C1-INH

Additional real-world studies show sustained HAE attack rate reduction after initiating ORLADEYO, regardless of C1-INH status, and patient preference for an oral LTP therapyRESEARCH TRIANGLE PARK, N.C., Oct. 24, 2024 (GLOBE NEWSWIRE) -- BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) today announced new real-world comparative research on the use of oral, once-daily ORLADEYO® (berotralstat) that found high rates of adherence and persistence for ORLADEYO, similar to the rates observed with two other long-term prophylactic (LTP) therapies for hereditary angioedema (HAE). The company also announced new real-world evidence showing statistically significant and sustained HAE attack rate reductions after initiating ORLADEYO in patients with HAE, regardless of their C1-inhibitor (C1-INH) deficiency status, and new findings from an HAE patient survey confirming patient preference for an oral LTP therapy. “These results build on previous research that highlights how the real-world effectiveness and convenience of our oral, once-daily prophylactic therapy are differentiators for patients. The strong adherence, persistence and preference for ORLADEYO we report here provide further evidence that enables physicians to optimize individualized treatment recommendations for each of their patients. We continue to generate real-world evidence demonstrating that ORLADEYO is a powerful, potentially life-changing treatment for many people with HAE,” said Dr. Donald S. Fong, chief medical officer of BioCryst. The data are being presented at the Annual Scientific Meeting of the American College of Allergy, Asthma & Immunology (ACAAI), which is taking place in Boston from October 24-28, 2024. High Adherence and Persistence Rates for ORLADEYO and Other LTP Therapies Poster #R072 explores adherence and persistence rates among patients with HAE following initiation of ORLADEYO (n=90) compared with lanadelumab (n=189) and subcutaneous plasma-derived C1-inhibitor (SC-pdC1-INH) (n=78). “Our findings reveal that among HAE patients managed with LTP, high adherence and persistence rates were demonstrated for ORLADEYO. There was a striking consistency between first line therapies with comparable results for lanadelumab and SC-pdC1-INH. ORLADEYO rates were equivalent to – and in some cases better than – these LTP counterparts. The outcomes of our study provide further support for a shared decision-making approach within the physician-patient partnership to inform LTP selection, incorporating effectiveness, safety, treatment burden and patient preference for each individual,” said Sandra Christiansen, MD, professor of medicine and director of translational research at the US HAEA Angioedema Center at the University of California, San Diego. Adherence And Persistence Among Hereditary Angioedema Patients Treated With Berotralstat, Lanadelumab, And Subcutaneous Plasma-Derived C1-Inhibitor; ePoster #R072; Friday, October 25, 2:30-2:45 p.m. ET; Monitor #19, Hall A Eighty-six percent of patients who took ORLADEYO (n=77), 91 percent who took lanadelumab (n=172) and 83 percent who took SC-pdC1-INH (n=65) filled at least two prescriptions during the 12-month follow-up period.Adherence rates among patients with at least two fills were high at 12 months of follow-up. Seventy-seven percent of patients taking ORLADEYO were adherent compared to 76 percent of patients taking lanadelumab and 80 percent of patients taking SC-pdC1-INH.Persistence rates among patients with at least two fills were high at 12 months of follow-up, with 71 percent of patients taking ORLADEYO persistent compared to 63 percent of patients taking lanadelumab and 63 percent of patients taking SC-pdC1-INH.No statistically significant differences in adherence or persistence were observed between the LTP patient cohorts. Methods Electronic health records linked to claims data were used to select mutually exclusive cohorts of patients aged 12 and above who initiated ORLADEYO, lanadelumab or pdC1-INH between June 22, 2017, and September 12, 2023.Adherence was defined as having a proportion of days covered greater than or equal to 0.80.Persistence was defined as fewer than 45 consecutive days without the index LTP treatment. Sustained HAE Attack Rate Reduction After Beginning ORLADEYO Regardless of C1-INH Status Posters #R092 and #R093 evaluate self-reported HAE attacks prior to and following ORLADEYO initiation among patients with and without HAE with C1-inhibitor deficiency (HAE-nl-C1-INH), respectively. “ORLADEYO was associated with statistically significant and sustained reductions in attack rates through 18 months (540 days) following ORLADEYO initiation, regardless of patients’ C1-INH status. Importantly, in this real-world study, patients with zero attacks at baseline were included, compared to the minimum of two attacks that was required at baseline in APeX-2. These data confirm that many already well-controlled HAE patients enjoy continued or improved attack control once they initiate ORLADEYO,” Dr. Fong added. Sustained Real-World Attack Reductions Following Berotralstat Initiation Among Patients with Hereditary Angioedema with C1-Inhibitor Deficiency; ePoster #R092; Friday, October 25, 3:30-3:45 p.m. ET; Monitor #20, Hall A Patients (n=466) had significantly lower attack rates at each follow-up interval, which ranged from 0.62 attacks per month at days 361-450 (n=185) to 0.79 at days 271-360 (n=217) versus baseline (2.62 at days 361-450 to 2.50 at days 271-360).Mean monthly attack rate reduction was -1.71 (p<0.05) at days 271-360 (n=217) and -1.96 (p<0.05) at days 451-540 (n=157). Sustained Real-World Attack Reductions Following Berotralstat Initiation Among Patients with Hereditary Angioedema without C1-Inhibitor Deficiency; ePoster #R093; Friday, October 25, 3:45-4:00 p.m. ET; Monitor #20, Hall A Patients (n=353) had significantly lower attack rates at each follow-up interval, which ranged from 1.63 attacks per month at days 181-270 (n=191) to 2.04 at days 1-90 (n=304) versus baseline (4.33 at days 181-270 to 4.63 at days 1-90).Mean monthly attack rate reduction was -2.91 (p<0.05) at days 271-360 (n=157) and -2.53 (p<0.05) at days 451-540 (n=108). Methods Outcomes were collected through BioCryst’s sole-source pharmacy and included U.S. patients who actively received ORLADEYO 110 or 150 mg QD from December 15, 2020, to January 8, 2024.Patient-reported HAE attack rates were collected at baseline and each refill (approximately every 30 days).To be included in the analysis of a given follow-up period, patients were required to have responded to a follow-up assessment within the period of interest and to the onboarding self-assessment of attacks. Approximately 96 percent of patients met these criteria at each interval. Patients with HAE Prefer Oral LTP Poster #R081 examines the LTP treatment preferences of patients with HAE, as collected through an online survey. “We are encouraged to see both effectiveness and convenience are drivers of treatment preference with patients preferring oral therapy over injectable therapy when efficacy is assumed equal. Given the benefits of treatment with ORLADEYO for patients who remain on therapy over the long term, we believe we will continue to see the preference towards oral therapy reflected in the strong commercial performance of our oral, once-daily prophylactic therapy for HAE,” Dr. Fong noted. Long-Term Prophylactic Treatment Preferences of Patients With Hereditary Angioedema; ePoster #R081; Friday, October 25, 4:45-5:00 p.m. ET; Monitor #19, Hall A LTP treatment attributes rated most important were effectiveness in attack prevention and effectiveness in reducing attack severity.When presented with the option of an equally effective oral or injectable LTP, 54 percent preferred an oral daily therapy over a biweekly or monthly subcutaneous injection.More than half (52 percent) preferred oral over injectable LTP as infrequently as every three months. Methods Results from an online survey of U.S. patients with HAE who were at least 18 years of age, self-reported their diagnosis and were receiving an HAE treatment (LTP, on-demand or both) or had experienced at least one HAE attack in the preceding three months (n=150). In addition to displaying in the exhibit hall at the noted times, ePosters are accessible online and on demand to registered attendees on ACAAI’s website. About ORLADEYO® (berotralstat)ORLADEYO® (berotralstat) is the first and only oral therapy designed specifically to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years and older. One capsule of ORLADEYO per day works to prevent HAE attacks by decreasing the activity of plasma kallikrein. U.S. Indication and Important Safety Information INDICATIONORLADEYO® (berotralstat) is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years and older. Limitations of useThe safety and effectiveness of ORLADEYO for the treatment of acute HAE attacks have not been established. ORLADEYO should not be used for the treatment of acute HAE attacks. Additional doses or dosages of ORLADEYO higher than 150 mg once daily are not recommended due to the potential for QT prolongation. IMPORTANT SAFETY INFORMATION An increase in QT prolongation was observed at dosages higher than the recommended 150 mg once-daily dosage and was concentration dependent. The most common adverse reactions (≥10% and higher than placebo) in patients receiving ORLADEYO were abdominal pain, vomiting, diarrhea, back pain, and gastroesophageal reflux disease. A reduced dosage of 110 mg taken orally once daily with food is recommended in patients with moderate or severe hepatic impairment (Child-Pugh B or C). Berotralstat is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein. P-gp inducers (eg, rifampin, St. John’s wort) may decrease berotralstat plasma concentration, leading to reduced efficacy of ORLADEYO. The use of P-gp inducers is not recommended with ORLADEYO. ORLADEYO at a dose of 150 mg is a moderate inhibitor of CYP2D6 and CYP3A4. For concomitant medications with a narrow therapeutic index that are predominantly metabolized by CYP2D6 or CYP3A4, appropriate monitoring and dose titration is recommended. ORLADEYO at a dose of 300 mg is a P-gp inhibitor. Appropriate monitoring and dose titration is recommended for P-gp substrates (eg, digoxin) when coadministering with ORLADEYO. The safety and effectiveness of ORLADEYO in pediatric patients <12 years of age have not been established. There are insufficient data available to inform drug-related risks with ORLADEYO use in pregnancy. There are no data on the presence of berotralstat in human milk, its effects on the breastfed infant, or its effects on milk production. To report SUSPECTED ADVERSE REACTIONS, contact BioCryst Pharmaceuticals, Inc. at 1-833-633-2279 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Please see full Prescribing Information. About BioCryst Pharmaceuticals BioCryst Pharmaceuticals is a global biotechnology company with a deep commitment to improving the lives of people living with complement-mediated and other rare diseases. BioCryst leverages its expertise in structure-guided drug design to develop first-in-class or best-in-class oral small-molecule and protein therapeutics to target difficult-to-treat diseases. BioCryst has commercialized ORLADEYO® (berotralstat), the first oral, once-daily plasma kallikrein inhibitor, and is advancing a pipeline of small-molecule and protein therapies. For more information, please visit www.biocryst.com or follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements, including statements regarding future results, performance or achievements and statements relating to ORLADEYO performance and patient preferences. These statements involve known and unknown risks, uncertainties and other factors which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and are subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Some of the factors that could affect the forward-looking statements contained herein include: BioCryst’s ability to successfully implement or maintain its commercialization plans for ORLADEYO, which could take longer or be more expensive than planned; the commercial viability of ORLADEYO, including its ability to achieve sustained market acceptance; the FDA or other applicable regulatory agency may require additional studies beyond the studies planned for products and product candidates, may not provide regulatory clearances which may result in delay of planned clinical trials, may impose certain restrictions, warnings, or other requirements on products and product candidates, may impose a clinical hold with respect to product candidates, or may withhold, delay, or withdraw market approval for products and product candidates; BioCryst’s ability to successfully manage its growth and compete effectively; and risks related to the international expansion of BioCryst’s business. Please refer to the documents BioCryst files periodically with the Securities and Exchange Commission, specifically BioCryst’s most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K, which identify important factors that could cause the actual results to differ materially from those contained in BioCryst’s forward-looking statements. BCRXW Contact:John Bluth+1 919 859 7910jbluth@biocryst.com

Data to be highlighted in a Distinguished Industry Oral Abstract presentation at the American College of Allergy, Asthma & Immunology (ACAAI) 2024 Scientific Meeting SAN DIEGO, Oct. 24, 2024 /PRNewswire/ -- Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage allogeneic cell therapy and genetic medicines company advancing differentiated non-viral treatments for patients with cancer, autoimmune, and rare diseases, today announced the upcoming presentation of new preclinical data supporting the potential of P-KLKB1-101, a liver-directed genetic medicine that uses the Company's Cas-CLOVER™ Site-Specific Gene Editing System, for the treatment of patients with hereditary angioedema (HAE). The data showed high-fidelity KLKB1 gene editing for the targeted correction of HAE, the ability for controlled dose response, favorable tolerability and liver editing within the predicted therapeutic range. "The newest preclinical data for P-KLKB1-101 support our goal to develop a gene editing treatment option for HAE with encouraging early tolerability, safety and efficacy results," said Blair Madison, Ph.D., Chief Scientific Officer, Gene Therapy at Poseida Therapeutics. "We achieved a highly effective, therapeutically relevant reduction of kallikrein in our new humanized pre-clinical mouse model at a low 0.125 mg/kg dose, marking an improvement in our lipid nanoparticle delivery efficiency. These tools could potentially enable therapeutic gene editing in other liver-relevant targets, considering the high fidelity editing of Cas-CLOVER and the promising delivery efficiency we are seeing with our proprietary lipid and LNP in pre-clinical studies." HAE is a rare inherited disorder characterized by recurrent episodes of fluid accumulation outside of blood vessels, causing rapid swelling of tissues. The swelling is caused by unchecked activation of the kallikrein-bradykinin cascade due to deficiency of the C1 esterase inhibitor, a protein that is involved in regulating vascular permeability and the contact system. Patients with HAE are in need of a durable, effective, and convenient treatment option that eliminates recurrent attacks. P-KLKB1-101 is a fully non-viral investigational gene editing therapy designed to enable high fidelity editing at the pre-kallikrein gene, or KLKB1, for correction of HAE. It utilizes the Cas-CLOVER nuclease, which is engineered for high specificity, to achieve site-specific gene editing. Key Highlights from P-KLKB1-101 Data to be Presented at ACAAI P-KLKB1-101 enabled highly efficient KLKB1 editing and reduction of kallikrein in cultured primary human hepatocytes, with all off-target edits consistently at or below 0.1%, including at high dose levels. P-KLKB1-101 yielded controlled, dose-dependent reductions in kallikrein protein levels and activity in a new humanized mouse model. The reduction in plasma kallikrein levels was stable and persisted for at least 180 days (latest time point assessed). In this model, the targeted therapeutic level of KLKB1 editing was achieved with a single dose, and a 58% reduction of kallikrein levels at the minimally effective dose of 0.125 mg/kg. Interim non-human primate (NHP) data demonstrate that P-KLKB1-101 had favorable tolerability and achieved liver editing approaching the desired therapeutic range. Ongoing lead optimization of P-KLKB1-101 yielded a 29% increase in potency (as measured by on-target KLKB1 editing) relative to a historical dose-matched benchmark. Poseida's novel ionizable lipid and lipid nanoparticle (LNP) enables potent in vivo delivery of P-KLKB1-101 and a controlled dose response. Presentation Details The data will be presented on Saturday, October 26 by Dr. Madison at the American College of Allergy, Asthma & Immunology (ACAAI) 2024 Scientific Meeting in Boston: Title: Highly Specific Non-Viral Gene Editing with P-KLKB1-101 for Hereditary Angioedema Abstract #: 8063 Session: Distinguished Industry & Late-breaking Oral Abstracts – Session 1 Session Date/Time: Saturday, October 26, 4:30-6:00 p.m. ET (presentation at 5:03 p.m. ET) About P-KLKB1-101 P-KLKB1-101 is an investigational liver-directed non-viral gene editing approach designed using the Cas-CLOVER™ Site-Specific Gene Editing System, Poseida's proprietary high-fidelity nuclease. P-KLKB1-101 is designed for site-specific gene editing of the KLKB1 gene for the treatment of hereditary angioedema (HAE). This rare inherited disorder results in the swelling of the skin, intestinal tract, and airways, which can be both debilitating and life-threatening. Preclinical data demonstrates therapeutically relevant reduction of pre-kallikrein levels in both mouse and non-human primate models. About Cas-CLOVER The Cas-CLOVER™ Site-Specific Gene Editing System employs dual RNA-guided DNA targeting for high fidelity editing. The dual guide RNA targeting provides spatial restrictions on each of two Cas-CLOVER molecules after interacting with specific DNA sequences. This interaction then allows Clo051 cutting at the target site. The result is a highly specific edit by the Cas-CLOVER nuclease, and a low incidence of unwanted off-target edits, with 25-fold greater fidelity than CRISPR/Cas9. About Poseida Therapeutics, Inc. Poseida Therapeutics is a clinical-stage biopharmaceutical company advancing differentiated allogeneic cell therapies and genetic medicines with the capacity to cure. The Company's pipeline includes investigational allogeneic CAR-T cell therapies for hematologic cancers, autoimmune diseases, and solid tumors, as well as investigational in vivo genetic medicines that address patient populations with high unmet medical need. The Company's approach is based on its proprietary genetic editing platforms, including its non-viral transposon-based DNA delivery system, Cas-CLOVER™ Site-Specific Gene Editing System, Booster Molecule and nanoparticle gene delivery technologies, as well as in-house GMP cell therapy manufacturing. The Company has formed strategic collaborations with Roche and Astellas to unlock the promise of cell therapies for cancer patients. Learn more at and connect with Poseida on X and LinkedIn. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the potential capabilities and benefits of the Company's technology platforms and product candidates, including P-KLKB1-101; the quote from Dr. Madison; and the Company's plans and strategy with respect to developing its technologies and product candidates. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These forward-looking statements are based upon the Company's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, the fact that interim data from the Company's preclinical trials may change as more data become available; the Company's reliance on third parties for various aspects of its business; risks and uncertainties associated with development and regulatory approval of novel product candidates in the biopharmaceutical industry; the Company's ability to retain key scientific or management personnel; whether any of the Company's product candidates will be shown to be effective, safe and reliable; and the other risks and uncertainties described in the Risk Factors section of Poseida's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on August 5, 2024, and in other filings Poseida makes with the SEC from time to time. All forward-looking statements contained in this press release speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. SOURCE Poseida Therapeutics, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

The promise of a one-and-done CRISPR infusion is beginning to look more real than ever. On Thursday, Intellia Therapeutics announced that an experimental gene editing therapy reduced dangerous and unpredictable swelling attacks caused by the disease hereditary angioedema. Hereditary angioedema can cause disfiguring or even fatal symptoms. But in the 27-person, Phase 2 study, patients who received the gene editing treatment saw the mean rate of monthly attacks fall by about 80%. And eight of 11 patients who got the mid-level dose of the drug have had zero attacks during a median follow-up of nine months since the infusion. “I was overwhelmed by the clinical response,” Danny Cohn, a doctor at Amsterdam University Medical Center who led the Phase 2 study, told Endpoints News in an interview. Cohn said the 10 patients treated at his hospital have all reported dramatic improvements. “These swellings can be disfiguring when the face is swollen, extremely painful when the intestines are swollen, or even fatal when the upper airways are involved,” he said. “So this has really been a game-changer.” The results, published in the New England Journal of Medicine , provide the first detailed look at a mid-stage study of a CRISPR therapy delivered to the liver using an infusion of lipid nanoparticles. Intellia is already recruiting for a larger 60-person Phase 3 study and aims to file for FDA approval in 2026. “Unless something changes, this will be the first in vivo CRISPR drug that’s approved,” Intellia CEO John Leonard told Endpoints News . So far, the CRISPR treatment seems safe. Intellia said that headache, fatigue and a common cold were the most frequent side effects. While the data are impressive, the roughly 80% reduction in attacks doesn’t look quite as high as the near-perfect results from a Phase 1 study which showed a remarkable 98% reduction through the latest data cutoff, with patients followed a median of 20 months. Cohn and Leonard both told Endpoints separately that they believe the lower response in the new Phase 2 study is likely due to patients not knowing if they got the CRISPR treatment or the placebo. Patients are taught to report signs of a potential swelling episode — which might manifest as a cramp, an itch, or a tingling sensation — and immediately take a drug to prevent a full-blown attack. In the earlier study, where everyone knew they got the treatment, patients may have been more likely to hold off on treating a potential attack. “What’s clear is the drug actively works. I mean, there’s no doubt about that,” Leonard said. Full relief from attacks, as the group of eight patients experienced, is not a result for patients that has been thought possible before, he said. Most people with hereditary angioedema have mutations in a gene for an enzyme called C1 esterase inhibitor. Proper functioning of that enzyme is needed to control another blood protein called kallikrein that kick-starts a process that causes inflammation, swelling and constriction of airways. Intellia’s therapy breaks the gene for kallikrein to prevent runaway swelling. The low dose reduced kallikrein levels in the blood by 55% and the medium dose reduced the protein by 86% at 16 weeks. “We are not targeting the gene that is causing the disease,” Cohn said. “But we are rebalancing the system by decreasing plasma kallikrein.” If the drug passes its next clinical trial, it will face competition from other therapies. Takeda’s commercial antibody Takhzyro also targets kallikrein. And Ionis is developing its own genetic medicine for the disease, a gene-silencing antisense oligonucleotide that reduced swelling attacks by 81% when taken every four weeks in a Phase 3 study. Ionis said in August that it was preparing to submit the drug to regulators. Leonard believes that Intellia’s one-and-done treatment will be an attractive alternative. “We think very quickly people will understand what’s possible and be very enthusiastic,” he said.