Temple Therapeutics BV Announces Publication of Key Mechanism Data for Evitar™

Below, we are re-publishing with permission the press-release issued by Temple Therapeutics BV on the 10th of September 2018

Supports Evitar’s™ Novel Approach for Preventing Acute Tissue Fibrosis (Surgical Adhesions)

Geleen, The Netherlands Temple Therapeutics BV (the “Company” or “Temple”)- September 10, 2018 – Temple, a clinical stage biopharmaceutical company focused in developing therapeutics for fibrosis and oncology, announces the publication of groundbreaking mechanistic data for Evitar™ in Reproductive Sciences, a peer reviewed journal of the Society of Reproductive Investigations. The publication includes data to support a credible hypothesis for Evitar™’s mechanism of action advanced by Temple’s CSO, Dr. Lynne Robertson. This hypothesis proposes that novel drug candidate Evitar™ modulates key upstream inflammatory mediators, such Hypoxia Inducible Factor 1 Alpha (HIF1-α) and Type 1 Collagen, which, when left unchecked, promote abnormal healing and tissue fibrosis.

Robertson, L., King, N., Diamond, M., & Saed, G., Evitar™(l-Alanyl-l-Glutamine) Regulates Key Signaling Molecules in the Pathogenesis of Postoperative Tissue Fibrosis, Reproductive Sciences, September 5, 2018

Additionally, data from the Evitar™ proof-of-concept randomized clinical trial was recently accepted for presentation at 47th Annual Global Congress of AAGL (American Association of Gynecologic Laparoscopists) scheduled for November 2018.

“Post-surgical adhesions are broadly recognized as the single greatest cause of surgical complications. Moreover, they have evaded effective intervention, until now” comments Sanj Singh, CEO of Temple. “These mechanism-of-action and randomized clinical trial data speak to the underlying biology driving surgical adhesions. We are pleased to note the publication’s acceptance in Reproductive Sciences, a high-impact, peer-reviewed journal. This publication and the forthcoming AAGL presentation further support the Evitar™ value proposition. Adhesion prevention is only the beginning. However, it provides a relevant model to further the study of both fibrosis and cancer pathophysiology. Temple is leveraging these insights to further its pipeline of first-in-class therapeutics for the management of adhesions, endometriosis and ovarian cancer.”

About Temple Therapeutics BV

Temple Therapeutics BV is a privately held Dutch based clinical stage development therapeutic drug company, developing first in class and best in class therapeutics to treat acute/chronic fibrosis and cancer. With novel targets linked by a common underlying biology, Temple’s platform has yielded three promising drug candidates to treat post-operative adhesions, endometriosis and ovarian cancer.

About Reproductive Sciences

Reproductive Sciences (RS) is a peer-reviewed, monthly journal publishing original research and reviews in obstetrics and gynecology making it one of the highest ranked and cited journals. RS is multi-disciplinary and includes research in basic reproductive biology and medicine, maternal-fetal medicine, obstetrics, gynecology, reproductive endocrinology, urogynecology, fertility/infertility, embryology, gynecologic/reproductive oncology, developmental biology, stem cell research, molecular/cellular biology and other related fields.

* The study was conducted by Clinical Accelerator

Posted in Biotech, Clinical Accelerator | Leave a comment

Clinical Accelerator announces collaboration with Oncolix for developing Prolanta™, a targeted therapeutic protein for the treatment of ovarian, breast and other cancers

Clinical Accelerator, a full-service contract research organization, is pleased to announce that it has entered into a collaboration with Oncolix, for conducting clinical studies for its analogue protein, Prolanta, to treat ovarian cancer. The trials will be conducted in the US as well as sites A and B in the Ukraine.

Ovarian Cancer is one of the leading causes of cancer-related death in women and gynecologic death[1]. 80-90% of patients initially respond to chemotherapy but of those, only 10-30% have long-term survival since the majority relapse. Currently, cytotoxic  drugs (chemotherapy) are the only forms of therapy that are available, but as shown, they are not particularly efficacious. Clearly there is a great need for new forms of treatment.

Prolanta is a prolactin receptor antagonist with a single amino acid mutation. This mutation would allow Prolanta to interfere with the binding of two normal prolactin receptors, which would usually cause cancer cell proliferation and also resistance to chemotherapy. It does so through its ability to bind to one prolactin receptor but not the other, blocking prolactin from initiating growth pathways such as the Jak2/STAT pathway. There is significant evidence that this mutated form of prolactin also induces autophagy in ovarian cancer cells.

The purpose of this Phase I study is to evaluate the safety, tolerability and pharmacokinetic parameters of Prolanta monotherapy in patients with recurrent or persistent ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.[2]  Three dosing levels will also be examined to establish the recommended Phase II dose.

About Clinical Accelerator

Clinical Accelerator is an independent clinical trial management organisation operating principally in Central and Eastern Europe. The organisation offers a broad range of clinical trial services together with dedicated patient enrolment support to worldwide clients in the pharmaceutical, biotechnological, nutraceutical and medical device industries. Clinical Accelerator’s model of operation is designed to achieve significant cost savings for its clients and to guarantee compact timelines for patient enrolment with a firm focus on the quality of clinical trial data.

About Oncolix

Oncolix is a Houston, Texas-based, clinical-stage bio-pharmaceutical company dedicated to the development of Prolanta for the treatment of breast, ovarian and other cancers. Oncolix has received approval by the FDA to designate Prolanta as an Orphan Drug for ovarian cancer due to the unmet medical needs.

[1] https://oncolixbio.com/our-science/ovarian-cancer-and-prolanta/

[2] https://www.clinicaltrials.gov/ct2/show/NCT02534922?term=oncolix&rank=1

Posted in Biotech, Central and Eastern Europe, Clinical Accelerator | Leave a comment

VisCardia Announces First Implant of the VisONE® System for Treating Heart Failure

Below, we are re-publishing with permission the press-release issued by VisCardia Inc. on the 1st of August 2018

PORTLAND, Ore.–VisCardia Inc., a privately held medical device developer, announced today the first implant of the VisONE® implantable system for heart failure, and the commencement of its VisONE Heart Failure pilot study in Ukraine*.

The VisONE implantable system delivers VisCardia’s proprietary Asymptomatic Diaphragmatic Stimulation (ADS) therapy to improve cardiac function. By electrically stimulating the diaphragm in an asymptomatic manner, transient intrathoracic pressures gaited to cardiac activity are applied against the cardiac walls, improving both cardiac filling and output. “Our preclinical and early feasibility studies demonstrated ADS improves acute hemodynamic parameters and chronic left ventricular ejection fraction, while remaining asymptomatic and with no adverse effects. With our newly developed implantable VisONE system, we intend to demonstrate ADS benefits the majority of moderate heart failure patients with reduced ejection fraction,” said Peter Bauer, VisCardia’s President and CEO.

“During this 12-month pilot study, we are optimistic VisONE will deliver comparable benefits as those observed during our ADS feasibility studies,” said Paul Erne, M.D., Professor Emeritus of Cardiology at the University Hospital of Basel and former Head of Cardiology at the Kantonsspital of Lucerne, Switzerland.

The implant took place at the Heart Institute, Kyiv, Ukraine, under the leadership of Institute Director Professor Borys Todurov, M.D., Ph.D., and Principal Investigator Dr. Vitaliy Demyanchuk, M.D., Ph.D. The patient, a 53-year-old male with a reduced ejection fraction of 17%, remained in symptomatic heart failure despite an optimally titrated medical regimen, and had no alternative treatment options. General Surgeon Dr. Oleksandr Plehutsa, M.D., Ph.D., who performed the laparoscopic implant, stated, “The practicality and expediency of this novel and minimally invasive approach reduces critical anesthesia times for this delicate heart failure population, enabling a quicker recovery versus established medical device therapies.” Furthermore, Dr. Todurov added, “We are excited at the potential of this therapy to address a significant gap in clinical care. Our center will be actively and methodically studying its impact on heart failure.”

Echocardiographic data will be analyzed at the University Hospital of Zurich under the direction of Professor Felix Tanner, M.D., with statistical analysis performed at the Robertson Centre for Biostatistics in Glasgow under the guidance of Professor John Cleland, M.D. Michael Mirro, M.D., VisCardia’s Director of Medical Affairs, commented, “Given the promising evidence to date, it is exciting to see two recognized groups engaged in studying this new therapy with the proper clinical rigor of a multicenter study used by prominent heart centers.”

About VisONE® ADS Therapy

ADS therapy utilizes a medical device with electrodes, implanted using a minimally invasive laparoscopic surgical procedure, to deliver electrical pulses to precise areas of the diaphragm. The therapy is non-invasively adjusted and programmed using an external programmer to improve hemodynamic benefit and eliminate undesired stimulatory side effects.

About VisCardia

VisCardia, based in Portland, OR, is developing a novel implantable device therapy for treating heart failure, a condition that afflicts 10 million patients in the U.S. and Europe. To learn more about VisCardia, visit: http://www.viscardia.com.

* The study is conducted by Clinical Accelerator

Posted in Central and Eastern Europe, Clinical Accelerator | Leave a comment

FDA inspections produce solid evidence of high quality clinical trial data originating in Central and Eastern Europe

Clinical Accelerator is a clinical CRO with a special focus on Central and Eastern Europe currently operating in 11 countries of that region: Bulgaria, Estonia, Georgia, Hungary, Latvia, Lithuania, Moldova, Poland, Romania, Russian Federation, and the Ukraine (listed alphabetically).

The quality of clinical trial data originating in our countries of operation and its acceptance by the FDA is a frequent topic of discussion with Clinical Accelerator’s partners and clients. In this post we present an analysis of the latest data made available by FDA.

We know first-hand that the clinical trials we conduct in Central and Eastern European countries produce data meeting all the standards set by regulatory agencies around the world. However, we’re also aware of the misconception that clinical research carried out in this region does not conform to the standards of data quality and Good Clinical Practice seen in Western Europe and Northern America.

 

How do countries in Central and Eastern Europe compare with the rest of the world?

Today, clinical trials operate on a global stage. According to the latest report of Office of Inspector General, US Department of Health and Human Services, more than 80% of the US FDA approved marketing applications now contain data acquired outside the US. Our countries of operation are well established contributors to this.

According to clinicaltrials.gov, for example, there are 5535 registered trials in Poland, 4080 in Russia, 3454 in Hungary and 2210 in Romania. It is unsurprising then, that the FDA is increasingly interested in foreign sites involved in conducting clinical trials.

 

Clinical trials sites

Central and Eastern Europe (CEE) is a major contributor of investigative sites to global clinical trials, currently providing 11% of all sites worldwide.

The region is especially attractive to sponsors thanks to the excellent levels of patient recruitment that are characteristic of CEE countries. The average reported recruitment rate in CEE is of 10.3 patients per site compared to 7.5 per site in Western Europe.

In Central and Eastern Europe, our countries of operation are amongst some of the highest ranking for the number of sites participating in industry-sponsored clinical trials: Poland (4320), Czech Republic (2201), Hungary (2115), Ukraine (2002), Romania (1618) and Bulgaria (1004). The number of sites participating in clinical trials in the Baltic countries stands at 386 for Lithuania, 320 for Estonia and 319 for Latvia.

By the number of sites participating in FDA-overseen clinical trials, Russia is currently ranked No. 2 in Europe (after Germany) and No. 4 in the world (after US, Canada and Germany) with 3340 sites. The Ukraine is also climbing up the list fast, currently being No. 11 in Europe and No. 19 in the world with 1141 sites. For comparison, there are 2831 sites overseen by FDA in the UK and 1866 sites in India.

 

FDA inspections

It is unsurprising that facilities operating in CEE have attracted scrutiny from the FDA, given the high number of clinical trials being operated in the region. In the last decade, 300 FDA inspections of Bioresearch Monitoring have been carried out in our countries of operation in CEE. The majority of inspections have been conducted in Poland (109)- pushing them up in ranking above Canada (88) and Germany (96). Other contributors to the number of FDA inspections in CEE are Hungary (34), and Romania (31), Russia (67), Ukraine (29), Latvia (4), Lithuania (6), Estonia (3) and Georgia (17).

This reflects the growing status of CEE countries as leading global locations to conduct clinical trials.

 

FDA inspection outcomes

The results of these inspections have proved to be somewhat unexpected for some critics of the so-called “emerging locations” in CEE.

Based on the most recent statistics available, our own analysis of FDA inspections outcomes based on the top 5 most inspected countries shows that our countries of operation such as Poland and Russia outperform Canada, Germany, and the UK. In the last decade, the percentage of NAI inspections (no objectionable conditions or practices were found during the inspection) was higher in Georgia (100%), Romania (74%), Ukraine (72%), Russia (66.3%), Hungary (65%) and Poland (58.5%), compared with Canada (54.4%), Germany (47.8%), and the UK (42.1%). For inspections where action was indicated, the average number of deficiency codes in Russia (1.24) and Poland (1.44) was lower than in Canada (1.67), the UK (1.95) and Germany (1.89).

Our own analysis is supported by previously published studies. A 2010 analysis of FDA data showed that Eastern Europe (with 264 US FDA inspections) has the best overall results worldwide, with only 3.3% of its site inspections having three or more deficiencies, 0.85% in Russia and 0% in the Ukraine, compared with 20.2% in Western Europe after 506 inspections.

A more recent analysis comparing CEE with Western Europe and the USA gives an equally positive account. Clinical trials in CEE are more likely to result in NAI (No Action Indicated) outcomes of FDA inspections. In our countries of operation 73% of inspections of Bioresearch Monitoring resulted in NAI in the last decade. In comparison, only 56% of inspections resulted in NAI in the USA. The average number of deficiencies per inspection is lower in CEE than in Western Europe and the USA, at 0.99, 1.99, and 1.59, respectively. Finally, the rate of inspections for which objectionable conditions were found, warranting regulatory and/or administrative sanctions, were lower in CEE (1%), than in the USA (2%) and Western Europe (4.5%).

Figure 1: FDA inspections of Bioresearch Monitoring:

Country Total NAI VAI OAI
Estonia 3 1 2 0
Georgia 17 17 0 0
Hungary 34 22 12 0
Latvia 4 2 2 0
Lithuania 6 2 4 0
Poland 109 79 30 0
Romania 31 23 8 0
Russia 67 52 15 0
Ukraine 29 21 8 0
UK 45 20 24 1
Canada 88 64 23 1
Germany 96 62 34 0
US 4,095 2,299 1,593 203
Australia 14 9 5 0

Repeated analysis of FDA inspection data has shown what we’ve always believed at Clinical Accelerator – that clinical trials conducted in CEE are of an equally high standard to those carried out in Western Europe and Northern America. We believe that all the extensive evidence of the quality of clinical trial data in CEE acquired as a result of FDA inspections over the last 5 years should be very reassuring for international companies considering placing their clinical trials in these regions.

Due to the fast growing contribution of these countries to global clinical trials and increasing interest of FDA, we expect more evidence of the quality of clinical trial data will emerge.

We will continue to monitor the data coming from FDA inspections and will re-visit this topic again in one of our future posts.

 

Posted in Central and Eastern Europe, ClinAccel.Net, Clinical Accelerator, FDA | Leave a comment

ARREST Phase IIb Top-Line 52 weeks results

Below, we are re-publishing with permission the press-release issued by Galmed Pharmaceuticals Ltd. on the 12th of June 2018

Galmed’s 600 mg Aramchol™ Achieved a Regulatory Approvable Endpoint Showing NASH Resolution Without Worsening of Fibrosis, in NASH Patients, in the Global Phase 2b ARREST 52-Week Study

  • Statistically significant reduction in liver fat was demonstrated by Magnetic Resonance Spectroscopy (MRS) in patients completing 52 weeks of treatment with Aramchol 400mg vs. placebo. Post hoc analysis of MRS responders, defined by a reduction of ≥5% absolute change from baseline, demonstrated a clinically and statistically significant effect of Aramchol 600mg vs. placebo.
  • Significantly more patients treated with Aramchol 600mg vs. placebo showed NASH resolution without worsening of fibrosis in the 52-week biopsy, a regulatory approvable endpoint.
  • A higher proportion of patients with at least one-point improvement in fibrosis score without worsening of NASH was demonstrated in Aramchol 600mg vs. placebo, in the 52-week biopsy, a regulatory approvable endpoint.
  • Statistically significant reductions in ALT and AST were demonstrated in Aramchol 400mg and 600mg vs. placebo.
  • Aramchol continues to show favorable safety and tolerability profile.

You can find more information here: http://galmedpharma.investorroom.com/2018-06-12-Galmeds-600-mg-Aramchol-TM-Achieved-a-Regulatory-Approvable-Endpoint-Showing-NASH-Resolution-Without-Worsening-of-Fibrosis-in-NASH-Patients-in-the-Global-Phase-2b-ARREST-52-Week-Study

* The study is conducted in part by Clinical Accelerator

Posted in Central and Eastern Europe, ClinAccel.Net, Clinical Accelerator | Leave a comment

DARRT-1 CLINICAL STUDY COMMENCES

Below, we are re-publishing with permission the press-release issued by Noxopharm Limited on the 5th of April 2018

     • Multi-national study testing ability of NOX66 to enhance radiotherapy
     • First cohort of patients treated
     • Direct and abscopal responses being evaluated

Sydney, 5 April 2018: Noxopharm (ASX: NOX) today announces that the first cohort of 4 patients has commenced treatment in the Company’s key DARRT-1 clinical study. The DARRT-1 study is being conducted at 11 centres in Australia, New Zealand and Georgia. It involves men with late-stage prostate cancer (metastatic, castrateresistant disease) receiving NOX66 in combination with a palliative (low) dose of radiotherapy. The first four patients have been recruited in Australia (1) and Georgia (3).

Patients with late-stage prostate cancer that have failed to respond to standard therapies typically have multiple secondary tumours in their skeleton and soft tissues such as lymph nodes. Radiotherapy often is used in an attempt to achieve relief from symptoms such as pain or spinal compression by irradiating a small number (1-3) of the largest tumours. Such treatment is referred to as palliative treatment because it is intended to provide symptomatic relief and not to be curative.

The rationale behind the DARRT-1 study, and the development of NOX66 in combination with radiotherapy, is that NOX66 potentially will enhance the anticancer effect of the radiation in two ways: first, that those tumours exposed to direct radiation will respond better and for longer; second, that all remaining tumours not exposed to radiation also will shrink (so-called abscopal response). The abscopal response is a rare phenomenon and would not be expected in these patients.

DARRT-1 involves exposing between 1 and 3 individual tumours to external beam radiotherapy, daily for 5 days. NOX66 is given daily for up to 15 days. The treatment is completed within 2 weeks; tumour response is assessed by scans after 6, 12 and 24 weeks. Side effects of treatment will be monitored throughout.

The study involves 24 men divided into 4 cohorts. The protocol calls for the first cohort of 4 men to undergo treatment with the lowest daily dosage (400 mg) of NOX66 as a safety review. If that treatment is well tolerated, as the Company anticipates, then the study will recruit a further 4 patients to receive 800 mg NOX66 (Cohort 2) , followed by a further patients to receive 1200 mg NOX66 (Cohort 3). The dose for the remaining 12 patients (Cohort 4) will be decided based on the review of the first 12 patients after all have been assessed at 6 weeks. It is anticipated that this milestone will be met in July 2018, with the remaining patients recruited into the study by August 2018.

………………
About NOX66
NOX66 is an innovative dosage formulation of the experimental anti-cancer drug, idronoxil, developed specifically to preserve the anti-cancer activity of idronoxil in the body and to enhance its drug-like behaviour. Idronoxil is a kinase inhibitor that works by inhibiting a range of enzymes including sphingosine kinase and PI3 kinase that regulate cell pro-survival mechanisms and which are over-expressed in cancer cells, as well as inhibiting external NADH oxidase Type 2 (ENOX 2) which is responsible for maintaining the transmembrane electron potential (TMEP) in the plasma membrane of cancer cells and whose expression is limited to cancer cells. Inhibition of these enzymes results in disruption of key downstream pro-survival mechanisms including resistance mechanisms, sensitizing the cancer cell to the cytotoxic effects of chemotherapy drugs and radiotherapies. Idronoxil also enhances tumour immunity by increasing the activity of human NK cells.

About DARRT Program
The DARRT program is Direct and Abscopal Response to Radiotherapy. It relates to the use of NOX66 to enhance the known abilities of radiotherapy both to kill cancer cells directly exposed to radiation (direct response), and to result in the death of cancer cells outside of the field of radiation (abscopal response). DARRT-1 involves men with metastatic castrate-resistant prostate cancer. Leter studies in this program will be conducted in patients with other forms of cancer, including rare and uncommon cancers.

About Noxopharm
Noxopharm is an Australian drug development company with offices in Sydney and Hong Kong. The Company has a primary focus on the development of drugs to sensitise cancer cells to radiotherapy and chemotherapy. NOX66 is the first pipeline product, with later generation drug candidates under development.

* The study is conducted by Clinical Accelerator

Posted in Uncategorized | Leave a comment

Replicor discloses long term functional control of HBV and HDV infection in high proportions of treated patients at EASL 2018

Below, we are re-publishing with permission the press-release issued by Replicor on the 13th of April 2018

MONTREAL, April 13, 2018 – Replicor Inc., a privately held biopharmaceutical company targeting a cure for patients with chronic hepatitis B virus (HBV) and chronic HBV and hepatitis delta virus (HDV) co-infection, presented today the evolving long-term follow-up data from its REP 301-LTF and REP 401 studies at the 2018 International Liver Conference of the European Association for the Study of the Liver (EASL) held April 11-15, 2018 in Paris, France.

Long term follow-up after completion of REP 2139-based combination therapy with pegylated interferon (pegIFN) or pegIFN and TDF is now extended up to 48 weeks in the REP 401 (NCT02565719) and up to 2 years in the REP 301-LTF (NCT02876419) protocols being conducted in patients with in HBeAg negative chronic HBV infection and HBV/HDV co-infection respectively.

In REP 401 patients completing treatment and at least 12 weeks of follow-up, functional control of HBV infection (HBV DNA < 1000 IU/mL or HBV DNA< LLOQ) currently persists in 25/33 patients (75%).  In patients with HBV/HDV co-infection completing treatment (with only a 15 week overlap of REP 2139-Ca and pegIFN) and 1.5-2 years of follow-up, functional control of HDV infection (HDV RNA target not detectable) currently persists in 7/11 patients (64%). Functional control of HBV infection also persists in 6/7 of these patients (86%).  In both trials, liver function during follow-up is persistently normal in most patients.  In the REP 401 study, HBsAg reductions of > 4 log from baseline during therapy were highly correlated with persistent functional control during follow-up.

Dr. Andrew Vaillant, CSO of Replicor commented, “the evolving follow-up analysis in these studies, continues to demonstrate the well tolerated nature of REP 2139-based combination regimens during treatment and during long-term follow-up, with clear improvement of liver function.”  Dr. Vaillant went on to add, “the continued positive clinical impact of profound reductions in HBsAg to below 1 IU/mL in restoring functional control of HBV and HDV infection in most patients illustrates the importance of this milestone in predicting positive treatment outcomes.”

Replicor’s presentations from EASL 2018 from the REP 301-LTF and REP 401 trials as well as an update on its ongoing collaboration with Dr. Harel Dahari at Loyola University on modeling viral kinetics in response to REP 2139 therapy are now available at www.replicor.com/science/conference-presentations.

About Replicor

Replicor is a privately held biopharmaceutical company with the most advanced animal and human clinical data in the development of the cure for HBV and HDV. The company is dedicated to accelerating the development of an effective treatment for patients with HBV and HBV/HDV co-infection. For further information about Replicor please visit our website at www.replicor.com.

* The study is conducted by Clinical Accelerator

Posted in Central and Eastern Europe, ClinAccel.Net, Clinical Accelerator, Conferences | Leave a comment