BDNF

Neuropsychiatric drug development is rife with clinical trial failures, but Alto Neuroscience aims to overcome these hurdles with a precision medicine approach that matches a patient to a drug. A clinical trial failure for an Alto depression drug is now casting doubt on this program and the technology that is the foundation for the biotech company’s approach. The Phase 2b failure of the drug, ALTO-100, comes nearly nine months after Mountain View , California-based Alto raised more than $128 million in an IPO priced at $16 per share. Alto shares opened Wednesday at $5.15 each, down 64.5% from Tuesday’s closing stock price. Alto’s platform technology analyzes brain-based biomarkers, looking for the biomarkers that predict response to a drug. Last year, an open-label Phase 2a test of ALTO-100 posted results showing the twice-daily pill led to significant improvement in depressive symptoms in patients characterized by impaired cognition, compared to patients who did not have objectively defined cognitive impairment. sponsored content Upcoming Webinar: Battle of the Budget: Employers vs. Rising Healthcare Costs Gain valuable knowledge and practical insights on how employers are addressing an increasingly complex healthcare budget landscape. By Personify Health The preliminary results announced after Tuesday’s market close are from a placebo-controlled Phase 2b test of ALTO-100, a novel small molecule that Alto acquired from Palisade Bio. The study enrolled 301 patients with major depressive disorder, or MDD, defined by an objective biomarker that was assessed before randomization. This biomarker is low levels of BDNF, a brain protein that promotes neuron survival and health. Participants included those who were already taking depressions drugs, in which case ALTO-100 was evaluated as an adjunct to those therapies. The main goal was measuring the change in score after six weeks according to a rating scale used to assess depression symptoms. Without reporting specific figures, Alto said patients treated with ALTO-100 did not show a statistically significant improvement in depressive symptoms compared to those given a placebo. The drug also failed to beat a placebo in patients who received the study drug as a monotherapy, which was a secondary trial goal. There’s more at stake than MDD. The negative data readout could affect Alto’s plans to test the drug in post-traumatic stress disorder and bipolar depression using the same biomarker as the one used for the MDD trial. William Blair analyst Myles Minter spoke with Alto executives, who told him the trial was well conducted and the placebo response was within historical norms. That’s important because in some depression trials, the test drug shows trending improvement but a high placebo response results in a study failure. If the placebo response in the ALTO-100 trial was normal, then the failure is likely due to the drug not working. Alto management reiterated to Minter that the company will analyze the full data set to determine the next steps for the drug in MDD. “While today’s data points draw increased scrutiny on the biomarker stratification approach, historically placebo-controlled MDD studies have been high-risk, and this one appears no different,” Minter wrote in a note sent to investors. “Still, in our discussions with management, it remained confident in the stratification approach, and we will await a fuller dataset to better understand this optimism despite the negative Phase 2b readout.” presented by Sponsored Post The Promise of Value-Based Care and MedTech Innovation Monica Vajani, Executive Director for mHUB’s MedTech Accelerator, discusses how mHUB is helping innovators transition healthcare towards value-based care. By Monica Vajani - mHUB Alto’s patient-selection strategy may yet prove itself. A Phase 2b test is ongoing for Alto’s ALTO-300 in MDD. This small molecule, which has the non-proprietary name agomelatine, has approvals in Europe and Australia and is sold in those markets by Servier. Novartis held U.S. rights to the molecule, but stopped Phase 3 tests due to liver toxicity. ALTO-300 is the lower of the two doses that Novartis had evaluated in Phase 3. Alto’s trial, which enrolled patients who have a biomarker that could predict response to ALTO-300, is expected to post preliminary data in the first half of 2025. Minter said that compared to ALTO-100, ALTO-300 has already demonstrated antidepressant efficacy in its commercialized markets. Also, this drug’s biomarker is less subjective than the one used for ALTO-100, “which bodes well for stratifying patients, albeit likely tougher to vet and we expect investors to remain cautious after today’s failure,” Minter said. So far, Alto does not have any internally discovered drugs. Besides ALTO-100 and ALT-300, the company’s pipeline includes two other in-licensed assets in development for MDD, both of them going after different targets. The company also has an in-licensed program in development for schizophrenia. As of the end of the second quarter of this year, Alto reported a cash position of $193 million, which it said would be sufficient to fund operations into 2027. Image: Jolygon, Getty Images

– Treatment with ALTO-100 did not demonstrate improvement in depressive symptoms compared to placebo in patients with a memory-based cognitive biomarker – – ALTO-100 demonstrated a favorable safety and tolerability profile, consistent with previously reported studies – – Strong cash position expected to fund Alto’s planned operations through multiple near-term milestones across pipeline of independent programs – 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 that the Phase 2b study of ALTO-100 in patients with major depressive disorder (MDD) did not meet its primary endpoint, assessed by a change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS), compared to placebo. The favorable safety and tolerability pro ALTO-100 was consistent with previously reported studies. “We are disheartened by the results from this study as the unmet need in this patient population is immense,” said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. “While the results are surprising and disappointing, I am proud of our team for conducting a first-of-its-kind precision biomarker-based study in psychiatry. We will move quickly to evaluate the full data set to better understand these findings and incorporate learnings from this large data set across our platform. We remain committed to our mission of helping patients get better faster by bringing precision medicine to psychiatry, and we expect our strong cash balance to support us through multiple near-term clinical milestones across our pipeline.” Topline results from the Phase 2b study The randomized, double-blind, placebo-controlled Phase 2b study was designed to evaluate ALTO-100 in adults with MDD, defined by an objective, memory based cognitive biomarker assessed prior to randomization. The primary endpoint was the change from baseline to the end of the 6-week double-blind treatment period on the MADRS, which is the standard regulatory endpoint in depression. The study was conducted across 34 sites in the U.S. and enrolled 301 adults with MDD. The biomarker-defined MDD patient group treated with ALTO-100 did not demonstrate a statistically significant improvement in depressive symptoms compared to placebo. ALTO-100 did not demonstrate benefit over placebo on the pre-specified key secondary analyses. ALTO-100 continued to demonstrate a favorable safety and tolerability profile, with no new safety signals observed in this study as compared to the previously completed clinical trials of ALTO-100. The most common adverse events from the trial related to treatment with ALTO-100 were headache, nausea, and abnormal dreams – all of which were experienced at similar rates to placebo. The Company expects to complete analysis of the full data set to determine the most appropriate next steps, if any, to further evaluate ALTO-100 in MDD. Adam Savitz, M.D., Ph.D., chief medical officer of Alto Neuroscience added, “While the Phase 2b results did not replicate the clinical results observed in the Phase 2a trial, we believe our approach to collecting and stratifying based on biomarkers represents an innovative approach to developing neuropsychiatric drugs. We are deeply grateful to the patients, physicians, trial site staff, and advocacy partners for their support.” ALTO-100 is also being evaluated as an adjunctive treatment in a Phase 2b study in bipolar depression. The Company expects its current cash position to fund planned operations into 2027 and through multiple upcoming clinical readouts, including two additional readouts in MDD with ALTO-203 and ALTO-300 expected in the first half 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, PTSD, schizophrenia, and other mental health conditions. For more information, visit 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 “believe,” “could,” “expects,” “look forward,” “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 with regard to the potential benefits, activity, effectiveness and safety of its product candidates and Precision Psychiatry Platform (“Platform”); Alto’s expectations with regard to the design and results of its research and development programs and clinical trials, including the timing and availability of data from such trials; Alto’s clinical development plans for its product candidates, including the timing or likelihood of approvals for its product candidates; Alto’s business strategy, financial position and the sufficiency of its financial resources to fund its operations through expected milestones, and other statements that are not historical fact. 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 clinical development of Alto’s product candidates; the risk that Alto may not realize the intended benefits of its Platform, availability and timing of results from clinical trials; whether initial or interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials; the risk that clinical trials may have unsatisfactory outcomes; the risk that Alto’s projections regarding its financial position and expected cash runway are inaccurate or that its conduct of its business requires more cash than anticipated; 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 the section titled “Risk Factors” in Alto’s Quarterly Report on Form 10-Q for the fiscal quarter ended June 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. Contacts Investor Contact: Nick Smith investors@altoneuroscience.com Media Contact: Mari Purpura media@altoneuroscience.com

The comprehensive cancer center’s experts will spotlight scientific data on how dietary choices, psychosocial support, massage therapy and mind-body calming practices can improve outcomes and the quality of life of people touched by cancer LOS ANGELES--(BUSINESS WIRE)--Researchers from City of Hope ® , one of the largest and most advanced cancer research and treatment organizations in the United States, ranked among the nation’s top 5 cancer centers by U.S. News & World Report and a national leader in providing cancer patients with best-in-class, integrated supportive care programs, will present new data on integrative oncology research and clinical trials at the 21st International Conference of the Society for Integrative Oncology taking place Oct. 25 to 27. Integrative oncology is a patient-centered field of cancer care that combines conventional cancer treatments with complementary, evidence-based therapies to improve outcomes and quality of life. The hybrid conference hosted by City of Hope in Costa Mesa, California, will include more than 170 oral and poster abstracts evaluating supplements and herbal therapies, traditional medicine such as acupuncture, lifestyle choices like diet and exercise, mind-body practices, and use of artificial intelligence and machine learning in integrative oncology. “City of Hope and other experts will share the best science that’s occurring in the field of integrative oncology, which aims to optimize health, quality of life and clinical outcomes,” said Richard T. Lee , M.D., Cherng Family Director’s Chair for the Center for Integrative Oncology at City of Hope, medical director of supportive and integrative medicine at City of Hope Orange County and co-chair of the SIO conference. “City of Hope is leading a national effort to make evidence-based integrative oncology a routine and interwoven part of optimal cancer care and survivorship. City of Hope is bringing together leaders in the field to create the most holistic approach to cancer care.” A $100 million gift from Panda Express Co-CEOs Andrew and Peggy Cherng has enabled City of Hope to lead efforts to accelerate research, therapeutic development and clinical trials for the advancement of evidence-based integrative oncology practices so that cancer patients nationwide and their doctors have access to safe, proven approaches. Some of the leading-edge data City of Hope will present include the following oral abstracts. Massage therapy during infusion lessens the side effects of chemotherapy in a pilot study Presentation time and location: Saturday, Oct. 26 in the Plaza Ballroom from 3 to 4:15 p.m. Christy DiCristofano, a City of Hope massage therapist, led a pilot study assessing the therapeutic effects of massage on cancer patients. The research team surveyed 232 individuals who collectively received 500 hand and/or foot massages while undergoing an infusion. They found that massage therapy is a beneficial additional treatment for symptoms induced by chemotherapy. The therapy had no reported side effects and proved useful in managing symptoms, such as anxiety, pain, shortness of breath, nausea and neuropathy, which is marked by shooting pain, numbness or tingling. Further research is needed to comprehensively evaluate the benefits of this intervention during infusion. Increasing white button mushroom intake could slow the progression of prostate cancer Presentation time and location: Sunday, Oct. 27 in the Lido Room from 10:45 a.m. to noon Bidirectional translational research led by Xiaoqiang Wang, M.D., Ph.D., City of Hope staff scientist, and Shiuan Chen , Ph.D., professor and chair of City of Hope’s Department of Cancer Biology and Molecular Medicine and the Lester M. and Irene C. Finkelstein Chair in Biology, revealed that consuming white button mushrooms can alter androgen levels and boost anti-cancer immunity. The comprehensive research included preclinical experiments, mouse models and prostate cancer patients participating in an ongoing phase 2 clinical trial. The physician-scientists collected blood samples from both mouse models and humans, analyzing myeloid-derived suppressor cells that are responsible for squelching immune responses and assisting tumor growth. They found that consuming white button mushrooms enhances anti-tumor immunity and slows prostate cancer progression. They expect to learn more once the phase 2 clinical trial is completed. Can intermittent fasting decrease the side effects of radiotherapy and enhance its efficacy? Presentation time and location: Friday, Oct. 25 in the Mesa Verde Room from 2:30 to 3:45 p.m. Several clinical and preclinical studies suggest that time-restricted eating, more commonly called intermittent fasting, may enhance anti-tumor response, decrease side effects and improve quality of life during systemic therapy. Ziyi Huang, M.D., City of Hope research fellow, and Yun Rose Li , M.D., Ph.D., assistant professor of radiation oncology at City of Hope, are leading an ongoing randomized phase 2 trial testing whether patients with pelvic malignancies who practice time-restricted eating could experience reduced levels of radiotherapy-induced side effects and enhanced radiotherapy efficacy. The time-restricted eating group are asked to fast for 12 to 14 hours on radiotherapy days. Researchers collect diet logs, stool, urine and blood samples alongside patient- and clinician-reported toxicities. Thus far, the results are encouraging and support the tolerability and feasibility of intermittent fasting during pelvic radiotherapy, especially among patients with prostate cancer. Enrollment in the trial is expected to be completed in spring 2025. Nurses can videoconference cancer patients to provide supportive care and improve quality of life Presentation time and location: Saturday, Oct. 26 in the Plaza Ballroom from 3 to 4:15 p.m. Psychosocial support services can be limited in small urban and rural areas. Up to 70% of patients with advanced cancer experience elevated levels of fear of cancer progression characterized by intrusive thoughts, distress and difficulty making future plans. Anne Reb , Ph.D. N.P., assistant professor of nursing research and education at City of Hope, and Betty Ferrell , Ph.D., M.S.N., CHPN, City of Hope director and professor of nursing research and education, led a pilot study to assess the feasibility and preliminary effects of a nurse-guided videoconferencing intervention to manage fear of cancer progression levels in patients with Stage 3 or 4 gynecologic or lung cancer. Some 82% of the 30 study participants completed all five nurse-led videoconferencing sessions and reported using the tools the nurses introduced like attention training and detached mindfulness to focus, connect with what is most important to them and gain control over daily life stressors. The intervention showed improvement in fear and other quality-of-life outcomes. Feasibility and acceptability was established in this small sample size and suggestions for improvement were established. The potential risk of drug interactions with cannabis use Presentation time and location: Saturday, Oct. 26 in the Plaza Ballroom from 11:30 a.m. to 12:45 p.m. In one of the first studies to assess cannabis-related drug interactions in patients receiving cancer treatment, Elyssa Kim, B.S., former City of Hope research assistant, and Richard T. Lee , M.D., City of Hope clinical professor of supportive and integrative medicine, found that a significant proportion of cannabis users are at risk of moderate to major potential medication interactions. Of the 313 participants, 61 were actively using a form of cannabis to address insomnia (46%), pain (41%) and mood (39%). The most common medications whose effectiveness could be compromised due to cannabis use were noted to be medications for pain or inflammation (acetaminophen, dexamethasone), anti-nausea (ondansetron) and even chemotherapy (paclitaxel, doxorubicin). Researchers say that more states are legalizing cannabis and more cancer patients turn to cannabis to alleviate cancer symptoms, but we need more data on the therapeutic effects and pitfalls of cannabis use during cancer treatment. A mix of mindfulness meditation, gentle exercise and spirituality is linked to improved emotional well-being among breast cancer survivors Presentation time and location: Saturday, Oct. 26 in the Lido Room from 11:30 a.m. to 12:45 p.m. Breast cancer survivors often report experiencing anxiety, depression, poor sleep and cognitive impairment. Frank Munoz, a City of Hope chaplain, conducted a pilot study of meditative movement effects on this patient population, taking blood samples to measure serotonin-related (HTR1F and SLC6A4) and mood/cognitive function-related (BDNF, IL6 and IL1b) gene expression levels. The intervention resulted in a biological change in scores of anxiety, depression, sleep quality and cognitive function. This small study, which demonstrated changes in gene expression, suggests that meditative movement such as tai chi and meditation may help breast cancer survivors recover from persistent mental and emotional symptoms. About City of Hope City of Hope’s mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest and most advanced cancer research and treatment organizations in the U.S., and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines , as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center that is ranked top 5 in the nation for cancer care by U.S. News & World Report at its core, City of Hope’s uniquely integrated model spans cancer care, research and development, academics and training, and a broad philanthropy program that powers its work. City of Hope’s growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHope™ . For more information about City of Hope, follow us on Facebook , X , YouTube , Instagram and LinkedIn . Contacts Zen Logsdon 626-409-9367 zlogsdon@coh.org