CR2

Second IND Clearance for ATA3219 Following Non-Hodgkin’s Lymphoma (NHL) and First in an Autoimmune Disease Indication Initial Clinical Data in NHL Anticipated in H2 2024 and for Lupus Nephritis in H1 2025 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 announced the U.S. Food and Drug Administration (FDA) has cleared an Investigational New Drug (IND) application for ATA3219, an allogeneic, anti-CD19 chimeric antigen receptor (CAR) T-cell monotherapy for the treatment of systemic lupus erythematosus (SLE) with kidney involvement (lupus nephritis [LN]). “Expanding upon an extensive clinical experience encompassing the treatment of over 600 patients using our allogeneic T-cell platform in both oncology and autoimmune diseases, we are excited to clinically evaluate the potential of our differentiated allogeneic CAR T-cell approach. We are eager to address the significant unmet need in lupus nephritis as we initiate our Phase 1 trial,” said Pascal Touchon, President and Chief Executive Officer of Atara. “We look forward to bringing the promise and accessibility of a potentially curative off-the-shelf cell therapy option to patients with severe autoimmune diseases, potentially eliminating the burdens of autologous CAR T therapies like costly infrastructure and treatment delays.” The multi-center, Phase 1, open-label, single-arm, dose-escalation study will evaluate the safety and preliminary efficacy of ATA3219 in subjects with LN. Subjects will receive lymphodepletion treatment followed by ATA3219 at a dose of 40, 80, or 160 x 106 CAR+ T cells. ATA3219 is designed to be given as a one-time infusion and followed for safety and efficacy. Each dose level is designed to enroll 3-6 patients, with the first subject expected to be enrolled in the second half of 2024. “Existing therapeutic agents for lupus nephritis yield suboptimal responses and have limitations due to their requirement for ongoing administration, susceptibility to treatment failures, and limited accessibility to inflamed tissues resulting in incomplete depletion of B cells,” said Rajani Dinavahi, Chief Medical Officer at Atara. “CAR T cells can naturally infiltrate deep into target tissues to mediate B-cell depletion and produce durable responses. Building on the encouraging academic data in lupus nephritis with autologous CD19 CAR T, ATA3219 is an off-the-shelf therapy that could significantly reduce constraints for patients and physicians like leukapheresis and long waiting times, therefore potentially improving access to a large population of patients.” Proof of concept for a CD19 CAR T approach in autoimmune disease was first demonstrated in early academic results from an investigator-sponsored study showing 100% (8/8) of LN patients rapidly attaining drug-free, durable remission with an autologous CD19-targeted CAR T therapy. The therapy eliminated the pathogenic, autoreactive B cells and allowed healthy B cells to return after treatment, enabling the patients’ immune system to function normally again with associated improvement of clinical symptoms.1 These early proof of concept clinical data with CD19 targeted CAR T support further development of CAR T for LN with differentiated and off-the-shelf allogeneic approaches. The ATA3219 IND submission included in vitro data reflecting the CD19 antigen-specific functional activity of ATA3219 and CAR-mediated activity against B cells from SLE patients. ATA3219 led to robust CD19-specific B-cell depletion compared to controls. LN is a serious and most common complication of SLE, a chronic multisystem autoimmune disease. The prevalence of SLE in the U.S. is 73 per 100,000 people, afflicting more than 200,000 U.S. patients alone, and occurs in women much more commonly than men. Up to 60% of adult patients with SLE develop renal disease during the course of their illness, and up to 70% of patients with LN are refractory to standard immunosuppressive therapies. Despite recent advances in treatment strategies, the response rate using existing therapies remains low, with significant risk of long-term morbidity and mortality associated with refractory LN. 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 (SLE) with kidney involvement (lupus nephritis [LN]). 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. 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 the development, data, timing and progress, as applicable, of: (1) the ATA3219 program; (2) the potential characteristics and benefits of ATA3219; (3) the Company’s planned clinical study of ATA3219 to treat lupus nephritis, including the timing and enrollment 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 ongoing 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. 1Mueller, F., et al. CD19-Targeted CAR-T Cells in Refractory Systemic Autoimmune Diseases: A Monocentric Experience from the First Fifteen Patients. Blood 2023; 142 (Supplement 1): 220.

In the world of biopharmaceuticals, we often speak of patience, perseverance, and the relentless march of scientific progress. Developing a drug, from inception to approval, is a journey that can span decades, involving countless trials, setbacks, and breakthroughs. But what happens when a crisis is thrust upon us? The biopharma market, it seems, becomes galvanized, and the pace of innovation and adoption accelerates exponentially. It’s in these moments when the urgency – and optimism – is palpable. We see an immediate spike in demand for bio innovation. In these cases, innovators do what we do best; we use our creativity to make the impossible possible. Over the years, the biopharma community has witnessed this phenomenon unfold on multiple occasions and we have learned some key lessons as a result. Perhaps the most high-profile example of this is the mRNA vaccine technology acceleration during the Covid pandemic. The Covid-19 crisis served as a catalyst for innovation as this technology, which had been quietly advancing for years, suddenly took center stage. The development of Covid-19 vaccines showed us how swiftly scientific progress can be achieved when we ignite our collective will towards a singular goal. Within months, these vaccines were not only developed but also globally adopted. Innovation won the day at a time of crisis. Now, since the value of these mRNA vaccines has been validated, development is underway for non-crisis-oriented indications including HIV, Epstein-Barr virus (EBV) and even cancer. Beyond the pandemic, the world is facing an ever-growing number of threats – both natural and man-made. Powerful earthquakes, raging floods, extreme temperatures, and fierce wildfires have killed and injured tens of thousands globally. Sadly, conflicts like the Russia-Ukraine war and the Israel-Hamas war, among others, have also added another layer of complexity to our global challenges. In the face of these multifaceted threats, the need for innovative healthcare solutions becomes increasingly urgent. It underscores the vital role of the biopharmaceutical industry in not only addressing immediate health crises but also contributing to the broader resilience and well-being of humanity in times of adversity. Many nations prepare for crisis by maintaining emergency medical stockpiles. These stockpiles include essential pharmaceuticals, equipment, personal protective gear, and critical supplies to address a range of urgent healthcare needs, in addition to specialized treatments for mass casualties, burns, and more. Nevertheless, some countries opt to not proactively invest in specific resources and acquire them on a contingency basis. Unfortunately, that critical day can come unexpectedly. For those involved in the production of biotech products that can assist during times of crisis, it is important to harness the value of your technology and work tirelessly to maximize government and health system preparedness with emergency stockpiles. We biotech innovators have the responsibility to strategically mobilize to help save lives and enhance well-being during extremely difficult situations. Here are three lessons for biopharma innovators as the world seeks new health solutions in times of crisis: Stay focused on your long-term strategy: Unwavering commitment to your long-term vision is crucial. It might take years for your product to gain recognition, but you must remain focused, persistent and stay on course. That way you are fully prepared when the need arises. While we are unable to predict when disaster might strike, remain steadfast in developing and commercializing an effective treatment that meets the needs of individuals impacted by the crisis. Mobilize when your solution meets an immediate need: The key to successful innovation in times of crisis is recognizing when your product can truly provide a timely solution. Biotech companies must remain agile and ready to mobilize when the need arises. Be prepared to act promptly when your innovation aligns with the needs of the moment. You may find your biologic suddenly become indispensable due to its ability to treat many people efficiently and effectively, reducing complexities, logistical and otherwise. Moreover, your swift response will prove pivotal in addressing the immediate medical need. Continue to educate relevant stakeholders: Biotech innovators with crisis-oriented drugs must always be proactive in educating relevant stakeholders about their products, ensuring that when the time comes, the market understands what is possible, and how it may be compatible with the overall crisis response strategies. While patiently advancing your drug’s development, take the time to educate health authorities, physicians and key industry leaders. For example, they can visit your manufacturing facility, understand the intricacies of your product, and become well-informed about its usage and benefits. As a result, when a crisis does hit, they will quickly understand the need for its mass deployment and be ready to move. As biotech innovators, we must stay focused on our long-term objectives, remain agile to address immediate needs, and continually educate those who can make a difference. These lessons are not just crucial for our own companies but also for the countless lives that depend on the innovations we bring to the world. During crises, our industry’s mission takes on a renewed significance. It becomes a duty to harness our scientific knowledge and technology for the acute need. As biotech innovators, we are entrusted with the incredible responsibility of using our research, dedication, and ingenuity to make a positive difference in the world. Our ultimate success is the profound, life-altering impact we have on those who depend on our innovations. In this, we find our true purpose and our most rewarding measure of success.

– Kriya anticipates up to 5 programs to enter clinic by the end of 2025 – – Current pipeline of gene therapies for common diseases spans three major therapeutics areas: ophthalmology, metabolic disease and neurology – – Company enters 2024 with cash balance of $325 million and runway into late 2026 – PALO ALTO, Calif. and RESEARCH TRIANGLE PARK, N.C., Jan. 08, 2024 (GLOBE NEWSWIRE) -- Kriya Therapeutics, Inc., ("Kriya") a biopharmaceutical company developing gene therapies for common diseases affecting millions of people around the world, today provided an update on its pipeline of gene therapies for prevalent conditions including geographic atrophy, thyroid eye disease, diabetes, NASH, trigeminal neuralgia and epilepsy. Kriya is advancing the first of its gene therapy product candidates into the clinic in 2024 and expects up to five programs in the clinic by the end of 2025. "Our mission is to revolutionize the field of medicine by delivering transformative, one-time gene therapies to patients suffering from common diseases," said Shankar Ramaswamy, M.D., Co-Founder and CEO of Kriya. "In parallel with our near-term goal of advancing up to five gene therapies into the clinic by the end of 2025, we remain deeply committed to our vision of significantly reducing the cost of manufacturing gene therapies through innovations in process sciences and product engineering.” Kriya's platform includes an end-to-end gene therapy product development engine that integrates cutting-edge research and computational biology with a scalable GMP manufacturing facility deploying next-generation processes and analytical characterization techniques. Kriya’s pipeline includes gene therapies across three major therapeutic areas: ophthalmology, metabolic disease and neurology. Its programs share the following features: direct-to-tissue delivery, validated biology, de-risked clinical and regulatory paths and large commercial markets. Kriya’s publicly disclosed programs are summarized below. Dr. Ramaswamy will share further information on Kriya’s portfolio during his presentation at the J.P. Morgan 42nd Annual Healthcare Conference on Tuesday, January 9th at 9:00 AM PT in San Francisco, California. Ophthalmology ProgramsGeographic Atrophy (GA): KRIYA-825 is designed as a one-time gene therapy expressing a fusion protein inhibiting complement C3 and C5, delivered by an in-office suprachoroidal injection with the objective of slowing GA lesion growth and vision loss. GA affects approximately two million people in the United States and the European Union. Existing treatment options require monthly or bimonthly physician-administered intravitreal injections that can be burdensome for patients. Kriya has designed KRIYA-825 for GA with the following potential goals in mind: Robust complement inhibition: A novel complement receptor 2 -complement receptor 1 (CR2-CR1) fusion protein—where the CR1 domain is designed to block the function of both C3 and C5, while the CR2 domain is designed to bind to cell surfaces where complement fragments deposit and cause damage;Multi-year durability: Adeno-associated virus (AAV)-mediated continuous expression of CR2-CR1 fusion protein following a one-time injection to eliminate the need for frequent intravitreal injections as required by currently available therapies for GA; andTargeted delivery: One-time suprachoroidal injection with the goal of achieving transduction of retinal cells while minimizing inflammation and overall patient burden. Thyroid Eye Disease (TED): KRIYA-586 is designed as a one-time gene therapy expressing an antibody blocking insulin-like growth factor-1 receptors (IGF-1R), delivered by an in-office peribulbar injection with the objective of reducing proptosis and diplopia as well as other key features of TED. Approximately one million people in the United States and the European Union have TED. The only FDA-approved treatment is an intravenously administered monoclonal antibody that works by blocking IGF-1R. Kriya has designed KRIYA-586 for TED with the following potential goals in mind: Minimized treatment burden: One-time, in-office peribulbar injection to eliminate the burdensome requirement for multiple infusions or injections;Focal delivery: Localized antibody expression in extraocular muscles and fat tissue to limit the potential for side effects that can be observed with systemically administered therapies; andLong-term durability: AAV-mediated antibody expression to deliver sustained improvements in proptosis and diplopia as well as other key manifestations of TED. For more information on Kriya's Ophthalmology programs, please visit the Ophthalmology page of our website. Metabolic Disease ProgramsDiabetes: KRIYA-839 is designed as a one-time gene therapy expressing insulin and glucokinase, delivered intramuscularly with the objective of driving durable glycemic control and reducing or eliminating the need for exogenous insulin. Of the approximately 90 million people in the United States and the European Union who have type 1 and type 2 diabetes, 17 million use insulin to manage their disease. Current treatments for type 1 diabetes require burdensome chronic insulin injections and constant treatment modification based on dietary intake and blood glucose monitoring. Kriya has designed KRIYA-839 for diabetes with the following potential goals in mind: Robust glycemic control: Improving time-in-range and lowering HbA1c to reduce the risk of long-term diabetic complications;Insulin independence: Enabling patients to achieve insulin independence while maintaining robust glycemic control; andMinimized treatment burden: Substantially reducing or eliminating the need for multiple daily injections of insulin with a one-time treatment. Nonalcoholic Steatohepatitis (NASH): KRIYA-497 is designed as a one-time gene therapy expressing the native FGF21 protein, delivered intramuscularly with the objective of reducing fibrosis, reversing steatosis, and improving the overall metabolic profile of patients with later stages of NASH with liver predominant pathology (F3 and compensated F4). NASH affects approximately 40 million people in the United States and the European Union. There are currently no FDA-approved therapies for the treatment of NASH. Kriya has designed KRIYA-497 for NASH with the following potential goals in mind: Robust anti-fibrotic activity: Expression of native FGF21 protein to drive natural ligand/receptor interactions and enhance biodistribution across multiple organs;Minimized treatment burden: One-time intramuscularly administered therapy to reduce complexity for patients who are often taking multiple other concomitant therapies; andContinuous expression: Consistent concentration of native FGF21 protein to limit Cmax-mediated gastrointestinal issues. For more information on Kriya's Metabolic Disease programs, please visit the Metabolic Disease page of our website. Neurology ProgramsTrigeminal Neuralgia (TN): KRIYA-748 is designed as a one-time gene therapy expressing a chemogenetically-gated ion channel, delivered through an injection into the trigeminal nerve with the objective of reducing the frequency and severity of debilitating paroxysmal pain attacks. Once expressed in the nerve, the channel is designed to selectively open in the presence of the orally-administered CNS-penetrant small molecule, varenicline (the FDA-approved generic medication for smoking cessation originally marketed under the brand name "Chantix®"), leading to the passage of chloride ions and reduced excitation of target neurons. Trigeminal Neuralgia affects approximately 400,000 people in the United States and the European Union. Current treatments include anticonvulsants, which can have significant tolerability issues and waning efficacy over time. Kriya has designed KRIYA-748 for trigeminal neuralgia with the following potential goals in mind: Pain reduction: Goal of reducing the frequency and severity of pain attacks by focally inhibiting neuronal hyperexcitability in the trigeminal nerve;Long-term durability: One-time administration of gene therapy to eliminate the need for cycling through anti-epileptic medications and surgical procedures; andRegulatable activity: Targeted delivery to the trigeminal nerve, additionally engineered with the ability to “turn off” the gene therapy through withdrawal of the orally-administered small molecule, varenicline. Focal Epilepsy: KRIYA-382 is designed as a one-time gene therapy expressing a chemogenetically-gated ion channel, delivered through a direct injection into epileptic foci within the brain with the objective of reducing the frequency and severity of seizures. Kriya’s epilepsy gene therapy uses a similar chemogenetic technology as is utilized in its trigeminal neuralgia program, described above. Focal epilepsy affects close to 5 million people in the United States and the European Union. Current treatments include first- and second-line antiseizure medications. A significant proportion of patients suffer from refractory epilepsy, many of whom are candidates for invasive neurosurgery. Kriya has designed KRIYA-382 for focal epilepsy with the following potential goals in mind: Seizure reduction: Goal of minimizing seizures by inhibiting neuronal hyperexcitability at epileptic foci;Long-term durability: One-time administration of gene therapy designed to eliminate the need for cycling through anti-epileptic medications; andRegulatable activity: Targeted delivery to epileptic foci, additionally engineered with the ability to “turn off” the gene therapy through withdrawal of the orally-administered small molecule, varenicline. For more information on Kriya's Neurology programs, please visit the Neurology page of our website. About Kriya TherapeuticsOur mission is to revolutionize medicine, with the ultimate goal of eliminating human suffering and enabling people to live without the burden of disease. Kriya is a biopharmaceutical company developing gene therapies to address common diseases affecting millions of people around the world. With operations in Palo Alto, California and Research Triangle Park, North Carolina, Kriya has raised over $600 million, which will be used to advance a broad pipeline of gene therapies for ophthalmology, metabolic disease and neurology. For more information, please visit www.kriyatx.com and follow us on LinkedIn and X.