Company News Archive - Lysoway Therapeutics

Lysoway showcases first-in-class TRPML1 agonist data and announces Phase I clinical plan at Michael J. Fox foundation’s PD Therapeutics Conference

Cambridge, MA, October 16, 2025 – Lysoway Therapeutics’ Senior Vice President and Head of Research and Translational Science, Valerie Cullen, PhD, today presented an invited talk and participated in a panel discussion at the 17th Michael J Fox Foundation’s Annual Parkinson’s Disease Therapeutics Conference (PDTC) in New York City. This prestigious conference is the only scientific meeting worldwide focused exclusively on Parkinson’s disease drug development. Each year, it brings together over 300 professionals to showcase the most exciting and innovative research from MJFF’s research portfolio.

Dr. Cullen delivered a presentation entitled “Development of a Potent, Selective, and Brain-Penetrant TRPML1 Agonist for Parkinson’s Disease Treatment” and also participated in a panel discussion focused on “Exploring Innovative Therapeutic Approaches for Endolysosomal Dysfunction in PD”.

Her presentation highlighted Lysoway’s compelling data on its Development Candidate, LW-1017, which is a highly brain penetrant, orally bioavailable, and potent small-molecule TRPML1 agonist. She presented robust in vivo efficacy data demonstrating a significant reduction of alpha-synuclein aggregation and inflammation, improved neuronal cell survival and augmented motor function in highly relevant PD models; outlined key results from our successfully completed IND-enabling studies; and confirmed plans to initiate a First-in-Human Phase I clinical study of LW-1017 in healthy volunteers beginning in 2026.

About Lysoway Therapeutics

Lysoway Therapeutics is a leader in lysosomal ion channel disease biology. We have developed unique technological approaches to screen and develop potent modulators of lysosomal ion channels, including TRPML1 and TMEM175. These ion channels serve as vital transducers of cellular signals and play crucial roles in maintaining cellular homeostasis, particularly within the autophagy/lysosomal pathway, which is frequently disrupted in a number of pathological conditions. Lysoway’s small molecule modulators hold immense potential for restoring autophagy/lysosomal function, offering potential treatment for neurodegenerative diseases associated with lysosomal deficiency and other rare diseases characterized by toxic accumulation of cellular wastes.

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www.lysoway.com

Targeting TRPML1: A Pharmaceutical Perspective on Treating Age-Related Neurodegenerative Diseases

Introduction

Despite decades of research, neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) remain among the most formidable challenges in medicine. Recent approvals of anti-Aβ antibodies have demonstrated, at least modestly, that removal of pathogenic protein aggregates can translate into clinical benefit for AD patients. These approvals have energized the field, fueling next-generation efforts to produce more brain-penetrant anti-Aβ antibodies and to extend the similar approach to other protein aggregates, including α-synuclein.

Yet antibody-based approaches face intrinsic limitations. Antibodies are largely restricted to extracellular targets, and thus cannot directly clear intracellular aggregates such as phosphorylated tau tangles or α-synuclein inclusions. Even when they succeed in aggregate removal, they do not address the upstream deficit that drives aggregate formation in the first place—the age-related decline of the autophagy–lysosomal pathway (ALP).

As neurons age, their capacity to recycle proteins and organelles diminishes, leading to accumulation of toxic substrates and progressive dysfunction. A more durable therapeutic strategy may lie in restoring the cell’s intrinsic housekeeping capacity—rejuvenating the ALP so neurons once again clear aggregates “from within,” much as they do in youth. This vision naturally leads to TRPML1, a lysosomal ion channel that sits at the center of lysosomal homeostasis and cellular clearance.

Genetic Linkage Between TRPML1 and Neurodegenerative Diseases

A common misconception is that TRPML1 is not genetically linked to age-related neurodegenerative diseases such as AD and PD, since most GWAS studies have not flagged it among the many ALP-related risk genes. This absence, however, reflects the rarity and nature of TRPML1 mutations rather than their biological relevance.

Unlike more frequently altered genes such as GBA1, pathogenic TRPML1 variants are extremely rare. Over 95% are frameshifts or deletions that abolish channel function, producing mucolipidosis type IV (MLIV)—a severe lysosomal storage disorder characterized by neurodevelopmental deficits and progressive neurodegeneration. These mutations provide a natural experiment: complete loss of TRPML1 function devastates lysosomal biology and the nervous system.

Even subtle disruptions reaffirm its role in neurodegeneration:

Single-point mutations that reduce TRPML1 activity cause severe oromandibular dystonia and early-onset parkinsonism (Ghasemi et al., CJNS, 2025).
Heterozygous variants are linked to Lewy Body Disease (LBD) and Alzheimer’s disease with Lewy Body Variant (ADLBV) (Clark et al., PLOS One, 2015).

Taken together, these insights establish TRPML1 as a genetically validated target. If complete loss leads to profound neurodegeneration and partial loss predisposes to PD- and AD-related phenotypes, then carefully restoring or enhancing its activity represents a rational therapeutic strategy. In fact, TRPML1 may be underappreciated by conventional GWAS precisely because of its rarity—yet as a master regulator of the autophagy–lysosomal pathway, it has the potential to deliver broader therapeutic benefit than interventions aimed at single risk genes.

This unique genetic profile not only underscores TRPML1’s causal role in neurodegeneration but also strengthens the case for therapeutic agonism—providing a foundation for why TRPML1 is such a compelling target for disease modification.

Why TRPML1 Is a Compelling Target

Building on its genetic validation, TRPML1 is far more than a regular risk gene — it functions as a master regulator of the autophagy–lysosomal pathway (ALP). Its activation initiates a cascade of protective processes, including lysosomal calcium release, TFEB/TFE3 activation, lysosome biogenesis, autophagosome formation, enhanced autophagic flux, and lysosomal exocytosis (Figure 1). In effect, TRPML1 sits at the top of the regulatory hierarchy that sustains cellular proteostasis and resilience.

This systemic control is what makes TRPML1 uniquely powerful. The pathology of AD, PD, and other neurodegenerative diseases arises not from the dysfunction of a single protein, but from the global decline in ALP activity with aging. Unlike antibody-based therapies that can only clear specific extracellular aggregates such as Aβ plaques—and are far less effective against intracellular lesions like pTau tangles or α-synuclein inclusions—TRPML1 agonism addresses the root cause: impaired cellular clearance capacity.

By reactivating the ALP at multiple levels simultaneously, TRPML1 agonists have the potential to restore homeostasis more effectively than interventions aimed at single downstream proteins. This systems-level approach is what distinguishes TRPML1 from nearly all other neurodegeneration targets currently under development.

Figure 1.
TRPML1 serves as a central switch for the autophagy–lysosomal pathway, coordinating multiple downstream mechanisms that restore proteostasis and resilience in aging neurons.

Challenges in Developing a Pharmaceutically Viable TRPML1 Agonist

Since the discovery of TRPML1 as an endolysosomal ion channel (Dong et al., Nature, 2008), many groups have attempted to develop agonists, but most efforts have stumbled on what one competitor aptly called a “physicochemical nightmare.” The root challenge lies in the binding pocket: deeply buried, highly hydrophobic, and shielded within the lipid bilayer (Figure 2).

As a result, potent agonists are often themselves highly hydrophobic, leading to poor solubility, metabolic instability, and limited bioavailability. Attempts to introduce polarity can improve solubility and oral exposure, but usually at the cost of brain penetration — which is non-negotiable for both efficacy in the target organ and maintaining an adequate therapeutic margin over systemic exposure.

Encouragingly, recent advances in structure-based drug design (SBDD) have shown that these trade-offs can be balanced. By carefully tuning non-polar interactions and metabolic stability, we have generated TRPML1 agonists that are highly brain-penetrant, orally bioavailable, and potent. One such molecule has now advanced through IND-enabling studies with a strong safety profile, positioning it to enter clinical testing. What once seemed an insurmountable barrier has become a tractable path forward.

Figure 2.
High resolution Cryo-EM structure of TRPML1 with both natural activator PI(3,5)P2 and synthetic agonist bound to two different binding pockets, one is highly hydrophilic and the other is extremely hydrophobic and buried deep inside the protein and lipid bilayer.

Translational Research Challenges: Choosing the Right Models

A central challenge in translating TRPML1 agonists is identifying models that reflect the biology of aging. While many in vitro and in vivo models exist for AD and PD, few capture the age-related decline in autophagy–lysosomal pathway (ALP) function — the core defect TRPML1 agonism is designed to restore.

Human iPSC-derived neurons (e.g., dopaminergic cells): These often show low TRPML1 and TFEB/TFE3 expression. In addition, culture stress can drive TFEB/TFE3 into the nucleus even without stimulation, masking TRPML1-dependent effects (unpublished Lysoway data). As such, they provide limited value for agonist testing.
Genetic AD/PD mouse models: While useful for studying protein aggregation, they lack the aging component. Because the therapeutic rationale for TRPML1 focuses on reversing age-related ALP decline, aged models are more relevant.

Recent work underscores this. Culley et al. (2025) demonstrated that aged brains share features with early-stage AD and are acutely vulnerable to Aβ injury, while younger brains compensate. Consistent with this, we observed that progranulin, a key neuroprotective factor, is significantly reduced in aged versus young midbrains (unpublished Lysoway data).

Taken together, these findings highlight the goal of TRPML1 agonism: rejuvenating the brain’s intrinsic clearance machinery, which falters with age. For this reason, aging-based models, while imperfect, are essential for demonstrating in vivo efficacy and ensuring meaningful translation to the clinic.

Safety Considerations

TRPML1 is a ubiquitous lysosomal channel, expressed across virtually all tissues. Over- or prolonged activation therefore carries risks of exaggerated pharmacology and systemic toxicity. To maximize the therapeutic margin, several design principles are critical:

High brain penetrance: Ensures therapeutic concentrations in the brain while minimizing peripheral exposure. At high doses, peripheral organ effects (e.g., in liver) have been observed in rodents and primates (internal and public reports). Agonists with lower brain-to-plasma ratios tend to have narrower margins.
Balanced PK profiles: An excessively long systemic half-life may keep TRPML1 open too long, causing toxicity. Activation should be potent but temporally controlled. For example, in rats administered twice daily (BID) at high dose levels, tolerance dropped sharply, likely from prolonged activation (unpublished Lysoway data).

The ideal TRPML1 agonist for neurodegeneration is therefore one that combines high brain penetrance, oral bioavailability, potency, and carefully tuned PK — features we have prioritized in our candidate now entering clinical development.

Outlook and Clinical Considerations

The critical question now is whether TRPML1 agonists can deliver on their promise in patients. Early clinical trials will need to go beyond safety to capture pharmacodynamic signals — e.g. biomarkers of ALP restoration, lysosomal biogenesis, and aggregate clearance, as well as disease-related molecular changes. Such readouts in Phase 1b/2a will be vital to shaping Phase 2b studies designed to demonstrate true clinical benefit.

With growing momentum in the field and the progress achieved at Lysoway, the outlook is highly encouraging. For the first time, the possibility of rejuvenating the brain’s intrinsic clearance systems — rather than merely compensating after their failure — is within reach.

Conclusion

Antibody therapies have validated the concept of protein clearance but remain downstream, targeting consequences rather than root causes. TRPML1 agonists represent a fundamentally different approach: restoring the aging brain’s capacity to take care of itself.

At Lysoway Therapeutics, we have overcome the medicinal chemistry barriers that constrained the field and are now advancing a potentially first and best-in-class, brain-penetrant, orally bioavailable TRPML1 agonist into clinical development. If successful, this work could mark the beginning of a new era in treating AD, PD, and other age-related neurodegenerative diseases.

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Lysoway Therapeutics Awarded Grant from The Michael J. Fox Foundation to Advance TRPML1 Agonist to Treat Parkinson’s Disease

Cambridge, MA, July 25, 2025 – Lysoway Therapeutics, a biopharmaceutical company developing small molecule modulators of lysosomal ion channels, today announced that it has received a research grant from The Michael J. Fox Foundation for Parkinson’s Research (MJFF). Support comes from MJFF’s Parkinson’s Disease Therapeutics Pipeline Program, which focuses on candidates with strong potential to slow or halt disease progression or alleviate burdensome symptoms for those living with Parkinson’s disease. Lysoway Therapeutics funding of $2.93 million will support the preclinical and translational development of Lysoway’s novel, highly brain-penetrant small molecule TRPML1 agonist.

The study aims to investigate whether activating TRPML1 by a novel, small molecule modulator, will enhance the lysosomal membrane calcium ion channel to restore lysosomal function and help with clearance of alpha-synuclein, the protein that is linked to the disease.

“We are honored to receive this generous grant from The Michael J. Fox Foundation,” said Valerie Cullen, PhD, Principal Investigator and SVP of Research and Translation at Lysoway. “TRPLML1 is a high value target due to its pivotal role in sensing and responding to cellular stress. By activating this ion channel, we can engage multiple beneficial pathways that restore autophagy/lysosomal homeostasis and bolster cellular resilience. Our lead development candidate is both orally bioavailable and highly brain-penetrant, offering strong potential to modify disease progression in Parkinson’s Disease.”

Yongchang Qiu, PhD, Founder and Chief Executive Officer of Lysoway Therapeutics, added “This funding underscores growing confidence in TRPML1 as a compelling target for Parkinson’s disease. It will allow us to accelerate development of our lead TRPML1 agonist and to establish key biomarkers for target engagement, with the goal of initiating first-in-human clinical trials early next year.”

About Lysoway Therapeutics

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www.lysoway.com

Lysoway Therapeutics Inc. appoints Valerie Cullen, PhD as Senior Vice President and Head of Research and Translational Science

Cambridge, MA, May 30, 2024 – Lysoway Therapeutics, a leading discovery-stage biotech company dedicated to developing next-generation treatments for patients with neurodegenerative diseases, today proudly announces the appointment of Valerie Cullen, PhD as Senior Vice President and Head of Research and Translational Science.

Dr. Cullen brings a wealth of cross-functional experience as a research leader, translational medicine expert and company builder and has a proven track record of success in building and translating innovative therapeutic programs.

“We are thrilled to welcome Valerie to the executive leadership team of Lysoway Therapeutics,” said Yongchang Qiu, CEO, President and Co-Founder of the company. “Valerie brings deep expertise in lysosomal biology and neurological disease and has led complex CNS drug development programs at the intersection of research, translation and clinical development. Her leadership will be invaluable to Lysoway as we build our pipeline and navigate key milestones in 2024 and beyond.”

Dr. Cullen brings almost 25 years of operational and leadership experience in research and development, with particular emphasis on drug discovery for neurodegenerative disorders. Most recently, she served as SVP of Research at Expansion Therapeutics, where she built the research group and helped raise over $80M in VC funding. Prior to that, she served as Vice President, Translation and Development at Generian Pharmaceuticals, Inc. At Lysosomal Therapeutics, Inc. Dr. Cullen was Vice President, Program and Alliance Management and acted as program lead for a clinical-stage asset in Parkinson’s Disease. She previously held roles of increasing responsibility in NeuroPhage, Aldeyra Therapeutics and Link Medicine.

Dr. Cullen earned a PhD and BSc (Hons) in pharmacology from the University of Dublin, Ireland and held postdoctoral fellowships at the Institute of Psychiatry, King’s College London and at the Center for Neurologic Diseases, Harvard Medical School. Her work has won various accolades including the Annals of Neurology Clinical Impact Award and she has been granted numerous patents worldwide for innovative therapies for neurological diseases.

“I’m delighted to join Lysoway’s executive team at this exciting juncture, as the organization advances towards delivering new treatment options for patients with neurodegenerative diseases,” said Dr. Cullen. “I look forward to making significant and meaningful contributions towards the company’s development of novel therapeutics with the potential to highly impact patient lives.”

About Lysoway Therapeutics

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www.lysoway.com

Lysoway Therapeutics appoints Chris Adams, PhD to its board of directors

Cambridge, MA, April 2, 2024 – Lysoway Therapeutics, a leading discovery-stage biotech company dedicated to developing next-generation treatments for patients with neurodegenerative diseases, today proudly announces the appointment of Chris Adams, PhD to its board of directors. Dr. Adams brings a wealth of experience as a distinguished business leader, entrepreneur and mentor, with a proven track record of guiding biotechnology companies towards maximizing program value and realizing their full potential.

“We are thrilled to welcome Chris to the Lysoway board of directors as we advance our pipeline into clinical studies next year,” said Yongchang Qiu, CEO & President, Co-Founder of Lysoway Therapeutics. “Chris’s extensive industry expertise and strategic guidance will be invaluable to Lysoway as we bolster our team and navigate key milestones in 2024 and beyond.”

Dr. Adams is a strategic biotech executive with over three decades of broad cross-functional expertise spanning all facets of biotech operations. His impressive background includes in-depth experience with start-up operations, fundraising, M&A, business development, strategic transactions, and company building. In 2013, he co-founded Cydan, an orphan drug accelerator focused on improving the lives of patients with rare genetic diseases. Together with the Cydan team, he successfully raised over $200M and co-founded and served on the Board of three startups: Vtesse, Imara and Tiburio. Prior to Cydan, he served as the Chief Business Officer of FoldRx Pharmaceuticals Inc., where he played a pivotal role in the development of VYNDAQEL® (tafamidis) for TTR amyloidosis, leading to its acquisition by Pfizer in 2010. Previously, he held various business development and marketing roles at ViaCell Inc., TKT Inc. and Ciba-Geigy AG. Currently Dr. Adams serves on the Board of Directors of Alkeus Pharmaceuticals Inc., Aviceda Therapeutics Inc. and Reveal Pharmaceuticals Inc. He holds a PhD in organic chemistry and a diploma in organic chemistry and biochemistry from the University of Zurich, and an MBA from INSEAD of Fontainebleau, France.

“It is a privilege to join Lysoway’s board as the organization advances towards delivering new treatment options for patients with neurodegenerative diseases, many of whom have been significantly underserved for decades,” said Dr. Adams “I look forward to working alongside this team and advancing a promising pipeline through development and towards the market.”

About Lysoway Therapeutics

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www.lysoway.com

Lysoway Therapeutics has received a research grant from the Silverstein Foundation to investigate the therapeutic potential of its lysosomal ion channel modulators in GBA-deficient Parkinson’s disease

Cambridge, MA and New York, NY, Jan. 5, 2023 – Lysoway Therapeutics, a startup biotech developing small molecule modulators of lysosomal ion channels and leader in lysosomal ion channel disease biology, announced today receiving a research grant from the Silverstein Foundation for Parkinson’s with GBA.

“We appreciate the generous support from the Silverstein Foundation, which underlines the importance of lysosomal ion channels as drug targets for Parkinson’s disease.” said Dr. Yongchang Qiu, chief executive officer of Lysoway Therapeutics. “This grant and our relationship with the Silverstein Foundation will bring us closer to the Parkinson’s disease research community and expedite our overall translational research effort. Lysoway plans to use the grant to investigate the therapeutic potential of its channel modulators in preclinical models of GBA-deficient Parkinson’s disease, particularly focusing on discovery and development of target engagement and pharmacodynamic biomarkers.”

About Lysoway Therapeutics

Lysoway Therapeutics is a leader in lysosomal ion channel disease biology. We have developed unique technological approaches to screen and develop potent modulators of lysosomal ion channels, including TRPML1 and TMEM175. These ion channels are essential transducers of cellular signals and are required to help maintain cellular homeostasis, especially the delicate balance within the autophagy/lysosomal pathway, which is often disrupted in a number of pathological conditions. Lysoway’s small molecule modulators have great potential to re-balance lysosomal function and autophagy to treat neurodegenerative diseases with lysosomal deficiency and rare diseases characterized by toxic accumulation of cellular wastes.

About The Silverstein Foundation for Parkinson’s with GBA

The Silverstein Foundation is a 501(c)(3) non-profit organization focused on investing in cutting-edge therapeutic approaches for the treatment and prevention of Parkinson’s disease in glucocerebrosidase (GBA-PD) mutation carriers. The Foundation collaborates with clinicians, scientists, and biotechnology companies to accelerate research and clinical trials in an effort to rapidly bring new disease-modifying therapeutic options to patients. The Foundation has funded 39 projects across a diverse set of therapeutic approaches since its inception in 2017. The Foundation applies a unique flexible funding model including both new company formation and traditional research grants to deliver in real-time on its mission of rapidly developing novel treatments for GBA-PD patients.

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www.lysoway.com

info@silversteinfoundation.org
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Lysoway Therapeutics has raised a total of $22m in Series A financing to advance novel therapies for neurodegenerative diseases and metabolic disorders

Lysoway Therapeutics, a Cambridge, MA based startup developing small molecule modulators of lysosomal ion channels, announced today raising a total of $22m in Series A financing since founding, led by Highlight Capital, 3E Bioventures, and Oceanpine Capital. Lysoway was founded in 2020 by CEO and biotech veteran Yongchang Qiu and Professor Haoxing Xu (University of Michigan, Zhejiang University), who is leading the frontier in lysosomal biology.

“We appreciate Highlight Capital, 3E Bioventures, and Oceanpine Capital’s strong support and confidence in our therapeutic approach and experienced team,” said Yongchang Qiu, chief executive officer of Lysoway Therapeutics. “Lysosomal deficiency has long been associated with many neurodegenerative diseases and metabolic disorders, both genetically and phenotypically. Lysosomal ion channels play key roles in the regulation of lysosome function and yet these channels have been neglected as therapeutic targets up until now. Having developed unique technological approaches to screen and develop potent modulators of lysosomal ion channels, we see tremendous potential to apply the breadth of our scientific expertise to advance the field. We are looking forward to accelerating the development of our lysosomal ion channel modulators to bring novel and best-in-class therapies to patients”.

Professor Xu added, “The lysosome, the cell’s recycling center, can mediate the degradation of a variety of biomaterials (proteins, lipids, and membranes) into smaller building-block molecules, which will be subsequently transported out of lysosomes for reutilization or energy. Activation of lysosomal channels by synthetic modulators, like those being developed at Lysoway, may boost lysosome function to maintain cellular health and promote cellular clearance in lysosome storage disorders.”

About Lysoway Therapeutics

Lysoway Therapeutics is a leader in lysosomal ion channel disease biology. We have developed unique technological approaches to screen and develop potent modulators of lysosomal ion channels, including TRPML1 and TMEM175. These ion channels are essential transducers of cellular signals and are required to help maintain cellular homeostasis, especially the delicate balance within the autophagy/lysosomal pathway, which is often disrupted in a number of pathological conditions. Lysoway’s small molecule modulators have great potential to re-balance autophagy/lysosomal function to treat neurodegenerative diseases with lysosomal deficiency and rare diseases characterized by toxic accumulation of cellular wastes.

About Highlight Capital

Highlight Capital is an investment company with a mission to promote technology innovations based on deep scientific and industrial insights. We focus on enabling high growth sectors such as healthcare, biotech and consumer, and we strive to create long-term value and deliver life wellness. We wholeheartedly partner with our entrusted entrepreneurs to drive long-term value creation and to deliver sustainable return.

About 3E Bio

3E Bioventures Capital is dedicated to investing in cutting-edge life sciences and biomedical technologies, with a focus on breakthrough first-in-class therapies and disruptive cross-disciplinary innovations in medical devices and diagnostics. 3E Bioventures takes on a science-driven, entrepreneur-friendly investment philosophy by working closely with companies and research institutions to develop drugs or products that have strong unmet medical needs.

About Oceanpine Capital

Oceanpine Capital is an institutional growth equity investment company formed by seasoned entrepreneurs and sophisticated investors with 20 years of in-depth industry operational and business building experiences in both China and the US. With a perspective of achieving successful growth over the long term, Oceanpine partners visionary entrepreneurs to build world-class companies together over a period of years rather than on the short-term impact.

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www.lysoway.com