Nexo Therapeutics, Inc.

Galapagos added chemoproteomic drug discovery as the next building block of its cancer portfolio refresh, thanks to a deal Wednesday with BridGene Biosciences.The drugmaker agreed to pay BridGene up to $27 million across upfront and preclinical milestone payments, and the latter is also eligible for more than $700 million in clinical and commercial milestones, plus tiered royalties.BridGene will use its chemoproteomics platform, IMTAC, to discover compounds to treat cancer. The technology screens tagged, drug-like small molecules from BridGene’s covalent library against all the proteins in live cells to discover candidates for hard-to-drug targets.The partnership continues Galpagos’ recent portfolio reboot following a series of clinical and regulatory disappointments since the biotech’s peak in early 2020, which have led to an 85% drop in its share price.Galapagos began reworking its pipeline in 2022 – catalysed by the hire of CEO Paul Stoffels, the former chief scientific officer of J&J – and the biotech has since affirmed its focus on oncology and immunology, while dropping programs in fibrosis and kidney disease. As part of the reboot, Galapagos acquired CellPoint and AboundBio in June 2022, giving it a foothold in next-generation CAR-T therapies. For more, see ViewPoints: Galapagos’ rebuilding plans start with pivot to cell therapy.Chemoproteomics in the spotlightLeveraging chemoproteomic platforms for drug discovery have become a more attractive strategy in the past few years, following the success of pioneer Vividion Therapeutics, which launched in 2017 with a chemoproteomic screening platform designed to identify small molecule drugs against traditionally hard-to-drug targets.  In 2021, Bayer acquired Vividion for $2 billion, which heralded several new entrants to the space.Last January, Belharra Therapeutics closed a $50 million Series A and nabbed $80 million upfront in a deal with Roche's Genentech unit to roll out its chemoproteomics platform.And in July, Nexo Therapeutics emerged from stealth with a $60 million series A round from investors including Versant Ventures – also a backer of Vividion. For more, see ViewPoints: Versant looks to expand druggable target space with Nexo launch.

None   Welcome to this week's Chutes & Ladders, our roundup of hirings, firings and retirings throughout the industry. Please send the good word—or the bad—from your shop to Max Bayer or Gabrielle Masson, and we will feature it here at the end of each week.  Pfizer shakes up R&D leadership in preparation of Seagen merger Pfizer Pfizer is preparing to close its $43 billion Seagen merger, which is expected later this year or in early 2024. Part of that prep includes changes to the Big Pharma’s research leadership team. Chief Scientific Officer Mikael Dolsten, M.D., Ph.D., is slated to take on more responsibilities while the company says goodbye to Chief Development Officer William Pao, M.D., Ph.D., who just took on the role in February 2022. Dolsten will expand his role to become chief scientific officer and president of R&D. While he had previously been responsible for all discovery and early-phase clinical development, he will now also “lead an end-to-end model across all of Pfizer’s other therapeutic areas,” according to the company.   Pao, who Pfizer snagged from Roche last year, is leaving “to pursue new opportunities outside the company.”  Pfizer also plans to promote Chris Boshoff, M.D., Ph.D, to serve as chief oncology research and development officer. He previously oversaw clinical research and product development activities for Pfizer’s oncology portfolio. In his new role, Boshoff will be in charge of integrating medicines from Seagen. Fierce Biotech  Industry vet Enrique Conterno resigns from FibroGen    FibroGen  FibroGen CEO Enrique Conterno has resigned from his post for “personal reasons,” according to a company release.  After a 27-year-run at Eli Lilly, Conterno joined Fibrogen in 2020, when hopes surrounding the company’s anemia drug roxadustat were high. During his time at Lilly, Conterno is credited with returning its diabetes business to the industry's top spot, with annual revenue hitting more than $10 billion.   However, his road at FibroGen proved much rockier, with the AstraZeneca-partnered drug roxadustat suffering an FDA rejection, commercial disappointments and a clinical trial flop. As FibroGen hunts for a permanent successor, Chief Commercial Officer Thane Wettig will take on the interim CEO title with support from Wettig, who will serve as a special advisor during the transition. Fierce Pharma  Editas snags Biogen vet as CSO Editas Medicine  Long-time Biogen veteran Linda Burkly, Ph.D., has landed at Editas Medicine, where she will serve as EVP and chief scientific officer. Burkly will lead the genome editing company’s drug discovery team and pipeline activities. The Biogen veteran ended a 37-year tenure last year after most recently leading neuroscience-focused research teams as VP and senior distinguished investigator. During her time at the big biotech, Burkly is credited with inventing a new anti-CD4 mAb that was developed into the HIV treatment Trogarzo and discovering new VLA-4/VCAM biology and uses of VLA-4 blockers including for Crohn’s disease, an indication of Tysabri. Release > AstraZeneca's Mene Pangalos, Ph.D., is set to step down as EVP of biopharmaceuticals R&D early next year after 14 years with the Big Pharma. Sharon Barr, who has headed up R&D at AstraZeneca’s rare disease unit Alexion since 2013, is set to fill the post. Fierce Biotech > Bicara Therapeutics has snagged former Amgen leader David Raben, M.D., to serve as the biotech’s chief medical officer. At Amgen, Raben most recently served as VP of global product development and product general manager of oncology, and before that held a leadership position at Genentech. Release   > Flagship’s Senda Biosciences has chosen Igor Matushansky, M.D., Ph.D., to serve as the company’s chief medical officer. He most recently served as CMO and global head of R&D at Hookipa Pharma, and has past experience at Daiichi Sankyo and Novartis. Release > On Oct. 1, Nuno Mendonça, M.D., will join AC Immune as chief medical officer, taking the reins from Johannes Streffer, M.D., who is leaving to pursue a new role outside the company. Previously, Mendonça has held roles at Bial and AbbVie. Release > Peter Powchik, M.D., is set to join Vaxxinity as EVP and global scientific director starting Oct. 1. Before Vaxxinity, he served as SVP and head of clinical development for Regeneron. Release > Annexon Biosciences has appointed Jamie Dananberg, M.D., to serve as chief medical officer. He most recently served as CMO for Unity Biotechnology, and has held past leadership roles at Takeda Pharmaceuticals and Eli Lilly. Release > Teva Pharmaceutical Industries has tapped Angus Grant, Ph.D., to take on the role of EVP of business development starting Aug. 1. Most recently, Grant was the chief business executive at BeiGene, and has also served as CEO of the Dementia Discovery Fund and held various leadership positions at Celgene. Release > Pheon Therapeutics has chosen Cyrus Mozayeni, M.D., to serve as CEO after former leader Bertrand Damour decided to step down. Mozayeni most recently co-founded and helmed Vedere Bio through its sale to Novartis. Release > Catalyst Pharmaceutical Co-Founder, Chair and CEO Patrick McEnany has told the board he plans to retire from his role as CEO by the end of this year. McEnany has led the company since its inception in 2002 and will continue to serve as non-executive chair of the board after his CEO position is filled. Release > Nexo Therapeutics has exited stealth with $60 million and CEO and co-founder Andrew Phillips, Ph.D., at the helm. He’s joined by co-founder and Chief Operating Officer Michael Kim, Ph.D.; VP, head of biology and co-founder Rhamy Zeid, Ph.D.; VP, head of operations and co-founder John Athanosopoulos; and VP and head of discovery Joe Patel, Ph.D. All of the leaders have previously worked at C4 Therapeutics, among other companies. Release > Starting Sept. 8, Modestus Obochi, Ph.D., will take up the role of chief business officer at cell therapy company Sernova. Obochi has held past roles at Pfizer and Baxter International, among others. Release

Amino acids play important roles in tumors, so targeting these molecules makes sense for cancer drug research. But much of this research has focused on just one of the 20 amino acids found in humans. It’s a key one to be sure, but Andrew Phillips, founder and CEO of Nexo Therapeutics, contends a broader approach is a better way to find new drugs capable of addressing some of cancer’s toughest targets. Nexo isn’t disclosing its targets for now, but the startup is ready to share some details about its research. The Versant Ventures-founded startup emerged from stealth this week with $60 million in Series A financing and an alliance with The University of Texas MD Anderson Cancer Center. “It really is to innovate chemistry and chemical biology to work on some of these elusive targets,” Phillips said. “None of us are fans of the term ‘undruggable.’ Many targets are viewed as undruggable for technology reasons. That’s not us.” Nexo, which is based in Littleton, Colorado, and has research labs in Watertown, Massachusetts, is working on what Phillips describes as the next wave of covalent drug discovery. Small molecules that form covalent bonds have a stronger connection to their targets. In addition to making the drugs more potent, covalency makes them more selective, meaning they’re less likely to hit other targets and cause adverse effects. The AbbVie and Janssen Biotech drug Imbruvica, Tagrisso from AstraZeneca, and Amgen’s Lumakras each address different cancer targets. However, these drugs all work by forming covalent bonds with an amino acid on their targets called cysteine. Other research efforts are underway targeting cysteine in some manner as a way of treating cancer. Nexo aims to go beyond cysteine. While chemistries exist to target other amino acids, no one has put them together into a single technology platform, Phillips said. Nexo actually has two platforms. The chemistry platform, called CODON, screens a library of covalent fragments at scale to find ligands, the molecules that can bind to a target. The chemical biology platform, called INFINI-T, yields insight into how deeply and how long a molecule most interact with its target to have a pharmacological effect. Phillips likened Nexo’s approach to rock climbing. A climber must choose the best route to take for the ascent. An undruggable or difficult-to-drug target is like a cliff face with no clear place to start a climb. The Nexo technologies help the startup find starting points for its drugs. “Covalency gives us that handhold on the cliff face,” Phillips said. “With that handhold on the cliff face, we can optimize our leads.” There are other companies also trying to bring covalent chemistry to additional amino acids. The research of South San Francisco-based Terremoto Biosciences focuses on developing small molecules that target lysine. Umbra Therapeutics, based in Lexington, Massachusetts, is researching approaches to both tyrosine and lysine. Carlo Rizzuto, managing director at Versant and a Nexo board member, said Nexo can stand apart by taking a broader view of the amino acids that are key to cancer. “Those companies are taking a very focused approach with a specific chemistry for one amino acid,” he said. “What we’re trying to do is be more comprehensive.” Phillips was the president and CEO of C4 Therapeutics, a clinical-stage biotech developing drugs that employ an approach called targeted protein degradation. In 2020, he joined Cormorant Asset Management. While there, he met the Versant team. Rizzuto said he and Phillips became excited about the opportunity to take covalent drug research beyond cysteine and they formed Nexo. Cancer is just the start for Nexo. Phillips said going beyond cysteine could also take the startup into immunology and perhaps neuroscience. Some of that research could be done through partnerships, he added. In the nearer term, the MD Anderson partnership will help Nexo bring its cancer drugs into the clinic. The startup will leverage MD Anderson’s Translational Research to Advance Therapeutics and Innovation in Oncology (TRACTION) platform, which gives the startup access to in vitro and in vivo models for its research. MD Anderson has similar agreements with other biotech companies. In 2021, the cancer center began a three-year alliance focused on an experimental Blueprint Medicines cancer therapy. Like the Blueprint deal, Nexo will provide MD Anderson with research funding and the cancer center is eligible to receive milestone payments and royalties from sales of commercialized products that stem from the collaboration. Nexo will keep all rights to its programs. Nexo’s new financing was led by Versant. New Enterprise Associates and Cormorant Asset Management also participated in the startup’s funding round.