TC-510

Genentech is severing ties with Adaptimmune, backing out of a 2021 deal the Roche company had paid $150 million cash for. In the same week that Genentech confirmed it's cutting 3% of its staff, the Roche subsidiary has terminated a cell therapy partnership with Adaptimmune Therapeutics worth up to $3 billion biobucks. The collaboration, inked in 2021, was a licensing deal focused on the development of two types of allogeneic T-cell therapies: off-the-shelf therapies directed to up to five targets and personalized therapies using αβ T-cell receptors isolated from a patient, with these therapies being administered to the same patient. At the time, Genentech paid out $150 million in cash. Since then, Adaptimmune has earned $35 million in milestone payments. The deal termination will set in 180 days after notice of the decision was received, meaning the terms of the pact are effective until then, according to Securities and Exchange Commission filings. Adaptimmune received word of the termination on Wednesday, according to the filing. The Adaptimmune news comes shortly after Genentech confirmed to Fierce Biotech that it would be trimming roughly 3% of its workforce across "several departments.” Earlier this year, the biotech's parent company Roche announced cuts to its product development team. “Note that this limited reduction will allow us to shift resources to the areas that we believe can provide the greatest impact for patients,” a Genentech spokesperson told Fierce Biotech in an emailed statement. “We are actively hiring in a number of areas to bring forward our most promising molecules and capabilities, and we project that the overall workforce across Roche will remain stable throughout 2024.” For Adaptimmune, the termination comes almost exactly one year after another pharma discontinued work with the biotech. In April 2023, GSK paid Adaptimmune $37.3 million to wipe its hands of two programs, one of which included lete-cel, an asset the company at one point touted as its leading cell therapy. Then, in November, Adaptimmune axed two programs dubbed Gavo-cel and TC-510. After a review of safety and efficacy data for both candidates, the U.K. company said it didn’t “see a path forward” for further development of either programs. Now, the company has zoomed in on launching afami-cel—which has snagged FDA priority review and is slated for an FDA decision by or on August 4 of this year—for patients with advanced synovial sarcoma. "We've had a very valuable collaboration with our partner Genentech, and we continue to believe in the long-term potential of our iPSC-based allogeneic platform,” Adaptimmune CEO Adrian Rawcliffe said in an April 12 release. “Over the past 12 months, we've been resolutely focused on our late-stage autologous pipeline—in particular, our sarcoma franchise. We have the resources to deliver afami-cel to market as planned, and I look forward to updating on progress at our investor day next week."

Adaptimmune Therapeutics, Monte Rosa Therapeutics and Intellia Therapeutics are all throwing programs to the discard pile. Many hoped the end of 2023 would bring some solace for biotech after nearly two years of challenging market conditions. As the year nears its end, that relief remains largely out of reach, as cuts to both teams and pipelines continue to climb. Today, at least three more biotechs have tossed candidates into the ever-growing pile of discontinued programs. First up is Adaptimmune Therapeutics, a biotech terminating two programs dubbed Gavo-cel and TC-510. After a review of safety and efficacy data for both candidates, the T-cell therapy company didn’t “see a path forward” for further development of either programs, according to a third-quarter earnings release. Gavo-vel was a phase 2 autologous cell therapy that had an overall response rate (ORR) of 11% across patients with ovarian cancer or mesothelioma. Meanwhile, cell therapy TC-510 was tied to one partial response in mesothelioma out of five patients with varying cancers but a high incidence of cytokine release syndrome and pneumonitis. The blow comes after GSK paid Adaptimmune 30 million pounds ($37.3 million) to wipe its hands of two programs this spring. One of the programs was lete-cel, an asset Adaptimmune had at one point touted as its leading cell therapy. As the biotech awaits an FDA approval decision for its investigational therapy targeting MAGE-A4 in solid tumors, dubbed Afami-cel, discovery work will continue with Roche’s Genentech on two allogeneic programs.    The second biotech cutting programs is Monte Rosa Therapeutics, a Boston-based biotech with a molecular glue platform. In a move to prioritize resources, the company is discontinuing an early-stage sickle cell program. Not much is known beyond that, as little was publicly revealed about the discovery program. The company will focus on other programs, such as its clinical-stage GSPT1-directed candidate called MRT-2359 and work with Roche, who inked a deal last month for the use of Monte Rosa’s QuEEN platform to target cancer and neurological diseases previously considered out of reach. Last but not least is Intellia Therapeutics, a Cambridge, Mass.-based company using CRISPR-based tech to build in vivo and ex vivo therapies. The biotech is halting all further preclinical activities for NTLA-2003, an asset designed to treat a rare, inherited disorder called AATD-associated liver disease. Instead, Intellia intends to advance a different AATD research-stage program that uses the company’s DNA writing technology. Intellia, which reported earnings this morning, saw its stock tumble 12% from $28.45 at market open this morning to $25.03 at 11 a.m. ET.  Less than a month ago, Intellia received the FDA green light to study NTLA-2001, an in vivo CRISPR-based gene editing therapy in the U.S. The company worked with sites in Europe and New Zealand to study the therapy in a phase 1 trial and showed NTLA-2001 may safely reduce levels of misfolded TTR, a protein that drives the rare, life-threatening disease ATTR amyloidosis. The new FDA allowance positions the company to start a phase 3 trial of the Regeneron-partnered candidate by the end of the year. Editor's note: This article was updated at 9:30 a.m. ET Nov. 10 with revisions to information provided about lete-cel.