incredible!

Author: Leaf

On December 7, European biopharmaceutical company Emergence Therapeutics announced the completion of 87 million Euro A round of financing to promote the clinical proof of concept of the new antibody conjugate drug ETx-22 and develop other ADC projects

According to information disclosed on the official website and financing news, Emergence’s current pipeline should only have the only ADC drug ETx-22 that targets Nectin-4

In terms of specific resolution, the anti-Nectin-4 antibody in the ETx-22 drug originated from the laboratory of Dr.

The toxin of ETx-22 comes from Heidelberg Pharma

The ATAC technology mainly uses THIOMAB antibody, using genetic engineering technology to insert cysteine ​​residues at the characteristic position of the antibody, and then reacting the sulfhydryl group on the cysteine ​​with maleimide to couple to the antibody at a specific point

However, Emergence modified Linker and Amanita muscarin again, and the PSARlink ™ modification technology used was also obtained from Mablink Bioscience through a license authorization cooperation

When Emergence used PSARlink™ technology, it replaced MMAE with amanita

As can be seen from the above, Emergence Therapeutics was able to complete the final “assembly” of ETx-22 through a number of license in cooperation, and this “assembly version” ADC that embodies Emergence's large number of innovative ideas and wisdom has also won the approval of many well-known venture capital institutions.

However, behind the investment of 87 million euros by venture capital institutions, they also value the expansion of the company's follow-up product pipeline

Nectin-4 is a transmembrane protein of the conjunctin family, which participates in tumorigenesis as a cell adhesion molecule

Emergence holds the exclusive rights of a series of Nectin-4 antibodies, from which it can screen out highly specific and advantageous antibodies to avoid off-target toxicity.

In short, Emergence originally did not have a technology platform, but after the operation of Yitong Shen, it has its own technology platform

Changes in the license in of Chinese pharmaceutical companies

License in, a business model that accelerates the availability of overseas innovative drugs in the domestic market, seems to have encountered a lot of controversy in China in the past two years

On the one hand, the License in model has helped a group of representative companies grow and grow in the early days.

More radical questioning voices even believe that: from the perspective of innovation, most innovative drugs under the License in mode are products that have entered the clinical stage.

Although the above point of view points out the problem, the across-the-board evaluation of the license in model also appears to be biased

Shanghai Miac and Shanghai Jinmant reached an authorized patent cooperation on human-derived anti-EGFR antibodies, and obtained the rights to develop, manufacture and commercialize their EGFR antibodies for ADC drugs.
Since then, they have reached two licensing cooperations with Synaffix and obtained its Right to use ADC technology
.
In 2021, Zai Lab reached 4 technology platform cooperations, and was granted the right to use related technologies or platforms to develop innovative drug products
.
In 2021, Innovent will also cooperate with Synaffix, Bolt Therapeutics and other companies to introduce antibody coupling technology and deploy product development platforms
.
Prior to this, Cinda Bio has obtained the right to use the Fabs-in-tandem immunoglobulin (FIT-Ig®) platform of Anmai Biosciences
.
In 2021, Huadong Medicine has invested in Nuo Ling Biology and announced that it will use its patented platform technology to create an ecosystem of Huadong Medicine ADC industry chain
.
Acquired 75% of Zhejiang Doer Biotechnology Co.
, Ltd.
and became its controlling shareholder, and obtained 6 innovative products and 4 major technology platforms (including PEG modification technology platform)
.
It is worth noting that Norlin Biotech's ADC technology and Doyle Bio-PEGylation are also similar to the hydrophilic masking part of the polysarcosine arm in PSARlink™ technology, which can be used to improve the overall hydrophobic properties of ADC drugs
.

Undoubtedly, the introduction of technology is different from the introduction of products.
It can be more integrated into the wisdom and innovation of the introducing party to achieve Emergence-like innovative development and iterative progress, and finally transformed into a new technological innovation platform for the enterprise and a source of continuous output of innovative products.
Motivation
.

Technological innovation ideas behind License in

At the moment when "the technology platform must be called", will the license in ruin the concept of "technology platform" again? This issue can only be discussed later
.
However, Emergence Therapeutics, a case of introducing technology and then integrating innovation, can indeed provide Chinese companies with new ideas on how to license in and make innovative drugs
.

On July 25th, the Pro public account of Medicaid Cube reported the preclinical data of LP-184 (a DNA alkylating agent in the preclinical stage) for the treatment of pancreatic cancer
.
As we all know, pancreatic cancer is called the "king of cancer", and there are real clinical unsatisfactions.
The current treatment drugs are mostly chemotherapy and there are few breakthroughs in innovative drugs
.
The preclinical data of LP-184 showed that it can significantly and rapidly reduce the tumor of pancreatic tumor xenograft mice by more than 90% within 8 weeks, while the tumor volume of untreated mice increased by more than 11 times within 8 weeks
.
Unfortunately, LP-184 is only suitable for tumors with high expression of PTGR1 enzyme
.

The reason for this result is that LP-184 can only be converted into an active metabolite under the catalysis of the PTGR1 enzyme to exert its effect
.
So, why can't the active metabolites be used directly? After all, there are already successful cases of active metabolites being developed into drugs
.
For the active metabolite of LP-184, it may be that ADMET is defective and cannot be made into medicine
.
The advent of ADC drugs provides an idea to solve this problem, such as antibody degradation of conjugated drugs
.

Galectin-9 (Galectin-9) is highly expressed in breast and pancreatic cancer and cholangiocarcinoma.
Galectin-9 interacts with T cells (PD-1) and macrophages (Dectin 1) to avoid the immune system killing and Promote tumor formation
.
LYT-200 is currently the only monoclonal antibody drug in the clinic.
According to the Fast follow strategy, it is natural to continue to develop Galectin-9 monoclonal antibody for the clinical development of pancreatic cancer treatment
.

However, according to Emergence's strategy, we can make the following assumptions
.
Through the introduction of LYT-200 rights, it will be used to develop ADC drugs
.
The ensuing question is whether Galectin-9 has an endocytosis function, which can be verified by many companies with the corresponding capabilities and platform technology
.
After confirming that Galectin-9 has endocytosis, it is no longer a problem for domestic companies to develop ADC drugs
.
If Galectin-9 has no endocytosis ability, in fact, similar technologies such as preCISION imported by Avacta from Tufts University can be used to release cytotoxic drugs outside the cell through specific enzymatic cleavage in the tumor microenvironment
.

Extracellular release is also an issue that should be considered for antibody immunostimulatory conjugates (ISAC) targeting extracellular innate immune effectors or pathways, or should not follow the endocytosis target antibody release in tumor cells
.
So far, we have also used the active metabolites of LYT-200 and LP-184 to form a product similar to the Emergence strategy, instead of simply introducing LYT-200
.
Even if LYT-200 fails clinically, as long as there is no problem with safety and targeting, the active metabolite of LP-184 provides a new guarantee for the success of the new product; compared with LP-184, this ADC drug can form a difference Patient population
.

Of course, Idea is cheap, everything needs data support, this assumption still has some problems that need to be further verified
.
In fact, this is exactly the charm of Emergence's License in model, showing the wisdom and innovation of the introducing party
.
At the same time, it got rid of the fate of License in "the dregs are mixed, the authenticity is chaotic, and the sand picks the gold, sometimes the treasure"
.

Reference materials:

[1]https://heidelberg-pharma.
com; https:// https://emergencetx.
com/

[2]DrugDiscovery Today: Technologies,Volume 27, July 2018, Pages 21-39

[3]Journal of Controlled Release, Volume 220, Part B, 28 December 2015, Pages 660-670

[4] Chem.
Sci.
, 2019, 10, 4048; Pharmaceuticals 2021, 14, 247