ADC research and development is normalizing Pfizer but "quietly" changed hands to others!

Pfizer began to "retreat" from the ADC field?

On March 18, Pfizer and American biotechnology company Pyxis Oncology (hereinafter referred to as "Pyxis") jointly announced that the two parties have reached a global licensing agreement for two ADC (antibody-drug conjugate) candidate products, but specific transactions The amount was not disclosed.

According to the license agreement, Pfizer will provide Pyxis with worldwide licensing, development and commercialization rights for two innovative ADC drug candidates, PYX-201 and PYX-203.

Pfizer will also receive advance payments and equity from Pyxis, and will be eligible for milestone payments based on development and sales, as well as tiered royalties for potential sales.

01 R&D while giving up

The PYX-201 in this transaction is a world-first non-internalized ADC drug developed by Pfizer.

After obtaining these two drugs, Pyxis will further develop and expand its ADC drug pipeline.

As a company only established in 2019, Pyxis has a lot of connections with Pfizer.

Dr.

As the world's first company to develop ADC drugs on the market, Pfizer's ADC drug research and development road is also very tortuous.

In May 2000, the US FDA approved the listing of Pfizer's ADC drug Mylotarg (gemtuzumab ozogamicin) for the treatment of patients over 60 years of age with CD33-positive acute myeloid leukemia (AML) who relapsed for the first time.

However, in subsequent trials, Mylotarg not only showed no obvious clinical benefits, but also had serious safety problems.

Today, Pfizer, which already has a number of ADC drugs on the market, is walking the path of giving up while developing.

In 2018, Pfizer terminated its five-year partnership with CytomX Therapeutics' drug Probody for the development and commercialization of several ADC drug development platforms for cancer.

While revenue fell 9% in the fourth quarter of 2019, Pfizer announced the termination of the development of ADC drug PF-06688992.

The sale of PYX-201 and PYX-203 is another "new move" of Pfizer in the ADC field.

02 Will the fiery ADC repeat the mistakes of PD-1?

Compared with the decade of loneliness in the ADC market after Mylotarg went on the market in 2000, the ADC field is already very hot today.

With the development and maturity of small molecule toxins, linkers, and coupling technologies, the ADC technology platform has undergone many iterations, and its safety and effectiveness have greatly increased, and the therapeutic window has been greatly expanded.

Currently, there are 11 ADC drugs on the market worldwide.
In 2019 alone, three ADC drugs were approved for marketing in the United States.
Obviously, the development of "biological missile" ADC drugs has been pushed to a climax.

The domestic pharmaceutical companies are no less enthusiastic about ADC research and development than those abroad.

According to ClinicalTrials.
gov, as of March 19, 2021, there are 155 ADC drug clinical trials in progress worldwide, of which 29 are domestic.
According to incomplete statistics, there are more than 20 domestic companies developing ADC drugs.

List of ADC drug research and development of some companies

At present, Rongchang Biotech's RC48 (Vidixituzumab) is the fastest-growing self-developed HER2 antibody-drug conjugate (ADC) drug in China.
It has submitted gastric cancer indications to the China National Medical Products Administration in August 2020.
The new drug listing application was included in the priority review and approval procedure.
In addition to the application of new drugs for gastric cancer, Vidicuzumab is also conducting phase II critical clinical studies of urothelial cancer, phase III clinical studies of HER2 low-expressing breast cancer, and phase I clinical studies of lung cancer and cholangiocarcinoma.
And obtained the Phase II clinical trial license for urothelial cancer in the United States.

In the first echelon of domestic ADC pharmaceutical companies, Toyo Pharmaceutical, its candidate core product TAA013 has entered the phase III clinical stage.
TAA013 is an antibody conjugate drug under development containing trastuzumab-maytansine derivative (trastuzumab-MCC-DM1), which aims to become an affordable alternative to Kadcyla for the treatment of HER2-positive breast cancer.

As a leading domestic innovative drug research and development company, Hengrui Pharmaceuticals not only joined the ADC battle, but also took a multi-pronged approach.
At present, Hengrui Medicine has disclosed the development progress of 4 ADC drugs.
ADC drugs targeting c-MET, SHR-A1403, HER2 targeting SHR-A1201 and SHR-A1811 are all in the clinical stage.
In January this year, the clinical trial application of Hengrui Medicine's fourth ADC drug SHR-A1904 was also accepted by NMPA.

In April 2020, the Trop-2 ADC drug Trodelvy developed by Immunomedic was approved for marketing in the United States.
Trodelvy is a blockbuster with far higher effects than traditional treatments and has become a new drug for triple-negative breast cancer that has attracted much attention.
As early as 2019, Genting Xinyao obtained Trodelvy's exclusive authorization for the development, registration and commercialization of all cancer indications in Greater China, South Korea, and some Southeast Asian countries and regions.
At present, Genting Shinyao is conducting a phase IIb clinical trial of Trodelvy in China for the treatment of metastatic triple-negative breast cancer that has received at least two lines of previous treatment.

As can be seen from the meeting minutes of the survey activities recently announced by Kelun Pharmaceuticals, Kelun Pharmaceuticals will focus on ADC drugs in 2021.
A166 targeting HER2 has submitted a key Phase II application to CDE; SKB264 targeting Trop-2 has obtained Phase I clinical data; ADC drugs targeting Claudin 18.
2 will enter the clinic in 2021.

The Claudin 18.
2 targeted ADC drug SYS1801 independently developed by CSPC is the first ADC drug targeted by Claudin 18.
2 in a domestic pharmaceutical company.
It was approved by the FDA as an orphan drug in November last year.
CSPC also plans to submit clinical trial applications in China and the United States this year.

However, such a hot ADC track may face the problem of "crowding" and "being unable to make ends meet".

In early March of this year, Biotech announced that it would abandon the clinical development of its ADC drugs BAT8003 and monoclonal antibody BAT1306.
In February, Biotech announced that another ADC drug, BAT8001, had failed the Phase III clinical trial.
According to calculations in the 2020 annual report published by Biotech, the three drugs caused Biotech to lose 340 million yuan in research and development investment costs.

Biotech’s BAT8001 was the first ADC drug targeting HER2 to enter clinical phase III in China, and has always been high hopes.
BAT8003 is also an ADC drug targeting the popular target Trop2.
However, the two popular drugs withdrew one after another, which undoubtedly poured "cold water" on Biotec and even ADC drugs.

Regarding the suspension of the research and development of BAT8003, Biotech stated that it is to rationally allocate the company's research and development resources and focus on advantageous projects in the research and development pipeline.

Biotech's "timely stop loss" also shows a serious imbalance between investment and income.
Behind the hot track means the increase in research and development costs, and it also hides the "price war" under a lot of future competing products.

And will the "crowded" PD-1 monoclonal antibody track become the "tomorrow" of ADC?