On December 9, 2019 Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of immune reset to more patients, reported that new results from its CD117-ADC patient preparation program were presented at the 61st Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, Magenta Therapeutics, DEC 9, 2019, View Source [SID1234552136]). These results, which were highlighted in an oral presentation at ASH (Free ASH Whitepaper) by John Tisdale, M.D., Director, Molecular and Clinical Hematology Section, National Institutes of Health, showed the first-ever successful transplant of gene-modified cells in non-human primates using a targeted, single-agent antibody-drug conjugate (ADC), without the use of chemotherapy or radiation.

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"Today’s conditioning regimens involve high doses of chemotherapy, often paired with radiation, to remove the disease-causing cells. As a result, patients undergoing gene therapy or stem cell transplant are all faced with a difficult choice: whether to endure severe toxicity and risk infertility and cancer for the chance for a cure. Magenta’s portfolio of targeted ADCs represents an extremely promising new option to prepare patients for gene therapy or transplant with no need for toxic chemotherapy or radiation," said Dr. Tisdale. "The results presented today show that a single dose of single agent CD117-ADC achieves the same level of depletion as four doses of busulfan chemotherapy to enable successful engraftment and persistence of stem cells modified with the β-globin gene, the gene that causes sickle cell disease and β-thalassemia when mutated. Importantly, the animals undergoing preparation with CD117-ADC showed none of the damaging toxicities associated with busulfan conditioning."

"Magenta is the only company with the people, platforms and a product engine committed to comprehensively transforming immune and blood system reset, which includes revolutionizing the toxic methods that are used to prepare patients for gene therapy and transplant today." said Jason Gardner, D.Phil., Chief Executive Officer and President, Magenta Therapeutics. "The gene therapy field has learned that higher levels of stem cell depletion, which meant higher doses of busulfan, were needed to ensure long-term engraftment of the gene-modified cells and persistence of gene therapy. Across all the modalities we have tested, we have seen that ADCs are most effective at achieving these high levels of stem cell depletion without chemotherapy to enable engraftment and long-term durability of the transplant. Today’s impressive results provide important validation of the ADC approach as well as the CD117 target for patient preparation and underscore Magenta’s leadership in the field of conditioning."

Results from the CD117-ADC Patient Preparation Program

Title: A Single Dose of CD117 Antibody Drug Conjugate Enables Autologous Gene-Modified Hematopoietic Stem Cell Transplant (Gene Therapy) in Nonhuman Primates (Abstract #610)
Presenter: John Tisdale, M.D., Director, Molecular and Clinical Hematology Section, National Institutes of Health, Bethesda, Md.

Magenta’s most advanced patient preparation program, CD117-ADC, targets CD117, a protein expressed on hematopoietic stem cells. CD117-ADC is designed to remove the genetically mutated cells in the bone marrow that cause certain genetic diseases, such as sickle cell disease, enabling curative stem cell transplant or gene therapy.

Results presented by Dr. Tisdale showed:

A single dose of a tool CD117-ADC fully depleted human hematopoietic stem cells in humanized mouse models.
A single dose of CD117-ADC selectively depleted hematopoietic stem cells in non-human primates, while sparing immune cells, which are important for recovery following transplant.
CD117-ADC was engineered to have a fast half-life to clear the body quickly and enabled transplant of the gene-modified cells within days of dosing in non-human primates.
A single dose of CD117-ADC in non-human primates enabled successful transplant and engraftment of hematopoietic stem cells modified with a lentiviral vector encoding the β-globin gene, the gene that causes sickle cell disease and β-thalassemia.
Vector copy number was stable beyond three months, the longest time point in the study, suggesting that the gene-modified cells persisted in the body. This was comparable to historical data with multiple doses of busulfan conditioning.
CD117-ADC was well tolerated in non-human primates with no evidence of the often severe side effects seen with busulfan conditioning, including veno-occlusive disease, weight loss, diarrhea, mucositis, vomiting, pulmonary fibrosis or seizures.
No ADC-related blood chemistry changes outside normal range were observed.
These proof-of-concept studies validate the use of CD117-ADC for targeted stem cell depletion prior to transplant and support its use as a new conditioning agent for gene therapy and stem cell transplant without toxic chemotherapy or radiation.

On December 9, 2019 Rafael Holdings, Inc., (NYSE: RFL), reported revenue of $1.2 million and a loss per share of $0.10 for the fiscal quarter ended October 31, 2019 (Press release, Rafael Pharmaceuticals, DEC 9, 2019, View Source [SID1234552153]).

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Recent Operational Highlights

Rafael Holdings became a New York Stock Exchange listed company on November 21, 2019.
Rafael Pharmaceuticals (Rafael Pharma) a clinical-stage pharmaceutical company in which the Company holds preferred equity and a warrant to increase ownership to 56% of the fully diluted equity interests, announced several significant expansions of ongoing clinical trials:
Its Phase 3 clinical trial (AVENGER 500) of CPI-613 (devimistat) for patients with metastatic pancreatic cancer had enrolled 100 patients at multiple sites in the United States, Europe and Israel. The trial was subsequently expanded to four sites in South Korea. The trial is expected to enroll up to 500 patients worldwide;
Expanded its Phase 3 clinical trial (ARMADA 2000) of CPI-613 (devimistat) in older patients with relapsed or refractory acute myeloid leukemia (AML) to four sites in South Korea. The trial is expected to enroll up to 500 patients worldwide;
Expanded its Phase 2 clinical trial of CPI-613 (devimistat) for patients with relapsed or refractory Burkitts lymphoma/leukemia to Massachusetts General Hospital. The initial trial sites were Memorial Sloan Kettering Cancer Center in New York City and City of Hope in Duarte, California;
José Octávio Costa Filho, M.D., joined Rafael Pharma as Co-Chief Medical Officer. He works alongside Timothy Pardee, M.D., Ph.D., who continues as Co-Chief Medical Officer.
On August 5th, 2019 Lipomedix Pharmaceuticals, in which the Company holds a majority interest, announced the addition of Miranda J. Toledano and Praveen Tyle, Ph.D., to its board of directors. The company also announced the formation of an executive committee of the board to enhance governance and support the company’s development. Ms. Toledano and Dr. Tyle will join Sanjeev Luther, chairman of the board, on the newly formed executive committee.
Remarks by Howard Jonas, Chairman and CEO of Rafael Holdings
"During the quarter, our key pharma holding, Rafael Pharma, continued enrolling patients in key clinical trials, including in its Phase 3 trials of CPI-613 (devimistat) for metastatic pancreatic cancer and AML, as well as its Phase 2 trial for Burkitt lymphoma.

"We’ve also put into place the foundation for our internal cancer metabolism drug development initiative, the Barer Institute, a wholly-owned early stage venture focused on developing a pipeline of therapeutic compounds, including compounds to regulate cancer metabolism. The venture is pursuing collaborative research agreements with leading scientists from top academic institutions."

"After the quarter closed, we were very pleased to begin our listing on the New York Stock Exchange with the enhanced visibility that the Big Board offers."

On December 9, 2019 Nouscom, an immuno-oncology company developing off-the-shelf and personalized cancer neoantigen vaccines, reported that the first patient has been dosed in a Phase 1 clinical trial evaluating its lead candidate, NOUS-209 (Press release, NousCom, DEC 9, 2019, View Source;first-patient-dosed-in-a-phase-1-trial-with-nous-209-an-off-the-shelf-neoantigen-cancer-vaccine-in-msi-high-solid-tumors-300971098.html [SID1234552169]). In this first-in-human trial NOUS-209, an off-the-shelf therapeutic vaccine based on shared tumor neoantigens, is being administered to patients with Microsatellite Instable High (MSI-H) gastric, colorectal and gastro-esophageal junction cancers (tumors characterized by a defective DNA mismatch repair system) in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab.

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NOUS-209-01 (NCT04041310) is a US multicenter Phase 1 open-label, dose-escalation study, assessing the safety and tolerability of the NOUS-209 vaccine in combination with pembrolizumab to determine the recommended Phase 2 dose. The study will evaluate vaccine-induced immune responses, as well as preliminary signs of anti-tumor activity in enrolled patients. Based on preclinical data, NOUS-209 is expected to induce potent and broad CD8+ and CD4+ responses in humans. Initial clinical data are expected in 2020.

Dr. Michael J. Overman, Principal Investigator of the trial and Professor in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, explained: "We have seen tremendous change in our approach to MSI-high metastatic solid tumors over the last few years, but the majority of patients do not respond to single agent immunotherapy. Hence, further optimization of our approach for MSI-high cancers is needed. Agents like NOUS-209 that stimulate the patient’s immune response and direct it specifically against the cancer cells reflect a tremendous scientific evolution in our understanding of these cancers and represents an extremely promising approach for these cancers."

Dr. Elisa Scarselli, Chief Scientific Officer and Co-Founder of Nouscom, said "This first-in-human trial evaluating NOUS-209 in combination with pembrolizumab is a significant milestone for Nouscom. NOUS-209 leverages a core strength of the company’s platform, namely the capacity of its proprietary viral vectors to encode a large number of neoantigens. NOUS-209 was named because it comprises 209 shared Frame Shift Peptides (FSPs) selected using a proprietary algorithm. This feature of NOUS-209 enables it to be developed as an off-the-shelf neoantigen vaccine that does not require patient screening prior to treatment. Furthermore, it is designed to have broad coverage across the MSI patient population by targeting multiple neoantigens in each patient, and as such is expected to address tumor heterogeneity. We look forward to the initial clinical data in 2020."

On December 9, 2019 Aptose Biosciences Inc. (NASDAQ: APTO, TSX: APS) reported that highlights from a corporate event and clinical update held at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Orlando, FL (Press release, Aptose Biosciences, DEC 9, 2019, View Source [SID1234552103]). The event was hosted by the Aptose management team and included Stephen B. Howell, MD, Acting Chief Medical Officer, Distinguished Professor of Medicine, Moores Cancer Center, University of California, San Diego (UCSD); with analysis by Rafael Bejar, MD, PhD, Aptose’s incoming Senior Vice President and Chief Medical Officer and currently the Director, MDS Center of Excellence, Moores Cancer Center, UCSD; and participation remotely by Brian J. Druker, MD, Chair of the Aptose Scientific Advisory Board, Professor of Medicine, Division of Hematology/Medical Oncology, Director, Knight Cancer Institute, Oregon Health & Science University.

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The slides are available and the recording of the presentation will be archived on Aptose’s website here shortly after the conclusion of the event.

As the first clinical data from CG-806 in patients with chronic lymphocytic leukemia (CLL) have begun to emerge, Drs. Howell, Bejar, and Druker highlighted the consistency between the drug’s robust preclinical profile and the early clinical observations on safety, tolerability, pharmacokinetics, and activity. William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose also provided a corporate update on the clinical activities of CG-806, Aptose’s highly potent pan-FLT3/pan-BTK inhibitor.

CG-806, an oral, first-in-class mutation-agnostic FLT3/BTK kinase inhibitor, is in a Phase 1 trial in patients with B cell malignancies, including CLL and non-Hodgkin lymphomas (NHL), who have failed or are intolerant to standard therapies. The first two dose levels, which required only one patient at each level, are complete. The first two patients, both of whom were CLL patients that had previously failed a host of other agents, completed multiple dose cycles at 150 mg BID and 300 mg BID, respectively. Screening is ongoing for the third dose level, which is planned to enroll three patients.

Key findings from dose levels 1 and 2 of CG-806 in heavily pretreated R/R CLL patients:

CG-806’s safety profile remains clean; no unexpected toxicities have been observed to date
Notably, no myelosuppression, no drug-related adverse events or dose-limiting toxicity

Early evidence of clinical response has already been observed in a R/R CLL patient at dose level 2
Robust increase in peripheral blood lymphocytes (lymphocytosis)

Evidence of Bruton’s tyrosine kinase (BTK) target engagement
Lymphocytosis, which is known as an indicator of BTK inhibition
Inhibition of Phospho-BTK, Phospho-SYK and Phospho-ERK have been observed with a plasma inhibitory assay (PIA) using plasma from the CLL patient on dose level 2

Meaningful oral absorption and predictable pharmacokinetic (PK) profile

Exposures are likely therapeutic for acute myeloid leukemia (AML) patients
A separate trial with CG-806 in relapsed/refractory AML patients is in the planning stage
APTO-253, the only clinical stage agent that directly targets the MYC oncogene, is demonstrating safety and MYC target engagement in a Phase 1b clinical trial for the treatment of patients with relapsed or refractory AML or high-risk myelodysplastic syndrome (MDS).

Key highlights:

Aptose has completed dosing of the first three cohorts (up to a dose of 66 mg/m2) of the Phase 1b trial with MYC inhibitor APTO-253 in patients with AML and MDS.

In the patients on the first three dose cohorts, no drug-related adverse events have been observed, including no myelosuppression, and dosing is planned to continue to ascend until a maximum tolerated dose is reached. The next expected dosing level is 100 mg/m2.

MYC biomarker data from AML and MDS patients in the first three cohorts continue to demonstrate reductions of MYC gene expression in their peripheral blood cells. The dose escalation portion of the study is designed to transition, as appropriate, to single-agent expansion cohorts in AML and MDS, followed by combination studies.
The Company continues to escalate dosing with both assets, as all current dose cohorts to date have exhibited favorable safety profiles and evidence of target engagement.

On December 9, 2019 Immunomedics, Inc. (NASDAQ: IMMU) ("Immunomedics" or the "Company"), a leading biopharmaceutical company in the area of antibody-drug conjugates (ADC), reported it has commenced an underwritten public offering of $250,000,000 of shares of its common stock (Press release, Immunomedics, DEC 9, 2019, View Source [SID1234552120]). In addition, Immunomedics expects to grant the underwriters a 30-day option to purchase up to an aggregate of an additional $37,500,000 of shares of common stock sold in connection with the offering at the public offering price.

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Immunomedics intends to use the net proceeds from this offering primarily to accelerate commercial launch readiness, pending FDA approval, of sacituzumab govitecan in the United States in metastatic triple-negative breast cancer, continue to expand the clinical development programs for sacituzumab govitecan, invest in the broader clinical development of the platform (including IMMU-130 and IMMU-140), continued scale-up of manufacturing and manufacturing process improvements, as well as for working capital and general corporate purposes.

Goldman Sachs & Co. LLC, BofA Securities, Cowen and Company, LLC and Jefferies LLC are acting as joint book-running managers for the offering. The offering is subject to market conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

The shares of common stock are being offered pursuant to a shelf registration statement on Form S-3 that Immunomedics filed with the Securities and Exchange Commission on June 11, 2018 and that became effective upon filing. A preliminary prospectus supplement and the accompanying prospectus relating to this offering are being filed with the SEC and will be available at the SEC’s website located at www.sec.gov. When available, copies of the preliminary prospectus supplement and the accompanying prospectus relating to this offering may also be obtained from Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, or by telephone at (866) 471-2526, or by email at [email protected]; BofA Securities, NC1-004-03-43, 200 North College Street, 3rd floor, Charlotte, NC 28255-0001, Attn: Prospectus Department, or by email at [email protected]; 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; or Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, or by telephone at 877-547-6340 or by email at [email protected].