SELLAS Life Sciences Group (WKN: A2PU3T)

Conducted under a Clinical Trial Collaboration and Supply Agreement with Merck & Co., Inc., Kenilworth, N.J. USA (known as MSD outside of the United States and Canada), the study is investigating the combination of GPS and pembrolizumab in treating patients diagnosed with second- or third-line WT1(+) relapsed or refractory platinum-resistant, advanced metastatic ovarian cancer. The WT1 antigen is one of the most widely expressed cancer antigens in multiple malignancies and has been ranked by the National Cancer Institute as the top priority among cancer antigens for immunotherapy.

The study details are as follows:

Eleven patients (median age: 63 years) who received at least three GPS doses, the last of which was combined with pembrolizumab, were evaluated for clinical responses and three of those patients were also evaluated for immune responses.
66.7 percent of evaluable patients were refractory to or had failed their second-line therapies, and 33.3 percent failed third-line therapy or later.
All enrolled patients (100 percent) were resistant to the standard of care platinum-based therapy. Expected overall survival for patients receiving standard of care platinum-based therapy is nine to 12 months.
Median overall survival among the patients in this trial is not yet known as all patients are still alive at the time of the analysis, which period of time exceeds nine months.
Disease Control Rate
An ad hoc analysis of clinical outcomes in the cohort of 11 patients shows a disease control rate (DCR), the sum of overall response rate and rate of stable disease, of 63.6 percent, with a median follow-up of 15.4 weeks. In December 2020, the Company reported initial data showing a DCR of 87.5 percent in eight patients, with a median follow-up of 9.4 weeks. In this very difficult treatment-resistant patient population, at the time of the follow-up analysis, median progression-free survival (PFS) was 11.8 weeks. The landmark PFS rate by log-rank analysis at six months (26 weeks) was 33 percent.

Analysis of the updated data, using a validated immunohistochemistry assay during the eligibility screening period, shows that the rate of WT1 ovarian tumor positivity in this patient population remained high at approximately 63.6 percent. As of the time of this analysis, all patients are alive, and five patients (45.5 percent) are continuing to receive investigational therapy. Enrollment for this study is ongoing, with a target of approximately 20 total evaluable patients.

The safety profile of the GPS-pembrolizumab combination was similar to that seen with pembrolizumab alone, with the addition of only low-grade, temporary local reactions at the GPS injection site, consistent with previously performed clinical studies with GPS.

Immunobiological Data
CD8+ and CD4+ T-lymphocytes were isolated from peripheral blood mononuclear cells from three patients from whom samples had been collected both at baseline and at the time of the sixth GPS dose (i.e., 18 weeks after starting investigational therapy). The T-cells were assayed ex-vivo for immune responses against the pool of the four peptides that comprise GPS using the validated assay intracellular cytokine staining with fluorescence-activated single cell sorting (ICS-FACS) (Scorpion Biological Services, San Antonio, Texas), with appropriate positive and negative controls.

A total of five cytokine “channels” were used for the analysis (i.e., interferon-g, TNF-a, interleukin-2, CD107a and MIP-1b). The peptide re-challenge incubation period was seven days. At the 18-week time point versus pre-vaccination baseline, the assay demonstrated a relative increase in WT1-specific T-lymphocyte frequencies in peripheral blood averaging +242 percent (range: +104 to +385 percent across five cytokines) for CD8+ and +80.5 percent (range: +1 to +174 percent) for CD4+. There was also evidence of polyfunctional T-cell activation (increases in secretion of >2 cytokines) in two out of three patients (66 percent).

“Considering the overall poor prognosis in this particular clinical setting and based on the observed median PFS, overall survival and DCR in this study, combining GPS with the PD1 inhibitor pembrolizumab appears to be clinically promising as compared to bevacizumab-free salvage chemotherapy regimens and without the toxicity burden associated with the latter,” said Angelos Stergiou, M.D., Sc.D. h.c., President and CEO, SELLAS. “Patients treated with GPS plus pembrolizumab also appear to maintain a considerable degree of stable disease, as evidenced by the median DCR of 63.6 percent – all evaluable patients are alive. Continuing to review the clinical data will help us determine the fundamental value of the combination approach to fighting this disease. The initial trends are promising, and further maturity of the data and studying additional patients will allow us to draw more definitive conclusions regarding the clinical benefit. We expect to perform another set of similar ad hoc clinical and immunobiological analyses over the next six months as the study progresses.”

“Based on this early data, it is encouraging to see the induction of WT1-specific T-cell immune responses with the administration of GPS in combination with pembrolizumab with a validated complex ex-vivo immune response assay on peripheral blood from patients with platinum-refractory metastatic ovarian cancer who had undergone numerous prior therapies,” added Jeffrey S. Weber, M.D., Ph.D.; Deputy Director of the Perlmutter Cancer Center at New York University (NYU)-Langone Health; Co-Director of its Melanoma Research Program Center; and Chair of SELLAS’ Scientific Advisory Board. “Expansion of these results with data from additional patients, as well as at time points longer than 18 weeks (when such patient samples become available for testing), will be key in getting a more comprehensive picture of the combination immunotherapy’s biological effect.”

About Ovarian Cancer
Ovarian cancer is one of the most common gynecologic malignancies and the fifth most frequent cause of cancer death in women in the United States. Over 22,000 cases are diagnosed annually, and there are an estimated 15,500 deaths per year. The majority of patients have widespread disease at presentation. The five-year survival for the advanced-stage disease remains less than 30 percent. Combining GPS with the checkpoint inhibitor pembrolizumab, which beneficially and profoundly alters the tumor microenvironment (TME), is hypothesized to increase the proportion of patients who develop an immune response against their cancer and potentially improve their clinical outcome over pembrolizumab monotherapy, without the burden of additional toxicities in macroscopically measurable malignancies.

About SELLAS Life Sciences Group, Inc.
SELLAS is a late-stage clinical biopharmaceutical company focused on developing novel cancer immunotherapeutics for a broad range of indications. SELLAS’ lead product candidate, GPS, is licensed from Memorial Sloan Kettering Cancer Center and targets the WT1 protein, which is present in an array of tumor types. GPS has potential both as a monotherapy and in combination to address a broad spectrum of hematologic malignancies and solid tumor indications. SELLAS’ second product candidate, nelipepimut-S (NPS), is a HER2-directed cancer immunotherapy with potential to treat patients with early-stage breast cancer with low to intermediate HER2 expression, otherwise known as HER2 1+ or 2+, which includes triple negative breast cancer patients, following the standard of care.

For more information on SELLAS, please visit www.sellaslifesciences.com.

Keytruda® is a registered trademark of Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside the United States and Canada), and is not a trademark of SELLAS. The manufacturer of this brand is not affiliated with and does not endorse SELLAS or its products.

“Sellas specializes in immunotherapy focused around the development of Wilms Tumor 1 antigen, which was designated as the number one immunotherapy target by the National Cancer Institute,” he said. WT1 antigen is expressed in the cell nuclei of 75% of mesotheliomas and 93% of ovarian serous carcinomas, for example. There are approximately 20 tumor types that overexpress WT-1 antigen, thus suggesting GPS could have substantial application.

GPS is made of four peptide chains. Two of those (CD4+ and CD8+) induce a strong innate response against the WT1 antigen and access multiple HLA types. When administered, therefore, the immune system recognizes and destroys cancer cells and can continue to do so, targeting recurring tumors and residual cancer cells. Consequently, Stergiou said, “Patients can stay in remission longer and, hopefully, this will translate into longer overall survival.”

In most cases, GPS is not envisioned as a stand-alone therapy. “GPS, when used alone, isn’t built to debulk tumors,” he said. Instead, it works synergistically with immunotherapies – notably, Opdivo® and Keytruda® – that modulate the hostile tumor microenvironment. Then, when GPS is injected, “GPS increases the antigen-specific effector T cells and shepherds them, focusing the immune response to specific epitopes for optimal T cell response,” Stergiou said.

Based on that mechanism of action, GPS may have potential as a monotherapy for patients who are in complete remission. That hypothesis is being tested in the ongoing Phase III study of AML patients.

“Our lead program (currently in Phase III) is in acute myeloid leukemia for patients in their second remission,” Stergiou said. Earlier, Phase II data, showed notably longer survival rates for patients in their second complete remission – 21 months for those receiving GPS therapy versus 5.4 months for those receiving standard of care treatment.

Bottom Line: Plenty of Cash to Get to the multibillion FDA Green light, Q1/2 which simultaneously triggers $50M in Milestone $
$14.2 Bal Sheet+ $3.4Prepaid March 10Q + $23.6 proceeds April Raise $41.2M / 4.4M shares- total 20.4 now
$41.2 +$1M 3D Med milestone Paid in Q2 $42.2 on hand - $6M qtrly burn rate -- 7 Qtrs Current Cash
Cash Impact Events
Debits Gfh009 License -$4.5M Q2 + an Additional $5.5 Q3, 2023
(well after AML FDA Approval knowledge)

Credits: Gps Phase 2 Merck Joint Combination trial concluded in Q1 = savings

$191.5 M in Milestone money remaining on the 3D Med Greater China License + Low double digit Royalties
+ $5 to $7.5M 3D Med milestones in Q3/4 2022 for 5 Phase 2 Trials initiating
+ $5M 3D Med Milestone for Joining Ph 3 REGAL in Greater China (per 10q) / EU 2nd Half 2022
+ $25M 3D Med Milestone for Positive Ph3 Result Q1/2 2023
+ $25M 3D Med Milestong for BLA (Gps has FDA Fast Track Rolling submission and Approval 1st Half 2023

GFH009 $200M Market Value for Rare Pediatric Priority Review Voucher 2023

Bottom Line SLS may never need raise cash again

wir haben hier warscheinlich den heiligen Krebs Gral in den haenden bei dieser kleinen 50 mio Dollar company und so geht es weiter :

Get ready for an amazing end of 2022 - List of "Known" Catalysts
1. Final Phase 2 Gps Keytruda Combo Results - July/Aug. Partnership + upfront money potential MRK Joint Analysis Immunological data supporting the specific action of GPS in extending disease free survival and overall survival presented in an 'upcoming medical conference' - analysis to correlate Survival with IR's

2. Final Memorial Sloan Kettering Gps Opdivo Meso Results in 2ND Half + BMY Partnership + upfront Money potential -OS more than doubled life expectancy 10.5 months of OS which continues to expand, vs 22 weeks w BAT > IMP Opdivo Yervoy combination approved after extending OS 4 months www.fiercepharma.com/pharma/...-mesothelioma-death-risk-by-26

Combining a WT1 Cancer Vaccine (Galinpepimut-S) with Checkpoint Inhibition (Nivolumab) in Patients with WT1-Expressing Malignant Pleural Mesothelioma: A Phase I Study
Purpose
The purpose of this study is to assess the safety and effects of a cancer vaccine given with nivolumab immunotherapy in patients with pleural mesothelioma that continues to grow despite prior treatment. The vaccine is called galinpepimut-S and targets a protein called WT1, which is found on the surface of mesothelioma cells. It is mixed with a substance called montanide, which boosts the immune response.

Nivolumab inhibits a protein that normally puts the brakes on the immune response, enhancing the power of the immune system to find and destroy cancer cells. It is used to treat several types of cancer; its use in this study is considered investigational. It is believed that giving nivolumab in combination with a cancer vaccine will further enhance the immune response. Galinpepimut-S is given as an injection and nivolumab is given intravenously (by vein).

3. REGAL Enrollment Complete by the end of the year - This will bring big money and will start the clock ticking on billions in additional Market capitalization for SLS - Be Fully loaded Prior

4. GFH009 Trial Safety Data complete in Q3 and Final Data by the end of the year
- CDK9 Efficacy has been established many times over in other trials. safety has been the issue and Gfh009 has no Dose limitation, and is showing efficacy in patients who failed 6! 6 prior treatments!

5. 5, 3D MED Trials Launching, by the end of the Year, will trigger Multiple Milestone payments $5 - 7.5M + the 2 big kahunas, a positive Ph 3 results triggers 2, $25M payments in 2 or 3 qtrs - Imp as shorts will not be getting and cheap shares to cover with.

6. IDMC Halt for Efficacy - at any time
More likely than not 32 months deep into a trial where the Lead investigator is Requesting expanded Access and sees actual data!
The CEO has repeatedly stated the IDMC can halt the trial at any time if they see a clear Efficacy signal. The previous Gps Moffitt Center Phase 2 OS of 21 months Vs 5.4w BAT. Only a matter of time.

7. Gps Phase 2/3 MRD+ Trial initiation/ news

8. Gps Symposium PR

9. FDA Green light Gps 1st half of 23 is worth about 2 b in market cap value. Cr2 is the initial indication, Overall AML market expected to be appx 1B in annual revenue. Over a Million patients with WT1 Cancer each year - GPS is a blockbuster waiting happen.

We can only win bigly here in time
Gps has extended survival durations in Every single trial to date - All of them and is now showing efficacy against the most serious of cancers in combination with Keytruda and Opdivo
Gps 21m of OS vs 5.4 Cr2 Moffitt Center Phase 2 - First Phase 3 in process
Gps 67m of OS vs 25 Memorial Sloan Kettering Phase 2
Gps Opdivo 47% S at 2 years vs 7% for Ovarian cancer
Gps Opdivo 49 weeks (and counting) of OS vs 20 - 24 weeks End stage Mesothelioma Patients
Gps Keytruda OS of 10.5 m and counting vs 10.5 w existing therapy for end stage, platinum Refractory Oc

MD Andersons Leukemia department chairman running the Ph 3, who sees all the open label trial results, requesting Expanded Access, virtually confirms 2 things; 1. Gps is doing what it has done in every trial, cure patients and extend survival well beyond existing treatment, and 2. Guarantees Immediate off-label prescription and ultimate FDA Approved Expanded label to Cr1 / PostASCT which is 5x the $200M
Cr2 initial niche revenue projected by Cantor Fitz.

Also, now SLS has a 2 year cash runway, the Share Price will only appreciate approaching these Massively Valuable Catalysts