In 2022, China's innovative drug license out transactions TOP10

In 2022, the most talked about keyword in the pharmaceutical industry besides "capital winter" may be "internationalization"
.
From the failure of Innovent PD-1 in the FDA examination at the beginning of the year, the successful approval of the legendary biological BCMA CAR-T cell therapy cedarchicel in the mainstream markets of Europe, the United States and Japan, to the successful overseas authorization of a number of domestic new drugs, and then to the clinical trials of all innovative drugs, basically we must simultaneously carry out Sino-US double reporting and carry out global multi-center.
.
.
The internationalization of innovative drugs seems to have become the norm for pharmaceutical people
.

At present, there are two main modes for Chinese innovative pharmaceutical companies to go overseas: First, they go overseas
independently.
That is, Chinese pharmaceutical companies independently carry out clinical trials overseas, and then apply for marketing and sell them after approval, such as BeiGene's BTK inhibitor zebratinib
.
The second is to use "ships" to go to sea, including license out, etc.
, that is, Chinese pharmaceutical companies sell the overseas or global rights and interests of their products to overseas enterprises, and overseas enterprises are responsible for follow-up clinical development, application for listing, production and sales
.
This is also the most commonly used "going overseas" method by Chinese enterprises
.

In the article: "China's Innovative Drug License Out is Gradually Getting Better", PharmaMofang takes stock
of the external licensing of China's innovative drugs/new technologies in recent years.
Next, we will summarize the overseas transactions of licensed innovative drugs/technologies this year and introduce
the TOP10 projects.

Even under the "capital winter", the total transaction value of China's innovative drugs/new technology licenses still reached an all-time high (US$17.
42 billion), an increase of 22.
8%
compared with 2021 (141.
86).
The number of transactions was also higher than in 2021 (42 vs 48).

This confirms the recognition of the innovative strength of Chinese enterprises by foreign enterprises, and also shows that even in the global capital market depression and tight cash flow, good projects can still find suitable "buyers"
.

Note: 1) Dark blue represents the total transaction amount; Light blue represents the down payment; The yellow line represents the number of trades

In terms of project types, innovative drug projects accounted for the highest proportion, reaching 71.
4%, and new technology and micro-innovation (improved) license out transactions accounted for 23.
4% and 5.
4%
respectively.
From the perspective of therapeutic areas, tumors and rare diseases are still hot trading areas, accounting for 35% and 19%
of the number of products, respectively.

Proportion of China's innovative drug/technology license out transaction type (left) and disease field distribution (right) (a project may contain several products)

Top 10 China license out projects in 2022 (US$100 million)

Note: Platform-based drug discovery and preclinical development projects are not counted (e.
g.
, Sanofi's transactions with Tianyan Pharmaceutical and Insilico)

NO.
1

Evocimab (PD-1/VEGF dual antibody)

Akeso → Summit Therapeutics

On the evening of December 6, Akeso announced that it entered into a licensing transaction cooperation with Summit for overseas rights (the United States, Europe, Japan and Canada) for PD-1/VEGF bispecific antibodies (Ewosi, AK112) with a down payment of 500 million US dollars and a total amount of up to 5 billion US dollars, which has attracted widespread attention
in the industry.

Recommended reading: Three highlights behind the $5 billion "going to sea" of domestic dual antibodies

AK112 is the world's first PD-1/VEGF bispecific antibody to enter the clinical research stage, and it is also the world's fastest PD-1/VEGF bispecific antibody
with the fastest clinical development progress.
AK112 has been recognized as a breakthrough therapy by CDE and has been studied in phase III in two clinical studies, including a phase III clinical study of single-agent versus pembrolizumab monotherapy for PD-L1-positive NSCLC, and a phase III clinical study
of EGFR TKI-resistant EGFR-mutant NSCLC in combination chemotherapy.

Whether it is the down payment or the total amount, the transaction is among the top
license out records in China.
However, different people have different opinions
on this deal.
Some people question the real intention
of Akeso to cooperate with Summit, which has $120 million in cash on its books and a market value of less than $200 million.
Some shareholders lamented
"boldly" after learning that the company's CEO was the legendary Robert Dugan (who served as chairman of the board of directors, CEO and largest investor of Pharmacyclics from 2008 to 2015, and single-handedly led Pharmacyclics' sale to AbbVie for $21 billion).
Some shareholders said that they should cherish companies like Akeso Biologics that hold heavy innovative varieties, because they may take off at any time~~

In general, this transaction not only fills the cash reserve for Akeso, comprehensively contributes to the company's subsequent drug development and strategic development process, but also paves a fast and winning path for the global development and commercialization process of Ewosi, which is also an important step
towards the global development of Akeso.

NO.
2

Oxatuzumab (Trop2-ADC)

Genting New Yao → Immunomedics

On August 16, Genting Xinyao announced that it has transferred exclusive rights to develop and commercialize Trodelvy (Gorsatuzumab) in Greater China, South Korea, Singapore, Indonesia, the Philippines, Vietnam, Thailand, Malaysia and Mongolia to Immunomedics
, a wholly owned subsidiary of Gilead.

Genting New Yao received consideration totalling US$455 million, including an upfront payment of US$280 million subject to relevant regulatory approvals and a potential future milestone payment of US$175 million
.

As early as April 2019, Genting Xinyao acquired Trodelvy's exclusive rights
in the above countries and regions from Immunomedics with an upfront payment of US$65 million + US$770 million.
With this refund, Genting Xinyao will not have to pay the remaining US$710 million
in milestone payments.
In other words, between "one buy and one sale", Genting Xinyao "net earned" 330 million US dollars
.

In the 3 years in hand, Genting Xinyao promoted the approval of Trodelvy in China and January 2022 in China and January 2022 for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have previously received at least two systemic therapies
.
Genting Xinyao also submitted a marketing application
for the product to the drug regulatory authorities in South Korea, Taiwan and Hong Kong.

As the core product of Genting Xinyao in the field of oncology, it was sold
.
The capital market apparently did not buy the deal, which also directly affected the company's share price, and Genting Xinyao's share price fell 19.
1%
by the time the news was announced.

NO.
3

JMKX002992（AR PROTAC）

Jimin Credible → Genentech (Roche)

In mid-August, Shanghai Jiyu Pharmaceutical, a subsidiary of Jimin, licensed the global development and commercialization rights of JMKX002992, an oral androgen receptor (AR) protein degrader (PROTAC), to Genentech, with a total amount of US$650 million
.

After inquiry, there are currently 5 AR PROTAC drug candidates in the world that have entered the clinical stage, and only Pfizer's ARV-110 has announced phase I/II clinical results, and Jimin's credible product candidate was bought at a high price in the preclinical stage, which is enough to prove Roche's optimism
about the future potential of such products.

Source: NextPharma database

In November 2021, Shanghai Jiyu and HUYABIO REACHED AN OVERSEAS LICENSING AGREEMENT FOR A KRAS INHIBITOR; On May 6 this year, it reached an overseas authorization with ORION for a new non-opioid analgesic drug, with a down payment of 15 million euros
.

NO.
4 AND NO.
5

SKB264（TROP2 ADC）、SKB315（CLDN18.
2 ADC）

Colombert → Merck

This year, Kelun Pharmaceutical has granted two solid tumor ADC drugs (Project A: TROP2 ADC and Project B: CLDN18.
2 ADC) rights
to Merck.
The down payment for the two drugs totaled $82 million, and the milestone payments totaled $2.
264 billion
.
In just two months, two blockbuster deals were reached with pharmaceutical giants, which is the key progress of Kelun Pharmaceutical to "imitation transformation", and also makes people change the stereotype of Kelun Pharmaceutical, the "infusion faucet"
.

Recommended reading: Over $900 million! Colombert licenses Merck another ADC drug

On December 6, Colombote presented the latest efficacy and safety data
of SKB264 in the Phase II Expansion Study in TNBC Patients at the 45th San Antonio Breast Cancer Symposium.
Among the 55 patients who could be evaluated for efficacy (21 in the 4 mg/kg group and 34 in the 5 mg/kg group), the confirmed objective response rate (ORR) was 40%, the disease control rate (DCR) was 80%, among which the confirmed ORR of patients with high TROP2 expression was 55.
2%, and the ORR confirmed by the TROP2 high expression 5 mg/kg dose group was as high as 62.
5
%.
The median progression-free survival (mPFS) was 5.
7 months, the median overall survival (mOS) was 14.
6 months, and the 12-month OS rate was 66.
4%.

This indicates a promising efficacy and controllable safety
profile of SKB264.

SKB315 (CLDN18.
2 ADC) is currently in Phase I clinical trials
.
Some time ago, Astellas first-in-class CLDN18.
2 monoclonal antibody two phase III studies successfully injected a shot of strength into the company developing CLDN18.
2 targeted drugs, which also made SKB315 a chance of success
.
As early as September 7 this year, Kelun Pharmaceutical announced that it had received a payment of $35 million from Merck for Project B
.

NO.
6

JS006 (TIGIT monoclonal antibody)

Junshi Biosciences → Coherus BioSciences

On January 10, Junshi and Coherus expanded their cooperation
in the field of tumor immunity reached in 2021.
Coherus exercised JS006 (anti-TIGIT anti-TIGIT) licensing option in the United States and Canada and made an upfront payment of $35 million to Junshi Biologics, a milestone payment of up to $255 million, and an 18% sales share of net product sales
.

TIGITs have been hailed as the hope of the immuno-oncology field, whether it is a large pharmaceutical company or a small pharmaceutical company, if there is no TIGIT targeted drug in the pipeline, it seems that it is not bright enough
.
However, the folding of Roche TIGIT antibody tiragolumab as a "leader" in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) indications also makes the future of this target full of uncertainty
.

Recommended reading: TIGIT targets frustrated, overshadowing pharmaceutical giants' $6 billion bet

Fortunately, Gilead/Arcus said on November 28 this year that the fourth interim analysis of the phase II ARC-7 trial of the anti-TIGIT antibody domvanalimab in the first-line treatment of metastatic NSCLC was positively updated, and in terms of multiple efficacy measures (including ORR, PFS, and 6-month landmark PFS), compared with zimberelimab (PD-1) monotherapy, Dovanalimab combined with zimberelimab continues to show clinically meaningful differences
.
Dovanalimab is well
tolerated.
Gilead said additional results
for further analysis of the ARC-7 dataset will be available during the ASCO Annual Meeting on December 20.
This also increases the confidence
of enterprises that develop later.

NO.
7

TLC599 (Dexamethasone sodium phosphate)

Taiwan Microliposomes → Endo International

On June 13, Taiwan Microliposome (TLC) signed an agreement with Endo Ventures to grant the latter the commercialization rights
to TLC599 (Dexamethasone sustained-release and controlled-release liposome formulation).
TLC599 is currently undergoing a Phase III clinical study
for the treatment of knee osteoarthritis (OA) pain.

TLC will receive $30 million in upfront payments and will be eligible for development, regulatory and milestone payments
of up to $110 million.
TLC will be eligible for payments based on certain commercial milestones, as well as royalties
based on the product's net sales in the United States.
In addition, TLC will be eligible for certain milestone payments
for future potential indications.

Current single- and repeated-dose intra-articular anti-inflammatory therapy for OA has potentially toxic side effects and may lead to disruption of cartilage-filling protein
.
Preclinical toxicity studies have shown no significant cartilage damage
after single and multiple doses of TLC599 compared to current treatment.
In addition, in a phase II clinical trial, a single injection of TLC599 showed statistically significant and clinically significant improvements
in the WOMAC Pain and Function Scale and VAS Pain Score compared with placebo at weeks 12, 16, and 24.

NO.
8

SYSA1801（CLDN18.
2 ADC）

Stone Medicine Megalithic Creatures → Elevation Oncology

On July 28, CSPC Jushi Biotechnology, a subsidiary of CSPC Group, entered into an exclusive licensing agreement
with Elevation Oncology for the development and commercialization of the first-of-its-kind anti-Claudin 18.
2 ADC outside Greater China, including Chinese mainland, Hong Kong, Macau and Taiwan.

In 2020 and 2021, the product was awarded orphan drug designation by the US FDA for the treatment of gastric cancer (including esophageal-gastric junction cancer) and pancreatic cancer
.
The product is currently in the phase I clinical stage
in China.

As a representative of traditional pharmaceutical enterprises, like Kelun Pharmaceutical, CSPC is also undergoing the strategic transformation
of "innovative drugs" + "internationalization".
Although at present, it is not possible to build its own R&D center and sales team
abroad like the "big brother" Hengrui Pharmaceutical.
However, allowing their own products to go abroad through the form of license out is also a big step
towards internationalization.

NO.
9

HBM7022 (CLDN18.
2/CD3 biantibody)

Harbour Pharmaceuticals → AstraZeneca

On April 7, Harbour Pharmaceuticals and AstraZeneca reached a global licensing agreement
for the development and commercialization of the CLDN18.
2/CD3 bispecific antibody HBM7022.
AstraZeneca will be licensed worldwide exclusively for the research, development, registration, manufacturing and commercialization of HBM7022 and will be responsible for all expenses
associated with the further preclinical development and commercialization of the product.
Harbour BioMed will receive an upfront payment of $25 million and milestone payments of up to $325 million, as well as royalties
based on future HBM7022 sales.

As a platform biotechnology company, Harbour Biopharma has reached the external licensing of 6 products this year, including multinational pharmaceutical giant AstraZeneca, star company Moderna, domestic traditional enterprise CSPC Pharmaceutical Group, and small biotechnology company Yingen Biotechnology
.

Source: NextPharma – Pharmaceutical Trading Module

Some time ago (November 15), Harbour Biologics handed over its Suzhou industrialization base to WuXi Hyde, a subsidiary of WuXi Biologics, for RMB 146 million, focusing on the development of innovative drugs
through its own antibody technology platform.
On the one hand, under the cold winter of capital, through the transfer of factories, enterprises can obtain a sum of cash, which can solve the urgent need for book funds to be stretched; On the other hand, this also reflects a clearer understanding of the company's development strategy, no longer wanting to become a biopharma, but becoming a small and beautiful Biotech, focusing on its own expertise
.

NO.
10

LM-302（CLDN18.
2 ADC）

Lixin Pharmaceutical → Turning Point (BMS)

On May 5, Lixin Pharma announced that it has entered into an exclusive licensing agreement with Turning Point of the United States, granting the latter the development and commercialization rights
of its self-developed anti-CLDN18.
2 ADC candidate LM-302 in countries and regions around the world except Greater China and South Korea.
LM-302 is the first CLDN18.
2 targeted drug
in China to license out to sea.
As introduced earlier, there are as many as 4 drugs involving CLDN18.
2 in the TOP 10 down payment amount
.
This further shows that pharmaceutical companies are optimistic
about the market prospects of this target.

On June 3, Bristol-Myers Squibb acquired Turning Point for $76 per share, totaling approximately $4.
1 billion, and LM-302 is now a BMS candidate
.

Founded in 2019, in just three years, the company has built a pipeline of 13 innovative drugs, of which 6 are undergoing phase I/II clinical trials
.
There is also a CLDN18.
2 monoclonal antibody in the Lixin pharmaceutical pipeline, which is currently undergoing phase I/II clinical trials
.