MEDI-2228

Pictured: AstraZeneca building/Bodo Marks/picture alliance/Getty Images As antibody-drug conjugates make a steady comeback, AstraZeneca strikes its second deal this year with a Chinese company. The Cambridge-based biopharma announced Friday it’s putting potentially $600 million on the line for LaNova Medicines’ preclinical stage ADC. The Shanghai-based biotech will score upfront payments of up to $55 million for LM-305, with an additional $545 million in potential milestones and tiered royalties. LM-305 has the potential to become a first-in-class GPRC5D-directed ADC for multiple myeloma, according to the press release. It comes to AstraZeneca with Investigational New Drug (IND) approvals already in place in the U.S. and China. The asset is a good fit for AstraZeneca since the company halted development of MEDI2228, an anti-BCMA ADC for multiple myeloma in 2021. AstraZeneca’s global head of multiple myeloma Nina Shah said in a statement that the LaNova deal “enriches our growing haematology pipeline.” AstraZeneca has experience in the space with its HER2-directed ADC, Enhertu, approved for unresectable or metastatic breast cancer in 2019, and later for gastric cancer and NSCLC. It’s the first HER2-directed treatment approved for NSCLC. Indications could continue racking up for the drug with 19 active studies currently listed on ClinicalTrials.gov. Developed in conjunction with Daiichi Sankyo, Enhertu made blockbuster status last year with sales over $1 billion. The ADC market has grown steadily over five years, reaching close to $7 billion in sales in 2022. AstraZeneca had already struck an ADC deal earlier this year for another Chinese-developed ADC. In February, the biopharma dropped $63 million upfront for global rights to KYM Biosciences’ potential first-in-class Claudin 18.2 ADC. CMG901 is currently in Phase I trials for Claudin 18.2–positive solid tumors. KYM has the chance to earn up to $1.1 billion in milestone payments in addition to royalties. LaNova also had an ADC targeting Claudin 18.2 in development that was scooped up by Turning Point Therapeutics in a deal for $220 million. The asset is now in the hands of Bristol Myers Squibb, since its $4.1 billion acquisition of Turning Point last summer. The ADC was granted orphan drug designation by the FDA for both gastric and pancreatic cancers and is positioned in BMS’ Phase I pipeline for advanced solid tumors. Eight ADCs were approved by the FDA between 2019 and 2022, making the technology an attractive option for lower-risk development for pharma companies expanding their pipelines via partnerships and acquisitions. Experts say the complexity of ADC development is another selling point as it reduces the chances of biosimilars hitting the market, allowing potential revenues to stay strong. Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.

Rob Stothard/Getty Images AstraZeneca reported its first-quarter financial reports. As is often the case, they updated their pipeline, and indicated they had dropped a few drugs, including a promising multiple myeloma drug. AstraZeneca CEO Pascal Soriot pictured above. (Rob Stothard/Getty Images) AstraZeneca reported its first-quarter financial reports. As is often the case, they updated their pipeline, and indicated they had dropped a few drugs, including a promising multiple myeloma drug. The first compound, MEDI2228, is an antibody-drug conjugate (ADC) targeting BCMA. BCMA (B-cell maturation antigen) is a transmembrane receptor found almost only on the surface of differentiated plasma cells. The company pushed MEDI2228 into Phase I trials in 2018, and in 2020, AstraZeneca reported a 61% objective response rate (ORR) at the maximum tolerated dose. There were no cases of keratopathy, a noninflammatory disease of the cornea, that had been observed in cases with a similar drug, GlaxoSmithKline’s Blenrep. There were other adverse effects. Blenrep was the first anti-BCMA drug to be approved by the U.S. Food and Drug Administration (FDA). In August 2020, the FDA approved Blenrep (belantamab mafodotin-blmf) as a monotherapy for adults with relapsed or refractory multiple myeloma who have received at least four previous therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor and an immunomodulatory agent. Multiple myeloma is the second most common blood cancer. It is generally treatable, but not curable. In the U.S. each year more than 32,000 people are diagnosed with multiple myeloma and about 13,000 die from it. There are a number of treatments for multiple myeloma, but many patients develop resistance to those drugs. This is partly why AstraZeneca apparently decided to drop development of MEDI2228 for this indication, because it not only faced competition from Blenrep, but from existing therapies. AstraZeneca and MedImmune, its global biologics research and development arm, also dropped MEDI6012, a lecithin-cholesterol acyltransferase (LCAT) for the treatment of atherosclerosis in patients with the most serious type of heart attack. This followed the wrap of a Phase II trial in adults with acute ST segment elevation myocardial infarction. In this case, it was abandoned for safety or efficacy reasons. Another project they dropped from the pipeline is its ATR kinase inhibitor ceralasertib in combination with Lynparza. It also ended a Phase I trial to evaluate ceralasertib and the BTK inhibitor Calquence, although it is continuing to study ceralasertib in other indications. AstraZeneca also removed AZD8154, an inhaled PI3Kgd inhibitor for asthma. After preclinical studies last year, they withdrew it and terminated the study, but the first-quarter report announced it had been officially pulled from the pipeline. Otherwise, the company reported revenue growth of 15% in the first quarter, of $7.32 billion. Not including the COVID-19 vaccine, revenue growth increased by 11% to $7.045 billion. “We delivered solid progress in the first quarter of 2021 and continued to advance our portfolio of life-changing medicines,” said Pascal Soriot, AstraZeneca’s chief executive officer. “Oncology grew 16% and New CVRM [Cardiovascular, Renal and Metabolism] grew 15%. New medicines contributed over half of revenue and all regions delivered encouraging growth. This performance ensured another quarter of strong revenue and earnings progression, continued profitability, and cash-flow generation, despite the pandemic’s ongoing negative impact on the diagnosis and treatment of many conditions. Given the performance in the first quarter, in line with our expectations, we reiterate our full-year guidance. We expect the impact of COVID to reduce and anticipate a performance acceleration in the second half of 2021.”