These Four Things Are Helping Minovia Therapeutics' Rare Disease Trials

By Natalie Yivgi-Ohana, Ph.D., Minovia Therapeutics

Designing clinical trials for ultra-rare pediatric diseases presents unique challenges. In conditions like Pearson syndrome, patients often experience multi-organ failure and highly variable symptoms, meaning that traditional clinical trial approaches—such as large, randomized control arms, rigid inclusion criteria, fixed assessment schedules, and single-organ primary endpoints—often do not apply. As Minovia Therapeutics prepares for pivotal MNV-201 trials in 2026, our experience highlights the importance of careful site selection, specialized operational expertise, multidisciplinary collaboration, and innovative trial design. These lessons may offer guidance for others navigating the complexities of ultra-rare disease research.

Population And Therapeutic Area Site Experience

One of the most critical early decisions in rare disease research is selecting the right clinical sites. With Pearson syndrome, we prioritize centers with extensive experience in pediatric hematology and rare mitochondrial diseases, as well as those actively conducting natural history studies. Natural history studies provide the essential baseline and comparator group for assessing efficacy in ultra-rare populations, for which randomized control arms are often not feasible . By partnering with sites familiar with the complexities of rare diseases, we ensure both rigorous data collection and high-quality patient care.

For example, our ongoing Phase 2 trial currently includes four patients and four compassionate use cases. Interim analyses have demonstrated promising outcomes. At six months post-treatment, two of the four patients showed improved growth parameters relative to baseline, as measured by height standard deviation scores, alongside better patient-reported quality of life. Each of these patients suffers different disease complexities and organ systems involvement, and the trial requires measurements of all different organ functions and the correlation to the primary endpoints. Selecting sites with experience managing such fragile and complex pediatric patients has been essential to achieving these outcomes safely and consistently.

Hands-On Expertise In Stem Cell Handling

Our lead product, MNV-201, is a first-in-class cell therapy that enriches a patient’s own hematopoietic stem and progenitor cells with healthy mitochondria derived from placental sources. The therapy’s success depends on precise collection, isolation, and handling of these cells. Any variation in procedure can significantly impact both safety and efficacy, making operational expertise a central criterion for site selection.

We have prioritized centers with a proven record of conducting stem cell procedures, including apheresis and CD34+ stem cells isolation and managing complex pediatric cell therapies.

In our Phase 2 trial, no treatment-related serious adverse events have been reported. Most adverse events observed were transient, procedure-related, and resolved within four days, reflecting the importance of working with sites capable of meticulous cellular handling and patient monitoring. This hands-on expertise will ensure future consistency across sites and will contribute to the integrity of the clinical data, particularly in trials where each patient’s outcome carries substantial weight.

Multidisciplinary Teams For Complex Diseases

Pearson syndrome is a multi-system disorder, affecting the bone marrow, pancreas, and other organs. Patients may present with sideroblastic anemia, metabolic crises, growth failure, and organ dysfunction. Treating such a complex disease has required a multidisciplinary clinical team, often involving hematologists, endocrinologists, neurologists, nephrologists, and supportive care specialists.

Multidisciplinary teams are essential not only for patient care but also for trial design and data collection. In ongoing studies, close coordination among specialists has enabled real-time communication around patient status, laboratory findings, and organ-specific safety signals, allowing care plans and assessment schedules to be adjusted collaboratively as patients’ conditions evolved. For example, in study MNV-101 and early MNV-201 cases, hematology, endocrinology, and nephrology teams worked together to align transfusion management, metabolic monitoring, and renal function assessments—particularly during periods of clinical instability—ensuring consistent endpoint collection while prioritizing patient safety. This level of cross-specialty coordination has been critical to managing the complexity of Pearson syndrome and generating reliable clinical data in an ultra-rare disease setting.

Trial Design Without Traditional Control Arms

Conducting trials in ultra-rare pediatric populations often precludes the use of randomized control arms. In these cases, natural history studies serve as external comparators, enabling meaningful assessment of therapeutic impact. Developing these studies requires the systematic collection of longitudinal clinical data from untreated patients, often gathered over several years through academic medical centers and patient registries. Data typically include growth trajectories, laboratory values, organ function assessments, and patient- or caregiver-reported outcomes, all collected using standardized protocols to ensure consistency and reliability.

For MNV-201, clinically objective and patient-centered endpoints—such as growth over time and quality-of-life measures—were informed by natural history data sets developed through academic collaborations, investigator-initiated studies, and published literature focused on Pearson syndrome. These data are typically generated by specialized academic centers that follow patients longitudinally and, in some cases, through patient registries established with appropriate ethical approvals and data-sharing agreements. Accessing and integrating these data requires early engagement with clinical investigators and institutions, as well as alignment on data standards and endpoints. In ultra-rare diseases, natural history studies are not always readily available, underscoring the importance of clinician and researcher awareness early in development. Without well-characterized natural history data, it becomes significantly more difficult to define meaningful endpoints, contextualize outcomes, or assess treatment impact, making these studies a foundational component of rare disease drug development.

Selecting clinical sites already engaged in natural history studies allows trial data to be directly contextualized against well-characterized disease trajectories. This alignment enables more robust comparisons between treated patients and historical controls, despite limited patient numbers. Interim Phase 2 results illustrate this approach: Two of four trial patients experienced measurable improvements in growth relative to their pretreatment trajectories, and all patients maintained organ stability — outcomes that differ from what is typically observed in the natural progressive course of the disease.

This framework demonstrates how thoughtfully designed natural history studies can support ethical and scientifically rigorous trials in ultra-rare pediatric populations. Best practices include longitudinal data collection using standardized, clinically meaningful measures; incorporation of both objective endpoints and patient- or caregiver-reported outcomes; and study designs that minimize patient burden by avoiding unnecessary procedures and aligning assessments with routine care. When executed well, natural history studies enable researchers to generate actionable insights while respecting the unique vulnerabilities of pediatric patients and their families.

Regulatory Engagement And Forward-Looking Perspective

Another critical component of successful rare disease trials is a proactive regulatory engagement. MNV-201 has received FDA Fast Track and Rare Pediatric Disease designations, underscoring both the urgent need for therapies and the promise of our approach. Fast Track facilitates increased interactions with the FDA, potential priority review, and the ability to submit a rolling BLA, while Rare Pediatric Disease designation offers eligibility for a pediatric priority review voucher, which can expedite future approvals. These designations have informed trial planning, site selection, and endpoint prioritization and highlight how regulatory strategy and operational considerations are intertwined in ultra-rare disease development.

Conclusion

Looking toward 2026, the pivotal registrational trial for MNV-201 in Pearson syndrome will build on the lessons learned from our Phase 2 experience. Careful site selection, operational expertise, and multidisciplinary collaboration will remain central, as will innovative trial designs leveraging natural history data. While every ultra-rare disease presents its own challenges, these strategies provide a road map for executing trials that are scientifically rigorous, patient-centered, and capable of generating actionable insights even in the smallest populations.

About The Author:

Natalie Yivgi Ohana, Ph.D., is a life science entrepreneur, scientific founder, and CEO of Minovia Therapeutics Ltd. She has led the company since incorporation in 2011 and holds a Ph.D. in biochemistry from the Hebrew University; Postdoctoral fellowship at the Weizmann Institute; Twenty+ years experience in mitochondrial research that led to the development of a novel mitochondrial cell therapy approach to treat mitochondrial diseases: from ideation to clinical stage; from a small start up to a global organization with a team of Biotech leaders. Raised $27M from private investors; established collaborations with top researchers and clinical centers around the world, as well as strategic partnership with a leading pharma company.