On December 9, 2019 Advaite Inc., a Chicago, IL based oncology-focused biotech company developing novel therapeutics and diagnostics to help patients suffering from debilitating diseases, has reported that it has entered into an exclusive license option agreement with the George Washington University with respect to the intellectual property of a novel AMES Negative HDAC6 inhibitor (Press release, Advaite, DEC 9, 2019, View Source [SID1234552171]). Histone Deacetylases modulate a multitude of cellular processes and are part of the regulation of cellular pathways involved in anti-tumor immunologic responses. Selective inhibition of HDAC6 slows tumor growth in various cancer models. Under terms of this agreement, Advaite has the option to exclusively license intellectual property covering methods of use and pharmaceutical compositions.

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"We look forward to future success by advancing the development of this novel HDAC6 inhibitor to treat a multitude of cancers, to ease suffering and extend life. This epigenetic regulator can have a potentially enormous therapeutic effect on patients who continue to suffer from debilitating cancer, as there is a great need for therapies that deliver an effective response, and specifically ones which are not limited by their toxicity profile. George Washington University’s expertise with HDACs provide a perfect relationship for Advaite to advance truly viable, state of the art, impactful technology," said Karthik Musunuri, CEO & Co-Founder of Advaite.

"The quest for newer and more effective ways of treating cancer has now led to an extensive focus on the involvement of the immune system and its capacity to recognize and engage tumor cells. Recent findings from several research groups have demonstrated that ultra-selective HDAC6 inhibitors have the unique capacity of remodeling of the cellular composition of tumors, favoring the recognition and killing of cancer cells by the immune system. Our novel HDAC6 inhibitor has shown to have reduced toxic effects, thus clearly differentiating from previous HDAC inhibitors used in the clinic," said Alejandro Villagra, Ph.D., Member of the Immunology and Microbial Oncology Research Program at the GW Cancer Center and Assistant Professor of Biochemistry and Molecular Medicine at the GW School of Medicine and Health Sciences.

On December 9, 2019 Astex Pharmaceuticals, Inc., a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., based in Tokyo, Japan, reported that topline data from the ASCERTAIN phase 3 trial of the orally administered fixed dose combination of cedazuridine and decitabine (ASTX727) in adults with intermediate and high-risk myelodysplastic syndromes (MDS) including chronic myelomonocytic leukemia (CMML) (Press release, Astex Pharmaceuticals, DEC 9, 2019, View Source [SID1234552105]). The data were featured in an oral presentation given today at the American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting in Orlando, Florida by Dr Guillermo Garcia-Manero, MD, Professor and Chief of Section of Myelodysplastic Syndromes, Department of Leukemia at The University of Texas MD Anderson Cancer Center, Houston, Texas, on behalf of the study investigators.

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The study was designed as a randomized crossover study comparing oral ASTX727 (100mg cedazuridine and 35mg decitabine fixed dose combination tablet given once daily for 5 days on a 28-day cycle) to IV decitabine (20mg/m2 administered as a daily 1-hour IV infusion for 5 days on a 28 day cycle) in the first 2 cycles with patients continuing to receive oral ASTX727 from Cycle 3 onwards. The data presented demonstrated that the ASCERTAIN study met the primary endpoint of total 5-Day decitabine Area-Under-The-Curve (AUC) equivalence of oral ASTX727 and IV decitabine. The oral/IV decitabine 5-day AUC was 98.9% with a 90% Confidence Interval between 92.7% and 105.6%. Safety findings from the study were consistent with those anticipated with IV decitabine, with no significant differences in the incidence of most common adverse events between ASTX727 and IV decitabine in the first 2 randomized cycles. The most common adverse events (AEs) of any grade >20% regardless of causality in patients in the first 2 randomized cycles who received ASTX727 were thrombocytopenia (43.8%); neutropenia (35.4%); anemia (36.9%); and fatigue (23.8%). Preliminary clinical activity as of the data cutoff was also consistent with published data for IV decitabine. In evaluable patients, the Complete Response (CR) rate was 12%, with an overall response rate, including hematological improvement, of 64%.

"The ASCERTAIN phase 3 study data confirms the hypothesis that by inhibiting cytidine deaminase in the gut, systemic therapeutic concentrations of decitabine can be delivered orally to achieve decitabine systemic exposure equivalent to IV dosing," said Dr Garcia-Manero. "The data support that ASTX727 could become an oral hypomethylating agent alternative to IV decitabine."

"Based on the data from the ASTX727 clinical program, including the ASCERTAIN phase 3 study, Astex is moving ahead with plans to file a New Drug Application (NDA) with the US Food & Drug Administration (FDA)," said Dr Mohammad Azab, MD, President & Chief Medical Officer of Astex Pharmaceuticals, Inc. "Subject to regulatory review and approval, ASTX727 may offer a new option for patients with MDS and CMML that saves them the burden of 5-day IV infusions every month during their treatment period. We are extremely grateful to all the patients, caregivers, partner research and manufacturing organizations, as well as the healthcare professionals who contributed to the clinical development program of ASTX727."

ASTX727 is an investigational compound and is not currently approved in any country.

Astex’s parent company, Otsuka Pharmaceutical Co., Ltd., and Taiho Pharmaceutical Co., Ltd. previously announced that, subject to regulatory approvals, commercialization of ASTX727 in the US and Canada will be conducted by Taiho Oncology, Inc. and Taiho Pharma Canada, Inc. respectively. Astex, Otsuka and Taiho are all members of the Otsuka group of companies.

The presentation can be downloaded from the Astex website at View Source

About Cedazuridine and Decitabine Fixed-Dose Combination (ASTX727)

ASTX727 is a novel, orally administered fixed dose combination of cedazuridine, an inhibitor of cytidine deaminase,1 with the anti-cancer DNA hypomethylating agent, decitabine.2 By inhibiting cytidine deaminase in the gut and the liver, ASTX727 is designed to allow for oral delivery of the approved DNA hypomethylating agent, decitabine, at exposures which emulate exposures achieved with the approved intravenous form of decitabine administered over 5 days.3

ASTX727 has been evaluated in a phase 1/2 pharmacokinetics-guided dose escalation and dose confirmation study in patients with MDS and CMML (see View Source NCT02103478) and a pivotal phase 3 study (ASCERTAIN) (see View Source NCT03306264) conducted at investigator sites in the US and Canada and designed to confirm the results from the phase 1/2 study. The phase 3 study is now being extended to include patients with acute myeloid leukemia (AML) unsuitable to receive intensive induction chemotherapy.

In September 2019 Astex announced that ASTX727 had received orphan drug designation for the treatment of MDS and CMML from the US FDA.

The concept of using cedazuridine to block the action of cytidine deaminase is also being evaluated in a low dose formulation of cedazuridine and decitabine for the treatment of lower risk MDS (see View Source NCT03502668).

About Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)

Myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell disorders characterized by dysplastic changes in myeloid, erythroid, and megakaryocytic progenitor cells, and associated with cytopenias affecting one or more of the three lineages. US incidence of MDS is estimated to be 10,000 cases per year, although the condition is thought to be under-diagnosed.4,5 The prevalence has been estimated to be from 60,000 to 170,000 in the US.6 MDS may evolve into acute myeloid leukemia (AML) in one-third of patients.7 The prognosis for MDS patients is poor; patients die from complications associated with cytopenias (infections and bleeding) or from transformation to AML. CMML is a clonal hematopoietic malignancy characterized by accumulation of abnormal monocytes in the bone marrow and in blood. The incidence of CMML in the US is approximately 1,100 new cases per year,8 and CMML may transform into AML in 15% to 30% of patients.9 The hypomethylating agents decitabine and azacitidine are effective treatment modalities for hematologic cancers and are FDA-approved for the treatment of higher risk MDS and CMML. These agents are administered by IV infusion, or by large-volume subcutaneous injections.

On December 9, 2019 Molecular Templates, Inc., (Nasdaq: MTEM) a clinical-stage biopharmaceutical company focused on the discovery and development of the Company’s proprietary engineered toxin bodies (ETBs), which are differentiated, targeted, biologic therapeutics, reported the presentations of two posters on its pipeline programs at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2019 Annual Meeting, taking place December 7-10, 2019 in Orlando, Florida (Press release, Molecular Templates, DEC 9, 2019, View Source [SID1234552122]). One of these posters includes final results from the Phase 1/1b study of MT-3724, in subjects with relapsed/refractory (R/R) diffuse large b-cell lymphoma (DLBCL).

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Poster Title: Monotherapy Activity with the First CD20-Targeted Immunotoxin, MT-3724, in Subjects with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)
Abstract Number: 4098
Presenter: Daniel Persky MD, University of Arizona Cancer Center
Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials
Time: Monday, December 9, 2019: 6:00 PM-8:00 PM ET
This is a multi-center, open-label, dose-escalation and dose-expansion study of MT-3724, the first CD20 targeted immunotoxin to enter clinical trials. The Phase 1/1b portion of the study consists of two Parts in which a total of 27 subjects with NHL were enrolled; 21 in Part 1 (dose escalation) and 6 in Part 2 (expansion cohort), both closed to enrollment. In total, 25 subjects were evaluable for efficacy, including 19 subjects with DLBCL or mixed DLBCL/follicular lymphoma.

MT-3724 competes for binding with rituximab (RTX) and other commercially available CD20-targeting monoclonal antibodies. Consistent with this competition, initial efficacy data from the dose expansion study revealed only one of eight subjects with measurable serum rituximab (RTX) levels had any suggestion of benefit (a mixed response) to MT-3724.

The expansion cohort mandated negative serum RTX levels for enrolled subjects. Of the 13 serum rituximab negative (RTX-neg) DLBCL or mixed DLBCL/FL subjects, 5 responded (38% objective response rate) across the range of 5 to 100 μg/kg doses. Of the 5 responses, 2 were complete responses (CRs) and 3 were partial responses (PRs). Three patients had stable disease (including 2 patients with 49% and 47% tumor reductions) and 5 patients had progressive disease.

Of the 5 serum RTX-neg subjects with DLBCL who received MT-3724 at 50 μg/kg, the maximum tolerated dose (MTD), 3 responded (2 CR, 1 PRs). Of all 25 subjects evaluable for efficacy, 13 developed anti-drug antibodies (ADAs) or neutralizing antibodies (NAbs); the development of ADAs or NAbs did not preclude benefit of MT-3724, consistent with what has been seen with other immunotoxins. Safety events were mostly mild to moderate, and dose limiting toxicities (DLTs) were indicative of innate immune response, including grade 2 capillary leak syndrome and grades 1-3 arthralgias and myalgias. No life-threatening toxicities were attributed to MT-3724.

A Phase 2 dose-expansion portion of the study (Part 3) has been initiated to investigate MT-3724 in serum RTX-neg subjects with DLBCL. This is actively enrolling globally. A tolerable dose and schedule for the Phase 2 has been identified: 50 μg/kg/dose with a cap of 6000 μg/dose infused over 1 hour on Days 1, 3, 5, 8, 10 and 12 of a 21-day cycle. (ClinicalTrials.gov Identifier: NCT02361346).

Poster Title: A Phase 2a Open-Label Study to Investigate Safety and Tolerability (including the MTD), Efficacy, Pharmacokinetics, Pharmacodynamics and Immunogenicity of MT-3724 in Combination with Lenalidomide in Subjects with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Presenter: Jason Tache, DO, BRCR Medical Center
Abstract #: 1597
Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials
Time and Location: Saturday, December 7, 2019: 5:30 PM-7:30 PM ET
MT-3724. a novel Engineered Toxin Body (ETB), possesses specific and high affinity for CD20+ cells and causes apoptosis via a unique mechanism of action, forced internalization of the ETB bound to the receptor, retrograde transport through the cytosol, and enzymatic deactivation of ribosomal function. Therefore, combining MT‑3724 with standard cytotoxic chemotherapy and/or immune modulatory agents may provide enhanced benefit in NHL treatment algorithms. This is a multi-center, open-label, multiple-dose Phase 2a study designed to evaluate MT-3724 in combination with lenalidomide in adult subjects with histologically confirmed, relapsed or refractory NHL. The primary objective is to determine safety and tolerability, including the MTD, of MT-3724 + lenalidomide. Secondary objectives include pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity and tumor response.

The study will be conducted in two parts: Part 1 will include MT-3724 dose escalation according to the modified 3+3 design to identify the MTD of MT-3724 in combination with standard doses of lenalidomide and will include up to 24 subjects with histologically confirmed NHL. Part 2 is designed to confirm the safety and tolerability of MT-3724 + lenalidomide in the MTD Expansion Cohort, where the dose declared as MTD of MT-3724 in Part 1 would be given in combination with lenalidomide in up to 40 subjects with CD20+ DLBCL. In addition, the PK, PD, immunogenicity and tumor response of MT-3724 + lenalidomide will be evaluated in Part 2.

The study is currently ongoing; eligible subjects will be identified and treated through competitive enrollment at multiple study centers (ClinicalTrials.gov Identifier: NCT03645395).

Copies of the posters presented at ASH (Free ASH Whitepaper) can be found in the Presentations section of Molecular Templates’ website at View Source

On December 9, 2019 Seattle Genetics, Inc. (Nasdaq:SGEN) and Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) reported additional analyses of results from the ECHELON-1 and ECHELON-2 frontline phase 3 trials of ADCETRIS (brentuximab vedotin) (Press release, Seattle Genetics, DEC 9, 2019, View Source [SID1234552140]). These analyses were presented at the 61st Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) taking place December 7-10, 2019 in Orlando, Fla. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical Hodgkin lymphoma and expressed on the surface of several types of peripheral T-cell lymphomas (PTCL).

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The ECHELON-1 analysis highlighted a four-year update of the phase 3 clinical trial in a poster presentation. ECHELON-1 is evaluating ADCETRIS in combination with AVD (Adriamycin [doxorubicin], vinblastine and dacarbazine) compared to ABVD (Adriamycin [doxorubicin], bleomycin, vinblastine and dacarbazine) in patients with Stage III or IV frontline classical Hodgkin lymphoma.

The ECHELON-2 phase 3 clinical trial data were presented in an oral session at ASH (Free ASH Whitepaper) and focused on the outcomes of the subset of patients who underwent consolidative stem cell transplant. ECHELON-2 is evaluating ADCETRIS in combination with CHP (cyclophosphamide, doxorubicin, prednisone) compared to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in frontline CD30-expressing PTCL.

"For decades, the standard of care for the treatment of frontline Hodgkin lymphoma has been combination chemotherapy, called ABVD. Unfortunately, approximately 30 percent of patients with advanced stage Hodgkin lymphoma do not respond or relapse following treatment with this therapy," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "The four-year update from the ECHELON-1 trial continues to support the robust and durable frontline treatment benefit of ADCETRIS plus AVD, including in both Stage III and IV disease settings, compared to ABVD across subgroups, regardless of PET2 status. These data reinforce ADCETRIS plus AVD as a treatment option that should be offered to all newly diagnosed advanced stage patients with Hodgkin lymphoma."

"Updated data from the ECHELON-1 trial and further insights from ECHELON-2 build upon our continued understanding of the potential ADCETRIS offers patients with CD30-positive lymphomas," said Phil Rowlands, Ph.D., Head, Oncology Therapeutic Area Unit, Takeda. "We’re especially encouraged by the promising four-year follow-up ECHELON-1 results being presented at ASH (Free ASH Whitepaper), as approximately one in three patients with advanced Hodgkin lymphoma do not achieve long-term remission after standard frontline therapy."

Brentuximab Vedotin with Chemotherapy for Stage 3/4 Classical Hodgkin Lymphoma (cHL): 4-Year Update of the ECHELON-1 Study (Abstract #4026, poster presentation on Monday, December 9, 2019)

As previously reported, the ECHELON-1 trial achieved its primary endpoint with the combination of ADCETRIS plus AVD resulting in a statistically significant improvement in modified progression-free survival (PFS) compared to the control arm of ABVD as assessed by independent review facility (IRF; hazard ratio (HR), 0.77; p=0.035). A four-year post-hoc exploratory analysis was conducted to examine PFS outcomes per investigator assessment in the intent-to-treat population of 1,334 patients, including results by PET2 status, age, stage and prognostic risk scores. Results include:

The four-year PFS rate for patients in the ADCETRIS plus AVD arm was 81.7 percent compared to 75.1 percent in the ABVD arm, a difference of 6.6 percent (HR, 0.69 [95% CI: 0.542, 0.881]). This represents a 31 percent reduction in the risk of progression or death. Median follow-up time was 48.4 months.
A PFS benefit at four-years for ADCETRIS plus AVD was observed for all patients independent of PET2 status, including in patients who are less than 60 years old.
PET2-negative result was 86.2 percent in the ADCETRIS plus AVD arm compared to 81.0 percent in the ABVD arm (HR, 0.69), a difference of 5.2 percent.
PET2-positive result was 62.1 percent in the ADCETRIS plus AVD arm compared to 47.7 percent in the ABVD arm (HR, 0.65), a difference of 14.4 percent.
Consistent improvement in PFS was observed among patients treated with ADCETRIS plus AVD compared with ABVD across the majority of pre-specified subgroups, including disease stage, age and prognostic score.
Notably, improvements compared to ABVD were observed in patients with Stage III (HR, 0.595; [95% CI: 0.386, 0.917]) and Stage IV (HR, 0.745; [95% CI: 0.555, 1.001]) disease.
As previously reported for the primary analysis, on the ADCETRIS plus AVD arm, peripheral neuropathy events were observed in 67 percent of patients compared to 43 percent in the ABVD arm. The four-year update shows that among patients with peripheral neuropathy, 83 percent in the ADCETRIS plus AVD arm and 84 percent in the ABVD arm reported complete resolution or improvement at last follow-up.
More than 45 countries and regions have approved ADCETRIS in combination with AVD for the treatment of patients with previously untreated Stage III or IV Hodgkin lymphoma. The U.S. Food and Drug Administration (FDA) approved ADCETRIS in combination with AVD for the treatment of adult patients with previously untreated stage III or IV classical Hodgkin lymphoma in March 2018, based on the results of the ECHELON-1 phase 3 clinical trial in which the primary endpoint was modified PFS. In February 2019, the European Commission (EC) approved ADCETRIS for the treatment of adult patients with previously untreated CD30+ Stage IV Hodgkin lymphoma in combination with AVD.

An Exploratory Analysis of Brentuximab Vedotin plus CHP (A+CHP) in the Frontline Treatment of Patients with CD30+ Peripheral T-Cell Lymphomas (ECHELON-2): Impact of Consolidative Stem Cell Transplant (Abstract #464, oral presentation on Sunday, December 8, 2019)

As previously reported, the ECHELON-2 trial met its primary endpoint with the combination of ADCETRIS plus CHP resulting in a statistically significant improvement in PFS versus the control arm of CHOP per blinded independent central review (HR, 0.71; p=0.0110). In addition, the overall survival benefit in the ADCETRIS plus CHP arm was statistically significant compared to CHOP (HR, 0.66; p=0.0244). A post-hoc exploratory analysis evaluated the impact of consolidative stem cell transplant in the ECHELON-2 study for the patients who achieved CR treated with ADCETRIS plus CHP. In the ADCETRIS plus CHP arm, this included 38 patients in CR who received a stem cell transplant and 76 patients in CR who did not. Key findings of this analysis include:

The PFS estimate favored the use of stem cell transplant (HR, 0.38; [95% CI: 0.18, 0.82]). After a median follow-up time of 35.9 months, the three-year PFS rate for the 38 patients who received a stem cell transplant was 76.1 percent. After a median follow-up time of 41.6 months, the three-year PFS rate for the 76 patients who did not receive a stem cell transplant was 53.3 percent.
As previously reported, the safety profile of ADCETRIS plus CHP in the ECHELON-2 trial was comparable to CHOP and consistent with the established safety profile of ADCETRIS in combination with chemotherapy.
About Classical Hodgkin Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Classical Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. The Reed-Sternberg cell expresses CD30.

According to the American Cancer Society, approximately 8,110 cases of Hodgkin lymphoma will be diagnosed in the United States during 2019 and 1,000 will die from the disease. Approximately half of all newly diagnosed Hodgkin lymphoma patients have Stage III/IV disease. According to the Lymphoma Coalition, over 62,000 people worldwide are diagnosed with Hodgkin lymphoma each year and approximately 25,000 people die each year from this cancer.

About T-Cell Lymphomas

There are more than 60 subtypes of non-Hodgkin lymphomas which are broadly divided into two major groups: B-cell lymphomas, which develop from abnormal B-lymphocytes, and T-cell lymphomas, which develop from abnormal T-lymphocytes. There are many different forms of T-cell lymphomas, some of which are extremely rare. T-cell lymphomas can be aggressive (fast-growing) or indolent (slow-growing). PTCL accounts for approximately 10 percent of non-Hodgkin lymphoma cases in the U.S. and Europe and may be as high as 24 percent in parts of Asia.

About ADCETRIS

ADCETRIS is being evaluated broadly in more than 70 clinical trials in CD30-expressing lymphomas. These include three completed phase 3 trials: ECHELON-2 trial in frontline peripheral T-cell lymphomas, ECHELON-1 in previously untreated Hodgkin lymphoma, and ALCANZA in cutaneous T-cell lymphoma.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS injection for intravenous infusion has received FDA approval for six indications in adult patients with: (1) previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone, (2) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine, (3) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (4) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (5) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (6) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

Health Canada granted ADCETRIS approval with conditions in 2013 for patients with (1) HL after failure of autologous stem cell transplant (ASCT) or after failure of at least two multi-agent chemotherapy regimens in patients who are not ASCT candidates and (2) sALCL after failure of at least one multi-agent chemotherapy regimen. Non-conditional approval was granted for (3) post-ASCT consolidation treatment of patients with HL at increased risk of relapse or progression in 2017, (4) adult patients with pcALCL or CD30-expressing MF who have received prior systemic therapy in 2018, (5) for previously untreated patients with Stage IV HL in combination with doxorubicin, vinblastine, and dacarbazine in 2019, and (6) for previously untreated adult patients with sALCL, peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) or angioimmunoblastic T-cell lymphoma (AITL), whose tumors express CD30, in combination with cyclophosphamide, doxorubicin, prednisone in 2019.

ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (2) for the treatment of adult patients with relapsed or refractory sALCL, (3) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy and (5) for the treatment of adult patients with previously untreated CD30-positive Stage IV Hodgkin lymphoma in combination with AVD (Adriamycin, vinblastine and dacarbazine).

ADCETRIS has received marketing authorization by regulatory authorities in 73 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See select important safety information, including Boxed Warning, below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

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.