GRPR inhibitors(Alpha-9 Theranostics)

The new FDA approval allows Jemperli to challenge Keytruda in the same endometrial cancer population. Merely a month into an FDA approval for a broad first-line endometrial cancer population, Merck’s Keytruda has some company.On Thursday, the FDA expanded the endometrial cancer use for GSK’s Jemperli, used in combination with chemotherapy, to include patients with mismatch repair proficient (pMMR) or microsatellite-stable (MSS) tumors.The new go-ahead rounds out the PD-1 inhibitor’s first-in-class nod a year ago, which was limited to a relatively small subgroup of patients with mismatch repair deficient (dMMR) or microsatellite instability-high (MIS-H) tumors. It also leveled the playing field for Jemperli in endometrial cancer against Keytruda, which in July earned a broad label regardless of the patient’s biomarker status.GSK sought the original nod quickly to make sure that it “moved with pace” in a competitive checkpoint inhibitor market, GSK’s head of oncology R&D, Hesham Abdullah, M.D., said in an interview with Fierce Pharma ahead of Thursday’s FDA decision.When competing with the omnipresent Keytruda, being first in an indication comes with a valuable edge. But the question is whether Jemperli has fully capitalized on that one-year head start and can maintain its momentum against the PD-1 leader. To Abdullah, there’s one more card Jemperli can play.“One of the things that we really wanted to do was make sure that we characterized the effect that [Jemperli], in combination with chemotherapy, was having on overall survival,” Abdullah said. PD-1 inhibitors are known to work well in dMMR tumors. In first-line endometrial cancer, both Jemperli and Keytruda have produced exceptional tumor progression-free survival benefits against chemo alone in the 70% range in dMMR patients in separate phase 3 trials.But by the time GSK sought the original nod, Jemperli’s use alongside chemo only led to a mild 24% reduction in the risk of progression or death versus chemo alone. By comparison, Keytruda got its broad label with a 40% progression-free survival showing in the pMMR group. More than 70% of endometrial cancers are pMMR.This time around, GSK armed Jemperli with data showing it could extend patients’ lives. Jemperli and chemo significantly cut the risk of death by 31% compared with chemo in part 1 of the phase 3 RUBY trial regardless of the patient’s biomarker status. In the pMMR subgroup specifically, the death risk reduction was 21% in favor of the combo, although the number doesn’t bear statistical significance.In contrast, Keytruda can’t claim an overall survival benefit yet. During an interim analysis of Keytruda’s phase 3 NRG-GY018 trial, only 12% deaths had happened in the dMMR cohort and 17% in the pMMR group.Abdullah argued that overall survival, as the gold standard for measuring oncology drug efficacy and safety, is important and gives Jemperli, a relatively newer product, additional credence. He also pointed to diverging results among PD-1 inhibitors in past clinical trials in other tumor types to show that one PD-1 inhibitor’s success is not necessarily a guarantee for another’s. But how that advantage can translate into uptake remains to be seen given doctors’ overall familiarity with Keytruda.During GSK’s first-quarter earnings call in May, Chief Commercial Officer Luke Miels acknowledged Keytruda’s leading position and as an “easier choice” in the PD-1 class. But he said GSK was seeing “quite a striking shift in terms of physicians’ assessment of Jemperli and willingness to try it.” He also pointed to potential guideline changes as another driver of growth given the weight of overall survival in those assessments.In the first quarter, Jemperli’s new patient share in first-line dMMR endometrial cancer nearly doubled to 33% compared with the end of 2023. There’s potential for GSK to further enhance Jemperli with the addition of the PARP inhibitor Zejula, especially in the pMMR population. That idea is being tested in part 2 of the RUBY trial, and it has shown stronger progression-free survival results in pMMR patients compared with Jemperli. GSK is still following that arm for long-term overall survival results. PAPR inhibitors have previously been linked to potential detriments to certain ovarian cancer patients over the long term.Keytruda’s NRG-GY018 trial doesn’t have a separate PARP arm. But Merck’s partner AstraZeneca is exploring the same idea for its PD-L1 inhibitor Imfinzi and the PARP drug Lynparza in the phase 3 DUO-E trial. Last month, Imfinzi and chemo—without Lynparza—also received a dMMR-only nod from the FDA based on that study.For Jemperli overall, GSK expects its PD-1 latecomer could reach more than £2 billion peak sales. The British pharma is exploring various combinations, including with TIGIT and its newly licensed B7-H3 and B7-H4 antibody-drug conjugates. Among them, Abdullah noted the B7-H4 candidate holds promise in endometrial and ovarian cancers.

JENA, Germany, July 30, 2024 (GLOBE NEWSWIRE) -- InflaRx N.V. (Nasdaq: IFRX), a biopharmaceutical company pioneering anti-inflammatory therapeutics targeting the complement system, today announced it will present preclinical data on the company’s novel oral C5aR inhibitor, INF904, at the 2024 European Meeting on Complement in Human Diseases (EMCHD) being held in Lübeck, Germany, September 2 – 6, 2024. In addition to two poster presentations, InflaRx representatives will participate in a C5a/C5aR-focused panel discussion as well as speak at a satellite symposium. EMCHD 2024 will focus on emerging developments in the complement field with a goal of translating basic scientific advancements into meaningful new therapeutic approaches to combat human diseases. A preliminary conference program can be found here. Given the company’s commitment to advancing science to treat complement-mediated conditions, InflaRx is also one of the corporate sponsors of this year’s meeting. Poster Presentations Poster title: INF904, a novel oral C5a receptor 1 (C5aR1) antagonist, shows promising therapeutic effects in inflammatory disease modelsPoster number: P19Authors: Zhongli Xu, Rui Liu, Ophelia Chen, Bruce P. Burnett, Maria Habel, Renfeng Guo Poster title: Preclinical pharmacological characterization of INF904, an oral small molecule antagonist to complement 5a receptor1 (C5aR1)Poster number: P20Authors: Rui Liu, Zhongli Xu, Ophelia Chen, Bruce P. Burnett, Maria Habel, Renfeng Guo Other Sessions Satellite symposium - oral session: Inhibition of the C5a/C5aR1 axis in inflammationSpeaker: Prof. Niels C. Riedemann, Chief Executive Officer and Founder of InflaRxDay/time: Monday, September 2, 3:00 – 3:30 pm CET Satellite symposium - panel discussion: Targeting C3 and/or C5 PathwaysInflaRx participant: Prof. Niels C. RiedemannDay/time: Monday, September 2, 4:00 – 5:00 pm CET Lunch seminar: Complement C5a/C5aR inhibition in human disease with best-in-class inhibitorsInflaRx speakers: Prof. Niels C. Riedemann, Chief Executive Officer and FounderDr. Renfeng Guo, Chief Scientific Officer and Founder Dr. Camilla Chong, Chief Medical OfficerDay/time: Tuesday, September 3, 1:00 – 1:45 pm CET About INF904 INF904 is an orally administered, small molecule inhibitor of the C5a receptor that has shown anti-inflammatory therapeutic effects in several pre-clinical disease models. Further, in contrast to the marketed C5aR inhibitor, in vitro experiments demonstrated that INF904 has minimal inhibition of the cytochrome P450 3A4/5 (CYP3A4/5) enzymes, which play an important role in the metabolism of a variety of metabolites and drugs, including glucocorticoids. Reported results from a first-in-human study demonstrated that INF904 is well tolerated in treated subjects and exhibits no safety signals of concern in single doses ranging from 3 mg to 240 mg or multiple doses ranging from 30 mg once per day (QD) to 90 mg twice per day (BID) for 14 days. Pharmacokinetic / pharmacodynamic data support best-in-class potential of INF904 with a ≥90% blockade of C5a-induced neutrophil activation achieved over the 14-day dosing period. About InflaRx InflaRx GmbH (Germany) and InflaRx Pharmaceuticals Inc. (USA) are wholly owned subsidiaries of InflaRx N.V. (together, InflaRx). InflaRx (Nasdaq: IFRX) is a biopharmaceutical company pioneering anti-inflammatory therapeutics by applying its proprietary anti-C5a and anti-C5aR technologies to discover, develop and commercialize highly potent and specific inhibitors of the complement activation factor C5a and its receptor C5aR. C5a is a powerful inflammatory mediator involved in the progression of a wide variety of inflammatory diseases. InflaRx’s lead product candidate, vilobelimab, is a novel, intravenously delivered, first-in-class, anti-C5a monoclonal antibody that selectively binds to free C5a and has demonstrated disease-modifying clinical activity and tolerability in multiple clinical studies in different indications. InflaRx is also developing INF904, an orally administered, small molecule inhibitor of the C5a receptor. InflaRx was founded in 2007, and the group has offices and subsidiaries in Jena and Munich, Germany, as well as Ann Arbor, MI, USA. For further information, please visit www.inflarx.com. Contacts: InflaRx N.V.MC Services AGJan Medina, CFAVice President, Head of Investor RelationsEmail: IR@inflarx.deKatja Arnold, Laurie Doyle, Dr. Regina LutzEmail: inflarx@mc-services.eu Europe: +49 89-210 2280U.S.: +1-339-832-0752 FORWARD-LOOKING STATEMENTSThis press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “estimate,” “believe,” “predict,” “potential” or “continue,” among others. Forward-looking statements appear in a number of places throughout this release and may include statements regarding our intentions, beliefs, projections, outlook, analyses and current expectations concerning, among other things, our ability to successfully commercialize and the receptiveness of GOHIBIC (vilobelimab) as a treatment for COVID-19 patients by U.S. hospitals, our ability to positively influence treatment recommendations by medical/healthcare institutes, guideline bodies and other third-party organizations; our expectations regarding the size of the patient populations for, market opportunity for, coverage and reimbursement for, estimated returns and return accruals for, and clinical utility of GOHIBIC (vilobelimab) in its approved or authorized indication or for vilobelimab and any other product candidates, under the EUA, and in the future if approved for commercial use in the United States or elsewhere; our ability to successfully implement The InflaRx Commitment Program and estimate future write-downs due to expiry and costs in the event of the price refunds, the success of our future clinical trials for vilobelimab's treatment of COVID-19 and other debilitating or life-threatening inflammatory indications, including ARDS, PG, and any other product candidates, including INF904, and whether such clinical results will reflect results seen in previously conducted pre-clinical studies and clinical trials; the timing, progress and results of preclinical studies and clinical trials of vilobelimab, INF904 and any other product candidates, including for the development of vilobelimab in several indications, including to treat PG, HS and CSU and statements regarding the timing of initiation and completion of studies or trials and related preparatory work, the period during which the results of the trials will become available, the costs of such trials and our research and development programs generally; our interactions with and the receptiveness and approval by regulators regarding the results of clinical trials and potential regulatory approval or authorization pathways including related to our MAA submission for vilobelimab and our BLA for GOHIBIC (vilobelimab); the timing and outcome of any discussions or submission of filings for regulatory approval or authorization of vilobelimab, INF904 or any other product candidate, and the timing of and our ability to obtain and maintain full regulatory approval or the EUA, of vilobelimab or GOHIBIC (vilobelimab) for any indication; our ability to leverage our proprietary anti-C5a and anti-C5aR technologies to discover and develop therapies to treat complement-mediated autoimmune and inflammatory diseases; our ability to protect, maintain and enforce our intellectual property protection for vilobelimab, INF904 and any other product candidates, and the scope of such protection; whether the FDA, or the EMA or any comparable foreign regulatory authority will accept or agree with the number, design, size, conduct or implementation of our clinical trials, including any proposed primary or secondary endpoints for such trials; the success of our future clinical trials for vilobelimab, INF904 and any other product candidates and whether such clinical results will reflect results seen in previously conducted preclinical studies and clinical trials; our expectations regarding the size of the patient populations for, the market opportunity for, the medical need for and clinical utility of vilobelimab, INF904 or any other product candidates, if approved or authorized for commercial use; our manufacturing capabilities and strategy, including the scalability and cost of our manufacturing methods and processes and the optimization of our manufacturing methods and processes, and our ability to continue to rely on our existing third-party manufacturers and our ability to engage additional third-party manufacturers for our planned future clinical trials and for commercial supply of vilobelimab and for the finished product GOHIBIC (vilobelimab); our estimates of our expenses, ongoing losses, future revenue, capital requirements and our needs for or ability to obtain additional financing; our expectations regarding the scope of any approved indication for vilobelimab; our ability to defend against liability claims resulting from the testing of our product candidates in the clinic or, if, approved or authorized, any commercial sales; if any of our product candidates obtain regulatory approval or authorization, our ability to comply with and satisfy ongoing drug regulatory obligations and continued regulatory overview; our ability to comply with enacted and future legislation in seeking marketing approval or authorization and commercialization; our future growth and ability to compete, which depends on our retaining key personnel and recruiting additional qualified personnel; and our competitive position and the development of and projections relating to our competitors in the development of C5a and C5aR inhibitors and other therapeutic products being developed in similar medical conditions in which vilobelimab, INF904 or any other of our product candidates is being developed or our industry; and the risks, uncertainties and other factors described under the heading “Risk Factors” in our periodic filings with the SEC. These statements speak only as of the date of this press release and involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these forward-looking statements, even if new information becomes available in the future, except as required by law.