IL-10

TARA-002 demonstrates 100% complete response rate at any time and 67% 12-month landmark complete response rate in BCG-Unresponsive patients TARA-002 demonstrates 76% complete response rate at any time and 43% 12-month landmark complete response rate in BCG-Naïve patients Favorable safety and tolerability profile with no Grade 3 or greater treatment-related adverse events On track to present updated interim data from approximately 25 six-month evaluable BCG-Unresponsive patients by the end of 2025 Company to host conference call and webcast on Monday, April 28, 2025, at 8:30 a.m. ET April 26, 2025 -- Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, today announced updated results from its ongoing Phase 2 open-label ADVANCED-2 trial assessing intravesical TARA-002, the Company’s investigational cell-based therapy, in high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) patients with carcinoma in situ, or CIS (± Ta/T1), who are Bacillus Calmette-Guérin (BCG)-Unresponsive or BCG-Naïve. The results will be featured today during an interactive poster session at the American Urological Association 2025 Annual Meeting in Las Vegas. “For patients with high-risk NMIBC, there are few effective and durable therapies available other than radical cystectomy, which we know is quite difficult for patients to tolerate,” said Tom Jayram, M.D., Director of the Advanced Therapeutics Center at Urology Associates, and ADVANCED-2 study investigator. “TARA-002 has shown impressive efficacy, safety profile, and 12-month durability in its Phase 2 trial. In the clinic, we have seen TARA-002 become easily integrated into workflow without major hurdles for the patients or staff. This combination of clinical activity and ease of use makes me optimistic about TARA-002 having a meaningful impact in clinical practice.” BCG-Unresponsive Cohort The BCG-Unresponsive dataset includes a total of five patients, all of whom were six- and nine-month evaluable, and three of whom were evaluable at 12 months as of an April 16, 2025 data cutoff. The complete response (CR) rate at any time in BCG-Unresponsive patients was 100% (5/5). The CR rate in BCG-Unresponsive patients was 100% (5/5) at six months, 80% (4/5) at nine months, and 67% (2/3) at 12 months. BCG-Naïve Cohort The BCG-Naïve dataset includes a total of 21 patients, including 16 evaluable at six months, eight at nine months, and seven at 12 months as of an April 16, 2025 data cutoff. The CR rate at any time in BCG-Naïve patients was 76% (16/21). The CR rate in BCG-Naïve patients was 63% (10/16) at six months, 63% (5/8) at nine months, and 43% (3/7) at 12 months. ADVANCED-2 (NCT05951179) is a Phase 2 open-label trial assessing intravesical TARA-002 in NMIBC patients with carcinoma in situ or CIS (± Ta/T1) who are Bacillus Calmette-Guérin (BCG)-Unresponsive (n≈100) and BCG-Naïve (n=31). The BCG-Unresponsive cohort has been designed to be registrational in alignment with the U.S. Food and Drug Administration’s 2024 BCG-Unresponsive Non-muscle Invasive Bladder Cancer: Developing Drugs and Biological Products for Treatment, Draft Guidance for Industry. TARA-002 is an investigational cell therapy in development for the treatment of NMIBC and of LMs, for which it has been granted Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, a broad immunopotentiator marketed as Piciban When TARA-002 is administered, it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a pro-inflammatory response with release of cytokines such as tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma IL-6, IL-10, IL-12. TARA-002 also directly kills tumor cells and triggers a host immune response by inducing immunogenic cell death, which further enhances the antitumor immune response. Bladder cancer is the 6th most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle. Protara is a clinical-stage biotechnology company committed to advancing transformative therapies for people with cancer and rare diseases. Protara’s portfolio includes its lead candidate, TARA-002, an investigational cell-based therapy in development for the treatment of non-muscle invasive bladder cancer (NMIBC) and lymphatic malformations (LMs). The Company is evaluating TARA-002 in an ongoing Phase 2 trial in NMIBC patients with carcinoma in situ (CIS) who are unresponsive or naïve to treatment with Bacillus Calmette-Guérin (BCG), as well as a Phase 2 trial in pediatric patients with LMs. Additionally, Protara is developing IV Choline Chloride, an investigational phospholipid substrate replacement for patients on parenteral nutrition who are otherwise unable to meet their choline needs via oral or enteral routes. The content above comes from the network. if any infringement, please contact us to modify.

First gamma-delta (γδ) TCE to demonstrate significant γδ T cell expansion and activation, potentially offering an alternative to conventional CD3-based approaches without significant adverse events such as cytokine release syndrome (CRS) INB-600 TCE platform significantly expands both Vδ1+ and Vδ2+ subsets to address the reduced cell counts that have limited earlier γδ TCE therapies in cancer patients INB-619 (CD19) and INB-633 (CD33) consistently show potent and highly targeted anti-cancer activity with deep tumor cell depletion in preclinical studies without the increased secretion of dangerous cytokines such as IL-6 Targeted B cell elimination (INB-619) highlights potential applications in B cell–driven autoimmune diseases as well as cancer NEW YORK, April 28, 2025 (GLOBE NEWSWIRE) -- IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company developing innovative gamma-delta (γδ) T cell therapies for cancer and autoimmune diseases, today announced new preclinical data from its innovative γδ T cell engager (γδ-TCE) platform. The data will be presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting on April 30, 2025. The data showed that IN8bio’s new γδ-TCE platform demonstrated potent and consistent cancer-killing activity across targets in leukemia models, while avoiding the secretion of cytokines that drive the dangerous side effects seen with other TCE based immune therapies. Unlike traditional TCEs that rely on CD3 to activate all T cells in the body – often triggering excessive inflammatory responses, potential T cell exhaustion and other serious side effects – IN8bio’s next-gen platform is designed to specifically activate only γδ T cells, a small but powerful subset of immune cells. These cells can naturally detect, phagocytose (eat) and kill tumors cells without needing to be "trained" to recognize specific targets. The platform’s lead molecules, INB-619 (targeting CD19) and INB-633 (targeting CD33), were able to eliminate cancer cells in preclinical studies with minimal release of inflammatory cytokines. This potentially offers a lower risk of cytokine release syndrome (CRS) or the neurotoxicity that can impact 60-75% of patients treated with conventional CD3 TCEs. William Ho, CEO and co-founder of IN8bio, commented, “Our INB-600 TCE platform combines the natural tumor-fighting abilities of γδ T cells with bispecific engagers to generate a more precise and powerful way to mobilize the immune system against cancer cells. These early results in leukemia models are exciting, and we believe this technology can eventually be applied to other hard-to-treat cancers, and even certain autoimmune diseases.” Key highlights from the in vitro studies: INB-619 and INB-633 both triggered strong and specific, linear dose-related killing of leukemia cells (ALL and AML) at low picomolar concentrations. Both molecules activated and expanded two key γδ T cell subsets (Vδ1+ and Vδ2+), which is critical since most cancer patients have reduced numbers of these cells. Both molecules promoted activation and degranulation, with dose-related increases in the expression of cellular markers indicating a transition to a powerful cancer-cell killing phenotype. Importantly, they did so with minimal, if any, changes in dangerous cytokines, such as IL-6, IL-10, and IL-17a – markers that are often linked to cytokine release syndrome (CRS) and other treatment-related toxicities. Because this new off-the-shelf platform can drive γδ T cell expansion without the need for genetic engineering, it has the potential to offer a more scalable and flexible approach to building next-generation immunotherapies. IN8bio continues to expand its γδ T cell therapeutic pipeline beyond genetically engineered and drug-resistant cellular therapies and is exploring various disease indications and any opportunities for partnership with the INB-600 platform. This preclinical data reinforces the company’s differentiated strategy to build modular and scalable therapeutic approaches to leverage the power of γδ T cells to target malignancies with increased precision and reduced toxicity. The AACR 2025 poster is available on the investor section of the company’s website at https://investors.in8bio.com. About IN8bio IN8bio is a clinical-stage biopharmaceutical company developing γδ T cell-based immunotherapies for cancer and autoimmune diseases. Gamma-delta T cells are a specialized population of T cells that possess unique properties, including the ability to differentiate between healthy and diseased tissue. The company's lead program, INB-100, is focused on acute myeloid leukemia evaluating haplo-matched allogeneic γδ T cells given to patients following a hematopoietic stem cell transplant. The company is also evaluating autologous DeltEx DRI γδ T cells, in combination with standard of care, for glioblastoma, and advancing novel γδ T cell engagers for potential oncology and autoimmune indications. For more information about IN8bio, visit www.IN8bio.com. Forward-Looking Statements This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding: the ability of the INB-600 platform to offer a scalable, flexible, more precise and more powerful alternative to conventional CD3-based approaches and have applications in autoimmune diseases as well as cancer; IN8bio’s plans to expand its pipeline beyond genetically engineered and drug-resistant cellular therapy and explore various disease indications and any opportunities for partnership with the INB-600 platform; and other statements that are not historical fact. IN8bio may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: risks to site initiation, clinical trial commencement, patient enrollment and follow-up, as well as IN8bio’s ability to meet anticipated deadlines and milestones; uncertainties inherent in the initiation and completion of preclinical studies and clinical trials and clinical development of IN8bio’s product candidates; the risk that IN8bio may be unable to raise additional capital and could be forced to delay, further reduce or to explore other strategic options for certain of its development programs, or even terminate its operations; IN8bio’s ability to continue to operate as a going concern; the risk that IN8bio may not realize the intended benefits of its γδ-TCE platform or DeltEx platform; the availability and timing of results from preclinical studies and clinical trials; whether the outcomes of preclinical studies will be predictive of clinical trial results; whether initial or interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials; the risk that trials and studies may be delayed and may not have satisfactory outcomes; potential adverse effects arising from the testing or use of IN8bio’s product candidates; the uncertainty of regulatory approvals to conduct trials or to market products; IN8bio’s reliance on third parties, including licensors and clinical research organizations; and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, which are described in greater detail in the section entitled “Risk Factors” in IN8bio’s Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on March 13, 2025, as well as in other filings IN8bio may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and IN8bio expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as otherwise required by law. Contacts: IN8bio, Inc. Patrick McCall 646.933.5603 pfmccall@IN8bio.com Media Contact: Kimberly Ha KKH Advisors 917.291.5744 kimberly.ha@kkhadvisors.com

Distinct groups of inflammatory proteins may contribute to the progression of heart problems in men and women with Fabry disease, a study suggests.While men exhibited a profile associated with a strong pro-inflammatory response, women had a profile that could be linked to accumulating scar tissue. The identified markers may be useful for detecting cardiac problems in Fabry patients early and the findings suggest anti-inflammatory treatments may help slow cardiac progression.The study, “Sex Differences in Circulating Inflammatory, Immune, and Tissue Growth Markers Associated with Fabry Disease-Related Cardiomyopathy,” was published in Cells.Fabry disease is caused by mutations in the GLA gene that lead to a lack of functional alpha-galactosidase A (alpha-Gal A) enzyme. Fatty molecules the enzyme would normally be responsible for breaking down accumulate to toxic levels in tissues throughout the body.Because it’s inherited on the X chromosome, Fabry tends to affect the sexes differently. Generally, men show more severe and earlier-onset symptoms, while the disease course in women is milder and with a later onset, although this can vary significantly.Heart disease is a common symptom of Fabry. Hypertrophic cardiomyopathy (HCM), where the heart muscle becomes abnormally thick and the heart has a harder time pumping blood, is particularly common. But there are sex differences in Fabry-related heart disease, with data suggesting women are typically affected at a later age than men. Moreover, while men characteristically develop progressive HCM with eventual fibrosis, women sometimes develop early fibrosis before overt HCM develops.It’s been proposed that inflammation in response to the buildup of fatty molecules may play a key role in Fabry disease progression, including contributing to cardiac damage. This raises the possibility that circulating inflammatory biomarkers could have potential in early screening for cardiac involvement in Fabry patients, said the scientists, who measured blood levels of inflammatory molecules called cytokines in adult Fabry patients and healthy people as part of an observational clinical study (NCT04724083). They also looked at certain growth factors that can drive remodeling of cardiac tissue that contributes to HCM.The analysis included 45 Fabry patients (21 men, 24 women), of whom 28 had HCM. Twenty healthy people, 10 men and 10 women, served as controls.While heart disease is generally considered to affect women at a later age, early-onset HCM was not uncommon in the study group. The youngest female with a mild form of HCM was 22 and the youngest male was 21.“Thus, the early detection of HCM in females with [Fabry disease] is crucial for effective disease management,” the researchers wrote.Biomarker analyses suggested that Fabry patients had differences in inflammatory markers from healthy controls, with distinct profiles in male and female patients. Various biomarkers were also specifically associated with HCM, again with sex-specific differences.Overall, the biomarker profile in men with HCM suggested activation of the inflammatory NFkB signaling pathway, with markers such as IL-10, IL-2, GM-CSF, and VEGF-A being implicated. This reflects that significant inflammation drives cardiac tissue remodeling that promotes HCM progression in men, said the researchers.On the other hand, women with HCM showed an inflammatory marker profile consistent with activation of the TNF-alpha, TNFR2, and TGF-beta signaling cluster, which may be related to fibrosis development. This may help explain why women with Fabry often show fibrosis early in the course of cardiac disease.“The pivotal roles these cytokines and growth factors play may render them valuable as biomarkers for the early detection and clinical staging of HCM,” the researchers wrote. “Such insights are crucial for healthcare providers to develop strategies for the effective management of [Fabry] patients with cardiac manifestations.”The findings could also inform future treatment strategies, with certain anti-inflammatory treatments having already shown promise for treating cardiovascular disease in the general population.“These findings support the role of inflammation as a therapeutic target in cardiovascular diseases, including Fabry cardiomyopathy, where adjunctive anti-inflammatory therapies may improve clinical outcomes when combined with disease-specific treatments,” they wrote.