Global Pharma Giants Ramp Up ADC Investments as Chinese Biotechs Gain Favor in Licensing Boom

October 27, 2023 / eMedClub News /--Recently,MSD and Daiichi Sankyo Jointly Announce Global Development and Commercialization Agreement for Three ADC Candidates from Daiichi Sankyo; Daiichi Sankyo to Retain Exclusive Rights in JapanAccording to the agreement, MSD will pay Daiichi Sankyo 4 billion US dollars in advance and 1.5 billion US dollars within the following 24 months. In addition, MSD may pay up to 16.5 billion US dollars in future commercial milestone payments.The total amount of cooperation can be as high as 22 billion US dollars.Affected by this news,Daiichi Sankyo's stock price surged nearly 18% during the day's trading, eventually closing up 14.4%, marking the largest increase in over a year.

The two companies said that the transaction combines"Daiichi Sankyo's mature ADC expertise" and Merck's "extensive experience in oncology and clinical development capabilities", in order to advance and expand the impact of ADC on patients with various types of cancer."By the mid-2030s, the "global commercial revenue potential" of each of these three drugs is expected to reach billions of dollars. 

These three ADC projects are patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd), and raludotatug deruxtecan (R-DXd),Designed using Daiichi Sankyo's proprietary DXd ADC technology，Generated by linking multiple topoisomerase I inhibitor payloads through a tetrapeptide-based cleavable linker to a monoclonal antibody.Currently, allIn clinical development, as a monotherapy or in combination with other therapies, for the treatment of various solid tumors.

▲ Image Source: MSD

Patritumab deruxtecan

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This drug (alias U3-1402, HER3-DXd) is aHER3 ADC Drug, was granted Breakthrough Therapy Designation by the U.S. FDA in December 2021,For the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR mutationsThese patients experienced disease progression during or after treatment with third-generation tyrosine kinase inhibitors (TKIs) and platinum-based drugs.

At the recently held IASLC 2023 World Conference on Lung Cancer, Daiichi Sankyo presented the pivotal Phase 2 clinical trial HERTHENA-Lung01 data for patritumab deruxtecan.

The results showed that, in 225 NSCLC patients with EGFR mutations, the confirmedObjective Response Rate (ORR) was 29.8%Among them, 1 case achieved complete response (CR), 66 cases achieved partial response (PR), and 99 cases had stable disease. The median duration of response (DOR) was 6.4 months, and the disease control rate (DCR) was 73.8%. As of the data cutoff date of May 18, 2023, the median progression-free survival (PFS) was 5.5 months, and the median overall survival was 11.9 months.

In terms of safety, the proportion of treatment-emergent adverse events (TEAEs) leading to discontinuation of patritumab deruxtecan was low (7.1%).

Daiichi Sankyo plans to submit the Biologics License Application (BLA) for the drug by the end of March 2024.

The drug (also known as I-DXd, DS-7300) is aB7-H3 ADC Drug, and is currently being evaluated in a phase 2 clinical trial named IDeate-01, forTreatment of patients with extensive-stage small cell lung cancer (SCLC) who have been previously treatedAt the recently held IASLC 2023 World Conference on Lung Cancer, Daiichi Sankyo presented updated results from a subgroup analysis of the phase 1/2 trial of ifinatamab deruxtecan for the treatment of SCLC.

Data show,The objective response rate of I-DXd was 52.4%, with a median progression-free survival of 5.6 months and a median overall survival of 12.2 months.

This drug (R-DXd, DS-6000) is aCDH6 ADC, at the European Society for Medical Oncology (ESMO) Congress,Daiichi Sankyo to Present Updated Data from the Ongoing Phase I Study of R-DXd in Previously Treated Ovarian Cancer PatientsAt the 2022 ASCO Annual Meeting, Daiichi Sankyo presented Phase 1 clinical trial data for DS-6000 in the treatment of RCC and OVC.Among 20 evaluable patients, 6 achieved PR, with an ORR of 30%.

Recently,GSK announced on its official website that it has reached an exclusive licensing agreement with Hansoh Pharma for HS-20089.According to the license agreement and its terms and conditions, Hansoh Pharma will receive an upfront payment of $85 million,Based on the achievement and eligible to receive milestone payments of up to $1.485 billion. This is aNovel B7-H4-Targeted Antibody-Drug Conjugate (ADC), with its payload being a topoisomerase inhibitor (TOPOi),Complements GSK's oncology portfolio and strategic disease area focus, as well as potential future portfolios.

Also in October this year, Yilian Biotech reached a collaboration worth over one billion US dollars with BioNTech to develop the highly promising cancer treatment target HER3, for which there are currently no approved therapies available globally.Yilian Biotech will grant BioNTech the exclusive rights to develop, manufacture, and commercialize one of its ADC products worldwide (excluding mainland China, Hong Kong, and Macao).By adopting the TMALIN® technology from Yilian Biotechnology, the project has demonstrated excellent efficacy and safety in various preclinical tumor models., and preliminary clinical data further supports the proof of concept for this project.

This BioNTech, which amassed billions during the pandemic through mRNA technology, has reached ADC collaborations with multiple biotech companies in China this year. Just two months ago,DualityBio (映恩生物) announced an expanded collaboration agreement with BioNTech.Following BioNTech's $1.67 billion acquisition of two ADCs from DualityBio in April 2023, the two parties will jointly advance the development, manufacturing, and commercialization of a third ADC candidate, DB-1305.DB-1305 isThird-generation ADC products based on the DITAC technology platform independently developed by Yingen BioA targeted ADC formed by conjugating the anti-Trop-2 antibody with a novel topoisomerase I inhibitor, P1021, through an enzymatically cleavable tetrapeptide linker.

VisibleChina's ADC innovative products have, to a certain extent, filled the gaps in the layout of introduced companies, enabling domestically produced ADCs to successfully掀起 an overseas "wave.". Many companies, like DualityBio, have repeatedly carried out ADC overseas expansion and cooperation.

At the beginning of this year, a subsidiary of CSPC GroupGiantstone Biologics of CSPC and Corbus Pharmaceuticals Enter into Exclusive Licensing Agreement, willNectin-4 ADCGranted Corbus the development and commercialization rights in multiple countries, including the United States and EU nations,The total contract amount is as high as 692.5 million US dollars.After the global first batch of Nectin-4 ADC Padcev achieved commercialization,Nectin-4 Target Becomes a Novel and Promising Target; CSPC’s Second ADC Drug Successfully Launched Overseas Also Utilizes This Target. As early as July 28, 2022,CSPC Group licensed Claudin 18.2 ADC to Elevation Oncology for $1.195 billion.The successive overseas expansions of new and old loves have made the ADC market increasingly prosperous and diverse.

May 2023,Lixuan Pharmaceuticals authorized the global, potential first-in-class ADC molecule LM-305 (GPRC5D ADC) to AstraZeneca for a total price of 6 billion US dollars.The latter will obtain the global development and commercialization rights for the drug.LM-305 is currently the world's only publicly known GPRC5D ADC product. GPRC5D is a promising target for the treatment of multiple myeloma following BCMA.Globally, a GPRC5D/CD3 bispecific antibody, talquetamab, is in the marketing application stage. In the ADC field, no company has ventured into it except for Limin.

In May, Biocytogen and Eisai jointly announced that they had reached a collaborative development agreement for BB-1701 targeting HER2.BellePharm Receives Up to $2 Billion in Development and Commercialization Milestone Payments, Plus Sales Royalties.