On March 27, 2019 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer and, through our license to Santen Pharmaceutical Co. Ltd., wet age-related macular degeneration, reported that preclinical data from TRC105 and TRC253, as well as Phase 2 clinical data from TRC102, will be presented at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, to be held from March 29 to April 3, 2019, in Philadelphia, PA (Press release, Tracon Pharmaceuticals, MAR 27, 2019, View Source [SID1234534674]).

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Dr. Mark Schoonderwoerd and colleagues from Leiden University will present a poster featuring data from preclinical studies of TRC105 and PD-1 checkpoint inhibitors. The presentation details are as follows:

Poster Title: Synergistic inhibition of cancer invasion and metastasis by combined anti-PD1-TRC105-mediated Endoglin targeting on cancer-associated fibroblasts and endothelial cells
Abstract Link: View Source!/6812/presentation/3044
Session Category: Combination Approaches to Novel Therapies
Location: Section 12, Poster Board 291/12
Date: Sunday, March 31, 2019
Time: 1:00pm – 5:00pm EDT
Dr. Tammy Bush and colleagues from Janssen Research and Development will present a poster featuring preclinical data from TRC253, a small molecule antagonist of mutant and wild-type androgen receptor. The presentation details are as follows:

Poster Title: Antitumor activity of JNJ-63576253 (TRC253), a small molecule antagonist of F877L mutant and wild-type androgen receptor
Abstract Link: View Source!/6812/presentation/6162
Session Category: Novel Therapeutics and Pathways
Location: Section 14, Poster Board 2179/1
Date: Monday, April 1, 2019
Time: 1:00pm – 5:00pm EDT
Dr. Geraldine Coyne and colleagues from the National Cancer Institute will present a poster featuring data from the Phase 2 clinical trial of TRC102 and Temodar (temozolomide) in subjects with colorectal cancer. The presentation details are as follows:

Poster Title: A Phase II trial of TRC102 (methoxyamine HCl) in combination with temozolomide in patients with relapsed metastatic colorectal carcinoma
Abstract Link: Late-Breaking Abstracts are embargoed until March 29, 2019
Session Category: Late-Breaking Research – Molecular and Cellular Biology/Genetics 2
Location: Section 41, Poster Board LB-293/10
Date: Wednesday, April 3, 2019
Time: 8:00am – 12:00pm EDT
Posters will be available on the company’s website following presentation.

About TRC105 (carotuximab)

TRC105, the oncology formulation of carotuximab, is a novel, clinical stage antibody to endoglin, a protein overexpressed on proliferating endothelial cells that is essential for angiogenesis, the process of new blood vessel formation. TRC105 is currently being studied in the pivotal Phase 3 TAPPAS trial in patients with angiosarcoma as well as multiple Phase 1 and Phase 2 clinical trials in other tumor types. TRC105 has received orphan designation for the treatment of soft tissue sarcoma in both the US and EU. The ophthalmic formulation of TRC105, DE-122, is currently being studied in the randomized Phase 2 AVANTE trial in patients with wet AMD. For more information about the clinical trials, please visit TRACON’s website at www.traconpharma.com/clinical_trials.php.

About TRC253

TRC253 is a novel, orally bioavailable small molecule that is a potent, high affinity competitive inhibitor of the androgen receptor (AR) and AR mutations, including the F877L mutation. The AR F877L mutation results in an alteration in the AR ligand binding domain that confers resistance to therapies for prostate cancer. Therapies targeting the AR have demonstrated clinical efficacy by extending time to disease progression, and in some cases, the survival of patients with metastatic castration-resistant prostate cancer. However, resistance to these agents is often observed and several molecular mechanisms of resistance have been identified, including gene amplification, overexpression, alternative splicing, and point mutation of the AR. TRC253 is currently being studied in a Phase 1/2 clinical trial in prostate cancer. For more information about the clinical trial, please visit TRACON’s website at www.traconpharma.com/clinical_trials.php

About TRC102

TRC102 (methoxyamine) is a novel, clinical-stage small molecule inhibitor of the DNA base excision repair pathway, which is a pathway that causes resistance to alkylating and antimetabolite chemotherapeutics. TRC102 is currently being studied in multiple Phase 1 and Phase 2 clinical trials sponsored by the National Cancer Institute or Case Comprehensive Cancer Center. For more information about the clinical trials, please visit TRACON’s website at www.traconpharma.com/clinical_trials.php.

On March 27, 2019 Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, reported three presentations of updated clinical and preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019, to be held March 29-April 3 in Atlanta and the 2019 American Association of Neurological Surgeons (AANS) Annual Meeting, to be held April 13-17 in San Diego (Press release, Tocagen, MAR 27, 2019, View Source;p=RssLanding&cat=news&id=2392515 [SID1234534696]).

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The clinical data includes details of immunologic trends in patients with recurrent high-grade glioma (rHGG) from a Phase 1 study of Toca 511 (vocimagene amiretrorepvec) and Toca FC (flucytosine, extended-release). Additionally, new preclinical data will be presented demonstrating increased survival from the combination of Toca 511 and flucytosine with either temozolomide or cyclophosphamide.

Summaries are provided below; full posters or presentations will be placed on Tocagen’s website following the presentation.

Details of the AACR (Free AACR Whitepaper) presentation are as follows:

Presentation Type: Poster (Abstract: 4771)
Title: The addition of Toca 511 and 5-FC to temozolomide improves response in a temozolomide-resistant murine glioblastoma model and correlates with Toca 511 dose
Presenter: Maria E. Rodriguez-Aguirre
Date and Time: Wednesday, April 3, 8:00 a.m.-12:00 p.m. ET
Summary:

This study aimed to assess the interaction of temozolomide with escalating doses of Toca 511 in an orthotopic temozolomide-resistant murine glioma model.
Even with lympho-depleting temozolomide treatment, survival was prolonged with moderate levels (30-50 percent) of tumor transduction of Toca 511 with 5-FC but not with lower transduction rates (10 percent).
Data from this study may inform the evaluation of Toca 511 & Toca FC in combination with temozolomide in patients with newly diagnosed glioblastoma (GBM).
Details of the AANS presentations are as follows:

Presentation Type: E-Poster displayed online (Abstract: 2120)
Title: Immune Monitoring of High-Grade Glioma Patients in a Phase 1 Clinical Trial of Toca 511 and Toca FC
Presenter: Steven Kalkanis, M.D.
Summary:

Human immune monitoring results from a Phase 1 clinical trial of Toca 511 & Toca FC support an immune-related mechanism of action for the regimen.
Univariate comparisons and multivariate models revealed pre-treatment tumor infiltrating cell subsets quantified via deconvolution of RNA sequencing data were associated with both objective responses and survival.
Post-treatment serum cytokine time-course results suggest that differences in temporal modulations are associated with both objective response and survival.
These results indicate the value of evaluating potential biomarkers of patient outcomes in the ongoing randomized Toca 5 Phase 3 trial in patients with recurrent HGG.
Presentation Type: Oral (Abstract: 481)
Title: Toca 511 and 5-FC in Combination with Metronomic Cyclophosphamide Reduces Treg Cells and Enhances Therapy Efficacy in a Preclinical Murine Model
Presenter: David Piccioni, M.D., Ph.D.
Date and Time: Wednesday, April 17, 4:49-4:52 p.m. PT
Summary:

This study aimed to determine if the addition of metronomic cyclophosphamide would provide therapeutic benefit when combined with Toca 511 and 5-FC (5-fluorocytosine) in a preclinical, subcutaneous glioma model.
The addition of metronomic cyclophosphamide improved tumor control and survival, and led to a superior CD8+/Treg ratio in the peripheral blood.
Results support the further evaluation of Toca 511 & Toca FC with metronomic dosing of cyclophosphamide and potentially other chemotherapeutics.
About Toca 511 & Toca FC
Tocagen’s lead product candidate is a two-part cancer-selective immunotherapy comprising an investigational biologic, Toca 511 (vocimagene amiretrorepvec), and an investigational small molecule, Toca FC (flucytosine, extended-release). Toca 511 is a retroviral replicating vector (RRV) that selectively infects cancer cells and delivers a gene for the enzyme, cytosine deaminase (CD). Through this targeted delivery, infected cancer cells carry the CD gene and produce CD. Toca FC is an orally administered prodrug, 5-fluorocytosine (5-FC), which is converted into an anti-cancer drug, 5-fluorouracil (5-FU), when it encounters CD. 5-FU kills cancer cells and immune-suppressive myeloid cells resulting in anti-cancer immune activation and subsequent tumor killing.

On March 27, 2019 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors, reported the pricing of an underwritten public offering of an aggregate of 5,250,000 units at a public offering price of $1.00 per unit (Press release, Moleculin, MAR 27, 2019, View Source [SID1234534675]). Each unit is comprised of one share of common stock and 0.5 of a warrant to purchase one share of common stock for a total of 5,250,000 shares of common stock and warrants to purchase 2,625,000 shares of common stock.

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Moleculin Biotech, Inc. is a clinical-stage pharmaceutical company focused on the treatment of highly resistant cancers. (PRNewsfoto/Moleculin Biotech, Inc.)

Each warrant will have an exercise price of $1.10 per share and is exercisable immediately. The warrants will expire five years from the date of issuance. The shares of common stock and the accompanying warrants included in the units can only be purchased together in this offering but will be issued separately and will be immediately separable upon issuance. The offering is expected to close on or about March 29, 2019, subject to customary closing conditions.

The gross proceeds of the offering are expected to be $5.25 million, prior to deducting the underwriting discount and other estimated offering expenses.

Oppenheimer & Co. Inc. is acting as the sole underwriter for the offering. Roth Capital Partners, LLC and Maxim Group LLC are acting as financial advisors to the Company.

The Company intends to use the net proceeds of the offering to fund its planned clinical trials, preclinical programs, for other research and development activities and for general corporate purposes.

The securities described above are being offered pursuant to a prospectus supplement and an accompanying prospectus forming part of a shelf registration statement on Form S-3 (No. 333-219434) previously filed with and declared effective by the Securities and Exchange Commission (SEC). A final prospectus supplement and the accompanying prospectus relating to and describing the terms of the offering will be filed with the SEC and will be available on the SEC’s website at View Source Copies of the final prospectus supplement and the accompanying prospectus may be obtained, when available, from Oppenheimer & Co. Inc., Attention: Syndicate Prospectus Department, 85 Broad Street, 26th Floor, New York, New York 10004, by telephone at (212) 667-8055, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On March 27, 2019 OncoSec Medical Incorporated (OncoSec) (NASDAQ: ONCS), a company developing intratumoral cancer immunotherapies, reported that the Company will host a Key Opinion Leader (KOL) Symposium focused on the potential of TAVO (tavokinogene telseplasmid), its lead immunotherapy investigational product candidate, on Friday, April 5, 2019 at 8:00 a.m. ET in New York City (Press release, OncoSec Medical, MAR 27, 2019, View Source [SID1234534659]).

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The KOL Symposium will feature a keynote presentation from Adil Daud, M.D., the Lead U.S. Investigator for KEYNOTE-695 and Clinical Professor of Medicine and Dermatology at University of California, San Francisco (UCSF), and Director of Melanoma Clinical Research at the UCSF Helen Diller Family Comprehensive Cancer Center.

Among other important topics, Dr. Daud’s presentation will:

Outline the significance of the emerging data from the KEYNOTE-695 trial where patients with anti-PD-1 checkpoint refractory metastatic melanoma are being treating with the combination of TAVO + KEYTRUDA
Provide insights of how TAVO is differentiated from other therapeutic approaches for patients with checkpoint refractory metastatic melanoma
Following Dr. Daud’s presentation, OncoSec’s management team will:

Outline the U.S. and EU accelerated approval pathway and timelines for the approval of TAVO to treat metastatic melanoma patients who are refractory to anti-PD-1 checkpoint therapy
Showcase OncoSec’s newly-developed proprietary visceral lesions applicator or VLA, which is designed to treat a variety of deep visceral tumors including gastrointestinal (GI) tumors, pancreatic tumors and hepatocellular carcinomas (HCC)
Provide an overview of data presented at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, highlighting OncoSec’s novel anti-tumor therapeutic product candidate
The FDA designated Fast Track Development Program status to OncoSec’s TAVO in combination with KEYTRUDA to stop or cause the regression of the tumor of patients with Stage III/IV melanoma who are progressing on either KEYTRUDA or OPDIVO. A drug that receives Fast Track designation is eligible for Accelerated Approval, if relevant criteria are met.

A live webcast of the event will be available. To access the live webcast, please visit the Investor Relations section of OncoSec’s website at ir.oncosec.com. An archived replay of the webcast will also be available at the same location.

On March 27, 2019 The Janssen Pharmaceutical Companies of Johnson & Johnson reported the submission of a Type II variation application to the European Medicines Agency (EMA) for DARZALEX▼ (daratumumab) in combination with bortezomib, thalidomide and dexamethasone (VTd) for newly diagnosed patients with multiple myeloma who are eligible for autologous stem cell transplant (ASCT) (Press release, Johnson & Johnson, MAR 27, 2019, View Source [SID1234534676]).

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The submission is supported by data from the Phase 3 CASSIOPEIA (MMY3006) study. Additional information about this study can be found at www.ClinicalTrials.gov (NCT02541383).

"With this regulatory submission, Janssen could help redefine treatment for transplant eligible patients by providing the opportunity to be treated with a daratumumab regimen for the very first time," said José Antonio Burón Vidal, Vice President, Medical Affairs, Europe, Middle East and Africa (EMEA), Janssen-Cilag, S.A. "We continue to deliver advances in multiple myeloma, and if approved, this could offer a broader range of frontline patients a new treatment option and improved outcomes."

Janssen has also submitted an application to the U.S. Food and Drug Administration (FDA) seeking approval of daratumumab-VTd for newly diagnosed patients with multiple myeloma who are eligible for autologous stem cell transplant (ASCT).

In Europe, daratumumab is indicated:1

in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant
as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on the last therapy
in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.
About the CASSIOPEIA Trial2

The randomised, open-label, two-arm, multicentre, Phase 3 study is sponsored by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen R&D, LLC. The study includes participants with previously untreated multiple myeloma eligible for high dose chemotherapy and ASCT. In the first part of the study, on which the filing is based, participants were randomised to receive either induction (before transplantation) and consolidation (after transplantation) treatment with daratumumab combined with bortezomib, thalidomide and dexamethasone or bortezomib, thalidomide and dexamethasone alone. The primary endpoint is the proportion of patients that achieve a stringent Complete Response (sCR) rate after consolidation therapy. In the second part of the study, patients that achieved a response will undergo a second randomisation to either receive maintenance treatment of daratumumab or no further treatment (observation). The primary endpoint of this part of the study is progression free survival (PFS). The total duration for each participant in the study will be approximately 138 weeks. The end of the study will occur approximately five years after the last participant is randomised in the second phase of the study. Disease assessments will be performed every four weeks in the first phase of the study and then every eight weeks in the second phase of the study.

About daratumumab

Daratumumab is a first-in-class3 biologic targeting CD38, a surface protein that is highly expressed across multiple myeloma cells, regardless of disease stage.4 Daratumumab is believed to induce tumour cell death through multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), as well as through apoptosis, in which a series of molecular steps in a cell lead to its death.1 A subset of myeloid derived suppressor cells (CD38+ MDSCs), CD38+ regulatory T cells (Tregs) and CD38+ B cells (Bregs) were decreased by daratumumab.1 Daratumumab is being evaluated in a comprehensive clinical development programme across a range of treatment settings in multiple myeloma, such as in frontline and relapsed settings.2,5,6,7,8,9,10,11 Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant haematologic diseases in which CD38 is expressed, such as smouldering myeloma.12,13 For more information, please see www.clinicaltrials.gov.

For further information on daratumumab, please see the Summary of Product Characteristics at View Source

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive licence to develop, manufacture and commercialise daratumumab.14

About Multiple Myeloma

Multiple myeloma (MM) is an incurable blood cancer that starts in the bone marrow and is characterised by an excessive proliferation of plasma cells.15 In Europe, more than 48,200 people were diagnosed with MM in 2018, and more than 30,800 patients died.16 Almost 40 percent of patients with MM do not reach five-year survival.17

Although treatment may result in remission, unfortunately, patients will most likely relapse as there is currently no cure.18 Refractory MM is when a patient’s disease progresses within 60 days of their last therapy.19,20 Relapsed cancer is when the disease has returned after a period of initial, partial or complete remission.21 While some patients with MM have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.22 Patients who relapse after treatment with standard therapies, including proteasome inhibitors and immunomodulatory agents, have poor prognoses and few treatment options available.23