On March 1, 2022 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported financial results for the fourth quarter and full year ended December 31, 2021, and provided recent corporate updates (Press release, Bicycle Therapeutics, MAR 1, 2022, View Source [SID1234609228]).

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"We are encouraged by the progress we continue to make across our oncology pipeline," said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. "As we previously reported, BT8009 and BT5528 have demonstrated anti-tumor activity in two tumor types, and we look forward to presenting interim results from our Phase I trial of BT8009 at a medical meeting and initiating the expansion cohorts in our clinical trial of BT5528 this year. We also are moving our Bicycle TICA programs forward, including BT7480, which entered the clinic in the fourth quarter of 2021. Our plans to advance our clinical programs, as well as to expand our discovery efforts and early development pipeline, are on track and are supported by a strong balance sheet, with sufficient cash to fund these initiatives and support operations through 2024."

Fourth Quarter 2021 and Recent Highlights

Announced Continued Progress in Ongoing Phase I/II Clinical Trials of BT8009, BT5528 and BT7480. In January 2022, Bicycle announced progress updates for its wholly owned oncology pipeline, including BTCs BT8009 and BT5528 and Bicycle TICA BT7480. In the ongoing Phase I portion of the Phase I/II clinical trial of BT8009, a second-generation BTC targeting Nectin-4, four out of 11 patients were previously reported to have a partial response under Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, including one out of four (25%) in the 2.5mg/m2 dose and three out of seven (43%) at the 5.0 mg/m2 cohorts. All four patients previously reported as responders have since received at least one subsequent scan, and all have been confirmed as ongoing RECIST 1.1 responses. One patient in the 5.0 mg/m2 cohort, who previously was reported to have a partial response with an 89% tumor reduction, has now received two subsequent scans, which each showed that total tumor volume has been reduced by 100%, constituting a confirmed complete response.

The Phase I/II trial of BT5528, Bicycle’s second-generation BTC targeting EphA2, is also ongoing, with initiation of expansion cohorts planned for this year, with an expected recommended Phase II dose of 6.5mg/m2 every-other-week.

Bicycle also initiated a Phase I clinical trial of BT7480, a novel, fully synthetic Bicycle TICA targeting Nectin-4 and agonizing CD137, in the fourth quarter of 2021, and dose escalation in that trial remains ongoing.
Announced Expansion of and Transition in Management Team. In January 2022, Michael Skynner, Ph.D., previously the company’s Chief Operating Officer (COO), was appointed to the newly created position of Chief Technology Officer, to focus on leading and overseeing the growth of Bicycle’s proprietary phage display discovery platform in oncology, as well as on creating innovative opportunities for the platform outside of oncology. Dr. Skynner joined the company in January 2016 as Vice President, Operations and Discovery and had served as COO since March 2018. Alistair Milnes, who served as the company’s Vice President, Human Resources and Communications since January 2021, has assumed the COO role. Mr. Milnes previously led human resources and communications at multinational energy and mineral companies. Both Dr. Skynner and Mr. Milnes are based in the United Kingdom.
Presented Preclinical BT7480 and BT7455 Data at the SITC (Free SITC Whitepaper) 36th Annual Meeting. In November 2021, Bicycle presented preclinical data for BT7480 and BT7455, an EphA2/CD137 Bicycle TICA. Results supported Bicycle’s decision to initiate a Phase I/II clinical trial of BT7480 and its prioritization of potential indications to target. Additionally, Bicycle has developed a pharmacokinetic/pharmacodynamic (PK/PD) modelling framework intended to predict preclinical biomarker level and tumor growth inhibition in response to changes in the BT7480 dose and dosing schedule. Bicycle found that plasma and tumor drug concentration levels may be associated with tumor growth inhibition.
Financial Results

Cash was $438.7 million as of December 31, 2021, compared to $136.0 million as of December 31, 2020. The net increase in cash is primarily due to financing activities during 2021, including net proceeds of $188.4 million from a public offering of Bicycle’s ADSs, net proceeds of $102.6 million from Bicycle’s at-the-market (ATM) offering program and net proceeds of $15.0 million from Bicycle’s debt facility with Hercules Capital, as well as $45.0 million received from Ionis Pharmaceuticals under the 2021 collaboration and license agreement, and $10.0 million received from Genentech for exercising an option to initiate an additional program under the 2020 collaboration agreement, offset by cash used for operating activities.
Research and development expenses were $13.0 million for the three months ended December 31, 2021 and $44.9 million for the year ended December 31, 2021, compared to $10.1 million for the three months ended December 31, 2020 and $33.1 million for the year ended December 31, 2020. The increase in expense of $2.9 million for the three months ended December 31, 2021 as compared to the same period in the prior year was primarily due to increased Bicycle TICA clinical program spend and other discovery and platform related expenses, as well as increased personnel related expenses, including $0.7 million of incremental non-cash share-based compensation expense. The increase in expense of $11.7 million for the year ended December 31, 2021 as compared to the same period in the prior year was primarily due to increased clinical program expenses for BT8009, Bicycle TICA and other discovery and platform related expenses and increased personnel-related expenses, including $2.4 million of incremental non-cash share-based compensation expense.
General and administrative expenses were $8.8 million for the three months ended December 31, 2021 and $32.4 million for the year ended December 31, 2021, compared to $10.9 million for the three months ended December 31, 2020 and $29.2 million for the year ended December 31, 2020. The decrease of $2.1 million for the three months ended December 31, 2021 as compared to the same period in the prior year was primarily due to the settlement and license agreement with Pepscan Systems B.V. ("Pepscan") entered into in November 2020, offset by increased costs to support operations as a public company and increased personnel-related costs, including $0.7 million of incremental non-cash share-based compensation expense. The increase of $3.2 million for the year ended December 31, 2021 as compared to the same period in the prior year was primarily due to increased personnel-related costs, including $3.2 million of incremental non-cash share-based compensation expense and increased costs to support operations as a public company, offset by a decrease in professional and consulting costs, and the settlement and license agreement with Pepscan entered into in November 2020.
Net loss was $18.0 million, or $(0.63) basic and diluted net loss per share, for the three months ended December 31, 2021, and net loss was $66.8 million, or $(2.67) basic and diluted net loss per share, for the year ended December 31, 2021, compared to net loss of $17.4 million, or $(0.83) basic and diluted net loss per share, for three months ended December 31, 2020, and net loss of $51.0 million, or $(2.66) basic and diluted net loss per share, for the year ended December 31, 2020.

On March 1, 2022 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:​HCM; HKEX:​13) reported that it has received approval to market fruquintinib (ELUNATE in China), a selective and potent oral inhibitor of vascular endothelial growth factor receptors ("VEGFR") 1, 2 and 3, in the Macau Special Administrative Region (Press release, Hutchison China MediTech, MAR 1, 2022, View Source [SID1234609227]).

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The approval follows the latest update to the provisions on new drug importation which allows drugs that have been approved in one or more specified jurisdictions to be authorized for use in Macau. Prior to the update, regulations required approval from at least two other jurisdictions. Fruquintinib was approved in Mainland China by the National Medical Products Administration ("NMPA") in September 2018 for the treatment of metastatic colorectal cancer ("CRC"). ELUNATE will become the first homegrown innovative oncology drug to be marketed in Macau based on its approval by the NMPA.

Dr. Karen Atkin, Chief Operating Officer of HUTCHMED, said, "With the rapid pace of innovation in China’s biotech sector in recent years, more homegrown innovative drugs are being developed and launched in China. We are encouraged by the Macau government’s policy for registration of novel therapies, such as ELUNATE, based on China clinical trial data. We now look forward to patients in Macau having full access to ELUNATE in the coming months."

About Fruquintinib

Fruquintinib is a highly selective and potent oral inhibitor of VEGFR-1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity to minimize off-target toxicities, improve tolerability and provide more consistent target coverage. The generally favorable tolerability in patients treated to date, along with fruquintinib’s low potential for drug-drug interactions based on preclinical assessment, suggests that it may also be highly suitable for combinations with other anti-cancer therapies.

About Fruquintinib Approval in China

Metastatic CRC in China: Fruquintinib was approved for marketing by the China NMPA in September 2018 and commercially launched in China in late November 2018 under the brand name ELUNATE. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. ELUNATE is indicated for the treatment of patients with metastatic CRC who have been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-EGFR therapy (RAS wild type). Results of the FRESCO study1, a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, were published in The Journal of the American Medical Association, JAMA, in June 2018 (clinicaltrials.gov identifier: NCT02314819).

About Fruquintinib Development

The safety and efficacy of fruquintinib for the following investigational uses have not been established and there is no guarantee that it will receive health authority approval or become commercially available in any country for the uses being investigated:

Metastatic CRC in the U.S., Europe, and Japan: The U.S. Food and Drug Administration ("FDA") granted Fast Track Designation for the development of fruquintinib for the treatment of patients with metastatic CRC in June 2020. A Phase III registration study of fruquintinib for the treatment of patients with metastatic CRC, FRESCO-2, is currently underway in the U.S., Europe, Japan and Australia. Additional details of the study may be found at clinicaltrials.gov, using identifier NCT04322539. The U.S. FDA has acknowledged that the totality of the fruquintinib clinical data, including the FRESCO-2 study (if positive), the prior positive Phase III FRESCO study demonstrating improvement in overall survival that led to fruquintinib approval for metastatic CRC in China in 2018, and additional completed and ongoing supporting studies in metastatic CRC, could potentially support a New Drug Application (NDA) for the treatment of patients with advanced metastatic CRC (third-line and above). The FRESCO-2 study design was also reviewed and endorsed by The European Medicines Agency (EMA) and Japanese Pharmaceuticals and Medical Devices Agency (PMDA).

Gastric Cancer ("GC") in China: In October 2017, HUTCHMED initiated the FRUTIGA study, a randomized, double-blind, Phase III trial evaluating the efficacy and safety of fruquintinib combined with paclitaxel for second-line treatment of advanced gastric or esophagogastric junction ("GEJ") adenocarcinoma. The trial is designed to enroll patients who did not respond to first-line standard chemotherapy. Subjects receive either fruquintinib combined with paclitaxel or placebo combined with paclitaxel. Patients are randomized at a 1:1 ratio and stratified according to factors such as stomach vs. GEJ tumor type and performance status. The primary efficacy endpoint is overall survival (OS). Secondary efficacy endpoints include progression-free survival (as defined by RECIST 1.1), objective response rate, disease control rate, duration of response, and quality-of-life score (EORTC QLQ-C30, version 3.0). Biomarkers related to the antitumor activity of fruquintinib will also be explored (clinicaltrials.gov identifier: NCT03223376). In June 2020, HUTCHMED completed a planned interim data review. Based on the preset criteria, the Independent Data Monitoring Committee (IDMC) recommended that the trial continue.

Immunotherapy combinations: HUTCHMED has entered into collaboration agreements to evaluate the safety, tolerability and efficacy of fruquintinib in combination with PD-1 monoclonal antibodies, including with tislelizumab (BGB-A317, developed by BeiGene, Ltd) and sintilimab (IBI308, developed by Innovent Biologics, Inc. and marketed as TYVYT in China).

●Metastatic breast and endometrial cancers in the U.S.: HUTCHMED initiated this open-label, multi-center, non-randomized, Phase Ib/II study in the U.S. to assess the safety and efficacy of fruquintinib in combination with tislelizumab in patients with advanced, refractory triple negative breast cancer ("TNBC") and endometrial cancer ("EMC"). This study is being conducted to investigate if the addition of fruquintinib can potentially induce activity to immune checkpoint inhibitor therapy in TNBC and EMC. Additional details of the study may be found at clinicaltrials.gov, using identifier NCT04577963. Safety and preliminary efficacy of fruquintinib were demonstrated in advanced solid tumors, including TNBC, in a Phase I study conducted in China (NCT01645215) and a Phase I/Ib study is ongoing in the United States (NCT03251378).

●Gastric, colorectal and non-small cell lung cancers in China & Korea: BeiGene, Ltd. initiated this open-label, multi-center, Phase II study to assess the safety and efficacy of fruquintinib in combination with tislelizumab in patients with advanced or metastatic, unresectable GC, CRC or non-small cell lung cancer ("NSCLC"). Additional details of the study may be found at clinicaltrials.gov, using identifier NCT04716634.

●Solid tumors in China: HUTCHMED initiated this open-label, multi-center, non-randomized, Phase II study to assess the safety and efficacy of fruquintinib in combination with sintilimab in patients with advanced EMC, cervical cancer, CRC, GC, hepatocellular carcinoma (HCC), NSCLC or renal cell carcinoma (RCC). Additional details of the study may be found at clinicaltrials.gov, using identifier NCT03903705. Preliminary results of certain cohorts were presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO) (Free ASCO Whitepaper) and the Chinese Society of Clinical Oncology Annual Meeting (CSCO).

On March 1, 2022 Candel Therapeutics, Inc. (Nasdaq: CADL) (the "Company" or "Candel"), a late clinical stage biopharmaceutical company developing novel oncolytic viral immunotherapies, reported that it has entered into a loan and security agreement with Silicon Valley Bank for $25 million, $20 million of which will be available immediately (Press release, Candel Therapeutics, MAR 1, 2022, View Source [SID1234609226]). An additional $5 million may be made available in the future if certain conditions and milestones are met. The loan agreement requires monthly payments of interest only for 24 months, after which the principal is repayable in 24 monthly payments. This financing extends the Company’s cash runway into the fourth quarter of 2023.

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"This access to additional capital positions us well ahead of important anticipated catalysts for the Company, including initial clinical data from the phase 2 clinical trial of CAN-2409 in non-small cell lung cancer, data from our phase 1 clinical trial of CAN-2409 in combination with Opdivo for the first-line treatment of high-grade glioma, data from our phase 1 clinical trial of CAN-3110 in recurrent high-grade glioma, and initiation of our phase 3 clinical trial of CAN-2409 in high-grade glioma," said Paul Peter Tak, MD, PhD, FMedSci, Chief Executive Officer of Candel. "We are especially pleased with the attractive terms and non-dilutive nature of this financing, which bolsters our cash position and provides additional operational flexibility."

On March 1, 2022 Intra-Cellular Therapies, Inc. (Nasdaq: ITCI), a biopharmaceutical company focused on the development and commercialization of therapeutics for central nervous system (CNS) disorders, reported its financial results for the fourth quarter and year ended December 31, 2021 and provided a corporate update (Press release, Intra-Cellular Therapies, MAR 1, 2022, View Source [SID1234609224]).

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"2021 was an extremely productive year for ITCI, culminating in the approval of CAPLYTA for the treatment of bipolar depression. This momentum has continued in 2022 with CAPLYTA’s robust prescription growth and I am very proud of our team’s efforts," said Dr. Sharon Mates, Chairman and CEO of Intra-Cellular Therapies. "We remain focused on maximizing CAPLYTA’s potential with continued progress in our late-stage programs in MDD and additional mood disorders to help more patients with major neuropsychiatric conditions. In addition, we continue to advance our other pipeline programs."

YE 2021 Financial Highlights:

Total revenues were $83.8 million for the full year 2021, compared to $22.8 million in total revenues for the full year 2020, representing an increase of 267%. Net product revenues of CAPLYTA were $81.7 million for the full year 2021, compared to $22.5 million in net product revenues of CAPLYTA for the full year 2020, representing an increase of 263%.

Net loss for the year ended December 31, 2021 was $284.1 million or $3.50 per share (basic and diluted) compared to a net loss of $227.0 million or $3.23 per share (basic and diluted) for the year ended December 31, 2020.

Cost of product sales was approximately $8.0 million for the year ended December 31, 2021, compared to $1.9 million for the year ended December 31, 2020.

Research and development (R&D) expenses for the year ended December 31, 2021 were $88.8 million, compared to $65.8 million for the year ended December 31, 2020. This increase is due to higher lumateperone clinical and non-clinical trial costs and an increase in share based compensation costs.

Selling, general and administrative (SG&A) expenses were $272.6 million for the year ended December 31, 2020, compared to $186.4 million for the year ended December 31, 2020. This increase is primarily due to an increase in marketing costs in addition to labor related and share-based compensation costs.

Cash, cash equivalents and investment securities totaled $412.3 million at December 31, 2021, compared to $657.4 million at December 31, 2020. Additionally, on January 7, 2022, the Company completed a public offering of common stock in which the Company sold 10,952,381 shares of common stock at an offering price of $42.00 per share for aggregate gross proceeds of $460.0 million. After deducting underwriting discounts, commissions and offering expenses, the net proceeds to the Company were approximately $433.7 million.

Fourth Quarter Financial Highlights:

Net product revenues of CAPLYTA were $25.5 million for the fourth quarter of 2021, compared to $12.4 million in net product revenues of CAPLYTA for the same period in 2020, representing a year-over-year increase of 106%. Net product revenues for the fourth quarter of 2021 increased $3.9 million or 18% from the prior quarter.

Net loss for the fourth quarter of 2021 was $85.7 million compared to a net loss of $60.7 million for the same period in 2020.

Cost of product sales were $2.5 million in the fourth quarter of 2021 compared to $1.1 million for the same period in 2020.

Research and development (R&D) expenses for the fourth quarter of 2021 were $29.5 million, compared to $14.3 million for the fourth quarter of 2020. This increase is due to higher lumateperone clinical and non-clinical trial costs and an increase in share-based compensation costs.

Selling, general and administrative (SG&A) expenses were $79.7 million for the fourth quarter of 2021, compared to $58.3 million for the same period in 2020. This increase is primarily due to an increase in commercialization, marketing and labor related costs.

COMMERCIAL HIGHLIGHTS

CAPLYTA was approved by the FDA for the treatment of bipolar depression in adults in late December 2021. CAPLYTA is the only FDA-approved treatment for depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults as monotherapy and as adjunctive therapy with lithium or valproate. We launched CAPLYTA in bipolar depression immediately following approval.

Robust initial prescription growth following CAPLYTA launch in bipolar depression. Comparing the first seven weeks of 2022 following the launch to the same period in the prior quarter, new prescriptions of CAPLYTA have grown by 48% and total prescriptions by 35%. These encouraging trends have been accompanied by positive physician receptivity to CAPLYTA’s bipolar approval in a broad patient population.

During 2021, our commercial organization delivered consistent quarter over quarter prescription growth with strong execution in a market environment impacted by the ongoing pandemic. Fourth quarter CAPLYTA total prescriptions increased by 15% versus the third quarter of 2021 and increased by 98% versus the same period in 2020.

CAPLYTA maintained broad coverage in the Medicare Part D and Medicaid channels, with greater than 98% of lives covered and expanded coverage in the commercial channel to over 80% of lives covered. Our LytaLink patient support program continues to be very effective in supporting patient access.

CLINICAL HIGHLIGHTS

CAPLYTA 2021 Journal Publications:

Announced the online publication of "Safety and tolerability of lumateperone 42 mg: An open-label antipsychotic switch study in outpatients with stable schizophrenia" (Correll et al., 2021) in the journal, Schizophrenia Research.

Announced the publication of Study 404, a Phase 3 clinical study evaluating lumateperone as monotherapy in patients with bipolar depression. The article titled "Efficacy and Safety of Lumateperone for Major Depressive Episodes Associated with Bipolar I or Bipolar II Disorder: A Phase 3 Randomized Placebo-Controlled Trial," was published in The American Journal of Psychiatry.

Lumateperone:

Adjunctive MDD program: In 2021, we initiated patient enrollment in pivotal studies 501 and 502. These are Phase 3 double blind, placebo-controlled, 6-week global studies evaluating lumateperone 42 mg as adjunctive treatment to anti-depressants. The primary endpoint is change from baseline versus placebo on the MADRS total score at week 6, and the CGI-S scale is the key secondary endpoint.

Mixed Features program: Study 403 is a global clinical trial evaluating lumateperone 42 mg in patients with MDD and in patients with bipolar depression who exhibit mixed features. Clinical conduct is ongoing.

Lumateperone Long Acting Injectable (LLAI) formulation: In 2021, we initiated Study ITI-007-025, a Phase 1 single ascending dose study of LLAI to evaluate the pharmacokinetics, safety and tolerability of our initial formulation of LLAI in patients with stable symptoms of schizophrenia. We have completed initial clinical conduct in this study and are encouraged by the safety and tolerability results we have seen to date. We are now exploring alternate sites of injection with this formulation as well as progressing other formulations. This will assist us in evaluating dosing strategies and formulation for our efficacy studies. The goal of our program is to develop LLAI formulations that are effective, safe and well-tolerated with treatment durations of one month and longer.

Other Programs:

ITI-1284-ODT-SL program: Our ITI-1284-ODT-SL program focused on the treatment of agitation in patients with probable Alzheimer’s disease (AD), dementia-related psychosis and certain depressive disorders in the elderly. We expect to commence clinical conduct in our AD agitation program in 2022. Additional studies in dementia-related psychosis, and certain depressive disorders in the elderly, are also planned for 2022.

Phosphodiesterase type I inhibitor (PDE1) program: Our PDE1 inhibitor program is focused on diseases in which the PDE1 enzyme activity is increased and/or deleterious immune cell changes lead to poor outcomes, including certain cancers. Lenrispodun (ITI-214) is our lead compound in this program.

Initiated our Phase 2 clinical program with lenrispodun for Parkinson’s disease and expect to commence patient enrollment in the first half of 2022.

Presented preclinical data describing the antitumor effects of PDE1 inhibitors when administered in conjunction with checkpoint inhibitor immunotherapy at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. Additional data from this program will be presented at upcoming conferences this year.

ITI-333 program in opioid use disorder: Study ITI-333-001, a Phase 1 single ascending dose study evaluating the safety, tolerability and pharmacokinetics of ITI-333 in healthy volunteers has been completed. In this study, ITI-333 was generally safe and well-tolerated and achieved plasma exposures at or above those required for efficacy.

Conference Call and Webcast Details

The Company will host a live conference call and webcast today at 8:30 AM Eastern Time to discuss the Company’s financial results and provide a corporate update. The live webcast and subsequent replay may be accessed by visiting the Company’s website at www.intracellulartherapies.com. Please connect to the Company’s website at least 5-10 minutes prior to the live webcast to ensure adequate time for any necessary software download. Alternatively, please call 1-(844) 835-6563 (U.S.) or 1-(970) 315-3916 (international) to listen to the live conference call. The conference ID number for the live call is 5899935. Please dial in approximately 10 minutes prior to the call.

CAPLYTA (lumateperone) is indicated in adults for the treatment of schizophrenia and depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate. CAPLYTA is available in 42 mg capsules.

Important Safety Information

Boxed Warning:

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis.

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adults in short-term studies. All anti-depressant-treated patients should be closely monitored for clinical worsening, and for emergence of suicidal thoughts and behaviors. The safety and effectiveness of CAPLYTA have not been established in pediatric patients.

Contraindications: CAPLYTA is contraindicated in patients with known hypersensitivity to lumateperone or any components of CAPLYTA. Reactions have included pruritus, rash (e.g., allergic dermatitis, papular rash, and generalized rash), and urticaria.

Warnings & Precautions: Antipsychotic drugs have been reported to cause:

Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis, including stroke and transient ischemic attack. See Boxed Warning above.

Neuroleptic Malignant Syndrome (NMS), which is a potentially fatal reaction. Signs and symptoms include: high fever, stiff muscles, confusion, changes in breathing, heart rate, and blood pressure, elevated creatinine phosphokinase, myoglobinuria (and/or rhabdomyolysis), and acute renal failure. Patients who experience signs and symptoms of NMS should immediately contact their doctor or go to the emergency room.

Tardive Dyskinesia, a syndrome of uncontrolled body movements in the face, tongue, or other body parts, which may increase with duration of treatment and total cumulative dose. TD may not go away, even if CAPLYTA is discontinued. It can also occur after CAPLYTA is discontinued.

Metabolic Changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with antipsychotics. Measure weight and assess fasting plasma glucose and lipids when initiating CAPLYTA and monitor periodically during long-term treatment.

Leukopenia, Neutropenia, and Agranulocytosis (including fatal cases). Complete blood counts should be performed in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. CAPLYTA should be discontinued if clinically significant decline in WBC occurs in absence of other causative factors.

Decreased Blood Pressure & Dizziness. Patients may feel lightheaded, dizzy or faint when they rise too quickly from a sitting or lying position (orthostatic hypotension). Heart rate and blood pressure should be monitored and patients should be warned with known cardiovascular or cerebrovascular disease. Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension.

Falls. CAPLYTA may cause sleepiness or dizziness and can slow thinking and motor skills, which may lead to falls and, consequently, fractures and other injuries. Patients should be assessed for risk when using CAPLYTA.

Seizures. CAPLYTA should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold.

Potential for Cognitive and Motor Impairment. Patients should use caution when operating machinery or motor vehicles until they know how CAPLYTA affects them.

Body Temperature Dysregulation. CAPLYTA should be used with caution in patients who may experience conditions that may increase core body temperature such as strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics.

Dysphagia. CAPLYTA should be used with caution in patients at risk for aspiration.

Drug Interactions: CAPLYTA should not be used with CYP3A4 inducers and moderate or strong CYP3A4 inhibitors.

Special Populations: Newborn infants exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Breastfeeding is not recommended. Use of CAPLYTA should be avoided in patients with moderate or severe liver problems.

Adverse Reactions: The most common adverse reactions in clinical trials with CAPLYTA vs. placebo were somnolence/sedation, dizziness, nausea, and dry mouth.

Please click here to see full Prescribing Information including Boxed Warning.

About CAPLYTA (lumateperone)

CAPLYTA 42 mg is an oral, once daily atypical antipsychotic approved in adults for the treatment of schizophrenia and depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate. While the mechanism of action of CAPLYTA is unknown, the efficacy of CAPLYTA could be mediated through a combination of antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors.

Lumateperone is being studied for the treatment of major depressive disorder, and other neuropsychiatric and neurological disorders. Lumateperone is not FDA-approved for these disorders.

On February 28, 2022 GENFIT (Nasdaq and Euronext: GNFT), a late- stage biopharmaceutical company dedicated to improving the lives of patients with severe chronic liver diseases, reported its cash position as of December 31, 2021 and revenues for 2021 (Press release, Genfit, MAR 1, 2022, View Source [SID1234609221]).

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Financials

As of December 31, 2021, the Company’s cash and cash equivalents amounted to €258.8 million compared with €171.0 million, as of December 31, 2020. This amount includes:

•A €120 million non-refundable upfront payment from Ipsen received in December 2021, as well as €24 million in VAT collected on that amount
•A €28 million equity investment from Ipsen in December 2021
•A €7.9 million Research Tax Credit 2020 reimbursement received in October 2021
•A €2.25 million subsidized loan from Bpifrance in November 2021 in addition to the State Guaranteed Loans received in June and July 2021

As of June 30, 2021, cash and cash equivalents amounted to €104.4 million.

The solid cash position as of December 31, 2021 takes into account the collaboration and license agreement signed with Ipsen in December 2021 which gives Ipsen exclusive worldwide2 license to develop, manufacture and commercialize GENFIT’s investigational treatment elafibranor for people living with Primary Biliary Cholangitis (PBC), in return for a €120 million upfront payment. In addition to the upfront payment GENFIT is eligible to receive up to €360 million in milestone payments as well as tiered double-digit royalties of up to 20%. To underscore the long-term commitment represented by this partnership, Ipsen also purchased newly issued GENFIT equity representing 8% post-issuance through a €28 million investment in GENFIT, becoming one of the largest shareholders.

1Unaudited financial information under IFRS
2With the exception of China, Hong Kong, Taiwan, and Macau where Terns Pharmaceuticals holds the exclusive license to develop and commercialize elafibranor

1 Pascal Prigent, CEO of GENFIT, commented: "This breakthrough strategic partnership with Ipsen marks the beginning of a new chapter for GENFIT. With a considerably improved financial situation, we’re now in a good position to accelerate our development."

Revenues3

Revenues for 2021 were €80.06 million compared to €0.76 million for 2020. This mainly results from the receipt of the €120 million upfront payment from Ipsen, out of which €80 million is recognized as 2021 revenue, after deduction of €40 million deferred revenue, which will gradually be recognized as revenue following the completion of the ELATIVE double-blind study, in accordance with the IFRS 15 norms.

As a comparison, revenues for 2020 mainly resulted from the licensing agreements with Labcorp to roll out the NIS4 diagnostic technology in NASH and the sale of goods and services provided pursuant to the collaboration and license agreement with Terns Pharmaceuticals.

A note about the COVID-19 pandemic and its potential consequences on our business

During this evolving crisis, our priorities continue to be to ensure the safety and well-being of our employees, of the patients and healthcare professionals involved in our clinical trials, as well as the integrity of our ongoing clinical trials. We remain committed to ensuring business continuity and have been monitoring the situation closely.

We have worked with our contract research organizations (CRO), trial sites and investigators to regularly revise our program execution estimations to take into account the evolution of the pandemic situation and its impact on our activities.

As a result of measures implemented in consultation with our CRO we were able to minimize disruption to our ELATIVE Phase 3 clinical trial of elafibranor in PBC, which enrolled its first patient in September 2020. At the start of the trial, and considering the pandemic situation, we had estimated that enrollment in the ELATIVE study would take approximately 18 months and so far, we have been broadly in-line with this estimate. However, the recent rapid expansion of the highly contagious Omicron strain of COVID has created additional complications for us in enrolling patients and in clinical trial operations generally. The rate of infection, as well as the containment measures put in place to control its growth have led to patients postponing site visits or having to be re-screened because they had fallen outside the screening window. This recent worsening of the COVID pandemic has also created significant additional administrative backlogs at sites and regulatory agencies, due to the combination of continued high volume of trials and staffing shortages. This has disproportionately impacted regions where there were already significant delays, such as Latin America. Although we currently do not anticipate these recent complexities to substantially change the guidance related to availability of the ELATIVE top line results, we are currently assessing with our CRO the extent of impact on enrollment timelines. We will provide an update during our next webcast scheduled for April 7, 2022.

3 Revenues recognized under IFRS 15

2 Upcoming Financial Communications

The Company will release its full-year 2021 financial results on April 7, 2022. The 2021 Universal Registration Document, the 2021 Annual Financial Report (included in the 2021 Universal Registration Document), and the Annual Report on Form 20-F will be published by the end of April 2022.