Delving into the Latest Updates on Pegarginase(Bio-Cancer Treatment International Ltd.) with Synapse

Overview

Basic Info

Drug Type

Enzyme

Synonyms

PEG-arginase, PEGylated recombinant human arginase, Pegarginase

+ [4]

Target

Arginine

Mechanism

Arginase replacements

Therapeutic Areas

NeoplasmsHemic and Lymphatic Diseases

Active Indication

Acute Myeloid Leukemia

Inactive Indication

Advanced Hepatocellular CarcinomaMetastatic hepatocellular carcinomaRefractory acute myeloid leukemia+ [1]

Originator Organization

Bio-Cancer Treatment International Limited.

Active Organization

Bio-Cancer Treatment International Limited.

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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PARC is an international phase I/II trial evaluating the safety and activity of pegylated recombinant human arginase (BCT-100) in children and young people with relapsed/refractory leukaemia, neuroblastoma, sarcoma and high grade gliomas (brain cancers).
Currently the outcomes for these patients are poor and the therapeutic options are limited with a significant toxicity burden. Therefore new treatments which work in different ways to standard chemotherapy are urgently needed. Research has shown that arginine (a nutrient) is important in the survival of cancer cells. BCT-100 is a drug which can deplete arginine levels and starve cancer cells - a completely new approach. BCT-100 has been tested in adults and shown to be active with almost no side-effects. This trial will test whether this dose of BCT-100 is also safe and active in children with relapsed/refractory leukaemia, neuroblastoma, sarcoma and high grade glioma. The trial will also study how BCT-100 is broken down in the body and look for new biological markers of treatment response. Up to 64 children with relapsed cancers will be recruited over 2 years.

Start Date28 Aug 2018

Sponsor / Collaborator

University of Birmingham

NCT02899286

/ Unknown statusPhase 2

A Phase II Open-label Study of the Efficacy and Safety of Recombinant Human Arginase 1 (PEG-BCT-100) in Patients With Relapsed or Refractory Acute Myeloid Leukemia

To evaluate the efficacy of PEG-BCT-100 in patients with relapsed or refractory acute myeloid leukemia (AML) in terms of remission rate.

Start Date01 Sep 2016

Sponsor / Collaborator

Bio-Cancer Treatment International Limited.

NCT02285101

/ CompletedPhase 1

Recombinant Human Arginase 1 (rhArg1) in Patients With Advanced Arginine Auxotrophic Solid Tumors: Dose Escalation, Safety and PK/PD

The goal of this clinical research study is to evaluate the safety of PEG-BCT- 100 given as an infusion to treat patients who bear advanced solid tumors that are dependent on arginine (melanoma, renal cell carcinoma, prostate cancer and hepatocellular carcinoma), and who have progressed after receiving approved or established therapies. This is a Phase 1 study; PEG-BCT-100 is an enzyme that degrades arginine and is an investigational drug.

Start Date01 Nov 2014

Sponsor / Collaborator

Bio-Cancer Treatment International Limited.

[+1]

100 Clinical Results associated with Pegarginase(Bio-Cancer Treatment International Ltd.)

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100 Translational Medicine associated with Pegarginase(Bio-Cancer Treatment International Ltd.)

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100 Patents (Medical) associated with Pegarginase(Bio-Cancer Treatment International Ltd.)

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314

Literatures (Medical) associated with Pegarginase(Bio-Cancer Treatment International Ltd.)

23 Jul 2024·Journal of Bone and Mineral Research

Skeletal consequences of preterm birth in pigs as a model for preterm infants

Article

Author: Adra, Amal ; Rasmussen, Martin B ; Ko, Frank C ; Sangild, Per T ; Moran, Meghan M ; Thymann, Thomas ; Sumner, Dale Rick ; Wilson, Brittany M

AbstractPreterm birth affects about 10% of all live births with many resultant health challenges, including metabolic bone disease of prematurity (MBDP), which is characterized by elevated alkaline phosphatase, suppressed phosphate, and deficient skeletal development. Because of the lack of an animal model, very little is known about bone structure, strength, and quality after preterm birth. This study investigated the utility of a pig model to replicate clinical features of preterm birth, including MBDP, and sought to determine if early postnatal administration of IGF-1 was an effective treatment. Preterm pigs, born by caesarean section at 90% gestation, were reared in intensive care facilities (respiratory, thermoregulatory, and nutritional support) and compared with sow-reared term pigs born vaginally. Preterm pigs were systemically treated with vehicle or IGF-1 (recombinant human IGF-1/BP-3, 2.25 mg/kg/d). Tissues were collected at postnatal days 1, 5, and 19 (the normal weaning period in pigs). Most bone-related outcomes were affected by preterm birth throughout the study period, whereas IGF-1 supplementation had almost no effect. By day 19, alkaline phosphatase was elevated, phosphate and calcium were reduced, and the bone resorption marker C-terminal crosslinks of type I collagen was elevated in preterm pigs compared to term pigs. Preterm pigs also had decrements in femoral cortical cross-sectional properties, consistent with reduced whole-bone strength. Thus, the preterm pig model replicates many features of preterm bone development in infants, including features of MBDP, and allows for direct interrogation of skeletal tissues, enhancing the field’s ability to examine underlying mechanisms.

01 May 2024·British Journal of Pharmacology

Intravenous recombinant cerebellin 1 treatment restores signalling by spinal glutamate delta 1 receptors and mitigates chronic pain

Article

Author: Chettiar, Poojashree B ; Dravid, Shashank M ; Thakur, Shriti S ; S Narasimhan, Kishore Kumar ; Asati, Devansh G ; Gakare, Sukanya G ; Sabnis, Siddhesh S ; Shelkar, Gajanan P

Background and PurposeChronic pain remains a major clinical problem that needs effective therapeutic agents. Glutamate delta 1 (GluD1) receptors and the protein cerebellin 1 (Cbln1) are down‐regulated in the central amygdala (CeA) in models of inflammatory and neuropathic pain. One treatment with Cbln1, intracerebroventricularly (ICV) or in CeA, normalized GluD1 and reduced AMPA receptor expression, resulting in lasting (7–10 days) pain relief. Unlike many CNS‐targeting biological agents, the structure of Cbln1 suggests potential blood–brain barrier penetration. Here, we have tested whether systemic administration of Cbln1 provides analgesic effects via action in the CNS.Experimental ApproachAnalgesic effects of intravenous recombinant Cbln1 was assessed in complete Freund's adjuvant inflammatory pain model in mice. GluD1 knockout and a mutant form of Cbln1 were used.Key ResultsA single intravenous injection of Cbln1 mitigated nocifensive and averse behaviour in both inflammatory and neuropathic pain models. This effect of Cbln1 was dependent on GluD1 receptors and required binding to the amino terminal domain of GluD1. Time course of analgesic effect was similar to previously reported ICV and intra‐CeA injection. GluD1 in both spinal cord and CeA was down –regulated in the inflammatory pain model, whereas GluD1 expression in spinal cord but not in CeA, was partly normalized by intravenous Cbln1. Importantly, recombinant Cbln1 was detected in the synaptoneurosomes in spinal cord but not in the CeA.Conclusions and ImplicationsOur results describe a novel mechanism by which systemic Cbln1 induces analgesia potentially by central actions involving normalization of signalling by spinal cord GluD1 receptors.

01 May 2024·Pediatric Research

Gut development following insulin-like growth factor-1 supplementation to preterm pigs

Article

Author: Bæk, Ole ; Burrin, Douglas G ; Thymann, Thomas ; Pankratova, Stanislava ; Rasmussen, Martin Bo ; Sangild, Per Torp ; Holgersen, Kristine

AbstractBackgroundReduced insulin-like growth factor-1 (IGF-1) levels may contribute to impaired organ development in preterm infants. Using preterm pigs as a model, we hypothesized that IGF-1 supplementation improves health and gut development during the first three weeks of life.MethodsFirst, clinical and organ endpoints were compared between artificially-reared, cesarean-delivered preterm pigs and vaginally-delivered, sow-reared term pigs at 5, 9 and 19 days. Next, preterm pigs were treated with recombinant human IGF-1 for 19 days (2.25 mg/kg/day, systemically).ResultsRelative to term pigs, preterm pigs had lower body weight, fat, bone contents, relative weights of liver and spleen and a longer and thinner intestine at 19 days. Preterm birth reduced intestinal villi heights and peptidase activities, but only at 5 and 9 days. In preterm pigs, IGF-1 reduced mortality primarily occurring from gastrointestinal complications and with a tendency towards salvaging smaller pigs. IGF-1 supplementation also increased spleen and kidney weights, small intestine length and maltase to lactase activity, reflecting gut maturation.ConclusionPreterm birth affects body composition and gut maturation in the first 1–2 weeks, but differences are marginal thereafter. Supplemental IGF-1 may improve gut health in pigs and infants in the first few weeks after preterm birth.Impact

Insulin-like growth factor 1 (IGF-1) supplementation may improve gut health and development in prematurity, but whether the effects are sustained beyond the immediate postnatal period is unclear.

In preterm pigs, the prematurity effects on IGF-1 and gut health deficiencies are most pronounced during the first week of life and diminishes thereafter.

In preterm pigs, IGF-1 supplementation beyond the first week of life reduced mortality.

The present study provides evidence of a sustained effect of IGF-1 supplementation on the gastrointestinal tract after the immediate postnatal period.

100 Deals associated with Pegarginase(Bio-Cancer Treatment International Ltd.)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Myeloid Leukemia	Phase 2	GB	Bio-Cancer Treatment International Limited.	10 Aug 2022
Refractory acute myeloid leukemia	Phase 1	HK	Bio-Cancer Treatment International Limited.	01 Sep 2016
Relapsing acute myeloid leukemia	Phase 1	HK	Bio-Cancer Treatment International Limited.	01 Sep 2016
Advanced Hepatocellular Carcinoma	Phase 1	HK	Bio-Cancer Treatment International Limited.	01 Apr 2014
Metastatic hepatocellular carcinoma	Phase 1	HK	Bio-Cancer Treatment International Limited.	01 Apr 2014

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01092091 (BCT-100-002, Pubmed \| Invest New Drugs) Manual	Phase 2	Hepatocellular Carcinoma ASS Negative	27	PEG-BCT-100	(kghpxuhpuw) = eqexswdldi dgebcpkvmb (gluhwhrkmw, 5.9 - 6.0) View more	Positive	01 Oct 2021
WCLC2016	Not Applicable	Malignant Pleural Mesothelioma	-	BCT-100	vunybesmbb(duyzewbmta) = wjngolictt fxdohzvtdq (nmpcmuytyd )	-	07 Dec 2016
SNO2015	Not Applicable	Glioma ASS1 \| ASL \| OTC	5	PEG-BCT-100 (rhArg1peg5000)	btrqeukycu(jvwcoeccmf) = jecvmrglbc ybnjskfyww (zhsvgvjpyk )	-	09 Nov 2015
SNO2015	Not Applicable	Glioma ASS1 \| ASL \| OTC	5	PEG-BCT-100 (Control (full culture medium))	btrqeukycu(jvwcoeccmf) = npqwtbukmb ybnjskfyww (zhsvgvjpyk )	-	09 Nov 2015
ASCO2010	Phase 1	Advanced Hepatocellular Carcinoma	15	Recombinant human arginase I (rhArgI)	idilgygtom(ylqasedjgd) = DLT was Gr 3 prolonged elevation of bilirubin in 2 patients at 2500 U/kg unnkwbkqji (msxsgsbcky ) View more	-	20 May 2010