A multiple-ascending-dose (MAD), randomized, placebo-controlled, blinded trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of Elafin in healthy adult subjects. The purpose of this study is to assess Elafin that is being developed for treatment of PAH. Elafin inhibits elastase, an enzyme that is increased in pulmonary hypertension and is a major factor in the development of PAH. Elafin will be administered subcutaneously daily for 7 days in normal healthy subjects followed over a 28 day time period.

Start Date18 Mar 2019

Sponsor / Collaborator

Stanford University

[+3]

EUCTR2008-000938-49-DE

/ Not yet recruitingNot Applicable

Placebo-controlled Randomized Trial to evaluate the Effect of Elafin on Cytokine Profiles after Major Surgery - Phase II - Elafin

Start Date18 Aug 2008

Sponsor / Collaborator-

100 Clinical Results associated with Tiprelestat(Proteo Biotech AG)

100 Translational Medicine associated with Tiprelestat(Proteo Biotech AG)

100 Patents (Medical) associated with Tiprelestat(Proteo Biotech AG)

270

Literatures (Medical) associated with Tiprelestat(Proteo Biotech AG)

08 May 2025·Beneficial Microbes

Production of human elafin by genetically modified Lactococcus lactis: evaluation of its anti-inflammatory effects in a murine model of intestinal mucositis

Article

Author: Langella, P. ; LeBlanc, J.G. ; Bermúdez-Humarán, L.G. ; Gontier, S. ; Levit, R. ; de Moreno de LeBlanc, A. ; Aucouturier, A.

Abstract:

The aim of this study was to develop a recombinant strain of Lactococcus lactis designed to produce human elafin, a serine protease inhibitor, through a Stress-Inducible Controlled Expression (SICE) System, and to evaluate its anti-inflammatory potential both in vitro and in vivo. The impact of this recombinant strain on the efficacy of 5-Fluorouracil (5-FU) was evaluated by in vitro assays with Caco-2 (human colonic cancer cells) and IEC-18 (non-cancerous intestinal cells) exposed to 5-FU with or without the recombinant bacterium. In vivo, a mouse model of intestinal mucositis (IM) was induced by daily injections of 5-FU, followed by oral administration of the recombinant strain twice daily. Key assessments included the occurrence of diarrhea, small intestinal morphology and histopathology, and serum cytokines levels. In vitro results showed that the elafin-producing strain enhanced 5-FU cytotoxicity against Caco-2 cells, while preserving IEC-18 cell viability in the presence of 5-FU. In vivo, the strain significantly reduced the occurrence of diarrhea, improved the villus height/crypt depth ratio and attenuated intestinal inflammation. In addition, the recombinant strain reduced serum levels of the pro-inflammatory cytokines IL-6 and TNF-α, while significantly increasing the anti-inflammatory cytokine IL-10. Importantly, the strain did not compromise the anti-cancer efficacy of 5-FU on tumor cells and protected non-cancer cells. These results confirm the in vivo anti-inflammatory effects of this elafin-producing strain against IM.

20 Sep 2024·MICROBIOLOGY-SGM

Use of Rgg quorum-sensing machinery to create an innovative recombinant protein expression system in Streptococcus thermophilus

Article

Author: Balvay, Aurélie ; Langella, Philippe ; Bermúdez-Humarán, Luis G. ; Mézange, Christine ; Monnet, Véronique ; Juillard, Vincent ; Maillot, Nathanael Jean ; Honvo-Houeto, Edith ; Gardan, Rozenn ; Rabot, Sylvie

Streptococcus thermophilus holds promise as a chassis for producing and secreting heterologous proteins. Used for thousands of years to ferment milk, this species has generally recognized as safe (GRAS) status in the USA and qualified presumption of safety (QPS) status in Europe. In addition, it can be easily genetically modified thanks to its natural competence, and it secretes very few endogenous proteins, which means less downstream processing is needed to purify target proteins, reducing costs. Extracellular degradation of heterologous proteins can be eliminated by introducing mutations that inactivate the genes encoding the bacterium’s three major surface proteases. Here, we constructed an inducible expression system that utilizes a peptide pheromone (SHP1358) and a transcriptional regulator (Rgg1358) involved in quorum-sensing regulation. We explored the functionality of a complete version of the system, in which the inducer is produced by the bacterium itself, by synthesizing a luciferase reporter protein. This complete version was assessed with bacteria grown in a chemically defined medium but also in vivo, in the faeces of germ-free mice. We also tested an incomplete version, in which the inducer had to be added to the culture medium, by synthesizing luciferase and a secreted form of elafin, a human protein with therapeutic properties. Our results show that, in our system, protein production can be modulated by employing different concentrations of the SHP1358 inducer or other SHPs with closed amino acid sequences. We also constructed a genetic background in which all system leakiness was eliminated. In conclusion, with this new inducible expression system, we have added to the set of tools currently used to produce secreted proteins in S. thermophilus, whose myriad applications include the delivery of therapeutic peptides or proteins.

01 Jul 2023·Indian journal of dermatology

Serum Elafin as a Potential Marker of Disease Activity in Behçet's Disease

Article

Author: Kose, Afet Akdag ; Kutlay, Armagan

Background::

Elafin is a serine protease inhibitor with anti-inflammatory properties. It is expressed in various epithelial tissues with increased production under inflammatory conditions. Increased tissue elafin expression in Behçet's disease (BD) lesions has previously been demonstrated.

Aims and Objectives::

We hypothesised that serum elafin might be increased in patients with BD and aimed to assess the relationship of serum elafin with disease activity and organ involvement in BD.

Materials and Methods::

Fifty-four BD patients (29 active, 25 inactive) and 30 healthy controls were included in this single-centre case-control study. Serum elafin was measured using ELISA. Complete blood count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) tests were also performed.

Results::

Serum elafin levels were significantly higher in patients with BD (1.58 ± 0.47 ng/ml, range: 0.67–2.96) compared to controls (1.10 ± 0.28 ng/ml, range: 0.65–1.49) (P < 0.001). Patients with active BD had higher elafin levels than patients with inactive BD (P = 0.008). Active arthritis was associated with an increase in elafin (P = 0.012), while the presence of mucocutaneous symptoms was not. Serum elafin correlated significantly with ESR (P = 0.001). The ideal cut-off value for the diagnosis of BD was determined as 1.24 ng/ml with a sensitivity and specificity of 72.2% and 70.0%, respectively.

Conclusion::

Serum elafin is significantly increased in patients with BD. It may serve as a marker of disease activity, especially articular involvement.

News (Medical) associated with Tiprelestat(Proteo Biotech AG)

09 Dec 2024

·pipelinereview.com

tiakis Biotech AG Reports Clinical Phase Ib/II Trial Results of Tiprelestat for the Treatment of Hospitalized COVID-19 Patients

Tiprelestat was safe and well tolerated, with initial signs of clinical efficacy KIEL, Germany I December 9, 2024 I tiakis Biotech AG , a clinical-stage biopharmaceutical company developing novel therapeutics for life-threatening pulmonary and cardiovascular diseases, today announced the results of its randomized, double-blind, placebo-controlled clinical Phase Ib/II COMCOVID trial evaluating Tiprelestat for the treatment of patients hospitalized due to COVID-19. In 2021, tiakis Biotech received support from the German Federal Ministry of Education and Research (“BMBF”) to initiate the COMCOVID trial. Tiprelestat (human recombinant Elafin) is an anti-inflammatory human protein and a reversible inhibitor of human neutrophil elastase and proteinase 3 as well as an inhibitor of the formation of neutrophil exosomes and neutrophil extracellular traps. The compound is in development as a potential therapeutic in diseases characterized by an adverse overreaction of innate immune responses, e.g., pulmonary arterial hypertension (PAH) or COVID-19. During the study period, tiakis had to adapt to changes in the COVID-19 pandemic, which led to a significant decrease in the rate of hospitalizations due to this disease. 17 patients could be recruited and treated (9 Tiprelestat, 8 placebo) until the end of the trial period. Even though the power of the small sample size of this study does not allow for a reliable efficacy assessment, it was decided to report all efficacy results. From an exploratory perspective, it is interesting to note that the number of days (mean ± SD) with any oxygen support (i.e. COVID-19 WHO-CPS ≥5 score points) was lower in the Tiprelestat group (2.4 ± 3.6 days) compared to placebo (4.0 ± 6.2 days). In addition, the number of days with relevant renal issues after day 1 was zero in the Tiprelestat group (0 ± 0) compared to the placebo group (1.5 ± 4.2). Consistent with previous clinical trials, the results regarding adverse events, clinical laboratory parameters and vital signs demonstrate that Tiprelestat was safe and well tolerated when administered via infusion in a multiple dose regimen over 7 days. In addition, results of pharmacokinetic evaluation show that Tiprelestat does not accumulate in blood plasma. “Although the trial did not reach the targeted patient number and we cannot draw a reliable conclusion on efficacy, the data reinforce our confidence in the safety profile of Tiprelestat, indicating that it can be administered repeatedly without significant adverse effects in this patient population aged up to 89 years and suffering from a severe inflammatory lung disease,” said Dr. Michael Dreher, Professor of Medicine / Pneumology and Head of the Department of Pneumology and Intensive Care Medicine at the University Hospital Aachen, Germany, and lead medical investigator of the COMCOVID trial. “The solid safety and supportive data in such a diverse and vulnerable patient population will strengthen the development of Tiprelestat in other pulmonary diseases. I would like to thank all our colleagues and partners for their fantastic work under such challenging and unprecedented pandemic conditions,” added Martin Voss, CEO of tiakis Biotech AG. The summary of the clinical study report is publicly available in the German Registry for Clinical Trials ( https://drks.de/search/en/trial/DRKS00031463 ). About tiakis Biotech tiakis Biotech AG is an innovative, clinical-stage pharmaceutical company specializing in groundbreaking approaches to protect human tissues and organ structures. The Company develops anti-inflammatory treatments to prevent severe organ damage and failure, particularly after invasive surgeries, with a primary focus on pulmonary arterial hypertension (PAH). tiakis´ lead candidate Tiprelestat is in clinical development and addresses unmet medical needs in life-threatening conditions. The Company is based in Kiel, Germany. For further information, please visit https://tiakis.bio. SOURCE: tiakis Biotech

Clinical ResultClinical Study

16 May 2023

·www.biospace.com

tiakis Biotech AG and Northway Biotech: Successful Tech Transfer and Expansion of Manufacturing Capabilities for Tiprelestat

KIEL, GERMANY / ACCESSWIRE / May 16, 2023 / tiakis Biotech AG (tiakis), in collaboration with its CDMO partner Northway Biotech, is pleased to announce the successful completion of a technology transfer and ramp-up of manufacturing capabilities for Tiprelestat, a pioneering anti-inflammatory and tissue-protective drug being developed for the prevention of postoperative inflammatory complications following major surgery, treatment of COVID-19 and pulmonary arterial hypertension. For the first time worldwide, a clinical trial is being supported by Tiprelestat study material produced at an industrial fermentation scale, representing a ten-fold increase in manufacturing potential to 3,000 L. tiakis Biotech AG and Northway Biotech collaboration tiakis Biotech AG and Northway Biotech: Successful Tech Transfer and Expansion of Manufacturing Capabilities for Tiprelestat "The marked increase in manufacturing capabilities lays the foundation for the next stage of tiakis' development programs, with the recent start of our COMCOVID phase Ib/II clinical trial being a prime example," said Martin Voss, tiakis Biotech AG co-CEO. The enhanced production capabilities is a result of the successful completion of a technology transfer and subsequent ramp-up program, achieved in a short time through close collaboration with end-to-end biologics CDMO Northway Biotech, based in Vilnius, Lithuania. Reflecting on this milestone, Vladas Algirdas Bumelis, CEO of Northway Biotech, stated: "The confidence our partners have placed in our two-decade-long expertise has enabled us to collaboratively scale up the process and meet tiakis' deadlines. Our state-of-the-art 3,000 L stainless-steel fermenter train was utilized to carry out the implementation successfully. We extend our sincere well-wishes to our partners as they move forward with their innovative drug through clinical trials, and we look forward to future collaborations." André Markmann, VP Business Development of Northway Biotech, added: "This partnership exemplifies our commitment to assist our partners in achieving their objectives by leveraging our technical expertise and operational capabilities. We are immensely proud to be part of this groundbreaking project, which addresses a significant unmet medical need." By attaining this pharmaceutical and technological milestone, tiakis and Northway Biotech have demonstrated their capabilities to pave the way towards groundbreaking achievements as pioneers in their respective fields. The success of this fast-paced project is characterized by strong collaborative interaction, mutual trust, and flexibility between the two companies. About Tiprelestat tiakis biopharmaceutical drug candidate Tiprelestat promises an excellent therapeutic benefit-risk pro use as an anti-inflammatory and tissue-protective drug. Tiprelestat is identical to the human protein elafin with high specificity for tissue-destroying and inflammation-promoting proteases. The development program of Tiprelestat is focused on the late-stage development of Tiprelestat in major surgery and early-stage development in pulmonary arterial hypertension (PAH) and COVID-19. About tiakis Biotech AG tiakis focuses on the discovery and development of therapeutic solutions based on its innovative biopharmaceutical Tiprelestat for life-threatening surgeries and life-threatening diseases such as PAH and COVID-19. tiakis seeks partners and investors for the development, commercial-scale manufacturing, marketing and distribution of the product. The company tiakis Biotech AG is located in Kiel, Germany ( ). About Northway Biotech Northway Biotech is a leading contract development and manufacturing organization (CDMO) supporting customers worldwide. Its highly experienced, professional team executes projects at any stage, from cell line construction and process development to cGMP manufacturing of biopharmaceutical products. The company's wide-ranging expertise and vertically integrated service offering translate to the ability to rapidly execute multiple projects from its state-of-the-art GMP facilities while ensuring full process and product compliance at all stages of research, development and commercial manufacturing. Northway Biotech is a privately owned company founded in 2004 and located in Vilnius, Lithuania, London, United Kingdom, and in Waltham, MA, US. Further information can be found on Northway's website . Contact Information Vladas Bumelis CEO and Chairman of the Board vladas.bumelis@northwaybiotech.com SOURCE: Northway Biotech View source version on accesswire.com:

100 Deals associated with Tiprelestat(Proteo Biotech AG)

External Link

KEGG	Wiki	ATC	Drug Bank
-	Tiprelestat(Proteo Biotech AG)	-	DB05161

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Myocardial Reperfusion Injury	Phase 2	United Kingdom	tiakis BIOTECH AG	28 Jul 2011
Post procedural inflammation	Phase 2	Germany	tiakis BIOTECH AG	27 Oct 2008
Pulmonary Arterial Hypertension	Phase 1	United States	Stanford University	18 Mar 2019
Lung transplant rejection	Preclinical	United States	Stanford University	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


DRKS00031463 (COMCOVID, PipelineReview) Manual	Phase 1/2	COVID-19	17	Tiprelestat	kshtobnedx(zfukdvovuc) = clotwmoecf uywjewksnk (oedxdjypsf, 3.6) View more	Positive	09 Dec 2024
				Placebo	kshtobnedx(zfukdvovuc) = odlikaprzc uywjewksnk (oedxdjypsf, 6.2) View more
WCD2023	Not Applicable	Acute Graft Versus Host Disease elafin	-	elafin (GVHD)	terhktelhe(wsznzavbud) = zrmaobwlti bpwoteudsr (iuivxaejka )	-	03 Jul 2023
				elafin (non-GVHD rash)	jsuzwcgazy(bpatjsteyn) = kytpuocrfx baxfnnbfoc (ozlnwbemwt )

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