On June 13, 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 positive topline results from the diagnostic Phase II SABRE trial (NCT05407311)1 with 64Cu-SAR-Bombesin in participants with PSMA-negative BCR of prostate cancer following definitive therapy (Press release, Clarity Pharmaceuticals, JUN 13, 2025, View Source [SID1234653843]). SAR-Bombesin targets the GRPR present on cells of a range of cancers, including prostate cancer.

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SABRE trial design
SABRE (Copper-64 SAR-Bombesin in Biochemical Recurrence of prostate cancer) was a Phase II multi-centre, single arm, non-randomised, open-label copper-64 labelled SAR-Bombesin PET imaging trial of patients with PSMA-negative BCR of prostate cancer following definitive therapy. To be considered for inclusion in the study, candidates were required to demonstrate negative or equivocal findings for prostate cancer on approved PSMA PET (68Ga-PSMA-11 or 18F-DCFPyL), anatomical imaging (CT and/or magnetic resonance imaging [MRI]) and any other SOC imaging, if available. The primary objectives of the trial were to investigate the safety and tolerability of the product as well as its ability to correctly detect recurrence of prostate cancer.

Study participants were dosed with 200 MBq of 64Cu-SAR-Bombesin and underwent PET/CT scans at 1-4 hours and 24 ± 6 hours post-dose (same-day and next-day imaging, respectively). The scans were interpreted by three blinded central readers. To determine the efficacy of 64Cu-SAR-Bombesin imaging, the same-day and next-day PET/CT results of the central readers were assessed against a composite reference standard that was determined by an independent, blinded, central expert panel. The reference standard consisted of histopathology, follow-up SOC imaging and/or confirmed prostate-specific antigen (PSA) response to focal therapy.

The primary efficacy endpoints were participant-level CDR (defined as the proportion of true-positive participants out of all scanned participants who had at least one evaluable reference standard datapoint collected) and region-level PPV (defined as the proportion of true-positive regions out of all positive regions on the 64Cu-SAR-Bombesin PET/CT scan with corresponding evaluable composite reference standard data), assessed independently for same-day and next-day imaging timepoints.

The design of the SABRE study followed advice from regulators to achieve the highest standards in clinical research in the BCR setting. Based on this guidance, the expert panel, who determined the reference standard, was blinded to the results of the 64Cu-SAR-Bombesin scans and distinct from the central readers assessing the 64Cu-SAR-Bombesin scans. This approach removed potential biases in the assessment of the reference standard, which was not the case for other studies conducted in this setting.

The SABRE study design also adopted a conservative approach to the analysis of both co-primary endpoints. If a lesion identified on the 64Cu-SAR-Bombesin scan was not biopsied, and it was also not present on follow-up SOC imaging (a suboptimal reference standard with known low sensitivity and in a patient population that was negative on SOC imaging at screening), it was considered as false-positive in the analysis by default.

Topline results
Fifty-three patients with negative or equivocal SOC scans at screening (which included approved PSMA PET and anatomical imaging) were enrolled and imaged. Forty-seven participants were evaluable for the primary efficacy endpoints. Approximately half of the participants enrolled had PSA less than or equal to 1.0 ng/mL at study entry.

The average detection rate across readers using 64Cu-SAR-Bombesin PET/CT was 35.2% on same-day imaging (24.5%-43.4% range) and 27.7% on next-day imaging (17%-37.7% range). Approximately 47 lesions were identified on same-day imaging (40-59 range) and approximately 52 on next-day imaging (24-95 range), despite these patients having negative or equivocal SOC scans prior to study entry, highlighting the potential clinical benefit that imaging with 64Cu-SAR-Bombesin can provide. The most common site of lesion detection was in the lymph nodes (LNs) and the prostate regions.

The participant-level CDR was 14.9% (95% CI: 6.2, 28.3) on same-day imaging and ranged from 4.3% to 14.9% (95% CI: 0.5-28.3) on next-day imaging across the readers. Region-level PPV ranged from 22.6% to 47.1% (95% CI: 9.6-72.2) on same-day imaging and from 22.2% to 37.5% (95% CI: 2.8-61.7) on next-day imaging.

The CDR and PPV results were substantially impacted by the large number of lesions that were detected on the 64Cu-SAR-Bombesin scans, but unable to be verified due to the lack of effective diagnostic options available for comparison and biopsy not being clinically appropriate in most cases. Three patients underwent biopsy (the ‘gold standard’ for verifying lesions) due to the findings of the 64Cu-SAR-Bombesin scan and a total of four biopsies were performed. All biopsies were positive for prostate cancer, including two pelvic LNs, one extra-pelvic LN and one bone lesion.

Administration of 64Cu-SAR-Bombesin at 200 MBq was shown to be safe and well tolerated. Only two participants had AEs related to 64Cu-SAR-Bombesin with all being mild (Grade 1) and resolving within 2 days of onset.

Case study
A participant with BCR of prostate cancer presented with a baseline PSA of 22.3 ng/mL, negative SOC PSMA PET (18F-DCFPyL, Figure 1, left image) and equivocal CT at screening. Imaging with 64Cu-SAR-Bombesin (middle image) revealed substantial disease burden with lesions detected in the pelvic LNs, extra-pelvic LNs, visceral/soft tissue, and bone. Subsequent biopsies of a right pelvic bone lesion and a supradiaphragmatic LN confirmed malignancy at both sites. A follow-up 18F-DCFPyL PET scan, conducted approximately 4 months after the screening with 18F-DCFPyL, failed to detect lesions in all regions except for the bone.

Clarity’s Executive Chairperson, Dr Alan Taylor, commented, "The SABRE trial represents an important milestone for Clarity, setting a new benchmark by seeking to identify lesions that do not express PSMA. This trial, which is Clarity’s first sponsored study with 64Cu-SAR-Bombesin, has now shown that this product can provide a solution where the current diagnostic options fall short and improve lesion detection beyond what is achievable with SOC PSMA-targeted imaging. Prostate cancer is characterised by significant biological heterogeneity, where some patients, or even individual lesions within the same patient, may lack PSMA expression and remain undetectable on PSMA-targeted imaging. A PET agent targeting an alternative receptor, such as GRPR, which is expressed in up to 100% of prostate cancers2-6, may allow for better staging and hence more accurate treatment of BCR prostate cancer. As seen in the SABRE trial, some patients have widespread metastatic disease that remains completely undetectable by all available SOC imaging for extended periods. These patients deserve access to advanced diagnostic tools, such as 64Cu-SAR-Bombesin PET, that can reveal otherwise hidden disease and open the door to more informed and effective treatment options.

"We are very pleased with these results of the SABRE trial as a first look into this extraordinary patient population that has virtually invisible disease using SOC imaging and therefore, by definition, a very high unmet medical need. The data confirms that 64Cu-SAR-Bombesin is safe, well tolerated, and effective at detecting prostate cancer recurrence. Up to approximately 43% of participants had a positive 64Cu-SAR-Bombesin PET/CT, demonstrating the potential scale of the diagnostic gap this novel agent may help address with no disease identified by SOC imaging. These results are also corroborated by the findings of an earlier investigator-initiated trial (IIT), BOP, conducted by Prof Louise Emmett at St Vincents Hospital Sydney, where 64Cu-SAR-Bombesin PET/CT identified disease recurrence in 44% of participants with BCR of prostate cancer and negative or equivocal 68Ga-PSMA-11 PET/CT7.

"The lack of any suitable diagnostic options for these men is made clear by the difficulty faced in validating lesions detected by 64Cu-SAR-Bombesin. Given we identified a large number of lesions with our product, it was not feasible nor ethical to verify all lesions with biopsy. Verification of the findings by other means, such as SOC imaging, was further complicated by the very nature of the trial, which specifically enrolled patients who were negative or equivocal on all available SOC imaging. These inherent challenges led to a high number of lesions not being confirmed as true-positives in the study. However, the fact that prostate cancer was confirmed in all 64Cu-SAR-Bombesin PET-positive lesions that were biopsied strongly reinforces the potential clinical value of this agent and the need it may fulfill within the current diagnostic landscape. SABRE has provided valuable insights into the performance of 64Cu-SAR-Bombesin relative to available SOC imaging. The study findings, including the potential for significantly improved lesion detection, will be carefully considered in the design of a registrational trial.

"We now have three exceptional diagnostic agents in various stages of clinical development, 64Cu-SAR-bisPSMA, 64Cu-SARTATE and 64Cu-SAR-Bombesin, and all three are showing impressive efficacy compared to SOC imaging. We look forward to sharing additional data readouts from all trials and progressing discussions with key medical experts to determine the most effective pathway for registration, particularly with this asset, 64Cu-SAR-Bombesin, as the pathway to commercialisation for 64Cu-SAR-bisPSMA and 64Cu-SARTATE is clearly defined and quickly progressing. We have already explored additional indications expressing GRPR with high unmet needs where 64Cu-SAR-Bombesin may significantly improve the diagnostic landscape, and we have seen some promising data on the benefits of 64Cu-SAR-Bombesin PET/CT in breast cancer patients from the C-BOBCAT IIT, also conducted by Professor Louise Emmett. Results from this study showed high lesion uptake of 64Cu-SAR-Bombesin in women with lobular subtype of metastatic breast cancer in comparison to SOC imaging (i.e. CT, bone scan and 18F-FDG PET/CT), indicating that our imaging agent could offer improved diagnostic options in this indication8.

"These encouraging findings from the SABRE, BOP and C-BOBCAT trials, as well as other trials with GRPR-targeted agents in other cancers, highlight the broad potential of 64Cu-SAR-Bombesin to become a best-in-class diagnostic agent in a number of indications. This reinforces our drive to advance Targeted Copper Theranostics in areas of significant clinical need, as these areas lack not only accurate diagnostics, but also effective therapeutics. The detection of GRPR-expressing cancers could represent a significant opportunity to enable more comprehensive disease assessment across varied tumour phenotypes. We look forward to working with key regulatory groups, such as the US Food and Drug Administration (FDA), to explore various avenues and indications with SAR-Bombesin further as we continually strive to improve diagnostic and theranostic options for patients and their clinicians."

About SAR-Bomesin
64Cu-SAR-Bombesin is a highly targeted pan-cancer radiopharmaceutical with broad cancer application. It targets the GRPR present on cells of a range of cancers, including but not limited to prostate, breast and ovarian cancers. GRPR is found in up to 100% of prostate cancers, including prostate cancers that don’t express PSMA (PSMA-negative)2-6. The product utilises Clarity’s proprietary sarcophagine (SAR) technology that securely holds copper isotopes inside a cage-like structure, called a chelator. Unlike other commercially available chelators, the SAR technology prevents copper leakage into the body. SAR-Bombesin is a Targeted Copper Theranostic (TCT) that can be used with isotopes of copper-64 (Cu-64 or 64Cu) for imaging and copper-67 (Cu-67 or 67Cu) for therapy.

About Prostate Cancer
Prostate cancer is the second most common cancer diagnosed in men globally and the fifth leading cause of cancer death in men worldwide9. The American Cancer Institute estimates in 2025 there will be about 313,780 new cases of prostate cancer in the US and around 35,770 deaths from the disease10.

Approximately 20-25% of prostate cancer patients with BCR have low or no uptake of PSMA-targeting tracer11-14. These patients are unlikely to show meaningful uptake of PSMA-targeted products, such as 68Ga-PSMA-11. Given the prostate cancer indication is one of the largest in oncology, there is a significant unmet medical need in this segment.

On June 12, 2025 Galapagos NV (Euronext & NASDAQ: GLPG) reported that it will present new data from the ongoing ATALANTA-1 Phase 1/2 study of its investigational CD19 CAR T-cell therapy, GLPG5101, in an oral presentation at the 30th European Hematology Association (EHA) (Free EHA Whitepaper) Congress (Press release, Galapagos, JUN 12, 2025, View Source [SID1234653875]). These data demonstrate encouraging safety outcomes, including low rates of high-grade toxicities, in R/R NHL. Additionally, with a rapid vein-to-vein time enabled by Galapagos’ decentralized manufacturing platform, 95% of patients treated in the study received fresh, non-cryopreserved GLPG5101, without the need for cytotoxic bridging therapy.

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"We are excited to share new promising safety and manufacturing data for GLPG5101 across multiple R/R NHL subtypes, reinforcing the potential of our novel rapid delivery approach," said Omotayo Fasan, M.D., Clinical Development Program Head at Galapagos. "By initiating lymphodepletion immediately after cell collection, we are able to infuse fresh product as soon as it becomes available, reducing patient attrition and potentially expanding access to CAR-T therapy. We observed a low 5% attrition rate, compared to rates of up to 30% reported in some clinical trials and real-world settings, and observed a manageable safety profile. These promising results suggest that rapid delivery of fresh, stem-like early memory cell therapies may offer meaningful clinical benefits for patients with R/R NHL."

"Decentralized cell therapy manufacturing is changing how we think about CAR-T eligibility. By enabling shorter vein-to-vein times and the use of fresh, early memory phenotype cells, this approach may allow for the inclusion of patients who would otherwise not be able to receive CAR-T therapy due to historically long manufacturing timelines," said Pim Mutsaers, M.D., Associate Professor, Department of Hematology, Erasmus MC Cancer Institute.

The new ATALANTA-1 data are summarized below:
The oral presentation at EHA (Free EHA Whitepaper) features new safety and longer follow-up data for GLPG5101 in 64 patients with R/R large B-cell lymphoma (DLBCL, n=17), mantle cell lymphoma (MCL, n=13), follicular lymphoma (FL, n=29), and marginal zone lymphoma (MZL, n=5) from the ongoing ATALANTA-1 Phase 1/2 study (data cut-off: October 14, 2024). The presentation also demonstrates the feasibility of Galapagos’ decentralized manufacturing platform to deliver fresh, stem-like early memory cell therapy with a median vein-to-vein time of seven days, robust in vivo expansion, and durable persistence.

As of 14 October 2024, 64 patients underwent leukapheresis, of whom 63 received lymphodepleting chemotherapy and 61 (95%) received an infusion of GLPG5101. Of those 61 patients:
95% (58 patients) received a fresh product
89% (54 patients) received it within 7 days post-leukapheresis
7% (4 patients) received it within 8-21 days
5% (3 patients) received a cryopreserved product
None of the patients who received a fresh product required cytotoxic bridging therapy.
GLPG5101 showed an encouraging safety profile in the context of robust CAR T-cell peak expansion and durable persistence, with the majority of Grade ≥ 3 treatment emergent adverse events being hematological. Cases of CRS and ICANS were few and predominantly low-grade with only a single Grade 3 report of each. Dose-limiting toxicities were found in 8% of patients (5/61).
Durable CAR T-cell persistence was observed up to 21 months across tumor types, phases, and dose levels.
Phase 1
(n=24) Phase 2
(n=37) All patients
(n=61)
CRS, n (%) 11 (45.8) 15 (40.5) 26 (42.6)
Grade 1, n (%) 5 (20.8) 8 (21.6) 13 (21.3)
Grade 2, n (%) 5 (20.8) 7 (18.9) 12 (19.7)
Grade 3, n (%) 1 (4.2) 0 1 (1.6)
Time to onset, median (range), days 7.5 (2–20) 7.0 (1–11) 7.0 (1–20)
Duration, median (range), days 3.0 (1–17) 3.0 (1–9) 3.0 (1–17)
CRS toxicity management, n (%)
Dexamethasone 4 (16.7) 7 (18.9) 11 (18.0)
Tocilizumab 6 (25.0) 9 (24.3) 15 (24.6)
Methylprednisolone 1 (4.2) - 1 (1.6)
Vasopressin 1 (4.2) - 1 (1.6)
ICANS, n (%) 8 (33.3) 4 (10.8) 12 (19.7)
Grade 1 8 (33.3) 3 (8.1) 11 (18.0)
Grade 2 0 0 0
Grade 3 0 1 (2.7) 1 (1.6)
Time to onset, median (range), days 14.0 (3–30) 8.5 (2–12) 11.5 (2–30)
Duration, median (range), days 2.5 (1–47) 1.5 (1–3) 2.0 (1–47)
ICANS toxicity management, n (%)
Dexamethasone (ICANS) 2 (8.3) 4 (10.8) 6 (9.8)
Tocilizumab (ICANS) 1 (4.2) 2 (5.4) 3 (4.9)
Infections, Grade ≥3, n (%) 2 (8.3) 1 (2.7) 3 (4.9)
Hemophagocytic lymphohistiocytosis, Grade ≥3, n (%) 2 (8.3) 0 2 (3.3)
Prolonged cytopenias,a Grade ≥3, n/n available (%)
30 days after infusion 8/21 (38.1) 11/37 (29.7) 19/58 (32.8)
60 days after infusion 5/21 (23.8) 9/33 (27.3) 14/54 (25.9)
90 days after infusion 4/20 (20.0) 8/30 (26.7) 12/50 (24.0)
a Includes all events related to neutropenia, thrombocytopenia, anemia, and lymphopenia.
CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome.
Table 1: Adverse events of special interest

About GLPG5101 and ATALANTA-1 (EudraCT 2021-003272-13; NCT 06561425)
GLPG5101 is a second generation anti-CD19/4-1BB CAR-T product candidate, administered as a single fixed intravenous dose. The safety, efficacy and feasibility of decentralized manufactured GLPG5101 are currently being evaluated in the ATALANTA-1 Phase 1/2 study in eight1 hematological malignancies with high unmet need. The primary objective of the Phase 1 part of the study is to evaluate safety and to determine the recommended dose for the Phase 2 part of the study. Secondary objectives include assessment of efficacy and feasibility of decentralized manufacturing of GLPG5101. The dose levels that were evaluated in Phase 1 are 50×106 (DL1), 110×106 (DL2) and 250×106 (DL3) CAR+ viable T-cells. The primary objective of the Phase 2 part of the study is to evaluate the Objective Response Rate (ORR) while the secondary objectives include Complete Response Rate (CRR), duration of response, progression free survival, overall survival, safety, pharmacokinetic profile, and the feasibility of decentralized manufacturing. Each enrolled patient will be followed for 24 months. The ATALANTA-1 study is currently enrolling patients in the U.S. and Europe.

On June 12, 2025 TheRas, Inc. d/b/a BBOT (the "Company"), a clinical-stage biopharmaceutical company focused on RAS-pathway malignancies, reported the publication of preclinical data supporting the potential for BBO-10203 to provide therapeutic benefit across multiple tumor types (Press release, BridgeBio Oncology Therapeutics, JUN 12, 2025, View Source [SID1234653871]). The publication, titled "BBO-10203 inhibits tumor growth without inducing hyperglycemia by blocking RAS-PI3Kα interaction" was published in the peer-reviewed journal Science.

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These data describe the discovery and preclinical evaluation of BBO-10203, a first-in-class, orally available inhibitor that selectively blocks the interaction between RAS proteins and PI3Kα without impairing insulin signaling. By covalently binding to a unique cysteine in the RAS-binding domain of PI3Kα, BBO-10203 effectively disrupts oncogenic RAS-driven activation of the PI3Kα pathway across a range of tumor types, including those with mutations in KRAS, PIK3CA, and HER2 amplification, without inducing hyperglycemia. The compound showed broad antitumor activity in vitro and in vivo and demonstrated enhanced efficacy when combined with targeted therapies such as CDK4/6 inhibitors, ER antagonists, HER2 inhibitors, and KRASG12C inhibitors. These findings support the potential of BBO-10203 as a well-tolerated, mechanistically distinct therapeutic for PI3Kα- and RAS-driven cancers.

"Because the contribution of the second most mutated signaling pathway in human cancers remains underappreciated, we searched for an entirely novel molecular mechanism that is not encumbered by known metabolic liabilities to inhibit PI3Kα signaling," said Pedro Beltran, PhD, Chief Scientific Officer of BBOT. "By blocking the crosstalk between RAS and PI3Kα in tumors, without interfering with physiological insulin signaling, we believe BBO-10203 represents a fundamentally differentiated approach with both biological and therapeutic promise."

"This work stemmed from our goal to elucidate the structural basis of RAS:PI3Kα binding and therapeutically target this interaction," said Dhirendra Simanshu, PhD, lead author and Principal Scientist at Frederick National Laboratory for Cancer Research (FNLCR). "Our findings show that targeting RAS-effector interactions is both structurally tractable and has potential across a range of cancers. BBO-10203 exemplifies a paradigm shift – rather than inhibiting RAS directly, it intercepts oncogenic signaling through effectors like PI3Kα, enabling tumor suppression while preserving essential physiological functions."

BBO-10203 is currently being evaluated in our Phase 1 BREAKER-101 study (NCT06625775) in patients with locally advanced or metastatic HER2+ breast cancer, HR+/HER2- breast cancer, KRAS mutant advanced CRC, and KRAS mutant advanced NSCLC. The discovery of BBO-10203 was the result of a collaboration between the RAS Initiative at Frederick National Laboratory, Lawrence Livermore National Laboratory, and BBOT.

"This work is an excellent example of chemistry bringing clarity to biology," said Frank McCormick, PhD, FRS, Chairman of the BBOT Board, Advisor to the National Cancer Institute’s RAS Initiative at Frederick National Laboratory for Cancer Research, and Professor of Tumor Biology and Cancer Research at UCSF. "The role of the RAS:PI3Kα interaction in cancer biology has long been suspected but challenging to pin down precisely. Now we understand which cancers depend on this interaction, some quite unexpected. With BBO-10203 now in the clinic, there’s real hope that these discoveries will translate into meaningful benefit for many cancer patients."

On June 12, 2025 Samsung Bioepis Co., Ltd. ("Samsung Bioepis") reported the long-term safety data of EPYSQLI (eculizumab; SB12), a biosimilar to Soliris1, in paroxysmal nocturnal hemoglobinuria (PNH) at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress 2025 held at Milan, Italy from June 12 to 15 (Press release, Samsung Bioepis, JUN 12, 2025, View Source [SID1234653870]).

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EPYSQLI was approved by the European Commission (EC) for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) in May 2023 and March 2024, respectively2.

The study assessed the long-term safety of EPYSQLI in PNH patients by evaluating the consistency of safety outcomes, particularly serious adverse events (SAEs) between the initial 52-week Phase 3 study period and the extended treatment (ET) period, spanning from 52 weeks to up to 158 weeks. The same maintenance dose of 900 mg EPYSQLI was administered every 2 weeks. A total of 46 patients from the Phase 3 study received ET. During ET, seven patients (15.2%) experienced a total of 14 SAEs with no occurrence of fatal cases, and all patients fully recovered without permanently discontinuing the treatment. The exposure-adjusted event rate (EAER) was comparable between initial 52-week period and ET period (EAER were 0.13 and 0.17, respectively), and there was no statistically difference between initial 52-week and ET period in EAER (p-value = 0.76). The study is consistent with the findings of the Phase 3 study with no newly identified safety signals and no fatal cases occurred throughout the entire treatment period with all SAEs resolving completely.

Details of the abstract are as follows3:

Abstract title: Long-Term Safety of SB12 in Paroxysmal Nocturnal Hemoglobinuria: Up to 2-year Extension Treatment Safety Data
Abstract number: PB2811
Type: Publication Only
Session title: Bone marrow failure syndromes incl. PNH – Clinical
Author(s): Jun Ho Jang, Siook Baek, Yumin Baek, Jinah Jung, Ciprian Tomuleasa, Hanna Oliynyk, Theerin Lanamtieng, Soo Min Lim
Besides approval by the EC, EPYSQLI is also approved by the U.S. Food and Drug Administration (FDA) and Korea’s Ministry of Food and Drug Safety (MFDS) as a biosimilar to Soliris. In countries where EPYSQLI is approved and available, EPYSQLI may not be prescribed and/or dispensed for its unapproved other indications for which Soliris is approved.

About EPYSQLI (Eculizumab Biosimilar) in the European Union (EU)
EPYSQLI is indicated in adults and children for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). EPYSQLI is not approved for and should not be used for the treatment of generalised myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD). EPYSQLI must be administered by a healthcare professional and under the supervision of a physician experienced in the management of patients with hematological disorders or renal disorders.

EPYSQLI EU Important Safety Information
The EU Summary of Product Characteristics for EPYSQLI includes the following Special warning and Precautions:

Meningococcal Infection
Due to its mechanism of action, the use of eculizumab increases the patient’s susceptibility to meningococcal infection (Neisseria meningitidis). Meningococcal disease due to any serogroup may occur. To reduce the risk of infection, all patients must be vaccinated at least 2 weeks prior to receiving eculizumab unless the risk of delaying eculizumab therapy outweighs the risks of developing a meningococcal infection. Patients who initiate eculizumab treatment less than 2 weeks after receiving a tetravalent meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Vaccines against serogroups A, C, Y, W 135 are recommended in preventing the commonly pathogenic meningococcal serogroups. Vaccine against serogroup B where available is also recommended. Patients must receive vaccination according to current national vaccination guidelines for vaccination use.

Vaccination may further activate complement. As a result, patients with complement-mediated diseases, including PNH and aHUS, may experience increased signs and symptoms of their underlying disease, such as haemolysis (PNH) or TMA (aHUS). Therefore, patients should be closely monitored for disease symptoms after recommended vaccination.

Vaccination may not be sufficient to prevent meningococcal infection. Consideration should be given to official guidance on the appropriate use of antibacterial agents. Cases of serious or fatal meningococcal infections have been reported in eculizumab-treated patients. Sepsis is a common presentation of meningococcal infections in patients treated with eculizumab. All patients should be monitored for early signs of meningococcal infection, evaluated immediately if infection is suspected, and treated with appropriate antibiotics if necessary. Patients should be informed of these signs and symptoms and steps taken to seek medical care immediately.

Other Systemic Infections
Patients may have increased susceptibility to other type of serious infections, especially with Neisseria and encapsulated bacteria.

Infusion Reactions
Administration of eculizumab may result in infusion reactions or immunogenicity that could cause allergic or hypersensitivity reactions (including anaphylaxis). Eculizumab administration should be interrupted in all patients experiencing severe infusion reactions and appropriate medical therapy administered.

Anticoagulant therapy
Treatment with eculizumab should not alter anticoagulant management.

PNH Laboratory Monitoring
PNH patients should be monitored for signs and symptoms of intravascular haemolysis, including serum lactate dehydrogenase (LDH) levels, and may require dose adjustment within the recommended 14±2 day dosing schedule during the maintenance phase (up to every 12 days).

aHUS Laboratory Monitoring
aHUS patients receiving eculizumab therapy should be monitored for thrombotic microangiopathy by measuring platelet counts, serum LDH and serum creatinine, and may require dose adjustment within the recommended 14±2 day dosing schedule during the maintenance phase (up to every 12 days).

Treatment Discontinuation for PNH
If patients discontinue treatment with eculizumab they should be closely monitored for signs and symptoms of serious intravascular haemolysis.

Treatment Discontinuation for aHUS
If aHUS patients discontinue treatment with eculizumab, they should be monitored closely for signs and symptoms of severe thrombotic microangiopathy complications.

The most common adverse reaction observed with eculizumab treatment in clinical trials was headache, (occurred mostly in the initial phase of dosing), and the most serious adverse reaction was found to be meningococcal infection.

Refer to the Summary of Product Characteristics for EPYSQLI’s full safety information.

On June 12, 2025 Schrödinger, Inc. (Nasdaq: SDGR) reported encouraging initial clinical data from its ongoing Phase 1, open-label, dose-escalation study of SGR-1505 in patients with relapsed/refractory B-cell malignancies (Press release, Schrodinger, JUN 12, 2025, View Source [SID1234653869]). SGR-1505 was observed to be safe, well tolerated, and clinically active, with responses observed in multiple histologies, including in patients with chronic lymphocytic leukemia (CLL) and Waldenström macroglobulinemia (WM). These data are being presented in a poster presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress.

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"We are very encouraged by the initial results from our Phase 1 study in patients with relapsed/refractory B-cell malignancies. The data presented today, coupled with the differentiated preclinical and safety profiles observed in our previously completed study in healthy volunteers, further increases our conviction about the potential for SGR-1505 to be a best-in-class therapy," said Margaret Dugan, M.D., chief medical officer at Schrödinger. "Dose escalation is complete, and we look forward to discussing these results and our proposed recommended Phase 2 dose with the FDA later this year."

"Despite recent advances in the treatment of B-cell malignancies, resistance to currently available therapies eventually results in treatment failure and disease progression for many patients," said Stephen Spurgeon, M.D., Associate Professor of Medicine, Oregon Health and Science University, and an investigator for the clinical study. "We know that MALT1 plays a critical role in key signaling pathways that drive cancer cell survival and proliferation, making it a promising target for a broad range of B-cell malignancies. Although these data are from an early-phase study, they suggest SGR-1505 demonstrates on-target activity resulting in potential clinical benefit. I look forward to seeing additional data as the study progresses, including response data in patients with aggressive histologies."

"The positive data reported today represent a key milestone for Schrödinger and follow the clinical successes of programs advanced by collaboration partners and companies we have co-founded," said Karen Akinsanya, Ph.D., president, head of therapeutics R&D and chief strategy officer, partnerships at Schrödinger. "These data reinforce the power of Schrödinger’s platform to enable the rapid design of differentiated molecules and the impact that our computational approach can have on a drug discovery and development program."

Major Takeaways from the Study

As of the data cut-off date, May 13, 2025, 49 patients were enrolled and evaluable for safety, including 18 patients with CLL/SLL, nine with diffuse large B-cell lymphoma (DLBCL), six with Waldenström macroglobulinemia (WM), and five with marginal zone lymphoma (MZL).
Patients had a median of four (range two-nine) prior lines of therapy, with the most common being Bruton’s tyrosine kinase (BTK) inhibitors (55.1%), BCL-2 inhibitors (18.4%) and BTK+BCL-2 inhibitors (18.4%).
SGR-1505 was well-tolerated with no dose-limiting toxicities or deaths due to treatment-emergent adverse events (TEAEs). Forty three percent of patients (n=21) experienced ≥ 1 treatment-related adverse event (TRAE), with the most common (≥ 10%) being rash (12%) and fatigue (12%). Ten patients (20%) experienced treatment-emergent serious adverse events (SAEs); one was treatment-related. All blood bilirubin increased TEAEs were asymptomatic, reported in patients with UGT1A1 polymorphisms and none were Grade 4.
Inhibition of IL-2 is a pharmacodynamic biomarker for target engagement and an exploratory endpoint in the study. Preliminary data indicated that SGR-1505 inhibits T-cell derived IL-2 upon ex vivo stimulation achieving the PD target of ~90% inhibition in the majority of PD-evaluable participants treated at ≥ 150 mg QD and all Q12H doses at steady state.
Preliminary efficacy data indicated SGR-1505 was clinically active as a monotherapy in a number of relapsed/refractory B-cell malignancies. Of the 49 participants, 45 patients had at least one follow-up disease assessment or disease progression and were evaluable for preliminary efficacy. The overall response rate (ORR) across all dose levels was 22% (n = 10/45). Thirteen of 49 patients had been on treatment for ≥120 days.
Among patients with indolent disease, 3/17 CLL/SLL, 5/5 WM, and 1/5 MZL patients responded. The responses of the three CLL responders were independently reviewed and confirmed, and two had a partial response (PR) with lymphocytosis (PR-L). Two of three CLL patients with partial responses were double-exposed to BTK and BCL-2 inhibitors, and all WM patients were exposed to BTK inhibitors.
The study recently began enrolling patients with aggressive lymphomas into the 300 mg QD and 100 mg Q12H cohorts. A PR was reported in one of four ABC-DLBCL patients.
Study Design
The Phase 1 dose-escalation study (NCT05544019) assessed SGR-1505 as a monotherapy treatment in patients with relapsed/refractory B-cell malignancies. The primary endpoint is the incidence and severity of adverse events and dose-limiting toxicities. Secondary endpoints include pharmacokinetic and pharmacodynamic measurements as well as objective response rate, duration of response and disease control rate.

EHA Poster Presentation Details
The full abstract (#PS1569) can be found online at www.ehaweb.org.

Poster Title: A Phase 1 study of SGR-1505, an oral, potent, MALT1 inhibitor for relapsed/refractory (R/R) B-cell malignancies, including chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL)
Presentation Date and Time: Saturday, June 14, 2025, 6:30-7:30PM CST (12:30-1:30PM ET)
Location: Poster Session 2

About SGR-1505
SGR-1505 is an oral investigational MALT1 inhibitor being evaluated for the treatment of relapsed/refractory B-cell malignancies. MALT1 plays a central role in key signaling pathways that drive cancer cell survival and proliferation, making its location downstream of BTK in the NF-κB signaling pathway an attractive target for the development of novel therapeutics for a potentially broad range of B-cell malignancies. In preclinical studies, SGR-1505 was observed to be highly potent and selective, and has demonstrated anti-tumor activity in preclinical models both as a monotherapy and in combination with BTK and BCL-2 inhibitors. There is also emerging therapeutic rationale supporting MALT1 inhibition as a potential treatment for inflammatory and autoimmune disorders.

SGR-1505 was designed using Schrödinger’s computational platform at scale and was discovered approximately 10 months after the company started its MALT1 program. Schrödinger believes that SGR-1505 is currently the most advanced MALT1 inhibitor known to be in clinical development and has both first-in-class and best-in-class potential. A Phase 1 study in patients with relapsed/refractory B-cell malignancies is ongoing (NCT05544019).

Webcast and Conference Call Information
Schrödinger will host a conference call on Thursday, June 12, 2025, at 8:00 a.m. ET to review the clinical opportunity for SGR-1505 and review the Phase 1 data presented at EHA (Free EHA Whitepaper). The live webcast can be accessed under "Events & Presentations" in the investors section of Schrödinger’s website, View Source To participate in the live call, please register for the call here. It is recommended that participants register at least 15 minutes in advance of the call. The archived webcast will be available on Schrödinger’s website for approximately 90 days following the event.