Antibody-drug conjugates (ADCs) are biopharmaceutical products in which a monoclonal antibody (mAB) is linked to a small molecule drug with a stable linker1. According to NCBI, most of the ADCs developed so far are for use in the treatment of cancer, but there is plenty of potential for using ADCs to treat other diseases1. A Nature publication confirmed that there are currently 12 FDA-approved ADCs on the market, and nine of these secured FDA approval in the past six years2. DDW’s Megan Thomas explores three trends in the market.
1. Financing
When it comes to looking to the future in the drug discovery industry, an important question to ask is: Where is the money? Where is it coming from, where is it going, and how is it being used?
Pfizer’s $43-billion buyout of Seagen earlier this year speaks volumes. Seagen is a major player in ADC technology, with four of the 12 FDA-approved and marketed ADCs using its technology industry-wide3.
“Pfizer is deploying its financial resources to advance the battle against cancer, a leading cause of death worldwide with a significant impact on public health,” said Dr Albert Bourla, Pfizer Chairman and CEO. “Together, Pfizer and Seagen seek to accelerate the next generation of cancer breakthroughs and bring new solutions to patients by combining the power of Seagen’s antibody-drug conjugate (ADC) technology with the scale and strength of Pfizer’s capabilities and expertise. Oncology continues to be the largest growth driver in global medicine, and this acquisition will enhance Pfizer’s position in this important space and contribute meaningfully to the achievement of Pfizer’s near- and long-term financial goals.”
On the other hand, in April 2023, Novo Holdings invested $105 million Series C Funding in Alentis Therapeutics, which will advance clinical development of two first-in-class anti-CLDN1 antibodies and the platform to engineer CLDN1 antibody drug conjugates (ADC) and bi-specific antibodies.
Dr. Roberto Iacone, CEO at Alentis Therapeutics, said: “There are huge unmet needs in organ fibrosis and cancer, and this funding enables us to continue with the important work we’re doing in the CLDN1 space and generate clinical data from both our programs. We can now aggressively develop CLDN1 biology in oncology and continue with the recruitment of our organ fibrosis trials while advancing our ADC and bi-specific antibodies.”
Meanwhile, Lonza, a global manufacturing partner to the pharmaceutical, biotech and nutraceutical markets, has acquired Synaffix, a biotechnology company focused on commercialising its clinical-stage technology platform for the development of ADCs. The acquisition comprises an initial financial consideration of €100 million in cash and up to €60 million in additional performance-based consideration
According to CEO Peter van de Sande, one of the key challenges for antibodies in the context of oncology treatment is that the vast majority of all antibodies are not capable of inducing cell killing simply by binding to the surface of a cancer cell. To overcome this challenge, Synaffix has developed an innovative technology platform that can rapidly and efficiently convert any antibody into an ADC. He told DDW: “These molecules are comprised of an antibody where a cytotoxic payload is covalently attached that is capable of killing any targeted cell upon binding and internalisation. The platform technology of Synaffix is capable of consistently converting any antibody into a best-in-class ADC (in terms of efficacy and safety profile) without any engineering of the genetic sequence of the antibody.”
2. China
Though the world and therefore the industry is increasingly interconnected, keeping an eye on where key players are moving (or remaining) highlights the most significant trends in terms of geography. Varying sources suggest that China has been one to watch over recent years and continues to be going forward.
A market research report published in late June 2018 by HTF market Intelligence Consulting suggested that the ADC market in China would grow exponentially by 20234. The study forecast growth to 2022 and presented an in-depth strategic assessment of the antibody-drug conjugates, highlighting a number of influencing factors impacting or reinforcing market environment, including government policy, technological changes, and market drivers4. The question is, was the forecast accurate?
According to GlobalData, antibody-drug conjugates have gained traction in the China oncology market4. The analytics company believes that the focus of several domestic companies in China has shifted to developing novel ADC-based treatment options for solid tumours like breast, gastric, and bladder cancer5. This appears to be supported by the number of Chinese collaborations, approvals and expansions in 2023 alone.
In May 2023, Japanese drug-maker Eisai entered into a joint development agreement with Chinese drug-developer Bliss Biopharmaceutical for BB-1701, an ADC with option rights for a strategic collaboration6. BB-1701 is an ADC that is composed of Eisai’s in-house developed anticancer agent eribulin, and anti-HER2 antibody using a linker, and is expected to have anti-tumour effects on breast, lung and other solid tumors that express HER2.6
Also in May 2023, Shanghai-native LaNova Medicines entered into an exclusive license agreement with AstraZeneca for LM-305, a pre-clinical stage ADC targeting G protein-coupled receptor, class C, group 5, member D (GPRC5D). Under the terms of the licensing agreement, AstraZeneca will be granted an exclusive global license to research, develop, and commercialize LM-305. LM-305 is the second product to emerge from LaNova’s proprietary ADC platform and has the potential to become a first-in-class GPRC5D-targeting ADC, with IND approvals in the United States and China.7
Making May 2023 a busy month for the ADC market in China, ProfoundBio, a clinical-stage biotechnology company focused on the development of novel antibody-based therapeutics, announced that dosing in the Phase I/II first-in-human trial of PRO1160 (NCT05721222) has initiated in the US, and the company received approval from National Medical Products Administration (NMPA) to initiate the PRO1160 trial in China. PRO1160 is an ADC comprising a CD70-directed antibody conjugated to the exatecan payload with ProfoundBio’s novel, proprietary hydrophilic linker.8
Last, but not least, in April 2023, BioNTech signed a $170 million licensing deal with Duality Biologics, a Chinese clinical-stage biotech company focusing on the discovery and development of next generation ADC therapeutics to treat patients with cancer and autoimmune diseases. This exclusive license and collaboration agreements was for two ADC assets to develop, manufacture and commercialise the two assets globally, excluding Mainland China, Hong Kong Special Administrative Region and Macau Special Administrative Region, where Duality Biologics will retain commercial rights.9
3. Trials and approvals
The more successful trials that researchers complete, the more scope there is for improvement and approvals and the more drugs that are approved for use, the more research can be done. The following are examples of trial results and approvals with regards to Trop2 targeting.
Bio-Thera Solutions, another Chinese commercial-stage biotech making headway in the ADC market, has dosed the first patients in a Phase I clinical study evaluating BAT8008, an ADC that targets Trop2. The multicenter, open-label Phase I clinical study in patients with advanced solid tumors aims to evaluate the safety and tolerability of BAT8008.10
Meanwhile, the FDA has granted expanded approval for Gilead Sciences’ Trodelvy (sacituzumab govitecan-hziy) for patients with HR-positive/HER2-negative metastatic breast cancer who have received hormonal therapy and at least two additional therapies in the metastatic setting. This is reportedly the first Trop-2 directed ADC to demonstrate overall survival benefit in HR+/HER2- metastatic breast cancer patients who had received prior endocrine-based therapy and at least two chemotherapies.11
References
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8628511/
- https://www.nature.com/articles/d41573-023-00060-6#:~:text=ADCs%20consist%20of%20antibodies%20attached,in%20the%20past%206%20years
- https://www.pfizer.com/news/press-release/press-release-detail/pfizer-invests-43-billion-battle-cancer
- https://www.adcreview.com/news/new-reports-suggests-antibody-drug-conjugates-market-to-set-phenomenal-growth-in-key-regions-by-2023/
- https://www.globaldata.com/media/pharma/antibody-drug-conjugates-gain-traction-in-china-oncology-market-says-globaldata/
- https://www.eisai.com/news/2023/news202330.html
- https://www.prnewswire.com/news-releases/lanova-medicines-announces-global-exclusive-license-agreement-with-astrazeneca-for-lm-305-a-novel-gprc5d-targeting-antibody-drug-conjugate-301823364.html
- https://www.prnewswire.com/news-releases/profoundbio-announces-further-advancement-of-lead-programs—pro1184-rinatabart-sesutecan-and-pro1160-in-the-clinic-301835477.html
- https://www.globenewswire.com/news-release/2023/04/03/2639380/0/en/BioNTech-and-DualityBio-Form-Global-Strategic-Partnership-to-Accelerate-Development-of-Differentiated-Antibody-Drug-Conjugate-Therapeutics-for-Solid-Tumors.html
- https://www.businesswire.com/news/home/20230308005366/en/Bio-Thera-Solutions-Announces-First-Patient-Dosed-in-Phase-1-Study-for-BAT8008-an-Antibody-Drug-Conjugate-Targeting-Trop2-for-the-Treatment-of-Advanced-Solid-Tumors
- https://www.gilead.com/news-and-press/press-room/press-releases/2023/2/us-fda-approves-trodelvy-in-pretreated-hrher2-metastatic-breast-cancer
