On December 9, 2019 Jasper Therapeutics, Inc., a new biotechnology company focused on enabling safer conditioning and therapeutic agents that expand the application of curative hematopoietic stem cell transplants and gene therapies, reported that initial results from an ongoing Phase 1 dose-escalation study of its lead product candidate, JSP191 (formerly AMG191), will be presented today in an oral session at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (Press release, Jasper Therapeutics, DEC 9, 2019, View Source [SID1234552156]).

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JSP191, a humanized antibody targeting CD117, is designed to replace or reduce the toxicity of chemotherapy and radiation therapy as a conditioning regimen to prepare patients for hematopoietic cell transplantation. The Phase 1 clinical trial is evaluating JSP191 as a conditioning agent to enable stem cell transplantation in patients with severe combined immunodeficiency (SCID) who received a prior stem cell transplant that had poor outcomes.

"Life-threatening disorders such as SCID, and other conditions including autoimmune diseases and hematologic cancers, can be cured by hematopoietic cell transplantation, and those with certain genetic diseases can be cured with stem cell-directed gene therapies. However, the number of patients who can benefit from these approaches is limited because of the severe toxicity of the chemotherapy used for pre-transplant conditioning that is needed to allow room in the bone marrow for the stem cells to engraft," said Judith Shizuru, M.D., Ph.D., co-founder and member of the Board of Directors of Jasper Therapeutics. "We are encouraged by the initial Phase 1 study results of JSP191 in these fragile patients with SCID and plan to expand clinical development of this antibody beyond patients with SCID. We expect to initiate clinical trials of JSP191 in 2020 to evaluate it as a conditioning agent in patients undergoing hematopoietic cell therapy for acute myeloid leukemia, myelodysplastic syndrome and Fanconi anemia, and IND-enabling studies for sickle cell disease and autoimmune indications."

Details of the oral presentation follow:

Abstract Title: Non-Genotoxic Anti-CD117 Antibody Conditioning Results in Successful Hematopoietic Stem Cell Engraftment in Patients with Severe Combined Immunodeficiency (abstract #800)
Session Name: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Innovative Approaches in Allogeneic Transplantation for Pediatric or Nonmalignant Disorders
Presenter: Rajni Agarwal, M.D., Associate Professor of Pediatrics and Stem Cell Transplantation, the Stanford University School of Medicine
Time: 3:00 p.m. ET
Location: W311EFGH, Level 3, Orange County Convention Center

About Stem Cell Transplantation

Blood-forming, or hematopoietic, stem cells are cells that reside in the bone marrow and are responsible for the generation and maintenance of all blood and immune cells. These stem cells can harbor inherited or acquired abnormalities that lead to a variety of disease states, including immune deficiencies, blood disorders or hematologic cancers. Successful transplantation of hematopoietic stem cells is the only cure for most of these life-threatening conditions. Replacement of the defective or malignant hematopoietic stem cells in the patient’s bone marrow is currently achieved by subjecting patients to toxic treatment with radiation and/or chemotherapy that cause DNA damage and lead to short- and long-term toxicities, including immune suppression and prolonged hospitalization. As a result, many patients who could benefit from a stem cell transplant are not eligible. New approaches that are effective but have minimal to no toxicity are urgently needed so more patients who could benefit from a curative stem cell transplant could receive the procedure.

Safer and more effective hematopoietic cell transplantation regimens could overcome these limitations and enable the broader application of hematopoietic cell transplants in the cure of many disorders. These disorders include hematologic cancers (e.g., myelodysplastic syndrome [MDS] and acute myeloid leukemia [AML]), autoimmune diseases (e.g., lupus, rheumatoid arthritis, multiple sclerosis and Type 1 diabetes), and genetic diseases that could be cured with genetically-corrected autologous stem cells (e.g., severe combined immunodeficiency syndrome [SCID], sickle cell disease, beta thalassemia, Fanconi anemia and other monogenic diseases).

About JSP191

JSP191 (formerly AMG191) is a first-in-class humanized monoclonal antibody in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow. JSP191 binds to human CD117, a receptor for stem cell factor (SCF) that is expressed on the surface of hematopoietic stem and progenitor cells. The interaction of SCF and CD117 is required for stem cells to survive. JSP191 blocks SCF from binding to CD117 and disrupts critical survival signals, causing the stem cells to undergo cell death and creating an empty space in the bone marrow for donor or gene-corrected transplanted cells to engraft.

Preclinical studies have shown that JSP191 as a single agent safely depletes normal and diseased hematopoietic stem cells, including in an animal model of MDS. This creates the space needed for transplanted normal donor or gene-corrected hematopoietic stem cells to successfully engraft in the host bone marrow. To date, JSP191 has been evaluated in more than 80 healthy volunteers and patients. It is currently being evaluated as a sole conditioning agent in a Phase 1 dose-escalation trial to achieve donor stem cell engraftment in patients undergoing hematopoietic cell transplant for SCID, which is curable only by this type of treatment. For more information about the design of the clinical trial, visit www.clinicaltrials.gov (NCT02963064). Clinical development of JSP191 will be expanded to also study patients with AML or MDS who are receiving hematopoietic cell transplant.

On December 9, 2019 Portola Pharmaceuticals, Inc. (Nasdaq: PTLA) reported new interim results from the Company’s ongoing Phase 2a study of cerdulatinib, an investigational, oral SYK/JAK inhibitor, in patients with relapsed/refractory follicular lymphoma (FL) receiving cerdulatinib alone or in combination with rituximab (Press release, Portola Pharmaceuticals, DEC 9, 2019, View Source [SID1234552155]). The data will be presented today during a poster session at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando (December 7-10).

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Data included safety and efficacy findings as of November 2019 for 42 patients who received single agent cerdulatinib at 30 mg twice daily (with the exception of two patients who initiated treatment at 35 mg) and 21 patients who received cerdulatinib at 30 mg twice daily in combination with a standard dosing regimen of rituximab. The number of prior treatment regimens including anti-CD20 antibody, bendamustine and other alkylating agents, and PI3K inhibitors ranged from one to 10, with a median of three.

Among the 42 patients in the cerdulatinib-only cohort, the overall response rate (ORR) was 48%; 7 patients (17%) achieved a complete response (CR), 13 patients (31%) achieved a partial response (PR) and 10 patients (24%) achieved stable disease (SD). To date, 16 of the 42 patients (38%) in the cerdulatinib-only cohort have been on study drug for at least 10 months.

Among the 21 patients evaluated for efficacy in the cerdulatinib and rituximab combination cohort, the ORR was 76%; 5 patients (24%) achieved a CR, 11 patients (52%) achieved a PR and 5 patients (24%) achieved SD. Of the 11 patients in this combination cohort who have been on one to three prior therapies, the ORR was 91% with a complete response rate of 36%.

Cerdulatinib was generally well-tolerated and the safety profile appeared similar in both the cerdulatinib-only and rituximab combination cohorts. The most common adverse events (AEs) occurring in ≥5% of all evaluable study patients were lipase increase (27%), neutropenia (18%), diarrhea (13%) and amylase increase (9%). The most common AEs in the combination cohort included lipase increase (32%), neutropenia (22%) and diarrhea (14%). The lipase and amylase changes were generally asymptomatic and not associated with pancreatitis. Additionally, there was no emergence of late-stage colitis, cardiac or liver abnormalities, or other evidence of cumulative toxicity.

"These interim results demonstrate that cerdulatinib provides sustained clinical activity and good tolerability in patients with relapsed/refractory follicular lymphoma, and that the tumor response to both monotherapy and combination therapy appears to deepen over time," said Paul Hamlin, M.D., medical director for the David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center. "It is encouraging that the combination of cerdulatinib and rituximab achieved an improved objective response rate (ORR) in heavily pre-treated patients compared to prior interim data, indicating it may have potential as a second-line therapy. We look forward to continuing the study and exploring an optimized dose of cerdulatinib and rituximab in this setting."

"Cerdulatinib is the most advanced SYK/JAK inhibitor of its kind in development for oncology, and has demonstrated its potential to inhibit two key survival pathways in Non-Hodgkin Lymphoma," said Jeff Myers, Portola’s interim chief medical officer. "The data presented at ASH (Free ASH Whitepaper) continues to demonstrate its safety and efficacy across a range of malignancies. Specific to follicular lymphoma, we are excited that the updated data showed an improved ORR with greater anti-tumor activity in combination with rituximab, and we look forward to exploring lower doses for potential use in the second-line setting."

ASH Poster Session Details – Monday, December 9, 2019, at 6:00 p.m. EST

Title:

Rapid and Durable Responses with the SYK/JAK Inhibitor Cerdulatinib in a Phase 2 Study in Relapsed/Refractory Follicular Lymphoma—Alone or in Combination with Rituximab

Session:

623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Poster III

Presenter:

Paul A. Hamlin, M.D., David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

Location:

Hall B, Level 2 (Orange County Convention Center)

About the Phase 2a Study
The Phase 2a, open-label study was designed to assess the safety and efficacy of cerdulatinib in patients with relapsed/refractory FL (alone or in combination with rituximab), small lymphocytic lymphoma (SLL) and specific subtypes of T-cell Non-Hodgkin Lymphoma, including PTCL, AITL and CTCL.

Tumor response in the two cohorts evaluating patients with relapsed/refractory FL was assessed by Lugano classification, with treatment continued until disease progression or unacceptable toxicity. Tumor response assessments were performed at the end of cycle two and every three cycles thereafter.

About Cerdulatinib
Cerdulatinib is an investigational oral, dual spleen tyrosine kinase (SYK) and janus kinase (JAK) inhibitor that uniquely inhibits two key cell signaling pathways implicated in certain hematologic malignancies and autoimmune diseases. There is a strong rationale for inhibiting both SYK (B-cell receptor pathway) and JAK (cytokine receptors) in B-cell malignancies where both targets have been shown to promote cancer cell growth and survival.

The U.S. Food and Drug Administration granted cerdulatinib Orphan Drug Designation for the treatment of PTCL in September 2018.

On December 9, 2019 SCYNEXIS, Inc. (NASDAQ : SCYX) reported that it has commenced an underwritten public offering of shares of its common stock and warrants (Press release, Scynexis, DEC 9, 2019, View Source [SID1234552154]). In addition, SCYNEXIS expects to grant the underwriter a 30-day option to purchase up to an additional 15% of the shares of common stock and warrants being offered on the same terms and conditions. All of the shares of common stock and warrants in the offering will be sold by SCYNEXIS. 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.

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H.C. Wainwright & Co. is acting as sole book-running manager for the offering.

A shelf registration statement relating to the shares being sold in this offering was filed with the U.S. Securities and Exchange Commission on August 31, 2018, and was declared effective on September 14, 2018. The offering will be made only by means of a prospectus supplement and accompanying prospectus. A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available for free on the SEC’s website located at View Source When available, electronic copies of the preliminary prospectus supplement and accompanying prospectus relating to the proposed public offering may be obtained by contacting H.C. Wainwright & Co., LLC, 430 Park Avenue, 3rd Floor, New York, NY 10022, or by telephone at (646) 975-6996, or by email to [email protected]. This press release shall not constitute an offer to sell or the 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 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 Gracell Biotechnologies Co., Ltd ("Gracell"), a clinical-stage immune cell therapy company, reported the progressive clinical outcomes for leading product candidates FasTCAR-19, Dual CAR-19-22, and Dual CAR-BCMA-19 at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando, Florida, held from December 7-10 (Press release, Gracell Biotechnologies, DEC 9, 2019, View Source [SID1234552152]). Multiple pilot studies intend to evaluate the safety and efficacy of Gracell’s first-in-class FasTCAR-19 (GC007F), Dual CAR-19-22 (GC012F) and Dual CAR-BCMA-19 (GC022F) cell therapy.

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FasTCAR-19
FasTCAR-19 or GC007F uses Gracell’s patented FasTCARTM solution, which genetically modifies a patient’s T-cells to express CD19-specific chimeric antigen receptor (CAR) for the treatment of B-cell acute lymphoblastic leukemia (B-ALL).

Utilizing the unique bioprocessing, FasTCAR-19 cells can be produced overnight through viral transfection in use of Gracell’s proprietary fully-closed manufacturing system (from apheresis to filling). These cells are considered far more potent and durable in comparison to current market alternatives. To date, all 37 patient samples have been successfully manufactured. The process has been proven efficient, stable and duplicable, with a median 36.8% (range 13.1%-70.3%) transfection success and a median copies of 0.95 (range 0.2-4.21).

As of November, this investigational study enrolled 37 adult and adolescent patients aged from 14 to 70 years, who suffered from r/r B-ALL and had failed to respond to multiple prior lines of therapy, from eight clinical centers. All patients received a single infusion of FasTCAR-19 at one of the three-dose level (low: 0.6*10^5/kg; mid: 1.0*10^5/kg, and high: 1.6*10^5/kg), followed by prior conditioning regimen of fludarabine-cyclophosphamide (FC).

The treatment efficacy was assessed in 35 patients over 28 days of follow-up, of which:

34 (97.1%) achieved a complete remission with or without complete blood count recovery (CR/CRi) on Day 28;
32 (91.4%) achieved minimum residual disease negative complete remission (MRD-CR);
During the over six month-durable remission period, FasTCAR-19 demonstrated a good level of persistence in line with previous clinical trials. In terms of safety, all 37 patients tolerated the single infusion of FasTCAR-19 at different dose levels, with no dose-limiting toxicities observed. The most common safety concerns were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) where mild to moderate side effects were observed. Across 30 patients in the low to mid doses group, only 5 (16.7%) manageable Grade 3 CRS and 5 (16.7%) manageable Grade 3 ICANS were reported; while the remaining 23 (76.7%) had Grade 1-2 CRS. The low to mid doses group will likely be selected for extensive study in future clinical trials.

Beyond single-antigen CAR, Dual CAR-T cells can deliver promising clinical outcomes
Single-antigen CAR-T cells have demonstrated considerable efficacy; however, antigen loss and high relapse rate have been observed in a significant number of patients. To combat this, treatments containing two separate CARs and dual transduction (GC022 targeting CD19 and CD22, GC012 targeting BCMA and CD19) were developed. Following positive results from in vitro and in vivo studies, human clinical trials have commenced testing the safety and feasibility of Dual CAR-19-22 and Dual CAR-BCMA-19 to treat B-ALL and MM, respectively.

Dual CAR-19-22
Dual CAR-19-22 or GC022 has achieved a manufacturing success rate of 20/20, without any patient loss due to manufacturing failure. Enrolled patients aged from 4-45 years old who has B-ALL, received a single infusion of Dual CAR-19-22 at one of the three-dose levels (low: 0.5*10^6/kg; mid: 2.0*10^6/kg, and high: 3.0*10^6/kg), under conventional bioprocessing. The study demonstrated a very good safety profile and high efficacy at mid to high doses.

The treatment efficacy was assessed in 20 patients with a 28-day follow-up, of which:

4 in the low dose group reported no response;
15 of 16 (93.8%) in mid and high dose groups achieved complete remission, and confirmed with MRD-CR, with or without complete blood count recovery (CR/CRi) on Day 28.
Dual CAR-19-22 proved effective on patients who had previously been treated with CD19 CAR-T cells and/or received allogeneic hematopoietic stem cell transplantation (allo-HSCT) for r/r B-ALL but failed to benefit from prior treatments. Among these five patients, four (80%) patients achieved MRD-CR with a 28-day follow-up. Surpassing the 3-month durable remission period, fifteen patients still retain ongoing response.

Furthermore, Dual CAR-19-22 demonstrated an excellent safety profile, with 6/20 (30%) patients indicating no CRS, 14/20 (70%) reporting Grade 1 CRS. No ICANS events were reported.

Dual CAR-BCMA-19
Dual CAR-BCMA-19 or GC012 has been demonstrated effective in eliminating multiple myeloma (MM) tumor cells both in vitro and in vivo. The first-in-human study showed a good safety profile and effectiveness. Beyond, FasTCARTM has successfully been applied to Dual CAR-BCMA-19, expected to enhance proliferation, potency, and migration in the human body.

"We are delighted to see that patients with relapsed/refractory B-ALL continue to gain substantial clinical benefit from FasTCAR-19. Furthermore, Dual CAR-19-22 with conventional bioprocess can generate promising clinical data. This marks our confidence to utilize FasTCAR technology to both Dual CAR programs for various indications," said Dr. William Cao, CEO of Gracell. "The results from our latest clinical trials reveal the immense potential of FasTCAR technology, and we are eager to see Gracell’s highly efficacious, yet affordable therapies benefit more patients in China and worldwide."

About B-ALL
Acute lymphoblastic leukemia (ALL), although rare, is one of the most common forms of cancer in children between the ages of two and five and adults over the age of 501. In 2015, ALL affected around 837,000 people globally and resulted in 110,000 deaths worldwide2. It is also the most common cause of cancer and death from cancer among children. ALL is typically treated initially with chemotherapy aimed at bringing about remission. This is then followed by further chemotherapy carried out over several years.

About MM
Multiple myeloma (MM) is a cancer that forms in a type of white blood cell known as a plasma cell. MM cells are abnormal plasma cells (a type of white blood cell) that build up in the bone marrow and form tumors in many bones of the body. Healthy plasma cells make antibodies to help the body fight infection and disease. As the number of MM cells increases, more antibodies are produced. This can cause the blood to thicken and keep the bone marrow from making enough healthy blood cells. MM cells can also damage and weaken the bone. In 2018, MM affected around 160,000 people globally and resulted in 106,000 deaths worldwide3. Different types of treatments are available for patients with plasma cell neoplasms. Chemotherapy and targeted therapy are typical treatments; while stem cell transplant, biologic therapy, and radiation therapy, even surgery are also adopted.