Methylprednisolone

27-year-old African American-Asian Woman with Active Lupus Nephritis Achieved DORIS Clinical Remission; Patient Remains On-study, in Clinical Remission, and Free of All Immunosuppressive Therapies Patient Treated with Fludarabine-free Conditioning and Single-dose FT819; Favorable Safety Profile with No Grade ≥3 Adverse Events and No Events of CRS, ICANS, or GvHD Reconstituted B Cell Compartment Predominantly Consists of Naïve, Non-class Switched B Cells with Deep Depletion of Aberrant B Cells and Plasmablasts, Indicative of Immune Reset Second Treatment Arm Adding FT819 to Maintenance Therapy without Conditioning Chemotherapy Opened for Enrollment SAN DIEGO, Nov. 18, 2024 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune disorders, today presented initial clinical and translational data from the first patient treated in its FT819 Phase 1 Autoimmunity study for moderate-to-severe systemic lupus erythematosus (SLE) at the American College of Rheumatology (ACR) Convergence being held in Washington, D.C. The patient, a 27-year-old African American-Asian woman diagnosed with lupus nephritis (LN) over ten years ago, received fludarabine-free conditioning followed by a single dose of FT819. The patient achieved DORIS (definition of remission in SLE) clinical remission and LLDAS (low lupus disease activity state) as of Month 6 follow-up. The patient continues on-study, in clinical remission, and free of all immunosuppressive therapies as of a data cutoff date of November 11, 2024. FT819 is the Company’s off-the-shelf, CD19-targeted, 1XX CAR T-cell product candidate comprised of CD8αβ+ T cells with a memory phenotype and high CXCR4 expression to promote tissue trafficking. “These initial results are incredibly promising. Our patient not only went into drug-free clinical remission but also had resolution of fatigue, something that we as rheumatologists struggle to improve with our treatments,” said Jennifer Medlin, M.D., and Principal Investigator at the University of Nebraska Medical Center. “If we continue to see similar results in other patients with an acceptable safety profile, off-the-shelf CAR T-cell therapy could be a complete game-changer for our sickest lupus patients. This gives me hope for a future where we can make a great impact on these patients with devastating disease.” Patient 1 Case Study The patient presented with active LN and severe disease, which was marked by renal BILAG A (British Isles Lupus Assessment Group) disease activity score based on biopsy, SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index) score of 20, FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) score of 33 (range 0-52, where a score of 52 indicates no fatigue) and PGA (Physician Global Assessment) score of 2.5 (where a score of 3 indicates most severe activity). Following administration of fludarabine-free conditioning and treatment with a single dose of FT819 at 360 million cells, the patient was discharged from the hospital without notable adverse events (AEs) after a protocol-required three-day stay. As of the data cutoff date, the patient has experienced no Grade ≥3 AEs, no serious adverse events (SAEs), and no events of any grade of cytokine release syndrome (CRS), immune effector-cell associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD). The patient reported that her debilitating fatigue had entirely resolved without further treatment, and treatment with methylprednisolone was discontinued at Month 3. The patient achieved DORIS clinical remission, including with resolution of arthritis and active urinary sediment and with a substantial reduction in proteinuria, as of Month 6 follow-up. As of the data cutoff date, the patient continues in DORIS clinical remission and remains free of all immunosuppressive therapy. Rapid elimination of CD19+ B cells in the periphery was observed following fludarabine-free conditioning and treatment with a single dose of FT819. B-cell recovery by Month 3 was predominantly comprised of naïve, non-class switched B cells with near-complete elimination of switched memory B cells and deep depletion of plasmablasts, indicative of an immune reset. Notably, the unique double-negative (DN) B-cell subset, previously described and associated with severe SLE, was nearly eliminated. “These seminal data with fludarabine-free conditioning and off-the-shelf CAR T-cell therapy in autoimmunity are exciting, and we are very pleased that the first patient with active lupus nephritis had a favorable clinical experience, achieved drug-free clinical remission, and continues on-study free of all immunosuppressive therapy,” said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. “We believe our highly-differentiated therapeutic approach has the potential to transform outcomes for patients with autoimmune diseases without requiring patient apheresis, discontinuation of maintenance therapy, intense conditioning chemotherapy, and extended hospitalization.” FT819 Phase 1 Autoimmunity Study The ongoing multi-center, Phase 1 clinical trial for patients with moderate-to-severe SLE is designed to evaluate the safety, pharmacokinetics, and anti-B cell activity of FT819 (NCT06308978). The first three patients, all of whom presented with active LN despite having been treated with multiple standard-of-care therapies, received fludarabine-free conditioning consisting of either cyclophosphamide alone or bendamustine alone, followed by a single dose of FT819 at 360 million cells. All three patients remain on-study, and there have been no dose-limiting toxicities (DLTs) and no events of any grade of CRS, ICANS, or GvHD. The Company plans to present clinical and translational data from the first three patients at the American Society of Hematology (ASH) Annual Meeting being held in San Diego, CA on December 7-10. The Company is also enrolling a second treatment arm under the FT819 Phase 1 Autoimmunity study to assess the safety, pharmacokinetics, and anti-B cell activity of a single dose of FT819 as an add-on to maintenance therapy without conditioning chemotherapy in patients with SLE. This new arm is being conducted in parallel with the study’s conditioning arm. About Fate Therapeutics’ iPSC Product Platform Human induced pluripotent stem cells (iPSCs) possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s proprietary iPSC product platform combines multiplexed-engineering of human iPSCs with single-cell selection to create clonal master iPSC lines. Analogous to master cell lines used to mass produce biopharmaceutical drug products such as monoclonal antibodies, the Company utilizes its clonal master iPSC lines as a starting cell source to manufacture engineered cell products which are well-defined and uniform in composition, can be stored in inventory for off-the-shelf availability, can be combined and administered with other therapies, and can potentially reach a broad patient population. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the manufacture of cell therapies using patient- or donor-sourced cells. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 500 issued patents and 500 pending patent applications. About Fate Therapeutics, Inc. Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune diseases. Using its proprietary iPSC product platform, the Company has established a leadership position in creating multiplexed-engineered master iPSC lines and in the manufacture and clinical development of off-the-shelf, iPSC-derived cell products. The Company’s pipeline includes iPSC-derived natural killer (NK) cell and T-cell product candidates, which are selectively designed, incorporate novel synthetic controls of cell function, and are intended to deliver multiple therapeutic mechanisms to patients. Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit www.fatetherapeutics.com. Forward-Looking Statements This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the safety and therapeutic potential of the Company’s iPSC-derived CAR T-cell product candidates, including FT819, the advancement of and plans related to the Company's product candidates, clinical studies and preclinical research and development programs, the Company’s progress, plans and timelines for the clinical investigation of its product candidates, including the expected clinical development plans for FT819, the initiation and continuation of enrollment in the Company’s clinical trials, the initiation of additional clinical trials and additional dose cohorts in ongoing clinical trials of the Company’s product candidates, the timing and availability of data from the Company’s clinical trials, the therapeutic and market potential of the Company’s research and development programs and product candidates, the Company’s clinical and product development strategy, and the Company’s expectations regarding progress, plans, and timelines. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that the Company’s research and development programs and product candidates, including those product candidates in clinical investigation, may not demonstrate the requisite safety, efficacy, or other attributes to warrant further development or to achieve regulatory approval, the risk that results observed in prior studies of the Company’s product candidates, including preclinical studies and clinical trials, will not be observed in ongoing or future studies involving these product candidates, the risk of a delay or difficulties in the initiation and conduct of, or enrollment of patients in, any clinical trials, the risk that the Company may cease or delay preclinical or clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials, changes in the therapeutic, regulatory, or competitive landscape for which the Company’s product candidates are being developed, the amount and type of data to be generated or otherwise to support regulatory approval, difficulties or delays in patient enrollment and continuation in the Company’s ongoing and planned clinical trials, difficulties or delays in manufacturing or supplying the Company’s product candidates for clinical testing, failure to demonstrate that a product candidate has the requisite safety, efficacy, or other attributes to warrant further development, and any adverse events or other negative results that may be observed during preclinical or clinical development), and the risk that its product candidates may not produce therapeutic benefits or may cause other unanticipated adverse effects. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Company’s periodic filings with the Securities and Exchange Commission, including but not limited to the Company’s most recently filed periodic report, and from time to time in the Company’s press releases and other investor communications. Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise. Contact: Christina Tartaglia Precision AQ 212.362.1200 christina.tartaglia@precisionaq.com Source: Fate Therapeutics, Inc.

-- Poster to be presented at ACR Convergence annual meeting --PARSIPPANY, N.J., Nov. 14, 2024 (GLOBE NEWSWIRE) -- Pacira BioSciences, Inc. (NASDAQ: PCRX), the industry leader in the delivery of innovative, non-opioid pain therapies to transform the lives of patients, today announced new data demonstrating its gene therapy for osteoarthritis candidate, PCRX-201 (enekinragene inzadenovec), provided sustained improvements in knee pain, stiffness, and function to 104 weeks following local administration, with a well-tolerated safety profile. The data, which indicate a potential for sustained clinical efficacy in patients with moderate to severe osteoarthritis of the knee (OAK), will be presented during a poster session at the American College of Rheumatology’s annual ACR Convergence meeting on Sunday, November 17 from 10:30 am – 12:30 pm EST. “The results of this large phase 1 study demonstrate durable pain relief across all levels of disease severity for at least 2 years following a single injection. This is promising, considering traditional pain management interventions provide an average of three to six months of effect,” said Stanley Cohen, MD, a board-certified rheumatologist and Co-Medical Director of the Metroplex Clinical Research Center in Dallas, TX, who was lead investigator in this trial and primary author on the poster presentation. “Unlike other treatments that temporarily alleviate symptoms, PCRX-201 addresses a root cause of osteoarthritis knee pain—inflammation—to help control patients’ pain for years rather than months.” The new data is derived from an open-label, phase 1 trial investigating the safety and efficacy of PCRX-201 administered via ultrasound-guided intraarticular injection in 72 patients with OAK graded at 2, 3, or 4 on the Kellgren-Lawrence scale, a semiquantitative method for evaluating the severity of osteoarthritis on a scale of 0-4. Participants were broken into two cohorts. The first cohort received one of three doses of PCRX-201. The second cohort received concurrent pretreatment with an intraarticular corticosteroid (methylprednisolone 40 mg), a technique common in gene therapy dosing to improve tolerability and gene transfer. Pain and function benefits were observed at all doses and across both cohorts over the full 104 weeks studied, with patients in the second cohort achieving greater pain reduction and fewer adverse events (AEs). Additional results in the pretreated cohort, across all doses, include: 48%-65% improvement in pain from baseline, as measured by the Western Ontario and McMaster Universities Arthritis Index-A (WOMAC-A)53%-72% improvement in stiffness from baseline, as measured by WOMAC-B Improvements in function from baseline, as measured by the Knee Injury and Osteoarthritis Outcome Score (KOOS) Activities of Daily Living (ADL) scale, that were similar to improvements in WOMAC-A and WOMAC-B By 16 weeks more than 70% of participants achieved greater than 50% reductions from baseline pain. No serious treatment-emergent AEs related to the treatment or procedure were reported regardless of steroid pretreatment or dose level administered. Treatment-related joint effusions (swelling) were the most common AE, occurring in 36% of patients who received steroid pretreatment vs 61% of patients who were not pretreated. The majority of effusions were mild to moderate in severity and resolved in a median of 33 days among patients in the pretreated group. “We look forward to continuing to advance the clinical investigation of PCRX-201 following these promising results, with a Phase 2, double-blind, active-controlled study planned for 2025,” said Frank D. Lee, chief executive officer of Pacira BioSciences. “Unlike traditional gene therapies, which are administered systemically and have primarily been limited to the treatment of rare diseases, we believe PCRX-201 holds the broad potential to provide a long-term pain management solution for the 14 million U.S. patients suffering from the negative impacts of osteoarthritis of the knee. With a local administration that delivers relief directly to the source—the knee joint capsule—PCRX-201 is on the leading edge of what could be possible for gene therapies and offers patients the hope for a long-lasting pain management solution that improves their ability to comfortably engage in activities of daily living, like climbing stairs and exercising.” PCRX-201 is a locally administered gene therapy, designed to produce interleukin-1 receptor antagonist (IL-1Ra), a naturally occurring, anti-inflammatory protein with a proven mechanism of action that reduces interleukin-1 (IL-1) signaling, a known factor in the development and progression of osteoarthritis of the knee. Unlike systemically administered gene therapies, PCRX-201 delivers the medicine where it matters to reduce pain and disability and potentially slow structural progression at the site of the disease. PCRX-201 uses an inducible promoter to mimic the body’s natural response to inflammation by “turning on” the expression of IL-1Ra when inflammation is present in the joint and turning off IL-1Ra expression once inflammation is quelled. In March 2024, PCRX-201 became the first-ever gene therapy product candidate in osteoarthritis to receive Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration (FDA). RMAT designation provides the benefits of intensive FDA guidance on efficient drug development, including the ability for early interactions with the FDA to discuss surrogate or intermediate endpoints, potential ways to support accelerated approval and satisfy post-approval requirements, potential priority review of the Biologics License Application (BLA), and other opportunities to expedite development and review. PCRX-201 was also granted Advanced Therapy Medicinal Products (ATMP) designation by the European Medicines Agency in May 2023. About Pacira BioSciencesPacira BioSciences delivers innovative, non-opioid pain therapies to transform the lives of patients. Pacira has three commercial-stage non-opioid treatments: EXPAREL® (bupivacaine liposome injectable suspension), a long-acting local analgesic currently approved for infiltration, fascial plane block, interscalene brachial plexus nerve block in adults, sciatic nerve block in the popliteal fossa in adults, and adductor canal block in adults for postsurgical pain management; ZILRETTA® (triamcinolone acetonide extended-release injectable suspension), an extended-release, intra-articular injection indicated for the management of osteoarthritis knee pain; and ioveraº®, a novel, handheld device for delivering immediate, long-acting, drug-free pain control using precise, controlled doses of cold temperature to a targeted nerve. The company is also advancing the development of PCRX-201, a novel locally administered gene therapy with the potential to treat large prevalent diseases like osteoarthritis. To learn more about Pacira, visit www.pacira.com. Forward-Looking StatementsAny statements in this press release about Pacira’s future expectations, plans, trends, outlook, projections and prospects, and other statements containing the words “anticipate,” “believe,” “can,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “project,” “should,” “will,” “would,” and similar expressions, constitute forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), and the Private Securities Litigation Reform Act of 1995, including, without limitation, statements related to our future outlook, our intellectual property and patent terms, our growth and future operating results and trends, our strategy, plans, objectives, expectations (financial or otherwise) and intentions, future financial results and growth potential, including our plans with respect to the repayment of our indebtedness, anticipated product portfolio, development programs, development of products, strategic alliances, plans with respect to the Non-Opioids Prevent Addiction in the Nation (“NOPAIN”) Act and other statements that are not historical facts. For this purpose, any statement that is not a statement of historical fact should be considered a forward-looking statement. We cannot assure you that our estimates, assumptions and expectations will prove to have been correct. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including risks relating to, among others: the integration of our new chief executive officer; risks associated with acquisitions, such as the risk that the acquired businesses will not be integrated successfully, that such integration may be more difficult, time-consuming or costly than expected or that the expected benefits of the transaction will not occur; our manufacturing and supply chain, global and U.S. economic conditions (including inflation and rising interest rates), and our business, including our revenues, financial condition, cash flow and results of operations; the success of our sales and manufacturing efforts in support of the commercialization of EXPAREL, ZILRETTA and iovera°; the rate and degree of market acceptance of EXPAREL, ZILRETTA and iovera°; the size and growth of the potential markets for EXPAREL, ZILRETTA and iovera° and our ability to serve those markets; our plans to expand the use of EXPAREL, ZILRETTA and iovera° to additional indications and opportunities, and the timing and success of any related clinical trials for EXPAREL, ZILRETTA and iovera°; the commercial success of EXPAREL, ZILRETTA and iovera°; the related timing and success of U.S. Food and Drug Administration supplemental New Drug Applications and premarket notification 510(k)s; the related timing and success of European Medicines Agency Marketing Authorization Applications; our plans to evaluate, develop and pursue additional product candidates utilizing our proprietary multivesicular liposome (“pMVL”) drug delivery technology; the approval of the commercialization of our products in other jurisdictions; clinical trials in support of an existing or potential pMVL-based product; our commercialization and marketing capabilities; our ability to successfully complete capital projects; the outcome of any litigation; the ability to successfully integrate any future acquisitions into our existing business; the recoverability of our deferred tax assets; assumptions associated with contingent consideration payments; assumptions used for estimated future cash flows associated with determining the fair value of the Company; the anticipated funding or benefits of our share repurchase program; and factors discussed in the “Risk Factors” of our most recent Annual Report on Form 10-K and in other filings that we periodically make with the Securities and Exchange Commission (the “SEC”). In addition, the forward-looking statements included in this press release represent our views as of the date of this press release. Important factors could cause actual results to differ materially from those indicated or implied by forward-looking statements, and as such we anticipate that subsequent events and developments will cause our views to change. Except as required by applicable law, we undertake no intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, and readers should not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this press release.