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Over the past year, the U.
S
.
biotech sector has experienced one of the biggest pullbacks in history, with many biotechs surviving this cold wave.
But there are always people who are exceptions, and Immunocore is the "exception" of "
exceptions".
In March this year, Immunocore also experienced a cold winter, and its stock price hit a record low, and its market value fell to $883 million
.
But soon, Immunocore broke free from gravity and went upstream
.
Today, Immunocore shares are up 243% at $63.
27 per share
.
After the stock price continued to rise, the company's market value has climbed to $3.
031 billion, constantly hitting new highs
.
Immunocore's fortunes were changed by its T-cell receptor (TCR) therapy Kimmtrak
, which was approved for marketing in January.
As the world's first TCR therapy approved for marketing, Kimmtrak did not disappoint Immunocore, and its rising sales led to higher market expectations for the company
.
Of course, Kimmtrak fueled not only Immunocore's share price, but also the TCR therapy war
.
/ 01 /
/ 01 /Expected to become the "nemesis" of solid tumors
Expected to become the "nemesis" of solid tumorsTo understand TCR treatment drugs, we must first understand the true face of TCR
.
TCR is a specific receptor on the surface of T cells capable of recognizing the histocompatibility complex-peptide complex (MHC).
The function of MHC is to present the fragment of the protein decomposed in the cell on the cell surface, TCR by combining with MHC to determine whether the target cell is normal, if the T cell finds that the protein fragment presented by MHC is mutated, it will immediately kill the target cell
.
In the human body, MHCs
are expressed on almost all cell surfaces.
If a batch of TCR that can specifically recognize tumor antigens can be selected and expressed on the surface of T cells, then these T cells can have the ability to
specifically kill tumors.
In fact, the concept of TCR therapy was proposed
as early as 1986 by Dr.
Michael Steinmetz of the Basel Institute for Immunology.
Michael Steinmetz converts the TCR of a T cell
The gene is transferred to another T cell, thereby giving the second T cell the same antigen specificity, the ancestor
of today's TCR therapies.
However, in the subsequent development of TCR therapy, there have been serious setbacks due to safety and other issues, resulting in slow
progress.
Later, due to the recent excellent success of CAR-T cell therapy, TCR therapy research was relatively less interesting
.
But that doesn't mean TCR therapy isn't worth paying attention to
.
Conversely, TCR therapy may be more advantageous
in the treatment of solid tumors.
The reason for this difference is that the mechanisms by which they recognize antigens are very different
.
CAR cells recognize tumor surface antigens, so they are more effective for hematological tumors with higher exposure to surface
antigens.
TCR can recognize the intracellular antigen fragment presented by MHC molecules, identify the cancer antigen inside the cell, and can penetrate into the tumor to function, making TCR more effective against solid tumors
.
And, since cell surface proteins make up no more than 10% of the total protein, the other proteins are inside
the cell.
Therefore, the number of targets that can be identified by TCR therapy can reach 90%, which far exceeds the number of
targets that can be identified by CAR.
With the increase in the number of targets, there is a broader imagination space
.
The advantages of TCR therapy have attracted many pharmaceutical companies to join the research and development
.
/ 02 /
/ 02 /Immunocore whose trajectory is altered by TCR therapy
Immunocore whose trajectory is altered by TCR therapyAmong the players, the first to hit the line was Immunocore
.
As mentioned above, in January this year, Immunocore won its first victory in this track, and its TCR therapy Kimmtrak was successfully approved for marketing
.
Kimmtrak is a bispecific antibody consisting of
engineered TCR and CD3-resistant scFv.
Among them, after engineering modification, the TCR domain can recognize and bind to the surface of tumor cells, and anti-CD3 antibodies will summon T cells to surround
tumor cells.
Simply put, Kimmtrak's two hands directly pull tumor cells and T cells together, allowing T cells to kill tumors
at close range.
In the Phase III clinical trial, Kimmtrak's performance did not disappoint
.
Results showed that with other therapies (82% pembrolizumab; 12% ipilimumab; 6% dacarbazine) compared to Kimmtrak monotherapy has advantages in overall survival:
Median overall survival was 21.
7 months in the Kimmtrak group versus 16.
0 months in the control group, with a 49%
lower risk of death.
Moreover, it is good in terms of safety, and there are no toxic side effects
above grade 4.
Based on the results of this study, on January 26 this year, the FDA approved Kimmtrak for the treatment of HLA-A*02:01 genotype, metastatic or unresectable uveal melanoma
.
It is worth mentioning that this is the first new treatment
for metastatic uveal melanoma in 40 years.
Based on this, Wall Street analysts are quite optimistic about this First in class drug, and Kimmtrak sales are expected to reach $157.
4 million
this year.
Judging from Immunocore's three quarterly reports, this goal does not seem difficult to achieve
.
In the first nine months, Kimmtrak's sales have reached £74.
5 million, or about $90 million
.
Wall Street's optimism about Immunocore is more intuitively reflected in the
stock price.
Even in the biopharmaceutical winter, Immunocore's stock price has continued to rise, from the low point at the beginning of the year, Immunocore's stock price has risen 243%
today.
Of course, Wall Street's optimism stems not only from expectations for Kimmtrak, but also from expectations for Immunocore technology
.
In addition to Kimmtrak, Immunocore has six therapies under development based on the same technology platform, all targeting clinically unmet diseases, such as hepatitis B and AIDS
.
Imagine if these products can replicate Kimmtrak's success, then the imagination behind it will definitely not be small
.
/ 03 /
/ 03 /The constant ignition of the TCR therapy war
The constant ignition of the TCR therapy warThe success of Kimmtrak is destined to have a profound
impact on TCR therapy as a whole.
Previously, global immune and cell therapy, only a few CAR-T therapies were approved for extramembrane targets with high expression of hematological tumor cells, and no cell therapy drugs have been approved
for intramembrane targets of solid tumor cells.
Although KIMMTRAK is not a TCR-T cell therapy, it has achieved efficacy
by simultaneously targeting T cell receptors and solid tumor cell transmembrane protein antigen targets, improving the lethality of T cells against solid tumors.
The potential of TCR therapy in the field of solid tumors determines the attractiveness
of this track.
After all, compared with hematological tumors, solid tumor owners have a wider world
.
As a result, the research and development of innovative drugs based on T cell receptors is getting hotter and hotter, and the hottest direction is TCR-T therapy
, a sibling of CAR-T therapy.
The transformation of CAR-T is to "change the head" of T cells, take out the T cells, artificially install the "navigation device" CAR and immune "starter" for tumor recognition, and then infuse them back into the human body to play a precise therapeutic role
.
TCR-T therapy is to directly modify the "probe" TCR of T cells to bind tumor antigens, screening out some TCR sequences that can specifically recognize tumors and introducing them into T cells, so that T cells that cannot recognize tumors can effectively identify and kill tumor cells
.
Overseas, Immunocore is the leader of TCR-T therapy, along with Immatics, Medigene, Adaptive, and Lion
TCR and other pharmaceutical companies are also catching up
in the TCR-T field.
In China, many players also see the opportunity of TCR-T therapy, including Xiangxue Pharmaceutical, Kerui Biologics, Euric Biologics, WuXi Junuitah and many other companies have joined this track
.
Although most of the contestants are still in the early stages of TCR therapy, the potential of TCR therapy is not low
.
It is expected that TCR therapy will also change the future
of solid tumor treatment in the same way that CAR-T changes the treatment of hematological tumors.
