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.

On April 22, 2019 Forbius, a clinical-stage company that develops novel biologics for the treatment of cancer and fibrosis, reported that the first patient has been dosed in a Phase 2a triple negative breast cancer (TNBC) clinical trial with AVID100, a novel, tumor-selective anti-epidermal growth factor receptor (EGFR) antibody-drug conjugate (ADC) (Press release, Forbius, APR 22, 2019, View Source [SID1234535316]).

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Approximately 20% of TNBC patients have tumors that highly overexpress EGFR. No targeted therapy is approved for EGFR-overexpressing TNBC.

The multicenter, dose-expansion Phase 2a trial (AVID100-01; NCT03094169) will evaluate the efficacy, safety, and tolerability of AVID100 in patients with advanced, EGFR-overexpressing TNBC (IHC 2+/3+). This is the third cohort that has been launched and follows the previously announced cohorts evaluating AVID100 in patients with advanced squamous non-small cell lung cancer (sqNSCLC) and squamous cell carcinoma of the head and neck (SCCHN). In total, approximately 100 patients will be evaluated across three EGFR-overexpressing tumor types: sqNSCLC, SCCHN, and TNBC.

About AVID100 and the AVID100-01 Trial
AVID100 is a highly potent EGFR-targeting ADC engineered to achieve enhanced anti-tumor efficacy without a corresponding increase in toxicity in skin or other EGFR-expressing normal tissues. In preclinical studies, AVID100 demonstrated significant anti-cancer activity in EGFR-overexpressing tumor models resistant to marketed EGFR inhibitors. AVID100 is the most advanced, broadly active anti-EGFR ADC in clinical development and targets both wild-type and mutant forms of EGFR.

A recommended Phase 2 dose (RP2D) of 220 mg/m2 (~6mg/kg) was established for AVID100 in a completed Phase 1 study. This RP2D is expected to be in the therapeutically active range based on preclinical efficacy studies. The majority of treatment-related adverse events in the Phase 1 trial at the RP2D were well-tolerated and grade 1 or 2 in severity.

AVID100-01 (NCT03094169) is an open-label, multicenter, dose-expansion study to evaluate the efficacy, safety, and tolerability of AVID100 in patients with confirmed EGFR-overexpressing sqNSCLC (IHC 3+), SCCHN (IHC 3+), and TNBC (IHC 2+/3+) (more than 50% of cells with EGFR 3+ or more than 75% of cells with EGFR 2+ staining).

On April 22, 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 it will host a conference call to discuss its significant discovery for lung cancer, FDA Fast Track Designation and recent corporate events (Press release, Moleculin, APR 22, 2019, View Source [SID1234535317]). The call will be at 4:30 p.m. ET on Wednesday, April 24, 2019.

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Participants can dial (800) 860-2442 or (412) 858-4600 to access the conference call, or can listen via a live webcast, which is available in the Investor Relations section of the Company’s website at www.moleculin.com. The Company will field live questions from equity analysts in a Q&A segment of this call. Participants may submit questions in advance for the Company to address in the Q&A segment by sending them to [email protected]. A webcast replay will be available in the Investors section of the Company’s website at www.moleculin.com for 90 days. A teleconference replay will be available at (877) 344-7529 or (412) 317-0088, confirmation code 10130980, through May 1, 2019.

On April 22, 2019 Poseida Therapeutics Inc., a clinical-stage biopharmaceutical company leveraging proprietary non-viral gene engineering technologies to create life-saving therapeutics, reported closing of a Series C financing round, raising $142 million led by a $75 million equity investment from Novartis Pharma AG, and joined by several new investors including Aisling Capital Management, Pentwater Capital Management, Perceptive Advisors as well as additional undisclosed institutional investors (Press release, Poseida Therapeutics, APR 22, 2019, View Source [SID1234536252]). Current investors Malin Corporation plc., Longitude Capital, Vivo Capital and Boxer Capital, LLC also participated in the financing.

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"We welcome the support and investment from Novartis, a leader in the cell and gene therapy field," said Eric Ostertag M.D., Ph.D., chief executive officer of Poseida. "They are joined by an impressive group of new investors whose commitment enables us to accelerate the pursuit of our bold vision to create gene therapy product candidates that could result in single-treatment cures for numerous oncologic indications and orphan genetic diseases, with an initial focus on chimeric antigen receptor T cell (CAR-T) therapies."

The company’s CAR-T product candidates are manufactured with Poseida’s non-viral piggyBac DNA Modification System, resulting in a high percentage of stem cell memory T cells (TSCM). Tscm cells are the only T cell that is self-renewing and long-lived, potentially resulting in product candidates that are more efficacious, less toxic and more durable. Poseida is currently developing the following CAR-T product candidates:

P-BCMA-101 is an autologous CAR-T therapy for the treatment of relapsed/refractory multiple myeloma, currently enrolling patients for a Phase 2 registrational trial with initial dosing expected in the first half of 2019.

P-PSMA-101 is an autologous CAR-T product candidate targeting PSMA-specific cancer cells in castrate resistant prostate cancer, with filing of an IND anticipated in the second half of 2019.

P-BCMA-ALLO1 is an allogeneic, or universal donor, CAR-T product candidate, manufactured using Poseida’s proprietary Cas-CLOVER site specific gene editing system and is being developed as a treatment for relapsed/refractory multiple myeloma, with an IND filing anticipated by late 2019 or early 2020.

P-MUC1C-101 is an autologous CAR-T product candidate in late-stage preclinical development for numerous solid tumor indications, including ovarian, breast, lung, colorectal, pancreatic and renal cancers, with filing of an IND anticipated in 2020.

Poseida plans to broadly advance its current CAR-T programs and emerging pipeline programs, including gene therapies for orphan genetic diseases.