Igrelimogene litadenorepvec

Results reinforce potential to develop TILT-123 as a systemic therapy HELSINKI, Finland, May 28, 2024 (GLOBE NEWSWIRE) -- TILT Biotherapeutics (TILT), a clinical-stage biotechnology company developing cancer immunotherapies, announces that it will present two abstracts at the American Society of Clinical Oncology (ASCO) Annual Meeting 2024. Abstract (5562) demonstrates promising safety and efficacy data of TILT-123 in ovarian cancer patients, whilst abstract (2658) demonstrates the potential for TILT-123 as an intravenous therapy. Abstract (5562)* covers the results of a Phase I clinical trial of TILT-123 in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA® (pembrolizumab), for the treatment of platinum-resistant or -refractory ovarian cancer, demonstrating the combination is safe and appears to induce disease control in a difficult-to-treat patient population. 14 patients (out of 15 enrolled) were evaluable for treatment response, with disease control achieved in 64.3%. Analysis of biological samples indicated the presence of TILT-123 and induction of T cells in injected and non-injected lesions. Long term survival was seen in some patients: Median progression free survival (PFS) and overall survival (OS) in all patients were 105 and 280 days. In patients with stable disease (SD) on day 92 by RECIST 1.1, median PFS was 174 days and median OS was 293 days. Abstract (2658) introduces the development of oncolytic adenovirus TILT-123 as an intravenous (IV) therapy. Results across three Phase I trials showed that IV delivery results in systemic tumor transduction and accumulation of lymphocytes at tumors. This means TILT-123 reached tumors, despite not being directly injected into them, and successfully triggered an immune system toward the cancer. The IV injection of TILT-123 results in persistence of the virus in peripheral blood for up to 7 days. Tumor transduction was observed in 75% of patients in three Phase I trials on day 8 post TILT-123 systemic administration. TILT Biotherapeutics’ founder and CEO, Akseli Hemminki, a cancer clinician who has personally treated hundreds of cancer patients with oncolytic viruses, said “This data presented at ASCO 2024 provides additional validation as we move forward in our clinical trials for patients with resistant or refractory ovarian cancer that have few other treatment options.” 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. TILT’s approach uses oncolytic viruses to selectively replicate in and lyse cancer cells, while simultaneously stimulating immune responses towards the tumor. References: Abstract (5562): Poster #433 presented 3 June at 09:00-12:00 Abstract (2658): Poster #137 presented 1 June at 09:00-12:00 *The work was supported by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense, in the amount of $2,098,194.00, through the Ovarian Cancer Research Program under Award No. HT9425-23-1-0988. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Assistant Secretary of Defense for Health Affairs or the Department of Defense. 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 (Merck & Co., Inc., Rahway, NJ, USA) 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

Pictured: Gloved hands amid a collage of cancer treatments/Taylor Tieden for BioSpace Parsing key trends from 7,200 abstracts on cancer-related research can be challenging—take it from someone who’s spent the past week trying to do it! But pretty quickly, a few key themes became apparent at the American Association for Cancer Research’s annual meeting. First and foremost, the programs presented are tackling difficult cancers with a high unmet need and a dire prognosis. Some of the presentations last weekend involved drug candidates targeting pancreatic cancer, for example. In 2023, the five-year survival rate for pancreatic cancer was just 12%, according to the American Cancer Society. Two presentations—one on Bristol Myers Squibb’s blockbuster immunotherapy Opdivo, the other on a messenger RNA vaccine in development by BioNTech and Genentech—showed promising signals. Opdivo’s trial, the first reported of a PD1 inhibitor in neoadjuvant pancreatic cancer, indicated that the drug may improve outcomes, while BioNTech and Genentech’s vaccine continued to show potential in a particularly difficult-to-treat form of the disease. This announcement also dovetailed with another prominent theme at AACR: the resurgence of cancer vaccines, which are also making inroads in advanced liver cancer, head and neck cancer, non-small cell lung cancer and glioblastoma. Glioblastoma is a particularly aggressive form of brain cancer that carries a 5-year survival rate of just 10%; patients typically survive between 15 and 18 months after being diagnosed. A Phase I study of Diakonos Oncology’s dendritic cell vaccine showed “substantially increased survival” in glioblastoma patients; 88% of patients remained alive a year after treatment, compared to a historical 53% of those on standard regimens. Other platforms and approaches also appear to be breaking through against difficult-to-treat cancers, though many of the results presented at AACR are still early stage. As anticipated, antibody-drug conjugates (ADCs) were a focus, with Vincerx Pharma presenting Phase I data in metastatic tumors and Merck and Kelun-Biotech reporting a potential survival benefit from their TROP2-directed ADC in gastric cancer. Several other modalities were also on display at AACR. Phase I data from Menlo Park, Calif.–based Synthekine, for example, showed that its α/β biased interleukin-2 (IL-2) partial agonist, STK-012, has thus far avoided the toxicities associated with IL-2 therapies while also demonstrating a “favorable” efficacy pro advanced solid tumors. And TILT Biotherapeutics reported that TILT-123, an oncolytic adenovirus armed with tumor necrosis factor alpha and IL-2, “demonstrated signs of efficacy” when combined with Merck’s Keytruda in a Phase I trial in patients with platinum-resistant and refractory ovarian cancer. Another therapy that drew attention at the meeting was AstraZeneca’s next-generation poly-ADP ribose polymerase 1 (PARP1) selective inhibitor, which experts are hopeful can negate some of the toxicities caused by drugs that inhibit both PARP1 and PARP2. Timothy Yap, vice president and head of clinical development in the Therapeutics Discovery Division at The University of Texas MD Anderson Cancer Center, noted in his presentation of the positive Phase I/II trial data that there is a “great opportunity” to combine a selective PARP1 inhibitor with other therapies. This was a point also made by David Weinstock, vice president of discovery oncology at Merck, who in March told BioSpace that we are moving toward a future “where we have enough medications that each work individually and have minimal side effects so that we can create even larger combinations, which offer the most benefit to people.” As a science journalist, it’s easy to get bogged down in the data, the results and biggest trends (ADCs for all!) and forget the human face of cancer. As a human being, it’s easy to get depressed by improvements that might seem incremental, but an additional six months can mean another birthday, another anniversary or the birth of another grandchild. Elevation Oncology CSO David Dornan told me that solid cancers “are almost equally as hard and different in their own right.” But progress is being made. In 2023, the five-year survival rate for pancreatic cancer increased by one percentage point from the previous year, marking the second year in a row survival has increased. Overall, the cancer death rate in the U.S. has declined by 33% since 1991. I, for one, am looking forward to reading about the next advances at the American Society of Clinical Oncology’s annual meeting in June. Heather McKenzie is a senior editor at BioSpace. You can reach her at heather.mckenzie@biospace.com. Also follow her on LinkedIn.