On January 28, 2020 Ikena Oncology, a clinical-stage biotechnology company that discovers and develops patient-directed, biomarker-driven therapies, reported dosing of the first patient in the first Phase 1 clinical trial evaluating IK-175 (formerly KYN-175), an internally-developed, orally administered, selective aryl hydrocarbon receptor (AHR) antagonist, in patients with advanced solid tumors (Press release, Ikena Oncology, JAN 28, 2020, View Source [SID1234553626]). This Phase 1 study is expected to enroll approximately 50 patients in the US across both the dose escalation and dose expansion portions of the study.

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 first-in-human, single-arm, open-label, dose-escalation and expansion study (NCT04200963) is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of IK-175 as a single-agent in patients with locally advanced or metastatic solid tumors, including urothelial carcinoma. The primary objectives of the study include determination of the maximum tolerated dose, characterizing dose-limiting toxicities, and identification of the recommended Phase 2 dose of single-agent IK-175. Secondary objectives include evaluating disease response, including overall response rate, progression-free survival, duration of treatment, disease control rate and duration of response, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Jason Luke, MD, FACP, associate professor of medicine in the Division of Hematology/Oncology and director of the Cancer Immunotherapeutics Center at the University of Pittsburg Medical Centre (UPMC) Hillman Cancer Immunology and Immunotherapy Program, and a clinical investigator on the IK-175 study, commented: "Activated AHR prevents immune recognition in a range of cancers which makes it a highly evocative drug target, especially in patients who do not fully benefit from standard-of-care, including checkpoint inhibitors. Compelling preclinical evidence supports the clinical potential of IK-175, including its ability to potently inhibit AHR activity. We look forward to further elucidating the safety, tolerability and preliminary efficacy of IK-175 in the clinic."

"Advancing IK-175 into the clinic, less than 3 years after we initiated the discovery program, is a key milestone for Ikena and we are delighted to commence investigation of this promising agent in patients with advanced solid tumors," said Mark Manfredi, Ph.D., President and Chief Executive Officer of Ikena Oncology. "This accelerated timeline is a testament to our ability to rapidly advance assets from the bench to patients. Assuming a positive outcome from the dose-escalation and expansion portion of this single-agent study, we plan to commence an additional portion of the study to evaluate IK-175 in combination with a checkpoint inhibitor. We look forward to providing updates over the course of the study."

About IK-175

IK-175 (formerly known as KYN-175) is an internally-developed, orally-administered, selective aryl hydrocarbon receptor (AHR)antagonist which prevents AHR-modulated tumor promotion through its influence on both the tumor and the immune system. Ikena Oncology recently commenced a first-in-human, Phase 1 clinical study (NCT04200963) in which the safety and antitumor activity of IK-175 is being evaluated as a single agent in advanced solid tumors. A patent application with claims directed to IK-175 has been allowed by the United States Patent and Trademark Office. The AHR antagonist program is the subject of a global strategic collaboration with Bristol-Myers Squibb.

On January 28, 2020 Avacta Group plc (AIM: AVCT), the developer of Affimer biotherapeutics and reagents, is reported that it has demonstrated initial proof-of-concept for its proprietary new class of drug conjugate, TMAC, in a pre-clinical animal model of cancer (Press release, Avacta, JAN 28, 2020, View Source [SID1234553627]). The study showed that AVA04-VbP outperformed Bavencio (Avelumab), a marketed anti-PD-L1 immunotherapy.

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!

Avacta’s tumour microenvironment activated drug conjugates (TMAC) are a ground-breaking new form of cancer immunotherapy, combining its Affimer biotherapeutics with chemotherapies in a single drug, using a linker (incorporating its proprietary pre|CISION substrate) that is designed to only release the chemotherapy in the tumour microenvironment through the action of an extracellular enzyme called FAPα. This mechanism overcomes the need to target an internalising cancer marker, as with conventional antibody drug conjugates (ADCs), and allows extremely potent chemotherapies to be combined with Affimer immune-checkpoint therapies. Combining pre|CISION technology with the Affimer platform is enabling Avacta to build a pipeline of novel and safe cancer therapies applicable to a broader range of cancer patients, including those who do not respond to existing immunotherapies.

AVA04-VbP combines an Affimer PD-L1 checkpoint inhibitor with an I-DASH chemotherapy warhead, addressing the acute systemic toxicity associated with I-DASH inhibitors by targeting the release of the drug warhead in the tumour microenvironment. The drug warhead induces a highly pro-inflammatory cell death, which in turn stimulates an immune response in the tumour, which is supported by the Affimer PD-L1/PD-1 signalling pathway blockade.

In a mouse syngeneic tumour model study, Avacta has shown that AVA04-VbP outperforms Bavencio; animals treated with AVA04-VbP showed a significant reduction in the rate of tumour growth with respect to those treated with Bavencio. A considerably higher level of the released I-DASH warhead was measured in the tumours compared with very low levels in the blood, indicating that healthy tissues are less exposed to the highly toxic warhead. This tumour targeting is central to the TMAC mechanism of action, and permits the use of the highly potent cancer-killing warheads.

On January 27, 2020 AstraZeneca’s and Daiichi Sankyo Company, Limited reported that High-level results from the positive registrational Phase II trial DESTINY-Gastric01 showed (Daiichi Sankyo)’s Enhertu (trastuzumab deruxtecan), achieved a statistically significant and clinically meaningful improvement in objective response rate (ORR) and overall survival (OS) in patients with HER2-positive unresectable or metastatic gastric or gastroesophageal junction cancer that had progressed following two or more treatment regimens including trastuzumab and chemotherapy (Press release, AstraZeneca, JAN 27, 2020, View Source [SID1234553546]).

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 trial met its primary endpoint of an improvement in ORR, as assessed by an independent review committee, in patients treated with Enhertu compared to investigator’s choice of chemotherapy (irinotecan or paclitaxel monotherapy). Enhertu also showed a statistically significant and clinically meaningful improvement in OS, a key secondary endpoint.

José Baselga, Executive Vice President, Oncology R&D, said: "Gastric cancer is usually diagnosed in the advanced stage and patients face markedly high mortality rates, making the need for new therapies especially urgent. Given the previous results seen in our HER2-positive development programme and now in HER2-positive metastatic gastric cancer, we believe this antibody drug conjugate has the potential to redefine the treatment of patients with HER2-expressing cancers."

Gilles Gallant, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo, said: "We are excited to report positive top-line results from this trial. Our development plan remains on track in gastric cancer, including an initial regulatory application in Japan where gastric cancer is highly prevalent, and where SAKIGAKE designation has been granted for this indication. We are strongly committed to bringing this therapy as rapidly as possible to patients in need."

The overall safety and tolerability profile of Enhertu in DESTINY-Gastric01 was consistent with that seen in the published Phase I trial in which the most common adverse events (≥30 percent, any grade) were haematologic and gastrointestinal including neutrophil count decrease, anaemia, nausea and decreased appetite. There were cases of treatment-related interstitial lung disease (ILD) and pneumonitis, the majority of which were Grade 1 and 2 with two Grade 3 and one Grade 4. No ILD-related deaths (Grade 5) occurred in gastric patients in the Phase I trial or in the DESTINY-Gastric01 trial.

These results confirm activity seen in the non-randomised Phase I trial of Enhertu in patients with HER2-positive advanced gastric cancer published in The Lancet Oncology.1 Data from DESTINY-Gastric01 will be presented at a forthcoming medical meeting.

In addition to the planned discussion with the Japan Ministry of Health, Labour and Welfare (MHLW), both companies plan to discuss the data with other health authorities. Enhertu recently received Accelerated Approval in the US for HER2-positive unresectable or metastatic breast cancer following two or more prior anti-HER2 based treatment regimens and additional global regulatory submissions in HER2-positive metastatic breast cancer are underway.

Enhertu is being jointly developed and commercialised worldwide with AstraZeneca except in Japan where Daiichi Sankyo maintains exclusive rights.

HER2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including gastric, breast and lung cancers. HER2 overexpression is often associated with aggressive disease and poorer prognosis.2 When a patient is diagnosed with gastric cancer, guidelines recommend evaluating HER2-expression levels by an immunohistochemistry (IHC) test.3 A finding of IHC 3+ is considered positive. A result of IHC 2+ is considered equivocal, in which case an additional testing method of in situ hybridisation (ISH) is recommended to confirm HER2 status.

Gastric cancer

Gastric (stomach) cancer is the fifth most common cancer worldwide and the third leading cause of cancer mortality; there were approximately one million new cases reported in 2018 and 783,000 deaths.4 Incidence rates for gastric cancer are markedly higher in eastern Asia, where approximately half of all cases occur.4 South Korea and Japan have the first and third highest incidence rates of gastric cancer worldwide, respectively; in 2018, the age-standardised rate in Japan was 27.5 per 100,000 and in South Korea it was 39.6 per 100,000.5

Approximately one in five gastric cancers are HER2 positive.6 Gastric cancer is usually diagnosed in the advanced stage, but even when diagnosed in earlier stages of the disease the survival rate remains modest.7 Recommended 1st-line treatment for HER2-positive advanced or metastatic gastric cancer is combination chemotherapy plus trastuzumab, an anti-HER2 medicine, which has been shown to improve survival outcomes when added to chemotherapy.8 For gastric cancer that progresses on trastuzumab, there are no other approved HER2-targeting medicines and subsequent treatment options are limited.9

DESTINY-Gastric01

DESTINY-Gastric01 is a registrational Phase II, open-label, multi-centre trial assessing the safety and efficacy of Enhertu in 189 patients from Japan and South Korea with HER2-expressing advanced gastric cancer or gastroesophageal junction adenocarcinoma (defined as IHC3+ or IHC2+/ISH+) who have progressed on two or more prior treatment regimens including fluoropyrimidine (5-FU) and platinum chemotherapy and trastuzumab. Patients were randomised 2:1 to receive Enhertu or investigator’s choice of chemotherapy (paclitaxel or irinotecan monotherapy). Patients were treated with Enhertu 6.4mg/kg once every three weeks or chemotherapy given on the same schedule. The primary endpoint of the trial is ORR. Secondary endpoints include OS, progression-free survival, duration of response, disease control rate and time to treatment failure as well as pharmacokinetic and safety endpoints.

Enhertu

Enhertu (fam-trastuzumab deruxtecan-nxki in the US only; trastuzumab deruxtecan outside the US) is a HER2-directed antibody drug conjugate (ADC) and is the lead product in the ADC Franchise of the Daiichi Sankyo Cancer Enterprise and the most advanced programme in AstraZeneca’s ADC scientific platform. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.

Enhertu clinical development

A comprehensive development programme is underway globally with five registrational trials in HER2-expressing metastatic breast and gastric cancers including a trial in patients with metastatic breast cancer and low levels of HER2 expression. Phase II trials are underway for HER2-expressing advanced colorectal cancer, as well as metastatic non-squamous HER2-overexpressing or HER2-mutated non-small cell lung cancer. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Collaboration between AstraZeneca and Daiichi Sankyo

In March 2019, AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu worldwide, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is solely responsible for manufacturing and supply.

AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca’s main capabilities, the Company is actively pursuing innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by the investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On January 27, 2020 IntelGenx Technologies Corp. (TSXV: IGX) (OTCQX: IGXT) (the "Company" or "IntelGenx") reported the pricing of an agency offering (the "Offering") of up to 20,000,000 units, subject to a minimum offering of 10,000,000 units (the "Units"), for gross proceeds of between $5,000,000 and $10,000,000, assuming no exercise of the over-allotment option granted to the Agent (as defined below), at a price of $0.50 per Unit (Press release, IntelGenx, JAN 27, 2020, View Source [SID1234553570]). Each Unit will consist of one share (each, an "Offered Share") of common stock of the Company ("Common Stock") and one warrant (each, a "Warrant") to purchase one share of Common Stock at an exercise price of $0.75 per share (a "Warrant Share"). The Warrants will be exercisable immediately and will expire on the third anniversary of the date of their issuance.

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 Offering is being conducted on a commercially reasonable best efforts basis by Echelon Wealth Partners Inc. (the "Agent") in the provinces of British Columbia, Alberta, Manitoba and Ontario. Closing of the Offering is expected to occur on or about February 11, 2020.

The Company has granted to the Agent an option to increase the size of the Offering by up to 15%, exercisable in whole or in part at any time for a period of 30 days after and including the closing date of the Offering.

The net proceeds from the Offering will be used for the Company’s Phase 2A Montelukast Study and general working capital requirements.

The Company has applied to list the Offered Shares, the Warrants and the Warrant Shares underlying the Units on the TSX Venture Exchange (the "TSXV"). The approval is subject to fulfillment by the Company of customary closing conditions of the TSXV.

The Company intends to file a final short form prospectus (the "Prospectus") in the provinces of British Columbia, Alberta, Manitoba, Ontario and Quebec, as well as an amended registration statement on Form S-1 (the "Registration Statement") with the United States Securities and Exchange Commission (the "SEC") with respect to the Offering today. The Offering is subject to certain customary conditions including, but not limited to, the receipt of all necessary approvals, including the SEC declaring the Registration Statement effective.

Before investing, you should read the Prospectus and the Registration Statement, as well as other documents the Company has filed or will file late today with the SEC and the Canadian securities regulators for more complete information about the Company and this Offering. A copy of the Prospectus is available under the Corporation’s profile at www.sedar.com and a copy of the Registration Statement can be obtained from the SEC’s website at www.sec.gov or by request to Echelon Wealth Partners Inc. at [email protected].

A registration statement relating to these securities has been filed with the SEC but has not yet become effective. These securities may not be sold nor may offers to buy be accepted prior to the time the registration statement becomes effective. No offer to buy the securities can be accepted and no part of the purchase price can be received until the registration statement has become effective, and any such offer may be withdrawn or revoked, without obligation or commitment of any kind, at any time prior to notice of its acceptance given after the effective date.

On January 27, 2020 Immunomic Therapeutics, Inc. reported that it will present data on its investigational nucleic acid platform, UNITE (UNiversal Intracellular Targeted Expression), that elicits potent immune responses and inhibits tumor growth when used with its investigational vaccine, ITI-4000, in mice (Press release, Immunomic Therapeutics, JAN 27, 2020, View Source [SID1234553591]). In preclinical studies, ITI-4000, a DNA vaccine targeting EBNA1, demonstrated robust activation of anti-tumor CD4 and CD8 T cells in vivo and promoted tumor infiltration with activated TNFα-producing CD8 T cells. Intratumoral IL-12-producing dendritic cells and iNOS-producing macrophages were also induced by the vaccine. This data will be presented at the SITC (Free SITC Whitepaper)-ASCO Clinical Immuno-Oncology Symposium in Orlando, Florida.

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!

"ITI-4000 is an innovative and novel approach to an EBV-tumor vaccine," says Rich Ambinder, M.D., Ph.D., Director of the Division of Hematologic Malignancies and Professor of Oncology at Johns Hopkins, Immunomic’s Scientific Advisory Board member, and expert in viral-driven malignancies.

Current treatment strategies for nasopharyngeal carcinoma are limited to radiation and chemotherapy, demonstrating a need for new, targeted therapies. Most nasopharyngeal carcinomas express Epstein-Barr nuclear antigen 1 (EBNA1), a sequence-specific DNA-binding protein involved in maintenance of the episomal virus genome that is required for EBV latency and associated transformation. Targeting EBNA1 allows for an immunotherapeutic approach by exploiting the potential of the immune system to recognize tumor cells through their expression of this viral antigen. We designed a DNA vaccine encoding EBNA1 using the UNITE platform (ITI-4000). The UNITE platform is based in part on lysosomal targeting technology which results in enhanced antigen presentation and a balanced T cell response. We report that the ITI-4000 induced IFNγ- and TNFα-producing effector memory CD4 T and CD8 T cells, with complete rejection of EBNA1-expressing tumors observed in 50% of mice. Mice rejecting tumors were protected from rechallenge with CT26-EBNA1, demonstrating that antigen-specific memory was induced in these animals. These pre-clinical data suggest that ITI-4000 has the potential to be used as an immunotherapeutic agent against EBV-associated cancers.

Poster Session B

Poster Title: The Effect of Lysosomal-associated membrane protein-1-targeting of Epstein–Barr virus nuclear antigen 1 (EBNA1) elicits potent immune responses and inhibits tumor growth in preclinical studies

Date and Time: 02/07/2020, 11:30 AM – 1:00 PM; 02/07/2020, 6:00 PM – 7:00 PM

Abstract ID: #74

About UNITE

ITI’s investigational UNITE platform, or UNiversal Intracellular Targeted Expression, is thought to work by encoding the Lysosomal Associated Membrane Protein, an endogenous protein in humans. In this way, ITI’s vaccines (DNA or RNA) have the potential to utilize the body’s natural biochemistry to develop a broad immune response including antibody production, cytokine release, and critical immunological memory. This approach could put UNITE technology at the crossroads of immunotherapies in a number of illnesses, including cancer, allergy, and infectious diseases. UNITE is currently being employed in Phase II clinical trials as a cancer immunotherapy. ITI is also collaborating with academic centers and biotechnology companies to study the use of UNITE in cancer types of high mortality, including cases where there are limited treatment options like glioblastoma and acute myeloid leukemia. ITI believes that these early clinical studies may provide a proof of concept for UNITE therapy in cancer, and if successful, set the stage for future studies, including combinations in these tumor types and others. Preclinical data is currently being developed to explore whether LAMP nucleic acid constructs may amplify and activate the immune response in highly immunogenic tumor types and be used to create immune responses to tumor types that otherwise do not provoke an immune response.