On May 23, 2019 Xynomic Pharmaceuticals Holdings, Inc. ("Xynomic"), a clinical stage US-China oncology drug development company (XYN), reported that long-term follow up data of exceptional responders to abexinostat/pazopanib will be presented by Dr. Rahul Aggarwal, a lead investigator at the University of California, San Francisco ("UCSF") (Press release, Xynomic Pharmaceuticals, MAY 23, 2019, http://xynomicpharma.com/en/xynomic-pharma-to-present-long-term-follow-up-data-showing-abexinostat-combined-with-pazopanib-has-durable-responses-in-patients-with-pre-treated-kidney-cancer/ [SID1234536538]). Dr. Aggarwal will present the information at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") Annual Meeting in Chicago, IL on June 1, 2019 in a presentation titled "Exceptional Responders to Abexinostat ("ABX") Plus Pazopanib ("PAZ") in Pre-Treated Renal Cell Carcinoma ("RCC") and Other Solid Tumors: Long-Term Follow Up of a Phase 1b Study" (Abstract No: 3022).

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The initial results from the Phase 1b study of Xynomic’s potent pan-HDAC inhibitor ABX plus PAZ demonstrated acceptable toxicity profile and encouraging anti-tumor activity (Aggarwal et al. Journal of Clinical Oncology, 2017). In this trial, 51 patients (including 22 RCC patients) were enrolled between June 2012 and October 2015. Among them, 10 patients (20%) had experienced disease progression on prior PAZ; 30 patients (59%) had received prior vascular endothelial growth factor ("VEGF") targeted therapy.

The ASCO (Free ASCO Whitepaper) presentation long-term follow up data of exceptional responders and additional correlative analyses associated with clinical outcomes. In particular, as of February 2019, among the 10 patients who had experienced disease progression on prior PAZ treatment, 5 patients achieved durable partial response ("PR") lasting for more than 2 years, and 1 patient who was previously a PAZ-refractory patient with RCC, remained on treatment with ongoing PR, for more than 6 years. In addition, higher peripheral blood HDAC2 expression was associated with prolonged progression-free survival (median PFS 5.9 vs. 3.5 months, log-rank p=0.02). Induction of histone acetylation on ABX lead-in treatment was associated with subsequent time to progression (p=0.002). On-treatment plasma VEGF levels were inversely correlated with PBMC histone acetylation (p=0.02). The new data demonstrate that (1) marketed durable responses with ABX + PAZ are achievable, including in patients with PAZ- and VEGF-refractory RCC and other solid tumor malignancies, and (2) host factors including HDAC expression and acetylation status may identify those patients most likely to benefit from this combination therapy.

A global, randomized pivotal Phase 3 trial is underway of ABX + PAZ as a first- or second-line therapy in patients with locally advanced or metastatic RCC (RENAVIV; NCT03592472). The U.S. Food and Drug Administration has granted Fast Track designation to abexinostat, in combination with pazopanib, as a first- or second-line treatment of RCC.

On May 23, 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 that Trovagene and Nektar have entered into a research collaboration to explore the combination of Trovagene’s PLK1 inhibitor, onvansertib, and Nektar’s topoisomerase I inhibitor, ONZEALD, for the treatment of metastatic colorectal cancer (mCRC) (Press release, Trovagene, MAY 23, 2019, View Source [SID1234536555]). Under the collaboration, the two companies will evaluate the antitumor activity and tolerability of the combination of onvansertib and ONZEALD in two (HT29 – BRAF mutant and HCT-116 – KRAS mutant) preclinical tumor models of colorectal cancer.

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ONZEALD is the first long-acting topoisomerase I-inhibitor (Topo I) designed to enhance the anti-cancer effects of topo I-inhibition while minimizing its toxicities. In a wide range of human xenograft tumors, including two colorectal models (HT29 and DLD-1), ONZEALD has shown superior antitumor activity, compared with irinotecan.1 ONZEALD is currently being evaluated in a Phase 3 study in patients with breast cancer who have stable brain metastases.

Onvansertib, an oral and highly-selective Polo-like Kinase 1 (PLK1) inhibitor, has shown strong antitumor activity in preclinical models of colorectal cancers, and demonstrated significant and durable synergistic antitumor activity in combination with irinotecan, and was greater than either drug alone. Trovagene has three active clinical trials: a Phase 1b/2 study in relapsed or refractory Acute Myeloid Leukemia (AML), a Phase 2 study in metastatic Castration-Resistant Prostate Cancer (mCRPC) and a Phase 1b/2 study in mCRC.

"We look forward to collaborating with Trovagene to explore a combination therapy with our respective drug candidates, ONZEALD and onvansertib, in tumor models of colorectal cancer," said Jonathan Zalevsky, PhD, Chief Scientific Officer of Nektar Therapeutics. "Importantly, this research collaboration will allow us to evaluate the efficacy of the combination in preclinical models, and potentially identify a promising treatment regimen that we would consider advancing into clinical studies."

"Our research partnership with Nektar is a key milestone achievement in the advancement of our onvansertib clinical development program," said Mark Erlander, PhD, Chief Scientific Officer of Trovagene. "We believe that the clinical data generated to date for ONZEALD, will potentially lead to an optimal treatment option, when combined with onvansertib, for patients with mCRC. Working together with Nektar will enable us to very quickly assess the potential value of the onvansertib/ONZEALD combination and our collective goal of developing an innovative and targeted treatment regimen that may have application in other cancer types beyond CRC."

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. 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 irinotecan, 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.

About ONZEALD

ONZEALD (etirinotecan pegol) is the first long-acting topoisomerase I-inhibitor (Topo I) designed to enhance the anti-cancer effects of topo I-inhibition while minimizing its toxicities. Nektar Therapeutics invented ONZEALD using their unique chemistry platform and is currently developing it for the treatment of advanced breast cancer patients with a history of brain metastases. In preclinical models, ONZEALD achieved a 300-fold increase in tumor concentration as compared to a first-generation topo I-inhibitor.2 Because ONZEALD is a large molecule, it is believed to penetrate the leaky vasculature within the tumor environment more readily than normal vasculature, concentrating and trapping ONZEALD in the tumor tissue.

On May 23, 2019 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel immunotherapy treatments for cancer and autoimmune diseases, is reported the grant of a new patent (number 3089749) entitled "Combined Preparations for the Treatment of Cancer" by the European Patent Office (Press release, Immutep, MAY 23, 2019, View Source [SID1234536539]).

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The new patent protects Immutep’s intellectual property relating to combined therapeutic preparations comprising its lead active immunotherapy candidate eftilagimod alpha ("efti" or "IMP321") and a chemotherapy agent. The chemotherapy agent is either a platinum-based anti-neoplastic agent, such as oxaliplatin or carboplatin, or a topoisomerase I inhibitor, such as topotecan.

Dr Frédéric Triebel, Immutep CSO and CMO, commented, "This new patent is important because platinum-based chemotherapy agents and topoisomerase I inhibitors continue to be commonly used forms of chemotherapy. In addition, the past couple of years has seen, for the first time, the marketing approval and adoption of first or second line combinations of chemotherapy and active immunotherapies for the treatment of advanced solid tumors.

As such, this new patent provides patent protection in Europe for a range of novel and highly relevant chemo-immunotherapies featuring efti that may be pursued in the future."

The patent expiry date is 19 December 2034.

On May 23, 2019 Tmunity Therapeutics, Inc., a private clinical-stage biotherapeutics company focused on saving and improving lives by delivering the full potential of next-generation T cell immunotherapy, reported that Usman "Oz" Azam, MD, President and Chief Executive Officer, and members of the management team plan to participate at an investor conference in June 2019 (Press release, Tmunity Therapeutics, MAY 23, 2019, View Source [SID1234536556]).

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Jefferies 2019 Global Healthcare Conference
Thursday, June 6, 2019
9:30 a.m. ET
New York, NY

On May 23, 2019 OncoSec Medical Incorporated (OncoSec) (NASDAQ: ONCS), a late-stage cancer biotechnology company developing intratumoral gene-delivery immunotherapies, reported that the first patient has been dosed in TRIFECTA, a triple combination clinical trial of OncoSec’s TAVO, an IDO1 drug (epacadostat) and KEYTRUDA in patients with unresectable squamous cell carcinoma head and neck (SCCHN) cancer (Press release, OncoSec Medical, MAY 23, 2019, View Source [SID1234536540]). The study is being led by Dr. Chase Heaton, M.D., a leading oncologic head and neck surgeon at UCSF, and was developed in collaboration with Dr. Alain Algazi, leader of the Head and Neck Medical Oncology Program at UCSF and Clinical Strategic Advisor to OncoSec. Preliminary data from the TRIFECTA study is anticipated later this year.

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The TRIFECTA study capitalizes on findings from a 2017 plot study of TAVO in head and neck cancer patients, which demonstrated impressive clinical and biological results including evidence of synergy between TAVO, and PD-1 antibodies in the disease. One of the patients in the 2017 pilot study, who experienced a remarkable tumor response following TAVO treatment, was featured in a LA Times in an article entitled, "I have terminal cancer and I know my friends want to ask, ‘Aren’t you dead yet?’"

A link to the LA Times article can be found here: View Source

The triple combination of IL-12, IDO1 and anti-PD-1 monoclonal antibody is a first-of-its-kind clinical trial and is seeking to exploit individual anti-tumor properties of each modality. The goal of the study is to evaluate this three-way combination in SCCHN cancer and, if promising, to potentially evaluate the triple combination in other tumor types.

TRIFECTA is an investigator-initiated, single-arm, open-label clinical trial in which 35 evaluable SCCHN patients will receive TAVO, pembrolizumab, and epacadostat. The primary endpoint of the study is overall response rate (ORR) by RECIST v1.1 and will be compared to historical data for pembrolizumab monotherapy in SCCHN and to existing data regarding the combination of pembrolizumab and epacadostat. The study is being conducted by the UCSF Helen Diller Family Comprehensive Cancer Center.

"Despite advancements in the field of immunotherapy, patients with unresectable SCCHN have had limited success when treated with anti-PD-1 antibodies as a monotherapy. Given TAVO’s ability to reverse anti-PD-1 resistance in patients with a variety of tumor types, we are hopeful this triplet combination will benefit this vulnerable patient population," said Daniel O’Connor, President and CEO of OncoSec. "The start of this investigator-initiated clinical trial marks an important milestone for OncoSec and we look forward to reporting preliminary data from this study later this year."