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Bluebird acknowledged in a regulatory filing that Gina Consylman, the company's CFO and treasurer, had given notice of her resignation, effective April 3.
Consylman joined Bluebird in September 2021 as CFO of its severe genetic business. She became CFO of the entire company after Bluebird spun off its seven clinical and six preclinical oncology programs into 2seventy bio. The surviving Bluebird Bio has three candidates and a research-and-development (R&D) focus on severe genetic diseases.
Bluebird said Consylman is expected to be succeeded by its Chief Business Officer, Jason F. Cole.
Three days before Consylman's resignation was disclosed, Bluebird raised questions about its ability to continue in business for 1 year after the date that its consolidated financial statements for the year ended December 31, 2021 are issued.
The company cited a drop in its cash, cash equivalents, and marketable securities since the separation of the Bluebird operations. As of December 31, 2021, that total stood at $396.6 million—down 22% from the ∼$507.2 million Bluebird had at the time of the separation (although the latter includes restricted cash).
“There is substantial doubt regarding our ability to continue as a going concern,” Bluebird acknowledged in its Form 10-K annual report for 2021. “We will need to raise additional financing in upcoming periods, which may not be available on acceptable terms, or at all.” 1
Bluebird disclosed its doubt upon releasing fourth-quarter and full-year 2021 results. The company finished 2021 with a net loss from continuing operations of $562.6 million on revenue of just $3.7 million, compared with a $561.1 million net loss from continuing operations for 2020, a year during which it recognized no revenue from continuing operations.
The company's accumulated deficit stood at $3.72 billion as of December 31, 2021.
Takeda, Code Bio Launch up to $2B Rare Disease Alliance
Takeda and Code Bio said they will design and develop a targeted gene therapy leveraging Code Bio's 3DNA platform for a liver-directed rare disease program, plus conduct additional studies for central nervous system-directed rare disease programs. Takeda has the right to exercise options for an exclusive license for four programs.
The companies said they will collaborate on research activities up to candidate selection, with Takeda assuming responsibility for further development and commercialization in each program for which it exercises its options.
Code Bio's targeted 3DNA nonviral genetic medicine delivery platform uses a synthetic multivalent design intended to enable cell-specific targeting, the delivery of large genetic payloads, and the potential for re-dosability.
Code Bio has cited preclinical data showing that targeted formulations are highly specific and effective at delivering genetic cargo to targeted cells and tissues with no evidence of platform-related off-target effects or safety concerns.
Takeda agreed to pay Code Bio an undisclosed double-digit million dollars in upfront, near-term milestone, and research funding payments. Code Bio is also eligible to receive from Takeda up to $2 billion tied to achieving development and commercial milestones for all four programs, plus tiered royalties.
“Code Bio's 3DNA platform will allow us to build upon the foundation we have established through our internal capabilities and external partnerships and will hopefully enable us to develop re-dosable and durable gene therapies that will be superior to current approaches,” said Madhu Natarajan, Head of Takeda's Rare Diseases Drug Discovery Unit. 2
Novartis, Voyager Target Neurological Disease in up to $1.7B Partnership
The capsids were generated through Voyager's Tropism Redirection of AAV by Cell type-specific Expression of RNA (TRACER™) capsid discovery platform
Novartis and Voyager plan to target neurological diseases that manifest in deep brain regions where commonly used vectors had not been shown to effectively target and penetrate.
According to Voyager, an initial set of AAV capsids derived from TRACER showed superior blood–brain barrier penetration, increased transduction in the brain and spinal cord, enhanced cardiac muscle tropism, and increased transgene expression in target tissues compared with conventional AAV capsids when dosed intravenously in nonhuman primates (NHPs). One capsid from this initial set showed more than 1,000-fold increased transgene expression levels as measured by mRNA level, compared with conventional AAV serotype 9 (AAV9) across a wide array of brain regions when dosed intravenously in NHPs.
“Voyager's growing and maturing library of proprietary TRACER-derived capsids have demonstrated markedly enhanced expression in nonhuman primates with more precise targeting of desired tissue and cell types, creating the potential for superior delivery and fewer off-target risks than conventional AAV,” said Glenn Pierce, MD, PhD, Voyager's interim chief scientific officer. 3
Novartis agreed to pay Voyager $54 million upfront, and up to $37.5 million in exercise fees for options for three initial CNS targets, exercisable by Novartis within 12 months of signing.
Should Novartis exercise its options to the two additional capsids, it has agreed to pay Voyager $18 million upon selection of each target, and a $12.5 million exercise fee for selection of a capsid for each target.
Voyager is also eligible to earn from Novartis up to $1.5 billion in payments tied to achieving development, regulatory, and commercial milestones for products using Voyager licensed capsids, as well as mid- to high-single-digit tiered royalties based on net sales of Novartis products incorporating the licensed capsids.
Amicus Retains Gene Therapy Assets, Ending Spinout Effort
Amicus said it and a special purpose acquisition company (SPAC), ARYA Sciences Acquisition Corp. IV, agreed to mutually terminate a previously announced Business Combination Agreement they entered into in September 2021.
“This decision results from unfavorable market conditions affecting IPOs, follow-on financings, and SPACs in the biotech sector as well as an increasingly challenging environment for stand-alone gene therapy companies,” Amicus said in a statement. 4
Amicus said it will assign priority in its R&D to gene therapy by continuing to invest in additional indications for its marketed Galaford® (migalastat), approved as a treatment for Fabry disease in adults with an amenable galactosidase alpha gene variant; as well as in AT-GAA, a two-component therapy for Pompe disease now under review by the U.S. Food and Drug Administration (FDA)—as well as in technologies designed to secure and advance the Fabry and Pompe franchises.
AT-GAA consists of cipaglucosidase alfa (ATB200) and miglustat. The FDA has set Prescription Drug User Fee Act action dates of May 29 for cipaglucosidase alfa and July 29 for miglustat.
Another priority, Amicus said, will be discovery efforts in core science and platform technologies that are designed to address safe and efficient gene transfer.
During Amicus' quarterly earnings call, Chairman and CEO John F. Crowley said the company will reduce its workforce by 7%, about 35 people, mostly in R&D positions: “This will allow us to continue to hire key personnel for the global growth of Galafold and the coming launches of AT-GAA, again, while keeping overall headcount at Amicus flat at about 500 employees globally.” 5
Crowley also said Amicus will suspend indefinitely its plans to build an internal gene therapy manufacturing organization and facility.
Amicus said it expected its prioritization of gene therapy and restructuring of its R&D organization to generate savings of ∼$400 million through 2026—the same amount that Amicus had projected generating from spinning off its gene therapy portfolio through the SPAC merger.
UCB to Build €200M Gene Therapy Facility
Construction is set to start in the second quarter of this year, with the new 17,000-square-meter (182,986-square-foot) facility expected to be operational in 2024.
The new facility is expected to create more than 100 jobs, and join UCB's network of sites in Belgium as well as China, Japan, Switzerland, Germany, the United States, and the United Kingdom. UCB bases gene therapy teams in Braine and Leuven, Belgium, as well as in Boston and Durham, NC.
UCB also said the new facility would be environmentally sustainable, with Building Research Establishment Environmental Assessment Method certification and a commitment from the company to drastically reduce both resource consumption and waste production.
“Upon completion of our new gene therapy development and clinical manufacturing facility, UCB will have complete ownership and control of its chemistry, manufacturing and controls (CMC) capabilities, this will enable agility, flexibility, unparalleled product and process understanding, scalability, and yield improvements, all translating to a significant competitive advantage for UCB and a smart investment in the technologically evolving gene therapy landscape,” said Kirsten Lund-Jurgensen, PhD, UCB's Executive Vice President and Head of Supply & Technology Solutions. 6
Synthego Grows Cell, Gene Therapy Capabilities with $200M Financing
Synthego's first phase of development, CEO and cofounder Paul Dabrowski recently explained, focused on developing tools and technologies that made CRISPR gene editing accessible to researchers. In the second phase, Synthego brought those tools and tech into the clinic, helping with validation, target ID, discovery, and general workflow.
“The third part of our mission is to make biologically engineered cell and gene therapies accessible to all patients,” Dabrowski said. “We've built out the tools and the platform. We've demonstrated the value in the clinical context, and now we're starting to move into that last phase. It all builds on each other.” 7
The Series E accounts for nearly half of the $450 million or more in total financing that the provider of genome engineering products and services has raised since it was founded in 2012 by Dabrowski and his brother Michael.
Synthego says proceeds from the latest financing will accelerate its creation of a cell and gene therapy discovery and development “ecosystem” intended to help researchers accelerate and simplify the translation of research discoveries into new therapeutics for serious diseases.
FDA Removes Hold on Selecta Methylmalonic Acidemia Program
Selecta expects to start its Phase I clinical trial of SEL-302 in the second half of 2022.
“We look forward to starting our Phase I clinical trial expeditiously and to bring hope to those patients and families seeking a potentially durable and lifelong treatment for this terrible disease,” said Carsten Brunn, PhD, Selecta's president and CEO. 8
SEL-302 consists of MMA-101, an adeno-associated virus serotype 8 (AAV8) vector-based gene therapy originally developed by Asklepios BioPharmaceutical (AskBio), and Selecta's immune tolerance platform ImmTOR™, which is designed to enable antigen-specific immunity and mitigate unwanted immune responses. According to Selecta, ImmTOR has the potential to induce AAV vector-specific immune tolerance, reducing the severity of the body's immune response to AAV gene therapies, and enabling repeat administrations.
Last year, Selecta acquired for an undisclosed price exclusive rights to the program from AskBio. At the time, AskBio disclosed that an IND submission for the program was being delayed until at least the fourth quarter of 2021 due to a third-party manufacturing issue.
The FDA issued the clinical hold in November 2021 on Selecta's Phase I/II trial, with the agency citing its needs to obtain additional information on the CMC related to MMA-101. The FDA raised no outstanding clinical or preclinical questions, and the trial had not yet been initiated, Selecta said. The company held off dosing patients until the hold was resolved.