The potential targets of Cinda’s layout, these companies are also doing

Text | Weiweiyang

On March 29, Cinda Bio announced its 2020 results.

The leading product, Daboshu®, gave full play to its advantages in medical insurance.

Domestic PD-1 outbreak

Last year sales nearly 9 billion yuan

So far, the sales of domestically produced PD-1s have almost been announced, and the cumulative sales of the four domestically produced PD-1s last year was nearly 9 billion.

At present, the competitive landscape of domestically produced PD-1 has basically been determined, and the follow-up strategy is generally towards actively expanding new indications, combining with targeted drugs, foreign authorized development, and relying on strong sales partners to grow bigger and stronger.

In terms of combination therapy, Sintilizumab combined with bevacizumab for the first-line treatment of advanced liver cancer has been reported for delivery.

Among the other indications of Sintilimab under investigation, many first-line therapies have entered the phase III clinical stage, including esophageal cancer, adenocarcinoma at the junction of the stomach and esophagus, and non-squamous non-small cell lung cancer.

The progress of Cinda PD-1's ongoing clinical trials

New targets and new drugs further demonstrate R&D strength

But as time goes by, more and more similar products will soon enter the market, and 84 PD-1/L1 products are under development! In the end, it is inevitable to fall into a fierce price war, and profits will gradually be diluted.

The progress of Cinda Bio's remaining new drugs under development

Analyzing the new drugs being developed by Cinda Biosciences, we can find that in addition to PD-1 monoclonal antibodies, 16 new drugs have entered the clinical stage, including 3 small molecule drugs, 7 monoclonal antibody drugs (including biosimilar drugs), and 5 Double antibody/double antibody fusion protein, a CAR-T cell therapy.

CD47 monoclonal antibody is the first echelon of global progress, and pharmaceutical giants have invested heavily

In recent years, CD47 has been recognized by the industry as the next important target in the field of tumor immunity after PD-1/PD-L1.

The first is Forty Seven's magrolimab.

The second paragraph is EpicentRx's RRx-001.

The third paragraph is Innovent IBI188, which is currently conducting phase Ib/III clinical studies for myelodysplastic syndrome (MDS).

The 2020 online annual meeting of the Society for Cancer Immunotherapy (SITC) announced for the first time the results of its IBI188 (letaplimab) phase 1a clinical study (NCT03763149) for the treatment of advanced malignant tumors in the United States.

Cinda stated that IBI188 has started phase 1b clinical trials in 2020 and plans to enter phase 3 or key clinical trials this year.

In China, Cinda is the fastest target of CD47 in the development of new drugs, followed by TJ011133 of Tianjing Biological.

CD47 target monoclonal antibodies currently under research in China and their progress

Multinational pharmaceutical giants have spared no expense in acquiring CD47 antibody drugs, which is enough to prove that the target has a promising future, and Cinda's target layout is already in the world's first echelon.

FGFR inhibitor Pemigatinib starts key clinical trials and is expected to accelerate approval

Pemigatinib is a potent and selective oral inhibitor targeting FGFR subtype 1/2/3.
It is one of the three clinical stage drug candidates for which Innovent and Incyte reached a strategic cooperation in December 2018.

In April 2020, Pemigatinib was approved by the U.
S.
FDA for use in adult patients with locally advanced or metastatic cholangiocarcinoma who have previously been treated with FGFR2 gene fusion or other rearrangements and are not resectable.
This is the first and only one to be approved by the FDA.
Approved therapeutic drugs for this indication.
Relevant clinical studies have shown that Pemigatinib has significant efficacy and good safety in patients with advanced cholangiocarcinoma, with an ORR of 36%, a duration of remission (DOR) of 7.
5 months, and an overall survival (OS) of 21.
1 months.

In China, Cinda launched the Phase II pivotal registration clinical trial of pemigatinib (R&D code: IBI375) as early as March last year to evaluate pemigatinib in Chinese patients with advanced cholangiocarcinoma who have received at least first-line system therapy, FGFR2 gene fusion or rearrangement in the past.
Cinda will submit an application for domestic marketing of the drug after the clinical data reaches the end point.

PI3K inhibitor Parsaclisib launches key clinical trials in China

Parsaclisib is a potent, highly selective, new-generation PI3Kδ oral inhibitor, and it is also one of the three clinical stage drug candidates for the strategic cooperation between Dabio and Incyte.

As early as ASH 2020, Cinda announced two phase II study data on Parsaclisib for the treatment of relapsed or refractory follicular lymphoma (CITADEL-203) and marginal zone lymphoma (CITADEL-204).
The data showed that the objective response rate (ORR) of the daily dose group was 75% and 56.
9%, respectively; the median duration of response (mDOR) of patients with follicular lymphoma was 14.
7 months, and the median progression-free survival (mPFS) ) Is 15.
8 months; the mDOR and mPFS of patients with marginal zone lymphoma have not yet reached.

In China, Cinda is carrying out a key phase II registration trial to evaluate the effectiveness and safety of Parsaclisib in patients with relapsed and refractory follicular lymphoma or marginal zone lymphoma.
After clinical success, it will be based on this As a result, a new drug marketing application was submitted in China.

At present, many PI3K inhibitors have been approved in the world, but no one has been approved in China.
Among them, Bayer's Copanlisib has submitted a marketing application, and Novartis's alpelisib and Roche GDC-0077 are in phase III clinical phase.
In addition, there are also a number of domestic pharmaceutical companies in the layout, and the companies whose R&D progress is in the first echelon include Chia Tai Tianqing, Cinda Biological, Hengrui Pharmaceutical, CSPC, etc.
, and many clinical developments are currently in phase II.

TIGIT monoclonal antibody drug, a good partner for PD-1/L1

IBI939 is a recombinant fully human anti-TIGIT monoclonal antibody that can directly bind to TIGIT, block the immunosuppression caused by the combination of TIGIT and CD155, relieve the inhibition and depletion of T cells and NK cells, and promote T cell and NK cell-mediated resistance.
Tumor effect.
At the same time, IBI939 is expected to cooperate with PD-1/PD-L1 antibody drugs to enhance the immune response and improve the anti-tumor effect.

At present, no TIGIT targeted drug has been approved in the world, but more than 10 new drugs under development have entered the clinical stage.
Among them, Roche Tiragolumab has entered phase III clinical trials the fastest.

At the ASCO annual meeting in May 2020, Roche announced the results of a phase II clinical trial (CITYSCAPE study) of the combination of Tiragolumab and Tecentriq in the treatment of non-small cell lung cancer.
In the intention-to-treat population, the objective response rate (ORR) of Tiragolumab combined with Tecentriq was 31.
3%, which was significantly better than that of the Tecentriq monotherapy group by 16.
2%.
The median PFS was 5.
4 months vs.
3.
6 months, and the risk of disease progression or death was reduced by 43%; In addition, in the population with high PD-L1 expression (TPS≥50%), the benefit of the Tiragolumab combined with Tecentriq group was further improved than that of the Tecentriq monotherapy group.
The ORR was 55.
2% and 17.
2%, respectively, and the median PFS was not yet compared with 3.
9 Within months, the risk of disease progression or death was reduced by 67%.

In China, Roche Tiragolumab has launched Phase III clinical trials.
In addition, many domestic companies are deploying TIGIT targets.
Among them, Cinda Biological, BeiGene, and Junshi Biological are in the domestic first echelon.
Cinda has already launched in May 2020.
A phase Ia/Ib clinical study of IBI939 as a single agent or in combination with Daboshu® in subjects with advanced cancer was initiated.
The follow-up clinical results are worthy of attention.

The clinical progress of TIGIT monoclonal antibodies under research in China

5 double-antibody drugs enter the clinical stage

Among the 16 new drugs of Cinda Biologics that have entered the clinical stage, 5 are dual-antibody drugs.
Among them, the PD-L1/PD-1 dual-antibody has the fastest progress and entered phase III clinical trials.
At present, a total of 9 dual-antibody drugs targeting PD-1 in China have entered the clinical stage, and Cinda's PD-1/L1 dual-antibody has the fastest progress.

Cinda’s other double antibodies under research have progressed relatively early, most of which are in clinical phase 1.
In addition, there is also a LAG-3/PD-L1 double antibody that has been approved for clinical use, and a PD-1/another target is not disclosed.
The dual antibody submitted IND.
There are currently 6 dual antibodies under development, and the number and progress of domestic deployment are in the first echelon.

Compared with monoclonal antibodies, the double antibody has certain advantages in terms of cost, side effects and efficacy, so it is regarded as the second-generation antibody therapy.
It has developed rapidly in recent years.
At present, only three double antibodies have been approved in the world.
Approved for domestic imports.
Although the domestic research and development of dual antibodies started late, they have developed very rapidly.
At present, companies such as Corning Jereh, Kangfang Biological, BeiGene, and Youzhiyou have also deployed more dual antibody product layouts.
Among them, Corning Jereh’s KN046 ( PD-L1/CTLA4) has progressed to phase III clinical, and it is expected to take the lead in opening the era of domestically produced double antibodies.