On September 30, 2019 Oragenics, Inc. (NYSE American:OGEN) ("Oragenics"), a leader in the development of novel antibiotics against infectious diseases and effective treatments for oral mucositis, reported initial data from its ongoing Phase 2, placebo-controlled, clinical trial of AG013 in oral mucositis presented in a poster session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2019 in Barcelona, Spain (Press release, Oragenics, SEP 30, 2019, View Source [SID1234539940]).

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Titled, "Severe oral mucositis (SOM) mitigation by genetically modified Lactococcus lactis bacteria (LLB) producing human trefoil factor 1 (hTFF1; AG013) in patients being treated with concomitant chemoradiation (CRT) for oral and oropharyngeal cancers (OCOPC)," was presented at the ESMO (Free ESMO Whitepaper) Congress 2019 in Barcelona, Spain. The poster can be found under the "Presentations" tab in the "News and Media" section of the Company’s website, located at www.oragenics.com.

The poster presentation describes the methods and initial blinded results from the ongoing Phase 2 clinical trial for the Company’s lead oral mucositis product candidate, AG013. The ongoing Phase 2 clinical trial is a double-blind, placebo-controlled, two-arm, multi-center trial, in which approximately 200 patients will be randomized in a 1:1 ratio to receive either AG013 or placebo three times daily following meals, beginning on the first day of chemoradiation therapy and continuing through the course of cancer treatment. The purpose of this Phase 2 clinical study, (NCT03234465), is to evaluate the efficacy (preventing the occurrence and shortening the duration of SOM), safety, and tolerability of a convenient topically administered rinse of AG013 compared to a placebo for reducing the incidence and severity of oral mucositis in patients undergoing traditional chemoradiation for the treatment of head and neck cancer. The initial data, submitted in the abstract, reflects the results for 42 of the 71 enrolled and randomized patients across 48 study sites and demonstrates that in the blinded, combined placebo and active treatment groups, there was sufficient evidence of efficacy and safety to continue the study.

Additional data accumulated since poster submission, indicates the blinded efficacy evaluation, which included any patient with SOM after week one of treatment and those receiving a cumulative dose of 55 Gy (week 6 of treatment), demonstrated an overall SOM incidence of 47%, which is lower than would be expected based on historical data in the head and neck cancer population receiving this chemoradiation regimen. The overall rate of SOM was reported in only 13.1 % (110 of 842) of evaluable visits. The overall safety profile is consistent with those adverse events that normally occur in cancer patients receiving chemoradiation therapy. As a reminder, the study remains blinded and individual treatment responses remain to be identified. The lead author for the poster presentation is Suraj Singh, M.D., of the MultiCare Regional Cancer Center in Tacoma, Washington.

Alan Joslyn, President & CEO of Oragenics, Inc. said, "As we recently announced, we are more than 75 percent enrolled in this study, and we continue to be encouraged by both the pace of enrollment and the overall clinical results as reported in this poster presentation. While it remains difficult to comment on efficacy outcomes based on these data, we are pleased with the safety profile we are seeing in the study. Due to the high incidence of SOM in head and neck cancer patients, and the blinded results seen to date, we maintain the belief that this compound will provide a convenient meaningful therapeutic benefit for these patients with limited treatment alternatives and no therapies available for prevention of their oral mucositis."

About Oral Mucositis

Oral mucositis is currently one of the most common and debilitating complications of cancer chemo- and radiation therapy. The condition is caused by the breakdown of the mucosal lining in the oral cavity resulting in the formation of painful mouth ulcers. When these mouth ulcers progress to World Health Organization (WHO) grade 3 and 4, patients by definition, have their ability to eat (grade 3) and drink (grade 4) impacted resulting in emergency room visits or hospitalization in order to provide pain control and nutritional support. During these periods, patients run the risk of interruption of their chemo- and radiation therapies with the potential risk of negative cancer treatment outcomes. The incidence of SOM is approximately 70% in oropharyngeal cancer patients.

About AG013

AG013, which has been granted Fast Track designation with the U.S. Food and Drug Administration and orphan drug status in Europe, is an ActoBiotics therapeutic candidate formulated to deliver the therapeutic molecule Trefoil Factor 1 to the mucosal tissues in the oral cavity in a convenient oral rinsing solution. Trefoil Factors are a class of peptides involved in the protection of gastrointestinal tissues against mucosal damage and play an important role in subsequent repair. The compound was designed by the company’s strategic partner, ActoBio Therapeutics, Inc., a wholly-owned subsidiary of Intrexon Corporation (NYSE:XON).

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 ASLAN Pharmaceuticals (Nasdaq:ASLN, TPEx:6497), a clinical-stage oncology and immunology focused biopharma company, and Bukwang Pharmaceutical (KRX:003000), a leading R&D focused Korean pharmaceutical company, reported that they have established a new joint venture to develop preclinical aryl hydrocarbon receptor (AhR) antagonists from ASLAN’s early stage pipeline (Press release, ASLAN Pharmaceuticals, SEP 30, 2019, View Source [SID1234539975]). The independent company, JAGUAHR Therapeutics, will focus on developing new immuno-oncology therapeutics for global markets targeting the AhR pathway and will be based in Singapore.

Under the terms of the agreement, ASLAN will transfer the global rights to all of the assets related to AhR technology, originally discovered and developed by ASLAN and its collaborator Dr Mark Graham, into JAGUAHR. Bukwang will invest US$5 million in JAGUAHR in two tranches to fund the development of the assets, identify a lead development compound and file an Investigational New Drug application.

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Dr Carl Firth, Chief Executive Officer, ASLAN Pharmaceuticals, said: "The launch of JAGUAHR Therapeutics is an important step by ASLAN to realise the value of our early stage assets and advance the development of our AhR antagonist technology at a time when focus is shifting towards AhR antagonists as a hot new area in immuno-oncology. Bukwang has a strong track record of achievement in the pharma business and creating this spinout together allows both companies to quickly progress these exciting compounds and potentially provide novel clinical assets to enrich the ASLAN pipeline. We look forward to working with the Bukwang team as we focus on identifying JAGUAHR’s first drug candidate."

Dr Hee-Won Yoo, Chief Executive Officer, Bukwang Pharmaceutical, added: ""We are impressed and delighted to partner with ASLAN to establish JAGUAHR Therapeutics. Bukwang has a strong heritage in R&D and this agreement is aligned to our strategy to strengthen our innovative development pipeline and broaden early access to promising technology for treating conditions with unmet needs. We are very excited as the AhR antagonists program further marks Bukwang’s formal participation in the immuno-oncology arena. We look forward to working together with ASLAN to progress these novel immuno-oncology compounds into clinical development in oncology."

AhR is a druggable transcription factor that acts as a master regulator of the immune system. The enzymes IDO1, IDO2 and TDO are frequently overexpressed in numerous tumour types and convert tryptophan into kynurenine (KYN) in the tumour microenvironment. KYN is then actively transported into dendritic cells and effector T-cells that are mobilised to detect and kill tumour cells. KYN signalling via AhR in these cell types converts them into regulatory T-cells, suppressing the immune system and preventing it from attacking tumour cells. Research has demonstrated

that the unique advantages of AhR antagonists include broadly inhibiting the signalling of all AhR ligands1 produced by any enzyme that metabolises tryptophan, and robust activation of the immune response to kill cancer cells.

Ends

Media and IR contacts

For ASLAN Pharmaceuticals Limited

Emma Thompson

Spurwing Communications

Tel: +65 6571 2021

Email: [email protected]

Robert Uhl

Westwicke Partners

Tel: +1 858 356 5932

Email: [email protected]

For Bukwang Pharmaceutical Co., Ltd.

Riswanto

Global Business Development

Tel: +82-2-828-8072

Email: [email protected]

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 [SID1234539908]). 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 Deciphera Pharmaceuticals, Inc. (Nasdaq:DCPH), a clinical-stage biopharmaceutical company addressing key mechanisms of tumor drug resistance, reported the late-breaking presentation of results from the INVICTUS pivotal Phase 3 clinical study of ripretinib in patients with advanced gastrointestinal stromal tumors (GIST) in an oral session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress (Press release, Deciphera Pharmaceuticals, SEP 30, 2019, View Source [SID1234539925]).

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"For GIST patients who have failed currently approved agents, there exists an urgent need for effective and well-tolerated treatment options," said Margaret von Mehren, MD, Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. "With a statistically significant improvement observed in progression free survival compared with placebo, and a clinically meaningful increase in overall survival compared with placebo, ripretinib represents a potential standard of care for patients harboring a broad spectrum of mutations known to drive GIST in patients who have no approved treatment options."

"Results from the INVICTUS study support our belief that ripretinib has the potential to transform the current treatment landscape for advanced GIST," said Steve Hoerter, President and Chief Executive Officer of Deciphera. "We are now working with the FDA as we prepare the NDA submission for ripretinib, which we expect in the first quarter of 2020."

Today’s presentation featured new data as well as top-line results previously announced by the Company in August 2019. A copy of the presentation will be available following the session at www.deciphera.com.

INVICTUS Study Results

The INVICTUS Phase 3 clinical study is a randomized (2:1), double-blind, placebo-controlled, international, multicenter study to evaluate the safety, tolerability, and efficacy of ripretinib compared to placebo in 129 patients with advanced GIST whose previous therapies have included at least imatinib, sunitinib, and regorafenib. As previously reported, the study achieved the primary endpoint of improved progression free survival (PFS) compared to placebo in patients with fourth-line and fourth-line plus GIST, as determined by blinded independent central radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Progression Free Survival (PFS)

Ripretinib significantly reduced the risk of disease progression or death by 85% compared to placebo and demonstrated a median PFS of 6.3 months compared to 1.0 month in the placebo arm (HR=0.15, 95% CI (0.09,0.25), p<0.0001). This PFS benefit was consistent across all assessed patient subgroups.

Objective Response Rate (ORR) and Duration of Response

Eight patients (9.4%) had a confirmed objective response with ripretinib (p=0.0504) compared to no confirmed responses in the placebo arm, as measured by blinded independent central review, which was not statistically significant. As of the cutoff date of May 31, 2019, the median duration of response had not been reached with seven of the eight patients still responding to treatment. All responders had partial responses.

Overall Survival (OS)

Ripretinib reduced the risk of death by 64% compared to placebo and demonstrated a median OS of 15.1 months vs. 6.6 months in the placebo arm (HR=0.36, 95% CI (0.20,0.62), nominal p=0.0004). Since statistical significance was not achieved for the secondary endpoint of ORR, the hypothesis testing of OS was not formally performed. According to the pre-specified hierarchical testing procedure of the endpoints, the hypothesis testing of OS cannot be formally conducted unless the test for ORR is statistically significant.

Safety

Ripretinib was generally well tolerated and the adverse events observed in INVICTUS were consistent with data from previously presented Phase 1 study results. Treatment-emergent adverse events (TEAEs) occurred in 99% of patients on the ripretinib arm compared to 98% on the placebo arm. Grade 3 or 4 TEAEs occurred in 49% of patients on the ripretinib arm compared to 44% on the placebo arm. Grade 3 or 4 TEAEs greater than 5% of patients on the ripretinib arm were anemia (9%), abdominal pain (7%) and hypertension (7%). Grade 3 or 4 TEAEs greater than 5% of patients on the placebo arm were anemia (14%). TEAEs leading to dose reduction occurred in 7% of patients on the ripretinib arm compared to 2% on the placebo arm. TEAEs leading to dose interruption occurred in 24% of patients on the ripretinib arm compared to 21% on the placebo arm. TEAEs leading to study treatment discontinuation occurred in 8% of patients on the ripretinib arm compared to 12% of patients on the placebo arm. TEAEs leading to death occurred in 6% of patients on the ripretinib arm compared to 23% on the placebo arm.

New Drug Application (NDA) Submission

Based on the positive INVICTUS data, the Company expects to submit an NDA to the U.S. Food and Drug Administration (FDA) for ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib in the first quarter of 2020.

About the INVICTUS Phase 3 Study

The INVICTUS Phase 3 clinical study is a randomized, double-blind, placebo-controlled, international, multicenter study to evaluate the safety, tolerability, and efficacy of ripretinib compared to placebo in patients with advanced GIST whose previous therapies have included imatinib, sunitinib, and regorafenib. This study was designed to provide evidence of clinical benefit in fourth-line and fourth-line plus patients with GIST that would be required to secure a regulatory approval. Patients were randomized 2:1 to either 150 mg of ripretinib or placebo once daily. The primary efficacy endpoint is progression-free survival (PFS) as determined by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints as determined by independent radiologic review using modified RECIST include Objective Response Rate (ORR), Time to Tumor Progression (TTP) and Overall Survival (OS). See www.clinicaltrials.gov for further information (NCT03353753).

About Ripretinib

Ripretinib is an investigational tyrosine kinase switch control inhibitor that was engineered to broadly inhibit KIT and PDGFRα mutated kinases by using a unique dual mechanism of action that regulates the kinase switch pocket and activation loop. Ripretinib is currently in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, including gastrointestinal stromal tumors, or GIST, systemic

mastocytosis, or SM, and other cancers. Ripretinib inhibits initiating and secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18, involved in GIST, as well as the primary D816V exon 17 mutation involved in SM. Ripretinib also inhibits primary PDGFRα mutations in exons 12, 14 and 18, including the exon 18 D842V mutation, involved in a subset of GIST. In June 2019, the U.S. FDA granted Fast Track Designation to ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib.

Deciphera Pharmaceuticals has an exclusive license agreement with Zai Lab (Shanghai) Co., Ltd. for the development and commercialization of ripretinib in Greater China (Mainland China, Hong Kong, Macau and Taiwan). Deciphera Pharmaceuticals retains development and commercial rights for ripretinib in the rest of the world.