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Corpus Pharmaceutical Holdings Company (Nasdaq: CRBP) recently reported positive data from a phase 1 study using CRB-701 to treat patients with metastatic urothelial carcinoma (mUC) and cervical cancer. However, this was the data that was reported By its partner CSPC in China. It has been observed that all patients who were given a dose >= 2.7 mg/kg of this drug were able to achieve some type of response. Not only that, although nectin-4 is a target antibody-drug conjugate (ADC), it has been shown to be safer than Pfizer (PFE) Nectin-4 ADC Badsafe. This is due to the way it was designed to reduce the free roaming of MMAE, resulting in fewer patients experiencing rashes and peripheral neuropathy.
The improved safety profile of CRB-701 in mUC and cervical cancer, coupled with superior cell killing potential, could give better results. This drug has a competitive advantage over BadSafe. If this stimulus has come and gone, why do I think investors might still have a chance here? This is because Corbus is also expected to publish data from a phase 1 study in the US and Europe, using CRB-701 to treat patients with cervical cancer in the first quarter of 2025. With proof of concept in the Chinese study I see no reason Because a similar data profile could not be produced for this other early study either.
This company is exciting outside of just ADC development with a proven track record. It is also developing CRB-913 to treat patients with obesity and then it is also developing CRB-601 to treat patients with tumors. Specifically, it is a selective anti-avb8 monoclonal antibody that blocks the activation of TGFb expression on cancer cells. Each of these other clinical products has a basis for working alone or in combination with other treatments. With another data reading expected early next year, as well as several other drugs in the pipeline with huge potential targeting multi-billion dollar markets, I think investors could benefit from any potential gains.
Potential antibody-drug conjugates moving forward
As I noted above, the main clinical product in Corbus Pharmaceuticals’ pipeline will be the development of CRB-701, which is being used to treat patients with metastatic urothelial carcinoma (mUC) and cervical cancer. However, the goal is to target nectin-4 expression in these specific types of cancer. The use of a Nectin-4 ADC targeting drug is being explored in two ongoing studies. One study to focus on first is a phase 1 study conducted by Corbus’s partner, CSPC, which was completed in China. This trial enrolled patients with solid tumors who failed or did not tolerate standard of care (SOC) treatment. In terms of recruitment, nectin-4 staining has been performed with cervical cancer patients. However, patients with mUC were already classified as nectin-4 positive and testing for this biomarker was not required previously.
The data presented at ASCO GU had a deadline of April 2024. Patients were dose escalated in 7 dose levels as follows: 0.2, 0.6, 1.2, 1.8, 2.7, 3.6, 4.5 mg/kg Q3W. Combined with the pharmacokinetic combinations 2.7 mg/kg and 3.6 mg/kg of the drug in the same dosing interval. A total of 37 patients have been recruited into this phase I China study so far, but only 25 were evaluable for efficacy.
data What has been revealed from this trial is encouraging It leads me to believe that data from the US and European phase 1 study to be released in the first quarter of 2025 will also be good. Data presented at the ASCO GU 2024 Medical Conference for the phase 1 study in China are as follows for each patient group:
- Metastatic urothelial carcinoma – 44% objective response rate (ORR) and 78% disease control rate (DCR)
- Cervical cancer – 43% ORR and 86% DCR.
All of these results were performed at a dose of CRB-701 ≥ 1.2 mg/kg. Better yet, the dose level reached without toxicity is dose level 7, which is 4.5 mg/kg of this drug. Why is this specific item a good result? This is because it can be escalated to higher doses in this trial. With the highest dose to date of 4.5 mg/kg, there were no dose-limiting toxicities (DLTs) or grade 4/5 adverse events. There were a few grade 3 adverse events for patients who took 3.6 mg/kg and 4.5 mg/kg of this drug respectively, but no new cases were ever observed thereafter.
The downside to advancing this program is that Phase 1 American and European study Just started in April 2024. This is an open-label trial that will evaluate the safety and efficacy of CRB-701 for the treatment of patients with nectin-4 solid tumors. This will follow a similar design to another phase 1 study in China, combining dose optimization and dose expansion parts. The goal is to find a good recommended phase 2 dose (RP2D) to move forward into the next phase of clinical testing.
If all goes well with this projected timeline, data in the first quarter of 2025 should be broadly similar to what was just released. Global urothelial cancer market It is expected to reach $6.82 billion in 2032. This is a huge market opportunity and the success of this indicator will be huge. The other market you’re going after isn’t too bad either. The global market for cervical cancer treatment is expected It could reach $12.63 billion by 2030. The thing is, although the nectin-4 ADC CRB-701 has huge potential in both markets, there is a competitor that it may eventually have to face.
I’m talking about taking on Pfizer’s PADSIF, which It is approved for the treatment of patients with urothelial carcinoma. This drug is a monster, and it will not be easy to confront it because it is expected to achieve a huge number of sales. Consider that Padcev’s global sales could reach $5 billion by 2028. That sounds tough, so how will Corbus compete with the CRB-701? This may be because this drug carries several major advantages over it.
For starters, CRB-701 has an increased half-life profile, which means the amount of dosing can be reduced. It only needs to be taken once every 3 weeks (Q3W) versus a competitor that needs to be taken approximately every 2 weeks. Another element that allows for less frequent dosing is the lower drug-to-antibody ratio (DAR) in place. The second competitive advantage is not only in producing the required efficiency, but also in achieving this through improving safety standards.
How is this possible? Well, because the third generation (next generation) site-specific nectin-4 ADC is used, it can reduce dose-limiting toxicities. This means that the CRB-701 was developed to reduce the amount of free roaming MMAE payload. This in turn actually led to this drug being able to reduce peripheral neuropathy (PN) and skin rashes. Padcev has a black box warning label for beginners. Not only that, but monotherapy with this Pfizer drug resulted in 58% of patients developing skin reactions and then 53% suffering from PN. When Keytruda was added to this combination regimen, the rates of rash and parenteral rash were 70% and 67% higher, respectively.
More than 25% of discontinuations that occur as a result of this treatment are due to PN. Think about the potential of CRB-701 to eliminate treatment discontinuations for cancer patients and how much of an impact that could have.
Finance
According to the 10-Q SEC Filing, Corbus Pharmaceuticals had cash, cash equivalents and investments worth US$120.1 million as of March 31, 2024. The reason this cash is available is because it was able to complete two financial transactions, which helped raise additional cash. Both transactions were executed during the same time period. The first deal that included Public offering to raise $94.5 million in gross proceeds. The second deal that was completed was to obtain $21.1 million from ATM sales. From these two deals, it was able to generate $116 million in additional capital.
I believe that the cash position of Corbus Pharmaceuticals Holdings, Inc. In good condition because she thinks she has enough money to buy Cash runway Until the first quarter of 2027 Burn cash It is $9.62 million per quarter.
Risks to the business
There are several risks that investors should be aware of before investing in Corbus Pharmaceuticals. the The first danger Something to consider would be for the ongoing Phase 1 program, which is using CRB-701 to treat patients with cervical cancer and cervical cancer. Although MUC patients and cervical cancer patients achieved an ORR of 44% and 43%, respectively, there is no guarantee that a similar outcome would be obtained in the US and European study.
the The second danger Something to consider will be regarding the competition that exists regarding the development of a Nectin-4 ADC targeting drug such as CRB-701 to treat patients with mUC and cervical cancer. This is because, as I mentioned above, Pfizer already markets a drug with a similar mechanism of action (MOA), known as Padcev. Even if Corpus is able to bring its drug to market, there is no guarantee that sales will be good. However, I think it’s likely due to the improved safety profile alone, which has already been noted. This does not include the possibility of seeing an improved efficacy profile with higher dose combinations of CRB-701.
a The third danger Something to consider would be the CRB1 inverse agonist you are developing, which is known as CRB-913. This particular drug is being developed to treat patients suffering from obesity. To date, in a mouse model of diet-induced obesity (DIO), monotherapy with this drug or in combination with other approved weight-loss drugs such as tirzepatide (as well as others) has shown a reduction in body weight, along with other metabolic improvements. A phase 1 study, using CRB-913 to treat these obese patients, is expected to begin in the first quarter of 2025. Although such significant weight loss was seen in clinical tests of the mouse model, there is no guarantee that a similar result would be observed. In this first phase of early study.
Conclusion
Corpus Pharmaceuticals has done well in developing its product line, developing several drugs. The most popular drug in clinical testing is CRB-701 as a nectin-4 ADC for the treatment of patients with mUC and cervical cancer. Again, I think the hypothesis here as to why investors are excited is that the US and European phase 1 study is similar to the already released phase 1 study in China. Such data is expected in early 2025, and if positive, I believe it will bolster the company in targeting nectin-4 for solid tumors. Especially since CRB-701 already has many competitive advantages over Padcev.
The scale of potential here does not even include the development of CRB-913 to treat patients with obesity, nor the development of CRB-601 to treat TGFb-expressing solid tumors. When this cancer drug was combined with PD-1 checkpoint inhibitor therapy, it was able to achieve enhanced antitumor activity compared to single-agent checkpoint inhibition alone. The first phase study, using this drug for patients with solid tumors, is expected to be conducted in the summer of 2024.
