Ulintoclax pegondrimer

Mene Pangalos, Ph.D., is set to step down as EVP of biopharmaceuticals R&D early next year. It’s all change at AstraZeneca. In a Friday morning full of announcements, the Anglo-Swedish drugmaker not only revealed its second-quarter earnings results but also disclosed the elimination of several pipeline programs, the purchase of a portfolio of preclinical gene therapies from Pfizer and the upcoming departure of a key, long-serving R&D executive.  On the pipeline side, the most advanced casualty is AZD4573, a CDK9 inhibitor that AstraZeneca took as far as phase 2 as a treatment for hematological malignancies. The company designed the drug to suppress MCL-1 and induce apoptosis in hematologic cancer cells and advanced it into phase 1/2 and phase 2 clinical trials as a monotherapy and combination treatment in 2021.  Now, AstraZeneca has discontinued the studies as part of its second-quarter pipeline update (PDF). The company attributed the decision to stop work in indications including peripheral T-cell lymphoma to its “strategic portfolio prioritization.” The second quarter clearout also affected a phase 1 hematologic cancer program. AstraZeneca kicked AZD0466 to the curb, stopping a pair of phase 1/2 blood cancer clinical trials, after assessing the benefit-risk profile.  AZD0466 is a BCL-22/XL inhibitor that was supposed to solve the shortcomings of another asset, AZD4320.  Dose-limiting cardiovascular toxicity, coupled to physicochemical properties, torpedoed AZD4320 before it reached the clinic. But AstraZeneca identified a path forward, teaming with Starpharma to create an AZD4320-dendrimer conjugate, later codenamed AZD0466, with an improved therapeutic index.  While AZD0466 and AZD4573 are leaving the pipeline at the same time, Susan Galbraith, Ph.D., EVP of oncology R&D at AstraZeneca, said the hematology pipeline remains “very robust.”  The two scrapped oncology assets are “both molecules that address a cell death mechanism for hematology,” Galbraith told Fierce Biotech on an earnings call with journalists this morning. “The therapeutic index for these is relatively narrow and overall the benefit-risk was not viewed to be one that we felt was able to go forward into subsequent trials.” AstraZeneca is also ending development of AZD3366 in cardiovascular disease. The drug candidate,  a recombinant form of human apyrase enzyme, showed anti-thrombotic, anti-inflammatory and tissue-protective properties in preclinical studies but has fallen at the first hurdle in the clinic. News of the pipeline updates emerged alongside details of other changes at the company. Mene Pangalos, Ph.D., is set to step down as EVP of biopharmaceuticals R&D early next year after five years in the role and 14 years at AstraZeneca. The Big Pharma has already found Pangalos’ replacement. Sharon Barr, who has headed up R&D at AstraZeneca’s rare disease unit Alexion since 2013, will fill the post vacated by Pangalos. On the call with the media, Pangalos said he has no job lined up for when he leaves AstraZeneca. Rather, the executive said he plans to “spend more time with my wife, my girls, see my family in Greece.” The idea is to step back and enjoy “a different pace of life,” he added. Barr is departing Alexion just as the rare disease group is getting an expanded preclinical pipeline. In yet another announcement this morning, AstraZeneca revealed that Alexion has agreed a deal worth “up to $1 billion” for “a portfolio of preclinical gene therapy programs and enabling technologies from Pfizer.” The deal, which will see employees move to Alexion, includes a number of novel adeno-associated virus capsids, a delivery technology that Pfizer has pulled back from as part of its recent early-stage R&D pivot.

Headline results for the second quarter: Revenue: $11.4 billion (forecasts of $10.97 billion), up 6% Profit: $1.8 billion, versus $360 million in the prior yearNote: All changes are versus the prior-year period unless otherwise statedWhat the company said:Commenting on performance for the year to date, AstraZeneca noted that each of its non-COVID-19 therapy areas saw double-digit revenue growth, with eight medicines delivering more than $1 billion of revenue in the first half of 2024. CEO Pascal Soriot said: “our pipeline momentum continues with eight positive pivotal trials for our oncology medicines so far this year, and we are encouraged by the positive data from TROPION-Lung01, the first pivotal trial of datopotamab deruxtecan. We look forward to sharing the data with the medical community at an upcoming medical congress and are proceeding to file the data with the FDA.”Other results: Oncology product sales: $4.4 billion, up 18% Tagrisso: $1.5 billion, up 7% Imfinzi: $1.1 billion, up 55% Lynparza: $717 million, up 7% Calquence: $653 million, up 34% Enhertu: $67 million, with the company also recording $255 million in alliance revenue from the product from partner Daiichi Sankyo Cardiovascular, renal and metabolic disease product sales: $2.7 billion, up 14% Farxiga: $1.5 billion, up 36% Brilinta: $331 million, down 5% Rare disease product sales: $2 billion, up 8% Soliris: $814 million, down 21% Ultomiris: $613 million, up 64% Respiratory and immunology product sales: $1.5 billion, up 7% Symbicort: $600 million, down 2% Fasenra: $406 million, up 15% Pulmicort: $124 million, up 7% Emerging market sales: $3.1 billion, up 12%, with sales in China flat at $1.4 billion AstraZeneca reported no sales of its COVID-19 vaccine versus $445 million in the second quarter of 2022.Looking ahead:AstraZeneca reaffirmed that it expects revenue this year to increase by a low-to-mid single-digit percentage on a constant exchange rate basis, while stripping out COVID-19 medicines is forecast to lead to a low double-digit percentage rise. The company indicated that sales in China are expected to return to growth and increase by a low to mid single-digit percentage. Meanwhile, core earnings per share are seen increasing by a high single-digit to low double-digit percentage.What analysts said:Morgan Stanley analysts noted: "the majority of the product sales beat was driven by Imfinzi (+17% ahead), which has been given a new lease of life in combination with Imjudo in liver, lung and biliary tract cancers, and strong demand for Farxiga (+11% ahead) in heart failure and kidney disease." They also noted that Enhertu beat consensus expectations by 11%, with global sales of $661m (versus $508m in 1Q23) reflecting rapid adoption in HER2-low breast cancer in the US and strong uptake in breast and gastric cancer in ex-US markets.Pipeline updates:AstraZeneca separately announced on Friday that it has acquired a portfolio of preclinical gene therapy assets from Pfizer. The company confirmed that its clinical development programme for brazikumab in inflammatory bowel diseases has been discontinued following a review of the drug’s development timeline and a Phase III trial evaluating Fasenra in bullous pemphigoid was discontinued for futility (efficacy). Phase II development of the CDK9 inhibitor AZD4573 in haematological malignancies has been discontinued and AZD0186 (oral GLP-1 in type 2 diabetes), AZD0466 (haematological malignancies) and AZD3366 (cardiovascular disease) have all been discontinued in Phase I.Phase III data for Enhertu (DESTINY-Breast06) in HER2-low breast cancer, Tagrisso (LAURA) in non-small cell lung cancer (NSCLC), and Imfinzi (NILE) in bladder cancer are expected in the first half of 2024, with AstraZeneca having previously guided to readout in the second half of this year