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Innovent Releases Phase 1a Results of CD47 Monoclonal Antibody (Letaplimab) in Monotherapy for Advanced Malignancies at SITC 2020

On November 10, 2020 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, reported that the results of the Phase 1a study (NCT03763149) of CD47 monoclonal antibody (IBI188, letaplimab) in monotherapy for advanced malignancies, were presented in the form of ePOSTER at the 35th annual meeting of Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC 2020) (Press release, Innovent Biologics, NOV 10, 2020, prnewswire.com/news-releases/innovent-releases-phase-1a-results-of-cd47-monoclonal-antibody-letaplimab-in-monotherapy-for-advanced-malignancies-at-sitc-2020-301170150.html [SID1234570628]).

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The NCT03763149 study is a phase 1a clinical study evaluating the tolerability, safety, and PK/PD properties of IBI188 (letaplimab) as monotherapy for advanced malignancies that failed in standard treatments. The study preset 7 dose groups ranging from 0.1mg/kg to 30mg/kg. Letaplimab was given once a week until disease progression, toxicity intolerance, or other conditions requiring treatment termination.

A total of 20 subjects were enrolled in this study. As of June 18, 2020, letaplimab completed all the preset doses (maximum dose was 30mg/kg QW) without dose-limiting toxicity and was well tolerated in general. Most of the treatment-related adverse events were grade 1-2, with no drug-related adverse reactions leading to permanent discontinuation and treatment-related deaths. In addition, the overall incidence of anemia was 15% (3/20), with only one subject (5%) had experienced grade 3 transient anemia on the first day of the study drug administration but recovered on the next day. Meanwhile, anti-tumor activity was observed in the monotherapy of letaplimab in this study, with multiple patients obtained stable disease for long period.

At present, Innovent successively completed the phase 1a studies in both United States and China to explore the safety of letaplimab with dose expansion up to 30mg/kg. With a total of over 60 subjects enrolled, letaplimab was well tolerated generally. Innovent is conducting a Phase 1b/3 study in China ‘Evaluating the Safety and Efficacy of IBI188 in Combination With Azacitidine in Subjects With Newly Diagnosed Higher Risk Myelodysplastic Syndrome (MDS)’ , and a Phase 1b/2 study in China ‘Efficacy and Safety Evaluation of IBI188 in Combination With Azacitidine in Treatment of Patients With Acute Myeloid Leukemia (AML)’ . In United States, Innovent is conducting a Phase 1b study ‘Evaluating the Safety and Efficacy of IBI188 in Combination With Azacitidine in Subjects With Newly Diagnosed Higher Risk Myelodysplastic Syndrome (MDS)’.

The principal investigator Amita Patnaik from South Texas Accelerated Research Therapeutics (START), stated: " In recent years, immune checkpoint inhibitors have become the focus of intensive research. Letaplimab developed by Innovent Biologics, is a recombinant fully humanized IgG4 monoclonal antibody targeting CD47. The present clinical study demonstrates that letaplimab is well tolerated, with a similar safety profile compared to other anti-CD47 antibodies. Evidence of durable stable disease was observed for letaplimab when administered as monotherapy during the study, which may serve as the rationale for investigating its role in future combinatorial strategies."

" Letaplimab is a global leading anti-CD47 antibody," said Dr. Hui Zhou, Vice President and Head of Medical Science and Strategy Oncology of Innovent. "CD47 is another well-known target after PD-1/PD-L1. Anti-CD47 molecules are under investigation by more than a dozen of companies worldwide, while most are still in phase 1a dose escalation stage. Innovent has successively completed the phase 1a studies in both United States and China, which explored the safety of letaplimab with dose expansion up to 30mg/kg in a total of over 60 subjects. Meanwhile, anemia during CD47 treatment has been one focus area of CD47 drugs, while the safety data in our phase 1a study showed that letaplimab was safe and generally well tolerated, which provides powerful support for the further investigation of letaplimab. Therefore subsequent clinical studies of letaplimab in combination with other agents in a variety of tumor types have already been planned."

"We are now conducting multiple clinical studies in China and United States, further exploring the efficacy and safety of letaplimab in MDS and AML indications. In addition, as an innate immune checkpoint inhibitor, letaplimab has a synergistic anti-tumor effect with T-cell immune checkpoint inhibitor. Innovent will conduct clinical studies of letaplimab combined with TYVYT(Sintilimab injection) in the treatment of multiple solid tumors."

About Letaplimab

Letaplimab, or IBI188, is a recombinant fully humanized IgG4 monoclonal antibody targeting CD47. CD47 is a transmembrane protein that blocks phagocytosis of macrophage by binding to the signaling regulatory protein (SIRP) on the surface of macrophage, to send a "don’t eat me" signal. After blocking this myeloid checkpoint, letaplimab enhanced phagocytosis of tumor cells and cross-activated T cells.

Preclinical data showed that letaplimab had clear target, clear mechanism of action and significant efficacy. The drug was administered continuously for 4 weeks, and the maximum dose without serious toxicity was 100 mg/kg QW. Phase 1a clinical data showed that the escalation of all the preset doses has completed, with the highest exploratory dose of 30mg/kg QW. No dose-limiting toxicity occurred in each dose group, and letaplimab was well tolerated generally.

About NCT03763149 Trial

NCT03763149 is a phase 1a clinical trial conducted in the United States to evaluate the tolerance, safety, and PK/PD properties of Letaplimab monotherapy for advanced malignancies.

In this study, 7 dose groups ranging from 0.1mg/kg to 30mg/kg were preset. Letaplimab was administered once a week until disease progression, toxicity intolerance, or other conditions requiring treatment termination.

Geron to Present at the Stifel Virtual Healthcare Conference

On November 10, 2020 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, reported that John A. Scarlett, M.D., Chairman and Chief Executive Officer, will present a company overview at the Stifel Virtual Healthcare Conference on Tuesday, November 17, 2020 at 2:40 p.m. ET (Press release, Geron, NOV 10, 2020, View Source [SID1234570578]).

A live audio webcast of the presentation will be available on Geron’s website, www.geron.com/investors/events. If you are unable to listen to the live presentation, an archived webcast will be available on the Company’s website for 30 days.

Soligenix Invited to Present at Upcoming Virtual Investor Conferences

On November 10, 2020 Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, reported that its President and Chief Executive Officer, Christopher J. Schaber, PhD, will deliver a corporate presentation at the upcoming virtual investor conferences below (Press release, Soligenix, NOV 10, 2020, View Source [SID1234570562]).

Virtual Fall Investor Summit held on November 16 through 18, 2020, with presentations, one-on-one meetings, round tables, and networking. The Soligenix presentation will be held on Tuesday, November 17 at 9:30AM ET. To view the live webcast, please visit View Source For more information about the Virtual Investor Summit, please refer to the conference website at View Source
A.G.P.’s Virtual Healthcare Symposium on November 19, with one-on-one meetings and executive panels throughout the day. For more information about the A.G.P. Virtual Healthcare Symposium, please refer to the conference website at View Source

Repertoire Immune Medicines Presents First Clinical Data on PRIME IL-15 Cell Therapy in Advanced Metastatic Cancers at Society for Immunotherapy of Cancer (SITC) Annual Meeting

On November 10, 2020 Repertoire Immune Medicines, a clinical-stage biotech company creating a new category of immune therapies for cancer, autoimmunity and infectious disease, reported that preliminary clinical and biomarker data of a Phase 1/2 clinical study for its PRIME IL-15 cell therapy (RPTR-147) in patients with advanced metastatic solid tumors. Preliminary results from the ongoing study will be available on the SITC (Free SITC Whitepaper) Virtual Poster Hall, November 11 – 14, from 9 a.m. to 5 p.m. EST (Press release, Repertoire, NOV 10, 2020, View Source [SID1234570558]). The poster is titled "PRIME IL-15 (RPTR-147): Preliminary clinical results and biomarker analysis from a first-in-human Phase 1 study of IL-15 loaded peripherally-derived autologous T cell therapy in solid tumor patients" (#801).

This first-in-human, multi-center Phase 1/2 study is designed to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity in patients with relapsed or refractory metastatic solid tumors. Following administration of PRIME IL-15, 10 of 17 patients with advanced metastatic disease had stable disease, of which four and patients were stable for more than six months.

Clinical biomarker data also provided evidence of PRIME IL-15 biological activity. Persistence of T cell clones derived from RPTR-147 was observed in both the blood and within the tumor. Further analysis using Repertoire’s DECODE platform is underway to determine the antigen specificity of those cells. Matched evaluable biopsies were obtained in seven patients. Increases in tumor-infiltrating T cell lymphocytes in solid tumor biopsies were observed post treatment in five of seven patients for CD8+ T cells and in four of seven patients for CD4+ T cells.

No dose-limiting toxicities, nor evidence of cytokine-release syndrome, neurotoxicity or other serious immune-related toxicity were observed. The Phase 1/2 study is ongoing and further dose escalation is planned.

"These preliminary PRIME IL-15 clinical results, showing that disease in 10 of 17 patients with aggressive cancers has stabilized, is encouraging," said Harriet Kluger, M.D., Professor of Medicine and Deputy Section Chief of Medical Oncology at the Yale School of Medicine. "Additional study of this new potential therapeutic modality is certainly warranted, and we look forward to continuing to evaluate PRIME IL-15, including at higher doses and in combination with other immune therapies."

PRIME IL-15 is a novel autologous, non-genetically modified multi-clonal T cell product loaded with an IL-15Fc nanogel designed to release this cytokine in a local and sustained manner, limiting systemic exposure and thus improving tolerability. The highest dose of PRIME IL-15 administered in the study to date contained approximately three times more IL-15Fc than the maximum tolerated dose of systemically administered IL-15Fc, but produced less than one tenth of the systemic exposure to free IL-15Fc.

"We are encouraged to see both CD4+ and CD8+ T cells infiltrating into solid tumors following the administration of PRIME IL-15. The use of our proprietary IL-15 nanogel technology coupled with antigen-activated T cells supports a favorable safety profile and our ability to increase dosing going forward," said Anthony Coyle, Ph.D., Repertoire’s President of Research and Development. "PRIME IL-15 is the first T cell investigational therapy with a cytokine nanogel payload and represents a novel class of immune medicines, which we will evaluate in a variety of cancer types. We will build on this research and expand Repertoire’s DECODE and DEPLOY platforms for the creation of targeted immune medicines."

About PRIME IL-15

PRIME IL-15 (RPTR-147) is Repertoire’s first investigational therapy, bringing together the company’s DECODE and DEPLOY technologies in an investigational treatment for a variety of solid tumor. While IL-15 is a cytokine known to regulate the activation and proliferation of T cells, systemic administration is hindered by tolerability. PRIME IL-15 is a novel autologous, non-genetically modified multi-clonal T cell product loaded with an IL-15Fc nanogel designed to release IL-15 in a local and sustained manner, limiting systemic exposure and thus improving tolerability. The product, derived from rare peripherally-derived anti-tumor T cell clones, is a repertoire of immune-enhanced T cells primed against a multi-antigen cassette containing tumor associated antigens (TAA), known to be over-expressed in specific tumor types. PRIME T cells stands for Primed Repertoire of Immune Encoded T cells.

InterVenn Biosciences Reports Results on Vista™ : a Multi-Indication Liquid Biopsy Research Panel Built on Glycoproteomics

On November 10, 2020 InterVenn Biosciences reported that its proprietary liquid biopsy glycoproteomic research panel, Vista, has demonstrated multi-indication performance in early cancer detection based on tests run in the company’s Bay Area laboratory (Press release, InterVenn Biosciences, NOV 10, 2020, View Source [SID1234570557]). InterVenn, in collaboration with several large pharma-biotech and diagnostic users of Vista, has been able to repeatedly and reliably generate multivariable glycopeptide classifiers for a range of different forms of cancer with sensitivities and specificities consistently above 90 and as high as 98 percent.

InterVenn and its research partners have used Vista to demonstrate the power of glycoproteomic profiles as biomarkers for over a dozen different oncology indications, including ovarian, renal, lung, liver, prostate, pancreas, nasopharyngeal, and colorectal cancer, as well as to predict the response to checkpoint-inhibitor treatment. Vista’s application-specific disease classifier panels each consist of a limited number of glycopeptide signatures provide highly targeted readouts with accuracy rates that the "one-size-fits-all approaches" pursued by others have so far generally failed to achieve.

"The push towards personalized medicine and matching patients to the most effective and safest therapy options based on their individual biology– particularly in cancer — has been limited because of our inability to fully understand all the complexities of the patient and the disease," said Aldo Carrascoso, Chief Executive Officer of InterVenn. "The sophisticated, differentiated approach we are taking acknowledges, and masters, the complexity of cancer, and takes the inherent heterogeneity among different malignancies appropriately into account enabling patients and their physicians to jointly make better treatment decisions."

While finding a "pan-cancer" diagnostic test has long been considered the holy grail of cancer screening, the results that have been made available to date have been mixed, generally falling short of the high sensitivity and specificity requirements needed for such screening tests to be clinically useful. Rather than utilizing sequencing technologies, InterVenn has focused its exploratory work on characterizing glycoprotein profiles, arguing that the considerably higher complexity and dynamic range of proteins and their post-translational modifications provide the deep repertoire of analytes that is likely required to yield the resolution needed for highly accurate biomarker panels. Scientists at InterVenn are focused on the glycoproteomic diversity inherent in specific malignancies, as opposed to seeking a "common denominator" that could serve as a generic cancer test.

"The elegance and power of InterVenn’s approach with Vista is that it can be deployed in a highly targeted fashion in individuals at high risk for a particular disease – such as women with BRCA mutations who have a 25-fold risk of ovarian cancer – but that it can also be used to assess the risk for a broad range of malignancies, by determining individual disease-specific risk classifiers of interest from within the entire Vista family. The repertoire of indications accessible through our platform already matches or exceeds that pursued by DNA-based platforms, and is being expanded aggressively," said Klaus Lindpaintner, MD, MPH, Chief Scientific and Medical Officer of InterVenn Biosciences.

InterVenn also recently announced that it has identified marked differences in the glycoproteomic profile of patients who became seriously ill with COVID-19 as compared to individuals who had also been infected with the SARS-CoV-2 virus but experienced no or minimal symptoms. These differences may shed important new light on the natural history of the disease and may relate to interindividual differences in susceptibility. The AI-enabled glycoproteomic analysis of nearly 100 blood samples was conducted in Intervenn’s South San Francisco lab, with additional studies in complementary COVID-19 patients and other reference cohorts still currently ongoing.

"We are very encouraged by the enthusiasm and eagerness we are encountering from scientists in academia as well as industry for this previously inaccessible layer of biology that our technology has opened up to be interrogated. The types of indications and applications our users present to us are a clear validation of the important role glycoproteomics plays in diagnostics as well as drug development. This supports our mission of applying our technology to improve the lives of patients," said Erwin Estigarribia, Chief Operating Officer of InterVenn.