On December 10, 2019 Tetra Bio-Pharma Inc. ("Tetra" or the "Company") (TSX-V:TBP) (OTCQB:TBPMF), a leader in cannabinoid-derived drug discovery and development, reported it will be requesting a meeting with the U.S. Food and Drug Administration (FDA) to discuss the drug development program for its Orphan Drug candidate HCC011, inhaled delta-9-tetrahydrocannabinol (THC), in the treatment of hepatocellular carcinoma (Press release, Tetra Bio Pharma, DEC 10, 2019, View Source [SID1234561119]).

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Hepatocellular carcinoma (HCC), also known as primary liver cancer, is the most common form of liver cancer and is responsible for 80 percent of the primary malignant liver tumors in adults. In addition to quality of life benefits to cancer patients, based on preclinical research, HCC011 should also have antitumor effects. The Phase 2 study of HCC011 will target patients with disease progression on Sorafenib, have measurable disease, and Child-Pugh Class A liver impairment. The Phase 2 trial will consist of a single arm. Patients will receive the HCC011 by inhalation three times daily, in combination with Sorafenib, until disease progression or unacceptable toxicity. The study design is similar to the ones used by recent drugs seeking accelerated approval. The Disease control rate will be assessed based on the Response Evaluation Criteria in Solid Tumors (RECIST); the overall survival and time to progression will be closely monitored over time. Patients will also beneficiate of the anti-emetic effect of HCC011, which will participate in improving their quality of life.

The company intends to file an NDA for HCC011 via the 505(b)(2) pathway. The FDA has three approval pathways by which drugs may gain approval and the 505(b)(2) new drug application (NDA) is one of the three ways created by the Hatch-Waxman Amendments of 1984, with 505(b)(2) referring to a specific section of the U.S. Federal Food, Drug, and Cosmetic Act. The provisions of a 505(b)(2) provide manufacturers who have certain types of drugs with an opportunity to acquire FDA approval without performing all the work that’s required with a standard 505(b)(1) NDA.

Additionally, 505(b)(2) pathway allows for the ability to pursue additional designations such as fast track and accelerated approval to complement its already granted Orphan Drug Designation for HCC011 in HCC. Orphan drug designation provides certain benefits and incentives, such as seven-year marketing exclusivity, protocol assistance from the FDA, tax credits of 50% of the clinical drug testing cost awarded upon approval, and a waiver of the prescription drug user fee. The company fully intends to seek out additional designations where appropriate.

The HCC011 orphan drug candidate benefits from Tetra’s significant clinical data on the pharmacokinetics, safety and pharmacodynamics of inhaled cannabinoids. The company will also benefit from its previous investment in its GMP compliant manufacturing facility for these inhaled new drugs that holds an active Drug Establishment License (DEL) from Health Canada.

"We are very excited to bring HCC011 to clinical trials to help patients suffering from hepatocellular carcinoma and believe the 505(b)(2) pathway is the right approach for us, as we will be able to leverage our data and the data of others," said Dr. Guy Chamberland, CEO and Chief Regulatory Officer of Tetra Bio-Pharma. "This regulatory strategy combined with the Orphan status will provide major cost savings to shareholders. Post our meeting with FDA, we hope to gain clarity on our filing and marketing requirements, including input from the Agency on the design of our planned Phase 2 trial for HCC011 in HCC. We plan to provide an update once we have concurrence with the FDA."

On December 10, 2019 Bloom Science, a biopharmaceutical company developing microbiome-derived therapeutics in multiple neurological conditions and oncology, reported the launch of a research agreement with Cedars-Sinai Medical Center (Press release, Bloom Science, DEC 10, 2019, View Source [SID1234556212]). The collaboration will focus on advancing the understanding of the microbiome in a Phase 1 study investigating the clinical utility of the ketogenic diet as an adjunctive treatment in combination with standard of care in glioblastoma.

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Preclinical and early clinical research has focused on elucidating the impact of the ketogenic diet in the treatment of glioblastoma multiforme, one of the deadliest primary brain tumors. Bloom Science will leverage its discovery platform to investigate the underlying contributions of the microbiota and related metabolites.

"For a disease like glioblastoma, where decades of clinical trials have resulted in only marginal improvement, we need to think differently about how to approach treatment. Although we still have a great deal to learn, it is clear that diet, metabolism, and the gut microbiome have a profound effect on health, disease, and treatment response," said principal investigator Jethro Hu MD, at Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute. "To reach the next level of scientific understanding, we need to bring leading edge research capabilities to the table, and that is precisely what this collaboration provides."

"The gut microbiome is a very promising frontier in both neurological and oncology drug development," said Christopher Reyes, PhD, CEO of Bloom Science. "This research agreement is key to expanding our discovery efforts into oncology, cancer related cognitive decline, and our commitment to working with leaders in the field, such as Dr. Hu to further advance the science."

On December 10, 2019 AffaMed Therapeutics, a biopharmaceutical company founded and funded by CBC Group, a healthcare private equity firm focused on the development and late-stage investment opportunities, reported it has received Clinical Trial Application (CTA) approval from the China National Medical Products Administration (NMPA) to conduct clinical trials for AMT901, or SB3, a proposed biosimilar for Herceptin (trastuzumab) being developed in collaboration with Samsung Bioepis as an intravenous trastuzumab for the treatment of HER2-positive breast cancer and it has been approved by the European Medicines Agency (EMA) and United States (US) Federal Drug Agency (FDA) (Press release, AffaMed Therapeutics, DEC 10, 2019, View Source [SID1234553305]). Clinical study preparation is on track and first patient visit is scheduled in Q1 2020.

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"This CTA approval is an important milestone for AffaMed as we transition to a clinical-stage biotechnological company," said Dr. Nathan Pang, CEO of AffaMed. "We are fully geared up to initiate this clinical development program, with the goal of providing AMT901 to help more Chinese patients at an affordable price."

The CTA approval was based on review of a comprehensive data package that demonstrated biosimilarity of AMT901 to Herceptin (trastuzumab). This includes results from a clinical comparative study that found no clinically meaningful differences in terms of efficacy and safety between AMT901 and the reference product for patients with HER2-positive breast cancer.

In February 2019, CBC Group formed AffaMed Therapeutics and announced a partnership agreement with Samsung Bioepis to collaborate on clinical development, regulatory registration, and commercialization of multiple next-generation biosimilars in China. In addition to the AMT901, AffaMed has a growing portfolio of product pipelines including in the ophthalmology therapeutic area, with biosimilars referencing Lucentis (ranibizumab) and Eylea (aflibercept) also in clinical development in collaboration with Samsung Bioepis.

On December 10, 2019 Medigene AG (FSE: MDG1, Prime Standard), a clinical stage immuno-oncology company focusing on the development of T cell immunotherapies, reported that Medigene’s researchers presented clinical immune monitoring data obtained during the first year of treatment from the ongoing Phase I/II clinical trial with Medigene’s DC vaccine for the treatment of acute myeloid leukemia (AML) at the 61st ASH (Free ASH Whitepaper) Annual Meeting (Orlando, USA) (Press release, MediGene, DEC 10, 2019, View Source [SID1234552258]).

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This ongoing DC vaccine clinical trial for the treatment of AML will be completed at the end of 2019 and topline data will be reported in the beginning of 2020.

The poster presentation focused on clinical immune monitoring data from the trial. Several assay systems were used to assess the impact of the DC vaccine on T cell responses (specific for WT-1 and PRAME antigens) and other immunological parameters. Furthermore, the recurrence of WT-1-positive and/or PRAME-positive AML blasts, as well as the occurrence of AML-specific mutations in bone marrow, were investigated. The results of the 1-year interim assessment show that, upon in vitro stimulation with WT-1 or PRAME, T cells from peripheral blood of 75% (6 of 8) of relapsing patients were capable of producing the pro-inflammatory cytokine IFNgamma, while such a response was detected in only in 25% (3 of 12) of the patients in remission.

Dr. Kai Pinkernell, CMO and CDO of Medigene AG, comments: "These interim clinical immune monitoring data from our DC trial after one year of treatment shed light on the potential functionality of our vaccine. We believe that the detection of reactive T cells in peripheral blood may be linked to the concomitant presence of AML blasts in the periphery of relapsing patients. In addition, in most patients in remission the stable or decreasing levels of WT-1 and/or PRAME mRNA in the bone marrow would be consistent with a local response against AML antigens, despite a negative IFN-gamma response in peripheral blood. Further monitoring of the patients in remission in the second year of vaccination may bring further insights into the role of DC vaccination in the prevention of AML recurrence."

The poster entitled "DC Vaccination Induces Antigen Specific Immune Responses in AML Patients: A 1-Year Interim Assessment" is available at Medigene’s company website at: View Source

About Medigene’s DC trial:
A total of 20 subjects (median age 59, range 24 to 73) with AML (risk groups good, intermediate, poor: 13, 5, 2), in morphologic complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) after induction or consolidation therapy, not eligible for allogeneic hematopoietic stem cell transplantation, were enrolled into this safety and feasibility Phase I/II trial, vaccinated and followed up for 12 months at the interim analysis timepoint. Subjects in this trial had AML that was positive for Wilms Tumor-1 (WT-1) antigen with or without positivity for Preferentially Expressed Antigen in Melanoma (PRAME). Vaccination with dendritic cells, presenting the antigens WT-1 and PRAME, was carried out monthly, with a higher frequency within the first 6 weeks. AML diagnoses had been established with a median of 9.8 months before the first vaccination (range 4.5 to 17.5 months), and the last chemotherapy infusion had been performed at a median of 6.9 months (range 2 to 14.8 months).

Interim results:
The vaccinations were well tolerated with no serious adverse events (SAEs) related to the treatment. The most common adverse events (AEs) were injection site related, accounting for 35% of all AEs and mild in nature (Grade 1). After a 12-month treatment period, the overall survival was 89% (18 of 20 patients, 95% confidence interval: 61 to 97%) and the progression free survival was 60% (12 of 20 patients, 95% confidence interval: 36 to 78%). Most relapses, 5 out of 8, occurred within the first 80 days after initiation of vaccination, suggesting a possible molecular relapse upon entering the study.

About Medigene’s DC vaccines:
In addition to Medigene’s development focus on T cell-receptor modified T cells (TCR-Ts), the Company has developed a new generation of antigen-tailored dendritic cell (DC) vaccines.
Dendritic cells (DC) can take up antigens, process them and present peptides on their surface in a form that can induce antigen-specific T cells to mature and proliferate. In this way, T cells recognize and eliminate tumor cells which bear the same antigen peptide on their surface. Dendritic cells can also induce natural killer cells (NK cells) to attack tumor cells. The scientific team of Medigene has developed new, fast and efficient methods for generating autologous (patient-specific) mature dendritic cells which have the relevant characteristics to generate very strong T cell and NK cell immune responses. The dendritic cells can be loaded with various tumor antigens to treat different forms of cancer. Since an immune response builds up over the total time of administration of the DC vaccine, this form of therapy is particularly designed for patients who suffer from a tumor disease which has been reduced to such an extent by chemotherapy that the prevention of the recurrence of the tumor disease is the main goal.

About acute myeloid leukemia (AML):
Acute myeloid leukemia is a malignant disease of the hematopoietic system, affecting mainly adults above 60 years of age. In Germany, about 3,600 cases are registered annually.
AML is caused by uncontrolled growth of dysfunctional hematopoietic precursor cells in the bone marrow. These cells prevent the generation of normal blood cells, causing a decrease in erythrocytes and platelets, for example. Typical symptoms of AML include anemia, fever, increased risk of infection, and bleeding. AML progresses rapidly and may be fatal within a few weeks or months, if untreated.
AML treatment is often started with intensive chemotherapy, followed by consolidation with or without allogeneic hematopoietic stem cell transplantation. Unfortunately, a significant proportion of patients suffer a relapse of the original disease. Depending on the biologic risk profile of the disease, age and co-morbidity the long-term survival is highly variable.

On December 10, 2019 Constellation Pharmaceuticals, Inc., (Nasdaq: CNST) a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported that it has priced an underwritten public offering of 6,500,000 shares of its common stock at a public offering price of $34.50 per share, for total gross proceeds of $224.3 million, before deducting underwriting discounts and commissions and expenses payable by Constellation (Press release, Constellation Pharmaceuticals, DEC 10, 2019, View Source [SID1234552232]). All of the shares in the offering are being sold by Constellation. In addition, Constellation has granted the underwriters a 30-day option to purchase up to 975,000 additional shares of its common stock at the public offering price, less the underwriting discount and commissions. The offering is expected to close on December 13, 2019, subject to customary closing conditions.

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J.P. Morgan, Jefferies and Cowen are acting as joint book-running managers for the offering. RBC Capital Markets is acting as a bookrunner, and SunTrust Robinson Humphrey is acting as lead manager for the offering.

The shares are being offered by Constellation pursuant to an automatically effective shelf registration statement that was previously filed with the Securities and Exchange Commission ("SEC") on December 9, 2019.

This offering is being made only by means of a prospectus and prospectus supplement that form a part of the registration statement. A preliminary prospectus supplement relating to and describing the terms of the offering has been filed with the SEC and is available on the SEC’s website at www.sec.gov. A final prospectus supplement relating to the offering will be filed with the SEC. When available, copies of the final prospectus supplement and the accompanying prospectus may also be obtained by contacting: J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, telephone: (866) 803-9204; Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, by telephone at 877-821-7388 or by email at [email protected]; or Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, Attn: Prospectus Department, by email at [email protected] or by telephone at (833) 297-2926.

This press release shall not constitute an offer to sell, or a solicitation of an offer to buy these securities, 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.