On August 2, 2021 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported that the first patient has been treated with FT819, an off-the-shelf chimeric antigen receptor (CAR) T-cell therapy targeting CD19+ malignancies (Press release, Fate Therapeutics, AUG 2, 2021, View Source [SID1234585566]). FT819 is the first-ever CAR T-cell therapy derived from a clonal master induced pluripotent stem cell (iPSC) line, a renewable cell source that enables mass production of high quality, allogeneic CAR T cells with greater product consistency, off-the-shelf availability, and broader patient accessibility. FT819 is engineered with several first-of-kind features designed to improve the safety and efficacy of CAR T-cell therapy.

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"Remarkable clinical outcomes have been achieved through treatment with patient-derived CAR T-cell therapy, however, next-generation approaches are necessary to reach more patients who are in need of these highly-effective therapies," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "Treatment of the first-ever patient with FT819 ushers in a new era for off-the-shelf CAR T-cell therapy, with the potential to overcome the real-world limitations of existing patient- and donor-derived therapeutic approaches and unlock the full potential of CAR T-cell therapy. We would like to thank our collaborators at Memorial Sloan Kettering Cancer Center, whose partnership over the past five years has profoundly contributed to this landmark achievement."

FT819 was designed to specifically address several limitations associated with the current generation of patient- and donor-derived CAR T-cell therapies. Under a collaboration with Memorial Sloan Kettering Cancer Center (MSK) led by Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering and Head, Gene Expression and Gene Transfer Laboratory, the Company incorporated several first-of-kind features into FT819 including:

Use of a clonal master engineered iPSC line as the starting cell source, which enables CAR T cells to be mass produced and delivered off-the-shelf for broad patient access;
Incorporation of a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion as described in the journal Nature Medicine (View Source);
Insertion of the CAR transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR expression and enhanced T-cell potency as described in the journal Nature (View Source); and
Complete bi-allelic disruption of T-cell receptor (TCR) expression for the prevention of graft-versus-host disease (GvHD), a potentially life-threatening complication associated with allogeneic T-cell therapy.
The multi-center Phase 1 clinical trial of FT819 is designed to determine the recommended Phase 2 dose and schedule of FT819 and assess its safety and clinical activity in adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and B-cell lymphomas (BCL). Three treatment regimens will be independently evaluated for each type of malignancy in dose escalation: Regimen A as a single dose of FT819; Regimen B as a single dose of FT819 with IL-2 cytokine support; and Regimen C as three fractionated doses of FT819. For each indication and regimen, dose-expansion cohorts may be enrolled to further evaluate the clinical activity of FT819. The first patient with relapsed / refractory ALL was enrolled in Regimen A and received a dose of 90 million cells.

At the 24th American Society of Gene & Cell Therapy Annual Meeting held in May 2021, the Company presented preclinical data demonstrating that FT819 exhibits uniform 1XX CAR expression with complete elimination of endogenous TCR expression. The product candidate was shown to contain a stem- and central-memory T-cell phenotype, and had high-level expression of the activation marker CD25 and the trafficking marker CXCR4 and very low-level expression of the checkpoint proteins PD1, TIM3, CTLA4 and LAG3. Additionally, data from functional assessments showed that FT819 had potent antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of healthy donor-derived CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia.

Pursuant to a license agreement with MSK, Fate Therapeutics has an exclusive license for all human therapeutic use to U.S. Patent No. 10,370,452, which covers compositions and uses of effector T cells expressing a CAR, where such T cells are derived from a pluripotent stem cell including an iPSC. In addition to the patent rights licensed from MSK, the Company owns an extensive intellectual property portfolio that broadly covers compositions and methods for the genome editing of iPSCs using CRISPR and other nucleases, including the use of CRISPR to insert a CAR in the TRAC locus for endogenous transcriptional control.

Fate Therapeutics has licensed intellectual property from MSK on which Dr. Sadelain is an inventor. As a result of the licensing arrangement, MSK has financial interests related to Fate Therapeutics.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT819
FT819 is an investigational, universal, off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line, which is engineered with the following features designed to improve the safety and efficacy of CAR19 T-cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion; integration of the CAR19 transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR19 expression and enhanced T-cell potency; and complete bi-allelic disruption of TCR expression for the prevention of graft-versus-host disease (GvHD). FT819 demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of primary CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia (Valamehr et al. 2020). FT819 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).

On August 2, 2021 Cerecor Inc. (NASDAQ: CERC), a biopharmaceutical company focused on becoming a leader in the development and commercialization of treatments for immunologic, immuno-oncologic and rare genetic disorders, reported recent business progress and second quarter 2021 financial results (Press release, Cerecor, AUG 2, 2021, View Source [SID1234585564]).

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"We are pleased with the progress made in the second quarter," said Mike Cola, Chief Executive Officer of Cerecor. "In addition to strengthening our cash position with the debt financing, we expanded our pipeline with an exciting collaboration with Sanford Burnham, and announced favorable results in one of our key programs, CERC-002 in moderate-to-severe Crohn’s disease. We are excited to continue the advancement of our programs, including the expansion of CERC-002 into moderate-to-severe ulcerative colitis refractory to anti-TNF alpha therapies. We look forward to the second half of 2021 with multiple data readouts including the second cohort of CERC-002 in Crohn’s disease."

Business Updates:

Announced positive results from Cohort 1 of its open-label proof-of-concept Phase 1b study of CERC-002 in patients with moderate-to-severe Crohn’s disease who had previously failed three or more lines of biologics therapies, including anti-TNF alpha treatments. Data demonstrated a rapid and dramatic mean reduction of LIGHT levels of approximately 80% compared to baseline that correlated to the pharmacodynamic effect of CERC-002 (1.0 mg/kg). A clinically meaningful benefit in mucosal healing as determined by colonoscopy (SES-CD score) was observed in 75% of the patients in Cohort 1 (3 of 4). CERC-002 was well-tolerated with no drug-related severe adverse events. The Company has completed enrollment of Cohort 2 (3.0 mg/kg) and anticipates data in the second half of 2021.

Cerecor entered into an exclusive license agreement with Sanford Burnham Prebys for the worldwide development and commercialization of an immune checkpoint program. The license further enhances the Company’s development pipeline of novel biologics that address immunology and immuno-oncology targets.

Cerecor strengthened and extended its financial resources with a $35 million debt financing agreement with Horizon Technology Finance. The Company received the initial tranche of $20 million at the loan closing in the second quarter and an additional $10 million in the third quarter (following the positive results from Cohort 1 of its open-label proof-of-concept Phase 1b study of CERC-002 in moderate-to-severe Crohn’s disease). The remaining $5 million may be funded upon achieving certain predetermined milestones.
Program Updates and Milestones:

CERC-002: Anti-LIGHT monoclonal antibody in clinical development for COVID-19 acute respiratory distress syndrome (ARDS), moderate-to-severe Crohn’s disease, and moderate-to-severe ulcerative colitis (UC) refractory to anti-TNF alpha therapies.
The Company announced the completion of enrollment in Cohort 2 (3.0 mg/kg) of its Phase 1b proof-of-concept study of CERC-002 in moderate-to-severe Crohn’s disease and anticipates data in the second half of 2021.
Based on the positive data from Cohort 1 (1.0 mg/kg) of its Phase 1b trial of CERC-002 in moderate-to-severe Crohn’s disease, the Company announced its plans to expand CERC-002 to include patients with moderate-to-severe UC who are refractory to anti-TNF alpha therapies.
The Company remains in dialogue with the FDA and is working through feedback to determine the trial design for a registrational study of CERC-002 in COVID-19 ARDS and accompanying timelines, including the potential expansion to a larger patient population in broader ARDS.
CERC-007: Anti-IL-18 monoclonal antibody for the treatment of multiple myeloma (MM) and Still’s disease (adult onset Still’s disease (AOSD) and systemic juvenile idiopathic arthritis (sJIA)).
Top-line data anticipated from the Phase 1b clinical trial in patients with relapsed or refractory MM in the second half of 2021.
Initial data anticipated from the Phase 1b clinical trial in AOSD in the third quarter of 2021.

CERC-006: Dual mTORc1/c2 small molecule inhibitor for complex lymphatic malformations.
Initial data anticipated from the Phase 1b proof-of-concept clinical study in the third quarter of 2021.
CERC-800 programs (CERC-801, CERC-802, and CERC-803): Therapeutic doses of monosaccharide therapies for congenital disorders of glycosylation (CDGs).
CERC-801 – In collaboration with the Frontiers in Congenital Disorders of Glycosylation Consortium clinical program, data from the pivotal trial evaluating the safety and efficacy of D-galactose in patients suffering from Phosphoglucomutase-1 deficiency related CDG (PGM1-CDG) are anticipated in the first quarter of 2022.
CERC-802 – Data from the pivotal trial evaluating the safety and efficacy of D-mannose in patients suffering from Mannose phosphate isomerase deficiency related CDG (MPI-CDG) are anticipated in the second half of 2021.
CERC-803 – Data from the pivotal trial evaluating the safety and efficacy of L-fucose in patients suffering from Leukocyte Adhesion Deficiency II (LAD II) are anticipated in the second half of 2021.
Second Quarter 2021 Financial Update:

As of June 30, 2021, Cerecor had $40.4 million in cash and cash equivalents, representing a $21.5 million increase as compared to December 31, 2020. The increase was driven by gross proceeds of $20 million from a debt financing agreement entered into in June 2021 and net proceeds of $37.7 million from an underwritten public offering completed in January 2021, partially offset by operating expenditures, the majority of which related to pipeline development. In the third quarter, the Company achieved a milestone triggering receipt of an additional $10 million debt tranche.

Net product revenue of the Company’s commercialized product, which the Company considers non-core, increased $1.4 million for the three months ended June 30, 2021 as compared to the three months ended June 30, 2020, which was driven by increased demand to backfill the short-dated inventory sold in the prior quarter.

Total operating expenses increased $7.3 million for the three months ended June 30, 2021 as compared to the three months ended June 30, 2020, which was the largest driver of the increase in net loss period over period. The increased operating expenses were largely driven by a $6.7 million increase in research and development expenses as a result of Cerecor’s continued advancement of its maturing pipeline, particularly as it relates to clinical and manufacturing expenses.

(a) The condensed consolidated balance sheets as of June 30, 2021 and December 31, 2020 have been derived from the reviewed and audited financial statements, respectively, but do not include all of the information and footnotes required by accounting principles accepted in the United States for complete financial statements.

(a) The unaudited condensed consolidated statements of operations for the three and six months ended June 30, 2021 and 2020 have been derived from the reviewed financial statements but do not include all of the information and footnotes required by accounting principles generally accepted in the United States for complete financial statements.

On August 2, 2021 Servier, a global pharmaceutical company, reported the global Phase 3 double blinded placebo controlled AGILE study of TIBSOVO (ivosidenib tablets) in combination with the chemotherapy azacitidine in adults with previously untreated IDH1-mutated acute myeloid leukemia (AML) met its primary endpoint of event-free survival (EFS)1,2 (Press release, Servier, AUG 2, 2021, View Source [SID1234585561]). Treatment with TIBSOVO in combination with azacitidine compared to azacitidine in combination with placebo demonstrated a statistically significant improvement in EFS. Additionally, the trial met all of its key secondary endpoints, including complete remission rate (CR rate), overall survival (OS), CR and complete remission with partial hematologic recovery rate (CRh rate) and objective response rate (ORR). The safety profile of TIBSOVO in combination with azacitidine was consistent with previously published data. The study recently halted further enrollment based on the recommendation of the Independent Data Monitoring Committee (IDMC), as a difference of clinical importance was noted between the treatment groups.

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"The results of AGILE represent a major breakthrough and will be welcome news for patients dealing with previously untreated IDH1-mutated acute myeloid leukemia," said Claude Bertrand, Executive Vice President, R&D, Servier Group. "We look forward to sharing the findings from this study with the medical community and with regulatory authorities around the world."

A full analysis of the AGILE trial will be submitted for a presentation at a future medical congress.

"Acute myeloid leukemia has a poor prognosis, especially for newly diagnosed patients who are not eligible for intensive chemotherapy," said Susan Pandya, M.D., Vice President Clinical Development, Servier Pharmaceuticals. "TIBSOVO monotherapy has been instrumental in transforming outcomes for adult patients with newly diagnosed or relapsed refractory AML harboring an IDH1 mutation. These promising results from the AGILE study support the added benefit of inhibiting the mutant IDH1 enzyme in combination with standard chemotherapy in the newly diagnosed intensive chemotherapy ineligible setting. We look forward to presenting the full results of the AGILE trial to show how TIBSOVO in combination with azacitidine may improve outcomes in previously untreated patients with IDH1-mutated acute myeloid leukemia."

TIBSOVO* is currently approved in the U.S. as monotherapy for the treatment of adults with IDH1-mutant relapsed or refractory acute myeloid leukemia (AML), and for adults with newly diagnosed IDH1-mutant AML who are ≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy. Recently, the U.S. Food and Drug Administration (FDA) accepted Servier’s supplemental New Drug Application (sNDA) for TIBSOVO as a potential treatment for patients with previously treated IDH1-mutated cholangiocarcinoma. The sNDA was granted Priority Review by the FDA.

About AGILE Phase 3 Trial
The AGILE trial is a global, Phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial designed to evaluate the efficacy and safety of TIBSOVO in combination with azacitidine compared to placebo in combination with azacitidine, in newly diagnosed AML patients non eligible for intensive chemotherapy. The study’s primary endpoint is event-free survival (EFS), defined as the time from randomization until treatment failure, relapse from remission, or death from any cause, whichever occurs first. Treatment failure is defined as failure to achieve complete remission (CR) by Week 24.

Other key secondary endpoints included complete remission rate (CR rate), defined as the proportion of participants who achieve a CR; overall survival (OS), defined as the time from date of randomization to the date of death due to any cause; CR and complete remission with partial hematologic recovery (CRh) rate, defined as the proportion of participants who achieve a CR or CRh; and objective response rate (ORR), defined as the rate of CR, CR with incomplete hematologic recovery (CRi) (including CR with incomplete platelet recovery [CRp]), partial remission (PR), and morphologic leukemia-free state (MLFS).

About Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML) is a cancer of the blood and bone marrow marked by rapid disease progression and is the most common acute leukemia affecting adults with approximately 20,000 new cases in the U.S., and 43,000 cases in Europe each year3,4. The majority of patients with AML eventually relapse. Relapsed or refractory AML has a poor prognosis5. The five-year survival rate is approximately 27%3. For 6 to 10 percent of AML patients, the mutated IDH1 enzyme blocks normal blood stem cell differentiation, contributing to the genesis of acute leukemia6.

On August 2, 2021 Hummingbird Bioscience, an innovative clinical-stage biotech company focused on developing precision therapies against hard-to-drug targets, reported that the UK Medicines and Healthcare Products Regulatory Agency (MHRA) has approved the clinical trial application (CTA) to initiate first-in-human phase 1 trial of HMBD-001 in patients with advanced cancers (Press release, Hummingbird Bioscience, AUG 2, 2021, View Source [SID1234585560]).

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HMBD-001 is a novel antibody with a unique, differentiated mechanism of action that fully inhibits HER3 activation of the MAPK/PI3K tumor growth signaling pathway. By binding to the HER3 dimerization interface, HMBD-001 blocks the formation of all HER3 dimers, regardless of NRG1 ligand-binding or HER2/EGFR overexpression. Pre-clinical studies in multiple HER3 cancer models, including those with NRG1-fusions, have shown that these differentiated properties of HMBD-001 result in robust and sustained tumor growth inhibition.

The phase 1 trial will be a multi-center, open-label, dose-escalation and -expansion study, to be conducted in two parts. First, the safety and tolerability profile and recommended phase 2 dose of HMBD-001 will be determined in patients with advanced tumors known to overexpress HER3. This will be followed by further evaluation of safety and preliminary anti-tumor activity of HMBD-001 as a monotherapy in biomarker-selected patients, including those with NRG1 fusions, as well as in combination with other selected targeted therapies. Under a clinical development partnership agreement, Cancer Research UK will be funding and conducting the phase 1 trial in the UK.

"This marks an exciting next step in our journey to deliver a potentially transformative therapy for hard-to-treat cancers that express HER3 and are resistant to standard of care treatments," said Jerome Boyd-Kirkup, Chief Scientific Officer and co-founder of Hummingbird Bioscience. "Our platform technology was developed specifically to tackle biologically relevant yet extremely challenging targets for which research efforts to-date have yet to generate effective treatments. HMBD-001 is the first of our growing pipeline of rationally designed antibodies to obtain clinical trial approval, demonstrating the power of the platform to develop highly differentiated, precision therapies."

About HMBD-001
HMBD-001 is a anti-HER3 neutralizing antibody, with a novel mechanism of action that offers significant potential for clinical benefit. Previous attempts to block the HER3 receptor, a key player in the PI3K/MAPK signaling pathways that promotes cell division and tumor growth in cancer, have not proven to be effective. HER3 is activated by the binding of NRG1, which stabilizes a transient open conformation to allow it to form heterodimers with HER2/EGFR. In the presence of abundant HER2/EGFR, heterodimers can form without NRG1.

Pre-clinical studies have shown that HMBD-001 potently inhibits the formation of these heterodimers, blocking activation of the signalling pathway – and consequently, prevents tumor growth. Cancer Research UK has partnered with Hummingbird Bioscience to advance this novel drug candidate into clinical trials for the treatment of HER3-driven cancers.

On August 2, 2021 Bionomics Limited (ASX: BNO,OTCQB: BNOEF), (Bionomics) a global, clinical stage biopharmaceutical company, reported that it plans to conduct a registered initial public offering of American Depositary Shares (ADSs) in the United States and a concurrent listing of ADSs on Nasdaq (Press release, Bionomics, AUG 2, 2021, View Source [SID1234585559]). The number of ADSs and price of the proposed offering have not yet been determined. The proposed offering is expected to commence after the U.S. Securities and Exchange Commission completes its review process of a registration statement relating to the proposed offering (the Registration Statement) that the company intends to file, and subject to market and other conditions, including the effectiveness of the Registration Statement and shareholder approval under Australian Securities Exchange (ASX) Listing Rule 7.1. Each ADS would represent a certain number of fully paid ordinary shares in Bionomics.

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No final decision has been made in respect of the Nasdaq listing and there can be no assurance as to the occurrence, timing or completion of such a listing. Following any Nasdaq listing Bionomics shares would continue to trade on ASX.

This press release is being made pursuant to and in accordance with Rule 135 under the U.S. Securities Act of 1933, as amended. This press release does not constitute an offer to sell or the solicitation of an offer to buy securities, and shall not constitute an offer, solicitation or sale in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of that jurisdiction.