Nearly $4 billion in gambling, revealing the top ten licenses in 2022

According to Meibai Capital, in the first ten months of this year, the number of cross-border license ins of domestic pharmaceutical companies was 58, down nearly 50% from the same period last year.

Not only did the number fall, but so did the total amount of licenses in. In 2021, the threshold for shortlisting the "Top 10 Cross-border License In Transactions" was $421 million; in 2022, this figure became $161 million.

Last year, there were two licenses that exceeded $1 billion, and this year's record was only $930 million. Obviously, the license in of domestic pharmaceutical companies is more cautious.

Of course, prudence is prudence. In 2022, the total amount of "Top 10 Cross-border License In Transactions" still reached nearly $4 billion.

Who will be the lucky ones?

01 

Chinese biopharmaceutical LAG-3/PD-L1 bi-antibody, 161 million US dollars

Ranking tenth in the "Top 10 Cross-border License In Transactions" is China Biopharma.

On June 23, China Biopharma acquired F-star for $161 million. The most clinically advanced product in F-star's pipeline is a LAG-3/PD-L1 dual antibody.

The combination of PD-1 and LAG-3 is believed to be familiar to most people.

In March this year, Bristol-Myers Squibb's PD-1+LAG-3 combination therapy was approved for marketing, making LAG-3 a "rookie" in the field of immunosuppressants.

The research and development of LAG-3 has also become popular, and many pharmaceutical companies at home and abroad have put LAG-3 and PD-1 combination therapy on the agenda.

Theoretically, LAG-3/PD-1 dual antibodies stimulate stronger T cell activation than combination therapies and have the potential to overcome PD-1 resistance.

In this context, it is understandable that Chinese biopharmaceuticals have opened the "buy, buy, buy" model. So, can Chinese biopharmaceuticals succeed?

02 

Hansen Pharmaceutical TU2670, 170 million US dollars

Ranking ninth in the "Top 10 Cross-border License In Transactions" is Hansen Pharmaceutical.

On August 8, Hansen Pharmaceutical announced that it has reached a cooperation agreement with biotech TiumBio of South Korea, obtaining the commercialization rights of the latter's drug TU2670 in China.

According to the agreement, Hansen Pharma needs to pay an upfront payment of US$4.5 million, a technology transfer fee of US$1.5 million, and a milestone payment of up to US$164 million.

So, where does TU2670 come from?

TU2670 is an oral non-peptide GnRH receptor antagonist that reduces estrogen levels by binding to pituitary GnRH receptors, inhibiting the secretion of luteinizing hormone and follicle-stimulating hormone, and reducing estrogen levels in humans.

Endometriosis and uterine fibroids are common diseases in women, the former can cause dysmenorrhea, infertility, etc., the latter is benign tumors but can induce abnormal uterine bleeding and other diseases.

Currently, non-surgical treatment for both types of diseases is limited. It may not come as a surprise that the TU2670 received a potential milestone of nearly $164 million as a potential non-surgical solution.

03 

Henlius Bifunctional Sialidase Fusion Protein, USD 197 million

Eighth place in the "Top 10 Cross-border License In Transactions" is Henlius.

While licensing biosimilars, Henlius is also introducing innovative drugs.

On June 28, Henlius and Palleon signed a cooperation agreement to introduce two sialidase bifunctional fusion proteins from Palleon. Under the agreement, Henlius will make a down payment and a milestone payment of up to US$196.5 million.

Among the nearly $200 million potential milestone collaboration, one product is pending, which is already known as the bifunctional HER2-sialidase fusion protein.

The bifunctional HER2-sialidase fusion protein is one of the fastest progressing products in Palleon's R&D pipeline and is about to enter clinical trial support studies.

Preclinical studies have shown that the product shows therapeutic potential in both HER2-low and HER2-expressing tumors expressing sialic acid glycans.

HER2 has always been an important therapeutic target in the field of breast cancer, and blockbusters have been frequently launched, such as the current dominant HER-2 ADC.

If the bifunctional HER2-sialidase fusion protein can stand out, it will certainly be worthy of the $196.5 million milestone.

04 

Genting Xinyao EDDC-2214, $214 million

Ranking seventh in the "Top 10 Cross-border License In Transactions" is Genting Xinyao.

In the case of the new crown prevention and control field has become a hot spot, Genting Xinyao has not relent in the introduction of the slightest. After heavily introducing mRNA vaccines, Genting Xinyao laid out the new crown oral medicine track.

On January 14, Genting Xinyao announced that it has obtained the global rights to a group of 3CL protease inhibitors at the Singapore Laboratory Drug Development Centre.

Under the agreement, Genting Xinyao is required to make an upfront payment of US$2.5 million, up to US$107 million in potential development milestones and US$15 million in potential sales milestones of US$105 million, for a total consideration of more than US$214 million.

It is also understandable that looking at the world, the current most effective new crown oral drug is Pfizer's Paxlovid. Paxlovid happens to be a compound formulation composed of 3CL protease inhibitors.

In this context, 3CL protease inhibitors will inevitably become the wind outlet and pour into many players. So, by introducing Genting Xinyao into the field of oral medicine of the bureau, is there a chance of victory?

05 

Hansen Pharmaceutical NKT2152, $218 million

Ranking sixth in the "Top 10 Cross-border License In Transactions" is Hansen Pharmaceutical.

On May 2, Hansen Pharmaceutical reached a strategic cooperation agreement with NiKang to introduce the commercialization rights of the latter's core product NKT2152 in China.

Under the agreement, Hansen Pharmaceuticals needs to make a down payment of $15 million, as well as a milestone payment of up to $203 million.

NKT2152 is a small molecule inhibitor of HIF2α.

HIF, or hypoxia-inducible factor, is a key oncogenic driver of renal cell carcinoma, while VHL is a tumor suppressor protein, when the tumor suppressor protein VHL is inactivated, HIF-2α protein accumulates in cancer cells, sending a false signal of hypoxia, activating the formation of blood vessels and stimulating tumor growth.

HIF2α small molecule inhibitors block cell growth, proliferation, and abnormal blood vessel formation by blocking heterodimerization of HIF-2α and HIF-1β.

It is worth noting that in the biomedical field, the acquisition of HIF-2α inhibitors is not uncommon.

In May 2019, Merck acquired Belzutifan, Petolon's HIF-2α inhibitor, with an initial payment of US$1.05 billion and a milestone payment of US$1.15 billion, and the product has been approved for marketing.

Currently, NKT2152 is undergoing phase I/II dose escalation and expansion trials. With a big deal ahead, once NKT2152 is clinically successful, Hansen Pharmaceutical may also be able to make a big profit.

06 

UrPharma RSV vaccine, $224 million

Ranking fifth in the "Top 10 Cross-border License In Transactions" is Yourui Pharmaceutical.

On March 21, Yourui reached an agreement with Bavarian Nordic to obtain the commercialization rights of the latter's RSV vaccine MVA-BN RSV in China, South Korea and other Southeast Asian regions.

Under the agreement, Yourui needs to pay $12.5 million and up to $212.5 million in milestones.

RSV vaccines are understandably expensive.

RSV, that is, respiratory syncytial virus, this is a very "cunning" virus, specifically "soft persimmon" pinch. Generally able-bodied young people are infected with RSV, a cold symptom of headache and brain fever.

But for vulnerable groups such as infants and the elderly, the threat of RSV virus can be said to be fatal. WHO estimates that 64 million children worldwide are infected with RSV each year, of which 160,000 die from RSV infection, which is an important cause of child death.

What's more, only one palivizumab has been approved for the RSV virus, but it is expensive and the vaccination procedure is complicated. Therefore, a vaccine to prevent the RSV virus has become a long-awaited one; SVB Leerink analysts estimate that the global RSV vaccine market is at least $10 billion.

Therefore, RSV vaccines are highly anticipated by the market. Now, the two RSV vaccines of Pfizer and GSK have taken the lead in standing out, can Yourui Pharma keep up?

07 

Chinese biopharmaceutical Lanifibranor, $300 million

Ranking fourth in the "Top 10 Cross-border License In Transactions" is China Biopharma.

On September 21, Chia Tai Tianqing, a subsidiary of Chinese biopharmaceuticals, reached an agreement with Inventiva to obtain the commercialization rights of the latter's core pipeline, lanifibranor, in China.

According to the agreement, Chia Tai Tianqing needs to pay an advance payment of $1,200 and a milestone of up to $290 million.

Lanifibranor is a pan-PPAR agonist with moderate agonist activity against all three PPARs (α/γ/δ). Currently, Inventiva is developing indications for nonalcoholic steatohepatitis and other potential metabolic diseases

The introduction of Lanifibranor by Chinese biopharmaceuticals is based on its potential for the treatment of non-alcoholic steatohepatitis. Based on Phase 2 clinical data published last year, Lanifibranor shows good potential. Today, the product is in Phase 3 clinical trials.

In the second half of the year, as companies such as Oramed and Akero released the latest research data, the NASH market became lively again.

So, can Chinese biopharmaceuticals successfully scratch the lottery?

08 

Pharmaceutical Pan-RAF, $482 million

Ranking third in the "Top 10 Cross-border License In Transactions" is Pharmatech.

On September 13, Pharmatech entered into a cooperation agreement with Voronoi of South Korea to obtain the global development and commercialization of the latter's pan-RAF inhibitor program.

Under the terms of the agreement, Pharmatech is required to make an upfront payment of US$1.7 million and a milestone payment of up to US$480.5 million.

BRAF is a protein kinase involved in the growth of cancer cells, and BRAF mutations are the most common mutated gene in tumor cells, with a mutation rate of about 8% in all human tumors.

At present, a number of BRAF V600E inhibitors have been approved for marketing, but only for about 45% of BRAF mutant populations. The focus of Voronoi's pan-RAF inhibitor is that it can target a larger (55%) patient population.

If Voronoi can successfully design successful molecules, Pharma Thai can undoubtedly make a lot of money. However, Korean companies have always had a lot of sinkholes, are you optimistic about Voronoi?

09

East China Medicine Arcalyst and Mavrilimumab, $660 million

Ranking second in the "Top 10 Cross-border License In Transactions" is Huadong Pharmaceutical.

On February 23, Huadong Pharmaceutical announced that its subsidiary, Sino-American Huadong, has obtained the commercialization rights of two products, Arcalyst and Mavrilimumab, Kiniksa, in 24 countries and regions including China, South Korea and Australia.

Under the agreement, East China requires an upfront payment of $22 million, up to a maximum milestone of $640 million. What is special about the 2 products introduced by East China Medicine?

Arcalyst is a recombinant dimer fusion protein that blocks signaling of interleukin-1α (IL-1α) and interleukin-1β (IL-1β).

In March 2021, Arcalyst received FDA approval for the treatment of recurrent pericarditis, making it the first and only FDA-approved drug for the treatment of recurrent pericarditis for people 12 years of age and older.

Mavrilimumab is a monoclonal antibody targeting granulocyte-macrophage colony-stimulating factor receptor α (GM-CSFRα). Currently, Kiniksa is preparing to carry out overseas phase II clinical trials of Mavrilimumab for GM-CSF-related cardiovascular diseases.

Huadong Medicine said that the purpose of introducing the two products is to open up the autoimmune and rare disease drug market. So, can East China Medicine get its wish?

10 

East China Medicine HDP-101, HDP-103, 930 million US dollars

Ranking first in the "Top 10 Cross-border License In Transactions" is Huadong Pharmaceutical.

On February 27, Huadong Pharmaceutical announced that it signed an equity investment agreement and exclusive product license agreement with Heidelberg, and Huadong Pharmaceutical obtained the exclusive license of HDP-101 and HDP-103 in 20 Asian countries, with a cooperation amount of up to 930 million US dollars.

However, for now, the cooperation may be full of uncertainty.

HDP-101 is an antibody conjugate that targets B-cell maturation antigen (BCMA). Currently, the product is undergoing overseas phase I/IIa clinical trials for the treatment of relapsed/refractory multiple myeloma.

There are two embarrassments about the product: first, the track pioneer GSK has broken and was revoked after the product was approved; Second, the strong emergence of BCMA dual antibodies has brought challenges to the ADC technical roadmap.

HDP-103 is an ADC drug that targets prostate-specific membrane antigen (PSMA). PSMA ADCs are not yet approved, but companies such as Ambrx are leading the way.

So, what will be the outcome of the best of License-in in 2022?