177Lu-PNT2003

Bristol Myers Squibb gained its first radiopharmaceutical candidates Tuesday after shelling out $4.1 billion to acquire RayzeBio, the biopharma’s third multi-billion dollar deal this quarter, and the second focused on oncology.The rapidfire dealmaking – and large sticker prices – reflect the growing pressure BMS is under to deliver on its near-term revenue and its late-stage pipeline as it faces looming patent cliffs in the latter half of this decade for some of its best-selling drugs, including cancer blockbuster Opdivo.  BMS agreed to acquire RayzeBio for $62.50 per share in cash, about a 250% premium over its September IPO price of $18 per share. RayzeBio was one of only 10 biotechs in 2023 that went public for more than $100 million, and had the best post-IPO performance in the group. BMS has now spent $24 billion across three major acquisitions this quarter. Days earlier, BMS paid $14 billion to take out CNS biotech Karuna, and in October, agreed to pay up to $5.8 billion for cancer platform company Mirati.Radiopharmaceutical entranceTuesday’s acquisition builds out BMS’s oncology portfolio with a new modality: radiopharmaceutical therapies (RPTs), which enable the targeted delivery of radiation directly to cancer cells. There are only two RPTs on the market, both from Novartis, leaving plenty of opportunity in the space – and investors are taking note. More than 20 VC-backed startups have raised new funds since the start of 2021 to advance RPT platforms and programmes.BMS gains one RPT programme in the clinic for both gastroenteropancreatic neuroendocrine tumours (GEP-NETs) and extensive stage small cell lung cancer (ES-SCLC), multiple preclinical assets, and a GMP manufacturing facility in Indiana that’s expected to begin drug production in 1H24.“RayzeBio’s platform has the potential to be a significant IND engine, generating several therapeutic candidates in the future by leveraging our global drug development capabilities and infrastructure,” said BMS EVP, CMO, Drug Development Samit Hirawat in a statement. RayzeBio’s lead candidate, RYZ101, is an actinium-based RPT that targets somatostatin receptor 2 (SSTR2). According to the company, the high potency and short firing range of the alpha-emitter of actinium-based RPTs could lead to improved efficacy and more targeted delivery than those on the market today.  RYZ101 is in a Phase III trial of patients with SSTR-positive GEP-NETs, and a Phase Ib study in patients with ES-SCLC in combination with standard-of-care therapy.Radiopharma M&A, data in the spotlightBMS isn’t the first large pharma to bet big on radiopharmaceuticals this year. In October, Eli Lilly proposed to buy Point Biopharma and its potential Pluvicto competitor for $1.4 billion. After several extensions and a lukewarm data readout, the deal is slated to close at last on Wednesday, according to an SEC filing. Point’s lead programmes are PNT2002, a PSMA-targeted radioligand therapy, and PNT2003, an SSTR-targeted radioligand being developed for GEP-NETs. Lantheus licensed exclusive rights to both under a deal late last year worth up to $2 billion.Lilly’s tender offer was extended multiple times, as shareholders were waiting on data for PNT2002 that might prompt a better offer. Topline data from the Phase III SPLASH trial in prostate cancer reported last week, however, showed PNT2002 did not seem to perform better than Pluvicto, and Point’s shares fell back below Lilly’s offer price.

Eli Lilly has entered into a definitive agreement to acquire Point Biopharma for $1.4bn, giving the company access to a pipeline of clinical and preclinical-stage radioligand therapies being developed to treat cancer. Radioligand therapy can enable the precise targeting of cancer by linking a radioisotope to a targeting molecule that delivers radiation directly to cancer cells, Lilly explained in a statement. Point currently has two lead programmes in late-stage development, including a somatostatin receptor-targeted radioligand therapy, PNT2003, being evaluated for use in patients with gastroenteropancreatic neuroendocrine tumours. The second is a prostate-specific membrane antigen-targeted radioligand therapy, PNT2002, being developed for patients with metastatic castration-resistant prostate cancer who have experienced disease progression after hormonal therapy. Jacob Van Naarden, president of Loxo@Lilly, the oncology unit of Eli Lilly and Company, said: "Over the past few years, we have seen how well-designed radiopharmaceuticals can demonstrate meaningful results for patients with cancer and rapidly integrate into standards of care, yet the field remains in the early days of the impact it may ultimately deliver. "We are excited by the potential of this emerging modality and see the acquisition of Point as the beginning of our investment in developing multiple meaningful radioligand medicines for hard-to-treat cancers, as we have done in small molecule and biologic oncology drug discovery and development." Under the terms of the agreement, Lilly will commence a tender offer to acquire all outstanding shares of Point for a purchase price of $12.50 per share in cash, amounting to approximately $1.4bn. Lilly will also get access to Point’s manufacturing campus for radiopharmaceuticals in Indianapolis, US, as well as a research and development centre in Toronto, Canada. Joe McCann, chief executive officer of Point, said: "The combination of Point's team, infrastructure and capabilities with Lilly's global resources and experience could significantly accelerate the discovery, development and global access to radiopharmaceuticals." The deal, which is expected to close by the end of this year, would add to Lilly’s growing number of acquisitions this year, including the $2.4bn purchase of Dice Therapeutics and the $1.9bn buyout of Versanis .