B2M

- Company is applying its T cell-selective lipid nanoparticle to develop siRNA therapeutics for T cell-driven autoimmune diseases - Lead target and indication to be announced MY 2025 - Cash balance of $185.2 million expected to fund operations into 2H 2027 CAMBRIDGE, MASS., March 13, 2025 (GLOBE NEWSWIRE) -- Generation Bio Co. (Nasdaq:GBIO), a biotechnology company working to change what’s possible for people living with T cell-driven autoimmune diseases, reported business highlights and fourth quarter and full year 2024 financial results. “Our T cell-selective lipid nanoparticle (LNP) is designed to overcome a long-standing challenge for siRNA therapeutics, which is to reach T cells while sparing broader immune cells and achieve potent knockdown of genetic targets in vivo,” said Geoff McDonough, M.D., chief executive officer of Generation Bio. “Significant classes of drugs in immune and inflammation indications modulate T cells, but their impact is constrained due to off-target effects. We believe that by combining the selective delivery of our cell-targeted LNP (ctLNP) platform with the genetic precision of siRNA, we can reach high-value targets that cause T cell-driven autoimmune diseases but are undruggable or poorly drugged by conventional modalities. This approach has the potential to offer predictable pharmacology and expand the therapeutic index, creating a new application space for T cell-specific therapies.” Business Highlights Applying T cell-selective LNP Delivery System to Develop siRNA Therapeutics for T Cell-driven Autoimmune Diseases: Generation Bio has designed a ctLNP that is specifically targeted to T cells to achieve selective delivery of siRNA and knockdown of targets in vivo, overcoming significant historical challenges for the development of siRNA therapeutics in T cells. The company has shown that its T cell-selective LNP containing an unoptimized siRNA achieved efficient delivery and approximately 98% knockdown of the B2M protein in human T cells in both in vitro and mouse studies. Delivering siRNA with a T cell-selective LNP could enable selective modulation of T cell activity involved in tissue inflammation and damage while sparing the broader immune system. The development of T cell-selective LNP-siRNA therapeutics could address targets that are undruggable or poorly drugged by conventional modalities and offer the potent, precise protein knockdown and wide therapeutic index required to fulfill unmet need in certain T cell-driven autoimmune diseases. Generation Bio plans to announce the target and indication for its lead ctLNP-siRNA program in mid-2025 and submit an investigational new drug (IND) application in the second half of 2026. Fourth Quarter and Full Year 2024 Financial Results Cash Position: Cash, cash equivalents and marketable securities were $185.2 million as of December 31, 2024, compared with $264.4 million in cash, cash equivalents, and marketable securities as of December 31, 2023. The company continues to believe that its cash, cash equivalents and marketable securities will fund its operating expenditures and capital expenditure requirements into the second half of 2027. R&D Expenses: Research and development (R&D) expenses were $15.5 million for the quarter ended December 31, 2024 and $61.3 million for the year ended December 31, 2024, compared to $27.9 million for the quarter ended December 31, 2023, including a one-time $5.1 million charge related to the company’s reduction in force, and $93.6 million for the year ended December 31, 2023. G&A Expenses: General and administrative (G&A) expenses were $8.7 million for the quarter ended December 31, 2024 and $37.8 million for the year ended December 31, 2024, compared to $13.4 million for the quarter ended December 31, 2023, including a one-time $1.9 million charge related to the company’s reduction in force, and $50.9 million for the year ended December 31, 2023. Loss on lease termination: During the three months and year ended December 31, 2024, we recognized a non-cash charge of $3.6 million and $63.2 million, respectively, in connection with the termination of the lease for our manufacturing facility in Waltham, Massachusetts. Net Loss: Net loss was $21.4 million, or $0.32 basic and diluted net loss per share, for the quarter ended December 31, 2024, and $131.7 million, or $1.98 basic and diluted net loss per share, for the year ended December 31, 2024, compared to a net loss of $35.2 million, or $0.53 basic and diluted net loss per share, for the quarter ended December 31, 2023, and $126.6 million, or $1.96 basic and diluted net loss per share, for the year ended December 31, 2023. About Generation Bio Generation Bio is a biotechnology company working to change what’s possible for people living with T cell-driven autoimmune diseases. The company is developing redosable therapeutics that reprogram T cells in vivo to reduce or eliminate the production and persistence of autoreactive T cells, which erroneously recognize and attack the body’s own tissues, causing autoimmune diseases. Generation Bio’s innovative approach leverages cell-targeted lipid nanoparticles (ctLNP) to selectively deliver small interfering RNA (siRNA) to T cells. This combination of selective delivery and an intracellular, genetically precise mechanism of target engagement could unlock a series of high-value, historically undruggable disease-driving genes in autoimmunity. For more information, please visit www.generationbio.com. Forward-Looking Statements Any statements in this press release about future expectations, plans and prospects for the company, including statements about the company’s strategic plans or objectives, cash resources, technology platforms, research and clinical development plans, and preclinical data and other statements containing the words “believes,” “anticipates,” “plans,” “expects,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: uncertainties inherent in the identification and development of product candidates, including the anticipated timing of identification of the company’s product candidates, the conduct of research activities, the initiation and completion of preclinical studies and clinical trials and clinical development of the company’s product candidates; uncertainties as to the availability and timing of results from preclinical studies and clinical trials; uncertainties regarding our novel technologies; whether results from preclinical studies will be predictive of the results of later preclinical studies and clinical trials; uncertainties regarding the anticipated timing of the submission of an investigational new drug application; whether the company’s cash resources are sufficient to fund the company’s operating expenses and capital expenditure requirements for the period anticipated; as well as the other risks and uncertainties set forth in the “Risk Factors” section of the company’s most recent annual report on Form 10-K and quarterly report on Form 10-Q, which are on file with the Securities and Exchange Commission, and in subsequent filings the company may make with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the company’s views as of the date hereof. The company anticipates that subsequent events and developments will cause the company’s views to change. However, while the company may elect to update these forward-looking statements at some point in the future, the company specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the company’s views as of any date subsequent to the date on which they were made. Investors and Media Contact Maren Killackey Generation Bio mkillackey@generationbio.com 857-371-4638

In vivo proof-of-concept achieved in humanized mice and non-human primates (NHPs) using Gene Writers encapsulated in proprietary lipid nanoparticles (LNPs) targeting long-term hematopoietic stem cells (LT-HSCs) to rewrite the hemoglobin subunit beta (HBB) gene, the genetic locus associated with sickle cell disease (SCD)Single intravenous infusion of Gene Writer formulated in proprietary LNP generated chimeric antigen receptor (CAR)-T cells in a tumor-bearing xenograft mouse model that expanded in vivo and cleared tumorIn a separate in vivo mouse model containing resting human T cells, an average of 30% CAR writing was achieved, with complete B cell depletion observed, highlighting its therapeutic potential in autoimmune diseases SOMERVILLE, Mass., Dec. 09, 2024 (GLOBE NEWSWIRE) -- Tessera Therapeutics, a biotechnology company pioneering a new approach to genome engineering through the development of its Gene Writing™ and delivery platforms, is presenting preclinical updates from its in vivo programs in sickle cell disease (SCD) and T cell therapies respectively. Data were presented highlighting delivery advances across hematopoietic stem cells (HSCs) and T cells, enabling efficient in vivo HSC rewriting in humanized mice and NHP, and tumor clearance and B cell depletion in mouse models with in vivo generated CAR-T cells. These new data were shared in one oral presentation and two poster presentations at the 66th American Society of Hematology (ASH) Annual Meeting taking place in San Diego, California, December 7 – 10, 2024. “We are excited by the totality of preclinical data presented at ASH, which underscores the ongoing progress of our Gene Writing and delivery platforms,” said Michael Severino, M.D., CEO of Tessera Therapeutics. “In our sickle cell disease program, we have shown in vivo editing of HBB in mouse models that surpass that of asymptomatic carriers of the sickle mutation, and for the first time in NHP, editing efficiencies that reach anticipated therapeutic levels. Additionally, we have achieved proof-of-concept for generating functional CAR-T cells across multiple mouse models, all with a single dose of an LNP-RNA composition, without toxic chemotherapy conditioning or lymphodepletion. Our focus on advancing groundbreaking in vivo treatments for sickle cell disease and novel T cell therapies remains steadfast.” In Vivo SCD Data Gene Writer formulated in a proprietary LNP for delivery to LT-HSCs achieved an average of 62% rewriting of the HBB gene, the locus responsible for SCD, in LT-HSCs of humanized mice after a single intravenous administrationEarly proof-of-concept study of Gene Writer formulated in a LNP achieved an average of 24% of HBB rewriting in LT-HSCs in NHP, reaching anticipated therapeutic levels established by human mixed-donor chimerism studies that demonstrate 20% chimerism can reverse the sickle phenotype in patients following allogeneic hematopoietic stem cell transplant1Proof-of-principle study demonstrated that in vivo rewriting in LT-HSCs with high efficiency is achievable using a single dose of Gene Writer with a surrogate reagent targeting beta-2 microglobulin (B2M). Rewriting efficiency of 76% was achieved in NHP, with stable editing out to day 84. B2M rewriting was observed across multi-lineages in peripheral blood, providing evidence that edited HSCs were functionally contributing to hematopoiesis and gave rise to edited blood cellsTessera’s non-viral delivery platform is critical to enabling these in vivo results, as well as successfully developing an in vivo therapeutic for SCD. Using a proprietary LNP developed for delivery to HSCs, both liver de-targeting and enhanced bone marrow delivery was achieved, resulting in 11-fold lower liver delivery and 52-fold higher bone marrow delivery of green fluorescent protein (GFP) as compared to a liver-tropic LNP in mice Advances Towards In Vivo T-Cell Therapies Gene Writers formulated in LNPs can integrate CAR transgenes targeting CD20 in resting NHP T cells, achieving an average of 60% CAR writing in vitroLNP delivery of Gene Writer and CAR template RNAs targeting B-cell maturation antigen (BCMA) to activated or resting T cells in vitro generated functional CAR-T cells that efficiently killed tumor cells in vitro and in vivo in tumor-bearing xenograft miceProof-of-concept studies in oncology demonstrated that with a single intravenous infusion of Gene Writer formulated in a proprietary LNP to tumor-bearing xenograft mice generated functional CD19-targeted CAR-T cells in vivo that were able to expand and eradicate tumor burdenLNP delivery of Gene Writer and CAR template RNAs targeting CD20 resulted in an average of 30% CAR writing in vivo in a naïve humanized mouse model containing resting T cells, which led to the elimination of human B cells in the blood compared to control, highlighting its therapeutic potential in autoimmune diseases 1Blood. 2017;130(17):1946-1948 About Tessera Therapeutics Tessera Therapeutics is pioneering a new approach to genome engineering through the development of its Gene Writing™ and delivery platforms, with the aim to unlock broad new therapeutic frontiers. Our Gene Writing platform is designed to write therapeutic messages into the genome by efficiently changing single or multiple DNA base pairs, precisely correcting insertions or deletions, or adding exon-length sequences and whole genes. Our proprietary lipid nanoparticle delivery platform is designed to enable the in vivo delivery of RNA to targeted cell types. We believe our Gene Writing and delivery platforms will enable transformative genetic medicines to not only cure diseases that arise from errors in a single gene, but also modify inherited risk factors for common diseases and create engineered cells to treat cancer and potentially autoimmune and other diseases. Tessera Therapeutics was founded in 2018 by Flagship Pioneering, a life sciences innovation enterprise that conceives, creates, resources, and develops first-in-category bioplatform companies to transform human health and sustainability. For more information about Tessera, please visit www.tesseratherapeutics.com. Contact Kristin Politi, PhDLifeSci Communications, LLCkpoliti@lifescicomms.com

SHANGHAI, Nov. 6, 2024 /PRNewswire/ -- CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, announces that the Company will present the clinical data of zevorcabtagene autoleucel, CT071, and CT0590 as posters at the 66th Annual Congress of the American Society of Hematology ("ASH") which is due to take place between Dec 7 – 10, 2024. The abstracts are available on ASH official website. "CARsgen is advancing therapeutic options for hematologic malignancies with robust CAR T-cell pipeline, which includes the autologous CAR T-cell therapy zevor-cel, the single-day-culture CT071, and the allogeneic CAR T-cell candidate CT0590. These initiatives underscore CARsgen's strong commitment to innovation in hematology. Leveraging proprietary technology platforms such as CARcelerate® and THANK-uCAR®, CARsgen is focused on developing differentiated CAR T-cell therapies to address the critical challenges faced by the clinical community. We are excited to share new data and are confident in the potential of our CAR T-cell therapies to benefit patients worldwide," said Raffaele Baffa, M.D., Ph.D., Chief Medical Officer of CARsgen Therapeutics. Subgroup Analyses of Phase 2 Study: Evaluating the Efficacy of Fully Human BCMA-Targeting CAR T Cells (Zevorcabtagene Autoleucel) in Patients with Relapsed/Refractory Multiple Myeloma Publication Number: 4762 Presentation Time: 6:00 PM - 8:00 PM, Monday, December 9, 2024 (PST) In 102 patients with RRMM who had received at least 3 prior lines of therapy including an immunomodulatory drug and a proteasome inhibitor, the objective response rate (ORR) was 92.2%, the stringent complete response (sCR) or complete response (CR) was 71.6%. The ORR or the CR/sCR rate was not affected by any of the baseline characteristics tested. With a median follow-up of 20.3 (range: 0.4 to 27) months, the median duration of response (DOR), progression-free survival (PFS), and overall survival (OS) data were not mature and therefore, 18-month (18m) and estimated 30-month (30m) event free rates were used as efficacy outcomes for subgroup analyses. The DOR, PFS and OS were not impacted by age or ISS. These subgroup analyses indicate that baseline characteristics have minimal impact on the clinical efficacy of zevorcabtagene autoleucel, demonstrating that even RRMM patients with poor prognostic factors can benefit from zevorcabtagene autoleucel. GPRC5D-Targeted CAR T-Cell Therapy CT071 for the Treatment of Refractory/Relapsed Multiple Myeloma Publication Number: 3451 Presentation Time: 6:00 PM - 8:00 PM, Sunday, December 8, 2024 (PST) CT071 is a fully human GPRC5D-targeting autologous CAR T-cell product manufactured using an expedited CARcelerate® platform which shortens the manufacturing process to around 30 hours resulting in shorter vein-to-vein time. Patients with RRMM who had previously received ≥ 3 prior lines of therapy (LOT) or patients who experienced progression or lack of response having been treated with a proteasome inhibitor and an immunomodulatory agent or those who were double class-refractory, all with ECOG score of 0-2 were enrolled. In 17 patients who had been dosed with CT071, 11 patients (64.7%) experienced cytokine release syndrome (CRS), all at Grade 1 (n=8) or 2 (n=3). No immune effector cell-associated neurotoxicity syndrome (ICANS) was observed. No dose limiting toxicity (DLT) occurred. The overall response rate (ORR) was 94.1% (16/17), and the stringent complete response (sCR) rate was 52.9% (9/17). Notably, 7 patients achieved complete response or better at week 4. All 4 patients with previous exposure to BCMA or BCMA/CD19 CAR T responded to CT071 (2 with sCR and 2 with partial response). A First-in-Human Study of CT0590, a Triple Knock-out, Allogeneic CAR T-Cell Therapy Targeting BCMA and NKG2A, in Subjects with Relapsed/Refractory Multiple Myeloma Publication Number: 4843 Presentation Time: 6:00 PM - 8:00 PM, Monday, December 9, 2024 (PST) CT0590 is an allogeneic dual CAR T-cell therapy deploying THANK-uCAR® technology that targets both BCMA and NKG2A (a membrane protein expressed in NK and T cells), featuring a triple knockout for TRAC/B2M/NKG2A which mitigates against graft-versus-host disease (GvHD), host immune rejection and fratricide. This is a first-in-human (FIH), open-label, single center, phase I study of CT0590 in subjects with RRMM to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of CT0590 (NCT05066022). As of 22-Apr-2024, 5 subjects were enrolled (4 subjects with RRMM and 1 subject with primary plasma cell leukemia [pPCL] under compassionate use). No ≥ 3 grade cytokine release syndrome (CRS) was observed. No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) or GvHD were observed. No dose limiting toxicities were reported and there were no withdrawal from the study or deaths due to adverse events. With a median follow-up time of 16.6 months (range: 5.1, 24.2), 3 subjects achieved confirmed responses including 2 subjects with stringent complete response (sCR) and 1 subject with partial response (PR). The 2 subjects with sCR include1 RRMM subject [sCR ongoing] with a DOR longer than 23 months as of data cut-off date and 1 pPCL subject with a duration of response (DOR) of 20 months. In the 2 subjects with sCR, CAR copies peaked at > 280,000 copies/µg genomic DNA. Preliminary results of this FIH study of the CT0590 allogeneic CAR T-cell therapy demonstrated a manageable safety profile while achieving deep and durable clinical responses. About Zevorcabtagene Autoleucel Zevorcabtagene autoleucel is a fully human, autologous BCMA CAR T-cell product for the treatment of Multiple Myeloma (MM). Zevorcabtagene autoleucel was approved by the NMPA on February 23, 2024 for the treatment of adult patients with R/R MM who have progressed after at least 3 prior lines of therapy (including a proteasome inhibitor and an immunomodulatory agent). CARsgen is conducting a separate Phase 1b/2 LUMMICAR STUDY 2 clinical trial in North America to evaluate the safety and efficacy of zevorcabtagene autoleucel in R/R MM. Zevorcabtagene autoleucel received Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug designations from the U.S. FDA in 2019, as well as Priority Medicines (PRIME) and Orphan Medicinal Product designations from the European Medicines Agency (EMA) in 2019 and 2020, respectively. About CT071 CT071 is a CAR T-cell therapy candidate developed utilizing the proprietary CARcelerate® platform of CARsgen targeting GPRC5D for the treatment of relapsed/refractory MM or relapsed/refractory plasma cell leukemia (PCL). An IIT (NCT05838131) is ongoing in China to evaluate the preliminary safety and efficacy of CT071 for the treatment of patients with relapsed/refractory multiple myeloma or plasma cell leukemia. A separate investigator-initiated trial (NCT06407947) is ongoing in China for the treatment of patients with newly diagnosed multiple myeloma (NDMM). About CT0590 CT0590 is a BCMA-targeting allogeneic CAR T-cell product candidate deploying CARsgen's THANK-uCAR® technology. An IIT is ongoing in China to evaluate the preliminary safety and efficacy of CT0590 for the treatment of R/R MM. About CARsgen Therapeutics Holdings Limited CARsgen is a biopharmaceutical company with operations in China and the U.S., focusing on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors. CARsgen has established a comprehensive CAR T-cell research and development platform that covers target discovery, innovative CAR T-cell development, clinical trials, and commercial-scale production. Internally, CARsgen has developed novel technologies and a product pipeline with global rights to address significant challenges faced by existing CAR T-cell therapies. Efforts include improving safety profile, enhancing the efficacy in treating solid tumors, and reducing treatment costs. CARsgen's mission is to become a global biopharmaceutical leader that provides innovative and differentiated cell therapies for cancer patients worldwide and makes cancer curable. Forward-looking Statements All statements in this press release that are not historical fact or that do not relate to present facts or current conditions are forward-looking statements. Such forward-looking statements express the Group's current views, projections, beliefs and expectations with respect to future events as of the date of this press release. Such forward-looking statements are based on a number of assumptions and factors beyond the Group's control. As a result, they are subject to significant risks and uncertainties, and actual events or results may differ materially from these forward-looking statements and the forward-looking events discussed in this press release might not occur. Such risks and uncertainties include, but are not limited to, those detailed under the heading "Principal Risks and Uncertainties" in our most recent annual report and interim report and other announcements and reports made available on our corporate website, . No representation or warranty is given as to the achievement or reasonableness of, and no reliance should be placed on, any projections, targets, estimates or forecasts contained in this press release. For more information, please visit SOURCE CARsgen Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED