Subasumstat

Takeda’s pipeline cull affected assets outside of oncology. Takeda’s vision of becoming a leader in oncology ran into more trouble Thursday when the drugmaker axed (PDF) a midphase immunocytokine and three early-stage CAR-T cell therapy prospects from its R&D pipeline. Under CEO Christophe Weber, Takeda has worked to establish itself as a leader in oncology. But, as the executive said on a quarterly results call with investors, the company has “had some wins ... [and] some setbacks.” The results brought news of more setbacks, with Takeda using the update to reveal it has dropped a clutch of cancer candidates led by modakafusp alfa. Formerly known as TAK-573, modakafusp alfa consists of two interferon alpha-2b molecules fused to an anti-CD38 monoclonal antibody. The idea was to activate innate and adaptive immune cells—while also directly stopping the proliferation of multiple myeloma cells—through targeted interferon signaling. Takeda began a phase 1/2a Darzalex combination trial one year ago, adding to the slate of studies run in support of the immunocytokine, but has now pulled the plug on the program. Andrew Plump, M.D., Ph.D., president of R&D at Takeda, explained the decision on the conference call with investors.  “This is a strategic decision based on a number of factors, including the existing data set, the rapidly evolving multiple myeloma treatment landscape and the long development timelines,” the R&D chief said.  Takeda pushed modakafusp alfa out of the door as part of a pipeline clear-out that also hit three phase 1 autologous CAR-T candidates. Two of the prospects, GPC3-targeted TAK-102 and mesothelin-directed TAK-103, were in development in solid tumors. The third asset, TAK-940, was a CD19-directed, Memorial Sloan Kettering Cancer Center-partnered program that used the 1XX domain to try to enhance efficacy. While Takeda axed a clutch of cancer candidates, Plump said the company “remains committed to oncology and will continue to develop therapies across hematologic and solid tumors.” The R&D chief highlighted the SUMO inhibitor subasumstat, a pair of STING agonists and two T-cell engagers from the Maverick Therapeutics acquisition as candidates to watch.  Plump also cited the appointment of PK Morrow, who joined Takeda from CRISPR Therapeutics last month, as a boost for the oncology unit. Morrow became head of the oncology therapeutic area unit at Takeda, having previously worked as chief medical officer of CRISPR, and held various roles at Amgen. Takeda’s pipeline cull also affected assets outside of oncology. The drugmaker removed three phase 2 drug candidates, namely the rare disease asset TAK-611—which flunked a trial last year—the Parkinson’s disease prospect TAK-071 and the depression molecule TAK-041. In phase 1, Takeda axed treatments for Alzheimer’s disease and nausea as well as a Zika vaccine candidate. Amid the changes, Takeda grew its R&D spend by 7.3%, although Chief Financial Officer Costa Saroukos said that “does reflect some phasing,” and the company is still aiming for a mid single digit increase over the full year. Saroukos made the comment on what looks set to be his last quarterly results conference call as CFO of Takeda.  Milano Furuta, president of Takeda’s Japan pharma business unit, is preparing to take over as CFO in April. Saroukos is leaving because “after 20 years working abroad, I’m ready to move back to Australia to be closer to my family,” the outgoing CFO told investors.

SEATTLE, Nov. 28, 2022 /PRNewswire/ -- Presage Biosciences, a biotechnology company whose mission is understanding the complexity of drug response in the tumor microenvironment, today announced completion of a first-of-its-kind Phase 0 clinical study utilizing its CIVO® (Comparative In Vivo Oncology) multiplexed microdosing technology. Presage evaluated an investigational immuno-oncology agent, subasumstat, alone and in combination with other immuno-oncology agents. The spatial biology and mechanistic insights generated from this fully-enrolled Phase 0 study not only provided additional target validation in patient tumors, but also delivered unique drug combination and pharmacodynamic biomarker data with the potential to inform further clinical development of the investigational therapy. "This pioneering collaboration has delivered important translational data early in the clinical development process to help elucidate the modulation of the tumor microenvironment by an investigational agent through detailed visualization and molecular profiling in patients with head and neck cancer," said Christopher Arendt, Head of Oncology Cell Therapy and Therapeutic Area Unit at Takeda. "Execution of this first-of-its-kind trial (NCT04065555) required innovation on multiple fronts: Development of novel technology, training and coordination of clinical trial sites; establishment of a novel regulatory path with the U.S. Food and Drug Administration, and exploration of a new dimension in spatial biology – pairing drug-exposure with molecular profiling technology," said Rich Klinghoffer, PhD, Presage CEO. "These achievements enabled us to successfully execute on a truly cutting-edge study and I am proud of the Presage Team's accomplishment." The Presage platform was developed to interrogate the highly complex tumor microenvironment that is unique to each individual patient, and to better understand the potential therapeutic response to treatment with investigational cancer agents. Accurate ex vivo modeling of tumors has proven difficult, and represents a fundamental challenge to early drug development. Under the conventional drug development paradigm, evidence of biological activity of a drug is typically not known until later stages of clinical development, and only after investment of significant time, resources, and cost. With a mission to address this fundamental issue, Presage Biosciences operates as a translational oncology research organization that is uniquely capable of providing spatial biology insights to help advance novel treatments for cancer patients. "Patients have unmet needs and require more options to reduce cancer burden, improve survival, and enhance their quality of life and Presage will continue to interrogate the tumor microenvironment and work towards furthering the precision and efficiency of cancer drug development," said Klinghoffer. Preliminary findings from the PBI-TAK-01 study were highlighted at the American Association for Cancer Research (AACR) 2022 Annual Meeting and additional spatial biology data was presented at the Society for Immunotherapy of Cancer (SITC) 2022 Annual Meeting. Presage has ongoing collaborations with Takeda and Merck for Phase 0 trials with CIVO. About CIVO Comparative In Vivo Oncology (CIVO) is Presage's patented platform that enables multiplexed intratumoral microdosing and generation of deep spatial biology insights. Presage's CIVO technology and analysis capabilities are unparalleled at providing insight into drug-exposed areas of the intact tumor microenvironment. Presage is pairing the use of CIVO with molecular profiling technologies in both preclinical and Phase 0 trials in order to inform and de-risk oncology drug development. About Presage Presage Biosciences is a translational oncology company dedicated to understanding the complexity of drug response in the tumor microenvironment. Presage partners with oncology-focused pharmaceutical companies through strategic alliances along with other innovators who are at the forefront of spatial biology and oncology drug development. Presage is privately held and based in Seattle. For more information, visit . Media Contact: Julie Rathbun Rathbun Communications (206) 769-9219 [email protected]