2025: A year of meaningful progress

We reflected on several important developments from 2025:

• In September, data from two adrabetadex studies were presented at the American Neurology Association and Child Neurology Society meetings. These included survival outcomes in infantile-onset NPC, which received the American Neurology Association Abstract of Distinction Award, and a biomarker analysis in individuals treated with adrabetadex.
• In early December, Mandos announced that the FDA granted Breakthrough Therapy designation to adrabetadex for individuals with infantile-onset NPC.
• Later in December, Mandos submitted an NDA to the FDA, marking a significant step in the regulatory review process. The NDA submission includes comprehensive evidence that considers data generated from the adrabetadex development program:
• The primary source of evidence in support of efficacy comes from survival analyses comparing integrated data from infantile-onset patients treated for up to 11 years in clinical studies and the Expanded Access Program (EAP) with matched external controls. The externally-controlled study showed that overall survival was substantially improved in infantile-onset NPC patients treated with adrabetadex. Efficacy is further supported by biomarker evidence demonstrating effects on the underlying pathophysiology of NPC, patient experience narratives, and nonclinical data.
• In addition to efficacy, safety data from the clinical trials and EAP suggest that adrabetadex is well-tolerated. The most common adverse events associated with treatment include hearing impairment (manageable with hearing aids if needed) and transient post-dose fatigue and/or ataxia.

None of this progress would be possible without the commitment of individuals living with NPC, their families and caregivers, and the investigator community. We are deeply grateful for your partnership and trust.

What the NDA means

An NDA is a formal request for FDA approval to market a new drug in the United States. The FDA’s review includes evaluation of clinical and non-clinical data, as well as manufacturing and quality information, to determine whether a treatment is safe and effective for its intended use.

What happens next

The FDA has up to 60 days to determine whether the NDA is complete and can be accepted for review. If accepted, the FDA will assign a review timeline—either Priority Review (approximately six months) or Standard Review (approximately ten months). Priority Review may be granted when a treatment addresses a serious condition and has the potential to provide meaningful improvement over existing options.

Looking Ahead in 2026

Our commitment to the NPC community extends beyond adrabetadex. In the coming year, we plan to:

• Continue engaging with healthcare providers to highlight the importance of early diagnosis and treatment urgency for infantile-onset NPC
• Help treatment centers establish the necessary workflows to care for individuals who may receive adrabetadex
• Build organizational capabilities to support potential commercialization
• Share data through scientific meetings and publications
• Review data from individuals with neurological onset at greater than 6 years of age
• Provide regular community updates through our website, newsletter, NNPDF, and other global advocacy partners
• Continue supporting the EAP, led by Dr. Berry-Kravis

Expanded Access Program Update

Adrabetadex is an investigational therapy that has not been approved by any regulatory authority and is therefore only available through an EAP in limited circumstances. We remain committed to providing adrabetadex to the more than 60 patients currently enrolled in the EAP, and to supporting continuity of care should adrabetadex receive regulatory approval.

Resources about the EAP are available on the NNPDF website and at MandosHealth.com. Our team does not provide medical advice or guarantee outcomes; rather, we offer information about the EAP and, if interested, advise that you speak to your healthcare provider regarding eligibility. Exploring expanded access does not mean committing to treatment – it simply helps determine whether adrabetadex may be appropriate for you or your loved one.

Stay Connected

We look forward to continuing the dialogue and plan to attend several NPC community meetings and conferences this year. To stay informed, please visit our community newsletter on our website and follow updates shared through NNPDF. If you have questions about the information discussed, please speak with your healthcare professional or visit our website www.mandoshealth.com for additional resources.

Please reach out to our team if you would like to connect with us at any future event: patientadvocacy@mandoshealth.com.

* Adrabetadex is an investigational drug that has not been approved by the U.S. Food and Drug Administration and has not been found to be safe or effective to treat NPC or any other condition. All data referenced are exploratory and subject to further validation. For more information, please contact patientadvocacy@mandoshealth.com

**Defined as neurological symptoms before 6 years of age.