A combined treatment with GM-CSF, fosfomycin and metronidazole for pouchitis in ulcerative colitis patients after restorative ileal pouch anal anastomosis surgeryA clinical safety and proof-of-concept study

Start Date06 Jul 2021

Sponsor / Collaborator-

NCT04739618 / Active, not recruitingPhase 2

A Phase 2 Trial of Non-ablative Cryosurgical Freezing and Multiplex Immunotherapy in Patients With Metastatic Solid Cancer

This study seeks to estimate the potential efficacy of the study treatment, as well as the occurrence of adverse events.

Start Date04 Mar 2021

Sponsor / Collaborator-

CTRI/2019/12/022516 / RecruitingNot ApplicableIIT

A Randomized controlled trial comparing Imipenem and Tigecycline Versus Imipenem and Tigecycline With GM-CSF for the management of Spontaneous Bacterial Peritonitis presenting with septic shock

Start Date25 Dec 2019

Sponsor / Collaborator

Institute of Liver & Biliary Sciences

100 Clinical Results associated with Molgramostim biosimilar(Reliance GeneMedix Ltd.)

100 Translational Medicine associated with Molgramostim biosimilar(Reliance GeneMedix Ltd.)

100 Patents (Medical) associated with Molgramostim biosimilar(Reliance GeneMedix Ltd.)

10,038

Literatures (Medical) associated with Molgramostim biosimilar(Reliance GeneMedix Ltd.)

01 Jan 2025·Brain, Behavior, and Immunity

The association of maternal COVID-19-infection during pregnancy on the neonatal immune profile and associations with later diagnosis of neurodevelopmental disorders

Article

Author: Ashwood, Paul ; Yolken, Robert H ; Kim, Danielle Hj ; Kim, Danielle HJ ; Alexeeff, Stacey ; de Water, Judy Van ; Iosif, Ana-Maria ; Croen, Lisa A ; Ames, Jennifer L ; Qian, Yinge

Despite the prevalence and significant concern of COVID-19 in maternal and offspring health, little is known about the impact of COVID-19 during pregnancy on newborn immunity and neurodevelopment. This study aimed to examine 1) the relationship between maternal COVID-19 during pregnancy and newborn immune profiles and investigate the 2) associations between specific newborn immune profiles and the risk of subsequent diagnosis of a neurodevelopmental disorder (NDD) among children with prenatal exposure to COVID-19. Newborn dried bloodspots (NBS) from 545 children born at Kaiser Permanente Northern California between January 2020 and September 2021 (460 [223 males, 237 females] to COVID-19-infected [COVID + ] mothers; 85 [45 males, 40 females] to COVID-19-uninfected [COVID-] mothers) were used to profile newborn immune molecules via a 42-plex cytokine/chemokine assay. Among the 460 children born to COVID + mothers, 73 (47 males, 27 females) were later diagnosed with an NDD. In the first set of analyses examining the association between maternal COVID-19 infection during pregnancy and newborn immune profile, the results adjusted for covariates but uncorrected for multiple comparisons showed that newborns of COVID + mothers had significantly higher levels of IL-22 (est. = 0.16, 95 % Cl 0.01, 0.3, p = 0.04) and GM-CSF (estimate [est.] = 0.27, 95 % Cl 0.09, 0.46, p = 0.004) compared to newborns of COVID- mothers. These differences were no longer statistically significant after multiple comparison adjustments. In the second analysis exploring the association between newborn profile and later diagnosis of NDD among newborns born to COVID + mothers, the results adjusted for covariates revealed an association between higher neonatal levels of IL-22 (HR = 0.49, 95 % Cl 0.33, 0.75, p = 0.001) and lower risk of a later diagnosis of an NDD, which remained significant after multiple comparison adjustments (p = 0.04). Other neonatal cytokines/chemokines/growth factors such as sCD40L (HR = 0.7, 95 % Cl 0.57, 0.9, p = 0.009), IP-10 (HR = 0.46, 95 % Cl 0.25, 0.83, p = 0.009), MIG (HR = 0.52, 95 % Cl 0.3, 0.9, p = 0.02), FLT-3L (HR = 0.45, 95 % Cl 0.24, 0.83, p = 0.01), PDGF AB/BB (HR = 0.56, 95 % Cl 0.36, 0.99, p = 0.046), VEGF (HR = 0.57, 95 % Cl 0.34, 0.98, p = 0.04), and IL-4 (HR = 0.48, 95 % Cl 0.26, 0.93, p = 0.03) were no longer statistically significant after multiple comparison adjustments. Despite the imbalance between the number of COVID-19 exposed and unexposed newborns in this study cohort, our novel findings enhance our understanding of the potential impact of maternal COVID-19 infection during pregnancy on the developing neonatal immune system. Our findings highlight the role of immune molecules, beyond those considered to be pro-inflammatory, that may be crucial in maternal and newborn immunity against COVID-19 infection during pregnancy. Furthermore, our results suggest that reduced levels of neonatal immune molecules in newborns of COVID + mothers may be linked to an increased risk of a subsequent diagnosis of an NDD.

31 Dec 2024·Human Vaccines & Immunotherapeutics

Long-term follow up of patients treated with a DNA vaccine (pTVG-hp) for PSA-recurrent prostate cancer

Article

Author: Eickhoff, Jens C. ; Tonelli, Tommaso P. ; McNeel, Douglas G. ; Liu, Glenn ; Johnson, Laura E.

We have previously reported two single-agent phase I trials, evaluating the dose or schedule, of a DNA vaccine (pTVG-HP) encoding prostatic acid phosphatase (PAP) administered with GM-CSF as the adjuvant. These were in patients with PSA-recurrent, radiographically non-metastatic, prostate cancer (PCa). We report here the long-term safety and overall survival of these patients. Specifically, 22 patients with non-metastatic, castration-sensitive PCa (nmCSPC) were treated with pTVG-HP, 100-1500 µg, administered over 12 weeks and followed for 15 y. 17 patients with non-metastatic castration-resistant PCa (nmCRPC) were treated with 100 µg pTVG-HP with different schedules of administration over 1 y and followed for 5 y. No adverse events were detected in long-term follow-up from either trial that were deemed possibly related to vaccination. Patients with nmCSPC had a median overall survival of 12.3 y, with 5/22 (23%) alive at 15 y. 8/22 (36%) died due to prostate cancer with a median survival of 11.0 y, and 9/22 (41%) died of other causes. Patients with nmCRPC had a median overall survival of 4.5 y, with 8/17 (47%) alive at 5 y. The presence of T-cells specific for the PAP target antigen was detectable in 6/10 (60%) individuals with nmCSPC, and 3/5 (60%) individuals with nmCRPC, many years after immunization. The detection of immune responses to the vaccine target years after immunization suggests durable immunity can be elicited in patients using a DNA vaccine encoding a tumor-associated antigen.Trial Registration: NCT00582140 and NCT00849121.

01 Dec 2024·Cellular and Molecular Life Sciences

Disrupting Smad3 potentiates immunostimulatory function of NK cells against lung carcinoma by promoting GM-CSF production

Article

Author: Lian, Guang-Yu ; Mak, Thomas Shiu-Kwong ; Wang, Qing-Ming ; Huang, Xiao-Ru ; Lan, Hui-Yao ; Yu, Xue-Qing

AbstractThrough Smad3-dependent signalings, transforming growth factor-β (TGF-β) suppresses the development, maturation, cytokine productions and cytolytic functions of NK cells in cancer. Silencing Smad3 remarkably restores the cytotoxicity of NK-92 against cancer in TGF-β-rich microenvironment, but its effects on the immunoregulatory functions of NK cells remain obscure. In this study, we identified Smad3 functioned as a transcriptional repressor for CSF2 (GM-CSF) in NK cells. Therefore, disrupting Smad3 largely mitigated TGF-β-mediated suppression on GM-CSF production by NK cells. Furthermore, silencing GM-CSF in Smad3 knockout NK cells substantially impaired their anti-lung carcinoma effects. In-depth study demonstrated that NK-derived GM-CSF strengthened T cell immune responses by stimulating dendritic cell differentiation and M1 macrophage polarization. Meanwhile, NK-derived GM-CSF promoted the survival of neutrophils, which in turn facilitated the terminal maturation of NK cells, and subsequently boosted NK-cell mediated cytotoxicity against lung carcinoma. Thus, Smad3-silenced NK-92 (NK-92-S3KD) may serve as a promising immunoadjuvant therapy with clinical translational value given its robust cytotoxicity against malignant cells and immunostimulatory functions to reinforce the therapeutic effects of other immunotherapies.

News (Medical) associated with Molgramostim biosimilar(Reliance GeneMedix Ltd.)

25 Oct 2024

·www.globenewswire.com

Ultimovacs Announces Publication of Phase II FOCUS Trial Results on medRxiv

Oslo, October 25, 2024: Ultimovacs ASA (“Ultimovacs”) (OSE ULTI), a clinical-stage biotechnology company developing immunotherapeutic cancer vaccines, today announced that the results from Phase II FOCUS trial (NCT05075122) have been published online on the preprint platform medRxiv. As previously reported, topline data readout demonstrated that adding UV1 to the standard of care pembrolizumab did not lead to clinical benefits in progression free survival or overall survival in the late-stage head and neck squamous cell carcinoma (HNSCC) patients recruited in the study. The study therefore did not meet its primary and secondary endpoints. UV1 continued to demonstrate a positive safety profile in line with other UV1 studies with similar events observed in the control arm and good tolerability. ==ENDS== About FOCUSThe FOCUS trial (First-line metastatic Or recurrent HNSCC/Checkpoint inhibitor UV1 Study) is an investigator-sponsored, randomized, open label Phase II clinical trial. The primary objective of this study is to determine the clinical performance of UV1 vaccination as add on to standard pembrolizumab treatment as a first-line treatment in metastatic patients or a second-line treatment in patients with recurrent PD-L1 positive head and neck squamous cell carcinoma. Professor Mascha Binder is the principal investigator for the trial, which is sponsored by the Medical Faculty, University of Halle-Wittenberg in Germany. The first patient in the FOCUS trial was enrolled in August 2021, and patients have been treated at 10 sites across Germany. The trial is investigating the tolerability and efficacy addition of UV1 to standard of care treatment with programmed death receptor-1 (PD 1)-blocking antibody pembrolizumab versus pembrolizumab monotherapy. The 75 patients indicated for treatment with pembrolizumab have been randomized 2-to-1 so that 50 patients will receive UV1 and pembrolizumab and 25 patients will receive pembrolizumab alone. The primary endpoint is PFS rate at 6 months after first administration of study medication. Secondary endpoints include PFS and OS (overall survival, by Kaplan-Meier estimate), objective response rate (ORR), duration of response (DOR) and safety, with minimum 12 months follow-up. As OS is recognized as the determining efficacy measure in guiding further development in this cancer indication, the topline results will be disclosed 12 months after enrollment of the last patient, allowing simultaneous disclosure of both PFS and OS. About UV1UV1 is a universal cancer vaccine designed to induce a specific T cell response against telomerase. UV1 consists of long, synthetic peptides, representing a sequence in the reverse transcriptase subunit of telomerase (hTERT), shown to induce CD4+ T cells. These CD4+ T cells have the potential to provide inflammatory signals and T cell support that are believed to be critical for triggering a strong anti-tumor immune response. Following intradermal injection, antigen presenting cells (APCs) in the skin are exposed to the vaccine peptides. These APCs will process the peptides, and present vaccine epitopes on Human Leukocyte Antigen (HLA) molecules to naïve T cells in the lymph nodes. Activated vaccine-specific T cells will then enter the circulation and search for cells displaying their cognate antigen in the context of HLA molecules. The UV1 peptides contain several epitopes, shown to be non-restrictive in terms of (HLA) alleles for presentation. It is therefore not required to perform HLA pre-screening of patients, which potentially enables broad population utilization of the vaccine. UV1 is administered over three months as eight intradermal injections together with the immune-modulator, GM-CSF. About UltimovacsUltimovacs is a clinical-stage biotechnology company developing novel immunotherapies against cancer. The product candidate UV1 is an off-the-shelf therapeutic cancer vaccine designed to enhance the benefits of immunotherapy and improve cancer treatment efficacy for patients. UV1 triggers an immune response against the shared cancer antigen telomerase, a target present in 85-90% of all cancer indications across disease stages. Ultimovacs is investigating the safety and efficacy of UV1 in a wide-ranging clinical development program including various cancer indications and different immunotherapy combinations. The ongoing Phase II program comprises five randomized clinical trials in melanoma, mesothelioma, head and neck cancer, ovarian cancer, and non-small cell lung cancer. More than 640 patients in the U.S., Europe, and Australia are being enrolled in all Phase I and Phase II trials in the current program. Furthermore, Ultimovacs is developing a novel conjugation technology, initially formed to support the expansion of our vaccine pipeline. With the objective of driving value and future pipeline growth, this flexible conjugation technology has the potential to be broadly applicable to a variety of therapeutic modalities, such as innovative drug conjugates with favorable pharmacological properties, and in multiple disease areas. Ultimovacs is listed on the Euronext Oslo Stock Exchange (OSE:ULTI). For further information, please see www.ultimovacs.com or contact: Carlos de Sousa, CEOEmail: carlos.desousa@ultimovacs.com Phone: +47 908 92507 Hans Vassgård Eid, CFO Email: hans.eid@ultimovacs.comPhone: +47 482 48632

Phase 2Clinical ResultVaccineImmunotherapyPhase 1

01 Aug 2024

·www.globenewswire.com

Ultimovacs Announces Poster Presentation of NIPU Phase II Trial Update at Upcoming ESMO Congress 2024

Oslo, August 1, 2024: Ultimovacs ASA (“Ultimovacs”) (OSE ULTI), a clinical-stage biotechnology company developing immunotherapeutic cancer vaccines, today announced that an update from the Phase II NIPU trial (NCT04300244) in patients with malignant mesothelioma will be presented in a poster presentation at the 2024 ESMO Congress. The conference will be held in Barcelona, Spain from September 13-17, 2024. Poster Presentation Details: Title: Updated survival and vaccine response from the NIPU trial; A randomised, phase II study evaluating nivolumab and ipilimumab with or without UV1 vaccination in patients with pleural mesotheliomaPresentation Number: 1917PSpeaker: Vilde D. Haakensen, MD, PhD, Project Group Leader at the Oslo University HospitalDate: Saturday, September 14, 2024 The first comprehensive data from the NIPU Phase II trial was presented at the ESMO Congress 2023. While the study did not meet its primary endpoint, UV1 in combination with the checkpoint inhibitors ipilimumab and nivolumab demonstrated clinically meaningful overall survival benefit with no added toxicities, compared to ipilimumab and nivolumab alone, in the second-line treatment of patients with malignant mesothelioma. The results were also published in the European Journal of Cancer in March 2024. ==ENDS== About NIPUNIPU (Nivolumab and Ipilimumab Plus/minus UV1 vaccination) is a randomized, multi-center phase II trial in which Ultimovacs’ universal cancer vaccine, UV1, is evaluated in combination with Bristol-Myers Squibb’s checkpoint inhibitors, nivolumab and ipilimumab, as second-line treatment of malignant mesothelioma. The trial sponsor is Oslo University Hospital, supported in the preparation and execution of the trial by Ultimovacs and Bristol-Myers Squibb. The 118 patients were randomized 1:1 into two treatment arms. All participants receive treatment with nivolumab (240 mg every 2 weeks) and ipilimumab (1 mg/kg every 6 weeks) until disease progression, unacceptable toxicity or for a maximum of 2 years. Patients randomized to the experimental arm received 8 intradermal injections of UV1 vaccine during the first three months of treatment. The objective of the study is to achieve a clinically meaningful benefit in patients with malignant mesothelioma (MPM) after progression on first-line standard platinum doublet chemotherapy. Subsequent events emerging in patients in both arms of the NIPU study will continue to be monitored beyond read-out of the primary endpoint. The ipilimumab and nivolumab combination has recently been approved as first-line treatment for patients with malignant pleural mesothelioma in Europe and the U.S. The trial was sized to detect a target PFS HR of 0.6, with 80% power and a 1-sided alpha of 0.1. Overall survival was calculated using the same method as for PFS. About UV1 UV1 is a universal cancer vaccine designed to induce a specific T-cell response against telomerase. UV1 consists of long, synthetic peptides representing a sequence in the reverse transcriptase subunit of telomerase (hTERT), shown to induce CD4+ T-cells. These CD4+ T-cells have the potential to provide inflammatory signals, and T-cell support is believed to be critical for triggering a strong anti-tumor immune response. Following intradermal injection, antigen-presenting cells (APCs) in the skin are exposed to the vaccine peptides. These APCs will process the peptides and present vaccine epitopes on Human Leukocyte Antigen (HLA) molecules to naïve T-cells in the lymph nodes. Activated vaccine-specific T-cells will then enter the circulation and search for cells displaying their cognate antigen in the context of HLA molecules.The UV1 peptides contain several epitopes, shown to be non-restrictive in terms of (HLA) alleles for presentation. It is, therefore not required to perform HLA pre-screening of patients, which potentially enables broad population utilization of the vaccine. UV1 is administered over three months as eight intradermal injections together with the immune-modulator GM-CSF. About Ultimovacs Ultimovacs is a clinical-stage biotechnology leader in novel immunotherapeutic cancer vaccines. The lead cancer vaccine candidate UV1 is an off-the-shelf vaccine directed against human telomerase (hTERT), an antigen present in 85-90% of cancers in all stages of tumor growth. A broad clinical program, with Phase II trials in five cancer indications enrolling more than 670 patients, aims to investigate UV1’s impact in combination with other immunotherapies in multiple cancer types. UV1 is a patented technology owned by Ultimovacs. In addition, Ultimovacs holds all rights of the proprietary TET technology platform for any possible future use of formulations in various solid tumor indications. The Company is listed on the Euronext Oslo Stock Exchange (ULTI). For further information, please contact: Carlos de Sousa, CEO Email: carlos.desousa@ultimovacs.comPhone: +47 908 92507 Hans Vassgård Eid, CFOE-mail: ir@ultimovacs.com This stock exchange announcement was published by Hans Vassgård Eid, CFO at Ultimovacs ASA, on August 1, 2024, at 17:20 CET.

Phase 2VaccineClinical ResultImmunotherapy

06 Jun 2024

·firstwordpharma.com

Replimune soars on melanoma data, aims for oncolytic virus launch next year

Shares of Replimune jumped 28% Thursday after the company shared that its oncolytic virus RP1, in combination with Opdivo (nivolumab), achieved a one-third overall response rate (ORR) in patients with melanoma who failed prior anti-PD-1 treatment.The company now plans to submit an application with the FDA next half for RP1, and begin enrolling the confirmatory IGNYTE-3 study in the third quarter. CEO Sushil Patel added that Replimune expects to commercially launch the therapy next year.Topline results from the Phase I/II IGNYTE-3 study demonstrate that, in 140 evaluable patients, RP1 plus Bristol Myers Squibb’s PD-1 inhibitor led to a median duration of response exceeding 35 months, with all responses lasting more than 6 months. Replimune said that the primary analysis by independent central review was triggered once all patients had been followed for at least 12 months. RP1 is a genetically modified strain of herpes simplex virus engineered with fusogenic protein GALV-GP R- and GM-CSF to boost potency, immunogenicity, and the activation of a systemic anti-tumor immune response.The company plans to present the primary analysis data, including key secondary endpoint data and subgroups, at an upcoming medical congress.

Clinical StudyClinical Result

100 Deals associated with Molgramostim biosimilar(Reliance GeneMedix Ltd.)

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	L03AA03	DB12525

R&D Status

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Neutropenia	-	Reliance GeneMedix Ltd.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


SITC2023	Not Applicable	Uveal Melanoma	18	Transarterial immune-embolization (TAIE) with GM-CSF	yrfrudxcpk(glwhjroxqc) = one of 13 (8%) patients requiring hospitalization for transient distributive shock (n=1), which resolved with supportive care jzgrjqdxay (pccqqkpgxe )	Positive	02 Nov 2023
EHA2023	Not Applicable	Neutropenia	9	GM-CSF therapy	jrjqhxiysz(zikiezrdml) = vowxylqczv vxjkxhwgpl (kouqtejnue ) View more	-	08 Jun 2023
AACR2022	Phase 1	Glioblastoma Multiforme Adjuvant	15	Pelareorep + GM-CSF + standard chemoradiotherapy	(uzmqerhqkw) = mvgtrqclnn brulpvdnvp (uwaudgyfst )	-	15 Jun 2022
				Standard chemoradiotherapy	(uzmqerhqkw) = mjnwxswosc brulpvdnvp (uwaudgyfst )
ASCO2021	Not Applicable	High Risk Neuroblastoma Consolidation	73	Naxitamab and GM-CSF	rittoqrcqf(loerunpdjn) = 2 qgxanwjdmt (ibdaixxqyg ) View more	Positive	28 May 2021
Tandem Meetings ASTCT and CIBMTR2020	Not Applicable	Neoplasms	-	G-CSF and GM-CSF	uvqokbxrsy(dbwnvnmrie) = xfmebksngy jbmzxladzx (rxqaivnews )	Positive	01 Mar 2020
				G-CSF (Healthy donors)	uvqokbxrsy(dbwnvnmrie) = qvtozkasan jbmzxladzx (rxqaivnews )
AACR2016	Phase 1	Ovarian Cancer	51	E39’	(aymcwhakdd) = jlidnvkseb fkogkkprha (koikqotqrq )	Positive	15 Jul 2016
				E39 + GM-CSF	(aymcwhakdd) = mhddjjlgtk fkogkkprha (koikqotqrq )
AACR2015	Phase 2	Adjuvant	301	AE37+GM-CSF	(yhvvulvotd) = ewxgilwipk itpjefjory (bwunrttaid )	-	01 Aug 2015
				GM-CSF alone	(yhvvulvotd) = jokxgovnum itpjefjory (bwunrttaid )
OPTiM (ASCO2015)	Phase 3	Melanoma	436	Talimogene laherparepvec	pzdzrrftjx(rarmknltfe) = mlmycjxqnj efxbthntcf (zwusqpgxlc )	-	20 May 2015
				Subcutaneous GM-CSF	pzdzrrftjx(rarmknltfe) = wuucljhhth efxbthntcf (zwusqpgxlc )
Tandem Meetings ASTCT and CIBMTR2015	Not Applicable	Multiple Myeloma	111	G-CSF	usgmergvsj(vawgtdwqiv) = cbcgmihtny qlwtqhfkew (dmvjwklmrx ) View more	Negative	01 Feb 2015
				GM-CSF	usgmergvsj(vawgtdwqiv) = jcuzxpcwki qlwtqhfkew (dmvjwklmrx ) View more
ANBL0931 (ASCO2014)	Phase 3	High Risk Neuroblastoma	105	ch14.18 combined with GM-CSF	dizecskbhs(qijhyubekw) = cfptalpxml adlwmhlxzw (leanpxkvqn ) View more	-	20 May 2014
				ch14.18 combined with IL2	dizecskbhs(qijhyubekw) = vpbwfmpqaa adlwmhlxzw (leanpxkvqn ) View more

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis