Ovarian Cancer and Important Update from Sellas
Summary
21 companies in our database with ovarian cancer drug candidates in clinical trials
SLS has an ovarian cancer data update scheduled for this quarter/month/week for its lead asset cancer vaccine, GPS plus the anti-PD1 Pembrolisimab.
Although long-term there is a lot of possible upside for SLS, in this current update, we are expecting a +/-10% move as long as there is not highly negative data, which appears unlikely given the December 2020 update for this trial.
Ovarian cancer is a very prevalent disease in the U.S. and globally. It is speculated that about 230,000 women are living with ovarian cancer in the US and 1.2% of women in the U.S. will be diagnosed with ovarian cancer in their lifetime. It is a solid tumor cancer and it is not easily detected with our current technology, which means that most ovarian cancer is detected in late stages (III or IV). The 5-year survival rate of ovarian cancer is around 50% (See NCI Ovarian cancer statistics).
We used our Pipeline search tool of our database on BPIQ.com of virtually all publicly traded biotech companies with a market cap of less than 5 billion dollars, and found 21 companies with an ovarian cancer drug candidate in clinical trials (Table 1). Of these ovarian cancer companies some have seen huge runups in stock price in 2021 thus far. These include ATOS, SLS and VSTM. ATOS and SLS appear to be moving on squeeze and/or meme-type activity, since their stock prices appear to have moved significantly without any important clinical or corporate updates (SLS, ATOS). It is noteworthy that ATOS was recently added to the Russell 2000 and 300 (Russell 2000, 3000) indices, but the stock increase since this announcement, seems much more than justified by that news.
Much of the jump in VSTM’s stock price is due to the FDA granting Breakthrough Therapy Designation (BTD) for VS-6766 + defactinib in ovarian cancer in May 2021. As noted in the BTD press release, in the most recent readout of VS-6766 + defactinib in low-grade serous ovarian cancer (LGSOC) (FRAME study) reported from the company: the overall response rate (ORR) was 52% (11 of 21 response evaluable patients), for patients with KRAS mutations the ORR was 70% (7 of 10 response evaluable patients), for KRAS wild-type patients the ORR was 44% (4 of 9 response evaluable patients), and for KRAS status undetermined patients the ORR was 0% (0 of 2 response evaluable patients). This is a phase 1 trial which enrolled about 20 women with low grade serous ovarian cancer. For more info about this drug candidate check out our BPIQ card. VSTM expects to report phase 2 data in June 2023 (Table 2). From our research, there is no widely accepted standard of care for LGSOC, but usually the first line-treatment is cytoreduction and then chemotherapy with or without bevacizumab. Cytoreduction alone leads to a median overall survival rate of 97 months (Low-grade Serous Ovarian Carcinoma).
Table 1. Ovarian Cancer Drug Candidates for Biotech Companies*
*Biotech companies with valuations between $100M and $5B
Table 2. Ovarian cancer drug candidate readouts
The ovarian cancer drug candidates of these biotech companies are a variety of small molecules and biologics (Table 3). Some of the drug candidates are targeting the tumor cells directly while others affect the immune response (i.e. immuno-oncology agents). There are 5 assets that are currently in phase 3 clinical trials with an ovarian cancer asset (Table 2). CLV’s phase 3 trial for the drug Rucaparib is expected to readout later this year. It is important to note that Rucaparib, which was developed and is marketed by Clovis (CLVS), is already approved for ovarian cancer and prostate cancer. In the pending trial, Clovis is testing CLVS to support a label expansion to first-line maintenance treatment monotherapy and for advanced ovarian cancer maintenance treatment. Rucaparib works by inhibiting the PARP1, 2 and 3 proteins which in turn allows tumor cells to die because the tumour cells damaged DNA does not get repaired and thus the immune system marks it for degradation/cell death (Rubraca information). There are a number of other approved PARP inhibitors for various lines of ovarian cancer and for prostate cancer, and Clovis is down -40.84% since 2020 as they have had trouble competing in this highly competitive marketplace.
Table 3. Ovarian cancer drug candidate details
Table 2 provides information about the next readout for these ovarian cancer therapeutic candidates. SLS, ATOS, IMV, HARP, CLVS, CGEN, IMGN, TCRR, ALKS, and STTK have readouts coming in 2021. With respect to ovarian cancer companies, we named SLS, one of the companies in our database with an ovarian cancer clinical trial readout this quarter, one of our big-mover stocks to watch. Although the ovarian cancer trial is not SELLAS’ most advanced trial, it appears to be an important trial for SELLAS’ lead product candidate, galinpepimut-S (GPS). GPS targets malignancies and tumors characterized by an overexpression of the WT1 antigen. SELLAS’ WT1 immunotherapeutic cancer vaccine candidate is comprised of four peptide chains, two of which are modified chains that induce a strong innate immune response (CD4+/CD8+) against the WT1 antigen and access a broad range of HLA types. In its Phase ½ trial that is about to read out additional data, GPS is combined with the anti-PD1 pembrolizimab to treat refractory or recurrent ovarian cancer, since the therapies have what should be complementary mechanisms of action.
GPS’s most advanced trial is in AML, a blood cancer. Thus, the ovarian cancer trial is an important trial to establish proof of concept that GPS can be effective in solid tumors, at least when combined with an anti-PD1 agent. In their initial phase 1 trial, SLS reported that progression free survival at one year was 70% for refractory ovarian cancer patients in their 2nd or 3rd remission who received 3 doses of GPS plus the anti-PD1 nivolumab (SELLAS Life Sciences Presents Interim Phase 1 Clinical Data of Galinpepimut-S (GPS) in Combination with Nivolumab to Treat Wilms Tumor 1 Positive (WT1+) Ovarian Cancer Patients at ASCO 2018). For the current Phase 1/2 trial, in December 2020 SLS reported that the first set of evaluable patients (n = 8) diagnosed with 2nd or 3rd line WT1(+) relapsed or refractory metastatic ovarian cancer demonstrated a disease control rate (the sum of overall response rate and rate of stable disease) of 87.5% with a median follow-up of 9.4 weeks (SELLAS Announces Promising Initial Clinical Data for Galinpepimut-S (GPS) in Combination with Checkpoint Inhibitors in Two Solid Tumor Indications). Furthermore, at the first assessment time-point of 6 weeks post-therapy initiation, 100% of the patients were free of disease progression.
The trial is scheduled to enroll 20 metastatic ovarian cancer patients (See NCT03761914). Since over 6 months will have passed since the December report-out, we should see data out to at least 12 weeks, and probably at least 16 weeks, possibly 6 months, for at least 8 patients and likely more early data from more patients. From its Phase 1 trial it appears that SELLAS is looking to beat a 50% one year PFS. Thus, PFS in the data update should still be at least 90% for patients out to 6 months. We will have PDL-1 status for this trial eventually as well, although we don’t know if any of that info will come with this Q2 2021 update. Of course, that biomarker info would be helpful to see, since PDL-1 expression is usually needed for anti-PD1 response.
It is interesting to note that in 2 prior studies of anti-PD1 therapies in late stage ovarian cancer, study 1 (see https://pubmed.ncbi.nlm.nih.gov/31046082/) and study 2 (see https://pubmed.ncbi.nlm.nih.gov/30522700/), PFS were only 2.1 months and 1.9 months, respectively. This is true even with patients having at least low level PD-L1 expression. In study 1, patients received 1-3 prior lines of treatment, and in study 2 they received at least 3 prior lines of treatment. Thus, these patients had a more advanced cancer, than the current trial, in which the patients had only 1 or 2 prior lines of treatment (See NCT03761914). Regardless, it does not appear that ovarian cancer without GPS is very responsive to anti-PD1s.
Given that there is no control anti-PD1 only arm, this is still an early readout in this trial, and this is not SLS’s lead trial, we don’t see this as a +/->25% moving event for SLS. When the initial data read out on December 21, 2020, the stock did not move more than 1%. Thus, although we named this a Big-Mover event because it is a significant efficacy update of a lead candidate and implied volatility was moderately high, upon further analys, it looks more like a readout that would stay within +/-15% and probably +/-10%, unless it is extremely negative. On the upside, it doesn’t seem that we would have enough patient data for a long-enough duration to reach positive results that would move the stock more than 10%. From a longer-term perspective, SLS’s market cap is only ~$200M. If it turns out that GPS + anti-PD1 has a place in the ovarian cancer treatment workflow for some patients, there is significant upside in the stock.
Maggie Vacchiano, Manny Vacchiano & the rest of the team at Amp/BPIQ.com
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