CD3ζ

THOUSAND OAKS, Calif.--( BUSINESS WIRE )-- Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leader in T-cell immunotherapy, leveraging its novel allogeneic Epstein-Barr virus (EBV) T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, today reported financial results for the second quarter 2024, recent business highlights, and key upcoming milestones for 2024. “ Building on the recent BLA acceptance with Priority Review for tab-cel, we are making significant progress with the agency towards the target action date of January 15, 2025, while supporting our partner Pierre Fabre with their U.S. launch preparation,” said Pascal Touchon, President and Chief Executive Officer of Atara. “ During the quarter we continued to advance the clinical development of our lead CAR T program, ATA3219, and remain on track to deliver key value creating milestones within the next 12 months. This is highlighted by initial data from our non-Hodgkin’s lymphoma study anticipated in the first quarter of 2025, which we believe will provide a read-through for ATA3219’s potential in autoimmune disease. On that front, we plan to initiate our ATA3219 Systemic Lupus Erythematosus trial in the fourth quarter, including the cohort without lymphodepletion, with initial data expected in mid-2025.” Dr. Touchon continued, “ Following the landmark milestone of the world’s first-ever approval of an allogeneic T-cell therapy and with the potential first U.S. approval approaching, we are advancing our differentiated allogeneic CAR-T programs into the clinic. With the Company in a strong position, I have decided to move into the role of Chairman for personal reasons to dedicate more time to my family. I look forward to having a very active and strategic advisory role as board chair and continuing to help Atara create value with the potential tab-cel U.S. approval and initial clinical data with ATA3219. I believe the future of Atara is bright under the leadership of Cokey Nguyen, Ph.D. who will be promoted to the role of President and CEO. Cokey is a visionary leader in the cell therapy field, and our Board of Directors values his deep commitment to our staff and to patients as well as his expertise across the breadth of our business.” “ I admire the strong foundation we built under Pascal’s leadership. I am honored to serve as Atara’s CEO at this pivotal time to continue our journey to get tab-cel approved in the U.S. and to unlock the disruptive potential of our allogeneic CAR-T platform,” said Cokey Nguyen, Ph.D. “ I look forward to working alongside our world-class and innovative teams to rapidly innovate and strive to develop better cell therapy treatment options for patients.” Tabelecleucel (tab-cel ® or Ebvallo ™ ) for Post-Transplant Lymphoproliferative Disease (PTLD) U.S. Food and Drug Administration (FDA) accepted the filing of Atara’s Biologics License Application (BLA) for tabelecleucel (tab-cel ® ) indicated as monotherapy for treatment of adult and pediatric patients two years of age and older with Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD) who have received at least one prior therapy. For solid organ transplant patients, prior therapy includes chemotherapy unless chemotherapy is inappropriate The BLA has been granted Priority Review with a Prescription Drug User Fee Act (PDUFA) target action date of January 15, 2025 The data package for the filing includes pivotal and supportive data covering more than 430 patients treated with tab-cel across multiple life-threatening diseases The BLA submission is supported by the latest pivotal ALLELE study data-cut that demonstrated a statistically significant 48.8% Objective Response Rate (ORR) (p<0.0001) and favorable safety profile consistent with previous analyses Atara received a $20 million milestone payment from Pierre Fabre Laboratories in August 2024, following the acceptance of the tab-cel BLA, with the potential to receive a $60 million milestone payment from Pierre Fabre contingent upon FDA approval of the tab-cel BLA ATA3219: CD19 Program in Lupus Nephritis (LN) Atara expects to initiate a Phase 1 study of ATA3219 as a monotherapy for the treatment of systemic lupus erythematosus (SLE) with kidney involvement (lupus nephritis [LN]) in Q4 2024 with initial clinical data anticipated in mid-2025 The Phase 1 open-label, dose-escalation study is designed to evaluate safety, preliminary efficacy, pharmacokinetics, and biomarkers of a single dose of ATA3219 administered to LN subjects refractory to one or more lines of treatment. Subjects will receive lymphodepletion treatment followed by ATA3219 at a dose of 40, 80, or 160 x 10 6 CAR+ T cells. Each dose level is designed to enroll 3-6 subjects Atara is positioned to potentially expand ATA3219 Phase 1 study into additional autoimmune indications via the same Investigational New Drug (IND) application previously cleared for the LN study Preclinical data supporting the potential of ATA3219 in SLE was presented in poster presentation at the International Society for Cell & Gene Therapy meeting. The data demonstrated that ATA3219 CAR T cells led to complete CD19-specific B-cell depletion against SLE or multiple sclerosis patient peripheral blood mononuclear cells Additional preclinical data presented in the poster showed that ATA3219 CAR T cells, which incorporate the next-generation 1XX costimulatory domain, released lower levels of pro-inflammatory cytokines while maintaining cytotoxic function and potency in response to stimulation with CD19+ target cells when compared to autologous CAR T controls. Mitigating inflammatory cytokine release that is typically seen with standard CD19 CAR T signaling may lead to reduced toxicity and better tolerability if confirmed in clinical trials ATA3219: CD19 Program in Severe Systemic Lupus Erythematosus (SLE) Without Lymphodepletion Atara plans to expand the Phase 1 LN study of ATA3219 and add a new cohort in severe SLE without lymphodepletion (LD) in Q4 2024 with initial clinical data anticipated in mid-2025 Eligible subjects with severe SLE will receive ATA3219 at a dose of 40, 80, or 240 × 10 6 CAR+ T cells The elimination of LD is designed to further simplify the treatment regimen and to potentially provide a differentiated safety profile to patients without comprising efficacy which may improve patient access There is compelling clinical and scientific rationale supporting the potential to eliminate the need for LD based on the EBV T-cell backbone and unique features of ATA3219, including: 1) low alloreactivity risk and favorable safety in over 600 patients treated without LD, due to T-cell receptor EBV specificity and partial human leukocyte antigen matching; 2) expansion and persistence data without LD correlating to efficacy in patients treated with tab-cel; and 3) the inclusion of clinically validated features into ATA3219 such as the 1XX costimulatory domain and memory phenotype that increase potency and persistence ATA3219: CD19 Program in Non-Hodgkin’s Lymphoma (NHL) Atara continues opening sites and initiating enrollment of a multi-center, Phase 1 open-label, dose-escalation clinical trial of ATA3219 in NHL, including large B-cell lymphomas, follicular lymphoma, and mantle cell lymphoma, with initial clinical data anticipated in Q1 2025 Study designed to evaluate safety, preliminary efficacy, pharmacokinetics, and biomarkers. Subjects will receive LD treatment followed by ATA3219 at a dose of 40, 80, 240, or 480 x 10 6 CAR+ T cells. Each dose level is designed to enroll 3-6 patients Previously presented preclinical data demonstrated superior in vivo persistence and CD19-specific anti-tumor efficacy compared to an autologous CD19 CAR T benchmark with no observed toxicity or alloreactivity ATA3431 : CD19/CD20 Program for B-Cell Malignancies Preclinical data presented at ASH 2023 demonstrated early evidence of potent antitumor activity, long-term persistence, and superior tumor growth inhibition compared to an autologous CD19/CD20 CAR T benchmark Dual CD19 and CD20 targeting designed to address CD19 escape and tumor variability and may provide additional efficacy in lymphoma Atara is progressing toward an IND submission in H2 2025 Leadership Updates Effective September 9, 2024: Cokey Nguyen, Ph.D., the Company's current Chief Scientific and Technical Officer, will be promoted to the role of President and CEO and Pascal Touchon, the Company's current President and CEO, will transition to the role of Chairman of the Board of Directors Cokey Nguyen, Ph.D., will be appointed to the Company’s Board of Directors Carol Gallagher, Pharm.D., current Chair of the Board, will transition to become Independent Lead Director Second Quarter 2024 Financial Results Cash, cash equivalents and short-term investments as of June 30, 2024 totaled $35.3 million, as compared to $46.2 million as of March 31, 2024 Q2 2024 accounts receivable totaled $2.4 million; however, this amount does not include the $20 million milestone payment owed by Pierre Fabre related to the tab-cel BLA acceptance, which was received in August 2024 On August 9, 2024, Pierre Fabre and Atara entered into an agreement for Pierre Fabre to purchase certain existing tab-cel intermediate inventory from Atara for $15.5 million, which is expected to be received from Pierre Fabre in September 2024 Together, cash, cash equivalents, short-term investments, accounts receivable as of June 30, 2024, the $20 million tab-cel BLA acceptance milestone payment, and the $15.5 million tab-cel intermediate inventory purchase amount total $73.2 million Net cash used in operating activities was $10.6 million for the second quarter 2024, as compared to $52.8 million in the same period in 2023 Q2 2024 net cash used in operating activities included a $20 million cash payment received from Pierre Fabre for a milestone payment achieved in March 2024, whereas Q2 2023 had no such cash receipts Total revenues were $28.6 million for the second quarter 2024, as compared to $1.0 million for the same period in 2023. Total revenues increased by $27.6 million year over year, primarily due to revenue recognized as a result of additional obligations for the expanded partnership with Pierre Fabre and accelerated recognition of existing deferred revenue due to the planned transition of substantially all activities relating to tab-cel at the time of BLA approval and transfer to Pierre Fabre Total costs and operating expenses include non-cash stock-based compensation, depreciation and amortization expenses of $7.7 million for the second quarter 2024, as compared to $13.8 million for the same period in 2023 Research and development expenses were $33.3 million for the second quarter 2024, as compared to $56.1 million for the same period in 2023 Research and development expenses include $3.3 million of non-cash stock-based compensation expenses for the second quarter 2024, as compared to $7.2 million for the same period in 2023 General and administrative expenses were $8.9 million for the second quarter 2024, as compared to $13.3 million for the same period in 2023 General and administrative expenses include $3.0 million of non-cash stock-based compensation expenses for the second quarter 2024, as compared to $5.4 million for the same period in 2023 Atara reported net losses of $19.0 million, or $3.10 per share, for the second quarter 2024, as compared to $71.1 million, or $16.91 per share, for the same period in 2023 2024 Outlook and Cash Runway Atara expects full year 2024 operating expenses to decrease by approximately 35% from 2023 The large majority of the year-over-year operating expense reduction began in Q2 2024 and is expected to continue for the remainder of the year Atara expects that cash, cash equivalents, short-term investments, and accounts receivable as of June 30, 2024, plus the items noted below, in total will enable funding of planned operations into 2027: $20 million milestone payment for the acceptance of the tab-cel BLA received from Pierre Fabre in August 2024 and $60 million contingent upon the approval of the tab-cel BLA; $15.5 million purchase by Pierre Fabre of tab-cel intermediate inventory to be received in September 2024 and additional anticipated purchases of tab-cel inventory through the manufacturing transfer date by Pierre Fabre; anticipated reimbursement for tab-cel global development costs through the BLA transfer by Pierre Fabre; operating efficiencies resulting from completed workforce reductions; the planned transition of substantially all activities relating to tab-cel at the time of the BLA transfer to Pierre Fabre potentially as early as Q1 2025, which will further reduce quarterly operating expenses; and anticipated royalties from sales of tab-cel by Pierre Fabre in the U.S. post BLA approval About ATA3219 ATA3219 combines the natural biology of unedited T cells with the benefits of an allogeneic therapy. It consists of allogeneic Epstein-Barr virus (EBV)-sensitized T cells that express a CD19 CAR construct for the treatment of CD19+ relapsed or refractory B-cell malignancies, including B-cell non-Hodgkin’s lymphoma and B-cell mediated autoimmune diseases including systemic lupus erythematosus. ATA3219 has been optimized to offer a potential best-in-class profile, featuring off-the-shelf availability. It incorporates multiple clinically validated technologies including a modified CD3ζ signaling domain (1XX) that optimizes expansion and mitigates exhaustion, enrichment during manufacturing for a less differentiated phenotype for robust expansion and persistence and retains the endogenous T-cell receptor without gene editing as a key survival signal for T cells contributing to persistence. About ATA3431 ATA3431 is an allogeneic, bispecific CAR directed against CD20 and CD19, built on Atara’s EBV T-cell platform. The design consists of a tandem CD20-CD19 design, with binders oriented to optimize potency. Dual targets address the limitations of single antigen loss and tumor variability. ATA3431 features a novel 1XX costimulatory domain, memory phenotype, and retained, unedited T-cell receptor. Preclinical data have demonstrated early evidence of antitumor activity, long-term persistence, and superior tumor growth inhibition compared to an autologous CD19/CD20 CAR T benchmark. Next-Generation Allogeneic CAR T Approach Atara is focused on applying Epstein-Barr virus (EBV) T-cell biology, featuring experience in over 600 patients treated with allogeneic EBV T cells, and novel chimeric antigen receptor (CAR) technologies to meet the current limitations of autologous and allogeneic CAR therapies head-on by advancing a potential best-in-class CAR T pipeline in oncology and autoimmune disease. Unlike gene-edited approaches aimed at inactivating T-cell receptor (TCR) function to reduce the risk for graft-vs-host disease, Atara’s allogeneic platform maintains expression of the native EBV TCR that promote in vivo functional persistence while also demonstrating inherently low alloreactivity due to their recognition of defined viral antigens and partial human leukocyte antigen (HLA) matching. A molecular toolkit of clinically-validated technologies—including the 1XX costimulatory domain designed for better cell fitness and less exhaustion while maintaining stemness—offers a differentiated approach to addressing significant unmet need with the next generation CAR T. About Atara Biotherapeutics, Inc. Atara is harnessing the natural power of the immune system to develop off-the-shelf cell therapies for difficult-to-treat cancers and autoimmune conditions that can be rapidly delivered to patients from inventory. With cutting-edge science and differentiated approach, Atara is the first company in the world to receive regulatory approval of an allogeneic T-cell immunotherapy. Our advanced and versatile T-cell platform does not require T-cell receptor or HLA gene editing and forms the basis of a diverse portfolio of investigational therapies that target EBV, the root cause of certain diseases, in addition to next-generation AlloCAR-Ts designed for best-in-class opportunities across a broad range of hematological malignancies and B-cell driven autoimmune diseases. Atara is headquartered in Southern California. For more information, visit atarabio.com and follow @Atarabio on X and LinkedIn . Forward-Looking Statements This press release contains or may imply "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. For example, forward-looking statements include statements regarding: (1) the development, timing and progress of tab-cel ® , including the BLA and potential indications, the potential characteristics and benefits of tab-cel ® , and the progress and results of, and prospects for, the global partnership with Pierre Fabre Laboratories involving tab-cel ® , and the potential financial benefits to Atara as a result of the global partnership with Pierre Fabre Laboratories, including the receipt, timing and amount of any payments to be received by Atara thereunder; (2) the development, timing and progress of Atara’s AlloCAR-T programs (including ATA3219 and ATA3431), including the timing of the start of any clinical trials, the timing of the availability of data from such clinical trials, the timing of submissions of regulatory applications, and the potential benefits, characteristics, safety and efficacy of such product candidates or product candidates emerging from such programs; (3) Atara’s cash runway, the timing and receipt of potential milestone and other payments, and operating expenses, including Atara’s ability to fund its planned operations into 2027; and (4) Atara’s planned transition of substantially all activities relating to tab-cel at the time of the BLA transfer to Pierre Fabre and the timing thereof. Because such statements deal with future events and are based on Atara’s current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Atara could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including, without limitation, risks and uncertainties associated with the costly and time-consuming pharmaceutical product development process and the uncertainty of clinical success; the COVID-19 pandemic and the wars in Ukraine and the Middle East, which may significantly impact (i) our business, research, clinical development plans and operations, including our operations in Southern California and Denver and at our clinical trial sites, as well as the business or operations of our third-party manufacturer, contract research organizations or other third parties with whom we conduct business, (ii) our ability to access capital, and (iii) the value of our common stock; the sufficiency of Atara’s cash resources and need for additional capital; and other risks and uncertainties affecting Atara’s and its development programs, including those discussed in Atara’s filings with the Securities and Exchange Commission, including in the “Risk Factors” and “ Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections of the Company’s most recently filed periodic reports on Form 10-K and Form 10-Q and subsequent filings and in the documents incorporated by reference therein. Except as otherwise required by law, Atara disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date hereof, whether as a result of new information, future events or circumstances or otherwise. Financials ATARA BIOTHERAPEUTICS, INC. Condensed Consolidated Balance Sheets (Unaudited) (In thousands) June 30, December 31, 2024 2023 Assets Current assets: Cash and cash equivalents $ 31,314 $ 25,841 Short-term investments 3,978 25,884 Restricted cash 146 146 Accounts receivable 2,422 34,108 Inventories 18,749 9,706 Other current assets 5,801 6,184 Total current assets 62,410 101,869 Property and equipment, net 2,317 3,856 Operating lease assets 48,948 54,935 Other assets 3,609 4,844 Total assets $ 117,284 $ 165,504 Liabilities and stockholders’ equity (deficit) Current liabilities: Accounts payable $ 5,253 $ 3,684 Accrued compensation 7,269 11,519 Accrued research and development expenses 2,014 17,364 Deferred revenue 107,582 77,833 Other current liabilities 26,149 31,826 Total current liabilities 148,267 142,226 Deferred revenue - long-term 567 37,562 Operating lease liabilities - long-term 38,703 45,693 Liability related to the sale of future revenues - long-term 36,448 34,623 Other long-term liabilities 4,167 4,631 Total liabilities $ 228,152 $ 264,735 Stockholders’ (deficit) equity: Common stock — — Additional paid-in capital 1,909,097 1,870,123 Accumulated other comprehensive loss (14 ) (204 ) Accumulated deficit (2,019,951 ) (1,969,150 ) Total stockholders’ (deficit) equity (110,868 ) (99,231 ) Total liabilities and stockholders’ (deficit) equity $ 117,284 $ 165,504 ATARA BIOTHERAPEUTICS, INC. Condensed Consolidated Statements of Operations and Comprehensive Loss (Unaudited) (In thousands, except per share amounts) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Commercialization revenue $ 28,640 $ 793 $ 55,997 $ 1,677 License and collaboration revenue — 164 — 506 Total revenue 28,640 957 55,997 2,183 Costs and operating expenses: Cost of commercialization revenue 4,627 2,895 6,612 3,111 Research and development expenses 33,332 56,141 78,838 118,297 General and administrative expenses 8,912 13,335 20,025 27,207 Total costs and operating expenses 46,871 72,371 105,475 148,615 Loss from operations (18,231 ) (71,414 ) (49,478 ) (146,432 ) Interest and other income (expense), net (818 ) 307 (1,299 ) 576 Loss before provision for income taxes (19,049 ) (71,107 ) (50,777 ) (145,856 ) Provision for income taxes — 1 24 23 Net loss $ (19,049 ) $ (71,108 ) $ (50,801 ) $ (145,879 ) Other comprehensive gain (loss): Unrealized gain (loss) on available-for-sale securities 41 304 190 1,134 Comprehensive loss $ (19,008 ) $ (70,804 ) $ (50,611 ) $ (144,745 ) Basic and diluted net loss per common share $ (3.10 ) $ (16.91 ) $ (8.64 ) $ (34.89 ) Basic and diluted weighted-average shares outstanding 6,143 4,204 5,883 4,181

Polyfunctionality correlates with a patient's remission lasting over 18 months with the CAR T cell therapy IRVINE, Calif., Aug. 7, 2024 /PRNewswire/ -- PeproMene Bio, Inc., a clinical-stage biotech company developing novel therapies for cancers and immune disorders, today announced that City of Hope-developed BAFF-R CAR T, known as PMB-CT01, demonstrated better polyfunctionality than CD19 CAR T cells, which are used in current Food and Drug Administration-approved CAR T cell therapies, according to a correlative study published in Blood Advances. Researchers used a single-cell platform, which found that PMB-CT01 CAR T cells, had more polyfunctionality, which is T cells' ability to perform several functions at the same time, than CD 19 CAR T cells. PMB-CT01 cells also produced more stimulatory cytokines, which can spur the immune system, and effector cytokines, which can directly kill cancer cells. Using the City of Hope-developed assay, researchers tested a BAFF-R CAR T cell product from a 57-year-old man with relapsed mantle cell lymphoma. The patient had not achieved remission with prior CD19 CAR T cell therapies. After receiving one infusion in City of Hope's Phase 1 trial using PMB-CT01 and experiencing minimal side effects, the man has been in complete remission over 18 months and continues to have undetectable cancer by sensitive molecular tests for minimal residual disease. The study reported robust indicators of polyfunctionality, which correlated with successful CAR T cell expansion post-infusion and the patient's ongoing remission. Researchers plan to use the assay to test CAR T cell products from five other patients in the trial, all of whom have experienced similar remissions to PMB-CT01. "We developed BAFFR-CAR T therapy as another treatment option for a significant number of patients with lymphomas and leukemias who relapse after receiving commercial CD19 CAR T cell therapy, and our results so far represent the ideal maximal efficacy with minimal toxicity," said Larry W. Kwak, M.D., Ph.D., vice president and deputy director of City of Hope's Comprehensive Cancer Center and PeproMene's scientific founder and compensated chair of its Scientific Advisory Board. Kwak has an equity interest in PeproMene. "We have developed a robust and reliable polyfunctional assay for CAR T cell products, with the potential to predict patient outcomes and accelerate the development of effective CAR T cell therapies." Elizabeth Budde, M.D., Ph.D., the trial's principal investigator, an associate professor of hematology and hematopoietic cell transplantation and the executive medical director for the Immune Effector Cell Therapy Program at City of Hope, presented initial trial results at the American Society of Hematology's conference in December 2023. "It's exciting to say that five patients with non-Hodgkin lymphoma and one with B-cell acute lymphoblastic leukemia have been treated with PMB-CT01 and 100% have demonstrated durable responses," Dr. Budde said. "Many of the trial patients relapsed had after CD19 CAR T therapy and/or were CD19 negative. PMB-CT01 could present a viable option for other patients who also face this dilemma." "This assay can be applied to current and future clinical trials to guide the development of PMB-CT01. PeproMene remains committed to the ongoing scientific and clinical development of this potentially promising new cell therapy" said Hazel Cheng Ph.D., COO of PeproMene Bio. About PMB-CT01 PMB-CT01 is a first-in-class, BAFF-R-targeted, autologous CAR T cell therapy. BAFF-R (B- Cell Activating Factor Receptor), a member of the tumor necrosis factor (TNF) receptor superfamily, is the main receptor for BAFF and is expressed almost exclusively on B cells. Since BAFF-R signaling promotes normal B-cell proliferation and appears to be required for B-cell survival, tumor cells are unlikely to escape therapy via loss of the BAFF-R antigen. This unique characteristic makes BAFFR CAR T therapy a highly promising option for treating B-cell malignancies. The BAFFR CAR was constructed using anti-BAFF-R single-chain fragment variable (scFv) antibodies and second-generation signaling domains CD3ζ and 4-1BB. Our research has demonstrated that BAFFR-CAR T cells effectively kill human lymphomas and leukemias both in vitro and in animal models. PeproMene Bio has licensed the intellectual property of PMB-CT01 from City of Hope. About PeproMene Bio PeproMene Bio, Inc. is a clinical-stage biotech company in Irvine, California developing novel therapies to treat cancers and immune disorders. PeproMene's lead candidate, PMB-CT01 (BAFFR-CAR T cells) is currently being investigated to treat relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL; NCT04690595) and B-cell non-Hodgkin lymphoma (B-NHL; NCT05370430) in phase 1 clinical trials. PeproMene Bio is also developing BAFFR Bispecific T Cell Engager and BAFFR-CAR NK cells. Contact: John Fry, [email protected] SOURCE PeproMene Bio, Inc.

Cell and gene therapy (CGT) is an emerging treatment strategy that stands out for its potential "one-time treatment, permanent cure" capability, offering many patients the possibility of long-term relief from their medical conditions. Data shows that in the first half of 2024, a total of 8 CGT therapies were approved globally:  1. Sarepta Therapeutics' Elevidy Receives Full FDA Approval: On June 20th, Sarepta announced the label expansion of its gene therapy Elevidys for Duchenne muscular dystrophy (DMD), now approved for patients aged 4 and above. For ambulatory patients, the FDA granted regular approval, while for non-ambulatory patients, it received accelerated approval. Sarepta has committed to conducting and submitting the results of a randomized controlled trial to verify and confirm the clinical benefit of Elevidys in non-ambulatory DMD patients, which is the ongoing ENVISION (SRP-9001-303) study. Elevidys was previously granted accelerated approval in June 2023 for pediatric DMD patients aged 4-5 years, and the expansion to ≥4 years old patients, regardless of their ambulatory status, marks a significant milestone in the treatment of DMD.   2. Geron's Rytelo Becomes the First FDA-Approved Oligonucleotide Telomerase Inhibitor: On June 6th, Geron announced that Rytelo was approved for the treatment of transfusion-dependent anemia in lower-risk myelodysplastic syndromes (LR-MDS) patients. The approval of Rytelo was based on the positive results of the Phase 3 IMerge trial published in The Lancet, which met its primary and key secondary endpoints, showing Rytelo's significant advantage over placebo in reducing the need for red blood cell transfusions, with durable and sustained responses in responders. This approval marks the fulfillment of a nearly 40-year-long pursuit of a telomerase-targeted therapy, and is viewed as one of the important therapies of the year. With the approval of Rytelo, Geron's stock price surged by 22%. Evaluate predicts that Rytelo's sales could reach $737 million by 2028, reflecting the market's recognition of the therapy's potential. Geron has set a clear pricing strategy for Rytelo, with a wholesale acquisition cost of $2,471 for a 47 mg single dose and $9,884 for a 188 mg single dose. The dosage will be adjusted based on the patient's weight.  3. Moderna's mRESVIA Vaccine: Moderna, Inc. (NASDAQ: MRNA) announced on May 31st that its mRNA respiratory syncytial virus (RSV) vaccine, mRESVIA (mRNA-1345), has been approved by the U.S. Food and Drug Administration (FDA) to protect adults aged 60 and above from RSV-associated lower respiratory tract disease. This vaccine, being the only RSV vaccine administered via a pre-filled syringe, marks the first approval of an mRNA vaccine for a non-COVID-19 disease. The approval was based on the positive results of the global Phase 3 ConquerRSV trial conducted in approximately 37,000 adults aged 60 or older across 22 countries. The primary analysis with a median follow-up of 3.7 months showed the vaccine had an efficacy of 83.7% (95.88% CI 66.0%, 92.2%) against RSV lower respiratory tract disease (LRTD). These results have been published in the New England Journal of Medicine. A longer-term analysis also showed the vaccine's protective effect against RSV LRTD persisted over a median follow-up of 8.6 months. No serious safety concerns were observed in the Phase 3 trial, with the most common adverse reactions including injection site pain, fatigue, headache, muscle pain, and joint pain.  4. Pfizer and its BEQVEZ gene therapy： On April 26, 2024, Pfizer announced that its adeno-associated virus (AAV) vector-based gene therapy BEQVEZ (fidanacogene elaparvovec-DZKT) has been approved by the US FDA for the treatment of adults (18 years and older) with moderate to severe hemophilia B who test negative for neutralizing antibodies to AAV serotype Rh74. The therapy is priced at $3.5 million, comparable to the price of UniQure's hemophilia B gene therapy Hemgenix. This approval was primarily based on the positive data from the Phase III BENEGENE-2 study (n=45), which showed that patients receiving a single dose of BEQVEZ had a significantly reduced annualized bleeding rate (ABR) compared to the standard preventive treatment group (1.3 vs. 4.43, P<0.0001) within 12 months, meeting non-inferiority and superiority endpoints. Currently, BEQVEZ is under review by the European Medicines Agency (EMA) and has been approved by the Canadian regulatory authorities. In addition to BEQVEZ, Pfizer is also investigating two phase III gene therapy programs for hemophilia A and Duchenne muscular dystrophy, as well as a novel anti-tissue factor pathway inhibitor marstacimab for the treatment of hemophilia A or B patients with factor VIII (FVIII) or factor IX (FIX) inhibitors. The FDA and EMA are currently reviewing the Biologics License Application and Marketing Authorization Application for marstacimab, respectively.  5. Orchard Therapeutics：  On March 18, the FDA approved Orchard Therapeutics' gene therapy Lenmeldy for the treatment of metachromatic leukodystrophy (MLD) in pediatric patients. The therapy is priced at $42.5 million, making it the most expensive drug in history. Lenmeldy is the only FDA-approved therapy for the treatment of early-onset MLD in children and has also been approved in the EU and UK. Lenmeldy (atidarsagene autotemcel, formerly OTL-200) utilizes Orchard's core technology, which involves ex vivo modification of autologous stem cells with a lentiviral vector encoding the arylsulfatase-A (ARSA) gene, with the aim of restoring ARSA expression in a single treatment to halt or slow disease progression. The FDA approval was based on data from 37 children, with a median follow-up of 6.76 years, which showed significantly improved overall survival and reduced incidence of motor dysfunction or death in patients receiving Lenmeldy. In terms of safety, Lenmeldy demonstrated good tolerability, with no treatment-related serious adverse events or deaths.  6. BMS's Breyanzi： On March 14, Bristol Myers Squibb (BMS) announced that the US Food and Drug Administration (FDA) has granted accelerated approval for its CD19-targeted CAR-T cell therapy Breyanzi (lisocabtagene maraleucel; liso-cel). This therapy is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (R/R CLL) or small lymphocytic lymphoma (SLL) who have received at least two prior therapies, including a Bruton's tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor. According to the company's press release, Breyanzi is the first CAR-T cell therapy approved for adult patients with R/R CLL or SLL.  As an autologous CAR-T cell therapy targeting CD19, Breyanzi has a defined composition and incorporates a 4-1BB co-stimulatory domain. The FDA had previously approved Breyanzi in February 2021 for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL) who have received two or more lines of systemic therapy. The unique feature of Breyanzi is its controlled ratio of CD8-positive and CD4-positive T cells, which helps to better manage the potential toxicities of cell therapy. Additionally, the 4-1BB signaling domain significantly enhances the expansion and persistence of the CAR-T cells. The accelerated approval for this indication was based on response rates and duration of response, and further approval will depend on the verification of clinical efficacy in a confirmatory trial. The TRANSCEND CLL 004 trial, which served as the basis for this approval, is an open-label, single-arm, multicenter Phase 1/2 study. The data analysis showed that 20% of patients with relapsed or refractory CLL or SLL achieved complete remission (CR) after receiving Breyanzi, and the safety profile has been established.  7. Carsgen Therapeutics' Selinexor Injection：  On March 1st, Carsgen Therapeutics announced that the new drug application (NDA) for its BCMA CAR-T product Carsgencel® (Selinexor Injection) has been approved by the National Medical Products Administration (NMPA) of China. The product is mainly used to treat adult patients with relapsed or refractory multiple myeloma, who have received at least 3 prior lines of therapy (having received at least one proteasome inhibitor and one immunomodulatory agent). Selinexor Injection is the fifth CAR-T therapy approved in China.  On March 5th, Carsgen Therapeutics announced the launch price of its CAR-T cell therapy Selinexor Injection (brand name: Carsgencel) at 1.15 million RMB. In collaboration with Huadong Medicine (000963.SZ), the company estimates the peak annual sales of this product to be over 1 billion RMB.  Carsgencel® is an autologous BCMA-targeted CAR-T cell product produced through lentiviral transduction. The lentiviral vector encodes a fully human BCMA-specific single-chain variable fragment (scFv), a human CD8α hinge structure, a CD8α transmembrane domain, a 4-1BB co-stimulatory domain, and a CD3ζ activation domain. Carsgen Therapeutics' in-house developed new fully human scFv has demonstrated high binding affinity and stability. Currently, Carsgen Therapeutics is conducting a Phase 1b/2 clinical trial (LUMMICAR STUDY 2) in North America to evaluate the safety and efficacy of Carsgencel® in the treatment of relapsed or refractory multiple myeloma.  In January 2023, Carsgen Therapeutics and Huadong Medicine reached a commercialization collaboration agreement for Carsgencel® in mainland China. According to this agreement, Carsgen Therapeutics has granted the exclusive commercial rights of Carsgencel® in mainland China to Huadong Medicine. In this collaboration, Huadong Medicine (Hangzhou) will pay a 200 million RMB upfront payment to Carsgen Therapeutics' wholly-owned subsidiary Kaixing Life, and Huadong Medicine will be responsible for up to 1.025 billion RMB in future registration and sales milestone payments. 8. Iovance Biotherapeutics, which announced on February 16th that its tumor-infiltrating lymphocyte (TIL) therapy Amtagvi (lifileucel) has received FDA accelerated approval for the treatment of advanced melanoma, with a price tag of $515,000. It is noteworthy that lifileucel is the world's first approved TIL cell therapy.  Amtagvi is a personalized autologous T-cell immunotherapy derived from the patient's tumor tissue. In the initial treatment, the patient's tumor tissue is removed, and T cells are isolated and further expanded in vitro, before being re-infused back into the patient in a single dose. Each Amtagvi dose contains 7.5 to 72 billion active cells, and the entire process from receiving the tumor tissue to completing the product preparation takes approximately 34 days.  Phase 2 clinical trial data showed that after a median follow-up of 27.6 months, the objective response rate (ORR) was 31.4%, including 8 complete responses (CR) and 40 partial responses (PR). In Iovance's 4-year follow-up data, the longest duration of response reached 55.8 months.   Looking ahead, it is expected that 5 other cell and gene therapies (CGTs) may be approved in 2024, including Carsgen's CAR-T therapy Selinexor Injection, Adaptimmune Therapeutics' TCR T-cell therapy, BioCardia's CardiAMP, Pfizer's novel gene therapy Fidanacogene elaparvovec, and Autolus Therapeutics' CAR-T therapy Obecabtagene autoleucel. However, Rocket Pharmaceuticals' gene therapy Kresladi and Abeona Therapeutics' autologous cell therapy Prademagene zamikeracel (pz-cel) were recently rejected by the FDA in June and April, respectively, due to chemistry, manufacturing, and control (CMC) related issues, and they currently need to provide additional CMC information to complete the review.