D3 receptor

Gothenburg, 29 October 2024 – IRLAB Therapeutics AB (Nasdaq Stockholm: IRLAB A), a company discovering and developing novel treatments for Parkinson’s disease, today reports several advances in the preparations for Phase III with its drug candidate mesdopetam. The regulatory authorities in Germany and Portugal are positive about IRLAB’s proposed study design for the Phase III program. New market research validates the high commercial potential of mesdopetam, and a meta-analysis recently presented at the MDS scientific conference confirms the pronounced effect against levodopa-induced dyskinesias in people with Parkinson’s disease. Gothenburg, 29 October 2024 – IRLAB Therapeutics AB (Nasdaq Stockholm: IRLAB A), a company discovering and developing novel treatments for Parkinson's disease, today reports several advances in the preparations for Phase III with its drug candidate mesdopetam. The regulatory authorities in Germany and Portugal are positive about IRLAB's proposed study design for the Phase III program. New market research validates the high commercial potential of mesdopetam, and a meta-analysis recently presented at the MDS scientific conference confirms the pronounced effect against levodopa-induced dyskinesias in people with Parkinson's disease. “The recent progress in the preparation for Phase III with mesdopetam strengthens our position in the ongoing discussions with potential partners. We continue to experience strong interest from various stakeholders and are now evaluating options in the further development and potential commercialization of our unique drug candidate, mesdopetam,” says IRLAB's CEO, Kristina Torfgård. Positive feedback from regulatory authorities IRLAB has recently held scientific advisory meetings with the German regulatory authority BfArM and its Portuguese counterpart INFARMED. In the meetings, both authorities provided clear guidance on, among other things, the critical components of the Phase III program, which are essentially in line with the plans agreed upon between IRLAB and the US Food and Drug Administration (FDA). As in the dialogues with the FDA, a consensus was reached on, among other things, the patient population, the primary and secondary endpoints, that the protocol follows regulatory guidelines of at least a 3-month treatment period, essential inclusion and exclusion criteria, the dose selection (7.5 mg twice daily), the number of participants in the program, as well as details on safety evaluation and documentation requirements. The interactions with BfArM and INFARMED are part of the strategic regulatory activities, including the previously successful End-of-Phase 2 meeting with the FDA and the upcoming interaction with the European Medicines Agency (EMA). The aim is to ensure that the Phase III program and further development of mesdopetam are designed to meet the regulatory requirements in both the US and Europe. New market research confirms the commercial potential IRLAB has recently conducted in-depth market research to guide the company and its future commercial partners in positioning for a future launch of mesdopetam in the US and Europe. Structured interviews have been carried out with healthcare organization officials in both regions to better understand current treatment practices and the medical need for new treatments that can reduce levodopa-induced dyskinesias in Parkinson's disease. The results of the market research indicate a high willingness to pay for an anti-dyskinetic drug with a novel and effective mechanism of action. Thus, providing significant commercial potential for mesdopetam in both the US and Europe. It also shows that the planned design of the Phase III program aligns with the desires of the healthcare funders. New meta-analysis highlights the medical benefits of mesdopetam A meta-analysis recently presented at the International Congress of Movement Disorders (MDS) in Philadelphia, USA, shows that treatment with mesdopetam provides clinically meaningful anti-dyskinetic efficacy without causing impairment of motor function. Further, the drug candidate reduces “OFF time", the total time of the day when classic Parkinson's symptoms recur. The meta-analysis is based on two previously conducted Phase II studies with four and twelve weeks of treatment, respectively. The acknowledgment of the meta-analysis for presentation at such a prestigious international conference underscores its quality and the medical relevance of the results. For more information Kristina Torfgård, CEO Phone: +46 730 60 70 99 E-mail: kristina.torfgard@irlab.se Nicholas Waters, EVP and Head of R&D Phone: +46 730 75 77 01 E-mail: nicholas.waters@irlab.se About mesdopetam The investigational drug mesdopetam (IRL790), a dopamine D3 receptor antagonist, is being developed as a treatment for Parkinson’s disease levodopa-induced dyskinesias (PD-LIDs). The objective is to improve the quality of life for people living with Parkinson’s and having a severe form of involuntary movements commonly occurring after chronic levodopa treatment. Around 25-40 percent of all people being treated for Parkinson’s develop LIDs, which equates to approximately 1.4-2.3 million people in the eight major markets globally (China, EU5, Japan and the US). Mesdopetam has also potential as a treatment for Parkinson’s disease Psychosis (PD-P), and other neurological conditions such as tardive dyskinesia, representing an even larger market. The Phase Ib and Phase IIa studies showed a good safety and tolerability profile as well as proof-of-concept with potential for a better anti-dyskinetic effect compared with current treatment options. A Phase IIb study, completed in 2023, showed that mesdopetam has a dose-dependent anti-dyskinetic and anti-parkinsonian effect in combination with a tolerability and safety profile on par with placebo. The mesdopetam program is now undergoing preparations for Phase III. About IRLAB IRLAB discovers and develops a portfolio of transformative treatments for all stages of Parkinson's disease. The company originates from Nobel Laureate Prof Arvid Carlsson's research group and the discovery of a link between brain neurotransmitter disorders and brain diseases. Mesdopetam (IRL790), under development for treating levodopa-induced dyskinesias, has completed Phase IIb and is in preparation for Phase III. Pirepemat (IRL752), currently in Phase IIb, is being evaluated for its effect on balance and fall frequency in Parkinson's disease. IRL757, a compound being developed for the treatment of apathy in neurodegenerative disorders, is in Phase I. In addition, the company is developing two preclinical programs, IRL942 and IRL1117, towards Phase I studies. IRLAB's pipeline has been generated by the company's proprietary systems biology-based research platform Integrative Screening Process (ISP). Headquartered in Sweden, IRLAB is listed on Nasdaq Stockholm (IRLAB A). For more information, please visit www.irlab.se. Attachments IRLAB reports continued progress ahead of the mesdopetam Phase III program

The first-in-human Phase 1 clinical study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic profile of ENX-104 in healthy volunteers SAN DIEGO, Sept. 18, 2024 (GLOBE NEWSWIRE) -- Engrail Therapeutics, a precision neuroscience company focused on the development of transformational therapies to improve the lives of patients, today announced initiation of a Phase 1 single ascending dose clinical study for ENX-104 in healthy volunteers. ENX-104 is a potent and selective dopamine D2/D3 receptor antagonist designed to enhance dopamine neurotransmission by preferential autoreceptor inhibition at low doses. The lead indication for ENX-104 is the treatment of major depressive disorder (MDD) characterized by anhedonia (aMDD). Anhedonia is the inability to experience pleasure in normally pleasurable activities and is a core symptom of MDD that is largely unresponsive to currently approved antidepressants. “Dysregulation of dopamine in the reward centers of the brain is believed to underlie anhedonia which is experienced by 60-70% of MDD patients. ENX-104 provides a novel and targeted approach to enhancing dopamine modulation and represents a potential new therapeutic modality for the treatment of patients with aMDD,” said Vikram Sudarsan, PhD, chief executive officer of Engrail. “The initiation of this Phase 1 study is a significant step forward for ENX-104 and an important milestone for Engrail as our second clinical-stage program.” The ENX-104 Phase 1 study is a randomized, double-blind, placebo-controlled single ascending dose clinical study that is expected to enroll up to 48 healthy adult volunteers. The primary objective is to evaluate the safety and tolerability of ENX-104 after a single oral administration of increasing doses in separate cohorts. Each dose cohort will include 8 subjects, with 6 subjects randomized to ENX-104 and 2 to placebo. The study is also designed to measure pharmacokinetics and explore the pharmacodynamic effects of ENX-104 on biomarkers associated with changes in dopamine neurotransmission in order to ascertain target engagement. About ENX-104ENX-104 is a potent dopamine D2/D3 receptor antagonist in development for major depressive disorder (MDD) characterized by anhedonia (aMDD). Dysregulated dopaminergic neurotransmission, particularly in brain reward systems, is believed to underlie anhedonia, a hallmark symptom of MDD. ENX-104 was designed to directly modulate dopaminergic transmission in brain reward systems by increasing dopamine release via potent antagonism of presynaptic D2/D3 autoreceptors at low doses. ENX-104 is in Phase 1 clinical development. About Engrail TherapeuticsEngrail is a clinical-stage pharmaceutical company with a rich pipeline of precision-targeted neuroscience programs designed to improve the lives of patients with neuropsychiatric and neurodevelopmental diseases. ENX-102, a next-generation GABAA positive allosteric modulator, is in Phase 2 clinical development for the treatment of generalized anxiety disorder. ENX-104, a potent dopamine D2/D3 receptor antagonist, is in Phase 1 clinical development for the treatment of major depressive disorder characterized by anhedonia. Additional programs in development are intended to address significant unmet medical needs for the treatment of posttraumatic stress disorder, anxiety-, mood- and stress-related disorders and rare neurological conditions. At Engrail, we apply precision chemistry and pharmacology to develop transformative medicines for patients who are underserved by existing treatments. For more information, visit engrail.com. Media Contact:Anil Vootkur, PharmDEngrail Therapeuticsanil@engrail.com

Gothenburg, Sweden, September 4, 2024 – IRLAB Therapeutics AB (Nasdaq Stockholm: IRLAB A), a company discovering and developing novel treatments for Parkinson’s disease, today announced that the company has been granted a new patent in Europe, which includes a new salt of mesdopetam used throughout the clinical development process and the process of its preparation. The patent that has now been granted extends the already strong patent protection for mesdopetam, the company’s most advanced project. Gothenburg, Sweden, September 4, 2024 – IRLAB Therapeutics AB (Nasdaq Stockholm: IRLAB A), a company discovering and developing novel treatments for Parkinson’s disease, today announced that the company has been granted a new patent in Europe, which includes a new salt of mesdopetam used throughout the clinical development process and the process of its preparation. The patent that has now been granted extends the already strong patent protection for mesdopetam, the company's most advanced project. “The already strong patent protection for mesdopetam is now expanded with a patent, EP3976581B1, which protects the active pharmaceutical ingredient of mesdopetam used in clinical development. With the extended protection, there is potential to extend market exclusivity for mesdopetam right up to the early 2040s, which is incredibly positive for the value of mesdopetam,” said Kristina Torfgård, CEO of IRLAB. Mesdopetam has a vast clinical potential for unmet medical needs in Parkinson’s disease. The drug candidate is intended to treat people with Parkinson’s who develop levodopa induced dyskinesias (PD-LIDs), which is more than 30 percent of all people living with Parkinson’s. This equates to more than 1.5 million affected individuals in the eight major markets worldwide. Mesdopetam has previously been granted a family of substance patents in all major markets worldwide. The newly approved patent covers a salt of mesdopetam which is used in the formulations in the ongoing clinical development. The patent expires in 2040. With the potential grant of a supplementary protection certificate (SPC) exclusivity can reach into the early 2040s. For more information Kristina Torfgård, CEO Phone: +46 730 60 70 99 E-mail: kristina.torfgard@irlab.se About mesdopetam The investigational drug mesdopetam (IRL790), a dopamine D3 receptor antagonist, is being developed as a treatment for Parkinson’s disease levodopa-induced dyskinesias (PD-LIDs). The objective is to improve the quality of life for people living with Parkinson’s and having a severe form of involuntary movements commonly occurring after chronic levodopa treatment. Around 25-40 percent of all people being treated for Parkinson’s develop LIDs, which equates to approximately 1.4-2.3 million people in the eight major markets globally (China, EU5, Japan and the US). Mesdopetam has also potential as a treatment for Parkinson’s disease Psychosis (PD-P), and other neurological conditions such as tardive dyskinesia, representing an even larger market. The Phase Ib and Phase IIa studies showed a good safety and tolerability profile as well as proof-of-concept with potential for a better anti-dyskinetic effect compared with current treatment options. A Phase IIb study, completed in 2023, showed that mesdopetam has a dose-dependent anti-dyskinetic and anti-parkinsonian effect in combination with a tolerability and safety profile on par with placebo. The mesdopetam program is now undergoing preparations for Phase III. About IRLAB IRLAB discovers and develops a portfolio of transformative treatments for all stages of Parkinson's disease. The company originates from Nobel Laureate Prof Arvid Carlsson's research group and the discovery of a link between brain neurotransmitter disorders and brain diseases. Mesdopetam (IRL790), under development for treating levodopa-induced dyskinesias, has completed Phase IIb and is in preparation for Phase III. Pirepemat (IRL752), currently in Phase IIb, is being evaluated for its effect on balance and fall frequency in Parkinson's disease. IRL757, a compound being developed for the treatment of apathy in neurodegenerative disorders, is in Phase I. In addition, the company is developing two preclinical programs, IRL942 and IRL1117, towards Phase I studies. IRLAB's pipeline has been generated by the company's proprietary systems biology-based research platform Integrative Screening Process (ISP). Headquartered in Sweden, IRLAB is listed on Nasdaq Stockholm (IRLAB A). For more information, please visit www.irlab.se. Attachments IRLAB is granted additional patent for drug candidate mesdopetam that expands its patent protection