On December 7, 2020 Trillium Therapeutics Inc. ("Trillium" or the "Company") (NASDAQ/TSX: TRIL), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place virtually from December 5-8, 2020, and provides guidance for 2021 (Press release, Trillium Therapeutics, DEC 7, 2020, View Source [SID1234572338]).

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"Our presentations at ASH (Free ASH Whitepaper), as of a data cutoff of November 3, build upon our last corporate update from September 8," said Jan Skvarka, President and CEO of Trillium Therapeutics. "We presented data where TTI-622 continued to demonstrate a strong safety profile, as well as further dose-dependent improvements in receptor occupancy and PK data. We completed a safety evaluation of the 12 mg/kg dose level, with results indicating no observed dose-limiting toxicity or other major safety concerns, and we escalated dosing to 18 mg/kg. As of the November 3 cutoff, one patient at the 12 mg/kg dose level achieved a stable disease assessment and continued on therapy. TTI-621 continued dosing at 2 mg/kg. We are looking forward to further progress in 2021, moving to combination studies in heme malignancies and solid tumors, and building on a foundation of demonstrated monotherapy activity of our molecules."

The posters and oral presentation described below were presented at ASH (Free ASH Whitepaper):

TTI-622: Poster Presentation, Publication Number 1191

Investigational CD47-Blocker TTI-622 Shows Single-Agent Activity in Patients with Advanced Relapsed or Refractory Lymphoma: Update from the Ongoing First-in-Human Dose Escalation Study

Presenter: Krish Patel, M.D., Center for Blood Disorders and Stem Cell Transplantation, Swedish Cancer Institute, Seattle, WA

Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)-Results from Prospective Clinical Trials: Poster I

This poster presentation provided a further update on the safety and anti-tumor activity observed in the ongoing open-label Phase 1 dose escalation study of TTI-622 in patients with relapsed or refractory lymphoma (NCT03530683). As of the data cutoff date of November 3, a total of 31 patients had been enrolled in the first seven cohorts, receiving weekly intravenous doses between 0.05-12 mg/kg. All dose levels were well tolerated and a maximum tolerated dose (MTD) was not reached. Adverse events (AEs) were predominantly Grade 1-2; related AEs ≥Grade 3 were neutropenia (13%), thrombocytopenia (3%) and anemia (3%). Dose-dependent increases in TTI-622 serum exposure supported continued dose escalation beyond 12 mg/kg, and dose-dependent increases in receptor occupancy (RO) durability were observed. Objective responses were achieved in 6 of 22 (27%) response-evaluable patients, with an overall response rate (ORR) of 35% (6/17) among response-evaluable patients at dose levels ≥0.8 mg/kg. All responses occurred within the first eight weeks of treatment across multiple lymphoma indications, and included one complete response (CR) and five partial responses. The CR patient treatment was ongoing at 534 days and showed evidence of expansion of new and existing T-cell clones. The study is currently dosing at 18 mg/kg.

TTI-621: Oral Presentation, Publication Number 646

Updates from Ongoing, First-in-Human Phase 1 Dose Escalation and Expansion Study of TTI-621, a Novel Biologic Targeting CD47, in Patients with Relapsed or Refractory Hematologic Malignancies

Presenter: Steven M. Horwitz, M.D., Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY

Session: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Immunotherapy in T/NK Cell Lymphoma

This oral presentation provided a further update on the safety and anti-tumor activity observed in the ongoing open-label Phase 1 dose escalation study of intravenous TTI-621 in patients with relapsed or refractory hematologic malignancies (NCT02663518). The study consists of four parts: (a) "Parts 1-3" in hematologic malignancies, with dosing up to 0.5 mg/kg, conducted under initial dose-limiting toxicity (DLT) criteria, now complete; and (b) "Part 4" in cutaneous T-cell lymphoma (CTCL), utilizing revised DLT criteria for thrombocytopenia and an amended protocol to allow for dosing above 0.5 mg/kg, currently ongoing. In Part 4, 17 CTCL patients, including two at the 2 mg/kg dose level, completed DLT evaluation as of the November 3, 2020 data cutoff. TTI-621 was well tolerated and an MTD in Part 4 was not reached. Across Parts 1-4, the most common treatment-related AEs were infusion-related reactions (44%) and thrombocytopenia (30%), which was transient and not dose-limiting. Monotherapy activity was observed in CTCL (17% ORR), peripheral T-cell lymphoma (18% ORR) and diffuse large B-cell lymphoma (29% ORR). The majority of these patients received doses of 0.5 mg/kg or lower; a dose-efficacy relationship in Part 4 was difficult to ascertain due to the small sample sizes. Dose-dependent increases in drug exposure and RO of 40-65% at doses 0.5-1.4 mg/kg were observed. Evidence of changes in both innate and adaptive immune cells was apparent in a responding CTCL patient. The study is currently enrolling at the 2 mg/kg dose level.

The posters are available in the Events & Presentations section of the Company’s website, and an updated corporate presentation can also be found on the Company’s website at www.trilliumtherapeutics.com.

2021 Guidance

Around the end of Q1 2021, Trillium plans to hold an R&D Day, in which the Company will:

Provide data updates on TTI-622 and TTI-621
Declare TTI-622 and TTI-621 priorities
Announce disease indication, patient setting and drug combination priorities
Outline high-level clinical development plans
Furthermore, Trillium anticipates initiating the following studies in 2021:

2-3 proof of concept studies in heme malignancies in combinations with other agents, and
Signal-seeking solid tumor study in a variety of indications and drug combinations
*****

Trillium will host a conference call on Monday, December 7, 2020 at 4:30PM EST to discuss the clinical update. The conference call may be accessed by telephone or webcast as described below.

International Dial-In Number: +1 236-389-2162

Conference ID: 3169183

Webcast link:

View Source

The archived webcast will be available on Trillium’s website for 30 days following the call.

On December 7, 2020 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported that it has commenced an underwritten public offering, subject to market and other conditions, to issue and sell $200,000,000 of shares of its common stock (Press release, Kura Oncology, DEC 7, 2020, View Source [SID1234572337]). In connection with the offering, Kura expects to grant the underwriters a 30-day option to purchase up to an additional $30,000,000 of the shares of common stock offered in the public offering. All of the shares in the proposed offering will be offered by Kura. There can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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SVB Leerink, Credit Suisse, Barclays and Stifel are acting as joint bookrunning managers in the offering.

The securities described above are being offered by Kura pursuant to a shelf registration statement on Form S-3, including a base prospectus, that was previously filed by Kura with and became effective by rule of the Securities and Exchange Commission (the "SEC") on December 7, 2020. A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available for free on the SEC’s website located at View Source Copies of the preliminary prospectus supplement and the accompanying prospectus relating to the offering, when available, may be obtained from: SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at (800) 808-7525, ext. 6132, or by email at [email protected]; Credit Suisse Securities (USA) LLC, Attention: Prospectus Department, 6933 Louis Stephens Drive, Morrisville, NC 27560, by telephone at (800) 221-1037, or by email at [email protected]; Barclays Capital Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by email at [email protected], or by telephone at (888) 603-5847; or Stifel, Nicolaus & Company, Incorporated, Attention: Syndicate, One Montgomery Street, Suite 3700, San Francisco, CA 94104, or by email at [email protected], or by telephone at (415) 364-2720.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

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.