On April 23, 2019 OncoSec Medical Incorporated (OncoSec) (NASDAQ:ONCS), a company developing intratumoral cancer immunotherapies, reported a triple combination clinical trial of OncoSec’s TAVO, epacadostat, and KEYTRUDA in patients with squamous cell carcinoma head and neck (SCCHN) cancer (Press release, OncoSec Medical, APR 23, 2019, View Source [SID1234535327]). This study, the "TRIFECTA" study, will be conducted by the UCSF Helen Diller Family Comprehensive Cancer Center.

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TRIFECTA, formally entitled, "The Trifecta Study: Optimizing Antitumor Immunity Using Tavokinogene Telseplasmid with Electroporation, Pembrolizumab, and Epacadostat in Squamous Cell Carcinoma of the Head and Neck," will evaluate the combination use of OncoSec’s TAVO (intratumoral IL-12 tavokinogene telseplasmid), epacadostat (IDO inhibitor), and KEYTRUDA (pembrolizumab, an anti-PD1 monoclonal antibody) in patients with SCCHN cancer.

TRIFECTA will be an investigator-initiated clinical trial by UCSF otolaryngologist, Dr. Chase Heaton, to determine whether the triple combination can increase the overall response rate (ORR) in SCCHN compared with historical data for KEYTRUDA as a monotherapy. The costs of this clinical trial will be shared with others and will require minimal financial commitment from OncoSec.

The response rate in patients with unresectable SCCHN is very low when treated with anti-PD1 antibodies as a monotherapy, with only 13-16%1 2 durable remissions. Treatment failures are more common in patients whose tumors either lack anti-tumor immune cells or have an overabundance of regulatory immune cells that suppress effective anti-tumor immune responses. TAVO has previously demonstrated the ability to reverse this type of anti-PD-1 resistance in patients with metastatic melanoma.

"Effective anticancer immune responses require three steps, including immune priming and tumor infiltration with T cells; activation of partially exhausted TILs; and selective modulation of T cell populations to maximize the ratio of effector to regulatory immune cells," said Dr. Alain Algazi, Associate Professor of Clinical Medicine at UCSF and Clinical Strategic Advisor to OncoSec. "Based on this framework, we hypothesize that the combination of TAVO’s tumor infiltration mechanism, with pembrolizumab’s TIL technology and epacadostat’s T cell modulating capabilities will substantially increase the ORR to pembrolizumab in patients with SCCHN and that the combination will be well tolerated in this population."

TRIFECTA is a single-arm open-label clinical trial in which 35 evaluable 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.

Melanoma patients in the anti-PD-1 refractory setting have found renewed clinical responses with the combination of KEYTRUDA with TAVO in the KEYNOTE-695 trial. TAVO’s mechanism of action may also enhance the activity of epacadostat as expression of IDO is driven by IFN-g, which, in TAVO-treated patients may create a broader target and therefore opportunity to limit this suppressive IDO axis. Due to its favorable safety profile, clinical activity and ability to trigger adaptive resistance (increases in both IDO and PD-L1 expression) via a robust IFN-g response, TAVO is a strong backbone for a combination strategy with epacadostat and Merck’s anti-PD-1 antibody, pembrolizumab.

"Supporting this investigator-initiated clinical is a very cost-effective way to learn if the three-way combination of TAVO, epacadostat and pembrolizumab can significantly improve the historical anti-PD-1 monotherapy durable remission response rate of 13-16%," said Daniel O’Connor, President and Chief Executive Officer of OncoSec. "Studies such as these continue to build on the body of clinical evidence in support of TAVO in a variety of combination therapies. We believe it is important to support investigator led studies such as this one, especially considering the prestige of the medical institution and the oncologists involved."

On April 23, 2019 Athenex, Inc. (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies for the treatment of cancer and related conditions, reported that four abstracts have been accepted for presentation at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held May 31 to June 4, 2019 at the McCormick Place Convention Center in Chicago, Illinois (Press release, Athenex, APR 23, 2019, View Source;p=RssLanding&cat=news&id=2395278 [SID1234535344]).

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"We are very pleased with the abstracts that have been accepted for presentation at ASCO (Free ASCO Whitepaper) this year," said Dr. Johnson Lau, Chairman and Chief Executive Officer of Athenex. "We look forward to sharing additional information on our lead, pivotal stage Oraxol (Oral paclitaxel and HM30181A) program as well as preliminary results from our Oratecan (Oral irinotecan and HM30181A) Phase I study and preclinical proof of concept data for our new arginine deprivation therapy platform, Pegtomarginase. We believe these will demonstrate the broad applicability of the Orascovery technology for a wide range of commonly used chemotherapy agents and the depth of our oncology-focused pipeline."

Presentation details:

Title: (Abstract TPS1116) KX-ORAX-001: An open label, randomized, multicenter, Phase III registrational study to determine the safety, tolerability, and tumor response of Oraxol (HM30181A + oral paclitaxel) and its comparability to IV paclitaxel in patients with metastatic breast cancer (MBC).
Poster Session: Breast Cancer—Metastatic
Session Date, Time, Location: Sunday June 2, 2019, 8:00 AM-11:00 AM Central Daylight Time, Hall A

Title: (Abstract 1084) Oral paclitaxel in the treatment of metastatic breast cancer (MBC) patients.
Poster Session: Breast Cancer—Metastatic
Session Date, Time, Location: Sunday June 2, 2019, 8:00 AM-11:00 AM Central Daylight Time, Hall A

Title: (Abstract 3032) A Phase 1 study of the oral administration of irinotecan in combination with the potent P-glycoprotein (P-gp) inhibitor HM30181A.
Poster Session: Developmental Therapeutics and Tumor Biology (Nonimmuno)
Session Date, Time, Location: Saturday June 1, 2019, 8:00 AM-11:00 AM Central Daylight Time, Hall A

Title: (Abstract 3090) Design, engineering, and characterization of a novel long-acting (Pegylated) single isomer human arginase for arginine depriving anti-cancer treatment.
Poster Session: Developmental Therapeutics and Tumor Biology (Nonimmuno)
Session Date, Time, Location: Saturday June 1, 2019, 8:00 AM-11:00 AM Central Daylight Time, Hall A

The abstract titles are currently available on the ASCO (Free ASCO Whitepaper) iPlanner website, with the full abstracts scheduled to be published on May 15, 2019.

Athenex has received approval of the International Nonproprietary Name (INN) "encequidar" for its novel P-gp pump inhibitor molecule, HM30181A. The Company may use the nomenclature "encequidar" in future communications.

The Orascovery platform was initially developed by Hanmi Pharmaceuticals and licensed exclusively to Athenex for all major worldwide territories except Korea, which is retained by Hanmi.

On April 22, 2019 Elpiscience BioPharma and Bio-Techne Corporation reported that the companies have entered into a strategic collaboration for the development of anti-cancer therapeutics (Press release, Elpiscience, APR 22, 2019, View Source;id=1313 [SID1234536921]). Under the terms of the agreement, Elpiscience will have access to multiple antibodies from Bio-Techne’s antibody library for use in preclinical, clinical and commercial pharmaceutical development.

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As a biotech company committed to leading the innovation and development of the next generation of cancer immunotherapy, Elpiscience, in collaboration with Bio-Techne, a global leader in life sciences and molecular diagnostics, will expand mutual capabilities in the field of cancer immunotherapy. This strategic collaboration also aims to accelerate the development of new biologics to address unmet medical needs in Oncology.

Dr. Darren Ji, CEO of Elpiscience, said: "We are very happy to enter into a strategic collaboration with Bio-Techne in therapeutic antibody research and development. This collaboration will leverage the strengths of both companies in the field of anti-cancer therapeutics and speed up the development of new cancer immunotherapies in order to bring more efficient treatment to cancer patients worldwide."

David Eansor, President of Bio-Techne’s Protein Sciences Segment commented "We are extremely excited to partner with Elpiscience in the development of novel cancer immunotherapies. It is our goal to increase our partnerships with therapeutics developers to unleash the potential of our vast library of high-quality antibodies towards the development of next generation immunotherapies."

On April 22, 2019 Molecular Templates, Inc., (Nasdaq: MTEM) a clinical stage biopharmaceutical company focused on the discovery and development of Engineered Toxin Bodies (ETBs), a new class of targeted biologic therapies that possess unique mechanisms of action in oncology, reported that the U.S. Food and Drug Administration (FDA) has accepted its Investigational New Drug (IND) application for MT-5111, an ETB targeting HER2 (Press release, Molecular Templates, APR 22, 2019, View Source [SID1234535314]). MTEM expects to start dosing in a Phase I study in relapsed/refractory patients with HER2-positive solid tumors in 3Q19.

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This Phase I study is an open-label, dose escalation and expansion study of MT-5111 given as monotherapy in subjects with HER2-positive solid tumors. The primary objective of the trial is to evaluate the safety and tolerability of MT-5111 and determine the recommended Phase II dose in subjects with advanced HER2-positive solid tumors.

"We are excited to be advancing MT-5111, which utilizes our proprietary de-immunized toxin scaffold, into the clinic for the treatment of patients with HER2-positive cancers. HER2 is a well validated target that is central to disease and when existing HER2-targeting therapies fail, the target persists, suggesting that a HER2-targeted therapy with a new mechanism of action has good potential to provide benefit to patients," said Eric Poma, Ph.D., CEO and CSO of Molecular Templates. "We have seen promising responses to our lead pipeline candidate MT-3724 in DLBCL and we are excited to further leverage the novel mechanism of action of our ETB platform with MT-5111. We look forward to providing an update on the Phase I study by year-end 2019."

About MT-5111
MT-5111 is an ETB consisting of a single chain variable fragment (scFv) with affinity for HER2, fused to the enzymatically active de-immunized Shiga-like toxin-A subunit (SLTA). MT-5111 specifically binds and kills HER2 expressing cells in a manner consistent with SLTA mediated cellular cytotoxicity. MT-5111 has been specifically designed to avoid competition with and to overcome the primary mechanisms of tumor resistance to current HER2 targeted therapies. To accomplish this, first, MT-5111 binds a HER2 domain that is distinct from the trastuzumab and pertuzumab binding sites, which results in MT-5111 HER2-mediated binding and cell kill even in the presence of these monoclonal antibodies. As such, MT-5111 may have the potential to be combined with other HER2 targeted therapies. Second, SLTA is a large molecule protein and is not a substrate of drug efflux transporters such as MDR1 which has been demonstrated to be one of the primary mechanisms of resistance to the antibody drug conjugate, T-DM1. Third, MT-5111 mediated ribosomal inhibition and cell death take place intracellularly so changes in the tumor microenvironment which inhibit immune-mediated mechanisms such as antibody-dependent cell-mediated cytotoxicity (ADCC) are not expected to inhibit MT-5111 activity. Finally, mutations to the HER2 kinase domain that can induce constitutive downstream signaling to drive tumor proliferation are not expected to interfere with MT-5111 activity, given that its mechanism of action is not dependent upon kinase domain binding and MT-5111 works directly on ribosomes to mediate ribosomal inhibition and cell death. Based on these mechanisms, MT-5111 represents a novel HER2 targeted therapy which could provide benefit in subjects with HER2-positive cancers and potentially overcome mechanisms of tumor resistance to existing HER2 targeted therapies.

On April 22, 2019 GlycoMimetics, Inc. (NASDAQ: GLYC) reported the publication of a paper in Nature Cell Biology that describes how tumor cells engage specific stromal components, most notably E-selectin, for propagation and outgrowth (Press release, GlycoMimetics, APR 22, 2019, View Source [SID1234535315]).1 The paper provides further scientific support for the clinical trial in breast cancer patients with bone metastasis that was recently announced by GlycoMimetics.

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Specifically, Esposito et. al. identify an E-selectin ligand expressed on tumor cells that is necessary for inducing mesenchymal-epithelial transition (MET) and that drives metastatic progression within the bone marrow microenvironment. Of note, in preclinical animal models of human breast cancer, inhibition of E-selectin with GlycoMimetics’ compound uproleselan (GMI-1271) prevented bone metastases progression and significantly attenuated bone metastases-associated bone degradation, resulting in a significant survival advantage in treated tumor-bearing mice. Previously published work also demonstrates a complimentary role for CXCR4. Together these observations support the testing of GMI-1359, GlycoMimetics’ dual-function antagonist, which targets both mechanisms.

"The scientific rationale for potential uses of GMI-1359 in oncology indications continues to build," said John L. Magnani, PhD, Chief Scientific Officer of GlycoMimetics. "This most recent paper contributes additional understanding to the critical role of E-selectin and to the potential uses of compounds that target this mechanism in cancer, in particular in cancers that metastasize to bone."

About GMI-1359

GMI-1359 is designed to simultaneously inhibit both E-selectin and CXCR4. E-selectin and CXCR4 are both adhesion molecules involved in tumor trafficking and metastatic spread. Preclinical studies indicate that targeting both E-selectin and CXCR4 with a single compound could improve efficacy in the treatment of cancers that involve the bone marrow such as AML and multiple myeloma or in solid tumors that metastasize to the bone, such as prostate cancer and breast cancer. GMI-1359 has completed a Phase 1 clinical trial in healthy volunteers.