Malaria, Vivax

Silence also announced positive topline 36-week data from ongoing phase 2 study of zerlasiran in patients with high lipoprotein(a) Company to host conference call and webcast today at 8 a.m. EDT / 12 p.m. GMT LONDON--(BUSINESS WIRE)-- Silence Therapeutics plc, Nasdaq: SLN (“Silence” or “the Company”), an experienced and innovative biotechnology company committed to transforming people’s lives by silencing diseases through precision engineered medicines, today reported its financial results for the full year ended December 31, 2023, and reviewed recent business highlights. “2023 was a year of strong execution across Silence as we advanced our proprietary pipeline in the clinic,” said Craig Tooman, President and CEO of Silence. “That’s clearly bearing fruit today with the positive topline 36-week data we announced from the ongoing phase 2 study of zerlasiran in patients with high Lp(a). We are excited about these data and the potential for zerlasiran to address the needs of up to 1.4 billion worldwide living with high Lp(a). In addition to zerlasiran, we’ve made excellent progress advancing divesiran in PV and remain on-track to report phase 1 data by June. On the partnering side, we were pleased for AstraZeneca to enter the clinic with the first product candidate under our collaboration last month, further highlighting the productivity of our mRNAi GOLD™ platform. We look forward to more clinical data unfolding in the coming year from our proprietary programs and building recognition of Silence as a true platform company.” Recent Business Highlights Zerlasiran for cardiovascular disease In November 2023, reported positive topline data in multiple dose portion of the APOLLO phase 1 study of zerlasiran in patients with high Lp(a). Today announced positive topline 36-week data from the ongoing ALPACAR-360 phase 2 study of zerlasiran in patients with a median baseline Lp(a) of approximately 215 nmol/L. Zerlasiran was administered at 300 mg subcutaneously every 16 or 24 weeks and 450 mg every 24 weeks. Study demonstrated highly significant reductions in Lp(a) compared with placebo to week 36 (primary endpoint) Median percentage reduction in Lp(a) of 90% or greater were observed for both doses at week 36 No new safety concerns were identified during this treatment period The 60-week study is ongoing and secondary endpoints, including change in Lp(a) from baseline to week 48 (end of treatment period), week 60 (end of study) and potential effects on other lipids/lipoproteins, will be evaluated 48-week topline data expected in the second quarter of 2024 Divesiran for hematological diseases Advanced enrollment in the SANRECO phase 1/2 study of divesiran in PV patients. Emerging data from the ongoing phase 1 open label portion of the study continue to look promising On-track to report phase 1 data in the second quarter of 2024 Collaborations In February 2024, achieved a $10 million milestone following the initiation of a phase 1 trial of the first product candidate under AstraZeneca collaboration. In March 2024, Mallinckrodt notified Silence that they will not pursue further development of SLN501 following the completion of the phase 1 clinical trial. This will conclude all activities and commitments under the collaboration agreement. “We ended December 2023 with approximately $68.8 million and significantly increased our cash position in early 2024 to over $200 million,” said Rhonda Hellums, Chief Financial Officer of Silence. “We are excited to have multiple programs advancing in the clinic, supported by a substantial cash position that extends our estimated runway into 2026. We also continue to evaluate partnering opportunities that could provide additional non-dilutive funding and further extend our cash runway. Looking ahead, we remain committed to responsibly investing in initiatives that will advance our pipeline and expand our platform into new targets where there is clear unmet need and opportunity to deliver value to patients.” Financial Highlights for Year End 2023 Cash Position: Cash and cash equivalents of £54.0 million ($68.8 million) as of December 2023, compared with £71.1 million as of December 31, 2022. Collaboration Revenue: Collaboration revenue was £25.4 million for the year ended December 31, 2023, and £17.5 million for the year ended December 31, 2022, and related to research services performed under the collaboration agreements with AstraZeneca, Hansoh and Mallinckrodt. R&D Expenses: Research and development (R&D) expenses were £44.0 million for the year ended December 31, 2023, compared to £35.6 million for the year ended December 31, 2022. The increase is a result of additional clinical studies and an increase in contract manufacturing activities for Silence’s proprietary programs. G&A Expenses: General and administrative (G&A) expenses were £20.6 million for the year ended December 31, 2023, compared to £19.6 million for the year ended December 31, 2022. The increase is primarily due to non-cash stock compensation costs. Net Loss: Net loss was £43.3 million, or 38.9 pence basic and diluted net loss per share for the year ended December 31, 2023, compared to a net loss of £40.5 million, or 41.9 pence basic and diluted net loss per share for the year ended December 31, 2022. Post-Period Financial Highlights In January 2024, received total proceeds of approximately $30 million (includes approximately $20 million from ADS sales under Silence’s Sales Agreement and approximately $10 million in R&D tax credit). In February 2024, announced a private placement of ADSs with gross proceeds of approximately $120 million (£94.5 million). In February 2024, achieved a $10 million clinical milestone under AstraZeneca collaboration. This will be received in April 2024. Total ADSs outstanding were approximately 46,502,272, as of March 1, 2024. Cash and Liquidity Update As of December 31, 2023, we had cash and cash equivalents of £54.0 million ($68.8 million). With the addition of gross proceeds from our private placement in February 2024 of $120 million (approximately £94.4 million) before deducting fees and estimated offering expenses, the $30 million from proceeds from sale of ADSs under our ATM and receipt of our UK R&D tax credit, and the receipt of the AstraZeneca $10 million milestone in the second quarter of 2024, we believe that our cash of over $200 million and anticipated milestones from current collaborations will be sufficient to fund our operating expenses and capital expenditure requirements into 2026. We may also achieve further milestones from our current collaboration partners which will further extend our cash runway. Conference Call & Webcast Details Company management will host a conference call and webcast today, Wednesday, March 13, 2024, at 8 a.m. EDT / 12:00 p.m. GMT. Webcast link: Conference call registration link: The conference call and webcast will also be archived on the Company’s website at . About Silence Therapeutics Silence Therapeutics is developing a new generation of medicines by harnessing the body's natural mechanism of RNA interference, or RNAi, to inhibit the expression of specific target genes thought to play a role in the pathology of diseases with significant unmet need. Silence's proprietary mRNAi GOLD™ platform can be used to create siRNAs (short interfering RNAs) that precisely target and silence disease-associated genes in the liver, which represents a substantial opportunity. Silence's wholly owned product candidates include zerlasiran (SLN360) designed to address the high and prevalent unmet medical need in reducing cardiovascular risk in people born with high levels of lipoprotein(a) and divesiran (SLN124) designed to address hematological diseases. Silence also maintains ongoing research and development collaborations with AstraZeneca and Hansoh Pharma, among others. For more information, please visit . Forward-Looking Statements Certain statements made in this announcement are forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and other securities laws, including with respect to the Company’s cash runway and forecast operating cash flow, the Company’s clinical and commercial prospects, regulatory approvals of the Company’s product candidates, potential partnerships or collaborations or payments under new and existing collaborations, the initiation or completion of the Company’s clinical trials and the anticipated timing or outcomes of data reports from the Company’s clinical trials. These forward-looking statements are not historical facts but rather are based on the Company's current assumptions, beliefs, expectations, estimates and projections about its industry. Words such as “anticipate,” “expect,” “intend,” “plan,” “believe,” “seek,” “estimate,” and similar expressions are intended to identify forward-looking statements. These statements are not guarantees of future performance and are subject to known and unknown risks, uncertainties, and other factors, some of which are beyond the Company's control, are difficult to predict, and could cause actual results to differ materially from those expressed or forecasted in the forward-looking statements, including those risks identified in the Company’s most recent Admission Document and its Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission on the date hereof. The Company cautions security holders and prospective security holders not to place undue reliance on these forward-looking statements, which reflect the view of the Company only as of the date of this announcement. The forward-looking statements made in this announcement relate only to events as of the date on which the statements are made. The Company will not undertake any obligation to release publicly any revisions or updates to these forward-looking statements to reflect events, circumstances, or unanticipated events occurring after the date of this announcement except as required by law or by any appropriate regulatory authority. SILENCE THERAPEUTICS plc CONSOLIDATED INCOME STATEMENTS (in thousands, except for loss per share) 2023 2022 2021 £000s £000s £000s Revenue 25,375 17,501 12,415 Cost of sales (10,318 ) (10,880 ) (7,456 ) Gross profit 15,057 6,621 4,959 Research and development costs (44,025 ) (35,605 ) (30,765 ) General and administrative expenses (20,636 ) (19,609 ) (20,008 ) Operating loss (49,604 ) (48,593 ) (45,814 ) Finance and other expenses (2,152 ) (47 ) (52 ) Finance and other income 1,446 1,272 10 Loss for the year before taxation (50,310 ) (47,368 ) (45,856 ) Taxation 7,043 6,879 6,446 Loss for the year after taxation (43,267 ) (40,489 ) (39,410 ) Loss per ordinary equity share (basic and diluted) (38.9) pence (41.9) pence (44.3) pence SILENCE THERAPEUTICS plc CONSOLIDATED BALANCE SHEETS (in thousands) December 31, 2023 2022 £000s £000s Non-current assets Property, plant and equipment 1,813 2,201 Goodwill 7,840 8,009 Other intangible assets 284 320 Other long term assets 2,580 Financial assets at amortized cost 284 284 12,801 10,814 Current assets Cash and cash equivalents 54,031 54,816 Financial assets at amortized cost - 16,328 R&D tax credit receivable 17,627 14,882 Other current assets 9,135 9,745 Trade receivables 228 915 81,021 96,686 Non-current liabilities Contract liabilities (58,910 ) (63,485 ) Lease liability (93 ) - (59,003 ) (63,485 ) Current liabilities Contract liabilities (5,161 ) (8,864 ) Trade and other payables (12,429 ) (12,633 ) Lease liability (179 ) (446 ) (17,769 ) (21,943 ) Net assets 17,050 22,072 Capital and reserves attributable to the owners of the parent Share capital 5,942 5,390 Capital reserves 313,769 277,860 Translation reserve 1,951 2,085 Accumulated losses (304,612 ) (263,263 ) Total shareholders equity 17,050 22,072

BURLINGTON, Mass.--( BUSINESS WIRE )-- PharmaEssentia USA Corporation , a subsidiary of PharmaEssentia Corporation (TWSE: 6446), a global biopharmaceutical innovator based in Taiwan leveraging deep expertise and proven scientific principles to deliver new biologics in hematology and oncology, today announced that the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines ® ) have recently been updated to include ropeginterferon alfa-2b-njft, marketed as BESREMi ® , as a preferred first-line cytoreductive therapy option for the treatment of adults with symptomatic, low-risk polycythemia vera (PV). Ropeginterferon alfa-2b-njft is the only preferred therapeutic option for both high-risk and low-risk (symptomatic) PV regardless of treatment history. 1 “ The recent update to the NCCN Guidelines ® reflects the ongoing shift in PV care towards earlier intervention, focusing on long-term patient health,” said Rami Komrokji, M.D., Vice Chair of the Malignant Hematology Department and Head of the Leukemia and MDS Section at Moffitt Cancer Center. National Comprehensive Cancer Network ® (NCCN ® ) is a well-recognized, not-for-profit alliance of leading cancer centers in the United States. Its treatment practice guidelines, which are reviewed and updated on a continual basis to reflect the most current evidence, are widely respected and followed by the U.S. physician community and serve to inform and facilitate coverage decisions with payers for oncology therapies. Based on its growing body of supporting clinical evidence and broad label, ropeginterferon alfa-2b-njft is now categorized by the latest NCCN Guidelines ® update as a preferred first-line cytoreductive therapy based on NCCN ® ’s determination of superior efficacy, safety and evidence 1 , as well as a category 2A therapy, which means that there is uniform NCCN ® consensus that the intervention is appropriate 1 . The updated NCCN Guidelines ® were released on December 21, 2023. “ This is another important milestone for BESREMi as a preferred, FDA-approved option for both symptomatic low- and high-risk PV patients,” said Albert Qin, M.D., Ph.D., Chief Medical Officer at PharmaEssentia Corporation. “ We are encouraged by the increasing dialogue across academic and community healthcare practitioners rethinking treatment approaches given the potential of BESREMi for this myeloproliferative neoplasm.” About Polycythemia Vera (PV) Polycythemia vera (PV) is a myeloproliferative neoplasm originating from a disease-initiating stem cell in the bone marrow resulting in a chronic increase of red blood cells, white blood cells, and platelets. PV may result in cardiovascular complications such as thrombosis and embolism, and often transforms to secondary myelofibrosis or leukemia. While the molecular mechanism underlying PV is still subject of intense research, current results point to a set of acquired mutations, the most important being a mutant form of JAK2. 2 About BESREMi ® (ropeginterferon alfa-2b-njft) BESREMi is an innovative monopegylated, long-acting interferon. With its unique pegylation technology, BESREMi has a long duration of activity in the body and is aimed to be administered once every two weeks (or every four weeks with hematological stability for at least one year), allowing flexible dosing that helps meet the individual needs of patients. BESREMi has orphan drug designation for the treatment of polycythemia vera (PV) in adults in the United States. The product was approved by the European Medicines Agency (EMA) in 2019, by the US Food and Drug Administration (FDA) in 2021 and has recently received approval in Taiwan and South Korea. The drug candidate was invented by PharmaEssentia and is manufactured in the company’s Taichung plant, which was cGMP certified by TFDA in 2017 and by EMA in January 2018. PharmaEssentia retains full global intellectual property rights for the product in all indications. BESREMi was approved with a boxed warning for risk of serious disorders including aggravation of neuropsychiatric, autoimmune, ischemic and infectious disorders. Please see full Prescribing Information , including Boxed Warning. Indication BESREMi is indicated for the treatment of adults with polycythemia vera. Important Safety Information WARNING: RISK OF SERIOUS DISORDERS Interferon alfa products may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping therapy. CONTRAINDICATIONS Existence of, or history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt Hypersensitivity to interferons including interferon alfa-2b or any of the inactive ingredients of BESREMi. Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment History or presence of active serious or untreated autoimmune disease Immunosuppressed transplant recipients WARNINGS AND PRECAUTIONS Depression and Suicide: Life-threatening or fatal neuropsychiatric reactions have occurred in patients receiving interferon alfa-2b products, including BESREMi. These reactions may occur in patients with and without previous psychiatric illness. Other central nervous system effects, including suicidal ideation, attempted suicide, aggression, bipolar disorder, mania and confusion have been observed with other interferon alfa products. Closely monitor patients for any symptoms of psychiatric disorders and consider psychiatric consultation and treatment if such symptoms emerge. If psychiatric symptoms worsen, it is recommended to discontinue BESREMi therapy. Endocrine Toxicity: These toxicities may include worsening hypothyroidism and hyperthyroidism. Do not use BESREMi in patients with active serious or untreated endocrine disorders associated with autoimmune disease. Evaluate thyroid function in patients who develop symptoms suggestive of thyroid disease during BESREMi therapy. Discontinue BESREMi in patients who develop endocrine disorders that cannot be adequately managed during treatment with BESREMi. Cardiovascular Toxicity: Toxicities may include cardiomyopathy, myocardial infarction, atrial fibrillation and coronary artery ischemia. Patients with a history of cardiovascular disorders should be closely monitored for cardiovascular toxicity during BESREMi therapy. Avoid use of BESREMi in patients with severe or unstable cardiovascular disease, (e.g., uncontrolled hypertension, congestive heart failure (≥ NYHA class 2), serious cardiac arrhythmia, significant coronary artery stenosis, unstable angina) or recent stroke or myocardial infarction. Decreased Peripheral Blood Counts: These toxicities may include thrombocytopenia (increasing the risk of bleeding), anemia, and leukopenia (increasing the risk of infection). Monitor complete blood counts at baseline, during titration and every 3-6 months during the maintenance phase. Monitor patients for signs and symptoms of infection or bleeding. Hypersensitivity Reactions: Toxicities may include serious, acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis). If such reactions occur, discontinue BESREMi and institute appropriate medical therapy immediately. Transient rashes may not necessitate interruption of treatment. Pancreatitis: Pancreatitis has occurred in 2.2% of patients receiving BESREMi. Symptoms may include nausea, vomiting, upper abdominal pain, bloating, and fever. Patients may experience elevated lipase, amylase, white blood cell count, or altered renal/hepatic function. Interrupt BESREMi treatment in patients with possible pancreatitis and evaluate promptly. Consider discontinuation of BESREMi in patients with confirmed pancreatitis. Colitis: Fatal and serious ulcerative or hemorrhagic/ischemic colitis have occurred in patients receiving interferon alfa products, some cases starting as early as 12 weeks after start of treatment. Symptoms may include abdominal pain, bloody diarrhea, and fever. Discontinue BESREMi in patients who develop these signs or symptoms. Colitis may resolve within 1 to 3 weeks of stopping treatment. Pulmonary Toxicity: Pulmonary toxicity may manifest as dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis. Some events have resulted in respiratory failure or death. Discontinue BESREMi in patients who develop pulmonary infiltrates or pulmonary function impairment. Ophthalmologic Toxicity: These toxicities may include severe eye disorders such as retinopathy, retinal hemorrhage, retinal exudates, retinal detachment and retinal artery or vein occlusion which may result in blindness. During BESREMi therapy, 23% of patients were identified with an eye disorder. Eyes disorders ≥5% included cataract (6%) and dry eye (5%). Advise patients to have eye examinations before and during BESREMi therapy, specifically in those patients with a retinopathy-associated disease such as diabetes mellitus or hypertension. Evaluate eye symptoms promptly. Discontinue BESREMi in patients who develop new or worsening eye disorders. Hyperlipidemia: Elevated triglycerides may result in pancreatitis. Monitor serum triglycerides before BESREMi treatment and intermittently during therapy and manage when elevated. Consider discontinuation of BESREMi in patients with persistently, markedly elevated triglycerides. Hepatotoxicity: These toxicities may include increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and bilirubin. Liver enzyme elevations have also been reported in patients after long-term BESREMi therapy. Monitor liver enzymes and hepatic function at baseline and during BESREMi treatment. Discontinue BESREMi in patients who develop evidence of hepatic decompensation (characterized by jaundice, ascites, hepatic encephalopathy, hepatorenal syndrome or variceal hemorrhage) during treatment. Renal Toxicity: Monitor serum creatinine at baseline and during therapy. Avoid use of BESREMi in patients with eGFR <30 mL/min. Discontinue BESREMi if severe renal impairment develops during treatment. Dental and Periodontal Toxicity: These toxicities may include dental and periodontal disorders, which may lead to loss of teeth. In addition, dry mouth could have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with BESREMi. Patients should have good oral hygiene and regular dental examinations. Dermatologic Toxicity: These toxicities have included skin rash, pruritus, alopecia, erythema, psoriasis, xeroderma, dermatitis acneiform, hyperkeratosis, and hyperhidrosis. Consider discontinuation of BESREMi if clinically significant dermatologic toxicity occurs. Driving and Operating Machinery: BESREMi may impact the ability to drive and use machinery. Patients should not drive or use heavy machinery until they know how BESREMi affects their abilities. Patients who experience dizziness, somnolence or hallucination during BESREMi therapy should avoid driving or using machinery. Embryo-Fetal Toxicity: Based on the mechanism of action, BESREMi can cause fetal harm when administered to a pregnant woman. Pregnancy testing is recommended in females of reproductive potential prior to treatment with BESREMi. Advise females of reproductive potential to use an effective method of contraception during treatment with BESREMi and for at least 8 weeks after the final dose. ADVERSE REACTIONS The most common adverse reactions reported in > 40% of patients in the PEGINVERA study (n=51) were influenza-like illness, arthralgia, fatigue, pruritis, nasopharyngitis, and musculoskeletal pain. In the pooled safety population (n=178), the most common adverse reactions greater than 10%, were liver enzyme elevations (20%), leukopenia (20%), thrombocytopenia (19%), arthralgia (13%), fatigue (12%), myalgia (11%), and influenza-like illness (11%). DRUG INTERACTIONS Patients on BESREMi who are receiving concomitant drugs which are CYP450 substrates with a narrow therapeutic index should be monitored to inform the need for dosage modification for these concomitant drugs. Avoid use with myelosuppressive agents and monitor patients receiving the combination for effects of excessive myelosuppression. Avoid use with narcotics, hypnotics or sedatives and monitor patients receiving the combination for effects of excessive CNS toxicity. USE IN SPECIFIC POPULATIONS Pregnancy: Based on mechanism of action and the role of interferon alfa in pregnancy and fetal development, BESREMi may cause fetal harm and should be assumed to have abortifacient potential when administered to a pregnant woman. There are adverse effects on maternal and fetal outcomes associated with polycythemia vera in pregnancy. Advise pregnant women of the potential risk to a fetus. Lactation: There are no data on the presence of BESREMi in human or animal milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children from BESREMi, advise women not to breastfeed during treatment and for 8 weeks after the final dose. Females of Reproductive Potential: BESREMi may cause embryo-fetal harm when administered to a pregnant woman. Pregnancy testing prior to BESREMi treatment is recommended for females of reproductive potential. Advise female patients of reproductive potential to use effective contraception during treatment with BESREMi and for at least 8 weeks after the final dose. Pediatric Use: Safety and effectiveness in pediatric patients have not been established. Geriatric Use: In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other therapy. About PharmaEssentia PharmaEssentia (TWSE: 6446), headquartered in Taipei, Taiwan, is a global and rapidly growing biopharmaceutical innovator. Leveraging deep expertise and proven scientific principles, PharmaEssentia aims to deliver effective new biologics for challenging diseases in the areas of hematology, oncology, and immunology with one approved product and a diversifying pipeline. Founded in 2003 by a team of Taiwanese-American executives and renowned scientists from U.S. biotechnology and pharmaceutical companies, today PharmaEssentia is expanding its global presence with operations in the U.S., Japan, China, and Korea, along with a world-class biologics production facility in Taichung, Taiwan. For more information about PharmaEssentia USA, visit the website , LinkedIn or Twitter . Forward Looking Statement This press release contains forward looking statements, including statements regarding our pipeline, research and development efforts, and market opportunity for our products. For those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995 and similar legislation and regulations under Taiwanese law. These forward-looking statements are based on management expectations and assumptions as of the date of this press release, and actual results may differ materially from those in these forward-looking statements as a result of various factors. These factors include risks and uncertainties related to the initiation, timing, progress and results of our research and development programs, preclinical studies, clinical trials, regulatory submissions, commercialization plans, customer and prescriber patterns or practices, and reimbursement activities and outcomes. Any forward-looking statements set forth in this press release speak only as of the date of this press release. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. © 2024 PharmaEssentia Corporation. All rights reserved. PharmaEssentia, the PharmaEssentia logo, and BESREMi are trademarks or registered trademarks of PharmaEssentia Corporation. 1 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myeloproliferative Neoplasms V.1.2024. © National Comprehensive Cancer network, Inc. 2023. All rights reserved. Accessed Jan 22, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 2 Cerquozzi S, Tefferi A. Blast transformation and fibrotic progression in polycythemia vera and essential thrombocythemia: a literature review of incidence and risk factors. Blood Cancer J . 2015;5, e366; DOI:10.1038/bcj.2015.95

Worldwide collaboration agreement executed with Takeda Pharmaceuticals, including a $300 million upfront payment for rusfertide in polycythemia vera and other hematological indications Cash runway extended through Q4 2027[1] Two articles published in the New England Journal of Medicine reporting results from the Phase 2b FRONTIER 1 study of JNJ-2113 and the Phase 2 REVIVE study of rusfertide Our Partner, Johnson & Johnson Innovative Medicine (formerly Janssen) initiated an expanded JNJ-2113 clinical development program with four Phase 3 studies in moderate-to-severe psoriasis and one Phase 2b study in moderately-to-severely active ulcerative colitis Protagonist achieved $60 million in milestones in Q4 related to JNJ-2113 NEWARK, CA / ACCESSWIRE / February 27, 2024 / Protagonist Therapeutics, Inc. (Nasdaq:PTGX) ("Protagonist" or "the Company") today reported financial results for the fourth quarter and full year ended December 31, 2023, and provided a corporate update. "The fourth quarter of 2023 was an extremely busy and productive time for Protagonist," said Dinesh V. Patel, Ph.D., the Company's President and CEO. "Our novel hepcidin mimetic rusfertide was well represented at the American Society of Hematology (ASH) Annual Meeting in December, including an oral presentation of the long-term follow-up data from the Phase 2 REVIVE study showing durability of hematocrit control and no new safety signals. We look forward to completing enrollment of the Phase 3 VERIFY study by the end of Q1 2024, and potentially filing an NDA next year after completion of the 52-week study. We are extremely pleased to have joined hands with our new partner Takeda in preparation for the potential commercial launch of rusfertide." Dr. Patel continued: "The JNJ-2113 clinical development program is progressing and expanding in a very impressive way, with four Phase 3 psoriasis studies and a Phase 2b study in ulcerative colitis. We believe that JNJ-2113 has the potential to be a major part of the Inflammation & Immunology franchise. Internally, we continue to expand our discovery efforts and are evaluating novel oral peptides against validated biological pathways with the aim of achieving major differentiation against the current standards of care and addressing significant unmet needs in various disease indications. In drug discovery, we plan to announce an oral peptide IL-17 development candidate by year end, maximizing our presence with first-in-class drug candidates for diseases mediated by the IL-17/IL-23 pathway." Fourth Quarter 2023 Recent Developments and Upcoming Milestones Rusfertide: Subcutaneous Injectable Hepcidin Mimetic for Polycythemia Vera (PV) and Other Blood Disorders On January 31, 2024, Takeda and Protagonist Therapeutics, Inc. announced that they had entered into a worldwide license and collaboration agreement for rusfertide. Under the terms of the agreement, Protagonist will receive an upfront payment of $300 million and is eligible to receive additional worldwide development, regulatory milestone and commercial milestones as well as tiered royalties on ex-U.S. net sales. Protagonist and Takeda will share equally in all operating profits and losses arising from the commercialization of rusfertide in the U.S. ("profit and loss sharing arrangement"). Protagonist remains responsible for research and development through the completion of the Phase VERIFY 3 clinical trial, as well as for U.S. regulatory filings. Takeda has rights for ex-U.S. development and is responsible for leading global commercialization activities. The Company also has the right to opt-out entirely from the profit and loss sharing arrangement in exchange for opt-out payments of up to $400 million and enhanced milestones and worldwide royalties. Five abstracts related to rusfertide were presented at the American Society of Hematology conference in December 2023. These presentations included: Long term follow-up from the REVIVE Phase 2 study which showed durable hematocrit control, decreased phlebotomy use, long-term tolerability, and no new safety signals in patients with PV. Prevalence of thromboembolic events (TEs) and secondary cancers in polycythemia vera based on a retrospective analysis of real-world claims data from a large US electronic health records database of patients not treated with rusfertide. These studies showed that PV patients experience high rates of arterial and venous TEs and increased risk of developing other cancers, particularly after exposure to hydroxyurea. On February 21, 2024, the complete Phase 2 REVIVE trial results, including efficacy and safety, were published in the New England Journal of Medicine . Enrollment in Phase 3 VERIFY trial remains on track for completion by the end of Q1 2024. JNJ-2113 (formerly PN-235): Oral IL-23 Receptor Antagonist Protagonist earned $60.0 million in the fourth quarter of 2023 for milestones achieved in the JNJ-2113 Phase 2b and Phase 3 clinical programs led by the Company's collaboration partner, J&J Innovative Medicines. These milestones comprised of (i) $50 million earned when the third patient was dosed in the ICONIC TOTAL Phase 3 clinical study of JNJ-2113 in patients with moderate-to-severe psoriasis and (ii) $10 million following the dosing of the third patient in ANTHEM-UC, a Phase 2b trial to evaluate the safety and effectiveness of JNJ-2113 compared with placebo in patients with moderately to severely active ulcerative colitis. On February 7, 2024, the JNJ-2113 Phase 2b FRONTIER 1 trial results in adults living with moderate-to-severe plaque psoriasis were published in the New England Journal of Medicine . The pivotal Phase 3 ICONIC clinical development program of JNJ-2113 in adult and adolescent patients with moderate-to-severe plaque psoriasis was initiated with two studies in Q4 2023 - ICONIC-LEAD and ICONIC-TOTAL. Other Phase 3 studies in the development program are expected to begin in Q1 2024, including ICONIC ADVANCE 1 and ICONIC ADVANCE 2, which will evaluate the safety and efficacy of JNJ-2113 compared with both placebo and deucravacitinib. The Phase 2b multicenter, randomized, placebo- controlled, dose-ranging study of JNJ-2113 for the treatment of moderately to severely active ulcerative colitis continues to enroll, with an estimated completion date of Q2 2025. Discovery Programs Protagonist announced an oral IL-17 discovery program in January 2024 with a development candidate expected later in 2024, and the company is pursuing the discovery of novel oral peptides against various clinically validated biological targets in hematology, inflammation and immunomodulatory and metabolic diseases. Fourth Quarter 2023 Financial Results Cash, Cash Equivalents and Marketable Securities : Cash, cash equivalents and marketable securities as of December 31, 2023, were $341.6 million as compared to $237.4 million in the previous year. [1] Based on Cash, Cash Equivalents and Marketable Securities as of December 31, 2023, and including the $300m upfront payment expected from the worldwide collaboration agreement with Takeda Pharmaceuticals, but excluding all future milestones, including those expected with respect to JNJ-2113. License and Collaboration Revenue: License and collaboration revenue of $60 million for both the fourth quarter and full year of 2023 was comprised of (i) $50 million earned when the third patient was dosed in the ICONIC TOTAL Phase 3 clinical study of JNJ-2113 in patients with moderate-to-severe psoriasis and (ii) $10 million following the dosing of the third patient in ANTHEM-UC, a Phase 2b trial to evaluate the safety and effectiveness of JNJ-2113 compared with placebo in participants with moderately to severely active ulcerative colitis. The full year 2022 results included a one-time $25.0 million milestone earned by the Company following the dosing of the third patient in the JNJ Phase 2b FRONTIER 1 clinical trial of JNJ-2113. Research and Development ("R&D") Expenses: The decrease in R&D expenses from the prior year quarter was primarily due to a decrease in PN-943 expenses, partially offset by an increase in rusfertide expenses related to the Phase 3 VERIFY clinical trial. The decrease in R&D expense from the prior year was primarily due to decreases in PN-943 expenses and costs related to preclinical and discovery research, partially offset by an increase in rusfertide expenses. General and Administrative ("G&A") Expenses: The increase in G&A expenses from the prior year quarter was primarily due to increases in payroll and stock-based compensation and general expenses. The increase in G&A expenses from the prior year was primarily due to increases in stock-based compensation, partially offset by one-time costs incurred in the first quarter of 2022. Net Income (Loss): Net income was $27.3 million, or $0.45 per basic share and $0.44 per diluted share, for the fourth quarter of 2023 as compared to a net loss of ($34.2) million, or ($0.69) per basic and diluted share, for the fourth quarter of 2022. Net loss was ($79.0) million, or ($1.39) per share, for the full year 2023, as compared to a net loss of $(127.4) million, or ($2.60) per share, for the full year 2022. About Protagonist Protagonist Therapeutics is a biopharmaceutical company with peptide-based new chemical entities (NCEs) rusfertide and JNJ-2113 (formerly PN-235) in advanced stages of clinical development, both derived from the Company's proprietary technology platform. Protagonist and JNJ scientists jointly discovered PN-235 (now known as JNJ-2113) as part of Protagonist's Interleukin-23 receptor (IL-23R) collaboration with JNJ and followed it through IND-enabling pre-clinical and Phase 1 studies, with JNJ assuming responsibility for further clinical development. Rusfertide, a mimetic of the natural hormone hepcidin, is the Company's lead drug candidate currently in a global Phase 3 development program. The randomized portion of the Phase 2 REVIVE study was unblinded, showing positive results and is now complete, with an open-label extension underway. The global Phase 3 VERIFY study of rusfertide in polycythemia vera is ongoing. Rusfertide will be co-developed and co-commercialized with Takeda pursuant to a worldwide collaboration and license agreement with Takeda entered into in January 2024. The agreement will be effective upon the termination or expiration of any applicable waiting periods under the Hart-Scott-Rodino Act. More information on Protagonist, its pipeline drug candidates and clinical studies can be found on the Company's website at . Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding the potential benefits of JNJ-2113, our expectations regarding the timing of enrollment completion in our clinical trial (VERIFY), filing of the rusfertide NDA, clinical development of JNJ-2113 and our ongoing IL-17 and other discovery research programs. In some cases, you can identify these statements by forward-looking words such as "anticipate," "believe," "may," "will," "expect," or the negative or plural of these words or similar expressions. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, our ability to develop and commercialize our product candidates, our ability to earn milestone payments under our collaboration agreement with JNJ, our ability to use and expand our programs to build a pipeline of product candidates, our ability to obtain and maintain regulatory approval of our product candidates, our ability to operate in a competitive industry and compete successfully against competitors that have greater resources than we do, and our ability to obtain and adequately protect intellectual property rights for our product candidates. Additional information concerning these and other risk factors affecting our business can be found in our periodic filings with the Securities and Exchange Commission, including under the heading "Risk Factors" contained in our most recently filed periodic reports on Form 10-K and Form 10-Q filed with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements, whether as a result of new information, future events or otherwise, after the date of this press release. Investor Relations Contact Corey Davis, Ph.D. LifeSci Advisors +1 212 915 2577 cdavis@lifesciadvisors.com Media Relations Contact Virginia Amann ENTENTE Network of Companies virginiaamann@ententeinc.com +1 833 500 0061 PROTAGONIST THERAPEUTICS, INC. Condensed Consolidated Statements of Operations (Amounts in thousands except share and per share data) Three Months Ended Twelve Months Ended December 31, December 31, 2023 2022 2023 2022 License and collaboration revenue $ 60,000 $ - $ 60,000 $ 26,581 Operating expenses: Research and development (1) 28,899 29,884 120,161 126,215 General and administrative (1) 8,052 6,632 33,491 31,739 Total operating expenses 36,951 36,516 153,652 157,954 Income (loss) from operations 23,049 (36,516 ) (93,652 ) (131,373 ) Interest income 4,242 2,251 14,898 4,060 Other expense, net 44 71 (201 ) (80 ) Net income (loss) $ 27,335 $ (34,194 ) $ (78,955 ) $ (127,393 ) Net income (loss) per share, basic $ 0.45 $ (0.69 ) $ (1.39 ) $ (2.60 ) Net income (loss) per share, diluted $ 0.44 $ (0.69 ) $ (1.39 ) $ (2.60 ) Weighted-average shares used to compute net income (loss) per share, basic 60,387,606 49,252,633 56,763,559 49,042,232 Weighted-average shares used to compute net income (loss) per share, diluted 61,796,205 49,252,633 56,763,559 49,042,232 Amount includes non-cash stock-based compensation expense. PROTAGONIST THERAPEUTICS, INC. Stock-based Compensation (In thousands) Three Months Ended Twelve Months Ended December 31, December 31, 2023 2022 2023 2022 Research and development $ 3,890 $ 3,429 $ 17,061 $ 14,719 General and administrative 2,711 2,083 12,232 9,483 Total stock-based compensation expense $ 6,601 $ 5,512 $ 29,293 $ 24,202 PROTAGONIST THERAPEUTICS, INC. Selected Consolidated Balance Sheet Data (In thousands) December 31, December 31, 2023 2022 Cash, cash equivalents and marketable securities$ $ 341,617 237,355 Working capital 334,303 211,898 Total assets 357,951 247,928 Accumulated deficit (615,710 ) (536,755 ) Total stockholders' equity 336,677 215,608 SOURCE: Protagonist Therapeutics, Inc. View the original press release on accesswire.com