Translational Drug Development LLC

Scientists have uncovered potential therapeutic avenues for metabolic diseases. "Metabolism" describes the body's chemical changes that create the necessary materials for growth and overall health. Metabolites are the substances made and used during these metabolic processes -- or, as a new discovery out of Scripps Research and its drug development arm, Calibr, indicates, they could also be potent molecules for treating severe diseases. In a study from Metabolites published in August 2022, the researchers used novel drug discovery technologies to uncover a metabolite that converts white fat cells ("bad" fat) to brown fat ("good" fat) cells. This discovery offers a potential way of addressing metabolic conditions like obesity, type 2 diabetes and cardiovascular disease. Even more, it speaks to the promise of using this creative drug discovery method to identify countless other potential therapeutics. "The reason many types of molecules don't go to market is because of toxicity," says co-senior author Gary Siuzdak, PhD, the senior director of the Scripps Center for Metabolomics and professor of Chemistry, Molecular and Computational Biology at Scripps Research. "With our technology, we can pull out endogenous metabolites -- meaning the ones that the body makes on its own -- that can have the same impact as a drug with less side effects. The potential of this approach is even evidenced by the FDA's recent approval of Relyvrio, the combination of two endogenous metabolites for the treatment of amyotrophic lateral sclerosis (ALS)." Metabolic diseases are often caused by an imbalance in energy homeostasis -- in other words, when the body takes in more energy than it expends. This is why certain therapeutic approaches have centered around converting white fat cells (known as adipocytes) into brown fat cells. White adipocytes store excess energy and can eventually result in metabolic diseases like obesity, while brown adipocytes dissolve this stored energy into heat -- ultimately increasing the body's energy expenditure and helping bring it back into balance. To uncover a therapy that could stimulate the production of brown adipocytes, the researchers searched through Calibr's ReFRAME drug-repurposing collection -- a library of 14,000 known drug compounds that have been approved by the FDA for other diseases or have been extensively tested for human safety. Using high-throughput screening -- an automated drug discovery method for searching through large pools of information -- the scientists scanned ReFRAME for a drug with these specific capabilities. This is how they uncovered zafirlukast, an FDA-approved drug used for treating asthma. Through a set of cell culture experiments, they found zafirlukast could turn adipocyte precursor cells (known as preadipocytes) into predominantly brown adipocytes, as well as convert white adipocytes into brown adipocytes. While an encouraging find, zafirlukast is toxic when administered at higher doses, and it wasn't entirely clear how zafirlukast was converting the fat cells. This is when the researchers partnered with Siuzdak and his team of metabolite experts. "We needed to use additional tools to break down the chemicals in zafirlukast's mechanism," says Kristen Johnson, PhD, co-senior author of the paper and a director in Translational Drug Discovery Research at Calibr. "Framed another way, could we find a metabolite that was providing the same functional effect that zafirlukast was, but without the side effects?" Siuzdak and his team designed a novel set of experiments, known as drug-initiated activity metabolomics (DIAM) screening, to help answer Johnson's question. DIAM uses technologies such as liquid chromatography (a tool that separates components in a mixture) and mass spectrometry (an analytical technique that separates particles by weight and charge) to pool through thousands of molecules and identify specific metabolites. In this case, the researchers were searching through adipose tissue for metabolites that could lead to brown adipocyte cell production. After reducing 30,000 metabolic features to just 17 metabolites, they found myristoylglycine -- an endogenous metabolite that prompted the creation of brown adipocytes, without harming the cell. Of the thousands of metabolic features measured in the analysis, only myristoylglycine had this special characteristic, even among nearly structurally identical metabolites. "Identifying myristoylglycine among the thousands of other molecules speaks to the power of Siuzdak's approach and these technologies," adds Johnson. "Our findings illustrate what happens when an analytical chemistry team and a drug discovery group closely collaborate with each other." In addition to Siuzdak and Johnson, authors of the study, "Drug-Initiated Activity Metabolomics Identifies Myristoylglycine as a Potent Endogenous Metabolite for Human Brown Fat Differentiation" include Carolos Guijas, J. Rafael Montenegro-Burke, Xavier Domingo-Almenara, Bernard P. Kok and Enrique Saez of Scripps Research;and Andrew To, Zaida Alipio-Gloria and Nicole H. Alvarez of Calibr. This research was partially funded by the National Institutes of Health and the NIH Cloud Credits Model Pilot.

- Neuroendocrine Prostate Cancer is Growing Unmet Medical Need - NEW YORK, Aug. 24, 2022 (GLOBE NEWSWIRE) -- SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) (“SELLAS’’ or the “Company”), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, today announced results from a new preclinical in vitro study for its highly selective CDK9 inhibitor, GFH009, in neuroendocrine prostate cancer (NEPC). The data shows that GFH009 demonstrated significant anti-tumor effects in the selected cell line at nanomolar concentrations and, in certain samples, complete growth inhibition with no viable cancer cells. NEPC, an aggressive variant of prostate cancer, is a rapidly growing indication which arises as a result of otherwise successful treatment of advanced prostate cancer. In up to 15 to 20 percent of patients treated with hormonal therapies for prostate adenocarcinoma, small-cell prostate cancer may develop in later stages of prostate cancer progression. This histologic transformation occurs as a mechanism of treatment resistance. Aggressive NEPC represents a lethal endpoint in the progression of prostate cancer from prostate adenocarcinoma to castration-resistant prostate cancer (CRPC) to NEPC. Median survival for NEPC patients whose cancer arose from prior prostate adenocarcinoma is estimated at only 5.4 months. The conversion to NEPC is associated with recurrent genetic lesions including mutation or deletion of RB1 and TP53 as well as the overexpression and genomic amplification of MYCN. SELLAS believes that all forms of MYC may be susceptible to CDK9 inhibition and the data from the in vitro study, conducted at an independent, third-party contract research organization, Translational Drug Development (TD2), supported this supposition, resulting in 38 nM median IC50 value. “We are very excited with this first confirmation of our hypothesis that GFH009 could address NEPC, a rapidly growing indication,” said Dragan Cicic, MD, Senior Vice President, Clinical Development, of SELLAS. “About one in eight men will be diagnosed with prostate cancer during his lifetime and any significant change in the course of treatment for this cancer has potential for outsized consequences.” About Translational Drug Development (TD2) TD2 is an oncology development organization that provides innovative services for oncology-focused companies. Using a dedicated team of professionals with broad experience and understanding in drug development, TD2 is uniquely positioned to support improved and accelerated development of medicines for life-threatening oncology diseases. TD2 applies rigorous and high-throughput translational preclinical development, combined with regulatory affairs expertise, to customize clinical trial design and execution. TD2’s suite of capabilities encourages the timely selection of patient populations who are most likely to benefit from a new agent, and the rapid identification of clinically significant endpoints. TD2 is committed to reducing the risks and uncertainty inherent in the drug development process and to the acceleration of patient access to promising treatments. For more information, visit www.TD2inc.com. About SELLAS Life Sciences Group, Inc. SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) is a late-stage clinical biopharmaceutical company focused on the development of novel therapeutics for a broad range of cancer indications. SELLAS’ lead product candidate, galinpepimut-S (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 as a monotherapy or in combination with other therapies to address a broad spectrum of hematologic malignancies and solid tumor indications. The Company is also developing GFH009, a small molecule, highly selective CDK9 inhibitor, which is licensed from GenFleet Therapeutics (Shanghai), Inc., for all therapeutic and diagnostic uses in the world outside of Greater China. For more information on SELLAS, please visit www.sellaslifesciences.com. Forward-Looking Statements This press release contains forward-looking statements. All statements other than statements of historical facts are “forward-looking statements,” including those relating to future events. In some cases, forward-looking statements can be identified by terminology such as “plan,” “expect,” “anticipate,” “may,” “might,” “will,” “should,” “project,” “believe,” “estimate,” “predict,” “potential,” “intend,” or “continue” and other words or terms of similar meaning. These statements include, without limitation, statements related to preclinical data for GFH009, plans for further development of GFH009, and the potential for GFH009 as a drug development candidate. These forward-looking statements are based on current plans, objectives, estimates, expectations and intentions, and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the COVID-19 pandemic and its impact on the Company’s clinical plans and business strategy, risks and uncertainties associated with oncology product development and clinical success thereof, the uncertainty of regulatory approval, and other risks and uncertainties affecting SELLAS and its development programs as set forth under the caption “Risk Factors” in SELLAS’ Annual Report on Form 10-K filed on March 31, 2022 and in its other SEC filings. Other risks and uncertainties of which SELLAS is not currently aware may also affect SELLAS’ forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. The forward-looking statements herein are made only as of the date hereof. SELLAS undertakes no obligation to update or supplement any forward-looking statements to reflect actual results, new information, future events, changes in its expectations or other circumstances that exist after the date as of which the forward-looking statements were made. Investor Contact Allison Soss KCSA Strategic Communications Email: SELLAS@kcsa.com Phone: 212.896.1267 Media Contacts Raquel Cona / Michaela Fawcett KCSA Strategic Communications Email: SELLAS@kcsa.com Phone: 212.896.1276

- Results Demonstrate Significant Anti-Tumor Effects on All Selected Cell Lines - - In Three of the Four Cell Lines, GFH009 Inhibited Cancer Growth by 90 to 100 Percent - NEW YORK, Aug. 09, 2022 (GLOBE NEWSWIRE) -- SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) (“SELLAS" or the “Company”), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, today announced results from preclinical in vitro studies for its highly selective CDK9 inhibitor, GFH009, in solid cancer and acute myeloid leukemia (AML) cell lines. The data shows that GFH009 demonstrated significant anti-tumor effects in all four selected cell lines. In three out of the four cell lines, GFH009 inhibited cancer cell growth by 90 to 100 percent. The in vitro studies were conducted at an independent, third-party contract research organization, Translational Drug Development (TD2), and the following cell lines were selected for the studies based on their unique characteristics, combined with GFH009’s mechanism of action: RH30: a pediatric soft tissue sarcoma cell line that is a model for studying high-risk pediatric rhabdomyosarcoma, an indication for which currently available treatments are limited to high-dose chemotherapy with unsatisfactory results. RH30 cells are driven by PAX3-FOXO1, a transcription factor whose expression is strictly needed for tumor cell survival. RH30 is also dependent on MYCN, a major target of CDK9 inhibition. Treatment with GFH009 resulted in 90 percent or more cancer inhibition at dose levels equivalent to those already demonstrated to be safe in patients in the ongoing Phase 1 trial with no viable cancer cells at the highest dose levels. NCI-H209: a small cell lung cancer cell line characterized by the loss of function of two major tumor suppressor genes, RB1 and TP53. This cell line also expresses MCL-1, a major target of CDK9 inhibition. Treatment with GFH009 resulted in 90 percent or more cancer inhibition at dose levels equivalent to those already demonstrated to be safe in patients in the ongoing Phase 1 trial with no viable cancer cells at highest dose levels. SKOV-3: an ovarian cancer cell line containing the wild type BRCA1 gene and highly expresses CDK9. Treatment with GFH009 resulted in more than 50 percent cancer inhibition at dose levels equivalent to those already demonstrated to be safe in patients in the ongoing Phase 1 trial. OCI-AML-2: an AML cell line that develops resistance to the chemotherapy venetoclax on exposure. Treatment with GFH009 resulted in 90 to 100 percent cancer inhibition at dose levels equivalent to those already demonstrated to be safe in patients in the ongoing Phase 1 trial with no viable cancer cells at the highest dose levels. “The data from preclinical studies that we are reporting today demonstrates that certain cancer cell lines, whose survival depends on specific changes in the cell, can be identified and treated with GFH009,” said Dragan Cicic, MD, Senior Vice President, Clinical Development, of SELLAS. “Through identifying specific genes in cancer cells, GFH009 has shown in these preclinical studies the ability to stop the transcription and expression from gene to protein, inhibiting cancer cell growth altogether. We will utilize this important information as we design our clinical development program for GFH009 in adult and pediatric tumor types.” About Translational Drug Development (TD2) TD2 is an oncology development organization that provides innovative services for oncology-focused companies. Using a dedicated team of professionals with broad experience and understanding in drug development, TD2 is uniquely positioned to support improved and accelerated development of medicines for life-threatening oncology diseases. TD2 applies rigorous and high-throughput translational preclinical development, combined with regulatory affairs expertise, to customize clinical trial design and execution. TD2’s suite of capabilities encourages the timely selection of patient populations who are most likely to benefit from a new agent, and the rapid identification of clinically significant endpoints. TD2 is committed to reducing the risks and uncertainty inherent in the drug development process and to the acceleration of patient access to promising treatments. For more information, visit . About SELLAS Life Sciences Group, Inc. SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) is a late-stage clinical biopharmaceutical company focused on the development of novel therapeutics for a broad range of cancer indications. SELLAS’ lead product candidate, galinpepimut-S (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 as a monotherapy or in combination with other therapies to address a broad spectrum of hematologic malignancies and solid tumor indications. The Company is also developing GFH009, a small molecule, highly selective CDK9 inhibitor, which is licensed from GenFleet Therapeutics (Shanghai), Inc., for all therapeutic and diagnostic uses in the world outside of Greater China. For more information on SELLAS, please visit . Forward-Looking Statements This press release contains forward-looking statements. All statements other than statements of historical facts are “forward-looking statements,” including those relating to future events. In some cases, forward-looking statements can be identified by terminology such as “plan,” “expect,” “anticipate,” “may,” “might,” “will,” “should,” “project,” “believe,” “estimate,” “predict,” “potential,” “intend,” or “continue” and other words or terms of similar meaning. These statements include, without limitation, statements related to preclinical data for GFH009, plans for further development of GFH009, and the potential for GFH009 as a drug development candidate. These forward-looking statements are based on current plans, objectives, estimates, expectations and intentions, and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the COVID-19 pandemic and its impact on the Company’s clinical plans and business strategy, risks and uncertainties associated with oncology product development and clinical success thereof, the uncertainty of regulatory approval, and other risks and uncertainties affecting SELLAS and its development programs as set forth under the caption “Risk Factors” in SELLAS’ Annual Report on Form 10-K filed on March 31, 2022 and in its other SEC filings. Other risks and uncertainties of which SELLAS is not currently aware may also affect SELLAS’ forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. The forward-looking statements herein are made only as of the date hereof. SELLAS undertakes no obligation to update or supplement any forward-looking statements to reflect actual results, new information, future events, changes in its expectations or other circumstances that exist after the date as of which the forward-looking statements were made. Investor Contact Allison Soss KCSA Strategic Communications Email: SELLAS@kcsa.com Phone: 212.896.1267 Media Contacts Raquel Cona / Michaela Fawcett KCSA Strategic Communications Email: SELLAS@kcsa.com Phone: 212.896.1276