Elritercept

BridGene will receive $46m in combined upfront and potential preclinical milestone payments. Credit: Klaus Vedfelt via Getty Images. Bridgene and Takeda have inked a deal worth $770m to develop small molecules for immunology and neurology. Takeda will pay $46m upfront to leverage BridGene’s chemoproteomics platform, dubbed IMTAC. The platform screens small molecules against all the proteins in live cells to discover drug candidates for “high value and hard-to-drug targets” that cause diseases, according to BridGene’s website. The company highlighted that about 90% of proteins associated with diseases cannot be targeted with traditional therapies due to the lack of a known addressable binding site. Takeda will hold exclusive rights to develop and commercialise any resulting drugs from the collaboration. In addition to the upfront payment, BridGene could receive up to $770m in additional milestone payments, along with tiered royalties. The companies previously teamed up in March 2021 for a similar deal worth $500m to start up to five drug discovery programmes. Using BridGene’s IMTAC platform, this programme focused on identifying targets believed to underlie neurodegenerative disease. BridGene announced that it had hit two milestones under the agreement in 2023. In the announcement accompanying the latest deal, Takeda’s chief scientific officer Christopher Arendt said: “By integrating BridGene’s IMTAC platform with Takeda’s scientific expertise, we aim to unlock a broader range of targets that have been considered undruggable, aligning with our core strategy in small molecule drug discovery.” Takeda has been on a wave of dealmaking over the last year. In December 2024, the Japanese pharma company spent $200m in exchange for Keros Therapeutics’ investigational activin inhibitor elritercept to treat anaemia. As part of the deal, Keros could secure up to $1.1bn in development, approval, and sales milestones. This follows on from a November 2024 agreement with Alloy Therapeutics to develop chimeric antigen receptor (CAR)-T therapies using Takeda’s proprietary induced pluripotent stem cell (iPSC) platforms, which aim to improve treatment options for both solid tumours and blood cancers. Two more billion-dollar deals with Takeda took place in May 2024. One was for AC Immune’s amyloid beta-targeting Alzheimer’s disease (AD) immunotherapy, in a deal worth up to $2.2bn . The second pact saw Takeda spend $1.2bn to develop molecular glue degraders with Degron Therapeutics for multiple targets in the three disease areas.

Previously, Takeda worked across 10 to 12 modalities. Now, the company has zeroed in on four modalities: small molecules, biologics, antibody-drug conjugates and allogeneic cell therapies. \n Amid a rapidly evolving macroenvironment, Takeda is changing up its R&D priorities and investment strategy.“There\'s an evolution of our economic model that starts with [the] IRA (Inflation Reduction Act), and will get worse and worse and worse, but I think there\'s so many opportunities for us to counter that with new ways of working,” Takeda\'s R&D head Andy Plump, M.D., Ph.D., told Fierce Biotech at the annual J.P. Morgan Healthcare Conference in San Francisco last week. The conference ended right as the U.S. government selected its second round of drugs up for Medicare price negotiations under the Inflation Reduction Act.After a wide-ranging restructure last year, Takeda now touts its “most robust late-stage pipeline” in the pharma’s history, consisting of six late-stage programs across 14 studies, according to Plump. Three of the candidates—a narcolepsy type 1 candidate, an oral TYK2 inhibitor for psoriasis and an injection for chronic blood cancer polycythemia vera—have phase 3 readouts slated for later this year.Developing a more mature pipeline meant that Takeda had to boost its standards, Plump said. Raising the bar resulted in several programs being left behind, including a midstage CD19 CAR-NK cell therapy, a small molecule known as subasumstat and a peptide agonist being studied as a nausea and vomiting candidate, all of which were discarded last May.Previously, Takeda worked across 10 to 12 modalities, according to Plump. Now, the company has zeroed in on four modalities: small molecules, biologics, antibody-drug conjugates and allogeneic cell therapies. Takeda chose the quartet based on past product wins and future need for patients, plus going into areas that the drugmaker can build out its internal capabilities for, Plump said.“That mindset shift is a really big one for our employees because you had people that were just used to getting essentially whatever they wanted or they needed to push every program in as many potential indications as fast as possible,” Plump said. “Now, we\'ll be more thoughtful and selective in where we do that.”  The new perspective also impacts how the pharma views partnerships. Previously, Takeda inked pacts to expand its pipeline and experiment with different modalities. Now, the company is tightening the reins and will be “more thoughtful” in terms of what it brings in, according to Plump.The drugmaker had previously invested “very heavily” in early-stage, higher-risk programs—of which many would fail, Plump explained. “That\'s not something that we can continue to do—and it\'s not something that we have to do anymore—because we have this late-stage pipeline,” he said.The pharma has a new investment thesis for earlier programs, Plump said, explaining that early programs will be stopped if they don’t rapidly reach an inflection point.The pharma is also putting a heavy focus on option-based deals, Plump said, echoing Takeda CEO Christophe Weber’s sentiments that were shared during the organization’s presentation at JPM.“The benefit of an option deal is that we don\'t have to spend our new dollars because our partners will run the programs,” Plump explained, underscoring the economic efficiency of the deal type. “Then you have the option, if things work, to buy the program and bring it in at a cost that\'s a fraction of what it normally would be.”Plump pointed to the deal Takeda penned with Keros Therapeutics in December, putting down $200 million upfront and offering up to $1.1 billion in biobucks for ex-China rights to Keros’ activin inhibitor elritercept. The candidate is being studied as a treatment for anemia tied to blood cancers, including myelodysplastic syndromes and myelofibrosis. The program, which is set to enter phase 3 testing, could challenge Bristol Myers Squibb’s Reblozyl in blood cancer indications if approved. While five of the six company’s late-stage programs are in rare diseases, Plump also insists that Takeda won’t be siloed as a specialty disease pharma.“We\'ve mistakenly been considered just a rare disease company. It\'s not true,” Takeda’s R&D president said. “We are a company that will go after transformative medicines for patients in both rare and more prevalent disease populations.”But Plump understands the misconception. Historically, the pharma’s late-stage pipeline has focused on candidates for ultrarare conditions, such as Adzynma, a recombinant protein product that snagged FDA approval in 2023 for a very rare congenital blood clotting disorder. Known as thrombotic thrombocytopenic purpura, the disease is estimated to affect fewer than 1,000 Americans.However, Plump says these ultrarare programs aren’t indicative of Takeda’s overarching investment strategy, arguing that the diseases the organization goes after have broad potential.      “These are rare diseases with very substantive patient populations, very high unmet medical needs and revenue projections that are in the billions well,” Plump said.  Today, Takeda has three core indications of focus: oncology, neuroscience and what the company calls GI-squared, which encompasses gastrointestinal and inflammation conditions.