Hot Pursuit for Antibody Drug Conjugates Continue as Merck Acquires VelosBio

After conquering the arena of checkpoint inhibitor therapies, Merck & Co. is now putting its time and energy into developing targeted therapies, especially antibody-drug conjugates (ADC). In that vein, the company announced a merger agreement with VelosBio, a clinical-stage biopharmaceutical company developing first-in-class ADC targeting ROR1 protein.

This deal comes two months after it made another deal with Seattle Genetics for developing its antibody-drug conjugate. The buyout will give Merck & Co. control of Velos’ ADC, VLS-101, which is currently being evaluated in Phase 1 and Phase 2 clinical trials to treat patients with hematologic malignancy and solid tumors, respectively.

“At Merck, we continue to bolster our growing oncology pipeline with strategic acquisitions that both complement our current portfolio and strengthen our long-term growth potential,” said Dr. Roger M. Perlmutter, Executive Vice President of Merck & Co. “Pioneering work by VelosBio scientists has yielded VLS-101, which in early studies has provided notable evidence of activity in heavily pretreated patients with refractory hematological malignancies, including mantel cell lymphoma and diffuse large B-cell lymphoma.”

Why is Merck Interested in VelsoBio?

VelosBio is developing a targeted therapy against a receptor tyrosine-protein kinase transmembrane receptor overexpressed in multiple cancers. At the end of this year, the company will present data from the Phase 1 trial in entirety at the 62nd American Society of Hematology Annual Meeting. But it gave a glimpse of the VLS-101’s efficacy in a statement.

According to Velos, VLS-101 showed objective clinical responses, including complete clinical responses in 47% of patients with mantle cell lymphoma and 80% of patients with diffuse large B-cell lymphoma. What is most interesting about this drug is that it worked with such great efficacy in patients on whom other anticancer medication failed to work. Also, this is the only ROR-1 directed therapy that has shown remarkable efficacy data.

So far, there are no approved ROR-1 directed therapies. However, there are a few in clinical development. Juno has a ROR-1 directed CAR-T therapy in Phase 1 development, NBE Therapeutics just began testing its anti-ROR1 monoclonal antibody in the clinic, and Kancera is developing a small molecule inhibitor of ROR1. But none are as exciting as VelosBio’s ADC. Following eye-catching Phase 1 data, VelosBio has begun testing its lead candidate in patients with solid tumors, including triple-negative breast cancer and non-small cell lung cancer in Phase 2 initiated last month.

Hot Pursuit of ADCs

ADCs are an emerging class of medicines designed for high-specificity targeting and destruction of cancer cells while preserving healthy cells. Previously, these molecules were considered a minor modality as they present a unique set of challenges. “Their development is complex, which necessitates stringent containment infrastructure, and their structural exceptionality requires expertise in a number of different technologies for small and large molecules.”

Besides their development, early ADCs also encountered major obstacles including, low blood residency time, low penetration capacity to the tumor microenvironment, low payload potency, immunogenicity, drug resistance, and the lack of stable linkage in blood circulation. However, extensive studies have been conducted to overcome these issues, and very recently, ADCs have started delivering remarkable data.

This has encouraged many companies to invest in the development of ADCs, and if this excitement remains, the ADC industry will reach 13 billion Euros by 2030. AstraZeneca reached a deal with Daiichi Sankyo this year in July for the global development of DS-1062, a TROP2 directed ADC, Gilead joined the ADC race by buying Immunomedics for its anti-Trop-2 ADC Trodelvy, and Merck made a pact with Seattle genetics to develop its antibody-drug conjugate, ladiratuzumab vedotin.

Two months back, Germany’s Merck KGaA invested 59 million Euros in the expansion of its HPAPI and ADC manufacturing capabilities and capacity at its facility near Madison, Wisconsin. “This investment will allow large-scale manufacturing of increasingly potent compounds for therapies that have the potential to treat cancer,” said Merck KGaA in a statement.

“ADCs have posted incredible growth over the last decade, and regulatory agencies’ approval in recent years demonstrate their promise as a targeted therapy,” said Andrew Bulpin, Head of Process Solutions, Life Science, at Merck KGaA. “With more than 35 years of experience in this space, we have been a frontrunner in the development and manufacturing of biologics, conjugation processes, and small molecules.”

By Ruchi Jhonsa, Ph.D.

Related Article: Merck Bets Big on Seattle Genetics for Two Oncology Drugs

References

1. https://velosbio.com/news-events/merck-to-acquire-velosbio
2. https://www.merck.com/news/merck-to-acquire-velosbio/
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359697/#:~:text=Early%20ADCs%20encountered%20major%20obstacles,stable%20linkage%20in%20blood%20circulation.
4. https://www.astrazeneca.com/media-centre/press-releases/2020/astrazeneca-and-daiichi-sankyo-enter-collaboration-to-develop-and-commercialise-new-antibody-drug-conjugate.html

Author

Ruchi Jhonsa