Platinum-Resistant Fallopian Tube Carcinoma

Shares in Shattuck fell 51% to $1.72 in premarket trading. Shattuck Labs has hammered another nail into the coffin of CD47. After seeing a “modest” effect on survival in blood cancer, the biotech axed its candidate, pivoted to a preclinical program and gave 40% of its employees pink slips.The dropped molecule is a dual-sided fusion protein with three functional domains, a design intended to enable macrophages to eat cancer cells while activating antigen-presenting cells and avoiding anemia. As other companies dropped out of the space, Shattuck’s SL-172154 became the leading CD47 candidate in acute myeloid leukemia (AML).However, hopes that the company could buck the trend in CD47 have faded throughout 2024. Shattuck’s share price fell after the publication of interim data in May and June, falling from above $10 to below $4. Now, a third look at the data has persuaded Shattuck to drop the program.The biotech said it saw “only modest improvement in median overall survival compared to azacitidine monotherapy benchmarks.” In AML, the current median overall survival (OS) in patients who received SL-172154 and the chemotherapy drug azacitidine is 10.5 months and, at best, could reach 11.7 months. The benchmark for TP53m AML patients treated with azacitidine alone is five to eight months. In TP53m higher-risk myelodysplastic syndromes, Shattuck reported a median OS of 10.6 months that won’t improve beyond 13.1 months in subsequent data cuts. The biotech’s benchmark in that setting is 9 to 12 months. The data prompted the biotech to move on to “opportunities with a higher probability of success,” Shattuck CEO Taylor Schreiber, M.D., Ph.D., said in a statement.Shattuck is now focused on SL-325, a DR3 antagonist antibody. The biotech has identified DR3 blockade as a way to treat inflammatory bowel disease. Shattuck is aiming to file to test the antibody in humans in the third quarter of 2025. SL-325 acts on the same pathway as TL1A, the target of a molecule Roche bought for $7.1 billion. Shattuck believes targeting DR3 rather than TL1A will improve potency.The company will need fewer employees to execute its revised strategy. Having ended last year with 75 full-time employees across two sites in Texas and North Carolina, Shattuck is now laying off 40% of its staffers. The change will result in restructuring charges of around $1.5 million but ultimately cut costs, extending the biotech’s cash runway into 2027 and beyond the delivery of phase 1 data on SL-325.Shattuck shared details of the changes alongside news of the end of its deal with Ono Pharmaceutical. Ono paid $2 million upfront in February to collaborate on bifunctional fusion proteins directed toward a pair of targets for the potential treatment of autoimmune and inflammatory diseases. The Japanese drug developer put up $3.4 million to fund the first six months of research. Rather than continue the collaboration, Shattuck and Ono have mutually agreed to terminate the license deal. The termination deprives Shattuck of the chance to pocket more payments from Ono, including up to $7 million tied to research milestones, but also frees the biotech from performance obligations.Shares in Shattuck fell 51% to $1.72 in premarket trading.

Results Reveal Mechanism of Action and Correlative Analyses Data HELSINKI, Finland, April 10, 2024 (GLOBE NEWSWIRE) -- TILT Biotherapeutics (TILT), a clinical-stage biotechnology company developing cancer immunotherapies presented promising preliminary safety and efficacy data from their ongoing Phase I clinical trial (NCT05271318) in platinum resistant or refractory ovarian cancer patients at the American Association for Cancer Research (AACR) Annual Meeting 2024. TILT-123 in combination with MSD’s (a tradename of Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA® (pembrolizumab) was safe and demonstrated signs of efficacy in both platinum resistant and refractory ovarian cancer patients. Analysis of biological samples revealed insights into mechanism of action, including an immunological pro predictive of clinical response. The study results were based on 15 patients who received intratumoral or intraperitoneal doses of TILT-123 therapy in combination with intravenous doses of pembrolizumab in an open label phase I clinical trial using a standard 3+3 dose escalation scheme. Notably, disease control was seen in 71% of evaluable patients including one long lasting partial response in a patient with mucinous carcinoma. Tumor size reductions and significant immunomodulation were seen in injected and non-injected tumors, indicating the potential for a systemic response. The results demonstrated that a strong humoral response and increased presence of IgE+ plasma cells significantly correlated with clinical response and overall survival. They also revealed insights into the mechanism of action of the combination therapy. TILT Biotherapeutics’ founder and CEO, Akseli Hemminki, a cancer clinician who has personally treated hundreds of cancer patients with oncolytic viruses, said “We are excited to see the latest ongoing positive potential to bring a more effective treatment to patients with refractory ovarian cancer that have few other treatment options. Importantly, an immune response and reduction in tumour size was seen from intratumoral injections of the combination therapy as well as those away from the tumour site, which demonstrates the potential for a systemic response.” TILT-123, an oncolytic adenovirus armed with tumor necrosis factor alpha (TNFα) and interleukin-2 (IL-2), is designed to enhance the efficacy of T-cell therapies, including immune checkpoint blockade or adoptive cell transfer for re-invigoration of the tumor microenvironment. TILT’s approach uses oncolytic viruses to selectively replicate in and lyse cancer cells, while simultaneously stimulating immune responses towards the tumor. The results presented at AACR 2024, along with data from other ongoing trials, underscore the promise of TILT-123 as a novel cancer therapy. Continued clinical evaluation, including ongoing trials (NCT04695327, NCT04217473, NCT06125197, and NCT05222932), will further elucidate the therapeutic potential of TILT-123 across various solid cancer types. Reference: Immunological activity of oncolytic adenovirus encoding TNFα and IL-2 (TILT-123) in combination with pembrolizumab in platinum resistant or refractory ovarian cancer patients KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Notes to Editors About TILT Biotherapeutics TILT Biotherapeutics is a clinical-stage biotechnology company developing cancer therapeutics based on its proprietary oncolytic adenoviruses armed with molecules including cytokines that can activate T cells and destroy cancer cells. The company’s patented TILT® technology can be delivered intravenously, locoregionally, or intratumorally. It modifies the tumor microenvironment and has a broader systemic effect. By making cold tumors hot, it eliminates cancer’s ability to evade immune responses, thereby enhancing T-cell therapies such as immune checkpoint inhibitors, tumor infiltrating lymphocyte (TIL) therapy, and CAR T therapies. TILT’s lead asset, TILT-123 also known as Igrelimogene litadenorepvec, is a 5/3 chimeric serotype adenovirus armed with two human cytokines: TNF alpha and IL-2. About fifty patients have been treated in four international trials sponsored by the company with promising initial efficacy responses observed in some of the patients. The company’s pioneering approach has been recognized by industry leaders. It has two collaborations with MSD, a tradename of Merck & Co., Inc., investigating TILT-123 in combination with KEYTRUDA® (pembrolizumab) in ovarian cancer (NCT05271318) and in refractory non-small cell lung cancer (NCT06125197). The company is also collaborating with Merck KGaA, Darmstadt, Germany, and investigating TILT-123 in combination with avelumab. Based in Helsinki, Finland, and with an office in Boston, the company was established over a decade ago as a spin-out from the University of Helsinki. It has funding from Lifeline Ventures, Finnish Industry Investment (TESI), angel investors, Business Finland, the European Innovation Council, and the U.S. Department of Defense. Media contacts TILT Biotherapeutics COO Aino Kalervo aino@tiltbio.com Scius Communications Katja Stout +447789435990 katja@sciuscommunications.com Daniel Gooch +447747875479 daniel@sciuscommunications.com

GUANGZHOU, China, March 25, 2024 /PRNewswire/ -- Bio-Thera Solutions, Ltd. (688177:SH), a commercial-stage biopharmaceutical company developing a pipeline of innovative therapies and biosimilars, today announced receiving IND clearance from the US FDA for a phase II Study for BAT8006, an innovative Antibody Drug Conjugate (ADC) targeting Folate Receptor α (FRα). The phase II study will investigate the use of BAT8006 for the treatment of subjects with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer. FRα is a folic acid-binding protein located on cell membranes that is overexpressed in a variety of solid tumors such as ovarian, lung, breast cancer, etc., but has a limited distribution and a lower level of expression in normal tissues. This differential expression makes FRα an attractive target for cancer drug development. BAT8006 is developed using Bio-Thera's proprietary anti-FRα antibody and proprietary ADC linker-payload combination that includes a systemically stable and cleavable linker and a small molecule topoisomerase I inhibitor. Preclinical studies have shown that BAT8006 demonstrates good stability and safety along with strong anti-tumor activity. The small molecule topoisomerase I inhibitor payload carried by BAT8006 has a strong cell membrane penetration ability, which enables the payload to kill nearby cancer cells after the cancer cells initially targeted by the ADC are killed. This bystander effect gives BAT8006 the potential to effectively overcome the heterogeneity of the tumor. Currently, a phase I study of BAT8006 is ongoing in China. In that trial, the dose escalation study has completed and the dose expansion and dose optimization study in a series of tumors are ongoing. The preliminary data indicated that BAT8006 could potentially be a best-in-class drug. Updated clinical data will be presented at future academic conference. About Bio-Thera Solutions Bio-Thera Solutions, Ltd., a leading innovative, global biopharmaceutical company in Guangzhou, China, is dedicated to researching and developing novel therapeutics for the treatment of cancer, autoimmune, cardiovascular, eye diseases, and other severe unmet medical needs, as well as biosimilars of existing, branded biologics to treat a range of cancer and autoimmune diseases. As a leader in next generation antibody discovery and engineering, the company has advanced multiple candidates into late-stage development, including three approved products: QLETLI® in China, and TOFIDENCE™/ BAT1806 and Avzivi®/Pobevcy® in the US and China. In addition, the company has more than 20 promising candidates in clinical trials, focusing on immuno-oncology in the post-PD-1 era and targeted therapies such as ADCs. For more information, please visit or follow us on Twitter (@bio_thera_sol) and WeChat (Bio-Thera). Cautionary Note Regarding Forward-Looking Statements This news release contains certain forward-looking statements relating to BAT8006 or the product pipelines in general of Bio-Thera Solutions. Readers are strongly cautioned that reliance on any forward-looking statements involves known and unknown risks and uncertainties. The forward-looking statements include, among others, those containing "could," "may," "should," "will," "would," "anticipate," "believe," "plan," "promising," "potentially," or similar expressions. They reflect the company's current views with respect to future events that are based on what the company believes are reasonable assumptions in view of information currently available to Bio-Thera Solutions, and are not a guarantee of future performance or developments. Actual results and events may differ materially from information contained in the forward-looking statements as a result of a number of factors, including, but not limited to, risks and uncertainties inherent in pharmaceutical research and development, such as the uncertainties of pre-clinical and clinical studies, for example, the development processes could be lengthy and high in vitro activity may not translate to desired results in vivo or successful clinical studies. Other risks and uncertainties include challenges in obtaining regulatory approvals, manufacturing, marketing, competition, intellectual property, product efficacy or safety, changes in global healthcare situation, changes in the company's financial conditions, and changes to applicable laws and regulations, etc. Forward-looking statements contained herein are made only as of the date of their initial publication. Unless required by laws or regulations, Bio-Thera Solutions undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, changes in the company's views or otherwise. 1. QLETLI® is a registered trademark of Bio-Thera Solutions, Ltd. 2. TOFIDENCETM is a trademark of Biogen MA, Inc. 3. AVZIVI® is a registered trademark of Sandoz AG 4. POBEVCY® is a registered trademark of Bio-Thera Solutions, Ltd. Contact Bio-Thera Solutions, Ltd.: Bert E. Thomas IV +1.410.627.1734 bethomas@bio-thera.com