TIGIT research and development has been setback!

On May 11, Roche announced the interim data of the SKYSCRAPER-01 study, its TIGIT antibody Tiragolumab combined with PD-L1 monoclonal antibody Tecentriq .

In March this year, the first-line Phase III clinical trial (SKYSCRAPER-02) of the "Tiragolumab + Tecentriq" combination for extensive-stage small cell lung cancer did not reach the PFS endpoint, which once aroused industry attenti.

At that time, because SCLC was classified as a highly malignant neuroendocrine tumor, and NSCLC, which accounted for more than 80% of lung cancer, had particularity in terms of biological characteristics and clinical treatment options, the industry was still unconvinced by the clinical trial results of Tiragolumab for the treatment of NSC.

However, the results of this NSCLC clinical trial directly poured cold water on the optimistic industry expectatio.

For the field of oncology, the failure of clinical trials of small cancers may have limited impact on the future market prospects of products, and the setbacks in clinical research and development of large cancers will not only affect the company's own research and development decisions, but also may change the industry prospects in subdivided fiel.

Immediately, overseas capital market investors "voted with their feet" on this data resu.

Local listed biopharmaceutical companies have not been spared eith.

Is success accidental or inevitable?

TIGIT's future is full of doubts

Roche is a pioneer in the field of TIGIT targets, and it is also the fastest "player" on the subdivision tra.

TIGIT is mainly expressed in T cells and NK cel.

During the 2020 ASCO, Roche announced that the phase II clinical CITYSCAPE trial of Tiragolumab in NSCLC found that the double-immunity drug combination produced a higher response rate in patients with PD-L1-positive lung cancer; at the same time, Roche also announced that Tiragolumab monotherapy had not made progre.

As a giant in the field of tumor immunotherapy, Merck also announced preliminary research data at ESMO 202 The compound preparation MK-7684A composed of TIGIT monoclonal antibody Vibostolimab and PD-1 monoclonal antibody pembrolizumab Keytruda is targeting non-small cel.

Seeing the rapid advancement of Roche and Merck in the subdivision field, TIGIT has become a hot fie.

In October 2020, AstraZeneca announced a collaboration with Arcus Biosciences to initiate a registrational Phase 3 clinical trial evaluating Arcus' investigational anti-TIGIT antibody domvanalimab (AB154) in combination with the PD-L1 inhibitor Imfinzi (durvalumab) in Afri.

In May 2021, Bristol-Myers Squibb (BMS) and Agenus announced that they had entered into an agreement to obtain an exclusive worldwide license to AGEN1777, the latter's proprietary bispecific antibody progr.

In June 2021, GlaxoSmithKline (GSK) entered the market with over US$2 billion and introduced the TIGIT monoclonal antibody EOS-448 developed by iTeos Therapeuti.

After only a few months, the situation took a turn for the wor.

Regarding the clinical trials and clinical trials of Tiragolumab in CITYSCAPE for non-small cell lung cancer and the study of SKYSCRAPER-02 for small cell lung cancer, although the success of phase II clinical trials does not necessarily mean the success of phase III clinical trials, the industry's confidence in "double-immunity" therapy has been compromis.

sha.

At that time, industry experts analyzed and pointed out that the success in the non-small cell lung cancer trial was mainly based on the screening of subjects with high PD-L1 expression (TPS ≥ 50%), and the Tecentriq "single immunity" was upgraded to "double immunit.

The immunity was further strengthened; in the clinical trial of small cell lung cancer, PD-L1 status was not selected, and the test results of Tecentriq+ chemotherapy compared with chemotherapy did not have outstanding effica.

On this basis, TIGIT was added for the test, the results showed , the combination of the two can neither improve the overall survival of patients, nor control tumor progressi.

It is not difficult to see that the industry still has expectations for the "screening of people with high PD-L1 expression (TPS ≥ 50%.

(Phase III)", are successes and failures accidental? At the same time, since PD-1 antibody drugs have not been able to achieve good breakthroughs in the field of small cell lung cancer, SKYSCRAPER-01 focuses on people with high PD-L1 expression (TPS ≥ 50%), and focuses on non-small cell lung canc.

Roche and the industry as a whole have extraordinary significan.

However, this time SKYSCRAPER-01 gave a heavy blow to the TIGIT fie.

Roche has been leading the clinical development of PD-L1+TIGIT for a long ti.

The data of Phase II clinical trials have given high hopes to the indust.

However, two large-scale Phase III clinical trials of small cell lung cancer and non-small cell lung cancer have successively fail.

Where is full of doub.

Large multinational pharmaceutical companies have "stepped on the pit" one after another, and the evaporation of the dollar is not only the market value, but also the market's re-evaluation of the innovation prospects of the sub-secto.

"Follow fast" to the intersection

Do you want to stick with Me-too to the end?

As one of the hot targets that are most likely to open up a new era of immunotherapy after PD-1, in addition to the active deployment of multinational pharmaceutical companies and rapid follow-up in areas with potential for new drugs with clinical value, the R&D pipelines of local Chinese pharmaceutical innovation companies can also be seen The figure of TIGIT monoclonal antibo.

In the domestic market, up to now, pharmaceutical companies such as BeiGene, Hengrui Medicine, Innovent Bio, Junshi Bio, Bio-Tech, Tianjing Bio, Kangfang Bio, and Zejing Bio have already entered the mark.

(incomplete statistics)

At the end of last year, BeiGene gave Novartis the overseas rights and interests of its TIGIT monoclonal antibody at a price of US$9 billion, which greatly increased the "ceiling" of the license-out of domestic innovative drugs and caused a sensation in the indust.

The capital market and innovative research and development look at the prospect of clinical demand and chase the market capacity expectatio.

Following this logic, innovative pharmaceutical companies have TIGIT antibody products in the pipeline, which is undoubtedly a "plus point for the company's innovation strength in the pa.

" "It is also an important way to gain recognition and premium from the capital mark.

However, "original new drugs and risks always follow" is an eternal truth in the field of pharmaceutical research and developme.

In the face of the major failures of the pioneers, many Me-too drugs, as the "sweet pastry" that pharmaceutical companies are competing to deploy in the IO R&D pipeline, are now becoming "hot potatoes", and the TIGIT drug field is encountering an unprecedented stage of tru.

The crisis obviously greatly reduced the market's future expectations for the TIGIT targ.

According to industry insiders, whether it is Biotech or Biopharma, Chinese pharmaceutical innovation companies are still in a period of rapid grow.

Unlike mature multinational pharmaceutical companies, there are still great uncertainties in fighting innovation ris.

Under the circumstance of high chemical capacity, any "turbulence" in the R&D pipeline may trigger a chain reacti.

"For multinational pharmaceutical companies, with a huge product pipeline and many target layouts, the failure of one or two products may only be a loss in research and development costs; however, for Chinese innovative companies, one or two product failures may be irreversib.

!"

However, risks also portend opportuniti.

For the leading multinational pharmaceutical companies with the fastest R&D progress, the results of failure may be difficult to reverse, which may also make the follow-up Chinese Me-too drugs possible to become First-in-cla.

But how easy is it to become a First-in-class?

At least in capital markets, the consequences of the loss of confidence are already starting to sh.

For Chinese pharmaceutical innovation companies, are they full of confidence in their targets and products and continue to burn money to advance clinical development, or wait and see changes and stop losses in time?

In the face of the cold winter of capital, these companies are now standing at the "crossroads" of life and dea.