WDR5

A small Northwestern University spinout attempting to develop a twist on biologics has pulled together a $30 million Series A. The startup, named Grove Biopharma, weathered the pandemic and, after more than a year of fundraising, pushed through the difficult financing environment in a bid to prove its platform can hit intracellular disease targets and potentially open up a new field of medicines. To get to this point, Grove had to rightsize its original ambition of raising a $50 million Series A, CEO Geoffrey Duyk said in an interview. The funding environment has been particularly difficult for startups like Grove that are attempting to create new platforms. Risk-averse investors have mostly concentrated their bets on clinical-stage assets or pipelines on the cusp of human trials. Duyk has seen both sides of the coin, having worked in R&D at Millennium and Exelixis in the 1990s and early 2000s before spending two decades on the investing side. “This is obviously the most challenging environment I’ve seen in my entire career,” Duyk said, “and I’ve been through many, many cycles.” The Series A, albeit smaller than planned, does come with industry validation via Eli Lilly, which took part in the DCVC Bio-led round. Grove previously raised about $8 million in seed funding, Duyk said. The nimble startup, which has about a dozen employees, is also part of the burgeoning Chicago biotech scene . Grove was incubated by local investor Portal Innovations, and it is housed in the same West Loop building as the Chan Zuckerberg Biohub Chicago. The startup’s platform seeks to make synthetic biomolecules that can go after intracellular targets. Whereas the industry has traditionally thought of materials as delivery mechanisms, Grove wants to flip the switch on that thinking. “It’s not just new drugs. It’s not just a new molecule. It’s a new way to develop drugs,” scientific founder and Northwestern professor Nathan Gianneschi said in an interview. “This is turning that around and saying, ‘Well, no, the material itself is the drug.'” Gianneschi and Duyk co-founded Grove in 2020 alongside chief technology officer Paul Bertin. Duyk called it a “three-men-in-a-garage” type of startup after it spun out from the university lab. “Nathan was asking some interesting questions: What if you rethought what a protein was? Instead of a protein being a linear polymer of amino acids, what if you made it a branch of polymer peptides?” Duyk said. Grove’s molecules look like little trees, hence the company’s name, according to Gianneschi. He and his team discovered a fully synthetic molecule that incorporated the critical features of an antibody but could also get inside a cell, Duyk said. “It was like a little bit of a dream to begin with, that you could mimic proteins using polymer chemistry,” Gianneschi said. Its first clinical attempt will be in prostate cancer with a molecule that goes after AR-V7, an androgen receptor splice variant. That said, the startup will likely need more financing to get into the first human trial, Duyk said. Grove’s other oncology programs include work in SHOC2, the MYC/WDR5 interaction, and the MYC transactivation domain. Its in-house R&D engine is also exploring neurodegenerative diseases by way of tau pathology and the Keap1-Nrf2 pathway. Grove is hopeful that its platform can lead to medicines that are delivered via IV, under-the-skin injections or even topicals, Duyk said. Work has yet to be done to see if they can be made available orally, he added. The company also plans to seek biopharma partnerships, saying its platform can be applied in multiple areas, including degraders. “We can use our molecules to do the equivalent of ADCs,” Duyk said. “We can use our molecules to do the equivalent of radiopharmaceuticals, so there’s a lot of interest in pursuing that.” Editor’s note: This story was updated to correct the AR-V7 program is in prostate cancer, not pancreatic.

$710M Gamble Fails as Celgene Terminates Two Phase Celgene has struck another collaborative deal, even as the large pharmaceutical company is in the process of being folded into the operations of its new owner, Bristol-Myers Squibb. Under terms of the deal, Celgene will pay Triphase $40 million in upfront funding. Celgene can then pay up to an additional $940 million if certain milestones are hit. Celgene has struck another collaborative deal, even as the large pharmaceutical company is in the process of being folded into the operations of its new owner , Bristol-Myers Squibb . This morning, privately-owned drug developer Triphase Accelerator , along with its majority shareholder FACIT, announced it had struck a collaborative deal with Celgene. The companies will harness their knowledge and resources to develop a first-in-class preclinical therapeutic targeting the WDR5 protein for the treatment of blood cancers including leukemia. The deal to develop TRPH-395, a novel small molecule inhibitor that disrupts WDR5 protein-protein interactions, could be worth up to nearly $1 billion. Under terms of the deal, Celgene will pay Triphase $40 million in upfront funding. Celgene can then pay up to an additional $940 million if certain milestones are hit. The deal provides Celgene with an option to acquire RPH-395 from Toronto-based Triphase Accelerator. According to Triphase, preclinical data for TRPH-395 showed that the compound demonstrated broad anti-proliferative activity across a wide range of cancer cell lines. Blood cancers like leukemia can result when WDR5-associated protein complexes are not appropriately regulated in the body. The WDR5 protein is critical for the formation and activities of certain protein complexes that are associated with DNA and indirectly modify genes. Drug compounds that can disrupt these cancer-causing cellular activities represent a novel therapeutic approach, which may also improve clinical outcomes in patients with solid tumors, Triphase Accelerator said in its statement. The preclinical work with TRPH-395 was completed by Propellon Therapeutics, in conjunction with researchers at the Ontario Institute for Cancer Research. Propellon was also provided seed funding by FACIT. David O’Neill, president of FACIT, said Propellon was tasked with commercializing the preclinical TRPH-395 and multiple offers came through, with Celgene being the winner. “The quality of the team and commitment by Triphase Accelerator to engage Ontario researchers and clinical sites in its high content studies, combined with its long-standing relationship with Celgene made this partnership the most compelling path to impact patients and the local economy,” O’Neill said in a statement. Ilse Treurnicht, executive chairperson of Triphase, noted that the deal with Celgene is a significant milestone for the company. Treurnicht said Triphase is excited about the potential or realizing the vision of advancing the TRPH-395 program toward clinical proof of concept. Celgene’s head of translational development Jorge DiMartino said the investment into the TRPH-395 program reflects the company’s “commitment to developing first-in-class epigenetic therapies for patients with hematological cancers.” Since BMS announced it was acquiring Celgene for $74 billion earlier this month, the California-based company has continued to strike collaborative research deals . A little more than 10 days ago, Celgene struck deals with two companies to develop immuno-oncology treatments and cell therapies. Celgene entered into agreements with Boston-based Kyn Therapeutics to develop novel immuno-oncology therapies and also forged a collaborative effort to develop cell therapies that target cancer with Obsidian Therapeutics.