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Taysha Gene Therapies, Inc. (NASDAQ:TSHA) reported positive preliminary results from the phase 1/2 adolescent and Adult REVEAL study, which used its gene therapy TSHA-102 for the treatment of patients with Rett Syndrome. The last time I wrote about this biotech was in August of 2023, where it only had released initial data from one patient. This was a Seeking Alpha article entitled “Taysha Gene Therapies: Rett Syndrome Data Makes This A Must Watch.“
Well, the latest data not only provides added positive outcomes for the 1st patient treated with TSHA-102, but also a second patient that was recruited into this particular study as well. Despite this data being shown, there is the possibility of further gains based on two additional catalysts that are approaching because of this news release.
The first catalyst of which involves the release of initial data from cohort 2 of the phase 1/2 adolescent and adult REVEAL study. The importance of this is that a higher dose was cleared to be used for this cohort and further data is expected in the 2nd half of 2024. However, before then, there is another earlier catalyst to keep an eye on for this program that is using TSHA-102 for Rett Syndrome. Data from the pediatric phase 1/2 REVEAL study is expected in mid-2024. This is going to include two pediatric patients. There could also be additional data to be released in the latter part of this year for these pediatric patients as well. The bottom line is that even though one catalyst has gone and past, that doesn’t mean there aren’t other opportunities to look forward to.
TSHA-102 For The Treatment Of Patients With Rett Syndrome Moves Forward
Thigs are shaping up well for Taysha Gene Therapies since I last wrote about this biotech. That’s because as I stated above, it had only released data from one patient. That was some evidence that the gene therapy TSHA-102 was working to help this patient with Rett Syndrome in the phase 1/2 REVEAL study. However, that was only 1 patient which in itself is some proof but maybe not enough. Well, the good news released as an update today shows that another patient benefited from treatment with this gene therapy as well. The thing is that the first cohort dealt with a lower dose of 5.7X10^14 of TSHA-102. It was shown that this patient experienced no treatment-emergent serious adverse events [SAEs] at week 35. In addition, to showing key improvements in multiple efficacy measures. In particular, a great improvement in RSBQ score.
To understand RSBQ score, it is first important to understand what Rett Syndrome is and what the possible market opportunity that could be obtained with an approved treatment. Rett Syndrome is a rare type of neurological disorder that primarily affects females and interrupts multiple development capabilities. It prevents them from being able to do everyday tasks, such as: Eating, walking, speaking and breathing. The global Rett Syndrome market is expected to reach $515.06 million by 2029. There are some symptoms that these patients with this neurological disorder experience and they are as follows: Loss of communication skills, slowed growth, breathing issues, seizures unusual hand movements and sleeping issues. The RSBQ score is a 45-item checklist that evaluates behavioral and emotional characteristics of this disorder. Each of the 45 items are rated from “0” which means there is hardly any problem to “2,” which is the symptom is often true.
Well, the first patient was able to achieve new improvement of this RSBQ score at 6-months, when given the low dose of 5.7X10^14 total vg of TSHA-102 in cohort 1. The second patient also fared well in the latest update on the clinical data released from the phase 1/2 adolescent and adult REVEAL 1/2 study. This patient has seen sustained improvement across multiple efficacy measures, including reduced seizure frequency and improvement in R-MBA scale at 12-weeks. All of this while have no treatment-emergent SAEs present during the 19-week evaluation period. One key thing to note is that the R-MBA scale is used by a neurologist to evaluate motor and behavioral symptoms of a Rett Syndrome patient. Thus, this is another tool to measure clinical efficacy of a therapy for this patient population.
The thing is that all of the positive preliminary data achieved thus far was only with respect to cohort 1 of this phase 1/2 adolescent and adult study, which used TSHA-102 for the treatment of patients with Rett Syndrome. More findings from this study can be seen with data shown here in this figure 1. Having said that, Taysha Gene Therapies got the green light from the Independent Data Monitoring Committee to move forward with cohort 2 of this study. That is, to give patients the higher dose of this gene therapy, which is 1X10^15 total vg.
The significance of this is that such higher dosing may lead to an improved clinical outcome for these patients, compared to what has been achieved thus far. Not only that, but it brings about a catalyst opportunity for investors to look forward to as well. It is expected that this company will release cohort 2 data from this phase 1/2 adolescent and adult REVEAL study in the 2nd half of 2024. Cohort 2 of this particular study will have a total of 3 patients enrolled and given this dose of TSHA-102.
Expansion Opportunity Of TSHA-102 For Pediatric Patient Population
The thing is that the positive preliminary data released thus far leads to another catalyst highlighted above. Well, it gets even better than that, because there is an expansion opportunity. Such an expansion opportunity would be to use TSHA-102 for the treatment of pediatric patients with Rett Syndrome as part of the REVEAL phase 1/2 study. This study is a bit behind, but in essence, follows the same design of the adolescent and adult study noted above.
For instance, cohort 1 is treating pediatric patients with the low dose of 5.7X10^14 total vg of TSHA-102. The thing is that in the pediatric study, there are going to be 3 patients enrolled in cohort 1. Regardless, initial data from this specific pediatric cohort is going to be released in mid-2024. From there, there will be another catalyst opportunity to expect. It is expected that initial safety and efficacy data from cohort 2 for pediatric patients will be released in the 2nd half of 2024. This cohort, like the other one noted above, will use the higher dose of TSHA-102, which is 1X10^15 total vg.
The bottom line is that both adolescent/adults and pediatric phase 1/2 studies are not only being done to see if efficacy is being achieved, but to find the maximum tolerated dose to move forward with in dose expansion cohorts.
Financials
According to the 10-K SEC Filing, Taysha Gene Therapies had cash and cash equivalents of $143.9 million as of December 31st of 2023. The reason for the cash on hand is because this biotech decided that it was best to establish a new loan security agreement for itself, along with giving rights of other gene therapies back to other entities. That is, these other institutions would move these other gene therapies forward, but at the same time given Taysha the freedom to only focus on advancing TSHA-102 for the treatment of patients with Rett Syndrome. The ability to perform this pipeline change on November 13th of 2023 is what allowed it to extend its cash runway. It now believes that it has enough cash on hand to fund its operations into 2026. With this type of guidance provided, I see no risk of near-term dilution. However, should management have a different motive in mind like another strategic transaction to consider, then it may elect to raise funds earlier than expected.
Risks To Business
There are several risks that investors should be aware before investing in Taysha Gene Therapies. The first risk to consider would be with respect to advancement of TSHA-102 for the treatment of patients with Rett Syndrome. Even though positive data has been achieved in cohort 1 using 5.7X10^14 total vg of this gene therapy, that doesn’t mean that other patients will have a positive outcome. In addition, that the higher dose of 1X10^15 total vg will yield to a superior outcome for them with respect to RSBQ, R-MBA or another clinical efficacy endpoint.
The second risk to consider would be with respect to the pipeline programs being deprioritized, as noted above. That’s because a lot of the gene therapy programs were transferred to other entities. However, there are several other gene therapies which still remain as part of the pipeline. The company stated that it intends to seek partnerships to advance the other gene therapies it didn’t divest. There is no assurance that Taysha will be able to find a partner willing to fund these other pipeline programs, nor that any funding will be achieved for them.
The third and final risk to consider would be with respect to competition in the Rett Syndrome space. That’s because Acadia Pharmaceuticals (ACAD) had received FDA approval of Daybue [trofinetide] for Rett Syndrome in adults and pediatric patients ages 2 and older. This is the first and only drug approved to treat these patients. This company seems to be doing well here generating Q4 2023 and full-year 2023 Daybue sales of $87.1 million and $177.2 million respectively. In order for Taysha Gene Therapies to do well on the market, should it pass all studies plus be approved, would be to show superior efficacy over it.
Conclusion
Taysha Gene Therapies, Inc. has shown further progress in being able to treat patients with Rett Syndrome. It has been able to achieve positive results for a second patient in cohort 1 in the phase 1/2 adolescent and adult REVEAL study. I believe a more important outcome would also be the fact that it received clearance to escalate to a higher dose due to no treatment-emergent SAEs being noted in cohort 1. This means that efficacy in using TSHA-102 for Rett Syndrome could progress further. This is not guaranteed to happen, but it won’t take a long time for this to be revealed. Especially, since it has been noted that the company intends to release cohort 2 data from this adolescent and adult REVEAL 1/2 study in the 2nd half of 2024.
That is not too far away, but that doesn’t mean that there aren’t any near-term catalysts for investors to focus on. It is expected that initial data from the pediatric phase 1/2 REVEAL study targeting Rett Syndrome will be released in mid-2024, which is going to entail the lower dose of 5.7X10^14 total vg of gene therapy. From there further data from this pediatric study is expected to be released in the 2nd half of 2024. This is going to be with respect to cohort 2, which is using the higher dose of 1X10^15 total vg of TSHA-102.
With initial data already released for the Rett Syndrome gene therapy being developed, plus several other catalysts for Taysha Gene Therapies, Inc. on the way, I believe that investors could benefit from any potential gains made.
