Delving into the Latest Updates on PSMA ADC(Progenics Pharmaceuticals) with Synapse

Overview

Basic Info

Drug Type

Antibody drug conjugate (ADC)

Synonyms

PSMA-ADC

Target

PSMA x Tubulin

Action

inhibitors

Mechanism

PSMA inhibitors(Prostate-specific membrane antigen inhibitors), Tubulin inhibitors

Therapeutic Areas

NeoplasmsNervous System DiseasesUrogenital Diseases+ [1]

Active Indication-

Inactive Indication

GlioblastomaGlioblastoma MultiformeGliosarcoma+ [2]

Originator Organization

Progenics Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

Rhode Island Hospital

Progenics Pharmaceuticals, Inc.

The University of Texas at Dallas

+ [1]

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC39H67N5O7

InChIKeyDASWEROEPLKSEI-UIJRFTGLSA-N

CAS Registry474645-27-7

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PSMA ADC 2301EXT is an open-label study to further assess the anti-tumor activity as measured by radiographic imaging and biomarkers, safety and tolerability of Prostate Specific Membrane Antigen Antibody Drug Conjugate (PSMA ADC) in subjects with mCRPC. Subjects who have participated in the PSMA ADC 2301 study and who, in the opinion of the Principal Investigator are likely to benefit from continued treatment with PSMA ADC are eligible for the PSMA ADC 2301 extension study. Subjects who are benefiting from treatment may be able to receive up to an additional eight to sixteen doses (every 3 weeks) of PSMA ADC.

Start Date01 Oct 2013

Sponsor / Collaborator

Progenics Pharmaceuticals, Inc.

NCT01856933

/ CompletedPhase 2IIT

BrUOG 263: PSMA ADC for Recurrent Glioblastoma Multiforme (GBM): A Phase II Brown University Oncology Research Group Study

The purpose of this study is to evaluate the effectiveness of Prostate Specific Membrane Antigen (PSMA ADC), as well as its safety and side effects for patients with advanced brain tumors. This study will also study how your body metabolizes (breaks down) PSMA ADC.

Start Date01 May 2013

Sponsor / Collaborator

Brown University

[+2]

NCT01695044

/ CompletedPhase 2

A Phase 2, Open-label, Multicenter Study of PSMA ADC in Subjects With Metastatic Castration-resistant Prostate Cancer

PSMA ADC 2301 is a Phase 2, open-label, study to assess the anti-tumor activity and tolerability of Prostate Specific Membrane Antigen Antibody Drug Conjugate (PSMA ADC) in two groups of subjects with metastatic castration-resistant prostate cancer (mCRPC). One group comprises subjects who must have received at least one taxane-containing chemotherapy regimen (e.g. docetaxel, cabazitaxel). The second group comprises subjects who are cytotoxic chemotherapy-naïve. Subjects who are cytotoxic chemotherapy-naïve must have received and progressed on-, be ineligible for, refused, have an intolerance to-, or not have access to Radium-223. Both groups of subjects must also have received and progressed on abiraterone acetate and/or enzalutamide. If a subject is unable to receive abiraterone acetate and/or enzalutamide, Sponsor approval is required for participation in the study. Subjects will receive up to eight doses of PSMA ADC approximately once every three weeks.

Start Date01 Sep 2012

Sponsor / Collaborator

Progenics Pharmaceuticals, Inc.

100 Clinical Results associated with PSMA ADC(Progenics Pharmaceuticals)

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100 Translational Medicine associated with PSMA ADC(Progenics Pharmaceuticals)

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100 Patents (Medical) associated with PSMA ADC(Progenics Pharmaceuticals)

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585

Literatures (Medical) associated with PSMA ADC(Progenics Pharmaceuticals)

03 Feb 2025·Angewandte Chemie International Edition

Benzyl Ammonium Carbamates Undergo Two‐Step Linker Cleavage and Improve the Properties of Antibody Conjugates

Article

Author: Patel, Nimit L. ; Schnermann, Martin J. ; Kalen, Joseph ; Li, Xiaoyi

AbstractTargeted payload delivery strategies, such as antibody‐drug conjugates (ADCs), have emerged as important therapeutics. Although considerable efforts have been made in the areas of antibody engineering and labeling methodology, improving the overall physicochemical properties of the linker/payload combination remains an important challenge. Here we report an approach to create an intrinsically hydrophilic linker domain. We find that benzyl α‐ammonium carbamates (BACs) undergo tandem 1,6–1,2‐elimination to release secondary amines. Using a fluorogenic hemicyanine as a model payload component, we show that a zwitterionic BAC linker improves labeling efficiency and reduces antibody aggregation when compared to a commonly used para‐amino benzyl (PAB) linker as well as a cationic BAC. Cellular and in vivo fluorescence imaging studies demonstrate that the model payload is specifically released in antigen‐expressing cells and tumors. The therapeutic potential of the BAC linker strategy was assessed using an MMAE payload, a potent microtubule‐disrupting agent frequently used for ADC applications. The BAC‐MMAE combination enhances labeling efficiency and cellular toxicity when compared to the routinely used PAB‐Val‐Cit ADC analogue. Broadly, this strategy provides a general approach to mask payload hydrophobicity and improve the properties of targeted agents.

01 Feb 2025·Tetrahedron

Drug-linker constructs bearing unique dual-mechanism tubulin binding payloads tethered through cleavable and non-cleavable linkers

Article

Author: VanNatta, Jennifer M ; Ford, Jacob W ; Pinney, Kevin G ; Trawick, Mary Lynn ; Hamel, Ernest ; Lin, Chen-Ming ; Bai, Ruoli ; Deng, Yuling ; Mondal, Deboprosad

Antibody-drug conjugates (ADCs) have advanced as a mainstay among the most promising cancer therapeutics, offering enhanced antigen targeting and encompassing wide diversity in their linker and payload components. Small-molecule inhibitors of tubulin polymerization have found success as payloads in FDA approved ADCs and represent further promise in next-generation, pre-clinical and developmental ADCs. Unique dual-mechanism payloads (previously designed and synthesized in our laboratories) function as both potent antiproliferative agents and promising vascular disrupting agents capable of imparting selective and effective damage to tumor-associated microvessels. These payloads have been incorporated into a variety of drug-linker constructs utilizing the clinically relevant cathepsin B cleavable Val-Cit dipeptide linker, employed within several FDA approved ADCs, along with other non-cleavable constructs. Various synthetic strategies were evaluated to prepare these drug-linker constructs. Aniline-based payloads were incorporated utilizing the Val-Cit dipeptide linker similar to FDA approved ADCs such as Adcetris^® (brentuximab vedotin). An additional self-immolative group, previously described in the literature for related model systems, was employed to tether the phenolic payloads. A variety of drug-linker constructs (with each bearing a unique dual mechanism payload) were synthesized and evaluated biologically for their enzyme-mediated release of payload and inhibition of tubulin polymerization. Following deactivation of the highly electrophilic maleimido terminus as its corresponding N-acetyl cysteine (NAC) derivative, the most promising construct (NAC-4) demonstrated approximately 90% release of an aniline-functionalized payload (1) upon treatment with cathepsins B or L over 90 minutes. Building on these promising results, future studies will examine the conjugation of drug-linker construct 4 to selected antibodies and engineered proteins and evaluate the biological activity of the resultant antibody-drug conjugates (ADCs).

15 Jan 2025·Bioconjugate Chemistry

Delivery of Monomethyl Auristatin F to the Tumor Microenvironment with Noninternalizing Fibroblast Activation Protein-Cleavable Small Molecule–Drug Conjugates Elicits Potent In Vivo Anticancer Activity

Article

Author: Bocci, Matilde ; Principi, Lucrezia ; Neri, Dario ; Gilardoni, Ettore ; Cazzamalli, Samuele ; Galbiati, Andrea

OncoFAP is an ultrahigh affinity ligand of fibroblast activation protein (FAP), a tumor-associated antigen overexpressed in the stroma of the majority of solid tumors. OncoFAP has been previously implemented as a tumor-homing moiety for the development of small molecule drug conjugates (SMDCs). In the same context, the glycine--proline dipeptide was included with the aim to selectively undergo cleavage only in the presence of the target FAP, triggering the consequent release of the cytotoxic payload in the tumor microenvironment. In this work, we evaluate the use of monomethyl auristatin F (MMAF) as a payload, a close derivative of MMAE bearing a charged carboxylic acid that hampers its cellular permeability, typically employed in the development of internalizing antibody-drug conjugates. The novel OncoFAP-GlyPro-MMAF and the previously described OncoFAP-GlyPro-MMAE were compared in a head-to-head therapeutic experiment in mice bearing FAP-positive tumors. Surprisingly, the MMAF conjugate mediated potent antitumor activity, despite its poor cellular permeability.

1

News (Medical) associated with PSMA ADC(Progenics Pharmaceuticals)

22 Nov 2022

·www.prnewswire.com

First Patient Dosed in Phase II 'IPAX-Linz' Study of TLX101 for Glioblastoma Therapy

MELBOURNE, Australia, Nov. 21, 2022 /PRNewswire/ -- Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) today announces that a first patient has been dosed in a Phase II investigator-initiated study of TLX101 in combination with external beam radiation therapy (EBRT) in patients with recurrent high-grade gliomas (HGG), including glioblastoma multiforme (GBM). TLX101 (4-L-[131I] iodo-phenylalanine, or 131I-IPA) is one of Telix's lead therapeutic clinical programs and has been granted orphan drug designation in the U.S. and Europe. TLX101 targets L-type amino acid transporter 1 (LAT-1), typically over-expressed in many malignant tumours, including HGG/GBM. The IPAX-Linz study, which is being led by Professor Josef Pichler at Kepler University Hospital in Linz, Austria, builds on data generated in the IPAX-1 study. The final results of the IPAX-1 study, reported in September 2022, demonstrated a favourable safety profile and encouraging preliminary therapeutic effect.[1] IPAX-Linz will continue to study the benefit of TLX101 to patients in the second line (refractory) setting at this leading neuro-oncology site in Europe. Targeting recruitment of 10 patients, the goal of this study is to gather additional data on clinical utility. IPAX-Linz will run concurrently with IPAX-2, which is evaluating TLX101 in combination with post-surgical standard of care comprised of EBRT and temozolomide in newly diagnosed (first line) GBM patients. Prof. Josef Pichler, Kepler University Hospital, Austria, Principal Investigator in the IPAX-Linz study said, "Based on promising safety and early efficacy data for TLX101 in the IPAX-1 study, I am pleased to continue to explore this therapeutic modality in a larger patient cohort, where there are currently few effective treatment options. Preliminary results are only achieved thanks to close and optimal cooperation with our colleagues at Ordensklinikum Linz, Barmherzige Schwestern and we are grateful for their contribution to this trial." Dr. Colin Hayward, Chief Medical Officer of Telix Pharmaceuticals added, "We are pleased to have commenced the IPAX-Linz study, which alongside IPAX-2 supports Telix's goal to expedite the development of a potential new therapy in an aggressive cancer with poor prognosis. We would like to thank Prof. Josef Pichler and his clinical team at Kepler University Hospital, as well as the patients who will contribute to this important study." About Telix Pharmaceuticals Limited Telix is a biopharmaceutical company focused on the development and commercialisation of diagnostic and therapeutic radiopharmaceuticals. Telix is headquartered in Melbourne, Australia with international operations in the United States, Europe (Belgium and Switzerland), and Japan. Telix is developing a portfolio of clinical-stage products that aims to address significant unmet medical need in oncology and rare diseases. Telix is listed on the Australian Securities Exchange (ASX: TLX). For more information visit www.telixpharma.com and follow Telix on Twitter (@TelixPharma) and LinkedIn. Telix's lead product, gallium-68 (68Ga) gozetotide (also known as 68Ga PSMA-11) injection, has been approved by the U.S. Food and Drug Administration (FDA),[2] and by the Australian Therapeutic Goods Administration (TGA),[3] and by Health Canada.[4]

Drug ApprovalPhase 2Orphan DrugRadiation Therapy

100 Deals associated with PSMA ADC(Progenics Pharmaceuticals)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glioblastoma Multiforme	Phase 2	United States	Progenics Pharmaceuticals, Inc.	01 May 2013
Gliosarcoma	Phase 2	United States	Progenics Pharmaceuticals, Inc.	01 May 2013
Metastatic castration-resistant prostate cancer	Phase 2	United States	Progenics Pharmaceuticals, Inc.	01 Sep 2012
Glioblastoma	Phase 2	-	Brown University	-
Glioblastoma	Phase 2	-	The University of Texas at Dallas	-
Glioblastoma	Phase 2	-	Rhode Island Hospital	-
Glioblastoma	Phase 2	-	Progenics Pharmaceuticals, Inc.	-
Prostatic Cancer	Phase 2	-	Rhode Island Hospital	-
Prostatic Cancer	Phase 2	-	The University of Texas at Dallas	-
Prostatic Cancer	Phase 2	-	Brown University	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01695044 (Pubmed \| Prostate) Manual	Phase 2	Metastatic castration-resistant prostate cancer	119	abiraterone+enzalutamide+PSMA ADC (all treated)	(mmjjcrpalt) = The most common serious AEs were dehydration, hyponatremia, febrile neutropenia, and constipation. hqsdfmlejr (ppkardioxf ) View more	Positive	01 Jan 2020
				abiraterone+enzalutamide+PSMA ADC (chemotherapy-naïve)
NCT01414283 (Pubmed \| Prostate) Manual	Phase 1	Prostatic Cancer	52	PSMA ADC	(satnxpexyb) = yfbgvgcvzj tmvzcycrez (bkqrlweple )	Positive	01 May 2019
ASCO2018	Not Applicable	Metastatic castration-resistant prostate cancer	18	PSMA theranostics (Patients with low PSMA-expression)	(oqszvhzzcc) = witutxgdfp ifpufvjcgv (mosusovqll, 1.7 - 4.4)	Negative	01 Jun 2018
				PSMA theranostics (Patients with discordant FDG-avid disease)	(oqszvhzzcc) = wosbscwqkq ifpufvjcgv (mosusovqll, 1.7 - 4.4)
NCT01856933 (CTgov)	Phase 2	Gliosarcoma \| Glioblastoma Multiforme	6	PSMA ADC	ujqlwpqnxh(lsoqfzzmes) = japalhtwus snnyyngppv (ksqhgzvmrb, ycxiqizdbz - jaarfybpih) View more	-	17 Jun 2015
AUA2015	Phase 2	Metastatic castration-resistant prostate cancer prostate specific antigen \| neuroendocrine serum markers \| PSMA expression	119	PSMA ADC 2.5 mg/kg	ujxzbcbwiy(yraimqwbjb) = lxctqhaolk gcoltoxfbg (nqzmqhjnfj ) View more	-	01 Apr 2015
				PSMA ADC 2.3 mg/kg	ujxzbcbwiy(yraimqwbjb) = jxobbaiwcf gcoltoxfbg (nqzmqhjnfj ) View more
NCT01695044 (ASCO_GU2015)	Phase 2	Metastatic castration-resistant prostate cancer	119	PSMA ADC 2.5 mg/kg	uybnrwdxjc(fhhnlhuihu) = ysxnudbpdz jfnsymsmxk (hbziislani )	-	01 Mar 2015
				PSMA ADC 2.3 mg/kg	uybnrwdxjc(fhhnlhuihu) = tzfeelwcaw jfnsymsmxk (hbziislani )
NCT02020135 (ASCO2014)	Phase 2	Metastatic castration-resistant prostate cancer	34	PSMA ADC at 2.3 mg/kg	nvbpsfmvdf(rmsjmzefdd) = utadyintcp cmprswehyw (asrnremaxr ) View more	-	20 May 2014
				PSMA ADC at 2.5 mg/kg	nvbpsfmvdf(rmsjmzefdd) = rjkzbllnzq cmprswehyw (asrnremaxr ) View more

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Translational Medicine

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Deal

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Clinical Trial

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Approval

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Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

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