Shares of Syros Pharmaceuticals Inc. (NASDAQ:SYRS) tumbled 86%, or $2.35, to trade at 86 cents after the firm said the phase III study testing tamibarotene in myelodysplastic syndrome (MDS) patients with RARA gene overexpression missed its primary endpoint of complete response (CR). Called Select-MDS-1, the trial testing the oral, selective, retinoic acid receptor alpha agonist showed that, in the first 190 enrolled patients, the CR rate by intent-to-treat in the tamibarotene plus azacitidine treatment arm was 23.8% compared to a CR rate of 18.8% in the placebo plus azacitidine control arm and was not statistically significant, resulting in a p-value of 0.2084. Cambridge, Mass.-based Syros is sifting the data and evaluating next steps.

Amgen stock holds steady as company dismisses analyst report

Amgen Inc. has shrugged off a Cantor Fitzgerald analyst report that wiped about $12 billion from the company’s market cap. The Nov. 12 analyst report noted supplemental data from the company’s phase I study of obesity drug Maritide showing bone mineral density loss in patients. The data could be important, the analysts noted, because this was previously an unknown from the study and could be relevant for the phase II study and commercial dynamics due to risks associated with the mechanism, which is GIPR antagonism. Amgen insisted that it does not see an association between Maritide administration and bone density changes. Amgen’s stock (NASDAQ:AMGN) dropped 7% on Nov. 12 but is holding steady with a 1.3% share price increase at midday on Nov. 13.

Another TCR T-cell win for Adaptimmune in rare sarcomas

On the heels of U.S. FDA approval of its first T-cell therapy, Adaptimmune Therapeutics plc reported positive results from a pivotal study for its second candidate, lete-cel, with plans for a rolling BLA filing in 2025. The primary analysis from 64 patients with synovial sarcoma or myxoid/round cell liposarcoma who received previous anthracycline-based therapy showed treatment with lete-cel produced RECISTv1.1 responses in 42% of patients, with six complete responses and 21 partial responses. Lete-cel, or letetresgene autoleucel, is an engineered TCR T-cell therapy targeting the solid tumor antigen NY-ESO-1 and comes from the same platform that produced Tecelra (afamitresgene autoleucel), a T-cell therapy targeting MAGE-A4 that won accelerated approval in August for treating advanced synovial sarcoma.

Daiichi Sankyo, Astrazeneca submit new BLA for Trop2 lung cancer ADC

Daiichi Sankyo Co. Ltd. and Astrazeneca plc have submitted a new BLA to the U.S. FDA for accelerated approval for datopotamab deruxtecan (dato-dxd) for treating locally advanced or metastatic epidermal growth factor receptor-mutated (EGFR-mutated) non-small-cell lung cancer (NSCLC) patients who have received prior systemic therapies. The companies have voluntarily withdrawn their dato-dxd BLA in the U.S. for patients with advanced or metastatic nonsquamous NSCLC based on the Tropion-Lung01 phase III trial. The decision to submit a new BLA for EGFR-mutated NSCLC and withdraw the previously submitted BLA for nonsquamous NSCLC was informed by feedback from the FDA, the companies said.

Apollo signs near-$1B deal for Sunshine’s FGF21/GLP-1 injection

Apollo Therapeutics Group Ltd. and Sunshine Lake Pharma Co. Ltd. inked a potential $938 million licensing deal for APL-18881 (HEC-88473), Sunshine’s dual fibroblast growth factor 21 (FGF21)/glucagon-like peptide-1 (GLP-1) receptor agonist currently in a phase II study for type 2 diabetes. The near-$1 billion deal for Sunshine’s subcutaneous therapeutic candidate includes $12 million in an up-front payment and up to $926 million in development, regulatory and commercial milestone payments, along with royalties. U.K.- and U.S.-based portfolio firm Apollo will, in turn, gain global but ex-China rights to develop, manufacture and commercialize APL-18881 for all current and future indications. Guangdong, China-based Sunshine will retain domestic development, manufacturing and commercialization rights.

Quiescent, but not quiet, cancer stem cells in glioblastoma relapse

Six main cell types form glioblastomas, the most aggressive brain cancer due to its high rate of recurrence. Of these six, quiescent cancer stem cells are responsible for resistance to therapy and the reappearance of the tumor, according to a study that identified the six groups and highlighted the importance of these stem cells for the design of more effective therapies. “During every single cell division, you might have some mutations accumulate. Most of them seem not really relevant for tumor formation, but some of them are really critical,” Xuanhua Xie told BioWorld. Xie, assistant professor at the University of Nebraska Medical Center and senior research scientist at the Memorial Sloan Kettering Cancer Center, is the lead author of the paper published in Neuron on Nov. 6, 2024.

BioWorld Insider podcast: Modifi gets creative on the rocky road to a multibillion-dollar buyout

Modifi Biosciences Inc. was recently acquired by Merck & Co. Inc. for $30 million up front. Modifi shareholders could receive milestones of up to $1.3 billion. It all happened in the dizzyingly short span of a little more than two years. Modifi’s founder, Ranjit Bindra, and a small group of advisers brought the company through preclinical work on DNA repair for treating glioblastoma and then twice faced running out of money and shutting down the company. Confounding the typical wisdom, Bindra and co-founder Kevin Rakin ended up putting the Merck deal together all by themselves. “People would actually ask, ‘Who is your banker that did the M&A deal?’ I said, ‘You're looking at them. It's me and Kevin Rakin.’ I learned a lot.” Bindra talks more about Modifi in the newest episode of the BioWorld Insider podcast.

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