Upamostat - Link Health Group/RedHill Biopharma
Alternative Names: Mesupron; RHB-107; WX-671Latest Information Update: 28 Feb 2024
At a glance
- Originator Wilex
- Developer Heidelberg Pharma AG; Link Health Group; RedHill Biopharma; WILEX AG
- Class Amines; Antineoplastics; Antivirals; Imides; Piperazines; Small molecules; Sulfonamides
- Mechanism of Action Serine endopeptidase inhibitors; Urokinase-type plasminogen activator inhibitors; Virus internalisation inhibitors; Virus replication inhibitors
-
Orphan Drug Status
Yes - Pancreatic cancer
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity Yes
Highest Development Phases
- Phase II/III COVID 2019 infections
- Phase II Breast cancer; Pancreatic cancer
- Clinical Phase Unknown Gastrointestinal disorders
- Preclinical Cholangiocarcinoma; Ebola virus infections; Influenza virus infections
- No development reported Cancer; Solid tumours
- Discontinued Head and neck cancer
Most Recent Events
- 28 Feb 2024 No recent reports of development identified for preclinical development in Solid-tumours in China (PO, Capsule)
- 02 Aug 2023 RedHill plans a phase III external non-dilutive funding trial for COVID 2019 infections US, Thailand, Ivory Coast, South Africa and Uganda
- 31 Jul 2023 Redhill Biopharma receives FDA clearance to start phase II trial
Development Overview
Introduction
Upamostat is a second-generation, once daily, oral serine protease inhibitor being developed by RedHill Biopharma and Link Health Group, for the treatment of multiple cancers, COVID-2019 infections, cholangiocarcinoma, inflammatory lung diseases and gastrointestinal disorders. Upamostat was discovered and originally developed by Wilex (now Heidelberg Pharma AG). The compound has since been licensed to RedHill Biopharma and Link Health Group. It also targets the urokinase plasminogen activator (uPA) system, and is a small molecule pro-drug of WX UK1 [see Adis Insight Drug profile 800012176]. The uPA system, an extracellular protease enzyme system, is over-expressed on certain tumours, and plays a major role in primary tumour growth and metastasis. When uPA binds to its receptor (uPAR), plasminogen is converted to plasmin, which degrades the extracellular matrix enabling the tumour to invade surrounding healthy tissues. Upamostat presents a promising new non-cytotoxic approach to cancer therapy with several potential mechanisms of action to inhibit both tumour metastasis and growth. The serine protease inhibitor targets human cell factors involved in viral entry and is therefore expected to be effective against emerging viral variants with mutations in the spike protein further upamostat also inhibits SARS-CoV-2 replication. The drug is also being assessed against multiple viral targets, including influenza and Ebola virus infections. Clinical development is ongoing worldwide. Preclinical development is ongoing in Israel.
Phase I development as monotherapy was underway in Germany. According to the Wilex pipeline as of March 2013, upamostat is no longer being developed in head and neck cancer.
RedHill Biopharma is prioritizing RHB 107 for rapidly advance upamostat late-stage development for outpatient treatment of COVID-19 [1] .
In October 2017, WILEX AG changed its name to Heidelberg Pharma AG [2] .
As of October 2020, no recent reports of development identified for clinical-Phase-Unknown development in Cancer(Combination therapy) in USA (PO, Capsule).
As at September 2021, no recent reports of development had been identified for clinical-Phase-Unknown development in Gastrointestinal-disorders in Unknown (PO).
As at February 2024, no recent reports of development had been identified for preclinical development in Solid-tumours in China (PO, Capsule).
Company Agreements
In April 2020, RedHill Biopharma and National Institute of Allergy and Infectious Diseases entered into a research and development agreement to evaluate upamostat in non-clinical studies for COVID-2019 infections. [3]
In March 2014, WILEX AG (now Heidelberg Pharma AG) entered into a licensing and development partnership for MESUPRON® with Link Health Co. Link Health will receive the exclusive licensing rights for the development and marketing of MESUPRON® in China, Hong Kong, Taiwan and Macao. Link Health will be responsible for performing and financing the entire clinical development of MESUPRON® in China in all oncological indications, including HER2-negative metastatic breast cancer and non-metastatic pancreatic cancer, as well as for the regulatory process and product marketing. Under the agreement, WILEX will receive a signing fee and milestone payments totalling more than 7 million Euro during clinical development in the first four indications to be developed by Link Health as well as staggered medium single digit royalties. In April 2016, Wilex received a milestone payment of approximately €500 000 after submission of IND. In January 2019, Heidelberg Pharma received milestone payment from Link Health following approval of the Chinese National Medical Product Administration (NMPA) to conduct clinical trials with the product candidate MESUPRON®. [4] [5] [6] [2]
In June 2014, WILEX AG (now Heidelberg Pharma AG) entered into an exclusive licensing agreement with RedHill Biopharma, under which the latter acquired the development and commercialisation rights to upamostat (MESUPRON®) for all indications in regions outside of China, Hong Kong, Taiwan and Macau. Wilex received an upfront payment of $US1 million and tiered royalties on net revenues, that may range from mid-teens upto 30%. RedHill Biopharma will be responsible for undertaking clinical trials, regulatory procedures and commercialisation of upamostat. [7] [8] [2]
In January 2017, RedHill Biopharma entered into a research agreement with Aarhus University, for the identification and further evaluation of additional high affinity molecular targets of upamostat, that may aid in optimal selection of patient sub-population for treatment efficacy in planned studies. The organisations, under a previous collaboration, elucidated on the structure activity relationships between upamostat's active metabolite, UK-1, and proteases [9] .
Key Development Milestones
Breast cancer
First-line therapy with upamostat in combination with capecitabine was well tolerated and increased progression free survival and objective tumour response compared with capecitabine alone in a phase II trial in 132 patients with HER2-receptor negative metastatic breast cancer (NCT00615940; EudraCT2007-006078-27) [10] [11] . The trial was conducted in the US, Brazil, Israel, Belgium and Germany, and was completed in April 2012 [12] [13] [14] . Wilex reported in its half-yearly report for 2013 that its partnering process was based on positive data from this trial [15] .
Cholangiocarcinoma
In June 2020, RedHill Biopharma presented pharmacodynamics data from a preclinical study in cholangiocarcinoma at the 111th Annual Meeting of the American Association for Cancer Research - II (AACR-2020) [16] .
In May 2021, Redhill Biopharma reported preclinical data that demonstrated combination treatment of opaganib and upamostat led to tumour regression [17] .
Head and neck cancer
In September 2007, Wilex completed a phase Ib study of upamostat monotherapy in patients with head and neck cancer, prior to surgical resection [18] . The study included 18 patients and was conducted in Germany. The double-blind, placebo-controlled study examined multiple escalating doses of the agent, and trial results have been reported [19] [20] . However, according to the company's pipeline as of March 2013, the compound is no longer being developed in this indication.
Pancreatic cancer
In October 2017, the US FDA granted the orphan drug designation to upamostat (MESUPRON) as an adjuvant treatment of pancreatic cancer [21] .
Wilex has completed a phase II trial of upamostat, in combination with gemcitabine, in patients with locally advanced, inoperable, non-metastatic pancreatic cancer (NCT00499265; EudraCT2006-005314-12) [22] . In this open-label trial, patients were randomised to receive upamostat at 200 or 400 mg, once-daily, plus gemcitabine, or gemcitabine alone. The final analysis confirms the preliminary data which demonstrated improvements in tumour response and an increase in overall survival in the upamostat treatment groups. A total of 95 patients were enrolled in Germany, Italy, Hungary, Spain, Russia and the Ukraine [23] [24] [25] [26] [27] [15] .
Solid tumours
In January 2016, Link Health submitted an IND application to the China Food and Drug Administration to initiate a phase I dose escalation trial of upamostat in patients with solid tumours. The open-label trial will assess the safety, efficacy, pharmacokinetics and pharmacodynamics of upamostat in Chinese patients. Once the biologically effective dose is confirmed, the company plans to initiate two phase II trials in cancer patients [28] [29] . As of December 2018, the Chinese National Medical Product Administration (NMPA) approved conduct of clinical trials (phase I and phase II trials) in China. Link Health intends to conduct phase II trial, after revising the clinical study protocol due to new regulatory situation [30] [31] [6] .
Wilex completed an open-label, single dose-escalating phase I study in July 2005, which investigated upamostat at four dose levels in 16 healthy male volunteers [32] [33] .
RedHill reported in March 2016, that non-clinical studies to further investigate the mechanism of action and define the patient population for upamostat are ongoing. Based on positive results of these studies the company intends to launch a phase II clinical trial in cancer in 2017. The study results are anticipated to support the clinical data from previous phase I and phase II studies with upamostat [34] [35] .
Gastrointestinal disorders
Clinical development is underway for inflammatory gastrointestinal disorders (RedHill Biopharma pipeline, August 2018) [36] .
COVID-2019 infections
In July 2023, US FDA accepted for inclusion in Austere environments Consortium for Enhanced Sepsis Outcomes' ACESO's PROTECT adaptive platform trial for early COVID-19 outpatient treatment to be conducted in the U.S., Thailand, Ivory Coast and South Africa. In September 2023, RedHill Biopharma and United States Department of Defence plans the phase II PROTECT-APT 1 (ACESO PROTECT) trial of upamostat for COVID-2019 infections in USA, Côte D'Ivoire, South Afrcia, Thailand (NCT05954286). This trial will be predominantly funded by U.S. Government Department of Defense's Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) [37] [38]
In August 2022, RedHill Biopharma suspended a phase II/III trial that was designed to assess the safety and efficacy of upamostat in patients with COVID-2019 infections (NCT04723537, RHB-107-01). The two-part, phase II/III, randomised, double-blind, placebo-controlled, parallel group study was initiated in February 2021, and intended to enrol approximately 310 patients in the US and South Africa. In November 2020, the US FDA had approved the IND application to initiate this trial. In the same month February 2021, the company announced that the first patient was dosed in its phase II/III trial. In September 2021, the South African Health Products Regulatory Authority (SAHPRA) approved the phase II/III trial to expand and initiate in South Africa, for patients with symptomatic COVID-19 who do not require hospital care [39] [40] [41] [42] [43] . In November 2021, The part A of the trial completed enrollment of 61 patients [44] . In March 2022, the company released efficacy and safety data from the trial. As of June 2022, the company is in discussion with regulatory authorities regarding the next steps for the study [45] [46] [47] .
As of June 2023, RHB 107 is part of several cooperative research projects with government and non-government bodies, assessing RHB 107 against multiple viral targets, including influenza and Ebola virus [48] .
As of November 2022, discussions with the US government are ongoing for pandemic preparedness and other government programs, both opaganib [see AdisInsight drug profile800019263] and RHB 107 demonstrated in vitro inhibition of Omicron BA.5 sub-variant. The in vitro testing was conducted at the University of Tennessee [49] .
In December 2021, RedHill Biopharma announced that upamostat is expected to be unaffected by mutations associated with Omicron and other known variants of concern as the upamostat proposed mechanism of action is not impacted by spike protein mutations [50] .
In October 2022, RedHill Biopharma reported preclinical data from an in vitro studies [51] .
In November 2020, RedHill Biopharma reported preclinical data from an in vitro human bronchial cell model [40] .
In March 2020, RedHill Biopharma reported that based on pre-clinical data and literature indicating potential anti-viral activity, the company is actively pursuing an exploratory program intended to investigate the activity of opaganib and upamostat [see Adis Insight Drug Profile 800021537], individually and in combination with hydroxychloroquine and other compounds in the treatment of COVID-2019 (novel coronavirus) [52] .
In non-clinical studies conducted by Aarhus University, molecular targets, including multiple proteases, were identified that may demonstrate higher sensitivity to upamostat, compared with urokinase plasminogen activator (uPA). Evaluation of these targets may aid in selection of patient population that would benefit with upamostat treatment in planned studies [9] .
Financing information
In December 2023, Redhill Biopharma announced new non-dilutive external funding, additional to the previously announced US Government funding, which now covers the entirety of the RHB 107 (upamostat) arm of the ACESO PROTECT adaptive platform trial for early COVID-19 outpatient treatment. This additional funding amounts to approximately $US4.8M directed towards evaluation of RHB 107 in the PROTECT study [53] .
In June 2022, Redhill Biopharma announced that it is seeking external funding through grants, platform studies and other public, private and industry partnerships to support development of upamostat [45] .
In January 2021, RedHill Biopharma announced its intention to raise $US10 million from a public offering. The company intends to use the funds for clinical development programs, commercialisation activities and for acquisitions and general corporate purposes [54] .
Patent Information
In May 2021, RedHill Biopharma received a Notice of Allowance from the US Patent and Trademark Office (PTO) for a new patent covering upamostat (RHB-107) as a method for the treatment of COVID-2019 caused by the SARS-CoV-2 virus. The patent, once granted, is expected to expire in 2041 [55] .
In November 2020, RedHill Biopharma received a Notice of Allowance from the US PTO for a new patent application related to the use of upamostat and opaganib (Yeliva®) [see Adis Insight profile 800019263] combination therapy for the treatment of solid tumors. The patent is expected to expire in 2036 [56] .
In September 2017, RedHill Biopharma received a notice of allowance from the USPTO regarding a patent to upamostat and Yeliva® [see Adis Insight profile 800019263], covering the use of proprietary investigational compounds in combination with a known antibiotic. The patent covers combination for the potential treatment of cancer, prevention of cancer recurrence or progression and inhibition of growth and proliferation of cancer cells [57] .
Upamostat is covered by several issued and pending patents worldwide, including crystalline modifications of N- a -(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamidino-(L)-phenylalanine 4-ethoxycarbonylpiperazide or salts, which can be used as pharmaceutical agents, pharmaceutical uses comprising these novel crystalline modifications; urokinase inhibitor compounds; methods for the production of phenylalanine derivatives and method of preparing methylhydroxyalkylcellulose, which are expected to expire in between 2018 and 2026. This patent portfolio was in-licensed by RedHill Biopharma from Wilex (RedHill Biopharma 10-K February 2015).
Drug Properties & Chemical Synopsis
- Route of administration PO
- Formulation Capsule, unspecified
- Class Amines, Antineoplastics, Antivirals, Imides, Piperazines, Small molecules, Sulfonamides
- Target Serine endopeptidase; Urokinase-type plasminogen activator; Virus internalisation; Virus replication
- Mechanism of Action Serine endopeptidase inhibitors; Urokinase-type plasminogen activator inhibitors; Virus internalisation inhibitors; Virus replication inhibitors
-
WHO ATC code
A03 (Drugs for Functional Gastrointestinal Disorders)
J05 (Antivirals for Systemic Use)
L01X (Other Antineoplastic Agents)
-
EPhMRA code
A3 (Functional Gastro-Intestinal Disorder Drugs)
J5 (Antivirals for Systemic Use)
L1X9 (All other antineoplastics)
- Chemical name ethyl 4-{(2S)-3-{3-[(E)-N'-hydroxycarbamimidoyl]phenyl}-2-[2,3,5-tri(propan-2-yl)benzenesulfonamido]propanoyl}piperazine-1-carboxylate
- Molecular formula C32 H47 N5 O6 S
- SMILES N1(CCN(CC1)C(C(CC1C=C(C=CC=1)C(N)=NO)NS(=O)(=O)C1=C(C=C(C=C1C(C)C)C(C)C)C(C)C)=O)C(=O)OCC
-
Chemical Structure
- CAS Registry Number 1191101-18-4
Biomarkers Sourced From Trials
Biomarker
| Drug Name | Biomarker Name | Biomarker Function |
|---|---|---|
| Upamostat - Link Health Group/RedHill Biopharma | C-reactive protein (CRP) | Outcome Measure |
| Cardiac Troponin I | Outcome Measure | |
| D-dimer | Outcome Measure | |
| HER2/ERBB2 | Eligibility Criteria |
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| Breast cancer | In combination with capecitabine | Combination therapy, First-line therapy, Metastatic disease | Phase II | Belgium, Brazil, Germany, Israel, USA | PO / Capsule | Heidelberg Pharma AG | 31 Jul 2008 |
| COVID 2019 infections | in adult patients who do not require inpatient care. in non-hospitalized patients | - | Phase II/III | South Africa, USA | PO / Capsule | RedHill Biopharma | 16 Feb 2021 |
| COVID 2019 infections | - | - | Preclinical | Israel | PO / unspecified | RedHill Biopharma | 13 Mar 2020 |
| Cancer | - | Combination therapy | No development reported (Clinical) | USA | PO / Capsule | RedHill Biopharma | 28 Oct 2020 |
| Cholangiocarcinoma | - | - | Preclinical | Israel | PO / unspecified | RedHill Biopharma | 01 Jun 2020 |
| Ebola virus infections | - | - | Preclinical | Israel | PO / unspecified | RedHill Biopharma | 12 Jun 2023 |
| Gastrointestinal disorders | - | - | Clinical Phase Unknown | Unknown | PO / unspecified | RedHill Biopharma | 13 Jan 2022 |
| Head and neck cancer | - | Monotherapy | Discontinued (I) | Germany | PO / Capsule | WILEX AG | 06 Mar 2013 |
| Influenza virus infections | - | - | Preclinical | Israel | PO / unspecified | RedHill Biopharma | 18 Jun 2023 |
| Pancreatic cancer | In combination with gemcitabine | Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease | Phase II | Germany, Hungary, Italy, Russia, Spain, Ukraine | PO / Capsule | Heidelberg Pharma AG | 09 Nov 2007 |
| Solid tumours | - | - | No development reported (Preclinical) | China | PO / Capsule | Heidelberg Pharma AG, Link Health Group | 28 Feb 2024 |
Orphan Status
| Indication | Patient Segment | Country | Organisation | Event Date |
|---|---|---|---|---|
| Pancreatic cancer | Adjuvant therapy | USA | RedHill Biopharma | 20 Oct 2017 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| Wilex | Originator | Germany |
| Heidelberg Pharma AG | Owner | Germany |
| Link Health Group | Licensee | China, Hong Kong, Macau, Taiwan |
| RedHill Biopharma | Licensee | World |
| United States Department of Defense | Funder | USA |
| Aarhus Universitetshospital | Collaborator | Denmark |
| National Institute of Allergy and Infectious Diseases | Collaborator | USA |
Brand Names
| Brand Name | Organisations | Indications | Countries |
|---|---|---|---|
| Mesupron | Heidelberg Pharma AG | Pancreatic cancer | World |
Scientific Summary
Pharmacokinetics
There were no drug-drug interactions in a phase II trial of combination therapy with upamostat and capecitabine in 132 patients with HER2-receptor negative metastatic breast cancer [10] [11] .
Upamostat (the prodrug) showed good oral bioavailability and conversion into the active drug WX UK1, when administered at multiple escalating doses in healthy male volunteers, in a phase I, double-blind, placebo-controlled study [20] .
According to a phase Ib study, analysis of the tissue from surgically removed tumours showed that significant concentrations of the active metabolite, WX UK1, could be achieved in tumour tissue [19] .
Adverse Events
Phase II/III
Results from a phase II part of the phase II/III trial in patients with COVID-2019 infections showed that RHB 107 was safe and well-tolerated [46] [47] .
Phase II
combination therapy with upamostat and capecitabine was safe and well tolerated as a first-line treatment in a phase II trial in 132 patients with HER2-receptor negative metastatic breast cancer [10] [11] .
Daily oral treatment with upamostat at 200 or 400 mg was safe and well tolerated in a phase II trial in 95 patients with locally advanced, inoperable and non-metastatic pancreatic cancer [23] [24] .
Phase I
upamostat appeared to be well tolerated at all multiple escalating dose levels tested in healthy male volunteers, in a phase I, double-blind, placebo-controlled trial [20] .
Pharmacodynamics
Summary
In a rat breast adenocarcinoma model, upamostat (0.01-10.0 mg/kg/day) given by oral gavage for 6 weeks, reduced median primary tumour size by 36-66%, with the least effect observed after the lowest dose. Upamostat also significantly reduced (33-42%) the median weight of the axillary lymph nodes at doses of ≥ 0.1 mg/kg, with the greatest reduction after the highest dose. Similarly, the agent reduced the median number of lung foci across all dose levels with significant reductions observed after doses of ≥ 0.1 mg/kg (33-44%). The effect of upamostat at doses of ≥ 0.01 mg/kg did not appear to be dose-related [59] .
In preclinical study, administration of upamostat and opaganib demonstrated tumour regression in mice model of cholangiocarcinoma. Body weights of the mice reported no differences in inter- or intra- group. The combination of upamostat and opaganib reported greater regression compared to either upamostat or opaganib alone. Change in tumour volumes at Day 42 was reported to be 102.0, 93.31, 86.09 for opaganib, upamostat and combination respectively with p values 0.0002, 0.0010 and 0.0008 [16] .
Updated in vitro result using a primary human nasal epithelial cell culture model of Omicron BA.5 indicated that RHB 107 and opaganib inhibited Omicron sub-variant BA.5 viral replication which is indicative of antiviral activity [49] [51] . In preclinical studies, upamostat demonstrated strong inhibition of SARS-CoV-2 viral replication in a human bronchial cell model, targets a host cell component involved in viral replication and minimising potential for resistance due to viral mutations [40] .
Therapeutic Trials
Breast cancer
first-line therapy with upamostat in combination with capecitabine increased progression free survival (PFS) and objective tumour response compared with capecitabine alone in a phase II trial in 132 patients with HER2-receptor negative metastatic breaks cancer. In the total intent to treat (ITT) study population, the capecitabine group had a median progression free survival of 7.5 months compared with 8.3 months in the combination therapy group. The objective tumour response rates were 9% and 17%, respectively, in the capecitabine and capecitabine plus upamostat groups. Subgroup analysis showed that there was an increase in PFS in caucasian patients from 7.5 months to 9.1 months in the combination therapy group. Additionally, patients who received adjuvant chemotherapy following the primary diagnosis of breast cancer, PFS rates were 4.3 months in the capecitabine group and 8.3 months in the combination therapy group [10] [11] .
Pancreatic cancer
daily oral treatment with upamostat at 200 or 400 mg in combination with gemcitabine, was associated with improvement in tumour response and an increase in overall survival compared with gemcitabine monotherapy, in a phase II trial in patients with pancreatic cancer. In this open-label trial, patients with locally advanced, inoperable, non-metastatic pancreatic cancer were randomised to receive either gemcitabine monotherapy, or gemcitabine plus upamostat (200 or 400 mg, once-daily), until disease progression [24] . According to the final results for 95 patients, gemcitabine alone demonstrated a tumour response rate of 15.4%, whereas co-administration of upamostat 200mg or 400mg resulted in response rated of 21.4% and 35.5%. Progression free survival (PFS) improved by 66%. In the group receiving gemcitabine alone, 16.2% of patients did not progress at 12 months, as determined by computer tomography. Co-administration of upamostat 200mg and 400mg improved PFS to 22.5% and 26.9% of patients, respectively. One year survival increased by 49%; with gemcitabine alone it was 33.9%. This increased to 40.7% and 50.6% with upamostat 200mg and 400mg, respectively. Median survival improved by 26% from 9.9 months with gemcitabine alone, to 12.5 months when combined with upamostat 400mg [23] .
COVID 2019 infections
phase II:-
Results from a phase II part of the phase II/III trial in patients with COVID-2019 infections met its primary endpoint demonstrating a favorable tolerability profile of RHB 107. The result showed highly promising efficacy results delivering a 100% reduction in hospitalization due to COVID-2019, with zero patients on RHB 107 hospitalized with COVID-2019 (0/41) compared to 15% on the placebo-controlled arm requiring hospitalization (3/20) (nominal p-value=0.0317). Furthermore, the study showed faster recovery from severe COVID-19 symptoms, an 87.8% reduction in reported new severe COVID-19 symptoms, with only one patient on RHB 107 (2.4%, 1/41) compared with 20% (4/20) of patients on the placebo-controlled arm experiencing new COVID-2019 related severe symptoms (nominal p-value=0.036). Patients were also tested for the specific viral strain with the most common variant being Delta, found in 62.5% of the patients that had next generation sequencing [41] [46] [47]
Future Events
| Expected Date | Event Type | Description | Updated |
|---|---|---|---|
| 30 Sep 2023 | Trial Update | RedHill Biopharma and United States Department of Defence plans the phase II PROTECT-APT 1 (ACESO PROTECT) trial for COVID-2019 infections (Prevention) in USA, Côte D'Ivoire, South Afrcia, Thailand (PO, Capsule) in September 2023 (NCT05954286) (700365861) [38] | 02 Aug 2023 |
| 28 Feb 2021 | Trial Update | RedHill Biopharma plans a phase II/III trial for COVID-2019 infections in USA (PO, Capsule) (NCT04723537) (700324475) | 24 Feb 2021 |
| 30 Jun 2018 | Trial Update | RedHill plans a phase I/II trial for Pancreatic cancer in Germany in the first half of 2018 [58] | 28 Aug 2017 |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 28 Feb 2024 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Solid-tumours in China (PO, Capsule) Updated 28 Feb 2024 |
| 02 Aug 2023 | Trial Update | RedHill plans a phase III external non-dilutive funding trial for COVID 2019 infections US, Thailand, Ivory Coast, South Africa and Uganda [38] [53] Updated 02 Aug 2023 |
| 31 Jul 2023 | Regulatory Status | Redhill Biopharma receives FDA clearance to start phase II trial [38] Updated 18 Oct 2023 |
| 31 Jul 2023 | Regulatory Status | US FDA accepts inclusion in ACESO's PROTECT adaptive platform trial for upamostat for COVID 20219 infections to be conducted in U.S., Thailand, Ivory Coast and South Africa [38] Updated 02 Aug 2023 |
| 31 Jul 2023 | Trial Update | RedHill Biopharma and United States Department of Defence plans the phase II PROTECT-APT 1 (ACESO PROTECT) trial for COVID-2019 infections (Prevention) in USA, Côte D'Ivoire, South Afrcia, Thailand (PO, Capsule) in September 2023 (NCT05954286) [38] Updated 02 Aug 2023 |
| 18 Jun 2023 | Phase Change - Preclinical | Preclinical trials in Influenza virus infections in Israel (PO) [48] Updated 18 Jun 2023 |
| 12 Jun 2023 | Phase Change - Preclinical | Preclinical trials in Ebola virus infections in Israel (PO) [48] Updated 18 Jun 2023 |
| 03 Oct 2022 | Scientific Update | Pharmacodynamics data from a preclinical trial in COVID-19 infection released by RedHill [51] , [49] Updated 10 Oct 2022 |
| 02 Aug 2022 | Trial Update | RedHill Biopharma suspends a phase II/III trial for COVID-2019 infections in USA and South Africa (PO) (NCT04723537) Updated 18 Aug 2022 |
| 01 Mar 2022 | Scientific Update | Efficacy and adverse events data from a phase II/III trial in COVID-2019 infections released by RedHill Biopharma [46] [47] Updated 03 Mar 2022 |
| 13 Jan 2022 | Active Status Review | Upamostat is still in phase II/III trials for gastrointestinal disease in USA (PO) Updated 09 Feb 2022 |
| 28 Sep 2021 | Phase Change - No development reported | No recent reports of development identified for clinical-Phase-Unknown development in Gastrointestinal-disorders in Unknown (PO) Updated 28 Sep 2021 |
| 20 Sep 2021 | Biomarker Update | Biomarkers information updated Updated 02 Oct 2021 |
| 13 Sep 2021 | Regulatory Status | South African Health Products Regulatory Authority (SAHPRA) approves IND application for Upamostat in COVID-2019 infections [39] Updated 16 Sep 2021 |
| 26 May 2021 | Patent Information | RedHill Biopharma receives patent allowance for upamostat in USA [55] Updated 31 May 2021 |
| 16 Feb 2021 | Phase Change - II/III | Phase-II/III clinical trials in COVID-2019 infections in South Africa (PO) (NCT04723537) Updated 24 Nov 2021 |
| 12 Feb 2021 | Phase Change - II/III | Phase-II/III clinical trials in COVID-2019 infections in USA (PO) (NCT04723537) Updated 24 Feb 2021 |
| 25 Jan 2021 | Trial Update | RedHill Biopharma plans a phase II/III trial for COVID-2019 infections in USA (PO, Capsule) (NCT04723537) Updated 24 Feb 2021 |
| 17 Nov 2020 | Regulatory Status | RedHill Biopharma files an IND application with the US FDA in USA for COVID-2019 infections, before November 2020 [40] Updated 19 Nov 2020 |
| 17 Nov 2020 | Regulatory Status | The US FDA approves IND application for upamostat in COVID-2019 infection [40] Updated 19 Nov 2020 |
| 17 Nov 2020 | Scientific Update | Pharmacodynamics data from a preclinical trial in COVID-2019 infections released by RedHill Biopharma [40] Updated 19 Nov 2020 |
| 04 Nov 2020 | Patent Information | Redhill Biopharma receives patent allowance for upamostat in the US [56] Updated 18 Nov 2020 |
| 28 Oct 2020 | Phase Change - No development reported | No recent reports of development identified for clinical-Phase-Unknown development in Cancer(Combination therapy) in USA (PO, Capsule) Updated 28 Oct 2020 |
| 01 Jul 2020 | Phase Change - II/III | Phase-II/III clinical trials in COVID-2019 infections in Israel (PO) before June 2020 Updated 06 Jul 2020 |
| 22 Jun 2020 | Scientific Update | Pharmacodynamics data from a preclinical study in Cholangiocarcinoma presented at the 111th Annual Meeting of the American Association for Cancer Research - II (AACR-2020) [16] Updated 28 Jul 2020 |
| 01 Jun 2020 | Phase Change - Preclinical | Preclinical trials in Cholangiocarcinoma in USA (PO), before June 2020 [16] Updated 28 Jul 2020 |
| 20 Apr 2020 | Licensing Status | RedHill Biopharma and National Institute of Allergy and Infectious Diseases agree to co-develop upamostat for COVID-2019 infections [3] Updated 22 Apr 2020 |
| 13 Mar 2020 | Phase Change - Preclinical | Preclinical trials in COVID-2019 infections in Israel (PO) [52] Updated 18 Mar 2020 |
| 13 Mar 2020 | Trial Update | RedHill Biopharma plans a phase II trial for Cholangiocarcinoma (Inoperable/Unresectable, Late-stage disease, Combination therapy, Second-line therapy or greater) in USA [52] Updated 18 Mar 2020 |
| 22 Jan 2019 | Trial Update | Link Health plans a phase II trial for Cancer in China [6] Updated 23 Jan 2019 |
| 31 Dec 2018 | Regulatory Status | The Chinese National Medical Product Administration approves IND application for upamostat in Cancer [30] [6] Updated 23 Jan 2019 |
| 01 Aug 2018 | Phase Change - Clinical | Clinical trials in Gastrointestinal disorders (PO) [36] (RedHill Biopharma pipeline, August 2018) Updated 08 Aug 2018 |
| 20 Oct 2017 | Regulatory Status | Upamostat receives Orphan Drug status for Pancreatic cancer (Adjuvant therapy) in USA [21] Updated 25 Oct 2017 |
| 19 Oct 2017 | Company Involvement | WILEX AG is now called Heidelberg Pharma AG Updated 20 Nov 2017 |
| 18 Sep 2017 | Phase Change - Clinical | Clinical trials in Cancer (Combination therapy) in USA (PO) [57] Updated 28 Sep 2017 |
| 18 Sep 2017 | Patent Information | RedHill Biopharma receives patent allowance for Yeliva® and Mesupron in USA [57] Updated 20 Sep 2017 |
| 10 Aug 2017 | Trial Update | RedHill plans a phase I/II trial for Pancreatic cancer in Germany in the first half of 2018 [58] Updated 28 Aug 2017 |
| 05 Jan 2017 | Licensing Status | RedHill Biopharma and Aarhus University enter into a research collaboration for evaluation of molecular targets of upamostat [9] Updated 09 Jan 2017 |
| 13 Jan 2016 | Regulatory Status | Link Health files an IND application with the China Food and Drug Administration in China for Solid tumours [28] Updated 14 Jan 2016 |
| 13 Jan 2016 | Trial Update | Link Health plans a phase I trial for Solid tumours in China [28] Updated 14 Jan 2016 |
| 13 Jan 2016 | Trial Update | Link Health plans two phase II trials in Cancer [28] Updated 14 Jan 2016 |
| 01 Jan 2016 | Phase Change - Preclinical | Preclinical trials in Solid tumours in China (PO) [31] Updated 28 Mar 2019 |
| 30 Jun 2015 | Active Status Review | Upamostat is still in phase II development for Breast cancer (Combination therapy, First-line therapy, Metastatic disease) in USA, Belgium, Brazil, Germany and Israel and for Pancreatic cancer (Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease) in Germany, Hungary, Italy, Russia, Spain and Ukraine Updated 24 Aug 2015 |
| 25 Feb 2015 | Patent Information | RedHill Biopharma has patent protection for upamostat worldwide Updated 27 Nov 2015 |
| 30 Jun 2014 | Licensing Status | Upamostat licensed to RedHill Biopharma worldwide excluding China, Hong Kong, Taiwan and Macau [7] Updated 01 Jul 2014 |
| 28 Mar 2014 | Licensing Status | Upamostat licensed to Link Health Group in China, Hong Kong, Taiwan & Macao [4] Updated 03 Apr 2014 |
| 06 Mar 2013 | Phase Change - Discontinued(I) | Discontinued - Phase-I for Head and neck cancer in Germany (PO) Updated 06 Mar 2013 |
| 27 Feb 2013 | Licensing Status | Upamostat is available for licensing as of 27 Feb 2013. www.wilex.com Updated 05 Mar 2013 |
| 15 Jun 2012 | Scientific Update | Efficacy, adverse events and pharmacokinetic data from a phase II trial in patients with HER2-receptor negative breast cancer released by Wilex [10] Updated 17 Jun 2012 |
| 30 Apr 2012 | Trial Update | Wilex completes a phase II trial in Breast cancer in USA, Brazil, Israel, Belgium & Germany (NCT00615940) Updated 18 Apr 2013 |
| 05 May 2011 | Trial Update | Wilex completes enrolment in its phase II trial for Breast cancer (Combination therapy, First-line therapy, Metastatic disease) in the US, Belgium, Brazil, Germany and Israel (NCT00615940) Updated 09 May 2011 |
| 07 Jun 2010 | Scientific Update | Final efficacy & adverse events data from the phase II WILEX-WX-60-004 trial in Pancreatic cancer presented at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO-2010) [23] Updated 10 Jun 2010 |
| 03 May 2010 | Scientific Update | Interim efficacy and adverse event data from a phase II trial in Pancreatic cancer released by Wilex (ADNM) Updated 06 May 2010 |
| 03 May 2010 | Trial Update | Wilex completes a phase II trial in Pancreatic cancer in the EU, Russia and the Ukraine Updated 06 May 2010 |
| 31 Jul 2008 | Phase Change - II | Phase-II clinical trials in Breast cancer in Belgium (PO) Updated 16 Feb 2009 |
| 31 Jul 2008 | Phase Change - II | Phase-II clinical trials in Breast cancer in Brazil (PO) Updated 16 Feb 2009 |
| 31 Jul 2008 | Phase Change - II | Phase-II clinical trials in Breast cancer in Germany (PO) Updated 16 Feb 2009 |
| 31 Jul 2008 | Phase Change - II | Phase-II clinical trials in Breast cancer in Israel (PO) Updated 16 Feb 2009 |
| 31 Jul 2008 | Phase Change - II | Phase-II clinical trials in Breast cancer in USA (PO) Updated 16 Feb 2009 |
| 24 Jul 2008 | Trial Update | Wilex completes enrolment in its phase II trial for Pancreatic cancer in Europe Updated 25 Jul 2008 |
| 28 Jan 2008 | Regulatory Status | US FDA approves IND application for WX 671 in metastatic Breast cancer Updated 31 Jan 2008 |
| 13 Oct 2007 | Phase Change - II | Phase-II clinical trials in Pancreatic cancer (Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease) in Spain (PO) Updated 06 Mar 2013 |
| 13 Oct 2007 | Phase Change - II | Phase-II clinical trials in Pancreatic cancer (Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease) in Italy (PO) Updated 06 Mar 2013 |
| 24 Sep 2007 | Trial Update | Wilex AG completes a phase Ib trial in head and neck cancer in Germany Updated 26 Sep 2007 |
| 07 Sep 2007 | Phase Change - II | Phase-II clinical trials in Pancreatic cancer (Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease) in Hungary (PO) Updated 06 Mar 2013 |
| 30 Jul 2007 | Phase Change - II | Phase-II clinical trials in Pancreatic cancer (Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease) in Germany (PO) Updated 06 Mar 2013 |
| 26 Jun 2007 | Phase Change - II | Phase-II clinical trials in Pancreatic cancer (Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease) in Ukraine (PO) Updated 16 Feb 2009 |
| 26 Jun 2007 | Phase Change - II | Phase-II clinical trials in Pancreatic cancer (Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease) in Russia (PO) Updated 16 Feb 2009 |
| 16 Aug 2006 | Scientific Update | Clinical data from a media release have been added to the adverse events and pharmacokinetics sections [20] Updated 17 Aug 2006 |
| 07 Aug 2006 | Phase Change - I | Phase-I clinical trials in Head and neck cancer in Germany (PO) Updated 16 Aug 2006 |
| 07 Aug 2006 | Trial Update | Wilex has completed the phase I, multiple escalating dosing trial for Solid tumours in Germany Updated 16 Aug 2006 |
| 30 Dec 2005 | Trial Update | Wilex has initiated a phase I, multiple escalating dosing trial for Solid tumours in Germany Updated 16 Aug 2006 |
| 27 Jul 2005 | Trial Update | Wilex has completed a phase I, single escalating dosing trial for Solid tumours in Germany Updated 28 Jul 2005 |
| 04 May 2005 | Scientific Update | Data presented at the 96th Annual Meeting of the American Association for Cancer Research (AACR-2005) have been added to the Cancer pharmacodynamics section [59] Updated 04 May 2005 |
| 20 Sep 2004 | Phase Change - I | Phase-I clinical trials in Solid tumours in Germany (PO) Updated 01 Oct 2004 |
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WILEX enters into licensing and development partnership for MESUPRON(Rm) in China with Link Health Group.
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Interim management statement on the first quarter of 2016.
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Heidelberg Pharma Receives Milestone Payment From Partner Link Health.
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WILEX and RedHill Biopharma enter into an exclusive license agreement for MESUPRON(Rm).
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Heidelberg Pharma AG: Partner RedHill Announces Orphan Drug Designation for MESUPRON.
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RedHill Biopharma Announces New Research Collaboration with Aarhus University for Oncology Drug MESUPRON.
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MESUPRON(Rm) met its primary objective of demonstrating efficacy in the proof of concept phase II breast cancer trial.
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A Phase 2, Two-Arm, Double-Blind, Multi-Center, Randomized Study of the Combination of Oral WX-671 [Wilex] Plus Capecitabine [Xeloda; Hoffman La Roche AG] vs. Capecitabine Monotherapy in First-Line Her2-Negative Metastatic Breast Cancer.
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WILEX reports on a successful financial year 2011.
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WILEX publishes half-yearly financial report 2013.
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WILEX completes Phase I program with anti-cancer drug WX-671 in healthy volunteers and conducts clinical Phase Ib study in cancer patients now.
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A randomized, open label, phase II proof of concept study of WX-671 in combination with gemcitabine vs. gemcitabine alone in patients with locally advanced, non resectable pancreatic cancer in order to evaluate the anti-tumor activity of the combination therapy.
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WILEX presents at ASCO positive final phase II data of MESUPRON(Rm) in pancreatic cancer.
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Final Phase II data of MESUPRON (Rm) confirm impressive increase in overall survival of patients with pancreatic cancer.
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Patient recruitment in Phase II trial with MESUPRON(R) (WX-671) in pancreatic cancer patients successfully completed.
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Patient recruitment started in clinical Phase II trial with WX-671 in pancreatic cancer.
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WILEX receives approval for clinical Phase II trial with oral WX-671 in pancreatic cancer.
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WILEX's partner Link Health submits IND application for clinical Phase I with the uPA inhibitor MESUPRON(R) in China.
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A phase I dose escalation study of Upamostat in Chinese patients with solid tumour
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Heidelberg Pharma AG: Interim Management Statement on the First Nine Months of 2019.
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Heidelberg Pharma announces financial figures for fiscal year 2018 and provides business update.
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Wilex successfully completes first clinical Phase I study with new anti-cancer drug WX-671.
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Wilex starts clinical trial with new anti-cancer compound WX-671.
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Interim Management Statement on the First Nine.
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RedHill Biopharma Provides Update on Development Pipeline and Expected Timing for RHB-105 Phase III Top-Line Results.
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RedHill Biopharma Elaborates on Its Announced Positive Top-Line Results from Phase III Study of RHB-104 in Crohns Disease.
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Master Protocol for Early Treatment and Post-Exposure Prophylaxis of COVID-19 Adaptive Platform Trial PROTECT-APT 1
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RedHill's RHB-107 Included in U.S. Government-Supported COVID-19 Platform Trial and Cleared for Initiation by FDA.
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RedHill Biopharma Accelerates Ongoing U.S. Phase 2/3 COVID-19 Study of Once-Daily Oral RHB-107 in Non-Hospitalized Patients with South African Approval.
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RedHill Biopharma's Second COVID-19 Candidate, RHB-107, Cleared by FDA for Phase 2/3 Study in Symptomatic COVID-19 Disease.
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RedHill Announces Positive Phase 2 Study Results with Oral RHB-107 in Non-Hospitalized COVID-19.
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RedHill's Oral Broad-Acting Antivirals, Opaganib and RHB-107, Inhibit Dominant Omicron Sub-Variant BA.5.
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RedHill Biopharma Announces $10 Million Bought Deal Offering.
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