On September 30, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium") reported that it will be attending the 2019 Cell & Gene Meeting on the Mesa being held October 2nd – October 4th in Carlsbad, CA (Press release, Actinium Pharmaceuticals, SEP 30, 2019, View Source;gene-meeting-on-the-mesa-300927503.html [SID1234539961]). Members of Actinium’s executive and R&D teams will highlight the Iomab-ACT program at the meeting. To schedule a meeting with Actinium please email Eileen Geoghegan, Ph.D., at [email protected] or through the meeting’s partnering system View Source

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Actinium is developing its Iomab-ACT program to be a universal lymphodepletion regimen to replace chemotherapy-based regimens such as Flu/Cy (Fludarabine and Cyclophosphamide) that are used in standard practice today. Actinium proposes that Iomab-ACT has a multi-modal mechanism of action that can; 1) deplete lymphocytes to create a suitable homeostatic cytokine environment; 2) deplete immune suppressive cell populations that may hinder activation of CAR-T cells; (3) deplete macrophages that may secrete cytokines implicated in CRS and neurotoxicity; and (4) potential anti-tumor effect on CD45+ blood cancer cells.

Iomab-ACT is an ARC or Antibody Radiation-Conjugate that targets the antigen CD45, which is uniquely expressed on leukemia, lymphoma and immune cells making it an ideal target for targeted condition prior to CAR-T and adoptive cell therapies. Iomab-ACT is a lower, outpatient, non-myeloablative dose of Actinium’s lead program, Iomab-B, which has been studied in over 300 patients and is currently being studied as a targeted conditioning agent prior to bone marrow transplant in a pivotal Phase 3 trial.

Actinium presented initial feasibility data for its ACT program at the Transplantation and Cellular Therapies Meeting in February 2019. The data demonstrated that a CD45 targeting antibody labeled with the radioisotope Iodine-131 effectively depleted greater than 90% of lymphocytes and other immune cells while sparing platelets, neutrophils and bone marrow stem cells in preclinical animal models (Click here for TCT poster). Additionally, in a preclinical model of adoptive cell therapy, the CD45-targeted ARC enabled improved tumor control. Actinium also presented data at the Society of Nuclear Medicine and Molecular Imaging demonstrating that the Iomab-ACT program could utilize the radioisotope Lutetium-177 with an anti-CD45 antibody to achieve targeted lymphodepletion prior to adoptive cell therapy (Click here for SNMMI poster).

About the Cell & Gene Meeting on the Mesa

The Cell & Gene Meeting on the Mesa is the sector’s foremost annual conference bringing together senior executives and top decision-makers in the industry to advance cutting-edge research into cures. Tackling the commercialization hurdles facing the cell and gene therapy sector today, this meeting covers a wide range of topics from clinical trial design to alternative payment models to scale-up and supply chain platforms for advanced therapies. The program features expert-led panels, extensive partnering capabilities, exclusive networking opportunities, and 70+ dedicated presentations by the leading publicly traded and privately held companies in the space. Attracting over 1,150 attendees – over 20% of which are C-level executives – this conference enables key partnerships through more than 2,200 one-on-one meetings while highlighting the significant clinical and commercial progress in the field.

On September 30, 2019 SkylineDx reported, during the European Society for Medical Oncology congress (Barcelona, EU), that it successfully validated the performance of their skin cancer (melanoma) diagnostic test on the first, independent, European dataset (Press release, SkylineDx, SEP 30, 2019, View Source [SID1234539960]). This melanoma test combines genetic information from a patient’s tumor cells (taken during a diagnostic biopsy) with tumor – and patient specific characteristics. Based on this unique combination, the test is able to accurately predict the risk of having metastasis present in the lymph nodes without a patient having to undergo a surgery to remove (part of the) lymph nodes. The discovery came from an US patient population and remains robust in the Dutch validation population, saving 41% of patients an unnecessary surgical intervention [2].

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These positive results follow last week’s announcement of launching a pilot study to evaluate and optimize the diagnostic services in clinical practice with a renowned US hospital in Q4 2019 and the start of a national trial in the US in 2020 [3]. "I am always anxious going into validation. If you optimize the performance of a test too much on the initial dataset, it will only work in that dataset and fails in an independent dataset," says Dharminder Chahal, CEO SkylineDx. "That we may present these positive results today during this major conference, is fantastic news for our team and gives everyone the needed energy and enthusiasm to continue the developments in our Falcon R&D Program to get this test from bench to bedside as quickly as possible."

On September 30, 2019 GlaxoSmithKline plc (LSE/NYSE: GSK ) reported an inducible T cell costimulatory molecule (ICOS) designed to selectively enhance T cell function The agonist antibody GSK3359609 exhibits promising antitumor activity in combination with pemizumab in the treatment of patients with head and neck squamous cell carcinoma (HNSCC) PD-1/L1 (Press release, GlaxoSmithKline, SEP 30, 2019, View Source;834146127.html [SID1234539959]). The results of the INDUCE-1 study also showed that GSK3359609 has a single drug activity in the treatment of patients with head and neck squamous cell carcinoma PD-1/L1.

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The safety and tolerability of GSK3359609 is consistent with the results reported in the INDUCE-1 (dose escalation phase). The data was released at the 2019 European Conference of Cancer Society in Barcelona, ​​Spain.

GlaxoSmithKline reported that the inducible T cell costimulatory molecule (ICOS) agonist antibody GSK3359609, which is designed to selectively enhance T cell function, is combined with pemizumab for the treatment of head and neck squamous cell carcinoma (HNSCC) PD- The 1/L1 initial treatment patient showed promising anti-tumor activity.

Dr. Axel Hoos , senior vice president and head of oncology research and development , said: "GSK3359609 and other immunotherapy are key components in the field of oncology. INDUCE-1 data demonstrates that GSK3359609 enhances antitumor activity (beyond We are encouraged by the potential of PD-1 to block the anti-tumor activity. The observed clinical response is very encouraging. Based on the precedent of CTLA-4 or PD-1, we want to prove our ICOS The main effect of agonists is to improve patient survival, and this requires further research. Based on these results, we will launch the INDUCE-3 registration trial, which combines the use of GSK3359609 and pemizumab to treat first-line recurrence/metascale head and neck scales. Potential survival benefits of patients with squamous cell carcinoma (PD-L1 positive)."

The published data comes from the development phase of INDUCE-1, the first open-label study in humans to study GSK3359609 as a monotherapy and a combination of other regimens. The patients in the study had relapsed or metastatic head and neck squamous cell carcinoma, and had previously received up to five therapies in the late stages. Patients in the monotherapy group were previously treated with PD-1/L1 and 1 mg/kg GSK3359609. Patients in the combination drug group received PD-1/L1 treatment for the first time, taking 0.3 mg/kg GSK3359609 and 200 mg pemizumab. Patients in both groups received a two-year assessment until the condition progressed or unacceptable toxicity occurred.

Of the 34 patients who received combination therapy, the overall response rate was 24% (n=8; 95% CI: 11,58.7). Remission in the combination drug group was long-lasting, and all responders maintained a 6-month or longer improvement (no median; 95% CI: 4.2 months, NR); median progression-free survival (PFS) ) for 5.6 months (95% CI: 2.4, 7.4). Among the 21 patients with known PD-L1 expression data, most responders and stable patients had a PD-L1 score of less than 20 points. Among the 16 patients who underwent monotherapy, the overall response rate was 6% (n = 1; 95% CI: 0.2, 30.2).

The INDUCE-1 study was conducted in accordance with an agreement between GlaxoSmithKline and Merck & Co, Inc. ("MSD" outside the United States and Canada). GlaxoSmithKline will continue to work with MSD to support the INDUCE-3 Phase II/III combination drug trials to be launched by the end of 2019.

Head and neck squamous cell carcinoma is a cancer developed from squamous cells in the mouth, nose and throat mucosa. It is the seventh most common cancer in the world, with approximately 600,000 newly diagnosed cases each year. i Although head and neck squamous cell carcinoma is more common in the over 50-year-old or 60-year-old men, but the incidence in younger individuals is increasing. Ii Head and neck squamous cell carcinoma tumors are highly immunogenic and have high expression of immunological checkpoint regulators (including ICOS and PD-1). Iii

The GSK3359609 Clinical Development Program
GSK3359609 clinical development program aims to investigate the anti-tumor potential of a variety of tumor-targeted ICOS receptors by single agonist antibodies in combination with other immunological checkpoint therapies.

GSK3359609 is not currently approved for use anywhere in the world.

i Genetics Home Reference. Head and neck squamous cell carcinoma – Genetics Home Reference – NIH. US National Library of Medicine. View Source Statistics. Published January 2015 . Accessed September 1, 2019 .

I National Institute of Health. Head and neck squamous cell carcinoma. US National Library of Medicine. View Source. Published August 20, 2019 .

Iii Canning M, et al. Heterogeneity of the Head and Neck Squamous Cell Carcinoma Immune Landscape and Its Impact on Immunotherapy. Front Cell Dev Biol. 2019; 7: 52.

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GlaxoSmithKline’s performance in the field of oncology

GlaxoSmithKline is committed to maximizing patient survival by converting drugs. GlaxoSmithKline focuses on immuno-oncology, cell therapy, cancer epigenetics and overall mortality. The company’s goal is to achieve a sustainable flow of new therapies based on a diverse portfolio of research drugs, using small molecules, antibodies, antibody drug combinations and cells, either alone or in combination.

On September 30, 2019 Debiopharm, a Swiss-based global biopharmaceutical company, reported, at the ESMO (Free ESMO Whitepaper) Congress (European Society for Medical Oncology), compelling results from a robust, randomized, Phase II study of Debio 1143 for the treatment of high-risk, locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) patients in combination with current standard of care, chemo-radiotherapy (CRT) (Press release, Debiopharm, SEP 30, 2019, View Source [SID1234539958]). Clinical results with Debio 1143, the most clinically advanced IAP antagonist, revealed a statistically significant improvement of the primary endpoint locoregional control rate (LRC – 21% improvement at 18 months after CRT vs. control arm) and a striking progression-free survival (PFS) benefit vs. the control arm after a 2-year follow-up period.

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This double-blind, randomized, control group study, combined Debio 1143 with CRT in patients with previously untreated stage III, IVA or IVB SCCHN. The majority of patients enrolled were considered high-risk, facing a poor prognosis, including HPV-negative oropharyngeal cancer (OPC) patients and heavy smokers (>10 pack-years). Ninety-six patients were enrolled at 19 centers across France and Switzerland. The study explored whether the addition of Debio 1143 at 200 mg/d to standard CRT could increase treatment efficacy compared to CRT and placebo. The primary endpoint of LRC-rate at 18 months was met. For key secondary endpoints, clinically compelling and statistically significant outcomes in Progression-Free survival (PFS) at 24-months were observed along with positive trends for overall survival (OS) and complete response (CR) rates in the active treatment group vs. CRT+placebo, although these parameters have not yet reached statistical maturity.

"Combined with the standard of care, Debio 1143 has demonstrated significant efficacy – especially in locoregional control rate and progression free survival – in high-risk previously untreated LA-SCCHN patients," commented Pr. Jean Bourhis, Head of the Radio-Oncology Department CHUV, Lausanne, Switzerland, and Lead Investigator of the study. "The chemo-radio-sensitizing effect of Debio 1143 constitutes a highly promising strategy to ultimately allow high-risk head and neck patients to achieve better control over their disease for longer."

"The positive topline results are very encouraging and support our efforts to provide head and neck cancer patients and clinicians with this potential new treatment option," said Bertrand Ducrey, CEO of Debiopharm International. "This data demonstrates proof of concept for the potential use of Debio 1143 in other CRT applications, potentially expanding therapeutic reach and making a difference in a wide range of indications."

In addition, Debio 1143 showed a predictable and manageable safety profile, without substantial additional toxicity to standard CRT.

ESMO 2019 Session Details

Abstract

Presenting investigator

Sept. 30th , 10:15am
Cordoba Auditorium
(Hall 7)

Preferred Paper –
Head and neck cancer

LBA65 – Double-blind Randomized Phase 2 Results
Comparing Concurrent Highdose Cisplatin Chemorradiation
(CRT) plus Debio 1143 or Placebo In High-risk Patients with
Locally Advanced Squamous Cell Carcinoma of the Head
and Neck (SCCHN): A GORTEC Study

Prof. Jean Bourhis,

Head of the Radio-
Oncology Department
CHUV, Lausanne,
Switzerland, Lead
study author

About Debio 1143
Debio 1143 is an antagonist of IAPs (inhibitor of apoptosis proteins), acting as chemo-radio-sensitizer to enhance treatment efficacy with a dual mode of action, promoting programmed cell death and fostering anti-tumor immunity. Currently in clinical development in a broad range of cancer types, the compound is being developed in combination with chemo-radiotherapy or with ICIs (PD-1/PD-L1), with reported data consistently showing a favorable safety profile. Over 200 patients have been treated so far with Debio 1143 in various indications and lines of treatment.

Trial information:

Head & neck cancers: patients.debiopharm.com/head-and-neck-cancer/
Small cell lung cancers: patients.debiopharm.com/small-cell-lung-cancer-sclc/
Gastrointestinal cancers: patients.debiopharm.com/gastrointestinal-cancers/
Gynecologic cancers: patients.debiopharm.com/gynecologic-cancer/
Debiopharm’s commitment to cancer patients
Debiopharm aims to develop innovative therapies that target high unmet medical needs in oncology. Bridging the gap between disruptive discovery products and real-world patient reach, we identify high-potential compounds for in-licensing, clinically demonstrate their safety and efficacy and then select large pharmaceutical commercialization partners to maximize patient access globally.

On September 30, 2019 GlaxoSmithKline plc (LSE / NYSE: GSK ) reported that the drug GSK3359609, an agonist antibody to inducible T-cell costimulators designed to selectively increase the function of T cells showed a promising antitumor activity in combination with pembrolizumab in patients with squamous cell carcinoma of the head and neck (HNSCC) without prior anti-PD-1 / L1 treatment (Press release, GlaxoSmithKline, SEP 30, 2019, View Source;811996364.html [SID1234539957]). The results of the INDUCE-1 study also suggested that GSK3359609 has activity as a single agent in patients with HNSCC with a history of anti-PD-1 / L1 treatment.

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The safety and tolerance profile of GSK3359609 was consistent with the results reported in the dose increase phase of the INDUCE-1 study. The data were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress in Barcelona , Spain.

Dr. Axel Hoos, Senior Vice President and Director of R&D in Oncology, commented: "Immunotherapies such as GSK3359609 are a crucial part of our line of cancer products, and we are encouraged by the data from the INDUCE-1 study that demonstrate the potential of this agent to improve Antitumor activity beyond what PD-1 blockade has demonstrated individually The clinical responses observed are encouraging, and based on the precedent with CTLA-4 or PD-1, we aim to demonstrate that the main effect of our ICOS agonist is an improvement in survival for patients, which requires additional studies.On the basis of these results we are initiating the INDUCE-3 study for initial authorization,in order to investigate the potential survival benefit of GSK3359609 with pembrolizumab as a first line in recurrent or metastatic HNSCC for patients positive for PD-L1 ".

The data presented arise from the expansion phase of INDUCE-1, an open study, first in humans, to investigate the drug GSK3359609 as monotherapy and in combination with other regimens. The patients included in the study had recurrent or metastatic HNSCC, and had received up to five lines of prior treatment in the advanced setting. Patients in the monotherapy cohort had received prior anti-PD-1 / L1 treatment, and were given 1 mg / kg of GSK3359609. Patients in the combined treatment cohort had not received prior anti-PD-1 / L1 treatment, and received 0.3 mg / kg of GSK3359609 and 200 mg of pembrolizumab. Patients were evaluated in both cohorts, until the disease progressed or the occurrence of an unacceptable toxicity, for a maximum of two years.

In the 34 evaluable patients who received the combined therapy, the overall response rate was 24% (n = 8; 95% CI: 11, 58.7). The responses in the combined treatment cohort were long lasting, and all patients with response maintained the benefit for 6 months or more (the median was not reached; 95% CI: 4.2 months, NR); The median progression-free survival (SSP) was 5.6 months (95% CI: 2.4, 7.4). Of the 21 patients with known PD-L1 expression data, the majority of patients with response and patients with stable disease had a PD-L1 score below 20. Of the 16 evaluable patients who received monotherapy, the rate of Overall response was 6% (n = 1; 95% CI: 0.2, 30.2).

The INDUCE-1 study was conducted in accordance with an agreement between GSK and Merck & Co, Inc., Kenilworth, NJ , USA. UU. (known as MSD outside the United States and Canada). GSK continues its relationship with MSD to support the combined phase II / III INDUCE-3 clinical study, which will begin in late 2019.

HNSCC is a cancer that develops from squamous cells in the mucous membranes of the mouth, nose and throat, and is the seventh cancer in terms of frequency worldwide, with approximately 600,000 new cases diagnosed each year. i Although HNSCC appears more frequently in men in the fifth or sixth decade of life, the incidence is growing among younger individuals. ii HNSCC tumors are highly immunogenic, and have high expression of immune control point modulators, including ICOS and PD-1. iii

GSK3359609 Clinical Development Program
The clinical development program for GSK3359609 seeks to investigate the anti-tumor potential of targeting the ICOS receptor through an agonist antibody alone and in combination with other therapies against immune control points for the treatment of a range of types of tumors

Currently GSK3359609 is not approved for use anywhere in the world.

GSK in oncology
GSK focuses on maximizing patient survival through transformative medications. The GSK product line focuses on immuno-oncology, cell therapy, cancer epigenetics and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational drugs that use modalities such as small molecules, antibodies, cells and antibody-drug conjugates, either alone or in combination.