Three Rare Disease Deals Kick Off Annual J.P. Morgan Healthcare Confab in SF

Two deals focus on gene editing—Pfizer’s $1.4 billion collaboration with Beam Therapeutics, Bayer’s $1 billion plus deal with Mammoth Biosciences—while Acadia Pharmaceuticals’ $967 million deal with Stoke Therapeutics is focused on RNA-based treatments.

Pfizer entered a four-year, exclusive research collaboration with Beam Therapeutics, valued at up to $1.4 billion, to advance Beam’s novel in vivo base editing programs for three targets for rare genetic diseases of the liver, muscle, and central nervous system. 

“We have a strong history in developing gene replacement therapies for rare diseases, and we see this collaboration with Beam as an opportunity to advance the next generation of gene editing therapies – an exciting scientific frontier – potentially leading to transformation for people living with rare genetic diseases,” said Mikael Dolsten, chief scientific officer and president, Worldwide Research, Development and Medical of Pfizer.

The deal combines Pfizer’s expertise global drug development and mRNA, lipid nanoparticles (LNPs), and gene therapy with Beam’s base editing and mRNA/LNP delivery technologies. Beam’s proprietary base editing technologies are designed to enable a new class of precision genetic medicines that target a single base in the genome without making a double-stranded break in the DNA. This approach aims to create a more precise and efficient edit compared to traditional gene editing methods, which operate by creating targeted double-stranded breaks in the DNA, resulting in potential challenges associated with

“Our leading platform for precision genetic medicine has greatly evolved over the last few years, and we are committed to ensuring the broadest reach of these potentially life-changing technologies,” said John Evans, CEO of Beam. “This collaboration will provide a unique opportunity to create potentially transformative base editing programs for indications with critical unmet needs, leveraging our proprietary base editing technology and expanding delivery capabilities.”

Under the terms of their agreement, Beam will conduct all research activities through development candidate selection for three undisclosed targets, which are not included in Beam’s existing programs. Pfizer may opt in to exclusive, worldwide licenses to each development candidate, after which it will be responsible for all development activities, as well as potential regulatory approvals and commercialization, for each such candidate. Beam has a right to opt in, at the end of phase 1/2 studies, upon the payment of an option exercise fee, to a global co-development and co-commercialization agreement with respect to one program licensed under the collaboration pursuant to which Pfizer and Beam would share net profits as well as development and commercialization costs in a 65 percent Pfizer and 35 percent Beam.

Beam will receive an upfront payment of $300 million and, assuming Pfizer exercises its opt-in license rights for all three targets, is eligible for development, regulatory and commercial milestone payments for potential total deal consideration of up to $1.4 billion. Beam is also eligible to receive royalties on global net sales for each licensed program. The collaboration has an initial term of four years and may be extended up to one additional year.

Big Pharma Bayer entered a strategic collaboration and option agreement with Mammoth Biosciences for the use of Mammoth’s ultra-small CRISPR systems to develop in vivo gene editing therapies.

Bayer believes Mammoth’s gene editing technology will significantly enhance its efforts to develop transformative therapies for patients faster and strengthen the company’s recently established new cell and gene therapy platform. Under the terms of the agreement the two companies will start their collaboration with a focus on liver-targeted diseases.

“Bringing together Mammoth’s novel CRISPR systems with our existing gene augmentation and our induced pluripotent stem cell (iPSC) platforms will allow us to unleash the full potential of our cell and gene therapy strategy,” said Stefan Oelrich, member of the Board of Management, Bayer and president of the Bayer’s Pharmaceuticals Division.

Gene editing serves as a key enabler for cell therapies when used outside the living body (ex vivo) and allows therapeutic targeting of a wide range of genetic diseases with a high unmet medical need when used inside the living body (in vivo). Mammoth Biosciences’ proprietary toolkit of ultra-small Cas enzymes, including Cas14 and Casɸ, allows for expanded gene editing to be combined with targeted systemic delivery. Under the agreement, Bayer gains access to this novel gene editing technology, which offers the potential of an advanced in vivo applicability due to the ultra-compact size of these novel CRISPR systems.

Under the terms of the agreement, Mammoth Biosciences will receive an upfront payment of $40 million and is eligible to receive target option exercise fees as well as potential future payments in the magnitude of more than $1 billion upon successful achievement of certain research, development, and commercial milestones across five preselected in vivo indications with a first focus on liver-targeted diseases. In addition, Bayer will pay research funding and tiered royalties up to low double-digit percentage of net sales. The companies are also exploring work on ex vivo projects on a nonexclusive basis.

“This joint effort has the potential to benefit patients by developing CRISPR-based approaches for the clinic with the appropriate urgency, while ensuring scientific excellence and safety,” said Peter Nell, chief business officer and head of Therapeutic Strategy at Mammoth.

Finally, Acadia Pharmaceuticals, which has focused on more common neurodevelopmental disorders, entered a collaboration with Stoke Therapeutics to discover, develop, and commercialize novel RNA-based medicines for the potential treatment of severe and rare genetic neurodevelopmental diseases of the central nervous system, including SYNGAP1 syndrome, Rett syndrome (MECP2), and an undisclosed neurodevelopmental target of mutual interest.

Stoke has initially applied its research platform TANGO (Targeted Augmentation of Nuclear Gene Output) to diseases in which one copy of a gene functions normally and the other is mutated, also called haploinsufficiencies. In these cases, the mutated gene does not produce its share of protein, resulting in disease. Using the TANGO approach and an understanding of RNA science, Stoke researchers design antisense oligonucleotides (ASOs) that bind to pre-mRNA and help the functional genes produce more protein. TANGO aims to restore missing proteins by increasing – or stoking – protein output from healthy genes, thus compensating for the mutant copy of the gene.

“Stoke’s RNA-based approach to upregulating healthy proteins offers very exciting new possibilities for the treatment of rare, neurodevelopmental diseases like Rett syndrome,” said Steve Davis, CEO of Acadia Pharmaceuticals. “Combining Stoke’s capabilities with Acadia’s extensive expertise in neuroscience drug development and commercialization enables us to push harder and faster in exploring some of the new frontiers in rare central nervous system disorders.”

Under the terms of the agreement, Stoke will receive an upfront payment of $60 million from Acadia and is eligible to receive up to $907 million in milestones as well as royalties on future sales. For the SYNGAP1 program, the two companies will jointly share global research, development and commercialization responsibilities and share 50/50 in all worldwide costs and future profits. In addition, Stoke is eligible to receive potential development, regulatory, first commercial sales and sales milestones. For the Rett syndrome (MECP2) and the undisclosed neurodevelopmental program, Stoke will lead research and pre-clinical development activities, while Acadia will lead clinical development and commercialization activities. Acadia will fully fund the research and preclinical development activities related to these two targets and Stoke is eligible to receive potential development, regulatory, first commercial sales and sales milestones as well as tiered royalty payments on worldwide sales starting in the mid-single digit range and escalating to the mid-teens based on revenue levels.

“Rett syndrome and SYNGAP1 syndrome are two severe, intractable diseases of the central nervous system and both are associated with developmental delays, motor function loss, autism, seizures and other comorbidities that impact quality of life for patients and their families,” said Edward Kaye, CEO of Stoke Therapeutics. “With Acadia, we believe we have a significant opportunity to improve treatment options by delivering new disease-modifying medicines to people who need them.”