BioMarin has announced that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), has adopted a positive opinion for the company’s Marketing Authorization Application (MAA) for Palynziq® (pegvaliase) Injection to reduce blood phenylalanine (Phe) concentrations in patients with phenylketonuria (PKU) aged 16 and older, who have inadequate blood Phe control (blood Phe levels greater than 600 micromol/L) despite prior management with available treatment options. In addition, the CHMP noted that the data collected in the Phase 3 trial and extension study was suggestive of an improvement in inattention and mood symptoms.
In May 2018, Palynziq, a PEGylated recombinant phenylalanine ammonia lyase enzyme, received regulatory approval from the U.S. Food and Drug Administration, making it the first approved enzyme substitution therapy to target the underlying cause of PKU by helping the body break down Phe.
“For more than a decade, BioMarin has been committed to providing meaningful new treatment options for the PKU community. Palynziq is the latest result of this commitment and represents the very first enzyme therapy for PKU; an important step forward in advancing the standard of care and in broadening available treatment options for PKU patients,” said Hank Fuchs, M.D., President Worldwide Research and Development at BioMarin. “We thank the CHMP for recognizing the potential of Palynziq to make a difference for patients living with PKU and are grateful to the PKU community for their continued support and participation in the clinical program.”
“People living with PKU have limited treatment options to manage their Phe levels. As a treating physician, I welcome the potential addition of a new option that could substantially lower Phe levels for more patients with this rare, genetic disease,” said Professor Francjan van Spronsen, Head of Metabolic Diseases at Beatrix Children’s Hospital, Center of Expertise for PKU and Tyrosinemia in The Netherlands. “This offers the potential to effectively control Phe levels in patients with PKU and allow for more normal nutritional intake.”
The CHMP is a scientific committee composed of representatives from the 28-member states of the EU, and Iceland, Norway and Liechtenstein. The committee reviews medical product applications on their scientific and clinical merit and provides advice to the European Commission (EC), which has the authority to approve medicines for the EU. The EC, which typically adheres to the recommendation of the CHMP, is expected to make its final decision on Palynziq in Q2 2019.
The CHMP based its opinion on the totality of data from the Palynziq clinical development program including a Phase 3 pivotal study, PRISM-2, which showed that a group of patients taking either 20 mg or 40 mg of Palynziq maintained mean blood Phe levels at 553.0 µmol/L and 566.3 µmol/L respectively, compared to their baseline in the randomized discontinuation trial (RDT) of 596.8 µmol/L and 410.9 µmol/L. The corresponding 20 mg and 40 mg placebo treated groups mean blood Phe levels increased to 1509.0 µmol/L and 1164 µmol/L compared to their RDT baselines of 563.9 µmol/L and 508.2 µmol/L respectively.The 8-week PRISM-2 double-blind, placebo-controlled, randomized drug discontinuation trial (RDT) consisted of 86 patients, who were randomized to either remain on Palynziq or receive matching placebo.
The CHMP also considered data from an ongoing open-label extension study at 36 months, where patients being treated with Palynziq showed durability and an increase in participants reaching blood Phe thresholds of physiologically normal (≤120 µmol/L), as well as thresholds recommended in the U.S. (≤360 µmol/L) and the European Union (E.U.) (≤600 µmol/L). At 36 months, 58% of the participants reached Phe levels of ≤120 µmol/L, 66% reached Phe levels of ≤360 µmol/L. and 72% reached Phe levels of ≤600 µmol/L. These results were observed concurrent with a median increase in protein intake from intact food of 25g over baseline after 36 months on treatment. In addition, the CHMP noted that the data collected in the Phase 3 trial and extension study was suggestive of an improvement in inattention and mood symptoms as measured by the inattention subscale of the investigator-rated Attention Deficient Hyperactivity Disorder Rating Scale (ADHD-RS IV) and the Profile of Mood States (POMS) tool that was modified to be specific to PKU (PKU-POMS).
PKU is a rare genetic disease that manifests at birth and results in a variety of cumulative toxic effects on the brain, and is marked by an inability to break down Phe, an amino acid that is found in all forms of protein. PKU affects approximately 50,000 diagnosed patients in the developed world, and in Europe, approximately 1 in every 10,000 newborn babies are affected by this disease.[i] Approximately, 18,000 patients aged 16 and older are affected by PKU in Europe and the Middle East. Left untreated, high levels of Phe become toxic to the brain and may lead to serious neurological and neuropsychiatric-related issues, affecting the way a person thinks, feels, and acts. Due to the seriousness of these symptoms, in many countries, infants are screened at birth to ensure that they are diagnosed early and treated to avoid intellectual disability and other complications.
Phase 3 Study Design
The Phase 3 program consists of two studies. PRISM-1 study was a Phase 3 open-label, randomized, multi-center study that enrolled 261 patients, and its primary objective was to characterize the safety and tolerability of Palynziq during induction, titration, and maintenance dosing. The secondary objective of the study was to evaluate blood Phe levels during induction, titration, and maintenance dosing to achieve a target dose of Palynziq 20mg/day or 40mg/day.
215 patients who completed PRISM-1 or PAL-003 (Phase 2 long term extension) enrolled into PRISM-2, which included a randomized, double-blind, placebo-controlled discontinuation study to evaluate the efficacy and safety of subcutaneous injections of Palynziq self-administered by adults with PKU, followed by an open-label extension. The primary efficacy endpoint is change from the RDT baseline in blood Phe at eight weeks.
Patients who reached a target dose and achieved ≥20% decrease in blood Phe from PRISM-1 baseline were randomized into the RDT portion of the study to either continue their Palynziq dose or to start matching placebo. Those participants not reaching a ≥20% reduction in blood Phe from PRISM-1 baseline did not match the inclusion criteria for the RDT and enrolled into the open label extension portion of the study. In the open-label extension, physicians were allowed to modify dose based on blood Phe response using a range of doses from 10 mg/day to 60 mg/day. Patients were evaluated for safety, changes in Phe levels and neurocognitive assessments focused on inattention and mood symptoms.
Medical Guidelines Support Lifelong Therapy to Manage PKU
Medical guidelines in both the United States and Europe support the need for lifelong management of phenylalanine (Phe) levels in patients with phenylketonuria or PKU. In Europe in 2017, The Lancet Diabetes & Endocrinology published shortened medical guidelines, and the Orphanet Journal of Rare Diseases published a full version of the Guidelines stating that untreated blood Phe concentrations greater than 600 μmol/l should be treated. Both publications can be accessed on the website of the European Society for Phenylketonuria (ESPKU).
In the U.S., the American College of Medical Genetics and Genomics (ACMG) issued guidelines in 2014, which state that treatment of PKU should be initiated as early as possible and must be continued throughout adulthood and “lifelong,” with a goal of maintaining blood levels of Phe for all patients between 120-360 umol/L. According to the guidelines “the primary goal of therapy is to lower blood Phe, and any interventions, including medications, or combination of therapies that help to achieve that goal in an individual, without other negative consequences, should be considered appropriate therapy.”
Het mooie voorjaarsweer nodigt uit tot het eten van een
ijsje. En nu we dankzij Amerikaanse wetenschappers de herkomst van onze aardbei
weten, smaakt het aardbeienijs nog lekkerder. Het zomerkoninkje blijkt maar
liefst vier voorouders te hebben. Twee uit Japan, een uit Azië en een van eigen
bodem, de supersmakelijke wilde bosaardbei uit Midden-Europa. Een kruising in
Alaska bracht de voorouders zo’n 1,1 miljoen jaar geleden bij elkaar, waarna de
soort zich snel verspreidde over heel Amerika. Uit de kruising van een Noord-
en een Zuid-Amerikaanse soort is vervolgens de Europese consumptie aardbei
ontstaan. Opvallend genoeg overheersen daarin de genen van de bosaardbei nog
steeds. Met zo’n indrukwekkende stamboom smaken de aardbeien je het vervolg vast
nog beter. Ook kunnen plantenveredelaars dankzij dit onderzoek de aardbei veel
gerichter en sneller veredelen. Zeker als ze daarbij de modernste gene-editing
technieken mogen gebruiken. En laat HollandBIO zich daar nou elke dag voor
inzetten!
Calypso Biotech, an emerging leader in the development of therapeutic antibodies for autoimmune diseases, closed a €20M Series A financing co-led by Gilde Healthcare and Inkef Capital. They are joined by Johnson & Johnson Innovation – JJDC, Inc. (JJDC), and the company’s founding investor M Ventures. Further, Calypso Biotech has become Resident Company at Johnson & Johnson Innovation JLABS at Beerse in Belgium (JLABS@BE). Arthur Franken from Gilde Healthcare will join Fiona MacLaughlin (Inkef Capital), Jeanne Bolger (JJDC) and Jasper Bos (M Ventures) on the Board of Directors.
The proceeds from this financing round will support the development of Calypso Biotech’s best-in class anti-Interleukin-15 (IL-15) antibody CALY-002 up to First-in-Patient studies in several autoimmune indications. IL-15 is an immune checkpoint cytokine that controls inflammation as well as multiple tissue-resident immune cells and recently attracted much attention in the immune-oncology space. Especially, IL-15 is being recognized as a key factor in the survival of tissue resident memory T cells, a population of immune cells involved in disease maintenance and recurrence. Calypso Biotech scientists believe that targeting tissue resident memory T cells offers significant advantages over traditional cytokine interventional approaches and could provide for unprecedented disease-modifying effects.
Calypso Biotech has chosen to develop CALY-002 in Eosinophilic Esophagitis (EoE) as well as in other undisclosed auto-immune indications. EoE is a severe and debilitating immune-related chronic disease of the esophagus that is the second leading cause of dysphagia (difficulty in swallowing) in adults. EoE has emerged as a frequent and significant cause of upper gastrointestinal morbidity particularly associated with important quality of life impairment and significant financial healthcare burden. CALY-002 has secured Orphan Drug Designation status from the European Medicines and Food & Drug Administration agencies for EoE.
“We believe the unique immunological insight and understanding for the role of IL15 in disease brought by founders Alain Vicari and Yolande Chvatchko is now ready for translation into a therapy for patients with EoE, for whom limited therapies are available today, as well as in several large auto-immune indications” said Fiona MacLaughlin, Inkef Capital.
Calypso Biotech is also announcing major strengthening of its team. Bernard Coulie, current president and CEO of Pliant Therapeutics, will be appointed as independent Chairman of the Board. Together with Alexandre LeBeaut, Executive Vice-President and CSO of Ipsen and current independent Director of Calypso Biotech, they will contribute to develop its strategic vision and corporate success. Prof. Bart Lambrecht, from the VIB-UGent Center for Inflammation Research (Belgium), a leading translational immunology expert, will join Calypso Biotech Scientific Advisory Board. Dr. Josephin-Beate Holz (ex Ablynx NV), Dr Greg Elson (ex Glenmark, Novimmune), Dr Susana Salgado (ex Novimmune), and Duc Tran (ex Prexton Therepeutics, Preglem, Pfizer) will join as medical, manufacturing, non-clinical development and strategic planning advisors, respectively.
“We appreciate the confidence placed in our team by a strong and well-balanced investor syndicate” said Alain Vicari, CEO and co-Founder of Calypso Biotech. “With the proceeds of the Series A and our newly recruited team of seasoned experts, we are now well positioned to advance CALY-002 towards value-creating near-term milestones”.
Response of EuropaBio to the recent agreement by the EU co-legislators on the Supplementary Protection Certificate (SPC) Export Waiver.
As the Association representing the European biotechnology industry, EuropaBio is fully committed to the development of a legislative environment which facilitates the creation of EU jobs and growth as well as new solutions to healthcare challenges. We therefore note, with utmost concern, the recent agreement by the EU co-legislators on the Supplementary Protection Certificate (SPC) Export Waiver, which was endorsed by the Member States’ Deputy Permanent Representatives today.
EuropaBio Secretary General, Joanna Dupont-Inglis, commented: “The revision of the EU IP framework, to introduce a SPC manufacturing waiver, is a regrettable example of well-meant but, ultimately, counterproductive policy making, with far-reaching negative impacts on EU competitiveness. It is the small healthcare biotech companies, which are at the cutting edge of creating innovative technologies addressing patient’s unmet needs, that will be hardest hit. These companies,seeking treatments for some of our most devastating and difficult to tackle diseases, take the highest financial risks and rely heavily on investors’ money, often without making any profits for years. They are, therefore, critically dependant on a robust and predictable IP framework.”
EuropaBio supports the overall objective of improving the global competitiveness of EU generic/biosimilar sector, but feels strongly that the agreement on the SPC Export Manufacturing Waiver is at odds with this goal.
In addition, allowing the stockpiling of SPC-protected products, beyond the original export intent, only serves to further undermine confidence in the stability of the EU IP framework at a time our industry is facing increasing global competition. It diminishes the value of investments already committed that had previously been directly incentivised by the SPC framework itself.
Concluding, Dupont-Inglis commented: “What’s needed now is a reinforced incentives framework in order to reassure the global investment community of the EU’s capacity and commitment towards delivering breakthrough care and cures to patients.”
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00hollandbiohttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svghollandbio2019-02-26 15:47:052019-02-26 15:47:08Export Manufacturing Waiver for SPCs: a red flag for investment in EU healthcare biotech← #nieuws
HollandBIO is blij met de beantwoording van Kamervragen door minister Bruins waarin hij, weliswaar voorzichtig, aangeeft dat hij open staat voor innovatieve vergoedingsmodellen die beter passen bij de aard van éénmalige, maar kostbare behandelingen zoals gentherapie. Dit kwam naar voren in de reactie van minister Bruins van 19 februari 2019 op vragen van PvdA-Kamerlid Lilianne Ploumen over de mogelijkheid om gentherapie toegankelijk en betaalbaar te houden voor wie dat nodig heeft. Vanuit het programma ‘Sneller en beter van lab naar patient’ is het ideaalbeeld van HollandBIO dat de vergoeding van nieuwe geneesmiddelen naadloos aansluit op het registratietraject. Op die manier krijgen patiënten sneller toegang tot therapieën waar zij op wachten! De reactie van minister Bruins biedt perspectief om hier, door ruimte voor innovatie in ons vergoedingssysteem, aan te werken.
De Kamervragen van Ploumen staan niet op zichzelf. Zij stelde deze naar aanleiding van het opinieartikel “Betaling gentherapieën kan in Nederland eerlijker en efficiënter” in het Financieele Dagblad. Daarin pleit Henk Eleveld, beleidsadviseur farmacie bij Menzis, voor een alternatief systeem waarbij de kosten van gentherapie-geneesmiddelen in vijf jaar, in vijf gelijke termijnen worden afbetaald volgens een no cure no pay model. Dat laatste zou moeten gebeuren onder bepaalde voorwaarden. Zo zou betaling alleen doorgaan als de patiënt nog in leven is, als een minimale kwaliteit van leven intact is en als de ziekte nog afwezig is.
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00hollandbiohttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svghollandbio2019-02-26 14:33:482019-02-26 17:09:20Minister Bruins staat open voor innovatieve vergoeding gentherapie← #nieuws
The thirteenth BIO-Europe Spring conference comes to Vienna on March 25–27, 2019. The conference annually attracts the international “who’s who” from biotech, pharma and finance for three days of high caliber networking. HollandBIO members are eligible for a € 300,- discount on the prevailing registration fee, more information can be found on our event page. Join this premier springtime partnering conference and register today.
You can meet HollandBIO
at the Health~Holland Pavilion, booth #59. Visit the pavilion and discover what
the Netherlands has to offer as business partner, business location and as
biotech career destination. And of course, you’re most welcome to join us for a
drink at the Health~Holland Pavilion on Tuesday March 26, 17.45h – 18.45h, at
the exhibition floor’s best-visited happy hour. Be on time, because we will
raffle a Dutch Loyens & Loeff bike!
Biotech in the
spotlight
You are invited to
showcase your companies’ innovations at the Biotech in the Spotlight Corner. Send
your corporate video or other digital materials to HollandBIO’s Fabian before Thursday March 21st.
Please save your video or presentation as a .mp4 file in 16.9 modus for the
best result. Keep in mind that we cannot play music sound effects at the booth.
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00hollandbiohttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svghollandbio2019-02-26 14:19:392019-02-26 14:19:41Plan your trip to BIO-Europe Spring← #nieuws
Hubrecht Organoid Technology (HUB) and Yamaha Motor have announced their collaboration to provide solutions that deepen our understanding in predictive diagnostic of patients.
HUB has announced an innovative collaboration with Yamaha
Motor to support organoid research applications in drug development and
personalized medicine. With
this collaboration, HUB aims to develop new methods for Organoid research and precision
medicine in a short timeframe
with as little material as possible. Automatization of this process by CELL
HANDLER*1 would greatly increase accuracy, efficiency and
throughput.
HUB Organoids
HUB exploits the
pioneering work of Prof. Hans Clevers, who discovered methods to grow stem
cell-derived human ‘mini-organs’ (HUB Organoids). Organoid Technology enables the generation of
in-vitro models of any epithelial disease from any patient. HUB Organoids mimic
organ functionality and are considered to be a clinically relevant model for
human diseases such as Cystic Fibrosis, oncology and toxicology. HUB Organoids perform
as “Patients in the Lab” and allow a better understanding of tumor heterogeneity
and drug response. HUB has established a “Living Biobank” that links
patient-specific genetic and phenotypic information to pre-clinical drug
discovery, compounds validation and clinical drug-responsiveness. As a drug
development tool, HUB organoids can efficiently identify novel therapeutic
targets, provide drug efficacy, safety and mechanistical data.
HUB offers licenses to
its patented HUB Organoid Technology for drug-screening and access to Organoids
in the HUB biobanks for pre-clinical drug discovery and validation. In addition, HUB is performing clinical
studies to validate the technologies used as a companion diagnostic.
Yamaha Motor’s CELL HANDLER
Beginning
with its foundation in motorcycle business, Yamaha Motor has leveraged its core competencies
of small-engine technology, vehicle body/hull technology, and control
technology to span a diverse range of businesses such as the marine business
(boats, outboard motors, etc.), power products business (snowmobiles,
generators, etc.), industrial robots, electrical power assisted bicycles, and
automobile engines. The Yamaha Motor Group includes 140 companies across 30
countries and regions worldwide, which work through product development,
manufacturing, and sales, to realize the Corporate Mission of being a
“Kando*2 Creating Company.”
Yamaha Motor has developed a cell picking and imaging system CELL HANDLER for scientific research. It adopts pick-and-place technology from industrial robots like ultra-fast and highly accurate surface mounters designed to mount electric components on printed circuit boards inside electronic devices, e.g., cellular phones and automobiles. CELL HANDLER saves time and efforts and enables cell quality control by simultaneously picking cells and capturing and processing images at a speed and accuracy that would be difficult to achieve when performed manually. As such, Yamaha aims to keep contributing to medical research and drug discovery fields.
*1For research use only. Not for use in diagnostic or therapeutic
procedures.
*2Kando is a Japanese word for the simultaneous feelings of deep satisfaction and intense excitement that we experience when we encounter something of exceptional value.
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00hollandbiohttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svghollandbio2019-02-25 12:18:232019-02-26 12:28:15HUB and Yamaha Motor Combine their Proprietary Technologies← #nieuws
Sapreme Technologies, a privately-held biotech company developing a technology platform to enable the cytosolic delivery of macromolecule therapeutics, has been awarded a 6.8 M€ grant together with a multidisciplinary consortium including 11 other academic and industrial parties. The grant was provided by the European Union (EU) through Horizon 2020 to develop a non-viral based gene therapy using Sapreme’s proprietary endosomal escape enhancers.
Ruben Postel, CSO of Sapreme Technologies, “We are pleased to see that the EU has recognized the great potential of the ENDOSCAPE project and the expert multi-disciplinary consortium developing a novel oligonucleotide delivery technology for treatment of cancer and haemophilia patients”
Ernst Geutjes, acting Managing Director, “The fact that the EU awarded the proposal with the maximum score demonstrates the potential of Sapreme’s proprietary endosomal escape enhancement technology as well as the exceptional quality of the proposal and the consortium spearheaded by Sapreme and Charité – Universitätsmedizin Berlin”
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00hollandbiohttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svghollandbio2019-02-20 15:49:032019-02-26 15:52:52Sapreme Technologies in a 6.8 M€ EU Alliance to Develop an Oligonucleotide Delivery Platform Based on Its Proprietary Endosomal Escape Enhancers← #nieuws
HollandBIO connects and supports the Dutch biotech industry. Today, we are proud to announce that Single Cell Discoveries B.V. has joined the community by becoming a member.
Single Cell Discoveries is a spin-off from the
Hubrecht Institute and Oncode Institute, launched in September 2018. The company offers a complete service
solution for single-cell RNA sequencing, with current customers in over 7
countries and more than 50 institutions.
Single-cell (RNA) sequencing is used to study
the transcriptome of individual cells in order to find rare cell types and
interesting subpopulations in a tissue of interest. It offers a much higher
resolution view of biology. This in contrast to ‘traditional’ bulk RNA
sequencing, which results in an average transcriptome profile of several thousands
to millions of cells.
Single-cell sequencing has a diverse range of
applications:
Cell type marker
discovery
Analysis of tumor
heterogeneity
Cell type identification
Stem-cell analysis in
developmental biology
The Single Cell Discoveries team has the means
and experience to assist their customers with the analysis of hundreds to many
thousands of cells individually. The company offers support on the complete
workflow: from project design to sample prep and data analysis. Single Cell
Discoveries is focusing on both providing excellent services to their
customers, as well as on R&D efforts to continually expand its service
portfolio.
Interested in their services or in collaboration? Please visit www.scdiscoveries.com.
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00hollandbiohttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svghollandbio2019-02-20 00:34:042019-02-20 00:35:06HollandBIO welcomes Single Cell Discoveries as new member← #nieuws
DSM
Venturing has made an equity investment in skin microbiome company S-Biomedic.
This investment completes S-Biomedic’s latest Series A financing round. S-Biomedic
is a Belgium based Life Sciences company pioneering a new approach to cosmetic
and therapeutic potential of the skin microbiome.
This
investment underlines DSM’s interest in the skin microbiome, an area it has
identified as having significant growth potential. DSM already holds a strong
position in gut microbiome research and solutions with its Culturelle® product
range.
“With its
long-established expertise in skin biology and in-depth knowledge in the field
of epidermal science DSM is well placed to extend its research and innovation
focus on the skin microbiome. We have already made encouraging discoveries
about how skin actives in our existing product portfolio work on the skin and
scalp microbiome. Through this investment, we hope to foster further innovation
in the field” commented Rishabh Pande, Vice President Marketing &
Innovation Personal Care & Aroma at DSM.
DSM Venturing has invested in more than 50 emerging innovative companies since its inception in 2001 and its current portfolio covers various industries. “DSM welcomes open innovation, as our history of investing in start-ups and taking on the role of incubator shows,” comments Rob Beudeker, Investment Director at DSM Venturing.
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00hollandbiohttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svghollandbio2019-02-20 00:01:292019-02-20 00:01:31DSM Venturing invests in skin microbiome research
BioMarin Receives Positive CHMP Opinion for PKU treatment Palynziq®
GezondheidBioMarin has announced that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), has adopted a positive opinion for the company’s Marketing Authorization Application (MAA) for Palynziq® (pegvaliase) Injection to reduce blood phenylalanine (Phe) concentrations in patients with phenylketonuria (PKU) aged 16 and older, who have inadequate blood Phe control (blood Phe levels greater than 600 micromol/L) despite prior management with available treatment options. In addition, the CHMP noted that the data collected in the Phase 3 trial and extension study was suggestive of an improvement in inattention and mood symptoms.
In May 2018, Palynziq, a PEGylated recombinant phenylalanine ammonia lyase enzyme, received regulatory approval from the U.S. Food and Drug Administration, making it the first approved enzyme substitution therapy to target the underlying cause of PKU by helping the body break down Phe.
“For more than a decade, BioMarin has been committed to providing meaningful new treatment options for the PKU community. Palynziq is the latest result of this commitment and represents the very first enzyme therapy for PKU; an important step forward in advancing the standard of care and in broadening available treatment options for PKU patients,” said Hank Fuchs, M.D., President Worldwide Research and Development at BioMarin. “We thank the CHMP for recognizing the potential of Palynziq to make a difference for patients living with PKU and are grateful to the PKU community for their continued support and participation in the clinical program.”
“People living with PKU have limited treatment options to manage their Phe levels. As a treating physician, I welcome the potential addition of a new option that could substantially lower Phe levels for more patients with this rare, genetic disease,” said Professor Francjan van Spronsen, Head of Metabolic Diseases at Beatrix Children’s Hospital, Center of Expertise for PKU and Tyrosinemia in The Netherlands. “This offers the potential to effectively control Phe levels in patients with PKU and allow for more normal nutritional intake.”
The CHMP is a scientific committee composed of representatives from the 28-member states of the EU, and Iceland, Norway and Liechtenstein. The committee reviews medical product applications on their scientific and clinical merit and provides advice to the European Commission (EC), which has the authority to approve medicines for the EU. The EC, which typically adheres to the recommendation of the CHMP, is expected to make its final decision on Palynziq in Q2 2019.
The CHMP based its opinion on the totality of data from the Palynziq clinical development program including a Phase 3 pivotal study, PRISM-2, which showed that a group of patients taking either 20 mg or 40 mg of Palynziq maintained mean blood Phe levels at 553.0 µmol/L and 566.3 µmol/L respectively, compared to their baseline in the randomized discontinuation trial (RDT) of 596.8 µmol/L and 410.9 µmol/L. The corresponding 20 mg and 40 mg placebo treated groups mean blood Phe levels increased to 1509.0 µmol/L and 1164 µmol/L compared to their RDT baselines of 563.9 µmol/L and 508.2 µmol/L respectively.The 8-week PRISM-2 double-blind, placebo-controlled, randomized drug discontinuation trial (RDT) consisted of 86 patients, who were randomized to either remain on Palynziq or receive matching placebo.
The CHMP also considered data from an ongoing open-label extension study at 36 months, where patients being treated with Palynziq showed durability and an increase in participants reaching blood Phe thresholds of physiologically normal (≤120 µmol/L), as well as thresholds recommended in the U.S. (≤360 µmol/L) and the European Union (E.U.) (≤600 µmol/L). At 36 months, 58% of the participants reached Phe levels of ≤120 µmol/L, 66% reached Phe levels of ≤360 µmol/L. and 72% reached Phe levels of ≤600 µmol/L. These results were observed concurrent with a median increase in protein intake from intact food of 25g over baseline after 36 months on treatment. In addition, the CHMP noted that the data collected in the Phase 3 trial and extension study was suggestive of an improvement in inattention and mood symptoms as measured by the inattention subscale of the investigator-rated Attention Deficient Hyperactivity Disorder Rating Scale (ADHD-RS IV) and the Profile of Mood States (POMS) tool that was modified to be specific to PKU (PKU-POMS).
PKU is a rare genetic disease that manifests at birth and results in a variety of cumulative toxic effects on the brain, and is marked by an inability to break down Phe, an amino acid that is found in all forms of protein. PKU affects approximately 50,000 diagnosed patients in the developed world, and in Europe, approximately 1 in every 10,000 newborn babies are affected by this disease.[i] Approximately, 18,000 patients aged 16 and older are affected by PKU in Europe and the Middle East. Left untreated, high levels of Phe become toxic to the brain and may lead to serious neurological and neuropsychiatric-related issues, affecting the way a person thinks, feels, and acts. Due to the seriousness of these symptoms, in many countries, infants are screened at birth to ensure that they are diagnosed early and treated to avoid intellectual disability and other complications.
Phase 3 Study Design
The Phase 3 program consists of two studies. PRISM-1 study was a Phase 3 open-label, randomized, multi-center study that enrolled 261 patients, and its primary objective was to characterize the safety and tolerability of Palynziq during induction, titration, and maintenance dosing. The secondary objective of the study was to evaluate blood Phe levels during induction, titration, and maintenance dosing to achieve a target dose of Palynziq 20mg/day or 40mg/day.
215 patients who completed PRISM-1 or PAL-003 (Phase 2 long term extension) enrolled into PRISM-2, which included a randomized, double-blind, placebo-controlled discontinuation study to evaluate the efficacy and safety of subcutaneous injections of Palynziq self-administered by adults with PKU, followed by an open-label extension. The primary efficacy endpoint is change from the RDT baseline in blood Phe at eight weeks.
Patients who reached a target dose and achieved ≥20% decrease in blood Phe from PRISM-1 baseline were randomized into the RDT portion of the study to either continue their Palynziq dose or to start matching placebo. Those participants not reaching a ≥20% reduction in blood Phe from PRISM-1 baseline did not match the inclusion criteria for the RDT and enrolled into the open label extension portion of the study. In the open-label extension, physicians were allowed to modify dose based on blood Phe response using a range of doses from 10 mg/day to 60 mg/day. Patients were evaluated for safety, changes in Phe levels and neurocognitive assessments focused on inattention and mood symptoms.
Medical Guidelines Support Lifelong Therapy to Manage PKU
Medical guidelines in both the United States and Europe support the need for lifelong management of phenylalanine (Phe) levels in patients with phenylketonuria or PKU. In Europe in 2017, The Lancet Diabetes & Endocrinology published shortened medical guidelines, and the Orphanet Journal of Rare Diseases published a full version of the Guidelines stating that untreated blood Phe concentrations greater than 600 μmol/l should be treated. Both publications can be accessed on the website of the European Society for Phenylketonuria (ESPKU).
In the U.S., the American College of Medical Genetics and Genomics (ACMG) issued guidelines in 2014, which state that treatment of PKU should be initiated as early as possible and must be continued throughout adulthood and “lifelong,” with a goal of maintaining blood levels of Phe for all patients between 120-360 umol/L. According to the guidelines “the primary goal of therapy is to lower blood Phe, and any interventions, including medications, or combination of therapies that help to achieve that goal in an individual, without other negative consequences, should be considered appropriate therapy.”
Source BioMarin
Mjam! Bosaardbeitjes ijs
Voedsel en materialenHet mooie voorjaarsweer nodigt uit tot het eten van een ijsje. En nu we dankzij Amerikaanse wetenschappers de herkomst van onze aardbei weten, smaakt het aardbeienijs nog lekkerder. Het zomerkoninkje blijkt maar liefst vier voorouders te hebben. Twee uit Japan, een uit Azië en een van eigen bodem, de supersmakelijke wilde bosaardbei uit Midden-Europa. Een kruising in Alaska bracht de voorouders zo’n 1,1 miljoen jaar geleden bij elkaar, waarna de soort zich snel verspreidde over heel Amerika. Uit de kruising van een Noord- en een Zuid-Amerikaanse soort is vervolgens de Europese consumptie aardbei ontstaan. Opvallend genoeg overheersen daarin de genen van de bosaardbei nog steeds. Met zo’n indrukwekkende stamboom smaken de aardbeien je het vervolg vast nog beter. Ook kunnen plantenveredelaars dankzij dit onderzoek de aardbei veel gerichter en sneller veredelen. Zeker als ze daarbij de modernste gene-editing technieken mogen gebruiken. En laat HollandBIO zich daar nou elke dag voor inzetten!
Bron: NRC
Calypso Biotech BV Secures 20 Million EUR
InnovatieklimaatCalypso Biotech, an emerging leader in the development of therapeutic antibodies for autoimmune diseases, closed a €20M Series A financing co-led by Gilde Healthcare and Inkef Capital. They are joined by Johnson & Johnson Innovation – JJDC, Inc. (JJDC), and the company’s founding investor M Ventures. Further, Calypso Biotech has become Resident Company at Johnson & Johnson Innovation JLABS at Beerse in Belgium (JLABS@BE). Arthur Franken from Gilde Healthcare will join Fiona MacLaughlin (Inkef Capital), Jeanne Bolger (JJDC) and Jasper Bos (M Ventures) on the Board of Directors.
The proceeds from this financing round will support the development of Calypso Biotech’s best-in class anti-Interleukin-15 (IL-15) antibody CALY-002 up to First-in-Patient studies in several autoimmune indications. IL-15 is an immune checkpoint cytokine that controls inflammation as well as multiple tissue-resident immune cells and recently attracted much attention in the immune-oncology space. Especially, IL-15 is being recognized as a key factor in the survival of tissue resident memory T cells, a population of immune cells involved in disease maintenance and recurrence. Calypso Biotech scientists believe that targeting tissue resident memory T cells offers significant advantages over traditional cytokine interventional approaches and could provide for unprecedented disease-modifying effects.
Calypso Biotech has chosen to develop CALY-002 in Eosinophilic Esophagitis (EoE) as well as in other undisclosed auto-immune indications. EoE is a severe and debilitating immune-related chronic disease of the esophagus that is the second leading cause of dysphagia (difficulty in swallowing) in adults. EoE has emerged as a frequent and significant cause of upper gastrointestinal morbidity particularly associated with important quality of life impairment and significant financial healthcare burden. CALY-002 has secured Orphan Drug Designation status from the European Medicines and Food & Drug Administration agencies for EoE.
“We believe the unique immunological insight and understanding for the role of IL15 in disease brought by founders Alain Vicari and Yolande Chvatchko is now ready for translation into a therapy for patients with EoE, for whom limited therapies are available today, as well as in several large auto-immune indications” said Fiona MacLaughlin, Inkef Capital.
Calypso Biotech is also announcing major strengthening of its team. Bernard Coulie, current president and CEO of Pliant Therapeutics, will be appointed as independent Chairman of the Board. Together with Alexandre LeBeaut, Executive Vice-President and CSO of Ipsen and current independent Director of Calypso Biotech, they will contribute to develop its strategic vision and corporate success. Prof. Bart Lambrecht, from the VIB-UGent Center for Inflammation Research (Belgium), a leading translational immunology expert, will join Calypso Biotech Scientific Advisory Board. Dr. Josephin-Beate Holz (ex Ablynx NV), Dr Greg Elson (ex Glenmark, Novimmune), Dr Susana Salgado (ex Novimmune), and Duc Tran (ex Prexton Therepeutics, Preglem, Pfizer) will join as medical, manufacturing, non-clinical development and strategic planning advisors, respectively.
“We appreciate the confidence placed in our team by a strong and well-balanced investor syndicate” said Alain Vicari, CEO and co-Founder of Calypso Biotech. “With the proceeds of the Series A and our newly recruited team of seasoned experts, we are now well positioned to advance CALY-002 towards value-creating near-term milestones”.
Source: Calypso Biotech
Export Manufacturing Waiver for SPCs: a red flag for investment in EU healthcare biotech
InnovatieklimaatResponse of EuropaBio to the recent agreement by the EU co-legislators on the Supplementary Protection Certificate (SPC) Export Waiver.
As the Association representing the European biotechnology industry, EuropaBio is fully committed to the development of a legislative environment which facilitates the creation of EU jobs and growth as well as new solutions to healthcare challenges. We therefore note, with utmost concern, the recent agreement by the EU co-legislators on the Supplementary Protection Certificate (SPC) Export Waiver, which was endorsed by the Member States’ Deputy Permanent Representatives today.
EuropaBio Secretary General, Joanna Dupont-Inglis, commented: “The revision of the EU IP framework, to introduce a SPC manufacturing waiver, is a regrettable example of well-meant but, ultimately, counterproductive policy making, with far-reaching negative impacts on EU competitiveness. It is the small healthcare biotech companies, which are at the cutting edge of creating innovative technologies addressing patient’s unmet needs, that will be hardest hit. These companies, seeking treatments for some of our most devastating and difficult to tackle diseases, take the highest financial risks and rely heavily on investors’ money, often without making any profits for years. They are, therefore, critically dependant on a robust and predictable IP framework.”
EuropaBio supports the overall objective of improving the global competitiveness of EU generic/biosimilar sector, but feels strongly that the agreement on the SPC Export Manufacturing Waiver is at odds with this goal.
In addition, allowing the stockpiling of SPC-protected products, beyond the original export intent, only serves to further undermine confidence in the stability of the EU IP framework at a time our industry is facing increasing global competition. It diminishes the value of investments already committed that had previously been directly incentivised by the SPC framework itself.
Concluding, Dupont-Inglis commented: “What’s needed now is a reinforced incentives framework in order to reassure the global investment community of the EU’s capacity and commitment towards delivering breakthrough care and cures to patients.”
Source: EuropaBIO
Minister Bruins staat open voor innovatieve vergoeding gentherapie
Gezondheid op maat, Hollandbio, GezondheidHollandBIO is blij met de beantwoording van Kamervragen door minister Bruins waarin hij, weliswaar voorzichtig, aangeeft dat hij open staat voor innovatieve vergoedingsmodellen die beter passen bij de aard van éénmalige, maar kostbare behandelingen zoals gentherapie. Dit kwam naar voren in de reactie van minister Bruins van 19 februari 2019 op vragen van PvdA-Kamerlid Lilianne Ploumen over de mogelijkheid om gentherapie toegankelijk en betaalbaar te houden voor wie dat nodig heeft. Vanuit het programma ‘Sneller en beter van lab naar patient’ is het ideaalbeeld van HollandBIO dat de vergoeding van nieuwe geneesmiddelen naadloos aansluit op het registratietraject. Op die manier krijgen patiënten sneller toegang tot therapieën waar zij op wachten! De reactie van minister Bruins biedt perspectief om hier, door ruimte voor innovatie in ons vergoedingssysteem, aan te werken.
De Kamervragen van Ploumen staan niet op zichzelf. Zij stelde deze naar aanleiding van het opinieartikel “Betaling gentherapieën kan in Nederland eerlijker en efficiënter” in het Financieele Dagblad. Daarin pleit Henk Eleveld, beleidsadviseur farmacie bij Menzis, voor een alternatief systeem waarbij de kosten van gentherapie-geneesmiddelen in vijf jaar, in vijf gelijke termijnen worden afbetaald volgens een no cure no pay model. Dat laatste zou moeten gebeuren onder bepaalde voorwaarden. Zo zou betaling alleen doorgaan als de patiënt nog in leven is, als een minimale kwaliteit van leven intact is en als de ziekte nog afwezig is.
Lees de hele brief van minister Bruins hier.
Plan your trip to BIO-Europe Spring
HollandbioThe thirteenth BIO-Europe Spring conference comes to Vienna on March 25–27, 2019. The conference annually attracts the international “who’s who” from biotech, pharma and finance for three days of high caliber networking. HollandBIO members are eligible for a € 300,- discount on the prevailing registration fee, more information can be found on our event page. Join this premier springtime partnering conference and register today.
You can meet HollandBIO at the Health~Holland Pavilion, booth #59. Visit the pavilion and discover what the Netherlands has to offer as business partner, business location and as biotech career destination. And of course, you’re most welcome to join us for a drink at the Health~Holland Pavilion on Tuesday March 26, 17.45h – 18.45h, at the exhibition floor’s best-visited happy hour. Be on time, because we will raffle a Dutch Loyens & Loeff bike!
Biotech in the spotlight
You are invited to showcase your companies’ innovations at the Biotech in the Spotlight Corner. Send your corporate video or other digital materials to HollandBIO’s Fabian before Thursday March 21st. Please save your video or presentation as a .mp4 file in 16.9 modus for the best result. Keep in mind that we cannot play music sound effects at the booth.
For more information, visit the event page: https://www.hollandbio.nl/event/bio-europe-spring-2019/
HUB and Yamaha Motor Combine their Proprietary Technologies
Gezondheid, InnovatieklimaatHubrecht Organoid Technology (HUB) and Yamaha Motor have announced their collaboration to provide solutions that deepen our understanding in predictive diagnostic of patients.
HUB has announced an innovative collaboration with Yamaha Motor to support organoid research applications in drug development and personalized medicine. With this collaboration, HUB aims to develop new methods for Organoid research and precision medicine in a short timeframe with as little material as possible. Automatization of this process by CELL HANDLER*1 would greatly increase accuracy, efficiency and throughput.
HUB Organoids
HUB exploits the pioneering work of Prof. Hans Clevers, who discovered methods to grow stem cell-derived human ‘mini-organs’ (HUB Organoids). Organoid Technology enables the generation of in-vitro models of any epithelial disease from any patient. HUB Organoids mimic organ functionality and are considered to be a clinically relevant model for human diseases such as Cystic Fibrosis, oncology and toxicology. HUB Organoids perform as “Patients in the Lab” and allow a better understanding of tumor heterogeneity and drug response. HUB has established a “Living Biobank” that links patient-specific genetic and phenotypic information to pre-clinical drug discovery, compounds validation and clinical drug-responsiveness. As a drug development tool, HUB organoids can efficiently identify novel therapeutic targets, provide drug efficacy, safety and mechanistical data.
HUB offers licenses to its patented HUB Organoid Technology for drug-screening and access to Organoids in the HUB biobanks for pre-clinical drug discovery and validation. In addition, HUB is performing clinical studies to validate the technologies used as a companion diagnostic.
Yamaha Motor’s CELL HANDLER
Beginning with its foundation in motorcycle business, Yamaha Motor has leveraged its core competencies of small-engine technology, vehicle body/hull technology, and control technology to span a diverse range of businesses such as the marine business (boats, outboard motors, etc.), power products business (snowmobiles, generators, etc.), industrial robots, electrical power assisted bicycles, and automobile engines. The Yamaha Motor Group includes 140 companies across 30 countries and regions worldwide, which work through product development, manufacturing, and sales, to realize the Corporate Mission of being a “Kando*2 Creating Company.”
Yamaha Motor has developed a cell picking and imaging system CELL HANDLER for scientific research. It adopts pick-and-place technology from industrial robots like ultra-fast and highly accurate surface mounters designed to mount electric components on printed circuit boards inside electronic devices, e.g., cellular phones and automobiles. CELL HANDLER saves time and efforts and enables cell quality control by simultaneously picking cells and capturing and processing images at a speed and accuracy that would be difficult to achieve when performed manually. As such, Yamaha aims to keep contributing to medical research and drug discovery fields.
*1For research use only. Not for use in diagnostic or therapeutic procedures.
*2Kando is a Japanese word for the simultaneous feelings of deep satisfaction and intense excitement that we experience when we encounter something of exceptional value.
Source: Hubrecht Organoid Technology (HUB)
Sapreme Technologies in a 6.8 M€ EU Alliance to Develop an Oligonucleotide Delivery Platform Based on Its Proprietary Endosomal Escape Enhancers
InnovatieklimaatSapreme Technologies, a privately-held biotech company developing a technology platform to enable the cytosolic delivery of macromolecule therapeutics, has been awarded a 6.8 M€ grant together with a multidisciplinary consortium including 11 other academic and industrial parties. The grant was provided by the European Union (EU) through Horizon 2020 to develop a non-viral based gene therapy using Sapreme’s proprietary endosomal escape enhancers.
Ruben Postel, CSO of Sapreme Technologies, “We are pleased to see that the EU has recognized the great potential of the ENDOSCAPE project and the expert multi-disciplinary consortium developing a novel oligonucleotide delivery technology for treatment of cancer and haemophilia patients”
Ernst Geutjes, acting Managing Director, “The fact that the EU awarded the proposal with the maximum score demonstrates the potential of Sapreme’s proprietary endosomal escape enhancement technology as well as the exceptional quality of the proposal and the consortium spearheaded by Sapreme and Charité – Universitätsmedizin Berlin”
Source: Sapreme Technologies
HollandBIO welcomes Single Cell Discoveries as new member
HollandbioHollandBIO connects and supports the Dutch biotech industry. Today, we are proud to announce that Single Cell Discoveries B.V. has joined the community by becoming a member.
Single Cell Discoveries is a spin-off from the Hubrecht Institute and Oncode Institute, launched in September 2018. The company offers a complete service solution for single-cell RNA sequencing, with current customers in over 7 countries and more than 50 institutions.
Single-cell (RNA) sequencing is used to study the transcriptome of individual cells in order to find rare cell types and interesting subpopulations in a tissue of interest. It offers a much higher resolution view of biology. This in contrast to ‘traditional’ bulk RNA sequencing, which results in an average transcriptome profile of several thousands to millions of cells.
Single-cell sequencing has a diverse range of applications:
The Single Cell Discoveries team has the means and experience to assist their customers with the analysis of hundreds to many thousands of cells individually. The company offers support on the complete workflow: from project design to sample prep and data analysis. Single Cell Discoveries is focusing on both providing excellent services to their customers, as well as on R&D efforts to continually expand its service portfolio.
Interested in their services or in collaboration? Please visit www.scdiscoveries.com.
DSM Venturing invests in skin microbiome research
Gezondheid, InnovatieklimaatDSM Venturing has made an equity investment in skin microbiome company S-Biomedic. This investment completes S-Biomedic’s latest Series A financing round. S-Biomedic is a Belgium based Life Sciences company pioneering a new approach to cosmetic and therapeutic potential of the skin microbiome.
This investment underlines DSM’s interest in the skin microbiome, an area it has identified as having significant growth potential. DSM already holds a strong position in gut microbiome research and solutions with its Culturelle® product range.
“With its long-established expertise in skin biology and in-depth knowledge in the field of epidermal science DSM is well placed to extend its research and innovation focus on the skin microbiome. We have already made encouraging discoveries about how skin actives in our existing product portfolio work on the skin and scalp microbiome. Through this investment, we hope to foster further innovation in the field” commented Rishabh Pande, Vice President Marketing & Innovation Personal Care & Aroma at DSM.
DSM Venturing has invested in more than 50 emerging innovative companies since its inception in 2001 and its current portfolio covers various industries. “DSM welcomes open innovation, as our history of investing in start-ups and taking on the role of incubator shows,” comments Rob Beudeker, Investment Director at DSM Venturing.
Source: DSM