Adaptimmune LLC

On August 2, 2024, the Food and Drug Administration granted accelerated approval to afamitresgene autoleucel (TECELRA, Adaptimmune, LLC), a melanoma-associated antigen A4 (MAGE-A4)-directed genetically modified autologous T cell immunotherapy, for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive and whose tumor expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices. Full prescribing information for TECELRA will be posted at 2024 Biological License Application Approvals. Efficacy was evaluated in SPEARHEAD-1, Cohort 1, a multicenter, single-arm, open-label clinical trial that enrolled HLA-A*02:01-03 and 06 allele positive patients with inoperable or metastatic synovial sarcoma who had received prior systemic therapy with either doxorubicin and/or ifosfamide and whose tumor expressed the MAGE-A4 tumor antigen. Patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide. Fifty-two patients with synovial sarcoma were enrolled and underwent leukapheresis, eight of whom did not receive afamitresgene autoleucel due to death (n=3), loss of eligibility prior to lymphodepleting chemotherapy (n=3), withdrawal by patient (n=1), and investigator decision (n=1). Forty-five patients received lymphodepletion and one patient withdrew consent before treatment, for a total of 44 patients who received a single infusion of afamitresgene autoleucel. The main efficacy outcome measure was overall response rate (ORR) according to RECIST v1.1 evaluated by independent review, supported by duration of response (DOR). ORR was 43.2% (95% Confidence Interval [CI]: 28.4, 59.0). The median time to response was 4.9 weeks (95% CI: 4.4 weeks, 8 weeks). The median DOR was 6 months (95% CI: 4.6, not reached). Among patients who were responsive to the treatment, 45.6% and 39.0% had a duration of response greater than or equal to 6 months and 12 months, respectively. The prescribing information includes a Boxed Warning for serious or fatal cytokine release syndrome (CRS), which may be severe or life-threatening. The most common nonlaboratory adverse reactions (≥ 20%) were cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, abdominal pain, non-cardiac chest pain, decreased appetite, tachycardia, back pain, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities (≥ 20%) were lymphocyte count decreased, neutrophil count decreased, white cell blood count decreased, red blood cell decreased, and platelet count decreased. The recommended afamitresgene autoleucel dose is between 2.68 x 109 to 10 x 109 MAGE-A4 T cell receptor (TCR) positive T cells, administered in one or more infusion bags. Do not use a leukodepleting filter or prophylactic systemic corticosteroids. This application is approved under the accelerated approval pathway. To verify the clinical benefit of afamitresgene autoleucel, the FDA and the sponsor agreed upon a postmarketing requirement for an ongoing study in adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive and whose tumor expresses the MAGE-A4 antigen. This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Regenerative Medicine Advanced Therapy, priority review, and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088. For assistance with single-patient INDs for investigational oncology products regulated by the Center for Biologics Evaluation and Research, healthcare professionals may email OTPRPMS@fda.hhs.gov. Follow the Oncology Center of Excellence on X: @FDAOncologyExternal Link Disclaimer. Content current as of: 08/02/2024 Regulated Product(s) Drugs 08/02/2024 Drugs Resources for Information | Approved Drugs Oncology (Cancer)/Hematologic Malignancies Approval Notifications Ongoing | Cancer Accelerated Approvals Verified Clinical Benefit | Cancer Accelerated Approvals Withdrawn | Cancer Accelerated Approvals Other | Cancer Accelerated Approvals Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) Short Description Oncology (Cancer)/Hematologic Malignancies Approval Notifications Ongoing | Cancer Accelerated Approvals Verified Clinical Benefit | Cancer Accelerated Approvals Withdrawn | Cancer Accelerated Approvals Other | Cancer Accelerated Approvals Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) Short Description

SILVER SPRING, Md., Aug. 2, 2024 /PRNewswire/ -- Today, the U.S. Food and Drug Administration approved Tecelra (afamitresgene autoleucel), a gene therapy indicated for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA antigen(s) A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive, and whose tumor expresses the MAGE-A4 antigen as determined by FDA authorized companion diagnostic devices. Synovial sarcoma is a rare form of cancer in which malignant cells develop and form a tumor in soft tissues of the body. This type of cancer can occur in many parts of the body, most commonly developing in the extremities. The cancerous cells may also spread to other parts of the body. Each year, synovial sarcoma impacts about 1,000 people in the U.S. and most often occurs in adult males in their 30s or younger. Treatment typically involves surgery to remove the tumor and may also include radiotherapy and/or chemotherapy if the tumor is larger, returns after being removed or has spread beyond its original location. "Potentially life-threatening cancers such as synovial sarcoma continue to have a devastating impact on individuals, especially those for whom standard treatments have limited efficacy due to tumor growth and progression," said Peter Marks, M.D., Ph.D., director of the FDA's Center for Biologics Evaluation and Research (CBER). "The approval of this state-of-the-art immunotherapy technology provides a critical new option for a patient population in need and demonstrates the FDA's dedication to the advancement of beneficial cancer treatments." Tecelra is also the first FDA-approved T cell receptor (TCR) gene therapy. The product is an autologous T cell immunotherapy composed of a patient's own T cells. T cells in Tecelra are modified to express a TCR that targets MAGE-A4, an antigen (substance that normally triggers your immune system) expressed by cancer cells in synovial sarcoma. The product is administered as a single intravenous dose. Tecelra was approved using the Accelerated Approval pathway, under which the FDA may approve drugs for serious or life-threatening diseases or conditions where there is an unmet medical need and the drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients (improving how patients feel or function, or whether they survive longer). This pathway can allow earlier approval while the company conducts further trials to verify the predicted clinical benefit. A confirmatory trial is ongoing to verify Tecelra's clinical benefit. "Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence," said Nicole Verdun, M.D., director of the Office of Therapeutic Products in CBER. "Today's approval represents a significant milestone in the development of an innovative, safe and effective therapy for patients with this rare but potentially fatal disease." The safety and effectiveness of Tecelra was evaluated in a multicenter, open-label clinical trial including patients with inoperable and metastatic synovial sarcoma who had received prior systemic therapy and whose tumor expressed the MAGE-A4 tumor antigen. Effectiveness was evaluated based on overall response rate and the duration of response to treatment with Tecelra. Among the 44 patients in the trial who received Tecelra, the overall response rate was 43.2% and the median duration of response was six months. The most common adverse reactions associated with Tecelra included nausea, vomiting, fatigue, infections, fever, constipation, dyspnea (shortness of breath), abdominal pain, non-cardiac chest pain, decreased appetite, tachycardia (abnormally fast heart rate), back pain, hypotension, diarrhea and edema (swelling due to buildup of fluid in body tissues). Patients treated with Tecelra may experience cytokine release syndrome (CRS), which is a dangerous type of aggressive immune system response, including potentially life-threatening reactions. CRS was observed following administration of Tecelra during clinical trials. A Boxed Warning is included in the label containing information about this risk. Patients may also exhibit Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS), an immune system-related syndrome that can occur following some immunotherapies, infections, secondary malignancies, or hypersensitivity reactions, and severe cytopenia (an abnormally low level of blood cells) for several weeks following lymphodepleting chemotherapy and Tecelra infusion. Patients receiving this product should be monitored for signs and symptoms of infection and are advised not to drive or engage in hazardous occupations or activities for at least four weeks after receiving Tecelra. The FDA granted Tecelra Orphan Drug, Regenerative Medicine Advanced Therapy and Priority Review designations for this indication. This application was reviewed using a coordinated, cross-agency approach, including CBER, the FDA's Oncology Center of Excellence and the Center for Devices and Radiological Health. The FDA granted the approval of Tecelra to Adaptimmune, LLC. Media Contact: Carly (Kempler) Pflaum, (240) 672-8872 Consumer Inquiries: Email or 888-INFO-FDA The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, radiation-emitting electronic products, and for regulating tobacco products. SOURCE U.S. Food and Drug Administration

Highlighted significant research, preclinical advances and platform technology progress at third annual R&D Day Appointed Kristin Yarema, Ph.D., as President, Cell Therapy, adding extensive oncology and allogeneic T cell immunotherapy experience to the Company's leadership team SAN DIEGO, May 9, 2023 /PRNewswire/ -- Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage cell and gene therapy company advancing a new class of treatments for patients with cancer and rare diseases, today announced updates and financial results for the first quarter ended March 31, 2023. "In the first quarter, we continued to advance our clinical and research stage efforts as well as enhanced our leadership with the recent appointment of Kristin Yarema, Ph.D., as President, Cell Therapy," said Mark Gergen, Chief Executive Officer of the Company. "In our allogeneic CAR-T portfolio, we are actively enrolling patients in the Phase 1 studies for P-MUC1C-ALLO1 and P-BCMA-ALLO1 and remain on track for an IND for P-CD19CD20-ALLO1 mid-year. These initial allogeneic clinical programs are designed to evaluate many aspects of our unique high-TSCM allogeneic platform including dosing strategies, pre-conditioning regimens, potential biomarkers and many other factors. In our gene therapy portfolio, we are in discussions with Takeda about our collaboration following the news that they have made some strategic decisions in their research priorities and will update when appropriate. In the meantime, we remain excited about the strong progress made on all gene therapy programs and look forward to giving six preclinical presentations at the American Society of Gene and Cell Therapy annual meeting next week." Program Updates CAR-T Programs In cell therapy, the Company is focused on three allogeneic CAR-T programs with two programs currently progressing in Phase 1 clinical trials and one expected IND during the year: MUC1-C Program P-MUC1C-ALLO1 is an allogeneic CAR-T product candidate targeting solid tumors derived from epithelial cells, including breast and ovarian cancers. The Company is currently evaluating P-MUC1C-ALLO1 in a Phase 1 clinical trial and presented early clinical data in December 2022 at the European Society for Medical Oncology Immuno-Oncology 2022 Annual Congress (ESMO I-O) in Geneva, Switzerland. The Company currently expects to present further clinical updates for the program at a medical meeting in 2023. BCMA Program P-BCMA-ALLO1 is an allogeneic CAR-T product candidate being developed to target relapsed/refractory multiple myeloma (R/R MM) in partnership with Roche. The Company is currently evaluating P-BCMA-ALLO1 in a Phase 1 clinical trial and shared early clinical data from the program at ESMO I-O in December 2022. The Company currently expects to present further clinical updates for the program at a medical meeting in 2023, subject to clearance with Roche. CD19CD20 Program P-CD19CD20-ALLO1 is a preclinical allogeneic CAR-T product being developed to target B-cell malignancies in partnership with Roche. P-CD19CD20-ALLO1 is the Company's first dual CAR program and contains two fully functional CAR molecules to target cells that express either CD19 or CD20. The Company believes that by targeting both CD19 and CD20, there is potential to overcome potential antigen escape that has been observed by others. The Company expects to file an IND for P-CD19CD20-ALLO1 in mid-2023. Gene Therapy Programs The Company is advancing multiple preclinical gene therapy programs in liver-directed diseases: OTC Program P-OTC-101 is an in vivo program for the treatment of urea cycle disease caused by congenital mutations in the ornithine transcarbamylase (OTC) gene. The Company is developing the P-OTC-101 program utilizing a hybrid delivery system and working on an updated timeline for the program. The Company presented data at its R&D Day in February 2023, highlighting continued advancements in preclinical models leading towards a potential functional cure of OTC Deficiency. FVIII Program The Company is advancing its P-FVIII-101 preclinical program partnered with Takeda, which is in development for the in vivo treatment of Hemophilia A. P-FVIII-101 utilizes piggyBac gene modification delivered via lipid nanoparticle that has demonstrated stable and sustained Factor VIII expression in animal models. The Company is presenting preclinical data from this program at the upcoming American Society of Gene and Cell Therapy (ASGCT) 26th Annual Meeting being held in Los Angeles on May 16-20, 2023. PAH Program Announced at the Company's R&D Day in February 2023, P-PAH-101 is a liver-directed gene therapy partnered with Takeda to treat Phenylketonuria (PKU), an inherited genetic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene resulting in buildup of phenylalanine in the body. If left untreated, PKU can affect a person's cognitive development. P-PAH-101 utilizes piggyBac technology combined with its hybrid adeno-associated virus (AAV) and nanoparticle delivery system. The Company's preclinical data has demonstrated the potential to resolve phenylalanine to normal levels following a single treatment in juvenile and adult mice. P-PAH-101 is currently in preclinical development. Leadership Updates Kristin Yarema, Ph.D., Appointed President, Cell Therapy In April 2023, the Company announced the appointment of Kristin Yarema, Ph.D., as President, Cell Therapy, to lead the Company's drug development programs in cell therapy, including its collaboration with Roche. She joined the Company after most recently serving as Chief Commercial Officer at Atara Biotherapeutics, where she led the commercialization of EBVALLO™, which became the world's first marketed allogeneic T cell therapy after receiving regulatory approval in Europe for the treatment of a rare lymphoma. Prior to Atara, she held a series of U.S. and global commercial leadership roles at Amgen and Novartis in hematology-oncology among other therapeutic areas. Rafael G. Amado, M.D., Appointed to Board of Directors In April 2023, Rafael G. Amado, M.D., was appointed to the Company's Board of Directors. Dr. Amado is currently President, Head of Global Oncology Research and Development at Zai Lab, a public biopharmaceutical company. Prior to Zai Lab, Dr. Amado served as Executive Vice President, Head of Research and Development and Chief Medical Officer from September 2019 to December 2022 at Allogene Therapeutics, Inc. and President of Research and Development from August 2018 to August 2019 and Chief Medical Officer from March 2015 to August 2018 at Adaptimmune, LLC. Financial Results for the First Quarter 2023 "We continue to be disciplined on spend and evaluate plans and options to help us further manage our cash burn rate," said Johanna Mylet, Chief Financial Officer at Poseida. "We have been operating at the low end of our guided cash utilization range and our current base plan should allow us to preserve our runway into at least mid-2024, and possibly further depending on other decisions, including business development opportunities." Revenues Revenues were $10.3 million for the first quarter ended March 31, 2023, compared to $1.4 million for the same period in 2022. The increase of revenues was primarily due to revenues earned from the collaboration and license agreement with Roche, which became effective in the third quarter of 2022. Research and Development Expenses Research and development expenses were $38.1 million for the first quarter ended March 31, 2023, compared to $48.9 million for the same period in 2022. The decrease was primarily driven by the wind-down of the Company's clinical development activities associated with our autologous programs and related contract termination expense in the prior year and the transition of manufacturing to the Company's internal pilot plant for P-BCMA-ALLO1, partially offset by increases in the number of ongoing clinical trials, including enrollment and manufacturing for the P-MUC1C-ALLO1 and P-BCMA-ALLO1 Phase 1 clinical trials, and increases related to the Company's preclinical stage programs due to an increase in research collaboration activity and personnel and facilities expenses as a result of increased headcount. General and Administrative Expenses General and administrative expenses for the first quarter ended March 31, 2023 were $11.8 million compared to $9.5 million for the same period in 2022. The increase was primarily related to an increase in stock-based compensation expense due to a one-time modification associated with the retirement of the Company's former Executive Chairman. Net Loss Net loss was $38.8 million for the first quarter ended March 31, 2023, compared to $58.1 million for the same period of 2022. Cash Position As of March 31, 2023, the Company's cash, cash equivalents and short-term investments balance was $247.2 million. The Company expects that its cash, cash equivalents and short-term investments together with the remaining near-term milestones and other payments from Roche will continue to be sufficient to fund operations into at least mid-2024. About Poseida Therapeutics, Inc. Poseida Therapeutics is a clinical-stage biopharmaceutical company advancing differentiated cell and gene therapies with the capacity to cure certain cancers and rare diseases. The Company's pipeline includes allogeneic CAR-T cell therapy product candidates for both solid and liquid tumors as well as in vivo gene therapy product candidates that address patient populations with high unmet medical need. The Company's approach to cell and gene therapies is based on its proprietary genetic editing platforms, including its non-viral piggyBac® DNA Delivery System, Cas-CLOVER™ Site-Specific Gene Editing System and nanoparticle and hybrid gene delivery technologies. The Company has formed global strategic collaborations with Roche and Takeda to unlock the promise of cell and gene therapies for patients. Learn more at and connect with Poseida on Twitter 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, expected plans with respect to clinical trials, including timing of regulatory submissions and approvals and clinical data updates; potential fees, milestones and other payments that the Company may receive pursuant to its collaboration agreements; anticipated timelines and milestones with respect to the Company's development programs and manufacturing activities and capabilities; the potential capabilities and benefits of the Company's technology platforms and product candidates; estimates of the Company's cash balance, expenses, capital requirements, any future revenue, and need for additional financing; the Company's ability to attract and/or retain new and existing collaborators with relevant expertise and its expectations regarding the potential benefits to be derived from any such collaborations; 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 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; the fact that the Company will have limited control over the efforts and resources that its strategic partners devote to advancing development programs under their respective collaboration agreements and the Company may not receive the potential fees and payments under the collaboration agreements and the ability of its strategic partners to early terminate the collaborations, such that the Company may not fully realize the benefits of such collaborations; and the other risks described in the Company's filings with the Securities and Exchange Commission. 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.