UNITED
STATES
SECURITIES
AND EXCHANGE COMMISSION
WASHINGTON,
D.C. 20549
on
FORM
10-K
For
the fiscal year ended December 31, 2025
or
Commission
File Number: 001-36357
LIPOCINE
INC.
(Exact
name of registrant as specified in its charter)
675 Arapeen Drive, Suite 202, Salt Lake City, Utah 84108
(Address of Principal Executive Offices) (Zip Code)
801-994-7383
(Registrant’s
telephone number, including area code)
Securities
registered pursuant to Section 12(b) of the Act:
Title of Each Class Trading Symbol(s) Name of Each Exchange on Which Registered
Common Stock, par value $0.0001 per share LPCN The NASDAQ Stock Market LLC
Securities
registered pursuant to Section 12(g) of the Act: None
Indicate
by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒
Indicate
by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No ☒
Indicate
by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange
Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports) and (2)
has been subject to such filing requirements for the past 90 days. Yes:☒ No ☐
Indicate
by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule
405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant
was required to submit such files). Yes☒ No ☐
Indicate
by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting
company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,”
“smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act:
Large accelerated filer ☐ Accelerated filer ☐
Non-accelerated filer ☒ Smaller reporting company ☒
Emerging growth company ☐
If
an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying
with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Indicate
by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness
of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered
public accounting firm that prepared or issued its audit report. ☐
If
securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant
included in the filing reflect the correction of an error to previously issued financial statements. ☐
Indicate
by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation
received by any of the registrant’s executive officers during the relevant recovery period pursuant to § 240.10D-1(b). ☐
Indicate
by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act). Yes ☐ No ☒
Outstanding
Shares
The
aggregate market value of the common stock held by non-affiliates of the registrant was $16.4 million as of June 30, 2025. For purposes
of calculating the aggregate market value of shares of our common stock held by non-affiliates as set forth on the cover page of this
Annual Report on Form 10-K, we have assumed that all outstanding shares are held by non-affiliates, except for shares held by each of
our executive officers, directors and 10% or greater stockholders. However, this assumption should not be deemed to constitute an admission
that all executive officers, directors and 10% or greater stockholders are, in fact, affiliates of our company, or that there are no
other persons who may be deemed to be affiliates of our company. Further information concerning shareholdings of our officers, directors
and principal stockholders is included or incorporated by reference in Part III, Item 12 of this Annual Report on Form 10-K.
As
of March 9, 2026, the registrant had 7,299,687 shares of common stock outstanding.
DOCUMENTS
INCORPORATED BY REFERENCE
Portions
of the definitive proxy statement relating to the annual meeting of shareholders to be held on June 3, 2026 are incorporated by reference
into Part III of this annual report.
TABLE
OF CONTENTS
Page
PART I
Item 1. Business 4
Item 1A. Risk Factors 21
Item 1B. Unresolved Staff Comments 48
Item 1C. Cybersecurity 48
Item 2. Properties 49
Item 3. Legal Proceedings 49
Item 4. Mine Safety Disclosures 49
PART II
Item 6. [Reserved] 50
Item 7A. Quantitative and Qualitative Disclosures About Market Risk 60
Item 8. Financial Statements and Supplementary Data 61
Item 9A. Controls and Procedures 88
Item 9B. Other Information 88
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 88
PART III
Item 10. Directors, Executive Officers and Corporate Governance 89
Item 11. Executive Compensation 89
Item 14. Principal Accountant Fees and Services 89
PART IV
Item 15. Exhibits and Financial Statement Schedules 90
FORWARD-LOOKING
STATEMENTS
THIS
ANNUAL REPORT ON FORM 10-K (THE “ANNUAL REPORT”), IN PARTICULAR “ITEM 7. MANAGEMENT’S DISCUSSION AND ANALYSIS
OF FINANCIAL CONDITION AND RESULTS OF OPERATION,” AND “ITEM 1. BUSINESS,” CONTAINS FORWARD-LOOKING STATEMENTS WITHIN
THE MEANING OF SECTION 27A OF THE SECURITIES ACT OF 1933, AS AMENDED (the “SECURITIES ACT”), AND SECTION 21E OF THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED (the “EXCHANGE ACT”), that involve risks and uncertainties. Forward-looking statements provide
current expectations of future events based on certain assumptions and include any statement that does not directly relate to any historical
or current fact. Forward-looking statements may refer to such matters as products, product benefits, pre-clinical and clinical development
timelines, clinical and regulatory expectations and plans, global political changes, particularly the transition in the U.S. presidential
administration, and their impact on the pharmaceutical industry, REGULATORY DEVELOPMENTS AND REQUIREMENTS, THE RECEIPT OF REGULATORY
APPROVALS, THE EXPECTATIONS FOR AND RESULTS OF CLINICAL TRIALS, PATIENT ACCEPTANCE OF LIPOCINE’S PRODUCTS, MANUFACTURING AND COMMERCIALIZATION
OF LIPOCINE’S PRODUCTS, anticipated financial performance, future revenues or earnings, business prospects, projected ventures,
new products and services, anticipated market performance, future expectations for liquidity and capital resources needs and similar
matters. Such words as “may,” “will,” “expect,” “continue,” “estimate,” “project,”
“intend,” and “potential” and similar terms and expressions are intended to identify forward looking statements.
Forward-looking statements are not guarantees of future performance and our actual results may differ significantly from the results
discussed in the forward-looking statements. Factors that might cause such differences include, but are not limited to, those discussed
in Part I, Item 1A “Risk Factors” of this ANNUAL REPORT. Except as required by applicable law, we assume no obligation to
revise or update any forward-looking statements for any reason.
There
are a number of risks, uncertainties and other important factors that could cause our actual results to differ materially from the forward-looking
statements contained in this Annual Report. Such risks, uncertainties and other important factors include, among others, the risks, uncertainties
and factors set forth in “Risk Factors,” and the following risks, uncertainties and factors:
● our ongoing and planned clinical trials;
● our ability to monetize product candidates;
● significant competition in our industry;
● our intellectual property position;
● loss of key members of management;
● failure to successfully execute our strategy;
● our failure to maintain effective internal controls.
There
may be other factors that may cause our actual results to differ materially from the forward-looking statements, including factors disclosed
in “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations.”
You should evaluate all forward-looking statements made in this Annual Report on Form 10-K in the context of these risks and uncertainties.
We
caution you that the risks, uncertainties and other factors referred to above may not contain all of the risks, uncertainties and other
factors that are important to you. In addition, we cannot assure you that we will realize the results, benefits or developments that
we expect or anticipate or, even if substantially realized, that they will result in the consequences or affect us or our business in
the way expected. All forward-looking statements in this Annual Report apply only as of the date made and are expressly qualified in
their entirety by the cautionary statements included in this Annual Report. We undertake no obligation to publicly update or revise any
forward-looking statements to reflect subsequent events or circumstances, except as otherwise
required by law.
PART
I
ITEM 1. BUSINESS
General
Lipocine
Inc. (“Lipocine” or the “Company”) is incorporated under the laws of the State of Delaware.
We
are a biopharmaceutical company focused on leveraging our proprietary technology platform to develop innovative products with effective
oral delivery of previously difficult to deliver molecules. Our proprietary delivery technologies are designed to improve patient compliance
and safety through orally available treatment options. Our primary development programs are based on oral delivery solutions for poorly
bioavailable drugs. We have a portfolio of differentiated innovative product candidates that target high unmet needs for neurological
and psychiatric CNS disorders, liver disease, and hormone supplementation for men and women.
On
January 12, 2024, we entered into a license agreement (the “Verity License Agreement”) with Gordon Silver Limited (“GSL”)
and Verity Pharmaceuticals, Inc. (“Verity” or our “Licensee”), pursuant to which we granted to Verity an exclusive,
royalty-bearing, sublicensable right and license to commercialize TLANDO for TRT in the U.S. and Canada (the “Licensed Verity Territory”).
The license agreement is for the development and commercialization of our product, TLANDO, an oral treatment indicated for testosterone
replacement therapy (“testosterone replacement therapy” or “TRT”) in adult males for conditions associated with
a deficiency or absence of endogenous testosterone (primary or hypogonadotropic hypogonadism) comprised of testosterone undecanoate (“testosterone
undecanoate” or “TU”) and any post-marketing studies required by the United States Food and Drug Administration (“FDA”)
will also be the responsibility of Verity. On January 31, 2024, our license agreement with the former licensee (the “Antares License
Agreement”), Antares Pharma, Inc. (“Antares”), was terminated and the transition of the U.S. commercial rights for
TLANDO from Antares to Verity was completed on February 1, 2024, for the distribution, marketing and sale of TLANDO. The Verity License
Agreement also provides Verity with a license to develop and commercialize LPCN 1111 (also referred to as TLANDO XR), the Company’s
potential next generation, once daily oral product candidate for testosterone replacement therapy comprised of testosterone tridecanoate
(“TT”), in the U.S. and Canada.
In
September 2024, we entered into a distribution and license agreement (the “SPC License Agreement”) for the development and
commercialization of TLANDO, an oral TRT with SPC Korea Limited (“SPC”), pursuant to which the Company granted to SPC a non-transferable,
exclusive, royalty-bearing license to commercialize our TLANDO product for TRT in South Korea (the “SPC Territory”). In October
2024, we entered into a distribution and supply agreement (the “Pharmalink Distribution Agreement”) with Pharmalink granting
a non-transferable, exclusive, license to commercialize our TLANDO product in the field specific to the Gulf Cooperation Council (“GCC”)
countries, including Saudi Arabia, Kuwait, the United Arab Emirates, Qatar, Bahrain, and Oman (the “Pharmalink Territory”).
In April 2025, we entered into a License and Supply Agreement (the “Aché License Agreement”) with Aché, pursuant
to which we granted to Aché an exclusive license to commercialize TLANDO with respect to the field, specific to Brazil (the “Aché
Territory”). Under the agreement, we are entitled to receive fees upon the achievement of certain regulatory milestones, royalties
on net sales and will supply TLANDO to Aché at an agreed transfer price. We retain development and commercialization rights for
TLANDO outside of the United States, Canada, South Korea, the GCC and Brazil.
Additional
clinical development pipeline candidates include: LPCN 1154 for postpartum depression (“PPD”); LPCN 2201 for major depressive
disorder (“MDD”); LPCN 2203 for essential tremor; LPCN 2101 for epilepsy; and LPCN 2401 for improved body composition in
obesity management. In addition to our clinical development product candidates, we have assets for which we expect to seek partnerships
to enable further development including TLANDO for territories outside of the United States, South Korea, the GCC, and Brazil, LPCN 1148
comprising a novel prodrug of testosterone and testosterone laurate (“testosterone laurate” or “TL”), for the
management of decompensated cirrhosis, and LPCN 1107, potentially the first oral hydroxy progesterone caproate (“HPC”) product
indicated for the prevention of recurrent PTB, which has completed a dose finding clinical study in pregnant women and has been granted
orphan drug designation by the FDA.
The
following chart summarizes the status of our product candidate development programs:
Corporate
Strategy
Our
goal is to become a leading biopharmaceutical company focused on leveraging our proprietary drug delivery technology platform to develop
differentiated products through oral delivery of previously difficult to deliver molecules. The key components of our strategy are to:
Advance
LPCN 1154 and other CNS product candidates. We intend to focus on the development of endogenous neuroactive steroids (“NASs”)
which have broad applicability in treating various CNS conditions where we can leverage our technology platform to develop highly differentiated
oral therapeutics. Our priority is the development of LPCN 1154, a fast-acting oral antidepressant for PPD with potential for outpatient
use.
Support
our Licensees, Verity, SPC, Pharmalink, and Aché in commercialization of our licensed oral TRT product. We believe the TRT
market needs a differentiated, convenient oral option. We have exclusively licensed rights to TLANDO to Verity for commercialization
of TLANDO in the Licensed Verity Territory, to SPC for commercialization in the SPC Territory, to Pharmalink in the Pharmalink Territory,
and to Aché in the Aché Territory (together, the “Currently Licensed TLANDO Territories”). We plan to support
Verity’s, SPC’s, Pharmalink’s, and Aché’s efforts to effectively enable the availability of TLANDO to
patients in a timely manner, in addition to receiving milestone payments, royalty payments, and/or payments for product sales associated
with TLANDO commercialization as agreed to in the Verity License Agreement, the SPC License Agreement, the Pharmalink Distribution Agreement
and the Aché License Agreement.
Develop
partnership(s) to continue the advancement of pipeline assets. We continuously strive to prioritize our resources in seeking partnerships
of our pipeline assets. We are currently exploring partnerships for our liver program LPCN 1148 for the management of decompensated cirrhosis
including prevention of the recurrence of overt hepatic encephalopathy (“overt hepatic encephalopathy” or “OHE”);
LPCN 2401 for improved body composition as adjunct therapy to incretin mimetics use in obesity management; and LPCN 1107, our candidate
for prevention of pre-term birth. We are also exploring the possibility of licensing LPCN 1021 (known as TLANDO in the United States)
to third parties outside of the Currently Licensed TLANDO Territories, although no additional licensing agreements have been entered
into by the Company in any other territories.
Our
Pipeline Product Candidates
Our
pipeline of clinical development candidates includes LPCN 1154 for PPD, LPCN 2201 for MDD, LPCN 2101 for epilepsy, and LPCN 2203 for
essential tremor. We will continue to explore other product development candidates targeting CNS indications with a significant unmet
need. We will also continue efforts to enter into partnership arrangements for the continued development and/or marketing of LPCN 1144,
LPCN 1148, LPCN 2401, LPCN 1107 as well as for the TRT Assets outside of the Currently Licensed TLANDO Territories.
Our
products are based on our proprietary drug delivery technology platform. TLANDO was approved by the FDA in March 2022. Our patented
technology is 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,
gastrointestinal pH and food effects for absorption. Our 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.
TRT
Franchise – TLANDO and LPCN 1111 (TLANDO XR)
TLANDO:
An Oral Product for Testosterone Replacement Therapy
As
previously described, under the Verity License Agreement, in January 2024, we granted to Verity an exclusive, royalty-bearing, sublicensable
right and license to develop and commercialize TLANDO, our product for TRT, in the U.S. and Canada effective February 1, 2024. TLANDO
received FDA approval on March 28, 2022. Any FDA requirement to conduct certain post-marketing studies will be the responsibility of
Verity. In addition, in September 2024, we granted SPC an exclusive, royalty-bearing license to commercialize TLANDO in South Korea,
in October 2024 we granted Pharmalink an exclusive license to commercialize TLANDO in the GCC countries and in April 2025, we granted
Aché an exclusive license to commercialize and supply TLANDO in Brazil.
Proof-of-concept
for TLANDO was initially established in 2006, and TLANDO was subsequently licensed in 2009 to Solvay Pharmaceuticals, Inc., which was
then acquired by Abbott Products, Inc. (“Abbott”). Following a portfolio review associated with the spin-off of AbbVie Inc.
by Abbott in 2011, we re-acquired the rights to TLANDO. All obligations under the prior license agreement have been completed except
that Lipocine will owe Abbott a perpetual 1% royalty on net sales of TLANDO. Such royalties were limited to $1 million in the first two
calendar years following product launch, after which period there is no cap on royalties and no maximum aggregate amount. If generic
versions of any such product are introduced, then royalties will be reduced by 50%. TLANDO was commercially launched on June 7, 2022.
During the years ended December 31, 2025 and 2024, we incurred royalty expense of approximately $40,000 and $24,000, respectively.
Since
TLANDO received full FDA approval, under the terms of the Verity License Agreement, Verity will need to assess the safety and effectiveness
of TLANDO in pediatric patients, as required by the Pediatric Research Equity Act. The FDA may also require certain post-marketing studies
to be conducted which will also be the responsibility of Verity. Similarly, SPC, Pharmalink, and Aché are responsible for obtaining
any regulatory/marketing approvals for TLANDO required for the SPC Territory, the Pharmalink Territory, and the Aché Territory
respectively.
Upon
execution of the Verity License Agreement, Verity paid us an initial payment of $2.5 million which was received on signing of the License
Agreement and $5 million which was received on February 1, 2024. Verity also made an additional payment of $2.5 million to us on December
30, 2024, and made the final license payment of $1 million to us on January 5, 2026. We are also eligible to receive milestone payments
of up to $259 million in the aggregate, depending on the achievement of certain sales milestones in a single calendar year and/or development
milestones with respect to products licensed by Verity under the Verity License Agreement. In addition, we will receive tiered royalty
payments at rates ranging from 12% up to 18% of net sales of all products licensed under the Verity License Agreement in the Licensed
Verity Territory.
SPC
paid us a non-refundable, non-creditable upfront fee in October 2024. We also received an additional payment for a non-refundable, non-creditable
prepayment in consideration for TLANDO product inventory, and we are eligible to receive additional payments for various marketing authorization
and sales milestones, and the Company will supply TLANDO to SPC and receive a supply price. In addition, we will receive royalties on
net sales in South Korea under the SPC License Agreement.
Upon
execution of the Pharmalink Distribution Agreement, Pharmalink paid a non-refundable, non-creditable upfront fee. Under the Pharmalink
Distribution Agreement, we could receive additional payments in regulatory authorization milestones and we will supply TLANDO to Pharmalink
at an agreed transfer price.
Upon
execution of the Aché License Agreement, Aché paid us a non-refundable, non-creditable upfront fee in May 2025. Under the
Aché License Agreement, we may receive additional payments in regulatory authorization milestones, royalties on net sales and
will supply TLANDO to Aché at an agreed transfer price.
We
are exploring the possibility of licensing LPCN 1021 (known as TLANDO in the United States) to third parties outside the Currently Licensed
TLANDO Territories, although no licensing agreement has been entered into by the Company in any other territories. If and when an agreement
is made with a partner, such an arrangement would likely be partially contingent upon obtaining local regulatory approval. No assurance
can be given that any license agreement will be completed or, if an agreement is completed, that such an agreement would be on terms
favorable to us.
Oral
Programs for CNS Disorders
Some
preferred endogenous or naturally occurring NAS present in the central nervous system act as positive allosteric modulators (“PAMs”)
of the GABAA receptor, the major biological target of the inhibitory neurotransmitter γ-aminobutyric acid (“GABAA”).
In
October 2024, we announced positive data from our qEEG study of our oral brexanolone with results indicating robust central nervous system
activity of oral brexanolone, with concentration- and time-dependent post-dose changes in qEEG as follows:
●
Quantitative Electroencephalogram (“qEEG”) in healthy subjects administered single doses of oral brexanolone, a neuroactive
steroid, confirmed GABAA modulation
●
Rapid and durable CNS target engagement confirms effective oral delivery of bioidentical brexanolone
●
Promising results support continued development of oral brexanolone for the treatment of neuropsychiatric disorders
We
believe through utilization of our proprietary technology we may have the ability to enable effective oral delivery of endogenous GABAA
receptor PAMs which historically had been deemed to be not orally bioavailable. As a novel drug class, NASs have received considerable
attention because of their potential to treat various neuropsychiatric conditions including depression, movement disorders, epilepsy,
anxiety, and neurodegenerative diseases. We have conducted Phase 1 pharmacokinetic (“PK”) studies for each of our three lead
NAS candidates which have demonstrated promising PK results, safety, and tolerability and we are evaluating additional undisclosed CNS-focused
candidates.
LPCN
1154: Product Candidate for PPD
Our
most advanced NAS candidate is LPCN 1154, a rapid onset, oral formulation of the neuroactive steroid brexanolone which we are developing
for the treatment of PPD. We have completed clinical oral PK studies including a pilot food effect study and a pilot PK bridge study.
In addition, as a prelude to a LPCN 1154 pivotal study, a multi-dose study was done confirming the dosing regimen for the PK bridge study
using the scaled up “to be marketed” formulation required for New Drug Application (“NDA”) filing. In June 2024,
we announced results from a dosing regimen confirmation study which demonstrated LPCN 1154 meets bioequivalence with comparator, IV brexanolone,
meeting standard bioequivalence criteria and Ctrough criteria. LPCN 1154 treatment was well-tolerated with no sedation nor
somnolence events observed in the dosing regimen confirmation study.
After
completing PK studies and labeling studies such as a food effect study and PK profiling in women with PPD, we met with the FDA in the
first quarter of 2025. In the meeting, we were advised that the FDA believes, in addition to the previously completed PK dosing regimen
confirmation data, an efficacy and safety study of oral LPCN 1154 in the target population will be required for 505(b)(2) NDA submission.
Based on observed comparable exposure of LPCN 1154 and IV brexanolone in the dosing confirmation study, we have confirmed the target
dosing regimen and initiated a Phase 3 safety and efficacy study and, as of February 18, 2026, we had completed enrollment, dosing
and the last patient’s last visit in the Phase 3 pivotal trial. We expect to report data from this Phase 3 trial in April 2026, and data from this trial are expected to support
a 505(b)(2) NDA submission for LPCN 1154 in 2026.
We
are exploring the possibility of partnering with a third party for the marketing and commercialization of LPCN 1154, although no partnering
agreement has been entered into by the Company. No assurance can be given that any partnering agreement will be completed, or, if an
agreement is completed, that such an agreement would be on terms favorable to us.
PPD
PPD,
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. PPD is a life-threatening condition with few existing treatment options. Maternal depression and suicide can have far-reaching
consequences for child development, family functioning, and the nation’s economy. Approximately 600,000 women are affected by PPD
annually with approximately 240,000 women diagnosed with PPD, and approximately 144,000 of those diagnosed patients treated with prescription
medication. We believe that PPD is a significant and growing market opportunity, and increased awareness of PPD and effective therapies
is expected to increase diagnosis for symptomatic women with PPD.
Disease
Overview - PPD
Associated
Risk Factors
Unmet
Medical Need
We
believe there is considerable unmet need within women with PPD due to lack of convenient and fast-acting oral therapies with good tolerability,
especially with respect to CNS depressant effects. Selective Serotonin Reuptake Inhibitors (“SSRIs”) have been the traditional
first-line choice for women with severe PPD and require weeks for onset of efficacy; therefore, a need for an oral treatment option with
a faster onset of action, short treatment duration, and improved tolerability remains a significant unmet need in treating PPD, especially
in mothers with moderate to severe depression prone to harmful actions.
Injectable
brexanolone (ZulressoTM, SAGE Therapeutics (“Sage”)) became the first FDA-approved treatment for postpartum depression.
However, numerous factors limited the utilization of injectable brexanolone such as method of administration, cost, and safety concerns,
and SAGE Therapeutics discontinued Zulresso in October 2024. In addition to Zulresso, SAGE received FDA approval for zuranolone (brand
name ZURZUVAETM) in August 2023 and ZURZUVAE was launched commercially in December 2023. Zuranolone, a synthetic neuroactive steroid
derivative, is an oral, once daily 14-day treatment for postpartum depression and is the first oral medication approved by the FDA for
the treatment of postpartum depression. Per label, besides long terminal half-life of approximately 19.7 to 24.6 hours and dosage modifications
needed for concomitant use with CYP3A4 modulators, warnings and precautions include CNS depressant effects, impaired ability to drive
or engage in other potentially hazardous activities and embryo-fetal toxicity. In June 2025, Sage announced the acquisition of Sage by
Supernus Pharmaceuticals (“Supernus”) and Supernus’ intention to strengthen their leading presence in neuropsychiatric
conditions with Sage’s innovative commercial product, ZURZUVAE. The transaction closed in the third quarter of 2025.
We
believe LPCN 1154 targets the unmet need for robust, rapid relief of PPD symptoms with a 48-hour dosing duration through a convenient
oral therapy candidate comprising bioidentical NASs with improved tolerability. If approved, we believe that LPCN 1154 has the potential
to be a first-line therapy option in treating PPD, providing the following advantages over current treatment options:
LPCN
2201: NAS for Major Depressive Disorders (“MDD”)
We
are currently advancing LPCN 2201, a unique oral brexanolone formulation, as a novel, rapid relief oral treatment option for MDD
with the goal of improving outcomes without the limitations of existing therapies. LPCN 2201 is chemically identical to the
endogenous human hormone allopregnanolone, a positive allosteric modulator of y-aminobutyric acid (GABAA) receptor. Post
planned clinical assessment of unique formulations, we plan to submit a protocol for a Phase 2 study to the FDA, and we may initiate
a study to evaluate LPCN 2201 for MDD, subject to resource prioritization.
Disease
Overview - MDD
MDD
affects approximately 21 million adults in the U.S., representing 8.4% of the population. While 12.8 million individuals receive
treatment, nearly 3.8 million patients continue to struggle with treatment-resistant depression (“TRD”), a condition
where symptoms persist despite multiple antidepressant therapies. These patients experience persistent, debilitating symptoms,
reduced quality of life, higher comorbidities, and significant social and occupational impairment. In 2018, the total annual burden
of medication-treated MDD in the U.S. was approximately $92.7 billion, with $43.8 billion (47%) attributable to TRD.
Unmet
Medical Need
Current
treatment options for MDD pose significant challenges. Most available antidepressants such as SSRIs and SNRIs require 4-6 weeks to show
meaningful effects and often fail to deliver adequate relief. Additionally, SSRIs and SNRIs can lead to metabolic issues, sexual dysfunction,
and heightened risk of cerebrovascular events in vulnerable populations. Even newer therapies that can be used for fast depression symptom
relief like Spravato® (esketamine) come with serious safety concerns, including black box warnings for sedation, dissociation,
cognitive impairment, and increased blood pressure. Beyond safety, access remains a major hurdle – esketamine, for example requires
intranasal administration in a clinical setting under a restricted program, limiting convenience and scalability.
Patients
and providers urgently need a convenient, well-tolerated, at-home rapid relief option for MDD. Ideal solutions should offer ease of use
without monitoring requirements, enabling treatment in outpatient or home settings. Improved treatments should deliver effective antidepressant
action with high and sustained remission rates, while maintaining a wide therapeutic index for safety and tolerability. Improved compliance,
better management of comorbid conditions such as anxiety, and enhanced patient experience are critical to addressing the gaps left by
current therapies.
We
believe LPCN 2201 has the potential to be a convenient, fastest time to action treatment through its fast-acting mechanism promoting
acute stabilization of symptoms with the freedom of at home dosing while presenting no significant risk of adverse reactions from exposure
to bioidentical brexanolone. LPCN 2201 could be an appealing option for patients for whom rapid improvement is a priority for the treatment
of moderate or severe MDD with suicidal ideation.
LPCN
2101: NAS for Epilepsy
We
are currently developing an additional NAS candidate, LPCN 2101, for epilepsy including Drug Resistant Epilepsy (“DRE”)
and women with epilepsy. We have completed pre-clinical and Phase 1 studies for LPCN 2101 which demonstrated promising PK results,
safety and tolerability. In July 2022 our IND was accepted by the FDA for LPCN 2101 for adults with epilepsy and we may initiate a
Phase 2 proof-of-concept study to evaluate the safety, tolerability, and efficacy of LPCN 2101, subject to resource
prioritization.
Disease
Overview – Epilepsy
Epilepsy
is one of the most common neurological disorders characterized by recurrent, unprovoked seizures caused by abnormal electrical activity
in the brain. Epilepsy is defined by the 1) occurrence of at least two unprovoked seizures more than 24 hours apart, 2) occurrence of
one unprovoked seizure and a probability of further seizures occurring over the next 10 years, and/or 3) diagnosis of an epilepsy syndrome.
Patients with epilepsy have increased risk of mortality due to direct effects of seizures (e.g., status epilepticus, car accidents) and
indirect effects of seizures (e.g., suicide, cardiovascular effects).
Epilepsy
is a disorder of the brain that causes seizures, affecting the physical, mental, and social well-being of persons, and is associated
with a 2 to 3 times greater mortality rate compared with the general population. About 60-65% of epilepsy is idiopathic and about 30%
of patients are refractory or have DRE (i.e., epilepsy not well managed with currently available Anti-Seizure Medications (“ASMs”)).
DRE:
There are about 2.9 million adults and 456,000 children with active epilepsy, meaning they are either taking medication or have had a
seizure in the past year, with approximately 150,000 new diagnoses annually. Approximately 38% of adults with epilepsy report having
a disability and the unemployment rate among adults with epilepsy is approximately 29%. DRE is a significant clinical challenge in epilepsy
care, with high social and occupational limitations. DRE affects 30-40% of epilepsy patients in the U.S. and DRE contributes heavily
to the $24.5 billion annual epilepsy-related healthcare costs and DRE poses significant treatment challenges due to limited success with
medications, and need for early identification.
Unmet
needs in DRE: Many patients with DRE cycle through multiple ASMs with limited success. Seizures may cause physical injuries,
and a minority may last long (status epilepticus) or recur in clusters and can be life-threatening. Rescue treatments (primarily benzodiazepines)
do not prevent future seizures, they only stop the current episode. DRE patients are at high risk of seizure recurrence within hours
or days after a cluster. There is a lack of post-rescue medications, especially for patients who experience recurrent seizure clusters
or drug-resistant epilepsy and a need to transition effectively to maintenance therapy and sustain seizure control after acute treatment
prevents status epilepticus and to prevent patients from requiring emergency room treatment for seizure management. There remains an
unmet need for medications with novel mechanism of action and minimal cognitive, mood, or systemic side effects, especially for patients
who experience recurrent seizure clusters or DRE.
WWE:
It is estimated that approximately 1,000,000 childbearing (“CB”) aged women suffer from active epilepsy in the U.S. Women
of CB age with epilepsy face many additional challenges due to hormonal influences on seizure activity and endocrine function throughout
the different phases of their reproductive cycles. Elevated estrogen or decreased progesterone levels can exacerbate seizure frequency.
Often, these women experience hormonal and endogenous NAS imbalances, coupled with fluctuations in the blood levels of ASMs that impact
control of seizures, efficacy of oral contraceptives, any coexisting anxiety and/or depression and any associated sleep impairment. Epileptic
patients are 5-20 times more likely to develop depression.
Women
with epilepsy were once counseled to avoid pregnancy, but epilepsy is no longer considered a contraindication to pregnancy. Caregivers
for WWE in the preconception phase either intending to start a family (planning pregnancy) or using contraception to prevent an unplanned
pregnancy face significant challenges to balance seizure control efficacy with the selection and dosage of ASMs and ASM-related risks
such as, among other risks, fetal-neonatal toxicity, contraception failure, and psychiatric side effects.
Several
ASMs are known to have teratogenic effects on the developing fetus (converging evidence from registry studies indicates that teratogenic
risks are highest with valproate, followed by carbamazepine and topiramate). Other commonly prescribed ASMs, including older generation
agents, such as phenobarbital and phenytoin, have been associated with higher risks as compared with lamotrigine, levetiracetam, clonazepam
and gabapentin (Vajda et al., 2014; Voinescu and Pennell, 2015). Moreover, risks associated with ASMs are considerable early in pregnancy;
therefore, it is necessary that WWE of CB age undergo counseling, monitoring, and adjustment to the most appropriate ASM prior to becoming
pregnant. It is preferable that WWE of CB age discuss seizure control with their doctor for at least 6 months before conception and,
if possible, cease ASM therapy or use the lowest effective dose of a single anticonvulsant according to the type of epilepsy and the
fetal toxicity of the ASM. Anxiety, depression, lack of adherence to ASM, and/or contraception failure may be experienced by women who
are worried about unplanned pregnancy or are late in confirming pregnancy, planned or unplanned. ASMs can reduce the efficacy of oral
contraceptives, compounding this problem.
Complex,
multidirectional interactions between female hormones, seizures, and ASMs exist. Most hormones act as NASs and can thus modulate brain
excitability. Any changes in endogenous or exogenous hormone levels can affect the occurrence of seizures, either directly or via PK
interactions that modify the plasma levels of ASMs (Harden, 2008). The PK interactions between oral contraceptives and ASMs are bidirectional
(Johnston and Crawford, 2014). The efficacy of hormonal contraception may be diminished for women taking CYP-P450 enzyme inducing ASMs.
Epilepsy is not a medical condition in which contraceptives are contraindicated. Contraceptive failure, possibly related to ASMs, may
be responsible for up to 1 in 4 unplanned pregnancies in WWE (~12.5% of all WWE pregnancies), versus a rate of 1% in healthy women.
Unmet
need to treat WWE in CB age
Approximately
30% of patients with epilepsy cannot efficiently control their condition with available ASMs, making consideration of newer pharmacological
treatment development options important, and managing uncontrolled seizures in WWE of CB age is the primary aim during preconception,
pregnancy, and postpartum phases. Therefore, uncompromised ASM efficacy with acceptable variability and less or no drug-drug interactions
achieved with lowest possible monotherapy dose to address fetal toxicity concerns remain highly unmet needs. Moreover, control of seizures
including prevention of breakthrough seizures is critical when planning for pregnancy and also during pregnancy, as it can also lead
to undesired falls or auto-accidents and compromise freedom to drive.
Select
ASMs have the potential to induce contraception failures, reproductive hormone imbalance, anxiety, and depression. There remains an unmet
need for an ASM without the aforementioned downsides, with no to low fetal-neonatal toxicity and without breast-feeding concerns, as
well as the potential to treat associated comorbidities.
While
over 30 molecules have been approved for the treatment of epilepsy in the U.S., no epilepsy drug has been specifically approved for WWE
of CB age. We believe our endogenous NASs as GABAA PAMs, while targeting the goal of seizure control, also have the potential
for additional benefits in psychiatric disorders comorbidities (e.g., anxiety and/or depression) and sleep impairment. Moreover, these
oral endogenous NASs could potentially address some of the fetal toxicity concerns related to unplanned or planned pregnancy in WWE.
(1)
LPCN
2203: Oral Product for Management of Essential Tremor
LPCN
2203 is an oral candidate for management of essential tremor (“ET”) comprising a bioidentical GABAA modulating
NAS. We have successfully completed oral pharmacokinetics with bioidentical GABAA modulating NAS and are planning to submit
a protocol for a proof-of-concept phase 2 study for ET to the FDA.
Disease
Overview - Essential Tremor
Essential
Tremor is one of the most common movement disorders in the United States, affecting an estimated 7 million in the U.S. For ET patients,
uncontrollable shaking of the hands, head, voice, or legs creates difficulty eating, dressing, writing, and pursuing other day-to-day
tasks. The etiology of ET is largely unknown, but reduced GABAA receptor levels and decreased GABAergic activity have been
observed in ET.
While
ET is often associated with aging populations, ET can begin much earlier in life, with a progressive disease course that can eventually
necessitate a care partner. Social anxiety and depressive symptoms can manifest in patients with ET as tremor severity increases and
may negatively impact a patient’s ability to work and engage in hobbies. In an interview study of ET patients and care partners,
the most common impacts on activities of daily living are pouring liquids and writing/typing (100%) and grooming/hygiene, drinking, dressing,
eating, and reading (80-85%). Overall, 90% of participants noted the emotional impact of ET, with 75% reporting tremor-related worry
or anxiety.
The
only FDA approved pharmacological treatment for ET was approved more than 50 years ago, and the majority of patients with ET experience
a sub-optimal response with standard-of-care treatments, highlighting numerous and compelling unmet needs in care such as daytime efficacy
and improved tolerability, a PRN (pro re nata) or “as needed” option, and a superior benefit-to-risk profile. (1) (2)
(1)
Ref: Louis ED, Ottman R. Tremor Other Kyperkinet Mov (NY). 2014;4:259.
(2)
Ref: Gerbasi et.al. Patient experiences in essential tremor: Mapping functional impacts to existing measures using qualitative research.
MDS 2023.
Other
Pipeline Candidates
We
continue to pursue opportunities for partnering and/or development arrangements for the continued development and/or marketing of LPCN
2401, LPCN 1148, and LPCN 1107. We do not currently anticipate conducting any further significant development activities with respect
to these products and product candidates without the participation of a partner. There can be no guarantee that we will be able to identify
or enter into partnering arrangements on terms that are beneficial to us or at all. Even if we do enter into partnering arrangements,
such arrangements may not be sufficient to successfully develop and commercialize these products.
LPCN
2401: Management of Incretin Mimetic Use in Obesity Management
LPCN
2401 is targeted to be a once daily oral formulation comprising a proprietary anabolic androgen receptor agonist. LPCN 2401 is expected
to have a favorable benefit to risk profile as a non-invasive option for use as an adjunct to GLP-1 chronic weight management therapies
for quality weight loss and/or as a monotherapy post cessation of GLP-1 chronic weight management therapies for weight and glycemic status
maintenance with demonstrated benefits to the liver.
LPCN
2401 has potential for use as an adjunct to incretin mimetics (GLP-1/GIP agonists) including amplification of GLP-1 insulinotropic actions
which is supported by studies demonstrating the role of androgen receptor agonist in regulation of GLP-1 through:
●
Enhancement of GLP-1-mediated insulin release from β cells through genomic- and non-genomic mechanisms
●
Increase in GLP-1 Receptor Expression in diabetics and non-diabetics
●
Promoting proliferation of β cells and improving insulin sensitivity
Target
benefits of LPCN 2401 in combination with GLP-1 agonists include inducing quality weight loss by attenuation of functionality and activities
of daily life while lessening lean mass loss, a serious unmet need, especially for elderly and sarcopenic adult GLP-1 agonist users who
are most vulnerable to accelerated lean mass loss and functional decline. In a recent study with 16 weeks of GLP-1 agonist use for weight
management in elderly (60 yr and above) patients, a rapid loss of lean mass was observed with a median percentage of total body weight
loss that is due to lean mass of 32% in 16 weeks. In addition, 43% of GLP-1 users lost ≥10% Stair Climb Power from baseline; the equivalent
of almost eight years of expected age-related stair climb power loss was observed in just 4 months of GLP-1 use.
Moreover,
as an adjunct to incretin mimetics, LPCN 2401 may help maintain or increase weight loss, particularly in diabetics, through increased
expression activity of GLP1R and increased effectiveness of GIP1 therapies secondary to actions at GLP1R (glucose lowering). LPCN 2401
could also be potentially used as monotherapy post discontinuation of GLP-1 agonist to manage weight/fat regain and durability of diabetes
remission.
Data
from preclinical and clinical studies support the potential of LPCN 2401 and LPCN 2401+E in improving body composition. In April 2024,
Lipocine announced results from a multi-center prospective, blinded Phase 2 study, which demonstrated increases in lean mass of 4.4%,
decreases in fat mass of 6.7%, reduction android fat 4.1%, and increased bone mineral content of 2.8% in a population consistent with
GLP-1 use for weight management. LPCN 2401 was well tolerated with minimal GI or androgenic adverse events and no reports of muscle spasms.
Per
FDA Guidance (2025), for efficacy claims related to changes in body composition, trial design should include appropriate choice of population
and selection of endpoints that measure how a patient feels, functions, or survives, to potentially support such a claim. We may initiate
a proof-of-concept study evaluating LPCN 2401 as an adjunct to GLP-1 agonist after we obtain additional regulatory clarity with respect
to development path and acceptable end points for improved body composition in obesity management pending available resources. We may
explore the possibility of partnering LPCN 2401 with a third party, although no partnering agreement has been entered into by us. No
assurance can be given that any license agreement will be completed, or, if an agreement is completed, that such an agreement would be
on terms favorable to us.
Disease
and Market Overview – GLP-1 Agonist Use and Obesity Management
Approximately
74% of U.S. adults aged 20 and older are either obese or overweight, and an estimated 30% of the U.S. adult population has a BMI ≥
30 kg/m2. Elderly and sarcopenic GLP-1 agonist users are the population of GLP-1 users who are most vulnerable to accelerated
lean mass loss and functional decline. Obesity is a chronic, relapsing health risk defined by excess body fat. Excess body fat increases
the risk of death and major comorbidities such as type 2 diabetes, hypertension, dyslipidemia, cardiovascular disease, osteoarthritis
of the knee, sleep apnea, and some cancers1. About 30% of overweight (BMI ≥ 25 kg/m2) adults 2 have
type 2 diabetes, 50%3 have dyslipidemia, and 67%4 have hypertension. In the U.S. alone, ~34M older adults aged 60+
years are obese (BMI at or above 30.0) and ~31M older adults aged 60+ years are overweight (BMI between 25.0 to 30).
It
is estimated that the total GLP-1 users in the U.S. may reach 30 million (around 9% of the overall population) by 20305.
Reportedly, ~24M6 obese elderly are most vulnerable to losing muscle mass. The rapid weight loss observed with the currently
approved chronic weight management GLP-1 receptor agonist medications includes unwanted lean mass loss, up to 40% of the patient’s
total weight lost. Moreover, discontinuation of these therapies frequently results in a rapid regain in weight. Loss of lean mass has
multiple negative health implications including weakness/fatigue, lowered metabolism which can cause a regain in fat mass, declines in
neuromuscular function, potential effects on emotion and psychological states, and increased risk of injury.
Several
recent studies showed that body composition, especially lean body mass (muscle) may play an independent role in survival of patients
with diseases such as cancer and cardiovascular diseases (DH Lee and EL Giovannucci, Exp Biol Med. 2018). Therefore, a focus on body
composition in obesity management to sustainably lose fat mass while maintaining lean mass should be an essential goal.
There
is a significant unmet need for an oral, efficacious, muscle preserving/gaining option for chronic obesity/weight management that ameliorates
the loss of lean mass associated with GLP-1/GIP agonist treatment, resulting in a higher quality weight loss. Moreover, there is a need
for a chronic long-term pharmacotherapy option to maintain weight upon cessation of incretin mimetic therapy, prevent fat/weight rebound
“overshoot” and minimize lag in muscle recovery to prevent collateral fattening as well as improve the durability of any
achieved diabetes remission while on GLP-1.
(1) Ref: Caterson and Hubbard et al. 2004; Calle and Thun et al. 1999
(2) https://news.harvard.edu/gazette/story/2012/03/the-big-setup/
(3) https://www.ncbi.nlm.nih.gov/books/NBK305895/
(6) Ref: Flynn et al. Morgan Stanley, February 27, 2024