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Argenx boosts pipeline with new version of lead drug

Argenx has the first data on a new subcutaneous formulation of its rare autoimmune disease drug efgartigimod that could make it a much more patient-friendly prospect.

The company already has an intravenous formulation of efgartigimod (ARGX-113) in trials for myasthenia gravis (MG), immune thrombocytopenia (ITP) and pemphigus vulgaris (PV), all of which are characterized by high levels of pathogenic immunoglobulin G antibodies. Now, Argenx has data showing that its subcutaneous formulation behaves in the same way as the IV version in the body, and seems to be equally effective at depleting IgG levels.

The results raise the hope that the antibody fragment-based drug could be delivered via an IV loading dose to begin with, and then given by simple injection—potentially by the patient at home—as a maintenance therapy.

That would provide “flexible dosing options and greater convenience for patients with severe auto-immune conditions requiring long-term treatment,” according to Argenx’s recently appointed COO Keith Woods, who said the new formulation has now been added to its product pipeline. “With an SC formulation, we also plan to explore the potential for an off-the-shelf delivery system using a fine bore needle size to allow patients additional optionality around administration,” he added.

The Belgian-Dutch biotech has been on a roll over the last few months, completing an impressive $115 million IPO on the Nasdaq, following that up with a $231 million additional offering as 2017 drew to a close, and reporting positive results for IV efgartigimod in MG. If approved, it would compete with big-selling drugs such as Alexion’s $3 billion blockbuster Soliris (eculizumab) in MG, but with a differentiated mechanism of action.

In that study, the drug achieved a clinically significant improvement in symptoms (muscle weakness) in 75% of patients, compared to 25% of the placebo group. Last week, the biotech said it had completed an end-of-study meeting with the FDA and is designing a pivotal, phase 3 trial that should get underway before the end of the year. And it’s also waiting for readouts from phase 2 trials of efgartigimod in ITP and PV in the second half.

Argenx also has a second R&D track focusing on cancer, headed by CD70 antagonist ARG-110 for patients newly diagnosed with acute myeloid leukemia (AML) which has progressed to phase 2 as a combination with widely used AML chemotherapeutic drug azacytidine, phase 1 candidate ARGX-111 for cancer metastases, and AbbVie-partnered cancer immunotherapy ARGX-115.

Source: FierceBiotech

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5 Million for ProQR to develop QR-313 as treatment of Dystrophic Epidermolysis Bullosa

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ProQR announced a collaboration with nonprofit organizations EB Research Partnership (EBRP) and EB Medical Research Foundation (EBMRF). ProQR is a company dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe genetic rare diseases. Under the agreement, EBRP and EBMRF will provide up to approximately $5 million in matching funding to ProQR under a venture philanthropy model. The funding will be used to develop QR-313 for patients with dystrophic epidermolysis bullosa (DEB) caused by mutations in exon 73 of the COL7A1 gene.

“The EB Research Partnership and EB Medical Research Foundation are exceptional organizations and we look forward to collaborate on our mission to develop a life changing treatment for patients with this devastating disease,” said Daniel A. de Boer, Chief Executive Officer of ProQR. “With the funding from these partners, we plan to accelerate the development of QR-313 for the treatment of DEB. And if we are successful with QR-313, we believe there is potential to expand this approach of exon skipping into other mutations that cause DEB and help even more patients.”

DEB is a rare debilitating skin disease caused by the absence of a protein called collagen type VII (C7). Symptoms are present from birth and include easy blistering of the skin, poorly healing wounds, skin infections and, in adulthood, some patients develop very aggressive forms of skin cancer. There are currently no approved treatment options for DEB. The WINGS trial, a first-in-human Phase 1/2 clinical trial of QR-313 in patients with DEB, is expected to initiate enrollment of patients in the first half of 2018. The trial is expected to report interim proof of mechanism results later this year, with full results expected in 2019.

“DEB has a huge impact on patients’ quality of life and there are currently no approved disease modifying treatment options beyond wound care,” said Alex Silver, founder and Chairman of EBRP and Paul Joseph, CFO of EBMRF. “Our organizations are excited to partner with the ProQR team, in the hopes that the development of QR-313 will provide a much-needed treatment option to this community.”

Source: ProQR

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Update Horizonscan Geneesmiddelen Zorginstituut

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Het Zorginstituut publiceert vandaag de update van de Horizonscan Geneesmiddelen. De scan heeft als doel om patiënten, behandelaars, ziekenhuizen, zorgverzekeraars en overheidsorganen vroegtijdig op de hoogte te stellen van de ontwikkelingen op het gebied van innovatieve geneesmiddelen. De Horizonscan bevat een overzicht van geneesmiddelen of indicatie-uitbreidingen die de komende twee jaar verwacht worden. Diverse HollandBIO leden leverden informatie aan voor een representatieve scan. Ook zijn, mede op aangeven van HollandBIO, verbeteringen aangebracht in de nieuwe editie van de Horizonscan.

Het Zorginstituut stelt de Horizonscan Geneesmiddelen samen op basis van input van “(Horizon)scanners”, werkgroepen van experts en geneesmiddelenontwikkelaars. Die laatsten kregen niet alleen de kans om in een vroeg stadium data aan te leveren, maar deze ook voor publicatie te actualiseren. Dit komt de voorspellende waarde van de Horizonscan ten goede.

Het Zorginstituut heeft ten opzichte van de vorige scan, die begin dit jaar verscheen, een aantal verbeteringen doorgevoerd. Zo heeft het maximaal patiëntvolume plaatsgemaakt voor een onderbouwd realistisch patiëntvolume. Dit leidt tot een nauwkeurigere schatting van de behandelkosten. Daarnaast maakt de nieuwe scan ook melding van de ontwikkelfase waarin de geneesmiddelen zich bevinden. Het zijn twee aanpassingen waar HollandBIO erg blij mee is.

Hoewel deze update net is afgerond, start het Zorginstituut eind juni weer met de uitvraag voor de volgende Horizonscan, die december 2018, januari 2019 live gaat. Die scan wordt nog vollediger: naast nieuwe geneesmiddelen en toepassingen zal deze ook generieke geneesmiddelen en biosimilars in kaart brengen. HollandBIO roept haar leden op om ook hier weer een bijdrage aan te leveren.

Benieuwd naar de Horizonscan?

Bekijk dan de website van de Horizonscan geneesmiddelen. We horen graag of de gegevens van jouw bedrijf er goed in staan en of je mogelijkheden tot verdere verbetering van de scan ziet. https://www.horizonscangeneesmiddelen.nl/

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Alexion and Complement Pharma co-develop complement inhibitor for neurodegenerative disorders

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Alexion and Complement Pharma announced a partnership to co-develop the preclinical C6 complement inhibitor CP010 for neurodegenerative disorders. C6 inhibition prevents the formation of the destructive membrane attack complex (MAC), a complex of terminal complement proteins that mediate cellular injury following complement activation, and has the potential to treat a variety of central nervous system disorders. Under the terms of the agreement, Alexion will provide Complement Pharma with up to € 14 million in milestone-dependent payments through Phase 1b development. The agreement also provides Alexion with the option to acquire Complement Pharma during the term of the agreement.

“Alexion has been a pioneer in complement biology since the development of Soliris, the world’s first complement inhibitor, which has demonstrated the significant impact that C5 inhibition can have on several diseases caused by uncontrolled complement activation,” said John Orloff, M.D., Executive Vice President and Head of Research & Development at Alexion. “This collaboration provides an exciting opportunity to expand on our more than two decades of complement expertise to potentially treat additional diseases by targeting C6, a different component of the complement system.”

“Our understanding of the role of complement in many disorders continues to increase and many neurodegenerative diseases show activation of the complement system, even in early stages of disease,” said Frank Baas, M.D., Ph.D., Chief Scientific Officer at Complement Pharma. “We believe that C6 inhibition has the potential to treat multiple neurodegenerative disorders, and we look forward to working with Alexion, a partner with a worldwide leading position in complement biology, to realize the possibilities of this approach.”

Under the terms of the agreement, Alexion and Complement Pharma will collaborate on the development program for CP010. Complement Pharma will be responsible for conducting preclinical and Phase 1 studies and for manufacturing CP010. The phased agreement extends through the completion of Phase 1b development. Alexion has the option to acquire Complement Pharma during the term of the agreement.

CP010 is a humanized monoclonal antibody in preclinical development that binds to C6 in circulation to inhibit its function throughout the body by preventing MAC formation in both the periphery and the central nervous system. An end product of the activated complement cascade, MAC has been shown to play a role in neurodegeneration. CP010 has demonstrated C6 inhibition in vitro and in vivo; C6 inhibition prevents the formation of the MAC following complement activation which may allow treatment of a variety of central nervous system disorders.

Source: Alexion

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Sanofi Pasteur and Translate Bio Launch mRNA Vaccine Partnership

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Sanofi’s global vaccines unit Sanofi Pasteur will partner with Translate Bio to develop mRNA vaccines for up to five undisclosed infectious disease pathogens, through a collaboration that the mRNA therapeutics developer said today could generate for it up to $805 million-plus.

During the collaboration’s initial three-year research term, Translate Bio said, it will join Sanofi Pasteur in jointly conducting R&D activities to advance mRNA vaccines. Sanofi Pasteur agreed to pay for all costs during the research term and receive exclusive worldwide commercialization rights.

In return, Sanofi Pasteur agreed to pay Translate Bio $45 million upfront, and up to $760 million in payments tied to achieving development, regulatory, and sales-related milestones across several vaccine targets, as well as option exercise fees if Sanofi Pasteur exercises its option related to development of vaccines for additional pathogens.

Translate Bio said it is also eligible to receive tiered royalty payments associated with worldwide sales of the developed vaccines.

Under the collaboration with Sanofi Pasteur, Translate Bio will be responsible for clinical manufacture and will be entitled to additional payments under a separate supply agreement to be established.

“We believe mRNA technology has significant potential for rapid and versatile manufacturing, reduced industrialization costs for multiple vaccines, and the improved breadth of immune response for infectious disease vaccines,” John Shiver, SVP, R&D, Sanofi Pasteur, said in a statement. “The Translate Bio platform may allow us to further address medical needs worldwide, including those not readily accessible using conventional vaccine strategies.”

 

Sales, Clinical Setbacks

Sanofi is looking to broaden Sanofi Pasteur’s R&D efforts following a 0.9% year-over-year dip in sales during the first quarter, to €711 million ($839 million). While sales grew 8.3% for all of 2017, to €5.101 billion ($6.020 billion), they only inched up 1.2% during Q4, to €1.385 billion ($1.635 billion).

The vaccine unit is looking to bounce back from setbacks: Sanofi took a fourth-quarter charge for its pioneering Dengue vaccine Dengvaxia® to reflect reduced sales after long-term clinical trial data showed the vaccine could increase the severity of the disease in people who were not previously infected.

And in December 2017, Sanofi halted development of its Clostridium difficile candidate after the Independent Data Monitoring Committee for the Phase III Cdiffense™ clinical trial (NCT01887912) concluded that the vaccine was unlikely to meet the study’s primary endpoint of efficacy in adults ages 50 years-plus who are at risk for C. difficile infection and received at least one injection of the vaccine.

Translate Bio says its mRNA therapeutic platform (MRT) is designed to develop product candidates that deliver mRNA carrying instructions to produce intracellular, transmembrane, and secreted proteins for therapeutic benefit.

The company reasons that it can apply the MRT platform to a broad range of diseases caused by insufficient protein production or where production of proteins can modify disease—including diseases that affect the lung, liver, eye, central nervous system, lymphatic system, and circulatory system.

mRNA Platform “Potential”

“We believe that this partnership validates the potential of our mRNA platform, and also enables us to apply our mRNA technology beyond the current therapeutic applications that we are pursuing in cystic fibrosis and ornithine transcarbamylase deficiency, ultimately advancing our goal of delivering innovative medicines to patients,” added Translate Bio CEO Ronald Renaud.

Translate Bio emerged in January 2017 under the name RaNA Therapeutics when it acquired the MRT mRNA therapy platform from Shire—whose subsidiaries developed the technology—for an undisclosed price. At the time, the group of Shire MRT employees who had focused on developing the technology since 2008 joined RaNA to continue advancing the platform in cystic fibrosis and urea cycle disorders.

On April 12, Translate Bio said it won FDA clearance to begin a first-in-humans Phase I/II trial to assess the mRNA candidate MRT5005 in cystic fibrosis, with dosing of patients expected to begin “in mid-2018.”

The randomized, double-blind, placebo-controlled trial is designed to enroll at least 32 adult patients with cystic fibrosis who have at least one Class I or Class II mutation. The trial’s primary endpoint will be the safety and tolerability of single and multiple escalating doses of MRT5005 administered by nebulization.

Translate Bio’s deal with Sanofi is subject to customary closing conditions, including the expiration of the applicable waiting period under the Hart–Scott–Rodino Antitrust Improvements Act of 1976 in the U.S.

Source: GEN

 

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AstraZeneca and MSD present new results about Lynparza

The two pharma giants report data which showed clinical improvement in median radiologic progression-free survival (rPFS) with Lynparza (olaparib) in combination with abiraterone compared to abiraterone monotherapy, a standard of care, in metastatic castration-resistant prostate cancer (mCRPC).

Lynparza is being jointly developed and commercialised by AstraZeneca and MSD.

Phase II trial

The results of Study 08, a randomised, double-blinded, multi-centre Phase II trial, comparing Lynparza in combination with abiraterone (n=71) to abiraterone monotherapy (n=71) in patients with previously-treated mCRPC, regardless of homologous recombination repair (HRR) mutation status, were presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, US, 1-5 June 2018 as a “Best of ASCO presentation” and were published online today in the Lancet Oncology. The primary endpoint was rPFS. Secondary endpoints included time to second progression or death (PFS2), overall survival (OS) and health-related quality of life.

“A previous trial demonstrated improvements in response rates with Lynparza monotherapy in metastatic castration-resistant patients with HRR mutations. The Study 08 combination data suggests that regardless of their mutation status, men with metastatic castration-resistant prostate cancer may potentially benefit from Lynparza in combination with abiraterone,” says Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca.

Source: Nordic

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Biogen Buys Option to TMS’ Phase II Stroke Candidate

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Biogen has acquired an exclusive option to TMS’ Phase II acute stroke candidate TMS-007 and backup compounds through a deal that could generate up to $357 million-plus for the Japanese biotech and is intended to reinforce the buyer’s commitment to stroke drugs by adding a potentially long-acting treatment to its acute neurology portfolio.

TMS-007 is a small-molecule plasminogen activator with a novel mechanism of action associated with breaking down blood clots, as well as an apparent ability to inhibit local inflammation at the site of thrombosis. Biogen reasons that the combination could position TMS-007 as a best-in-class thrombolytic for patients with acute ischemic stroke (AIS), with the potential for a more extended treatment window than current thrombolytic agents.

TMS-007 is now under study in Japan in a Phase IIa trial (JapicCTI-183842) in which the first patient was enrolled in December 2017 and dosed in February. The double-blind, placebo-controlled study is designed to investigate the safety and efficacy of a single IV administration of TMS-007 in approximately 60 to 90 patients with AIS up to 12 hours after stroke onset.

In a Phase I study (JapicCTI-142654) completed in 2015, TMS-007 has shown an acceptable safety profile and has also reduced the area of dead tissue resulting from failure of blood supply or infarct volume in experimental rodent and primate embolic and thrombotic stroke models.

Biogen has agreed to pay TMS $4 million upfront, $18 million upon exercising the exclusive option, and up to $335 million in payments tied to achieving development and commercialization milestones, plus royalties.

Based in Fuchu-shi, Tokyo, TMS is a privately held biotech that was founded in 2005 to develop therapeutics based on novel discoveries to modulate the fibrinolytic system. Those discoveries were identified by a team of scientists at Tokyo University of Agriculture and Technology (TUAT) led by Keiji Hasumi, Ph.D., who serves as the company’s CEO.

 

Complementing Phase III-Ready Stroke Candidate

Michael Ehlers, M.D., Ph.D., Biogen EVP, research and development, said in a statement that TMS-007 complemented the company’s broader efforts in stroke, led by its Phase III-ready candidate BIIB093 (glibenclamide IV), designed to target prevention and treatment of edema in one of the most severe types of stroke, large hemispheric infarction (LHI).

Biogen plans a Phase III study assessing BIIB093 in severe cerebral edema following LHI (CHARM; NCT02864953). The study had yet to recruit patients as of March 22, the date of the most recent update on ClinicalTrials.gov.

According to Biogen, clinical proof-of-concept studies have shown the potential of BIIB093 to reduce brain swelling, disability, and the risk of death in LHI patients. Preclinical studies have shown BIIB093 to block SUR1-TRPM4 channels that mediate stroke related brain swelling.

“By growing our acute neurology portfolio, we aim to make new advances in a disease that in the past decades has seen limited therapeutic innovation,” Dr. Ehlers stated.

During Biogen’s most recent conference call with analysts on April 24, CEO Michel Vounatsos said BIIB093 is one of several late-stage candidates Biogen hopes to launch in the early 2020s, while CFO Jeff Capello said the company was committed to pipeline growth.

“Our premium is on adding to the pipeline, given our commercial footprint and our manufacturing footprint, and trying to bring in assets that are closer to being market ready. So there’s certainly a preference to kind of look at those types of transactions,” Capello said. “As we go along, we’ll continue to add to the pipeline with mid-stage assets and lower-stage assets where they fill in.”

Source: GEN

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MDxHealth licensing agreement with Philips facilitates launch InformMDx(TM)

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MDxHealth announced a worldwide licensing agreement with Philips for the rights to manufacture and market Philips’ recently validated prognostic biomarker for prostate cancer, phosphodiesterase-4D7 (“PDE4D7”), as a prognostic test. The test is based on technology which was jointly developed by Philips Research and The University of Glasgow.

The agreement enables MDxHealth to prepare the launch of its InformMDx(TM) test for prostate cancer, a tissue-based test utilising PDE4D7 that can stratify patients according to their risk of disease progression and the development of secondary tumors. The Company anticipates that InformMDx will provide actionable information to help clinicians guide post-biopsy treatment decisions at the time of diagnosis, as well as post-surgical treatment decisions following prostatectomy. In the US alone, over 150,000 patients per year could benefit from the InformMDx test.

PDE4D7 has recently been validated in a 503 patient study published in the journal European Urology Focus which confirmed, based on 10-15 years of follow-up data, the independent prognostic and incremental value of PDE4D7 compared to the established clinical risk metric (https://www.eu-focus.europeanurology.com).

Source: MDxHealth

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Speeding Drug Development with Clinical Trials in a Dish

The average time to bring a new drug to market is 12 years—assuming it makes it through the rigorous regulatory hurdles. Any technology or methodology that can expedite the drug development process or increase the likelihood of FDA approval is advantageous to both companies and patients. Now, a new study from investigators at Coyne Scientific provides a unique look at a novel strategy—clinical trials in a dish (CTiD)—that bridges preclinical testing and clinical trials. Findings from the new study were published recently in SLAS Discovery, in an article entitled “Clinical Trials in a Dish: A Perspective on the Coming Revolution in Drug Development.”

“The pharmaceutical industry is facing unprecedented challenges as the cost of developing new drugs has reached unsustainable levels, fueled in large parts by a high attrition rate in clinical development,” the authors wrote. “Strategies to bridge studies between preclinical testing and clinical trials are needed to reduce the knowledge gap and allow earlier decisions to be made on the continuation or discontinuation of further development of drugs.”

This new CTiD platform allows pharmaceutical companies to test, at the population level, novel drugs on patient cells before moving into actual clinical trials. Because current preclinical strategies don’t follow this principle, CTiD offers the potential to impact drug discovery and development significantly.

Recent demonstrations have shown various human induced pluripotent stem cell-derived (hiPSCs) cell types (cardiac, neuronal, hepatic) recapitulate a specific individual’s drug response (rather than that of a generic human being) and have opened new avenues that support the concept of screening for cell-based safety and toxicity at the level of a population.

“The discovery and development of human induced pluripotent stem cells (hiPSCs) have opened up new avenues that support the concept of screening for cell-based safety and toxicity at the level of a population,” the authors penned. The researchers continued, stating that CTiD “allows testing medical therapies for safety or efficacy on cells collected from a representative sample of human patients, before moving into actual clinical trials. It can be applied to the development of drugs for specific populations, and it allows predicting not only the magnitude of effects but also the incidence of patients in a population who will benefit or be harmed by these drugs. This, in turn, can lead to the selection of safer drugs to move into clinical development, resulting in a reduction in attrition.”

The concept of CTiD is to satisfy, in an in vitro setting, the defining biological truth that establishes the need for a multipatient clinical trial, which is that drug responses vary by human. CTiD studies are efficient, allow the study of a range of clinical doses, and can be executed at a fraction of the cost outside of the rigid and heavily regulated clinical testing environment.

CTiD studies are poised to revolutionize thinking about practical, immediate, and near-term applications in the field of drug discovery and development. CTiD can lead to insights that cannot be obtained so early and economically in drug development by any other approach. Although still requiring improvements and enhancements, CTiD offers to refine the selection of drugs to move into clinical development, leading to reduced attrition and enabling safe drugs that address unmet medical needs to reach patients more quickly.

Source: GEN

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Glycostem and MolMed collaborate on allogenic CAR-NK therapies

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Glycostem and MolMed signed a binding term sheet for the development and manufacturing of new NK cells–based allogeneic CAR (Chimeric Antigen Receptors). The Master Agreement will be finalized by September 30th, 2018.

According to the agreement, Glycostem and MolMed will collaborate on an exclusive base in developing and manufacturing engineered NK cells targeted to three tumor antigens: Glycostem will be responsible for the final product GMP manufacturing and release, while MolMed will have exclusive rights for the exploitation of the resulting products and Glycostem will receive upfront payments, milestones and royalties on the developed products.

Troels Jordansen, Glycostem CEO, commented: “We are very proud to be teaming up with one of the most innovative cellular therapy companies around and jointly develop mold-breaking products for the help of doctors and patients. The synergy between MolMed and Glycostem is tangible and we are confident it could lead to exciting results in the short term. This is also the initiation of Glycostem’s in-house development program in our new state-of-the-art facility in the Netherlands. It is out of the same facility that we expect to have GMP approval for our closed-system production system by the end of 2018. This will allow us to expand our clinical trial program and enter pivotal for oNKord early 2019.”

Source: PivotPark

 

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