Delving into the Latest Updates on Orano Med LLC with Synapse

Overview

Tags

Neoplasms

Digestive System Disorders

Respiratory Diseases

Therapeutic radiopharmaceuticals

Peptide Conjugate Radionuclide

Radionuclide Drug Conjugates (RDC)

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Neoplasms	5

Top 5 Drug Type	Count

Therapeutic radiopharmaceuticals	4
Peptide Conjugate Radionuclide	2
Radionuclide Drug Conjugates (RDC)	2
Small molecule drug	1

Top 5 Target	Count

MMP14(Matrix metalloproteinase 14)	1
GRPR(Gastrin releasing peptide receptor)	1
DLL3(Delta-like protein 3)	1
SSTR(Somatostatin receptor)	1
TRPV6(Transient receptor potential cation channel subfamily V member 6)	1

AlphaMedix™ (²¹²Pb-DOTAMTATE) is a radiotherapeutic drug indicated in subjects with unresectable, metastatic somatostatin receptor (SSTR) positive neuroendocrine tumors (NETs). Because 212Pb is an in vivo generator of alpha particles, it is particularly suitable for SSTR therapy applications.
This drug addresses an unmet need in the field of peptide receptor radionuclide therapy (PRRT) for NETs. Substitution of an alpha emitter (²¹²Pb) for the beta emitters currently being used (i.e., 177Lu or 90Y) will provide significantly higher Linear Energy Transfer (LET) and a shorter path length. Higher LET particles should cause more tumor cell death. Shorter path length should result in less collateral damage of the normal tissue and therefore less side effects for subjects receiving the drug.

Start Date05 Feb 2018

Sponsor / Collaborator

RadioMedix, Inc.

[+1]

100 Clinical Results associated with Orano Med LLC

Login to view more data

0 Patents (Medical) associated with Orano Med LLC

Login to view more data

13

Literatures (Medical) associated with Orano Med LLC

01 Nov 2024·Journal of Nuclear Medicine

Preclinical Investigation of [²¹²Pb]Pb-DOTAM-GRPR1 for Peptide Receptor Radionuclide Therapy in a Prostate Tumor Model

Article

Author: Wong, Amy G ; Wong, Amy G. ; Torgue, Julien J. ; Stallons, Tania A. ; Stallons, Tania A ; Saidi, Amal ; Torgue, Julien J

The role of gastrin-releasing peptide receptor (GRPR) in various diseases, including cancer, has been extensively studied and has emerged as a promising therapeutic target. In this study, we successfully achieved the use of [²¹²Pb]Pb-DOTAM-GRPR1, comprising the α-particle generator, ²¹²Pb, combined with a GRPR-targeting peptide, GRPR1, in a prostate cancer model. Methods: Pharmacokinetics, toxicity, radiation dosimetry, and efficacy were assessed in GRPR-positive prostate tumor-bearing mice after intravenous administration of [²¹²Pb]Pb-DOTAM-GRPR1 (where DOTAM is 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane). Results: Preclinical studies have shown tumor targeting of up to 5 percent injected dose per gram over 24 h, and optimization of the drug formulation and quantity has led to minimized oxidation and off-target binding, respectively. Particularly, an increase in peptide amount from 28 to 280 ng was shown to reduce off-target uptake, especially at the level of the pancreas, by about 30%. Furthermore, dosimetry studies confirmed the kidney as the dose-limiting organ, and toxicity studies revealed that a nontoxic dose of up to 1,665 kBq could be injected into mice. Efficacy studies indicated a median survival time of 9 wk in the control group, which received only a buffer solution, compared with 19 wk in the group that received 4 injections of 370 kBq at 3-wk intervals. Conclusion: Taken together, these combined data demonstrate the safety, tolerability, and efficacy of [²¹²Pb]Pb-DOTAM-GRPR1, thus warranting further exploration in clinical trials.

01 Jun 2024·Journal of Clinical Oncology

Safety, tolerability and efficacy of ²¹²Pb-DOTAMTATE as a targeted alpha therapy for subjects with unresectable or metastatic somatostatin receptor-expressing gastroenteropancreatic neuroendocrine tumors (SSTR+ GEP-NETs): A phase 2 study.

Author: Maluccio, Mary Alice ; Strosberg, Jonathan R. ; Wagner, Volker Jean ; Cohn, Allen Lee ; Manuel, Allison ; Delpassand, Ebrahim S ; Naqvi, Shagufta ; Woloski, Rachel ; Tworowska, Izabela ; Torgue, Julien

4020 Background: 212Pb-DOTAMTATE is a Targeted Alpha Therapy (TAT) in clinical development for subjects with SSTR+ neuroendocrine tumors. A phase I dose-escalation study has already been completed (Delpassand et al. J Nucl Med 2022). TAT holds the promise to improve outcomes versus Peptide Receptor Radionuclide Therapy (PRRT) with beta-emitters like 177Lu-DOTATATE, currently considered the standard of care for subjects with GEP-NETs. Methods: ALPHAMEDIX 02 is a Phase II, open-label, multicenter study evaluating the safety, tolerability and efficacy of 212Pb-DOTAMTATE in PRRT-naïve (Cohort 1, N = 36) and PRRT-refractory (Cohort 2, Target N = 30) subjects with histologically confirmed unresectable or metastatic GEP-NETs, positive somatostatin analogue imaging and at least 1 site of measurable disease per RECIST 1.1. 212Pb-DOTAMTATE was administered at 67.6 μCi/kg per cycle, with a maximum activity administered per cycle of 5.5 mCi every 8 weeks, for up to 4 cycles. Primary endpoints include overall response rate (ORR) per RECIST1.1, and incidence and severity of adverse events (AEs). Secondary endpoints include progression free survival, overall survival , and health-related quality of life. Initial results of the already completed cohort 1 are presented. Results: In cohort 1, 17 out of 36 subjects with metastatic SSTR+ GEP-NETs achieved a confirmed response (ORR 47.2% (32.0-63.0%)). In the Phase I trial, five out of eight PRRT- naïve subjects with SSTR+ GEP-NETs treated with the same regimen of 212Pb-DOTAMTATE achieved a response (ORR 62.5% (30.6-86.3%)): the combined ORR from both studies is 50% (22 out of 44, 95%-CI:36% - 64%). Median Duration of Response (DOR) has not been reached in both studies. Four out of five subjects (80%) with confirmed response in Phase I had a DOR of ≥ 12 months. In the ongoing Phase II study the response follow-up for 10 subjects with confirmed response is currently shorter than 6 months: so far 7 out of 17 subjects (41%) with confirmed response had a DOR of ≥ 6 months, and one of these subjects had a DOR of ≥ 12 months. Lymphocytopenia is a lead cause of the 59% grade 3 and 4 AEs reported in subjects in cohort 1. Overall, 4 fatal AEs were reported: death / progressive disease (N = 2), carcinoid syndrome (N = 1) and sepsis (N = 1). Conclusions: In PRRT-naïve subjects with SSTR+ unresectable or metastatic GEP-NETs treatment with up to 4 cycles of ²¹²Pb-DOTAMTATE (67.6 μCi/kg/cycle) was well-tolerated, with a safety profile consistent with the underlying disease and expected toxicities of radioligand therapy, similar to 177Lu-DOTATATE. The ORR of 47.2% in cohort 1 (50% in the pooled dataset) appears to be substantially higher than the ORR previously reported for 177Lu-DOTATATE in the pivotal NETTER-1 study (ORR 18% (10–25%)). Clinical trial information: NCT05153772 .

04 Mar 2024·Inorganic Chemistry

Enhancing r₁ Relaxivity in GdDOTA-Monoamide Complexes through Polar Group-Mediated Ordering of Second-Sphere Water Molecules

Article

Author: Kretschmer, Jan ; Jurek, Paul ; Buchanan, Emily ; Chiaffarelli, Remy ; Martins, André F. ; Paranawithana, Namini N. ; Kiefer, Garry ; Sherry, A. Dean ; Lopez, Katherine ; Zhao, Piyu

This study was designed to test whether the single appended phosphonate group in GdDOTA-1AmP is sufficient for catalyzing the exchange of proton from the single inner-sphere water-exchanging molecule. Unlike the other phosphonate derivatives in this series, GdDOTA-1AmP showed a surprisingly smooth increase in r₁ relaxivity from 3.0 to 6.3 mM^-1 s^-1 at 20 MHz as the pH was lowered from 9 to 2.5. In comparison to the bis-, tris-, and tetrakis-phosphonate analogues, which all show a biphasic dependence of r₁ with changes in pH, the unique r₁ versus pH characteristics of GdDOTA-1AmP are shown to closely parallel deprotonation of the single appended phosphonate group. Although the tissue biodistribution and clearance rates of GdDOTA-1AmP are more favorable than the other more highly charged phosphonate derivatives, the pH dependency of r₁ is substantially reduced at magnetic fields typically used for small animal imaging (7 and 9.4T), so the attractiveness of this new molecule for quantitative imaging of tissue pH is diminished. However, this study provides some new insights into the feasibility of designing pH-responsive MRI contrast agents based upon fundamental acid-base prototropic mechanisms.

100 Deals associated with Orano Med LLC

Login to view more data

100 Translational Medicine associated with Orano Med LLC

Login to view more data

Corporation Tree

Boost your research with our corporation tree data.

login

or

view full example data

Boost your research with our corporation tree data.

Pipeline

Pipeline Snapshot as of 11 Feb 2025

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

Discovery

1

2

Preclinical

Phase 1 Clinical

1

Phase 2 Clinical

Other

2

Login to view more data

Current Projects

Drug(Targets)	Indications	Global Highest Phase

212Pb-AR-RMX ( SSTR )	Somatostatin Receptor-Positive Neuroendocrine Tumor More	Phase 2
212Pb-DOTAM-GRPR1 ( GRPR )	Non-Small Cell Lung Cancer More	Phase 1
Pb-BCY20603 ( MMP14 )	Neoplasms More	Preclinical
DLL3(Molecular Partners) ( DLL3 )	Solid tumor More	Preclinical
212Pb peptide receptor radionuclide therapy (Orano Med) ( TRPV6 )	Solid tumor More	Discovery