Delving into the Latest Updates on PRCL-02 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

CRAC

Action

inhibitors

Mechanism

CRAC inhibitors(calcium release activated channel inhibitors)

Therapeutic Areas

Immune System DiseasesSkin and Musculoskeletal Diseases

Active Indication

Psoriasis

Inactive Indication

Chronic large plaque psoriasisPlaque psoriasisPsoriasis vulgaris

Originator Organization

Madrigal Pharmaceuticals, Inc.

Active Organization

Madrigal Pharmaceuticals, Inc.

Inactive Organization

PRCL Research Inc.

License Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC21H16FN5O2

InChIKeyXUABYEHHPVTMJV-UHFFFAOYSA-N

CAS Registry1407886-90-1

Background.Calcineurin inhibitors successfully control rejection of transplanted organs but also cause nephrotoxicity. This study, using a rhesus monkey renal transplantation model, sought to determine the applicability of a new immunomodulatory drug inhibiting the store-operated calcium release–activated calcium channel of lymphocytes to control transplant rejection without nephrotoxicity.Methods.Animals underwent kidney transplantation and were treated with tacrolimus alone (n = 3), a CRACM1 inhibitor (PRCL-02) (n = 6) alone, or with initial tacrolimus monotherapy followed by gradual conversion at 3 weeks to PRCL-02 alone (n = 3). PRCL-02 was administered via a surgically inserted gastrostomy tube BID.Results.Dose-related drug exposure in monkeys was established and renal transplants were then performed using PRCL-02 monotherapy. Oral dosing of PRCL-02 was well tolerated and resulted in suppressed T-cell proliferation in in vitro MLR comparable to animals in the tacrolimus control arm. Animals receiving tacrolimus monotherapy were e on day 100 without rejection. PRCL-02 monotherapy only marginally prolonged graft survival (MST = 13.16 d; group 2) compared with untreated controls. Animals treated initially with tacrolimus and converted to PRCL-02 monotherapy had a mean graft survival of 35.3 days which was prolonged compared with PRCL-02 monotherapy but not compared with the tacrolimus-treated group. Pharmacokinetic studies showed inconsistent drug exposures despite attempts to adjust dose and exposure which may have contributed to the rejections.Conclusions.We conclude that, in this nonhuman primate model of kidney transplantation, PRCL-02 demonstrated evidence of in vivo immunosuppressive activity but was inferior to tacrolimus treatment with respect to suppressing immune transplant rejection.

100 Deals associated with PRCL-02

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Psoriasis	Phase 2	-	Madrigal Pharmaceuticals, Inc.	-
Plaque psoriasis	Preclinical	Canada	PRCL Research Inc.	25 Sep 2018
Plaque psoriasis	Preclinical	Ukraine	PRCL Research Inc.	25 Sep 2018
Plaque psoriasis	Preclinical	Slovakia	PRCL Research Inc.	25 Sep 2018
Psoriasis vulgaris	Preclinical	Canada	PRCL Research Inc.	25 Sep 2018
Psoriasis vulgaris	Preclinical	Ukraine	PRCL Research Inc.	25 Sep 2018
Psoriasis vulgaris	Preclinical	Slovakia	PRCL Research Inc.	25 Sep 2018
Chronic large plaque psoriasis	Preclinical	Canada	PRCL Research Inc.	20 Feb 2017

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03614078 (CTgov)	Phase 2	Plaque psoriasis \| Psoriasis vulgaris	92	Placebo	gouvdydhto(hznxjdbvew) = grlmslchzi afxgwqrenv (cbzkavpfyu, icbtkhdswq - uptszlnpbs) View more	-	30 Mar 2020