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AUSTIN, Texas, June 04, 2024 (GLOBE NEWSWIRE) -- Lumos Pharma, Inc. (NASDAQ:LUMO), a clinical-stage biopharmaceutical company focused on therapeutics for rare diseases, announced today details of new analyses of data from its Phase 2 OraGrowtH212 clinical trial presented in two posters at the 2024 Annual Meeting of the Endocrine Society (ENDO), held in Boston, MA, June 1-4, 2024. The posters were presented in parallel sessions on Monday June 3, 2024. “The new analyses of data from our OraGrowtH212 Trial further characterized LUM-201’s unique ability to augment the natural pulsatile secretion of growth hormone, producing comparable growth to injectable rhGH with significantly less exposure to circulating growth hormone,” said John C. McKew, PhD, President and Chief Scientific Officer of Lumos Pharma. “The presented results also provide additional support for our planned approach to a placebo-controlled Phase 3 trial of LUM-201 in moderate PGHD, a trial design proposed by the FDA as an appropriate option for oral LUM-201 given its differentiated mechanism as a growth hormone secretagogue.” In the poster MON-111, titled, Oral LUM-201 Restores Pulsatile Growth Hormone Secretion and Growth Response in Moderate Pediatric Growth Hormone Deficiency (PGHD): Key Discoveries from Phase 2 of OraGrowtH212 Trial (Cassorla, F, et al) [poster link], investigators evaluated growth hormone pulsatility data obtained at baseline and at six months following treatment with LUM-201. Results showed that at six months on LUM-201, a significant increase over baseline in key parameters was observed for the 1.6 mg/kg/day dose. At baseline GH secretion was 0.19 ±0.09 μg/kg/12-hrs; pulsatile GH was 1.17 ±0.66 μg/kg/12-hrs; and total GH was 1.35 ±0.66 μg/kg/12-hrs.At 6 months each parameter increased significantly: GH secretion to 0.36 ±0.21 μg/kg/12-hrs, pulsatile GH to 1.8 ±0.74 μg/kg/12-hrs, and total GH to 2.2 ±0.89 μg/kg/12-hrsA similar level of increase was observed in the 3.2 mg/kg/day dose cohortInvestigators combined data from both dose cohorts and conducted a deconvolution analysis on GH secretion. It was determined that at six months GH secretion was 3.3 ±1.8 to 4.4 ±2.1 μg/kg/day compared to 5.0 ±1.3 μg/kg/day derived from published data in normal children, indicating restoration of approximately normal GH secretion by LUM-201.Conclusion – at 6 months LUM-201 was able to restore endogenous GH pulsatile secretion to a similar level seen in normal children while also normalizing serum IGF-1 concentrations. Results indicate that by restoring endogenous GH secretion, LUM-201 facilitates growth utilizing a much lower amount of GH than that provided by daily exogenous rhGH. By providing an oral therapy that attains physiological GH profiles, investigational LUM-201 treatment aligns with the fundamental objectives of endocrine therapies, specifically the restoration of normal hormonal homeostasis. In a late-breaking poster (MON-704) titled, Growth Response to Oral Growth Hormone Secretagogue LUM-201 in Children with Moderate GH Deficiency (GHD) is Dependent on the Pattern of Pulsatile GH Secretion Stimulated by LUM-201 (Stevens, A, et al), [poster link], investigators evaluated pulsatile GH profiles and growth response to LUM-201. Data from OraGrowtH212 pulse assessments at Day 1 (D1) and at 6 months (M6) were analyzed utilizing a univariate Spearman’s rank correlations matrix to screen for relationships between D1 characteristics, D1 height velocity, 6M Annualized Height Velocity and interpulse, pulsatile, and total GH secretion at D1 and M6.The 12-hour pattern of pulsatile secretion was characterized using Functional Principal Component Analysis (FPCA) to identify dominant modes of variation in the functional data. Subjects were grouped into tertiles based on 6M AHV. The 12-hour profiles were grouped into three 4-hour intervals.Results: All parameters increased from D1 to M6D1 pulsatile GH secretion was positively associated with D1 AHVWhile 6M AHV increased compared to baseline, GH Secretion at D1 and M6 was not apparently correlated with 6M AHVIn the FPCA, difference in interquartile range (IQR) for mean GH secretion was highest in 0-4 hrs in subjects in the high and medium AHV tertiles, while subjects with low AHV at 6 months had the highest difference at 8-12 hours Conclusions – LUM-201 stimulates significant increases in GH secretion over 6 months in patients with moderate PGHD. The relationship between growth response and both the amount and pattern of pulsatile GH secretion, with the highest growth observed in OraGrowtH212 associated with greatest pulsatile activity early in the 12 hour profile. Restoring GH secretion with LUM-201 in moderate PGHD results in both an increase in the overall amount of GH, and importantly, an alteration of the pattern of the pulse profile, with distinct differences in these patterns between the best and lower responders. About Lumos Pharma Lumos Pharma, Inc. is a clinical stage biopharmaceutical company focused on the development and commercialization of therapeutics for rare diseases. The Company was founded and is led by a management team with longstanding experience in rare disease drug development. Lumos Pharma’s lead therapeutic candidate, LUM-201, is a novel, oral growth hormone (GH) secretagogue, seeking to transform the ~$4.7B global GH market from injectable to oral therapy. LUM-201 is currently being evaluated in multiple Phase 2 clinical studies in Pediatric Growth Hormone Deficiency (PGHD) and has received Orphan Drug Designation in both the US and EU. For more information, please visit https://lumos-pharma.com/. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements of Lumos Pharma, Inc. that involve substantial risks and uncertainties. All such statements contained in this press release are forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. A law that, in part, gives us the opportunity to share our outlook for the future without fear of litigation if it turns out our predictions were not correct. We are passionate about our business - including LUM-201 and the potential it may have to help patients in the clinic. This passion feeds our optimism that our efforts will be successful and bring about meaningful change for patients. Please keep in mind that actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. We have attempted to identify forward-looking statements by using words such as “projected,” "upcoming," "will," “would,” "plan," “intend,” "anticipate," "approximate," "expect," “potential,” “imminent,” and similar references to future periods or the negative of these terms. Not all forward-looking statements contain these identifying words. Examples of forward-looking statements include, among others, statements we make regarding the advancement of oral LUM-201 to Phase 3, the potential for LUM-201 to be the first oral therapeutic for PGHD, and any other statements other than statements of historical fact. We wish we were able to predict the future with 100% accuracy, but that just is not possible. Our forward-looking statements are neither historical facts nor assurances of future performance. You should not rely on any of these forward-looking statements and, to help you make your own risk determinations, we have provided an extensive discussion of risks that could cause actual results to differ materially from our forward-looking statements including risks related to the timing and ability of Lumos Pharma to structure our Phase 3 trial in an effective and timely manner, the ability to initiate and advance a pivotal Phase 3 trial, as well as advance our clinical and corporate strategy in general, our ability to project future cash utilization and reserves needed for contingent future liabilities and business operations, the ability to successfully develop our product candidate, the effects of pandemics, other widespread health problems or military conflicts including the Ukraine-Russia conflict and the Middle East conflict and other risks that could cause actual results to differ materially from those matters expressed in or implied by such forward-looking statements including information in the "Risk Factors" section and elsewhere in Lumos Pharma’s Quarterly Report on Form 10-Q for the period ended September 30, 2023, as well as other subsequent reports filed with the SEC. All of these documents are available on our website. Before making any decisions concerning our stock, you should read and understand those documents. We anticipate that subsequent events and developments will cause our views to change. We may choose to update these forward-looking statements at some point in the future, however, we disclaim any obligation to do so. As a result, you should not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this press release. Investor & Media Contact: Lisa MillerLumos Pharma Investor Relations512-792-5454ir@lumos-pharma.com Source: Lumos Pharma, Inc.

Neuroscientists find two distinct cell populations in the striatum are affected differently by Huntington's disease. They believe neurodegeneration of one of these populations leads to motor impairments, while damage to the other population, located in a structure called the striosome, may account for the mood disorders that are often see in the early stages of the disease. In patients with Huntington's disease, neurons in a part of the brain called the striatum are among the hardest-hit. Degeneration of these neurons contributes to patients' loss of motor control, which is one of the major hallmarks of the disease. Neuroscientists at MIT have now shown that two distinct cell populations in the striatum are affected differently by Huntington's disease. They believe that neurodegeneration of one of these populations leads to motor impairments, while damage to the other population, located in structures called striosomes, may account for the mood disorders that are often see in the early stages of the disease. "As many as 10 years ahead of the motor diagnosis, Huntington's patients can experience mood disorders, and one possibility is that the striosomes might be involved in these," says Ann Graybiel, an MIT Institute Professor, a member of MIT's McGovern Institute for Brain Research, and one of the senior authors of the study. Using single-cell RNA sequencing to analyze the genes expressed in mouse models of Huntington's disease and postmortem brain samples from Huntington's patients, the researchers found that cells of the striosomes and another structure, the matrix, begin to lose their distinguishing features as the disease progresses. The researchers hope that their mapping of the striatum and how it is affected by Huntington's could help lead to new treatments that target specific cells within the brain. This kind of analysis could also shed light on other brain disorders that affect the striatum, such as Parkinson's disease and autism spectrum disorder, the researchers say. Myriam Heiman, an associate professor in MIT's Department of Brain and Cognitive Sciences and a member of the Picower Institute for Learning and Memory, and Manolis Kellis, a professor of computer science in MIT's Computer Science and Artificial Intelligence Laboratory (CSAIL) and a member of the Broad Institute of MIT and Harvard, are also senior authors of the study. Ayano Matsushima, a McGovern Institute research scientist, and Sergio Sebastian Pineda, an MIT graduate student, are the lead authors of the paper, which appears in Nature Communications. Neuron vulnerability Huntington's disease leads to degeneration of brain structures called the basal ganglia, which are responsible for control of movement and also play roles in other behaviors, as well as emotions. For many years, Graybiel has been studying the striatum, a part of the basal ganglia that is involved in making decisions that require evaluating the outcomes of a particular action. Many years ago, Graybiel discovered that the striatum is divided into striosomes, which are clusters of neurons, and the matrix, which surrounds the striosomes. She has also shown that striosomes are necessary for making decisions that require an anxiety-provoking cost-benefit analysis. In a 2007 study, Richard Faull of the University of Auckland discovered that in postmortem brain tissue from Huntington's patients, the striosomes showed a great deal of degeneration. Faull also found that while those patients were alive, many of them had shown signs of mood disorders such as depression before their motor symptoms developed. To further explore the connections between the striatum and the mood and motor effects of Huntington's, Graybiel teamed up with Kellis and Heiman to study the gene expression patterns of striosomal and matrix cells. To do that, the researchers used single-cell RNA sequencing to analyze human brain samples and brain tissue from two mouse models of Huntington's disease. Within the striatum, neurons can be classified as either D1 or D2 neurons. D1 neurons are involved in the "go" pathway, which initiates an action, and D2 neurons are part of the "no-go" pathway, which suppresses an action. D1 and D2 neurons can both be found within either the striosomes and the matrix. The analysis of RNA expression in each of these types of cells revealed that striosomal neurons are harder hit by Huntington's than matrix neurons. Furthermore, within the striosomes, D2 neurons are more vulnerable than D1. The researchers also found that these four major cell types begin to lose their identifying molecular identities and become more difficult to distinguish from one another in Huntington's disease. "Overall, the distinction between striosomes and matrix becomes really blurry," Graybiel says. Striosomal disorders The findings suggest that damage to the striosomes, which are known to be involved in regulating mood, may be responsible for the mood disorders that strike Huntington's patients in the early stages of the disease. Later on, degeneration of the matrix neurons likely contributes to the decline of motor function, the researchers say. In future work, the researchers hope to explore how degeneration or abnormal gene expression in the striosomes may contribute to other brain disorders. Previous research has shown that overactivity of striosomes can lead to the development of repetitive behaviors such as those seen in autism, obsessive compulsive disorder, and Tourette's syndrome. In this study, at least one of the genes that the researchers discovered was overexpressed in the striosomes of Huntington's brains is also linked to autism. Additionally, many striosome neurons project to the part of the brain that is most affected by Parkinson's disease (the substantia nigra, which produces most of the brain's dopamine). "There are many, many disorders that probably involve the striatum, and now, partly through transcriptomics, we're working to understand how all of this could fit together," Graybiel says. The research was funded by the Saks Kavanaugh Foundation, the CHDI Foundation, the National Institutes of Health, the Nancy Lurie Marks Family Foundation, the Simons Foundation, the JPB Foundation, the Kristin R. Pressman and Jessica J. Pourian '13 Fund, and Robert Buxton.

Emalex Biosciences closed an upsized and oversubscribed Series D funding round Thursday, counting $250 million in earnings, much of which will bankroll a Phase III trial of ecopipam for Tourette syndrome. The funding round was led by Bain Capital Life Sciences. Paragon Biosciences, which founded Emalex in 2018, participated in the financing push alongside Valor Equity Partners and Fidelity Management & Research Company. In a statement, Emalex founder and Paragon CEO Jeff Aronin said that the Chicago-based neuroscience biotech was created specifically to address neurological conditions with high unmet need, like Tourette Syndrome. He added that Emalex recognizes “that drug development for neurologic conditions is exceptionally difficult and few companies are willing to invest in bringing new options to these patients.” With an enrollment target of over 220 patients across some 90 sites, Emalex is aiming for the largest Tourette trial ever conducted in North America. The Phase III study will assess the company’s ecopipam, a first-in-class investigational compound that disrupts the interaction of the neurotransmitter dopamine with the D1 receptor. Current therapies for Tourette target the D2 family of dopamine receptors. Ecopipam targets the D1 family, the super-sensitivity of which has been named in recent studies as a potential contributor to Tourette tics. The Phase IIb D1AMOND clinical trial confirmed ecopipam’s mode of action, showing that treatment with the candidate led to reduced motor and phonic tics as compared with placebo. The investigational drug was also well-tolerated, with the most common side effects being headache, fatigue and somnolence. There was no evidence of movement-related or metabolic adverse events. The FDA has granted ecopipam the Orphan Drug and Fast Track designations. Big Bucks in Brain Diseases Emalex’s oversubscribed financing round is only the latest development in the high-value neuroscience therapeutic space. In early October, Neumora Therapeutics raised $112 million in its Series B financing round to help it develop its neuroscience portfolio further. In particular, the company plans on using the proceeds to advance its lead candidate NMRA-140, a kappa opioid receptor antagonist for major depressive disorder. The money will also be channeled into Neumora’s other precision medicine programs for neuropsychiatric diseases. The company had previously raised $500 million in 2021. Soon after Neumora’s payday, Astellas put forth $50 million in a strategic equity investment and licensing deal, acquiring 15% of Taysha Gene Therapies. The agreement gives Astellas the exclusive option to license Taysha’s TSHA-102, a gene therapy for the severe genetic neurodevelopmental disorder Rett syndrome. The deal also includes TSHA-120, also a gene therapy under investigation for giant axonal neuropathy.