On August 18, 2025 Aptose Biosciences Inc. ("Aptose" or the "Company") (OTC: APTOF, TSX: APS), a clinical-stage precision oncology company developing the tuspetinib (TUS)-based triple drug frontline therapy to treat patients with newly diagnosed AML, reported a data update from the Phase 1/2 TUSCANY trial in newly diagnosed AML (Press release, Aptose Biosciences, AUG 18, 2025, View Source [SID1234655342]). The trial was initiated in December 2024, and the growing body of positive data includes the recently completed third cohort of 120 mg TUS in the TUS+VEN+AZA triplet therapy. Data to date from ten (10) patients across all three cohorts, 40 mg, 80 mg or 120 mg TUS dose in TUS+VEN+AZA, support the use of TUS with standard of care treatment across all AML populations, including those carrying mutations that are the most difficult to treat and those with mutated and unmutated (wildtype) FLT3 genes.

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The TUS+VEN+AZA triplet is being developed as a safe and well-tolerated mutation agnostic frontline therapy to treat large, mutationally diverse populations of newly diagnosed AML patients who are ineligible to receive induction chemotherapy. At the 120 mg TUS dose level in combination with VEN+AZA, as with the prior reported 40 mg and 80 mg TUS dose cohorts, no significant safety concerns or dose limiting toxicities (DLTs) have been observed in the TUSCANY trial, including no prolonged myelosuppression in Cycle 1 of subjects in remission, no reports of drug-related QTc prolongation or differentiation syndrome (DS), and no treatment-related deaths. Nine out of ten dosed patients remain on study across all dose cohorts and enrollment is being advanced to the 160 mg TUS dose level following the Cohort Safety Review Committee (CSRC) meeting.

"We already have data from three different TUS dose levels in the TUSCANY trial, and the data continue to strengthen at higher doses of TUS and over time. We are building a strong case for TUS+VEN+AZA as a triplet frontline therapy of choice to address a broad AML population, including subgroups with the most adverse of mutations," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose.

Data highlights:

Comparison of CR/CRh1 Response rates2-5:

VEN+AZA2 TUS+VEN+AZA
All subjects 65% 90% (9/10)
NPM1-mutant 67% 100% (2/2)
FLT3-ITD 61% 100% (2/2)
TP53-mutant 52% 100% (2/2)

Comparison of MRD-negativity6 rates among All Subjects and among CR/CRh Responders3:

VEN+AZA2,3 TUS+VEN+AZA
Among All Subjects 23.4% 70% (7/10)
Among CR/CRh Responders 40.9% 78% (7/9)

Comparison of MRD-negativity rates among more difficult-to-treat Patient Subpopulations defined as Lower Benefit (TP53-mutated) and Intermediate Benefit (FLT3-ITD or RAS-mutated) relative to VEN+AZA5:

VEN+AZA3,5 TUS+VEN+AZA
Intermediate Benefit 27.9% 100% (3/3)
Lower Benefit 14.5% 100% (2/2)

TUS+VEN+AZA – CR/CRh and MRD-negativity rates among Subjects with Adverse Mutations:

TP53, FLT3-ITD, RAS mutations: Achieved CR/CRh and MRD-negativity
100% (5/5)

"As illustrated in the data highlights, the addition of TUS to VEN+AZA appears to boost response rates and MRD-negativity while maintaining favorable safety and tolerability," said Rafael Bejar, M.D., Ph.D., Chief Medical Officer of Aptose, "and the 100% CR/CRh and 100% MRD-negativity rates among the five biallelic TP53-mutant, FLT3-ITD, and RAS-mutant AML cases are exciting to see, as this can correlate with longer overall survival. We have observed a trend towards achieving CRs more quickly at the higher dose levels, so we are keen to see the activity as we advance into the 160 mg TUS dose cohort."

Key messages:

Addition of TUS to VEN+AZA demonstrates excellent CR/CRh rates
100% CR/CRh among all subjects treated at 80 mg and 120 mg TUS dose levels
Appear to be achieving CR earlier with 120 mg TUS than with 40 mg or 80 mg
Addition of TUS to VEN+AZA demonstrates excellent MRD-negativity rates
MRD-negativity in 7 of 9 (78%) already achieved in patients who responded to therapy
Expect patient survival to be extended with continued long-term treatment
Excellent safety and well tolerated with no dose-limiting toxicities (No DLT) at completed dose levels
Broad-spectrum activity including patients with adverse TP53, RAS and FLT3-ITD mutations
No loss of MRD-negativity observed to date, including in one patient with over 7 months of follow up
MRD-negativity and remissions continue to mature over time on therapy
No relapses reported to date and no treatment related deaths
The only non-responder was a patient at the initial TUS dose level (40 mg) that did not achieve TUS exposures previously associated with response
Additional data are included in the new Aptose corporate presentation here.

TUSCANY: TUS+VEN+AZA Triplet Phase 1/2 Study

The tuspetinib-based TUS+VEN+AZA triplet therapy is being advanced in the TUSCANY Phase 1/2 trial with the goal of creating an improved frontline therapy for newly diagnosed AML patients that is active across diverse AML populations, durable, and well tolerated.

The TUSCANY triplet Phase 1/2 study, being conducted at 10 leading U.S. clinical sites by elite clinical investigators, is designed to test various doses and schedules of TUS in combination with standard dosing of AZA and VEN for patients with AML who are ineligible to receive induction chemotherapy. A convenient, once daily oral agent, TUS is being administered in 28-day cycles. Multiple U.S. sites are enrolling in the TUSCANY trial with anticipated enrollment of 18-24 patients by late 2025. Data will be released as it becomes available.

More information on the TUSCANY Phase 1/2 study can be found on www.clinicaltrials.gov (here: View Source).

On August 18, 2025 Merck & Co. reported that Ifinatamab deruxtecan (I-DXd) has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with extensive-stage small cell lung cancer with disease progression on or after platinum-based chemotherapy (Press release, Merck & Co, AUG 18, 2025, View Source [SID1234655360]).

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Ifinatamab deruxtecan is a specifically engineered, potential first-in-class B7-H3 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and Merck (NYSE: MRK), known as MSD outside of the United States and Canada.

The FDA BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat a serious condition and address a significant unmet medical need. The medicine is required to have shown encouraging preliminary clinical results that demonstrate substantial improvement on a clinically significant endpoint over currently available medicines.

The FDA granted the BTD based on data from the IDeate-Lung01 Phase 2 trial, with support from the IDeate-PanTumor01 Phase 1/2 trial. Results from the primary analysis of IDeate-Lung01 will be presented in a late-breaking oral presentation at the IASLC 2025 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (#WCLC25). This is the first BTD for ifinatamab deruxtecan and represents the first BTD since the start of the Daiichi Sankyo and Merck collaboration.

"This Breakthrough Therapy Designation granted by the FDA to ifinatamab deruxtecan highlights the urgent need for new treatment options for patients with pretreated extensive-stage small cell lung cancer," said Ken Takeshita, MD, global head, R&D, Daiichi Sankyo. "We are committed to advancing this medicine with the goal of bringing the first B7-H3 directed antibody drug conjugate to patients in order to transform the outcomes of those facing this aggressive disease."

"Patients living with extensive-stage small cell lung cancer often have limited therapeutic options following disease progression after standard of care treatments," said Eliav Barr, MD, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. "This Breakthrough Therapy Designation reinforces our confidence in the promise of ifinatamab deruxtecan to play an important role in the treatment of extensive-stage small cell lung cancer, and we are looking forward to sharing data at the upcoming IASLC 2025 World Conference on Lung Cancer that show the potential of this novel option."

About IDeate-Lung01

IDeate-Lung01 is a global, multicenter, randomized, open-label, two-part Phase 2 trial evaluating the safety and efficacy of ifinatamab deruxtecan in patients with extensive-stage small cell lung cancer who were previously treated with at least one prior line of platinum-based chemotherapy and a maximum of three prior lines of therapy. Patients with asymptomatic brain metastases (untreated or previously treated) were eligible.

In the first part of the trial (dose optimization), patients were randomized 1:1 to receive ifinatamab deruxtecan 8 or 12 mg/kg intravenously Q3W. In the second part of the trial (dose expansion), patients received ifinatamab deruxtecan 12 mg/kg intravenously Q3W.

The primary endpoint is objective response rate (ORR) as assessed by blinded independent central review (BICR) per RECIST v1.1. Secondary endpoints included duration of response, progression-free survival, disease control rate, time to response, overall survival, pharmacokinetics and safety. Intracranial ORR was assessed by BICR as an exploratory analysis.

IDeate-Lung01 enrolled 187 patients in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

About IDeate-PanTumor01

IDeate-PanTumor01 is a global, multicenter, first-in-human, open-label Phase 1/2 trial evaluating the safety and efficacy of ifinatamab deruxtecan in patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerable to standard treatment or for whom no standard treatment exists.

The Phase 1 part of the trial (dose escalation) is assessing the safety and tolerability of increasing doses of ifinatamab deruxtecan to determine the maximum tolerated dose and recommended dose for expansion (RDE). The Phase 2 part of the trial (dose expansion) is evaluating the safety and efficacy of ifinatamab deruxtecan at the RDE of 12 mg/kg in patients with squamous non-small cell lung cancer, metastatic castration-resistance prostate cancer or esophageal squamous cell carcinoma.

The dose escalation part of the trial is evaluating dose-limiting toxicity and safety. The dose expansion part of the trial is evaluating overall response rate, duration of response, disease control rate, progression-free survival, overall survival and safety. Pharmacokinetic endpoints, exploratory biomarker and immunogenicity endpoints will also be assessed.

IDeate-PanTumor01 enrolled approximately 250 patients in Asia and North America. For more information about the trial, visit ClinicalTrials.gov.

About small cell lung cancer

More than 2.48 million lung cancer cases were diagnosed globally in 2022. Small cell lung cancer (SCLC) is the second most common type of lung cancer, accounting for approximately 15% of cases. SCLC is aggressive and progresses rapidly to the distant metastatic stage, which has a low five-year survival rate. While conventional standard of care treatments for patients with advanced SCLC may help improve outcomes, there is a need for additional subsequent treatment approaches.

About B7-H3

B7-H3 is a transmembrane protein that belongs to the B7 family of proteins, which bind to the CD28 family of receptors that includes PD-1. B7-H3 is overexpressed in a wide range of cancer types, including SCLC, and its overexpression has been shown to correlate with poor prognosis, making B7-H3 a promising therapeutic target. There are currently no B7-H3 directed medicines approved for the treatment of any cancer.

About ifinatamab deruxtecan

Ifinatamab deruxtecan (I-DXd) is an investigational potential first-in-class B7-H3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ifinatamab deruxtecan is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Ifinatamab deruxtecan has been granted orphan drug designation by the U.S. FDA, European Commission, Japan Ministry of Health, Labour and Welfare and Taiwan Food and Drug Administration for the treatment of SCLC.

About the ifinatamab deruxtecan clinical development program

A comprehensive global clinical development program is underway evaluating the efficacy and safety of ifinatamab deruxtecan monotherapy and in combination with other anticancer medicines across multiple cancers.

On August 18, 2025 SystImmune Inc. (SystImmune), a clinical-stage biotechnology company, and Bristol Myers Squibb reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to izalontamab brengitecan (iza-bren) for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (Press release, Bristol-Myers Squibb, AUG 18, 2025, View Source;FDA-for-Patients-with-Previously-Treated-Advanced-EGFR-Mutated-Non-Small-Cell-Lung-Cancer/default.aspx [SID1234655343]).

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Iza-bren is a potential first-in-class bispecific antibody-drug conjugate (ADC) which targets both epidermal growth factor receptor and human epidermal growth factor receptor 3 (EGFRxHER3) with a topoisomerase 1 inhibitor payload. Iza-bren is being developed by Biokin in China and jointly developed by SystImmune and Bristol Myers Squibb under a collaboration and exclusive license agreement in territories outside of China.

The granting of BTD underscores the strength of these data and highlights the potential of iza-bren to address the significant clinical unmet need patients face after EGFR TKI and platinum-based chemotherapy treatment. While EGFR TKIs have shown clinical efficacy in the frontline setting, most patients eventually see their cancer progress after about 18 months. Subsequent treatment options often contain platinum-based chemotherapy, which are of limited efficacy and come with significant toxicities. Breakthrough Therapy Designation from the US FDA is intended to expedite the development and review of drugs that may demonstrate significant benefit over current standards of care.

The FDA’s decision was based on efficacy and safety data from three ongoing clinical trials: BL-B01D1-101 and BL-B01D1-203, conducted in China by Sichuan Biokin Pharmaceutical Co., Ltd., and the global BL-B01D1-LUNG-101 study conducted by SystImmune across the United States, Europe and Japan. Across these trials, iza-bren demonstrated evidence to suggest improved efficacy with a manageable safety profile in patients with EGFR-mutant NSCLC who had progressed after third-generation EGFR TKIs and platinum-based chemotherapy.

"The FDA’s granting of Breakthrough Therapy Designation underscores the potential of iza-bren to meaningfully improve clinical outcomes for patients with previously treated epidermal growth factor receptor mutation NSCLC," said Dr. Jonathan Cheng, Chief Medical Officer of SystImmune. "The data we have generated to date suggest that iza-bren could address a critical unmet need in patient care, and we look forward to working closely with the FDA to conduct the relevant clinical studies and seek regulatory approval."

About EGFRmt NSCLC

Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancer cases, which remains the leading cause of cancer-related death worldwide. Among patients with NSCLC, 10% to 15% in Western populations and up to 50% in Asian populations harbor activating EGFR mutations. These tumors, most commonly of non-squamous histology, initially respond to EGFR TKIs such as osimertinib. However, resistance is nearly universal, often occurring after about 18 months, and treatment options beyond TKIs and platinum-based chemotherapy provide limited clinical benefit with significant toxicities, highlighting the critical need for new, effective therapies.

About iza-bren

SystImmune, in collaboration with BMS outside of China, is developing iza-bren (BL-B01D1), a bispecific antibody-drug conjugate (ADC) that targets both EGFR and HER3 targets that are highly expressed in various epithelial cancers and are known to be associated with cancer cell proliferation and survival. Iza-bren’s dual mechanism of action blocks EGFR and HER3 signals to cancer cells, reducing proliferation and survival signals. In addition, upon antibody mediated internalization, iza-bren’s therapeutic payload is released causing genotoxic stress that leads to cancer cell death.

On August 18, 2025 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported agenda topics for its in-person R&D Day in conjunction with the company’s 10-Year Anniversary on September 8, 2025 in New York from 8:00-10:30am EST (Press release, Ideaya Biosciences, AUG 18, 2025, View Source [SID1234655361]).

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Members of IDEAYA’s senior leadership team will provide an overview of the company’s progress to date, including presentation of new clinical data on darovasertib in neoadjuvant uveal melanoma (UM), IDE849 (DLL3 TOP1 ADC) and IDE397 (MAT2A), and outline key areas of focus as part of their future growth strategy. Details of the R&D Day agenda are below.

Agenda topics

IDEAYA 10-Year Anniversary and R&D Day Introduction
Darovasertib (PKC)
Phase 2 Neoadjuvant UM Data in Plaque Brachytherapy-eligible Patients
IDE849 (DLL3 TOP1 ADC)
Phase 1 SCLC Data from the 2025 World Conference on Lung Cancer (WCLC)
Mechanistic Data from 2025 WCLC to Support Combination of TOP1-ADCs with IDE161/PARG
IDE397 (MAT2A)
Combination Rationale with Trodelvy (TROP2 TOP1 ADC) in MTAP-deletion solid tumors
Initial Phase 1 Clinical Data from IDE397/Trodelvy Combination in MTAP-deletion urothelial cancer
IDE892 (PRMT5)
Potentially Best-in-Class PRMT5 Profile and Combination Opportunity with IDE397 (MAT2A) in MTAP-deletion solid tumors
Application of AI/ML in Our Discovery Capabilities
Closing Remarks and Q&A
Joining IDEAYA’s leadership team at the R&D Day will be Dr. Arun D. Singh, Director of the Department of Ophthalmic Oncology at the Cole Eye Institute, Cleveland Clinic. Dr. Singh will present data from IDEAYA’s Phase 2 trial of darovasertib in the neoadjuvant setting of UM and discuss the design and objectives of IDEAYA’s recently initiated Phase 3 OptimUM-10 trial to support a potential approval in this indication.

A live question and answer session will follow the presentation. Registration for this event can be accessed here or through the IDEAYA website View Source

On August 18, 2025 Foresight Diagnostics, a leader in ultrasensitive minimal residual disease (MRD) detection, reported the publication of a landmark pooled analysis in the Journal of Clinical Oncology demonstrating that MRD analysis using Foresight CLARITY at end of therapy provided greater prognostic accuracy than PET/CT in large B-cell lymphoma (LBCL) (Press release, Foresight Diagnostics, AUG 18, 2025, View Source [SID1234655362]). The findings highlight the potential of ultrasensitive MRD testing as a robust and reliable tool for remission assessment following frontline treatment.

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The study integrated data from five prospective clinical studies and included 137 patients treated with curative-intent chemotherapy. MRD was measured using the Foresight CLARITY assay, which leverages PhasED-Seq, a next-generation circulating-tumor DNA detection technology capable of identifying fewer than one mutant molecule per million.1

Key findings from the study include:

ctDNA-MRD assessment was prognostic as early as after two cycles of frontline chemotherapy. Patients with undetectable MRD after 2 cycles achieved a 2-year progression-free survival (PFS) of 96% compared to 67% for patients with detectable MRD (hazard ratio 6.9; p=0.0025).

ctDNA-MRD assessment was most prognostic at end of therapy: 78% of patients were MRD-negative and had a 2-year PFS of 97%, compared to just 29% among MRD-positive patients (hazard ratio 28.7; p<0.0001). By comparison, PET/CT status at end of therapy was less predictive, with a hazard ratio of 3.6.

MRD status further stratified risk within both PET-negative and PET-positive groups at end of therapy. Patients with detectable MRD faced a higher risk of relapse even if their imaging was negative. Conversely, PET-positive patients with undetectable MRD had significantly better outcomes than patients with both positive imaging and MRD results.

Overall, Foresight CLARITY demonstrated 86% clinical sensitivity for relapse detection and 91% clinical specificity for remission at end of therapy, based on a median follow-up of 37 months.2
"These findings highlight the clinical value of achieving ctDNA-MRD negativity at the end of treatment and underscore the limitations of relying solely on PET/CT for remission assessment," said Dr. David Kurtz, Chief Medical Officer at Foresight Diagnostics and co-author on the analysis. "With the ultra-high sensitivity of Foresight CLARITY, we can detect disease that imaging misses, offering clinicians a more accurate and actionable tool for post-treatment risk stratification."

"Our study illustrates the potential of ctDNA-MRD detection to more precisely define remission in B-cell lymphoma," said Dr. Mark Roschewski, Senior Clinician and Deputy Branch Chief of the Lymphoid Malignancies Branch at the Center for Cancer Research and lead author of the publication. "The results support the incorporation of novel surrogate endpoints such as molecular response into prospective studies evaluating how they could aid clinical decisions following frontline therapy."

Ongoing trials are already evaluating ctDNA-guided treatment decisions in B-cell lymphoma. These include the ALPHA3 trial (NCT06500273), which is enrolling patients who achieve remission following frontline treatment but retain detectable ctDNA-MRD, and the SHORTEN-ctDNA study (NCT06693830), which is evaluating early ctDNA-MRD clearance as a potential marker to support frontline chemotherapy de-escalation.

Additionally, the results from this pooled analysis were included in Foresight’s clinical recommendations to the National Comprehensive Cancer Network (NCCN) and supported the December 2024 update to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for B-Cell Lymphomas, which incorporated ctDNA-MRD testing as a tool to adjudicate PET-positive end-of-therapy scans.3

The full manuscript, titled "Remission Assessment by Circulating Tumor DNA in Large B-Cell Lymphoma," is available online in the Journal of Clinical Oncology. These findings were previously presented at the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and the 2023 International Conference on Malignant Lymphoma (ICML).