Polycythemia Vera

NEWARK, CA / ACCESSWIRE / March 18, 2024 / Protagonist Therapeutics, Inc. ("Protagonist" or the "Company") today announces the closing of the worldwide collaboration and license agreement for rusfertide with Takeda, a leading values-based, R&D-driven biopharmaceutical company, disclosed on January 31, 2024. Closing of the transaction was contingent on completion of review under the Hart-Scott-Rodino (HSR) Antitrust Improvements Act of 1976 in the United States. Protagonist will receive the $300 million upfront payment associated with the transaction in the second quarter of 2024. 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. More information on Protagonist, its pipeline drug candidates and clinical studies can be found on the Company's website at . Investor Relations Contact Corey Davis, Ph.D. LifeSci Advisors +1 212 915 2577 cdavis@lifesciadvisors.com Media Contact Virginia Amann, Founder/CEO ENTENTE Network of Companies virginiaamann@ententeinc.com SOURCE: Protagonist Therapeutics, Inc. View the original press release on accesswire.com

Study met primary endpoint and demonstrated highly significant reductions in Lp(a) to week 36 Lipoprotein(a) reduction was consistent with phase 1 results Topline 48-week data expected in 2Q 2024 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 announced positive topline 36-week data from the ongoing ALPACAR-360 phase 2 study of zerlasiran (SLN360) in 178 subjects with baseline lipoprotein(a), or Lp(a), levels at or over 125 nmol/L at high risk of atherosclerotic cardiovascular disease (ASCVD) events. Zerlasiran is a siRNA (short interfering RNA) designed to lower the body’s production of Lp(a), a key genetic risk factor for cardiovascular disease affecting up to 20% of the world’s population. In the double-blind placebo-controlled treatment period, zerlasiran was administered at 300 mg subcutaneously every 16 or 24 weeks and 450 mg every 24 weeks to patients with a median baseline Lp(a) of approximately 215 nmol/L. These data demonstrated a highly significant reduction from baseline in Lp(a) compared to placebo to 36 weeks (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 48 weeks (end of treatment period), 60 weeks (end of study) and potential effects on other lipids/lipoproteins, will be evaluated. “We are excited about the emerging phase 2 data, which are very consistent with phase 1 results and support a competitive pro treating patients with high Lp(a),” said Steven Romano, MD, Head of Research and Development at Silence. “We look forward to reviewing the 48-week data and advancing zerlasiran as a potential treatment to address this major unmet need in cardiovascular disease.” Silence plans to report topline 48-week data from the ALPACAR-360 study in the second quarter of this year. 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 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 designed to address hematological diseases, including polycythemia vera. 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 March 15, 2023. 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.

Long-term extension (LTE) FRONTIER 2 study demonstrated sustained efficacy and similar safety results from Week 16 to Week 52, consistent with previously reported FRONTIER 1 16-week Phase 2b study The proportion of patients achieving PASI 75, 90 and 100 response rates at Week 16 were maintained through Week 52, confirming the durability of response 59.5% and 64.3% of patients in the highest dose group (100 mg BID) achieved a PASI 90 response at Weeks 16 and 52 respectively; PASI 90 is a co-primary endpoint for multiple Phase 3 studies in the ICONIC clinical development program No evidence of dose-dependent increase in AEs across the JNJ-2113 treatment groups NEWARK, CA / ACCESSWIRE / March 11, 2024 / Protagonist Therapeutics, Inc. ("Protagonist" or "the Company") today announced a late-breaking presentation at the American Academy of Dermatology (AAD) 2024 Annual Meeting with positive results from the Phase 2b FRONTIER 2 long-term extension study evaluating JNJ-2113, the first and only investigational targeted oral peptide designed to block the IL-23 receptor, for adult patients with moderate-to-severe plaque psoriasis (PsO). JNJ-2113 is being developed by J&J Innovative Medicine, Inc. (see today's accompanying press release from J&J), under a license and collaboration agreement with Protagonist, and is currently enrolling four pivotal Phase 3 psoriasis studies in the ICONIC clinical development program and one Phase 2b ulcerative colitis study. FRONTIER 2 enrolled patients who completed the 16-week dose ranging FRONTIER 1 Phase 2b study and evaluated patients from Week 17 through Week 52. In FRONTIER 2, JNJ-2113 maintained high rates of skin clearance through 52 weeks in adults with moderate-to-severe plaque psoriasis, as measured by Psoriasis Area and Severity Index (PASI) response rates of 75%, 90% and 100%. Recently, results from FRONTIER 1 were published in The New England Journal of Medicine and showed superior efficacy of JNJ-2113 at all doses tested and similar safety compared to placebo at Week 16. "The positive and consistent results from the 52-week FRONTIER 2 study demonstrate the durability of response observed in the 16-week FRONTIER 1 study and reaffirm JNJ-2113's potential as the best-in-class oral agent for psoriasis," said Dinesh V. Patel, PhD, President and CEO of Protagonist. "We continue to believe that JNJ-2113 can potentially have a transformative impact on the treatment of psoriasis and look forward to its assessment across a spectrum of other IL-23-mediated diseases, including the Phase 2b ANTHEM ulcerative colitis study." In FRONTIER 2, JNJ-2113 maintained high rates of skin clearance through 52 weeks in adults with moderate-to-severe plaque psoriasis. In the five JNJ-2113 treatment groups, response rates were maintained from Week 16 to Week 52 with the highest PASI 75 response observed in the 100 mg twice daily group (78.6% at 16 weeks and 76.2% at 52 weeks). Similar to the primary endpoint, responses were maintained through Week 52 for all five JNJ-2113 treatment groups for the key secondary endpoints of PASI 90 (59.5% at 16 weeks and 64.3% at 52 weeks), PASI 100 (40.5% at 16 weeks and 40.5% at 52 weeks), Investigator's Global Assessment (IGA) 0/1 (64.3% at 16 weeks and 73.8% at 52 weeks) and IGA 0 (45.2% at 16 weeks and 42.9% at 52 weeks). A summary of PASI responder data from the FRONTIER 2 study at Week 52: # Cohort PASI 75 (%) PASI 90 (%) PASI 100 (%) 1 25 mg daily (n=43) 48.8 27.9 14.0 2 25 mg twice daily (n=41) 58.5 36.6 17.1 3 50 mg daily (n=43) 69.8 41.9 20.9 4 100 mg daily (n=43) 65.1 51.2 25.6 5 100 mg twice daily (n=42) 76.2 64.3 40.5 6 Placebo switched to 100 mg daily (n=43) 65.7 57.1 34.3 Safety in the FRONTIER 2 long-term extension study (Week 17 through Week 52) was found to be consistent with the observations made in the FRONTIER 1 study. Treatment was generally well tolerated, and the proportions of patients with adverse events were comparable between patient groups. There was no evidence of dose-dependent increase in AEs across the treatment groups. The four Phase 3 ICONIC studies in the clinical development program are currently underway to evaluate the safety and efficacy of JNJ-2113 in adults with moderate-to-severe plaque PsO, including the ICONIC-LEAD and ICONIC-TOTAL studies. The ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2 will evaluate the safety and efficacy of JNJ-2113 compared with both placebo and deucravacitinib. In addition, J&J is enrolling the Phase 2b ANTHEM-UC study to evaluate the safety and effectiveness of JNJ-2113 compared with placebo in participants with moderately-to-severely active ulcerative colitis. About FRONTIER 2 FRONTIER 2 (NCT05364554) is a Phase 2b multicenter, double-blind, long-term extension, dose-ranging study to evaluate the efficacy and safety of JNJ-77242113 (JNJ-2113) for the treatment of moderate-to-severe plaque psoriasis. The study evaluated four once-daily and two twice-daily dosages of JNJ-2113 taken orally. The originating study (FRONTIER 1) began with its first participant screened on February 3, 2022. A total of 337 participants were screened of which 255 participants were randomized into six treatment groups (Placebo (n=43), 25 mg daily (n=43), 50 mg daily (n=43), 25 mg twice daily (n=41), 100 mg daily (n=43), 100mg twice daily (n=43)). At Week 16, a total of 227 participants from FRONTIER 1 entered FRONTIER 2, the long-term extension study, and received at least one dose of study intervention (Placebo switched to 100 mg daily (n=35), 25 mg daily (n=35), 50 mg daily (n=39), 25 mg twice daily (n=40), 100 mg daily (n=40), 100 mg twice daily (n=38)). The first participant in FRONTIER 2 study was dosed on June 10, 2023. The total duration of the trial was 52 weeks. About JNJ-77242113 (JNJ-2113) JNJ-2113 was jointly discovered and is being developed pursuant to the license and collaboration agreement between Protagonist and J&J, which retains exclusive worldwide rights to develop JNJ-2113 in Phase 2 clinical trials and beyond, and to commercialize compounds derived from the research conducted pursuant to the agreement against a broad range of indications. The license and collaboration agreement, established in 2017, enabled the companies to work together to discover and develop next-generation compounds that ultimately led to JNJ-2113. Investigational JNJ-2113 is the first targeted oral peptide designed to block the IL-23 receptor, which underpins the inflammatory response in moderate-to-severe plaque psoriasis (PsO) and other IL-23-mediated diseases. JNJ-2113 binds to the IL-23 receptor with single-digit picomolar affinity and has demonstrated potent, selective inhibition of IL-23 signaling in human T cells. IL-23 plays a critical role in pathogenic T-cell activation in moderate-to-severe plaque PsO and underpins the inflammatory response in PsO and other dermatological, rheumatological and gastroenterological IL-23-mediated diseases. 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 clinical pro JNJ-2113. 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 Contact: Virginia Amann, Founder/CEO ENTENTE Network of Companies virginiaamann@ententeinc.com SOURCE: Protagonist Therapeutics View the original press release on accesswire.com