On December 7, 2020 Treadwell Therapeutics, a clinical-stage biotechnology company developing novel, small molecule therapeutics for highly aggressive cancers, reported two presentations for the Company’s CFI-400945 program, an oral, first-in-class inhibitor of Polo-like Kinase 4 (PLK4) a critical regulator of mitotic progression, at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held virtually from December 5-8, 2020 (Press release, Treadwell Therapeutics, DEC 7, 2020, View Source [SID1234572373]). The first presentation described the efficacy results from an investigator-initiated Phase 1 dose escalation study in AML/MDS. The second was a "Trials in Progress" presentation on the upcoming Treadwell sponsored study in relapsed or refractory AML, MDS or CMML with study initiation planned for the first quarter of 2021.

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"We are very encouraged by the promising preliminary Phase 1 study results which included single agent, durable remissions. This compelling early data supports the continued investigation of CFI-400945 for the potential treatment of patients with acute myeloid leukemia (AML)," said Principal Investigator, Karen W.L. Yee, Leukemia Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.

"Abnormal genetics, complex karyotypes, genomic instability characterize poor prognosis in AML. CFI-400945 inhibits PLK4, a highly conserved master regulator of centriole duplication, and is critical for maintenance of genomic integrity, making it an ideal candidate for the potential treatment of AML," said Dr. Mark R. Bray, Chief Scientific Officer at Treadwell Therapeutics. "We are excited by the compelling Phase 1 trial results in AML and look forward to continuing to evaluate the promise of our lead candidate in company sponsored Phase 2 studies."

2020 ASH (Free ASH Whitepaper) Poster Presentations and Details:

Preliminary Results from a Phase 1 Study of CFI-400945, a PLK4 Inhibitor, in Patients with Acute Myeloid Leukemia and High Risk MDS
Publication Number: 1050
Session: 616; Poster I
Date and Time: December 5, 2020, 7:00 AM-3:30 PM
A Phase 2 Open-Label, Multicenter, Dose Optimization Clinical Study of the Safety, Tolerability, Pharmacokinetic (PK) and Pharmacodynamic (PD) Profiles of CFI-400945 as a Single Agent or in Combination with Azacitidine or Decitabine in Patients with Acute Myeloid Leukemia, Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
Publication Number: 1974
Session: 616; Poster II
Date and Time: Sunday, December 6 th, 7:00 AM-3:30 PM
In the presentation titled, "Preliminary Results from a Phase 1 Study of CFI-400945, a PLK4 Inhibitor, in Patients with Acute Myeloid Leukemia and High Risk MDS," CFI-400945 demonstrated promising activity as a monotherapy in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) and a tolerable safety profile in an open-label, dose escalation, safety and pharmacokinetic study. Data showed that of six patients evaluable for response, two (33%) achieved complete remission (CR) as best response with 3 patients achieving stable disease (SD). Onset of response tended to be within 1 or 2 cycles. One CR occurred in a complex karyotype patient with a p53 mutation who previously failed 7+3 induction and had a durability of ~90 days. The second CR was in a previously untreated AML patient with a 5q deletion who is still in response after >200 days. One subject achieving SD as best response with duration of > 200 days was a previously untreated AML patient with a p53 mutation and had blast reduction from 38% to 9%, but complete blood counts remained below PR criteria. The most common non-hematological drug related toxicities of any grade, which occurred in over 20%, were diarrhea (44%), headache (44%), colitis (33%), vomiting (33%), bilirubin increase (22%), dizziness (22%), fatigue (22%), and nausea (22%).

A second presentation titled, "A Phase 2 Open-Label, Multicenter, Dose Optimization Clinical Study of the Safety, Tolerability, and Pharmacokinetic (PK) and Pharmacodynamic (PD) Profiles of CFI-400945 as a Single Agent or in Combination with Azacitidine or Decitabine in Patients with Acute Myeloid Leukemia," details the study design for a Treadwell sponsored trial examining CFI-400945 in AML, MDS and chronic myelomonocytic leukemia (CMML). The study will use a standard 3 + 3 design and have four parts: Part 1A (1A), a single agent dose optimization lead-in, Part 1B (1B), a food effect portion once the MTD of 1A is determined, and Part 2, combinations with azacitidine (2A), and decitabine (2B). The efficacy endpoints for AML, MDS, and CMML include the overall response rate, and the CR rate per standard criteria.

About CFI-400945

CFI-400945 is a potent, selective, orally administered, first-in-class inhibitor of the serine/threonine kinase, polo-like kinase 4 (PLK4). PLK4 is a highly conserved master regulator of centriole duplication and is critical for maintenance of genomic integrity. PLK4 is overexpressed in a variety of solid tumors and elevated expression is associated with poor clinical outcomes. Depletion of PLK4 expression in cancer cells by RNA interference leads to mitotic defects and cell death. PLK4 was identified as a drug target based on functional screening to identify vulnerabilities of genomically unstable breast cancers.

Anti-tumor activity of CFI-400945 has been shown in mice bearing human cancer xenografts, including robust tumor growth inhibition and durable tumor regression in primary tumor xenografts from breast cancer. CFI-400945 is a potent, selective, orally administered, first-in-class inhibitor of the serine/threonine kinase, polo-like kinase 4 (PLK4). CFI-400945 is currently in multiple investigator-initiated studies in solid and liquid malignancies, with a company sponsored trial in relapsed or refractory leukemia to commence in the first quarter of 2021.

On December 7, 2020 The Janssen Pharmaceutical Companies of Johnson & Johnson reported new data from the randomised Phase 2 GRIFFIN study showing that the addition of DARZALEX▼ (daratumumab) to lenalidomide, bortezomib and dexamethasone (D-RVd), followed by daratumumab plus lenalidomide (D-R) maintenance therapy, resulted in deeper and improved responses, including minimal residual disease (MRD) negativity, compared to RVd followed by R alone, in newly diagnosed, stem cell transplant-eligible patients with multiple myeloma (Press release, Janssen Pharmaceuticals, DEC 7, 2020, View Source [SID1234572372]).1 These data investigating the use of daratumumab in combination with RVd, which were shared in separate oral and poster presentations at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2020 Annual Meeting, provide further evidence that this regimen may provide greater efficacy for transplant-eligible, newly diagnosed multiple myeloma (NDMM) patients than standard therapy. This morning’s oral presentation (Abstract #549) shared longer-term follow-up data, and the poster presentation (Abstract #3243) featured additional data from the safety run-in cohort.1,2

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"The long-term GRIFFIN data show that maintenance therapy with daratumumab in combination with lenalidomide (D-R) resulted in deeper and longer responses compared to R alone in patients with multiple myeloma who are newly diagnosed and transplant-eligible," said Peter Voorhees, M.D.,* Atrium Health’s Levine Cancer Institute and GRIFFIN study investigator. "These data indicate that the addition of daratumumab to RVd followed by R maintenance results in improved response rates and depth of response during induction, consolidation and maintenance treatment cycles."

Key Findings from GRIFFIN (Abstract #549):
The GRIFFIN oral presentation featured updated safety and efficacy data based on longer follow-up for D-RVd and evaluated the potential role of D-R for maintenance therapy in patients with NDMM.1

Initial findings of GRIFFIN:
At the end of post-transplant consolidation (median follow-up, 13.5 months) in the response-evaluable population, the stringent complete response (sCR) rate favoured D-RVd vs. RVd (42.4 percent vs. 32.0 percent, P=0.0253).1
The complete response (CR) or better rate also favoured D-RVd vs. RVd (51.5 percent vs. 42.3 percent; P=0.0014).1
No new safety concerns were observed in the D-RVd arm receiving D-R maintenance therapy.1
The most common Grade 3/4 treatment-emergent adverse events (TEAEs) in the D-RVd arm receiving D-R maintenance therapy were neutropenia (43 percent), lymphopenia (23 percent), leukopenia (16 percent) and thrombocytopenia (15 percent).1
With an additional 12 months of D-R or R maintenance therapy (median follow up of 27.4 months), responses continued to deepen and remained higher for the daratumumab-containing arm.1
At the clinical cutoff date, the sCR rate favoured the daratumumab-containing arm (63.6 percent vs. 47.4 percent; P=0.0253).1
The CR or better rate continued to favour D-RVd vs. RVd (81.8 percent vs. 60.8 percent; P=0.0014).1
MRD negativity favoured D-RVd vs. RVd (62.5 percent vs. 27.2 percent, P=0.0001).1
No new safety concerns were observed with the D-R maintenance therapy.1
The 24-month progression-free survival (PFS) rate was 94.5 percent for D-RVd and 90.8 percent for RVd.1
Key Findings from GRIFFIN (Abstract #3243):
The poster presentation shared final results of the safety run-in cohort (n=16 patients) of the GRIFFIN study. These additional data showed that maintenance therapy with daratumumab and lenalidomide (D-R) improved both the sCR rate and MRD negativity rate in patients with NDMM who underwent D-RVd induction, autologous stem cell transplant (ASCT) and D-RVd consolidation. This deepening of responses was associated with durable remissions, and no new safety signals were observed with maintenance therapy.2

Initial findings from the safety run-in cohort for GRIFFIN:
By the end of post-transplant consolidation, the sCR rate was 56 percent.2
MRD negativity (10-5) at the end of consolidation was observed in 50 percent of patients, and no patients were MRD negative at 10-6.2
New findings:
The sCR rate improved to 94 percent by the end of both 12 and 24 months of D-R maintenance therapy.2
By the end of 24 months of D-R maintenance therapy, 81 percent of patients were MRD negative at 10-5, with five patients (31 percent) MRD negative at 10-6.2
At a median follow-up of 40.8 months, three of 16 patients had progressed, with estimated 24-month and 36-month PFS rates of 94 percent and 78 percent, respectively.2
With longer follow-up including two years of D-R maintenance therapy, no new safety concerns were identified.2
"The stringent complete response and minimal residual disease negativity rates with daratumumab combination maintenance therapy for transplant-eligible patients further solidify daratumumab as a foundational treatment for multiple myeloma," said Dr Catherine Taylor, Vice President, Medical Affairs Therapeutic Area Strategy, Europe, Middle East and Africa (EMEA), Janssen-Cilag Ltd., Middle East. "At Janssen, we remain focused on pursuing effective treatment combinations and investigating different endpoints, such as minimal residual disease, in order to provide effective treatments to patients across the spectrum of multiple myeloma."

"We continue to be encouraged by the GRIFFIN data showing deeper and improved responses in patients with newly diagnosed, ASCT-eligible multiple myeloma," said Andree Amelsberg, M.D., MBA, Vice President, U.S. Medical Affairs, Oncology Medical Affairs, Janssen Scientific Affairs, LLC. "These data show promising results for patients with newly diagnosed multiple myeloma and we remain committed to exploring the full potential of daratumumab and daratumumab subcutaneous formulation."

*Peter Voorhees is lead investigator of the GRIFFIN study and was not compensated for any media work.

#ENDS#

About the GRIFFIN Study3
The Phase 2 GRIFFIN (NCT02874742) study has enrolled and treated more than 200 adults ages 18-70 years with NDMM and who are eligible for high-dose therapy/autologous stem cell therapy (ASCT).

In the safety run-in cohort, patients received 25 mg of lenalidomide orally on Days 1-14; 1.3 mg/m2 of bortezomib subcutaneously on Days 1, 4, 8 and 11; and 20 mg of dexamethasone on Days 1, 2, 8, 9, 15 and 16, every 21 days during the induction and consolidation phases (Cycles 1-6). Daratumumab 16 mg/kg IV was given on Days 1, 8 and 15 of Cycles 1-4 and on Day 1 of Cycles 5-6.

During maintenance phase (Cycles 7-32), patients received 10 mg daily of lenalidomide (15 mg beginning at Cycle 10 if tolerated) on Days 1-21 every 28 days and daratumumab 16 mg/kg IV every 56 days; this was amended to every 28 days based upon emerging clinical pharmacokinetic data demonstrating improved target saturation with every 4-week maintenance dosing. Maintenance therapy with lenalidomide may be continued beyond Cycle 32 in both arms, per local standard of care.

In the subsequent randomised Phase 2 portion of the study, approximately 200 patients were randomised and received treatment with RVd, induction and consolidation, ASCT and maintenance therapy with lenalidomide; or daratumumab and RVd, ASCT and maintenance therapy with daratumumab and lenalidomide.

About daratumumab and daratumumab SC
In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialise daratumumab. Since launch, it is estimated that more than 154,000 patients have been treated with daratumumab worldwide.4 Daratumumab is the only CD38-directed antibody approved to be given subcutaneously to treat patients with multiple myeloma. Daratumumab SC is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology.5

CD38 is a surface protein that is highly expressed across multiple myeloma cells, regardless of the stage of disease. Daratumumab SC binds to CD38 and induces myeloma cell death through multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), as well as through apoptosis, in which a series of molecular steps in a cell lead to its death.6

Data across nine Phase 3 clinical trials in multiple myeloma and light chain (AL) amyloidosis, in both the frontline and relapsed settings, have shown that daratumumab-based regimens resulted in significant improvement in progression-free survival and/or overall survival.7,8,9,10,11,12,13,14 Additional studies are underway to assess the efficacy and safety of daratumumab SC in the treatment of other malignant and pre-malignant haematologic diseases in which CD38 is expressed, including smouldering myeloma and AL amyloidosis.15,16

For further information on daratumumab, please see the Summary of Product Characteristics at View Source

About Multiple Myeloma
Multiple myeloma (MM) is an incurable blood cancer that starts in the bone marrow and is characterised by an excessive proliferation of plasma cells.17 In Europe, more than 48,200 people were diagnosed with MM in 2018, and more than 30,800 patients died.18 Around 50 percent of newly diagnosed patients do not reach five-year survival,19,20 and almost 29 percent of patients with multiple myeloma will die within one year of diagnosis.21

Although treatment may result in remission, unfortunately, patients will most likely relapse as there is currently no cure.22 Relapsed and refractory myeloma is defined as disease that is nonresponsive while on salvage therapy, or progresses within 60 days of last therapy in patients who have achieved minimal response (MR) or better at some point previously before then progressing in their disease course.23 While some patients with MM have no symptoms at all, others are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.24 Patients who relapse after treatment with standard therapies, including proteasome inhibitors and immunomodulatory agents, have poor prognoses and require new therapies for continued disease control.25

On December 7, 2020 CEL-SCI Corporation (NYSE American: CVM) reported that the Phase 3 study is in the final stage of review which involves statistical analysis of all study data (Press release, Cel-Sci, DEC 7, 2020, View Source [SID1234572371]).. Data lock has already been completed.

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Since the required number of events to allow statistical analysis of CEL-SCI’s Phase 3 study in head and neck cancer was reached earlier this year, the Clinical Research Organizations (CROs) managing CEL-SCI’s Phase 3 study, Ergomed and ICON, had been performing data base lock of the study results. Data base lock is a very important and time intensive process that needs to be completed to ensure any study’s data are accurate and as complete as possible before the results of the study can be statistically evaluated and reliable conclusions drawn regarding the study’s outcome(s). This process was particularly complicated for CEL-SCI’s Phase 3 study because the study was conducted in over 20 countries on three continents, and many of these countries had, and still have, severe shutdowns due to the COVID-19 pandemic.

The statistical analysis of our Phase 3 study data is being performed according to a statistical analysis plan that was approved in advance of data lock. The analysis is being conducted by independent unbiased contractors. CEL-SCI is not involved in this process. Once the analysis has been completed, CEL-SCI will become privy to the study results. At that time, shareholders will be advised of the results through a public announcement. CEL-SCI also plans to publish the results in peer reviewed scientific journals.

"Our goal has been to create a cancer drug that is both non-toxic and works with the body’s immune system to increase the ‘intent to cure’ success rate of the first-line cancer treatment. We believe that immunotherapy should be administered before, not after, surgery, radiation and chemotherapy have damaged the immune system. We further believe that success in head and neck cancer should lead to many new ways of helping cancer patients." said Geert Kersten, CEO of CEL-SCI Corporation. "We are grateful to our shareholders for believing in us and supporting us during the very long Phase 3 study."

On December 7, 2020 OncoMyx Therapeutics, a privately-held oncolytic immunotherapy company, reported that The University of Western Ontario (Western) has assigned to OncoMyx the technology and patent rights associated with pioneering research on the use of myxoma virus in the treatment of cancer (Press release, OncoMyx Therapeutics, DEC 7, 2020, View Source [SID1234572370]). This research was led by OncoMyx cofounder Grant McFadden, Ph.D., when he was a Professor at Western and the Robarts Research Institute.

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Lisa Cechetto, the Executive Director of WORLDiscoveriesTM, the technology transfer office for Western, Robarts Research Institute, and Lawson Research Institute, said, "We are pleased to assign these patents to OncoMyx, as it is important that the outputs of pioneering research, such as Dr. McFadden’s use of myxoma virus to create novel oncolytic therapies, be further developed to improve the lives of cancer patients or others who may benefit."

"The assignment of this technology and intellectual property to OncoMyx further reinforces our IP portfolio protecting our use of myxoma virus and our pipeline of myxoma virotherapies for the treatment of cancer," said Steve Potts, Ph.D., MBA, cofounder and chief executive officer of OncoMyx. "The myxoma virus has a number of important attributes that we are leveraging to develop potentially impactful oncolytic immunotherapies with the goal of increasing the number of cancer patients who could benefit from immunotherapies."

"Oncolytic viruses are emerging as a new pillar of cancer care with the potential to expand the effectiveness of immunotherapies, such as immune checkpoint inhibitors," said Dr. McFadden. "I am pleased that OncoMyx has been assigned the patent rights associated with the pioneering myxoma research that was done at Western, as the myxoma virus is unique as a technology platform to build oncolytic immunotherapies."

About Myxoma Virotherapy for the Treatment of Cancer

The myxoma virus is highly immuno-interactive and can selectively infect and kill a broad range of cancer cell types. Because myxoma virus is not pathogenic to humans, myxoma virotherapy does not have to overcome pre-existing immunity. As a large dsDNA poxvirus, myxoma is engineerable to express multiple transgenic payloads, such as immunomodulatory proteins, to target multiple points in the cancer immunity cycle. The company’s preclinical data demonstrates efficacy of multi-armed myxoma virotherapies via intravenous (IV) and intratumoral (IT) delivery in a number of tumor models across multiple cancer indications and supports a pan-tumor approach to expand the therapeutic effectiveness of immunotherapies.

On December 7, 2020 Artiva Biotherapeutics, Inc., an oncology company focused on developing and commercializing primary allogeneic natural killer (NK) cell therapies to treat cancer, reported U.S. Food and Drug Administration (FDA) allowance of the company’s investigational new drug (IND) application for AB-101, an optimized and cryopreserved off-the-shelf NK cell therapy (Press release, Artiva Biotherapeutics, DEC 7, 2020, View Source [SID1234572369]). Artiva plans to conduct a Phase 1/2 clinical trial at up to 20 U.S. cancer centers to assess the safety and clinical activity of AB-101 alone and in combination with the anti-CD20 monoclonal antibody, rituximab, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL) who have progressed beyond two or more prior lines of therapy.

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"Monoclonal antibodies are mainstays of cancer therapy, but many patients have sub-optimal responses, and those who progress have limited options," said Tom Farrell, President and CEO of Artiva. "With AB-101, we intend to leverage our proprietary off-the-shelf NK cell platform to enhance and extend the clinical application of monoclonal antibodies and other cancer targeted therapies that rely on NK cells to mediate their anti-cancer activity."

AB-101 is a cryopreserved NK cell product candidate with high and consistent expression of tumor-engaging receptors including the high-affinity variant of CD16. These NK cell attributes have demonstrated improved outcomes for cancer patients in both the transplant and therapeutic monoclonal antibody settings. Furthermore, in preclinical models, AB-101 demonstrates enhanced antibody-dependent cellular cytotoxicity with a variety of therapeutic antibodies.

"Allogeneic NK cells have been tested in clinical trials for more than a decade. Based on this experience, we expect that AB-101 will be well tolerated. This contrasts with T-cell therapies that are associated with life-threatening cytokine release syndrome, neurotoxicity, and graft-versus-host-disease," said Jason Litten, MD, Chief Medical Officer of Artiva.

About the Clinical Trial

After receiving standard lymphodepleting chemotherapy, patients will receive eight weekly doses of up to four billion NK cells per AB-101 dose. The primary endpoint is objective response rate, per the 2014 Lugano Criteria. In Phase 2, indolent and aggressive NHL patients will receive AB-101 plus rituximab combination therapy in two parallel Simon two-Stage designed cohorts, each with independent interim analyses for objective clinical response.

About AB-101 NK Cell Therapy

Leveraging a proprietary manufacturing platform that enables expansion and cryopreservation of cord blood-derived NK cells, Artiva is advancing AB-101 as a universal primary NK cell product candidate for use in combination with targeting therapies such as monoclonal antibodies or NK cell engagers. Starting cord blood units are selected for B-KIR haplotype and the homozygous polymorphism of CD16 that confers high affinity binding to antibodies, including monoclonal antibody therapies. Starting cells are isolated then expanded and activated utilizing a proprietary campaign-based manufacturing process in a state-of the art GMP facility. AB-101 is delivered as cryopreserved vials of one billion highly active NK cells in an infusion-ready media for thawing and administration on demand at the clinical trial site. The manufacturing process generates thousands of cryovials of AB-101 from a single cord blood unit.