Pharmaceutical companies need to spend money in order to make money, and the looming loss of patent exclusivity for numerous products has these companies out in force striking business deals to fill their pipelines with new drugs offering blockbuster potential. A recent report tallied $36 billion splashed out by big pharma in business deals in October and November alone.
One of those deals was the $1.2 billion Takeda Pharmaceutical paid for rights to two Innovent Biologics drugs, both in clinical development for a range of solid tumors. As upfront payments go, it’s a massive sum. Andy Plump, Takeda’s president, research and development, calls it a bargain.
Oncology is one of Takeda’s three core therapeutic areas alongside neuroscience and gastrointestinal/inflammatory diseases. But the company’s oncology research has had some stumbles. In 2023, Takeda voluntarily withdrew Exkivity from the market after the non-small cell lung cancer drug failed the confirmatory study required of its accelerated FDA approval. This past fall, Takeda discontinued its cell therapy research, which included assets from its 2021 GammaDelta Therapeutics acquisition. An earlier Takeda effort to develop bispecific antibodies included the 2021 acquisition of partner Maverick Therapeutics. But last spring, the Japanese pharma company stopped work on the two bispecific drugs that came from Maverick.
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“We made big investments internally, and many of those investments didn’t yield, but we learned from them, and we’ve gotten better, we’ve grown our talent base,” Plump said in an interview this week during the annual J.P. Morgan Healthcare Conference in San Francisco. “And we now have an extremely exciting oncology pipeline, and a large part of that is from the Innovent deal.”
Innovent brings Takeda back to bispecific antibodies, but in a different way. The main asset from the transaction, now code-named TAK-928, is a bispecific antibody fusion protein designed to block PD-1, a checkpoint protein that stops the immune response. The drug simultaneously activates the IL-2 pathway to spark an additional immune response to the cancer. This part of the drug is biased to the alpha subunit of the IL-2 receptor, an approach intended to offer less toxicity and better safety.
There’s been a surge of R&D and business development activity around bispecific antibodies for cancer. Much of the focus has turned to drugs in this class that inhibit two particular proteins, PD-1 on immune cells and VEGF on cancer cells. Several of Takeda’s big pharma peers, including Pfizer, Merck, and Bristol Myers Squibb, have all struck business deals for drugs in this class of cancer medicines. The newest member of the club is AbbVie, which earlier this week agreed to pay $650 million up front for a clinical-stage PD-1/VEGF bispecific drug developed by China-based RemeGen.
Plump counts about a dozen PD-1/VEGF bispecific antibodies in development across the industry. Meanwhile, he said Innovent’s PD-1/IL-2 drug is the only one of its kind. Furthermore, he said this drug offers the potential to work in areas where PD-1/VEGF-targeting drugs do not, such as non-small cell lung cancer that’s refractory to immunotherapy. In areas where PD-1/VEGF bispecifics work, Plump said a PD-1/IL-2 bispecific could perhaps be even better.
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Part of the excitement around PD-1/VEGF bispecifics is the potential to use these drugs as backbones for combinations with other types of cancer therapies. Takeda’s first studies with TAK-928 will evaluate the drug as a monotherapy. As the company explores use of the drug as a frontline treatment, Plump said combination studies will be likely.
The other asset from the Innovent deal is TAK-921, an antibody drug conjugate (ADC) designed to target claudin 18.2, a protein abundant on tumors in gastrointestinal cancers. The 2024 FDA approval of Astellas Pharma’s Vyloy in gastric or gastroesophageal junction adenocarcinoma marked the first regulatory approval for a claudin 18.2-targeting drug. Continued interest in the target has made claudin 18.2 drug research a crowded space for drug research, Plump said.
Takeda thinks TAK-921 can stand apart from the crowd with better efficacy and safety. Nausea, constipation, and diarrhea are among the side effects of Vyloy, and many claudin 18.2-targeting drugs in development have also shown severe gastrointestinal adverse effects. Plump said Takeda has not observed such problems with its new ADC, which he attributed to the drug’s molecular design. While the market potential of TAK-921 is not as broad as that of the PD-1/IL-2 bispecific antibody from Innovent, Takeda believes the ADC has best-in-class potential in pancreatic and gastric cancers.
Included in the $1.2 billion that Takeda paid Innovent is a $100 million equity investment. As the assets licensed by Takeda progress, Innovent could receive up to $10.2 billion more in milestone payments.
“Our feeling is that in the end, it’s going to prove to be one of the huge bargains, probably one of the greatest deals the industry has seen,” Plump said. “We’ll see. Of course, time will tell.”
Photo by Takeda Pharmaceutical