Treeline Biosciences, 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.

Jiangsu Hengrui Pharmaceuticals has out-licensed global rights, excluding China, for its anti-TSLP monoclonal antibody SHR-1905 to One Bio. The deal comes with a $21.5-million upfront payment, but Jiangsu Hengrui could be entitled to over $1 billion in development and sales milestones if the drug is approved in the US, Japan and select European countries. It is also eligible for double-digit tiered royalties.Given that TSLP is an upstream mediator triggered early in the inflammatory response, Jiangsu Hengrui says SHR-1905 could be suitable for patients with severe asthma, regardless of phenotype and biomarker limitations, allowing for "greater market potential compared to other target drugs." Regulators in China greenlit SHR-1905 for clinical trials to treat asthma in 2021 and for chronic sinusitis with nasal polyps this past May. Both are currently in Phase II."This marks the second out-licensing deal by Jiangsu Hengrui this year, demonstrating its strong R&D strength and pipeline quality," Morgan Stanley analysts remarked in a note to clients. The company licensed its EZH2 inhibitor SHR-2554 to Treeline Biosciences in February as part of a deal potentially worth as much as $706 million. Jiangsu Hengrui is developing SHR-2554 in China as a treatment for peripheral T-cell lymphoma.Meanwhile, AstraZeneca and Amgen's Tezspire (tezepelumab-ekko), another TSLP-blocking drug, is approved to treat severe asthma regardless of phenotype or biomarker limitations in several markets, including the US, EU and Japan. Amgen recently reported that the drug's sales more than doubled to reach $133 million in the second quarter, benefitting from the introduction of a self-administered, pre-filled, single-use pen approved by the FDA earlier this year.

Nexo Therapeutics, a new covalent drug startup, said Wednesday it raised $60 million and unveiled a five-year research partnership with the University of Texas MD Anderson Cancer Center.Backed by Versant Ventures, New Enterprise Associates and Cormorant Asset Management, the biotechnology company was co-founded by Andrew Phillips, the former CEO of cancer drug developer C4 Therapeutics.Phillips left C4 in 2020 and joined Cormorant, where he worked with later-stage biotechs. But he wanted to return to the startup world and was drawn to the idea of building a company around covalent drugs, or medicines that firmly lock onto their targets.He was already talking with Carlo Rizzuto, a managing director at Versant who he knew from serving together on two other companies boards of directors. By August, Phillips had begun working on what would become Nexo, which has facilities in Colorado and Massachusetts.Nexo, which in Portuguese means connection, is at the intersection of emerging science, drug discovery, academia and biotech, where we think we can create value, Phillips said.The company said its technology can better identify promising compounds, particularly against targets that historically havent been easy to reach with covalent drugs.Typically, these medicines bind in some fashion to the amino acid cysteine on their target protein. But cysteine isnt always present or easy to aim at, limiting how covalent drugs can be deployed. Scientists at Nexo believed their technology could help them move beyond cysteine-based binding.With its approach, Nexo is taking part in a wave of new research to more thoughtfully design covalent drugs, which historically were often discovered by accident. These drugs, which include common medicines like aspirin and penicillin, tightly bind to their targets.Those strong bonds can mean a more potent drug effect, but they also increase the challenge of finding the right target as well as raise the risk of more serious side effects.In recent years, pharmaceutical firms such as AbbVie and AstraZeneca have had success with covalent drugs for cancer, like Imbruvica and Tagrisso.Startups have joined in, too, with young biotechs like Matchpoint Therapeutics, Terremoto Biosciences, Enlaza Therapeutics and now Nexo raising sizable funding rounds of late.Nexo has not disclosed which cancers it is targeting, and may explore other diseases in the future.Joining Phillips on Nexos leadership team are several of his former colleagues from C4, including Joe Patel, a former executive at Treeline Biosciences, and John Athanosopoulos, who oversaw operations at Jnana Therapeutics and Proteovant Therapeutics.The collaboration with MD Anderson gives Nexo access to the Houston-based research centers tumor models and clinical knowledge.Its hard to build 100 years of institutional knowledge when youre a startup, so thats what we get from making that partnership, Rizzuto said.Recently, biotech investors appeared to have cooled on oncology biotechs. Only 10 cancer drugmakers have priced initial public offerings over the past two years, compared to nearly 90 in the two years prior, according to BioPharma Dive data.The pendulum has swung in terms of investor appetite, Rizzuto said. The fallout from the Inflation Reduction Act has also made investors second guess their usual investments in oncology, he added.The $60 million Nexo raised in its Series A round will help them identify at least one drug candidate, the company said.By the time Nexo needs to raise more capital, the pendulum may have come back a bit, Rizzuto said. '