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Business Wire
5 days ago
- Business
- Business Wire
Alto Neuroscience Reports Second Quarter 2025 Financial Results and Recent Business Highlights
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 reported financial results for the quarter ended June 30, 2025, and highlighted recent progress across its pipeline of clinical-stage product candidates. 'We have had an exciting past few months marked by a promising addition to our pipeline with ALTO-207 and encouraging clinical data that provide further validation of our biomarker-driven approach to drug development,' said Amit Etkin, M.D., Ph.D., Founder and CEO of Alto Neuroscience. 'The robust clinical effects of pramipexole observed in the PAX-D study give us strong conviction in the therapeutic potential of ALTO-207 to become a meaningful option for patients with treatment resistant depression (TRD), and we look forward to initiating a potentially pivotal Phase 2b trial by mid-2026. We continued our diligent execution across our pipeline to enroll high-quality subjects and are looking forward to the upcoming clinical study readouts.' Dr. Etkin continued, 'The recent data from our exploratory study of ALTO-203 highlights our ability to better guide indication selection and trial design through our use of biomarkers, which we believe will drive better patient outcomes. Recent clinical readouts in cognitive impairment in schizophrenia (CIAS) further our view that this is an area of incredible unmet need. To our knowledge, ALTO-101, which previously demonstrated pro-cognitive effects, now represents the most advanced therapeutic candidate in a space with no currently approved treatments. We look forward to completing the ongoing study this year to further guide its development.' Pipeline Highlights ALTO-207: Acquired novel combination product with robust clinical validation; Phase 2b trial, designed to be a potentially pivotal study, in patients with treatment resistant depression expected to initiate by mid-2026. ALTO-207 is a fixed-dose combination of pramipexole, a dopamine D3-preferring D3/D2 agonist, approved for the treatment of Parkinson's disease with demonstrated antidepressant effect, and ondansetron, an antiemetic, selective 5-HT3 receptor antagonist. As a fixed-dose combination, ALTO-207 is designed to enable rapid titration and higher dosing by mitigating the dose-limiting adverse events typically experienced with pramipexole. ALTO-207 is being developed to address the significant unmet need for patients with TRD. The planned Phase 2b trial of ALTO-207, designed to be a potentially pivotal study, is expected to initiate by mid-2026. In May 2025, the Company acquired from Chase Therapeutics Corporation (Chase) a portfolio of potentially best-in-class dopamine agonist combination product candidates, including ALTO-207, formerly known as CTC-501. The link to the conference call replay is accessible on the Company's website and here. Prior to the acquisition by Alto, Chase completed a randomized, placebo-controlled Phase 2a clinical trial evaluating CTC-501 in 32 patients with depression. The primary endpoint was achieved in the study. Patients randomized to receive CTC-501 reached a mean dose of 4.1mg per day, with 67% of patients achieving the highest allowable dose of 5mg/day. CTC-501 was generally well tolerated in the maintenance period of the study. The clinical efficacy measures were evaluated as secondary endpoints and across measures CTC-501 demonstrated large, clinically meaningful effects. CTC-501 demonstrated statistically significant and clinically meaningful improvements from baseline compared to placebo on depression symptoms as measured by the Montgomery Åsberg Depression Rating Scale, or MADRS (LSM Δ vs. placebo at Week 8 = -8.2, p=0.025, Cohen's d=1.1). CTC-501 also demonstrated a significantly greater improvement compared to placebo on the Clinician Global Impression Scale of Severity, or CGI-S (LSM Δ vs. placebo at Week 8 = -0.76, p=0.04, Cohen's d=1.0). The acquisition of ALTO-207 was prompted by Alto's novel insights on dopamine biomarkers in TRD patients and the robust antidepressant effects of pramipexole exhibited in the PAX-D study conducted by the University of Oxford. Results, which were recently published in The Lancet Psychiatry, showed pramipexole augmentation of antidepressant treatment, at a target dose of 2.5mg, demonstrated a large (Cohen's d =0.87) reduction in symptoms relative to placebo at 12 weeks, but was associated with a high rate of adverse effects. The link to the online publication can be found here. The Company plans to collaborate with the National Health Service network, including PAX-D clinical sites for the planned Phase 2b trial of ALTO-207. ALTO-101: Enrollment is ongoing in Phase 2 POC CIAS trial; topline data expected in the second half of 2025. ALTO-101, a brain-penetrant PDE4 inhibitor designed as a novel transdermal formulation, is being developed for the treatment of CIAS. The novel formulation is designed to retain the desired brain effects shown with the oral formulation while avoiding the tolerability challenges and adverse effects known to be associated with PDE4 inhibitors. Enrollment remains ongoing in the Phase 2 POC trial in CIAS, with topline data expected in the second half of 2025. The Phase 2 POC trial consists of a dose-escalating treatment with ALTO-101 and is designed to enroll approximately 70 adult participants with schizophrenia between the ages of 21 and 55. The primary outcome in the study is the effect of ALTO-101 on theta band activity, the EEG measure shown to be most clearly associated with CIAS in replicated analyses of large schizophrenia datasets. Objective cognitive performance is also being evaluated. ALTO-300: Enrollment ongoing in Phase 2b adjunctive major depressive disorder trial; data expected in mid-2026. ALTO-300, also known as agomelatine, is an oral, small molecule designed to act as a melatonin agonist and 5-HT2C antagonist, and is being developed at 25mg as an adjunctive treatment in the United States for patients with major depressive disorder (MDD), characterized by an EEG biomarker. Agomelatine is an approved antidepressant medication in Europe and Australia, at both 25mg and 50mg, but has not been approved in the United States. In comparison to the 50mg dose of agomelatine, the 25mg dose has been shown to have equivalent antidepressant efficacy and has not been associated with reversible, low liver enzyme elevations observed with the 50mg dose. Topline data from the double-blind, placebo-controlled, randomized Phase 2b trial is expected in mid-2026. The Company expects to enroll approximately 200 biomarker positive patients for the final analysis sample. In the ongoing Phase 2b trial, patients who have had an inadequate response to their current antidepressant are randomized to receive either 25mg of ALTO-300 or placebo over a six-week treatment period. The study medication is being taken in addition to a patient's background antidepressant. The primary outcome is the change from baseline in MADRS score in patients with the EEG biomarker. In May 2025, the Company presented additional analyses at the American Society of Clinical Psychopharmacology Annual Meeting (ASCP) Annual Meeting supporting the unique biomarker opportunity for patient stratification and reinforcing the well-established safety and tolerability profile for ALTO-300 in MDD. The most common adverse event observed in the completed Phase 2a trial of ALTO-300 was headache. Additionally, the Phase 2a and Phase 2b trials have involved monitoring for elevated liver enzymes (≥ 3 times the upper limit of normal), with the Phase 2b trial including a stopping rule for elevated liver enzymes. No liver function test (LFT) elevations ≥ 3 times the upper limit of normal were observed in the Company's 239-patient completed Phase 2a trial, and no patients have been stopped in the ongoing Phase 2b trial due to liver enzyme elevation, which remains blinded. The ALTO-300 biomarker signal likely reflects increased neural noise due to elevated 5-HT2C tone and reduced dopaminergic activity. Increasing 5-HT2C activity in a preclinical rodent model or directly depleting dopamine in a healthy human volunteer study—both the opposite mechanistic effect of ALTO-300—resulted in greater EEG irregularity, consistent with a biomarker positive profile. These data reinforce the direct link between ALTO-300 and the EEG biomarker used to identify MDD patients who are more likely to be responders to treatment. ALTO-100: Enrollment ongoing in Phase 2b bipolar depression trial; data expected in the second half of 2026. ALTO-100, a first-in-class, oral small molecule believed to work through enhancing neuroplasticity, is in development for the treatment of bipolar depression (BPD) in patients characterized by a cognitive biomarker. Enrollment in the randomized, double-blind, placebo-controlled Phase 2b trial remains ongoing with topline data expected in the second half of 2026. The Company expects to enroll approximately 200 patients with BPD. Patients will be evaluated over a six-week treatment period and the primary endpoint is the change from baseline on the MADRS in the patient population characterized by a cognitive biomarker. The completed Phase 2b trial evaluating ALTO-100 as a treatment for MDD demonstrated a clinically meaningful signal in the adjunctive subgroup and evidence of biomarker enrichment in the compliant subset of patients. These data support the ongoing Phase 2b trial of ALTO-100 as an adjunctive treatment in BPD. ALTO-203: Reported topline results from Phase 2 POC MDD trial. ALTO-203 is a novel, oral small molecule designed to uniquely act as a histamine H3 inverse agonist, designed to modulate circuits underlying cognition, wakefulness, and alertness. In June 2025, the Company announced the identification of a patient selection biomarker and positive pharmacodynamic results from its exploratory Phase 2 POC trial of ALTO-203 in MDD patients with elevated levels of anhedonia. The findings in the study replicated results from the Phase 1 study in healthy volunteers, where ALTO-203 treatment led to improvements in sustained attention and reductions in the EEG theta/beta ratio. Baseline EEG theta/beta ratio predicted attentional benefits of ALTO-203 in both the Phase 1 study and Phase 2 POC trial. Alto plans to report additional results from this exploratory study at a future medical meeting and expects to determine the next development steps for ALTO-203 following the complete analysis of the data set. Corporate Updates In August 2025, the Company appointed to its Board of Directors, Raymond Sanchez, M.D., a highly accomplished executive with a strong background in medicine and over 20 years of strategic experience in the life sciences industries. With the addition of Ray, Alto's Board has increased to six members. Upcoming Milestones and Events Near-Term Expected Milestones 2H 2025 — ALTO-101 Phase 2 POC CIAS trial topline data Mid-2026 — ALTO-300 Phase 2b MDD trial topline data Mid-2026 — ALTO-207 Phase 2b TRD trial initiation 2H 2026 — ALTO-100 Phase 2b BPD trial topline data Upcoming Conferences The Company is expected to present at the following upcoming conferences: H.C. Wainwright 27th Annual Global Investment Conference: September 8-10, 2025 Baird 2025 Global Healthcare Conference: September 10, 2025 TD Cowen's 5th Annual Novel Mechanisms in Neuropsychiatry & Epilepsy Summit: September 17-18, 2025 Second Quarter 2025 Financial Highlights Cash Position: As of June 30, 2025 the Company had cash, cash equivalents, and restricted cash of approximately $148.1 million, compared to approximately $168.7 million in cash, cash equivalents, and restricted cash as of December 31, 2024. The Company expects its cash balance to support planned operations into 2028. R&D Expenses: Research and development expenses for the quarter ended June 30, 2025 were $13.1 million, as compared to $13.2 million for the same period in 2024. G&A Expenses: General and administrative expenses for the quarter ended June 30, 2025 were $5.6 million, as compared to $5.2 million for the same period in 2024. Net Loss: The Company incurred a net loss of $17.7 million for the quarter ended June 30, 2025, as compared to $16.0 million for the quarter ended June 30, 2024. 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 bipolar depression, major depressive disorder, treatment resistant depression, and 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 'aims,' 'anticipates,' 'believes,' 'could,' 'estimates,' 'expects,' 'forecasts,' 'goal,' 'intends,' 'look forward,' 'may,' 'plans,' 'possible,' 'potential,' 'seeks,' '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 of enrollment and the timing and availability of data from such trials; Alto's clinical and regulatory development plans for its product candidates, including the timing or likelihood of regulatory filings and approvals for its product candidates; Alto's business strategy, financial position, including anticipated cash runway, 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 Alto's Annual Report on Form 10-K for the fiscal year ended December 31, 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.
UPI
11-07-2025
- UPI
Watch: California woman's home flooded with unwanted Amazon packages
July 11 (UPI) -- A California woman said her house is being flooded with unwanted Amazon packages that have been arriving for about a year. The San Jose resident, who wanted to remain anonymous, said each box contains a faux-leather car seat cover from the brand Etkin and sold by Chinese Amazon seller Liusandedian. The woman's address was apparently listed as the company's address for returns. The online seller's reviews are filled with complaints about seat covers not fitting, the high cost of returns and failure to receive refunds. "Oftentimes, what it costs to return it is about more than 50% of what they paid for it," the woman told KGO-TV. "Plus, these consumers aren't getting their money back!" She said the packages continued to pour in despite Amazon's repeated assurances to fix the issue. "We've apologized to the customer and are working directly with her to pick up any packages while taking steps to permanently resolve this issue," Amazon said in a statement. Company representatives visited the woman's home on Tuesday to remove the packages. John DeFiore of Woodside, Calif., faced a similar issue last year, when dozens of unwanted Amazon packages started arriving at his home. DeFiore's series of deliveries resembled a brushing scam, which involves Amazon sellers sending packages to random addresses so they can artificially inflate their number of positive reviews. Joelle Angleheart of Chapleau, Ontario, was targeted by an apparent brushing scam in 2023 when she received a box containing 1,020 condoms she never ordered and was charged $500. Cindy Smith, of Prince William County, Va., was the target of a similar scheme when she received more than 100 Amazon packages she had never ordered at her home earlier in 2023. Amazon investigated Smith's case and discovered the vendor was having packages shipped to random addresses to remove unsold merchandise from Amazon fulfillment centers.
CTV News
09-07-2025
- Automotive
- CTV News
‘It's been hell': Hundreds of Amazon packages mistakenly shipped to U.S. woman's home for over a year
Hundreds of Amazon packages mistakenly shipped to U.S. woman's home for over a year. KGO via CNN Newsource It's an Amazon nightmare. Imagine hundreds of oversized packages appear on your doorstep -- and you have no clue why. You never ordered them. Yet, the shipping spree to your street continues for more than a year. That's what happened to a San Jose woman. And as 7 On Your Side explains, her frustrating scenario is linked to an overseas online seller who appears to be violating Amazon's return policy. 'Kay' (not her real name) is utterly confused as to why scores of these large boxes filled with car seat covers keep appearing at her doorstep. She says it's non-stop. The mystery 'shipping spree' is now haunting half of her car port. 'What you see now is a fraction, because I have refused delivery on more packages than you see here,' Kay said. Inside each package is a set of faux-leather car seat covers from a Chinese online seller called 'Liusandedian.' The online seller's Amazon listing advertises the brand Etkin, selling seat covers supposedly made to fit various makes and models of sedans and SUVs. But as you can see from Kay's house -- in many of these cases-- the covers didn't fit and consumers said they were forced to pay out of pocket to return them to the company's 'return center.' One person commented online: 'Why haven't I received my refund? Was sent thru UPS 3 weeks ago.' Yet, little do they know -- they're just piling up in Kay's garage. In part because, the online seller put Kay's address on their return labels, leaving her stuck in this mess. Meanwhile, reviews indicate consumers are stuck without their refunds. In one case, a viewer wrote: 'It's going to cost me $124 to return this item!!!' -- an item that she already paid at least $129 for. 'Oftentimes, what it costs to return it is about more than 50% of what they paid for it,' Kay said. 'Plus, these consumers aren't getting their money back!' Kay says she's contacted Amazon countless times to try and resolve this over the past year, including filing six complaint tickets. 'And every time I was absolutely assured this will stop... you won't get any more of these packages, you'll hear from us in 24, 48 hours...' Kay said she was even offered a $100 Amazon gift balance. Nope. Each month, she says, they just kept coming. They blocked her driveway, mail carrier and doorway, making it hard for her 88-year-old mom, who is disabled. 'When we come home, it was like this,' Kay said pointing to the packages crowding her doorstep. 'I couldn't even get my mother in the just been another form of hell.' And to make matters worse, she says Amazon put the onus on her to fix the issue -- suggesting she give the packages away, donate them, or take them back to USPS and FedEx. However, Amazon denies encouraging Kay to return boxes to USPS or FedEx. 'Why is it my responsibility to get rid of this, when your seller is not following your rules Amazon?' she asked. According to Amazon's policy, international sellers must either provide a U.S. address to which to send the return, issue a 'returnless refund' where the buyer does not have to ship the product back, or provide a pre-paid international shipping label within two days of the return request. If sellers don't respond within that timeframe, Amazon may refund the customer on the seller's behalf and charge the amount to the seller. That means 'Liusandedian' would have to lose all proceeds from the sale or pay return shipping to China. Pretty pricey! Amazon also requires that third-party sellers on its marketplace platform display a physical mailing address on their profile, but does not specify that it needs to be within the U.S. So instead -- consumers get stuck with the bill. 'This is thousands of dollars they've paid to send these boxes back to my house!' Kay said as she pointed to the pile as tall as her BBQ. More than 40% of Liusandedian's Amazon reviews have a one-star rating. And unlike other companies, this one has no way for consumers to contact them if an issue like this comes up. Not to mention, there's no trace of a website online showing this seller exists. 7 On Your Side asked Amazon what they're doing to resolve this, and if there's any vetting process to determine if companies selling on their platform actually are who they say they are. While we didn't get a direct answer, the tech giant told us: 'We'd like to thank ABC 7 On Your Side for bringing this to our attention. We've apologized to the customer and are working directly with her to pick-up any packages while taking steps to permanently resolve this issue.' And finally, after a year of waiting, some good news for Kay. The company removed all the packages on her property this morning, vowing to crack down on these practices. 'I am so eternally grateful that you guys are here for us... because reaching out to you, I was in tears that somebody actually got back to me... after a year of trying to get somebody to just listen to me,' Kay told 7 On Your Side's Stephanie Sierra. 'It was such a relief!'
The Independent
09-07-2025
- The Independent
Prime mistake! Woman sent hundreds of returned Amazon packages after Chinese company used her address on labels
A San Jose woman's life was made 'hell' after being inundated with hundreds of Amazon packages linked to a Chinese seller. It all 'started with one package,' said the woman, who has declined to be publicly identified. She said the boxes began appearing on her doorstep last year. 'I was like it's got my address, but it's not for me,' she told ABC 7 News under a pseudonym. 'I went to my neighbors and I was like, 'Oh, has somebody put the wrong last digit on the address?'' For about a year, the woman said she has received large, heavy packages to her home 'non-stop,' blocking her driveway, mail carrier and doorway. It made access particularly difficult for her 88-year-old mother, who is disabled. 'I couldn't even get my mother in the house,' she said. 'It's just been another form of hell.' Each package contained a similar set of items: faux-leather car seat covers from a Chinese online seller called Liusandedian. According to ABC 7 News, the company sold the $129 seat covers under the brand name Etkin, claiming they fit a wide range of sedans and SUVs. But dozens of frustrated buyers said the covers didn't fit and were hit with steep return shipping fees to send them back to Liusandedian's so-called 'return center.' Unbeknownst to them, the return labels listed Holton's home address. Hundreds of boxes piled up on her yard, but Holton says that it was a 'fraction' of what could have arrived, as she often refused delivery. The Amazon listing – now marked as 'currently unavailable' with customer reviews disabled – was previously flooded with negative feedback. Over 40 percent of Liusandedian's reviews were one-star, and buyers had no direct way to contact the seller. 'Why haven't I received my refund? Was sent thru UPS 3 weeks ago,' one customer wrote, according to the station. 'It's going to cost me $124 to return this item!!!,' said another. Liusandedian allegedly violated Amazon's policy, which requires international sellers to either offer a U.S. return address, give a returnless refund, or provide a prepaid return label within two days. Holton claimed she filed six separate complaint tickets to Amazon over the past year to try to resolve the issue. Instead, she claimed Amazon told her to donate the packages, give them away, or return them to USPS or FedEx. Following ABC 7 News's investigation, Amazon said in a statement that it had 'apologized to the customer and are working directly with her to pick up any packages.' An Amazon staff member was filmed finally removing all the packages from her property on Tuesday. The company vowed to crack down on these practices, according to the news station.
Business Wire
03-06-2025
- Business
- Business Wire
Alto Neuroscience Announces Acquisition of Novel Dopamine Agonist Combination Product Candidate, Adding Late-Stage Readout in Treatment Resistant Depression Within Current Cash Runway
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 it entered into an asset purchase agreement with Chase Therapeutics Corporation for a portfolio of potentially best-in-class dopamine agonist drug combinations, including ALTO-207, formerly known as CTC-501, for treatment resistant depression (TRD), generally defined as a failure on two or more antidepressants. The most advanced program, ALTO-207 (formerly known as CTC-501), is a fixed-dose combination of pramipexole, a dopamine D3-preferring D3/D2 agonist, approved for the treatment of Parkinson's disease with demonstrated antidepressant effect, and ondansetron, an antiemetic, selective 5-HT3 receptor antagonist. As a fixed-dose combination, ALTO-207 is designed to enable rapid titration and higher dosing by mitigating the dose-limiting adverse events typically experienced with pramipexole. ALTO-207 is being developed to address the significant unmet need for patients with TRD. 'The expansion of our pipeline aligns with Alto's mission to drive innovation in psychiatry through novel therapeutic solutions,' said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. 'With proprietary insights on dopamine biomarkers in depression that enable targeted neuropsychiatric drug development, we are uniquely positioned to advance ALTO-207, a differentiated, late-stage product candidate with robust clinical effects to date, which are supported with historical pramipexole data. The fixed-dose combination of pramipexole and ondansetron offers a novel treatment strategy designed to optimize for a rapid treatment effect with faster titration, and balance safety and tolerability at high doses. We believe the convenience of a single prescribable agent will also improve compliance and support clinician and patient adoption. Leveraging our targeted biomarker approach to stratify for TRD patients most likely to respond to treatment, we look forward to building on the positive Phase 2a results and initiating a Phase 2b trial, with a potentially pivotal design, by mid-2026.' Dr. Etkin continued, 'The strategic transaction with Chase Therapeutics allows us to add a major late-stage clinical readout to our pipeline without changing our current cash runway guidance into 2028. Broadly, we believe this opportunity underscores the robust value of our precision platform and bolsters our prospects for long-term growth through driving innovation in psychiatry.' Thomas Chase, M.D., President and Chief Executive Officer of Chase Therapeutics Corporation, added, 'Supported by the robust clinical effects in our completed Phase 2a study, we believe CTC-501, has the potential to address the critical need for more effective, mechanistically distinct interventions for patients with TRD. Given Alto's expertise in dopamine-related products in depression, we believe they are an ideal partner to maximize the therapeutic potential of our portfolio in depression and Parkinson's disease. We look forward to seeing Alto continue this exciting momentum as they work toward realizing our shared vision for patients.' Michael Browning, DPhil, MRCP, MRCPsych, Professor of Computational Psychiatry, University of Oxford, commented, 'I am highly encouraged by the recently completed PAX-D study of pramipexole, which suggests a greater and more durable effect than other available TRD treatments. However, pramipexole is not well tolerated and when it is, it requires slow titration due to dose-limiting AEs. The clinical utility of pramipexole would be greatly enhanced by improving the dose-limiting tolerability profile. Emerging data suggests that ALTO-207 could address these challenges, and be well positioned to treat this large and underserved patient population.' Alto acquired CTC-501 (now ALTO-207), in development for depression, and CTC-413 (now ALTO-208), in development for Parkinson's disease. Both product candidates are novel patent-protected dopamine agonists. About the Completed Phase 2a Trial for CTC-501 Chase Therapeutics completed a randomized, placebo-controlled Phase 2a clinical trial evaluating CTC-501 in 32 patients with depression. The study consisted of two periods, a dose titration period in which patients were dosed with increasing dose levels of CTC-501 or placebo at increments of 1 mg/day (or matching placebo) until the maximum allowed dose (or first intolerable dose) was reached. Patients were then maintained for an eight-week treatment period at either the maximum allowed dose or their maximum tolerated dose (1 mg/day lower than their first intolerable dose in the titration period). The primary endpoint in the study was defined as overall tolerability and achievement of higher dose levels of pramipexole when combined with ondansetron. Clinical efficacy was evaluated as a secondary exploratory endpoint in the study. The primary endpoint was achieved in the study. Patients randomized to receive CTC-501 reached a mean dose of 4.1mg per day with 67% of patients achieving the highest allowable dose of 5mg/day. CTC-501 was generally well tolerated in the maintenance period of the study. The clinical efficacy measures were evaluated as secondary endpoints and across measures CTC-501 demonstrated large, clinically meaningful, effects. CTC-501 demonstrated statistically significant and clinically meaningful improvements from baseline compared to placebo on depression symptoms as measured by the Montgomery Åsberg Depression Rating Scalef, or MADRS (LSM Δ vs. placebo at Week 8 = -8.2, p=0.025, Cohen's d=1.1). CTC-501 also demonstrated a significantly greater improvement compared to placebo on the Clinician Global Impression Scale of Severity, or CGI-S (LSM Δ vs. placebo at Week 8 = -0.76, p=0.04, Cohen's d=1.0). About the Completed Phase 2a Trial for CTC-413 ALTO-208 is a fixed-dose combination of pramipexole and aprepitant, an antiemetic, neurokinin-1 (NK-1) receptor antagonist. ALTO-208 is being developed for patients with Parkinson's disease (PD). Chase Therapeutics completed a blinded Phase 2a clinical trial evaluating CTC-413 (pramipexole co-administered with aprepitant) in 13 patients with PD. The study consisted of two periods. Patients in the treatment group were initially titrated to the maximum allowed dose of standard pramipexole extended release (4.5 mg/day). Patients were then switched to CTC-413 until the maximum allowed dose of 9mg/day (or first intolerable dose) was reached. Following three months of maintenance, patients returned to their pre-study regimen for final assessment. The mean tolerated dose of CTC-413 significantly exceeded pramipexole (p<0.001). Six subjects (67%) tolerated CTC-413 at the maximum dose of 9.0mg/day and all but one remained on that dose throughout the final three-month treatment period. CTC-413 demonstrated favorable safety and tolerability with no unexpected, serious or persistent issues. About the Transaction Under the terms of the asset purchase agreement, Alto paid Chase Therapeutics an upfront payment of $1.75 million, and Chase Therapeutics will be eligible for up to an aggregate of $71.5 million in future milestone payments related to prespecified development and commercial milestones. $41 million of the potential future milestone payments are tied to commercial success of the product candidates. Alto's financial guidance remains unchanged. The Company expects its current cash balance to support planned operations into 2028, now through five clinical trial readouts across its pipeline programs. Conference Call and Webcast at 8:00 a.m. ET Today Alto Neuroscience will host a conference call today at 8:00 a.m. ET to discuss the acquisition of a novel dopamine agonist combination product candidate. The call will feature Michael Browning, Professor of Computational Psychiatry at the University of Oxford, and Alan Schatzberg, M.D., Professor of Psychiatry and Behavioral Sciences at Stanford University. To listen to the live webcast, please visit Alto's investor relations website. Participants may register for the call here. A replay of the webcast will be available following the conclusion of the live call and will be accessible on the Company's website. 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 bipolar depression, major depressive disorder, treatment resistant depression (TRD), and 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 '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 about 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 clinical trials; the reproducibility of positive clinical data seen in prior trials of CTC-501/ALTO-207; Alto's clinical and regulatory development plans for ALTO-207; the competitive landscape and potential market opportunities for ALTO-207; and Alto's anticipated cash runway. 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 Annual Report on Form 10-K for the fiscal year ended December 31, 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.
