Unlocking the potential of the AmorphOX technology 

After successful formulation and in-vitro testing, we proceeded with a first in-vivo study combining the AmorphOX technology with semaglutide. The study showed promising data with higher bioavailability than the commercially available oral tablet of semaglutide. This is the first in-vivo study, and based on the encouraging data, we will continue refining the formulation to enable higher dosing and prepare for an additional in-vivo proof-of-concept study before proceeding with the first exploratory trial in humans.

Data from the first in-vivo study are promising, as they confirm once again that AmorphOX is applicable to large molecules and that the technology can deliver GLP-1 agonists and, in all likelihood, other peptides via the nasal route. From a long-term strategic perspective, it opens a pathway for Orexo into one of the largest and fastest growing pharmaceutical categories currently, the GLP-1 agonists for diabetes, weight loss and likely even within CNS diseases.

Another important step was the award from BARDA, where we will initially receive USD 8 million for the development of OX390. In total the partnership is valued at up to USD 51 million, pending milestones and deliverables, and will cover the majority of the development expenses of the OX390 project. OX390 is targeting the growing issue with adulteration of opioids and more specifically adulteration with alpha-2 agonists. When opioids are mixed with alpha-2 agonists the first responders have increased difficulty getting the patient back to consciousness and in-vivo studies indicate an alpha-2 agonist may increase the effect of opioid-induced respiratory depression up to 100 times.²

The formulation work has been ongoing for a while and we have completed a first pre-IND meeting with FDA. We are now finalizing the first AmorphOX formulations in preparation of the first in-vivo proof-of-concept study planned early next year. The BARDA award covers the majority of the development expenses, and the first payment, to cover incured costs, will be reported as income and have a positive impact on EBITDA starting Q4.

In parallel we continue to work with potential partners to test the AmorphOX technology on their active substances. We have completed an external market assessment of the AmorphOX technology and believe there is a significant potential in large molecules moving forward, from peptides to protein-based pharmaceuticals, such as vaccines. The feedback from potential partners in the market assessment shows the importance of clinical evidence of the technology and ability to manufacture at scale which reinforces the importance of investments in advancing products to clinical stage.

² Page 4, Acosta-Mares P, Violante-Soria V, Browne T Jr, Cruz SL. Xylazine potentiates the lethal but not the rewarding effects of fentanyl in mice. Drug Alcohol Depend. 2023 Dec 1;253:110993. Page 6, Substance Abuse and Mental Health Services Administration

During the quarter we have made good progress addressing the concerns raised by FDA related to Izipry, our overdose rescue medication, and initiated commercial scale manufacturing with the device and secondary packaging. Getting an AmorphOX product approved is a significant accomplishment. Based on discussions with regulatory agencies about our other AmorphOX-based pipeline products, there is significant value in having a product approved that is supported by the technology. However, the market for Izipry is highly competitive and we will continuously review the best go-to-market strategy to limit the financial exposure of the company.

For OX640, our nasal epinephrine rescue medication, we have started the process to upscale the manufacturing, leveraging the supply chain established for Izipry. In parallel, the first competing nasal product has been approved and launched in both the US and Europe. However, despite significant market investments, the first product on the market has yet to reach a sales trajectory in line with expectations. During the fourth quarter we will conduct a market survey to test the key differentiating parameters with OX640 and confirm the market potential of this product in light of the current market dynamics. We remain convinced that treatment of anaphylaxis will follow the same pattern as for opioid overdose, moving from injectable rescue medications to nasal delivery.

The Zubsolv sales to wholesalers and their reported sales to pharmacies show a steady development during 2025 with about 1 percent decline both comparing YTD with last year and quarter over quarter. However, net sales are significantly impacted by quarterly volatility of wholesalers’ inventory of Zubsolv explaining most of the movement to Q2 2025. The inventory level entering 2025 was about 60 percent higher than the inventory level when exiting Q3 2025. Both of these numbers are extremes but follow a normal annual pattern with inventory levels being low in Q3 and increasing in the fourth quarter. Compared to last year net sales are impacted by some decline in demand led by the previous exclusive contract within United Health Group and Humana. We expect the inventory levels to normalize during the fourth quarter and contribute to an improvement in sales.

For 2026 most insurance companies have published their formularies, and we are pleased to maintain our 99 percent coverage within the commercial segment without any rebate changes. In the less profitable public segment the coverage is 48 percent, a decrease with 1 percentage point due to a change at a minor Medicare insurance plan.

Moving into the fourth quarter we will finalize our plans for 2026 and are reviewing all of our activities to ensure we invest in the areas with the highest value potential for our shareholders. The plans for 2026 will take into account our financial situation to ensure we maintain good liquidity. The BARDA grant will cover a significant amount of the costs for one of our key projects, but we will also work diligently to ensure we have the financial capacity to advance our other core projects, through leveraging our existing assets and partnering of projects.