In less than a month, AstraZeneca has made another move, acquiring Allorion Therapeutics' EGFR L858R inhibitor.

Allorion Therapeutics Announces Exclusive Option and Global Licensing Agreement with AstraZeneca to Develop and Commercialize a Novel Allosteric Inhibitor Targeting EGFR L858R Mutation for the Potential Treatment of Advanced EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC). Under the terms of the agreement, AstraZeneca will obtain an exclusive license for the global development and commercialization of a novel EGFR L858R allosteric inhibitor; Allorion Therapeutics will receive up to $40 million in upfront and near-term payments, over $500 million in development and commercial milestones, as well as tiered royalties on global net sales.

In fact, AstraZeneca has been making frequent moves in the global market recently, and has been particularly "generous" towards Chinese companies, frequently making headlines. In addition to this collaboration with Allorion Therapeutics, on December 12, 2023, AstraZeneca acquired Icosavax for $1.1 billion, gaining a combined RSV/MPV vaccine; on December 26, 2023, AstraZeneca spent $1.2 billion to acquire Gracell Biotechnologies, a Chinese CAR-T therapy company, continuously acquiring high-quality resources.

Some argue that in recent years, while multinational corporations (MNCs) have been cutting back on their pipelines, they have also been expanding into new areas through mergers and acquisitions to create new growth curves for themselves. AstraZeneca's actions suggest its renewed value-driven goal of expanding business segments, especially after successfully betting on trastuzumab deruxtecan (Enhertu, DS-8201). AstraZeneca seems to be looking for the next opportunity for explosive growth.

It is reported that AstraZeneca has been granted an exclusive option for Allorion Therapeutics' novel EGFR L858R allosteric inhibitor. This innovative product aims to address the current drug resistance challenges faced by EGFR inhibitors. Moreover, when used in combination therapy, this allosteric inhibitor has the potential to enhance treatment efficacy.

As a classic target, targeted drug development around EGFR has advanced generation after generation. From the first-generation gefitinib and erlotinib to the second-generation afatinib and dacomitinib, and then to the third-generation osimertinib and almonertinib, the market entry of EGFR-TKI-related products has significantly improved the survival rate of EGFR-positive NSCLC patients. Among these, the most renowned is AstraZeneca's Osimertinib.

Since its launch, Osimertinib has shown strong sales momentum. According to relevant statistics, the sales of Osimertinib were $0.19 billion in 2015, soared to $4.23 billion in 2016, and reached as high as $9.55 billion in 2017. In 2022, the global sales of Osimertinib reached $5.45 billion, making it the best-selling drug of AstraZeneca.

Facing the huge market, pharmaceutical companies have joined the competition one after another. Targeting the drug resistance issue of Osimertinib, multiple pharmaceutical enterprises have taken this as a breakthrough point and launched a concerted attack on Osimertinib.

For instance, at the previous 2023 ESMO Congress, Johnson & Johnson released the head-to-head Phase III clinical trial results of its core product Amivantamab and Osimertinib. Amivantamab is a bispecific antibody targeting EGFR and c-MET, which not only inhibits the expression of EGFR and cMet as well as their downstream pathways but also blocks cancer cells in the G1 phase and induces apoptosis. Amivantamab was approved by the FDA for marketing in May 2021 for the treatment of NSCLC with EGFR exon 20 insertion mutations (Ex20ins) that have progressed after platinum-based chemotherapy.

Data show that the combination of amivantamab and lazertinib (another EGFR-TKI from Johnson & Johnson) reduces the risk of disease progression or death by 30% compared to osimertinib; the median progression-free survival (PFS) reaches 23.7 months, which is 7.1 months longer than osimertinib; overall survival (OS) data are not yet mature but have shown a positive trend.

In overcoming osimertinib resistance, Daiichi Sankyo's HER3 ADC drug—U3-1402 (HER3-DXd, Patritumab deruxtecan)—has also made initial progress. In addition, multiple fourth-generation EGFR-TKIs, monoclonal antibodies, PROTACs, and combination therapies are aggressively positioning themselves to encroach on osimertinib’s market share.

Market observers pointed out that one of the reasons AstraZeneca introduced Allorion Therapeutics' EGFR L858R allosteric inhibitor for a total price of $540 million is precisely because the product has the potential to address the current issue of resistance to EGFR inhibitors; the second reason is that it can enhance its activity when used in combination with osimertinib. Therefore, whether as a post-osimertinib resistance treatment or as part of a combination therapy, this set of EGFR drug combinations is expected to consolidate Osimertinib's leading position.

When it comes to AstraZeneca's acquisitions, the news of its $39 billion purchase of Alexion in the rare disease field is still fresh in memory.

Throughout 2023, AstraZeneca once again targeted new fields, making multiple acquisitions in both domestic and international markets. Only in the Chinese market, AstraZeneca reached several cooperation deals, making multi-point layouts in ADC pipelines, metabolic disease areas, and cell therapy fields. Among them, on December 26, AstraZeneca's acquisition of Gracell Biotechnologies, a leading CAR-T company in China for $1.2 billion, facilitated the first-ever complete acquisition of a Chinese Biotech company by an MNC in the history of China's biopharmaceutical industry.

AstraZeneca's Partnerships/Acquisitions in 2023

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CinCor focuses on developing novel therapies for treatment-resistant and uncontrolled hypertension as well as chronic kidney disease. The company's lead product is the enzyme inhibitor baxdrostat (CIN-107), which targets therapy-resistant hypertension. Baxdrostat is an aldosterone synthase inhibitor (ASI) intended for blood pressure reduction in resistant hypertension and can directly inhibit aldosterone production.

It is reported that aldosterone is involved in a variety of diseases. From Cincor's pipeline distribution, it can be seen that its pipeline basically covers all related disease areas. In addition, Cincor is advancing pipelines for hypertension, chronic kidney disease, and primary aldosteronism, with a very comprehensive pipeline layout. This acquisition strengthens AstraZeneca's pipeline of novel drugs under research in the cardio-renal disease field.

In the field of ADC drugs targeting Claudin18.2, AstraZeneca has chosen to invest in CMG901 developed by Connaught/LePu Biopharma. In November 2023, at the ASCO conference, the results of the Phase I clinical trial (Abstract 434420) of CMG901 in subjects with advanced gastric cancer/gastroesophageal junction adenocarcinoma were released. All subjects had received at least one line of standard treatment (median prior lines of treatment was two), and 74% of the subjects had previously undergone anti-PD-1/PD-L1 therapy. Among 89 evaluable Claudin 18.2-positive gastric cancer/gastroesophageal junction adenocarcinoma subjects across three dose groups, the confirmed objective response rate (ORR) was 33%, and the confirmed disease control rate (DCR) was 70%. Specifically, in the 2.2mg/kg dose group, the confirmed ORR was 42%, with a median progression-free survival (mPFS) of 4.8 months.

In the highly competitive GLP-1 field, ECC5004, co-developed by AstraZeneca and Eternity Bioscience, is currently undergoing Phase I clinical trials in the United States to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the drug in healthy subjects and those with type 2 diabetes (T2DM). The single ascending dose (SAD) portion in healthy subjects has been completed, while the multiple ascending dose (MAD) portion in T2DM subjects is currently ongoing.

In fact, AstraZeneca has been strategically positioned in the cardiovascular and metabolic disease fields for many years, from clinical development to commercialization. For example, in the diabetes sector, global sales of its SGLT2 inhibitors are experiencing rapid growth. Additionally, during the clinical development phase, AstraZeneca is also developing other peptide-based GLP-1 receptor agonists. At the same time, AstraZeneca is advancing multiple pipeline projects, showing potential to provide several products that could be used in combination with ECC5004.

The year-end acquisition drama concluded with AstraZeneca's $1 billion upfront purchase of Gracell Biotechnologies. This marks the first time a Chinese innovative pharmaceutical company has been fully acquired by a multinational pharmaceutical corporation.

Through this acquisition, AstraZeneca aims to gain access to Gracell Biotechnologies' CAR-T platform and multiple cell therapy products, including the dual-target autologous CAR-T (GC012F) targeting BCMA/CD19. Compared to other multinational pharmaceutical companies such as Novartis and Johnson & Johnson, AstraZeneca's progress in the CAR-T field has been relatively slower. However, in recent years, AstraZeneca has accelerated its efforts in the cell therapy sector, gradually building multiple CAR-T and TCR-T pipelines targeting solid tumors. AstraZeneca’s acquisition of Gracell Biotechnologies is also seen as a "doubling down" on the CAR-T field.

AstraZeneca's Key Pipeline Layout Includes Not Only Highly Competitive and Popular Fields But Also Niche Rare Disease Investments, Reflecting the Intense Market Competition in Recent Years. Whether in Oncology Drugs, Weight-Loss Medications, ASO Therapies, or Immunology, Leading Pharmaceutical Companies Are Pouring Significant Funds into These Areas.

Industry insiders pointed out that, under the pressure of the global market environment, there is an urgent need to explore more business possibilities. MNCs are also expanding into new areas through mergers and acquisitions, looking at other fields where market competition is relatively less intense or where unmet needs still exist. This might also be a way for pharmaceutical companies to explore and build their next growth curve.