On December 9, 2025 Enterome, a clinical-stage company pioneering OncoMimics, a new class of off-the-shelf, multi-targeted in vivo immune therapies that induce a fast and potent expansion of memory T-cells to fight cancer, reported highly encouraging updated interim data from two cohorts of patients with low tumor-burden follicular lymphoma in the ongoing SIDNEY Phase 2 trial of its lead OncoMimics immunotherapy EO2463. The data were presented at the 67th meeting of the American Society for Hematology (ASH) (Free ASH Whitepaper) in Orlando, Florida.

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In Cohort 3, 100% (6/6) ORR was achieved with EO2463 plus rituximab as first-line treatment for previously untreated patients with low tumor-burden follicular lymphoma in need of treatment. In this feasibility assessment among the 6 patients, 5 had a complete response, and one a partial response. The median time to OR was 17 weeks, and to CR 18 weeks. These results marked an improvement over preliminary data submitted in the abstract for ASH (Free ASH Whitepaper).

"These new results are encouraging, despite the limited number of patients. The potent and rapid expansion of specific CD8 T-cells induced by EO2463 supports our understanding that OncoMimics trigger memory T-cells to generate sustained immune responses. The data suggest that the combination therapy given as a first-line treatment in patients with low-tumor burden follicular lymphoma should be evaluated in further studies," said Dr Stephen Smith, principal study investigator at the Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA, who presented the data.

Data from Cohort 2 continue to show that EO2463 monotherapy produces excellent response rates when offered to patients with newly diagnosed follicular lymphoma or marginal zone lymphoma as an alternative to the standard watch-and-wait regime. Previously undisclosed data from 19 evaluable patients with follicular lymphoma showed a 52.6% ORR as of October. The ORR in the total group of 21 patients with follicular lymphoma or marginal zone lymphoma was 47.6% (14.3% CR and 33.3% PR). Current standard of practice is that, while patients often have visibly swollen lymph nodes, no treatment other than watchful waiting is suggested, as long as they do not show troublesome symptoms. Nevertheless, these patients often are understandably anxious about their disease, which progresses in the majority of cases, and then leads to a decreased quality of life.

"These new data with EO2463 contribute more compelling evidence and further strengthen our belief in the potential of our OncoMimics multi-targeted in vivo immune therapies for blood cancers. I’m looking forward to initiating Phase 3 testing of EO2463 in patients in the watch-and-wait setting in 2026," said Pierre Belichard, CEO of Enterome.

Follicular Lymphoma, one of several types of indolent Non-Hodgkin Lymphoma, is a difficult to treat chronic condition with relapses, characterized by slow progression and few symptoms, and reduced life expectancy. It is usually diagnosed by the appearance of swollen lymph nodes, and the early stages of the disease can be characterized by a lack of troublesome symptoms such as night sweats, fever or weight loss. There is a widespread consensus among leading investigators on the need for a well-tolerated and effective monotherapy to stop or slow progression for patients in the watch-and-wait setting.

EO2463 is an innovative, off-the-shelf OncoMimics active immunotherapy that combines four synthetic peptides. These non-self, microbial-derived peptides correspond to CD8 HLA-A2 epitopes that exhibit molecular mimicry with the B lymphocyte-specific lineage markers CD20, CD22, CD37, and CD268 (BAFF receptor). It also includes the helper peptide (CD4+ epitope) universal cancer peptide 2 (UCP2). The unique ability of EO2463 to selectively target multiple B cell markers enables the destruction of malignant B lymphocytes. By ensuring broad target coverage across malignant B cells, this novel approach aims to simultaneously improve safety and maximize efficacy, reducing the tumor cells’ capacity to develop immune-resistance mechanisms such as antigen escape.

OncoMimics consist of bacteria-derived peptide antigens that closely mimic tumor-associated antigens (TAAs) of solid tumors, or cell linage markers as for B cell lymphomas. These antigens induce a fast and potent in vivo expansion of cytotoxic memory CD8+ T cells that were primed by gut bacteria, and are cross-reactive with TAAs/B cell markers. Because the peptides are "non-self", OncoMimics avoid the self-tolerance that limits many cancer immunotherapies to enable rapid, potent, and durable responses to tumors. The synthetically produced peptides are designed in silico, mining Enterome’s proprietary database of 23 million commensal bacteria genes. Each product combines multiple high-affinity peptides to broaden target coverage and mitigate tumor heterogeneity.

OncoMimics are easy to manufacture, store, distribute and administer as an "off-the-shelf" subcutaneous injection. OncoMimics have achieved rapid and potent responses in clinical testing in over 230 patients to date, with a benign safety profile.

(Press release, Enterome, DEC 9, 2025, View Source [SID1234661312])

On December 9, 2025 Eli Lilly and Company (NYSE: LLY) reported results from the Phase 3 BRUIN CLL-313 clinical trial of Jaypirca (pirtobrutinib), a non-covalent Bruton tyrosine kinase (BTK) inhibitor, versus bendamustine plus rituximab (BR), in treatment-naïve patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) without 17p deletions. Pirtobrutinib met its primary endpoint demonstrating a reduction in the risk of disease progression or death by 80% (HR=0.20 [95% CI, 0.11-0.37]; p<0.0001).

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These data will be highlighted in a late-breaking oral presentation at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place in Orlando, Florida and simultaneously published in the Journal of Clinical Oncology.

"The results from BRUIN CLL-313 show a significant effect size, among the most pronounced ever observed for a single agent BTK inhibitor in a front-line CLL study," said Wojciech Jurczak, MD, PhD, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland. "The magnitude of the progression-free survival benefit, early overall survival trend and safety profile observed in BRUIN CLL-313 offer highly compelling evidence for the potential role of pirtobrutinib in treatment-naïve CLL."

BRUIN CLL-313 is the first prospective, randomized Phase 3 study examining the efficacy and safety of a non-covalent BTK inhibitor, pirtobrutinib, exclusively in patients with treatment-naïve CLL/SLL. BRUIN CLL-313 enrolled 282 patients with previously untreated CLL/SLL without del(17p), who were randomized 1:1 to receive continuous pirtobrutinib monotherapy (n=141) or BR (n=141). Crossover to the pirtobrutinib arm was allowed after independent review committee (IRC)-confirmed disease progression. The efficacy results are based on a July 11, 2025, data cutoff.

At a median follow-up of 28.1 months, the primary endpoint of IRC-assessed progression-free survival (PFS) was significantly improved with pirtobrutinib compared to BR (HR=0.20 [95% CI, 0.11–0.37]; p<0.0001). PFS results favored pirtobrutinib across all pre‑specified subgroups, including those with high-risk molecular features such as TP53 mutations, complex karyotype, and unmutated IGHV, and was consistently observed among investigator assessments.

Overall survival (OS), a key secondary endpoint, remains immature, but a trend favoring pirtobrutinib was observed (HR=0.257 [95% CI, 0.070–0.934]; p=0.0261) despite over half (52.9%) of patients treated with BR crossing over to receive pirtobrutinib after IRC-confirmed disease progression. Final testing of OS superiority is planned at a future date.

The overall safety profile of patients treated with pirtobrutinib in BRUIN CLL-313 was similar to previously reported trials. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 40.0% of patients who received pirtobrutinib versus 67.4% with BR. Fewer adverse event-related dose reductions (3.6% versus 31.1%) and TEAE-related discontinuations (4.3% versus 15.2%) were seen with pirtobrutinib versus BR. The incidence of all-grade and high-grade atrial fibrillation/flutter were similar between pirtobrutinib and BR, a notable finding as BR is not a regimen associated with increased risk of this side effect (1.4% versus 1.5% and 0.7% versus 0.8%, respectively).

"These findings support the potential use of pirtobrutinib in certain treatment-naïve patients and underscore its unique position as the only BTK inhibitor to show promise in treating both newly diagnosed patients with CLL or SLL and those who have progressed on a covalent BTK inhibitor," said Jacob Van Naarden, executive vice president and president, Lilly Oncology. "Alongside the recently presented BRUIN-CLL 314 results, we are excited about how collectively these data may advance the therapeutic landscape in treatment-naïve CLL and are hopeful we will receive regulatory approvals for pirtobrutinib in earlier disease settings sometime next year, further expanding treatment options for patients."

Lilly has begun submitting results from BRUIN CLL-313 and BRUIN CLL-314 studies to regulatory authorities with the goal of further expanding Jaypirca’s label into earlier lines of therapy.

Lilly is studying Jaypirca in CLL/SLL in multiple Phase 3 studies. Details on the trials can be found by visiting clinicaltrials.gov.

About BRUIN CLL-313
BRUIN CLL-313 is a Phase 3, global, randomized, open-label study of pirtobrutinib versus chemoimmunotherapy (bendamustine plus rituximab) in people with CLL/SLL without 17p deletions who have not been previously treated. The trial enrolled 282 patients who were randomized 1:1 to receive pirtobrutinib (200 mg orally, once daily) or bendamustine plus rituximab (BR) per labeled doses. BR is a chemoimmunotherapy regimen used in the treatment of CLL. The primary endpoint is PFS as assessed by blinded IRC. Secondary endpoints include investigator and IRC assessed overall response rate (ORR), duration of response (DoR), and PFS, OS, time to next treatment (TTNT), safety and tolerability and patient-reported outcomes (PRO).

About Jaypirca (pirtobrutinib)
Jaypirca (pirtobrutinib, formerly known as LOXO-305) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent (reversible) inhibitor of the enzyme BTK.1 BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).2,3 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity.

About Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are forms of slow-growing non-Hodgkin lymphoma that develop from white blood cells known as lymphocytes.4 CLL is one of the most common types of leukemia in adults.4 In the U.S., CLL accounts for about one-quarter of the new cases of leukemia and there will be approximately 23,690 new cases of CLL diagnosed this year.4,5 SLL is identical to CLL from a pathologic and immunophenotypic standpoint, with the main difference between them being the location of the cancer cells.4 In CLL, the cancer cells are present in the blood, and in SLL, the cancer cells are found in the lymph nodes.4

INDICATIONS FOR JAYPIRCA (pirtobrutinib)
Jaypirca is indicated for the treatment of

Adult patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have previously been treated with a covalent BTK inhibitor.
Adult patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical trial benefit in a confirmatory trial.
IMPORTANT SAFETY INFORMATION FOR JAYPIRCA (pirtobrutinib)

Infections: Fatal and serious infections (including bacterial, viral, fungal) and opportunistic infections occurred in Jaypirca-treated patients. Across clinical trials, Grade ≥3 infections occurred (25%), most commonly pneumonia (20%); fatal infections (5%), sepsis (6%), and febrile neutropenia (3.8%) occurred. In patients with CLL/SLL, Grade ≥3 infections occurred (32%), with fatal infections occurring in 8%. Opportunistic infections included Pneumocystis jirovecii pneumonia and fungal infection. Consider prophylaxis, including vaccinations and antimicrobial prophylaxis, in patients at increased risk for infection, including opportunistic infections. Monitor for signs and symptoms, evaluate, and treat. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Hemorrhage: Fatal and serious hemorrhage has occurred with Jaypirca. Across clinical trials, major hemorrhage (Grade ≥3 bleeding or any central nervous system bleeding) occurred (2.6%), including gastrointestinal hemorrhage; fatal hemorrhage occurred (0.3%). Bleeding of any grade, excluding bruising and petechiae, occurred (16%). Major hemorrhage occurred when taking Jaypirca with (2.0%) and without (0.6%) antithrombotic agents. Consider risks/benefits of co-administering antithrombotic agents with Jaypirca. Monitor for signs of bleeding. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca. Consider withholding Jaypirca 3-7 days pre- and post-surgery based on surgery type and bleeding risk.

Cytopenias: Jaypirca can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. Across clinical trials, Grade 3 or 4 cytopenias, including decreased neutrophils (27%), decreased platelets (13%), and decreased hemoglobin (11%), developed. Grade 4 decreased neutrophils (15%) and Grade 4 decreased platelets (6%) developed. Monitor complete blood counts regularly. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Cardiac Arrhythmias: Cardiac arrhythmias occurred in patients taking Jaypirca. Across clinical trials, atrial fibrillation or flutter were reported in 3.4% of Jaypirca treated patients, with Grade 3 or 4 atrial fibrillation or flutter in 1.6%. Other serious cardiac arrhythmias such as supraventricular tachycardia and cardiac arrest occurred (0.4%). Cardiac risk factors such as hypertension or previous arrhythmias may increase risk. Monitor and manage signs and symptoms of arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea). Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Second Primary Malignancies: Across clinical trials, second primary malignancies, including non-skin carcinomas, developed in 9% of Jaypirca-treated patients, most frequently non-melanoma skin cancer (4.4%). Other second primary malignancies included solid tumors (including genitourinary and breast cancers) and melanoma. Advise patients to use sun protection and monitor for development of second primary malignancies.

Hepatotoxicity, Including Drug-Induced Liver Injury (DILI): Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of DILI, has occurred in patients treated with BTK inhibitors, including Jaypirca. Evaluate bilirubin and transaminases at baseline and throughout Jaypirca treatment. For patients who develop abnormal liver tests after Jaypirca, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold Jaypirca. If DILI is confirmed, discontinue Jaypirca.

Embryo-Fetal Toxicity: Jaypirca can cause fetal harm. Administration of pirtobrutinib to pregnant rats caused embryo-fetal toxicity, including embryo-fetal mortality and malformations at maternal exposures (AUC) approximately 3-times the recommended 200 mg/day dose. Advise pregnant women of fetal risk and females of reproductive potential to use effective contraception during treatment and for one week after last dose.

Adverse Reactions (ARs) in Patients Who Received Jaypirca

The most common (≥30%) ARs in the pooled safety population of patients with hematologic malignancies (n=704) were decreased neutrophil count (54%), decreased hemoglobin (43%), decreased leukocytes (32%), fatigue (31%), decreased platelets (31%), decreased lymphocyte count (31%), calcium decreased (30%).

Mantle Cell Lymphoma

Serious ARs occurred in 38% of patients, with pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), hemorrhage (2.3%), pleural effusion (2.3%), and sepsis (2.3%) occurring in ≥2% of patients. Fatal ARs within 28 days of last dose occurred in 7% of patients, most commonly due to infections (4.7%), including COVID-19 (3.1% of all patients).

Dose Modifications and Discontinuations Due to ARs: Dose reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. Permanent discontinuation in >1% of patients included pneumonia.

Most common ARs (≥15%) and Select Laboratory Abnormalities (≥10%) (all Grades %; Grade 3-4 %): hemoglobin decreased (42; 9), platelet count decreased (39; 14), neutrophil count decreased (36; 16), lymphocyte count decreased (32; 15), creatinine increased (30; 1.6), fatigue (29; 1.6), musculoskeletal pain (27; 3.9), calcium decreased (19; 1.6), diarrhea (19; -), edema (18; 0.8), dyspnea (17; 2.3), AST increased (17; 1.6), pneumonia (16; 14), bruising (16; -), potassium decreased (13; 1.6), sodium decreased (13; -), lipase increased (12; 4.4), ALT increased (11; 1.6), potassium increased (11; 0.8), alkaline phosphatase increased (11; -). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (10), platelets decreased (7), lymphocytes decreased (6).

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma from Single-Arm and Randomized Controlled Clinical Trials

Serious ARs occurred in 47-56% of patients across clinical trials. Serious ARs in ≥5% of patients in the single-arm trial were pneumonia (18%), COVID-19 (9%), sepsis (7%), febrile neutropenia (7%). Serious ARs in ≥3% of patients in the randomized controlled trial were pneumonia (21%), COVID-19 (5%), sepsis (3.4%). Fatal ARs within 28-30 days of last Jaypirca dose occurred in 8-11% of patients, most commonly due to infections (7-10%), including sepsis (5%), COVID-19 (2.7-5%), and pneumonia (3.4%).

Dose Modifications and Discontinuations Due to ARs: Dose reductions in 3.6-10%, treatment interruption in 42-51%, and permanent discontinuation of Jaypirca in 9-17% of patients. Permanent discontinuation in >1% of patients included second primary malignancy, pneumonia, COVID-19, neutropenia, sepsis, anemia, and cardiac arrythmias.

Most common ARs and Select Laboratory Abnormalities (≥20%) (all Grades %, Grade 3-4 %)–in a randomized controlled trial: neutrophil count decreased (54; 26), hemoglobin decreased (45; 10), platelet count decreased (37; 17), pneumonia (28; 16), ALT increased (25; 1.8), creatinine increased (25; -), calcium decreased (23; 0.9), sodium decreased (22; 0.9), bilirubin increased (21; 0.9), upper respiratory tract infections (21; 0.9); in a single-arm trial: neutrophil count decreased (63; 45), hemoglobin decreased (48; 19), calcium decreased (40; 2.8), fatigue (36; 2.7), bruising (36; -), cough (33; -), musculoskeletal pain (32; 0.9), platelet count decreased (30; 15), sodium decreased (30; -), COVID-19 (28; 7), pneumonia (27; 16), diarrhea (26; -), abdominal pain (25; 2.7), lymphocyte count decreased (23; 8), ALT increased (23; 2.8), AST increased (23; 1.9), creatinine increased (23; -), dyspnea (22; 2.7), hemorrhage (22; 2.7), lipase increased (21; 7), alkaline phosphatase increased (21; -), edema (21; -), nausea (21; -), pyrexia (20; 2.7), headache (20; 0.9). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (23).

Drug Interactions

Strong CYP3A Inhibitors: Concomitant use increased pirtobrutinib systemic exposure, which may increase risk of Jaypirca ARs. Avoid using strong CYP3A inhibitors with Jaypirca. If concomitant use is unavoidable, reduce Jaypirca dose according to approved labeling.

Strong or Moderate CYP3A Inducers: Concomitant use decreased pirtobrutinib systemic exposure, which may reduce Jaypirca efficacy. Avoid using Jaypirca with strong or moderate CYP3A inducers. If concomitant use with moderate CYP3A inducers is unavoidable, increase Jaypirca dose according to approved labeling.

Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP Substrates: Use with Jaypirca increased their plasma concentrations, which may increase risk of ARs related to these substrates for drugs sensitive to minimal concentration changes. Follow recommendations for these sensitive substrates in their approved labeling.

Use in Specific Populations

Pregnancy and Lactation: Due to potential for Jaypirca to cause fetal harm, verify pregnancy status in females of reproductive potential prior to starting Jaypirca. Presence of pirtobrutinib in human milk is unknown. Advise women to use effective contraception and to not breastfeed while taking Jaypirca and for one week after last dose.

Geriatric Use: In the pooled safety population of patients with hematologic malignancies, patients aged ≥65 years experienced higher rates of Grade ≥3 ARs and serious ARs compared to patients <65 years of age.

Renal Impairment: Because severe renal impairment increases pirtobrutinib exposure, reduce Jaypirca dose in these patients according to approved labeling.

PT HCP ISI MCL_CLL Q42025

Please see Prescribing Information and Patient Information for Jaypirca.

(Press release, Eli Lilly, DEC 9, 2025, View Source [SID1234661311])

On December 9, 2025 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of emavusertib (CA-4948), an orally available, small molecule IRAK4 and FLT3 inhibitor, reported updated clinical data from the ongoing frontline Acute Myeloid Leukemia (AML) triplet study (CA-4948-104) in a poster presentation at the 67th ASH (Free ASH Whitepaper) Annual Meeting (ASH) (Free ASH Whitepaper).

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The AML triplet study is evaluating the addition of emavusertib (ema) to the combination of venetoclax and azacitidine (ven-aza) in AML patients who have achieved complete remission on ven-aza but remain MRD-positive (MRD+), with the goal of enabling patients to achieve uMRD. The first two cohorts in the study evaluate patients who received emavusertib for either 7 or 14 days in a 28-day cycle, in addition to their ven-aza treatment regimen.

In the ASH (Free ASH Whitepaper) abstract, the company reported initial data showing 4 of 8 patients (50%) had achieved uMRD as of July 2, 2025. These data were updated in the poster presented at ASH (Free ASH Whitepaper) with 5 of 8 patients (62.5%) achieving uMRD, with no change in safety profile, as of October 12, 2025.

"These data are very promising and warrant further evaluation of additional triplet (ema/ven/aza) regimens to determine the optimal dose and schedule for safety and efficacy to improve patient outcomes in a difficult to treat population," said James Dentzer, Curis’s Chief Executive Officer.

(Press release, Curis, DEC 9, 2025, View Source [SID1234661310])

On December 9, 2025 Clarity Pharmaceuticals (ASX: CU6) ("Clarity" or "Company"), a clinical-stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for patients with cancer, reported the acceptance of an abstract and poster on the Phase II DISCO trial (NCT04438304)1 data exploring 64Cu-SARTATE in patients with known or suspected neuroendocrine tumours (NETs) to the prestigious American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal (GI) Cancers Symposium 2026 held on the 8-10th January. The abstract is titled "Diagnostic performance of 64Cu-SARTATE compared to 68Ga-DOTATATE in patients with known or suspected neuroendocrine tumors with focus on liver findings".

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The data to be presented builds on some of the previously announced results2 that 64Cu-SARTATE positron emission tomography (PET) / computed tomography (CT) lesion detection was substantially higher than that of the current standard-of-care (SOC), 68Ga-DOTATATE PET/CT. 64Cu-SARTATE was deemed safe and well tolerated. Out of 45 participants enrolled in the trial, only seven (15.6%) trial participants experienced a total of nine 64Cu-SARTATE-related adverse events: eight were Grade 1 and one was Grade 2, with most resolving within 2 days.

The mean number of lesions detected by 64Cu-SARTATE was approximately double that observed with 68Ga-DOTATATE (441 vs. 227 lesions, respectively; averages across readers and both PET/CT timepoints for 64Cu-SARTATE). Overall, a total of 238 discordant lesions (lesions that were only detected by one of the scans, either 64Cu-SARTATE or 68Ga-DOTATATE PET/CT) were identified in 34 subjects with scan pairs across all body regions, representing a large difference between detection abilities of the two agents. Of these discordant lesions, 223 were detected by 64Cu-SARTATE alone and only 15 by 68Ga-DOTATATE alone. Importantly, for the 122 discordant lesions with evaluable standard of truth ([SOT] biopsy and/or follow-up conventional imaging), the difference in sensitivity between the agents was highly significant, favouring 64Cu-SARTATE (the sensitivities of 64Cu-SARTATE vs. 68Ga-DOTATATE were 94.7% [95% CI 65.1, 99.5] and 5.4% [95% CI 0.5, 34.9], respectively; p<0.001). This clearly demonstrates the considerable difference in sensitivity between 64Cu-SARTATE and SOC imaging, based on lesions detected by either of the agents, showing that 64Cu-SARTATE detected significantly more additional true-positive lesions compared to 68Ga-DOTATATE in the same patients.

New data which is being presented at ASCO (Free ASCO Whitepaper) GI shows that the liver had the highest number of lesions detected by both tracers among all organs/regions assessed: 64Cu-SARTATE PET/CT scans showed 352 lesions while 68Ga-DOTATATE PET/CT only showed 180 lesions. The liver is the most common metastatic site for patients with gastroenteropancreatic (GEP)-NETs, and hepatic metastatic burden is clinically important as it is strongly associated with patient outcomes and significantly influences the clinical management of the disease3. Therefore, the enhanced diagnostic performance offered by 64Cu-SARTATE, especially in key organs such as the liver, may allow clinicians to make treatment decisions with a greater degree of accuracy and confidence, with direct impact on patient outcomes. A Phase III study of 64Cu-SARTATE is being planned.

Clarity’s Executive Chairperson, Dr Alan Taylor, commented, "We are thrilled to continue generating valuable data, building further evidence of the best-in-class potential of our pipeline of products in development. As we are moving SARTATE towards commercialisation, it highlights our commitment to developing products for cancer indications with high unmet needs.

"Patients with NETs are often misdiagnosed and experience delays in receiving the correct diagnosis, which may lead to the identification of their cancer at later stages4. Visualising NET lesions earlier and more accurately at various stages of disease, especially in a critical organ like the liver, may have a significant impact on patient outcomes as it equips clinicians with crucial information on disease burden, helping to determine an optimal treatment plan.

"There are currently two key approved agents in the NETs PET imaging space, 68Ga-DOTATATE and 64Cu-DOTATATE, and both have substantial limitations when it comes to providing accurate and timely disease identification. These two products utilise the same chelator (i.e. cage), called DOTA, to hold diagnostic radioisotopes, while binding somatostatin receptor 2 (SSTR2), which is highly expressed in NETs. The key difference between the two agents is the isotope used to image patients, gallium-68 or copper-64. As we have seen with 68Ga-DOTATATE in the DISCO trial, its sensitivity was very low among discordant lesions, meaning several lesions would go undetected until they grew larger in size, if at all. This limitation is primarily due to the short half-life of gallium-68 which underpins the requirement for imaging within 1 hour post-administration. We have seen first-hand that once radiopharmaceutical products are administered, they take time to find the lesion whilst also needing to clear from non-target organs, providing greater contrast, known as tumour-to-background ratio5. Having greater contrast is especially important to identify smaller or more difficult to find cancers. This is where the benefits of using copper-64 with its longer half-life play an important role. However, despite using copper-64, 64Cu-DOTATATE has an important disadvantage where the DOTA chelator leaks copper in vivo6. Free copper-64 isotopes then accumulate in the liver, creating substantial background noise on PET scans which renders identification of lesions in the liver challenging. This is a key drawback with important clinical implications, as the presence of liver metastatic lesions is a notable prognostic factor in survival of these NET patients3.

"64Cu-SARTATE offers considerable advantages compared to approved SSRT2-targeted imaging agents, addressing some of their fundamental limitations and potentially providing patients and clinicians a chance to more accurately identify disease. As with all our products, we continue to rely on strong scientific foundations to develop 64Cu-SARTATE, design its clinical trials and progress the agent towards commercialisation. While employing the same SSTR2 targeting molecule as the existing competitors, which have established safety and efficacy, we have circumvented the issue of copper leakage with the sarcophagine (SAR) cage, enabling optimal imaging timepoints. The proprietary SAR Technology, developed through outstanding Australian benchtop science from the Australian National University and the University of Melbourne, is able to securely hold copper, ensuring there is minimal background in the liver. The combination of optimal imaging timepoints, enabled by copper-64, and secure chelating of the isotopes, made possible by the SAR Technology, is what clearly differentiates 64Cu-SARTATE from the competition, with the benefit of earlier and/or more accurate identification of lesions in NETs.

"With the improved diagnostic performance of 64Cu-SARTATE, based on data generated to date, and the potential of improving treatment outcomes of patients with NETs through reliable and accurate disease identification, we are already planning a registrational Phase III trial of 64Cu-SARTATE in NETs, aiming to expedite this unique agent to market."

About DISCO trial
DISCO is a "Diagnostic Imaging Study of 64COpper-SARTATE Using PET on Patients with Known or Suspected Neuroendocrine Tumours". It assessed the performance of Clarity’s SARTATE imaging product as a potential new method to diagnose and manage NETs. The trial aimed to build on earlier clinical experience with 64Cu-SARTATE in patients with NETs, which demonstrated that the diagnostic has excellent imaging characteristics and suggested that 64Cu-SARTATE PET/CT provides comparable or superior lesion detection to 68Ga-DOTATATE PET/CT in all patients, especially in the liver5.

DISCO recruited 45 participants with Gastroenteropancreatic NETs (GEP-NETs) across 4 sites in Australia, comparing the diagnostic performance of 64Cu-SARTATE PET at an average of 4 hours (between 3 and 5 hours) and approximately 20 hours post-administration (same-day and next-day imaging, respectively) to the current SOC, 68Ga-DOTATATE PET. Out of the 45, there were 41 participants with known NETs and 4 cases of suspected NETs. Most subjects had stage 3 or 4 disease.

Participants were required to have undergone a pre-study 68Ga-DOTATATE PET/CT scan within 5 weeks, but not closer than 6 hours prior to the administration of 64Cu-SARTATE as part of their routine clinical care.

About SARTATE
SARTATE is a next generation, highly targeted theranostic radiopharmaceutical. It is being developed for diagnosing, staging and subsequently treating cancers that express SSTR2, such as NETs. Like all Clarity products, the SARTATE product can be used with copper-64 (64Cu) for imaging (64Cu-SARTATE) or copper-67 (67Cu) for therapy (67Cu-SARTATE).

Disclaimer
64Cu-SARTATE is an unregistered product. The safety and efficacy of 64Cu-SARTATE have not been assessed by health authorities such as the US Food and Drug Administration or the Therapeutic Goods Administration. There is no guarantee that this product will become commercially available.

About NETs
NETs, also known as well-differentiated neuroendocrine neoplasms or carcinoids, represent a heterogeneous group of malignant transformations of cells of the diffuse neuroendocrine system7. They most commonly occur in the gastrointestinal tract (48%), lung (25%), and pancreas (9%), but may also originate in other areas, including the breast, prostate, thymus and skin8. NETs can either be benign or malignant, as well as non-functional and functional9. NETs traditionally have been considered uncommon; however, the incidence has been increasing as a worldwide phenomenon10.

Overall, it is estimated that more than 20,000 people in the United States are diagnosed with a NET each year11, and approximately 190,000 people are living with this diagnosis12. Patients with NETs present with subtle clinical symptoms, which can lead to a delay in diagnosis of more than 4 years13. As such, about 30-75% of NETs patients have distant metastases at the time of diagnosis14. A 10-year relative survival rate for patients with metastatic GEP-NETs is 3–36%.

(Press release, Clarity Pharmaceuticals, DEC 9, 2025, View Source [SID1234661309])

On December 9, 2025 BioNTech SE (Nasdaq: BNTX, "BioNTech") and Bristol Myers Squibb Company (NYSE: BMY, "BMS") reported the first interim data from a global randomized Phase 2 trial (NCT06449222) evaluating pumitamig (BNT327/BMS986545), an investigational bispecific antibody targeting PD-L1 and VEGF-A, plus chemotherapy in patients with locally advanced/metastatic triple-negative breast cancer ("TNBC") irrespective of PD-L1 expression levels.

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The data showed encouraging anti-tumor responses and a manageable safety profile for pumitamig plus chemotherapy in first-line and second-line treatment setting. The data will be presented at the 2025 San Antonio Breast Cancer Symposium ("SABCS").

"Triple-negative breast cancer is a highly aggressive disease with a poor prognosis and 5-year survival rate of just 15% in advanced stages.1 There remains an urgent need for new treatment options – particularly for patients with PD-L1 low or negative tumors (CPS<10), a subgroup for whom the current standard of care is chemotherapy alone and existing PD-(L)1 inhibitors have historically shown limited benefit," said Peter Schmid, M.D., Ph.D., Lead Investigator and Director of the Breast Cancer Centre at St. Bartholomew’s Hospital, London, UK. "The anti-tumor efficacy observed in this interim analysis is encouraging and supports the ongoing investigation of pumitamig in the Phase 3 ROSETTA BREAST-01 trial."

The trial evaluated pumitamig in two dose levels and in combination with four different chemotherapeutic agents in the first- and second-line treatment of participants with locally advanced/metastatic TNBC. In Cohort 1, reported in this analysis, patients received pumitamig (15 or 20 mg/kg Q2W) plus nab-paclitaxel until disease progression or unacceptable toxicity. In Cohort 2, patients received the flat-dose equivalent of 20 mg/kg in combination with three different chemotherapy regimens (Arm 1: paclitaxel; Arm 2: gemcitabine + carboplatin; Arm 3: eribulin).

The interim analysis at the October 1, 2025 data cut-off included 74 patients with 1L/2L+ locally advanced/metastatic TNBC who received pumitamig in combination with standard of care chemotherapy. Key data highlights are provided below:

Efficacy:

Among 39 efficacy-evaluable first-line and second-line patients, all in Cohort 1, the confirmed objective response rate ("cORR") was 61.5% (24/39), the unconfirmed objective response rate ("uORR") was 71.8% (28/39) and the disease control rate ("DCR") was 92.3% (36/39).
Efficacy was encouraging across dose levels, PD-L1 expression levels and lines of treatment and higher doses correlated with higher response (dose levels: uORR: 63.2% at 15 mg/kg dose; 80.0% at 20 mg/kg dose; PD-L1 expression levels: uORR: 70.6% in CPS ≥10; 70.6% in CPS <10; lines of treatment: uORR: 76.5% in 1L and 68.2% in 2L).
The progression-free survival ("PFS") rate at 9 months was 59.3%. Median PFS, median duration of response ("DOR") and median overall survival ("OS") were not mature at the time of analysis.
Safety:

Pumitamig plus chemotherapy demonstrated a manageable safety profile in both Cohorts in combination with all four chemotherapy regimens.
Grade ≥3 treatment-related adverse events (TRAEs) were reported in 17/40 (42.54%) and 13/34 (38.2%) patients in Cohorts 1 and 2, respectively, with no pumitamig-related deaths reported.
"We are encouraged by these first locally advanced/metastatic TNBC data from a global patient population that indicate the potential of pumitamig in patients with advanced TNBC irrespective of PD-L1 status," said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. "The activity we see in TNBC is consistent with findings in other solid tumors and further supports the pan-tumor potential of pumitamig, which we are advancing together with BMS in a broad development program that also includes novel/novel combination regimens."

"These data add to the growing evidence from global pumitamig studies across multiple indications," said Anne Kerber, Senior Vice President, Head of Development, Hematology, Oncology, Cell Therapy at Bristol Myers Squibb. "The encouraging results are especially meaningful in patients with PD-L1 low or negative tumors (CPS<10), representing the potential of pumitamig to deliver meaningful benefit across PD-L1 expression levels, including patients who historically have had fewer effective treatments."

A global randomized Phase 3 trial, ROSETTA-BREAST-01 (NCT07173751), is evaluating pumitamig plus chemotherapy versus placebo plus chemotherapy in patients with previously untreated locally advanced/metastatic TNBC determined ineligible for PD-(L)1 therapy based on PD-L1 negative disease. Pumitamig is also being studied in more than 20 clinical trials as monotherapy, in combination with chemotherapy, or with other novel treatment modalities in more than 10 solid tumor indications.

About the BNT327-02 Phase 2 clinical trial
The global randomized, open-label Phase 2 clinical trial (BNT327-02; NCT06449222) evaluated pumitamig (BNT327/ BMS986545) in combination with chemotherapeutic agents in the first- and second-line treatment of participants with locally advanced/metastatic TNBC. In Cohort 1, patients received pumitamig Q2W (15 or 20 mg/kg) plus chemotherapy (nab-paclitaxel) until disease progression or unacceptable toxicity. In Cohort 2, patients received the flat dose equivalent of 20 mg/kg in combination with chemotherapy (Arm 1: paclitaxel Q2W; Arm 2: gemcitabine + carboplatin Q3W; Arm 3: eribulin Q3W). The primary endpoints of the trial were objective response rate (ORR) per investigator’s assessment (RECIST 1.1), change in tumor size and early tumor shrinkage, and safety per NCI CTCAE v5.0. Secondary endpoints include duration of response (DoR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS).

About Triple-Negative Breast Cancer
Triple-negative breast cancer (TNBC), which is defined by a lack of hormone receptors (estrogen or progesterone) and HER2 protein, accounts for about 10-15% of all invasive breast cancer cases.1 It is an aggressive type of breast cancer that tends to grow and spread faster and has a worse prognosis compared to other breast cancer types. The addition of PD-(L)1 immune checkpoint inhibitors to chemotherapy for the first-line treatment of TNBC has improved outcomes in patients with high levels of PD-L1 expression (CPS ≥ 10) on the surface of tumor cells, but many patients experience relapse. In addition, for patients with PD-L1 negative TNBC (CPS<10), the current standard of care is chemotherapy alone, as other PD-(L)1 inhibitors have historically demonstrated poor efficacy in this subgroup. The 5-year survival rate for patients with advanced TNBC is only 15%, emphasizing the need for new treatment options.1

About pumitamig (also known as BNT327 or BMS986545)
Pumitamig is a novel investigational bispecific antibody, jointly developed by BioNTech and BMS, combining two complementary, validated mechanisms in oncology into one single molecule. Pumitamig combines PD-L1 checkpoint inhibition aimed at restoring T cells’ ability to recognize and destroy tumor cells with the neutralization of VEGF-A. The blocking of VEGF-A is aimed at reversing the tumor’s immuno-suppressive effect in its microenvironment and cutting off the blood and oxygen supply that feeds tumor cells (anti-angiogenesis effect), with the intention of preventing the tumor from growing and proliferating. Pumitamig may be differentiated via its mechanism of action of targeting PD-L1 on tumor cells to localize anti-VEGF activity within the tumor microenvironment, aiming to enhance therapeutic precision and minimize systemic exposure.

More than 1,400 patients have been treated with pumitamig in clinical trials to date. More than 20 clinical trials are currently ongoing or planned to evaluate pumitamig either as a monotherapy or in combination with other treatment modalities targeting different oncogenic pathways in more than 10 solid tumor indications. Multiple global trials are ongoing or planned to start, including five global clinical trials with registrational potential evaluating pumitamig plus chemotherapy compared to standard of care treatments in first-line small cell lung cancer (ROSETTA LUNG-01; NCT06712355), first-line non-small cell lung cancer (ROSETTA LUNG-02; NCT06712316), first-line triple-negative breast cancer (ROSETTA BREAST-01, NCT07173751), first-line microsatellite stable colorectal cancer (ROSETTA CRC-203; NCT07221357), and first-line gastric cancer (ROSETTA GASTRIC-204, NCT07221149). Additional trials are ongoing exploring novel treatment combinations of pumitamig, including combinations with BioNTech’s proprietary antibody-drug conjugate candidates ("ADCs") or immunomodulator candidates.

(Press release, BioNTech, DEC 9, 2025, View Source [SID1234661308])