On December 7, 2020 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that it plans to offer and sell, subject to market and other conditions, shares of its common stock in an underwritten public offering (Press release, Syndax, DEC 7, 2020, View Source [SID1234572340]). There can be no assurance as to whether or when the offering may be completed, or the actual size or terms of the offering. Syndax also expects to grant the underwriters a 30-day option to purchase up to an additional 15% of the number of shares sold in the public offering. All of the shares in the proposed offering are to be sold by Syndax.

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Goldman Sachs & Co. LLC, Citigroup and Cowen are acting as joint book-running managers for the offering. BTIG is acting as lead manager for the offering. Baird is acting as co-manager for the offering.

The shares are being offered pursuant to a "shelf" registration statement previously filed and declared effective by the Securities and Exchange Commission (SEC). A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available on the website of the SEC at www.sec.gov. When available, copies of the preliminary prospectus supplement and accompanying prospectus relating to the offering may be obtained from: Goldman Sachs and Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, telephone: 866-471-2526, facsimile: 212-902-9316 or by emailing [email protected]; or Citigroup Global Markets Inc., c/o Broadridge Financial Services, 1155 Long Island Avenue, Edgewood, NY 11717, or by phone at (800) 831-9146; or Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, or by email at [email protected], or by phone at (833) 297-2926.

This press release shall not constitute an offer to sell, or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. Any offer, if at all, will be made only by means of a prospectus supplement and accompanying prospectus, which are a part of the effective registration statement.

On December 7, 2020 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, reported that four oral presentations and six poster presentations containing clinical data and analyses related to imetelstat, the Company’s first-in-class telomerase inhibitor, were presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Geron, DEC 7, 2020, View Source [SID1234572339]). The presentations are available at www.geron.com/r-d/publications.

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"Our imetelstat presentations at this year’s ASH (Free ASH Whitepaper) provide strong support for our two registration-enabling Phase 3 clinical trials: IMerge, in lower risk MDS and IMpactMF, in refractory MF," said Aleksandra Rizo, M.D., Ph.D., Geron’s Chief Medical Officer. "We believe the analyses and data from our Phase 2 IMerge and IMbark trials provide strong evidence of imetelstat’s disease-modifying activity, as well as clinical benefits of durable transfusion independence in MDS and improvement in overall survival in MF."

Lower Risk Myelodysplastic Syndromes (MDS) – Oral Presentation

Title: Treatment with Imetelstat Provides Durable Transfusion Independence (TI) in Heavily Transfused Non-del(5q) Lower Risk MDS (LR-MDS) Relapsed/Refractory (R/R) to Erythropoiesis Stimulating Agents (ESAs) (Abstract #658)

The oral presentation reported long-term efficacy, safety and biomarker data from 38 patients in the IMerge Phase 2 clinical trial, based on a February 4, 2020 cut-off date and a median follow-up of 24 months. Consistent with prior presentations, 42% of patients achieved >8-week red blood cell transfusion independence (RBC-TI) with a median duration of 20 months, which is the longest so far reported with any agent in relapsed/refractory non-del(5q) lower risk MDS. In addition, 29% of patients were transfusion free more than a year. Reduction in the SF3B1 mutation, one of the key mutations correlated with ineffective erythropoiesis in lower risk MDS, correlated with longer transfusion independence and shorter onset to achieve transfusion independence. These biomarker data together with the durability of transfusion independence provide evidence for the disease-modifying activity of imetelstat. These data were previously presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress in June.

Relapsed/Refractory Myelofibrosis (MF) – Three Oral Presentations

Title: Potential Disease-Modifying Activity of Imetelstat Demonstrated By Reduction in Cytogenetically Abnormal Clones and Mutation Burden Leads to Clinical Benefits in Relapsed/Refractory Myelofibrosis Patients (Abstract #346)

This oral presentation reported significant dose-dependent reduction of mutation burden by imetelstat, including complete elimination of mutations in MF driver and non-driver genes. A greater than 20% reduction in variant allele frequency by imetelstat treatment correlated with improved clinical benefits, including higher rates of spleen and symptom responses, bone marrow fibrosis improvement and longer overall survival (OS). As concluded in the presentation, imetelstat demonstrated disease-modifying activity by targeting malignant clones, improvement in bone marrow fibrosis and OS.

Title: Telomerase Activity, Telomere Length and hTERT Expression Correlate with Clinical Outcomes in Higher-Risk Myelofibrosis (MF) Relapsed/Refractory (R/R) to Janus Kinase Inhibitor Treated with Imetelstat (Abstract #347)

This oral presentation reported dose-dependent inhibition of telomerase, as evaluated by reductions in telomerase activity, human reverse transcriptase (hTERT) levels and telomere length in patients treated with imetelstat in the IMbark Phase 2 clinical trial. Analyses of these biomarker data correlated with clinical responses and longer OS. In addition, dose-dependent reduction in variant allele frequency of driver mutations was noted, indicating that imetelstat has disease-modifying activity by targeting the underlying MF malignant clones. As expected for a telomerase inhibitor, treatment with imetelstat at 9.4 mg/kg improved clinical outcomes in patients with shorter telomeres and higher hTERT expression at baseline. These data are consistent with telomere biology in cancer cells and provide evidence for on-target mechanism of action of imetelstat through telomerase inhibition. These results were previously reported as a poster presentation at the EHA (Free EHA Whitepaper) Annual Congress in June.

Title: Favorable Overall Survival with Imetelstat Treatment Correlates with Other Clinical Benefits in Intermediate-2 or High-Risk Myelofibrosis Relapsed/Refractory to Janus Kinase Inhibitor (Abstract #53)

This oral presentation reported the correlation of overall survival results from the IMbark Phase 2 with clinical benefits observed with imetelstat treatment. The correlation analyses showed a trend of longer OS in patients who achieved symptom response, spleen volume reductions ranging from > 10% to > 35%, and statistically significant improvement in OS in patients with improved bone marrow fibrosis, in a dose-dependent manner. These results were previously reported as a poster presentation at the EHA (Free EHA Whitepaper) Annual Congress in June.

Relapsed/Refractory Myelofibrosis (MF) – Three Poster Presentations

Collectively, these poster presentations described on-target and disease-modifying activity of the higher dose of imetelstat from the IMbark Phase 2, and how that relates to better clinical outcomes, including OS, fibrosis improvement and symptom response, especially in a subset of patients defined as triple negative MF, known to have poor outcome.

Title: Correlation Analyses of Imetelstat Exposure with Pharmacodynamic Effect, Efficacy and Safety in A Phase 2 Study in Patients with Higher-risk Myelofibrosis Refractory to Janus Kinase Inhibitor Identified an Optimal Dosing Regimen for Phase 3 Study (Abstract #1283)

Title:Imetelstat Treatment Results in Clinical Benefits, Including Improved Overall Survival, in Patients with Higher-Risk Triple Negative Myelofibrosis Relapsed/Refractory to Janus Kinase Inhibitors (JAKi) (Abstract #3084)

Title:Treatment with Imetelstat Improves Myelofibrosis-Related Symptoms and Other Patient-Reported Outcomes in Patients with Relapsed or Refractory Higher-Risk Myelofibrosis (Abstract #3088)

Myeloproliferative Neoplasms (MPN) – Poster Presentation

Title: Imetelstat Inhibits Telomerase and Prevents Propagation of ADAR1-Activated Myeloproliferative Neoplasm and Leukemia Stem Cells (Abstract #1264)

Collaborators at UC San Diego reported non-clinical data on hTERT and ADAR1 activity in pre-leukemia stem cells and leukemia stem cells (LSC). In various lab experiments and animal models, treatment with imetelstat prevented pre-leukemia stem cells from evolving into LSCs, suggesting telomerase inhibition may be an effective strategy for preventing MPN progression.

Two Trials in Progress Poster Presentations – Ongoing IMerge Phase 3 and Upcoming IMpactMF Phase 3

Title:IMerge: A Phase 3 Study to Evaluate Imetelstat in Transfusion-Dependent Subjects with IPSS Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) that is Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment (Abstract #3113)

The IMerge Phase 3 clinical trial is a double-blind, randomized, placebo-controlled clinical trial with registration intent. The trial is designed to enroll approximately 170 transfusion dependent patients with Low or Intermediate-1 risk myelodysplastic syndromes (MDS), also referred to as lower risk MDS, who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA). The IMerge Phase 3 is currently enrolling patients.

The primary endpoint is the rate of red blood cell (RBC) transfusion independence (TI) for any consecutive period of eight weeks or longer, or 8-week RBC-TI rate. Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks, or 24-week RBC-TI rate, and the rate of hematologic improvement-erythroid (HI-E), defined as a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden.

Title:A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat Versus Best Available Therapy in Patients with Intermediate-2 or High-risk Myelofibrosis (MF) Refractory to Janus Kinase (JAK) Inhibitor (Abstract #2194)

The IMpactMF Phase 3 clinical trial in refractory MF is a registration-enabling trial with OS as the primary endpoint. Approximately 320 patients with Intermediate-2 or High-risk MF will be randomized to receive either imetelstat or best available therapy, which will exclude JAK inhibitors. Key secondary endpoints include symptom response, spleen response, progression free survival, complete response, partial response, clinical improvement, duration of response, safety, pharmacokinetics, and patient reported outcomes.

Geron expects the trial to be open for screening and enrollment in the first quarter of 2021.

About Phase 2 IMerge and IMbark Trials

The IMerge Phase 2 was an open label, single arm trial to assess the safety and efficacy of a 7.5 mg/kg dose of imetelstat administered as an intravenous infusion every four weeks in transfusion dependent lower risk MDS patients who had relapsed after or were refractory to prior treatment with ESA. The IMerge Phase 2 is no longer enrolling patients, and patients remaining in the treatment phase continue to receive imetelstat treatment, per investigator discretion.

The IMbark Phase 2 was designed to evaluate two dosing regimens of imetelstat (either 4.7 mg/kg or 9.4 mg/kg administered by intravenous infusion every three weeks) in patients with Intermediate-2 or High-risk myelofibrosis (MF) who have relapsed after or are refractory to prior treatment with a janus kinase inhibitor (JAKi). The co-primary efficacy endpoints for IMbark were spleen response rate, defined as the proportion of patients who achieve a reduction of at least 35% in spleen volume as assessed by imaging, and symptom response rate, defined as the proportion of patients who achieve a reduction of at least 50% in Total Symptom Score (TSS), at 24 weeks. Key secondary endpoints were overall survival (OS) and safety. The trial is complete and closed.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Early clinical data strongly suggest that imetelstat has disease-modifying activity through the apoptosis of malignant stem and progenitor cells, which allows potential recovery of normal hematopoiesis. Current clinical studies of imetelstat include IMerge, an ongoing Phase 2/3 trial in lower risk myelodysplastic syndromes (MDS), and IMpactMF, an upcoming Phase 3 clinical trial in refractory myelofibrosis (MF). Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis-stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus kinase (JAK) inhibitor treatment.

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