TCRR - TCR² Therapeutics: Refocused Pipeline Puts It On A Solid Path

Summary

• Reprioritization of pipeline sees 40% reduction of workforce with enough cash to fund pipeline into early 2025.
• Proof of concept established using gavo-cel for the treatment of patients with mesothelin tumors; Focus shift more towards targeting ovarian cancer patients with expected data 2nd half of 2023.
• TC-510 is an enhanced version of gavo-cel which expresses a PD-1:CD28 chimeric switch receptor which can possibly enhance response; Data from phase 1 study expected 2nd half of 2023.
• TC-520 is a CD70 targeting drug which has the ability to not only go after solid tumors but hematological malignancies as well.

TCR² Therapeutics ( TCRR ) is a great speculative biotech play to look into. The reason why I state that is because it has refocused its pipeline to a few specific clinical products. With the narrowing down of the pipeline, it had also reduced its workforce by 40% to conserve cash. With this workforce reduction, it now believes that it will have enough cash to fund its operations into early 2025. The main drug in the pipeline is gavo-cel, which is being explored in a phase 2 study treating patients with ovarian cancer. Then, it has shifted its focus on two next-generation clinical products in its pipeline which are TC-510 and TC-520 for a variety types of cancers. TC-510 has a focus on solid tumors, while TC-520 has a focus on both solid tumors and hematological malignancies. A more important reason to bring up this biotech is because there are two catalysts which are expected in the latter part of 2023. One catalyst would be the release of the ovarian cancer cohort data from the phase 2 clinical study using gavo-cel, which is expected in the 2nd half of 2023. A second catalyst would be data from an ongoing phase 1 clinical trial, using TC-510 in mesothelin tumors which is also expected in the 2nd half of 2023. With a refocused pipeline, plus the ability to generate meaningful data in the latter part of 2023, these are the reasons why I believe it is a great speculative biotech play to look into.

Gavo-Cel For The Treatment Of Patients With Ovarian Cancer

The main clinical program to go over in the pipeline is the use of gavo-cel, which is being developed for the treatment of mesothelin-positive solid tumors. This program is in great shape, because TCR² Therapeutics released positive results from the phase 1 portion of the clinical study already. This study recruited a total of 32 patients in total, with the population being split as followed:

• 23 patients with mesothelioma
• 8 patients with ovarian cancer
• 1 patient with cholangiocarcinoma

It was noted that tumor regression was observed in 28 out of the 30 (93%) of evaluable patients with a disease control rate (DCR) of 77% who took gavo-cel. It wasn't that bad with respect to the other endpoint measurements as well, such as those relating to progression-free survival [PFS] and overall survival [OS]. PFS was 5.6 months and then OS was 11.2 months, which is pretty good durability for this patient population. This is not bad clinical data either, especially since TCR² Therapeutics was forced to go down a few dose levels after many cohorts. Why is that? That's because at dose levels 5 and 3.5 it noted that there were a lot of toxicity issues, thus it eventually went with the established recommended phase 2 dose (RP2D) of DL3 (1x10 ⁸ cells/m ² following lymphodepletion). With the move towards this particular dose, there were no new dose-limiting toxicities (DLTs) observed. This was good data which was released from this phase 1 portion of the study and the reason why I state that is because these were patients in dire shape. Matter of fact, patients on average had received a median of 5 prior lines of therapy before receiving gavo-cel.

The phase 2 portion of the trial continued as planned, but the biotech is taking steps to change its approach to see if it can further extend/improve clinical outcomes. In particular, it has shifted resources of using gavo-cel to primarily focus on treating ovarian cancer patients. The reason why the focus has now shifted towards the ovarian cancer patient population was because of two reasons in particular. The first reason is that there were a few partial responses achieved in this patient population for starters. A second reason is because this is a much larger market opportunity to explore. It is said that the global ovarian cancer market could reach $13.9 billion by 2029 . It won't be long to see if gavo-cel produces meaningful clinical results in this ovarian cancer patient population either, because additional results targeting this specific patient population are going to be released in the 2nd half of 2023.

Additional Clinical Products Provide A Few Other Shots On Goal

As I noted in the beginning above, there are two other clinical products which are being developed in the pipeline, which are TC-520 and TC-510. TC-520 at the moment is still being advanced to TC-520 Investigational New Drug [IND] status. The focus of this drug is targeting the CD70 protein, thus the use of it can be explored in both hematological malignancies and solid tumors. TC-510 is further along and it is primarily being advanced in a phase 1 clinical study targeting cancer patients with mesothelin tumors. A key thing to note about this drug is that it is an enhanced version of gavo-cel which co-expresses a PD-1:CD28 chimeric switch receptor. It is believed that such an addition could possibly lead to deeper responses and a more durable benefit as well. This brings about another catalyst opportunity for investors to look forward to, which is the release of results from this phase 1 study in the 2nd half of 2023. This is another shot on goal to prove that TCR²'s mesothelin targeting tumor drugs are capable of producing deep response rates.

Financials

According to the 10-Q SEC Filing , TCR² Therapeutics had cash, cash equivalents, and investments of $176 million as of December 31, 2022. Net cash had increased in Q3 of 2022 with $25.8 million of net cash used. However, this will likely not be the case going forward. The reason why I state this is because it wanted to reprioritize its pipeline to conserve cash. Plus, the need to put resources to good use in advancing specific programs in the pipeline it believes will boost shareholder value. It enacted a workforce reduction of 40% so that it would only focus on the few clinical products noted above. Before this reduction of workforce, it anticipated that its cash would be enough to fund its operations into 2024. With the reduction of its workforce, it now believes that it has enough cash to fund its operations into early 2025.

Risks To Business

There are several risks that traders/investors should be aware of before investing in TCR² Therapeutics. The biggest risk would be with respect to the ongoing program involving the use of gavo-cel in the phase 2 portion of the study treating patients with ovarian cancer. Even though the biotech was able to achieve some partial responses [PR] in this specific patient population, this does not mean that it will be able to achieve similar success with the addition of patients. Especially, when there will be additional results to be released from the phase 2 portion of this study in the 2nd half of 2023. A second risk to consider would be the use of TC-510 for the treatment patients with mesothelin tumors. That's because results from a phase 1 study, using this drug for the treatment of this population, are expected in the 2nd half of 2023. It is believed that since TC-510 is an enhanced version of gavo-cel, which co-expresses a PD-1:CD28 chimeric switch receptor, it may help to boost durability in these mesothelin positive tumor patients.

Conclusion

The final conclusion is that TCR² Therapeutics is a great speculative biotech play to look into. The primary reason why is that gavo-cel has already established proof of concept in being able to treat patients with mesothelin tumors in a phase 1 portion study. More importantly, there are two data readouts expected in the 2nd half of 2023. The first data readout would be the use of gavo-cel for the treatment of patients with ovarian cancer in the phase 2 portion of the study during this period. While gavo-cel has done well to help some ovarian cancer patients achieve a partial response [PR], there is no guarantee that a similar outcome will be achieved when additional results from this study are released during the latter part of this year. A second catalyst would be the enhanced version of gavo-cel, which is known as TC-510. Results from a phase 1 study, using TC-510 for the treatment of patients with mesothelin tumors, are expected in the 2nd half of 2023. With proof of concept established using gavo-cel for the treatment of ovarian cancer patients, plus a few catalysts expected in the 2nd half of 2023, these are the reasons why I believe it is a good speculative biotech play to look into.

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