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Topline Summary
Greenwich LifeSciences, Inc. (NASDAQ:GLSI) is a late-stage biotech company focused on developing a novel immunotherapy treatment for breast cancer. Their current pipeline focuses on one drug and one phase 3 trial aimed at preventing breast cancer recurrence after surgery. This presents a clear opportunity, since getting to phase 3 study is frequently the last step before being able to apply for approval of a drug. Today, let’s take a look at the prospects of their ongoing study, and the outlook for the GLSI investment thesis on the whole.
Pipeline Overview
GLSI-100
The sole drug candidate being pursued by GLSI at this time is GLSI-100, a therapeutic vaccine incorporating GM-CSF along with GP2, a small piece of the HER2 protein. The ultimate goal of this approach is to train the body to recognize and attack HER2 protein expressed on the cell, most notably on any remnant HER2-positive breast cancer cells that may still be present after surgery.
So-called “adjuvant” therapy has been the standard of care for resectable HER2-positive breast cancer for a very long time now, with patients receiving post-operative trastuzumab, with or without other HER2-targeting therapies, based on findings from studies like BCIRG 006 and APHINITY.
GLSI completed a phase 2b study (reported at SABCS 2020) randomizing patients to receive GM-CSF or GM-CSF plus GP2 in patients with HER2 IHC-positive (1+ to 3+) breast cancer after surgery and adjuvant trastuzumab (as well as chemotherapy in the majority of patients). Among the patients who received GP2 in the HER2 IHC 3+ cohort, the 5-year disease-free survival rate was 100%, compared with 89.4% among patients who received placebo.
For reference (and being mindful to be cautious about cross-trial comparisons), the APHINITY trial showed 94.1% 3-year invasive disease-free survival when adding pertuzumab to trastuzumab, compared with 93.2% for trastuzumab alone. At 6 years, these rates were 90.6% and 87.8%, respectively. Of course, APHINITY was massively more well powered, enrolling over 4500 patients to find conclusively that these rates were a statistical improvement, and “invasive” disease-free survival is not the same endpoint as disease-free survival that was used in GLSI’s study.
Still, the phase 2 trial paints a compelling picture. And GLSI is conducting a phase 3 trial (FLAMINGO-01), enrolling patients with HER2-positive breast cancer with residual disease after neoadjuvant treatment and surgery to receive trastuzumab-based adjuvant therapy followed by randomization to receive placebo or GLSI-100. Notably, only patients who are HLA-A*02 positive are randomized; patients who are not this HLA haplotype are receiving GLSI-100 as part of a non-randomized cohort.
FLAMINGO-01 was initiated in August 2022 and has a primary estimated completion date of December 2026, according to clinicaltrials.gov. In February, the trial enrollment was expanded to sites in various countries in Europe. Also in February, GLSI provided an update on the trial, mainly related to a meeting of the steering committee at SABCS 2023. An interim analysis of the study is to be conducted after at least 14 invasive disease-free survival events have occurred.
No clear expectation was provided as to when this analysis could occur, other than to say that the company expects to complete full enrollment of the study before seeing this endpoint be reached, and that is expected as early as late-2024.
Financial Overview
As of their latest quarterly filing, GLSI held $5.5 million in cash as current assets. Meanwhile, their operating expenses, or cash burn, reached $2.5 million for the quarter, implying a cash runway of approximately 2 quarters to continue their work.
This does not consider proceedings generated through a securities purchase agreement with the GLSI CEO, raising another $2.5 million and buying the company time into 2025.
Strengths and Risks
Strength – A late-stage clinical candidate deep in phase 3 study
Getting to a phase 3 trial is no small feat, and GLSI has demonstrated clearly, in my opinion, that their vaccine is worth considering in late-stage study. I may have reservations about over-interpreting the phase 2b trial, but there is definitely promise here, and if it’s successful, this trial should be sufficient for an application for approval.
Risk – Early-stage HER2-positive breast cancer is a tough needle to move
When you look at studies involving adjuvant treatment for HER2-positive breast cancer, it’s awe-inspiring to see the kinds of lengths they go to when improving the standard of care, which is currently very good. Looking at even GLSI’s phase 2b study (which is minimal overall), and you see a greater-than-80% 5-year disease-free survival rate in the control arm. Trastuzumab alone does very well in this group, and it has historically been quite tough to improve on what’s working. This means that any optimistic timelines or considerations from management should be taken with a grain of salt.
Risk – Very limited resources
As mentioned, GLSI is operating on the narrowest of edges, with funds sufficient to continue operating on a nearly month-to-month basis. The recent private placement helps to shore this up by a bit, and it does seem like an expression of the CEO’s optimism about the eventual outcome of the FLAMINGO-01 study.
But we do not know when we’ll have a clear readout of the trial, and we should be cautious about over-interpreting the “possible” interim analysis being an early savior. GLSI-100 would need to have overwhelming efficacy in this study to warrant early termination.
Barring that, we should expect that the study’s project completion date, sometime in 2026, is more likely than not, and GLSI has not provided guidance on how they will fund operations through that time.
Bottom-Line Summary
GLSI presents a very high-risk situation, when you couple a pretty long trial runway and the limited resources they have to fund operations. To me, it screams of not being the right time to even consider buying, since the FLAMINGO-01 trial will likely need at least another year to mature before we see even an announcement of its status, let alone results.
Therefore, at best GLSI is likely going to operate in a holding pattern, but my stronger suspicion is that they will continue to dwindle in value through 2024. To that end, my sentiment for now is a weak “Sell,” but at best a “Do Not Buy” for now, with strong reason to pick the story back up in 2025.
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