On June 24, 2021 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on developing novel cancer immunotherapies for a broad range of indications, reported that encouraging updated clinical data from a Phase 1 investigator-sponsored clinical trial of its lead clinical candidate, galinpepimut-S (GPS), combined with the checkpoint inhibitor nivolumab (Opdivo) in patients with macroscopic (measurable) deposits of malignant pleural mesothelioma (MPM).

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The study details are as follows:

Four evaluable male patients, aged approximately 67.3 + 4.1 (standard deviation), received GPS plus nivolumab for at least one month. Initial tumor stages were II (one patient), IIB (one patient) and IV (two patients).
All patients had the MPM epithelioid and/or sarcomatoid variant, a tumor which is universally expressing Wilms Tumor 1 (WT1), one of the most widely expressed cancer antigens, ranked by the National Cancer Institute as the top priority among cancer antigens for immunotherapy.
Patients have received and progressed with, or are refractory to, frontline pemetrexed-based chemotherapy.
Average overall survival (OS) was 35.3 + 24.0 weeks with a median OS of 35.4 weeks, while average progression-free survival (PFS) was 8.8 + 4.2 weeks with a median PFS of seven weeks, both at a median follow-up of 35.4 weeks.
The safety profile of the GPS-nivolumab combination was similar to that seen with nivolumab alone, with the addition of only low-grade, temporary local reactions at the GPS injection site, consistent with previously performed clinical studies with GPS.
With approximately 3,300 cases in the United States each year, accompanied by a rising incidence in developing countries, MPM is notoriously difficult to treat and can lead to poor clinical outcomes with respect to both overall survival and progression-free survival, especially for those patients with the sarcomatoid variant who show a median overall survival of approximately 4.0 to 5.0 months. In relapsed and refractory patients who progressed after the first line standard of care pemetrexed, a similar patient population to that in the GPS nivolumab combination trial, the common treatment regimen is vinorelbine and overall survival in those patients is reported to be between 4.5 and 6.2 months. In patients treated with other chemotherapy regimens, such as carboplatin and irinotecan, median overall survival is reported to be approximately 7.0 months.

"Considering the overall poor prognosis in this particular clinical setting, these preliminary data suggest that the combination of GPS with the PD1 inhibitor nivolumab may provide meaningful clinical benefit to patients with MPM. Surprisingly, the only sarcomatoid mesothelioma patient enrolled, who was diagnosed with Stage IV cancer, experienced a survival of 25 months and is still alive," said Angelos Stergiou, M.D., Sc.D. h.c., President and CEO, SELLAS. "Patients treated with GPS plus nivolumab combination therapy appear to be surviving significantly longer than expected. We believe that this could potentially be due to the persistence of a residual cellular immunity-mediated antitumor effect with this immunotherapy combination. Studying additional patients along with longer follow-up of existing patients will hopefully provide further clarity on these data, which we expect to review over the next six months as the study progresses."

SELLAS expects to report additional clinical and immune response data in Q4 2021, including an assessment of CD8+ and CD4+ T-cell responses to the WT1 peptide pool in the GPS mixture, as well as epitope spreading (ES) by testing for antibody presence (IgG’s) directed specifically against the full-length WT1 protein (intra-antigenic ES) and IgG’s presence against other key oncofetal antigens expressed in MPM (inter-antigenic epitope spreading).

On June 24, 2021 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to adagrasib for the potential treatment of patients with non-small cell lung cancer (NSCLC) who harbor the KRASG12C mutation following prior systemic therapy (Press release, Mirati, JUN 24, 2021, View Source [SID1234584341]).

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Breakthrough Therapy Designation is an FDA program designed to expedite the development and regulatory review of drugs that have demonstrated preliminary clinical evidence of a substantial improvement over available therapy in the treatment of patients with serious diseases on at least one clinically significant endpoint.

The designation for adagrasib is supported by preliminary results from the registrational Phase 1/2 KRYSTAL-01 trial in patients with advanced NSCLC, whose cancer had progressed following prior treatment with immunotherapy and/or chemotherapy.

"We are pleased to receive this breakthrough therapy designation for adagrasib, which emphasizes the significant need for new treatment options for patients with lung cancer who harbor the KRASG12C mutation," said Charles M. Baum, M.D., Ph.D., president and chief executive officer, Mirati Therapeutics, Inc. "We look forward to submitting a New Drug Application for adagrasib in the second half of this year and further advancing adagrasib across a broad development plan with the goal of improving clinical outcomes in patients with KRASG12C mutated cancers."

About KRASG12C in Non-Small Cell Lung Cancer

Lung cancer is one of the most common cancers worldwide, accounting for 2.21 million new cases and 1.8 million deaths worldwide in 2020. Lung cancer consists of non-small cell lung cancer (NSCLC) in approximately 85 percent of cases and small cell lung cancer (SCLC) in approximately 15 percent of cases. KRASG12C is the most common KRAS mutation in NSCLC, present in approximately 14 percent of patients with lung adenocarcinoma, and is a biomarker mutation of poor prognosis.

About Adagrasib (MRTX849)

Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C mutated cancers, as the KRASG12C protein regenerates every 24-48 hours. Studies of adagrasib have shown that the drug has a long half-life, extensive tissue distribution and is well tolerated. Adagrasib has also shown single-agent responses in non-small cell lung cancer (NSCLC), colorectal cancer, pancreatic cancer, and other solid tumors with KRASG12C mutations. Adagrasib is a being evaluated in several clinical trials in combination with other anti-cancer therapies with strong scientific rationale in patients with advanced solid tumors. Registration-enabling studies are ongoing in NSCLC and colorectal cancer. For more information visit Mirati.com/science.

On June 24, 2021 Aileron Therapeutics (NASDAQ:ALRN), a chemoprotection oncology company focused on fundamentally transforming the experience of chemotherapy for cancer patients, reported that it is set to join the Russell Microcap Index at the conclusion of the 2021 Russell indexes annual reconstitution, effective after the U.S. market opens on June 28, 2021 (Press release, Aileron Therapeutics, JUN 24, 2021, View Source [SID1234584309]).

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Membership in the Russell Microcap Index, which remains in place for one year, means automatic inclusion in the appropriate growth and value style indexes. FTSE Russell determines membership for its Russell indexes primarily by objective, market-capitalization rankings and style attributes.

"Protection against chemotherapy-induced toxicities represents a significant, largely unaddressed need in the oncology space, and one for which there is now increasing progress and momentum," said Manuel Aivado, M.D., Ph.D., President and Chief Executive Officer at Aileron. "Precision medicine has truly revolutionized cancer treatment. In line with that transformation, our use of the p53 biomarker gives us the potential to selectively chemoprotect healthy cells in a very large number of patients given that nearly one million cancer patients are annually diagnosed with a p53-mutated cancer in the United States alone. Our inclusion in the Russell Microcap Index will expand our investor base as we work to transform the experience of cancer patients undergoing chemotherapy."

Russell indexes are widely used by investment managers and institutional investors for index funds and as benchmarks for active investment strategies. Approximately $10.6 trillion in assets are benchmarked against Russell’s US indexes. Russell indexes are part of FTSE Russell, a leading global index provider. For more information on the Russell Microcap Index and the Russell indexes reconstitution, go to the "Russell Reconstitution" section on the FTSE Russell website.

On June 24, 2021 Sirnaomics, Inc., a biopharmaceutical company engaged in the discovery and development of RNAi therapeutics against cancer and fibrotic diseases, reported that dose administration for the first patient in a Phase 1 U.S. clinical study for liver cancer treatment, with the company’s siRNA (small interfering RNA) drug candidate, STP705 (Press release, Sirnaomics, JUN 24, 2021, View Source [SID1234584326]). STP705 takes advantage of a dual-targeted inhibitory property and polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down both TGF-β1 and COX-2 gene expression.

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This Phase 1 trial is a multicenter, open-Label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of STP705, with an intratumoral administration. In this "basket study" of up to 50 subjects suffering from cholangiocarcinoma, hepatocellular carcinoma, or liver metastases from colorectal cancer, the patients with advanced/metastatic or surgically unresectable solid tumors and are refractory to standard therapy will be treated with STP705. This therapeutic regimen is designed to take advantage of a dual-targeted inhibitory property of siRNAs and polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down both TGF-β1 and COX-2 gene expressions. Early pre-clinical and clinical studies using STP705 have shown an increase of active T cell infiltration into the tumor microenvironment. In addition, knocking down TGF-β1 and COX-2 gene expressions in animal fibrosis tissue can activate fibroblast apoptosis with significant antifibrotic efficacy.

"Advancing STP705 from skin cancer to liver cancer is a major milestone for Sirnaomics’ clinical programs, especially with a basket study design that consists of multiple tumor types. We are particularly interested in learning whether the mechanism of action validated in the skin cancer clinical study can be further verified in this liver cancer study," said Patrick Lu, Ph.D., founder, President and Chief Executive Officer of Sirnaomics. "We are expecting that the combination of anti-fibrotic effects and enhanced tumor immunity will provide a novel approach for the treatment of cholangiocarcinoma and hepatocellular carcinoma using our novel siRNA therapeutics. Sirnaomics is committed to advancing our polypeptide nanoparticle delivery system for innovative RNAi-based cancer therapy."

"Liver cancer is a devastating disease for patients with high mortality and high unmet medical need," stated Michael Molyneaux, MD, Chief Medical Officer of Sirnaomics. "The company is excited to announce first dosing, as we hope to gain important insight into the potential safety and efficacy of STP705 in this Phase 1 trial and build on the data from this study to expand into other oncology indications."

Sirnaomics expects to report initial clinical data from the Phase 1 trial in the second half of 2021. Additional information about this clinical trial is available at clinicaltrials.gov using the identifier: NCT04676633

Wechat 01
About Liver Cancer

Liver cancer is a global health problem, with liver neoplasms representing the second-most frequent cause of cancer-related death. There are many different types of liver cancers including hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), liver angiosarcoma, hepatoblastoma and others. Additionally, liver is a highly metastasis-permissive organ. It is the most frequently afflicted organ by metastasis and liver metastases are much more common than primary hepatic tumors. The distinctive biology of the liver renders it intrinsically susceptible to metastases. The true prevalence of liver metastasis is unknown, but between 30% and 70% of patients dying of cancer have liver metastases and most patients with liver metastases will die of their disease.

STP705 and Liver Cancer

Over expressions of TGF-β1 and COX-2 have been well-characterized as playing key regulatory roles in tumorigenesis. TGF-β is produced by different liver cells and is demonstrated to induce tumor cell migration and survival. TGF-β has been found to be overexpressed in metastatic HCC tissues. Overexpression of TGF-β is generally accepted to be associated with metastasis and poor prognosis. COX-2 is reported to be highly expressed in cancer stem cells and promotes cell migration in HCC cell lines. Additionally, inhibition of COX-2 suppresses cell migration and induces apoptosis. As such TGF-β1 and COX-2 are excellent therapeutic targets for treatment of liver cancer.

STP705 is composed of two siRNA oligonucleotides targeting TGF-β1 and COX-2 mRNA respectively and formulated in nanoparticles with a proprietary Histidine-Lysine Co-Polymer (HKP) peptide. Each individual siRNA has demonstrated the ability to inhibit the expression of their target mRNA and combining the two siRNAs produces a synergistic effect that diminishes pro-fibrogenic, pro-inflammatory, and pro-tumorigenic factors. Sirnaomics has completed several pre-clinical studies that demonstrate that inhibition of TGF-β1 and COX-2 is expected to result in the inhibition of tumor growth and provide an alternative approach for the treatment of various liver cancers. Molecular analyses of the effects of administering the combination demonstrated that the inhibition of these targets had effects on downstream gene products associated with numerous oncology targets.

Additional immunohistochemistry and image analyses of the liver and tumor tissues demonstrated that animals treated with STP705 resulted in increased CD4+ and CD8+ T cell infiltration within the tumor microenvironment. Using STP705 for treatments of hepatocellular carcinoma and cholangiocarcinoma have been designated as Orphan Drug indications by U.S. FDA. STP705 has also been evaluated in a Phase 2a clinical trial for treatment of Non-melanoma skin cancer.

On June 24, 2021 Sirnaomics, Inc., a biopharmaceutical company engaged in the discovery and development of RNAi therapeutics against cancer and fibrotic diseases, reported dose administration for the first patient in a Phase 1 U.S. clinical study for liver cancer treatment, with the company’s siRNA (small interfering RNA) drug candidate, STP705 (Press release, Sirnaomics, JUN 24, 2021, View Source [SID1234584342]). STP705 takes advantage of a dual-targeted inhibitory property and polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down both TGF-β1 and COX-2 gene expression.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This Phase 1 trial is a multicenter, open-Label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of STP705, with an intratumoral administration. In this "basket study" of up to 50 subjects suffering from cholangiocarcinoma, hepatocellular carcinoma, or liver metastases from colorectal cancer, the patients with advanced/metastatic or surgically unresectable solid tumors and are refractory to standard therapy will be treated with STP705. This therapeutic regimen is designed to take advantage of a dual-targeted inhibitory property of siRNAs and polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down both TGF-β1 and COX-2 gene expressions. Early pre-clinical and clinical studies using STP705 have shown an increase of active T cell infiltration into the tumor microenvironment. In addition, knocking down TGF-β1 and COX-2 gene expressions in animal fibrosis tissue can activate fibroblast apoptosis with significant antifibrotic efficacy.

"Advancing STP705 from skin cancer to liver cancer is a major milestone for Sirnaomics’ clinical programs, especially with a basket study design that consists of multiple tumor types. We are particularly interested in learning whether the mechanism of action validated in the skin cancer clinical study can be further verified in this liver cancer study," said Patrick Lu, Ph.D., founder, President and Chief Executive Officer of Sirnaomics. "We are expecting that the combination of anti-fibrotic effects and enhanced tumor immunity will provide a novel approach for the treatment of cholangiocarcinoma and hepatocellular carcinoma using our novel siRNA therapeutics. Sirnaomics is committed to advancing our polypeptide nanoparticle delivery system for innovative RNAi-based cancer therapy."

"Liver cancer is a devastating disease for patients with high mortality and high unmet medical need," stated Michael Molyneaux, MD, Chief Medical Officer of Sirnaomics. "The company is excited to announce first dosing, as we hope to gain important insight into the potential safety and efficacy of STP705 in this Phase 1 trial and build on the data from this study to expand into other oncology indications."

Sirnaomics expects to report initial clinical data from the Phase 1 trial in the second half of 2021. Additional information about this clinical trial is available at clinicaltrials.gov using the identifier: NCT04676633

About Liver Cancer
Liver cancer is a global health problem, with liver neoplasms representing the second-most frequent cause of cancer-related death. There are many different types of liver cancers including hepatocellular carcinoma (HCC), cholangiocarcinoma, liver angiosarcoma, hepatoblastoma, and others. Additionally, the liver is a highly metastasis-permissive organ. It is the most frequently afflicted organ by metastasis and liver metastases are much more common than primary hepatic tumors. The distinctive biology of the liver renders it intrinsically susceptible to metastases. The true prevalence of liver metastasis is unknown, but between 30% and 70% of patients dying of cancer have liver metastases and most patients with liver metastases will die of their disease.

STP705 and Liver Cancer
Over expressions of TGF-β1 and COX-2 have been well-characterized as playing key regulatory roles in tumorigenesis. TGF-β is produced by different liver cells and is demonstrated to induce tumor cell migration and survival. TGF-β has been found to be overexpressed in metastatic HCC tissues. Overexpression of TGF-β is generally accepted to be associated with metastasis and poor prognosis. COX-2 is reported to be highly expressed in cancer stem cells and promotes cell migration in HCC cell lines. Additionally, inhibition of COX-2 suppresses cell migration and induces apoptosis. As such TGF-β1 and COX-2 are excellent therapeutic targets for treatment of liver cancer.

STP705 is composed of two siRNA oligonucleotides targeting TGF-β1 and COX-2 mRNA respectively and formulated in nanoparticles with a proprietary Histidine-Lysine Co-Polymer (HKP) peptide. Each individual siRNA has demonstrated the ability to inhibit the expression of their target mRNA and combining the two siRNAs produces a synergistic effect that diminishes pro-fibrogenic, pro-inflammatory, and pro-tumorigenic factors. Sirnaomics has completed several pre-clinical studies that demonstrate that inhibition of TGF-β1 and COX-2 and is expected to result in the inhibition of tumor growth and provide an alternative approach for the treatment of various liver cancers. Molecular analyses of the effects of administering the combination demonstrated that the inhibition of these targets had effects on downstream gene products associated with numerous oncology targets.

Additional immunohistochemistry and image analyses of the liver and tumor tissues demonstrated that animals treated with STP705 resulted in increased CD4+ and CD8+ T cell infiltration within the tumor microenvironment. Using STP705 for treatments of hepatocellular carcinoma and cholangiocarcinoma have been designated as Orphan Drug indications by U.S. FDA. STP705 has also been evaluated in a Phase 2a clinical trial for treatment of non-melanoma skin cancer.