On December 10, 2019 Spherix Incorporated (Nasdaq: SPEX) reported that it has closed the CBM BioPharma, Inc. transaction and is working to develop these cancer drugs (Press release, Spherix, DEC 10, 2019, View Source [SID1234552194]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Building on its successful investment in Hoth Therapeutics, Inc., Spherix now owns a diverse portfolio of early stage small-molecule anti-cancer therapeutics. The Spherix platform contains patented technology from leading universities and researchers and we seek to develop our innovative drugs through strong partnership with world renowned institutions, such as The University of Texas at Austin and Wake Forest University. The Company’s diverse pipeline of therapeutics includes therapies for pancreatic cancer, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Its pancreatic treatment has shown positive preclinical results for inhibiting pancreatic tumor growth in clinically relevant transgenic mouse models. The drug has also demonstrated the potential to overcome tumor cell resistance to current chemotherapeutic drugs. The Company’s AML drug is a next generation targeted therapeutic designed to overcome multiple resistance mechanisms observed with the current standard of care. In addition, Spherix is continually seeking to grow its pipeline to treat unmet medical needs in oncology.

Anthony Hayes, CEO of Spherix, stated, "The acquisition of these assets is yet another step in the transformation of Spherix into a diversified biotechnology company. These are exciting drugs and we intend to provide additional information about these drugs and the development plan moving forward. As the deal has evolved, we have successfully improved the terms for Spherix shareholders, we thank our shareholders for their support during this process."

On December 10, 2019 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for cancer, reported that the company will participate in the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2019 in Geneva, Switzerland, December 11-14, including a poster presentation on December 12th (Press release, Personalis, DEC 10, 2019, View Source [SID1234552210]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The poster presentation, titled "A comprehensive tumor immunogenomics platform for precision immunotherapy: Enabling simultaneous characterization of tumors and the TME from a single FFPE sample," will describe the Personalis universal cancer immunogenomics platform, ImmunoID NeXT. The poster will provide an overview of how the platform can be used to explore critical immunotherapy-related resistance mechanisms and novel composite biomarkers of response; utilizing analytics including: human leukocyte antigen (HLA) typing and HLA loss of heterozygosity (LOH), neoantigen prediction and load, immune repertoire characterization, oncoviral detection, immune cell deconvolution, as well as the evaluation of tumor mutational burden (TMB) and microsatellite instability (MSI) status.

ImmunoID NeXT is the first platform to enable comprehensive analysis of both a tumor and its immune microenvironment from a single sample. The platform can be used to investigate the key tumor- and immune-related areas of cancer biology, consolidating multiple oncology biomarker assays into one and maximizing the biological information that can be generated from a single tumor specimen.

The presentation will be delivered by Robert Power, M.S., Product Manager, for Personalis.

Personalis will also be exhibiting during the conference (Exhibit #9). Representatives will be available to answer questions about the company’s cancer immunogenomics capabilities.

On December 10, 2019 Stemline Therapeutics, Inc. (Nasdaq: STML), a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics, reported data from ELZONRIS (tagraxofusp) Phase 1/2 clinical trials in myelofibrosis (oral presentation) and multiple myeloma, at the 2019 ASH (Free ASH Whitepaper) annual meeting (Press release, Stemline Therapeutics, DEC 10, 2019, View Source [SID1234552195]). The presentations are now available on the Stemline website, www.stemline.com, under the Scientific Presentations tab. Highlights of results are presented below.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Myelofibrosis: Clinical Trial of ELZONRIS in Patients with Intermediate or High-Risk, Relapsed/Refractory Myelofibrosis (MF) – Oral presentation

ELZONRIS demonstrated efficacy (spleen size reductions and total symptom score [TSS] reductions) with a predictable and manageable safety profile, including in patients with poor prognostic factors, such as thrombocytopenia, CMML-type features/monocytosis, and clonal evolution
45% (9/20) of patients had symptom burden reduction, including 3 with symptom response per IWG-MRT 2013 MF response criteria
53% (8/15) of patients with baseline splenomegaly >= 5cm experienced a spleen size reduction; 20% (3/15) had a reduction >35% (specifically 100%, 47% and 46% reductions)
° 100% (5/5) of patients with CMML-type features/monocytosis experienced a spleen size reduction, and 40% (2/5) of these patients had a reduction >35%
° 64% (7/11) of patients with thrombocytopenia (platelet count < 100×109/L) experienced a spleen size reduction, and 18% (2/11) had a reduction >35%; 60% (3/5) of patients with thrombocytopenia (platelet count < 50×109/L) experienced a spleen size reduction, and 20% (1/5) had a reduction >35%

Most common treatment related adverse events (TRAEs) include alanine aminotransferase increase, headache, hypoalbuminemia (all 17%), anemia, and thrombocytopenia (both 14%)
° There was one case of capillary leak syndrome (CLS), which was grade 3
43% overall survival (OS) at 18 months; 29% OS at 2 years
Next Steps

Expansion of Phase 2 trial to include additional sites is underway
Patient enrollment and follow up continues to inform design of potential registration-directed trial of ELZONRIS in patients with relapsed/refractory MF, including poor prognosis patients with:
° Thrombocytopenia, and/or
° Monocytosis (CD123-overexpressed subsets)
Other areas of evaluation in MF

An additional ASH (Free ASH Whitepaper) presentation demonstrated that ELZONRIS, either alone or in combination with ruxolitinib, had preclinical activity against primary MF patient samples, including those in accelerated phase and with high molecular risk profiles where current therapeutic options beyond ruxolitinib are limited and CD123 expression is evident. These data support further evaluation of tagraxofusp in MF, not only as single agent but potentially in combination with Jak inhibitors.
Multiple Myeloma: Clinical Trial of ELZONRIS in Patients with Relapsed/Refractory Multiple Myeloma (MM)

ELZONRIS, in combination with pomalidomide (POM) and dexamethasone (DEX), demonstrated activity and a predictable and manageable safety profile in heavily pretreated patients with relapsed/refractory MM
56% of patients (5/9) who received ELZONRIS in combination with POM+DEX had partial responses (PRs)
° Notably, these patients also had decreases in their plasmacytoid dendritic cells (pDCs), a cell type implicated in myeloma growth and aggressiveness, and the cell of origin of blastic plasmacytoid dendritic cell neoplasm (BPDCN)
Given these clinical data, ELZONRIS may offer a novel mechanism of action and future therapeutic option for patients with MM
Next Steps

Given these encouraging early results, potential avenues for further ELZONRIS development are being assessed, including evaluating additional patients with this and/or potentially other regimens including in combination with daratumumab or novel agents such as XPO1 inhibitors. Moreover, the clinical knockdown of pDCs in MM patients may also be relevant with respect to other diseases, such as chronic myelomonocytic leukemia (CMML), MF and certain acute myeloid leukemia (AML) patient subsets, where pDCs have been similarly implicated in the aggressiveness of these malignancies.
About ELZONRIS
ELZONRIS (tagraxofusp), a CD123-directed cytotoxin, is approved by the U.S. Food and Drug Administration (FDA) and commercially available in the U.S. for the treatment of adult and pediatric patients, two years or older, with blastic plasmacytoid dendritic cell neoplasm (BPDCN). For full prescribing information in the U.S., visit www.ELZONRIS.com. In Europe, a marketing authorization application (MAA) is under review by the European Medicines Agency (EMA). ELZONRIS is also being evaluated in additional clinical trials in other indications including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), and acute myeloid leukemia (AML).

About BPDCN
BPDCN is an aggressive hematologic malignancy with historically poor outcomes and an area of unmet medical need. BPDCN typically presents in the bone marrow and/or skin and may also involve lymph nodes and viscera. The BPDCN cell of origin is the plasmacytoid dendritic cell (pDC) precursor. The diagnosis of BPDCN is based on the immunophenotypic diagnostic triad of CD123, CD4, and CD56, as well as other markers. For more information, please visit the BPDCN disease awareness website at www.bpdcninfo.com.

About CD123
CD123 is a cell surface target expressed on a wide range of myeloid tumors including blastic plasmacytoid dendritic cell neoplasm (BPDCN), certain myeloproliferative neoplasms (MPNs) including chronic myelomonocytic leukemia (CMML) and myelofibrosis (MF), acute myeloid leukemia (AML) (and potentially enriched in certain AML subsets), myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). CD123 has also been reported on certain lymphoid malignancies including multiple myeloma (MM), acute lymphoid leukemia (ALL), hairy cell leukemia (HCL), Hodgkin’s lymphoma (HL), and certain Non-Hodgkin’s lymphomas (NHL). In addition, CD123 has been detected on some solid tumors as well as autoimmune disorders including cutaneous lupus and scleroderma.

On December 10, 2019 CStone Pharmaceuticals ("CStone" or the "Company", HKEX: 2616) reported that the on-going, global Phase III VOYAGER clinical trial of avapritinib, an investigational drug discovered by CStone’s partner, Blueprint Medicines, has completed target patient enrollment in China (Press release, CStone Pharmaceauticals, DEC 10, 2019, View Source [SID1234552211]). In addition, the VOYAGER trial’s enrollment target has been reached globally. The study was designed to evaluate the safety and efficacy of avapritinib as a third- or fourth-line treatment for patients with advanced gastrointestinal stromal tumors (GIST), in comparison with that of regorafenib, the current standard-of-care treatment for third-line GIST. On July 10, 2019, CStone announced the dosing of the first patient in China for the VOYAGER trial.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Blueprint Medicines expects to report top-line VOYAGER trial data in the second quarter of 2020. In August 2019, the U.S. Food & Drug Administration (FDA) accepted Blueprint Medicines’ New Drug Application (NDA) for avapritinib for the treatment of adult patients with PDGFRA Exon 18 mutant GIST, regardless of prior therapy, and fourth-line GIST. Subject to an initial approval of avapritinib, Blueprint Medicines plans to submit a supplemental NDA to the U.S. FDA for avapritinib for third-line GIST in the second half of 2020. CStone plans to submit an NDA for the treatment of third-line GIST to the China National Medical Products Administration (NMPA) in the second half of 2020.

GIST is the most common mesenchymal tumor of the GI tract, and it is most prevalent in patients aged 50 to 80. Around 90% of all GIST cases are associated with dysregulated cell growth due to mutations in KIT and PDGFRA tyrosine kinases. Existing data on regorafenib, the current standard third-line GIST treatment, shows a median progression-free survival of 4.8 months and an objective response rate (ORR) of only about 5%. There is currently no approved treatment for GIST patients who have failed third-line treatment. Thus, there are high unmet clinical needs in patients with third-line and later GIST.

Avapritinib is an investigational, orally available, potent and highly selective inhibitor of KIT and PDGFRA. Clinical data on avapritinib have demonstrated encouraging anti-tumor activity and benign tolerability in patients with PDGFRA Exon 18 mutants (primarily includes patients with the D842V mutation) and fourth-line GIST, two patient populations currently lacking effective therapies.

Data from the on-going Phase I NAVIGATOR trial were presented in November 2019 at the Connective Tissue Oncology Society Annual Meeting. As of the data cutoff date of November 16, 2018, these results showed:

An ORR of 86% (one response pending confirmation) in 43 response-evaluable patients with PDGFRA Exon 18 mutant GIST (including 38 patients with PDGFRα D842V-mutant GIST), and the median duration of response (DOR) was not reached.
An ORR of 22% (one response pending confirmation) and a median DOR of 10.2 months in 111 response-evaluable patients with fourth-line GIST.
Avapritinib was generally well-tolerated, and most adverse events were Grade 1 or 2 as assessed by investigators.
"We are pleased that in China, the global Phase III VOYAGER trial has completed its enrollment target sooner than planned, and this rapid progress reaffirms the urgent clinical needs of GIST patients in China," said Dr. Frank Jiang, Chairman and CEO of CStone. "With the appointment of Ms. Shirley Zhao, a seasoned pharmaceutical executive who has led the successful launches of numerous major brands, to the position of General Manager for Greater China and Head of Commercial, we are more confident than ever in our ability to accelerate CStone’s transition toward a commercial-stage company and to potentially bring avapritinib and other key assets to the China market."

CStone’s Chief Medical Officer, Dr. Jason Yang, noted: "GIST is a rare disease, and completing target enrollment in China in less than 4 months is a testament to the effective collaborations among CStone, investigators, and business partners. Currently available data on this highly selective inhibitor of KIT and PDGFRA mutant kinases has already demonstrated its clinical potential. At the same time, we are also conducting a Phase I/II bridging study of avapritinib in patients with advanced GIST in China."

About Avapritinib

Avapritinib is an investigational, oral precision therapy that selectively and potently inhibits KIT and PDGFRA mutant kinases. It is a type 1 inhibitor designed to target the active kinase conformation; all oncogenic kinases signal via this conformation. Avapritinib has demonstrated broad inhibition of KIT and PDGFRA mutations associated with GIST, including potent activity against activation loop mutations that are associated with resistance to currently approved therapies.

Blueprint Medicines is initially developing avapritinib for the treatment of advanced GIST, advanced systemic mastocytosis (SM), and indolent and smoldering SM. The U.S. FDA has granted Breakthrough Therapy Designation to avapritinib for two indications: one for the treatment of unresectable or metastatic GIST harboring the PDGFRA D842V mutation and one for the treatment of advanced SM, including the subtypes of aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of avapritinib and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for avapritinib in the rest of the world.

On December 10, 2019 Celyad (Euronext Brussels and Paris, and Nasdaq: CYAD), a clinical-stage biopharmaceutical company focused on the development of CAR-T cell therapies, reported updates to the company’s autologous NKG2D-based CAR-T development program for the treatment of relapsed/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) at the American Society of Hematology (ASH) (Free ASH Whitepaper) 61st Annual Meeting, which is being held from December 7-10, 2019 in Orlando, Florida (Press release, Celyad, DEC 10, 2019, View Source [SID1234552196]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Filippo Petti, CEO of Celyad, commented, "Over the past few months we have worked diligently to transition our proprietary OptimAb manufacturing process to become the cornerstone of our autologous CAR-T program for the treatment of relapsed/refractory acute myeloid leukemia and myelodysplastic syndromes. We are encouraged by the body of data generated to date by our lead autologous candidate CYAD-01 for the treatment of AML and MDS, especially given its tolerability profile and anti-leukemic activity."

"We are excited to further evaluate our NKG2D-based CAR-T approach using our OptimAb manufacturing process, which generates a higher frequency of less differentiated CAR-T cells that exhibit enhanced anti-tumor activity in preclinical studies. Overall, we believe the process gives us the best opportunity for success across both autologous product candidates, CYAD-01 and CYAD-02. Along with our ongoing DEPLETHINK trial, the key next steps for our broad r/r AML and MDS program include the expansion of the THINK trial and initiation of the CYCLE-1 trial as we look to establish NKG2D as an important target for the treatment of difficult-to-treat malignancies", continued Mr. Petti.

CYAD-01 THINK Phase 1 Trial

Sixteen patients have been enrolled to date in the trial evaluating CYAD-01 administered as a multiple injection with a biweekly schedule and an additional nine patients have been enrolled in the dose dense (weekly) schedule in the dose escalation segment of the trial
CYAD-01 without preconditioning chemotherapy was generally reported to be well-tolerated, with 11 out of 25 patients experiencing grade 3/4 treatment-related adverse events (AEs). Cytokine release syndrome (CRS) occurred in 13 patients, with four grade 3 and two grade 4 events, which showed rapid resolution following the appropriate treatment, including tocilizumab. Two dose-limiting toxicities were reported at dose level 3 (3 billion cells per infusion), including one CRS grade 4 (biweekly) and one CRS grade 3 (dose dense schedule). No treatment-related neurotoxicity AEs were reported
Overall, eight patients out of 15 evaluable patients treated with CYAD-01 produced with the prior manufacturing process demonstrated anti-leukemic activity. Five out of the eight patients exhibited an objective response. In addition, one patient is exhibiting disease stabilization of over three months
Patients treated within the CYAD-01 dose-dense (weekly) schedule cohorts of the trial did not demonstrate an improvement in clinical outcome as compared to patients treated with the biweekly dosing schedule. However, patients enrolled in the dose-dense schedule cohorts appeared to have greater bone marrow blasts infiltration and to be more pancytopenic at baseline compared to patients enrolled in the biweekly dose escalation segment of the trial
Most of the anti-leukemic activity observed in the trial, except for the two patients who bridged to an allogeneic human stem cell transplant, experienced a short durability of response
To date, anti-leukemic activity appears predominantly observed in patients initially diagnosed with non-adverse (ELN 2017, AML) or non-very high (IPSS-R, MDS) risk stratification categories. Additional patients are needed in the trial to better assess the observation
Company plans to progress to the expansion segment of the THINK trial to further evaluate CYAD-01 produced with the OptimAb manufacturing process. Enrollment in the expansion segment of the trial is expected to begin in first quarter 2020 with preliminary data anticipated by the end of first half 2020
CYAD-01 DEPLETHINK Phase 1 Trial

Nine patients have been enrolled in the trial evaluating CYAD-01 produced with the prior mAb manufacturing process following preconditioning chemotherapy cyclophosphamide and fludarabine, or CyFlu, at the first two dose levels of the dose escalation segment of the trial
CYAD-01 produced with the mAb manufacturing process was generally reported to be well-tolerated following preconditioning chemotherapy. At the first CYAD-01 infusion of the consolidation cycle (3 billion cells per infusion), one patient experienced both grade 4 cytokine release syndrome (CRS) and grade 3 CAR-T cell-related encephalopathy and another patient experienced grade 3 CRS. Both patients recovered following the appropriate treatment, including tocilizumab
Preconditioning chemotherapy led to improved, dose-dependent engraftment of CYAD-01 cells as compared to cells infused with no preconditioning
To date, no objective response has been observed at the first two dose levels of the trial in patients treated with CYAD-01 produced with the mAb manufacturing process
In September 2019, the company announced the successful administration of CYAD-01 produced with the OptimAb manufacturing process to a patient enrolled in cohort 3 (300 million cells per infusion) of the trial
Enrollment in the trial is ongoing with plans to dose escalate up to one billion cells per infusion in cohort 4. Preliminary data evaluating CYAD-01 produced with the OptimAb manufacturing process from cohorts 3 and 4 are expected by the end of first half 2020
CYAD-02 CYCLE-1 Phase 1 Trial

In November 2019, the company initiated the dose-escalation Phase 1 CYCLE-1 trial (NCT04167696), which will evaluate the safety and clinical activity of the next-generation, autologous NKG2D-based CAR-T candidate CYAD-02, produced with the OptimAb manufacturing process following preconditioning chemotherapy CyFlu in patients with r/r AML and MDS
CYAD-02 incorporates shRNA SMARTvector technology licensed from Horizon Discovery to target the NKG2D ligands MICA and MICB. shRNA-mediated knockdown of MICA and MICB expression on NKG2D CAR-T cells has been shown to enhance in vitro expansion of the CAR-T cells and enhanced engraftment and persistence in preclinical models as compared to CYAD-01 produced with the mAb process
Enrollment in the CYCLE-1 trial is expected to begin in early 2020 with preliminary data anticipated during second half 2020
About THINK Phase 1 Trial

The THINK trial (NCT03018405) is an open-label, dose-escalation Phase 1 trial assessing the safety and clinical activity of multiple CYAD-01 administrations without prior preconditioning. The dose escalation segment of the trial evaluated three dose levels (300 million, 1 billion and 3 billion cells per infusion) of one cycle of three CYAD-01 administrations with two-week intervals. In 2018, the THINK trial was amended to add two cohorts to assess a more frequent dosing schedule of CYAD-01 for the treatment of r/r AML. The cohorts will evaluate six injections of CYAD-01 without preconditioning over two months of administration. The first cycle includes three infusions of CYAD-01 separated by one-week intervals. The second cycle includes three infusions of CYAD-01 separated by two-week intervals. Patients will either receive 1 billion cells per infusion (Cohort 10) or 3 billion cells per infusion (Cohort 11). The primary endpoint of the trial is safety and secondary endpoints include clinical activity and pharmacokinetics.

About DEPLETHINK Phase 1 Trial

In October 2018, Celyad initiated the DEPLETHINK Phase 1 trial (NCT03466320). The open-label, dose-escalation trial is designed to evaluate a single infusion of CYAD-01 following treatment with the standard preconditioning regimen of cyclophosphamide (300 mg/m²) and fludarabine (30 mg/m²), or CyFlu. The trial includes two different intervals between lymphodepletion and administration of CYAD-01. In addition, the trial is evaluating three dose levels of CYAD-01 including 100 million, 300 million and 1 billion cells per infusion, respectively. The primary endpoint of the trial is safety and secondary endpoints include clinical activity and pharmacokinetics.

About OptimAb Manufacturing Process

Celyad’s proprietary OptimAb manufacturing process utilizes a shortened cell culture and incorporates a selective PI3K inhibitor. This results in a product that is enriched for T cells with a memory-like phenotype. Preclinical data demonstrate that NKG2D-based CAR-T cell therapies produced using the OptimAb manufacturing process drive improved anti-tumor activity in an aggressive AML model compared to alternative manufacturing process.