On December 7, 2020 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported updated data from its ongoing Phase 1, open-label, dose escalation study of CA-4948, an IRAK4 kinase inhibitor, for the treatment of patients with relapsed or refractory (R/R) non-Hodgkin’s lymphoma (NHL), including patients with diffuse large B-cell lymphoma (DLBCL), Waldenström’s macroglobulinemia (WM) and oncogenic MYD88 mutations, and also declared the recommended Phase 2 dose of the investigational drug (Press release, Curis, DEC 7, 2020, View Source [SID1234572336]). The new results, which will be shared in a virtual oral presentation at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, show that the recommended Phase 2 dose of 300 mg BID of CA-4948 monotherapy provides potent and durable anti-cancer activity in patients with relapsed or refractory non-Hodgkin’s lymphoma.

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"We are tremendously pleased to report that IRAK4 inhibition with CA-4948 monotherapy could potentially offer a novel treatment approach for patients with NHL," said James Dentzer, President and Chief Executive Officer of Curis. "We believe these preliminary data, demonstrating the tolerability and durable anti-cancer activity of single-agent CA-4948 therapy for these extremely sick patients, validate our development approach for this program and reaffirm our enthusiasm for the therapeutic potential of a combination therapy with proven synergistic treatments like ibrutinib. Anti-cancer activity was observed across multiple dose levels, which provides additional flexibility as we continue to develop CA-4948 for NHL. Among the active dose levels, we believe that 300 mg twice-daily has the potential to strike the most favorable balance of durable anti-cancer activity and tolerability for long-term treatment. We are also highly encouraged by the data gathered on our two exploratory biomarkers, which we believe support a compelling patient enrichment strategy. We are eager to work with our investigators, clinicians, and the broader patient community to advance the development of this novel treatment approach in a patient population in need of better treatment options."

"CA-4948 consistently reduced tumor burden at the recommended Phase 2 dose of 300 mg twice daily. Data like these, even at this early stage, are compelling for the patients and physicians contending with this degree of relapsed or refractory disease," said Robert Martell, Head of R&D of Curis. "These are patients facing the poorest prognoses after numerous prior lines of other therapies failed to meaningfully temper their disease progression. For these patients, any degree of tumor reduction may represent a significant improvement. Equally promising is the prospect of long-term tumor reduction and tolerability. This profile, along with the unique synergistic potential of a CA-4948/BTK inhibitor combination, could potentially offer a groundbreaking development in a disease area with considerable need."

The reported updated preliminary data are from Curis’s ongoing Phase 1, open-label, dose escalation 3+3 study designed to evaluate the safety and tolerability of CA-4948, in addition to pharmacokinetics, pharmacodynamics, anti-cancer activity, and biomarker correlations, in patients with R/R NHL. Seven dosing cohorts have been treated in continuous 21-day cycles at levels of 50 mg and 100 mg once-daily (QD), and 50 mg, 100 mg, 200 mg, 300 mg, or 400 mg twice-daily (BID). The data being reported from this ongoing trial are preliminary and subject to change.

Key findings from the ongoing Phase 1 study include:

CA-4948 was demonstrated to be generally well-tolerated, most AEs have been Grade 1-2.
Preliminary tolerability profile supports potential long-term treatment and combination with other active drugs against NHL.
Enrolled patients include those with DLBCL, WM, marginal zone lymphoma (MZL), follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), transformed high-grade-B-Cell lymphoma (HGBCL), and mantle cell lymphoma (MCL).
Patients enrolled experienced a median of 4 prior lines of treatment (range 1-8).
Anti-cancer activity, as measured by reduction of tumor burden, was observed in:
6 of 7 evaluable patients receiving RP2D of 300 mg BID, with a mean reduction of 27% (ranging from 6% to 67%).
One patient with WM, who dose escalated from 50mg to 100mg to 200mg to 300mg (all doses, BID), experienced dose-dependent reductions in tumor burden at each dose level, eventually reaching a tumor burden reduction of 67% (partial response) following escalation to the 300mg BID dose. This patient continues to remain on therapy after 728 days (as of December 7th, 2020).
3 patients have been on therapy for greater than 1 year.
Encouraging early data for two potential biomarkers (NF-κB p-p50 and MYD88).
Early data for NF-κB p-p50 biomarker may support patient selection:
Patients whose tumors do not exhibit NF-κB activity may not be amenable to NF-κB downregulation.
7 of 7 patients testing negative for p-p50 at baseline experienced disease progression.
2 of these patients were dosed at 200mg BID.
Patients whose tumors do exhibit NF-κB activity may be amenable to NF-κB downregulation.
6 of 7 patients testing positive for p-p50 at baseline achieved stable disease or tumor shrinkage.
1 of these patients was dosed at 300mg BID.
Early data for MYD88 biomarker may support patient enrichment:
Both patients identified as positive for MYD88 mutation experienced tumor reduction, including a partial response.
More data are needed to confirm this potential predictive biomarker, but we believe positive patient outcomes are consistent with the thesis that patients with MYD88-mutated tumors should benefit from IRAK4 inhibition.
Webcast Event Information

Curis management will host a virtual KOL event tomorrow, December 8, 2020 at 8:00 am ET to discuss these results with Dr. Amit Verma, Professor of Medicine-Oncology at Albert Einstein College of Medicine, and Director of the MDS Program at Montefiore Medical Center located in Bronx, NY. To access the webcast, please visit the Events and Presentations section of the Curis website at View Source

On December 7, 2020 KaliVir Immunotherapeutics LLC (CEO: Helena Chaye, Ph.D., J.D., "KaliVir") and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported that they entered into a worldwide licensing agreement for the research, development, and commercialization of VET2-L2, an intravenously administered oncolytic virus for Immuno-Oncology, as well as a research collaboration to generate a Second Product, a follow-on virus (Press release, Astellas, DEC 7, 2020, View Source [SID1234572335]).

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KaliVir holds its unique technology platform based on genetically modified vaccinia virus, and is developing VET2-L2, an oncolytic vaccinia virus as their lead program. VET2-L2, which is delivered by intravenous administration, reaches and destroys cancer cells and activates anti-cancer immunity through expression of therapeutic transgenes. KaliVir’s vaccinia virus-based oncolytic viral immunotherapies can be delivered intravenously to cancer patients, eliminating the need for complicated procedures of the direct intra-tumoral administration and enables access for a broader patient population. VET2-L2 is in preclinical stage.

This collaboration, which combines KaliVir’s expertise in the development of oncolytic viruses with Astellas’ capabilities in advanced drug development and its global business experience, will enable both parties to develop new Immuno-Oncology therapies.

Under the terms of the agreement, Astellas will pay to KaliVir up to US$56 million in the form of an upfront payment and other payments to support research and preclinical activities related to VET2-L2 and the Second Product. Additionally, Astellas may pay up to US$307 million and up to US$271 million for development, regulatory and commercialization of VET2-L2 and Second Product, respectively. Astellas also may make royalty payments on net sales of each licensed product.

"We are thrilled that Astellas has chosen KaliVir, and specifically VET2-L2, our lead product candidate, to add to their oncology program. VET2-L2, a multi-mechanistic, intravenously-delivered oncolytic vaccinia virus, has demonstrated strong precinical data prompting us to plan our initial clinical trial for VET2-L2," said KaliVir CEO Helena Chaye, Ph.D., J.D. "With Astellas’ excellent track record for drug development and commercialization, we believe that their commitment to collaborating with KaliVir represents strong third-party validation for our VET platform. We are commited to bringing this exciting product to cancer patients and believe that our collaboration with Astellas will expedite our ability to do this."

Naoki Okamura, Representative Director, Corporate Executive Vice President, Chief Strategy Officer and Chief Financial Officer, at Astellas said, "We, at Astellas, have positioned Immuno-Oncology as one of the Primary Focuses of our R&D strategy, and we are committed to developing the next generation of Immuno-Oncology therapies through new modalities and technologies. Oncolytic viruses are one of the therapies in which we are particularly focused as we strive to provide new options for patients who have no effective treatment options. We expect this KaliVir collaboration to enhance our pipeline and further expand our cancer treatment options as we work to develop innovative medical solutions that turn innovative science into VALUE for patients."

On December 7, 2020 Researchers from SWOG Cancer Research Network, a cancer clinical trials group funded by the National Cancer Institute (NCI), part of the National Institutes of Health, reported that have shown that isatuximab, a monoclonal antibody approved for the treatment of multiple myeloma, can effectively treat relapsed refractory AL amyloidosis, findings to be announced at the 2020 Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, SWOG Cancer Research Network, DEC 7, 2020, View Source [SID1234572334]).

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AL amyloidosis is a rare disease, with about 4,500 cases diagnosed each year in the United States. Like its cancerous cousin, multiple myeloma, AL amyloidosis involves plasma cells, in this case causing them to produce abnormal protein fibers that build up in tissues and organs, leading to vital organ dysfunction, failure, and death. Many drugs that work for multiple myeloma also work for people with AL amyloidosis. However, many AL amyloidosis patients see their disease return after initial treatment, creating a need for new therapy options. The SWOG team wanted to put isatuximab to the test with these relapsed refractory patients.

Emma Scott, MD, a medical director at the pharmaceutical company GSK and an adjunct associate professor in the Division of Hematology and Medical Oncology at Oregon Health & Science University (OHSU), designed the phase II trial while working full-time at OHSU. The trial is now led by Terri Parker, MD, of Yale Cancer Center, and Vaishali Sanchorawala, MD, of Boston Medical Center. The trial, S1702, enrolled 43 patients from 32 hospitals and clinics. All patients had previously been treated for AL amyloidosis, and 35 were eligible to receive the study drug. Patients received isatuximab intravenously every week for one 28-day cycle, then every other week for as many as 24 cycles. The median treatment time was about 12 months.

Researchers’ main objective was to determine patients’ hematologic response – a blood cell count that can be a good indicator of how well the treatment is working. Of the 35 patients who took isatuximab on S1702, there was an overall response rate of 77 percent. Of the 35 patients, hematological complete response was observed in one patient, very-good-partial response was found in 19 patients, and partial response was found in seven patients.

"This is encouraging news for patients who’ve already been treated for AL amyloidosis and who are looking for another, more effective treatment," Parker said. "This is the first study of isatuximab in this disease population, and if a phase III study confirms our results, we’ve opened up another treatment option for patients with this rare disease."

The SWOG team also gathered important safety information. Overall, 19 of the 35 patients stopped treatment, the most common reasons being adverse events, disease progression, sub-optimal response, and concerns related to COVID-19. The most common drug-related side effects were generally mild. They included infusion related reactions in 17 patients, or 49 percent of those taking the study drug, along with anemia and lymphopenia. Overall, researchers found a good safety profile, one similar to other monoclonal antibodies tested in AL amyloidosis.

Parker will share results of the SWOG study in an oral presentation on Dec. 7 at 1:30 p.m. PT at the 200 ASH (Free ASH Whitepaper) meeting. The ASH (Free ASH Whitepaper) abstract number is 728, and can be found here.

S1702 was supported by the National Institutes of Health through National Cancer Institute awards CA180888, CA180819, CA180820, and CA180821 and in part by Sanofi US.

Along with Parker and Sanchorawala, the SWOG team also includes Adam Rosenthal, MS, of the SWOG Statistics and Data Management Center; Heather J. Landau, MD, of Memorial Sloan Kettering Cancer Center; Erica L. Campagnaro, MD, of University of Michigan Rogel Cancer Center; Prashant Kapoor, MD, of Mayo Clinic; Natalia Neparidze, MD, of Yale University School of Medicine; Patrick Hagen, MD, of Loyola University Medical Center; Shayna Sarosiek, MD, of Boston University Medical Center; Emma C. Scott, MD, of GSK; Antje Hoering, PhD, the SWOG Statistics and Data Management Center; Brian G.M. Durie, MD, of Cedars-Sinai Medical Center; Saad Z. Usmani, MD, of Levine Cancer Institute; and Robert Z. Orlowski, MD, PhD, of The University of Texas MD Anderson Cancer Center.

On December 7, 2020 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of cancer and autoimmune diseases, reported it has entered into a research collaboration and license agreement with Janssen Biotech, Inc. (Janssen) (Press release, Xencor, DEC 7, 2020, View Source [SID1234572333]). The research and license agreement is focused on the discovery of XmAb bispecific antibodies against CD28, an immune co-stimulatory receptor on T cells, and an undisclosed prostate tumor target, for the potential treatment of patients with prostate cancer. Additionally, Xencor has a right to access select, predefined agents from Janssen’s portfolio of clinical-stage drug candidates and commercialized medicines to evaluate potential combination therapies in prostate cancer with agents in its own pipeline in non-registrational clinical studies. Janssen has the same right with Xencor’s portfolio of clinical-stage drug candidates to evaluate potential combination therapies in prostate cancer, as well.

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"Our XmAb bispecific Fc domains enable the creation of a wide range of multi-specific antibody and protein structures, such as bispecific antibodies in our new CD28 platform. These antibodies can co-stimulate T cells in a tumor-target dependent manner and can synergize with both checkpoint inhibitor therapies and other tumor-targeted agents, like CD3 bispecific antibodies, in order to enhance anti-tumor activity," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "In addition, the ability to study combinations of therapies from both companies’ prostate cancer portfolios leverages Xencor’s broad clinical pipeline and the leading prostate cancer therapeutics portfolio at Janssen. This collaboration with Janssen expands the use of our CD28 platform and complements our first wholly owned internal candidate, a B7-H3 x CD28 bispecific antibody designed to treat a range of solid tumors, which is currently advancing through preclinical development."

Under the terms of the agreement, Xencor will apply its XmAb bispecific Fc technology to create and characterize XmAb CD28 bispecific antibody candidates against the tumor target specified by Janssen. Preclinical activities and all clinical development, regulatory and commercial activities will be conducted by Janssen, which has exclusive worldwide rights to develop and commercialize the novel drug candidates. Xencor will receive an upfront payment of $50 million and will be eligible to receive development, regulatory and sales milestone payments and high-single digit to low-double digit percent royalties on net sales.

Upon clinical proof of concept for a bispecific antibody candidate, Xencor has the right to opt-in to fund 20 percent of development costs and to perform up to 30 percent of the detailing efforts in the United States; Xencor would be eligible for milestone payments and low-double digit to mid-teen percent royalties on net sales.

The agreement is subject to customary closing conditions, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act, and closing is expected to occur by year end.

On December 7, 2020 Helix BioPharma Corp. (TSX: "HBP") ("Helix" or the "Company"), an immunooncology company developing innovative drug candidates for the prevention and treatment of cancer, reported it has closed a private placement financing for gross proceeds of $1,100,000 (Press release, Helix BioPharma, DEC 7, 2020, View Source [SID1234572332]).

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The terms of the placement are for the purchase of units at $0.50 per unit. Each unit is comprised of one common share and one common share purchase warrant. Each common share purchase warrant will entitle the holder to purchase one common share at an exercise price of $0.70 and have an expiry of five years from the date of issuance. Helix intends to use the net proceeds of the private placement for working capital and research and development activities.

ACM Alpha Consulting Management AG provided financial advisory services to Helix in connection with the private placement.