Introducing SELLAS Lifesciences Group, Inc.

Sellas Life Sciences Group is a client of PCG Advisory, Inc., an investor relations and communications firm. Please see our disclosures on our website www.pcgadvisory.com.

SELLAS is a late-stage clinical biopharmaceutical company focused on the development of novel cancer immunotherapeutics for a broad range of cancer indications. SELLAS’ lead product candidate, galinpepimut-S, GPS, is licensed from Memorial Sloan Kettering Cancer Center (MSKCC) and targets the WT1 protein, which is present in an array of tumor types. GPS has potential as a monotherapy or in combination to address a broad spectrum of hematologic malignancies and solid tumor indications.  SELLAS is currently in a pivotal, Phase 3 study of GPS in acute myeloid leukemia as well as in Phase 1 and 2 studies of GPS in combination with checkpoint blockade, PD-1 drugs, in a basket study design, including ovarian cancer, under a collaboration agreement with Merck as well as in a mesothelioma study under an IST with MSKCC and Bristol Myers Squibb.

CEO Insights

Your company's advanced immunotherapy platform is focused on developing galinpepimut-S (GPS). Why take this path?

We have chosen the path of developing innovative therapeutic vaccines for cancer, also called onco-vaccines, as this is a class of agents that works directly at the level of the immune system to boost the body's natural defenses to fight a cancer.
Our flagship product galinpepimut-S, or, for short, GPS, is a peptide-based immunotherapeutic with highly sophisticated and broadly differentiating features, targeting the Wilms Tumor-1 (WT1) protein, a well-validated cancer antigen, which was independently prioritized as the # 1 target antigen for vaccine development by the National Cancer Institute (NCI) based on stringent criteria. It is frequently - and typically densely- expressed in more than 20 cancers, both solid tumors and hematologic malignancies, while at the same time present in very sparse amounts in only a few normal (non-cancerous) tissues. Importantly, WT1 is also expressed (and therefore can be targeted) not only in replicating cancer cells (which make the bulk of any cancer), but also in cancer stem cells, the tiny fraction of non-replicating tumor cells that are responsible for resistance against various cancer therapies, and eventual clinical relapse (tumor ‘escape’ from therapy and progression). GPS attacks the specific WT1 antigen through stimulation and activation of the patient’s own immune cells, a much higher selectivity for cancer, which spares normal tissues from damage, and the ability to ‘shepherd’ these activated immune cells right into the tumor deposits.

GPS is a unique mixture of 4 small peptides that are by design chosen to be the most immunogenic fragments of the WT1 protein. It was invented at Memorial Sloan Kettering Cancer Center in Dr. David Scheinberg’s lab, where it underwent extensive preclinical testing, including validation assays for antigenicity and immunogenicity, as well as the ability to induce T-lymphocytes that could lyse (kill) WT1-expressing cancer cells ex vivo (i.e., antigen-specific cytotoxicity).  Importantly, two of the 4 peptides in the GPS mixture are artificially and highly engineered mutated by design, using the heteroclitic principle, whereby the mutated fragment sequences evoke a stronger immune response than the ‘native’, naturally occurring sequences, but at the same time that response cross-reacts with the ‘native’ ones which are expressed in cancer cells. To our knowledge, this is the first anticancer vaccine that uses the heteroclitic technology.  GPS is a product that is stable, off-the shelf, does not involve cells (like cell-based vaccines, with their associated complex and expensive manufacturing and distribution attributes), is open to practically all HLA types, and is by design able to both mitigate against immune tolerance (which leads to lessened clinical anticancer effect) and also induce and activate both CD8+ cytotoxic T-lymphocytes (which are responsible for tumor cell kill) and CD4+ T-cells (a fraction of T-cells that is responsible for establishing long-term immunologic ‘memory’, which is crucial to keep tumor growth ‘in check’). Further, GPS  is WT1-specific and, crucially, is not marred by severe or serious toxicities, such as development of cytokine-release syndrome (like CAR-T, TIL and some TCR-T and NK cell approaches) or induction of autoimmunity (seen often with checkpoint inhibitors). 

Phase 1/ pilot clinical trials in acute myeloid leukemia (AML) and thoracic cancers in the early 2010’s demonstrated safety and immunogenicity, as well as preliminary evidence of clinical activity, as survival was longer than expected for these patients.  Phase 2 studies in AML, multiple myeloma, ovarian cancer, and a rare thoracic malignancy called mesothelioma demonstrated a very ‘benign’ safety profile (mainly low-grade local skin reactions at the site of subcutaneous injection and mild, transitory flu-like symptoms), potent immunogenicity and clinical effect. In high-risk multiple myeloma patients, we saw evidence of intra-antigenic epitope spreading, which is the harbinger of clinically efficacious vaccine. We have treated close to 145 patients in various clinical trials to-date, 50 of whom had myeloid malignancies, mainly AML. When we use GPS as the only therapy (monotherapy), we do so in settings where the cancer has been already extensively debulked with the prior application of standard therapy, that is, we allow GPS to activate the immune system to attack a very low burden of microscopic residual cancer, thus maximizing its chances for clinical success. Therefore, GPS monotherapy is used in the maintenance or ‘adjuvant’ setting and can be given in a wide variety of tumor types sequentially after initially successful standard therapy to ‘control’ minimal residual disease. The goal of GPS monotherapy then is to delay or prevent relapse of the cancer. We measure the efficacy of this approach by estimating either the overall survival or progression (or relapse)-free survival. Moreover, GPS can also be combined with simultaneous administration of other types of cancer immunotherapy, most notably checkpoint inhibitors (such as PD1 and PDL-1 blockers), when one desires to attack macroscopic advanced or metastatic disease deposits. In this setting, the goal is to increase the proportion of cancer cells killed by combination regimen. We measure the efficacy of this approach by assessing the overall response rate to the combination regimen, while also checking for the possibility of inducing a higher rate of complete responses, which are typically low with checkpoint inhibitor therapy alone for most tumor types even today. 

In sum, we believe that using GPS, a truly innovative ‘wide spectrum’, highly optimized, multivalent and heteroclitic peptide vaccine, we are very well positioned both for the current and the future landscape of cancer immunotherapy, which fully justifies our choice of this type of immuno-oncology therapeutic platform.

Your registration-enabling phase III trial is catching the eye of investors. What’s special about this trial in targeting AML?

Before delving into the crux of this question, it is worth providing some background. As noted in the previous part of our discussion, we have successfully completed a Phase 1 and Phase 2 program using GPS monotherapy in AML in patients who have achieved a status of ‘complete remission’, or CR. We have tested GPS in a very advanced patient population, who initially were diagnosed with AML, received appropriate frontline therapy, but relapsed. These patients then were treated with ‘second-line’ or ‘salvage’ standard antileukemic therapies and successfully achieved their 2nd CR (CR2). This is more of a Pyrrhean victory for such patients, as despite the fact that the hematologic evidence of their disease has receded, they still harbor minimal residual disease, which will inexorably grow rapidly leading to their second relapse, which is typically lethal. Left untreated, AML patients in CR2 typically live on average 5 months. The only treatment nowadays that can offer a potential for disease eradication (‘cure’) is allogeneic stem cell transplant (in short, allo-SCT), which is a complex and risky procedure, with relatively limited applicability, especially in elderly patients (which represent the majority of AML patients at this advanced stage of the disease). In this setting, in an independent pilot clinical trial performed at the Moffitt Cancer Center, we found that GPS-treated patients have a median overall survival of 21 months, when compared to a contemporaneously treated group of patients with very comparable patient demographics and disease characteristics treated by the same team of physicians and nurses in the same institution. The ‘control’ patients had a much shorter median overall survival of 5.4 months, which is typical of the natural history of AML at that advanced stage. The difference in favor of GPS was highly statistically significant and clinically extremely meaningful. Notably, the clinical effect was accompanied by induction of antigen (WT1)-specific potent and prolonged immune responses. 

In addition to the pilot study of GPS in AML CR2 patients, we have tested GPS in the setting of first complete remission, or CR1, which is achieved in many patients after frontline antileukemic therapy. Again, the vast majority of patients still have minimal residual disease and will predictably relapse without further therapy. In this setting, for most younger patients and a proportion of patients >60 years of age, the route of allogeneic stem cell transplant is followed, as it remains the only curative-intent therapy with validated long-term clinical benefit. Again, this is a complex and risky treatment, associated with early mortality and morbidity due to the transplant procedure itself, but also post-transplant development of a syndrome called ‘graft-versus-host disease’, or, for short, GVHD. Moreover, several ‘targeted’ therapies have been FDA-approved and progressively more often used both to bring patients into CR1 and maintain them in this state afterward (as maintenance therapy). Unfortunately, not all patients can tolerate or be accorded benefit by these more novel treatments which target specific genetic and genomic abnormalities within the AML cancerous cells (and can/should be given only to those patients whose cells carry such abnormalities). Considering the above, there is still a very large medical need for less toxic, more efficacious therapies in this patient population. We have completed both a pilot/Phase 1 and a Phase 2 study in AML patients in CR1 with GPS, showing a median overall survival of 67.6 months with the vaccine as compared to 17.5-25 mos with standard of care in patients of all ages. Specifically for patients of age > 60 years, patients treated with GPS lived on average 35.5 months, as compared to only 12-14.5 months in those who received standard therapies. Again, we documented induction of immune responses against WT1 in almost 90% of vaccinated patients, while overall survival and progression-free survival tended to correlate with the aforementioned immune response to GPS. 

Based on the totality of the data above, we designed the currently ongoing randomized pivotal, potentially registration-enabling Phase 3 trial of GPS in AML CR2 patients (all ages), named the REGAL study. SELLAS’ clinical program is the most advanced AML peptide vaccine program in AML globally to-date, and to our estimates at least 3-4 years ahead of even the ‘closest’ competitor in the ‘space’. As you can appreciate, with the initiation of the REGAL trial, SELLAS is entering an exciting period of transition as a company, whereby the phase 3 design and treatment regimen has been truly optimized, along with a really elegant statistical analysis plan, which maximizes the probability of eventual clinical success. The REGAL study offers us the opportunity to potentially register and commercialize the first-ever directly immunizing therapy of the vaccine type in leukemias. It is important to note that REGAL is a relatively small study, with a total number of patients of 116, has an open-label design (agreed upon by FDA), and is, or will be, accruing in key AML clinical centers both in the US and in Europe. Moreover, the study design and key characteristics (such as enrollment criteria) resonate very well with top AML clinical trial leaders in the various centers participating (or soon to participate) in the study. All the above attributes portend for a highly-cost effective execution and delivery of this trial, along with an accelerated timeline toward the study’s final milestone (primary endpoint). To ensure our commitment to the Phase 3 study effort, we have established an independent data monitoring committee (IDMC), as well as a Study Steering Committee, the latter headed by Dr. Hagop Kantarjian, MD, Head of the Leukemia Department at the MD Anderson Cancer Center in Houston, Texas, who is also the global Principal Investigator for our study and one of the most renowned AML clinical researcher and physician in the world. We expect results from the only interim analysis of data from this study sometime in the 4th quarter of 2021. 

We are indeed quite excited to be at this stage of the company’s evolution, because – as mentioned above- if GPS is proven effective, it would be the only and first-in-class successful immunotherapy in AML (other than allotransplant), a therapy also associated with significant differentiative advantages over potential competitors. Further, an FDA approval would open a wide palette of opportunities for future development of GPS in other clinical settings in AML (for example, the CR1 setting or in patients after allotransplant), but also in several other indications, including but not limited to myelodysplastic syndromes (MDS) and multiple myeloma, as well as solid tumor indications, such as ovarian cancer, mesothelioma, and potentially several others (for example, small-cell lung cancer and triple-negative breast cancer). Of note, we believe that in solid tumors, a more optimal path for GPS would be a combinatorial approach with checkpoint inhibitors, such as PD1 and PDL-1 blockers. In this vein, we also have started another clinical study, in collaboration with Merck & Co., whereby we are investigating the combination of the PD1 inhibitor pembrolizumab with GPS in an open-label, non-randomized Phase 1/2 multi-arm ‘basket’ trial in 5 tumor types (including ovarian cancer, small-cell lung cancer and triple-negative breast cancer). This is essentially a ‘signal-seeking’ study, as we are trying to discern whether addition of GPS meaningfully increases the overall response rate to pembolizumab (based on historical estimates for this endpoint); this is done with a fairly sophisticated statistical design. We will also be checking the emergence of WT1-specific CD8+ and CD4+ T-cell responses and their time dynamics in these patients. The study is planned to accrue 15-20 patients per arm, to a total of up to 90 patients. We expect first interpretable results from this study by the first half of 2021.

Another development program that can drive shareholder value higher is with nelipepimut-S (NPS). What is your strategy behind this program, and should this program be looked upon by investors as possibly delivering near-term catalysts, i.e., partnerships, licensing, etc.?

Nelipepimut-S (NPS or NeuVaxTM) is a peptide immunizing monovalent vaccine against the most immunogenic peptide fragment of the HER2 protein, which is expressed predominantly in breast cancer, but also in a few other malignancies, such as gastric, prostate, ovarian and endometrial cancers.
NPS has been around for about 15 years. The discovery/preclinical biology phase for NPS was completed initially by Dr. George Peoples and collaborators at the MD Anderson Cancer Center in Houston, Texas, and this product has been fully in-licensed by SELLAS through our reverse merger in December 2017. The vaccine is given intradermally (in-between the uppermost skin layers). Correlative studies in more than 800 patients overt the years have shown that NPS is capable of inducing NPS (antigen)-specific CD8+ cytotoxic lymphocytes, as well as, interestingly and notably for a monovalent vaccine, activating antigen-specific CD4+ T-cells (responsible for immunologic ‘memory’) activation, and demonstrating cross-epitopic reactivity against many fragments of HER2 for which the patients were not specifically immunized (vaccinated), an effect akin to ‘epitope spreading’. The vaccine has broad HLA-specificity, ‘covering’ the majority of the US and Western hemisphere population, and ~80% of Asian/Pacific basin countries. Similarly to GPS, NPS is an ‘off-the-shelf’ product, with low cost of goods, and lack of serious or severe side effects. 

NPS has completed a successful Phase 2 program, spread out across several academic institutions over the last  10 years, including the Cancer Vaccine Development Program, or CVDP, a US Army research network, having demonstrated meaningful clinical activity as monotherapy in the adjuvant setting in patients with breast (BC) whose tumors express the HER2 protein at low levels, so called HER2 low-expressing BC. The NPS vaccine is given after upfront standard first-line therapy with either neoadjuvant or adjuvant chemotherapy and surgery. Novel results became available in 2018 from both an interim and final analysis of data from a prospective, randomized, single-blinded, controlled Phase 2b clinical study of the combination of trastuzumab (Herceptin®) +/- NPS targeting HER2 low-expressing BC patients (the ML25749 trial; ClinicalTrials.gov identifier: NCT01570036). The final results of this study showed clinically meaningful and statistically significant efficacy outcome differences in favor of the combination arm in the subgroup of study patients with triple-negative breast cancer, for short, TNBC, defined as tumors that tested negative for both estrogen and progesterone receptor whilst expressing HER2 at low levels (HER2 stain intensity by immunohistochemistry [IHC] of 1+ or 2+; in contradistinction to HER2 ‘positive’ tumors which have a HER stain intensity of IHC 3+). In more detail, combining NPS with trastuzumab led to an impressive 75.2% reduction in risk of relapse or death (p=0.013) and a 72.5% decrease in the total number of clinically detectable relapses across time (p=0.004) in comparison to trastuzumab alone, both with a median follow-up of 26.1 months. The primary endpoint of the 24-month disease-free survival (DFS) rate (percentage) was highly significant in favor of the combination in the TNBC subgroup. This study was led nationally by Dr. Elizabeth Mittendorf (currently at the Dana-Farber Cancer Institute in Boston, MA) and was published in the prestigious journal Clinical Cancer Research in February of this year. 

Since the advent of the aforementioned unprecedented results in TNBC, which is a very difficult to manage and clinical aggressive malignancy, we have aimed to meaningfully advance the development of NPS through a prospective, double-blinded, randomized, global Phase 3 pivotal clinical study of NPS plus trastuzumab vs control for the adjuvant treatment of early-stage TNBC after initial neoadjuvant chemotherapy and surgery. The aim of the study would be to prevent or delay disease recurrence or death, as reflected by the 24-month DFS rate (percentage) in a ‘landmark’ analysis. The clinical study design was discussed with the FDA and has been agreed upon in principle in mid-February this year. Thus, we believe that we have determined a ‘base-case’ regulatory path for the NPS plus trastuzumab combination in early-stage high-risk TNBC. Finally, we have initiated and continue business development and licensing activities and our BD efforts are underway as this is an asset we are looking to partner out while we remain fully focused on our GPS lead asset and programs. 

Dr. Angelos M. Stergiou, MD, ScD hc is an entrepreneurial scientist and physician who founded SELLAS Life Sciences Group about ten years ago. He continues pioneering cancer vaccination research and working on a promising drug, known as the WT1 cancer vaccine (galinpepimut-S), that could save countless lives worldwide.

PCG had the opportunity to sit down with the SELLAS President & Chief Executive Officer for more insights into the company's unique product development program.

Dr Angelos Stergiou 

President & CEO

Nasdaq:SLS