Pramipexole Dihydrochloride

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, announced today that, following a successful outcome from a recent FDA meeting, it plans to accelerate the development of ALTO-207 for people with treatment resistant depression (TRD). The $50 million private placement announced today supports expanded development of ALTO-207, and the Company expects to initiate a Phase 3 study by early 2027 following Phase 3 readiness work and alignment with the FDA on the planned study design. “The successful outcome of our recent FDA meeting for ALTO-207 was a critical step forward, and the financing we announced provides us with the resources to expedite its path toward pivotal studies and potential future approval," said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. “We believe we are well-positioned to advance ALTO-207 for the many patients who are not adequately served by current therapies.” ALTO-207 Planned Milestones - Alto expects to initiate a Phase 2b, potentially pivotal, clinical trial of ALTO-207 in people with TRD by mid-2026. - Alto now expects to initiate a Phase 3 clinical trial by early 2027 pending protocol alignment with the FDA and planned Phase 3 readiness work following the recent FDA discussion. Additional Pipeline Updates - ALTO-100 and ALTO-101: Positive results from blinded PK analysis supports enhanced clinical trial execution efforts to mitigate non-compliance risk. A blinded PK analysis from the first cohort of patients in the ongoing Phase 2 study evaluating ALTO-100 as a treatment for bipolar depression and ALTO-101 for cognitive impairment associated with schizophrenia (CIAS) demonstrated that 96% of samples for ALTO-100 and 100% of samples tested for ALTO-101 qualified as PK positive. A sample was considered PK positive if observed drug levels were above a pre-specified minimum threshold. The result for ALTO-100 significantly exceeds typical compliance rates seen in similar CNS trials and underscores the effectiveness of the operational adjustments made to trial design and execution. The Company believes this is a strong indicator of patient tolerability and engagement with the treatment regimen. - Updated guidance on topline data timing for ALTO-101: Enrollment remains ongoing in the Phase 2, proof-of-concept study of ALTO-101 in CIAS, and the Company expects to report topline data from this study in 1Q 2026. About ALTO-207 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 treatment resistant depression. In a randomized, placebo-controlled Phase 2a clinical trial evaluating ALTO-207 in 32 patients with depression, ALTO-207 met primary and secondary endpoints demonstrating significantly greater improvements on MADRS compared to placebo. Patients randomized to receive ALTO-207 reached a mean dose of 4.1mg per day. ALTO-207 was well tolerated in the maintenance period of the study with an adverse event rate similar to placebo. 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 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 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, the anticipated use of proceeds from the Company’s recently announced private placement transaction and the Company’s expectations about the closing of the private placement, including the satisfaction of customary closing conditions; statements regarding Alto’s expectations about the potential benefits, activity, effectiveness, tolerability, and safety of its product candidates and Precision Psychiatry Platform (“Platform”); statements regarding patient compliance and the effectiveness of Alto’s clinical trial execution measures; statements regarding Alto’s expectations for the design, progress and results of both its ongoing Phase 2 trial of ALTO-100 in bipolar depression and its Phase 2 POC trial of ALTO-101 in CIAS; Alto’s expectations with regard to the general 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 business strategy and financial position, including its anticipated cash runway and expectations regarding funding, operating and working capital expenditures; 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 (including the Phase 2 trial of ALTO-100 in bipolar depression and the Phase 2 POC trial of ALTO-101) and whether the indicative PK data translates into verified patient compliance in the final results of both trials, the availability and timing of results from clinical trials, the risk that Alto’s projections regarding its financial position and expected cash runway are inaccurate or that the 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 each of Alto’s Annual Report on Form 10-K for the fiscal year ended December 31, 2024 and Alto’s Quarterly Report on Form 10-Q for the fiscal quarter ended June 30, 2025 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.

Investigational cell therapy bemdaneprocel continues to demonstrate a favorable safety profile at 36 months in Phase I trial participants Secondary clinical efficacy endpoints related to motor outcomes remain stable compared to 24 months and continue to show positive trends from baseline Data were presented on October 6th at the International Congress of Parkinson’s Disease and Movements Disorders® WHIPPANY, N.J.--(BUSINESS WIRE)--Bayer AG and its wholly owned, independently operated subsidiary BlueRock Therapeutics LP, a clinical stage cell therapy company, today announced positive 36-month data from exPDite, a Phase I clinical trial of bemdaneprocel, an investigational cell therapy for the treatment of Parkinson's disease (PD). The data were presented on October 6th at the International Congress of Parkinson’s Disease and Movements Disorders. “Bemdaneprocel represents a new approach to restoring the dopamine inputs that are lost in Parkinson’s, and leverages substantial advances in stem cell technology,” said Claire Henchcliffe, MD, chair of the UC Irvine School of Medicine’s Department of Neurology at the University of California, Irvine and one of the study’s Principal Investigators. “The new 3-year data is a critical next step to evaluate longer term safety. While there is a need for caution in interpreting the positive trends in clinical outcomes, initial signals are there, particularly in the higher dose cohort and the upcoming exPDite-2 clinical trial should shed further light on potential benefits.” Bemdaneprocel’s safety profile at 36 months is consistent with earlier findings, demonstrating that it continues to be well tolerated by patients, with no adverse events reported related to the therapy or surgical procedure. F-Dopa imaging suggests that transplanted cells continue to survive and engraft in the brain after discontinuing immunosuppression therapy at 12 months as outlined in the study’s protocol. In addition, secondary clinical endpoints related to motor symptoms continue to show positive trends from baseline through the duration of follow-up, with more encouraging trends in the high dose cohort than those in the low dose cohort. These were assessed by the MDS-Unified Parkinson’s Disease Rating Scale Part II and III (MDS-UPDRS Part II & III) and the Parkinson’s disease Diary, tools used to assess Parkinson’s disease severity in motor symptoms. “The 36-month data from this Phase I study underscores our hope that bemdaneprocel could be a potentially meaningful and durable therapeutic option for treating people living with Parkinson’s disease,” said Gabi Belfort, MD, PhD, Senior Vice President and Bemdaneprocel Product Lead at BlueRock Therapeutics. “We are excited to share these data with the Parkinson’s disease community and are committed to advancing bemdaneprocel through the next stage of clinical testing.” In the high dose cohort (n=7), the 36-month measurement of the effects of bemdaneprocel on motor symptoms using the MDS-UPDRS Part III measured in the “OFF”-medication state, showed a mean reduction of 17.9 points compared with baseline. The low dose cohort (N=4) showed a mean decrease of 13.5 points. Both are considered to be clinically meaningful.1 Using the PD Diary, which categorizes patients as being in the “ON” state when their symptoms are well controlled and in the “OFF” state when they experience a worsening of their symptoms, participants in the high dose cohort showed a mean increase of 1 hour in time spent in the “Good ON” state (without troublesome dyskinesias) compared with baseline after 36 months. Two participants in the high dose cohort did not submit a 36-month PD Diary. Time spent in the “OFF” state showed a mean decrease of - 0.93 hours from baseline after 36 months. The participants in the low dose cohort showed a mean increase of 0.23 hours in the “Good ON” state time compared with baseline and a corresponding mean decrease of –1.15 hours in “OFF” state time. In the high dose cohort, the 36-month measurement of the effects of bemdaneprocel on activities of daily living using the MDS-UPDRS Part II measured a mean reduction of -4.3 points compared with baseline. The low dose cohort showed a mean increase of 0.2 points. Participants in both cohorts continue in the long term Continued Evaluation Study. “The results for bemdaneprocel after 36 months mark another motivating milestone,” said Christian Rommel, Global Head of Research and Development of the Pharmaceuticals Division at Bayer. “They reinforce our commitment to developing urgently needed new treatment options for Parkinson's patients.” About bemdaneprocel (BRT-DA01) Bemdaneprocel (BRT-DA01) is an investigational cell therapy designed to replace the dopamine producing neurons that are lost in Parkinson’s disease. These dopaminergic neuron precursors are derived from human embryonic pluripotent stem cells that continue developing into mature dopamine neurons after implantation. In a surgical procedure, these neuron precursors are implanted into the brain of a person with Parkinson’s disease. When transplanted, they have the potential to re-form neural networks that have been severely affected by Parkinson’s disease and to potentially restore motor and non-motor function to patients. In 2021 bemdaneprocel received Fast Track Designation and in 2024 a Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA. A pivotal Phase III trial to assess the efficacy, safety and overall impact of bemdaneprocel compared to sham surgery control is currently enrolling participants. Bemdaneprocel has not been approved for treatment of any disease or medical condition by any health authority. About Parkinson’s disease Parkinson’s disease (PD) is a progressive neurodegenerative disease. It has a significant impact on a person’s daily life. In PD, the death of dopamine producing nerve cells in the brain leads to the continuous loss of motor function. Symptoms include tremors, muscle rigidity, and slowness of movement. Additionally, people with PD experience non-motor symptoms, including fatigue and lack of energy, cognitive issues, and depression. Symptoms typically intensify over time and make everyday tasks demanding. The prevalence of PD has doubled over the past 25 years. Today, more than 10 million people worldwide are estimated to be living with PD. This makes it the world’s second most prevalent neurodegenerative disease. It is also the most frequent movement disorder. At present there is no cure, and current treatment options are inadequate and lack holistic management of symptoms so there is an urgent need for new therapies. About BlueRock Therapeutics LP BlueRock Therapeutics LP is a clinical stage cell therapy company focused on creating cellular medicines to treat devastating diseases. We are harnessing the power of cell therapy to create a pipeline of new medicines for people suffering from neurological and ophthalmic diseases. Two of our novel investigational cell therapies, bemdaneprocel (BRT-DA01) for the treatment of Parkinson’s disease and OpCT-001 for the treatment of primary photoreceptor diseases are clinical stage programs. Bemdaneprocel has RMAT (Regenerative Medicine Advanced Therapy) and Fast Track designation from the US FDA (Food and Drug Administration) and is being tested in a Phase III clinical trial, exPDite-2. OpCT-001 has Fast Track designation from the FDA and is being tested in a Phase I clinical trial, Clarico. BlueRock was founded in 2016 as a joint venture of Versant Ventures and Leaps by Bayer, the impact investing arm of Bayer AG that invests in paradigm-shifting breakthrough innovation. In late 2019, BlueRock became a wholly owned, independently operated subsidiary of Bayer AG. Our culture is defined by the courage to persist regardless of the challenge, the urgency to transform medicine and deliver hope, integrity guided by mission, and community-mindedness with the understanding that we are all part of something bigger than ourselves. For more information, visit www.bluerocktx.com. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2024, the Group employed around 93,000 people and had sales of 46.6 billion euros. R&D expenses amounted to 6.2 billion euros. For more information, go to www.bayer.com. Find more information at https://pharma.bayer.com/ Follow us on Facebook: http://www.facebook.com/bayer Find information at www.bluerocktx.com Follow us on LinkedIN: www.linkedin.com/company/bluerocktx Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. ____________________ 1 Hauser RA, Gordon MF, Mizuno Y, Poewe W, Barone P, Schapira AH, Rascol O, Debieuvre C, Fräßdorf M. Minimal clinically important difference in Parkinson's disease as assessed in pivotal trials of pramipexole extended release. Parkinsons Dis. 2014;2014:467131. doi: 10.1155/2014/467131. Epub 2014 Apr 1. PMID: 24800101; PMCID: PMC3995302.