About Lipocine

Lipocine Inc. operates as a clinical-stage biopharmaceutical company. The company focuses on leveraging its proprietary Lip'ral platform to develop differentiated products through the oral delivery of previously difficult to deliver molecules, focuses on treating Central Nervous System (CNS) disorders. The company's proprietary delivery technologies are designed to improve patient compliance and safety through orally available treatment options. The company's primary development programs are based on oral delivery solutions for poorly bioavailable drugs. The company has a portfolio of differentiated innovative product candidates that target high unmet needs for neurological and psychiatric central nervous system (CNS) disorders, liver diseases, and hormone supplementation for men and women. The company has a license agreement for the development and commercialization its product candidate, TLANDO, an oral testosterone replacement therapy (TRT) consisted of testosterone undecanoate (TU). TLANDO is a registered trademark assigned to Antares. In 2021, the company entered into a license agreement (the Antares License Agreement) with Antares Pharma, Inc. (Antares or Licensee), pursuant to which it granted to Antares an exclusive, royalty-bearing, sublicensable right and license to develop and commercialize, upon final approval of TLANDO from the United States Food and Drug Administration (FDA), the TLANDO product for TRT in the U.S. Any FDA required post-marketing studies will also be the responsibility of the company's licensee, Antares Pharma, Inc. (Antares). On March 28, 2022, approval was received from the FDA for TLANDO as a TRT in adult males for conditions associated with a deficiency of endogenous testosterone, also known as hypogonadism. TLANDO is an oral treatment indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone (primary or hypogonadotropic hypogonadism). Additional clinical development pipeline candidates include LPCN 1154 for postpartum depression (PPD); LPCN 2101 for epilepsy; and LPCN 1148 comprising a novel prodrug of testosterone, testosterone laurate (TL), for the management of decompensated cirrhosis. In addition to its CNS product candidates, the company has non-core assets for which it expects to seek partnerships to enable further development which the company do not plan to devote significant resources to developing in the future without a partnership or out licensing agreement. These non-core assets include LPCN 1148 which the company intends to explore partnering once completion of the Phase 2 study is complete, LPCN 1144, an oral prodrug of androgen receptor modulator for the treatment of non-cirrhotic non-alcoholic steatohepatitis (NASH) which has completed Phase 2 testing; LPCN 1111, a next generation oral TRT product comprised of testosterone tridecanoate (TT) with the potential for once daily dosing which has completed Phase 2 testing; and LPCN 1107, potentially the first oral hydroxy progesterone caproate (HPC) product indicated for the prevention of recurrent preterm birth (PTB), which has completed a dose finding clinical study in pregnant women and has been granted orphan drug designation by the FDA. Strategy The key components of the company's strategy are to support its licensee in commercialization of its licensed oral TRT option; advance LPCN 1154 and other CNS product candidates; and develop partnership(s) to continue the advancement of pipeline assets. Development Pipeline Product Candidates The company's pipeline of clinical development candidates includes LPCN 1154 for postpartum depression (PPD), LPCN 2101 for epilepsy, and LPCN 1148, an androgen therapy for the management of cirrhosis. The company continues to explore other product development candidates targeting CNS indications with a significant unmet need. The company also continue efforts to enter into partnership arrangements for the continued development and/or marketing of LPCN 1144, LPCN 1148, LPCN 1111, LPCN 1107 and TLANDO outside of the United States. The company's products are based on its proprietary Lip'ral drug delivery technology platform. Lip'ral-based TLANDO was approved in March 2022. Lip'ral technology is a patented technology based on lipidic compositions which form an optimal dispersed phase in the gastrointestinal environment for improved absorption of insoluble drugs. The drug loaded dispersed phase presents the solubilized drug efficiently at the absorption site (gastrointestinal tract membrane) thus improving the absorption process and making the drug less dependent on physiological variables, such as dilution, gastro-intestinal pH and food effects for absorption. Lip'ral-based formulation enables improved solubilization and higher drug-loading capacity, which can lead to improved bioavailability, reduced dose, faster and more consistent absorption, reduced variability, reduced sensitivity to food effects, improved patient compliance, and targeted lymphatic delivery where appropriate. Oral Programs for CNS Disorders As a novel drug class, NAS have received considerable attention because of their potential to treat various neuropsychiatric conditions including depression, movement disorders, epilepsy, anxiety, and neurodegenerative diseases. The company has conducted Phase 1 pharmacokinetic (PK) studies for each of its two lead NAS candidates which has demonstrated promising PK results, safety, and tolerability and it is evaluating additional undisclosed CNS-focused candidates. LPCN 1154: Product Candidate for PPD The company's most advanced NAS candidate is LPCN 1154, a non-invasive, oral formulation of the neuroactive steroid brexanolone, which the company is developing for the treatment of PPD. The FDA recently agreed with the company's proposal for establishing the efficacy of LPCN 1154 through a pivotal PK bridge to an approved IV infusion brexanolone via a 505(b)(2) NDA filing. Based on feedback from the FDA, the company has initiated a pilot PK bridge study of LPCN 1154, a prelude to a pivotal study required for NDA filing, and results from the pilot PK bridge study are expected in the first half of 2023. The company has previously completed an oral PK study and a food effect study with LPCN 1154. PPD PPD (Postpartum depression), a type of major depressive disorder with onset either during pregnancy or within four weeks of delivery, refers to depression persisting up to 12 months after childbirth. PPD can be clinically segmented by the severity of symptoms and presence of a comorbidity, including epilepsy. Approximately 1 in 8 mothers suffers from PPD in the United States alone; this equates to approximately 500,000 women being affected by PPD annually. LPCN 2101: NAS for Epilepsy The company is evaluating an additional NAS candidate, LPCN 2101, for women with epilepsy (WWE). The company has completed pre-clinical and Phase 1 studies for LPCN 2101 which demonstrated promising PK results, safety and tolerability. In July 2022 its IND was accepted by the FDA for LPCN 2101 for adults with epilepsy and the company plans to initiate a Phase 2 IND opening proof-of-concept study to evaluate the safety, tolerability, and efficacy of LPCN 2101 in 2023 subject to the availability of additional resources. LPCN 1148: Oral Product Candidate for the Management of Decompensated Cirrhosis The company is evaluating LPCN 1148 comprising testosterone laurate (TL) for the management of decompensated cirrhosis. LPCN 1148 targets unmet needs for cirrhosis subjects, including improvement in the quality of life of patients while on the liver transplant waiting list, prevention or reduction in the occurrence of new decompensation events, and improvement in post liver transplant survival. The company is conducting a Phase 2 POC study (NCT04874350) in male cirrhotic subjects to evaluate the therapeutic potential of LPCN 1148 for the management of sarcopenia. The ongoing Phase 2 POC study is a prospective, multi-center, randomized, placebo-controlled study in male sarcopenic cirrhotic patients. Subjects will be randomized 1:1 to one of two arms. The treatment arm is an oral dose of LPCN 1148, and the second arm is a matching placebo. The primary endpoint is change in skeletal muscle index at week 24 with key secondary endpoints, including change in liver frailty index, rates of breakthrough hepatic encephalopathy, and number of waitlist events, including all-cause mortality. Total treatment is expected to be 52 weeks. Enrollment in the Phase 2 study was completed in the fourth quarter of 2022 and top-line 24-week results are expected in mid-2023. Partnership Pipeline Product Candidates The company continues to pursue opportunities for partnering arrangements for the continued development and/or marketing of LPCN 1144, LPCN 1148, LPCN 1111, LPCN 1107 and TLANDO outside of the U.S. TLANDO: An Oral Product for Testosterone Replacement Therapy The company granted to Antares an exclusive, royalty-bearing, sublicensable right and license to develop and commercialize TLANDO, the company's product for TRT in the U.S. TLANDO received FDA approval on March 28, 2022. The company is exploring the possibility of licensing LPCN 1021 (known as TLANDO in the United States) to third parties outside the United States. LPCN 1144: An Oral Prodrug of Bioidentical Testosterone Product Candidate for the Treatment of NASH The company is exploring the possibility of partnering LPCN 1144 to a third party, although no partnering agreement has been entered into by the company. The LiFT clinical study was a prospective, multi-center, randomized, double-blind, placebo-controlled multiple-arm study in biopsy-confirmed hypogonadal and eugonadal male NASH subjects with grade F1-F3 fibrosis and a target NAFLD Activity Score = 4 with a 36-week treatment period. The LiFT clinical study enrolled 56 biopsy confirmed NASH male subjects. In November 2021, the FDA granted Fast Track Designation to LPCN 1144 as a treatment for non-cirrhotic NASH. The company had a written only response from FDA for a LPCN 1144 Type C meeting with the FDA in January 2022 to discuss the development path forward with LPCN 1144. The company has completed the LiFT Phase 2 clinical study in biopsy-confirmed non-cirrhotic NASH subjects. The company had a written only response from FDA for a LPCN 1144 Type C meeting with the FDA in January 2022 to discuss the development path forward with LPCN 1144. In July 2022, Lipocine held an End of Phase 2 meeting with FDA for LPCN 1144 in NASH. LPCN 1111: A Next-Generation Long-Acting Oral Product Candidate for TRT The company is in the process of scaling up the manufacturing process and generation of supplies of LPCN 1111 to enable potential partners to conduct pivotal studies for registration. The company is exploring the possibility of partnering LPCN 1111 to a third party, although no partnering agreement has been entered into by the company. LPCN 1111: is a next-generation, novel ester prodrug of testosterone consisted of testosterone tridecanoate (TT) which uses the proprietary delivery technology to enhance solubility and improve systemic absorption. The company completed a Phase 2b dose finding study in hypogonadal men in the third quarter of 2016. In February 2018, the company had a meeting with the FDA to discuss these pre-clinical results and to discuss the Phase 3 clinical study and path forward for LPCN 1111. Based on the results of the FDA meeting and additional pre-clinical studies conducted after the FDA meeting, the company has proposed a Phase 3 protocol for LPCN 1111 and has solicited FDA feedback. Based on initial FDA feedback, it expects the Phase 3 clinical trial design to follow the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines and will include at least a three-month efficacy treatment period and a one-year safety component for approximately 100 subjects. The company is seeking further clarification from FDA with respect to the total subject LPCN 1111 exposure information needed for an NDA filing. The company continues to refine the Phase 3 protocol and plan to request FDA approval of the protocol once it is finalized. LPCN 1107: An Oral Product Candidate for the Prevention of Preterm Birth The company has completed a multi-dose PK dose selection study in pregnant women. The company had an End-of-Phase 2 meeting and subsequent guidance meetings with the FDA to define a pivotal Phase 2b/3 development plan for LPCN 1107. Research and Development In 2022, the company spent $ 8.6 million on research and development. Intellectual Property Drug Delivery Technologies for Lipophilic Drug Substances The company's patent portfolio is directed to various types of compositions and methods for delivery of lipophilic drugs, which are drugs that are soluble in lipids. The company's licensed product, TLANDO, is an oral formulation of the lipophilic prodrug TU, utilizing its proprietary technology for improved delivery of lipophilic therapeutic agents. As of March 7, 2023, the company's intellectual property patent portfolio consists of various issued patents and patent applications related to Oral TU, LPCN 1111, LPCN 1107, LPCN 1144/1148, and Neurosteroids/CNS treatment both in the U.S. and in multiple countries outside of the U.S. The company also holds license rights in fields other than cough and cold, to 2 U.S. patents and 1 U.S. application (and related foreign patents and applications) that it previously assigned to Spriaso LLC, which could be possibly used with future product candidates. Additionally, the company has 12 U.S. patents that it plans to list in the FDA Orange Book for TLANDO that are expected to expire in 2029 and 2030. Government Regulation In the United States, the company's activities are potentially subject to regulation by various federal, state and local authorities in addition to the FDA, including but not limited, to the Centers for Medicare and Medicaid Services and other divisions of the United States government, including the U.S. Federal Communications Commission, the Department of Health and Human Services, the U.S. Department of Justice and individual U.S. Attorney offices within the Department of Justice, and state and local governments. For example, if a drug product is reimbursed by Medicare, Medicaid, or other federal or state healthcare programs, the company, including its sales, marketing and scientific/educational grant programs, among others, must comply with federal healthcare laws, including but not limited to, the federal Anti-Kickback Statute, false claims laws, civil monetary penalties laws, healthcare fraud and false statement provisions and data privacy and security provisions under the Health Insurance Portability and Accountability Act, or HIPAA, the Physician Payment Sunshine Act, and any analogous state laws. If a drug product is reimbursed by Medicare or Medicaid, pricing and rebate programs must comply with, as applicable, the Medicaid rebate requirements of the Omnibus Budget Reconciliation Act of 1990 (OBRA), and the Medicare Prescription Drug Improvement and Modernization Act of 2003. Any pharmaceutical products for which the company receives FDA approvals 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 safety and efficacy information, product sampling and distribution requirements, complying with certain electronic records and signature requirements and complying with the FDA promotion and advertising requirements, which include, among others, standards for direct-to-consumer advertising, prohibitions on promoting pharmaceutical products for uses or in patient populations that are not described in the pharmaceutical product's approved labeling (known as off-label use), industry-sponsored scientific and educational activities and promotional activities involving the internet. History Lipocine Inc. was founded in 1997.