M1

Our body movements profoundly impact how our brain processes sensory information. Historically, it was believed that the brain's primary motor cortex played a key role in modulating sensory experiences during movement. However, a new study has challenged this view. By selectively inhibiting different neural pathways in the mouse brain, they discovered that regions beyond the primary motor cortex significantly influence the primary sensory cortex during movement. Our body movements profoundly impact how our brain processes sensory information. Historically, it was believed that the brain's primary motor cortex played a key role in modulating sensory experiences during movement. However, a new study led by researchers from Fujita Health University has challenged this view. By selectively inhibiting different neural pathways in the mouse brain, they discovered that regions beyond the primary motor cortex significantly influence the primary sensory cortex during movement. The brain is widely considered the most complex organ in the human body. The intricate mechanisms through which it processes sensory information and how this information affects and is affected by motor control have captivated neuroscientists for more than a century. Today, thanks to advanced laboratory tools and techniques, researchers can use animal models to solve this puzzle, especially in the mouse brain. During the 20th century, experiments with anesthetized mice proved that sensory inputs primarily define neuronal activity in the primary sensory cortices -- the brain regions processing sensory information, including touch, vision, and audition. However, over the past few decades, studies involving awake mice revealed that spontaneous behavior, such as exploratory motion and movement of the whiskers called whisking, actually regulates the activity of the sensory responses in the primary sensory cortices. In other words, sensations at the neuronal level appear substantially modulated by body movements, even though the corresponding neuronal circuits and the underlying mechanisms are not fully understood. To address this knowledge gap, a research team from Japan investigated the primary somatosensory barrel cortex (S1) -- a region of the mouse brain that handles tactile input from the whiskers. Their latest study, published in The Journal of Neuroscience on December 1, 2023, was conducted by Professor Takayuki Yamashita from Fujita Health University (FHU) and Dr. Masahiro Kawatani, affiliated with FHU and Nagoya University, along with their team. The S1 region receives input through the axons from several other areas, including the secondary somatosensory cortex (S2), the primary motor cortex (M1), and the sensory thalamus (TLM). To investigate how these regions modulate activity in S1, the researchers turned to optogenetics (a technique for controlling activities of specific neuronal populations by light) involving eOPN3, which is a recently discovered light-sensitive protein enabling effective inhibition of specific neural pathways in response to light. Using viruses as a vector, they introduced the gene coding for this protein into the M1, S2, and TLM regions in mice. Then, they measured neural activity in S1 in awake mice performing spontaneous whisking. During this process, they selectively inhibited different signal inputs going to S1 using light as an ON/OFF switch and observed the effect at S1. Interestingly, only signal inputs from S2 and TLM to S1, not from M1 to S1, modulated neuronal activity in S1 during spontaneous whisking. Specifically, the pathway from S2 to S1 seems to convey information about the motion state of the whiskers. Additionally, the TLM-to-S1 pathway appeared to relay information related to the phase of spontaneous whisking, which follows a repetitive and rhythmic pattern. These results challenge the established view that neuronal activity in sensory cortices is modulated primarily by motor cortices during movement, as Prof. Yamashita remarks: "Our findings provoke a reconsideration of the role of motor-sensory projections in sensorimotor integration and bring to light a new function for S2-to-S1 projections." A better understanding of how distinct brain regions modulate activities among each other in response to movement could lead to progress in myriad applied fields. These research insights have far-reaching implications, potentially revolutionizing fields like artificial intelligence (AI), prosthetics, and brain-computer interfaces. "Understanding these neural mechanisms could greatly enhance the development of AI systems that mimic human sensory-motor integration and aid in creating more intuitive prosthetics and interfaces for those with disabilities," Prof. Yamashita adds. In summary, this study sheds light on the intricate workings of the brain. It also paves the way for researching the connection between body motion and sensory perception. As we continue to explore brain-related enigmas, studies like this offer vital clues in our quest to understand the most complex organ in the human body.

SAN DIEGO--(BUSINESS WIRE)-- Pipeline Therapeutics, Inc. (the Company) announced today that it has changed its name to Contineum Therapeutics, Inc. (Contineum). The Company chose Contineum (pronounced "Con-tin-E-um") to represent its continuous dedication to the pursuit of scientific discovery and cutting-edge solutions designed to benefit patients. Contineum is focused on discovering and developing novel, oral small molecule therapies for neuroscience, inflammation and immunology (NI&I) indications with high unmet need. "Our goal is to create precision small molecules that can alter the course of clinical impairment in neurology, inflammation and immunology diseases. The Company’s recent expansion into fibrotic diseases expands the potential of our pipeline and this name change is an exciting reflection of that progress,” said Carmine Stengone, CEO of Contineum. “We are building a nimble biopharmaceutical company with multiple clinical indications, large potential market opportunities such as IPF and multiple sclerosis, and a discovery platform targeting clinically validated mechanisms like LPA1 and M1 aimed at modulating innate pathways to restore function in NI&I indications. We look forward to continuing to grow Contineum under our new moniker to develop product candidates to improve patients’ lives.” In conjunction with the corporate name change, the Company will have a new website address: . About Contineum Therapeutics Contineum Therapeutics is a clinical stage biopharmaceutical company focused on discovering and developing novel, oral small molecule therapies for NI&I indications with high unmet need. Contineum is focused on targeting biological pathways associated with specific clinical impairments, that the Company believes, once modulated, can demonstrably impact the course of disease. The Company has a pipeline of internally-developed programs to address multiple NI&I disorders, including PIPE-791, an LPA1 receptor antagonist, in Phase 1 for idiopathic pulmonary fibrosis and progressive multiple sclerosis, and PIPE-307, a potentially first-in-class selective inhibitor of the M1 receptor in Phase 2 for relapse-remitting multiple sclerosis and with a Phase 2 for depression planned to initiate in mid-2024. Contineum is developing PIPE-307 in collaboration with Johnson & Johnson Innovative Medicines. In addition, Contineum is advancing discovery efforts targeting other NI&I indications where the Company’s internally-discovered molecules and approach may have therapeutic potential. Contineum is headquartered in San Diego, CA. For more information, please visit or engage with us on LinkedIn.

CEO Richard Gonzalez was clear that AbbVie did its due diligence and he does not expect big problems from the U.S. Federal Trade Commission. AbbVie’s $8.7 billion acquisition of Cerevel will help fill in gaps in the Chicago pharma’s pipeline with new areas to explore in neuroscience, but will regulators play ball? CEO Richard Gonzalez was clear that AbbVie did its due diligence and he does not expect big problems from the U.S. Federal Trade Commission, even though both companies have a schizophrenia drug. “Obviously we looked very carefully at the FTC risk before we proceeded forward. I can tell you, this acquisition is not anti-competitive,” Gonzalez said in a Thursday investor call. He noted that psychiatry is a very “crowded and fragmented” market with “literally dozens” of available medicines. Most entrants only capture portions of the market, leaving plenty of room for new options. Gonzalez also said that there are no overlapping mechanisms between Cerevel’s pipeline and AbbVie. Cerevel’s emraclidine is a muscarinic M4 selective positive allosteric modulator currently in phase 2 testing. As for Vraylar, which AbbVie markets for schizophrenia, Gonzalez said the therapy has a pretty low share of that market with the bulk of sales coming from bipolar disorder. “We have a lot of confidence that we will be able to get this through the FTC,” Gonzelez said. Analysts seemed to agree with Gonzalez. Mizuho Securities flagged overlap in schizophrenia, Parkinson's disease and major depressive disorder as areas that the FTC could take a closer look at—specifically the former. Mizuho’s Graig Suvannavejh, Ph.D., similarly noted the fragmented market that already exists in schizophrenia, with more than 20 available treatments and many companies involved. So even if the FTC does zoom in on this area of the overlapping portfolios, “we don't see a particular reason to be concerned,” Suvannavejh wrote. William Blair analysts similarly pointed to schizophrenia and the deal’s focus, emraclidine, but suggested there are other areas that could draw some additional scrutiny including Parkinson’s, where AbbVie has Duopa/Duodopa approved and ABBV-951 in development. Cerevel has tavapadon in phase 3 in the indication. “Despite the overlap, we note that these assets are all exploring different mechanisms and different lines of use, and the CNS space offers multiple generic and brand therapies that lessen the risk of market concentration,” William Blair wrote in a Thursday morning note.   A well-behaving molecule Emraclidine emerged as the highlight of the deal on AbbVie’s investor call. Chief Operating Officer Robert Michael called the therapy a “multibillion-dollar peak-sales opportunity” with significant potential to contribute to AbbVie’s growth in the 2030s. The therapy is going up against Karuna Therapeutics’ KarXT in the muscarinic class. That therapy was recently accepted by the FDA for review. Michael said that Cerevel’s asset is differentiated as a positive allosteric modulator that targets the M4 subtype, compared to KarXT which activates M1 and M4. Emraclidine is also just one active ingredient, whereas KarXT is a combination of xanomeline and trospium. Cerevel’s option is dosed once daily and does not need titration. Ease of dosing is key with the schizophrenia population, Michael noted. “The molecule itself, it behaves quite well. It has a good half-life and has minimal food effect. It is once a day, and I think that's a critical differentiator, especially in schizophrenia,” said Roopal Thakker, M.D., chief medical officer. Finally, “contrary to what has been reported for the most advanced muscarinic receptor modulator,” emraclidine has also had low rates of gastrointestinal side effects such as nausea, vomiting, dyspepsia and constipation. AbbVie plans to quickly bulk up the emraclidine program once the deal closes. Michael detailed a plan to add additional studies to expand the use case in schizophrenia, particularly in international markets such as Europe and Japan. The company will also target an adjunctive indication to pair emraclidine with existing anti-psychotic drugs which could help address an unmet need in psychiatric care. The drug will also be developed in a long-acting injectable formulation, which could help with patient adherence, Michael said. Other potential indications for emraclidine include dementia-related psychosis in patients with Alzheimer's and Parkinson's diseases. Thakker expects an initial approval for emraclidine in 2026 with international regulatory clearance in the following years. “It is clear to us that the majority of the deal value is likely ascribed to emraclidine,” William Blair wrote. But Cerevel also brings tavapadon, a dopamine D1/D5 selective partial agonist for Parkinson’s, darigabat for treatment-resistant epilepsy and CVL-871 for dementia-related apathy.   Done deals This is AbbVie’s second acquisition in a week, following the $10.1 billion cash offer for ImmunoGen, the maker of antibody-drug conjugate ovarian cancer treatment Elahere. Gonzalez has made no secret of his desire for deals on recent earnings calls and suggested today that these two could quell his appetite for bigger outlays—for now. “We have previously said that our BD efforts were focused on identifying assets that can drive growth in the next decade and we've accomplished that by adding to our oncology and neuropsych pipeline through both the Immunogen and Cerevel deals,” Michael said. “I would not anticipate similar-sized transactions for the foreseeable future. That said, we will continue to pursue smaller size, early stage opportunities that can further support growth in the next decade.” And that’s not because AbbVie can’t do another big deal. Michael said the company has the balance sheet capacity. “It's because of the strength of our current on market and pipeline portfolio, plus five key growth areas which both Immunogen and Cerevel both very nicely complement,” he said. Mizuho expects the deal will go ahead as announced, with both boards already in support and few outside pharmas likely to make a better bid.