Agomelatine

Caption: The Biotech CEO Sisterhood and Breaking 7% gathered with allies for the first time at JPM25.\n Take a look back at the biggest stories of the week with Fierce Biotech’s conference\'s kickoff coverage here and the full lowdown from Day 2 here.Check out all the latest news below... Wednesday 6 p.m. ET Jan. 15Nkarta CEO Paul Hastings, a San Francisco local, attributed the thinner crowds to the unusually beautiful weather the city is having this week. “Every year that we have this conference, it\'s rained. This year it\'s been sunny, so there\'s a lot of people outside,” he explained. “We\'ve had very unique, wonderful weather for this time of year, and I think people have been enjoying the outdoors, and because the city\'s done such a nice job of making it safe and protecting everybody, people are outside and enjoying the sunshine. So, you\'re seeing less people crammed into lobbies and elevator spaces and umbrellas and things—I just did an interview outside on Union Square.”When asked about Nkarta’s shift in focus to autoimmune and priorities for the new year, Hastings said the company is singularly focused on enrolling patients in two clinical trials assessing NKX019, the biotech’s allogeneic, off-the-shelf, engineered natural killer (NK) cell therapy, “in order to get a transformative therapy available to patients as quickly as possible.” Wednesday 5 p.m. ET Jan. 15On the third day of the conference, Alto Neuroscience founder and CEO Amit Etkin, M.D., Ph.D., said there’s “definitely lighter attendance this year.”Etkin highlighted the year’s biggest acquisition thus far—Johnson & Johnson’s $14.6 billion buyout of CNS biotech Intra-Cellular Therapies—which was announced the first day of the conference.“What that says is that these disorders that affect many, many, many people, if you have a drug that\'s approved—and in their case, already selling—there\'s a lot of interest because there\'s a lot of need,” Etkin said.“That begs the question, with all the recent failures across companies, how do we actually go forward in this high-need place?” he continued.This has been top of mind since the Alto\'s phase 2b trial assessing ALTO-100 in major depressive disorder missed its primary and key secondary endpoints. However, Etkin said that after looking over the data, they identified “very high rates of compliance with a medication in the adjunctive arm, which explains the clinical effect, and much lower rates of compliance in the monotherapy arm, and that noncompliance came disproportionately from certain sites.”The problem—deemed to be so-called professional patients—has been a part of the field for a long time and is only getting worse, according to Etkin. Professional patients are people who participate in clinical trials but are exaggerating symptoms, don’t take the drug, or are motivated by money or attention.“Any one of these things leads you to not be an informative patient, and so you\'re not actually testing the drug,” Etkin said. “So, we took that to heart and said this is a problem we really need to fix.”To avoid this problem in another study of a depression drug candidate called ALTO-300, Alto conducted a blinded review of all patients in a separate phase 2b trial, removing 52 patients from the 200-person trial for a variety of reasons that “were indicative of site conduct issues and patient appropriateness,” according to Etkin. “And now we\'re going to be doing an interim analysis of that trial to make sure that we\'re—with these people—on the right track in terms of outcome empowering. And hopefully that gets us beyond this.”Going into 2025, the biotech’s mantra is to “rethink everything,” the CEO said. That includes reimagining how drug development happens, reconsidering challenges in trial execution and conduct that has plagued the field, and rethinking how tech is leveraged.All that rethinking is necessary, “because we just can\'t keep doing what we\'re doing as a field and expecting a different outcome,” Etkin concluded. “There has to be a better way to do this, and that is literally our motto.” Wednesday 3:30 a.m. ET Jan. 15Yesterday, spots of pink could be seen on the streets of San Francisco, and it wasn’t a coincidence. Members of the Biotech CEO Sisterhood urged allies to wear the color to underscore how few women continue to be represented in the throngs of blue suits at the conference.The effort was designed to highlight the need for continued leadership representation and access to opportunity, a spokesperson told Fierce Biotech. Wednesday 3:00 a.m. ET Jan. 15GSK’s Chief Scientific Officer Tony Wood, Ph.D., talks M&A, what the Big Pharma seeks in a partner, and how the company is looking to go beyond the current crop of GLP-1s and obesity. Story.

MOUNTAIN VIEW, Calif.--( BUSINESS WIRE )--Alto Neuroscience, Inc. (“Alto”) (NYSE: ANRO) a clinical-stage biopharmaceutical company focused on the development of novel precision medicines for neuropsychiatric disorders, today announced multiple presentations at the 63 rd annual meeting of the American College of Neuropsychopharmacology (ACNP), in Phoenix, Arizona, held December 8-11, 2024. “At this year’s ACNP meeting, we highlighted the continued progress across our pipeline and precision psychiatry platform,” said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. “Notably, we shared exciting new mechanistic findings that support the ALTO-300 biomarker. Extensive literature suggests that dopaminergic activity stabilizes neural signaling and ALTO-300, which blocks the 5-HT2C serotonin receptor, has been shown to increase dopamine release. As demonstrated by new data, the ALTO-300 biomarker is a measure of reduced neural signal stability and can be generated by activating the 5-HT2C receptor. These insights enhance our understanding of the patient phenotype we are studying in our ongoing Phase 2b study and provide clear mechanistic relevance to our machine-learning derived biomarker. We believe the reverse translation of this biomarker underscores the promise of our precision medicine approach and brings us closer to developing more effective, targeted treatments through a deeper understanding of neurobiological processes in defined patient subtypes. This is enhanced by the scalability of our EEG biomarker, which is calculated based on signal from a single electrode.” The details of each presentation are as follows: Presentation Title : Neural and Molecular Mechanistic Correlates of an EEG Biomarker Predictive of the Antidepressant Response to ALTO-300 in Patients with Major Depression Presentation Highlights : Background: ALTO-300, an oral, small molecule designed to act as a melatonin agonist and 5-HT2C antagonist, is an approved antidepressant medication in Europe and Australia. Along with a range of synergistic neurobiological effects, ALTO-300 has been shown to enhance dopaminergic and noradrenergic input to the frontal cortex and rescue anhedonia-like behavioral deficits. Response to ALTO-300 is predicted by greater levels of sample entropy, a measure of resting-state EEG (rsEEG) irregularity. Human connectivity analysis: Greater sample entropy is associated with decreased neural connectivity. Across multiple independent datasets (N=784), biomarker positive patients demonstrated reduced medial prefrontal neural connectivity, a brain region frequently implicated in MDD. Reverse-translation preclinical study: In mice (N=13), administration of a 5-HT2C agonist (R0-0175) led to a dose-related increase in sample entropy, consistent with a biomarker positive phenotype. These results tie the human-discovered EEG biomarker to ALTO-300’s molecular mechanism of action, as a 5-HT2C antagonist. Key Takeaway: The ALTO-300 biomarker is characterized by reduced medial prefrontal neural connectivity, providing functional evidence of the consequence of more irregular neural signal, which may reflect an increase in 5-HT2C activity in patients. This biomarker, which was previously identified and prospectively replicated, is being used to select patients for the ongoing Phase 2b study of ALTO-300 as an adjunctive treatment in patients with MDD (NCT05922878). Presentation Title : Validation of Assessments for Reward Processing for Use in a Phase 2 Study of a Novel Histamine H3 Inverse Agonist, ALTO-203, in Major Depression Presentation Highlights : Background: Established tests of reward processing tend to be lengthy and poorly tolerated. Two novel computerized cognitive tests for different aspects of reward processing and motivation were developed, validated and examined in relationship to anhedonia. Effort Tapping is a paradigm where participants can earn +10 (low reward) or +100 points (high reward) based on rate of finger tapping. Anhedonia was hypothesized to relate to the ability to mobilize effort and achieve greater reward. The Probabilistic Instrumental Learning Task (PILT) is an adaptation of a classic, two-choice learning test, which measures the ability to learn arbitrary stimulus-reward probabilistic associations. Anhedonia was hypothesized to be associated with a lower learning rate and increased decision noise, as dopamine release has been shown to be a driver of learning in similar paradigms. Results: Compared to established tests of reward processing, Effort Tapping and PILT showed strong test-retest reliability, are shorter and better tolerated, and display stronger evidence of construct and external validity through association with anhedonia and motivation, than established reward tasks. Associations were furthermore replicated across two large studies. Key Takeaway: These novel tasks may be used to more effectively characterize pharmacodynamic effects of ALTO-203 in the ongoing Phase 2 proof-of-concept trial in patients with MDD and anhedonia (NCT06391593). Presentation Title : Prevalence and Correlates of Cognitive Impairment in Depression: Findings from the Texas Resilience Against Depression Study Presentation Highlights : Background: Cognitive impairment (CI) in MDD is associated with worse clinical and functional outcomes in depression. Results: Across participants (N=391), 51% met the criteria for CI, a highly stable phenotype similarly evident across age groups and different levels of premorbid cognitive function. Individuals with CI and depression are no more depressed or anxious than non-CI depressed, but are more likely to report impairments in activities, worse quality of life, and greater anhedonia and suicidality. Key Takeaway: Findings from the Texas Resilience Against Depression study (T-RAD; NCT02919280) underscore the high unmet need for patients with MDD who experience CI, comprising approximately 50% of the overall MDD population. During ACNP, Dr. Etkin participated in a panel discussion, titled Neuroimaging in Psychiatry: Toward Mechanistic Insights and Clinical Utility to discuss advances and the implementation of neuroimaging tools for psychiatric treatment development, both in industry and academia. Today, the Company also announced that it plans to conduct an interim analysis for the ongoing Phase 2b trial of ALTO-300. Following the completion of the ALTO-100 Phase 2b trial in MDD, the Company conducted a thorough review of patients included in its ongoing trials. Based on learnings from this review, the Company expects the planned interim analysis to be used to inform the final sample size needed to achieve adequate powering of the ALTO-300 Phase 2b trial. The Company expects to conduct and report the outcome from the interim analysis in the first quarter of 2025. About Alto Neuroscience Alto Neuroscience is a clinical-stage biopharmaceutical company with a mission to redefine psychiatry by leveraging neurobiology to develop personalized and highly effective treatment options. Alto’s Precision Psychiatry Platform™ measures brain biomarkers by analyzing EEG activity, neurocognitive assessments, wearable data, and other factors to better identify which patients are more likely to respond to Alto product candidates. Alto’s clinical-stage pipeline includes novel drug candidates in depression, schizophrenia, and other mental health conditions. For more information, visit www.altoneuroscience.com or follow Alto on X . Forward-Looking Statements This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “expects,” “plans,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding Alto’s expectations for the timing and results of Alto’s Phase 2b study of ALTO-300. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including uncertainties inherent in the initiation, progress and completion of clinical trials and other important factors, any of which could cause Alto’s actual results to differ from those contained in the forward-looking statements, which are described in greater detail in the section titled “Risk Factors” in Alto’s Quarterly Report on Form 10-Q for the fiscal quarter ended September 30, 2024 filed with the Securities and Exchange Commission (“SEC”) as well as in other filings Alto may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Alto expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as required by law. Availability of Information on Alto’s Website Alto routinely uses its investor relations website to post presentations to investors and other important information, including information that may be material. Accordingly, Alto encourages investors and others interested in Alto to review the information it makes public on its investor relations website.