Lipocine Announces Positive LPCN 2401 Clinical Results Showing Improved Body Composition in Participants with Obesity LPCN 2401 treatment resulted in statistically significant body composition improvement in men Increase

Announces Positive LPCN 2401 Clinical Results Showing Improved Body Composition in Participants with Obesity

LAKE CITY, April 11, 2024 /PRNewswire/ - Lipocine Inc. (NASDAQ: LPCN), a biopharmaceutical company, today announced results from

a Phase 2 clinical trial (NCT04134091) which includes LPCN 2401, an oral proprietary combination of anabolic androgen receptor agonist

and -tocopherol, an antioxidant. The results showed significant improvement in body composition through decreased FM and increased

LM or fat free mass (FFM) in patients with BMI 30 (obese) or BMI 27 with at least one weight-related comorbidity.

are pleased with these results demonstrating that LPCN 2401 improves body composition by gaining lean mass and reducing fat mass,"

said Dr. Mahesh Patel, President and CEO of Lipocine Inc. "As an adjunct therapy to GLP-1/GIP agonists, we believe LPCN 2401 may

improve muscle mass, quality, and functionality while maintaining weight loss and amplifying fat loss. Furthermore LPCN 2401 could help

to attenuate collateral fattening and rebound fat/weight "overshoot" associated with discontinuation of GLP-1/GIP agonists.

We look forward to meeting with the FDA to discuss the further development of LPCN 2401 as an aid to weight management interventions."

multi-center prospective, blinded Phase 2 study included participants with obesity (BMI 30) and participants with BMI 27 with

at least one weight-related comorbidity (e.g. hypertension, type 2 diabetes, dyslipidemia), a population consistent with FDA guidance

for developing products for weight management. Participants were randomized to receive one of three treatments for 36 weeks: A) testosterone

ester monotherapy capsule, B) T ester + -tocopherol capsule (LPCN 2401), or C) matching placebo. Participants underwent Dual-Energy

X-Ray Absorptiometry (DEXA) scans to measure body composition at baseline and Weeks 20 and 36. Safety and tolerability were monitored

throughout the 36 weeks. Analyses of body composition parameters, including prespecified endpoints of whole body LM and whole-body FM,

are reported in the table below.

treatments B and C, 27 participants were randomized and completed the baseline and at least one post-baseline DEXA. At baseline, mean

BMI was 36.0 kg/m2 and mean age was 52.4 yrs. LPCN 2401 intervention resulted in significant FM lost and LM gained compared

to placebo; a significant improvement was noted as early as Week 20. A significant reduction in AF (fat in the area roughly between the

pelvis and ribs) and a significant increase in BMC were observed in treatment B, the LPCN 2401 intervention arm. The intervention was

observed to be weight neutral, with fat lost offset by lean mass gained. An overall improvement in body composition is evidenced by substantial

decrease in the fat mass to lean mass ratio.

Mean Changes in Body Composition with LPCN 2401

% of total mass; ** % of fat mass; BMC = bone mineral content; FM = fat mass; LM = lean mass, CBL = change from baseline

set includes all randomized participants (ITT) who have baseline DEXA data and at least one post-baseline DEXA scan. Data are arithmetic

means, last observation carried forward (LOCF).

2401 resulted in numerically greater fat mass loss than Treatment A (monotherapy). Numerical trends towards improvement in blood pressure

and HbA1c with LPCN 2401 support the benefit of Treatment B relative to both placebo and Treatment A. LPCN 2401 was well-tolerated with

the frequency and severity of observed treatment-emergent AEs comparable to placebo. No GI or muscle spasm adverse events were reported

by participants receiving LPCN 2401.

Jaime Almandoz, MD, Medical Director of the Weight Wellness Program, and an Associate Professor of Internal Medicine at UT Southwestern

Medical Center, added "Treatment with LPCN 2401 resulted in loss of fat mass and significant gains in lean mass in men with obesity.

Although the reductions in total body weight were modest, this is very exciting as many popular interventions for treating obesity lead

to reductions in lean mass, which can result in negative clinical outcomes."

Frank Greenway, MD, Professor, and Medical Director of the Pennington Biomedical Research Center of the LSU System and recipient of the

Distinguished Leader Award from the American Board of Obesity Medicine in 2018 stated, "The medical risk of obesity is associated

with excess fat tissue. Men with obesity distribute their excess fat primarily in the abdominal area which is associated with a greater

risk of cardiovascular disease. Despite this greater medical risk, men are under-represented in trials of medications to treat obesity.

On the strength of these data, LPCN 2401 has the potential to fill an unmet medical need in men by reducing body fat, increasing lean

mass and increasing bone mass to achieve a healthier composition of the body. As expected, this change in body composition is associated

with healthier blood pressure and healthier blood sugar measurements."

approved, incretin mimetics (e.g. semaglutide, Wegovy , tirzepatide, Zepbound ) are widely used in chronic weight management.

However, the rapid weight loss observed with these medications includes a substantial proportion of lean mass loss, ~25-40% of the patient's

total weight lost. Lower LM can lead to higher fat rebound (collateral fattening) post cessation of a weight loss intervention. The Week

36 LPCN 2401 results support its potential for improved body composition in chronic weight management with incretin mimetics.

Chronic Obesity Management and Unmet Need

74% of US adults age 20 and older are either obese or overweight, and an estimated 30% of the US adult population have BMI 30 kg/m2.

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 cancers

(Caterson and Hubbard et al. 2004; Calle and Thun et al. 1999). Reportedly (Flynn et al. Morgan Stanley, February 27, 2024), ~24M obese

elderly are most vulnerable to losing muscle mass.

rapid weight loss observed with the approved weight management medications includes unwanted LM 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 LM 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.

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 FM while maintaining LM should be an essential goal.

is a significant unmet need for an oral, efficacious, muscle preserving/gaining option for chronic obesity/weight management that ameliorates

the loss of LM 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.

2401 is an oral formulation of a proprietary combination of anabolic androgen receptor agonist and -alpha tocopherol, an antioxidant

metabolic modifier. Data from preclinical and clinical studies support the potential of LPCN 2401 in gaining lean mass while losing fat

mass. As adjunct therapy to incretin mimetics, LPCN 2401 has potential to attenuate weight rebound, ameliorate loss of muscle mass, improve

muscle quality and functionality, amplify fat mass loss with improved body composition, and potential to maintain weight, prevent "fat

overshoot," and accelerate muscle rebound post incretin mimetic discontinuation.

management will host a conference call and webcast with slides beginning at 8:30 a.m. Eastern Time today to discuss the Phase 2 clinical

study results and answer questions. To participate via telephone, please dial 1-877-451-6152 or 1-201-389-0879 (ex-U.S. toll dial-in

number) using the conference ID 13745946.

can also click the Call me link, https://viavid.webcasts.com/starthere.jsp?ei=1666049&tp_key=c017f4b96c

for instant telephone access to the event. The Call me link will be made active 15 minutes prior to scheduled start

webcast is available to view here and also at www.lipocine.com. It will be available for replay for 180 days.

is a biopharmaceutical company leveraging its proprietary technology platform to augment therapeutics through effective oral delivery

to develop differentiated products for CNS disorders. Lipocine has drug candidates in development as well as drug candidates for which

we are exploring partnerships. Our drug candidates represent enablement of differentiated, patient friendly oral delivery options for

favorable benefit to risk profile which target large addressable markets with significant unmet medical needs.

clinical development candidates include: LPCN 1154, oral brexanolone, for the potential treatment of postpartum depression, LPCN 2101

for the potential treatment of epilepsy, LPCN 2203 an oral candidate targeted for the management of essential tremor, LPCN 2401 an oral

proprietary combination of anabolic androgen receptor agonist and -tocopherol, an antioxidant, as an adjunct therapy to incretin

mimetics, as an aid for improved body composition in chronic weight management and LPCN 1148, a novel androgen receptor agonist prodrug

for oral administration targeted for the management of symptoms associated with liver cirrhosis including prevention of the recurrence

of overt hepatic encephalopathy. Lipocine is exploring partnering opportunities for LPCN 1107, our candidate for prevention of preterm

birth, LPCN 1154, for rapid relief of postpartum depression, LPCN 1148, for the management of decompensated cirrhosis, and LPCN 1144,

our candidate for treatment of non-cirrhotic NASH. TLANDO, a novel oral prodrug of testosterone containing testosterone undecanoate developed

by Lipocine, is approved by the FDA for conditions associated with a deficiency of endogenous testosterone, also known as hypogonadism,

in adult males. For more information, please visit www.lipocine.com.

release contains "forward-looking statements" that are made pursuant to the safe harbor provisions of the Private Securities

Litigation Reform Act of 1995 and include statements that are not historical facts regarding the development and commercialization of

LPCN 2401 and the potential uses and benefits of LPCN 2401 for the improvement of body composition in obesity management. This release

also contains statements regarding the potential uses and benefits of our other product candidates. Investors are cautioned that all

such forward-looking statements involve risks and uncertainties, including, without limitation, the risks that we may not be successful

in developing product candidates to treat obesity disorders, we may not have sufficient capital to complete the development processes

for our product candidates, we may not be able to enter into partnerships or other strategic relationships to monetize our non-core assets,

the FDA will not approve any of our products, risks related to our products, expected product benefits not being realized, clinical and

regulatory expectations and plans not being realized, new regulatory developments and requirements, risks related to the FDA approval