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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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EMA’s digital transformation: new Orphan Drug Designation application system

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As of June 15th, the European Medicines Agency (EMA) starts the voluntary use of its Scientific and Regulatory Evaluation Procedure Support (S-REPS) for Orphan Drug Designation applications. From September 15th onwards, S-REPS will become mandatory for these applications, replacing the current PDF and Word form-based submission.

Application through S-REPS

S-REPS is a cloud-based end-to-end submission system. It is important to timely arrange for submission through this platform. Companies applying through S-REPS need to establish a User Account and Access Management. They should pre-register themselves through the organisations management services (OMS) in the substance, product, organisation and referential  (SPOR) web-portal. In addition, their substance should be pre-registered via the EU Telematics Controlled Terms (EUTCT) list. Finally, the company needs to request a Research Product Identifier before they can draft and submit applications. To support applicants in this new process, EMA currently develops a guidebook and training videos.

S-REPS extension to PRIME and Business Pipeline Meetings

Although June 15th marks the launch of S-REPS for Orphan Drug Designations applications, EMA acknowledges that this project is the first step in the EMA’s wider digital transformation strategy. Therefore, over time, S-REPS use may be extended to other scientific regulatory processes. The next procedures in line are PRIME and Business Pipeline Meetings.

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Leestip(s) – Kinder- of naschoolse opvang: mag ik je vaccinatieboekje even zien?

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Een compleet ‘geel boekje’ als toegangsbewijs voor kinder- en naschoolse opvang, daar pleiten universitair docent rechtsfilosofie Roland Pierik en hoogleraar filosofie Marcel Verweij in de Volkskrant voor. Net als HollandBIO maken beide heren zich zorgen over de dalende vaccinatiegraad: “Zolang de trend van de langzaam maar zeker afnemende vaccinatiegraad niet wordt gekeerd, is het niet de vraag of mazelen ergens in Nederland gaat uitbreken, maar wanneer en waar.”

Elders in Europa zijn de eerste mazelenuitbraken al een feit. Italië, Griekenland, Frankrijk en Roemenië hebben het zelfs zwaar te verduren, zo bracht het NOS recent naar buiten. EU-wijd zijn in 2017 bijna 15 000 gevallen en 56 doden gemeld. En dat terwijl deze ziekte met een prikje te voorkomen is.

Het is daarom hoog tijd voor actie. Pierik en Verweij roepen op tot indirect overheidsingrijpen. Geen vaccinatie? Dan ook geen toegang tot kinder- en naschoolse opvang. Als de overheid deze maatregel invoert, neemt zij haar verantwoordelijkheid om kinderen, burgers en de samenleving tegen ernstige infectieziekten te beschermen. HollandBIO is erg benieuwd of de overheid gehoor geeft aan deze oproep, ook nu verschillende D66-Kamerleden hier vragen over stellen. Elke stap die bijdraagt aan een heldere visie op de bestrijding van infectieziekten is welkom.

Lees ook het opinieartikel in de Volkskrant en het achtergrondartikel van de NOS. De Kamervragen van D66 zijn hier in te zien.

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Janssen taking Legend CAR T therapy to clinic

Janssen said FDA cleared an IND for CAR T therapy JNJ-68284528 to treat multiple myeloma. Next half, the unit of Johnson & Johnson expects to start a U.S. and European Phase Ib/II study of Legend Biotech’s therapy targeting BCMA.

At last year’s American Society of Clinical Oncology (ASCO) meeting, Legend reported JNJ-68284528 led to a 100% objective response rate among 19 MM patients in the first phase of the Chinese Phase I/II LEGEND-2 study. No neurotoxicities, which can plague anti-CD19 CAR T therapies, were observed.

In December 2017, Janssen obtained a global license to the therapy from the Legend Biotech USA Inc. and Legend Biotech Ireland Ltd. subsidiaries of Genscript Biotech Corp. The partners are developing JNJ-68284528 jointly worldwide.

The therapy is Janssen’s first in the CAR T space. At the time of the deal, Janssen’s Global Therapeutic Area Head of Oncology Peter Lebowitz told BioCentury BCMA was the first target to meet the company’s safety and efficacy standards for the CAR T modality (see BioCentury, Jan. 5).

Janssen said the primary efficacy endpoint in the Phase II portion of its planned trial to treat relapsed or refractory MM will be overall response rate (ORR) as defined by the International Myeloma Working Group response criteria.

Source: Biocentury

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