Arthropathy, Progressive Pseudorheumatoid, of Childhood

SALT LAKE CITY, March 7, 2024 /PRNewswire/ -- Lipocine Inc. (NASDAQ: LPCN), a biopharmaceutical company focused on treating Central Nervous System ("CNS") disorders, today announced financial results for the year ended December 31, 2023 and provided a corporate update. Neuroactive Steroids Lipocine announced positive topline results from a pharmacokinetics ("PK") pilot bridge study of LPCN 1154 (oral brexanolone). Lipocine is developing LPCN 1154 for postpartum depression ("PPD") The bridge study results demonstrated comparative pharmacokinetics of LPCN 1154 to an approved IV infusion brexanolone The study identified a dosing regimen of LPCN 1154 to be tested in a single confirmatory pivotal PK study required for NDA filing LPCN 1154 treatment was well-tolerated with no hypoxia or sedation-related adverse events The Company completed a successful meeting with the U.S. Food and Drug Administration ("FDA") during which it confirmed with the FDA its proposal for a 505(b)(2) NDA filing based on a single pivotal study comparing exposure of LPCN 1154 with the approved IV infusion of brexanolone. The use of exposure parameters and criteria to assess comparable exposure to IV infusion brexanolone was also agreed upon In January 2024, Lipocine completed a single arm PK study (N=8) utilizing the "to be marketed" LPCN 1154 formulation and target dosing regimen. PK exposure results of the scaled-up formulation were consistent with the PK performance of the formulation evaluated in the pilot study. The study results confirm the 48-hour dosing regimen for the planned pivotal PK study The company anticipates beginning the LPCN 1154 pivotal study in Q1 '24. Top line results from the study are expected by the end of Q2 '24. Assuming the study meets expectations, the company plans to file an NDA at the end of Q4 '24 Lipocine has identified a lead neuroactive steroid candidate for the management of essential tremor and is planning to submit a protocol for a proof-of-concept phase 2 study for Essential Tremor ("ET") in the first half of 2024 LPCN 1148 Lipocine announced positive topline results from its Phase 2 proof-of-concept ("POC") study evaluating LPCN 1148 for the management of decompensated cirrhosis The study met the primary endpoint: treatment with LPCN 1148 increased L3 skeletal muscle index (L3-SMI) relative to placebo (P <0.01) Fewer hepatic encephalopathy (HE) events of grade >1 were observed in the LPCN 1148 treatment arm relative to placebo (P < 0.05) More patients on LPCN 1148 reported symptom improvement compared to those on placebo (P < 0.05) LPCN 1148 was well-tolerated, with AE rates and severities similar to placebo Posters on LPCN 1148 and LPCN 1144 were presented at the European Association for the Study of the Liver (EASL) Congress 2023, in Vienna, Austria, June 21 – 24, 2023 Updated results from the Phase 2 POC study were presented at The American Association for the Study of Liver Diseases (AASLD) – The Liver Meeting® 2023, in Boston, MA, November 2023 After week 24, all patients in the study entered into a single arm open-label extension ("OLE") stage and received LPCN 1148. Patients converting from placebo to LPCN 1148 in this OLE showed improvement in sarcopenia End of study results from the POC study are expected by the end of Q2 '24 TLANDO™ In January 2024, Lipocine and Verity Pharma entered into an exclusive License Agreement under which Verity Pharma will market TLANDO in the United States and, if approved, in Canada Verity Pharma is responsible for regulatory and marketing obligations in the U.S. and Canada, and for all further development of TLANDO and TLANDO XR Verity Pharma agreed to pay Lipocine a license fee totaling $11 million. Upon execution of the agreement and upon transition of the commercialization of TLANDO to Verity, Lipocine received initial payments of $2.5 million and $5 million. Further payments of $2.5 million and $1 million are due from Verity Pharma no later than January 1, 2025, and January 1, 2026, respectively Lipocine is entitled to receive up to $259 million in development and sales-based commercial milestone payments, as well as tiered royalty payments ranging from 12% up to 18% on net sales of TLANDO franchise products Year Ended December 31, 2023 Financial Results Lipocine reported a net loss of $16.4 million, or ($3.14) per diluted share, for the year ended December 31, 2023, compared with a net loss of $10.8 million, or ($2.15) per diluted share, for the year ended December 31, 2022. During 2023 Lipocine recognized a non-cash minimum guaranteed royalties reversal of variable consideration revenue of $2.9 million related to the termination of the Antares License Agreement. The reversal of revenue is due to the fact that, as a result of the termination of the license agreement, the Company will not receive anticipated minimum royalties that were previously recorded for the Antares License Agreement. In 2022, the Company recorded revenue of $500,000 related to a non-refundable cash fee received from Antares. Research and development expenses were $10.2 million and $8.6 million, respectively, for the years ended December 31, 2023 and 2022. The increase in research and development expenses was primarily due to an increase in contract research organization expense related to the LPCN 1154 clinical studies, an increase in TLANDO manufacturing related costs, an increase related to the LPCN 1148 Phase 2 POC study in male patients with cirrhosis, and an increase in personnel expense. These increases were offset by a decrease related to expenses incurred in 2022 for LPCN 1111 scale up costs, LPCN 1107 clinical study costs, and other research and development activities. General and administrative expenses were $4.9 million and $4.1 million, respectively, for the years ended December 31, 2023 and 2022. The increase in general and administrative expenses was primarily due to an increase in business development and strategic advisory services expenses, an increase in legal fees, an increase in personnel related costs, an increase in franchise taxes, an increase in director fees, and an increase in other general and administrative expenses. These increases were offset by a decrease in corporate insurance expense, a decrease related to 2022 expenses for the recruitment of two additional directors, and a decrease in various consulting and professional fees. As of December 31, 2023, Lipocine had $22.0 million of unrestricted cash, cash equivalents and marketable investment securities compared to $32.5 million at December 31, 2022. Subsequent to year end, Lipocine received payments of $2.5 million and $5 million as part of the initial license fee from Verity Pharma in connection with the agreement entered into in January 2024 whereby Verity will take over commercialization of TLANDO, as described above. About Lipocine Lipocine 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 partnering. 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. Lipocine's 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 for the potential treatment of essential tremor and LPCN 1148, a novel androgen receptor agonist prodrug for oral administration targeted for the management of symptoms associated with liver cirrhosis. Lipocine is exploring partnering opportunities for LPCN 1107, our candidate for prevention of preterm birth, LPCN1154, 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 . Forward-Looking Statements This 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 our product development efforts, the application of our proprietary platform in developing new treatments for CNS disorders, our lead neuroactive steroid candidate for the management of essential tremor, the timing of studies and clinical trials, our product candidates and related clinical trials, our development of and filing of a NDA with the FDA for LPCN 1154, the receipt of license fees, milestone payments and royalty payments under our license agreement with Verity Pharma, and the potential uses and benefits of our 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 CNS 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 process including the receipt of regulatory approvals and our ability to utilize a streamlined approval pathway for LPCN 1154, the results and timing of clinical trials, patient acceptance of Lipocine's products, the manufacturing and commercialization of Lipocine's products, and other risks detailed in Lipocine's filings with the SEC, including, without limitation, its Form 10-K and other reports on Forms 8-K and 10-Q, all of which can be obtained on the SEC website at . Lipocine assumes no obligation to update or revise publicly any forward-looking statements contained in this release, except as required by law. SOURCE Lipocine Inc.

Phase 2b clinical trial of GH001 in patients with treatment-resistant depression on track for expected completion of double-blind phase in Q3 2024Phase 2a clinical trial of GH001 in postpartum depression on track for expected completion in Q3 2024Successfully completed Phase 1, dose-ranging clinical pharmacology trial of intravenous GH002 in healthy volunteersAdditional patents granted in EuropeCash, cash equivalents, other financial assets and marketable securities of $222.7 million expected to provide cash runway into 2026 DUBLIN, Ireland, Feb. 29, 2024 (GLOBE NEWSWIRE) -- GH Research PLC (Nasdaq: GHRS), a clinical-stage biopharmaceutical company dedicated to transforming the treatment of psychiatric and neurological disorders, today reported financial results for the year ended December 31, 2023, and provided updates on its business. Business Updates GH001 in Patients with TRD GH001, our proprietary inhalable mebufotenin (5-MeO-DMT) product candidate, is currently being investigated in a multi-center, randomized, double-blind, placebo-controlled Phase 2b trial in approximately 80 patients with treatment-resistant depression (TRD) (GH001-TRD-201). We have now initiated approximately 20 sites across seven European countries, and continue to see strong recruitment, supporting the expected completion of the double-blind phase of this trial in the third quarter of 2024, with top-line data expected to be available in the third or the fourth quarter of 2024. In this trial, GH001 is administered using an externally-sourced inhalation device. Consistent with previously completed trials, GH001 is administered on a single initial dosing day, without additional mandated visits for psychotherapy or psychological support before or after dosing. GH001 in Patients with PPD and BDII GH001 is also currently being investigated in proof-of-concept clinical trials in patients with postpartum depression (PPD) (GH001-PPD-203) and in patients with bipolar II disorder with a current depressive episode (BDII) (GH001-BD-202). As announced in November 2023, both trials were recruiting slower than anticipated, in part due to the closure, for business reasons, of one of the two sites activated in each trial. Subsequently, we have implemented measures to strengthen recruitment of both trials, including the addition of further clinical trial sites. For the trial in patients with PPD (GH001-PPD-203), we now expect completion and availability of top-line data in the third quarter of 2024. For the trial in patients with BDII (GH001-BD-202), we need to further assess the impact of these measures on recruitment before we can provide an updated timeline. GH002 Our Phase 1, dose-ranging clinical pharmacology trial of GH002 (GH002-HV-105), our proprietary intravenous mebufotenin (5-MeO-DMT) product candidate, in healthy volunteers has been successfully completed in the fourth quarter of 2023. Top-line results demonstrate that GH002 was well-tolerated and produced potent and ultra-rapid psychoactive effects. This trial enrolled 64 healthy volunteers into a double-blind, placebo-controlled part where 56 subjects received single doses of GH002 or placebo in seven dose groups, and an open-label part where 8 subjects received an individualized dosing regimen (IDR) of up to three escalating doses of GH002 on a single day with a scheduled 1-hour interval between doses. The follow-up period was 7 days. GH002 was administered without additional mandated visits for psychological support before or after dosing. In this trial GH002 was found to be well-tolerated with no severe or serious adverse events. GH002 demonstrated potent pharmacodynamic (PD) effects, as assessed by psychoactive effect intensity, with an ultra-rapid onset and a short duration of the psychoactive experience. The pharmacokinetic (PK) profile of GH002 correlated with the ultra-rapid profile of the psychoactive effects. Further trial results are described in our corporate presentation, which is available in the investor section on our website. The analyses of the PK/PD relationship and various other secondary endpoints are ongoing and will inform the further clinical development strategy for GH002. Intellectual Property Updates As announced in January 2024, the European Patent Office (EPO) has granted patent EP3927337 to GH Research with claims directed to mebufotenin (5-MeO-DMT) or a pharmaceutically acceptable salt thereof for use in treating patients diagnosed with major depressive disorder (MDD) and treatment-resistant forms of MDD, such as TRD. This patent is now effective, with an expiry date of no earlier than 2040, and is expected to cover all mebufotenin and mebufotenin salt products marketed to treat MDD and TRD, including but not limited to products administered through pulmonary inhalation, intravenous and intranasal routes. More recently, the European Patent Office has granted two more patents to GH Research. Newly granted patent EP4313945 is directed to crystalline hydrobromide salt of mebufotenin, and will have an effective date of March 13, 2024, and an expiry date of no earlier than 2043. Newly granted patent EP3986864 is directed to a specific method of purifying mebufotenin, and will have an effective date of March 13, 2024, and an expiry date of no earlier than 2040. Update on IND for GH001 As previously announced, our Investigational New Drug Application (IND) for GH001 administered using our proprietary aerosol delivery device has been placed on clinical hold by the U.S. Food and Drug Administration (FDA), with the FDA requesting that we provide (i) an inhalation toxicology study in a non-rodent species and an additional inhalation toxicology study in rats, (ii) additional device design verification information and (iii) updates to our investigator brochure, to resolve the hold. We are working to respond to the FDA’s requests and we have initiated the requested nonclinical studies and are preparing the requested device design verification information. In addition, we have recently requested a meeting with the FDA to discuss certain aspects of the FDA’s feedback. We intend to provide an update regarding the IND response submission and the planned Phase 1 healthy volunteer clinical pharmacology trial (GH001-HV-106) in the second quarter of 2024. In parallel, to mitigate a potential delay to the GH001 program, we are also progressing preparations to potentially conduct the Phase 1 healthy volunteer clinical pharmacology trial (GH001-HV-106) in Europe. Full Year 2023 Financial Highlights Cash position Cash, cash equivalents, other financial assets and marketable securities were $222.7 million as of December 31, 2023, compared to cash, cash equivalents and marketable securities of $251.7 million as of December 31, 2022. Other financial assets are comprised of money market funds, and marketable securities are comprised of investment grade bonds. We believe that our existing cash, cash equivalents, other financial assets and marketable securities will be sufficient for us to fund our operating expenses and capital expenditure requirements into 2026. Research and development expenses R&D expenses were $29.8 million for the year ended December 31, 2023, compared to $20.5 million for the full year 2022. The increase was primarily due to an increase in clinical trial expenses, increased expenses relating to our technical development, and increased employee expenses to support these activities. These increases have been partly offset by a decrease in nonclinical and regulatory expenses. General and administrative expenses G&A expenses were $11.4 million for the year ended December 31, 2023, compared to $10.1 million for the full year 2022. The increase was primarily due to higher professional fees, communications and IT costs and facility expenses, as well as increased employee expenses. These were partly offset by a decrease in insurance costs. Net loss Net loss was $35.6 million, or $0.68 loss per share, for the year ended December 31, 2023, compared to $22.5 million, or $0.43 loss per share, for the full year 2022. About GH Research PLC GH Research PLC is a clinical-stage biopharmaceutical company dedicated to transforming the treatment of psychiatric and neurological disorders. GH Research PLC's initial focus is on developing its novel and proprietary mebufotenin (5-MeO-DMT) therapies for the treatment of patients with treatment-resistant depression (TRD). About GH001 Our lead product candidate, GH001, is formulated for mebufotenin (5-MeO-DMT) administration via a proprietary inhalation approach. With GH001, we have completed two Phase 1 healthy volunteer clinical trials and a Phase 1/2 clinical trial in patients with TRD. Based on the observed clinical activity, where 87.5% of patients with TRD were brought into an ultra-rapid remission with our GH001 individualized single-day dosing regimen in the Phase 2 part of the trial, we believe that GH001 has potential to change the way TRD is treated today. GH001 is currently in a multi-center, randomized, double-blind, placebo-controlled Phase 2b trial in patients with TRD and in two Phase 2a proof-of-concept trials in patients with bipolar II disorder and a current depressive episode and in patients with postpartum depression. About GH002 and GH003 GH002 is our mebufotenin (5-MeO-DMT) product candidate formulated for administration via a proprietary intravenous approach. We have completed a Phase 1 trial of GH002 in healthy volunteers. GH003 is our mebufotenin (5-MeO-DMT) product candidate formulated for administration via a proprietary intranasal administration approach. GH003 is currently in preclinical development. We anticipate developing GH002 and GH003 within our focus area of psychiatric and neurological disorders. Forward-Looking Statements This press release contains statements that are, or may be deemed to be, forward-looking statements. All statements other than statements of historical fact included in this press release, including statements regarding our future results of operations and financial position, business strategy, product candidates, medical devices required to deliver these product candidates, research pipeline, ongoing and currently planned preclinical studies and clinical trials, regulatory submissions and approvals and their effects on our business strategy, including our plans and expectations for discussions with the FDA and the outcomes and resolution of such discussions related to the clinical hold on the GH001 IND, research and development costs, cash runway, timing and likelihood of success, as well as plans and objectives of management for future operations, are forward-looking statements. Forward-looking statements appear in a number of places in this press release and include, but are not limited to, statements regarding our intent, belief or current expectations. Forward-looking statements are based on our management’s beliefs and assumptions and on information currently available to our management. Such statements are subject to risks and uncertainties, and actual results may differ materially from those expressed or implied in the forward-looking statements due to various factors, including, but not limited to, those described in our filings with the U.S. Securities and Exchange Commission. No assurance can be given that such future results will be achieved. Such forward-looking statements contained in this press release speak only as of the date hereof. We expressly disclaim any obligation or undertaking to update these forward-looking statements contained in this press release to reflect any change in our expectations or any change in events, conditions, or circumstances on which such statements are based unless required to do so by applicable law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Investor Relations:Julie RyanGH Research PLCinvestors@ghres.com GH RESEARCH PLCConsolidated Statement of Comprehensive Income (Unaudited)(in thousands, except share and per share amounts) Year endedDecember 31, 20232022 $’000$’000Operating expenses Research and development(29,821)(20,484)General and administration(11,401)(10,070)Loss from operations(41,222)(30,554) Finance income8,9781,166Finance expense(723)(123)Movement of expected credit loss1(121)Foreign exchange (loss)/gain(2,621)7,176Total other income5,6358,098 Loss before tax(35,587)(22,456)Tax charge/(credit)——Loss for the year(35,587)(22,456) Other comprehensive (expense)/income Items that may be reclassified to profit or loss Fair value movement on marketable securities(95)558Currency translation adjustment2,528(7,132)Total comprehensive loss for the year(33,154)(29,030) Attributable to owners: Loss for the year(35,587)(22,456)Total comprehensive loss for the year(33,154)(29,030) Loss per share Basic and diluted loss per share (in USD)(0.68)(0.43) GH RESEARCH PLCConsolidated Balance Sheet (Unaudited)(in thousands) At December 31, 20232022 $’000$’000ASSETS Current assets Cash and cash equivalents78,420165,955Other financial assets55,615—Marketable securities27,525—Other current assets2,5292,586Total current assets164,089168,541Non-current assets Marketable securities61,14285,724Property, plant and equipment1,06997Total non-current assets62,21185,821Total assets226,300254,362 LIABILITIES AND EQUITY Current liabilities Trade payables3,4901,868Lease liability343—Other current liabilities2,8682,678Total current liabilities6,7014,546Non-current liabilities Lease liability631—Total non-current liabilities631—Total liabilities7,3324,546 Equity attributable to owners Share capital1,3011,301Additional paid-in capital291,463291,448Other reserves4,6512,595Foreign currency translation reserve(10,507)(13,035)Accumulated deficit(67,940)(32,493)Total equity218,968249,816Total liabilities and equity226,300254,362

Pictured: Unhappy woman with her head in her hands in front of her baby's stroller/iStock, AndreyPopov Despite launching with just days left in 2023, Sage Therapeutics’ postpartum depression therapy Zurzuvae (zuranolone) made $1.6 million in sales, the Massachusetts-based biotech reported in Wednesday’ s fourth-quarter and full-year earnings results. CEO Barry Greene in an investor call said that Zurzuvae launched in mid-December 2023, “giving us about 10 days in 2023 where women with [postpartum depression (PPD)] in need of treatment could access” the drug. In that short amount of time, Sage was able to deliver approximately 120 prescriptions of Zurzuvae at the end of the fourth quarter. In the U.S., Sage is looking at a market of around 500,000 women who experience PPD after giving birth each year. “It’s early but I do believe that Zurzuvae is the key to unlock the blockbuster potential of PPD, enabling us to help many women suffering from postpartum depression,” Greene said during the call, adding that the company expects the market to grow even further as the industry and healthcare system increasingly recognize PPD as an urgent and serious medical condition. Greene also reported “encouraging developments across the treatment landscape,” including a specialty distribution network that delivers Zurzuvae to patients’ homes, ongoing conversations that lower PPD stigma as well as patients themselves advocating for Zurzuvae. “We’re early in launch days, and there are aspects of launch we certainly need to optimize, but the initial response and uptake are highly encouraging,” Greene said. Zurzuvae is an orally available neuroactive steroid that works by binding to the GABA-A receptor, modulating its response to the inhibitory neurotransmitter GABA. Sage is developing and commercializing Zurzuvae in partnership with Biogen, with which is splits the revenues. Approved in August 2023, Zurzuvae is the first pill cleared for PPD. At the time, however, Zurzuvae missed out on the FDA’s greenlight for major depressive disorder, which would have given it access to a much larger market. Following that FDA rejection, Sage’s shares tanked and the company reduced its workforce by 40% weeks later. Sage appears to have recouped some of its losses since then, but it has yet to fully recover. During the fourth quarter of 2023, the biotech reported a net product revenue of nearly $1.99 million, down from nearly $2.87 million during the same period the prior year. Sage’s net revenue in the quarter sat just below $78 million, driven heavily by a $75 million license and milestone boost from Biogen. By the end of December 2023, Sage had over $753 million in cash, cash equivalents and marketable securities, down from the nearly $1.3 billion it had in 2022. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.