The next PD-1 for "dystocia"

As early as the 18th century, people began to seek therapeutic strategies that used the immune system to recognize and clear tumor cells, but they have had little

It wasn't until 2013 that this dilemma was truly reversed

Later stories, we may not be too unfamiliar

In the face of attractive prospects, the expectations of innovative pharmaceutical companies around the world for tumor immunotherapy are getting higher and higher, and entrants are flocking to find the next PD-1

But there is always a huge gap

This may tell us a cruel truth: although PD-1 has brought tumors into a new era of immunotherapy, it is not easy

/ 01 /

The "Next PD-1" with successive folds

The success of PD-1 has made immune checkpoint antibodies one of the hottest branches

After PD-1, there were indeed two targets – LAG-3 and CTLA-4 – that ushered in a breakthrough

Both are difficult to prescribe alone, both are approved based on combination therapies, and the indications are not rapidly expanded, and the commercial prospects are limited

Of course, LAG-3 and CATL-4 are lucky enough, because more immune checkpoint antibodies are currently facing a

For example, TIGIT monoclonal antibodies, which have high hopes

However, since the beginning of this year, Roche TIGIT monoclonal antibody combination therapy has successively folded in the indications for small cell lung cancer and non-small cell lung cancer, so that market confidence has gradually disappeared

The dilemma of TIGIT monoclonal antibody is only a microcosm

Innate announced that its NKG2A antibody Monalizumab failed

NKG2A antibodies are not the last potential players

The next PD-1 tour seems to be more difficult

/ 02 /

Immunotherapy "dilemma"

It is not surprising
that immunotherapy development is difficult.
While there are already success stories, our knowledge of the immune system is still extremely limited
.

Overall, the complexity and heterogeneity of the tumor immunosuppressive microenvironment is an important reason
hindering the progress of immunotherapy.

Let's start by looking at the complexity of the tumor immunosuppressive microenvironment
.
The tumor immunosuppressive microenvironment, coordinated by multiple immunosuppressive signals in the regulatory network, does not necessarily have an effect
on controlling a certain pathway.

Indeed, we have identified many potential targets
for tumor therapy.
But for these targets, our cognition is still very limited, and there are naturally great challenges
in the use of proprietary medicines.

For example, how many receptors does the LAG-3 protein bind to? The answer is currently unknown
.
Therefore, in the case of only the single key we found, lag-3 single drug clinical effect is not good
.

Let's look at heterogeneity
.
The tumor immunosuppressive microenvironment is in a dynamic state, and in the process of clinical tumor treatment, due to microenvironmental factors such as tumor type, stage, and histological characteristics, the heterogeneity of the tumor microenvironment will cause immunosuppression, which in turn will lead to differences in the efficacy of
immunotherapy.

All in all, although there are currently three immune checkpoint drugs approved for marketing around the world, our understanding of immune checkpoints is still not clear
enough.

Among the vast number of immune checkpoints, the development of a successful target such as PD-1 is due to
the combination of luck and strength.

However, good luck is not always there, but difficulties are always there
.

/ 03 /

The unattainable Path to Biotech Transition

"PD-1" is unattainable, and it is certainly not a good thing for global pharmaceutical companies, especially Biotech
.

If a Biotech wants to transform into Biopharma, it must have one or two blockbuster products in hand, and the overseas Gilead and Regeneration Yuan are the same
.

To some extent, the development of the domestic innovative drug industry is extremely fortunate
.
Because in the early stage of development, domestic pharmaceutical companies encountered the PD-1 era
.

Domestic pharmaceutical companies can rely on domestic substitution dividends to seize the fruits
of PD-1's victory.
Based on this, Biopharma, including BeiGene, Innovent Biologics, and Junshi Biologics, stands out; The big brother Hengrui Pharmaceutical has also successfully found an important growth point
in the field of innovative drugs.

However, the dividends brought by PD-1 come and go quickly
.
In just two years, the former PD-1 nugget field has become a shura field, where more than a dozen pharmaceutical companies are fighting
.

For the domestic Biotech, life will continue, find the next PD-1, and the pace of attacking Biopharma cannot be stopped
.

But as mentioned above, while PD-1 has helped us push the door to immunotherapy, the process of going down this path won't get any easier
.

The success of PD-1 is not the norm
in the development of innovative drugs.
Who this product will be in the future has no answer
.
For domestic Biotech, the "PD-1 opportunity" is destined to be simply copied and repeated
.