BioByte 086: Recursion and Exscientia join forces, music as a brain-computer interface, microglial rescue patterns in neurodegenerative disease, and ribonucleoprotein granules and protein synthesis
BioByte 086: Recursion and Exscientia join forces, music as a brain-computer interface, microglial rescue patterns in neurodegenerative disease, and ribonucleoprotein granules and protein synthesis
Welcome to Decoding Bio’s BioByte: each week our writing collective highlight notable news—from the latest scientific papers to the latest funding rounds—and everything in between. All in one place.
Hot off the press – this week, Recursion Pharmaceuticals and Exscientia have announced a merger. The combined entity will use the Recursion name and will be led by Recursion co-founder and CEO Chris Gibson, with Exscientia’s interim CEO, David Hallett, leading the company’s science function. Recursion is reportedly spending $688 million in the all-stock deal, resulting in the combined pipeline:
As always, we’ve got you covered here at Decoding Bio. Dive in for more on this transaction, and other biotech happenings this week!
What we read
Two Brothers, a Big Biotech Bet and an $8 Billion Payout [Peter Rudegeair, WSJ, April 2024 ]
This story on the WSJ dives into Baker Brothers’ investment in Seagen. In 2023, Pfizer acquired Seagen for $43B. The hedge fund firm Baker Bros. advisors, run by Felix and Julian Baker, held nearly 25% stake and reaped about $10B in proceeds.
The hedge fund firm manages around $22B (FY23), only employs 18 investors and makes extremely concentrated investments. Seagen was about half of the value of its publicly disclosed stockholdings before the acquisition. This is in contrast to some of the most sought after hedge funds which employ huge numbers of traders which avoid concentrated bets. Concentration, especially in biotech stocks, comes with high volatility. The firm was down 19% and 25% in 2022 and 2021 respectively.
Felix, an MD PhD, and Julian, a PE investor at Credit Suisse, partnered in 1994 to make biotech investments for the Tish family and launched Baker Bros. in 2000. In 2003, Baker Bros. bought $16M of Seagen preferred stock. Over the years, the firm loaded up on stock – at one point owning almost one third of the company.
Felix assumed the role of chairman upon Co-Founder Clay Siegall’s resignation. A few months after a meeting at the JPM Healthcare Conference with Pfizer, the companies unveiled the $43B deal. Baker Bros. gave most of the proceeds back to investors.
Microglia rescue neurons from aggregate-induced neuronal dysfunction and death through tunneling nanotubes [Sheiblech et al., Neuron, July 2024]
A paper out in Neuron investigates how microglia interact with neurons to alleviate the burden of toxic protein aggregates (α-synuclein, involved in Parkinson’s and tau, involved in Alzheimer’s) in neurodegenerative diseases. Microglia play a crucial role in neurodegenerative diseases by recognizing, engulfing, and clearing protein aggregates, thereby maintaining neural homeostasis and mitigating disease progression. The conventional view that microglia only encounter these aggregates after neuronal death is challenged, instead proposing that microglia can actively extract aggregates from living neurons via tunneling nanotubes (TNTs).
Using a combination of primary cell cultures, advanced imaging techniques, electrophysiology, and transcriptomics, the authors demonstrated that microglia form TNTs with neurons containing these aggregates. These connections facilitate the transfer of aggregates from neurons to microglia for degradation, as well as the donation of healthy mitochondria from microglia to affected neurons. This bidirectional exchange reduces oxidative stress and improves neuronal health and function. The process is regulated by Rac-PAK signaling pathways.
Importantly, the study found that disease-associated mutations in LRRK2 and TREM2 impair the ability of microglia to rescue neurons through these mechanisms. These findings suggest that enhancing TNT-mediated transfer and microglial degradation of aggregates could be a potential therapeutic strategy for neurodegenerative diseases.
Direct observation of translational activation by a ribonucleoprotein granule [Chen et al, Nature Cell Biology, July 2024]
Germ cells hold a unique position in the human body, as they are the only cells capable of immortality across generations, responsible for the creation of an entire organism. However, the mechanisms governing their specification remain less understood compared to other cell types. Maternal mRNAs, cytoplasmic factors inherited from the egg, play a crucial role in this process. Many of these mRNAs are stored in membrane-less ribonucleoprotein (RNP) granules, recently discovered in the germ cell-forming region of embryos.
Researchers from the Lehmann lab have investigated the function of these germ granules in regulating maternal mRNA localization and translation. They found that nanos, a key mRNA for germ cell specification, is only translated within these RNPs, despite being present throughout the cell. The team used high resolution imaging with the SunTag construct. This finding provides the first direct evidence of a condensate regulating translation, potentially influencing germ cell specification.
This research is significant as it establishes condensates as direct regulators of translation, highlighting their potential role in germ cell fate determination. If these structures prove critical for this process, scientists may be able to engineer germ cell specification from adult stem cells, a major breakthrough for reproductive medicine and regenerative therapies.
Brain responsive music enables non-invasive, targeted, and unobtrusive neurostimulation [Zaaimi et al., bioRxiv, July 2024]
Oscillations in frequency bands are an integral measure of brain activity and health. Abnormal frequency activity in different brain areas has been implicated in a multitude of neurological conditions—such as Alzheimer’s, depression, epilepsy, and ADHD—making modulating these bands all the more paramount.
A recent study by Zaaimi et al. investigates the use of brain-responsive music as closed-loop auditory stimulation (CLAS) generated by noninvasive BCI for regulating theta and alpha frequencies (5-10 Hz) in targeted brain areas. Using MEG–and later EEG–focused on specific locations within the frontal and temporal lobes, the authors recorded samples that were band-pass filtered and phase-shifted in playback to achieve real-time synchronicity with the observed oscillations. The study found significant amplification and attenuation of brain frequencies of interest across participants, with a slightly greater effect observed in the attenuation of the brain signals.
Whether these effects can be replicated in other frequency bands (delta, beta, gamma) as well as in individuals presenting with specific neurological disorders remains to be seen, though results from this study encourage an optimistic outlook.
The paper broaches an interesting crossover between science and art. With the potential for wide-reaching therapeutic applications, it is an exciting time for BCIs, especially as such technology is increasingly commercialized and accessible to the consumer.
Data science in pharmaceutical R&D: the DISRUPT-DS industry roundtable [Khan et al., Nature Reviews Drug Discovery, July 2024]
The DISRUPT-DS roundtable, a new industry forum comprising leaders from 12 of the top 20 pharmaceutical companies, has been established to drive innovation in data science and AI across pharmaceutical R&D. Originating in 2022 and expanding globally in 2023, the roundtable meets virtually 3-4 times annually to discuss topics ranging from data science use cases to organizational strategies. A recent benchmarking exercise revealed diverse approaches to data science across participating companies, with varying degrees of adoption and impact measurement.
The roundtable has identified five grand challenges for the industry: ensuring responsible and ethical use of AI, defining core data science activities for pharma R&D, scaling data science and AI deployment, managing talent, and establishing proper infrastructure. Moving forward, DISRUPT-DS aims to address these challenges through collaborative efforts, sharing findings via publications and partnering with external stakeholders. By focusing on these key areas, particularly the development of ethical AI frameworks, the roundtable seeks to shape industry-level topics and accelerate innovation across the pharmaceutical sector and broader healthcare ecosystem.
Notable Deals
The AI biotechs are merging to create a major player in drug discovery, combining their unique strengths. Over the past decade, Exscientia has developed an advanced AI-powered medicinal chemistry platform and moved several assets into clinical trials. Meanwhile, Recursion has built significant expertise in target biology, infrastructure, and data science, though its chemistry capabilities have been less developed. By integrating their technologies, the combined company is expected to save $100 million per year. Additionally, merging Exscientia’s chemistry expertise with Recursion’s biology and data science will encourage innovative collaboration and strengthen their numerous pharmaceutical partnerships. In the current challenging financial environment, this deal is a strategic move that leverages their combined capabilities to drive growth and efficiency.
NILO Therapeutics, a biotech startup founded by scientists who recently published research on how inflammatory cytokines influence neural function through vagal neurons, has secured $101 million in Series A funding from TCG, DCVC, and Lux. The company believes these findings could lead to a pipeline of autoimmune treatments.
Eisai inks molecular glue deal with SEED Therapeutics for up to $1.5B
Roche/Genentech exercises its $30M to license Recursion’s neuroscience phenomap.
Arie Belldegrun launches Symbiotic Capital with $600M to spend on loans for clinical stage biotechs.
Airna raises $60M for RNA editing therapies in the lung, cardiovascular system and blood diseases.
Field Trip
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