2 weeks Ago
Image Source Repare Therapeutics Inc. ( NASDAQ: RPTX ) is gearing up to report results from its phase 1 MYTHIC trial, which is using lunresertib [RP-6306] in combination with camonsertib [RP-3500] for the treatment of patients with platinum-resistant ovarian and endometrial cancers. This will be a major inflection point because it will prove whether its SNIPRx platform is capable of being able to develop Synthetic Lethality [SL] drugs to treat patients with advanced solid tumors such as these.
The current guidance is that such data will be released from this early-stage trial in Q4 of 2024. If everything goes well for the data, then it will be on track to initiate a phase 3 study for this program using the recommended phase 2 dose [RP2D] from the prior study. What's good about lunresertib is that there are a few other shots on goal for it.
It had data released from the phase 1 MINOTAUR study showing that when this drug was combined with FOLFIRI in patients with advanced solid tumors, there was an overall response rate [ORR] of 18.2% across gastrointestinal tumors with specific genetic mutations. The second expansion opportunity is in terms of an expanded module 4 cohort as part of the phase 1 MYTHIC trial, which would be using lunresertib in combination with Debio 0123 for the treatment of advanced solid tumors like ovarian cancer.
Initial data from this module cohort is expected to be released in 2025. Two Drugs From Pipeline Are Setting Up A Major Inflection Point By End Of This Year As I noted above, the goal of Repare Therapeutics is to use lunresertib in combination with camonsertib for the treatment of patients with platinum-resistant ovarian and endometrial cancers who harbor mutations. This drug combination is being explored for the treatment of this patient population in the ongoing phase 1 MYTHIC trial.
Before going over this early-stage study, plus any catalysts to come out of this program, it is first important to understand what each type of cancer is and what the possible market opportunity is. Ovarian cancer is a type of disease whereby malignant cells form on the ovaries. The problem with this type of cancer is that such cancerous cells start to overwhelm the healthy cells that exist and cause damage.
The ovaries are a significant part of the reproductive organ for females, plus the fact that they produce hormones as well. The global ovarian cancer market is expected to reach $11.18 billion by 2029 .
This is a considerable market opportunity for this, but it is critical to put into perspective what lunresertib can target. First, it's essential to note that this drug is a PKMYT1 inhibitor. The importance of this is that it targets tumors with genetic amplification of CCNE1, FBXW7, and/or PPP2R1A.
In the U.S., European and U.
K. markets, it is said that there are 20% or 6,300 patients with these types of mutations. The key here is that if this drug is successful, regarding these markets targeting many other types of tumors, it could go after a population of 90,000 patients.
It is believed that adding an oral small molecule inhibitor of ATR camonsertib into the mix as a DNA repair damage agent could result in improved clinical outcomes for these patients. To test and see if lunresertib + camonsertib are capable of being able to help these patients with platinum-resistant ovarian cancer and endometrial cancers who harbor such genetic alterations noted above, it has been running the phase 1 MYTHIC study . This particular trial aims to see if this combination can help this specific pool of patients.
I believe that it was important to bring this program up because it is expected that data from 20 to 30 patients in each cohort from this MYTHIC study, will be released in Q4 of 2024. It remains to be seen what the final data will look like and whether the recommended phase 2 dose [RP2D] delivers, but there has been some early data which has been released from it. The most promising data stems from 26 pre-treated gynecologic cancer patients who received the RP2D of 80 mg twice daily of lunresertib and camonsertib.
It was shown that there was a 38.5% objective response [OR] observed for this patient population. The clinical benefit rate [CBR] achieved was 57.
7%. Lastly, the preliminary RECIST response from this very same cohort of only 10 patients was 50%. Thus, it's important to note that the final data to be released with the Q4 of 2024 catalyst will be the 20 to 30 ovarian and endometrial cancer patients given the RP2D.
Again, should the data turn out to be excellent, then the next catalyst to come into play would be the initiation of a phase 3 study using this combination to target these patients with genomic alterations in 2025. Financials According to the 10-Q SEC Filing , Repare Therapeutics had cash, cash equivalents and marketable securities of $208.1 million as of June 30th, 2024.
At the time of its Q2 earnings release , it noted that it would only have enough cash to fund its operations, or cash runway , to last into mid-2026. This was due to a $37 million operating loss, or cash burn , in Q2. However, a significant recent event is going to lead to a bit of a longer cash runway.
One by which is likely to reduce cash burn going forward. It was announced that it would reprioritize its pipeline to only focus on developing lunresertib, camonsertib, RP-1664, and RP-3467. While these programs are to remain in place as part of its pipeline, it is reducing the amount of preclinical research and discovery activities.
Unfortunately, it is going to reduce its overall workforce by 25% to achieve this strategic move. While it would lead to less new drugs being produced in the pipeline, it expects to have annual savings of $15 million. Why is this an important measure? That's because the cash runway has now been extended from mid-2026 to 2nd half of 2026.
Risks To Business There are several risks that investors should be aware of before investing in Repare Therapeutics. The first risk to consider would be in terms of the ongoing phase 1 MYTHIC study. This is using lunresertib + camonsertib for the treatment of patients with platinum-resistant ovarian cancer and endometrial cancer who harbor genomic alterations of CCNE1, FBXW7, and/or PPP2R1A.
Even though prior data was shown to achieve positive data from 10 patients with RP2D, there is no assurance that the final data to be shown in the last quarter of this year will turn out similar or better. The second risk to consider would be in terms of the phase 1 MINOTAUR study, which is using lunresertib + FOLFIRI for the treatment of patients with advanced solid gastrointestinal tumors. Initial data released showed an 18.
2% ORR. There is no guarantee that additional data to be released from this study in a new batch of patients will turn out to be positive. Nor, that the data will be strong enough to warrant further investigation into the next stage of clinical testing.
The third and final risk to consider would be in terms of the module 4 cohort as part of the phase 1 MYTHIC trial. This is using lunresertib in combination with Debio 0123 for the treatment of patients with advanced solid tumors like ovarian cancer. Initial data from this module cohort going to be released in 2025 and there is no assurance that the data from the study will be positive.
Furthermore, there is no guarantee that adding in Debio 0123, which is a WEE1 inhibitor, is going to allow the company to see improved response rates for advanced solid tumors with genetic modifications. Conclusion Repare Therapeutics has been able to do well in advancing its lead drugs for its pipeline, lunresertib + camonsertib. The most important inflection point that investors will have to keep an eye on would be the release of updated data from the RP2D of this combination from the phase 1 MYTHIC study.
Such data, to be released in Q4 of 2024 in patients with genomic alterations of platinum-resistant ovarian cancer and endometrial cancer, will be a major inflection point. Why is that? That's because if data underperforms or is not positive to move forward with for phase 3 testing, then that will set this company back. It would have to rely on its lunresertib expansion opportunities targeting gastrointestinal tumors with FOLFIRI and Debio 0123 for other advanced solid tumors targeting ovarian cancer patients.
There is a promising monotherapy program of camonsertib targeting patients with non-small cell lung cancer [NSCLC] in the ongoing phase 1/2 TRESR clinical trial. Initial results from this early-stage monotherapy study are expected in 2025 and if positive, then this would be another shot on goal for its pipeline. With two data readouts from the phase 1 MYTHIC study using the lunresertib + camonsertib combination in Q4 of 2024, plus the advancement of these two candidates alone or in combination with other drugs, I believe that investors could benefit from any potential gains made here.
This article is published by Terry Chrisomalis, who runs the Biotech Analysis Central pharmaceutical service on Seeking Alpha Marketplace. If you like what you read here and would like to subscribe to, I'm currently offering a two-week free trial period for subscribers to take advantage of. My service offers a deep-dive analysis of many pharmaceutical companies.
The Biotech Analysis Central SA marketplace is $49 per month, but for those who sign up for the yearly plan will be able to take advantage of a 33.50% discount price of $399 per year. Terry Chrisomalis is a private investor in the Biotech sector with years of experience utilizing his Applied Science background to generate long term value from Healthcare.
He is the author of the investing group Biotech Analysis Central which contains a library of 600+ Biotech investing articles, a model portfolio of 10+ small and mid-cap stocks with deep analysis for each, live chat, and a range of analysis and news reports to help Healthcare investors make informed decisions. Analyst’s Disclosure: I/we have no stock, option or similar derivative position in any of the companies mentioned, and no plans to initiate any such positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions.
I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article. Seeking Alpha's Disclosure: Past performance is no guarantee of future results.
No recommendation or advice is being given as to whether any investment is suitable for a particular investor. Any views or opinions expressed above may not reflect those of Seeking Alpha as a whole. Seeking Alpha is not a licensed securities dealer, broker or US investment adviser or investment bank.
Our analysts are third party authors that include both professional investors and individual investors who may not be licensed or certified by any institute or regulatory body..
