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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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Treeway prepares phase 3 study for TW001 to treat ALS

Phase 1 study suggests that novel oral formulation improves bioavailability while remaining well tolerated.

Treeway, a biotech company developing therapies against amyotrophic lateral sclerosis (ALS), announced the completion of its Phase I trial of lead program TW001, an oral formulation of edaravone. The study compared the bioavailability of TW001 in its novel market formulation to Radicava, an FDA approved, intravenous formulation of edaravone, indicated for the treatment of ALS. The study indicates increased bioavailability of TW001 in a single-dose treatment whilst no safety concerns developed within the subject group, implying the potential of the novel formulation to improve treatment strategies for ALS patients. Based on these results, Treeway has initiated the upscaling program and preparations for a pivotal Phase 3 study. Edaravone is a neuroprotective agent that reduces oxidative stress, a key contributor to neuronal death in ALS.

“It is Treeway’s mission to identify novel treatment routes for ALS patients and we believe that this study indicates that an oral formulation of edavarone may offer patients a better quality-of-life through a simpler and more effective route of administration,” said Ronald van der Geest, Chief Development Officer of Treeway. “Given the nature of this program and based on the positive results we have seen in this comparative study, we can initiate a pivotal Phase 3 study and move rapidly toward bringing TW001 to patients.”

The randomized, cross-over comparative bioavailability trial tested a single oral dose of 140 mg TW001, compared to a 1-hour intravenous infusion of 60 mg edaravone in 18 healthy subjects. In this study, the bioavailability of the novel oral formulation exceeded the bioavailability of the intravenous infusion of Radicava. Within the subject group of the study the treatment was well-tolerated and no safety concerns arose during the conduct of the study. Furthermore, ongoing formulation studies also suggest that the formulation is stable.

Merit Cudkowicz, MD, Chief Neurology Service and Director of the ALS Clinic at the Massachusetts General Hospital, a key advisor to the company, commented:

“The results of this Phase I study are a promising sign for ALS patients, who are in high need of better and more patient-friendly treatments for their disease. I regard this study to be a key milestone for the development of TW001 in ALS and I look forward to supporting the company’s scientific and clinical progress.”

Source: BusinessWire

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Hartwig Medical Foundation and ttopstart announce collaboration

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Hartwig Medical Foundation and ttopstart are pleased to announce collaboration to accelerate the implementation of clinical decision support systems for personalised cancer treatment in the Netherlands.

Hartwig Medical Foundation is developing innovative clinical decision support systems to enable personalised cancer treatment in the Netherlands. As a part of this, Hartwig Medical Foundation provides access to a unique databank of Whole Genome Sequencing and clinical data of thousands of patients. This will enable a substantial improvement in the quality of diagnosis and treatment of cancer patients, stimulate scientific research into methods of treatment and cancer therapies, and reduce the cost of care and over-treatment. Furthermore, Hartwig Medical Foundation has developed a unique patient report that provides clinicians with an actionable assessment of the genetic characteristics of the tumour to guide clinical decision-making for personalised cancer treatment.

Hartwig Medical Foundation is making important progress in advancing the implementation of DNA sequencing technology and clinical-decision making for personalised cancer care. To accelerate this process, Hartwig Medical Foundation and ttopstart co-design smarter strategies and develop new business models to support patient access to precision medicine in a timely and responsible manner and the introduction of actionable patient reporting for clinical decision-making in personalised cancer treatment. In addition, ttopstart will provide ongoing project management support for the different key partnerships of Hartwig Medical Foundation.

Source: ttopstart

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Merus’ MCLA-158 Phase I clinical trial has started

Merus, a clinical-stage immuno-oncology company developing innovative bispecific antibody therapeutic, announced that the first patient has been dosed in a Phase 1, first-in human clinical trial of MCLA-158 in patients with solid tumors with an initial focus on metastatic colorectal cancer. The trial will be conducted in Europe, where several Clinical Trial Applications (CTAs) have been approved to date. The Company also announced the submission of an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for MCLA-158, which was accepted by the FDA in April 2018. With this acceptance, Merus plans to open additional sites for this trial in the United States.

MCLA-158 is designed to bind to cancer stem cells expressing leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and epidermal growth factor receptors (EGFR). MCLA-158 was identified from a large library of bispecific antibodies targeting molecules belonging to the Wnt and receptor tyrosine kinase signaling pathways as part of work performed by the suppresSTEM consortium, a project that was funded by the European Union. Functional evaluation of patient-derived colorectal tumors, including those harboring RAS and/or PI3K mutations, demonstrated that MCLA-158 was more effective at inhibiting tumor growth and promoting apoptosis than an approved targeted therapy comparator for metastatic colorectal cancer, cetuximab. In preclinical studies, Merus also observed that the growth inhibitory activity of MCLA-158 was greater for colon tumors compared to normal colon tissue, consistent with its good safety profile in non-human primates.

“The commencement of our Phase 1 clinical trial of MCLA-158 is an important milestone for the advancement of our pipeline of bispecific antibodies obtained from our Biclonics technology platform,” said Ton Logtenberg, Ph.D., Chief Executive Officer. “We believe MCLA-158 has the potential to address features that limit currently approved colorectal cancer-targeted therapies, including issues with off-target toxicity and inability to target tumor stem cells, and thus, potentially treat a broader population of patients more effectively.”

The Phase 1, open-label, multicenter clinical trial of MCLA-158 consists of two parts, a dose escalation and a dose expansion. The dose escalation part is intended to determine the appropriate dose of MCLA-158. The dose expansion part will evaluate the safety and tolerability of the defined dose of MCLA-158 in patients with solid tumors. The dose escalation and expansion parts of the trial will also examine the preliminary antitumor activity of single-agent MCLA-158.

Source: GlobeNewsWire

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