On November 5, 2019 Inovio Pharmaceuticals, Inc. (NASDAQ: INO) reported positive interim results from Inovio’s Phase 2 study (NCT03491683) of newly diagnosed glioblastoma multiforme (GBM) combining Inovio’s INO-5401, a T cell-activating immunotherapy encoding for three tumor-associated antigens (hTERT, WT1, and PSMA), and INO-9012, an immune activator encoding IL-12, in combination with Libtayo (cemiplimab), a PD-1 blocking antibody developed by Regeneron Pharmaceuticals (NASDAQ: REGN) in collaboration with Sanofi (Press release, Inovio, NOV 5, 2019, View Source [SID1234550328]). The data will be featured in a late-breaking poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2019 Annual Meeting in National Harbor, Maryland, November 6-10.

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Key interim data from the 52-patient clinical trial showed that 80% (16 of 20) of MGMT gene promoter methylated patients and 75% (24 of 32) of unmethylated patients were progression-free at six months (PFS6) measured from the time of their first dose, substantially exceeding historical standard-of-care data.

This immunotherapy combination with a PD-1 checkpoint inhibitor also exhibited supportive safety, tolerability, and immunogenicity data and suggested an acceptable safety profile consistent with that of Libtayo and Inovio’s platform technology. The majority of patients tested had a T cell immune response to one or more tumor-associated antigens encoded by INO-5401. Immune responses to all three tumor-associated antigens were demonstrated in this study. Inovio plans to report 12- and 18-month overall survival data next year.

Dr. David Reardon, M.D., Coordinating Principal Investigator of the study and the Clinical Director for Neuro-Oncology at the Dana-Farber Cancer Institute, said, "This innovative trial provides promising information that the combination of INO-5401 plus INO-9012, a T cell-promoting therapy, combined with Libtayo, a checkpoint inhibitor, may provide clinically meaningful benefit in this very difficult to treat disease."

Dr. J. Joseph Kim, Inovio’s President & CEO, said, "Our new data demonstrates the potential of our immunotherapies utilizing tumor-associated antigens in cancer treatments. Our goal in this GBM trial is to increase progression-free and overall survival of patients facing a disease where neither the standard of care nor clinical outcomes have significantly advanced in decades. Previously, other checkpoint inhibitor treatment alone in GBM trials did not show any meaningful clinical benefit over standard of care. However, the addition of INO-5401 and its ability to generate antigen-specific T cells demonstrated early efficacy signals in progression-free survival. We look forward to reporting additional data including overall survival at months 12 and 18 from the trial in the coming year."

Poster Details

Poster 858:

An Open-Label, Multi-center Trial of INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination with Cemiplimab in Subjects with Newly-Diagnosed Glioblastoma (GBM)

Category:

Late-Breaker

Date/Time:

Friday, Nov. 8th, 12:30 – 2 p.m. and Saturday, Nov. 9th 12:35 – 2:05 p.m.

Location:

Displayed in the Potomac Foyer (outside the Plenary session room, Potomac Ballroom)

Study Design

The trial was designed to evaluate safety, immunogenicity and preliminary efficacy of INO-5401 and INO-9012 in combination with Libtayo, with radiation and chemotherapy, in subjects with newly-diagnosed glioblastoma (GBM). This is a Phase 1/2, open-label, multi-center trial conducted in 52 evaluable patients with GBM. There were 2 cohorts in this trial. Cohort A were participants with a tumor with an unmethylated O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) promoter. Cohort B included participants with a tumor with a MGMT methylated promoter or who have indeterminate MGMT status. Both cohorts received INO-5401 and INO-9012 and Libtayo at the same doses and on the same dosing schedule, and both cohorts received radiation and temozolomide (TMZ), if clinically indicated. Interim data presented here and at SITC (Free SITC Whitepaper) was obtained as of October 2019 and final study data is expected in Q4 2020. For more information of the clinical study, see www.clinicaltrials.gov, identifier NCT03491683.

About Glioblastoma Multiforme (GBM)

GBM is the most common and aggressive type of brain cancer and remains a devastating disease for both patients and caregivers. Its prognosis is extremely poor, despite a limited number of new therapies approved over the last 10 years. The median overall survival for patients receiving standard of care therapy is approximately 15 months and the median progression-free survival is approximately 7 months. In the U.S., the estimated annual incidence of GBM is 11,362 cases or 3.21 cases per 100,000 persons and the median age at diagnosis is 65 years.

About INO-5401 and INO-9012

INO-5401 encodes for Inovio’s SynCon antigens for hTERT, WT1, and PSMA, and has the potential to be a powerful cancer immunotherapy in combination with checkpoint inhibitors. The National Cancer Institute previously highlighted hTERT, WT1, and PSMA among a list of important cancer antigens, designating them as high priorities for cancer immunotherapy development. These three antigens were reported to be over-expressed, and often mutated, in a variety of human cancers, and targeting these antigens may prove efficacious in the treatment of patients with cancer. INO-9012 encodes for IL-12, which is a T cell immune activator.

On November 5, 2019 IMV Inc. (Nasdaq: IMV; TSX: IMV), a clinical stage biopharmaceutical company pioneering a novel class of immunotherapies, reported that translational data, including comprehensive immune profiling of clinical samples from subjects treated with IMV’s lead compound, DPX-Survivac, will be presented during the 34th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), being held on November 6 – 10, 2019 in National Harbor, MD (Press release, IMV, NOV 5, 2019, View Source [SID1234550327]).

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In connection with DeCidE1, IMV’s ongoing Phase 1b/2 study of DPX-Survivac in advanced recurrent ovarian cancer, the Company conducted immune-profiling of peripheral blood mononuclear cell (PBMC) and tumor samples to evaluate the program’s underlying mechanism of action. The data suggest that the treatment regimen per the study protocol induced robust and sustained survivin-specific T cell responses from nearly all evaluable subjects and T cell infiltration into tumors without loss of functionality. Specifically, a comparison of T cell receptor ²-chain repertoire analyses between pre- and on-treatment tumor biopsies shows new clonotypes can represent up to 90% of the intratumoral T cell population.

"We are very pleased to present these translational clinical data in advanced recurrent ovarian cancer at this important scientific venue. Taken together with earlier data, this comprehensive analysis continues to validate our new T cell therapy mechanism," said Frederic Ors, President and Chief Executive Officer at IMV. "We find these data highly encouraging, as they highlight some of the key distinctive features of our promising new treatment for patients with this hard-to-reach cancer, as well as for patients with one of the numerous other tumor types that express survivin. We look forward to demonstrating how this effect translates into patient benefits with upcoming topline data from this study."

Poster Presentation Details:

Poster Title: Comprehensive immune profiling of clinical samples from subjects with advanced recurrent epithelial ovarian cancer treated with a novel T cell activating therapy, DPX-Survivac

Presenter: Brennan S. Dirk, PhD – IMV Inc, Dartmouth, Nova Scotia

Abstract Number: P586

Date and Time: Poster will be displayed all day on Nov. 9, 2019, 7:00 am – 8:30 pm EST

Location: Poster Hall (Prince George AB)

SITC has published the official abstracts on its meeting website in advance of the SITC (Free SITC Whitepaper) Annual Meeting. The poster will be available under Events, Webcasts and Presentations in the investors section of IMV’s website on the day of presentation.

About DPX-Survivac

DPX-Survivac is the lead candidate in IMV’s new class of immunotherapies that program targeted T cells in vivo. It has demonstrated the potential for targeted, persistent, and durable T cell generation. IMV believes this mechanism of action (MOA) is key to generating durable solid tumor regressions. DPX-Survivac consists of survivin-based peptides formulated in IMV’s proprietary DPX drug delivery platform. DPX-Survivac is designed to work by eliciting a CD8+ T cell immune response against cancer cells presenting survivin peptides on their surface.

Survivin, recognized by the National Cancer Institute (NCI) as a promising tumor-associated antigen, is broadly over-expressed in most cancer types, and plays an essential role in antagonizing cell death, supporting tumor-associated angiogenesis and promoting resistance to chemotherapies. IMV has identified over 20 cancer indications in which survivin can be targeted by DPX-Survivac.

DPX-Survivac has received Fast Track designation from the U.S. Food and Drug Administration (FDA) as maintenance therapy in advanced ovarian cancer, as well as orphan drug designation status from the U.S. FDA and the European Medicines Agency (EMA) in the ovarian cancer indication.

On November 5, 2019 Genocea Biosciences, Inc. (NASDAQ: GNCA), a biopharmaceutical company developing next-generation neoantigen immunotherapies, reported preclinical and clinical data demonstrating that ATLAS can identify relevant neoantigens and exclude inhibitory neoantigens that suppress anti-tumor immune responses at the 34th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), taking place from November 6 – 10, 2019 in National Harbor, Maryland (Press release, Genocea Biosciences, NOV 5, 2019, View Source [SID1234550326]). ATLAS is Genocea’s unique platform that profiles each patient’s T cell responses to every candidate neoantigen to select those driving pre-existing anti-tumor responses. Additional data will also be presented, demonstrating that inhibitory neoantigen profiles may predict if a patient will respond to immunotherapy and confirming broad immune response data for the company’s novel neoantigen therapy GEN-009.

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"Our preclinical findings represent exciting and powerful new discoveries in the role that inhibitory neoantigens play in response to immunotherapies," said Tom Davis, M.D., Chief Medical Officer, Genocea. "Through these data, we demonstrate the power of the ATLAS platform to identify and target only those neoantigens with a high propensity to drive anti-tumor responses while excluding inhibitory, immunosuppressive antigens. We are also pleased to share additional GEN-009 results, which round out the GEN-009 clinical immunogenicity data set from our initial patient cohort and confirm the relevance of these preclinical findings in advancing patient treatment."

The following posters will be located in Prince George’s Exhibition Halls AB. Odd-numbered posters will be presented on Friday, November 8th from 12:30 – 2:00 p.m. ET and 6:30 – 8:00 p.m. ET, and even-numbered posters will be presented on Saturday, November 9th from 12:35 – 2:05 p.m. ET and 7:00 – 8:30 p.m. ET.

Summary of Poster #P678 – Vaccine neoantigens empirically identified through the ex vivo ATLAS platform promote potent therapeutic responses to cancer in mice

ATLAS screening of mutations from B16F10 melanoma identified approximately 4 percent of mutations as neoantigens, and 3.5 percent of mutations as eliciting potentially deleterious inhibitory T cell responses; the majority were not algorithm-predicted.

When an ATLAS-identified stimulatory neoantigen was combined in a vaccine formulation and therapeutically administered as monotherapy into tumor-bearing mice, tumor growth was either significantly delayed or completely abrogated in all mice.

Vaccination with inhibitory neoantigens suppresses anti-tumor immune responses.

Summary of Poster #P417 – ATLAS identifies relevant neoantigens for therapeutic anti-tumor vaccination and may serve as a biomarker for efficacy of immunotherapy of solid tumors

In an analysis of the first six patients who participated in the GEN-009 phase 1/2a study, ATLAS identified neoantigens by recalling both stimulatory and inhibitory neoantigen-specific T cell responses; many of which were not predicted using in silico approaches.

Post-vaccination predicted neoantigens were not more immunogenic than not predicted neoantigens.

In a separate analysis including non-vaccinated subjects, the proportion of inhibitory to stimulatory neoantigen-specific responses may be a biomarker of immunotherapy success.

Summary of Poster #P420 – Broad immunogenicity from GEN-009, a neoantigen vaccine using ATLAS, an autologous immune assay, to identify immunogenic and inhibitory tumor neoantigens

GEN-009-101 is a phase 1/2a study testing safety, immunogenicity and clinical activity in immune responsive tumors (NCT03633110).

The vaccine was well-tolerated with only grade 1/2 adverse events reported.

With data from patients enrolled (n=5), vaccination elicited both CD8+ and CD4+ T cell responses in all subjects, as measured by ex vivo and in vitro stimulation fluorospot assays, and confirms broad immune responses generated against 98 percent of all immunized neoantigens with a range of tumor types.

On November 5, 2019 G1 Therapeutics, Inc. (Nasdaq: GTHX), a clinical-stage oncology company, reported a corporate and financial update for the third quarter ended September 30, 2019 (Press release, G1 Therapeutics, NOV 5, 2019, View Source [SID1234550325]).

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"Based on written feedback from the FDA following our pre-NDA meeting in September, we will submit a New Drug Application for myelopreservation in small cell lung cancer. We expect to complete the submission in the second quarter of 2020," said Mark Velleca, M.D., Ph.D., Chief Executive Officer. "Our vision is for trilaciclib to become a new standard of care to mitigate myelosuppression in patients receiving chemotherapy. We are committed to making trilaciclib available to small cell lung cancer patients as quickly as possible, and are executing on a regulatory and development strategy to evaluate the myelopreservation benefits of trilaciclib in the most commonly used chemotherapy regimens. We expect to initiate a Phase 3 trial in colorectal cancer in the second half of 2020. In addition, we will continue to explore trilaciclib in triple-negative breast cancer, where preliminary data has demonstrated a survival benefit."

Third Quarter Regulatory and Clinical Highlights

The company plans to submit an NDA for trilaciclib in small cell lung cancer (SCLC) based on written feedback from FDA. Based on written feedback from its pre-NDA meeting with the U.S. Food and Drug Administration (FDA) in September, the company will file an NDA for trilaciclib in SCLC. The company expects to complete the NDA submission in the second quarter of 2020. Earlier this year, trilaciclib received Breakthrough Therapy Designation (BTD) from the FDA based on positive myelopreservation data in SCLC patients from three randomized Phase 2 clinical trials. The BTD program is designed to expedite development and review of drugs intended for serious or life-threatening conditions.

ESMO presentations: data from Phase 2 clinical trials of trilaciclib in metastatic triple-negative breast cancer (mTNBC) and SCLC and data from Phase 1 clinical trial of G1T48 in ER+, HER2- breast cancer. In an oral presentation on data from a randomized Phase 2 trial of trilaciclib, preliminary overall survival (OS) results demonstrated that women with mTNBC lived significantly longer when receiving trilaciclib and chemotherapy compared with women receiving chemotherapy alone. Data were published simultaneously in The Lancet Oncology. The company also presented updated Phase 2 results in SCLC patients receiving trilaciclib and chemotherapy in combination with Tecentriq (atezolizumab) (press release here) and the first clinical data on its oral selective estrogen receptor degrader (SERD), G1T48. Preliminary results from the ongoing Phase 1/2a dose-escalation trial of G1T48 in patients with estrogen receptor- positive, HER2-negative (ER+, HER2-) breast cancer showed G1T48 was well tolerated and demonstrated evidence of anti-tumor activity in heavily pre-treated patients. Based on safety and tolerability findings in the Phase 1b portion of this trial, the company selected the 600 mg and 1,000 mg doses of G1T48 for evaluation in the ongoing Phase 2a portion (press release here).

Third Quarter 2019 Financial Highlights

Cash Position: Cash, cash equivalents and short-term investments totaled $299.9 million as of September 30, 2019, compared to $369.3 million as of December 31, 2018.

Operating Expenses: Operating expenses were $34.0 million for the third quarter of 2019, compared to $20.8 million for the third quarter of 2018. GAAP operating expenses include stock-based compensation expense of $4.4 million for the third quarter of 2019, compared to $3.3 million for the third quarter of 2018.

Research and Development Expenses: Research and development (R&D) expenses for the third quarter of 2019 were $22.9 million, compared to $15.9 million for the third quarter of 2018. The increase in R&D expense was primarily due to an increase in clinical program costs, costs for manufacturing pharmaceutical active ingredients, and personnel costs due to additional headcount.

General and Administrative Expenses: General and administrative (G&A) expenses for the third quarter of 2019 were $11.1 million, compared to $4.9 million for the third quarter of 2018. The increase in G&A expense was largely due to an increase in compensation due to additional headcount, increase in pre-commercialization activities, increase in medical affairs costs, and an increase in professional fees and other administrative costs necessary to support our operations.

Net Loss: G1 reported a net loss of $32.4 million for the third quarter of 2019, compared to $19.9 million for the third quarter of 2018.

2019 Guidance: The company expects to end the year with $265-$270 million in cash and cash equivalents.

Anticipated Milestones

Begin rolling NDA submission for trilaciclib in SCLC in 4Q19, which the company expects to complete in 2Q20; submit Marketing Authorization Application to the European Medicines Agency in 2H20.

Initiate clinical trials of trilaciclib in colorectal cancer and TNBC in 2020.

Present additional data from the Phase 1b/2a clinical trial of lerociclib + Faslodex (fulvestrant) at the 2019 San Antonio Breast Cancer Symposium (SABCS) on December 11, 2019.

Identify dose and schedule of lerociclib and G1T48 for pivotal trials in ER+, HER2- breast cancer.

Webcast and Conference Call

The management team will host a webcast and conference call at 4:30 p.m. ET today to provide a corporate and financial update for the third quarter 2019 ended September 30, 2019. The live call may be accessed by dialing 866-763-6020 (domestic) or 210-874-7713 (international) and entering the conference code: 3374256. A live and archived webcast will be available on the Events & Presentations page of the company’s website: www.g1therapeutics.com. The webcast will be archived on the same page for 90 days following the event.

On November 5, 2019 Forbius, a clinical-stage protein engineering company that develops biotherapeutics to treat fibrosis and cancer, reported that it will present the first clinical data from its Phase 1a oncology trial with AVID200 in a late-breaking poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting 2019in National Harbor, Maryland (Nov. 6-10) (Press release, Forbius, NOV 5, 2019, View Source [SID1234550324]).

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AVID200 is a first-in-class, selective inhibitor of TGF-beta 1 & 3, the main pathogenic TGF-beta isoforms. AVID200 spares TGF-beta 2 for optimal safety.

The presentation will feature results from a Phase 1a monotherapy dose-escalation trial in patients with advanced solid tumor malignancies (AVID200-03, NCT03834662). The highest tested dose level was 30 mg/kg (1100 mg/m2)administered iv q3w, and the maximum tolerated dose (MTD) was not reached. Pharmacokinetics (PK), target engagement results as well as preliminary clinical efficacy will also be disclosed in the poster presentation.

Details of the Presentation:

Title:

AVID200, first-in-class TGF-beta 1 and beta 3 selective inhibitor: Results of a Phase 1 monotherapy dose escalation study in solid tumors and evidence of target engagement in patients (Abstract # P856)

Presenter:

Dr. Timothy Yap, Associate Professor, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, MD Anderson Cancer Center

Poster Viewing:

Friday, Nov. 8 / 12:30 – 2:00 p.m. and 6:30 – 8:00 p.m.

Saturday, Nov. 9 / 12:35 – 2:05 p.m. and 7:00 – 8:30 p.m.

Location:

Prince George’s Exhibition Halls AB

About TGF-beta 1 & 3

TGF-beta 1 & 3 are the main oncogenic TGF-beta isoforms expressed by many solid tumors. They are believed to play a major role in T-cell suppression, fibrosis and resistance to anti-PD-(L)1 therapies such as nivolumab (Opdivo) and pembrolizumab (Keytruda) (Chakravarthy, Nature Comm., 2018; Tauriello, Nature, 2018; Mariathasan, Nature, 2018).

About AVID200 and the AVID200-03 Trial (NCT03834662)

AVID200 is an isoform-selective and highly potent inhibitor of TGF-beta 1 & 3 undergoing Phase 1 clinical testing in solid tumors and fibrotic diseases. TGF-beta 1 & 3 are the principal disease-driving isoforms, while TGF-beta 2 is responsible for normal cardiac function and hematopoiesis.

AVID200’s selectivity for TGF-beta 1 & 3 was designed to achieve optimal efficacy while circumventing cardiac and other safety issues that have limited the applicability of earlier-generation, non-selective TGF-beta inhibitors. Therefore, AVID200 is positioned to be an effective and well-tolerated therapeutic in a variety of clinical settings, including in combination with anti-PD-(L)1 therapy.

AVID200-03 (NCT03834662) is an open label, multicenter, dose-escalation study to evaluate the safety, pharmacokinetics, pharmacodynamics and antitumor effects of AVID200 in patients with advanced or metastatic solid tumor malignancies.