difficulty maintaining a stable, therapeutic serum level. Preclinical studies of SC XP-8121 showed a sustained plasma exposure profile and similar Cmax when compared with equivalent doses of the oral formulation. We are currently conducting a Phase 1 study of XP-8121 to evaluate the pharmacokinetics, safety and tolerability, and potential for weekly dosing in the treatment of hypothyroidism. The Phase 1 clinical study is a single ascending dose crossover design in 30 healthy participants to compare matching doses of oral levothyroxine (Synthroid®) and subcutaneous XP-8121. The primary endpoints of the study are to characterize the absorption and elimination kinetics of XP-8121 and compare bioavailability of XP-8121 to oral levothyroxine. Secondary endpoints are safety and tolerability of XP-8121. Market Opportunity There are more than 100 million prescriptions written for oral levothyroxine per year, making it one of the most prescribed therapies in the United States. Non-adherence to daily therapy, resistant hypothyroidism, and limited GI absorption are some of the major reasons for treatment failure or suboptimal treatment with oral levothyroxine. We believe these challenges could be mitigated by XP-8121, if approved, and translate into the long-term health benefit of achieving a euthyroid state for patients. It is estimated that 47% of patients have an associated GI condition o 15% experience inadequate control of symptoms. Assuming 56 million weekly doses per year and $30 per dose comparable to branded orals, this represents a $1 to $2 billion market opportunity. XeriSol Pramlintide-Insulin Co-formulation (XP-3924) Xeris Pharma has developed a novel, investigational fixed-ratio co-formulation of pramlintide and regular human insulin (XP-3924) to improve glycemic control in adult and pediatric patients with diabetes mellitus (T1D and T2D). Xeris’ proprietary formulation technology (XeriSol™) enables the 2 peptides (pramlintide and insulin), which require different aqueous pH environments for optimal stability, to be co-formulated in a stable ready-to-use solution. The current formulation patent exists through at least Q4 2032, expected to extend to 2036 with successful prosecution of the currently pending continuation application, and through 2041-2042 with the ongoing formulation development work XP-3924 Market Opportunity We believe XP-3924 has the opportunity to serve a large unmet need in patients on mealtime insulin, with the market opportunity estimated at $3-4 billion in the United States. It is estimated that ~1/3 of patients on mealtime insulin are not achieving their A1C goals despite optimized insulin therapy. Additional therapeutic options for patients with advanced diabetes not well-controlled on mealtime insulin are limited. The only pharmacological therapy indicated for such patients is pramlintide (Symlin®). We have an open IND for XP-3924, recently completed a Phase 2 clinical trial in adults with Type 1 Diabetes and obtained FDA feedback on the clinical development and regulatory requirements for submitting a 351(a) stand-alone BLA. We are currently seeking partners to license the development and commercialization rights to XP-3924 in the US. Ready-to-Use Diazepam (XP-0863) XP-0863 is a liquid formulation of diazepam for intramuscular injection being studied for the treatment of ARS. Xeris’ patent protected technology XeriSol™ has been used to develop a room-temperature stable, ready-to-use, small-volume solution of diazepam for intramuscular injection delivered by an auto-injector, which will provide patients and caregivers an alternative to rectal and nasal administrations of benzodiazepines. XP-0863 is designed to address variable absorption, and suboptimal PK profiles of the currently marketed formulations of benzodiazepines, by offering a longer duration of action, consistent absorption of drug delivered through intramuscular administration, and a convenient and reliable form factor of the autoinjector. XP-0863 has been granted an orphan designation by the FDA for the treatment of ARS and Dravet syndrome in patients with epilepsy. Approximately 160,000 people in the United States experience ARS. Injectable and rectal gel formulations of diazepam are the current standard of care for the emergency treatment of epileptic seizures. In 2018, diazepam formulations generated total U.S. sales of approximately $86 million, of which Diastat® Rectal Gel and its generic formulations comprised $74 million. Diastat requires a multi-step procedure which makes it more difficult to administer while a patient is experiencing seizures. Additionally, the use of rectal gel in both middle school children and young adults with ARS is reduced because of social stigma. These characteristics are limitations that may diminish the specific demand for rectal diazepam products. Due to this limitation, we believe the market for diazepam in ARS is underpenetrated. We believe that a ready-to-use diazepam injectable rescue pen would improve patient quality of life and drive adoption of diazepam to treat ARS. We believe that, if approved, XP-0863 would have the opportunity to fill the unmet need in ARS for a reliable, user-friendly treatment option with adequate onset of action and durable effect sufficient to break the seizure cluster and prevent recurrence. The market opportunity is estimated at ~$650-1.3B. We have completed a Phase 1a and a Phase 1b single dose studies in healthy subjects vs. Diastat® which demonstrated Cmax comparable to and Tmax longer than Diastat®, comparable partial AUCs across early timepoints, increased overall exposure (AUC0- ∞) when compared to Diastat®, and dose proportionality. XP-0863 was safe and well-tolerated with minimal sedation, minimal injection site reactions and no serious adverse events. In addition to the orphan designation, the FDA has granted Fast Track designation and aligned on the proposed clinical development plan of a single Phase 3, single arm safety study in patients with epilepsy as well as a 505(b)(2) submission. A primary container and device partner has been identified to develop a pre-filled syringe 17
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