On April 23, 2020 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported updated clinical data from its ongoing Phase 2 clinical trial of DKN-01, its anti-Dickkopf-1 (DKK1) antibody, as both a monotherapy and in combination with paclitaxel chemotherapy in patients with advanced gynecological malignancies (Press release, Leap Therapeutics, APR 23, 2020, View Source [SID1234556534]). Leap will host a conference call with Rebecca Arend, M.D., Assistant Professor and Associate Scientist, Gynecologic Oncology Clinic, The University of Alabama at Birmingham School of Medicine Comprehensive Cancer Center Experimental Therapeutics Program, today, April 23, 2020, at 8:30 A.M. EDT to discuss the data.

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"We are seeing clinically meaningful monotherapy activity of DKN-01 in heavily pre-treated endometrial cancer and carcinosarcoma populations, including a complete response, a partial response, and durable tumor reductions in many patients. In combination with paclitaxel, DKN-01 is generating durable responses and disease control in paclitaxel-experienced patients," said Dr. Arend.

"This study also demonstrates the importance of mechanism of action based biomarkers for DKN-01 therapy, as patients with high tumor DKK1 expression or Wnt activating mutations had enhanced progression-free survival and overall survival. These biomarkers should be the foundation for additional DKN-01 studies in endometrial and carcinosarcoma patients, as monotherapy and in combination with other active agents," continued Dr. Arend.

The P204 Study in Gynecologic Cancers

The P204 study is a Phase 2 basket study evaluating DKN-01 as a monotherapy and in combination with paclitaxel in patients with relapsed/refractory epithelial endometrial cancer (EEC), epithelial ovarian cancer (EOC), or carcinosarcoma (also known as Malignant Mixed Mullerian Tumor (MMMT)). As of the cut-off date of December 30, 2019, 105 heavily pretreated patients had been enrolled across the six groups of the study. Approximately 67% of all patients had tumors with identified Wnt pathway alterations, which included approximately 20% with Wnt activating mutations. Patients with EEC and carcinosarcoma had higher tumor DKK1 expression and a higher percentage of Wnt activating mutations than the ovarian cancer patients. Patients whose tumors had Wnt activating mutations expressed 15 times higher levels of tumoral DKK1.

Key Findings from the P204 Study

·DKN-01 single agent activity

oEndometrial Cancer: Twenty-nine EEC patients were enrolled in the DKN-01 monotherapy arm, over 75% of whom had experienced three or more prior lines of therapy. Of those patients, 26 were evaluable for response. In the 20 patients with a Wnt signaling alteration, one patient (5%) has an ongoing complete response, one patient (5%) had a partial response, eight patients (40%) had a best response of stable disease, and 10 patients (50%) had progressive disease, representing an overall response rate (ORR) of 10% and a disease control rate (DCR) of 50%. In the group of six patients without any Wnt signaling alterations, one patient (16.6%) had a best response of stable disease and five patients (83.3%) had progressive disease.

oCarcinosarcoma: Ten patients with carcinosarcoma have been enrolled in the DKN-01 monotherapy arm, five of whom were evaluable for response as of the data-cut off date. Two patients (40%) had a best response of stable disease, one of which has continued on monotherapy for nearly two years, and three patients (60%) had progressive disease. Five patients had not reached their first tumor assessment.

·DKN-01 plus paclitaxel combination activity

oCarcinosarcoma: Fifteen patients with carcinosarcoma were enrolled in the DKN-01 plus paclitaxel arm, six of whom were evaluable for response as of the data-cut off date. Two patients (33%) have had a partial response, one patient (17%) has had a best response of stable disease, and three patients (50%) had progressive disease, representing an ORR of 33% and a DCR of 50%. Nine patients had not reached their first tumor assessment.

oEndometrial Cancer: Twenty-five patients with heavily pretreated EEC were enrolled in the DKN-01 plus paclitaxel arm. All of these patients had previously received paclitaxel, 44% had received hormonal therapies, 32% had received bevacizumab, 20% had received immunotherapy, and 12% had received a PARP inhibitor. Of those patients, 22 were evaluable for response. A total of 12 patients (55%) have had a best response of stable disease, and ten patients (45%) had progressive disease.

·Monotherapy Patients with Wnt activating mutations have longer Progression-Free Survival (PFS) and Overall Survival (OS): In a pooled analysis of all DKN-01 monotherapy patients, patients with Wnt activating mutations have demonstrated a longer median PFS of 168 days as compared to patients without Wnt activating mutations with median PFS of 56 days. Median OS has not been reached in the Wnt activating mutation group in the pooled analysis as compared to median OS of 328 days in the non-Wnt activating mutation group.

·Monotherapy Patients with DKK1-high tumors have longer PFS and OS: DKK1 expression as measured by in situ hybridization RNAscope assay is currently available for 68 of the patients on the study, 32 of whom were treated with DKN-01 monotherapy. Seven patients (22%) were identified as having DKK1-high tumoral expression. Consistent with the results from Leap’s study in patients with esophagogastric cancer, patients whose tumors are DKK1-high have prolonged median PFS of 168 days as compared to patients with tumors that are DKK1-low with median PFS of 56 days. Median OS was 450 days in the DKK1-high group in the pooled analysis as compared 276 days in the DKK1-low group.

Conference Call Details:

U.S. Dial-in Number: (866) 589-0108

International Dial-in Number: (409) 231-2048

Conference ID: 1190677

The presentation will be webcast live and may be accessed on the Investors page of the company’s website at View Source, where the presentation slides and a replay of the event will also be available for a limited time.

About Gynecological Cancers

There are numerous forms of gynecologic cancers, but two of the most prevalent types are cancers of the uterus or ovaries. According to the National Cancer Institute, there are more than 61,000 patients diagnosed with uterine cancer. There are currently very few post-surgical treatment options for these patients, typically consisting of chemotherapy, local radiation therapy, and hormonal agents, and poor treatment outcomes. Patients with endometrial cancers have a high frequency of mutations in a protein known as beta-catenin, with alterations estimated at approximiately 30% of cases by The Cancer Genome Atlas. These beta-catenin mutations are often driver mutations leading to rapid disease progression and poor outcomes. Carcinosarcoma, or Malignant Mixed Mullerian Tumor, is a uterine cancer comprised of carcinoma and sarcoma cells and accounts for less than five percent of all uterine cancer. Carcinosarcoma is an aggressive tumor with poor patient prognosis and poor response to chemotherapy.

About DKN-01

DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein, a modulator of Wnt/Beta-catenin signaling, a signaling pathway frequently implicated in tumorigenesis and suppressing the immune system. DKK1 has an important role in tumor cell signaling and in mediating an immuno-suppressive tumor microenvironment through enhancing the activity of myeloid-derived suppressor cells and downregulating NK ligands on tumor cells.

On April 23, 2020 INmune Bio, Inc. (NASDAQ: INMB) (the "Company"), an immunology company developing treatments that harness the patient’s innate immune system to fight disease, reported publication of an invited review in Frontiers in Oncology: Tumor Necrosis Factor α Blockade: an Opportunity to Tackle Breast Cancer, by Dr. Roxana Schillaci, in the Lab of Molecular Mechanisms, Instituto de Biología y Medicina Experimental-CONICET, Argentina (Press release, INmune Bio, APR 23, 2020, View Source [SID1234556533]).

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This publication is part of the evolving body of work by Dr. Schillaci and her team in the role of soluble TNF in resistance to oncology immunotherapies including trastuzumab and other therapies. Trastuzumab is the leading therapy for women with HER2+ breast cancer. Dr. Schillaci’s has previously reported that women with MUC4 expressing HER2+ breast cancers are resistant to trastuzumab.

"This novel work was first presented at the San Antonio Breast Cancer Symposium in 2018," said RJ Tesi MD, Chief Executive Officer of INmune Bio. "Dr. Schillaci showed that MUC4 expression is driven by soluble TNF. When soluble TNF is neutralized with INB03, MUC4 expression is decreased and the cancer becomes sensitive to trastuzumab."

"This review is one of the first to address the impact of TNFɑ on breast cancer subtypes progression and metastasis and to discuss the participation of soluble and transmembrane TNFɑ in breast cancer," said Dr. Schillaci. "We demonstrate the potential efficacy of TNF blocking agents in the treatment of breast cancer because soluble TNF is involved in resistance to most of the breast cancer therapies, ranging from chemotherapy, hormone therapy to anti-checkpoint inhibitors."

Dr. Schillaci’s work in MUC4 induced resistance to trastuzumab in women with HER2+ breast cancer is the basis for INMB’s planned Phase II trial in women with metastatic HER2+ breast cancer. The article is part of a three article Research Topic in this issue of Frontiers in Oncology entitled, The Tumor Necrosis Factor Superfamily: an Increasing Role in Breast Cancer.

On April 23, 2020 Immunomic Therapeutics, Inc., ("ITI") a privately-held clinical-stage biotechnology company pioneering the study of nucleic acid immunotherapy platforms, reported the close of a $61.3M financing led by HLB Co., LTD, a global pharmaceutical company focused on developing novel cancer drugs (Press release, Immunomic Therapeutics, APR 23, 2020, View Source [SID1234556532]). This represents the second closing in the investment process for the HLB Consortium, ($10M was placed in February 2020), and substantially increases their holding in Immunomic Therapeutics to 47.6% of the common stock. HLB also secured an option to make further investment into the company in the months ahead.

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"We are pleased to welcome HLB as a significant shareholder of Immunomic Therapeutics and look forward to working with them within the framework of the HLB Bio family of companies. They have a proven track record of success in Asia and share our commitment and passion for developing best-in-class therapies for cancer and other serious diseases," said Dr. William Hearl, CEO of Immunomic Therapeutics. "With HLB’s support, we are well-positioned to accelerate our efforts in immuno-oncology, in particular glioblastoma multiforme, and rapidly advance other key candidates in our pipeline, including our most recent initiative into infectious diseases with development of our vaccine candidate for COVID-19."

Proceeds from the financing will support the acceleration of ITI’s Phase II clinical trial of ITI-1000 for the treatment of glioblastoma multiforme (GBM), advance its emerging pipeline, and expand upon the current applications of its UNITE platform. The financing will also enable Immunomic to expand its team and infrastructure to support the future growth of the company.

In addition, ITI and HLB intend to establish an Asian Brain Cancer Research Center in Seoul that will bring together the world’s leading experts and cutting-edge science to advance research in the GBM field and to deploy ITI-1000 to the Asian population. ITI-1000 is a cell therapy powered by ITI’s UNITE platform that is currently being evaluated in a Phase II clinical trial (ATTAC-II) in collaboration with researchers at the University of Florida (Dr. Duane Mitchell) and Duke University (Dr. John Sampson). ITI-1001 is an alternative, cell-free approach to treating GBM. The company held a successful pre-IND meeting earlier this year for ITI-1001 and expects to be able to file an Investigational New Drug Application (IND) with the U.S. Food and Drug Administration (FDA) by the end of 2020.

Concurrent with the financing, five (5) members from HLB Co., LTD will be joining the Immunomic Therapeutics Board of Directors.

About UNITE

ITI’s investigational UNITE platform, or UNiversal Intracellular Targeted Expression, works by fusing pathogenic antigens with the Lysosomal Associated Membrane Protein, an endogenous protein in humans, for immune processing. 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.

On April 23, 2020, Heat Biologics, Inc. (the "Company") reported that it has entered into Amendment No. 1, dated April 23, 2020 (the "Amendment"), to that certain At Market Issuance Sales Agreement, by and between the Company and B. Riley FBR, Inc. ("B. Riley FBR") dated April 3, 2019 (together with the Amendment, the "Sales Agreement") pursuant to which the Company may offer and sell, from time to time, at its option, shares of the Company’s common stock, par value $0.0002 per share, through B. Riley FBR, as sales agent (the "Sales Agent") in an "at the market" offering (the "ATM Offering") (Filing, 8-K, Heat Biologics, APR 23, 2020, View Source [SID1234556531]). The Amendment will be effective at the time the Company’s Registration Statement on Form S-3 (File No. 333-237808) (the "New Registration Statement") is declared effective by the Securities and Exchange Commission.

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The original Sales Agreement provided for the issuance and sale of shares of common stock in the ATM Offering pursuant to the Company’s shelf Registration Statement on Form S-3 (File No. 333-221201)(the "Prior Registration Statement"), which includes a base prospectus and a prospectus supplement dated April 3, 2019 (the "Prior Prospectus"), providing for the sale of up to $18 million of shares of common stock in the ATM Offering. As of April 20, 2020, the Company has issued and sold an aggregate of 15,551,075 shares of common stock for aggregate gross proceeds of approximately $12,843,702 pursuant to the Sales Agreement under the Prior Registration Statement, utilizing the Prior Prospectus.

The Amendment provides for the issuance and sale of shares of common stock in the ATM Offering pursuant to the New Registration Statement. The issuance and sale of shares of common stock in the ATM Offering will be made under the New Registration Statement, once it is declared effective, pursuant to a prospectus, which consists of a base prospectus and a prospectus (the "ATM Prospectus"), each of which has been filed with the New Registration Statement. The ATM Prospectus provides for the sale of up to $50 million of shares of common stock in the ATM Offering under the New Registration Statement.

Under the terms of the Sales Agreement, in no event will the Company issue or sell through the Sales Agent such number or dollar amount of shares of common stock that would (i) exceed the number or dollar amount of shares of common stock registered and available on the Registration Statement, (ii) exceed the number of authorized but unissued shares of common stock, (iii) exceed the number or dollar amount of shares of common stock permitted to be sold under Form S-3 (including General Instruction I.B.6 thereof, if applicable), or (iv) exceed the number or dollar amount of common stock for which the Company has filed a prospectus supplement to the Registration Statement.

Under the terms of the Sales Agreement, the Company may sell shares of its common stock through B. Riley FBR by any method permitted that is deemed an "at the market offering" as defined in Rule 415 under the Securities Act of 1933, as amended (the "Securities Act"). B. Riley FBR will use its commercially reasonable efforts consistent with its normal trading and sales practices and applicable state and federal laws, rules and regulations to sell the Company’s common stock from time to time, based upon the Company’s instructions (including any price, time or size limits or other customary parameters or conditions the Company may impose). Actual sales will depend on a variety of factors to be determined by the Company from time to time, including (among others) market conditions, the trading price of the Company’s common stock, capital needs and determinations by the Company of the appropriate sources of funding for the Company. The Company is not obligated to make any sales of common stock under the Sales Agreement and the Company cannot provide any assurances that it will issue any shares pursuant to the Sales Agreement. The Company will pay a commission rate of up to 3.0% of the gross sales price per share sold and agreed to reimburse B. Riley FBR for certain specified expenses, including the fees and disbursements of its legal counsel in an amount not to exceed $50,000 and have agreed to reimburse B. Riley FBR an amount not to exceed $2,500 per quarter during the term of the sales agreement for legal fees to be incurred by B. Riley FBR. The Company has also agreed pursuant to the Sales Agreement to provide B. Riley FBR with customary indemnification and contribution rights.

On April 23, 2020 GlaxoSmithKline plc reported data from an updated analysis of the GARNET trial, which demonstrated that dostarlimab, an investigational anti-programmed death-1 (PD-1) monoclonal antibody, provided clinically meaningful results in women with recurrent or advanced mismatch repair-deficient (dMMR) endometrial cancer who progressed on or after a platinum-based regimen (Press release, GlaxoSmithKline, APR 23, 2020, View Source [SID1234556530]).

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This updated analysis included patients with dMMR endometrial cancer who had measurable disease at baseline and ≥6 months of follow-up by the data cutoff (n=71). Patients received 500 mg of dostarlimab once every three weeks for four doses, followed by 1,000 mg once every six weeks until disease progression. The primary endpoints were confirmed objective response rate (ORR) and duration of response (DoR), as assessed against RECIST v 1.1 by blinded independent central review. GARNET is the largest dataset evaluating an anti-PD-1 in endometrial cancer.

Treatment with dostarlimab showed an ORR of 42% (95% CI; 31-55) and a disease control rate of 58% (95% CI; 45-69). Overall, 13% of patients had a complete response and 30% of patients had a partial response. At the time of data cutoff, with a median follow up of 11.2 months, the median DOR had not been reached (1.87+ to 19.61+ months).

Dr. Axel Hoos, Senior Vice President and Head Oncology R&D, GSK said: "We are committed to developing medicines for patients who face high unmet medical need. We believe in the clinical potential of dostarlimab for women with advanced or recurrent dMMR endometrial cancer who urgently need additional treatment options for this incurable disease."

Dr. Ana Oaknin, Head of the Gynaecologic Cancer Program at Vall d’Hebron Institute of Oncology, Barcelona, and primary investigator for GARNET said: "There are limited treatment options for women with advanced or recurrent endometrial cancer, and prognosis of these patients is poor. The results observed in the GARNET trial indicate the potential of dostarlimab to offer a new treatment option for women with this challenging disease."

The safety population included all patients with dMMR endometrial cancer who received at least one dose of dostarlimab (n=104). Results showed that dostarlimab was well tolerated with a low discontinuation rate (2%) due to treatment-related adverse events (TRAEs), consistent with the safety profiles of other anti-PD-1 therapies. The most commonly reported TRAEs were asthenia (15%), diarrhoea (15%), fatigue (14%), and nausea (13%). No deaths associated with dostarlimab were reported in the study.

Dostarlimab is not currently approved for use anywhere in the world.

About GARNET
The ongoing phase I GARNET trial is evaluating dostarlimab as monotherapy in patients with advanced solid tumours. Part 2B of the study includes five expansion cohorts: dMMR/MSI-H endometrial cancer (cohort A1), mismatch repair proficient endometrial cancer (cohort A2), non-small cell lung cancer (cohort E), dMMR/MSI-H non-endometrial cancer (cohort F), and platinum-resistant ovarian cancer without BRCA mutations (cohort G). GARNET is still enrolling patients.[1,2]

About Dostarlimab
Dostarlimab is an investigational humanised anti-PD-1 monoclonal antibody that binds with high affinity to the PD-1 receptor and blocks its interaction with the ligands PD-L1 and PD-L2.[3]

In addition to GARNET, dostarlimab is being investigated for women with recurrent or primary advanced endometrial cancer in combination with standard of care (chemotherapy) in the phase III RUBY trial.[4] Dostarlimab is also being evaluated in combination with other therapeutic agents for patients with advanced solid tumours or metastatic cancer.

About endometrial cancer[v]
Endometrial cancer is a main type of uterine cancer that forms in the inner lining of the uterus, known as the endometrium. Endometrial cancer can be classified as mismatch repair-deficient/microsatellite instability-high or mismatch repair-proficient/microsatellite stable. There are limited treatment options for women whose disease progresses on or after first-line therapy. Endometrial cancer is the sixth most common cancer in women worldwide.[6]

GSK in Oncology
GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.