In het zicht van de haven kreeg Galapagos afgelopen week een flinke knauw van de Amerikaanse Food and Drug Administration (FDA): kroonjuweel filgotinib verschijnt dit jaar nog niet op de Amerikaanse markt. De FDA wil de resultaten van een lopende studie naar het effect op de mannelijke vruchtbaarheid afwachten. Voor CEO Onno van der Stolpe kwam het nieuws als een donderslag bij heldere hemel. Toch laat hij zich niet uit het veld slaan, meldt hij het FD: “Dit is een tijdelijke tegenslag. We gaan hier sterker uitkomen.”
Het is niet de eerste en ook zeker niet de laatste keer dat HollandBIO binnen de biotech getuige is van een plottwist als deze. De route van lab naar patiënt blijkt eens te meer lang en bezaaid met hordes.
Feike Sijbesma, speciaal gezant corona, rondt zijn werkzaamheden in september af. Sinds 26 maart heeft de heer Sijbesma het kabinet geholpen in de coronacrisis, onder andere met het testbeleid en de vaccinstrategie van ons land.
Zo heeft hij eraan bijgedragen dat er genoeg testen beschikbaar zijn om sinds eind mei iedereen in Nederland met klachten te laten testen. Later is de heer Sijbesma door het kabinet gevraagd te helpen bij het in kaart brengen van de ontwikkelingen van mogelijke coronavaccins. In de afgelopen periode heeft de Europese Commissie, mede namens Nederland, succesvol onderhandeld waardoor Nederland de beschikking heeft over mogelijke vaccins.
Sijbesma verrichtte al deze tijdelijke werkzaamheden geheel onbezoldigd. Het kabinet kan in de toekomst, indien gewenst en mogelijk, een beroep op hem blijven doen mocht dat nodig zijn.
Minister-president Rutte en minister De Jonge zijn Feike Sijbesma zeer erkentelijk voor zijn werk van de afgelopen maanden: “Met zijn expertise, ervaring en contacten heeft hij een grote en belangrijke bijdrage geleverd in de strijd tegen het coronavirus. Op diverse onderwerpen heeft hij zich maandenlang, schijnbaar onvermoeibaar, ingezet. Het is fijn dat het kabinet ook in de toekomst een beroep op hem kan blijven doen.”
Johnson & Johnson (NYSE:JNJ) announced it has entered into a definitive agreement to acquire Momenta Pharmaceuticals, Inc. (Momenta), a company that discovers and develops novel therapies for immune-mediated diseases, in an all cash transaction for approximately $6.5 billion.
This acquisition provides an opportunity for the Janssen Pharmaceutical Companies of Johnson & Johnson to broaden its leadership in immune-mediated diseases and drive further growth through expansion into autoantibody-driven disease. The transaction will include full global rights to nipocalimab (M281), a clinically validated, potentially best-in-class anti-FcRn antibody. Nipocalimab gives Janssen the opportunity to reach significantly more patients by pursuing indications across many autoimmune diseases with substantial unmet medical need in maternal-fetal disorders, neuro-inflammatory disorders, rheumatology, dermatology and autoimmune hematology. Nipocalimab recently received a rare pediatric disease designation from the U.S. Food and Drug Administration. Momenta’s expertise in FcRn mechanisms is especially important for nipocalimab as it supports and accelerates the development of a medicine designed to target a number of autoantibody-driven conditions across several of Janssen’s established therapeutic areas. Janssen expects nipocalimab to contribute to its goals of achieving above-market growth over the mid and long term.
Autoimmune diseases driven partially or completely by autoantibodies represent a novel area where Janssen can significantly improve health outcomes for patients. In autoantibody-driven diseases, the body’s antibodies attack or damage its own proteins, cells and tissues, often with devastating consequences. Autoantibody-driven diseases include Myasthenia Gravis, Hemolytic Diseases of the Fetus and Newborn, warm Autoimmune Hemolytic Anemia, and other serious dermatologic, rheumatic, neurologic, hematologic and renal diseases. An estimated 2.5 percent of the population, or approximately 195 million people worldwide, suffer from some form of autoantibody-driven disease, many of which are orphan and rare diseases.
With competitively differentiated, parallel development programs and full worldwide commercial rights for nipocalimab, Janssen will have the potential to introduce multiple launches, many as first-in-class indications with potential for significant peak year sales, some of which could exceed $1 billion, supporting Janssen’s goal of continuing to deliver above-market performance over the long term.
“This acquisition broadens Janssen’s leadership in autoimmune diseases and provides us with a major catalyst for sustained growth. Autoantibody-driven diseases are often serious, and patients are underserved by current treatment options,” said Jennifer Taubert, Executive Vice President, Worldwide Chairman, Pharmaceuticals, Johnson & Johnson. “We’re excited by the opportunity to further advance patient care by combining Johnson & Johnson’s world-class R&D, commercial and supply chain capabilities with Momenta’s talented people, pipeline and deep expertise in this important area.”
In addition to Momenta’s employees and lead asset nipocalimab, Janssen will acquire Momenta’s pipeline of clinical and pre-clinical assets. The acquisition was driven by the significant opportunity seen in nipocalimab, along with the scientific capability Janssen is acquiring with the Momenta team. Janssen’s plans for additional assets in the Momenta pipeline will be determined as more data become available and could offer further upside potential.
“Nipocalimab, and the rest of Momenta’s pipeline, built over many years by outstanding scientists who have turned important insights into actionable biology, expands and complements our portfolio by giving us clinical-stage and discovery-stage compounds in autoantibody biological pathways. Combining Momenta’s discoveries with our 20-year heritage in immunology, global scope, and scientific and medical expertise, we see a real opportunity to create an entire ‘pipeline in a pathway,’ ” said Mathai Mammen, M.D., Ph.D., Global Head of Janssen Research & Development, Johnson & Johnson. “We are excited about the significant potential to expand on Momenta’s excellent progress in rare diseases, and to increase our impact on patients both within and beyond our current focus areas.”
Janssen plans to retain Momenta’s presence in Cambridge, Massachusetts. This site will increase Johnson & Johnson’s existing innovation footprint and capabilities in the greater Boston area given Momenta’s talented scientists, suite of proprietary technologies, sophisticated laboratories and proximity to top talent in this innovation hub.
Source: Janssen Pharmaceutical Companies of Johnson & Johnson(Press release)
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00HollandBIOhttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svgHollandBIO2020-08-25 14:45:212020-08-25 14:45:22Johnson & Johnson to Acquire Momenta Pharmaceuticals, Inc., Expanding Janssen’s Leadership in Novel Treatments for Autoimmune Diseases← #nieuws
Sanofi and Principia Biopharma Inc. (NASDAQ: PRNB), a late-stage biopharmaceutical company focused on developing treatments for immune-mediated diseases, entered into a definitive agreement under which Sanofi will acquire all of the outstanding shares of Principia for $100 per share in cash, which represents an aggregate equity value of approximately $3.68 billion (on a fully diluted basis). The Sanofi and Principia Boards of Directors unanimously approved the transaction.
“This acquisition advances our ongoing R&D transformation to accelerate development of the most promising medicines that will address significant patient needs,” said Paul Hudson, Sanofi Chief Executive Officer. “The addition of multiple BTK inhibitors to our pipeline demonstrates our commitment to strategic product acquisitions in our priority therapeutic areas. Full ownership of our brain-penetrant BTK inhibitor ‘168 removes complexities for this priority development program and simplifies future commercialization.”
“The Phase 2b data in relapsing multiple sclerosis showed the strong potential of ‘168 to address disability and disease progression, and triggered the start of Phase 3 studies across the full spectrum of MS. Through this acquisition, we will be able to expand and accelerate development of BTK inhibitors across multiple indications. Both ‘168 and rilzabrutinib, have ‘pipeline in a product’ potential, and we look forward to unlocking their full treatment benefits across an array of diseases,” said John Reed, M.D., Ph.D., Global Head of Research & Development at Sanofi.
“Principia’s successful design and development of a whole portfolio of BTK inhibitors for immunology is aimed to transform the treatment for patients with immune-mediated diseases. By combining with Sanofi, we will bring significant resources to expand and accelerate the potential benefits of these therapies. The benefit of developing several BTK inhibitors will allow us to target specific organ systems for optimal patient benefit. The merger will provide global resources to get these novel therapies to patients faster,” said Martin Babler, President and CEO at Principia Biopharma.
Principia’s Bruton tyrosine kinase (BTK) inhibitors add to Sanofi’s efforts to accelerate and build a portfolio of the next generation of transformative treatments for autoimmune diseases. BTK is present in the signaling pathways of key innate and adaptive cell types of the immune system. Being able to block or disrupt these signaling processes can help in stopping inflammation and tissue destruction related to autoimmune diseases and target some of the underlying pathophysiology.
A consortium of 37 renowned academic institutions, research organisations and biopharmaceutical companies will receive a grant of €77.7 million via the Innovative Medicines Initiative. The consortium will screen libraries to identify existing compounds that can be repurposed for use against COVID-19 and perform in silico screening to find new small molecules against SARS-CoV-2 and similar disease. Read more.
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00HollandBIOhttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svgHollandBIO2020-08-25 14:31:542020-08-25 14:31:55Consortium receives grant of €77.7 million for identifying existing compounds that can be repurposed for use against COVID-19← #nieuws
“Ontwikkel een slecht antibioticum, en niemand wil het gebruiken. Ontwikkel een heel goed antibioticum, en al helemaal niemand wil het gebruiken.” In slechts twee regels maakt deze bizarre paradox duidelijk hoe verknipt de markt voor de ontwikkeling van nieuwe antibiotica is. Aan de hand van de biotech Paratek Pharmaceuticals diept Nature de uitdagingen in het veld verder uit.
Hoewel Paratek met succes een nieuw antibioticum ontwikkeld heeft, wil dat allerminst zeggen dat het bedrijf binnenloopt. Sterker nog: de overleving van het bedrijf was lange tijd onzeker. De redding komt uiteindelijk uit onverwachte hoek, van de Amerikaanse Biomedical Advanced Research and Development Authority (BARDA). Wederom een succesvol voorbeeld van launching customership door de overheid, waar we vorige week ook over schreven.
Antibioticaresistentie is een tikkende tijdbom. Daarom is HollandBIO trots dat Nederland nog altijd biotech-parels zoals AGILeBiotics en Madam Therapeutics kent die werk maken van de ontwikkeling van nieuwe antibiotica. Nature laat zien dat ze daar best een handje hulp bij kunnen gebruiken. Overheid, leest u mee?
Byondis B.V. (formerly Synthon Biopharmaceuticals B.V.) today announced that the first patients have started treatment in a Phase I study of its investigational antibody-drug conjugate (ADC) [vic-]trastuzumab duocarmazine (SYD985) in combination with niraparib in patients with a HER2-expressing locally advanced or metastatic solid tumor.
A Two-part Phase I Study With the Antibody-drug Conjugate SYD985 in Combination With Niraparib to Evaluate Safety, Pharmacokinetics and Efficacy in Patients With HER2-expressing Locally Advanced or Metastatic Solid Tumors (SYD985.004) will enroll up to 120 patients who progressed on standard therapy or for whom no standard therapy of proven benefit exists. The first part of the study is taking place in leading European oncology centers in Belgium, United Kingdom and the Netherlands. Leading centers in France, Spain and Poland will join this trial at a later stage.
“We are excited to move to the clinical study phase of [vic-]trastuzumab duocarmazine in combination with PARP inhibitor niraparib,” said Byondis CEO Marco Timmers, Ph.D. “Preclinical investigation of SYD985 in combination with PARP inhibitors in HER2-expressing tumor cells suggested synergistic effects and we hope to confirm these effects in the clinic.”
SYD985 is Byondis’ most advanced ADC, in development for the treatment of a range of HER2-expressing tumor types including breast and endometrial cancer. Previously, the U.S. Food & Drug Administration granted SYD985 fast track designation based on promising data from heavily pre-treated last-line HER2-positive metastatic breast cancer patients participating in a two-part Phase I clinical study (SYD985.001). The pivotal Phase III TULIP® study (SYD985.002) comparing the efficacy and safety of SYD985 to physician’s choice treatment in patients with HER2-positive unresectable locally advanced or metastatic breast cancer is ongoing. In addition, Byondis recently announced the start of a Phase II study (SYD985.003) evaluating the safety and efficacy of SYD985 in patients with HER2-expressing recurrent, advanced or metastatic endometrial (uterine) cancer.
SYD985.004 will explore the preclinically proven synergistic anti-tumor effects of the SYD985 and niraparib combination, which may result in increased efficacy. As both drugs will be given at lower doses than when applied as single agents, this could coincide with reduced toxicity. The study’s primary endpoint is dose-limiting toxicities in the first cycle (21 days). Secondary objectives include overall safety, pharmacokinetic and preliminary efficacy assessments for the combination treatment.
SYD985.004 will be conducted in two parts: Dose Escalation and Dose Expansion. Part 1, Dose Escalation, is expected to enroll about 30 patients with any HER2-expressing solid tumor to determine the maximum tolerated dose (MTD) and recommended dose for expansion (RDE). Part 2, Dose Expansion, is expected to enroll between 48 and 90 patients with one of three types of locally advanced or metastatic cancers: breast, ovarian or endometrial. All patients will be treated with SYD985 infusions once every three weeks in combination with oral niraparib. The latter will be administered once daily for one, two or three weeks, depending on the safety of the combination and the study cohort.
SYD985 uses Byondis’ proprietary linker-drug (LD) technology. Although in general, marketed ADCs have improved therapeutic indices compared to classical non-targeted chemotherapeutic agents, there is still room for improvement.
The ADC [vic-]trastuzumab duocarmazine is comprised of the monoclonal antibody trastuzumab and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA). The antibody part of SYD985 binds to the HER2 antigen on the surface of the cancer cell and the ADC is internalized by the cell. After proteolytic cleavage of the linker, the inactive cytotoxin is activated and DNA damage is induced, resulting in tumor cell death. SYD985 can be considered a form of targeted chemotherapy.
In traditional chemotherapy, a cytotoxin enters the bloodstream and moves through the body to kill rapidly dividing cells that are common in tumors. The problem is that it also attacks rapidly dividing cells in normal tissue, potentially resulting in severe side effects.
Monoclonal antibodies are created to allow improved specificity by targeting receptors expressed on tumor cell membranes. In order to improve the cell-killing capability of antibodies, cytotoxic drugs can be attached to antibodies using a linker molecule, forming antibody-drug conjugates or ADCs.
While earlier generation ADCs improved targeting and cell killing, they were unstable in the bloodstream, which resulted in early release of the cytotoxic payload that impacted healthy tissue and narrowed the therapeutic window. Byondis’ next generation ADCs carry an intricate, inactivated cytotoxic drug that rapidly self-destructs in case it is prematurely released, limiting damage to healthy tissue and improving the therapeutic window.
Byondis’ differentiated linker-drug, vc-seco-DUBA, owes its potent antitumor activity to a synthetic duocarmycin-based cytotoxin. Duocarmycins, first isolated from Streptomyces bacteria in the 1970s, bind to the minor groove of DNA and disrupt the nucleic acid architecture, which eventually leads to tumor cell death.
The distinctive design of the selectively cleavable linker connecting the antibody to the duocarmycin drug leads to high stability in circulation and induces efficient release of the cytotoxin in the tumor. Uptake of the activated payload by neighboring tumor cells with lower HER2 expression may improve the efficacy potential, the so-called bystander effect.
Niraparib is a PARP inhibitor (PARPi) used in cancer therapy. PARP inhibitors are a type of targeted therapy used to treat cancers with existing defects in DNA repair. They block critical DNA repair pathways that these cancers rely on to repair their DNA as they grow and divide, thereby inducing tumor cell death. PARP inhibitors are used in ovarian, breast, prostate and pancreatic cancer.
Combining the DNA-alkylating cytotoxic mechanism of SYD985 with PARP inhibitors theoretically increases the sensitivity of tumors for the cytotoxic payload of the antibody-drug conjugate SYD985, resulting in synergistic effects on tumor cell killing. This was corroborated by Byondis’ preclinical data.
The SYD985.004 study is registered in ClinicalTrials.gov with identifier NCT04235101.
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00HollandBIOhttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svgHollandBIO2020-08-25 10:37:052020-08-25 10:37:06Byondis Initiates Phase I Study of ADC [Vic-]Trastuzumab Duocarmazine + Niraparib in HER2-Expressing Solid Tumors← #nieuws
Byondis B.V. (formerly Synthon Biopharmaceuticals B.V.) announced that the first cancer patients have started treatment with its investigational antibody-drug conjugate (ADC) SYD1875.
The First-in-Human Dose-Escalation and Expansion Study with the Antibody-Drug Conjugate SYD1875 will evaluate the safety, pharmacokinetics and preliminary efficacy of SYD1875 in patients with 5T4-expressing, locally advanced or metastatic solid tumors. While 5T4 plays an important role in the development of cancer, there are currently no drugs that target this specific tumor antigen. Patients are currently being enrolled in leading European oncology centers: Institut Jules Bordet in Brussels, Belgium; Institut Bergonié in Bordeaux, France; and Centre Oscar Lambret in Lille, France.
“It is exciting and gratifying to know that SYD1875 has progressed to the clinical study phase, giving us the opportunity to explore the potential of another promising antibody-drug conjugate,” said Byondis CEO Marco Timmers, Ph.D. “Our ADC technologies aim to outsmart relentless cancers and improve patient outcomes by offering better tumor-killing properties with lower side effects.”
SYD1875 is the second Byondis ADC to progress to clinical studies. The company’s anti-HER2 ADC [vic-]trastuzumab duocarmazine (SYD985) is its most advanced ADC, targeting a range of HER2-expressing cancers such as metastatic breast cancer and endometrial (uterine) cancer.
The SYD1875.001 study will recruit roughly 90 patients, aged 18 and over, with histologically-confirmed, locally advanced or metastatic cancers that have progressed on standard therapy or for which no standard therapy exists. The study will be conducted in two parts: Dose Escalation and Dose Expansion.
Part 1, Dose Escalation, will enroll patients with any tumor type to determine the Maximum Tolerated Dose (MTD) and Recommended Dose for Expansion (RDE). Part 2, Dose Expansion, will enroll groups of patients with one of three types of cancers. These patients will receive the RDE determined in Part 1 to evaluate the efficacy and safety of SYD1875 in these cohorts. All patients in both parts of the study will receive SYD1875 infusions every three weeks until cancer progression or unacceptable toxicity.
SYD1875 uses Byondis’ unique, proprietary linker-drug (LD) and site-specific conjugation technologies. Although marketed ADCs have improved therapeutic indices compared to classical non-targeted chemotherapeutic agents, there is still room for improvement.
SYD1875 is a next generation ADC, comprised of a humanized IgG1 mAb (monoclonal antibody), and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA), targeting the 5T4 oncofetal antigen employing the site-specific conjugation of HC-41C. The antibody part of SYD1875 binds to 5T4 on the surface of the cancer cell and the ADC is internalized by the cell. After proteolytic cleavage of the linker, the inactive cytotoxin is activated and DNA damage is induced, resulting in tumor cell death. SYD1875 can be considered a form of targeted chemotherapy.
For the manufacturing of SYD1875, this ADC is relying on a single-step, selective reduction of the engineered cysteines, instead of a two-step reduction/oxidation protocol that is commonly used for these types of ADCs and that can lead to undesired side-products.
In traditional chemotherapy, a cytotoxin enters the bloodstream and moves through the body to kill rapidly dividing cells that are common in tumors. The problem is that it also attacks rapidly dividing cells in normal tissue, potentially resulting in severe side effects.
Monoclonal antibodies are created to allow improved specificity by targeting receptors expressed on tumor cell membranes. To improve the cell-killing capability of antibodies, cytotoxic drugs can be attached to the antibodies using a linker molecule, forming antibody-drug conjugates or ADCs.
While earlier generation ADCs improved targeting and cell killing, they can be unstable in the bloodstream, and that can lead to an early release of the cytotoxic payload, impacting healthy tissue and narrowing the therapeutic window. Byondis’ next generation ADCs carry an intricate, inactivated cytotoxic drug that rapidly self-destructs in case it is prematurely released, limiting damage to healthy tissue and improving the therapeutic window.
Byondis’ differentiating linker-drug, vc-seco-DUBA, owes its potent antitumor activity to a synthetic duocarmycin-based cytotoxin. Duocarmycins, first isolated from Streptomyces bacteria in the 1970s, bind to the minor groove of DNA and disrupt the nucleic acid architecture, which eventually leads to tumor cell death.
The unique design of the selectively cleavable linker connecting the antibody to the duocarmycin drug leads to high stability in circulation and induces efficient release of the cytotoxin in the tumor. Finally, the site-specific conjugation of the linker-drug results in enhanced in vivo antitumor activity, as was demonstrated in preclinical models.
The SYD1875 study is registered in ClinicalTrials.gov with identifier NCT04202705.
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00HollandBIOhttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svgHollandBIO2020-08-24 15:33:342020-08-24 15:33:35Byondis Initiates Phase I Study of Antibody-Drug Conjugate SYD1875← #nieuws
Een belangrijke vraag voor ontwikkelaars van nieuwe medicijnen: breekt je lichaam een geneesmiddel wel goed af? TNO’s Accelerator Mass Spectrometer (AMS) kan tegenwoordig sneller en eerder antwoord vinden op deze prangende vraag. Hoe? Dat licht Wouter Vaes bij BNR toe. Een prachtig voorbeeld van innovatie in de geneesmiddelontwikkeling!
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00HollandBIOhttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svgHollandBIO2020-08-19 09:55:032020-08-19 09:55:04Medicijnontwikkeling kan sneller en beter met de massaspectrometer← #nieuws
“Het zijn écht twee verschillende dingen, benadrukt onderzoeker Jeroen de Ridder van het UMC Utrecht: werken aan de oplossing van een wetenschappelijk probleem en vervolgens die oplossing uitbouwen tot een commercieel product waar patiënten daadwerkelijk iets aan hebben. Voor die tweede stap zijn andere eigenschappen en vaardigheden nodig. Het is dan ook niet vanzelfsprekend dat wetenschappers, die gedurende hun onderzoek nieuwe waardevolle inzichten opdoen, die tweede stap zetten. Ook Jeroen had een duwtje in de rug nodig.” Het UMC Utrecht heeft een lezenswaardig verhaal opgetekend over de ondernemende onderzoeker. Hier lees je meer over de uitdaging die Jeroen aangaat om met zijn start-up Cyclomics een bruikbaar medisch product te ontwikkelen om snel en goedkoop kanker op te sporen met bloedonderzoek.
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00HollandBIOhttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svgHollandBIO2020-08-19 09:54:182020-08-19 09:54:19Onderzoekers hebben soms een duwtje in de rug nodig met ondernemen
Tegenvaller voor Galapagos
GezondheidIn het zicht van de haven kreeg Galapagos afgelopen week een flinke knauw van de Amerikaanse Food and Drug Administration (FDA): kroonjuweel filgotinib verschijnt dit jaar nog niet op de Amerikaanse markt. De FDA wil de resultaten van een lopende studie naar het effect op de mannelijke vruchtbaarheid afwachten. Voor CEO Onno van der Stolpe kwam het nieuws als een donderslag bij heldere hemel. Toch laat hij zich niet uit het veld slaan, meldt hij het FD: “Dit is een tijdelijke tegenslag. We gaan hier sterker uitkomen.”
Het is niet de eerste en ook zeker niet de laatste keer dat HollandBIO binnen de biotech getuige is van een plottwist als deze. De route van lab naar patiënt blijkt eens te meer lang en bezaaid met hordes.
Feike Sijbesma rondt coronawerkzaamheden af
GezondheidFeike Sijbesma, speciaal gezant corona, rondt zijn werkzaamheden in september af. Sinds 26 maart heeft de heer Sijbesma het kabinet geholpen in de coronacrisis, onder andere met het testbeleid en de vaccinstrategie van ons land.
Zo heeft hij eraan bijgedragen dat er genoeg testen beschikbaar zijn om sinds eind mei iedereen in Nederland met klachten te laten testen. Later is de heer Sijbesma door het kabinet gevraagd te helpen bij het in kaart brengen van de ontwikkelingen van mogelijke coronavaccins. In de afgelopen periode heeft de Europese Commissie, mede namens Nederland, succesvol onderhandeld waardoor Nederland de beschikking heeft over mogelijke vaccins.
Sijbesma verrichtte al deze tijdelijke werkzaamheden geheel onbezoldigd. Het kabinet kan in de toekomst, indien gewenst en mogelijk, een beroep op hem blijven doen mocht dat nodig zijn.
Minister-president Rutte en minister De Jonge zijn Feike Sijbesma zeer erkentelijk voor zijn werk van de afgelopen maanden: “Met zijn expertise, ervaring en contacten heeft hij een grote en belangrijke bijdrage geleverd in de strijd tegen het coronavirus. Op diverse onderwerpen heeft hij zich maandenlang, schijnbaar onvermoeibaar, ingezet. Het is fijn dat het kabinet ook in de toekomst een beroep op hem kan blijven doen.”
Bron: Rijksoverheid (Nieuwsbericht)
Johnson & Johnson to Acquire Momenta Pharmaceuticals, Inc., Expanding Janssen’s Leadership in Novel Treatments for Autoimmune Diseases
InnovatieklimaatJohnson & Johnson (NYSE:JNJ) announced it has entered into a definitive agreement to acquire Momenta Pharmaceuticals, Inc. (Momenta), a company that discovers and develops novel therapies for immune-mediated diseases, in an all cash transaction for approximately $6.5 billion.
This acquisition provides an opportunity for the Janssen Pharmaceutical Companies of Johnson & Johnson to broaden its leadership in immune-mediated diseases and drive further growth through expansion into autoantibody-driven disease. The transaction will include full global rights to nipocalimab (M281), a clinically validated, potentially best-in-class anti-FcRn antibody. Nipocalimab gives Janssen the opportunity to reach significantly more patients by pursuing indications across many autoimmune diseases with substantial unmet medical need in maternal-fetal disorders, neuro-inflammatory disorders, rheumatology, dermatology and autoimmune hematology. Nipocalimab recently received a rare pediatric disease designation from the U.S. Food and Drug Administration. Momenta’s expertise in FcRn mechanisms is especially important for nipocalimab as it supports and accelerates the development of a medicine designed to target a number of autoantibody-driven conditions across several of Janssen’s established therapeutic areas. Janssen expects nipocalimab to contribute to its goals of achieving above-market growth over the mid and long term.
Autoimmune diseases driven partially or completely by autoantibodies represent a novel area where Janssen can significantly improve health outcomes for patients. In autoantibody-driven diseases, the body’s antibodies attack or damage its own proteins, cells and tissues, often with devastating consequences. Autoantibody-driven diseases include Myasthenia Gravis, Hemolytic Diseases of the Fetus and Newborn, warm Autoimmune Hemolytic Anemia, and other serious dermatologic, rheumatic, neurologic, hematologic and renal diseases. An estimated 2.5 percent of the population, or approximately 195 million people worldwide, suffer from some form of autoantibody-driven disease, many of which are orphan and rare diseases.
With competitively differentiated, parallel development programs and full worldwide commercial rights for nipocalimab, Janssen will have the potential to introduce multiple launches, many as first-in-class indications with potential for significant peak year sales, some of which could exceed $1 billion, supporting Janssen’s goal of continuing to deliver above-market performance over the long term.
“This acquisition broadens Janssen’s leadership in autoimmune diseases and provides us with a major catalyst for sustained growth. Autoantibody-driven diseases are often serious, and patients are underserved by current treatment options,” said Jennifer Taubert, Executive Vice President, Worldwide Chairman, Pharmaceuticals, Johnson & Johnson. “We’re excited by the opportunity to further advance patient care by combining Johnson & Johnson’s world-class R&D, commercial and supply chain capabilities with Momenta’s talented people, pipeline and deep expertise in this important area.”
In addition to Momenta’s employees and lead asset nipocalimab, Janssen will acquire Momenta’s pipeline of clinical and pre-clinical assets. The acquisition was driven by the significant opportunity seen in nipocalimab, along with the scientific capability Janssen is acquiring with the Momenta team. Janssen’s plans for additional assets in the Momenta pipeline will be determined as more data become available and could offer further upside potential.
“Nipocalimab, and the rest of Momenta’s pipeline, built over many years by outstanding scientists who have turned important insights into actionable biology, expands and complements our portfolio by giving us clinical-stage and discovery-stage compounds in autoantibody biological pathways. Combining Momenta’s discoveries with our 20-year heritage in immunology, global scope, and scientific and medical expertise, we see a real opportunity to create an entire ‘pipeline in a pathway,’ ” said Mathai Mammen, M.D., Ph.D., Global Head of Janssen Research & Development, Johnson & Johnson. “We are excited about the significant potential to expand on Momenta’s excellent progress in rare diseases, and to increase our impact on patients both within and beyond our current focus areas.”
Janssen plans to retain Momenta’s presence in Cambridge, Massachusetts. This site will increase Johnson & Johnson’s existing innovation footprint and capabilities in the greater Boston area given Momenta’s talented scientists, suite of proprietary technologies, sophisticated laboratories and proximity to top talent in this innovation hub.
Source: Janssen Pharmaceutical Companies of Johnson & Johnson (Press release)
Sanofi to acquire Principia Biopharma
InnovatieklimaatSanofi and Principia Biopharma Inc. (NASDAQ: PRNB), a late-stage biopharmaceutical company focused on developing treatments for immune-mediated diseases, entered into a definitive agreement under which Sanofi will acquire all of the outstanding shares of Principia for $100 per share in cash, which represents an aggregate equity value of approximately $3.68 billion (on a fully diluted basis). The Sanofi and Principia Boards of Directors unanimously approved the transaction.
“This acquisition advances our ongoing R&D transformation to accelerate development of the most promising medicines that will address significant patient needs,” said Paul Hudson, Sanofi Chief Executive Officer. “The addition of multiple BTK inhibitors to our pipeline demonstrates our commitment to strategic product acquisitions in our priority therapeutic areas. Full ownership of our brain-penetrant BTK inhibitor ‘168 removes complexities for this priority development program and simplifies future commercialization.”
“The Phase 2b data in relapsing multiple sclerosis showed the strong potential of ‘168 to address disability and disease progression, and triggered the start of Phase 3 studies across the full spectrum of MS. Through this acquisition, we will be able to expand and accelerate development of BTK inhibitors across multiple indications. Both ‘168 and rilzabrutinib, have ‘pipeline in a product’ potential, and we look forward to unlocking their full treatment benefits across an array of diseases,” said John Reed, M.D., Ph.D., Global Head of Research & Development at Sanofi.
“Principia’s successful design and development of a whole portfolio of BTK inhibitors for immunology is aimed to transform the treatment for patients with immune-mediated diseases. By combining with Sanofi, we will bring significant resources to expand and accelerate the potential benefits of these therapies. The benefit of developing several BTK inhibitors will allow us to target specific organ systems for optimal patient benefit. The merger will provide global resources to get these novel therapies to patients faster,” said Martin Babler, President and CEO at Principia Biopharma.
Principia’s Bruton tyrosine kinase (BTK) inhibitors add to Sanofi’s efforts to accelerate and build a portfolio of the next generation of transformative treatments for autoimmune diseases. BTK is present in the signaling pathways of key innate and adaptive cell types of the immune system. Being able to block or disrupt these signaling processes can help in stopping inflammation and tissue destruction related to autoimmune diseases and target some of the underlying pathophysiology.
Source: Sanofi (Press release)
Consortium receives grant of €77.7 million for identifying existing compounds that can be repurposed for use against COVID-19
GezondheidA consortium of 37 renowned academic institutions, research organisations and biopharmaceutical companies will receive a grant of €77.7 million via the Innovative Medicines Initiative. The consortium will screen libraries to identify existing compounds that can be repurposed for use against COVID-19 and perform in silico screening to find new small molecules against SARS-CoV-2 and similar disease. Read more.
Antibioticaresistentieparadox
Gezondheid“Ontwikkel een slecht antibioticum, en niemand wil het gebruiken. Ontwikkel een heel goed antibioticum, en al helemaal niemand wil het gebruiken.” In slechts twee regels maakt deze bizarre paradox duidelijk hoe verknipt de markt voor de ontwikkeling van nieuwe antibiotica is. Aan de hand van de biotech Paratek Pharmaceuticals diept Nature de uitdagingen in het veld verder uit.
Hoewel Paratek met succes een nieuw antibioticum ontwikkeld heeft, wil dat allerminst zeggen dat het bedrijf binnenloopt. Sterker nog: de overleving van het bedrijf was lange tijd onzeker. De redding komt uiteindelijk uit onverwachte hoek, van de Amerikaanse Biomedical Advanced Research and Development Authority (BARDA). Wederom een succesvol voorbeeld van launching customership door de overheid, waar we vorige week ook over schreven.
Antibioticaresistentie is een tikkende tijdbom. Daarom is HollandBIO trots dat Nederland nog altijd biotech-parels zoals AGILeBiotics en Madam Therapeutics kent die werk maken van de ontwikkeling van nieuwe antibiotica. Nature laat zien dat ze daar best een handje hulp bij kunnen gebruiken. Overheid, leest u mee?
Byondis Initiates Phase I Study of ADC [Vic-]Trastuzumab Duocarmazine + Niraparib in HER2-Expressing Solid Tumors
GezondheidByondis B.V. (formerly Synthon Biopharmaceuticals B.V.) today announced that the first patients have started treatment in a Phase I study of its investigational antibody-drug conjugate (ADC) [vic-]trastuzumab duocarmazine (SYD985) in combination with niraparib in patients with a HER2-expressing locally advanced or metastatic solid tumor.
A Two-part Phase I Study With the Antibody-drug Conjugate SYD985 in Combination With Niraparib to Evaluate Safety, Pharmacokinetics and Efficacy in Patients With HER2-expressing Locally Advanced or Metastatic Solid Tumors (SYD985.004) will enroll up to 120 patients who progressed on standard therapy or for whom no standard therapy of proven benefit exists. The first part of the study is taking place in leading European oncology centers in Belgium, United Kingdom and the Netherlands. Leading centers in France, Spain and Poland will join this trial at a later stage.
“We are excited to move to the clinical study phase of [vic-]trastuzumab duocarmazine in combination with PARP inhibitor niraparib,” said Byondis CEO Marco Timmers, Ph.D. “Preclinical investigation of SYD985 in combination with PARP inhibitors in HER2-expressing tumor cells suggested synergistic effects and we hope to confirm these effects in the clinic.”
SYD985 is Byondis’ most advanced ADC, in development for the treatment of a range of HER2-expressing tumor types including breast and endometrial cancer. Previously, the U.S. Food & Drug Administration granted SYD985 fast track designation based on promising data from heavily pre-treated last-line HER2-positive metastatic breast cancer patients participating in a two-part Phase I clinical study (SYD985.001). The pivotal Phase III TULIP® study (SYD985.002) comparing the efficacy and safety of SYD985 to physician’s choice treatment in patients with HER2-positive unresectable locally advanced or metastatic breast cancer is ongoing. In addition, Byondis recently announced the start of a Phase II study (SYD985.003) evaluating the safety and efficacy of SYD985 in patients with HER2-expressing recurrent, advanced or metastatic endometrial (uterine) cancer.
SYD985.004 will explore the preclinically proven synergistic anti-tumor effects of the SYD985 and niraparib combination, which may result in increased efficacy. As both drugs will be given at lower doses than when applied as single agents, this could coincide with reduced toxicity. The study’s primary endpoint is dose-limiting toxicities in the first cycle (21 days). Secondary objectives include overall safety, pharmacokinetic and preliminary efficacy assessments for the combination treatment.
SYD985.004 will be conducted in two parts: Dose Escalation and Dose Expansion. Part 1, Dose Escalation, is expected to enroll about 30 patients with any HER2-expressing solid tumor to determine the maximum tolerated dose (MTD) and recommended dose for expansion (RDE). Part 2, Dose Expansion, is expected to enroll between 48 and 90 patients with one of three types of locally advanced or metastatic cancers: breast, ovarian or endometrial. All patients will be treated with SYD985 infusions once every three weeks in combination with oral niraparib. The latter will be administered once daily for one, two or three weeks, depending on the safety of the combination and the study cohort.
SYD985 uses Byondis’ proprietary linker-drug (LD) technology. Although in general, marketed ADCs have improved therapeutic indices compared to classical non-targeted chemotherapeutic agents, there is still room for improvement.
The ADC [vic-]trastuzumab duocarmazine is comprised of the monoclonal antibody trastuzumab and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA). The antibody part of SYD985 binds to the HER2 antigen on the surface of the cancer cell and the ADC is internalized by the cell. After proteolytic cleavage of the linker, the inactive cytotoxin is activated and DNA damage is induced, resulting in tumor cell death. SYD985 can be considered a form of targeted chemotherapy.
In traditional chemotherapy, a cytotoxin enters the bloodstream and moves through the body to kill rapidly dividing cells that are common in tumors. The problem is that it also attacks rapidly dividing cells in normal tissue, potentially resulting in severe side effects.
Monoclonal antibodies are created to allow improved specificity by targeting receptors expressed on tumor cell membranes. In order to improve the cell-killing capability of antibodies, cytotoxic drugs can be attached to antibodies using a linker molecule, forming antibody-drug conjugates or ADCs.
While earlier generation ADCs improved targeting and cell killing, they were unstable in the bloodstream, which resulted in early release of the cytotoxic payload that impacted healthy tissue and narrowed the therapeutic window. Byondis’ next generation ADCs carry an intricate, inactivated cytotoxic drug that rapidly self-destructs in case it is prematurely released, limiting damage to healthy tissue and improving the therapeutic window.
Byondis’ differentiated linker-drug, vc-seco-DUBA, owes its potent antitumor activity to a synthetic duocarmycin-based cytotoxin. Duocarmycins, first isolated from Streptomyces bacteria in the 1970s, bind to the minor groove of DNA and disrupt the nucleic acid architecture, which eventually leads to tumor cell death.
The distinctive design of the selectively cleavable linker connecting the antibody to the duocarmycin drug leads to high stability in circulation and induces efficient release of the cytotoxin in the tumor. Uptake of the activated payload by neighboring tumor cells with lower HER2 expression may improve the efficacy potential, the so-called bystander effect.
Niraparib is a PARP inhibitor (PARPi) used in cancer therapy. PARP inhibitors are a type of targeted therapy used to treat cancers with existing defects in DNA repair. They block critical DNA repair pathways that these cancers rely on to repair their DNA as they grow and divide, thereby inducing tumor cell death. PARP inhibitors are used in ovarian, breast, prostate and pancreatic cancer.
Combining the DNA-alkylating cytotoxic mechanism of SYD985 with PARP inhibitors theoretically increases the sensitivity of tumors for the cytotoxic payload of the antibody-drug conjugate SYD985, resulting in synergistic effects on tumor cell killing. This was corroborated by Byondis’ preclinical data.
The SYD985.004 study is registered in ClinicalTrials.gov with identifier NCT04235101.
Source: Byondis (Press release)
Byondis Initiates Phase I Study of Antibody-Drug Conjugate SYD1875
GezondheidByondis B.V. (formerly Synthon Biopharmaceuticals B.V.) announced that the first cancer patients have started treatment with its investigational antibody-drug conjugate (ADC) SYD1875.
The First-in-Human Dose-Escalation and Expansion Study with the Antibody-Drug Conjugate SYD1875 will evaluate the safety, pharmacokinetics and preliminary efficacy of SYD1875 in patients with 5T4-expressing, locally advanced or metastatic solid tumors. While 5T4 plays an important role in the development of cancer, there are currently no drugs that target this specific tumor antigen. Patients are currently being enrolled in leading European oncology centers: Institut Jules Bordet in Brussels, Belgium; Institut Bergonié in Bordeaux, France; and Centre Oscar Lambret in Lille, France.
“It is exciting and gratifying to know that SYD1875 has progressed to the clinical study phase, giving us the opportunity to explore the potential of another promising antibody-drug conjugate,” said Byondis CEO Marco Timmers, Ph.D. “Our ADC technologies aim to outsmart relentless cancers and improve patient outcomes by offering better tumor-killing properties with lower side effects.”
SYD1875 is the second Byondis ADC to progress to clinical studies. The company’s anti-HER2 ADC [vic-]trastuzumab duocarmazine (SYD985) is its most advanced ADC, targeting a range of HER2-expressing cancers such as metastatic breast cancer and endometrial (uterine) cancer.
The SYD1875.001 study will recruit roughly 90 patients, aged 18 and over, with histologically-confirmed, locally advanced or metastatic cancers that have progressed on standard therapy or for which no standard therapy exists. The study will be conducted in two parts: Dose Escalation and Dose Expansion.
Part 1, Dose Escalation, will enroll patients with any tumor type to determine the Maximum Tolerated Dose (MTD) and Recommended Dose for Expansion (RDE). Part 2, Dose Expansion, will enroll groups of patients with one of three types of cancers. These patients will receive the RDE determined in Part 1 to evaluate the efficacy and safety of SYD1875 in these cohorts. All patients in both parts of the study will receive SYD1875 infusions every three weeks until cancer progression or unacceptable toxicity.
SYD1875 uses Byondis’ unique, proprietary linker-drug (LD) and site-specific conjugation technologies. Although marketed ADCs have improved therapeutic indices compared to classical non-targeted chemotherapeutic agents, there is still room for improvement.
SYD1875 is a next generation ADC, comprised of a humanized IgG1 mAb (monoclonal antibody), and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA), targeting the 5T4 oncofetal antigen employing the site-specific conjugation of HC-41C. The antibody part of SYD1875 binds to 5T4 on the surface of the cancer cell and the ADC is internalized by the cell. After proteolytic cleavage of the linker, the inactive cytotoxin is activated and DNA damage is induced, resulting in tumor cell death. SYD1875 can be considered a form of targeted chemotherapy.
For the manufacturing of SYD1875, this ADC is relying on a single-step, selective reduction of the engineered cysteines, instead of a two-step reduction/oxidation protocol that is commonly used for these types of ADCs and that can lead to undesired side-products.
In traditional chemotherapy, a cytotoxin enters the bloodstream and moves through the body to kill rapidly dividing cells that are common in tumors. The problem is that it also attacks rapidly dividing cells in normal tissue, potentially resulting in severe side effects.
Monoclonal antibodies are created to allow improved specificity by targeting receptors expressed on tumor cell membranes. To improve the cell-killing capability of antibodies, cytotoxic drugs can be attached to the antibodies using a linker molecule, forming antibody-drug conjugates or ADCs.
While earlier generation ADCs improved targeting and cell killing, they can be unstable in the bloodstream, and that can lead to an early release of the cytotoxic payload, impacting healthy tissue and narrowing the therapeutic window. Byondis’ next generation ADCs carry an intricate, inactivated cytotoxic drug that rapidly self-destructs in case it is prematurely released, limiting damage to healthy tissue and improving the therapeutic window.
Byondis’ differentiating linker-drug, vc-seco-DUBA, owes its potent antitumor activity to a synthetic duocarmycin-based cytotoxin. Duocarmycins, first isolated from Streptomyces bacteria in the 1970s, bind to the minor groove of DNA and disrupt the nucleic acid architecture, which eventually leads to tumor cell death.
The unique design of the selectively cleavable linker connecting the antibody to the duocarmycin drug leads to high stability in circulation and induces efficient release of the cytotoxin in the tumor. Finally, the site-specific conjugation of the linker-drug results in enhanced in vivo antitumor activity, as was demonstrated in preclinical models.
The SYD1875 study is registered in ClinicalTrials.gov with identifier NCT04202705.
Source: Byondis (Press release)
Medicijnontwikkeling kan sneller en beter met de massaspectrometer
GezondheidEen belangrijke vraag voor ontwikkelaars van nieuwe medicijnen: breekt je lichaam een geneesmiddel wel goed af? TNO’s Accelerator Mass Spectrometer (AMS) kan tegenwoordig sneller en eerder antwoord vinden op deze prangende vraag. Hoe? Dat licht Wouter Vaes bij BNR toe. Een prachtig voorbeeld van innovatie in de geneesmiddelontwikkeling!
Onderzoekers hebben soms een duwtje in de rug nodig met ondernemen
Gezondheid, Innovatieklimaat“Het zijn écht twee verschillende dingen, benadrukt onderzoeker Jeroen de Ridder van het UMC Utrecht: werken aan de oplossing van een wetenschappelijk probleem en vervolgens die oplossing uitbouwen tot een commercieel product waar patiënten daadwerkelijk iets aan hebben. Voor die tweede stap zijn andere eigenschappen en vaardigheden nodig. Het is dan ook niet vanzelfsprekend dat wetenschappers, die gedurende hun onderzoek nieuwe waardevolle inzichten opdoen, die tweede stap zetten. Ook Jeroen had een duwtje in de rug nodig.” Het UMC Utrecht heeft een lezenswaardig verhaal opgetekend over de ondernemende onderzoeker. Hier lees je meer over de uitdaging die Jeroen aangaat om met zijn start-up Cyclomics een bruikbaar medisch product te ontwikkelen om snel en goedkoop kanker op te sporen met bloedonderzoek.