Prospective study to evaluate the value of uPAR-targeted PET/MR scan using the tracer 68Ga-NOTA-AE105 in patients with newly diagnosed prostate cancer

Start Date21 Nov 2017

Sponsor / Collaborator

Rigshospitalet

NCT03278275 / CompletedPhase 2IIT

PET/CT Imaging of uPAR-expression in Patients With Neuroendocrine Tumors Using 68Ga-NOTA-AE105

The aim of this non-randomised, prospective study is to investigate the applicability and prognostic value of uPAR PET/CT with the radioligand 68Ga-NOTA-AE105 in patients with neuroendocrine tumors (NETs).

Start Date01 Nov 2017

Sponsor / Collaborator

Rigshospitalet

NCT02964988 / TerminatedPhase 2IIT

uPAR PET/CT in Radium-223-dichloride Treatment of Patients With Metastatic Castration-resistant Prostate Cancer

The purpose of this study is to investigate the applicability of urokinase plasminogen activator receptor (uPAR) Positron Emission Tomography (PET) / CT molecular imaging in patients with metastatic castration-resistant prostate cancer (mCRPC)

Start Date01 Jan 2017

Sponsor / Collaborator

Rigshospitalet

100 Clinical Results associated with Gallium-68 NOTA AE105(Curasight A/S)

100 Translational Medicine associated with Gallium-68 NOTA AE105(Curasight A/S)

100 Patents (Medical) associated with Gallium-68 NOTA AE105(Curasight A/S)

Literatures (Medical) associated with Gallium-68 NOTA AE105(Curasight A/S)

17 Apr 2024·Journal of Agricultural and Food Chemistry

Digestive and Absorptive Properties of the Antarctic Krill Tripeptide Phe-Pro-Phe (FPF) and Its Auxiliary Memory-Enhancing Effect

Article

Author: Ding, Jie ; Yang, Jingqi ; Lin, Songyi ; Lu, Zhiqiang ; Zhu, Beiwei

Aging and stress have contributed to the development of memory disorders. Phe-Pro-Phe (FPF) was identified with high stability by mass spectrometry from simulated gastrointestinal digestion and everted gut sac products of the Antarctic krill peptide Ser-Ser-Asp-Ala-Phe-Phe-Pro-Phe-Arg (SSDAFFPFR) which was found to have a positive impact on memory enhancement. This study investigated the digestive stability, absorption, and memory-enhancing effects of FPF using nuclear magnetic resonance spectroscopy, simulated gastrointestinal digestion, in vivo fluorescence distribution analysis, mouse behavioral experiments, acetylcholine function, Nissl staining, immunofluorescence, and immunohistochemistry. FPF crossed the blood-brain barrier into the brain after digestion, significantly reduced shock time, working memory errors, and reference memory errors, and increased the recognition index. Additionally, FPF elevated ACh content; Nissl body counts; and CREB, SYN, and PSD-95 expression levels, while reducing AChE activity (P < 0.05). This implies that FPF prevents scopolamine-induced memory impairment and provides a basis for future research on memory disorders.

01 Sep 2022·Journal of Nuclear MedicineQ1 · MEDICINE

Prospective Phase II Trial of Prognostication by ⁶⁸Ga-NOTA-AE105 uPAR PET in Patients with Neuroendocrine Neoplasms: Implications for uPAR-Targeted Therapy

Q1 · MEDICINE

Article

Author: Knigge, Ulrich ; Loft, Annika ; Carlsen, Esben Andreas ; Kjaer, Andreas ; Berthelsen, Anne Kiil ; Loft, Mathias ; Langer, Seppo W

The clinical course for patients with neuroendocrine neoplasms (NENs) ranges from indolent to highly aggressive. Noninvasive tools to improve prognostication and guide decisions on treatment are warranted. Expression of urokinase plasminogen activator receptor (uPAR) is present in many cancer types and associated with a poor outcome. Therefore, using an in-house-developed uPAR PET tracer [⁶⁸Ga]Ga-NOTA-Asp-Cha-Phe-D-Ser-D-Arg-Tyr-Leu-Trp-Ser-OH (⁶⁸Ga-NOTA-AE105), we aimed to assess uPAR expression in NENs. We hypothesized that uPAR expression was detectable in a significant proportion of patients and associated with a poorer outcome. In addition, as uPAR-targeted radionuclide therapy has previously proven effective in preclinical models, the study would also indicate the potential for uPAR-targeted radionuclide therapy in NEN patients. Methods: In a prospective clinical phase II trial, we included 116 patients with NENs of all grades, of whom 96 subsequently had uPAR PET/CT performed with evaluable lesions. PET/CT was performed 20 min after injection of approximately 200 MBq of ⁶⁸Ga-NOTA-AE105. uPAR target-to-liver ratio was used to define lesions as uPAR-positive when lesion SUV_max-to-liver SUV_mean ratio was at least 2. Patients were followed for at least 1 y to assess progression-free and overall survival. Results: Most patients had small intestinal NENs (n = 61) and metastatic disease (n = 86). uPAR-positive lesions were seen in 68% (n = 65) of all patients and in 75% (n = 18) of patients with high-grade (grade 3) NENs. During follow-up (median, 28 mo), 59 patients (62%) experienced progressive disease and 28 patients (30%) died. High uPAR expression, defined as a uPAR target-to-liver ratio above median, had a hazard ratio of 1.87 (95% CI, 1.11-3.17) and 2.64 (95% CI, 1.19-5.88) for progression-free and overall survival, respectively (P < 0.05 for both). Conclusion: When ⁶⁸Ga-NOTA-AE105 PET was used to image uPAR in patients with NENs, uPAR-positive lesions were seen in most patients, notably in patients with both low-grade and high-grade NENs. Furthermore, uPAR expression was associated with a worse prognosis. We suggest that uPAR PET is relevant for risk stratification and that uPAR may be a promising target for therapy in patients with NENs.

01 Aug 2022·Journal of Nuclear Medicine

Prognostic Value of Urokinase-Type Plasminogen Activator Receptor PET/CT in Head and Neck Squamous Cell Carcinomas and Comparison with ¹⁸F-FDG PET/CT: A Single-Center Prospective Study

Article

Author: Kjaer, Andreas ; Friborg, Jeppe ; Ujmajuridze, Zaza ; Andersen, Kim F ; Loft, Annika ; Clausen, Malene M ; Risør, Louise M ; Farhadi, Mohammed

The aim of this phase II clinical trial (NCT02965001) was to evaluate the prognostic value of urokinase-type plasminogen activator receptor (uPAR) PET/CT with the novel ligand ⁶⁸Ga-NOTA-AE105 in head and neck cancer and compare it with ¹⁸F-FDG. Methods: Patients with head and neck squamous cell carcinoma referred for curatively intended radiotherapy were eligible and prospectively included in this study. ⁶⁸Ga-uPAR and ¹⁸F-FDG PET/CT were performed before initiation of curatively intended radiotherapy, and the SUV_max of the primary tumor was measured on both PET/CT studies by 2 independent readers. Relapse-free survival (RFS) and overall survival (OS) were calculated, and optimal cutoffs were established for ⁶⁸Ga-uPAR and ¹⁸F-FDG PET independently and compared using log rank and Kaplan-Meier statistics, as well as univariate and multivariate analysis in a Cox proportional-hazards model. Results: In total, 57 patients were included and followed for a median of 33.8 mo (range, 2.30-47.2, mo). The median SUV_max of the primary tumors was 2.98 (range, 1.94-5.24) for ⁶⁸Ga-uPAR and 15.7 (range, 4.24-45.5) for ¹⁸F-FDG. The optimal cutoffs for ⁶⁸Ga-NOTA-AE105 SUV_max in the primary tumor were 2.63 for RFS and 2.66 for OS. A high uptake of ⁶⁸Ga-NOTA-AE105 (SUV_max above cutoff) was significantly associated with poor RFS and OS (log-rank P = 0.012 and P = 0.022). ⁶⁸Ga-NOTA-AE105 uptake in the primary tumor was significantly associated with poor RFS in univariate analysis (hazard ratio [HR], 8.53 [95% CI, 1.12-64.7]; P = 0.038), and borderline-associated with OS (HR, 7.44 [95% CI, 0.98-56.4]; P = 0.052). For ¹⁸F-FDG PET, the optimal cutoffs were 22.7 for RFS and 22.9 for OS. An ¹⁸F-FDG SUV_max above the cutoff was significantly associated with reduced RFS (log-rank P = 0.012) and OS (log-rank P = 0.000). ¹⁸F-FDG uptake was significantly associated with reduced RFS (HR, 3.27 [95% CI, 1.237-8.66]; P = 0.017) and OS (HR, 7.10 [95% CI, 2.60-19.4]; P < 0.001) in univariate analysis. In a multivariate analysis including ⁶⁸Ga-uPAR SUV_max, ¹⁸F-FDG SUV_max, TNM stage, and p16 status, only ⁶⁸Ga-uPAR SUV_max remained significant (HR, 8.51 [95% CI, 1.08-66.9]; P = 0.042) for RFS. For OS, only TNM stage and ¹⁸F-FDG remained significant. Conclusion: The current trial showed promising results for the use of ⁶⁸Ga-uPAR PET SUV_max in the primary tumor to predict RFS in head and neck squamous cell carcinoma patients referred for curatively intended radiotherapy when compared with ¹⁸F-FDG PET, TNM stage, and p16 status. ⁶⁸Ga-uPAR PET could potentially become valuable for identification of patients suited for deescalation of treatment and risk-stratified follow-up schemes.

News (Medical) associated with Gallium-68 NOTA AE105(Curasight A/S)

13 Feb 2024

·www.prnewswire.com

Curasight resolves on a rights issue of up to DKK 51.2 million to accelerate its therapeutic strategy

COPENHAGEN, Denmark, Feb. 13, 2024 /PRNewswire/ -- Curasight A/S "Curasight" or the "Company" – (TICKER: CURAS) has today resolved on a new issue of shares with preferential rights for the Company's existing shareholders of up to DKK 51.2 million before transaction costs (the "Rights Issue"). The proceeds are intended to be used to strengthen the Company's capital structure and secure funding for the acceleration of clinical activities, including the preparation, planning and enrolment of the first patients in a therapy phase I/IIa basket trial in various cancer types, as well as to strengthen Curasight's pipeline through preclinical development of new peptide-based radioligands. "We are committed to advancing the theranostic approach in cancer care, aiming to provide clinicians and patients with innovative solutions that support a combined diagnostic and treatment approach for certain cancers. The Rights Issue enables us to expedite our therapeutic development activities including the launch of our therapeutic basket trial, so that we can develop both uTRACE® and uTREAT® in parallel. Additionally, it will allow us to secure a robust balance sheet that both supports our accelerated clinical strategy and ensures we are in a strong position when negotiating potential partnerships." said CEO Ulrich Krasilnikoff. Summary of the Rights Issue Each existing share in the Company, as of the record date on 22 February 2024, entitles the holder to one (1) subscription right. Seven (7) subscription rights entitle the holder to subscribe for one (1) new share at a subscription price of DKK 18 per share. The subscription period runs from 23 February 2024, up to and including 7 March 2024. The last day of trading in the shares with the right to receive subscription rights in the Rights Issue is 20 February 2024. The Company's management team, consisting of Ulrich Krasilnikoff (CEO and CFO), Andreas Kjær (CSO/CMO and co-founder) and Hanne Damgaard Jensen (CDO/COO), have committed to subscribe for shares in the rights issue for a total of approx. DKK 1.3 million, corresponding to 2.5 percent of the rights issue. The Company intends to publish an information memorandum regarding the Rights Issue around 22 February 2024 (the " Information Memorandum"). The proceeds are intended to be used to strengthen the Company's capital structure and secure funding for the acceleration of clinical activities, including the preparation, planning and enrolment of the first patients in a therapy phase I/IIa basket trial in various cancer types (brain, neuroendocrine, head and neck, non-small cell lung and pancreatic cancer), as well as to strengthen Curasight's preclinical pipeline through development of new peptide-based radioligands. Reasons for the Rights Issue Curasight focuses on addressing the need for improved diagnosis and treatment of several cancer indications and has developed a highly specific PET imaging ligand, uTRACE (radioactive tracer) and uTREAT - both targeting the uPAR receptor. uPAR is expressed in many types of human cancers and the expression levels of uPAR have been shown to be strongly associated with metastatic disease, i.e. cancer aggressiveness, and subsequent poor prognosis. Curasight's clinical PET ligand uTRACE has been succesfully validated in more than 400 patients in several clinical PET imaging trials with uTRACE in brain, prostate, head & neck, neuroendocrine, oral, breast and urinary bladder cancer with promising results. Based on these results with uTRACE, combined with the strong preclinical results with uTREAT, both targeting the strong biomarker (uPAR) in human cancer, Curasight's Board and management projects that uTREAT, together with its companion diagnostics, the uPAR-PET imaging ligand uTRACE, could become a successful radioligand therapy. It is foreseen that such a targeted radioligand therapy could become a game-changer in the treatment and management of cancer patients across several cancer indications. Curasight will therefore pursue uPAR targeted radioligand therapy using the uTRACE ligand but "armed" with radiation therapy. By combining anti-cancer radiotherapy uTREAT (therapy) with uTRACE (diagnostics), the technology jointly known as theranostics, is foreseen to treat cancer in a much more gentle and efficient way than today's method of external radiation therapy. To further advance and commercialize the uPAR Theranostics platform with uTREAT and uTRACE for improved diagnosis and treatment across several cancer diseases, Curasight is now conducting a Right Issue of shares of up to DKK 51.2 million. The proceeds from the Rights Issue will primarily finance the preparation, planning and enrolment of the first patients in a therapeutic phase I/IIa basket trial that will in parallel assess the therapeutic safety and efficacy of uTREAT in brain cancer (glioblastoma multiforme), neuroendocrine tumors, head and neck cancer, non-small scell lung cancer, and pancreatic cancer. Furthermore, the proceeds from the issue will be used to broaden the pipeline through development of new next generation peptide-based radioligand therapies. Subscription Commitments The Company's management team, consisting of Ulrich Krasilnikoff (CEO and CFO), Andreas Kjær (CSO/CMO and co-founder) and Hanne Damgaard Jensen (CDO/COO), have committed to subscribe for shares in the rights issue for a total of approx. DKK 1.3 million, corresponding to 2.5 percent of the rights issue. Information Memorandum Full terms and conditions for the Rights Issue as well as other information about the Company and further information about subscription commitments, will be included in the Information Memorandum that the Company is expected to publish around 22 February 2024. Preliminary Timetable for the Rights Issue Shares and Dilution Assuming full subscription in the Rights Issue, the share capital will increase by DKK 142,099.20, from DKK 994,694.55 to DKK 1,136,793.75 through the issuance of 2,841,984 shares, resulting in the total number of shares increasing from 19,893,891 to 22,735,875, representing a dilution effect of approximately 12.5 percent of the share capital and number of shares. Shareholders who do not participate in the Rights Issue have the opportunity to financially compensate themselves for this dilution by selling their subscription rights. Advisors Redeye AB is acting as a financial advisor to Curasight. DLA Piper Denmark Advokatpartnerselskab is acting as the legal adviser of Curasight. VP Euronext Securities A/S is the Company's issuing agent and Nordic Issuing is acting as the settlement agent. For more information regarding Curasight, please contact: Ulrich Krasilnikoff, CEO Phone: +45 22 83 01 60 E-mail: [email protected] The following files are available for download: SOURCE Curasight

Radiation TherapyClinical Study

13 Feb 2024

·www.prnewswire.com

Curasight announces acceleration of therapeutic strategy to strengthen position as a radiopharmaceutical theranostic company

Coming Phase I/IIa basket trial planned to include five select cancer indications Study will apply Curasight's uPAR theranostic platform approach combining diagnosis (uTRACE®) and therapy (uTREAT®) First patients expected to be dosed in the beginning of 2025 with expected first efficacy data in 2025. COPENHAGEN, Denmark, Feb. 13, 2024 /PRNewswire/ -- Curasight A/S ("Curasight" or the "Company" (XSAT: CURAS) announces today that it is accelerating and expanding its clinical therapeutic strategy with the addition of a new Phase I/IIa trial to include a total of five cancer indications in a so called basket trial design. The trial will investigate Curasight's theranostic (therapeutics/diagnostics) approach by testing the diagnostic platform uTRACE® and the treatment platform uTREAT® in brain cancer (Glioblastoma), neuroendocrine tumors (NET), head-and-neck cancer (HNSCC), non-small cell lung cancer (NSCLC), and pancreatic cancer. To strengthen the Company's capital structure and secure funding for the acceleration of clinical activities, Curasight intends to launch a rights issue during the first quarter of 2024. Details of the rights issue are to be announced in a separate press release immediately following this release. "We believe the theranostic approach using radiopharmaceuticals to both diagnose and treat certain types of cancer has the potential to provide important new solutions to clinicians and patients," said Curasight's CEO, Ulrich Krasilnikoff. "We have already achieved important results in most of the indications with our diagnostics platform uTRACE as well as positive preclinical results in brain and lung cancer using our therapeutic solution uTREAT. By launching this basket trial, we can accelerate development of both uTRACE and uTREAT (theranostic) in parallel and potentially have therapeutic efficacy data already during 2025. The trial of five cancer types in parallel takes advantage of our theranostic platform working across tumor types as uPAR is expressed in the majority of all solid cancers. This also increases the likelihood of entering into partnering with pharma companies." The Phase I/IIa basket trial is part of Curasight's strategy to be a leader in the field of theranostics within radiopharmaceuticals and diagnostics, combining improved diagnosis with more targeted, gentler and efficient treatment of cancers. The new study is in addition to Curasight's ongoing Phase II trial investigating uTRACE in prostate cancer as part of the partnership agreement with Curium Inc., where the first interim data is expected Q3 2024. Under the terms of the deal, Curasight is responsible for development until regulatory approval with Curium responsible for manufacturing and commercialisation. Curasight is entitled to receive up to mUSD 70 in development and commercial milestones as well as double-digit percentage royalties on sales in major markets upon eventual commercialization. About the uPAR Theranostics platform Curasight has developed a novel and innovative Theranostics platform for improved cancer diagnosis and treatment. The combination of using targeted radionuclide therapy to treat cancer, and a non-invasive PET imaging for diagnosing and monitoring, is known as Theranostics (Therapy + Diagnostics = Theranostics). Curasight's solution combines the technologies uTREAT (targeted radionuclide therapy) and uTRACE (based on non-invasive PET imaging), both of which target uPAR. By performing imaging, and using the same substance for treatment, it can be more precisely predicted where the therapy will go. This information is such information that Curasight A/S is obliged to publish in accordance with the EU Market Abuse Regulation. The information was submitted, through the care of the above contact person, for publication on 13 February 2024. For more information regarding Curasight, please contact: Ulrich Krasilnikoff, CEO Phone: +45 22 83 01 60 E-mail: [email protected] The following files are available for download: SOURCE Curasight

License out/inPhase 2

22 Jan 2024

·www.prnewswire.com

Curasight A/S Achieves First Milestone under collaboration with Curium Inc.

USD 500.000 payment is the first milestone under the global license and collaboration agreement for the development and commercialization of uTRACE® for use in prostate cancer between Curasight A/S and Curium Inc. Milestone relates to the validation of GMP manufacturing of finished product and illustrates progress in the development plan for uTRACE® PET imaging technology Under the agreement signed in 2023 Curasight is eligible to receive up to mUSD 70 in development milestones plus additional commercial milestones and double-digit royalties on sales upon commercialization COPENHAGEN, Jan. 22, 2024 /PRNewswire/ -- Curasight A/S ("Curasight" or "the Company") – (TICKER: CURAS) today announced the achievement of the first milestone under the agreement with Curium inc., to develop Curasight's uTRACE® PET imaging technology for the improved diagnosis of prostate cancer. The milestone relates to the validation of GMP manufacturing of finished product. The USD 500.000 milestone is the first in the agreement signed with Curium Inc. in May 2023. Under the terms of the deal Curasight will develop its proprietary uTRACE® technology for use in prostate cancer until regulatory approval is granted in the EU and USA with Curium responsible for the commercial manufacture of uTRACE® and world-wide commercialization. Curasight is eligible to receive up to mUSD 70 in development and commercial milestones as well as double-digit percentage royalties on sales in major markets upon eventual commercialization. "Reaching this milestone illustrates the strong progress being made under our agreement with Curium – a global leader in nuclear medicine and an expert in developing, manufacturing and commercializing world-class radiopharmaceutical products," said Curasight's CEO Ulrich Krasilnikoff. "Today's news is also a testament to the hard work and commitment of our team in pursuing our mission to use Curasight's uPAR theranostic platform to improve cancer treatment with more accurate diagnosis using uTRACE® and a more efficient, gentle, and targeted treatment with uTREAT®" About the Phase 2 trial with uTRACE® in prostate cancer The primary objective of the phase 2 trial is to investigate Curasight's first-in-class PET tracer, 64Cu-DOTA-AE105 as a non-invasive grading tool of prostate cancer patients that are followed in active surveillance. Patients in active surveillance are continuously monitored for changes in the aggressiveness of their prostate cancer and can be followed for years without identifying the need for treatment. The trial design is informed from research and earlier studies with uTRACE® as well as protocol discussions with the US Food and Drug Administration (FDA). The phase 2 trial is part of the development framework agreed under the deal with Curium. About the uPAR diagnostic platform The uTRACE® platform is part of Curasights uPAR theranostic solution, made up of its uTRACE® diagnostic technology and its uTREAT® targeted treatment technology. In prostate cancer, uTRACE® is presently developed for diagnostic purposes only. Curasight's ambition is to develop both uTREAT® and uTRACE® to improve diagnosis and treatment solutions of certain cancers. About Curium Curium is a global leader in radiopharmaceuticals. Curium develops, manufactures, and distributes world-class radiopharmaceutical products to help patients around the globe. Their proven heritage combined with a pioneering approach are the hallmarks to deliver innovation, excellence, and unparalleled service. With manufacturing facilities across Europe and the United States, Curium delivers SPECT, PET, and therapeutic radiopharmaceutical solutions for life-threatening diseases to over 14 million patients annually. . For more information regarding Curasight, please contact: Ulrich Krasilnikoff, CEO Phone: +45 22 83 01 60 E-mail: [email protected] The following files are available for download:

License out/inPhase 2

100 Deals associated with Gallium-68 NOTA AE105(Curasight A/S)

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Neuroendocrine Tumors	Phase 1	DK	Rigshospitalet	01 Nov 2017
Prostatic Cancer	Phase 1	DK	Rigshospitalet	22 Sep 2016
Glioblastoma	Phase 1	DK	Rigshospitalet	28 Aug 2016
Oropharyngeal Neoplasms	Phase 1	DK	Rigshospitalet	11 Aug 2016
Bladder Cancer	Phase 1	DK	Rigshospitalet	28 Jun 2016
Mesothelioma	Phase 1	DK	Rigshospitalet	01 Apr 2016
Non-Small Cell Lung Cancer	Phase 1	DK	Rigshospitalet	22 Mar 2016
Aggression	Phase 1	DK	Curasight A/S	01 May 2015
Aggression	Phase 1	DK	Rigshospitalet	01 May 2015
Invasive Carcinoma	Phase 1	DK	Rigshospitalet	01 May 2015

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


SNMMI2016	Not Applicable	-	-	68Ga-NOTA-AE105	fhyhdceaec(iuqcmnqexj) = pjgjozffnw evxfniyfuq (nocmhnwaup )	-	24 May 2016

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