MRTX-1719

Bristol Myers Squibb’s (BMS) KRAS inhibitor Krazati (adagrasib) has been granted accelerated approval by the US Food and Drug Administration (FDA) as part of a combination treatment for a subset of colorectal cancer (CRC) patients. The drug has been authorised for use alongside cetuximab as a targeted treatment option for adults with locally advanced or metastatic cases of the disease who are carrying the KRASG12C mutation, which occurs in approximately up to 4% of CRC patients and has historically been challenging to treat. Eligible patients will also have received prior treatment with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy. CRC is the third most commonly diagnosed cancer globally, with more than 106,000 new cases of the disease expected to be diagnosed in the US this year. Taken orally twice daily, Krazati is a small-molecule inhibitor of KRASG12C and is already approved in the US to treat specific cases of non-small cell cancer (NSCLC). The FDA’s latest decision was supported by positive results from cohorts of the phase 1/2 KRYSTAL-1 study, in which Krazati plus cetuximab demonstrated a confirmed objective response rate of 34% and a median duration of response of 5.8 months. As per the regulator’s accelerated approval pathway, continued authorisation for the drug in this indication may be contingent on results from a confirmatory trial. Wendy Short Bartie, senior vice president, US oncology and haematology at BMS, described the new approval as “an important milestone” for the company and the patients it serves. “We are proud to make Krazati – the first KRASG12C inhibitor to be FDA approved beyond NSCLC – available to CRC patients, and look forward to further evaluating Krazati through our ongoing development programme,” she said. BMS gained access to Krazati through its recent $5.8bn acquisition of Mirati Therapeutics. The deal, which closed in January, also included multiple other targeted oncology assets, such as MRTX1719, which BMS said had shown “encouraging” early efficacy data across several tumour types, including NSCLC and melanoma. Giovanni Caforio, the then chief executive officer at BMS, said at the time of the buyout announcement in October: “We are excited to add these assets to our portfolio and to accelerate their development as we seek to deliver more treatments for cancer patients.”

Pictured: Abstract handshake/Taylor Tieden for BioSpace With the post-pandemic slump firmly in the rearview mirror, merger and acquisition activity in the biopharma sector continued to rebound in the early part of 2024. In addition to dominating early-stage investments of late, oncology was the most active therapeutic area for M&As in the first quarter. Of note, AstraZeneca and BMS each agreed to or completed two multibillion-dollar purchases, while AbbVie made the biggest splash when it wrapped up its $10.1 billion takeover of ImmunoGen. Here, BioSpace looks back at the biggest oncology-related M&A deals that were announced or completed in the biopharma sector in Q1, highlighting continued Big Pharma interest in antibody-drug conjugates (ADCs) and radiopharmaceuticals. For more deals covering the entire biopharma landscape, follow our regularly updated M&A tracker. 1. AbbVie Acquires ADC Developer ImmunoGen Status: Completed Feb. 12 Deal value: $10.1 billion AbbVie bought its way into the red-hot ADC market by acquiring ImmunoGen for $31.26 per share, the largest oncology M&A of the quarter. The deal, announced in November 2023, offers AbbVie access to ImmunoGen’s ADC Elahere, which the FDA granted accelerated approval in 2022, as well as the smaller company’s follow-on pipeline of ADCs. These include several in development for solid tumors, acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm. 2. BMS Buys Mirati Therapeutics to Boost Cancer Pipeline Status: Completed Jan. 23 Deal value: $4.8 billion Bristol Myers Squibb completed a deal announced last October, taking over cancer-focused Mirati Therapeutics at a cost of $58 per share. Mirati shareholders also received nontradeable value rights worth up to $12 per share, contingent on the FDA accepting the New Drug Application for Mirati’s candidate MRTX1719 within seven years. That puts the potential total value as high as $5.8 billion. MRTX1719 is a potentially first-in-class PRMT5 inhibitor in early-stage development for several tumor types, including non-small cell lung cancer. The compound has entered Phase II studies, according to Pharmaceutical Technology. 3. BMS Enters Radiotherapeutics Market with RayzeBio Purchase Status: Completed Feb. 26 Deal value: $4.1 billion BMS bought its way into another soaring market, radiopharmaceuticals, with a $62.50-per-share takeover of RayzeBio and its pipeline of candidates for solid tumors. RayzeBio’s portfolio includes RYZ101, an SSTR2-targeting radiotherapeutic that is currently in Phase III testing for gastroenteropancreatic neuroendocrine tumors and is also being trialed for small cell lung cancer. The deal was announced in late 2023, just a few months after RayzeBio completed a $311 initial public offering. 4. Novartis to Buy MorphoSys Despite Mixed Phase III Trial Results Status: Announced Feb. 5; anticipated closing Q2 Deal value: $2.9 billion Novartis reached an agreement with MorphoSys to acquire the German biotech for more than $73 per share in cash. At the center of the merger is pelabresib, an investigational small molecule inhibitor of the BET protein that suppresses the expression of abnormal genes involved in cancer development. In November, MorphoSys reported mixed findings for a Phase III trial of pelabresib with myelofibrosis patients. MorphoSys itself acquired pelabresib when it spent $1.7 billion on Constellation Pharmaceuticals in 2021. Novartis and MorphoSys received U.S. antitrust clearance in March and expect the acquisition to close by midyear. 5. AstraZeneca to Take Over Radiopharma Developer Fusion Pharmaceuticals Status: Announced March 19; anticipated closing Q2 Deal value: Up to $2.4 billion AstraZeneca joined the radiopharma oncology parade by announcing plans to acquire company Fusion Pharmaceuticals for $2 billion, or $21 per share in cash. An unspecified contingent value right of $3 per share could add another $400 million to the value of the deal. Fusion CEO John Valliant indicated that the companies will develop next-generation radioconjugate therapies. Fusion’s lead candidate, FPI-2265, now in a Phase II trial, targets the prostate-specific membrane antigen to fight metastatic castration-resistant prostate cancer. The company is also developing two earlier-stage actinium-based therapeutic candidates for solid tumors. 6. J&J Buys Ambrx to Enhance ADC Pipeline in Cancer Status: Completed March 7 Deal value: $2 billion Johnson & Johnson shelled out $28 per share to acquire ADC developer Ambrx Biopharma, a drug developer working on ADCs. In the Jan. 8 deal announcement, J&J said that it would work with Ambrx investigators to accelerate the Phase I/II APEX-01 study of ARX517, an ADC for metastatic castration-resistant prostate cancer. The anti-PSMA therapy earned FDA fast-track designation last year. This is the latest of several moves by J&J in the ADC space. In early 2022, the company’s Janssen subsidiary paid $40 million upfront and more than $1 billion in biobucks for a collaboration designed to produce proprietary antibodies with Mersana Therapeutics. Late last year, Janssen bought licensing rights for a LegoChem Biosciences ADC for $100 million upfront, with $1.7 billion available in potential milestones. 7. AstraZeneca Buys Chinese CAR-T Company Gracell Status: Completed Feb. 22 Deal value: Up to $1.2 billion AstraZeneca closed its acquisition of Chinese cell therapy company Gracell Biotechnologies, giving the pharma giant ownership of the investigational cell therapy GC012F, a dual-targeting autologous CAR-T therapy being developed for multiple myeloma and other hematologic cancers, as well as Gracell’s FasTCAR platform for CAR-T development. The transaction, announced Dec. 23 as part of a flurry of big-dollar dealmaking to end 2023, is valued at $2 per share. Unspecified regulatory milestone payments could bring the total value to $1.2 billion. Neil Versel is the business editor at BioSpace. You can reach him at neil.versel@biospace.com. Follow him on LinkedIn or X.