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InteRNA Presents Expanded Preclinical Proof-of-concept Data

InteRNA Technologies announced results from a set of confirmatory in vitro and in vivo studies further validating the unique mechanism of action (MoA) of InteRNA’s lead microRNA drug candidate, INT-1B3, for the treatment of cancer. Most strikingly, the company was able to demonstrate that INT-1B3’s earlier reported long-term memory immune protection activity against re-challenge with tumor cells is cytotoxic CD8+ T cell-mediated. INT-1B3 is a lipid nanoparticle (LNP) formulated, chemically modified microRNA 193a-3p mimic, a known tumor-suppressor microRNA, that has been shown to induce immune-modulation of the tumor microenvironment, reduction of metastases development leading to improved animal survival, and pronounced long-term immunity with a good safety and tolerability profile. The data were presented in two posters at the 14th Annual Oligonucleotide Therapeutics Society (OTS) Meeting, held in Seattle, WA from September 30 – October 3, 2018.

“These confirmatory results are consistent with the original preclinical proof-of-concept data we presented at the AACR Annual Meeting this year and thereby serve as a fundamental validation of INT-1B3’s differentiated mechanism of action,” said Dr. Roel Schaapveld, CEO of InteRNA. “It is also very exciting that we were able to demonstrate that the pronounced long-term anti-tumor immunity we have seen is CD8+ T cell-dependent which further clarifies a key aspect of these promising effects. We are convinced that INT-1B3, next to its potential in combination regimens, represents a unique and novel monotherapeutic opportunity in immuno-oncology and we look forward to evaluating its efficacy in cancer patients.”

The data presented at the 14th Annual OTS Meeting confirm and expand on the preclinical data presented at AACR in April 2018 as summarized in the following announcement http://bit.ly/2NnruRI.

In a syngeneic orthotopic mouse model of triple negative breast cancer (TNBC 4T1), systemic administration of INT-1B3 was proven to efficiently modulate the immunosuppressive tumor microenvironment. Upon resection of the primary tumors, this resulted in: 1) the inhibition of tumor re-growth, 2) reduction of distant (lung and intraperitoneal) metastases development with significant impact on animal survival, and 3) long-term immunity to newly injected 4T1 tumor cells in the absence of further drug treatment. Most notably, CD8+ T cell depletion greatly impacted protection of surviving INT-1B3-treated animals against such re-challenge with 4T1 tumor cells, suggesting a CD8+ T cell-dependent long-term immune protection. Furthermore, the results presented in a second poster verify that upon transfection in a wide panel of human tumor cell lines, the microRNA 193a-3p mimic was able to inhibit tumor cell proliferation and survival, modulate the tumor cell cycle, induce apoptosis and/or senescence and decrease tumor cell migration and invasion. In addition, and consistent with results in cell-based assays, significant anti-tumor efficacy of INT-1B3 was demonstrated in several human xenografts and in an extended panel of syngeneic subcutaneous mouse tumor models. Based on these results, INT-1B3 provides a novel and promising therapeutic approach in the immuno-oncology armamentarium.

MicroRNAs are naturally occurring small RNA interfering molecules which represent a part of the body’s arsenal to regulate gene expression, each targeting a specific set of genes that have gained recent attention as a novel therapeutic approach in a variety of disease states. MicroRNA 193a-3p specifically is a known tumor suppressor microRNA that is downregulated in many cancers. InteRNA’s formulated and chemically modified synthetic mimic combines anti-tumor activity with modulation of the immunosuppressive tumor microenvironment, and long-term immunity upon systemic delivery to cancer cells upregulating microRNA 193a-3p’s original function across the pathways involved in the initiation and progression of cancer and the evasion of the immune system in parallel.

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European Biotechweek 2018: 7 days showcasing creativity, passion and expertise in transformative technology

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European Biotech Week 2018 begins on Monday the 24th September, with more than 120 events taking place across 18 European countries. The events, hosted at national and local level by a variety of organisations, companies and other biotech enthusiasts, aim to raise awareness, to fuel curiosity and to engage communities in exploring the benefits of biotechnology and discussing its potential for the future.

Commenting on this, EuropaBio Secretary General, Joanna Dupont-Inglis noted: “Biotech already enables us to use precious resources more efficiently, improves nutrition, helps develop new crops to feed a growing population and develops treatments that respond to unmet medical needs. This week enables us to highlight the best and brightest examples of this, live and direct across Europe”

Initiatives throughout the week are as diverse as the organisers themselves. They include conferences, workshops, hands on laboratories, exhibitions and open-door days with companies, laboratories, research institutes and museums. In Brussels, events will include a week-long exhibition, highlighting the role of biotech in delivering on the UN Sustainable Development Goals, which takes on Place Luxembourg, in the heart of Europe’s capital. This will be followed by a film screening of the documentary Well Fed at the world famous BOZAR Centre For Fine Arts.

EuropaBio Chair, Tjerk de Ruiter concluded: “Biotechnology already improves lives in so many ways – but people are often unaware of it. It’s one of the most exciting and innovative technologies that we have and we’re part of a community that’s passionate about it. When you’re passionate about something, you want to share it and that’s what biotech week is really all about.”

To learn more about activities taking place near you visit www.biotechweek.org

Source: EuropaBIO

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Vroege toegang: sneller en beter van lab naar patiënt

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Wetenschappers verbonden aan het Erasmus Medisch Centrum publiceerden in Health Policy een overzicht van de ontwikkelingen op het gebied van vroege toegang tot nieuwe geneesmiddelen. Op dit moment kunnen patiënten voor wie geen standaard levensverlengende behandelopties (meer) beschikbaar zijn, via zogenaamde compassionate use programma’s in aanmerking komen voor vroege toegang tot nieuwe, experimentele geneesmiddelen. In Nederland wordt echter weinig gebruik gemaakt van regelingen voor vroege toegang.

Eline Bunnik, Nikkie Aarts en Suzanne van de Vathorst zochten uit waarom dat zo is. Zij concludeerden dat het zorgstelsel weliswaar de mogelijkheid biedt, maar patiënten in nood niet ondersteunt in het krijgen van toegang tot experimentele middelen. De onderzoekers gaan in op drie ontwikkelingen die de status quo doorbreken en de ethische implicaties hiervan: door van compassionate use geen uitzondering, maar een mainstream optie te maken, door bedrijven geld te laten vragen voor vroege toegang en door data te verzamelen over het gebruik van geneesmiddelen binnen compassionate use programma’s. HollandBIO participeerde in het valorisatiepanel van het onderzoek.

Veilige en verantwoorde vroege toegang is ook één van de oplossingen binnen HollandBIO’s programma Sneller & Beter van lab naar patiënt. Met dit programma maakt HollandBIO werk van oplossingen waarbij gezondheidswinst, innovatie en betaalbaarheid hand in hand gaan. En die zijn hard nodig, want alleen dan kan de sector haar ambitie realiseren om op een dag elke patiënt van een effectieve behandeling te voorzien. Kortom: wat ons betreft is de publicatie niet alleen een absolute leestip, maar ook de basis van een broodnodige maatschappelijke discussie over hoe patiënten zo snel en breed mogelijk kunnen profiteren van de innovatieve kracht van de biotech sector.

Tot 23 oktober is de publicatie vrij toegankelijk via: https://authors.elsevier.com/a/1Xf~~cP6mzq6I

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Third patient treated in uniQure’s Phase IIb study patients with Hemophilia B

uniQure, a leading gene therapy company advancing transformative therapies for patients with severe unmet medical needs, announced that the third patient has been treated in the Company’s Phase IIb dose-confirmation study of AMT-061, an investigational AAV5-based gene therapy incorporating the FIX-Padua variant for the treatment of patients with severe and moderately severe hemophilia B. AMT-061 has been granted Breakthrough Therapy Designation by the United States Food and Drug Administration and access to Priority Medicine (PRIME) regulatory initiative by the European Medicines Agency.

The Phase IIb dose-confirmation study is an open-label, single-arm, single-dose trial being conducted in the United States to confirm the dose of AMT-061 prior to patient treatment in the ongoing Phase III HOPE-B pivotal trial. Three patients received a single intravenous (IV) infusion of 2×1013 vc/kg over the past month and are currently under evaluation to assess safety and Factor IX (FIX) activity.

“We are very pleased with the progress we have made in the clinical development of AMT-061, our lead gene therapy product candidate for hemophilia B,” stated Matthew Kapusta, chief executive officer of uniQure. “The treatment of the third patient puts us in the position to present topline data and confirm dosing for our Phase III HOPE-B pivotal study by the end of the year.”

“We also have made advancements in the execution of the HOPE-B pivotal study, which now includes multiple recruiting sites and enrolled patients,” he added. “We believe that AMT-061 has the potential to be a leading gene therapy treatment that provides durable, clinically relevant increases in FIX activity with a favorable immunogenicity profile which could expand patient eligibility for treatment with our gene therapy.”

Phase III HOPE-B Pivotal Trial

Patient enrollment is also underway in the global Phase III HOPE-B clinical trial to evaluate the safety and efficacy of AMT-061. Approximately 50 adult hemophilia B patients classified as severe and moderately-severe will be enrolled in a six-month observational period during which time they will continue to use their current standard of care to establish a baseline comparator. After the six-month lead-in period, patients will go on to receive a single intravenous administration of AMT-061. Dosing of patients in the HOPE-B pivotal trial is expected to start early in the first quarter of 2019.

Source: Forbion

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Onderzoek: HPV-vaccin is veilig

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Onderzoek van het RIVM toont geen verband tussen het vaccin tegen baarmoederhalskanker (HPV) en langdurige vermoeidheidsklachten bij meisjes. Resultaten van recent epidemiologisch onderzoek in Nederland komen overeen met de uitkomsten van eerder verschenen internationale onderzoeken.

Meisjes krijgen het HPV-vaccin in het jaar dat zij 13 worden. Voor introductie van vaccinatie tegen HPV, kwamen ernstige vermoeidheidsklachten bij ongeveer 1 op de 5 meisjes voor in deze leeftijdscategorie en bij ongeveer de helft daarvan houden deze klachten langer dan drie maanden aan. Het RIVM onderzocht of deze langdurige vermoeidheidsklachten vaker voorkomen bij gevaccineerde meisjes dan bij meisjes die niet zijn ingeënt. Het onderzoek werd uitgevoerd naar aanleiding van meldingen van vermoeidheidsklachten die langer dan twee maanden duurden na de HPV-vaccinatie bij Bijwerkingencentrum Lareb. De meeste van deze meldingen kwamen binnen na media-aandacht rondom het HPV-vaccin in 2012 en 2015.

Resultaten van het onderzoek

Voor het onderzoek werden bijna 70 duizend meisjes geselecteerd uit een groot huisartsenregistratiesysteem van het Erasmus MC. Uit gegevens bleek dat langdurige vermoeidheid vóór invoering van de HPV-vaccinatie even vaak voor kwam als na de invoering. De diagnose chronisch vermoeidheidssyndroom werd maar weinig gesteld door de huisarts, namelijk 0 tot 1 keer per jaar per tien duizend meisjes zowel vóór als na invoering van HPV-vaccinatie.
In de studie gaven 49 meisjes die langer dan 6 maanden vermoeidheidsklachten hebben gehad toestemming om hun gezondheidsgegevens te koppelen aan hun vaccinatiegegevens. Van hen waren 37 gevaccineerd. Binnen een jaar na de HPV-vaccinatie bezochten zij niet vaker een huisarts met langdurige vermoeidheidsklachten dan vóór of langer dan een jaar na de vaccinatie.

In lijn met eerdere onderzoeken

De resultaten zijn in lijn met de uitkomsten van eerdere internationale onderzoeken. Het is op basis van al deze onderzoeken duidelijk dat HPV-vaccinatie veilig is. Meer informatie over HPV en het vaccin tegen baarmoederhalskanker is te vinden op de website van het Rijksvaccinatieprogramma. Op deze website is ook meer te lezen over bijwerkingen.

Volledig artikel

Het volledige artikel ‘No evidence found for an increased risk of long-term fatigue following human papillomavirus vaccination of adolescent girls‘ (door T.M. Schurink-van t Klooster, J.M. Kemmeren, N.A.T. van der Maas, E.M. van de Putte, M. ter Wolbeek, S.L. Nijhof, A.M. Vanrolleghem, J.A. van Vliet, M. Sturkenboom, H.E. de Melker) is te lezen op de website van het tijdschrift Vaccine.

Bron: RIVM

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MSD ontvangt positieve CHMP-opinie voor twee nieuwe AIDS behandelingen

Het Comité voor geneesmiddelen voor menselijk gebruik (CHMP) van het Europees Geneesmiddelenbureau (EMA) heeft een positief advies afgegeven voor het verlenen van een handelsvergunning voor twee nieuwe hiv-1-geneesmiddelen. Dat heeft MSD vandaag bekendgemaakt. Het positieve advies betreft DELSTRIGO™ (een eenmaal daags tablet met vaste dosis van doravirine (100 mg), lamivudine (3TC, 300 mg) en tenofovirdisoproxilfumaraat (TDF, 300 mg) en PIFELTRO™ (doravirine, 100 mg), een nieuwe NNRTI (non-nucleoside reverse transcriptase-remmer) die moet worden toegediend in combinatie met andere antiretrovirale geneesmiddelen.

 

MSD zet zich al meer dan 30 jaar in voor onderzoek en behandeling van hiv. Het positieve advies van het CHMP betekent een stap voorwaarts bij het bevorderen van nieuwe behandelingen voor mensen met hiv. Dr. George Hanna, hoofd van Global Clinical Development voor infectieziekten: “Dit brengt onze inspanningen om tegemoet te komen aan de onvervulde behoeften van de hiv-gemeenschap wereldwijd verder.”

 

De twee geneesmiddelen worden momenteel beoordeeld door het Europees Geneesmiddelen-bureau voor de behandeling van volwassenen met een hiv-1-infectie zonder bewijs van resistentie tegen de non-nucleoside reverse transcriptaseklasse, lamivudine of tenofovir, al dan niet aanwezig. De aanbevelingen zullen nu door de Europese Commissie worden beoordeeld voor handelsvergunningen in de Europese Unie. Handelsvergunningen voor beide geneesmiddelen worden ook beoordeeld in andere landen, waaronder Canada, Australië en Zwitserland. In de Verenigde Staten zijn beide geneesmiddelen op 30 augustus 2018 goedgekeurd door de gezondheidsautoriteit FDA.

 

Sinds 1986 houdt MSD zich bezig met onderzoek naar de behandeling van hiv. Deze inspanningen zorgden er mede voor dat er 10 jaar later een behandeling kwam waardoor mensen niet meer overleden aan aids. In de loop der jaren is hiv hierdoor veranderd van een dodelijke naar een chronische ziekte. MSD heeft zich al die tijd ingezet voor een betere hiv/aids-zorg wereldwijd. En ook nu nog ondersteunen we op diverse plekken in de wereld projecten rond preventie, behandeling, zorg en ondersteuning voor mensen met hiv en aids. Meer hierover kun je lezen op https://msd.nl/hiv/

Bron: MSD

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Amicus Expands into Gene Therapy with Celenex Acquisition

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Amicus Therapeutics said it has acquired Nationwide Children’s Hospital spinout Celenex for up to $452 million, in a deal that expands the rare disease drug developer into gene therapy with a portfolio of 10 clinical and preclinical programs in neurologic lysosomal storage disorders (LSDs).

The 10 adeno-associated virus 9 (AAV9) gene therapy programs—developed at the hospital’s Center for Gene Therapy and The Ohio State University, both based in Columbus, OH—include lead programs in CLN6, CLN3, and CLN8 Batten disease that are potential first-to-market curative treatments, Amicus said.

The other programs include efforts to develop gene therapies for Niemann Pick C, Wolman disease, Tay Sachs disease, and LSDs for other unspecified CNS disorders, according to a presentation for investors by Amicus.

“The groundbreaking work of [principal investigators] Brian Kaspar, Ph.D. and Kathrin Meyer, Ph.D., at Nationwide Children’s Hospital, along with collaborator, Arthur Burghes, Ph.D., professor at The Ohio State University, on these programs has led to remarkably strong and consistent preclinical results and now, in CLN6 Batten disease, encouraging early results in children. This is science and biotechnology at its best,” Amicus Chairman and CEO John F. Crowley said in a statement.

Recruiting of patients has begun for a Phase I/II clinical trial of the CLN6 therapy (NCT02725580), while the first patient is expected to be dosed in a Phase I/II trial of the CLN3 program “in coming months,” Amicus stated in its presentation.

According to Amicus, a single administration of the CLN6 gene therapy generated “encouraging” preliminary efficacy data in the first two patients treated: Two years post-treatment, Hamburg motor and language scores indicated no disease progression in the younger sibling, while disease progression in older sibling showed evidence of stabilization. Additional data for CLN6 will be presented in 2019.

The CLN6, CLN3, and CLN8 programs gave all generated promising preclinical data in mouse models: “The preclinical proof-of-concept we have seen to date in CLN6, CLN3, and CLN8 further support the applicability of the AAV vector we developed at Nationwide Children’s in genetic disease of the CNS,” Dr. Meyer adds.

Billion-Dollar Vision

Amicus said the deal would more than achieve its vision of growing into a rare disease developer whose therapies treat more than 5,000 patients, and generate more than $1 billion in worldwide sales by 2023. Amicus generated $38.005 million in the first half of this year and $36.93 million for all of 2017 in net product sales, all from its sole marketed drug, the Fabry disease treatment Galafold™ (migalastat), authorized in Europe since 2016 and only approved in the U.S. last month.

Of the Celenex programs, Amicus said in the presentation, the largest estimated addressable patient population is the 5,000 projected for the CLN3 treatment, followed by the 3,500 for the Niemann Pick C, Wolman disease, Tay Sachs disease, and other CNS LSD programs. Another 1,000 patients are estimated for the CLN6 treatment, and 750 for the CLN8 therapy.

Amicus has agreed to pay Celenex shareholders $100 million cash upfront, $15 million in payments tied to achieving development milestones, and $262 million in regulatory submission and approval milestones across multiple programs. Amicus said it expected to shell out no more than $75 million over the next four years in milestone payments, and would not pay out any royalties.

Celenex shareholders are also eligible for up to $75 million in payments tied to tiered sales milestones (tiers of $500 million/$750 million). The acquisition and several years of related development costs for all of the gene therapy programs will be financed through a new $150 million debt facility to be provided by BioPharma Credit, an investment fund managed by Pharmakon Advisors.

The transaction was closed immediately following approval by the boards of Amicus and Celenex.

Columbus-based Celenex was established by Gordon Gray, producer of movies that include Secretariat, and his wife, Kristen Gray, whose daughters Charlotte and Gwenyth were both diagnosed with Batten’s disease in 2015, at ages 4 and 2, respectively. The Grays established the Charlotte and Gwenyth Gray Foundation, created to fund research and clinical studies toward Batten disease treatments.

The Celenex acquisition comes after Amicus on August 10 won FDA accelerated approval for Galafold 123 mg capsules, an oral pharmacological chaperone of alpha-Galactosidase A (alpha-Gal A) taken every other day. Galafold was approved based on reduction in kidney interstitial capillary cell globotriaosylceramide (KIC GL-3) substrate. As a condition of accelerated approval, Amicus agreed to continue studying Galafold in a confirmatory Phase IV program.

Amicus is also conducting a global Phase I/II study (NCT02675465) for another clinical candidate, AT-GAA for Pompe disease. AT-GAA consists of ATB200, a recombinant human acid alpha-glucosidase enzyme with optimized carbohydrate structures, particularly mannose-6 phosphate, co-administered with AT2221, a pharmacological chaperone. Clinical results are expected to be shared at the 23rdInternational Congress of the World Muscle Society, set for October 2-6 in Mendoza, Argentina.

Source: GEN

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Clearing out old cells might help the brain

A new pack of anti-aging companies like Unity Biotech, Cleara Biotech, and Oisín Biotechnologies think there’s a connection between so-called senescent cells—those that no longer divide—and the effects of growing old.

Clear out cells that have gone into this sleeplike state, the thinking goes, and youthful vigor will return. But not much has been known about how these cells affect the brain.

Now scientists who have taken a careful look at the brains of mice think senescent cells could have a role in neurodegeneration and memory loss.

In the new study, senior author Darren Baker of the Mayo Clinic in Minnesota found that if researchers removed senescent cells or prevented them from building up, they could prevent brain degeneration in mice prone to it.

The results, published in Nature, are among the first to take a careful look at senescence and its possible connection to conditions like Alzheimer’s and Parkinson’s disease. “I think this is a very interesting new avenue, a new way to look at aging,” says Li-Huei Tsai, director of the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology and the author of an editorial accompanying the study. “I am kind of optimistic that this new idea is going to stimulate a lot of people to think about this.”

Baker, a molecular biologist, says the concept of clearing out detrimental cells from the brain is nowhere near ready to try on people. Early tests of this anti-aging concept, like one under way at Unity (which holds patents naming Baker as a co-inventor), are so far targeting specific diseases, like arthritis in the knees, rather than aging as a whole.

Baker got interested in senescence about 15 years ago after genetically altering a mouse to make it more cancer-prone. Instead, the changes accidentally sped up its aging process, he says, and there was evidence senescent cells were involved.

Targeting these old cells has become a major quest among a few anti-aging companies. Baker says he’s unsure whether targeting senescent cells in the brain will be helpful or have side effects like triggering cancer. “We really have no idea right now,” he says.

Because mature neurons naturally don’t divide anyway, it hasn’t been clear how they are affected by senescence. The new study suggests it is the “helper” cells—the microglia and astrocytes surrounding the neurons—that are at the center of the effect.

Source: MIT technology review

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Proefschrift: vaccinaties redden duizenden levens in Nederland

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Vaccineren helpt, constateert kersverse doctor Maarten van Wijhe. Met succes verdedigde hij vorige week aan de Rijksuniversiteit Groningen zijn proefschrift over de impact van vaccinatieprogramma’s in Nederland. Zijn conclusie liegt er niet om. Door tegen zeven aandoeningen te vaccineren, zijn tussen 1953 en 1992 ruim zesduizend tot twaalfduizend gevallen van kindersterfte voorkomen. Het proefschrift is een stevige bevestiging van belang van het Rijksvaccinatieprogramma. HollandBIO is van mening dat verdere uitbreiding van dit programma, dat inmiddels tegen twaalf ziekten beschermt, Nederland in staat stelt nóg meer gezondheidswinst te verzilveren, zowel op collectief als individueel niveau. HollandBIO roept daarom op tot een breed gedragen, proactieve overheidsvisie op de preventie van infectieziekten. Wij zijn immers pas écht tevreden als alle vaccineerbare aandoeningen de wereld uit zijn.

Benieuwd naar het proefschrift van Maarten? Lees (delen van) ‘The public health impact of vaccination programmes in the Netherlands – A historical analysis of mortality, morbidity, and costs’ hier: https://www.rug.nl/research/portal/en/publications/the-public-health-impact-of-vaccination-programmes-in-the-netherlands(29a46600-ad10-447d-a38c-df8f1bdc7ed1).html

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Van prikken naar plakken: de grieppleister

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Geen griepprik, maar grieppleisters: daar werken de onderzoekers van het Disease Research Institute in Seattle hard aan. Een prachtige innovatie, vindt ook HollandBIO. Pleisters zijn immers minder invasief, vereisen geen gekoeld transport en zijn makkelijker te verspreiden tijdens een epidemie. Gewoon, via de post.

Toch zijn er, zoals dat gaat met innovatie, nog wel wat hordes te overwinnen voordat de eerste grieppleisters op je mat vallen. Hoe houd je toezicht op correcte toediening, bijvoorbeeld. Of hoe vaak moet je de pleister plakken. Zo zijn de eerste proefpersonen vooralsnog niet na één, maar pas na twee pleisters beschermd tegen de griep. Tot slot is nog niet duidelijk of het productieproces op te schalen is, bijvoorbeeld in het geval van een pandemie. Aan PostNL zal het in elk geval niet liggen – zij zijn er al helemaal klaar voor.

Meer weten over de grieppleister? Lees dan dit artikel uit de Volkskrant.

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