Scleroderma, Diffuse

Designations Follow Recent Investigational New Drug (IND) Application Clearance for the RESOLUTION Basket Study of ALLO-329 in Rheumatology Dual CD19/CD70 CAR T Specifically Designed to Enhance Therapeutic Benefit, Expanding Treatment Potential Across a Range of Autoimmune Indications Leverages Proprietary Dagger® Technology to Reduce or Eliminate Lymphodepletion, Potentially Expanding Access to a Broader Patient Population Phase 1 RESOLUTION Trial Initiation Planned for Mid-2025 with Initial Proof-of-Concept by Year-End 2025 April 07, 2025 -- Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T™) products for cancer and autoimmune disease, today announced that ALLO-329, an investigational dual-targeted CD19/CD70 allogeneic CAR T, has received three Fast Track Designations (FTD) from the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with: active refractory moderate-to-severe systemic lupus erythematous (SLE); active severe/refractory idiopathic inflammatory myopathy (IIM), specifically dermatomyositis, immune mediated necrotizing myopathy and anti-synthetase syndrome; and active refractory diffuse systemic sclerosis (SSc). "Receiving these designations for ALLO-329 underscores the versatility and transformative promise of this next-generation allogeneic CAR T investigational product in redefining the autoimmune treatment landscape," said Zachary Roberts, M.D., Ph.D., EVP of Research and Development and Chief Medical Officer of Allogene. "Leveraging our extensive expertise, we've developed this off-the-shelf CAR T specifically for autoimmune diseases, prioritizing both scalability and the reduction or elimination of lymphodepletion – a key barrier in this patient population." The Company expects to initiate the Phase 1 RESOLUTION basket trial in mid-2025. The trial is designed to evaluate the safety and preliminary efficacy of ALLO-329 in patients with SLE, IIM, and SSc. This innovative trial design, which leverages the clinically validated Dagger® technology to drive CAR T cell expansion and prevent rejection, includes two distinct lymphodepletion arms: one using a dose of cyclophosphamide alone, which is used by rheumatologists, and another that eliminates lymphodepletion entirely. Proof-of-concept from the RESOLUTION trial is expected by year-end 2025, aiming to provide critical insights into the potential of ALLO-329 to transform the treatment landscape for autoimmune diseases. FDA's Fast Track designation is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening diseases and that demonstrate the potential to address unmet medical needs. ALLO-329 is a CD19/CD70 dual AlloCAR T™ investigational product being developed for the treatment of autoimmune diseases. ALLO-329 utilizes CRISPR-based site-specific integration for dual CAR expression. This approach targets both CD19+ B cells and CD70+ T cells, which play a role in autoimmune disease pathogenesis. Additionally, ALLO-329 incorporates Allogene's clinically validated Dagger® technology, designed to reduce or eliminate the need for lymphodepletion, a pre-treatment regimen that may be a significant barrier to CAR T cell therapy adoption in autoimmune indications. Allogene Therapeutics, with headquarters in South San Francisco, is a clinical-stage biotechnology company pioneering the development of allogeneic chimeric antigen receptor T cell (AlloCAR T™) products for cancer and autoimmune disease. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of “off-the-shelf” CAR T cell product candidates with the goal of delivering readily available cell therapy on-demand, more reliably, and at greater scale to more patients. The content above comes from the network. if any infringement, please contact us to modify.

Sanofi is buying a B cell-depleting antibody developed by Dren Bio as a therapy for cancer and autoimmune diseases. The pharma said on Thursday that it will pay $600 million in cash upfront for the early-stage product, with a potential $1.3 billion to be handed over if the drug hits certain development and launch milestones. The asset in question, called DR-0201, was best known for its potential application in cancer, but Sanofi sees it as a step toward the company’s ambition to become a leader in immunology. The Dren Bio asset is in two Phase 1 trials: one in relapsed/refractory B cell non-Hodgkin lymphoma and another, newly started, in a range of autoimmune conditions. These include systemic and cutaneous lupus erythematosus and progressive systemic sclerosis. Both trials look likely to report data next year. DR-0201 is a CD20-directed bispecific intended to engage specific myeloid cells, prompting them to destroy B cells via phagocytosis. Sanofi said that deep B cell depletion might be able to reset the adaptive immune system, treating refractory B cell-mediated autoimmune diseases such as lupus. The drug has shown “robust” B cell depletion in early clinical studies, Sanofi said, and could work in patients who have not responded to other therapies. Dren has a more advanced asset, the anti-CD94 antibody it calls DR-01, designed to deplete cytotoxic cells including autoreactive CD8 T cells. That’s in a Phase 1/2 study in certain blood cancers, as well as an early-stage trial in alopecia and vitiligo. But DR-0201 is the most advanced product to have emerged from Dren’s myeloid engager and phagocytosis platform. Dren has done deals with pharma companies before, but never an outright sale and never for an asset this advanced. In 2022, it hooked Pfizer as a collaborator, gaining $25 million upfront and potential biobucks worth $1 billion. That deal centered on an unnamed discovery-stage bispecific for solid tumors. And last year it signed up Novartis , again for preclinical assets. That pact covered an undisclosed number of cancer candidates, with the upfront coming in at $150 million, including $25 million in equity, and milestones potentially totaling $2.85 billion. The Sanofi deal announced Thursday is structured as a company acquisition. The French company will buy a Dren Bio affiliate called Dren-0201; if regulators approve, the acquisition should close during the coming quarter. Dren Bio will remain independent.

Century Therapeutics has decided it\'s time to join a burgeoning trend, discarding a cancer trial to jump on the autoimmune bandwagon.\n Century Therapeutics has joined the onslaught of cell therapy biotechs taking hits, discontinuing a phase 1 cancer study to turn its focus toward autoimmune diseases.The move isn’t shocking, as it follows Century’s acquisition of autoimmune cell therapy biotech Clade Therapeutics last year and mirrors an industrywide pattern as numerous other companies turn from cancer to autoimmune.For Century, the change means ending a study of CNTY-101, the company’s first allogeneic cell therapy candidate that was being tested among patients with late-stage relapsed-refractory non-Hodgkin lymphoma, according to an annual financial report shared after market close March 19.The program, dubbed Elipse-1, launched in the beginning of 2023 and had an estimated enrollment of 75 patients, according to ClinicalTrials.gov. While Century called the therapy’s clinical activity and tolerability profile encouraging, the data didn’t meet the company’s standard to be considered “transformational” for the patient population, according to the release.The Philadelphia-based biotech said it was “committed to providing continued treatment access in the Elipse-1 trial for patients showing benefit.”Century is pointing to the Elipse-1 data as reason to move CNTY-101 into autoimmune diseases, citing deep B-cell depletion and evidence of the therapy trafficking to lymph nodes. The company plans to share more data from the trial later this year, it said in a statement.  The cell therapy company is now launching a new trial for its sole clinical asset, this time for patients with B-cell-mediated autoimmune diseases. The early-stage study, called Calipso-1, is slated to start dosing this month at U.S. sites, with plans to expand to certain European countries later this year.“We believe CNTY-101 is well-positioned to potentially impact the standard of care meaningfully in B-cell-mediated autoimmune diseases,” Century CEO Brent Pfeiffenberger said in the release.The company also expects further insights on the CD19 CAR-iNK cell therapy candidate to come from a phase 1/2 investigator-initiated clinical trial, dubbed Caramel.The study will be sponsored by the Friedrich-Alexander University Erlangen-Nürnberg in Germany and will enroll patients with systemic lupus erythematosus, lupus nephritis, idiopathic inflammatory myopathy and diffuse cutaneous systemic sclerosis. The study is expected to launch in mid-2025.Analysts with William Blair view the discontinuation as \"as unfortunate but necessary,\" citing a competitive treatment landscape for non-Hodgkin lymphoma in a March 20 note. Leerink Partners echoed the sentiment, citing a challenging financing environment for early-stage cell therapy companies. The analyst said it supported Century\'s decision to continue development of CNTY-101 in autoimmune diseases. Meanwhile, the biotech is prioritizing its preclinical pipeline to feature four programs, led by CNTY-308, a CD19-targeted CAR-iT cell therapy. The therapy is being developed for B-cell-mediated autoimmune diseases and malignancies.Another of Century’s candidates is CNTY-341, a CD19/CD22 dual-targeted CAR-iT cell therapy. The prioritized preclinical programs all use induced-pluripotent-stem-cell-derived “tunable” CD4+/CD8+ ab T cells, according to Century.“In the case of CNTY-308 and CNTY-341 in B-cell-mediated diseases, we are aiming for comparable or better performance to approved autologous CAR-T therapies,” Century Chief Scientific Officer Chad Cowan, Ph.D., said in the release. “With our combined expertise in protein engineering, cell differentiation and manufacturing, we aim to launch allogeneic cell therapies at antibody-like scale and cost. For our solid tumor and non-immune cell programs, this brings the potential to expand access to cell therapies much more broadly.”The company will host a live webcast April 22 to discuss each of the programs in more detail. The biotech’s pipeline pivot follows Bristol Myers Squibb’s own “portfolio prioritization efforts” that eliminated a pact with Century in December.Century had entered a collaboration with BMS back in 2022 in which the partners were working to develop stem-cell-derived, engineered natural killer cell and gamma delta T-cell candidates for blood cancers. The Big Pharma paid out $150 million in cash and an equity investment and offered up more than $3 billion in biobucks.After reviewing its own portfolio, BMS axed the entire deal “without cause,” a dissolution that became effective March 12.Century still lists two preclinical cancer candidates—named CNTY-104 and CNTY-106—that were being developed with BMS on its site.As of Dec. 31, 2024, Century had $220 million in cash and marketable securities, a runway expected to bring the biotech into the final quarter of 2026.  Editor\'s note: This story was updated at 10 a.m. ET on March 20 to include analyst commentary.