After a frozen period of IPOs, the biotech industry seems to have ushered in a reversal.
On January 25, CG Oncology became the first biotech company to successfully IPO in 2024. It is worth noting that it raised 3$800 million, exceeding the original expectation of $200 million.
The performance that exceeded expectations also continued to the secondary market. After the opening of the first day of trading, CG Oncology's stock price continued to rise, and finally closed up more than 95%. Currently, CG Oncology's latest market cap reaches 22$2.4 billion.
Of course, the reason why CG Oncology is being chased by the market is inseparable from its own factors. At present, its core pipeline cretostimogene has entered phase III clinical trials and has the potential to become a disruptor in the field of bladder cancer.
In essence, this is also the market's optimism about the bladder cancer field.
Not only CG Oncology, but also ImmunityBio, which has become a disruptor in the field, saw its share price rise nearly 2 times in the fourth quarter of last year, with the latest market capitalization reaching 21$9.7 billion.
Clearly, the outstanding performance of these biotechs indicates that the chase for the bladder cancer market has begun.
01 A blue ocean worth looking forward to
CG Oncology's deep cultivation of bladder cancer can be called a blue ocean market.
First, there is the larger size of the patient population. In terms of incidence, bladder cancer is not the first, it is the sixth most common cancer type in the United States, with an annual new patient rate of 8About 20,000 people. However, due to factors such as the high rate, the scale of the stock of patients is huge, and the United States alone has reached 7250,000 people.
Therefore, the patient base of bladder cancer is not small, and the potential demand will be extremely strong. According to Evaluate Pharma, the global bladder cancer** market will reach $9.9 billion by 2028.
Secondly, the means are relatively limited.
Currently, the conventional approach for patients with early-stage bladder cancer (non-muscle-invasive (NMIBC) is surgery, followed by one year of bladder infusion drugs**, mainly BCG, which can reduce the risk of progression and progression.
But in reality, about 50% of BCG patients will**. After that, BCG perfusion** or a different drug will need to be continued. Unfortunately, "other drugs" are scarce and the pain points are clear.
At present, the "other drugs" approved for marketing include chemotherapy, PD-1 antibody K drugs and gene **Firadenovec. Among them, the weakest are chemotherapy drugs, and the complete response rate for patients with BCG refractory NMIBC is only 18%.
The effect of K medicine is also unsatisfactory. According to the data of the Phase 2 clinical study called Keynote-057, the effect of drug K is as high as 41% at 3 months, and this number drops to 19% at 1 year.
In addition, the safety problem of the K drug ** group is very prominent, about 26% of the patients have more than 3 levels of toxicity, and 10% of the patients have to stop the drug because of safety problems.
Firadenovec's bug is that the efficacy is relatively limited, and the ** rate is extremely high. In the BCG-unresponsive cohort of NMIBC patients, 51% of patients with CIS achieved complete remission within 3 months of the first dose.
However, data from 3-year follow-up showed that only 25 patients had complete remission at 3 months5% (14 out of 55) have no senior level**. In addition, the safety brought by the A** viral vector, repeated exposure to the production of neutralizing antibodies, etc., will also limit the use of the drug in clinical practice.
For patients, if the follow-up measures are still ineffective, they will face the fate of having their bladder removed, and they will be accompanied by urine bags for the rest of their lives. Obviously, this can cause great discomfort to the patient. In the United States, only about 6% of patients are willing to have their bladder removed.
Therefore, in the field of bladder cancer, there is a great unmet need, and an effective one will be very imaginative. CG Oncology is highly sought after by the market because of its potential to stand out in the field.
02 A kind of potential**
The only pipeline of CG Oncology is the oncolytic virus **Cretostimogene. According to its design, it has the ability to double hit tumor cells.
On the one hand, Cretostimogene inserts into the E2F-1 promoter, which is able to selectively lyse RB regulation-deficient tumor cells, but not healthy cells with intact RB pathways;
On the other hand, Cretostimogene also embeds the cytokine granulocyte-macrophage colony gene stimulating factor (GM-CSF). GM-CSF is widely regarded as an effective stimulator of long-term anti-tumor activity, and CG Oncology is designed to mobilize the immune system to kill tumor cells.
At present, cretostimogene has entered phase 3 clinical trial, and has shown the characteristics of high response rate, good effect and high safety. According to its ongoing Phase 3 clinical BOND-003 trial, 50 of the 66 patients (75.) were present at the interim analysis node7%) achieved complete remission after dosing, and the response time was relatively durable.
Of these, 42 (84.)0%) maintained a response for at least three months, and 32 (74.)4%) maintained a response for at least six months. In patients who do not respond after the initial dose, it is possible to achieve complete remission by continuing the drug in the future. Overall, the three-month remission rate was 682%, and the 6-month complete response rate was 636%。
From the perspective of monotherapy effect, cretostimogene is undoubtedly better than Firadenovec and K drugs.
And, the security of this ** stands out. At the time of the interim analysis, there were no level 3 or higher traes, and no TREAs were stopped** due to traes.
Based on its excellent efficacy and safety profile, Cretostimogene has also been granted Breakthrough** Designation and Fast Track Designation by the FDA. Obviously, in the blue ocean market for bladder cancer, Cretostimogene is a player to look forward to.
03 An unfinished race
Of course, the race for the bladder cancer market is far from the end. For now, the breakthrough in efficacy in this field will continue, and the core goal is to cover a wider range of people:
From high-risk BCG non-responsive NMIBC, to high-risk NMIBC not receiving BCG, to more advanced muscle-invasive bladder cancer (MIBC).
There are no fewer ways to get there. At present, many pharmaceutical companies around the world will focus on drugs with different mechanisms. For example, only in late-stage trials of high-risk non-muscle-invasive bladder cancer, there are many potential candidates.
ImmunityBio's fusion protein N-803, which targets IL-15, is a potential dark horse. In the study of N-803 in combination with BCG, patients with or without papillary neoplasms (CIS cohorts) showed a complete response rate of 71%, with a median duration of 24 months. In the papillary tumor group (non-CIS cohort), the disease-free rate was 57% at 1 year and 48% at 2 years.
Overall, a significant proportion of patients (91% in the CIS cohort and 95% in the non-CIS cohort) were able to temporarily avoid cystectomy, and the safety profile of the combination was also good, with no serious *** associated with **
In the long run, joint exploration is bound to push the competition to a higher dimension. At present, Cretostimogene is also combining PD-1 inhibitors (K drug, O drug), hoping to find a better partner.
Of course, in addition to efficacy and safety, there are some additional factors that may need to be addressed by pharmaceutical companies.
For example, BCG is a direction worth exploring. Due to factors such as the small number of entrants and the long production cycle, BCG has been in short supply in the United States.
At present, BCG in the U.S. market only accounts for about 70% of the demand, and it may continue to be in short supply in the future. If the advantages of Xin** are based on the combination of BCG, then future commercialization is bound to be affected.
At the same time, the best means of higher compliance are also a direction worth exploring.
The core method of administration, including cretostimogene, is perfusion** (insertion of the catheter from the urethra and then slowly injecting the drug through the catheter), which is relatively painful and prone to induce some adverse effects. Therefore, finding a more convenient way to administer drugs will be an ongoing theme.
In general, the bladder cancer drug market is bound to continue to rise. In this process, domestic pharmaceutical companies will not be absent.
For example, Lepu Biotech has introduced Cretostimogene, and has many potential players such as PD-1 and ADC, which may be able to bring better choices to domestic patients in the near future.
In addition, players, including Yahong Pharmaceutical, are also hoping to bring better means through independent research and development. For example, Yahong Pharmaceutical's oral Metap2 inhibitor Viscor, which is expected to bring improved efficacy and compliance to patients around the world.
In the future, it is not impossible for domestic pharmaceutical companies to replicate the CG Oncology-style myth.