clinically and preclinically, seen with Annamycin across a broad range of cancers, we believe this represents a great opportunity to address this high unmet need."

In connection with the planned study, Moleculin will supply Annamycin and be responsible for submitting and maintaining an Investigational New Drug Application (IND) with the U.S. Food and Drug Administration (FDA), and Dr. Alistar of Atlantic Health will be responsible for conducting the Phase 1B/2 study. Moleculin estimates the additional cost to run this trial from 2026 into 2030 (for long-term follow-up) will be approximately $1 million, mainly for drug supply and outside laboratory testing.

Annamycin, also known by its non-proprietary name of naxtarubicin, currently has Fast Track Status and Orphan Drug Designation from the FDA for the treatment of relapsed or refractory AML, in addition to Orphan Drug Designation for the treatment of STS lung mets. Furthermore, Annamycin has Orphan Drug Designation for the treatment of relapsed or refractory AML from the EMA.

Moleculin is currently conducting pivotal Phase 2B/3, multi-center, randomized, double-blind, placebo-controlled, adaptive design study of Annamycin in combination with cytarabine (also known as "Ara-C" and for which the combination of Annamycin and Ara-C is referred to as "AnnAraC") for the treatment of adult patients with acute myeloid leukemia (AML) who are refractory to or relapsed (R/R) after induction therapy (R/R AML). This Phase 3 "MIRACLE" trial (derived from Moleculin R/R AML AnnAraC Clinical Evaluation) is a global approval trial, including sites in the US, Europe and the Middle East.

For more information about the MIRACLE trial, visit clinicaltrials.gov and reference identifier NCT06788756. Additionally, the clinical trial in the EU is on euclinicaltrials.eu and the reference identifier there is 2024-518359-47-00.

(Press release, Moleculin, OCT 23, 2025, View Source [SID1234656950])

On October 23, 2025 Immunome, Inc. (Nasdaq: IMNM), a biotechnology company focused on developing first-in-class and best-in-class targeted cancer therapies, reported preclinical data showing its proprietary antibody-drug conjugate (ADC) payload HC74 overcomes multiple mechanisms of ADC resistance, including payload efflux and target heterogeneity.

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HC74 is a novel topoisomerase I inhibitor that serves as the payload in IM-1021, a ROR1-targeted ADC currently in a Phase 1 trial for solid and liquid tumors, and as the payload in several preclinical candidates within the Immunome pipeline.

The data were presented on Oct. 23, 2025, in a poster entitled "HC74, a novel topoisomerase I inhibitor payload for antibody-drug conjugates that overcomes multi-drug resistance" at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in Boston.

Highlights of the poster include:

Over-expression of drug efflux transporters such as ABCC1 and ABCB1 drives primary and acquired resistance to approved ADC payloads and standard chemotherapies but not to HC74
HC74 exhibits high membrane permeability, leading to enhanced cytotoxicity and robust bystander activity
ADCs incorporating HC74 show meaningful efficacy in multiple preclinical tumor models, including:
Colorectal cancer refractory to trastuzumab-DXd and irinotecan
Models with acquired resistance to trastuzumab-DXd
Non-small cell lung cancer with heterogenous target expression
"HC74 is designed to overcome key limitations of existing ADC payloads," said Immunome’s Chief Scientific Officer, Jack Higgins, Ph.D. "Clinical data show high levels of efflux transporters and target heterogeneity can reduce ADC efficacy. We believe HC74’s ability to overcome those resistance mechanisms supports its potential as a best-in-class payload. We look forward to advancing IM-1021 and our broader HC74 pipeline."

A copy of the poster is available in the "Events & Presentations" portion of Immunome’s website.

(Press release, Immunome, OCT 23, 2025, View Source [SID1234656967])