Curon Biopharmaceutical Ltd.

SAN DIEGO — AstraZeneca is getting ready to step on the gas in the world of bispecific T cell engagers. The company presented some of its first Phase 1 data for its CD3xCD19 bispecific known as AZD0486 — which is being tested in multiple B cell malignancies — at the American Society of Hematology’s annual meeting this weekend. Data come from a larger study where AstraZeneca is testing the program against a broad range of blood cancers, where the company tested four dose levels. Researchers touted results in later-line follicular lymphoma and diffuse large B cell lymphoma (DLBCL). In 27 patients with follicular lymphoma who received any of the three highest doses, AZD0486 induced a 96% objective response rate and an 85% complete response rate, AstraZeneca said. Additionally, in the two middle dose levels, 17 of 19 patients achieved undetectable minimal residual disease — an endpoint where the FDA is proving increasingly receptive toward in other blood cancers — by 12 weeks. In DLBCL, a much harder disease to treat, the responses were less potent, according to last month’s abstract. At the dose expected to move into further studies, nine of 19 patients (47%) responded, with eight of 19 (42%) reaching a complete response. AstraZeneca is expected to break down additional DLBCL results in a presentation Monday evening Pacific time. But most promising about these data is how even patients who had previously taken CAR-T or anti-CD20 therapies were seeing responses, AstraZeneca’s executive VP for oncology R&D Susan Galbraith told Endpoints News . Among 14 individuals who progressed after CAR-T in the study at the target dose level, the ORR was 36% and the complete response rate was 29%. Patients whose cancers progress after taking CAR-T, in particular, have extremely limited treatment options, Galbraith said, but bispecifics as a whole appear to be emerging as a new alternative. “I think that bodes well, not just for an option for those patients, but also the potential for those to be really quite efficacious in the early lines of treatments as well,” she said. “We’ve got work to do to deliver all of that data, but so far, I’m quite excited about potential for this market.” AZD0486 came to AstraZeneca in its buyout of TeneoTwo, acquired in 2022 for up to $1.27 billion, including milestones (AstraZeneca paid only $100 million upfront). TeneoTwo is itself an offshoot from Teneobio, which spun it off after being bought by Amgen in 2021 for $900 million upfront and another $1.6 billion in milestones. The only other approved CD3xCD19 bispecific is Amgen’s Blincyto, which was first approved in 2014. Blincyto has since racked up half a dozen other approvals, but they’ve all come in different settings for acute lymphoblastic leukemia (ALL). In 2023, Amgen reported $861 million in worldwide Blincyto sales. Galbraith said the lack of other such drugs has given AstraZeneca the right opportunity to design their compound in a way where it can best take advantage of the market. There is still the potential for combination therapies, particularly for the DLBCL setting, that have yet to be explored in the clinic. Other companies have taken note recently, with a slew of CD19 bispecific deals announced in recent months. In August, Merck paid $700 million upfront for Curon Biopharmaceutical’s CD3xCD19 compound, and GSK spent $300 million upfront in October for a bispecific from Chimagen Biosciences to test it in autoimmune disease. But Galbraith also believes AZD0486 can be more efficacious, too. “I don’t think you get to the same level of exposure with [Blincyto] as we can achieve with this,” Galbraith said. “And it’s early days yet. But I’m encouraged by the profile that we’re seeing and the potential to have a better CD19 bispecific option for patients in ALL.”

iStock, Sundry Photography Offsetting Merck’s growth in the third quarter were disappointing revenues from its HPV vaccine Gardasil and type 2 diabetes pill Januvia, with the company on Thursday narrowing its 2024 sales and adjusted profit outlooks. Merck on Thursday reported 7% year-over-year growth in third-quarter revenues, which came in ahead of analyst forecasts, driven by its blockbuster cancer therapy Keytruda as well as strong product launches. However, the company narrowed its full-year sales forecast and lowered its adjusted profit guidance. The pharma brought in more than $16.6 billion in Q3 versus the consensus estimate of $16.46 billion—a 1% beat. Non-GAAP earnings-per-share (EPS) was $1.57, which topped the $1.48 projection by 6%. Keytruda, a PD-1 inhibitor that has become a cornerstone therapy for many cancers, was a strong driver of Merck’s Q3 beat, growing 21% to bring in nearly $7.5 billion. Analysts had expected the blockbuster immunotherapy to generate sales of around $7.3 billion in the quarter. According to Merck, the growth in Keytruda sales was driven by greater uptake in earlier-stage settings including triple-negative breast cancer, renal cell carcinoma and non-small cell lung cancer. Keytruda also saw “continued strong demand” in its other metastatic indications. Merck reported strong product launches in Q3 including the pulmonary arterial hypertension Winrevair, which secured $149 million and surpassed analyst estimates of $129 million. The company also touted its pneumococcal vaccine Capvaxive, which the FDA approved in June 2024 and the CDC recommended for use in adults 50 years and older last week . However, offsetting Merck’s strong growth in Q3 were disappointing sales of its nine-valent HPV vaccine Gardasil and its type 2 diabetes pill Januvia. Gardasil absorbed a 10% year-over-year revenue hit, bringing in a little more than $2.3 billion in the quarter and missing the consensus estimate of more than $2.57 billion. Meanwhile, Januvia sales nosedived 49% with sales of $278 million, missing the forecast of $421 million. Looking ahead to the rest of the year, Merck lowered its full-year EPS guidance to $7.72 to $7.77—versus the previously announced range of $7.94 to $8.04—to reflect one-time charges associated with transactions with Harpoon Therapeutics, EyeBio and Curon Biopharmaceutical. The company also narrowed its sales forecast to $63.6 billion to $64.1 billion. The pharma’s previously announced projection ranged from $63.4 billion to $64.4 billion. Guggenheim Partners analyst Vamil Divan in a note to investors called Merck’s overall performance in Q3 “solid” but said the pharma needs to provide more clarity regarding its expectations for Winrevair and Capvaxive for the coming quarters—as well as its outlook for Keytruda and Gardasil as market pressures mount. BMO Capital Markets analyst Evan Seigerman noted that “Merck’s commercial story remains strong” as “Keytruda continued its usual dominance,” pointing out that Merck has properly positioned itself for continued growth in the coming years, despite Keytruda’s impending loss of exclusivity (LOE). “We believe Merck’s developing cardiovascular portfolio, advancements in I&I (immunology and inflammation) through the Prometheus transaction, and partnership with Daiichi are likely to position the company to grow through its Keytruda LOE and add to the company’s topline for several years,” Seigerman wrote. At the same time, he commented that “another sequential Gardasil miss ($2.31B vs $2.58B) suggests issues from 2Q24 are persisting” and “remains a concern” with the HPV vaccine’s revenues down 10% versus consensus “likely continued to be impacted by problems in China.”

Mestag’s pipeline consists of antibody therapies based on fibroblast-immune interactions as a treatment for cancer and inflammatory diseases. Image credit: Sergiy Palamarchuk / Shutterstock. MSD ( Merck & Co) has signed a license and collaboration agreement with Mestag Therapeutics to develop new fibroblast therapies for inflammatory diseases – a deal potentially worth $1.9bn The companies did not disclose the particulars of the deal, noting that the agreement allows MSD the option to get exclusive development and marketing licences to “a prespecified number of potential targets.” The UK-based biotech in return will receive an upfront payment, and access fees and will be in line to receive option fees and “downstream payments”. Fibroblasts form the connective tissue and are responsible for synthesising extracellular matrix components and collagen, the structural framework of the body. They also play an important role in wound healing, inflammation, and tissue repair. Mestag’s pipeline consists of antibody therapies based on fibroblast-immune interactions as a treatment for cancer and inflammatory diseases. The company’s lead candidate, MST-0300, is a bispecific antibody. The therapy targets lymphotoxin beta receptor (LTBR) in the tumour on co-engagement of fibroblast activation protein (FAP), a tumour-specific marker expressed by cancer-associated fibroblasts, to induce the formation of tertiary lymphoid structures (TLSs) in solid tumours. The presence of these TLSs can be predictive of improved patient outcomes and better therapeutic response. Mestag plans to file an investigational new drug (IND) application in the second half of 2025. Another preclinical candidate in the company’s pipeline is M402, a stromal checkpoint agonist antibody. The therapy is designed to inhibit specific immune cell populations, including myeloid cells. Mestag states that M402 has the “potential to benefit patients across inflammatory diseases including rheumatoid arthritis, lupus, Sjogren’s, graft-versus-host disease and others.” See Also: Clinical Dose Companies in Contract Manufacturing for the Pharmaceutical Industry Innovent and ASK Pharm to commercialise limertinib for lung cancer MSD has been steadily investing in expanding its antibody therapies pipeline. In August, the company acquired Curon Biopharmaceutical , a Chinese biopharmaceutical company specialising in developing bispecific antibodies. The deal is worth approximately $1.3bn in upfront and milestone-based payments. Mestag had previously collaborated with Johnson & Johnson (J&J) in 2021. The licensing agreement allowed J&J the option of an exclusive license to develop and commercialise up to two therapies for the treatment of inflammatory disease.