Loxo Oncology, Inc.

Josh Bilenker and Jeff Engelman’s secretive startup Treeline Biosciences has another $421 million, according to a new SEC filing . The funding, which closed today according to the filing, ranks as one of the biggest of the year in biotech. Thursday’s filing, combined with previous SEC disclosures, suggests Treeline has raised nearly $900 million since its founding in 2021. The newest filing may be Treeline drawing down on previously committed capital, rather than a new funding round. Bilenker didn’t immediately respond to a request for comment, and an outside spokesperson for the company declined to answer questions about the financing. The Stamford, CT-based startup has raised hundreds of millions of dollars but said little about its financing or its research programs. Bilenker, Treeline’s co-founder and CEO, previously sold Loxo Oncology to Eli Lilly for $8 billion in cash and then had a short stint running the Loxo unit at Lilly. Engelman, Treeline’s other co-founder and chief scientific officer, was previously the global head of oncology at the Novartis Institutes for BioMedical Research. They provided a glimpse into the company in a now-three-year-old blog post outlining a vision of a biotech on the “outer edge of scientific possibility.” At the time, Treeline said it was working on molecular targets in oncology that were difficult to drug, as well as other therapeutic areas. Its work spans small molecules, covalent modifiers, molecular glue degraders, allosteric approaches, machine learning and AI. According to Thursday’s SEC filing, Treeline’s board includes leaders at the investment firms ARCH, KKR, Aisling Capital, OrbiMed, GV and AI Life Sciences, an affiliate of Access Industries.

None The confetti is still flying from Eli Lilly’s party celebrating the approval of Alzheimer’s disease therapy donanemab, but the company is yet again facing the harsh reality of the neurodegenerative disease with the failure of an early tau-targeting med.Lilly Chief Scientific Officer and President, Lilly Research Laboratories Daniel Skovronsky, M.D., Ph.D., said the O-GlcNAcase Inhibitor called LY3372689 failed on the primary endpoint of a phase 2 clinical trial recently. The therapy, which targets the OGA enzyme, did not spur a change in baseline to endpoint time in a rating scale of Alzheimer’s severity in either dose tested.“While this negative outcome was disappointing, we remain committed to tap as a high conviction target in Alzheimer's disease and plan to continue studying tau biology,” Skovronsky said, speaking on a second-quarter earnings call Thursday. The executive said the company is currently reviewing the data for presentation at an upcoming medical conference.LY3372689 was a key part of Lilly’s next wave of Alzheimer’s efforts. After getting donanemab approved in July, to be marketed as Kisunla, the company was hoping that tau would be the next front in the fight against the memory-robbing disease. Behind Kisunla, Lilly has remternetug in phase 3 development, which targets amyloid plaques in the brain. Positive allosteric modulator mevidalen is in phase 2 testing. The company also has two undisclosed neurodegeneration medicines in phase 1.Lilly also trimmed around the edges of other programs after getting some early data on a few candidates.They include LOXO-783, a highly mutant-selective, brain-penetrant, allosteric small molecule PI3Kα H1047R inhibitor that was acquired as part of the acquisition of Loxo Oncology. The drug was being investigated in a phase 1 study in patients with PIK3CA H1047R-mutant advanced breast cancer and other solid tumors.Lilly had taken LOXO-783 into the clinic on the basis of preclinical data showing activity without on-target wild-type PI3Kα mediated toxicity.“We evaluated the ongoing clinical data for the program and compared the molecule to next-generation candidates that we have progressed from our discovery efforts,” Skovronsky said on the call. “We believe our next molecules have greater potential benefits to patients.”Also on the discard pile is an unnamed NRG4 agonist. Neuregulin 4 acts locally on brown and white adipose tissue and works to protect against obesity-related inflammatory and hypoxic events. The Big Pharma had halted work on the asset as “the profile is insufficient for further clinical development,” Skovronsky explained. A GITR antagonist has also been removed from the phase 1 immunology pipeline “due to insufficient efficacy,” Skovronsky said. At the time of publication, Lilly had not confirmed to Fierce whether this was LY3461767, a GITR antagonist that was being evaluated in a phase 1 trial of the drug in patients with chronic heart failure with reduced ejection fraction.Acadamic researchers have named glucocorticoid-induced tumor necrosis factor receptor (GITR), a co-stimulatory immune checkpoint protein, as playing a pivotal in cardiovascular disease. It’s also been suggested as a potential target to enhance immunotherapy, in particular immune checkpoint inhibitors.

The FDA on Wednesday granted Eli Lilly’s selective RET kinase inhibitor Retevmo (selpercatinib) accelerated approval to treat children two years and older with certain RET-mutated thyroid and solid tumours. According to the US regulator, it’s the first targeted cancer therapy for paediatric patients younger than 12 with RET alterations.Specifically, Retevmo was cleared for advanced or metastatic medullary thyroid cancer with a RET mutation; advanced or metastatic thyroid cancer with a RET gene fusion in patients who are radioactive iodine-refractory; and locally advanced or metastatic solid tumours with a RET gene fusion in patients who have progressed on a prior systemic therapy. The RET inhibitor already holds accelerated approval for the thyroid cancer indications in adults and paediatric patients older than 12, as well as the solid tumour indication in adults.Supporting dataThe new paediatric approval was based on results of the Phase I/II LIBRETTO-121 study in 25 patients ages 2 to 20 with locally advanced or metastatic RET-activated solid tumours non-responsive to available therapies.Retevmo led to a confirmed overall response rate (ORR) of 48%. Additionally, the median duration of response (DOR) was not reached, with 92% of responders still seeing a treatment effect at 12 months.The most common adverse reactions seen in more than a quarter of patients were musculoskeletal pain, diarrhoea, headache, nausea, vomiting and fatigue, among others.Lily gained Retevmo through its $8-billion acquisition of Loxo Oncology in 2019.