On May 5, 2025 NANOBIOTIX (Euronext: NANO –– NASDAQ: NBTX – the ‘‘Company’’), a late-stage clinical biotechnology company pioneering nanotherapeutic approaches to improve treatment outcomes for patients with cancer, reported the presentation of full results from the completed dose escalation and dose expansion phases of a Phase 1 study evaluating JNJ-1900 (NBTXR3) in patients with locally advanced or borderline resectable pancreatic cancer (Press release, Nanobiotix, MAY 5, 2025, View Source [SID1234652514]). The study, conducted by The University of Texas MD Anderson Cancer Center ("MD Anderson"), was presented by principal investigator Dr. Eugene Koay at the 2025 Annual Meeting of the European Society for Radiotherapy and Oncology (ESTRO 2025).

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Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, driven by aggressive tumor biology and limited responsiveness to standard therapies. For patients with locally advanced ("LAPC") or borderline resectable ("BRPC") disease, the current standard-of-care ("SOC")—induction chemotherapy followed by chemoradiation—rarely delivers curative outcomes, underscoring the need for novel treatment approaches.

"Patients with locally advanced or borderline resectable pancreatic cancer face a particularly urgent unmet need for therapeutic innovation that can provide a meaningful survival benefit with an acceptable safety profile," said Eugene Koay, MD, PhD, Associate Professor of Radiation Oncology at MD Anderson. "We are encouraged by the results from the completed cohorts and look forward to the continued evaluation of JNJ-1900 (NBTXR3) in combination with standard-of-care chemoradiation after induction chemotherapy."

PRESENTATION #E25-2265: NANORAY Pancreas: A Phase 1 Study of NBTXR3 (JNJ-1900) Activated by Radiotherapy for Locally Advanced or Borderline Resectable Pancreatic Cancer (LAPC or BRPC)
Koay EJ, Liu S, Guerrero P, Stokes E, Katz MHG, Ikoma N, Snyder RA, Tzeng CD, Overman MJ, Pant S, Wolff RA, Javle M, Holliday EB, Ludmir EB, Das P, Noticewala S, Koong AC, Tamm EP, Bhutani M

This MD Anderson-sponsored Phase 1 study evaluated the potential of radiotherapy("RT")-activated JNJ-1900 (NBTXR3) activated by radiation therapy (45 Gy in 15 fractions) to overcome inherent radioresistance in patients with LAPC or BRPC. The majority of patients in the study (20/22) were diagnosed with locally advanced, unresectable disease (LAPC). For clarity, patients with LAPC or BRPC are traditionally treated with induction chemotherapy followed by concurrent chemoradiation. The treatment regimen in the completed dose escalation and dose expansion parts of this Phase 1 study replaced concurrent chemoradiation with RT-activated JNJ-1900 (NBTXR3) after induction chemotherapy.

Key Results:

Favorable safety profile and injection feasibility were observed (n=22)
Median overall survival ("mOS"): 23 months from diagnosis [95% CI; 17 months – not reached]
For context, an MD Anderson historical review of 144 patients with LAPC treated at the same center showed a mOS of 19.2 months. Patients in the historical review received induction chemotherapy followed by RT with or without concurrent or maintenance chemotherapy (80% received RT with concurrent chemotherapy)
Median local progression-free survival ("mLPFS"): 13.3 months from completion of radiation
Two LAPC patients achieved R0 surgical resection
Exploratory Biomarker Analyses:

Of the 20 patients for whom circulating Tumor Mutational Burden (cTMB) data was available, a notable proportion (40%; 8/20) exhibited increased cTMB, and investigators observed an association between increased cTMB and improved LPFS and OS
Normalization of CA19-9, a surrogate for overall survival benefit, was observed in 59% of patients (11/22) and was associated with longer survival in the study.
For context, an MD Anderson historical review of 243 patients with LAPC treated at the same center showed normalization of CA19-9 in approximately 17% of patients treated with the standard of care who had elevated CA19-9 levels at diagnosis
Based on the safety and preliminary efficacy findings, investigators concluded that further evaluation of JNJ-1900 (NBTXR3) is warranted in a randomized study.

"Our collaboration with MD Anderson has always been driven by a shared commitment to exploring bold new approaches for patients with high unmet need," said Louis Kayitalire, MD, Chief Medical Officer at Nanobiotix. "Given the extremely poor survival rates in LAPC and BRPC, the results from this Phase 1 study give us confidence in the potential of JNJ-1900 (NBTXR3) to serve as a meaningful addition to the treatment landscape. We are particularly excited about the potential to further enhance outcomes through combination of JNJ-1900 (NBTXR3) with SOC chemoradiation in the study’s new active cohort, and we look forward to advancing this program in pancreatic cancer."

MD Anderson received FDA clearance to expand the study to include a new cohort that combines of JNJ-1900 (NBTXR3) with SOC concurrent chemoradiation after induction chemotherapy. The first patient in the new cohort has been injected, and recruitment is ongoing.

On May 5, 2025 Lantern Pharma Inc. (Nasdaq: LTRN), an artificial intelligence company developing targeted and transformative cancer therapies using its proprietary AI platform, RADR, reported that it has received clearance of its Investigational New Drug Application (IND) from the U.S. Food and Drug Administration (FDA) for a Phase 1b/2 clinical trial for LP-184 in Triple Negative Breast Cancer (Press release, Lantern Pharma, MAY 5, 2025, View Source [SID1234652530]). This achievement builds on the previous regulatory momentum including Orphan Drug Designation in 2023 and Fast Track Designation in 2024.

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Strategic Trial Design to Address Critical Treatment Gap in TNBC

The innovative dual-approach in the clinical trial is designed to evaluate LP-184 in recurrent, advanced-stage TNBC patients through:

Monotherapy Arm: An open-label study involving approximately 30 patients with advanced-stage TNBC, focusing on dose optimization to evaluate, enhance and optimize safety and potential efficacy for TNBC patients.
Combination Therapy: Evaluation of LP-184 in combination with olaparib in second-line settings for patients with advanced-stage TNBC harboring BRCA1 or BRCA2 alterations, with primary endpoints including safety and efficacy parameters that could potentially support a pathway to regulatory approval.
This strategic approach focuses on addressing a significant unmet medical need, with average survival for newly diagnosed metastatic TNBC estimated at 10 to 18 months, representing an annual market opportunity exceeding $4 billion USD.

LP-184 Background in TNBC & Mechanistic Rationale

LP-184 is a synthetically lethal small molecule that induces DNA double strand breaks upon bioactivation by the enzyme prostaglandin reductase 1 (PTGR1) in cancer cells. Preclinical studies and artificial intelligence-driven in silico modeling suggest that cancers with DDR gene alterations may preferentially respond to LP-184.2

Preclinical findings also suggest that LP-184 is particularly well positioned for TNBC with striking data from in vivo models including complete regression seen in several PARP resistant as well as PARP sensitive PDXs (see Figure 1).

Nearly 70% of TNBCs are noted to harbor deficiency in homologous recombination pathways, making them likely to be particularly sensitive tumors for targeting with drug-candidate LP-184. In addition, it is estimated that up to 46% percent of women with TNBC will develop brain metastasis3, and LP-184 has shown blood brain barrier (BBB) penetration, with evidence of activity in preclinical brain metastasis models.

LP-184 Phase 1b/2 TNBC Trial Overview – Monotherapy

The monotherapy phase 1b/2 trial is designed to evaluate LP-184 in patients with advanced-stage TNBC. The study is designed to focus on dose optimization to evaluate and enhance both safety and potential efficacy ultimately aiding in the potential determination of the best clinical position for LP-184 in advanced-stage TNBC patients. The design of the dose optimization phase, provides for evaluation of the safety, efficacy and pharmacokinetics of LP-184 using 2 dose levels in an open-label monotherapy study involving around 30 patients to be dosed with LP-184.

LP-184 Phase 1b/2 TNBC Trial Overview – Combination Therapy with PARP inhibitor

LP-184 has also been shown in preclinical studies to be highly potent in combination with the PARP inhibitor, olaparib, including in tumors that are resistant to PARP inhibitors. In preclinical studies, treatment of a HBCx-28 TNBC PDX model, with BRCA-1 LOH and an HRD score of 63 that was resistant to the PARP inhibitor, showed evidence of re-sensitization in combination with LP-184 (See Figure 2). These data, which were initially presented at the San Antonio Breast Cancer Symposium, support the clinical evaluation of LP-184 in combination with PARPi in an earlier line of treatment. Treating patients in an earlier clinical setting has the potential to reach more patients and potentially generate a more durable and deeper earlier control of the disease.

The design of the combination phase 1b/2 trial provides for LP-184 to be evaluated in a second-line setting in patients with advanced-stage TNBC whose primary tumor harbors alterations in BRCA1 or BRCA2. The primary end points of the study are expected to include safety and efficacy, with the aim of supporting a potential pathway to a regulatory approval process.

Multi-Region Clinical Strategy with Focus on High-Incidence Countries

The trials are planned to be conducted at select centers in the United States as well as academic cancer centers and institutions in India and Nigeria, where TNBC incidence rates are particularly high—comprising nearly 40% of initial breast cancer diagnoses. This strategic site selection is focused on leveraging established collaborative research networks that have a track record of successful collaborative cancer studies with US and European pharma companies. Lantern’s planned objective will be to ensure proper local experience and support for this clinical trial while addressing regions with significant disease burden and high clinical demand.

"This IND clearance for LP-184 in a Phase 1b/2 study represents a pivotal advancement in our mission to bring precisely targeted, AI-developed medicines to patients with aggressive cancers and limited treatment options," said Panna Sharma, CEO and President of Lantern Pharma. "The strategic design of our clinical program reflects both the compelling mechanistic rationale and the encouraging data supporting LP-184’s potential in TNBC."

Expanding Therapeutic Potential Across Multiple Indications

Beyond TNBC, LP-184 shows promise for the potential treatment of other cancers harboring DNA damage repair mutations, including lung, bladder, pancreatic, and ovarian cancers. Additional clinical trials in these targeted indications are in planning stages, with several being considered as Investigator Initiated Trials. LP-184 has received multiple Orphan Drug, Fast Track, and Rare Pediatric Disease Designations from the FDA across various solid tumor indications.

The global TNBC market is estimated at $3-5 billion USD annually, with over 300,000 new cases diagnosed worldwide each year. While homologous recombination deficient TNBCs are often initially treated with PARP inhibitors, resistance inevitably develops, underscoring the critical need for novel therapeutic approaches.

On May 5, 2025 Aptose Biosciences Inc. ("Aptose" or the "Company") (TSX: APS; OTC: APTOF), a clinical-stage precision oncology company, reported updated and new data from Aptose’s Phase 1/2 TUSCANY trial in newly diagnosed acute myeloid leukemia (AML) patients dosed with a 40 mg or 80 mg dose of tuspetinib (TUS) in combination with standard of care dosing of venetoclax and azacitidine (TUS+VEN+AZA triplet) (Press release, Aptose Biosciences, MAY 5, 2025, View Source [SID1234652497]). The TUS+VEN+AZA triplet is being developed as a safe and mutation agnostic frontline therapy to treat large, mutationally diverse populations of newly diagnosed AML patients who are ineligible to receive induction chemotherapy.

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Earlier this year, Aptose announced the initiation of the TUSCANY trial and dosing in newly diagnosed AML patients at an initial dose of 40 mg TUS in the first cohort of four patients. The second cohort of patients is now receiving 80 mg TUS. Data from the first two cohorts, with a 40 mg or 80 mg dose of tuspetinib in the TUS+VEN+AZA combination, reveal promising clinical safety and antileukemic activity.

To date, four newly diagnosed AML patients received the initial dose of TUS (40 mg) as part of the (TUS+VEN+AZA) combination.
Notably, a patient with biallelic TP53 mutations and a complex karyotype (TP53-mutated/CK) and FLT3-wildtype achieved a complete remission (CR) and the clinical site reported no measurable residual disease (MRD-negative status) in this patient.
One FLT3-wildtype patient having an IDH-2 mutation achieved a CR and MRD-negative status.
Another FLT3-wildtype patient achieved a CRi during Cycle 1 and MRD-negative status.
The first three patients continue on treatment, while a fourth patient did not respond at this 40 mg dose level of TUS and was discontinued.
The 40 mg dose of the TUS+VEN+AZA triplet remains safe, and no dose-limiting toxicities (DLTs) have been reported.
To date, three newly diagnosed AML patients having diverse mutation profiles have received the 80 mg of TUS, as part of the TUS+VEN+AZA combination. The 80 mg TUS dose has been considered the optimal dose that has demonstrated safety and consistent blood exposure levels that exert potent antileukemic activity.
All patients achieved blast reductions in Cycle 1 that met the criteria for complete remissions (CR or CRi) and continue on treatment.
Notably, another TP53-mutated/CK and FLT3-wildtype patient achieved blast reductions that met CRi criteria in Cycle 1 and is now receiving additional therapy in Cycle 2.
The second patient, having FLT3-wildtype status, achieved a CR.
The third patient, having FLT3-ITD and NPM1 mutations and entering the trial with a 75% bone marrow blast count, achieved a CRi.
All three patients are early in their course of treatment and are expected to show further improvements in their disease status as they are all continuing with treatment, and MRD status will be monitored as the patients move through their courses of therapy.
The 80 mg dose of TUS, as part of the TUS+VEN+AZA triplet, continues to show favorable safety with no dose-limiting toxicities (DLTs) having been reported.
"The treatment paradigm for AML is shifting to triplet combination therapy," said Rafael Bejar, M.D., Ph.D., Chief Medical Officer of Aptose. "We have always maintained that tuspetinib, with its notable safety profile and ability to treat the larger, difficult-to-treat AML populations with high-risk mutations, could be an ideal drug for a triplet combination therapy in the frontline setting. With the majority of patients already achieving complete responses — including early responses in patients with adverse mutations — the clinical findings to date are bearing that out."

William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose, will review the data at a presentation today, Monday, May 5th, 2025, 3:00 p.m. EDT, at the 2025 Bloom Burton & Co. Healthcare Investor Conference. The presentation and webcast can be accessed here and will be available on the Aptose website.

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

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. Earlier APTIVATE trials of TUS as a single agent and in combination as TUS+VEN demonstrated favorable safety and broad activity in diverse relapsed or refractory (R/R) AML populations that went beyond the more prognostically favorable NPM1 and IDH mutant subgroups. Responses to TUS were also observed in those with prior-VEN and prior-FLT3 inhibitor (FLT3i) therapies, those with highly adverse TP53 and RAS mutations, and those with mutated or unmutated (wildtype) FLT3 genes.

The TUSCANY triplet Phase 1/2 study 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 will be administered in 28-day cycles, beginning at 40mg once daily, with dose escalations planned after a safety review of each dose level. Multiple U.S. sites are enrolling in the TUSCANY trial with anticipated enrollment of 18-24 patients by mid-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).

On May 5, 2025 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported financial results and operational updates for the quarter ended March 31, 2025 (Press release, ORIC Pharmaceuticals, MAY 5, 2025, View Source [SID1234652515]).

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"In the first quarter, we made significant progress across our pipeline, announced focused registrational development plans for our two lead programs, extended our cash runway, and accelerated key corporate milestones," stated Jacob M. Chacko, M.D., president and chief executive officer. "Looking ahead, we expect to share multiple clinical data updates across both programs over the next fifteen months. We remain on track to initiate the first Phase 3 trial of ORIC-944 in mCRPC in the first half of 2026, with registrational development of ORIC-114 in first-line NSCLC expected to begin later that year."

First Quarter 2025 and Other Recent Highlights

ORIC-944: a potent and selective allosteric inhibitor of PRC2

Reported encouraging early safety and efficacy data in ongoing dose escalation trial for ORIC-944 in combination with apalutamide in patients with metastatic castration resistant prostate cancer (mCRPC).
Presented preclinical ORIC-944 data demonstrating synergistic activity and improved progression-free survival (PFS) when combined with androgen receptor pathway inhibitors (ARPIs) in models of prostate cancer at the 2025 AACR (Free AACR Whitepaper) Annual Meeting.
Announced updated program milestones and development plans to initiate first Phase 3 registrational trial for ORIC-944 in mCRPC in 1H 2026.
ORIC-114: a brain penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor

Announced a clinical trial collaboration and supply agreement with Johnson & Johnson and initiated a trial to evaluate ORIC-114 in combination with subcutaneous (SC) amivantamab for the 1L treatment of patients with non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations.
Announced updated program milestones and registrational development plans to focus ORIC-114 in 1L NSCLC and plans to initiate first Phase 3 trial in 2026.
Corporate Highlights:

Extended projected cash runway into 2027 (from previous guidance of late 2026), and accelerated/augmented corporate milestones, based upon favorable enrollment and focused registrational clinical development plans for two lead programs.
Anticipated Program Milestones:

ORIC anticipates the following upcoming milestones:

ORIC-944 (mCRPC):
1H 2025: Combination dose escalation data with AR inhibitors(s)
2H 2025: Updated combination dose escalation data with AR inhibitors(s)
4Q 2025 / 1Q 2026: Combination dose optimization data with AR inhibitor(s)
ORIC-114 (NSCLC):
2H 2025: 1L EGFR exon 20, 2L EGFR exon 20, 2L+ HER2 exon 20 and 2L+ EGFR atypical data
Mid-2026: 1L EGFR exon 20 combination with SC amivantamab and 1L EGFR atypical data
First Quarter 2025 Financial Results

Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments totaled $223.8 million as of March 31, 2025, which is expected to fund the current operating plan into 2027.
R&D Expenses: Research and development (R&D) expenses were $24.6 million for the three months ended March 31, 2025, compared to $22.0 million for the three months ended March 31, 2024, an increase of $2.7 million. The increase was due to a net increase in external expenses related to the advancement of product candidates, as well as higher personnel costs, including additional non-cash stock-based compensation.
G&A Expenses: General and administrative (G&A) expenses were $8.1 million for the three months ended March 31, 2025, compared to $7.0 million for the three months ended March 31, 2024, an increase of $1.0 million. The increase was primarily due to higher personnel costs, including additional non-cash stock-based compensation.

On May 5, 2025 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and precision medicine, reported the results of a study led by Stanford University School of Medicine for the evaluation of Signatera, Natera’s personalized molecular residual disease (MRD) test, in patients with soft tissue and bone sarcomas (Press release, Natera, MAY 5, 2025, View Source [SID1234652531]). Results of the study (Utilizing Circulating Tumor DNA to Monitor Sarcoma Treatment and Recurrence) were presented at the 2025 Society of Surgical Oncology (SSO) Annual Meeting in March.

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With evaluation of approximately 200 patients and more than 2,100 plasma samples across multiple distinct subtypes, this is the largest sarcoma cohort to date using personalized circulating-tumor DNA (ctDNA) monitoring. The study assessed the correlation of Signatera results with imaging, stratified by sarcoma subtype, and followed patients through treatment, disease progression, and surveillance.

Key findings included:

The results demonstrated excellent test performance, with overall sensitivity to recurrence of 89% and specificity of 100%.
In leiomyosarcoma, the most common subtype in the cohort, sensitivity was 93%, with specificity of 100%.
For leiomyosarcoma patients who experienced progression, ctDNA kinetics during subsequent therapy were highly correlated with treatment response (90%).
Sarcomas are a heterogeneous group of rare cancers, with more than 70 distinct histologic subtypes1, making treatment response and recurrence especially difficult to monitor through standard imaging and clinical evaluation. There are approximately 17,000 new cases of sarcoma diagnosed annually in the United States.2

"This data represents a major step forward in understanding how ctDNA monitoring can be applied across a diverse range of sarcoma subtypes," said Beatrice J. Sun, M.D., department of surgery at Stanford University. "With the ability to noninvasively detect disease recurrence and monitor treatment response, Signatera demonstrates the potential to meaningfully improve personalized care for patients with sarcoma."

"This is the most comprehensive dataset to date on ctDNA monitoring in sarcoma, and it shows excellent performance of Signatera in a difficult-to-monitor cancer," said Alexey Aleshin, M.D., corporate chief medical officer and general manager of oncology at Natera. "The heterogeneity of sarcoma demands a personalized approach, and these results support Signatera’s unique ability to track disease status with precision across a broad spectrum of subtypes."

This retrospective real-world study demonstrates the promise of Signatera as a tool to monitor disease recurrence and treatment response. To build on these findings, the team intends to launch a prospective study to further demonstrate Signatera’s clinical utility and explore its role in informing treatment decisions and improving future sarcoma care.

About Signatera

Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard of care tools, and help optimize treatment decisions. The test is available for clinical and research use and has coverage by Medicare across a broad range of indications. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 100 peer-reviewed papers.