On May 13, 2019 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for CLR 131 in fourth line or later relapse/refractory multiple myeloma (Press release, Cellectar Biosciences, MAY 13, 2019, View Source [SID1234536216]). CLR 131 is the company’s small-molecule radiotherapeutic phospholipid drug conjugate (PDC) designed to deliver cytotoxic radiation directly and selectively to cancer cells and cancer stem cells. It is currently being evaluated in Cellectar’s ongoing CLOVER-1 Phase 2 clinical study in patients with relapsed or refractory multiple myeloma and other select B-Cell lymphomas.

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"Fast Track Designation furthers our efforts to expeditiously develop CLR 131 as a new, innovative therapy for patients with relapse/refractory multiple myeloma", said James Caruso, president and CEO of Cellectar. "Patients with third line or later relapsed/refractory multiple myeloma have a poor prognosis and low rates of survival as a result of limited effective treatment options. Based on data in the initial patient cohort from our ongoing CLOVER-1 trial where patients showed a 30% response rate after receiving a single 25.0 mCi/m2 dose as a seventh line of therapy on average, we are optimistic that CLR 131 has the potential to provide a meaningful treatment option for these patients."

Fast Track Designation

Fast Track Designation is granted to drugs being developed for the treatment of serious or life-threatening diseases or conditions where there is an unmet medical need. The purpose of the Fast Track Designation provision is to help facilitate development and expedite the review of drugs to treat serious and life-threatening conditions.

Sponsors of drugs that receive Fast Track Designation have the opportunity for more frequent interactions with the FDA review team throughout the development program. These interactions may include meetings to discuss study design, data required to support approval, or other aspects of the clinical program. Additionally, products that have been granted Fast Track Designation may be eligible for priority review of a New Drug Application (NDA) and the FDA may consider reviewing portions of an NDA before the sponsor submits the complete application (Rolling Review).

About the Phase 2 CLOVER-1 Trial

CLOVER-1 is a Phase 2 study of CLR 131 being conducted in approximately 10 leading cancer centers in the United States in patients with relapsed or refractory B-cell hematologic cancers. The hematologic cancers being studied in the trial include multiple myeloma (MM), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL).

The study’s primary endpoint is clinical benefit response (CBR), with additional endpoints of overall response rate (ORR), progression free survival (PFS), median overall survival (OS) and other markers of efficacy following a fractionated dose of 15.625 mCi/m2 dose of CLR 131 administered on day 1 and day 8, with the option for a second dose cycle approximately 75-180 days later.

In addition to receiving the two fractionated doses of CLR 131, MM patients will receive 40 mg oral dexamethasone weekly for up to 12 weeks. Efficacy responses will be determined by the latest International Multiple Myeloma Working Group criteria. Efficacy for all lymphoma patients will be determined according to Lugano criteria. Cellectar was awarded approximately $2 million in non-dilutive grant funding from the National Cancer Institute to help fund the trial. More information about the trial, including eligibility requirements, can be found at www.clinicaltrials.gov, reference NCT02952508.

About CLR 131

CLR 131 is a small-molecule, cancer-targeting radiotherapeutic PDC designed to deliver cytotoxic radiation directly and selectively to cancer cells and cancer stem cells. CLR 131 is the company’s lead therapeutic PDC product candidate and is currently being evaluated in both Phase 2 and Phase 1 clinical studies. In December 2014, the FDA granted orphan drug designation for CLR 131 for the treatment of multiple myeloma. In 2018, the FDA granted orphan drug and rare pediatric disease designations for CLR 131 for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma. In addition to the ongoing Phase 1 dose-escalation study and the Phase 2 CLOVER-1 trial, the company recently initiated a Phase 1 open-label, dose-escalating study in pediatric solid tumors and lymphoma to evaluate the safety and tolerability of a single intravenous administration of CLR 131 in up to 30 children and adolescents with cancers including neuroblastoma, sarcomas, lymphomas (including Hodgkin’s lymphoma) and malignant brain tumors.

On May 13, 2019 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular" or "Molecular Templates"), a clinical-stage oncology company focused on the discovery and development of the company’s proprietary engineered toxin bodies (ETBs), which are differentiated, targeted, biologic therapeutics for cancer, reported financial results for the first quarter of 2019 (Press release, Molecular Templates, MAY 13, 2019, View Source [SID1234536215]). As of March 31, 2019, Molecular’s cash and investments totaled $84 million, and is expected to fund operations into the first half of 2021.

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"So far in 2019, we have made substantial progress in advancing our pipeline and platform. We now have three Phase II studies open for our lead program, MT-3724, and our HER2 ETB, MT-5111, now has an open IND and Phase I dosing will begin in 3Q," said Eric Poma, Ph.D., Molecular Templates’ Chief Executive and Scientific Officer. "At the recent American Association of Cancer Research ("AACR") Annual Meeting, preclinical data was presented that showed that our second-generation ETBs utilizing our de-immunized scaffold have improved potency, greatly improved tolerability, and potential for less frequent dosing. These improvements have been demonstrated in preclinical studies with our ETBs targeting CD38, HER2, and PD-L1, all of which are expected to generate clinical data in the next 12 months."

Company Highlights and Upcoming Milestones

Corporate

Molecular presented new data on its pipeline programs and technology platform in four posters at the AACR (Free AACR Whitepaper) Annual Meeting 2019, March 29 – Apr 3, 2019 in Atlanta, Georgia. Presentations featured data on 1) CD38-targeted ETB TAK-169, 2) CD20-targeted ETB MT-3724 in combination with chemotherapy or IMiDs, 3) PD-L1-targeted ETB for direct cell kill approach to PD-L1 expressing cancers, 4) bispecific ETBs for targeted cancer treatment.
TAK-169

Takeda and Molecular expect to file an IND and start a Phase I multiple myeloma trial in 2019 for TAK-169 (CD38 targeted ETB).
MT-3724

Molecular is conducting a Phase II monotherapy study of MT-3724 in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). This study has the potential to be pivotal. Molecular expects to provide an update on this study in 2H19.
Molecular is also conducting two Phase II studies in earlier lines of DLBCL; one with MT-3724 in combination chemotherapy (GemOx) and the other with MT-3724 in combination with Revlimid. Molecular expects to report an update on both MT-3724 combination studies with MT-3724 in 2H19.
MT-5111

Molecular announced the acceptance of its IND filing for MT-5111, its ETB targeting HER2, in April 2019. The Phase I study in patients with HER2 positive solid tumors is expected to start dosing in 3Q19. Molecular expects to report an update on this study in 2H19.
Research

Molecular expects to file an IND application for MT-6035, its ETB targeting PD-L1 (with antigen seeding), in 2H19.
Several other ETB candidates are in preclinical development, targeting both solid and hematological cancers.
Takeda Multi-Target Collaboration

Takeda and Molecular are conducting lead optimization for ETBs against two undisclosed targets selected by Takeda under the collaboration. Should Takeda exercise its option to license ETBs for both targets, Molecular would receive $25 million and would be eligible to receive up to $547 million in milestone payments and tiered royalties on sales.
Financial Results

The net loss attributable to common shareholders for the first quarter of 2019 was $6.2 million, or $0.17 per basic and diluted share. This compares with a net loss attributable to common shareholders of $8.7 million, or $0.32 per basic and diluted share, for the same period in 2018.

Revenues for the first quarter of 2019 were $7.0 million, compared to $0.5 million for the same period in 2018. Revenues for the first quarter of 2019 were comprised of revenues from collaborative research and development agreements with Takeda, and grant revenue from CPRIT. Total research and development expenses for the first quarter of 2019 were $8.5 million, compared with $6.7 million for the same period in 2018. Total general and administrative expenses for the first quarter of 2019 were $4.9 million, compared with $2.9 million for the same period in 2018.

On May 13, 2019 Transgene (Euronext Paris: TNG) (Paris:TNG), a biotech company that designs and develops virus-based immunotherapies against cancers and infectious diseases to transform the fight against solid tumors and infectious diseases, reported its business update for the quarter ending March 31, 2019 (Press release, Transgene, MAY 13, 2019, View Source [SID1234536214]).

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Operating revenue:

The following table summarizes the first quarter operating revenue for 2019 compared to the same period in 2018:

Q1
In millions of euros 2019 2018

Revenue from collaborative and licensing agreements 0.4 0.2
Government financing for research expenditures 1.5 1.6

Operating revenue 1.9 1.8
During the first quarter of 2019, revenue from collaborative and licensing agreements was mainly composed of research services and royalties.

As of March 31, 2019, government financing for research expenditures mainly consisted of 25% of the research tax credit expected for 2019 (€1.5 million in the first quarter of 2019, compared to €1.6 million for the same period in 2018).

Cash, cash equivalents, available-for-sale financial assets and other financial assets:

In the first quarter of 2019, Transgene’s cash burn was €7.8 million, compared to €5.8 million for the same period in 2018. Cash, cash equivalents, available-for-sale financial assets and other financial assets stood at €9.1 million as of March 31, 2019, compared to €16.9 million as of December 31, 2018. This cash position does not include the €20 million credit facility available for the Company or the $10 million receivable from AstraZeneca.

Key achievements:

Finance:
Transgene secured a €20 million revolving credit facility with a 30-month term with Natixis. Transgene will be able to draw on and repay the facility at its discretion. Transgene has used its shares in the Chinese biotech company Tasly Biopharmaceuticals as collateral for this loan (press release distributed on March 18, 2019). As of May 13, 2019, the Company has not drawn down on this facility.
Invir.IO:
Transgene and AstraZeneca signed a collaborative research, option and exclusive license agreement to co-develop five armed oncolytic vaccinia virus candidates deriving from the Invir.IO platform.
Transgene is to receive $10 million in Q2 2019 and additional pre-clinical success milestones of up to $3 million. Transgene is eligible to receive an option exercise payment on each candidate in the event AstraZeneca exercises one or more of its license option, as well as development and commercial milestones and royalties (press release distributed on May 2, 2019).
Transgene and BioInvent extend their collaboration to develop additional multifunctional oncolytic viruses encoding for antibodies capable of treating a broad range of solid tumors (press release distributed on March 26, 2019).
myvac:
Transgene announced that the NEOVIVA project, that is focused on Transgene’s individualized immunotherapy platform myvac, was selected by the "Investments for the Future" Program (Programme d’Investissements d’Avenir) operated by Bpifrance. The NEOVIVA project will receive €5.2 million over the five-year duration of the program from Bpifrance, of which Transgene will receive €2.6 million (press release distributed on March 13, 2019).
TG4050:
Transgene announced its decision to initiate clinical developments of its lead myvac candidate, TG4050, and the finalization of its collaboration agreement with NEC (press release distributed on March 5, 2019).
Transgene received FDA IND clearance for TG4050 to commence clinical development in ovarian cancer (press release distributed on May 13, 2019).
Outlook:

Transgene expects its cash burn for 2019 to be between €15 million and €20 million, based on its current development plan and cash-in from the collaboration with AstraZeneca.

As a result of the financing agreement with Natixis and the signing of the collaboration with AstraZeneca, Transgene has extended its financial visibility to Q4 2020.

Transgene confirms that it expects readouts from its key clinical trials in the second half of 2019.

On May 13, 2019 Ayala Pharmaceuticals, a clinical-stage company developing medicines for cancers that are genetically defined, reported that it has been granted Orphan Drug Designation from the U.S. Food and Drug Administration’s (FDA) Office of Orphan Products Development (OOPD) for AL101, a potent and selective inhibitor of gamma secretase-mediated Notch signalling, for the treatment of ACC AL101 is currently in Phase 2 for adenoid cystic carcinoma patients with tumor bearing Notch activating mutations (ACCURACY) (Press release, Ayala Pharmaceuticals, MAY 13, 2019, View Source [SID1234536212]). For additional information about AL101 ACCURACY clinical trial, please go to www.clinicaltrials.gov. Interested patients and physicians can contact Medical Affairs at Ayala for more information at: [email protected] or call refer +1-857-444-0553..

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Orphan Drug Designation is granted to drug therapies intended to treat diseases or conditions that affect fewer than 200,000 people in the United States. Orphan Drug Designation by the FDA entitles Ayala to seven years of market exclusivity for the use of AL101 for the treatment of ACC, if approved, plus significant development incentives, including tax credits related to clinical trial expenses, an exemption from the FDA-user fee, and FDA assistance in clinical trial design.

"Receiving Orphan Drug Designation from the FDA signifies our continued progress and commitment to develop AL101 as a potential treatment for people with ACC," said Roni Mamluk, Ph.D., Chief Executive Officer at Ayala Pharmaceuticals. "Given the proof of concept demonstrating that AL101 has a significant inhibitory effect on tumor growth in a mouse model using implanted ACC patient-derived xenograft tumors coupled with the significant unmet need in ACC, we look forward to accelerating AL101 development for patients in the U.S."

ACC is a rare form of cancer. In the U.S., there are approximately 566,000 people diagnosed with cancer each year, and only about 1,224 of them are diagnosed with ACC. According to the Adenoid Cystic Carcinoma Organization International, there are approximately 14,873 Americans alive today living with this disease. Current treatment options include surgery, chemotherapy and/or radiation therapy; however, there is no approved drug for the treatment of ACC.

About AL101

AL101 is a gamma secretase inhibitor developed as a Notch inhibitor for oncology indications. Notch signaling pathway plays an important role in tumorigenesis in several solid and hematological malignancies. Upon ligand binding of the Notch receptor, an important step in the activation of Notch receptors is cleavage by gamma secretase, which frees the Notch intracellular signaling domain.

AL101 is currently in Phase 2 for adenoid cystic carcinoma patients with tumor bearing Notch activating mutations (ACCURACY). For additional information about AL101 ACCURACY clinical trial, please go to www.clinicaltrials.gov. Interested patients and physicians can contact Medical Affairs at Ayala for more information at: [email protected] or call refer +1-857-444-0553.

On May 13, 2019 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a biotechnology company focused on developing targeted cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that its research partner, the University of Northern Colorado, has bioengineered a human cell line designed to activate a cannabinoid prodrug in its quest to develop a Cell-in-a-Box/cannabinoid therapy for serious forms of cancer, particularly brain cancer (Press release, PharmaCyte Biotech, MAY 13, 2019, View Source [SID1234536211]).

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Mark L. Rabe, MD, PharmaCyte’s Director of Cannabis Program Development, commenting on the bioengineered cell line said, "We now have a cell line into which the gene for a putative cannabinoid prodrug-activating enzyme has been ‘transfected’ or inserted into the cell’s DNA. The gene was synthesized de novo using knowledge of the underlying genetic code of the cell. The cell line is the same human cell line that will be used in PharmaCyte’s planned clinical trial in locally advanced, inoperable pancreatic cancer (LAPC).

"The next step is to test the efficiency of the transfected cells in converting cannabinoid prodrugs into their active cancer-fighting forms. If the cells are suitably active, they would then be propagated to the point that they can then be encapsulated using the Cell-in-a-Box technology. Also, we will continue our analysis of other genes of interest that could be used in a similar way."

PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, stated, "As we advance our Cell-in-a-Box + ifosfamide therapy for LAPC with the U.S. FDA through preparation and submission of an Investigational New Drug application, we are pleased to report on the work done at the University of Northern Colorado. Such news as this serves to contribute to PharmaCyte’s efforts as we work diligently to develop treatments for deadly diseases and build shareholder value."

The current objective of PharmaCyte’s Cannabis Program is to develop targeted cannabinoid-based chemotherapy by bioengineering a cell line that produces a cannabinoid prodrug-activating enzyme, encapsulating this cell line utilizing the Cell-in-a-Box platform and implanting the encapsulated cells near the site of a tumor. A cannabinoid prodrug would then be administered and activated at the site of the tumor where its anti-cancer effects are needed. PharmaCyte’s research conducted by the University of Northern Colorado has confirmed that a cannabis-based approach may prove to be efficacious in the treatment of several different types of cancers.