About AcelRx Pharmaceuticals

Talphera, Inc. (Talphera) operates as a specialty pharmaceutical company. The company is focused on the development and commercialization of innovative therapies for use in medically supervised settings. Portfolio The company’s portfolio consists of nafamostat product candidates and pre-filled syringe product candidates, as further described below. Nafamostat Product Candidates Niyad The company is developing Niyad to become the first and only FDA-approved regional anticoagulant for injection into the extracorporeal circuit, such as the dialysis circuit during continuous renal replacement therapy, or CRRT, for acute kidney injury, or AKI, patients in the hospital, and for chronic kidney disease patients undergoing intermittent hemodialysis, or IHD, in dialysis centers. Niyad is expected to be used during renal replacement therapy for AKI patients in the hospital and for end-stage renal disease, or ESRD, patients receiving dialysis in outpatient clinics. Niyad is being studied under an Investigational Device Exemption, or IDE, and has received Breakthrough Device Designation from the FDA and an ICD-10 procedural code from the U.S. Centers for Medicare & Medicaid Services. While not approved for commercial use in the United States, the active drug component of Niyad, nafamostat, has been approved in Japan and South Korea as a regional anticoagulant for the dialysis circuit, disseminated intravascular coagulation and acute pancreatitis. Niyad has the potential for six years of data exclusivity upon FDA approval of the device. Niyad is a lyophilized formulation of nafamostat, a broad-spectrum, synthetic serine protease inhibitor, which has a half-life of 8 minutes, with anticoagulant, anti-inflammatory and potential anti-viral activities. The Niyad NEPHRO CRRT Study, which has received both IDE approval from the FDA and central Institutional Review Board, or IRB, approval, is designed as a prospective, double-blinded trial to be conducted at up to 10 U.S. hospital intensive care units. NEPHRO CRRT stands for Nafamostat Efficacy in Phase 3 Registrational Continuous Renal Replacement Therapy Study. The NEPHRO study is set to begin enrolling patients in the first quarter of 2024, with top-line data expected by the third quarter of 2024 and submission of an application for PMA planned by the end of 2024. The study will enroll and evaluate 166 adult patients undergoing renal replacement therapy, who cannot tolerate heparin or are at risk for bleeding. The primary endpoint of the study is mean post-filter activated clotting time using Niyad versus placebo over the first 24 hours. Key secondary endpoints include filter lifespan, number of filter changes over 72 hours, number of transfusions over 72 hours and dialysis efficacy (based on urea concentration) over the first 24 hours. Nafamostat studies on anticoagulation of the extracorporeal circuit can help guide and support the company’s Niyad development efforts. LTX-608 LTX-608 is the company’s nafamostat formulation for direct IV infusion being explored as an investigational product for one or more of the following indications: antiviral treatment, or treatment of ARDS, DIC or acute pancreatitis. For example, third-party studies have been conducted outside the U.S. in COVID patients where initial results demonstrated that nafamostat shortens time to clinical improvement, increasing the recovery rate and lowering the mortality rate when combined with standard of care, or SOC, compared to SOC alone, in the category of the sickest COVID patients. The company is evaluating the initial indication on which the company will target and focus its resources. Nafamostat is already approved for DIC and acute pancreatitis in Japan and South Korea, which may favor focusing on one of those indications first. Nafamostat has the potential for five years of data exclusivity as a new chemical entity, or NCE, upon the first FDA approval of a new drug application that is independent from any exclusivity arising from issuance of the company’s pending patent applications. The company has a pending patent application for Niyad with claims drawn to priming of the extracorporeal circuit and blood flow when using nafamostat, and multiple LTX-608 pending patent applications that include claims drawn to use of nafamostat in DIC, acute pancreatitis, as an antiviral agent, in ARDS and in other conditions. Pre-filled Syringe (PFS) Product Candidates Fedsyra and Phenylephrine The PFS product candidates are ready-to-use formulations of active ingredients that are currently approved in the United States in concentrated formulations that must be diluted prior to administration to patients, and more recently in ready-to-use vial, and in the case of ephedrine, ready-to-use pre-filled syringe formulations. Hospitals purchase ready-to-use, pre-filled syringe presentations of these active ingredients mainly from compounding facilities that have not obtained FDA approval for the products, or manually dilute the products in-house. There have been two recently FDA-approved pre-filled ephedrine syringe products made available on the market. The company’s product candidates have been developed in a ready-to-use strength and pre-filled into syringes that can be immediately administered to patients, eliminating the need for calculations and additional dilution and filling steps. Aguettant pre-filled syringes are focused on delivering commonly used medicines safely and efficiently. Perioperative medication errors continue, and pre-filled syringes are preferred for improving safety while containing costs. If approved, the company’s pre-filled syringe products may offer significant benefits to hospitals and surgery centers and avoid potential disadvantages of the available compounded products. The company is evaluating the timing of submitting the NDA for its ephedrine pre-filled syringe given the two other FDA-approved products recently made available on the market. The Market Opportunity for Nafamostat Products LTX-608 is the name for the company’s potential second nafamostat product candidate. The company is evaluating the first targeted indication for LTX-608; however, since nafamostat is approved in Japan and South Korea for DIC and acute pancreatitis, one of these may be the first targeted indication for LTX-608. The company has pending patent applications directed to the use of nafamostat in DIC, acute pancreatitis, as an antiviral agent, in ARDS and other conditions. The Market Opportunity for Pre-Filled Syringe Products The company’s product candidates are innovative ready-to-use formulations of molecules that are approved in a concentrated formulation that must be diluted prior to administration to patients, and more recently in ready-to-use vial and, in the case of ephedrine, pre-filled syringe formulations. The company’s product candidates have been developed in a ready-to-use strength and pre-filled into syringes that can be immediately administered to patients, potentially eliminating the need for on-the-spot calculations and additional dilution and filling steps. If approved, the company’s products could offer significant benefits to hospitals and surgery centers over the current compounded products. The company is evaluating the timing of an NDA submission for the company’s ephedrine pre-filled syringe product candidate given two other ephedrine pre-filled syringe products have recently been FDA-approved and are being marketed. Strategy The company’s strategy is focused on developing, obtaining approval, and commercializing the company’s product candidates, first and foremost, Niyad. Accordingly, the company divested DSUVIA to Alora Pharmaceuticals, LLC, or Alora, in April 2023, who will continue to commercialize the product and pay the company royalties, sales-based milestone and other payments, as defined in the DSUVIA Agreement. Further, the company will continue marketing DSUVIA to the Department of Defense, or DoD. This will maximize the value of DSUVIA as Alora has more available resources to invest on DSUVIA commercialization and as a result can execute a more robust commercial plan to support DSUVIA sales expansion. The company has no plans to further develop or commercialize any of its other sufentanil sublingual products that were previously the company’s product candidates. As described below, the company entered into an agreement with XOMA (US) LLC, or XOMA, whereby the company has sold its rights to all royalties, milestones and other payments until XOMA receives a certain specified return on its investment, after which the company will share equally in the royalties earned on sales to the DoD, milestones and other payments from Alora. This transaction was consummated to provide further funding for the development of the company’s lead product candidate, Niyad. The company is focused on submitting its PMA application for Niyad by the end of 2024 and expects to enroll the first patient in the company’s Niyad registrational study in the first quarter of 2024. In April 2023, Vertical Pharmaceuticals, LLC, a wholly owned subsidiary of Alora acquired certain assets and assumed certain liabilities of Talphera relating to the company’s sufentanil sublingual tablet product referred to as DSUVIA or DZUVEO, or any other single-dose pharmaceutical product for use in medically supervised settings containing a sublingual tablet that includes sufentanil as the sole active ingredient, as a 30 mcg tablet or other dosage form or strength as reasonably necessary for lifecycle management, or the Product, pursuant to that certain Asset Purchase Agreement, or the DSUVIA Agreement. The company does not have plans to further develop any sufentanil sublingual product candidates. In July 2021, the company entered into a License and Commercialization Agreement, or the DZUVEO Agreement, with Aguettant, pursuant to which Aguettant obtained the exclusive right to develop and commercialize DZUVEO in the European Union, Norway, Iceland, Liechtenstein, Andorra, Vatican City, Monaco, Switzerland and the United Kingdom, or the DZUVEO Territory, for the management of acute moderate to severe pain in adults in medically monitored settings. The company supplied Aguettant with primary packaged product and Aguettant then completed secondary packaging of the finished product. Pursuant to the DSUVIA Agreement, the company and Aguettant entered into an amendment to the DZUVEO Agreement, or the Amended DZUVEO Agreement, and an amendment and restatement to the supply agreement with respect to the manufacture and supply of DZUVEO, or the Amended and Restated Supply Agreement. The rights and obligations under the Amended DZUVEO Agreement and the Amended and Restated Supply Agreement were assumed by Alora, as part of the DSUVIA asset divestment agreement. In July 2021, the company entered into a License and Commercialization Agreement, or the PFS Agreement, with Aguettant, pursuant to which the company obtained the exclusive right to develop and, subject to FDA approval, commercialize in the United States (i) an ephedrine pre-filled syringe for injection and (ii) a phenylephrine pre-filled syringe for injection. Aguettant will supply the company with the products for use in commercialization. Sales and Marketing The company’s sales and marketing resources are focused on pre-launch activities for Niyad. The company is evaluating the market opportunity, as well as the strategy for a potential launch of Niyad with either internal resources, or with a potential commercial partner. The pre-filled syringe product candidates will not require a significant sales force as the company expects this will mainly be sold through contracting with hospital networks, wholesalers and group purchasing organizations. Intellectual Property The company has recently filed for additional patent coverage in the United States and Europe. If issued, and if the appropriate maintenance, renewal, annuity or other governmental fees are paid, the company expects that these patents will extend into 2040, excluding any additional term for potential patent term adjustments or patent term extensions in the United States. Pursuant to the DSUVIA Agreement, Alora acquired all patents and trademarks related to DSUVIA and DZUVEO. In addition, the company and Alora entered into an intellectual property agreement pursuant to which Alora granted fully-paid, royalty-free and perpetual licenses to the company under certain specified intellectual property rights acquired by Alora under the DSUVIA Agreement for, among other things, the development, manufacture, commercialization and exploitation of certain products, including Zalviso. ‘Niyad’ and ‘Fedsyra’ are trademarks, and ‘Zalviso’ are registered trademarks, all owned by Talphera. Government Regulation Any drug products for which the company receives FDA approval are subject to continuing regulation by the FDA, including among other things, record-keeping requirements, reporting of adverse experiences with the product, providing the FDA with updated clinical safety and efficacy information, product sampling and distribution requirements, complying with certain electronic records and signature requirements and complying with FDA promotion and advertising requirements. Niyad, the company’s nafamostat product in development for use as a regional anticoagulant for injection into the extracorporeal circuit, is regulated by the FDA as a medical device since it achieves its primary intended purposes outside the body. Niyad is being studied under an Investigational Device Exemption, or IDE, and has received Breakthrough Device Designation from the FDA. Niyad is a Class III device as it is novel and not eligible to demonstrate substantial equivalence to a predicate device under the 510(k) process. History The company was founded in 2005. It was incorporated in Delaware in 2005. The company was formerly known as SuRx, Inc. and changed its name to AcelRx Pharmaceuticals, Inc. in 2006 and then to Talphera, Inc. in January 2024.