With a total financing of 558 million US dollars, how can ADC therapeutics promote ADC drug research and development?

In July 2019, ADC therapeutics (ADCT), a Swiss biotech company, received an additional US $25 million round e financing, with a cumulative round e financing amount of US $303 million ADCT focuses on the development of antibody drug conjugate (ADC) and non antibody drug conjugate The company's core pipeline covers the fields of hematological system tumor and solid tumor The emerging of ADC drugs, antibody drug conjugate (ADC), is a kind of drugs widely concerned in the field of cancer ADC connects the small molecule drugs with biological activity to the monoclonal antibody through a chemical link, and the monoclonal antibody acts as a carrier to transport the small molecule drugs to the target cells The combination of this chemical and antibody drug makes ADC drug have both the specificity and stability of antibody drug, and the powerful tumor killing effect of small molecule cytotoxic drug
The research of antibody coupling drugs can be traced back to 1980s, but it was not until 2000 that Mylotarg, the first antibody coupling drug developed by Pfizer, was approved by FDA for the treatment of acute myeloid leukemia However, due to the limitations of coupling technology, targeting, effectiveness, etc., the complete antibody coupling drugs were unstable in the blood, leading to the production of lethal toxicity In 2010, Mylotarg was withdrawn from the market in the United States, ADC The prospect of drug research has also been questioned The establishment of ADCT coincided with the emergence of ADC drugs again In 2011, Takeda pharmaceutical and Seattle genetics company developed a new antibody coupling drug adcetris through the transformation of the original ADC technology, which was approved by FDA for the treatment of Hodgkin's lymphomas and systemic anaplastic large cell lymphoma In the same year, ADCT was established as a subsidiary of private equity company auven therapeutics (hereinafter referred to as auven) Since then, in 2013, kadcyla, the first antibody coupling drug for solid tumors jointly developed by Roche and immunogen, has been approved by FDA for HER2 positive breast cancer, and ADC drugs have again set off a research and development boom Team: from a large bio pharmaceutical company, ADCT has established a compound team, which has completed 558 million financing since its establishment, and more than 10 ADC drug pipelines are under research Dr Chris Martin, the current CEO and co-founder, is a key figure in ADCT's development Chris Martin held a key position on the board of directors when ADCT was founded At the same time, he was also the CEO and co-founder of spirogen, a biotechnology company Spirogen focused on the research and development of ADC drugs and developed ADC drugs based on PBD Dr Martin is a member of the society of chemical engineers and a leader in ADC field His spirogen won the "best scientific innovation award" in 2014 In 2012, spirogen reached a cooperation with ADCT, which will share PBD based antibody drug coupling technology (ADC) with spirogen In 2013, led by Chris Martin, MedImmune, AstraZeneca's global biopharmaceutical R & D department, purchased spirogen for $440 million, invested $20 million in ADCT's equity, and established a business partnership with ADCT's two ADC pipelines under research Chris Martin has played an important role in promoting ADCT's core pipeline and helping ADCT get support from AstraZeneca, a pharmaceutical giant The first task of ADCT with abundant funds is to expand its team In 2014, ADCT introduced nearly 10 core executives, including former executives of AstraZeneca, Novartis, MSD, Amgen and other pharmaceutical giants, including scientists or experts in antibody drug development, pharmacology and toxicology, biological product production, law, finance and other fields Among them: Dr Jay Feingold, who will be ADCT's chief medical officer and head of cancer clinical research and development With over 25 years of industry, academic and clinical experience, Feingold has served as vice president of U.S medical affairs and chairman of the global medical affairs oversight committee of the first medical company, and vice president of clinical development of Wyeth Dr Karin havenith, who will be a senior bioanalytic scientist in ADCT's bioanalytic team, was once the chief scientist of genmab, focusing on bioanalytical methods of antibody therapy; Simon Dr Chivers, who will be the pharmacology director of ADCT project research and development, once served as the director and executive director of Novartis global biologics safety assessment, and served as executives in AstraZeneca, Kuntai, etc.; Michael Dr mulkerrin, who will join the CMC (chemical manufacturing and control) department, has worked as an executive in Amgen, Roche and other companies, and has more than 20 years of experience in the field of biological products manufacturing Dr Lisa Skelton, who will be senior project manager of adct-301, one of ADCT's core pipelines Dr Skelton has more than 20 years of industry experience, served as norgine project management director and Amgen senior project manager In 2015, Chris Martin was appointed CEO of ADCT Michael forer, the former CEO, will be the executive vice president of ADCT, responsible for corporate financing, business cooperation, etc Since the founding of ADCT, ADCT has completed a total of 558 million US dollars in financing (disclosed on the official website) In general, ADCT's operating capital mainly comes from the founding shareholders auven therapeutics, AstraZeneca, and later from redmile group In terms of time, ADCT obtained a total of US $385 million in financing from 2015 to 2017, which is also closely related to the positive clinical data of ADCT pipeline under research Core technology of ADCT financing process: Based on PBD, ADC drug development platform has three components in its structure: antigen-specific antibody, stable linker (linker), and effective cytotoxic molecule (warhead drug) The properties of antibody play a decisive role in the key links of ADC entering target cell, such as the binding of antibody and target cell surface antigen, antibody internalization, etc
There are two characteristics of a suitable joint: 1 The stability of the human circulatory system Before the ADC reaches the target cell, no cytotoxic molecules (warhead drugs) can be released by cracking in the circulatory system, otherwise cytotoxic molecules will be generated; 2 After entering the target cell, the joint needs to be broken quickly and effectively to release the cytotoxic molecules and play their due pharmacological activities Warhead drugs are the core components of ADC drugs, so they need to have high activity Because warhead drugs need to be coupled with antibodies, they must also have certain chemical modifiability and water solubility, so as to ensure that warhead drugs can be carried into cells by antibodies and play an effective role Among the drugs in the field of ADC, most of the cytotoxic molecules are medetonin and otostatin analogues The special feature of ADC drugs developed by ADCT is that it uses a new generation of highly effective pyrrolidine benzodiazepine (PBD) dimer toxins as warhead drugs PBD is a class of antitumor antibiotics, which is formed by two PBD monomers and can bind to the minor groove of DNA, which will persist in DNA PBD, as a warhead drug of ADC, targets tumor cells by McAb, blocks tumor cell replication and makes them apoptosis This kind of drug does not depend on the cell replication cycle, will not distort the DNA double helix structure, and will not break the DNA double strand structure like medetone Therefore, it can effectively avoid the repair mechanism of DNA, and the DNA damage caused by it is difficult to repair, reflecting better cytotoxicity Based on its PBD dimer technology, ADCT has developed a wealth of ADC drug pipelines, involving CD19, CD25, CD22, Axl, DLK1, kaag1 and other targets, covering the field of blood tumors and solid tumors, including 5 pipelines that have been in clinical research stage, and 2 pipelines for solid tumors are in pre clinical research ADCT is looking for multi-party cooperation in pipeline research to make up for the technical shortcomings Although ADCT has obtained the authorization of spirogen's PBD based core technology, as mentioned above, the activity of ADC drugs is closely related to specific antibodies and connectors Since 2013, ADCT has been seeking suitable targets and specific antibodies through licensing, joint development and other ways to make up for the short board in antibody drugs and connectors In June 2013, genmab and ADCT reached an agreement to jointly develop ADC drugs based on genmab's humax TAC antibody and ADCT's PBD warhead drugs (adct-301) in July 2013, ADCT obtained an exclusive license and cooperation agreement from bzl biology for antibody drugs for the treatment of PSMA positive prostate cancer PSMA is a highly expressed cell surface antigen in prostate cancer cells, and the monoclonal antibody targeting PSMA will be an ideal target for ADC (adct-401) in November 2013, ADCT entered into a partnership with five prime, from which ADCT will obtain exclusive licenses for five antibody drugs, which target different tumors with undisclosed targets In October 2016, ADCT obtained the patent technology license of glycoconnect and hydraspace from synafix, a Dutch biotechnology company Glycoconnect is a site-specific and stable antibody coupling technology, and hydraspace is an antibody drug coupling enhancement spacer technology In April 2019, ADCT and adagene reached a cooperation ADCT will obtain the license of safebody, an antibody precision masking technology independently developed by Tianyan pharmaceutical Safebody's technology platform can enable the antibody to be specifically activated in tumor tissue and reduce the systemic toxicity of the drug In August 2019, ADCT and freenome reached a cooperation, ADCT will identify patients sensitive to adct-402 treatment through freenome's comprehensive multi-component detection platform In October 2019, ADCT obtained avacta's exclusive license for afimer protein to be used in ADC drug development, and avacta will provide ADCT with optimized afimer binders for three undisclosed cancer targets Since 2014, ADCT's pipeline under research has entered clinical trials and achieved positive results In 2014, adct-401, an ADC drug for PSMA positive prostate cancer, entered the human trial, which was jointly developed by ADCT and AstraZeneca In December 2015, adct-402, an ADCT drug targeting CD19 for Hodgkin's lymphoma (NHL) and B-cell acute lymphoblastic leukemia (all), was approved for phase I clinical trial In June 2017, adct-402 was identified as an orphan drug for the treatment of R / R DLBCL and MCL (mantle cell lymphoma) by FDA In February 2016, adct-301, an ADC drug developed by ADCT for acute myeloid leukemia (AML), entered phase I clinical trial In October 2016, ADCT obtained the patent technology license of glycoconnect and hydraspace from synafix, a Dutch biotechnology company Glycoconnect is a site-specific and stable antibody coupling technology, and hydraspace is an antibody drug coupling enhancement spacer technology In 2017, ADCT was active in national and international conferences such as AACR, International Conference on malignant lymphoma, annual meeting of American Hematology Society 2017 and so on, demonstrating its positive clinical performance in research pipeline These positive data also made ADCT widely sought after by capital From 2014 to 2017, ADCT accumulated 380 million US dollars in financing However, drug development is not always smooth In April 2018, ADCT announced to terminate the development of adct-502 for HER2 positive cancer In September 2019, ADCT once planned to go to the U.S for IPO after the e-round financing, but finally cancelled the listing plan the afternoon before the listing, because the current market conditions are not ideal The prospectus shows that ADC therapeutics has been at a net loss since its inception In 2017 and 2018, ADC therapeutics had net losses of US $89.9 million and US $123.1 million, respectively, most of which were R & D investment and labor costs Investment in R & D of the company in 2017 and 2018