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.

On December 10, 2019 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic and other major diseases, reported that the latest clinical data of Fully-human BCMA CAR-T, a potential best-in-class cell therapy co-developed with IASO Biotherapeutics (IASO BIO) (Innovent:IBI326, IASO BIO: CT103A), has been presented in an oral session at the prestigious 61st Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting & Exposition convened in Orlando, FL, from 7 December 2019 to 10 December 2019 [Abstract #582] (Press release, Innovent Biologics, DEC 10, 2019, View Source [SID1234552220]). The oral presentation title is "Efficacy and Safety of Fully Human BCMA Targeting CAR T Cell Therapy in Relapsed Refractory Multiple Myeloma".

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The oral presentation highlighted the impressive safety, efficacy and persistence of an IIT study of anti-BCMA CAR-T for the treatment of Relapsed/Refractory Multiple Myeloma conducted by Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology. With 17 of the 18 patients evaluable, the objective response rate (ORR) was 100% in the study. In addition, 70.6% of patients achieved a best response of stringent complete or complete response (sCR/CR), and 88.2% achieved a best response of very good partial response (VGPR) or better. CRS occurred in 17 of 18 patients (Grade 1&2- 72.2% (13), Grade 3- 16.7% (3), Grade 4- 5.6% (1)), but was generally manageable with no neurotoxicity. At the lowest dose (1 x106 cells/kg), IBI326 still maintained 100% ORR, with 78% of these patients achieving a best response of very good partial response (VGPR) or better. As well, toxicity was manageable with 88% of these patients experiencing grade 2 CRS or less.

Furthermore, 4 patients participating in the study had relapsed from a prior murine CAR-T infusion. Their response and the overall performance indicate that IBI326 may also can provide a potential first-line treatment option for patients who have relapsed from prior CAR-T infusions.

Dr. Hui Zhou, Vice President and Head of Oncology Strategy and Medical Sciences of Innovent, said: "It is a fruitful year for us, as the clinical progress of BCMA CAR-T has also been presented at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) earlier this year before ASH (Free ASH Whitepaper). We are very happy to see the prolonged patient remission to this therapy and look forward to starting our phase II clinical trials by early next year. Hope more patients suffering from multiple myeloma could benefit from that."

The Ib/II chimeric protocol of IBI326 has been granted IND approval by the National Medical Products Administration (NMPA), and the phase II clinical trials are about to be initiated by early next year.

About Relapsed/Refractory Multiple Myeloma

Multiple Myeloma is a deadly blood cancer that often infiltrates the bone marrow causing anemia, kidney failure, immune problems and bone fractures. With a global annual incidence rate at 2/100,000, it is one of the most commonly diagnosed blood cancers, second only to non-Hodgkin lymphoma.

For newly treated patients with multiple myeloma, common first-line treatment drugs include proteasome inhibitors, immunoregulatory drugs and alkane agents. For most patients, the commonly used first-line treatment can stabilize the patient’s condition for 3-5 years, but a small number of patients show primary drug resistance at the time of initial treatment, and the disease cannot be effectively controlled. Relapse patients are those who have a reoccurrence after complete remission of the disease. Refractory patients are those with primary drug resistance or those who have finished first-line treatment and do not achieve remission, or patients whose disease progress within 60 days after achieving minimal response. With effective treatment, the majority of patients will inevitably enter the stage of relapse and refractory after 3-5 years of disease stabilization. For these patients, the overall effective rate of existing second-line treatment is about 40% to 70%, with short remission time.

About IBI326 (BCMA CAR-T)

IBI326 is an innovative therapy co-developed by Innovent and IASO BIO. Previous studies indicate patients with relapsed/refractory multiple myeloma (RRMM) who received high-dose BCMA-targeting CAR-T cells may achieve better remission but have worse adverse events. Moreover, once the disease progresses again, the re-infusion of CAR-T cells will be not effective. To solve this dilemma, IBI326 has been developed, A lentiviral vector containing a CAR structure with a fully human scFv, CD8a hinger and transmembrane, 4-1BB co-stimulatory and CD3z activation domains. Based on strict selection and screening, utilizing a proprietary in-house optimization platform, the construct of the BCMA CAR-T is potent and persistent.