After scrapping plans to grab a quick FDA nod for Rova-T, AbbVie is licensing CAR-T technology from Calibr to create safer, “switchable” CAR-T treatments for solid tumors.

AbbVie will pay an undisclosed license fee in return for exclusive access to Calibr’s platform for up to four years. While its primary focus is solid tumors—historically difficult to treat with CAR-T—the Big Pharma has the option to identify other targets, including blood cancers, and to license Calibr’s cell therapy programs that are already under way. This includes Calibr’s lead program, which is set to enter the clinic for lymphoma next year.

The pair will share responsibility for preclinical development, and AbbVie will take on clinical development and commercialization. Calibr will stand to reap success-based milestone payments and royalties.

Aside from challenges in solid tumors, researchers and companies working on CAR-T have run into issues with safety, specificity and patient relapse. The treatment essentially involves taking a patient’s T cells, modifying them to better recognize and attack a certain cancer, and putting them back into the patient, after which their activity can’t be controlled.

Calibr’s CAR-T platform is antigen agnostic and is “absolutely dependent” on antibody-based switches, said Travis Young, director of protein sciences at Calibr.

Calibr hopes its tech will lead to a universal CAR-T system, in which T cells would be modified the same way for each patient, regardless of tumor type, rather than developing a new CAR-T for each indication. The type of antibody switch used would determine the target, “switch on” the treatment and control its strength, Young said.

In addition to controlling CAR-T activity, the switches could also combat patient relapse, which happens when a patient’s cancer “hides” from the CAR-T cells by “losing” the antigen the cells are engineered to find. In this case, Young said, a different switch targeting a different antigen could be deployed.

“We’ve been working on this for a long time. We’re excited to see ‘switchable’ CAR-Ts getting a lot of attention now,” said Calibr COO Matt Tremblay. “AbbVie has a fresh perspective, it’s not in the cell therapy space in any significant way now that’s well known. […] It’s the right time to team up with somebody who is bold enough to go for a collaboration of the scope you see outlined [here].”

Many players are working on what is being called CAR-T 2.0, the next generation of CAR-T treatments designed to be safer and less complicated and time-consuming to produce. Researchers from Boston University are working on a split, programmable, universal system that aims to solve the same problems Calibr is trying to address. And researchers at Cellectis are incorporating a safety switch into CAR-T constructs themselves to eliminate the risk of imbalanced populations of safeguard molecules and CAR-T cells.

Source: FierceBiotech

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

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