How many "dark horses" can domestic ADCs run?

Source: Yaodu

Written by: Huang ZhongpingEditor: Maruko

Recently, Goxatuzumab, a new ADC drug introduced by Genting Xinyao for US$835 million, was officially approved for marketing in China, which is the first TROP-2 ADC approved for marketing in Chi.

The approval of the drug also pushed the recent lively ADC track to a clim.

At this year's ASCO 2022 annual meeting, Rongchang Bio received a rare "special session" arrangement, showing the industry's recognition of the efficacy of vedicitum.

Vidicitumumab is the first new ADC drug independently developed by a Chinese compa.

Due to its significant clinical efficacy, it has attracted much attention before it was officially approved and has become a complete "dark horse" among AD.

This is exciting, after all, there are not many examples of new Chinese-created medicines receiving so much attention on the international sta.

But slowly, with the continuous advancement of the domestic ADC pipeline under research, we found that excellent domestic ADCs continue to emerge, and it seems that many "dark horses" are rushing .

01

budding

At this ASCO 2022 annual meeting, Rongchang Biotech presented three research results on velidistumumab, namely:

Preliminary results of a phase Ib/II study of RC48-ADC combined with PD-1 toripalimab in patients with locally advanced or metastatic urothelial carcinoma

Phase II clinical study of RC48-ADC in patients with HER2-negative locally advanced or metastatic urothelial carcinoma

RC48-ADC in the treatment of HER2-overexpressing (2+ or 3+ immunohistochemical) metastatic urothelial carcinoma: a comprehensive analysis of the RC48-C005 and RC48-C009 clinical tria.

The results of these three clinical studies have once again demonstrated the obvious advantages of vellicitumab in the treatment of urothelial canc.

Everyone is familiar with the story of Vidicitumab setting a new record in the overseas transaction value of Chinese innovative drugs with a license-out of US$6 billion in total transaction value, so I won't repeat it he.

Vidicitumab, source: Rongchang Bio official website

What we need to dig out are those "dark horses" that haven't been seen y.

In fact, at this ASCO 2022 annual meeting, the A166 (HER2 ADC) data from Colombotei was also very eye-catchi.

The data of the phase I dose-expansion study of A166 in HER2+ breast cancer patients after multi-line treatment showed that the objective response rate (ORR) of the 8 mg/kg group was 79%, the median PFS was 13 months, and the adverse reactions were controllab.

Compared with DS8201 of Daiichi Sankyo, which has also undergone multi-line treatment, the objective response rate (ORR) of breast cancer indications is 63%, and the mPFS is 14 mont.

The objective response rate (ORR) of Columbus is high.

The efficacy and safety of A166 have been verified again, and the future can be expect.

However, this is not the most promising ADC from Colom.

On May 13, Colombo gave its biomacromolecule tumor project with independent intellectual property rights to Merck with a license-out of over 4 billion US dolla.

The market speculated that the drug should be TROP-2 ADC, with the R&D code SKB26

SKB264 (TROP2-ADC) updated the phase I study data at the 2021 Chinese Society of Clinical Oncology (CSCO) academic annual meeting in September last year: a total of 17 patients received at least one efficacy evaluation showed that the overall response rate (ORR) of SKB264 ) of more than 40% and the disease control rate (DCR) of more than 70%, the results of this study are encouragi.

However, SKB264 can sell for such a price, which is still greatly unexpect.

Source: Kelun Pharmaceutical official website

Also in May of this year, Lixin Pharmaceutical, which is still in the financing stage, launched its self-developed Claudin12 ADC drug LM-302 in the world except Greater China andThe license-out of development and commercialization rights in countries and regions other than Korea was given to Turning Point in the United States, with a down payment of US$25 million, and the total amount exceeded US$1 billi.

Lixin Pharmaceutical has not disclosed much information about LM-302, but what we can know is that the Claudin 12 track is currently a Red Sea competiti.

At present, there are nearly 30 different types of drugs targeting Claudin12, such as monoclonal antibody, double antibody, ADC and CAR-T, which have entered the clinic, and there are more than 40 preclinical produc.

LM-302 can be favored by Turning Point, and the advantages of R&D progress may also be considered mor.

Currently, LM-302 is in the phase I/II clinical trial sta.

Just entered June, and there is good news from D.

On June 1, DorhillBio announced that it has reached a cooperation and licensing agreement with Janssen Pharmaceuticals, a subsidiary of Johnson & Johns.

According to the agreement, Dorhill will use its unique ADC innovation platform and the unique antibodies provided by Janssen, and both parties will develop new ADC drugs for up to 5 targe.

Through this cooperation agreement, Dorhill will fully utilize its proprietary intellectual property rights and proprietary ADC platform, and Janssen will provide its unique antibodies and promote clinical development and commercializati.

Dorhill Bio will receive upfront payments, cost reimbursement and milestone payments, as well as royalties on global sales of the produ.

In addition to these domestic ADCs that have already sold at a good price, are there other domestic ADCs under development that can be played?

02

Looking for a "dark horse"

At present, the competition of Chinese ADCs has been extended to the commercialization sta.

In 2020, Velbutuximab (Adcetris) and Enmetrastuzumab (Kadcyla) were approved in China for lymphoma and HER2-positive breast cancer respectively, marking the first year of ADC commercialization in China; 2021 In June, Rongchang's new ADC drug Vidicitumab was approved for third-line treatment of locally advanced or metastatic gastric cancer with HER2 overexpression, becoming the first domestically produced new ADC drug; Monoclonal antibody was approved; in June 2022, Goxatuzumab, an ADC targeting Trop-2, was approved for breast cancer treatme.

The competition of domestic research projects is in a state of blooming, with more than 150 research projects at various stag.

As of June 2022, domestic pharmaceutical companies have applied for clinical trials of 64 new ADC dru.

In terms of target distribution, HER2 is the most popular target with 17 models, followed by TROP-2 and Claudin 12, with 8 and 7 models respective.

However, among these research pipelines, there are not many independent research and development projects that have reached the final clinical sta.

TAA -013 (HER2) of TOT BIOPHARM is the fastest-growing domestic self-developed ADC
TAA013 is composed of a stable thioether bond connecting trastuzumab and a microtubule inhibitor maytansin derivati.

It not only has the dual anti-tumor effects of trastuzumab in blocking HER2 signaling and triggering ADCC effect, but also Utilizing the targeting effect of trastuzumab, the maytansine derivatives were delivered to HER2-positive tumor cells for cytotoxic killi.

TAA013 is a similar drug of T-DM1, and the two have similar structur.

In non-clinical pharmacodynamics and pharmacokinetic studies, TAA013 and T-DM1 have similar characteristi.

The results of the phase I clinical study of TAA013 showed that in HER2-positive breast cancer treated with multiple lines of trastuzumab, lapatinib, and pyrotinib, the objective response rate (ORR) after treatment with TAA013 was 10% , the disease control rate was 70%, and the median PFS was more than 5 mont.

At the same time, TAA013 has good safety and no restrictive side effec.

Only a few patients have a decrease in platelet count and an increase in transaminase, but they are all safe and controllab.

The Phase III clinical study of TAA013 is currently underw.

Source: TOT BIOPHARM’s official website

In terms of layout, Hengrui Medicine, Lepu Bio, Rongchang Bio, and Duoxi Bio have strong strength in independent research and development, and have applied for more clinical projec.

Hengrui Medicine has 6 ADCs in clinical stage

Research and development progress of SHR-A1811, source: Hengrui Medicine 2021 Annual Report

Lepu Bio has acquired a number of ADC drugs and ADC R&D platforms that are still in the early stage due to the acquisition of the controlling stake in Shanghai Meiya, and has become a leading pharmaceutical company in the domestic ADC trac.

MRG003 is a domestically advanced ADC targeting EGFR, and is undergoing Phase II clinical trials in many solid tumors; MRG002 is a HER2-targeting ADC, and a number of Phase II clinical trials in solid tumors are currently underw.

The progress of the Duoxi biological pipeline, source: Duoxi biological official website

In addition to Vidicitumumab, Rongchang Bio has also deployed mesothelin-targeted RC88, c-MET-targeted RC108, and Claudin 12-targeted RC118, which are currently in clinical phase I, and several are in preclinical Phase undisclosed projects

Bio-Tech was once one of the leaders in the domestic ADC circuit, but unfortunately, it fell due to the failure of two heavy ADCs

In February 2021, Bio-Tech announced that the main efficacy index of its ADC drug BAT8001 in Phase III clinical trials did not reach the preset superior efficacy target compared with the control group, and decided to terminate the clinical trial of the project; less than a month later, Bio-Tech was It also announced the termination of clinical development of BAT8003 (TROP-2 AD.

Among the new generation of ADC companies, Yinen Bio, Yilian Bio, and Pufang Bio are the representativ.

03

Epilogue

When talking about the development of domestic innovative drugs, some people always like to emphasize "involutio.

References:"China's New ADC Drug Breakthrough TAA013 Phase III Clinical Trial Chess to Mid-Range", Zhitong Finance, 2021-7-10"It's Not Too Late, Looking Forward to Rising Stars - Overview of ADC Drug Development in China" ", Biological Frontier, 2022-5-26"Competitive Landscape of Domestic ADCs", Armstrong Biopharmaceutical Information, 2022-06-11