CK1δ

THURSDAY, March 30, 2023 -- Cluster headache and migraine are highly circadian, according to a review published online March 29 in Neurology . Barlas Benkli, M.D., from UT Health Houston, and colleagues conducted a systematic review of 72 studies to examine circadian features of cluster headache and migraine. In addition, a genetic analysis for genes with a circadian pattern of expression (clock controlled genes [CCGs]) was conducted by cross-referencing 16 genome-wide association studies of headache, one nonhuman primate study of CCGs in various tissues, and 16 imaging reviews of brain areas relevant in headache disorders. The researchers found that for cluster headache, a meta-analysis across 16 studies showed a circadian pattern of attacks in 70.5 percent of participants, with a clear circadian peak between 21.00 and 03.00, and with circannual peaks in spring and autumn. Across studies, chronotype was highly variable. Lower melatonin and higher cortisol levels were reported at the systems level. Cluster headache was associated with core circadian genes CLOCK and REV-ERB α at the cellular level; five of nine cluster headache susceptibility genes were CCGs. For migraine, 50.1 percent of participants across eight studies showed a clear circadian pattern of attacks, with a clear circadian trough between 23.00 and 07.00, and a broad circannual peak between April and October. Across studies, chronotype was highly variable. Urinary melatonin levels were lower in migraine participants at the systems level and were even lower during an attack. Migraine was associated with core circadian genes CK1δ and RORα at the cellular level; 110 of 168 migraine susceptibility genes were CCGs. "These results raise the potential for using circadian-based treatments for headache disorders," a coauthor said in a statement. One author disclosed financial ties to Lundbeck. Abstract/Full Text (subscription or payment may be required) Editorial (subscription or payment may be required) Posted March 2023

Investors are dropping dollars into the life sciences industry like the trees are dropping their leaves. Here’s who’s raking in the cash this week. Neumora Therapeutics Uncloaking with a massive $500 million in financing, neuroscience-focused Neumora has hit the ground running. A strategic partnership with mega biotech Amgen will develop and commercialize assets targeting casein kinase 1 delta and glucocerebrosidase for neurodegenerative diseases. With a portfolio of eight programs in varying stages from internal discovery assets, Neumora is developing precision medicines for complex brain diseases. Paul L. Berns, cofounder, chairman and CEO said the company was founded to approach drug development in a “smarter, more precise way.” “Neumora is built at scale to pioneer potential best-in-class precision medicines for brain diseases, and we believe that integrating data sciences is the key.” Pyxis Oncology Mere months after its $152 million Series B round, this Cambridge-based company hopped on the Nasdaq’s ticker board with the symbol PYXS. Selling at $16 a share, Pyxis drew in about $168 million in its IPO last week. The biotech develops ADCs and monoclonal antibodies targeting different forms of cancer. Most of the funds are earmarked for Pyxis’ three lead ADC programs, taking the candidates through preclinical research, NDA and Phase I trials. CinCor Pharma Cincinnati’s CinCor just finished its $143 million Series B financing round to support the development of its lead drug for hypertension, primary aldosteronism and chronic kidney disease. CIN-107 is an oral small molecule that inhibits aldosterone synthase. The funds will be used to complete ongoing Phase II trials for patients with resistant hypertension and hypertensive patients with primary aldosteronism. The round will also fuel two new Phase II trials in patients with uncontrolled hypertension and to study the drugs impact on blood pressure and kidney function in CKD patients. Twin Health AI drives the future of medical devices and services, treating and preventing disease through technology. Last week, Twin Health scooped up a $140 million Series C to scale services of its Whole Body Digital Twin. The precision health service builds a dynamic representation of each patient’s unique metabolism through non-invasive wearable sensors and patient tracking to help reverse and prevent chronic metabolic diseases. With the idea that your body can “heal itself,” the program provides real-time health insights with recommendations to address the root cause of chronic metabolic diseases like type 2 diabetes. In a randomized controlled trial, over 90% of patients achieved type 2 diabetes reversal with 92% able to eliminate all diabetes drugs. Isoplexis With stock listed at $15 a share, IsoPlexis scored $125 million from its IPO. Developing tech to support drug R&D is the company’s focus. Its commercialized technology platform, based on tech licensed from Yale, assists biopharma companies in analyzing proteins. Initially focused on applications for cancer immunology and cell and gene therapies, IsoPlexis is expanding its scope to include infectious and neurologic disease as well as inflammatory conditions. Proceeds will be used for general corporate purposes. Intergalactic Therapeutics Launching off with $75 million in seed funding, Intergalactic is one of the handful of biotech companies aiming to create non-viral gene therapies. Currently approved gene therapies rely on viruses to deliver the DNA strands. While effective, viruses can cause safety concerns and limit treatments to one-time use. Intergalactic is relying on technique with 40 years of research behind it, electroporation, which uses electrical fields to open doorways into cells. Like many gene editing companies, this one will start by targeting diseases affecting the eye, as well as respiratory disease and cancer. The goal is for in-human trials within two years. Cognition Therapeutics Since Biogen’s landmark approval of Aduhelm, the industry is seeing a fresh surge of interest in targeting amyloid proteins to treat the devastating disease of Alzheimer’s. Cognition is developing small molecules to break up amyloid in the brain with its lead drug. By jumping on the Nasdaq, the company now has a fresh $45.2 million to push forward CT1812 to Phase II testing in patients with mild-to-moderate Alzheimer’s. A second candidate is targeting wet form of age-related macular degeneration. $16.2 million of the IPO raise will funnel into that program’s Phase II. Chance Pharmaceuticals Out of Hangzhou, China, Chance has the “leading particle engineering knowhow” for developing inhaled therapeutics for today’s debilitating diseases. With seven products in the early stages of its pipeline, the company lists its R&D as including diseases like chronic obstructive pulmonary disease, asthma, pulmonary arterial hypertension, and central nervous system disorders. This week Chance scored $30 million in Series C financing to advance the pipeline, initiate collaborations and accelerate construction on a manufacturing facility.

Fresh out of the gates with $500 million in financing, neuroscience-focused Neumora Therapeutics forged a strategic partnership with Amgen to develop and commercialize assets owned by the pharma giant, targeting casein kinase 1 delta and glucocerebrosidase for neurodegenerative diseases. Massachusetts-based Neumora launched a portfolio of eight clinical, preclinical and discovery stage programs from internal discovery efforts and the assets from the agreement with Amgen, which backed the company with a $100 million equity investment. Neumora intends to develop precision medicines for complex brain diseases that have, so far, seen high failure rates by other drug development companies. Neumora’s data science platform is designed to identify and define patient subtypes by mapping the mechanisms that drive brain diseases. Ahead of its launch this morning, the company secured multiple open-source and proprietary datasets across neuropsychiatric disorders and neurodegenerative diseases. With those tools, Neumora can then match patient populations with targeted therapeutics. This can de-risk clinical trials and improve patient outcomes. Paul L. Berns, cofounder, chairman and CEO of Neumora, said the company was founded to approach drug development in a “smarter, more precise way.” Berns said they want to take the same approach to neurological diseases that oncology-focused companies took when delving into cell biology of cancer tumors. By doing so, those drug developers were better able to target cancer, and Berns said Neumora wants to do the same with diseases of the brain. “Neumora is built at scale to pioneer potential best-in-class precision medicines for brain diseases, and we believe that integrating data sciences is the key,” Berns said in a statement. For its partnership with Amgen, the companies will harness Neumora’s Data Biopsy Signatures and Precision Phenotypes technology and combine it with assets generated by Amgen’s deCODE genetics and human data research capabilities. Those assets, now under license by Neumora, includes NMRA-140, a KOR antagonist currently in Phase II development for treating patients with major depressive disorder (MDD) with anhedonia. Additionally, Neumora gains the Phase I anxiety therapeutic NMRA-511, a V1aR antagonist. Other assets include a sleep disorder medication and other assets aimed at undisclosed neuropsychiatric disorders. Berns said Neumora is excited to expand its pipeline with potential best-in-class programs targeting casein kinase 1 delta and glucocerebrosidase for neurodegenerative diseases. He added that with Amgen’s support, Neumora is poised to become a pioneer in precision drug development for brain diseases. They are looking forward to working with Amgen to advance promising new medicines for patients in need of better treatment options. Dr. David M. Reese, Amgen’s head of research and development, said the collaboration with Neumora leverages his company’s “unique capabilities” from deCODE and Neumora’s “focus and expertise in brain diseases” to discover and develop potentially best-in-class precision therapies. “Although Amgen is not currently engaged in neuroscience research and early development internally, this approach addresses our commitment to remain engaged in neuroscience through external collaborations, and we are excited to work with Neumora to propel R&D for brain diseases into the future and advance promising new medicines,” Reese said in a statement. In addition to Amgen's $100 million equity investment, Neumora’s $500 million launch was supported by Series A investors led by ARCH Venture Partners. Other participants included Alexandria Venture Investments, Altitude Life Science Ventures, Catalio Capital Management, F-Prime Capital, Invus, Logos Capital, Mubadala Capital, Newpath Partners, Polaris Partners, re.Mind Capital (Apeiron), Softbank Vision Fund 2, Surveyor Capital (a Citadel company) and Waycross Ventures (Byers Capital). Additionally, the Series A included support from other undisclosed investors. “We built Neumora to pioneer the future of precision medicines for brain diseases. Traditional neuroscience R&D is constrained by a ‘one-size-fits-all’ treatment approach, often leading to underwhelming efficacy, high placebo response and routine clinical trial failures. Patients deserve better,” Kristina Burow, co-founder and director of Neumora and managing director at ARCH Venture Partners said in a statement.