Abstract
Lilly said the deal will also broaden its commitment to address otherwise fatal genetic forms of neurodegenerative disease through new modalities.
Prevail's lead clinical-phase gene therapies are PR001, a treatment for Parkinson's disease with GBA1 mutations and neuronopathic Gaucher disease, and PR006, a treatment for frontotemporal dementia with GRN mutations.
Prevail has also developed preclinical candidates that include PR004, a treatment for specific synucleinopathies, as well as potential gene therapies for Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and other neurodegenerative disorders.
“The acquisition of Prevail will bring critical technology and highly skilled teams to complement our existing expertise at Lilly, as we build a new gene therapy program anchored by well-researched assets,” said Mark Mintun, MD, vice president of pain and neurodegeneration research at Lilly. 1
Lilly plans to acquire all outstanding shares of Prevail for $22.50 per share cash (∼$880 million)—an 80% premium from the December 14 closing price of $12.50—plus one nontradeable contingent value right (CVR). The CVR entitles Prevail stockholders to up to an additional $4 per share cash (∼$160 million) payable upon the first commercial approval of a Prevail product in the United States, Japan, United Kingdom, Germany, France, Italy, or Spain. After December 31, 2024, however, the value of the CVR will drop by ∼8.3 cents per month until December 1, 2028, when the CVR expires.
The deal is expected to close in the first quarter of 2021, subject to customary closing conditions, including regulatory approvals and the tender of a majority of outstanding shares of Prevail's common stock.
GENE-EDITED THERAPY SHOWS POSITIVE RESULTS FOR SICKLE-CELL DISEASE AND BETA THALASSEMIA
According to data published in the New England Journal of Medicine (NEJM) and presented on December 6 at the annual American Society of Hematology (ASH) Meeting and Exposition, all seven patients with transfusion-dependent beta thalassemia (TDT)—including three who have either a severe or b0/b0 genotype—were transfusion independent at the last follow-up in the TDT trial, which is known as CLIMB-111 (NCT03655678). 2
In another trial assessing CTX001 in SCD, CLIMB-121 (NCT03745287), all three patients with SCD were free of vaso-occlusive crises from infusion with the therapy through last follow-up. These include Victoria Gray, an African American SCD patient from Mississippi who has been followed for the past 18 months in a series of National Public Radio stories. 2
“We are pleased with the data presented at ASH, which demonstrate potential benefit and durability among a larger population of patients with transfusion-dependent beta thalassemia and sickle cell disease,” CRISPR Therapeutics CEO Samarth Kulkarni, PhD, said in a statement. 3
The new data came more than a year after CRISPR Therapeutics and Vertex released preliminary mostly positive safety and efficacy data from the first two patients enrolled in the two trials evaluating CTX001, an autologous ex vivo CRISPR-Cas9 gene-edited therapy designed as a one-time curative therapy for both TDT and SCD.
Through CTX001, a patient's hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF) in red blood cells. This gene, active during gestation, is naturally shut down shortly after birth. CTX001 restores expression by interfering with an upstream regulatory pathway that typically keeps the HbF gene dormant.
BAYER BUILDS “PLATFORM” FOR GENE THERAPY GROWTH
The C> platform will offer expertise in research and preclinical development; chemistry, manufacturing, and controls (CMC); clinical development; commercial development; strategy implementation; and project management. By orchestrating operations from research to commercial launch, the platform aims to help Bayer generate and maintain a sustainable pipeline.
“With the establishment of Bayer's own C> Platform, our company will propel its presence in this area. This will complement our existing C> pipeline which already includes five advanced assets with at least three investigational new drugs annually for the next years,” said Stefan Oelrich, member of Bayer's board of management and president of the company's pharmaceuticals division. 4
Bayer's C> platform follows recent efforts to position the company as a leader in cell and gene therapy.
In October, Bayer committed up to $4 billion—half of that in upfront cash—to acquire gene therapy developer Asklepios BioPharmaceutical (AskBio), a deal that brings to Bayer a contract development and manufacturing organization intended to enable future partnerships centered on AAV gene therapies. Bayer also committed up to $600 million in 2019 toward buying BlueRock Therapeutics, which develops engineered cell therapies for neurology, cardiology, and immunology disorders using its own induced pluripotent stem cell platform. Both companies continue to operate independently within Bayer.
Bayer has named a member of its executive leadership team, Wolfram Carius, as head of the C> platform, among his duties since being named in October as executive vice president, cell and gene therapy.
PASSAGE BIO'S NEW LABORATORY ENABLES IN-HOUSE CMC
The new laboratory, slated to open in the second quarter of 2021, will support both viral vector manufacturing and clinical development. The laboratory will initially focus on analytical capabilities, clinical assay development and validation, biomarker assay validation, and clinical product testing.
“Investing in an in-house CMC lab puts us in greater control of our vector manufacturing and quality control processes as we advance our gene therapy product candidates into the clinic in 2021 and beyond,” said Bruce Goldsmith, PhD, president and CEO of Passage Bio. 5
The company has agreed to lease ∼62,000 square feet (∼5,760 square meters) at Princeton West, a 1.2 million-square-foot (111,484 square meter), multipurpose research and development and biologic/pharmaceutical manufacturing campus. Passage Bio plans to create >20 new positions at the new laboratory in 2021.
Passage Bio said the CMC laboratory is a key component of its strategy of expanding internal manufacturing capabilities, to support its lead gene therapy programs as they advance into the clinic and toward commercialization.
The new laboratory also complements the opening last year of Passage Bio's dedicated current Good Manufacturing Practices (cGMP) manufacturing suite at Catalent's Harmans/BWI campus in Harmans, MD. According to Passage Bio, the Harmans and Princeton West facilities serve as the foundation of an integrated manufacturing supply chain that will enable the company to support clinical trials for multiple gene therapy programs worldwide.
NEUROGENE CLOSES $115M SERIES B TO TREAT RARE NEUROLOGICAL DISEASES
Proceeds from the financing will advance Neurogene's portfolio of multiple gene therapy programs into the clinic, accelerate investment in its technology platform addressing key limitations in conventional gene therapy, as well as in novel gene therapy product designs; and build out its AAV vector GMP manufacturing capabilities.
“We believe our focus on improved product design, innovative technology, cutting-edge vector manufacturing and premier analytics will help fulfill the potential of genetic treatments,” said Neurogene Founder and CEO Rachel McMinn, PhD. 6
EcoR1 Capital led the financing round, with participation from existing investors Redmile Group, Samsara BioCapital, Cormorant Asset Management, and an undisclosed leading health care investment fund. New investors included funds and accounts managed by BlackRock, funds managed by Janus Henderson Investors, Casdin Capital, Avidity Partners, Ascendant BioCapital, Arrowmark Partners, and Alexandria Venture Investments.
TAYSHA PLANS $75M cGMP MANUFACTURING FACILITY
Taysha said it will invest $75 million and create ∼200 jobs over 2.5 years to build out development, analytical, manufacturing, and quality control testing capability for its portfolio of gene therapies. The facility's multiple production suites are expected to be fully commissioned by 2023.
“With our outstanding team of experts leading the charge, we expect this facility will serve as a center of excellence for gene therapy development, from preclinical studies through commercialization, and will further our leadership position in gene therapy as well as support our next phase of growth,” said Taysha president, founder, and CEO RA Session II. 7
The facility will establish 2,000 L of capacity and will be designed to support all aspects of scalable manufacturing of gene therapy material for Taysha's pipeline and to meet the foreseeable clinical and commercial demand. This internal capability will bolster the current capacity from Taysha's existing manufacturing collaborations with Catalent and The University of Texas (UT) Southwestern's gene therapy program.
The facility is part of Taysha's three-pillar manufacturing strategy, designed to meet the supply needs of multiple clinical programs emerging from its gene therapy pipeline as the company anticipates having four open investigational new drug applications in 2021.
In return for its planned investment, Taysha will receive up to $9.4 million in state and local economic incentives.
THERMO FISHER CONSTRUCTING MANUFACTURING SITE IN CARLSBAD, CA
The 67,000-square-foot facility will rise on the Carlsbad campus of Thermo Fisher's center of excellence for life sciences solutions. The facility, expected to be completed in the first half of 2021, will feature single use equipment with up to 1,000 L scale, digital connectivity, and data visibility for operator training and operational efficiencies.
The new commercial facility will add ∼150 jobs over the next 12 months, Thermo Fisher said.
“Our new state-of-the art site will not only tackle the supply bottleneck for our customers, but also uniquely positions us to deliver robust, end-to-end cell and gene therapy capabilities,” said Mike Shafer, Thermo Fisher's senior vice president and president, pharma services. “Our customers can leverage our deep industry knowledge and expertise in the complexities of cell and gene therapy at all points along the pathway to commercialization—from research and preclinical development to clinical and now expanded commercial and supply chain services.” 8
The Carlsbad facility joins Thermo Fisher cell and gene therapy services facilities that integrate the company's development and manufacturing capabilities. Thermo Fisher provides viral vector services at three Massachusetts sites (Cambridge, Lexington, and Plainville) as well as Alachua, FL. The company also runs a new cell therapy manufacturing facility in Princeton, NJ, and a new dedicated cryocenter in Weil am Rhein, Germany, that is designed to provide specialized cryogenic and cold chain supply chain services to support clinical trials across Europe and globally.
JANSSEN BUYS RIGHTS TO LATE-STAGE AGE-RELATED MACULAR DEGENERATION GENE THERAPY
HMR59 is a one-time outpatient intravitreal injection designed to help preserve vision in patients with geographic atrophy by increasing the ability of retina cells to make a soluble form of CD59, helping to prevent further damage to the retina and preserve vision.
“Our aim with this novel, single-administration gene therapy is to use our development expertise and deep heritage in vision care to help improve patient outcomes by intervening early, halting the progression to blindness, and preserving more years of sight,” said James F. List, MD, PhD, Global Therapeutic Area Head, Cardiovascular & Metabolism, Janssen Research & Development. 9
Hemera has completed a Phase I trial (NCT03144999) evaluating HMR59 in patients with geographic atrophy. A second Phase I study (NCT03585556) assessing HMR59 in patients with wet-AMD is currently conducting follow-up visits to evaluate long-term safety.
ATSENA RAISES $55M
Atsena has exclusively licensed the rights to the LCA1 gene therapy from Sanofi, which originally licensed it from University of Florida.
The financing will also enable Atsena to expand its team to support research and development of novel gene therapies. Those efforts include advancement of two preclinical programs in inherited retinal diseases toward the clinic, and development of the company's AAV technology platform.
“The Series A financing provides financial runway to reach the key inflection point of reading out efficacy data from our LCA1 clinical trial,” said Atsena CEO Patrick Ritschel, MBA. “While we continue expeditiously advancing this trial and our preclinical programs, we are excited to accelerate our growth as a leading ophthalmic gene therapy company.” 10
Sofinnova Investments led the financing, with participation from additional new investors Abingworth and Lightstone Ventures. Founding investors Hatteras Venture Partners and the Foundation Fighting Blindness' RD Fund, also participated in the round, along with existing investors Osage University Partners, University of Florida, and Manning Family Foundation.
Sarah Bhagat, PhD, partner at Sofinnova; Jackie Grant, PhD, principal at Abingworth; and Jason Lettmann, general partner at Lightstone, will join Atsena's board of directors.