On November 9, 2020 Alkermes plc (Nasdaq: ALKS) reported the presentation of new data from the ARTISTRY clinical development program for ALKS 4230, Alkermes’ investigational engineered interleukin-2 (IL-2) variant immunotherapy, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 35th Anniversary Annual Meeting, being held virtually Nov. 11-14, 2020 (Press release, Alkermes, NOV 9, 2020, View Source [SID1234570663]). The company will present preliminary safety, tolerability and pharmacokinetic/pharmacodynamic data from the dose-escalation stage of ARTISTRY-2, the ongoing phase 1/2 study evaluating ALKS 4230 administered subcutaneously (SC) either once-weekly or once-every-three-weeks. A detailed analysis of clinical responses observed in ovarian cancer patients and other new updates from ARTISTRY-1, the ongoing phase 1/2 study investigating ALKS 4230 administered intravenously (IV), will also be presented. Both studies are evaluating ALKS 4230 as a monotherapy and in combination with the PD-1 inhibitor pembrolizumab (KEYTRUDA) in patients with heavily pretreated advanced solid tumors.

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!

"Accumulating evidence across the ARTISTRY clinical program provides insight into ALKS 4230’s potential as a novel treatment option, both as monotherapy in melanoma and in combination with pembrolizumab, for a number of tumor types that do not typically respond to current standards of care. The responses observed with the combination regimen in platinum-resistant ovarian cancer, triple negative breast cancer, and recently in cervical cancer, are encouraging signs of ALKS 4230’s potential utility in these cancers," said Ira Winer, M.D., Ph.D., Associate Professor, Division of Gynecologic Oncology, Wayne State University and Karmanos Cancer Institute. "In addition, the data presented at SITC (Free SITC Whitepaper) from ARTISTRY-2 in patients with advanced solid tumors showed a safety profile and immune response comparable to ALKS 4230 administered intravenously, indicating that ALKS 4230 may offer an alternate subcutaneous dosing option for patients."

"The ALKS 4230 subcutaneous dose-escalation data in heavily pretreated patients with certain solid tumors demonstrated expansion of tumor-killing CD8+ T cells and NK cells consistent with the expansion observed with intravenous dosing of ALKS 4230. These data support the potential for once-weekly or once-every-three-week subcutaneous dosing of ALKS 4230, for which we expect to identify our recommended phase 2 dose by year-end," said Craig Hopkinson, M.D., Chief Medical Officer and Executive Vice President of Research & Development at Alkermes. "Further, based on the durable complete and partial responses observed in the ARTISTRY-1 intravenous dosing study in tumor types with high unmet need and limited treatment options for patients, we are considering potential regulatory strategies that may support expeditious development paths in both monotherapy and combination settings."

The two posters are available on the SITC (Free SITC Whitepaper) website at View Source Highlights from the poster presentations, which reflect data as of Sept. 29, 2020 unless otherwise noted, include:

Poster #671: Phase 1/2 Study of Subcutaneously Administered ALKS 4230, a Novel Engineered Cytokine, as Monotherapy and in Combination With Pembrolizumab, in Patients With Advanced Solid Tumors: ARTISTRY-2
The ongoing dose-escalation stage of ARTISTRY-2 is evaluating the safety and tolerability of ascending doses of SC ALKS 4230 administered either once-weekly (Q7) or once-every-three-weeks (Q21) as lead-in monotherapy for six weeks, followed by combination with pembrolizumab. The pharmacokinetic/pharmacodynamic (PK/PD) data presented include seven dose-escalation cohorts of SC ALKS 4230 (Q7: 0.3, 0.6, 1, 3 mg; Q21: 1, 3, 10 mg):

ALKS 4230 was assessed in 43 heavily pretreated patients with refractory solid tumors. Of these, 30 patients completed the monotherapy lead-in portion of the study and initiated combination treatment with pembrolizumab.
Treatment with SC ALKS 4230 resulted in a dose-dependent increase in circulating natural killer (NK) cells and CD8+ T cells, with an approximately 16-fold and 3-fold expansion, respectively, at the 3 mg Q7 dose. At the 10 mg Q21 dose there was an approximately 6-fold and 3-fold expansion in NK cells and CD8+ T cells, respectively. There was a minimal, non-dose-dependent change in regulatory T (Treg) cells.
The NK and CD8+ T cell expansions observed for the 3 mg Q7 and 10 mg Q21 SC doses were equivalent or greater compared to the expansions observed in ARTISTRY-1 at the 3 µg/kg/day and 6 µg/kg/day IV doses of ALKS 4230, respectively.
Compared to the 6 µg/kg/day IV dose, the recommended phase 2 dose (RP2D) identified for ARTISTRY-1, the 3 mg and 10 mg doses of SC ALKS 4230 induced higher levels of interferon gamma, a cytokine that has been associated with antitumor efficacy in clinical studies.1 Relative to IV ALKS 4230, SC ALKS 4230 induced a lower, transient upregulation of IL-6 concentrations.
ALKS 4230 at the SC doses studied showed a safety and tolerability profile consistent with the anticipated pharmacologic effects and what has been observed with IV ALKS 4230. The most commonly reported adverse events (AEs) across the ARTISTRY-2 study were injection site reactions, fever, chills, fatigue, nausea and lymphopenia. One patient experienced dose-limiting AEs at the 10 mg Q21 dose (grade 3 nausea, vomiting, and fatigue). Following a dose reduction, the patient continued on study.
Preliminary clinical benefit was observed, even in immunotherapy-pretreated patients. As of the data cutoff date, 11 patients had continued on therapy for more than 6 months.
The maximum tolerated dose and the RP2D for SC ALKS 4230 have not yet been determined.
Poster #689: Clinical Outcomes of Ovarian Cancer Patients Treated With ALKS 4230, a Novel Engineered Cytokine, in Combination With Pembrolizumab: ARTISTRY-1 Trial
Data presented from the ongoing ARTISTRY-1 study focused on the subset of PD-1/L1 unapproved patients with progressive, resistant ovarian cancer who received ALKS 4230 administered intravenously in combination with pembrolizumab. These data provide an updated and more in-depth view of responses previously reported at the 2020 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress. In addition, new data on the effects of IV ALKS 4230 monotherapy on the tumor microenvironment (TME) and additional updates from other tumor types were presented.

Of the 13 evaluable ovarian cancer patients in the PD-1/L1 unapproved cohort, five patients with platinum-resistant ovarian cancer experienced clinical benefit, both in terms of durability and deepening of response. As of the data cutoff date, these five patients remained on therapy for a range of approximately 5 to 21 months.
Antitumor activity has also been observed in patients with certain other women’s cancers who received IV ALKS 4230 in combination with pembrolizumab, including a durable immune partial response in triple negative breast cancer and a new partial response in cervical cancer.
An analysis of paired biopsies taken from a melanoma patient who received the 6 µg/kg/day monotherapy dose of IV ALKS 4230 in the dose-escalation phase of ARTISTRY-1 showed an increase in tumor-infiltrating CD8+ T cells and an increase in PD-L1 expression in the TME. In addition, the ratio of CD8+ T cells to Treg cells increased in this patient. High CD8+ T cell/Treg cell ratios, independent of treatment type, have been reported to be associated with better prognosis among multiple tumor types, including ovarian tumors.2 These data provide supporting evidence of ALKS 4230’s immunostimulatory impact on the TME and provide rationale for combining ALKS 4230 with pembrolizumab in ovarian cancer patients.
Among patients in the PD-1/L1 unapproved cohort, treatment-related AEs have been generally transient and manageable, with the majority being grade 1 or 2 in severity. The most commonly reported AEs in this cohort were chills, fever and nausea.
Based on the durable and deepening responses observed with ALKS 4230 in combination with pembrolizumab in ovarian cancer, the company is planning a new prospective study to evaluate this combination regimen in platinum-resistant and bevacizumab-experienced ovarian cancer patients.
About ALKS 4230
ALKS 4230 is an investigational, novel, engineered fusion protein comprised of modified interleukin-2 (IL-2) and the high affinity IL-2 alpha receptor chain, designed to selectively expand tumor-killing immune cells while avoiding the activation of immunosuppressive cells by preferentially binding to the intermediate-affinity IL-2 receptor complex. The selectivity of ALKS 4230 is designed to leverage the proven antitumor effects of existing IL-2 therapy while mitigating certain limitations.

About the ARTISTRY Clinical Development Program
ARTISTRY is an Alkermes-sponsored clinical development program evaluating ALKS 4230 in patients with advanced solid tumors.

ARTISTRY-1 and ARTISTRY-2 are phase 1/2 studies evaluating the safety, tolerability, efficacy and pharmacokinetic and pharmacodynamic effects of ALKS 4230 in patients with refractory advanced solid tumors, in both monotherapy and combination settings with the PD-1 inhibitor pembrolizumab (KEYTRUDA). In ARTISTRY-1, ALKS 4230 is administered as an intravenous infusion daily for five consecutive days. In ARTISTRY-2, ALKS 4230 is administered subcutaneously and is being evaluated with once-weekly and once-every-three-week dosing schedules.

ARTISTRY-3 is a phase 2 study evaluating the clinical and immunologic effects of ALKS 4230 monotherapy administered intravenously on the tumor microenvironment of a variety of advanced, malignant solid tumors.

On November 9, 2020 Vigeo Therapeutics, a clinical-stage immuno-oncology company pioneering novel cancer therapies, reported that interim clinical data from its ongoing Phase 1/2 study evaluating single-agent activities of VT1021 in patients with advanced solid tumors, will be presented in a poster session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 2020 Annual Meeting, taking place from November 9-14, 2020 (Press release, Vigeo Therapeutics, NOV 9, 2020, View Source [SID1234570662]).

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!

VT1021 is a first-in-class, dual-modulating compound that blocks the CD47 immune checkpoint and activates CD36, stimulating cytotoxic T-cell functions, inducing apoptosis in tumor and endothelial cells, and increasing the phagocytosis of the tumor by M1 macrophages by stimulating the production of thrombospondin-1 (Tsp-1). Vigeo is developing VT1021 as a therapeutic agent across a range of cancers, with a current focus on solid tumors.

"The data being presented at SITC (Free SITC Whitepaper) are important because they demonstrate that VT1021 as a single-agent has a favorable safety profile, and is showing early signals of clinical activity across a wide variety of solid tumors, including pancreatic cancer and glioblastoma," said Dr. Devalingam Mahalingam, Associate Professor of Medicine at Northwestern University Feinberg School of Medicine, member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and lead author of the study. "Notably, in the dose escalation cohort we observed a durable partial response rate in a patient with thymoma and a 43% disease control rate in subjects with tumors expressing both high CD47 and high CD36, which speaks to the potential of this dual-modulating agent in subsets of patients with advanced chemo-refractory solid tumors."

Lou Vaickus, MD, FACP, interim Chief Medical Officer at Vigeo, stated, "Patients who have high levels of either CD36 or CD47 have a worse prognosis and a greater likelihood of developing resistance to conventional therapies, and currently there are no therapeutics that simultaneously target both receptors. VT1021 is unique because it stimulates the expression of Tsp-1 which then binds with high affinity to its natural receptors CD47 and CD36, blocking CD47 and the ‘do not eat me’ signal and activating CD36, leading to a cascade of beneficial changes to the TME that are believed to enhance anti-tumor effects. We are highly encouraged by this new data and look forward to further elucidating the clinical activity of VT1021 in the dose expansion portion of this study and in combination studies slated to begin during the first half of 2021."

Key Findings

VT1021 was found to be safe and well tolerated across all doses tested.
PK analysis has demonstrated dose proportionality across all dose levels.
Dose escalation cohort showed preliminary efficacy: Of 28 evaluable patients, one showed partial response (PR) and 11 others achieved stable disease (SD) in 9 different solid tumors with a median of 4.5 prior lines of therapy for a disease control rate of 43%.
Of the 12 patients who achieved PR/SD’s in the dose escalation cohort, 9 (75%) have showed high CD36 and high CD47 expression as determined by an immunohistochemical (IHC) assay.
The RP2D of VT1021 has been determined as 11.8mg/kg.
Details for the SITC (Free SITC Whitepaper) 2020 presentation are as follows:

Title: A first-in-human Phase 1/2 open label trial evaluating the safety, pharmacology, and preliminary efficacy of VT1021 in subjects with advanced solid tumors
Presenter: Devalingam Mahalingam, Associate Professor of Medicine, Feinberg School of Medicine, Northwestern University
Session Type: Poster Session
Abstract Number: 374
Date and Time: Thursday, November 12 from 4:50–5:20 p.m. EST and Saturday, November 14 from 1–1:30 p.m. EST

About VT1021
Vigeo’s lead asset, VT1021, is a first-in-class dual modulating compound that blocks the CD47 immune checkpoint and activates CD36, which induces apoptosis and increases the M1:M2 macrophage ratio. VT1021 achieves this through stimulation of thrombospondin-1 (Tsp-1). The goal of these dual-modulating effects is conversion of immuno-suppressive, or "cold," tumors that don’t respond to immuno-oncology agents, to immuno-stimulated, or "hot," tumors that are potentially more receptive to immuno-oncology agents. Vigeo is developing VT1021 as a therapeutic agent across a range of cancers, with a current focus on solid tumors. Pre-clinical results have demonstrated that single-agent VT1021 causes tumor regression at both the primary and metastatic sites.

Single-agent VT1021 is currently being evaluated in a Phase 1/2, open label, multicenter trial (NCT03364400) that assesses the drug’s safety, tolerability, and preliminary anti-tumor efficacy. The trial’s dose escalation phase is now concluded, and the dose expansion phase has been initiated. The expansion phase is expected to enroll 75-100 `patients into one of three cohorts: pancreatic cancer, glioblastoma, and a basket cohort with cancers expressing both high CD47 and high CD36.

On November 9, 2020 BioInvent International AB ("BioInvent") (OMXS: BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, reported that new data on BI-1808, a monoclonal antibody to tumor necrosis factor receptor 2 (TNFR2) which is expected to enter Phase I/IIa clinical development before the end of 2020 (Press release, BioInvent, NOV 9, 2020, View Source [SID1234570661]).

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!

The poster presentation at the 35th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), entitled "Pre-clinical development of TNFR2 ligand-blocking BI-1808 for cancer immunotherapy" (Abstract number: 725), describes the results from a preclinical toxicology study of BI-1808 in cynomolgus macaques. Three doses of BI-1808 (2, 20 and 200 mg/kg) were administered weekly for four consecutive weeks followed by a recovery period of eight weeks. In addition, results from T-cell stimulation assays and a humanized mouse model evaluating cytokine release were also presented. The data showed that BI-1808 had an expected pharmacokinetic (PK) profile and was well tolerated in doses up to 200 mg/kg. Using a BI-1808 mouse surrogate antibody in a tumor model, a close correlation between dose, exposure, receptor occupancy and anti-tumor response was demonstrated. These data have been used to calculate the starting dose for the upcoming First-in-human (FIH) trial.

The poster will be available in the Virtual Poster Hall November 11-14, 2020, 9:00 a.m. – 5:00 p.m. EST (3:00 – 11:00 p.m. CET). The presenting authors will answer questions on Wednesday, November 11 from 5:15 to 5:45 p.m. EST (11:15 – 11: 45 p.m. CET) and Friday, November 13 from 4:40 to 5:10 p.m. EST (10:40 – 11: 10 p.m. CET).

TNFR2 is particularly upregulated on tumor-associated regulatory T cells (Tregs) and has been shown to be important for their expansion and survival. As a part of its Treg program, BioInvent identified and characterized a wide panel of TNFR2-specific antibodies, generated from its proprietary n-CoDeR library and unique F.I.R.S.TTM discovery tool, of which BI-1808 is the lead development candidate.

"BI-1808 is a very promising drug candidate which further validates the productivity of BioInvent’s proprietary n-CoDeR/F.I.R.S.T platforms. BI-1808 has demonstrated exceptionally strong anti-tumor effects in a several of murine tumor models. It depletes intra-tumoral Tregs, induces and expands intra-tumoral CD8+ T-cells in vivo and synergizes with anti-PD1 treatment. Based on these strong preclinical data, we are looking forward to testing the ability of BI-1808 to treat cancer patients," said Martin Welschof, CEO of BioInvent

BI-1808 is expected to enter clinical development before the end of 2020, further expanding BioInvent’s clinical pipeline of novel drug candidates. BioInvent is assessing BI-1206 in Phase I/IIa studies for the treatment of hematological cancers and solid tumors. In partnership with Transgene, BioInvent is also about to enter clinical development with BT-001, a next generation oncolytic virus expressing a proprietary anti-CTLA4 antibody.

On November 9, 2020 OncoSec Medical Incorporated (NASDAQ:ONCS) (the "Company" or "OncoSec") reported new positive interim data from its KEYNOTE-695 registration-enabled Phase 2b clinical trial evaluating TAVO (tavokinogene telseplasmid), a DNA plasmid-based interleukin-12 (IL-12), in combination with KEYTRUDA (pembrolizumab) in rigorously defined anti-PD1 checkpoint resistant metastatic melanoma patients (Press release, OncoSec Medical, NOV 9, 2020, View Source [SID1234570660]).

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!

TAVO + KEYTRUDA led to a 30% ORR in the first 54 out of 100 planned patients. This interim investigator assessed ORR is much higher than the primary efficacy endpoint for the study, which is a 20% ORR determined by blinded independent review. The data were selected for a Poster Walk discussion and will be additionally presented in the virtual Poster Hall on Wednesday, November 11 and Friday November 13 and as part of a Company Symposium on November 11th at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 35th Anniversary Annual Meeting.

"Achieving an overall response rate of 30% with several complete responses and no serious adverse events is extremely encouraging for checkpoint resistant metastatic melanoma patients who currently rely on systemic administration of immune-stimulating drugs associated with severe toxicity. The data reported, in addition to its ease of use, demonstrate the potential of TAVO in combination with pembrolizumab as a next-generation intratumoral IL-12 therapy that can induce regression of both locally treated and untreated distant and visceral lesions," said Paolo A. Ascierto, M.D., Director of the Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy at the National Tumor Institute Fondazione G. Pascale in Naples, Italy.

Key highlights of KEYNOTE-695 include:

Of the first 54 out of 100 planned patients evaluated by investigator-assessed RECIST v1.1:
ORR was 30% (95%CI [18.0%, 43.6%]) (16/54)
Complete response rate was 6% (3/54)
All responses were confirmed by scans taken no earlier than after 6 months on study
9% (5/54) patients had 100% reduction of target lesions
ORR was 35% (n=6/17) in patients with Stage IV M1c/M1d disease
ORR was 40% (n=6/15) in patients with prior exposure to ipilimumab
Median duration of response (mDOR) is currently 12.2 months (95% CI, 5.6-NE)
Median study follow-up was 13.5 months
Excellent safety profile resulting from intramural treatment approach
Only 5.4% Grade 3 treatment-related AEs
No grade 4/5 treatment-related AEs
This study enrolled rapidly progressing patients with a short interval of 1.2 months (median) between the last dose of anti-PD-1 and study treatment
Adil Daud, M.D., a Professor of Medicine at The University of California, San Francisco, Director of the Melanoma Clinical Research, and lead author of the study added, "the TAVO-electroporation (TAVO-EP) delivery system works by optimizing cellular uptake of DNA-based IL-12 in the tumor microenvironment, leading to local, sustained production of IL-12 in the tumor, where it matters, with negligible systemic exposure. This recruits and primes immune cancer-fighting cells in the tumor leading to systemic immune responses without systemic toxicity. The totality of the safety and efficacy data establishes TAVO-EP as a best-in-class intratumoral therapy."

Daniel O’Connor, Chief Executive Officer of OncoSec, added "Patients with recurrent metastatic melanoma are in great need of effective treatment options. We believe this data demonstrates not only strong levels of efficacy, but also very low treatment related adverse events with the TAVO + pembrolizumab combo. This, combined with its ease of administration to accessible lesions within minutes in an outpatient setting, plus TAVO’s low-cost/simple manufacturing process and its off-the-shelf availability, build a strong case that the TAVO + pembrolizumab combination, in a real-world setting, could equip clinicians with more options for their patients."

OncoSec also announced pre-clinical data showing that CORVax12 triggers an immune response against the SARS-CoV-2 virus. CORVax12 combines OncoSec’s novel DNA-encodable vaccine immuno-stimulant IL-12 expression platform, TAVO with the National Institute of Health (NIH)’s COVID-19 "spike" protein. On November 3, the Company announced FDA clearance of its Investigational New Drug (IND) application for a first-in-human Phase 1 trial to evaluate the safety and immunogenicity of CORVax12.

Mr. O’Connor continued, "Older adults or immuno-compromised patients, such as cancer patients, may not receive adequate protection from any one of the seven vaccine candidates currently being tested in humans in the U.S. The addition of our proprietary IL-12 delivery system may optimize the immune response to these vaccines and better protect these vulnerable populations. We believe that CORVAx12 represents a second-generation vaccine that has the potential to contribute to the eradication of COVID-19."

Additionally, the company presented preclinical data in murine models of triple negative breast cancer (TNBC) demonstrating that intratumoral injection of TAVO followed by electroporation prior to anti-PD-1 therapy led to complete tumor regression and long-term survival in a significant proportion of mice.

Additional details about the poster presentations, Symposium and Investor & Analyst Day are as follows:

Oral Poster Walk Presentation (by invitation only) and General Poster Presentation
Title: Durable responses and immune activation with intratumoral electroporation of pIL-12 plus pembrolizumab in actively progressing anti-PD-1 refractory advanced melanoma: KEYNOTE 695 interim data
Poster #: 799
Date/Time: Wednesday, Nov. 11, from 5:15-5:45 p.m. EST and Friday, Nov. 13, from 4:40-5:10 p.m. EST. at the virtual Poster Hall.
Presenter: Adil Daud, M.D., HS Clinical Professor, Department of Medicine (Hematology/Oncology), University of California, San Francisco (UCSF); Director, Melanoma Clinical Research, UCSF Helen Diller Family Comprehensive Cancer Center

Company Symposium
Event Name: DNA Plasmid-Based IL-12 Delivered Intratumoral Electroporation: Achieving Meaningful Tumor Response while Avoiding Systemic Toxicities
Date/Time: Thursday, Nov. 12, 2020 from 7:30 – 8:30 a.m. ET
Presenters:

Paulo Ascierto, M.D., Director Dept. of Melanoma, Cancer Immunotherapy, Development Therapeutics, Ist. Naz. Tumori IRCCS Pascale
Deborah Charych, Ph.D., Founder and Chief Technology Officer at RayzeBio
Richard Heller, Ph.D., Professor at University of South Florida
Michael Pritchett, D.O. and M.P.H. ,Director of Thoracic Oncology; Director, Chest Center of the Carolinas; FirstHealth of the Carolinas; Pinehurst Medical Clinic Pulmonary & Critical Care Medicine
Chris Twitty, Ph.D., Chief Scientific Officer (moderator)
OncoSec Live Investor & Analyst Day Webcast
Date/Time: Wednesday, Nov.11, 2020 from 8:30-10:30 a.m. ET
Presenters:

Tara Mitchell, M.D., Penn Medicine
Adil Daud, M.D., University of California San Francisco
Alain Algazi, M.D., University of California, San Francisco
Matteo Carlino, M.D., University of Sydney
Rohit Joshi, M.D. Calvary Central Districts Hospital
Bernard Fox, Ph.D., Earle A. Chiles Research Institute
Additional Poster Presentations

Title: Intratumoral plasmid IL-12 expands CD8+ T cells and induces a clinically validated CXCR3 signature in triple-negative breast cancer
Poster #: 789
Date/Time: Wednesday, November 11, 2020 from 5:15–5:45 p.m. ET and Friday, November 13 from 4:40–5:10 p.m. ET
Session: Virtual Poster Hall
Presenter: Erika J. Crosby, Ph.D., Department of Surgery, Duke University Medical Center

Title: Preliminary evaluation of a novel coronavirus vaccine (CORVax) using electroporation of plasmid DNA encoding a stabilized prefusion SARS-CoV-2 spike protein alone or with transfection of plasmid IL-12
Poster #: 480
Date/Time: Thursday, November 12, 2020 from 4:50–5:20 p.m. EST and Saturday, November 14 from 1–1:30 p.m. ET
Session: Virtual Poster Hall
Presenter: Shawn M. Jensen, Ph.D., Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center

Copies of the posters will be archived and available in the Investors section of the Company’s website at www.oncosec.com. The live video webcast of the Investor & Analyst day call will be accessible under Events and Presentations in the Investors section of the Company’s website. The archived audio webcast will be available on the OncoSec website following the call and will be available for 30 days.

About KEYNOTE-695
KEYNOTE-695 is OncoSec’s registration-directed Phase 2b trial (NCT#03132675) evaluating TAVO (tavokinogene telseplasmid), a DNA plasmid-based interleukin-12 (IL-12) + KEYTRUDA (pembrolizumab) in patients with rigorously confirmed anti-PD-1 checkpoint resistant metastatic melanoma. The trial aims to enroll up to 100 patients with refractory, locally advanced or metastatic disease defined as unresectable Stage III/IV metastatic melanoma that had definitively progressed on a full-course of anti-PD-1 treatment with KEYTRUDA (pembrolizumab) or OPDIVO (nivolumab). TAVO has received Fast Track Designation from the U.S. Food and Drug Administration (FDA) for the treatment of metastatic melanoma following progression on KEYTRUDA or OPDIVO.

About TAVO
OncoSec’s gene therapy technology combines TAVOTM (tavokinogene telseplasmid), a DNA plasmid-based interleukin-12 (IL-12), with an intra-tumoral electroporation gene delivery platform to achieve endogenous IL-12 production in the tumor microenvironment that enables the immune system to target and attack tumors throughout the body. TAVO has demonstrated a local and systemic anti-tumor response in several clinical trials, including the pivotal Phase 2b trial KEYNOTE-695 for metastatic melanoma and the KEYNOTE-895 Phase 2 trial in triple negative breast cancer (TNBC). TAVO has received Orphan Drug and Fast-Track Designation by the U.S. Food & Drug Administration (FDA) for the treatment of metastatic melanoma following progression on KEYTRUDA or OPDIVO.

About Advanced Metastatic Melanoma
Metastatic melanoma refers to stage IV melanoma, which has typically spread through the lymph nodes to distant sites in the body such as the liver, lungs, bones and brain. Every year, approximately 100,000 adults in the United States are diagnosed with metastatic melanoma. Due to this metastatic tumor burden, stage IV melanoma is often very difficult to treat. Available treatment options frequently combine surgery with immunotherapy or targeted therapy. The 5-year survival rate for metastatic melanoma is approximately 25%.

About Metastatic Triple Negative Breast Cancer (TNBC)
Metastatic triple negative breast cancer (mTNBC) is an aggressive type of breast cancer with a high recurrence rate within the first five years following diagnosis, which accounts for 10-20% of all breast cancers. Unlike some other breast cancers, mTNBC does not express estrogen or progesterone receptors or human epidermal growth factor receptor 2 (HER2), and it does not respond to existing cancer drugs designed to target these markers. mTNBC is difficult to treat and there are very few FDA approved treatment options for these patients, which mostly rely on surgery, radiation, and chemotherapy. The 5-year survival rate for these patients is approximately 11%.

About CORVax12
CORVax12 is the only DNA vaccine that uses an immune stimulant to promote an immune response against the SARS-CoV-2 virus. The CORVax12 vaccine approach combines the co-administration of TAVO (plasmid IL-12) with a DNA-encodable version of the SARS-CoV-2 spike or "S" glycoprotein to enhance immunogenicity of the component developed by scientists at the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center. CORVax12 is designed to drive a coordinated vaccine response, capable of drawing upon the innate and adaptive humoral and cellular arms. This multi-pronged innate, adaptive and cellular immune response has the potential to generate a robust anti-viral response.

On November 9, 2020 Pierre Fabre reported the initiation of an international Phase I clinical study in patients with relapsed or refractory solid tumors for its investigational product W0180, an innovative monoclonal antibody targeting VISTA, developed by Pierre Fabre Medical Care R&D teams (Press release, Pierre Fabre, NOV 9, 2020, View Source [SID1234570659]). The study started at the University Clinic of Navarra, Spain, under the supervision of Pr. Ignacio Melero, Immunologist and Senior Investigator at Centro de Investigación Médica Aplicada (CIMA).

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 clinical research is led by Principal Investigator Pr. Aurelien Marabelle of the Gustave Roussy Cancer Institute (Villejuif, France). Pr. Marabelle is the Clinical Director of the Cancer Immunotherapy Program at Gustave Roussy and Senior Medical Oncologist within its Drug Development Department (DITEP). The study will involve other sites in France and Spain, including at the Toulouse University Hospital (IUCT) located at the Toulouse-Oncopole Campus.

Aurelien Marabelle said: "VISTA is a new immune-checkpoint molecule highly expressed in the tumor microenvironment. There are great expectations within the medico-scientific community for this new target and its biology. With this clinical study and its extensive translational medicine plan, we are delighted to contribute to improve the knowledge on VISTA for the benefit of cancer patients."

Jean-Luc Lowinski, Pierre Fabre Medical Care CEO, added: "At Pierre Fabre, innovation in oncology is at the top of our strategic priorities and we are all very keen to bring this new molecule to clinical evaluation. Immunotherapy has already been a revolution for cancer patients in many indications, but the medical need is still incredibly huge. Our oncology R&D teams are fully committed to identify and develop innovative therapies for patients who are refractory or resistant to current treatments."

W0180 is a first-in-class antibody targeting VISTA (V-domain Ig suppressor of T cell Activation). VISTA is a negative checkpoint regulator of T cell response. VISTA is expressed within the tumor microenvironment, where its inhibition can enhance antitumor immune responses. Furthermore, an increase in VISTA expression has been reported after treatment by anti-PD1/L1 and anti-CTLA4. This confirms that VISTA may play a key role as a mechanism of resistance to the currently used immunotherapies. W0180 given to patients as a single agent or in combination with anti-PD1/L1 therapy has a potential in multiple cancer indications, including those with myeloid immunosuppressive infiltrates where VISTA pathway is expressed.

Pierre Fabre has presented 3 communications about W0180 to the Annual Meetings of the American Association of Cancer Research (AACR 2019 and AACR (Free AACR Whitepaper) 2020) and is preparing an upcoming communication to the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 35th Anniversary Annual Meeting to be held virtually on November 9-14, 2020. The SITC (Free SITC Whitepaper) communication is entitled "W0180 novel anti-VISTA antibody: rationale for target patient population and first-in-human trial design in monotherapy and in combination with anti-PD1 antibody."