On April 2, 2019 Heat Biologics, Inc. (NASDAQ: HTBX), a biopharmaceutical company developing immunotherapies designed to activate a patient’s immune system against cancer, reported that it delivered a poster presentation yesterday, April 1, 2019, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Heat Biologics, APR 2, 2019, View Source [SID1234534901]). The Company’s presentation, entitled, ”Generation of a novel, allogeneic cell-based, Gp96-Ig/OX40L cancer vaccine, improves anti-tumor immunity and long-term memory T-cell generation,” is available online here.

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The poster presentation featured the Company’s next generation cellular vaccine platform, ComPACT (COMbination Pan-Antigen Cytotoxic Therapy), which incorporates a tumor antigen chaperone (gp96-Ig) with T-cell costimulation (OX40L-Ig), simulating a single tumor cell line source that secretes both products. The presentation modeled how the addition of human HS-130, which secretes OX40L-Ig, to HS-110 may ImPACT anti-tumor immune responses. This combination generated a three-fold increase in CD8+ T-cell expansion, increased numbers of long-lived tumor-specific T-cells, and potent short-lived killer T-cells required for tumor growth control.

Matt Seavey, Ph.D., Heat’s Senior Director of Research, commented, ”We are highly encouraged by these preliminary results in a mouse model, which demonstrate that the combination of HS-110 with OX40L co-stimulation has the potential to dramatically enhance anti-tumor immune responses. Moreover, this study further informed our selection of the ideal ratio of gp96 to OX40L, which will be helpful as we prepare to file an IND for our HS-130 ComPACT trial later this quarter.”

About AACR (Free AACR Whitepaper) Annual Meeting 2019

The AACR (Free AACR Whitepaper) Annual Meeting program covers the latest discoveries across the spectrum of cancer research – from population science and prevention; to cancer biology, translational, and clinical studies; to survivorship and advocacy – and highlights the work of the best minds in research and medicine from institutions all over the world.

On April 2, 2019 Alder BioPharmaceuticals, Inc. (NASDAQ:ALDR), a biopharmaceutical company focused on developing novel therapeutic antibodies for the treatment of migraine, reported that members of the management team will provide a business overview and update at the 18th Annual Needham Healthcare Conference at 10:40 am ET on Tuesday, April 9, 2019 in New York, NY (Press release, Alder Biopharmaceuticals, APR 2, 2019, View Source [SID1234534900]).

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The presentation will be webcast live on the Events & Presentations page of the Investors section of Alder’s website at View Source, or by following the link below in your web browser. An archived replay of the webcast will be available on Alder’s website for at least 30 days after the live event concludes.

On April 2, 2019 Odonate Therapeutics, Inc. (NASDAQ: ODT), a pharmaceutical company dedicated to the development of best-in-class therapeutics that improve and extend the lives of patients with cancer, reported its results of preclinical studies of tesetaxel, Odonate’s investigational, orally administered taxane, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 (Press release, Odonate Therapeutics, APR 2, 2019, View Source [SID1234534899]). The presentation is entitled, "Tesetaxel, a novel, oral taxane, crosses intact blood-brain barrier (BBB) at therapeutically relevant concentrations" (Poster Board #12; Abstract 3087).

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These preclinical results indicate that, following oral administration, tesetaxel achieves brain concentrations that exceed concentrations required for tumor killing for a sustained period of time. This is in contrast to paclitaxel and docetaxel, the most commonly prescribed taxanes, which do not substantially cross the BBB.

"The development of effective treatment options for patients with brain metastases remains an enormous unmet medical need", said Nancy Lin, M.D., Associate Chief of Breast Oncology, Susan F. Smith Center for Women’s Cancers, and Director of the EMBRACE Metastatic Breast Cancer Program, Dana-Farber Cancer Institute. "Taxanes are one of the most active and widely used classes of chemotherapy agents for the treatment of both early stage and metastatic breast cancer, but conventional taxanes do not cross the blood-brain barrier. The preclinical results showing tesetaxel penetration across an intact blood-brain barrier are compelling and raise the potential for both treatment and prevention of brain metastases. We look forward to investigating the possible translation of this finding into clinical outcomes in CONTESSA, CONTESSA 2 and CONTESSA TRIO, each of which allows enrollment of patients with brain metastases."

About Tesetaxel

Tesetaxel is an investigational, orally administered chemotherapy agent that belongs to a class of drugs known as taxanes, which are widely used in the treatment of cancer. Tesetaxel has several pharmacologic properties that make it unique among taxanes, including: oral administration with a low pill burden; a long (~8-day) terminal plasma half-life in humans, enabling the maintenance of adequate drug levels with relatively infrequent dosing; no history of hypersensitivity (allergic) reactions; and significant activity against chemotherapy-resistant tumors. In patients with metastatic breast cancer, tesetaxel was shown to have significant, single-agent antitumor activity in two multicenter, Phase 2 studies.

About CONTESSA

CONTESSA is a multinational, multicenter, randomized, Phase 3 study of tesetaxel, an investigational, orally administered taxane, in patients with locally advanced or metastatic breast cancer (LA/MBC). CONTESSA is comparing tesetaxel dosed orally at 27 mg/m2 on the first day of each 21-day cycle plus a reduced dose of capecitabine (1,650 mg/m2/day dosed orally for 14 days of each 21-day cycle) to the approved dose of capecitabine alone (2,500 mg/m2/day dosed orally for 14 days of each 21-day cycle) in approximately 600 patients randomized 1:1 with human epidermal growth factor receptor 2 (HER2) negative, hormone receptor (HR) positive LA/MBC previously treated with a taxane in the neoadjuvant or adjuvant setting. Capecitabine is an oral chemotherapy agent that is considered a standard-of-care treatment in LA/MBC. Where indicated, patients must have received endocrine therapy with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor. The primary endpoint is progression-free survival (PFS) as assessed by an Independent Radiologic Review Committee (IRC). CONTESSA’s secondary efficacy endpoints are overall survival (OS), objective response rate (ORR) as assessed by the IRC and disease control rate (DCR) as assessed by the IRC. To learn more, please visit www.contessastudy.com.

About CONTESSA 2

CONTESSA 2 is a multinational, multicenter, Phase 2 study of tesetaxel, an investigational, orally administered taxane, in patients with locally advanced or metastatic breast cancer (LA/MBC). CONTESSA 2 is investigating tesetaxel dosed orally at 27 mg/m2 on the first day of each 21-day cycle plus a reduced dose of capecitabine (1,650 mg/m2/day dosed orally for 14 days of each 21-day cycle) in approximately 125 patients with human epidermal growth factor receptor 2 (HER2) negative, hormone receptor (HR) positive LA/MBC not previously treated with a taxane. Capecitabine is an oral chemotherapy agent that is considered a standard-of-care treatment in LA/MBC. Where indicated, patients must have received endocrine therapy with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor. The primary endpoint is objective response rate (ORR) as assessed by an Independent Radiologic Review Committee (IRC). The secondary efficacy endpoints are duration of response (DoR) as assessed by the IRC, progression-free survival (PFS) as assessed by the IRC, disease control rate (DCR) as assessed by the IRC and overall survival (OS).

About CONTESSA TRIO

CONTESSA TRIO is a multi-cohort, multicenter, Phase 2 study of tesetaxel, an investigational, orally administered taxane, in patients with locally advanced or metastatic breast cancer (LA/MBC). In Cohort 1, approximately 90 patients (with potential expansion to up to 150 patients) with locally advanced or metastatic triple-negative breast cancer (TNBC) who have not received prior chemotherapy for advanced disease will be randomized 1:1:1 to receive tesetaxel dosed orally at 27 mg/m2 on the first day of each 21-day cycle plus either: (1) nivolumab at 360 mg by intravenous infusion on the first day of each 21-day cycle; (2) pembrolizumab at 200 mg by intravenous infusion on the first day of each 21-day cycle; or (3) atezolizumab at 1,200 mg by intravenous infusion on the first day of each 21-day cycle. Nivolumab and pembrolizumab (PD-1 inhibitors) and atezolizumab (a PD-L1 inhibitor) are immuno-oncology (IO) agents approved for the treatment of multiple types of cancer. One of these agents, atezolizumab, in combination with the intravenously delivered taxane, nab-paclitaxel, was recently approved by the U.S. Food and Drug Administration (FDA) as a first-line treatment for patients with metastatic TNBC. The dual primary endpoints for Cohort 1 are objective response rate (ORR) and progression-free survival (PFS). Secondary endpoints include duration of response (DoR) and overall survival (OS). Efficacy results for each of the three PD-(L)1 inhibitor combinations will be assessed for correlation with the results of each of the three approved PD-L1 diagnostic assays. In Cohort 2, approximately 40 elderly patients (with potential expansion to up to 60 patients) with human epidermal growth factor receptor 2 (HER2) negative MBC will receive tesetaxel monotherapy dosed orally at 27 mg/m2 on the first day of each 21-day cycle. The primary endpoint for Cohort 2 is ORR. Secondary endpoints include PFS, DoR and OS. Patients with central nervous system metastases are eligible for both cohorts.

On April 2, 2019 OncoSec Medical Incorporated (OncoSec) (NASDAQ: ONCS), a company developing novel cancer immunotherapies, reported its pre-clinical data highlighting its novel anti-tumor product candidate, SPARK, and its improved electroporation generator, "APOLLO," during a poster presentation at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Atlanta, Georgia (Press release, OncoSec Medical, APR 2, 2019, View Source [SID1234534898]).

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The poster, entitled, "Intratumoral electroporation of plasmid IL-12 and CXCL9 with membrane-bound anti-CD3 elicits robust anti-tumor immunity," provides new preclinical data demonstrating robust anti-tumor responses driven by significant enhancements made to OncoSec’s proprietary cancer immunotherapy platform.

"The data presented at AACR (Free AACR Whitepaper) highlight OncoSec’s potentially game-changing approach to drug development. With this data, we show the ability to not only identify the right genes to have anti-cancer effect, but, importantly, that we can deliver those genes directly into tumor cells. We are able to do this with any gene that is identified as having an anti-cancer effect, without having to expose the patient to a systemic therapy, in an expeditious and cost-effective manner. In doing so, these cells convert immunologically cold tumors into inflamed immunogenic lesions, which is fundamental to generating objective responses in both treated and untreated distant tumors," said Daniel J. O’Connor, President and CEO of OncoSec. "Many immunotherapies are stalled for serious toxicity issues associated with treatment, including cytokine release syndrome. In contrast, our clinical studies, in more than 180 patients with several different tumor types, have demonstrated that TAVO has broad clinical activity without the toxicity commonly associated with IL-12. The foundation of our DNA-based immunotherapy relies on electroporation, which bypasses the pitfalls associated with viral vectors or systemic cytokines."

The Company’s research laboratory discovered complimentary anti-tumor immunological pathways related to IL-12 derived from samples of previously treated TAVO patients. These discoveries resulted in the selection of two new genes, CXCL9 and aCD3 (expressing membrane-bound anti-CD3), to further drive a now enhanced version of IL-12, utilizing P2A in place IRES (TAVOPLUS). In parallel, OncoSec’s researchers reengineered the Company’s existing electroporation generator. The new generator, APOLLO, greatly increases DNA-plasmid cellular transfection rates in order to deliver more anti-cancer fighting genes directly into tumor cells. These independent evolutions of both components of OncoSec’s proprietary cancer immunotherapy platform converged in the design of its new product candidate, SPARK.

Highlights of the data presented at AACR (Free AACR Whitepaper) regarding SPARK and APOLLO demonstrate that:

APOLLO, using lower voltage and a longer pulse width, greatly increased DNA-plasmid cellular transfection rates to deliver more anti-cancer fighting genes directory into tumor cells;
TAVOPLUS, OncoSec’s new proprietary IL-12 enhanced DNA-plasmid, which expresses full-length IL-12 via bicistronic expression of both the p35 and p40 subunits, coupled with APOLLO, meaningfully improves anti-cancer responses;
SPARK, OncoSec’s new proprietary product candidate, drives strong anti-tumor immune responses by combining two novel anti-cancer genes, CXCL9 and aCD3, with TAVOPLUS
CXCL9 with TAVOPLUS
Productively modulates immune/tumor microenvironment
Significantly increases antigen-specific CD8+ CTL
Augments abscopal response of TAVOPLUS
aCD3, expressing membrane bound anti-CD3, with TAVOPLUS
Drives polyclonal T cell expansion and antigen-specific killing in vivo
Augments abscopal response when combined with TAVOPLUS
aCD3 complements CXC by strongly increasing cytotoxic anti-cancer tumor inflammation; and
SPARK, when delivered via APOLLO, significantly improves regression of untreated (distant) tumors in a difficult to treat preclinical melanoma model
"The encouraging data presented at AACR (Free AACR Whitepaper) demonstrate the potential of SPARK to integrate three key immunotherapeutic elements, IL-12, CXCL9 and anti-CD3 complimentary, into a single novel, multi-gene expression platform that we believe will have broad applicability across numerous tumor types," said Christopher G. Twitty, Chief Scientific Officer of OncoSec. "Importantly, SPARK builds upon our plasmid-based cancer immunotherapy platform by amplifying the power of intratumoral IL-12 through the sequenced addition of both CXCL9, a critical T cell chemokine and anti-CD3, a membrane-bound strong pan T cell stimulator. We look forward to filing an Investigational New Drug (IND) application for SPARK."

On April 2, 2019 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage oncology therapeutics company, taking a precision medicine approach to develop drugs that target cell division (mitosis) for the treatment of leukemias, lymphomas and solid tumor cancers, reported early data from its ongoing Phase 2 study evaluating Onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC) (Press release, Trovagene, APR 2, 2019, View Source [SID1234534897]).

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The data, featured at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) shows clinical activity as measured by prostate specific antigen (PSA) response when onvansertib is added to Zytiga in patients showing early signs of resistance to Zytiga.

Presentation Highlights

Preliminary Efficacy:

Early PSA response was observed with the addition of onvansertib to daily abiraterone in 2 of 6 patients, with 1 patient achieving the efficacy endpoint of disease control and a 30% decrease in tumor size by RECIST criteria (unconfirmed Partial Response to be confirmed with subsequent CT scan in May 2019)
PSA trajectory in the patient achieving the primary efficacy endpoint changed from 100% increase (16.05ng/ml to 34.23 ng/ml) in the 60 days prior to study to 8.4% increase during 84 days on study, indicating alteration of the natural history of early abiraterone resistance
Both patients that showed an early response (at C1D8) with decreases in PSA levels, also tested positive for AR-V7, a highly aggressive androgen receptor variant (AR-V7) which is resistant to Zytiga because it no longer needs androgen for tumor growth
Safety and Tolerability:

The combination of onvansertib and Zytiga is safe and well tolerated as demonstrated in the safety lead-in segment of the trial
No unexpected, off-target toxicities have been reported in patients treated to-date
"We are encouraged by the signs of clinical activity observed to-date and intrigued by the potential to be able to effectively treat patients who are AR-V7 positive," said Dr. Mark Erlander, Chief Scientific Officer of Trovagene. "There are limited options, other than intensive chemotherapy which has a poor prognosis, in patients who are showing initial signs of resistance to treatment with Zytiga and those that harbor the highly aggressive androgen receptor variant (AR-V7). We believe the combination regimen may provide a much-needed new therapeutic option for these patients."

Details of the poster presentation are provided below:

Title: A Phase 2 Study of the Polo-like Kinase 1 (PLK1) Inhibitor Onvansertib in Combination with Abiraterone (Abi) and Prednisone in Patients with Metastatic Castration-Resistant Prostate Cancer

Session Title: Phase I-III Trials in Progress: Part 2

Session Date and Time: Tuesday, April 2, 2019; 8:00 AM – 12:00 PM EDT

Session Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 17

About the Ongoing Onvansertib Phase 2 Trial in mCRPC

In this multi-center, open-label, Phase 2 trial, Onvansertib in combination with the standard dose of Zytiga (abiraterone acetate) and prednisone, all administered orally, is being evaluated for safety and efficacy. The trial will enroll up to 45 patients with mCRPC showing early signs of disease progression demonstrated by two rising PSA values separated by at least one week, while on Zytiga/prednisone therapy. The primary efficacy endpoint is the proportion of patients achieving disease control after 12 weeks of study treatment, as defined by lack of prostate specific antigen (PSA) progression in patients who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or asymptomatic) while currently receiving abiraterone acetate and prednisone (NCT03414034). The trial is being conducted at Beth Israel Deaconess Medical Center (BIDMC), Dana Farber Cancer Institute (DFCI) and Massachusetts General Hospital (MGH).

About Onvansertib

Onvansertib is a first-in-class, 3rd generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK 1) enzyme, which is over-expressed in multiple cancers, including leukemias, lymphomas and solid tumors. Separate studies with other PLK inhibitors have shown that inhibition of polo-like-kinases can lead to tumor cell death, including a Phase 2 study in Acute Myeloid Leukemia (AML) where response rates of up to 31% were observed when combined with a standard therapy for AML (low-dose cytarabine-LDAC) versus treatment with LDAC alone with a 13.3% response rate. A Phase 1 open-label, dose escalation safety study of Onvansertib has been completed in patients with advanced metastatic solid tumor cancers and published in Investigational New Drugs. The maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) in this trial was 24 mg/m2. Trovagene has an ongoing Phase 1b/2 clinical trial with onvansertib in AML that was accepted by the National Library of Medicine (NLM) and is now publicly viewable on www.clinicaltrials.gov. The NCT number assigned by clinicaltrials.gov for this study is NCT03303339. Onvansertib has been granted Orphan Drug Designation by the FDA in the U.S. and by the EC in the European Union (EU) for the treatment of patients with AML.

Onvansertib targets the PLK1 isoform, only (not PLK2 or PLK3), is orally administered, has a 24-hour drug half-life with only mild to moderate side effects reported. Trovagene believes that targeting only PLK1 and having a favorable safety and tolerability profile, along with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.

Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including FLT3 and HDAC inhibitors, taxanes, and cytotoxins. Trovagene believes the combination of its targeted PLK1 inhibitor, onvansertib, with other compounds has the potential to improve clinical efficacy in Acute Myeloid Leukemia (AML), metastatic Castration-Resistant Prostate Cancer (mCRPC), Non-Hodgkin Lymphoma (NHL), Colorectal Cancer, Triple Negative Breast Cancer (TNBC), as well as other types of cancer.