Feliza Mirasol is the science editor for 

Feliza Mirasol

On Dec. 18, 2023, Andelyn Biosciences, a contract development and manufacturing organization, announced that Ultragenyx has selected it to perform late-stage process performance qualification (PPQ) manufacturing of UX111, Ultragenyx’s investigational gene therapy under development for the potential treatment of Sanfilippo Syndrome (MPS IIIA).

MPS IIIA is related to a deficiency of the sulfamidase enzyme. This deficiency is responsible for abnormal accumulation of glycosaminoglycans in the brain and throughout the body, which leads to progressive cell damage and neurodevelopmental and physical decline, according to a company press release.

UX111 is a one-time intravenous infusion that uses a self-complementary adeno-associated virus 9 (AAV9) vector to deliver a functional copy of the N-sulfoglucosamine sulfohydrolase (SGSH) gene to central nervous system cells and peripheral organs. The gene therapy candidate has received regenerative medicine advanced therapy, fast track, rare pediatric disease, and orphan drug designations in the United States, and priority medicine and orphan medicinal product designations in the European Union.

Currently, Andelyn has been manufacturing good manufacturing practice supply of UX111 for patient dosing. With this new agreement, it will begin manufacturing PPQ batches that may be required for future regulatory filings at its Columbus, Ohio, facility.

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Andelyn Biosciences has been selected by Ultragenyx to manufacture UX111, that company’s gene therapy for treating Sanfilippo Syndrome.

Ultragenyx Picks Andelyn Biosciences to Manufacture Novel Gene Therapy for Sanfilippo Syndrome

France-based Depixus, a life science technology company specializing in magnetic force spectroscopy-based technology, has formed a collaboration with Daiichi Sankyo under which Depixus will use its MAGNA technology to accelerate an RNA-targeted drug discovery program.

According to a Dec. 12, 2023 company press release, MAGNA enables high-throughput analysis of dynamic biomolecular interactions in real time with single-molecule resolution. Used on RNA, this analysis can reveal how small molecules and proteins bind to three-dimensional RNA structures. The technology can furthermore provide valuable information about binding kinetics and mode of action.

Under the collaboration, Daiichi Sankyo’s team will use MAGNA to explore the interactions of lead molecules with a number of undisclosed RNA targets. The data from these studies will inform hit-to-lead selection and lead optimization. Daiichi Sankyo anticipates that the technology will accelerate and de-risk its RNA-targeted therapeutics pipeline as candidates in that pipeline move towards the clinic.

In comparison with other analytical techniques that provide static snapshots, averaged bulk data, or indirect measurements of molecular interactions, MAGNA generates direct readouts of dynamic binding and conformational changes from thousands of individual molecules, according to Depixus. The technology can be used to study a wide range of molecular interactions, such as interactions between DNA, RNA, proteins, and small-molecule therapeutics. It can also have applications in areas such as RNA-targeted drug discovery, protein–protein interactions, proteolysis targeting chimeras, and molecular glues, the company stated in its press release.

“The world of RNA-targeted therapeutics has huge potential, yet is largely unexplored. We are excited to partner with Daiichi Sankyo to put MAGNA to work in pursuit of our shared vision of creating novel medicines to treat diseases with high unmet need,” said Gordon Hamilton, CEO of Depixus, in the press release.

Under a collaboration, Daiichi Sankyo and Depixus will use Depixus’ MAGNA technology to accelerate drug discovery efforts of RNA-targeted therapeutics.

Daiichi Sankyo Partners with Depixus to Accelerate RNA-Targeted Drug Discovery

US-based NightHawk Biosciences (NightHawk) announced in December 2023 that it will pivot to focus solely on being a contract development and manufacturing organization (CDMO), specializing in large-molecule biomanufacturing and development. The changeover follows the divestiture of certain non-core assets, as well as the separating out of its Elusys subsidiary, which the newly named entity will retain.

NightHawk will instead focus on its growing business, Scorpius BioManufacturing, with the changeover. On its first full year of operation Scorpus is expected to generate over $20 million in revenue. With this shift into a pure-play CDMO, NightHawk has eliminated most of its R&D and associated expenses to focus resources on growing and expanding Scorpius.

The divested assets will be acquired by a private company established by NightHawk’s CEO, Jeff Wolf, which will assume Elusys’ contracted financial commitments, currently estimated at over $40 million. Under the transaction, the private company will provide an upfront payment of $500,000, a note for $2.25 million (convertible into shares of NightHawk’s common stock), and royalties of 3% on all of Elusys’ gross sales until June 30, 2031, according to a Dec. 12, 2023 company press release.

“There is a significant shortage of clinical-scale biologic manufacturing capacity within the industry as a result of growing demand for large molecule CDMO services. In turn, this has led to significant M&A [merger and acquisition] activity within the sector. We believe we are extremely well positioned to capitalize on these trends … ” said Jeff Wolf, CEO of NightHawk and Elusys, in the press release.

“The divestiture of our non-core assets enables NightHawk to focus its resources on growing its Scorpius subsidiary and will result in the immediate elimination of approximately $40 million of contractual obligations and reduction of over $13 million in operating expenses per year,” said John Prendergast, NightHawk’s lead director, in the press release. “Moreover, NightHawk will receive an upfront cash payment, as well as a $2.25 million convertible loan and at least $5 million in royalties on future Elusys gross payment receipts for approximately 7.5 years.”

Following the divestiture of its Elusys subsidiary and other non-core assets, NightHawk Biosciences will transform into a pure-play large-molecule CDMO. 

NightHawk Biosciences Shifts into a Pure-Play Large-Molecule CDMO 

Bristol Myers Squibb and SystImmune, a clinical-stage biopharmaceutical company, have entered into an exclusive license and collaboration agreement potentially worth up to $8.4 billion to jointly develop and commercialize SystImmune’s BL-B01D1, an epidermal growth factor receptor and human epidermal growth factor receptor 3 (EGFRxHER3) bispecific antibody-drug conjugate (ADC), in the United States.

Under the agreement, SystImmune will receive an $800 million upfront payment from Bristol Myers Squibb. The company can also receive up to $500 million in contingent near-term payments. SystImmune is further eligible to receive additional payments of up to $7.1 billion upon achieving certain development, regulatory, and sales performance milestones.

Also under the agreement, SystImmune will retain exclusive development and commercialization rights to BL-B01D1, through its affiliates, in mainland China. Bristol Myers Squibb will receive a royalty on net sales in that market. Outside the US and mainland China, SystImmune will receive a tiered royalty on net sales.

SystImmune (through its affiliates) will have sole responsibility for the development, commercialization, and manufacturing in Mainland China and will be responsible for manufacturing certain drug supplies for use outside of Mainland China. Bristol Myers Squibb, meanwhile, will assume sole responsibility for development and commercialization in the rest of the world.

BL-B01D1 is currently in a global multi-center Phase I study in metastatic or unresectable non-small cell lung cancer (NSCLC). Data from earlier clinical studies demonstrated promising anti-tumor activity in patients with a range of solid tumors, including NSCLC and breast cancer, who had progressed after standard of care treatments, according to a Dec. 11, 2023 company press release.

“Recent BL-B01D1 trials have shown broad potential across different solid tumors as well as a manageable safety profile,” said Yi Zhu, CEO, SystImmune, in the press release. “We have long admired Bristol Myers Squibb’s global clinical development and commercialization capabilities in oncology, and this strategic collaboration is an exciting step forward in delivering potential antitumor medicines to patients worldwide. We look forward to a productive partnership.”

“Our collaboration with SystImmune allows us to strengthen our leadership in oncology and is consistent with our strategy to diversify beyond immuno-oncology to transform patient care,” said Samit Hirawat, executive vice-president, chief medical officer, Drug Development, Bristol Myers Squibb, in the press release. “SystImmune’s BL-B01D1 adds yet another ADC to our diverse pipeline and helps strengthen our approach of matching the most appropriate therapeutic modality to areas of unmet medical need across solid tumor oncology. We look forward to working with SystImmune to advance BL-B01D1 in hopes of offering a differentiated treatment option for patients in need.”

Bristol Myers Squibb and SystImmune plan to co-develop and co-commercialize lead ADC candidate for cancer treatment in US.

Bristol Myers Squibb and SystImmune Enter Global ADC Collaboration Worth Potentially up to $8.4 Billion 

On Dec. 11, 2023, RoslinCT, a UK-based cell and gene therapy contract development and manufacturing organization (CDMO), announced that it will manufacture Vertex Pharmaceuticals’ Casgevy (exagamglogene autotemcel [exa-cel]), a recently approved clustered regularly interspaced short palindromic repeats (CRISPR)-based gene therapy for treating sickle cell disease (SCD) and β thalassemia.

FDA approved Casgevy on Dec. 8, 2023 for treating SCD in patients 12 years and older in the United States, and the United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA) approved it for treating SCD and transfusion-dependent β thalassemia (TDT) in the UK on Nov. 16, 2023 (1). The gene therapy is also under review by FDA for treating TDT in the US, with a decision expected by March 20, 2024. In its press release, FDA stated that Casgevy is “the first FDA-approved treatment to utilize a type of novel genome editing technology, signaling an innovative advancement in the field of gene therapy.” CRISPR technology, being so new, 

led to quite a stir when the MHRA approved Casgevy in November

RoslinCT has been working with Vertex on an adaptive basis while Vertex moved through clinical and regulatory development of Casgevy. The collaboration has positioned RoslinRT in a place to support the manufacturing of a broad range of highly complex autologous and allogeneic cell therapies beyond Casgevy. The company runs manufacturing facilities in Edinburgh, Scotland and Boston, Mass., which are purpose-built for cell therapy products.

“We are delighted that patients in both the US and UK are now able to access this transformational medicine. This approval by [FDA] further demonstrates our … capabilities in development, support, and manufactur[ing] … cell and gene therapies such as Casgevy. We are proud to have supported Vertex in achieving this significant milestone and look forward to supporting their team as they bring the first approved CRISPR treatment to patients in the US, UK, and beyond.”

In addition to Casgevy, FDA also approved bluebird bio’s Lyfgenia (lovotibeglogene autotemcel) for treating SCD in patients 12 years and older on Dec. 8, 2023. Lyfgenia uses a lentiviral vector for genetic modification.

“Sickle cell disease is a rare, debilitating, and life-threatening blood disorder with significant unmet need, and we are excited to advance the field especially for individuals whose lives have been severely disrupted by the disease by approving two cell-based gene therapies today,” said Nicole Verdun, director of the Office of Therapeutic Products within FDA’s Center for Biologics Evaluation and Research (CBER), in the agency’s press release. “Gene therapy holds the promise of delivering more targeted and effective treatments, especially for individuals with rare diseases where the current treatment options are limited.”

“These approvals represent an important medical advance with the use of innovative cell-based gene therapies to target potentially devastating diseases and improve public health,” said Peter Marks, director of CBER, in the release. “Today’s actions follow rigorous evaluations of the scientific and clinical data needed to support approval, reflecting [FDA’s] commitment to facilitating development of safe and effective treatments for conditions with severe impacts on human health.”

FDA granted both Casgevy and Lyfgenia priority review, orphan drug, fast track, and regenerative medicine advanced therapy designations.

1. Vertex Pharmaceuticals. Vertex and CRISPR Therapeutics Announce Authorization of the First CRISPR/Cas9 Gene-Edited Therapy, CASGEVY (exagamglogene autotemcel), by the United Kingdom MHRA for the Treatment of Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia. Press Release, Nov. 16, 2023.

RoslinCT will manufacture Vertex Pharmaceuticals’ CRISPR-based gene therapy, Casgevy, recently approved for treating sickle cell disease and β thalassemia.

RoslinCT to Manufacture CRISPR-Based Gene Therapy Casgevy

On Dec. 11, 2023, Sanofi announced that it will be terminating its licensing agreement with Maze Therapeutics for the development of a rare disease drug candidate. Sanofi released a statement expressing its disappointment with the Federal Trade Commission’s (FTC’s) same-day announcement that the agency is seeking a preliminary injunction against the proposed licensing agreement between Sanofi and Maze. Sanofi had announced the licensing agreement on May 1, 2023 for MZE001, Maze’s glycogen synthase 1 (GYS1) inhibitor program, which completed Phase I and is in development for Pompe Disease, a rare, inherited disorder that disables the heart and skeletal muscles and is often fatal.

In its statement, Sanofi said, “We respectfully disagree with the action by the FTC which also delays potential advancements that could impact the lives of patients. The Maze partnership was designed to apply Sanofi’s resources, knowledge, and expertise to accelerate the development of MZE001, with the hope of addressing unmet medical needs for this devastating condition. The delay associated with a long litigation has led Sanofi to conclude that it would not be in the best interests of patients to contest this litigation, and Sanofi will therefore be terminating the agreement with Maze in accordance with its terms. Sanofi remains committed to address the Pompe patient community’s unmet needs.”

FTC sought to block the proposed deal, issuing an administrative complaint and authorizing a lawsuit in federal court that alleged the deal, valued at up to $755 million, would eliminate a competitor that could challenge Sanofi’s monopoly in the Pompe disease therapy market. FTC stated in its press release that “Sanofi is a monopoly supplier of Food and Drug Administration (FDA) approved drugs to treat the disease.”

According to FTC’s complaint, MZE001 “threatens to undermine this monopoly as the first oral medication available for Pompe disease patients.” The complaint also names Genzyme, Sanofi’s subsidiary, which was seeking to license the drug from Maze. In its complaint, FTC alleges that the transaction would protect Sanofi’s monopoly and eliminate competition between Sanofi and Maze to develop new Pompe drugs. FTC cautioned in its complaint that this deal would deny patients and doctors the benefits of competition, including lower prices and greater innovation.

“Sanofi’s acquisition of Maze’s Pompe disease drug threatens to deprive patients of a new, innovative treatment and maintain a status quo of exorbitant pricing for essential life-saving medicines,” said Nate Soderstrom, acting deputy director of FTC’s Bureau of Competition, in the agency press release. “The FTC is challenging Sanofi’s deal with Maze because it’s critical that patients and doctors have access to innovative, affordable treatment options.”

In its complaint, FTC also pointed out that “Sanofi singled out MZE001 as a significant threat to its lucrative Pompe monopoly shortly after Maze publicly revealed its development plans in 2021. MZE001 threatens to not only capture substantial market share from Sanofi, but also potentially replace Sanofi’s treatments as the standard of care for Pompe disease altogether.”

In addition to the administrative complaint, FTC has authorized its staff to seek a temporary restraining order and preliminary injunction in federal district court with the aim of preventing Sanofi from acquiring MZE001, pending the agency’s administrative proceeding. FTC’s federal court complaint will be filed in the US District Court for the District of Massachusetts, and a public version of the complaint will be made available at a later time, according to the agency.

Sanofi has issued a statement expressing its disappointment with FTC’s decision to block an exclusive licensing agreement with Maze Therapeutics for a rare disease drug candidate.