Three photos with rounded corners, one is of two technicians in a lab, one is of lab equipment, the last is of a neuron on a blue background.

Inspired by Patients “To Remember”

Age is the most significant risk factor for developing neurodegenerative diseases that affect key brain functions like cognition. As the global population ages, the prevalence of neurodegenerative diseases is growing. Disorders like Alzheimer’s, Parkinson’s and Multiple Sclerosis result in disability and death of millions of patients around the globe and incur nearly $1.5T annually in health care costs in the EU and US alone.

Muna colleagues work tirelessly to discover and develop disease modifying small molecule therapies for disorders that impact memory, movement, language, behavior, and personality. We transform groundbreaking science into life-changing therapies that preserve cognition and other brain functions and enhance resilience to neurodegeneration. Our name reflects our focus on preserving key brain functions, like cognition, so patients can live their best lives: Muna means “to remember” in Old Norse.

A couple in their 50’s outside, the man’s arm around the woman as they smile at each other.

Leveraging Science to Benefit Patients

Alzheimer’s, Parkinson’s and Multiple Sclerosis, among other neurodegenerative diseases, share features of neuroinflammation, cellular dysfunction, and neuronal cell loss. Our scientific focus includes studying brain resilience to discover and develop new medicines that can slow or stop the progression of these processes and preserve brain functions like cognition.

Resilience is the brain’s ability to protect core functions, like cognition, despite the presence of misfolded protein pathology that is a hallmark of many neurodegenerative diseases. About a third of non-demented elderly individuals have substantial misfolded protein pathology in the brain, but despite the presence of this pathology, maintain high cognitive and other functions

Muna colleagues have deep expertise in the biology of resilience to neurodegeneration. We have identified brain cells that are key for maintaining resilience, and, within those cells, gene networks, signaling pathways, protein-protein interactions, and potential new drug targets.

A photo over the shoulder of a lab technician as they pipette into a tray.

MiND-MAP: All-In-Human Target Discovery and Validation Platform

Muna’s all-in-human target discovery and validation approach, called MiND-MAP, uses single cell spatial multi-omics and bioinformatics analyses in unique cohorts of patient samples to focus on the genetic, molecular and cellular mechanisms that underlie resilience to disease pathology. We use this information to identify proteins potentially involved in resilience, and assess the role of these protein targets in human cells, humanized animal models, and patient tissue and biofluid samples.

Our in-house structural biology and computational chemistry toolbox allow us to rapidly identify and develop small molecules that modulate resilience targets and have potential to become future medicines.

Future Medicines To Change Disease Outcomes

Muna’s portfolio of disease-modifying small molecule potential therapies includes two programs that address the functions of a key cell type, called microglia, which respond to and exacerbate neurodegeneration and compromise neuronal function. Our work, together with the work of scientists around the globe, suggests that normalizing the function of microglia may be an important aspect of brain resilience. Our most advanced microglial-focused drug program is being prepared for clinical testing in healthy volunteers and patients. Other programs that address microglial and neuronal resilience are in early preclinical stages.

Muna scientist working in the lab

TREM2 Agonism for Alzheimer’s Disease

Our most advanced program is TREM2 agonism for early-stage AD. TREM2 is a key signaling node for microglial activation and modulates how these cells clear pathologic hallmarks of disease and preserve brain functions. Genetic studies suggest TREM2 variants can be protective or risk factors for AD, and microglia play central roles in disease. TREM2 agonism can enhance microglia function, resolving misfolded protein pathology and protecting neurons from degeneration. Muna small molecule compounds exhibit selectivity for TREM2, low concentration (single digit nM) potency as agonists and have efficacy similar to antibodies currently in clinical testing. Small molecules have a number of intrinsic advantages over antibodies for the treatment of neurodegenerative diseases that occur over several decades of life.

Our understanding of TREM2 biology is enhanced by insights from our structural and protein chemistry studies, and the identification of small molecule modulators of TREM2 with distinct binding sites. Novel TREM2 functions elicited by these novel binding sites are being evaluated in the context of different stages of AD and in other neurodegenerative diseases.

In animal models, our small molecules show excellent oral exposure and brain exposure. In mice xeno-transplanted with human iPSCs, TREM2 agonism activates xenografted human microglia in vivo, a process that is monitored with proprietary biomarkers from human cells. These biomarkers may translate to better monitoring in patients, allowing us to identify those most likely to benefit from our treatment.

Muna scientist working in the lab

Kv1.3 Blockade for Parkinson’s Disease and Multiple Sclerosis

Kv1.3 is a voltage-gated potassium channel and important regulator of microglia reactivity, the release of pro-inflammatory cytokines and chemokines, and of mitochondrial and other functions. Kv1.3 expression is upregulated in human brain and other cells in several disorders. Blockade of Kv1.3 with naturally occurring peptides and small molecule tool compounds is neuroprotective in rodent models of several neurodegenerative diseases, including Parkinson’s and Multiple Sclerosis. Understanding of Kv1.3’s role in microglia, neurons and other cells, together with strong evidence that Kv1.3 blockade can abrogate neuroinflammation and slow or stop neurodegeneration, support developing Kv1.3 blockers into future medicines.

Muna’s structural biology and protein chemistry capabilities enabled us to identify small molecule candidate compounds that exhibit low concentration (single digit nM) potency, high selectivity for Kv1.3 compared to other Kv1 family channels, good oral bioavailability, and excellent brain exposure compared to other known Kv1.3 inhibitors. These small molecules are currently being optimized and tested in preclinical studies.