Phase I, Open-Label Study of the Safety and Dosimetry of a 3-Dose Regimen of Escalating Doses of 177Lu-DOTA-EB-TATE in Adult Patients With Advanced, Well- Differentiated Neuroendocrine Tumors

This is a Phase I clinical trial to assess the safety and dosimetry profiles of 177Lu-DOTA-EB-TATE in patients with advanced, metastatic or inoperable, somatostatin receptor-positive, well-differentiated GEP-NETs.

Start Date18 Jun 2022

Sponsor / Collaborator

Molecular Targeting Technologies, Inc.

[+1]

NCT05177640 / CompletedPhase 1IIT

Early Prediction of Tumor Response to Treatment: Translation of 99mTc-Duramycin

Conduct a first-in-human study in healthy volunteers to show safety, biodistribution and dosimetry of [99mTc]Duramycin.

Start Date17 Jun 2021

Sponsor / Collaborator

Antwerp University Hospital

[+1]

NCT00614354 / CompletedPhase 2

Phase II Study of 99mTc-glucarate in Chest Pain Patients Suspected With ACS With no Obvious Signs of AMI and With Known Previous CAD.

The purpose of this clinical trial is to study the ability of a radioactive drug called "Technetium Glucarate" to detect whether the cause of chest pain in patients entering the emergency department with no obvious signs of heart attack is due to a condition called Acute Coronary Syndrome (ACS). The drug will be injected intravenously. After one or two hours the patient will undergo an imaging procedure to detect if the drug has accumulated in the heart. Uptake of the radioactive drug in the heart is indicative of reduced blood flow to the heart.

Start Date01 Oct 2008

Sponsor / Collaborator

Molecular Targeting Technologies, Inc.

[+5]

100 Clinical Results associated with Molecular Targeting Technologies, Inc.

0 Patents (Medical) associated with Molecular Targeting Technologies, Inc.

Literatures (Medical) associated with Molecular Targeting Technologies, Inc.

01 Apr 2024·JOURNAL OF NUCLEAR MEDICINE

Efficacy of [⁶⁷Cu]Cu-EB-TATE Theranostic Against Somatostatin Receptor Subtype-2-Positive Neuroendocrine Tumors.

Article

Author: Njotu, Fabrice Ngoh ; Uppalapati, Maruti ; Fonge, Humphrey ; Babeker, Hanan ; Gray, Brian D ; Tikum, Anjong Florence ; Pak, Koon Y ; Ketchemen, Jessica Pougoue

β^--emitting ¹⁷⁷Lu-octreotate is an approved somatostatin receptor subtype 2 (SSTR2)-directed peptide receptor radionuclide therapy for the treatment of gastroenteropancreatic neuroendocrine tumors (NETs). However,¹⁷⁷Lu-octreotate has fast pharmacokinetics, requiring up to 4 treatment doses. Moreover, ¹⁷⁷Lu is less than ideal for theranostics because of the low branching ratio of its γ-emissions, which limits its SPECT imaging capability. Compared with ¹⁷⁷Lu, ⁶⁷Cu has better decay properties for use as a theranostic. Here, we report the preclinical evaluation of a long-lived somatostatin analog, [⁶⁷Cu]Cu-DOTA-Evans blue-TATE (EB-TATE), against SSTR2-positive NETs. Methods: The in vitro cytotoxicity of [⁶⁷Cu]Cu-EB-TATE was investigated on 2-dimensional cells and 3-dimensional spheroids. In vivo pharmacokinetics and dosimetry were studied in healthy BALB/c mice, whereas ex vivo biodistribution, micro-SPECT/CT imaging, and therapy studies were done on athymic nude mice bearing QGP1.SSTR2 and BON1.SSTR2 xenografts. Therapeutic efficacy was compared with [¹⁷⁷Lu]Lu-EB-TATE. Results: Projected human effective doses of [⁶⁷Cu]Cu-EB-TATE for male (0.066 mSv/MBq) and female (0.085 mSv/MBq) patients are tolerable. In vivo micro-SPECT/CT imaging of SSTR2-positive xenografts with [⁶⁷Cu]Cu-EB-TATE showed tumor-specific uptake and prolonged accumulation. Biodistribution showed tumor accumulation, with concurrent clearance from major organs over a period of 72 h. [⁶⁷Cu]Cu-EB-TATE was more effective (60%) at eliminating tumors that were smaller than 50 mm³ within the first 15 d of therapy than was [¹⁷⁷Lu]Lu-EB-TATE (20%) after treatment with 2 doses of 15 MBq administered 10 d apart. Mean survival of [⁶⁷Cu]Cu-EB-TATE-treated groups was 90 d and more than 90 d, whereas that of [¹⁷⁷Lu]Lu-EB-TATE was more than 90 d and 89 d against vehicle control groups (26 d and 53 d), for QGP1.SSTR2 and BON1.SSTR2 xenografts, respectively. Conclusion: [⁶⁷Cu]Cu-EB-TATE exhibited high SSTR2-positive NET uptake and retention, with favorable dosimetry and SPECT/CT imaging capabilities. The antitumor efficacy of [⁶⁷Cu]Cu-EB-TATE is comparable to that of [¹⁷⁷Lu]Lu-EB-TATE, with [⁶⁷Cu]Cu-EB-TATE being slightly more effective than [¹⁷⁷Lu]Lu-EB-TATE for complete remission of small tumors. [⁶⁷Cu]Cu-EB-TATE therefore warrants clinical development.

01 Oct 2021·Journal for immunotherapy of cancerQ2 · MEDICINE

Novel phosphatidylserine-binding molecule enhances antitumor T-cell responses by targeting immunosuppressive exosomes in human tumor microenvironments

Q2 · MEDICINE

ArticleOA

Author: Linette, Gerald ; Carreno, Beatriz M ; Kelleher, Raymond J ; Bankert, Richard B ; Minderman, Hans ; Odunsi, Kunle ; Conway, Alexis ; Bapardekar, Meghana ; Shenoy, Gautam N ; Pak, Koon Yan ; Balu-Iyer, Sathy V ; Bhatta, Maulasri ; Gray, Brian D ; Loyall, Jenni L ; Shultz, Leonard D

Background:

The human tumor microenvironment (TME) is a complex and dynamic milieu of diverse acellular and cellular components, creating an immunosuppressive environment, which contributes to tumor progression. We have previously shown that phosphatidylserine (PS) expressed on the surface of exosomes isolated from human TMEs is causally linked to T-cell immunosuppression, representing a potential immunotherapeutic target. In this study, we investigated the effect of ExoBlock, a novel PS-binding molecule, on T-cell responses in the TME.

Methods:

We designed and synthesized a new compound, (ZnDPA)6-DP-15K, a multivalent PS binder named ExoBlock. The PS-binding avidity of ExoBlock was tested using an in vitro competition assay. The ability of this molecule to reverse exosome-mediated immunosuppression in vitro was tested using human T-cell activation assays. The in vivo therapeutic efficacy of ExoBlock was then tested in two different human tumor xenograft models, the melanoma-based xenomimetic (X-)mouse model, and the ovarian tumor-based omental tumor xenograft (OTX) model.

Results:

ExoBlock was able to bind PS with high avidity and was found to consistently and significantly block the immunosuppressive activity of human ovarian tumor and melanoma-associated exosomes in vitro. ExoBlock was also able to significantly enhance T cell-mediated tumor suppression in vivo in both the X-mouse and the OTX model. In the X-mouse model, ExoBlock suppressed tumor recurrence in a T cell-dependent manner. In the OTX model, ExoBlock treatment resulted in an increase in the number as well as function of CD4 and CD8 T cells in the TME, which was associated with a reduction in tumor burden and metastasis, as well as in the number of circulating PS+ exosomes in tumor-bearing mice.

Conclusion:

Our results establish that targeting exosomal PS in TMEs with ExoBlock represents a promising strategy to enhance antitumor T-cell responses.

01 Nov 2019·Nuclear medicine and biologyQ4 · MEDICINE

Targeting phosphatidylethanolamine and phosphatidylserine for imaging apoptosis in cancer

Q4 · MEDICINE

Article

Author: Gray, Brian D ; Ng, Chin K ; Li, Junling ; Pak, Koon Y

INTRODUCTION:

Both phosphatidylethanolamine (PE) and phosphatidylserine (PS) can be externalized to the outer cell membrane in apoptosis. Thus the objective was to determine whether PE-targeting ¹⁸F-duramycin and PS-targeting ¹⁸F-Zn-DPA could be used for imaging apoptosis.

METHODS:

Duramycin and Zn-DPA were labeled with either ¹⁸F-Al or ¹⁸F-SFB. U937 cells were incubated with four different concentrations of camptothecin (CPT). For assessing the effect of incubation time on uptake, 37 MBq of radiotracer was added to cells incubated for 15, 30, 60, and 120 min at 37 °C. For blocking experiments, 150 μg duramycin and 40 μg Zn-DPA were added to cells for 15 min prior to the addition of either duramycin or Zn-DPA labeled with ¹⁸F. Apoptosis was measured by flow cytometry using an annexin-V/PI kit. Cells were co-stained with Hoechst, Cy5-duramycin, and PSVue480 (FITC-Zn-DPA) to localize fluorescent dye uptake in cells.

RESULTS:

Apoptosis in cells increased proportionally with CTP as confirmed by both flow cytometry and fluorescent staining. Both FITC-Zn-DPA and FITC-duramycin localized mainly on the cell membrane during early apoptosis and then translocated to the inside during late apoptosis. Uptake of FITC-duramycin, however, was higher than that of FITC-Zn-DPA. Cellular uptake of four different radiotracers was also proportional to the degree of apoptosis, increasing slightly over time and reaching a plateau at about 1 h. The blocking experiments demonstrated that uptake in all the control groups was predominantly non-specific, whereas the specific uptake in all the treated groups was at least 50% for both ¹⁸F labeled duramycin and Zn-DPA.

CONCLUSION:

Both PE-targeting ¹⁸F-duramycin and PS-targeting ¹⁸F-Zn-DPA could be considered as potential radiotracers for imaging cellular apoptosis. Advances in knowledge and implications for patient care: Cellular data support the further development of radiotracers targeting either PE or PS for imaging apoptosis, which can associate with clinical outcome for cancer patients.

News (Medical) associated with Molecular Targeting Technologies, Inc.

09 Dec 2024

·pipelinereview.com

MTTI 225Ac-EBTATE is Highly Effective Against Neuroendocrine Tumors

WEST CHESTER, PA, USA I December 09, 2024 I Molecular Targeting Technologies, Inc. (MTTI) published preclinical study results for their proprietary 225 Ac-EBTATE against SSTR2 NET cancers online in the European Journal of Nuclear Medicine. (“Long acting 225 Ac-EBTATE is highly efficacious against somatostatin receptor-2-positive neuroendocrine tumors” ( https://rdcu.be/d2lCG ). Professor Humphrey Fonge of the Université de Laval and lead author commented, “At just 40% of the administered dose reported for 225 Ac-DOTATATE, 225 Ac-EBTATE produces enhanced anti-tumor efficacy in Small Cell lung cancer (SCLC) and Pan-neuroendocrine tumor (NET) models as shown with complete tumor remissions. At a therapeutic dose of 2x 34 kBq, 225 Ac-EBTATE showed general safety for 28 days after blood biochemistry analysis, CBC, and histopathological examination of major organs and tissues. We demonstrated that 225 Ac-EBTATE was effective against human small-cell lung cancer (SCLC) with 80% complete remission and 100% survival in preclinical models.” MTTI has licensed commercial use rights for the patented Evans blue (EB) technology from the National Institute of Biomedical Imaging and Bioengineering (“ NIBIB ”), part of the National Institutes of Health (“ NIH ”). This platform is the basis for the best-in-class, new generation, collection of targeted radiopharmaceuticals (TRP). EB binds to serum albumin, extending in vivo circulatory half-life and tumor residence time, enhancing up to 30-fold uptake at a tumor and enabling good efficacy with significantly lower radiopharmaceutical activity and fewer dosing cycles vs. the current standard of care. Our 3-year follow up of 177 Lu-EBTATE in patients* (N=30) with metastatic neuroendocrine tumors, demonstrated good safety with no nephro- or hepatoxicity and 86% disease control rate using only 40% of the administered dose of 177 Lu-DOTATATE. Dr. Jean-Mathieu Beauregard, MD, Associate Professor of Department of Radiology of Université Laval, said, “I am encouraged to see the positive results of 225 Ac-EBTATE in treating small cell lung cancer and Pan-neuroendocrine tumor (NET) in preclinical studies. I look forward to working with MTTI and Professor Fonge to translate this into the clinic.” Dr. Chris Pak, President & CEO of MTTI commented “ 225 Ac-EBTATE effectiveness was encouraging, paralleling the clinical superiority of 177 Lu-EBTATE. We look forward to collaborating with Professors Beauregard and Fonge to drive 225 Ac-EBTATE into clinical trials in 2025.” Molecular Targeting Technologies, Inc. (MTTI) . Molecular Targeting Technologies, Inc. is a private, clinical stage biotech developing targeted radiopharmaceuticals (TRP) for rare cancers. MTTI is committed to building value by translating innovative TRP to improve human health. For more information: www.mtarget.com . *Jiang Y, Liu Q, Wang G, et al. Safety and efficacy of peptide receptor radionuclide therapy with 177 Lu-DOTA-EB-TATE in patients with metastatic neuroendocrine tumors. Theranostics. 2022;12(15):6437-6445. SOURCE: Molecular Targeting Technologies Inc

Clinical Result

12 Sep 2024

·www.businesswire.com

MTTI Reports on Fast-Acting Sprayable Molecule to Visualize Tumors for Real-Time Fluorescence-Guided Cytoreductive Surgery

WEST CHESTER, Pa.--( BUSINESS WIRE )--Molecular Targeting Technologies, Inc. (MTTI) will update findings on its proprietary topical near-infrared fluorescent dye, CypH-11 (Cmetglo), at the World Molecular Imaging Conference (WMIC) meeting in Montreal from September 9-13 and at the Peritoneal Surface Oncology Group International (PSOGI) meeting in Lyon from September 26-28, 2024. This convenient fast-acting technology* shows promise as an effective real-time tool for oncologists in fluorescence-guided surgery (FGS). This will allow clinicians to see small tumor residue and achieve a more complete resection of cancer in the abdominal cavity. We expect that Cmetglo may improve patient outcomes by avoiding unnecessary damage to normal tissue and increase progression-free survival of patients with peritoneal surface malignancies (PM). Dr. Johnny Ong, MD, Associate Professor, Department of Sarcoma, Peritoneal and Rare Tumors, National Cancer Centre Singapore** commented: “One of the limitations of cytoreductive surgery (CRS) is the difficulty in distinguishing tumors from normal and scar tissues. Here, we performed ex vivo validation of patient tissues to evaluate the clinical utility of Cmetglo in detecting PM via topical administration. Preliminary analysis suggests that the best clinical utility of Cmetglo could be in patients with colorectal malignancy, with the possibility of expanding its use to other histological subtypes.” Dr. Brian D Gray, SVP Research and Development noted: “MTTI’s Cmetglo makes the invisible visible. Tumor margins and metastases glow under near-infrared light. It can be a valuable addition to the surgeon’s’ armamentarium to achieve maximal cytoreduction during FGS.” Dr. Seung Koo Lee, Assistant Professor of Cell Biology Research, in Radiology at Weill Cornell Medicine***, commented: “CypH-11 is a sprayable pH-responsive fluorogenic probe that exhibits minimal fluorescence at neutral pH; however, it fluoresces brightly in an acidic environment which is a universal signature of cancer cell proliferation. Its capability of detecting small-sized ovarian tumors was further demonstrated by the spray of CypH-11 in a disseminated high-grade serous ovarian cancer (HGSOC) model.” Chris Pak, President & CEO of MTTI commented: “This groundbreaking molecule builds on MTTI’s innovative legacy in targeted diagnostics and therapeutics. We’re pursuing its use in colorectal, ovarian, and brain cancers, adding value to patients, surgeons, and other stakeholders.” Molecular Targeting Technologies, Inc. (MTTI) . MTTI is a private, clinical stage biotech developing targeted radiotherapeutics for rare cancers. MTTI is committed to building value by translating innovative diagnostics and radiopharmaceuticals to improve human health. For more information: www.mtarget.com . *This research is supported by the National Cancer Institute (NCI) for a SBIR phase II grant # R44CA275434 to MTTI. **This research is also supported by the Singapore Ministry of Health through the National Medical Research Council (NMRC) Office, MOH Holdings Pte Ltd and administered by National Health Innovation Centre (NHIC) under its Innovation to Industry (I2I) grant (NHIC Ref No.: NHIC-I2I-2306016) to National Cancer Centre Singapore. Any opinions, findings and conclusions or recommendations expressed in this material are those of the authors and do not reflect the views of NHIC ***Weill Cornell Medicine and MTTI hold intellectual property and financial interests in Cmetglo technology under development by MTTI.

21 May 2024

·www.biospace.com

MTTI Reports on 225Ac-EBTATE and 177Lu-EBTATE Radiopharmaceuticals at 2024 Society of Nuclear Medicine and Molecular Imaging Annual Meeting

WEST CHESTER, Pa.--(BUSINESS WIRE)-- Molecular Targeting Technologies, Inc. (MTTI), will update findings on both 177Lu-EBTATE clinical and 225Ac-EBTATE preclinical work during the 2024 SNMMI meeting in Toronto June 8-11 (exhibition booth #1819). 177Lu-EBTATE® an EvaThera drug, is the first patented long-acting peptide targeted radiotherapeutic drugs. It selectively targets and binds to somatostatin receptor 2 on neuroendocrine and other tumors, which are then killed by the radionuclide payload. Evans blue in EBTATE binds to serum albumin, extending in vivo circulatory half-life and tumor residence time, enabling effective use of significantly lower radiopharmaceutical activity and fewer dosing cycles vs. the current standard of care (SOC). These benefits are also evident in recent studies of the 225Ac-EBTATE homolog. Professor Zhaohui Zhu, MD, Peking Union Medical College Hospital, reflected “In our 3-year follow up on 30 patients* with metastatic neuroendocrine tumors (mNETs), 177Lu-EBTATE demonstrated good safety, with no nephro- or hepatoxicity and 86% disease control rate using 60% less radioactivity than 177Lu-DOTATATE. We observed low incidence of grade 3 hematoxicity (3.4% vs 15% of reported SOC) and no long-term nephrotoxicity of any grade.” The study “Long acting 225Ac-EBTATE is highly efficacious against somatostatin receptor-2-positive small-cell lung cancer (SCLC)**” has been accepted for presentation at 2024 SNMMI. Professor Humphrey Fonge of the University of Saskatchewan commented, "225Ac-EBTATE (2x 30 kBq administered 10 days apart) was effective against SCLC with 80% complete remissions and 100% survival. Treatment yielded a 2-fold greater tumor growth inhibition when compared with 225Ac-DOTATATE, at 60% less administered radioactivity. Toxicity, as measured by body weight, blood counts, and chemistry showed that 225Ac-EBTATE was well tolerated at a highly effective dose. 225Ac-EBTATE shows great promise against SCLC." Chris Pak, President & CEO of MTTI commented: “We are pleased to learn that 177Lu-EBTATE exhibited no safety concerns and was effective at a lower dose than SOC in mNET patients. We are also encouraged that 225Ac-EBTATE out-performed 225Ac-DOTATATE, providing a 2-fold greater tumor growth inhibition in preclinical findings using a much lower dose of radioactivity. We look forward to advancing our clinical trials with these radiotherapeutic drugs in small-cell lung and other cancers.” Molecular Targeting Technologies, Inc. (MTTI). MTTI is a private, clinical stage biotech developing targeted radiotherapeutics for rare cancers. MTTI is committed to building value by translating innovative radiopharmaceuticals to improve human health. For more information: . *Safety and efficacy of peptide receptor radionuclide therapy with 177Lu-DOTA-EB-TATE in patients with metastatic neuroendocrine tumors. Theranostics 2022; 12: 6437-6445 **The data will be presented in 2024 SNMMI. Fabrice Njotu, Humphrey Fonge et al. of the University of Saskatchewan, and Molecular Targeting Technologies, Inc. View source version on businesswire.com: Contacts Chris Pak, Email: cpak@mtarget.com Source: Molecular Targeting Technologies, Inc. View this news release online at:

Clinical Result

100 Deals associated with Molecular Targeting Technologies, Inc.

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Pipeline

Pipeline Snapshot as of 23 Dec 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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Phase 2

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

Rabies mAB(Molecular Targeting Technologies, Inc.) ( RABV-G )	Rabies More	Phase 3
Nca 177 Lu-EBTATE ( SSTR2 )	Thyroid Cancer, Hurthle Cell More	Phase 1/2
TDURA(Molecular Targeting Technologies, Inc.)	Colorectal Cancer More	Phase 1
177Lu-DOTA-EB-TATE ( SSTR )	Apudoma More	Phase 1
BPRDP056(Molecular Targeting Technologies, Inc.) ( Phosphatidylserine )	Neoplasms More	Phase 1

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