8-K
CURIS INC (CRIS)
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event Reported): December 7, 2020
Curis, Inc.
(Exact Name of Registrant as Specified in Charter)
| Delaware | 000-30347 | 04-3505116 |
|---|---|---|
| (State or Other Jurisdiction<br> <br>of Incorporation) | (Commission<br> <br>File Number) | (I.R.S. Employer<br> <br>Identification Number) |
| 128 Spring Street, Building C - Suite 500, Lexington, MA 02421 | ||
| --- | ||
| (Address of Principal Executive Offices) (Zip Code) |
(617) 503-6500
(Registrant’s telephone number, including area code)
Not Applicable
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| ☐ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
|---|---|
| ☐ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
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| ☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| --- | --- |
| ☐ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
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Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trading<br> <br>Symbol(s) | Name of each exchange<br> <br>on which registered |
|---|---|---|
| Common Stock, Par Value $0.01 per share | CRIS | Nasdaq Global Market |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
| Item 7.01. | Regulation FD Disclosure. |
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From time to time, Curis, Inc. (“Curis” or the “Company”) conducts meetings with third parties in which the Company utilizes a corporate slide presentation. A copy of the Company’s current corporate slide presentation is attached as Exhibit 99.1 to this Current Report on Form 8-K. The attached presentation is incorporated herein by reference.
The information in this Item 7.01 (including Exhibit 99.1 attached hereto) shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933 or the Exchange Act, except as expressly set forth by specific reference in such a filing.
| Item 8.01. | Other Events. |
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On December 7, 2020, the Company issued a press release announcing updated preliminary 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 non-Hodgkin’s lymphoma, including patients with diffuse large B-cell lymphoma, Waldenström’s macroglobulinemia and oncogenic MYD88 mutations, and the recommended Phase 2 dose of the investigational drug.
On December 8, 2020, the Company issued a press release announcing preliminary data from its ongoing open-label, single arm Phase 1 dose escalation study of CA-4948 in patients with acute myeloid leukemia or high-risk myelodysplastic syndromes.
The full text of the press releases issued in connection with these announcements are attached as Exhibits 99.2 and 99.3 to this Current Report on Form 8-K and incorporated herein by reference.
Cautionary Note Regarding Forward-Looking Statements
This Current Report on Form 8-K and the exhibits attached hereto contain forward-looking statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, including, without limitation, statements regarding any expectations of the potential for the Company’s proprietary drug candidate CA-4948, including with respect to the potency, anti-cancer activity, durability and tolerability of CA-4948, future studies with respect to CA-4948, the potential advantages and benefits of CA-4948 and small molecule checkpoint antagonists, statements with respect to the timing of the Company’s studies, including enrollment and reporting of data, and the Company’s plans to advance its development programs. Forward-looking statements may contain the words “believes,” “expects,” “anticipates,” “plans,” “seeks,” “estimates,” “assumes,” “will,” “may,” “could,” “predict,” “project,” “target,” or the negative of these terms or other similar expressions. These forward-looking statements are not guarantees of future performance and involve risks, uncertainties, assumptions and other important factors that may cause actual results to be materially different from those indicated by such forward-looking statements. For example, Curis may experience adverse results, delays and/or failures in its drug development programs and may not be able to successfully advance the development of its drug candidates in the time frames it projects, if at all. Curis’s drug candidates may fail to demonstrate sufficient safety and efficacy in clinical studies and/or may never receive regulatory approval. Favorable results seen in preclinical studies and early clinical trials of Curis’s drug candidates may not be replicated in later trials. There can be no guarantee that Curis’s collaborations with Aurigene and ImmuNext will continue for their full terms and receive sufficient financing and other resources, or that the parties will successfully discover, develop or commercialize drug candidates under the collaborations. Regulatory authorities may delay or restrict Genentech’s and/or Roche’s ability to continue to develop or commercialize Erivedge in BCC. Erivedge may not merit further development in disease indications other than BCC. Competing drugs may be developed that are superior to Erivedge. Curis faces risks relating to the transfer and encumbrance of certain royalty and royalty-related payments on commercial sales of Erivedge, which could have a material adverse effect on its business, financial condition and stock price. Based on its available cash resources, Curis does not have sufficient cash on hand to support current operations for the next 12 months. If it is not able to obtain sufficient funding, it will be forced to delay, reduce in scope or eliminate some of its research and
development programs, including related clinical trials and operating expenses, potentially delaying the time to market for, or preventing the marketing of, any of its product candidates, which could adversely affect its ability to continue operations and pursue its business strategies. Curis faces substantial competition. Curis also faces the risk of potential adverse decisions made by the FDA and other regulatory authorities, investigational review boards, and publication review bodies. Curis may not obtain or maintain necessary patent protection and could become involved in expensive and time-consuming patent proceedings. Unstable market and economic conditions, natural disasters, public health crises, political crises, and other events outside of Curis’s control could significantly disrupt its operations or the operations of third parties on which Curis depends. For example, the COVID-19 pandemic may result in closures of third party facilities, impact clinical trial enrollment or impact sales of Erivedge. The extent to which the COVID-19 pandemic may impact Curis’s business or operating results is uncertain. Important factors that may cause or contribute to such differences include the factors set forth under the caption “Risk Factors” in Curis’s most recent Form 10-K and Form 10-Q and the factors that are discussed in other filings that Curis periodically makes with the Securities and Exchange Commission. In addition, any forward-looking statements represent the views of Curis only as of as of the date of this Form 8-K and should not be relied upon as representing Curis’s views as of any subsequent date. Curis disclaims any intention or obligation to update any of the forward-looking statements after the date of this Form 8-K whether as a result of new information, future events or otherwise, except as may be required by law.
| Item 9.01. | Financial Statements and Exhibits. |
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(d) Exhibits.
| Exhibit<br> <br>Number | Description |
|---|---|
| 99.1 | Corporate Presentation |
| 99.2 | Press Release dated December 7, 2020 |
| 99.3 | Press Release dated December 8, 2020 |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) |
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Curis, Inc. | ||
|---|---|---|
| Date: December 8, 2020 | By: | /s/ JAMES E. DENTZER |
| James E. Dentzer | ||
| President and Chief Executive Officer |
EX-99.1
Corporate Presentation NASDAQ: CRIS Exhibit 99.1
Cautionary Note Regarding Forward Looking Statements This presentation contains certain forward-looking statements about Curis, Inc. (“we,” “us,” or the “Company”) within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as “expect(s),” “believe(s),” “will,” “may,” “anticipate(s),” “focus(es),” “plans,” “mission,” “strategy,” “potential,” “estimate(s)”, "intend," "project," "seek," "should," "would" and similar expressions are intended to identify forward-looking statements. Forward-looking statements are statements that are not historical facts, reflect management’s expectations as of the date of this presentation, and involve important risks and uncertainties. Forward-looking statements herein include, but are not limited to, statements with respect to the timing and results of future clinical and pre-clinical milestones; the timing of future preclinical studies and clinical trials and results of these studies and trials; the clinical and therapeutic potential of our drug candidates; and management’s ability to successfully achieve its goals. These forward-looking statements are based on our current expectations and may differ materially from actual results due to a variety of important factors including, without limitation, risks relating to: whether any of our drug candidates will advance further in the clinical development process and whether and when, if at all, they will receive approval from the U.S. Food and Drug Administration or equivalent foreign regulatory agencies; whether historical preclinical results will be predictive of future clinical trial results; whether historical clinical trial results will be predictive of future trial results; whether any of our drug candidate discovery and development efforts will be successful; whether any of our drug candidates will be successfully marketed if approved; our ability to achieve the benefits contemplated by our collaboration agreements; management’s ability to successfully achieve its goals; the sufficiency of our cash resources; our ability to raise additional capital to fund our operations on terms acceptable to us or the use of proceeds of any offering of securities or other financing; general economic conditions; competition; and the other risk factors contained in our periodic and interim reports filed with the Securities and Exchange Commission which are available on the SEC website at www.sec.gov. You are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof, and we do not undertake any obligation to revise and disseminate forward-looking statements to reflect events or circumstances after the date hereof, or to reflect the occurrence of or non-occurrence of any events, except as required by law.
Curis Mission & Strategy Developing the New Generation of Targeted Cancer Drugs Translational Biology Clinical Development Mission Work relentlessly to develop innovative and differentiated therapeutics that improve the lives of cancer patients Strategy Selectthe right targets Designthe right drugs Studythe right patients Design Execution Innovation People Precision Medicine
Company Overview Investment Thesis Curis seeks to develop novel, first-in-class, cancer therapeutics that we believe have significant potential in areas of unmet patient need Robust Pipeline CA-4948:first-in-class inhibitor of IRAK4 in oncology There are no drugs currently approved for IRAK4 inhibition in oncology CI-8993:first-in-class antagonist of VISTA There are no drugs currently approved for VISTA inhibition Corporate Experienced management team with proven capabilities Curis R&D pioneered the first-in-class inhibitor of the Hedgehog pathway (Erivedge®) partnered with and commercialized by Genentech/Roche for advanced basal cell carcinoma Cash and cash equivalents of $26.3M as of Nov 30, 2020
Evolution of Curis Progressing through Clinical Studies on the Path to Potential Registration Registrational Strategy Initiate Combination Study of CA-4948 and ibrutinib in NHL and evaluate potential paths for registration Report expanded Ph1 data for CA-4948 study in AML/MDS and identify Recommended Phase 2 Dose (RP2D) Initiate the clinical and non-clinical research collaboration with the NCI under the CRADA for CA-4948 Report initial clinical data for CI-8993 Ph1 study targeting VISTA in solid tumors 2019 2020 2021 Expand Clinical Opportunities Report expanded Ph1 data for CA-4948 study in NHL and identify Recommended Phase 2 Dose (RP2D) Initiate a Ph1 study of CA-4948 in AML/MDS including patients expressing IRAK4-L and report initial Ph1 data Acquire exclusive option to license the leading VISTA monoclonal antibody program (CI-8993) and initiate a Ph1 study Initial Clinical Data Report initial Ph1 data for CA-4948 in NHL Evaluate new published research in IRAK4-L expression and the potential opportunity for CA-4948 in AML/MDS
Indication Proof of Principle Safety Dose Optimization Clinical Activity Pivotal Commercial Heme Malignancies CA-4948* IRAK4 MYD88/TLR-altered Lymphoma (NHL) CA-4948* IRAK4 IRAK4L-expressing Leukemia (AML/MDS) Fimepinostat HDAC/PI3K MYC-altered Cancers Immune Checkpoint Inhibitors CI-8993** VISTA VISTA-expressing Cancers CA-327* PDL1/TIM3 PDL1/TIM3-expressing Cancers CA-170* PDL1/VISTA PDL1/VISTA-expressing Cancers Approved Drug Erivedge*** Hedgehog Basal Cell Carcinoma Pipeline All Curis programs are novel, first-in-class CLINICAL MARKETED *IP licensed from Aurigene **Option to license IP from ImmuNext ***IP licensed to Genentech (Curis receives royalty income) 6 PRE-CLINICAL
IRAK4 Targeted Program in NHL CA-4948: In development for treatment of cancers driven by NF-kB and the TLR/Myddosome
CA-4948 Overview Data from Curis preclinical study Booher et al. AACR 2017 (poster #1168) Smith et al. Nat Cell Biol 2019 Profile Value Proposition First-in-class IRAK4 inhibitor in cancer Specific malignancies in Lymphoma are characterized by overactivity of NF-kB and the TLR/myddosome (which is dependent upon IRAK4) Specific malignancies in Leukemia are characterized by spliceosome mutations that cause an overexpression of IRAK4-L (the oncogenic isoform of IRAK4) Composition-of-matter IP extends into 2035 Target Patient Population Lymphoma: 100% of patients treated w/ibrutinib (IRAK4i combination with BTKi) Leukemia: >50% of AML/MDS patients (population which overexpresses IRAK4-L) Product Candidate Description Potent and orally bioavailable inhibitor of IRAK4 for treatment of NF-kB driven lymphomas and IRAK4-L driven leukemia In Lymphoma: Potent suppressor of NF-kB signal transduction2 Phospho-protein levels in AML cells after treatment with CA-4948 Affinity Kinase Kd (nM) IRAK4 23 IRAK1 12,000 IRAK2 >20,000 IRAK3 8,500 Designed to be best-in-class IRAK4 inhibitor1 First-in-Class Inhibitor of IRAK4 in Oncology In Leukemia: >50% of AML/MDS patients overexpress IRAK4-L3 Unstimulated Control 10 1.0 0.1 mM P-IKKa/b P-NF-kB P-ERK
CA-4948 Novel Mechanism of Action for Addressing NF-κB Pathway is Oncogenic Pathway activates NF-κB Pathway is dependent upon BTK Pathway is Oncogenic2,3,4 Pathway activates NF-κB Pathway is dependent upon IRAK4 Signaling requires myddosome, which requires IRAK4 IMBRUVICA Package Insert. Rev 08/2018 Ngo et al. Nature. 2011 Feb 3;470(7332):115-9 Küppers et al. J Exp Med. 2015. 212(13): 2184 Smith et al. Nat Cell Biol 2019 TLR1 B cell receptor Lymphoma1 (NHL) IRAK1 BTK CARD11 MALT1 BCL10 ibrutinib TLR2 TLR4 TLR5 TLR6 TLR7 TLR8 TLR9 Myddosome MYD88 CA-4948 IRAK4 BTK Pathway TLR Pathway Leukemia2 (AML/MDS) Endosome p65 p50 NF-κB BTK and TLR are parallel pathways and primary independent activators of NF-κB In Nov 2020, the NCI selected CA-4948 and entered into a CRADA agreement with Curis to conduct non-clinical and clinical studies of CA-4948 as a potential anti-cancer agent that works via suppression of the TLR Pathway
CA-4948 in Lymphoma Trial Design Study Objectives Primary: Safety and tolerability Secondary:Pharmacokinetic (PK) profile, preliminary anti-cancer activity Study Population Relapsed/Refractory disease Histopathologically confirmed B-cell NHL, including WM/LPL Age ≥ 18 years ECOG performance status of ≤ 1 Dosing Oral, QD or BID continuous dosing 21-day cycles Dose Levels, 3+3 Design QD: 50, 100mg BID: 50, 100, 200, 300 or 400mg Baseline Characteristics of Ph1 Patients Overall (N=31) Male 26(84%) Female 5(16%) Median Age 69yrs Histology Diffuse large B-cell lymphoma (DLBCL) 14(45%) Transformed follicular lymphoma (t-FL/DLBCL) 6(19%) Waldenström’s Macroglobulinemia (WM) 4(13%) Other Lymphoma* 7(23%) Prior Therapies Median prior lines of therapy 4 prior lines BTK inhibitor, n (%) 6(19%) CAR-T, n (%) 5(16%) ASCT , n (%) 7(23%) Other 13(42%) MYD88 Status Positive, n (%) 2(6%) Negative, n (%) 18(58%) Unknown, n (%) 11(35%) *includes Lymphoplasmacytic (n=2), Mantle Cell (n=2), Marginal Zone (n=2), High Grade MYC-BCL6 (n=1) Data cut-off: 23Nov2020
CA-4948 in Lymphoma Two Potential Biomarkers Identified NF-κB phospho-p50 Positive expression of NF-κB phospho-p50 indicates that the NF-κB complex is active MYD88 Mutation Genetic alteration of MYD88 at baseline causes constitutive activation of the myddosome and is a driver of NF-κB activity ❷ Is NF-κB activity driven by the TLR/myddosomal axis? ❶ Is NF-κB is active? TLR1 B cell receptor Lymphoma1 (NHL) IRAK1 BTK CARD11 MALT1 BCL10 ibrutinib TLR2 TLR4 TLR5 TLR6 TLR7 TLR8 TLR9 Myddosome MYD88 CA-4948 IRAK4 BTK Pathway TLR Pathway Leukemia2 (AML/MDS) Endosome p65 p50 NF-κB IMBRUVICA Package Insert. Rev 08/2018 Ngo et al. Nature. 2011 Feb 3;470(7332):115-9 This potential biomarker may support patient selection and provide evidence that CA-4948 is hitting the direct target (IRAK4) and inhibiting the downstream target (the NF-κB complex) This potential predictive biomarker may support patient enrichment by identifying patients with excessive myddosome activity (who may therefore be good candidates for IRAK4 inhibition)
CA-4948 in Lymphoma Early Biomarker Data from Phase 1 patients Patient Best Response 12-1002 +86% PD 018-2004 +156% PD 001-4002 +7% PD 002-4004 +75% PD 012-4004 +125% PD 012-5006 +190% PD 013-6001 +98% PD NEGATIVE at baseline NFκB phospho-p50 expression before treatment with CA-4948 Patient Best Response 19-1001 -35% SD 02-1001 -23% SD 02-3003 +22% SD 012-5007 -34% SD 002-6007 +25% SD 002-6008 +16% SD 15-1001 +66% PD POSITIVE at baseline NFκB phospho-p50 expression before treatment with CA-4948 NF-κB phospho-p50 NF-κB phospho-p50 protein expression at baseline (indicator of NF-κB activity) correlates with patient outcomes Note: data included for all patients for whom pre/post samples were available as of Nov 23, 2020 Before After NEGATIVE after treatment with CA-4948 POSITIVE at baseline (Day 20) Treatment with CA-4948 Phospho-p50 Expression in Pre/Post Tumor Biopsies Also Provides Evidence that CA-4948 is Hitting the Target (IRAK4) and Downregulating NF-κB Activity After treating the patient with CA-4948, their tumor no longer expresses NF-κB phospho-p50 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 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 (012-5007) was dosed at 300mg BID MYD88 Biomarker May Support Patient Enrichment Both patients whose tumor tested positive for MYD88 mutation saw tumor reduction Observed tumor reduction is consistent with our thesis that patients with MYD88-mutated tumors should benefit from IRAK4 inhibition This clinical study is ongoing, more data are needed to confirm these potential biomarkers
Demonstrated Anti-Cancer Activity Objective Response observed at 300mg BID (RP2D) Demonstrated Dose Response Tumor burden decreased with each increase in dose CA-4948 in Lymphoma Anti-Cancer Activity and Dose Response in a Patient with Waldenströms Macroglobulinemia (WM) Note: This WM patient is one of the two patients in the Ph1 study who tested positive for MYD88 (dotted line indicates ongoing treatment) Data cut-off: 23Nov2020
CA-4948 in Lymphoma In Updated Ph1 Data, 300mg BID (RP2D) Offered Best Balance of Tolerability and Anti-Cancer Activity 200mg BID or 400mg BID 300mg BID (RP2D) Clear Single Agent Anti-Cancer Activity at RP2D Tumor reduction 6 of 7 pts in a heavily pretreated population (4 prior lines of therapy) Durable Tolerability Profile at RP2D Patients receiving 300mg BID have remained on therapy for extended periods of time (1 to 2 years) Data cut-off: 23Nov2020
CA-4948 in Lymphoma In Updated Ph1 Data, 300mg BID (RP2D) Offered Best Balance of Tolerability and Anti-Cancer Activity Patients Dosed at Recommended Ph2 Dose (300mg BID) Days on Study (dotted line indicates ongoing treatment) Data cut-off: 23Nov2020 Clear Single Agent Anti-Cancer Activity at RP2D Tumor reduction 6 of 7 pts in a heavily pretreated population (4 prior lines of therapy) Durable Tolerability Profile at RP2D Patients receiving 300mg BID have remained on therapy for extended periods of time (1 to 2 years)
CA-4948 in Lymphoma 2021 Plan: Initiate Clinical Study in Combination Therapy (CA-4948 + ibrutinib) Days of Treatment vehicle ibrutinib Combination Therapy (CA-4948 + ibrutinib) CA-4948 Monotherapy 0 5 10 15 20 25 30 0 300 600 900 1200 1500 Mean Tumor Volume (mm3) ± SEM Anti-Cancer Activity in Monotherapy and Combination Therapy in MYD88-altered DLBCL preclinical model (OCI-Ly10) Mechanism of Action Supports Combination CA-4948 potentially offers a novel mechanism for reducing NF-κB activity by targeting the TLR/myddosome (a parallel and complementary pathway to BTK) Clear Single Agent Anti-Cancer Activity Monotherapy anti-cancer activity demonstrated in both preclinical models and initial Ph1 data Clear Synergy with ibrutinib CA-4948 and ibrutinib show clear synergy in preclinical models Next Step: initiate clinical study of CA-4948 and ibrutinib Booher et al. Waldenstrom Roadmap Symposium 2019
CA-4948 in Lymphoma (planned combination study) Trial Design Study Objectives Primary: Safety and tolerability of CA-4948 in combination with ibrutinib Secondary:Pharmacokinetic (PK) profile, preliminary anti-cancer activity Study Population Relapsed/Refractory disease Histopathologically confirmed B-cell NHL, including WM/LPL Age ≥ 18 years ECOG performance Status of ≤ 1 Dosing CA-4948 – Oral twice daily ibrutinib – Oral daily at labeled dose 21-day cycles 3+3 escalation design for CA-4948 (1st cohort will be 200mg BID) Additional Patient Cohorts to be Studied in Planned Expansion BTK-naïve, Marginal Zone Lymphoma (MZL) BTK-naïve, ABC-DLBCL BTK-naïve, Primary CNS Lymphoma (PCNSL) Patients with adaptive resistance to ibrutinib
IRAK4 Targeted Program in AML/MDS CA-4948: In development for treatment of cancers driven by IRAK4-L
CA-4948 in AML/MDS Landscape of Disease Targets in AML/MDS Non-targeted therapies administered in monotherapy have historically provided limited clinical benefit, especially in relapsed/refractory patients Targeted therapies (e.g., FLT3, IDH) have been limited by the size of their respective target patient populations IRAK4-L is a novel target in AML/MDS and has been shown to be preferentially expressed in >50% of the AML/MDS patient population Disease Driver % of Patient Population IRAK4-L > 50%1 FLT3 25-30%2 TET2 10-20%3 IDH2 9-13%4 IDH1 6-10%4 CEBPA ~10%3 Smith et al. Nat Cell Biol 2019 Saygin, et al. J Hematol Oncol. 2017 Apr 18 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142505/ DiNardo et al. N Engl J Med 2018
IRAK4-L provides a genetic link to oncogenic immune signaling in AML/MDS CA-4948 in AML/MDS IRAK4-L is a Novel Target in AML/MDS Specific Genetic Mutations Drive the Expression of the Long Isoform of IRAK4 (IRAK4-L) Oncogenic IRAK4-L, which is driven by spliceosome mutations (incl. SF3B1 and U2AF1), is preferentially expressed >50% of AML/MDS patients CA-4948 treatment appears to reduce leukemic blasts in patient-derived xenografts IRAK4-L is Oncogenic CA-4948 Directly Targets IRAK4 Direct inhibition of the protein associated with disease (IRAK4) may offer accelerated regulatory path Blocking IRAK4-L appears to reduce the formation of leukemia colonies in preclinical studies Smith et al. Nat Cell Biol. 2019 Choudhary et al. AACR 2017
CA-4948 in AML/MDS Trial Design Study Objectives Primary: Maximum tolerated dose and recommended Phase 2 dose Secondary:Pharmacokinetic (PK) profile, preliminary anti-cancer activity Study Population Relapsed/Refractory disease Histopathologically confirmed AML or High-Risk MDS Age ≥ 18 years ECOG performance Status of ≤ 2 Dosing Oral 28-day cycles 3+3 escalation design (200mg BID, 300mg BID, and 400mg BID) Baseline Characteristics of Ph1 Patients Overall (N=6) Male (%) 5(83%) Female (%) 1(17%) Median Age (range) 72 (32-84) Median Prior Therapies (range) 3 (1-4) Histology Acute Myelogenous Leukemia (AML) 4(67%) Myelodysplastic Syndrome (MDS) 2(33%) Data cut-off: 23Nov2020
CA-4948 in AML/MDS Monotherapy Anti-Cancer Activity Observed in Early Ph1 Data Blasts Baseline Blasts Best Resp Change AML 005-2003 32% 26% -19% AML 005-2002 39% 25% -36% AML 003-1002 24% 9% -63% hrMDS 003-1003 4% 2% -50% hrMDS 003-1001 11% 2% -82% Marrow CR AML 005-2001 23% 1% -96% Marrow CR 1st patient dosed in Q3 2020 Consistent reduction of Marrow Blasts across population (6 patients) 2 patients have achieved Marrow CR 300mg 300mg 200mg Normal Range 300mg 200mg 200mg Note:To achieve Marrow CR, a patient’s blast count must be elevated at baseline (>5%) and, after treatment, decrease by ≥ 50% from baseline into the normal range (≤5%) AML hrMDS Data cut-off: 23Nov2020
VISTA Targeted Program in Solid Tumors CI-8993: In development for treatment of cancers driven by VISTA-mediated Immune Suppression
CI-8993 Overview In Development for VISTA Expressing and Infiltrated Cancers Profile Value Proposition First-in-class monoclonal antibody antagonist of VISTA Composition-of-matter IP extends into 2034 Target Patient Population Patients with VISTA-expressing cancers (incl. Mesothelioma, NSCLC, and TNBC) Patients receiving PD1/PDL1 or CTLA4 antibody therapy (or those who have already received it and have developed resistance to it) Product Description Monoclonal antibody developed by ImmuNext/Janssen in partnership with Randy Noelle’s lab at Dartmouth (the co-discoverer of VISTA) Curis is the first to advance an oral small molecule checkpoint inhibitor into the clinic
CI-8993 Target Background VISTA is an Important Checkpoint Regulator CTLA-4, PD-1, and VISTA are the three main players in controlling checkpoint blockade VISTA controls early T cell activation events Blockade of VISTA will allow for an expanded T cell response against tumors Eltanbouly et al. Science. 2020 Eltanbouly et al. Science. 2020
CI-8993 Target Background Role of VISTA in Immune Suppression in the Tumor Microenvironment (TME) Temporary Immune Activation ❷ MDSC T cells Activated after PD1 Treatment Y Normal Immune Suppression ❶ T Cell Exhausted MDSC Alleviation of Immune Suppression ❹ Y Y Y Y Y Y MDSC Y Y Y T cells Re-Activated after VISTA Treatment Y Y T Cell Y Y Activated Y Y VISTA-mediated Immune Suppression ❸ Y MDSC T Cell Exhausted Y Blocking PD-1 activates T cells VISTA re-suppresses T cells1 Blocking VISTA re-activates T cells2 1 Gao et al. Nature. 2017. 23: 551–555 2 Data from ImmuNext preclinical studies T cells Suppressed by VISTA after PD1 Treatment blocking PD1 causes up to 5x increase in VISTA expression1 PD1/PDL1 Tumor Cells VISTA VISTA VISTA VISTA Tumor Cells PD1/PDL1 VISTA VISTA VISTA VISTA VISTA VISTA VISTA VISTA Y Tumor Cells T Cell Activated Y PD1/PDL1 PD1/PDL1 Tumor Cells
αPD1 + αCTLA4 + αVISTA αPD1 + αCTLA4 + isotype CI-8993 Preclinical Data Preclinical anti-cancer activity demonstrated in both monotherapy & combination therapy 1 Le Mercier et al. Cancer Res. 2014 Apr 1 Anti-VISTA inhibited tumor growth in B16ova melanoma model1 Anti-VISTA inhibited xenograft growth in checkpoint resistant CT26 model2 Monotherapy Combination Therapy Day 0 Day 2 Day 4 Day 6 Day 8 Control n=14 aVISTA n=14 Days Tumor Size (mm2) 80% 100% Days pre/post dosing Percent survival -14 0 20 40 60 αPD1 + αCTLA4 + αVISTA αPD1 + αCTLA4 + isotype 2 J. Lines, IEBMC Conference 2019 60% 40% 20%
CI-8993 Clinical Plan Phase 1 dose escalation study design Patient Population Patients with advanced refractory solid tumors (includes mesothelioma, melanoma, NSCLC, TNBC) Treatment Bi-weekly dosing Mitigate potential toxicities by desensitization, premedication, dosing interval and duration Objective Safety, PK/PD, tolerability during dose escalation Anti-cancer activity during expansion CI-8993 was originally developed by Janssen (JNJ-61610588) JNJ licensed VISTA IP from ImmuNext in 2012 and initiated a Ph1 study in 2016 12 patients were enrolled; initial dose level was 0.005mg/kg Low-grade transient Cytokine Release Syndrome (CRS) seen at 0.15mg/kg and above JNJ halted study after 1 DLT at sub-therapeutic dose level The only patient treated at 0.3mg/kg experienced grade 3 CRS-associated encephalopathy after 36hrs on treatment Patient was initially treated w/antibiotics; symptoms resolved after treatment with tocilizumab JNJ opted to halt the study and return IP to ImmuNext Prior clinical development of CI-8993: Target range for expected anti-cancer activity (0.5 – 2.0mg/kg) was never reached Continue dose escalation until RP2D is identified Higher Doses n=3 [+3] Level 3 n=3 [+3] Level 2 n=3 [+3] 0.15mg/kg n=3 [+3] Curis Design for Ph1 Dose Escalation Study Curis Design for Ph1 Study Design Incorporates Key Learnings from Janssen Ph1 Study CRS is likely an on-target toxicity; indicates drug is hitting the target and inducing inflammatory response Oncology community is now familiar with managing CRS; NCCN guidelines were issued in 2018 FDA cleared the study IND which outlined our plan for managing CRS and enabling escalation to therapeutic dose levels
Targeted Programs in Heme Malignancies Fimepinostat: In development for treatment of MYC-altered cancers
Fimepinostat Overview In Development for Patients with MYC-Altered Cancers Qian et.al. Clin Cancer Res. 2012. 18: 4104 Sun et.al. Mol Cancer Ther. 2017. 6: 285 Chen et al. Nature. 2018 Feb 23. 3:5 Profile Value Proposition First-in-class drug candidate with demonstrated anti-cancer activity as a single agent in MYC-altered patients in Ph1 and Ph2 trials Composition-of-matter IP extends into 2032 Target Patient Population Patients with MYC-altered cancer (>50% of all cancers are effected by MYC)3 Collaborating with DarwinHealth on characterization of biomarkers and tumor type alignments to identify potential therapeutic opportunities Product Candidate Description Potent and orally bioavailable dual inhibitor of HDAC and PI3K enzymes1 Favorable tolerability profile in over 200 patients HDACi PI3Ki Mechanism #1 The HDAC component Suppresses MYC transcription2 Mechanism #2 The PI3K component Enhances MYC destruction2 Protein levels in DLBCL cells after treatment with Fimepinostat (Curis Preclinical Study) Control 1000 100 10 1 0.1 Ac-H3 pAKT MYC Tubulin (nM) Dual Mechanism leads to potent and dose-dependent downregulation of MYC protein
Fimepinostat Overview Clinical Anti-Cancer Activity in Patients with MYC-Altered Cancers in Ph1 and Ph2 Studies Deep Responses 8 complete responses (CR); 6 partial responses (PR) 2 patients able to proceed to transplant Durable Responses Median duration = 13.6 months Fast Track designation received Following FDA review of Ph1 and Ph2 clinical data CR/PR DH DE DE DH DH DE DE DE DE MY MY MY MY MY MY MY MY DE DHDouble-Hit DEDouble-Expressor MYMYC only SD/PD Deep Responses in MYC-altered patients (49 evaluable patients; 60 ITT patients) Currently evaluating assays, biomarkers, and potential companion diagnostics in research collaboration with DarwinHealth to help identify specific patient populations for potential future clinical development
Company Summary Investment Thesis Curis seeks to develop novel, first-in-class, cancer therapeutics that we believe have significant potential in areas of unmet patient need Robust Pipeline CA-4948:first-in-class inhibitor of IRAK4 in oncology There are no drugs currently approved for IRAK4 inhibition in oncology CI-8993:first-in-class antagonist of VISTA There are no drugs currently approved for VISTA inhibition Potential Catalysts 1H 2021:Initiate combination study of CA-4948 and ibrutinib in NHL patients 2H 2021:Report expanded data in CA-4948 Ph1 study in AML/MDS patients 2H 2021:Report initial data in CI-8993 dose escalation Ph1 study
Curis Leadership Team Reinhard von Roemeling Head, Clinical Development Raul Soikes Head, Portfolio Management Nancy Soohoo General Counsel William Steinkrauss Chief Financial Officer Mark Noel Head, Intellectual Property Rachel Blasbalg Head, Human Resources James Dentzer President & CEO Christine Guertin Head, Regulatory Robert Martell Head, R&D
End of Corporate Presentation NASDAQ: CRIS
EX-99.2
Exhibit 99.2
PRESS RELEASE
Curis Announces Updated Preliminary Data from Ongoing Phase 1 Study of CA-4948 Showing Durable and Dose-Dependent Reductions in Tumor Burden in Patients with Relapsed or Refractory Non-Hodgkin’s Lymphoma
- Tumor reductions observed in 6 of 7 patients treated at 300 mg BID following median 4 prior lines of therapy -
- Patients receiving 300 mg BID have remained on therapy for extended periods of time (1 to 2 years) -
- Two potential biomarkers identified that demonstrate target engagement and highlight potential for patient enrichment strategy -
- Recommended Phase 2 dose of 300 mg BID balances durable anti-cancer activity and extended tolerability profile –
- Management to host virtual KOL event Tuesday, December 8 at 8:00 a.m. ET -
LEXINGTON, Mass., December 7, 2020 /PRNewswire/ — Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, today announced 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. The new results, which will be shared in a virtual oral presentation at the 62^nd^ American Society of Hematology (ASH) 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.
“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<br>been Grade 1-2. |
|---|---|
| • | Preliminary tolerability profile supports potential long-term treatment and combination with other active drugs<br>against NHL. |
| --- | --- |
| • | Enrolled patients include those with DLBCL, WM, marginal zone lymphoma (MZL), follicular lymphoma (FL),<br>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<br>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%).<br> |
| --- | --- |
| • | One patient with WM, who dose escalated from 50mg to 100mg to 200mg to 300mg (all doses, BID), experienced<br>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<br>December 7^th^, 2020). |
| --- | --- |
| • | 3 patients have been on therapy for greater than 1 year. |
| --- | --- |
| • | Encouraging early data for two potential biomarkers<br>(NF-KB p-p50 and MYD88). |
| --- | --- |
| • | Early data for NF-KB<br>p-p50 biomarker may support patient selection: |
| --- | --- |
| • | Patients whose tumors do not exhibit NF-KB activity may<br>not be amenable to NF-KB downregulation. |
| --- | --- |
| • | 7 of 7 patients testing negative for p-p50 at baseline experienced<br>disease progression. |
| --- | --- |
| • | 2 of these patients were dosed at 200mg BID. |
| --- | --- |
| • | Patients whose tumors do exhibit NF-KB activity may be<br>amenable to NF-KB downregulation. |
| --- | --- |
| • | 6 of 7 patients testing positive for p-p50 at baseline achieved stable<br>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<br>response. |
| --- | --- |
| • | More data are needed to confirm this potential predictive biomarker, but we believe positive patient outcomes are<br>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 https://www.curis.com/.
About Curis, Inc.
Curis is a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer. In 2015, Curis entered into a collaboration with Aurigene in the areas of immuno-oncology and precision oncology. As part of this collaboration, Curis has exclusive licenses to oral small molecule antagonists of immune checkpoints including the VISTA/PDL1 antagonist CA-170, and the TIM3/PDL1 antagonist CA-327, as well as the IRAK4 kinase
inhibitor, CA-4948. CA-4948 is currently undergoing testing in a Phase 1 trial in patients with non-Hodgkin’s lymphoma and in a Phase 1 trial in patients with acute myeloid leukemia and myelodysplastic syndromes. In addition, Curis is engaged in a collaboration with ImmuNext for development of CI-8993, a monoclonal anti-VISTA antibody, which is currently undergoing testing in a Phase 1a/1b trial in patients with solid tumors. Curis is also party to a collaboration with Genentech, a member of the Roche Group, under which Genentech and Roche are commercializing Erivedge^®^ for the treatment of advanced basal cell carcinoma. For more information, visit Curis’ website at www.curis.com.
Forward-Looking Statements:
This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, including, without limitation, statements regarding any expectations of the potential for the Company’s proprietary drug candidate CA-4948, including with respect to the potency, anti-cancer activity, durability and tolerability of CA-4948, future studies with respect to CA-4948, the potential advantages and benefits of CA-4948 and small molecule checkpoint antagonists, and the Company’s plans to advance its development programs. Forward-looking statements may contain the words “believes,” “expects,” “anticipates,” “plans,” “intends,” “seeks,” “estimates,” “assumes,” “will,” “may,” “could” or similar expressions. These forward-looking statements are not guarantees of future performance and involve risks, uncertainties, assumptions and other important factors that may cause actual results to be materially different from those indicated by such forward-looking statements. For example, Curis may experience adverse results, delays and/or failures in its drug development programs and may not be able to successfully advance the development of its drug candidates in the time frames it projects, if at all. Curis’s drug candidates may fail to demonstrate sufficient safety and efficacy in clinical studies and/or may never receive regulatory approval. Favorable results seen in preclinical studies and early clinical trials of Curis’s drug candidates may not be replicated in later trials. There can be no guarantee that Curis’s collaborations with Aurigene and ImmuNext will continue for their full terms and receive sufficient financing and other resources, or that the parties will successfully discover, develop or commercialize drug candidates under the collaborations. Regulatory authorities may delay or restrict Genentech’s and/or Roche’s ability to continue to develop or commercialize Erivedge in BCC. Erivedge may not merit further development in disease indications other than BCC. Competing drugs may be developed that are superior to Erivedge. Curis faces risks relating to the transfer and encumbrance of certain royalty and royalty-related payments on commercial sales of Erivedge, which could have a material adverse effect on its business, financial condition and stock price. Based on its available cash resources, Curis does not have sufficient cash on hand to support current operations for the next 12 months. If it is not able to obtain sufficient funding, it will be forced to delay, reduce in scope or eliminate some of its research and development programs, including related clinical trials and operating expenses, potentially delaying the time to market for, or preventing the marketing of, any of its product candidates, which could adversely affect its ability to continue operations and pursue its business strategies. Curis faces substantial
competition. Curis also faces the risk of potential adverse decisions made by the FDA and other regulatory authorities, investigational review boards, and publication review bodies. Curis may not obtain or maintain necessary patent protection and could become involved in expensive and time-consuming patent proceedings. Unstable market and economic conditions, natural disasters, public health crises, political crises, and other events outside of Curis’s control could significantly disrupt its operations or the operations of third parties on which Curis depends. For example, the COVID-19 pandemic may result in closures of third-party facilities, impact clinical trial enrollment or impact sales of Erivedge. The extent to which the COVID-19 pandemic may impact Curis’s business is uncertain. Other important factors that may cause or contribute to actual results being materially different from those indicated by forward-looking statements include the factors set forth under the caption “Risk Factors” in Curis’s most recent Form 10-K and Form 10-Q and the factors that are discussed in other filings that Curis periodically makes with the Securities and Exchange Commission (“SEC”). In addition, any forward-looking statements represent the views of Curis only as of today and should not be relied upon as representing Curis’s views as of any subsequent date. Curis disclaims any intention or obligation to update any of the forward-looking statements after the date of this press release whether as a result of new information, future events or otherwise, except as may be required by law.
Contacts
Investor Relations
Stephanie Ascher
Stern Investor Relations, Inc.
(212) 362-1200
stephanie.ascher@sternir.com
EX-99.3
Exhibit 99.3
PRESS RELEASE
Curis Announces Positive Preliminary Data from Ongoing Phase 1 Study of CA-4948 Monotherapy in Patients with Relapsed or Refractory Acute Myeloid Leukemia and Myelodysplastic Syndromes
- Reduction of marrow blasts observed in all evaluablepatients -
- Marrow complete response observed in 2 patients -
- Management to host virtual KOL event today, Tuesday, December 8 at 8:00 a.m. ET -
LEXINGTON, Mass., December 8, 2020 /PRNewswire/ — Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, today announced positive preliminary data from its ongoing open-label, single arm Phase 1 dose escalation study of CA-4948, a novel, small molecule IRAK4 kinase inhibitor, in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS). IRAK4 plays an essential role in the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways, and these pathways are frequently dysregulated in patients with AML and MDS. Third parties have recently discovered that the long form of IRAK4 (IRAK4-L) is oncogenic and preferentially expressed in over half of patients with AML and MDS. A variety of drivers are believed to cause this, including specific spliceosome mutations.
“We are highly encouraged by the breadth of clinical activity with CA-4948 seen with this early data, especially as this study is both monotherapy and in a late line, relapsed/refractory population. Historically, monotherapy studies in AML and MDS have proven underwhelming; monotherapy studies in a relapsed/refractory setting have been especially challenging,” said James Dentzer, President and Chief Executive Officer of Curis. “We also have been pleased by the pace at which our trial partners have been able to enroll patients. We look forward to continuing to advance CA-4948 and reporting additional Phase 1 data in the second half of 2021.”
“As a clinician intimately familiar with the treatment challenges faced by patients with AML or high-risk MDS, I am very encouraged by the early data coming out of this study,” said Dr. Guillermo Garcia-Manero, Chief of the Section of Myelodysplastic Syndromes within the Department of Leukemia at The University of Texas MD Anderson Cancer Center. “While there have been important advancements in the development of new therapeutics for patients with previously untreated AML or MDS in recent years, relapsed and refractory patients are still in need of better treatment options. These preliminary data suggest, for the first time in a clinical setting, that successfully targeting the long isoform of IRAK4, which we know to be preferentially expressed in over half of AML and MDS patients, could be the first major breakthrough in over a decade for patients with these diseases.”
The reported preliminary data are from Curis’s ongoing open-label, single arm Phase 1 dose escalation 3+3 study of orally administered CA-4948 monotherapy in adult patients with AML or high-risk MDS. A minimum of 3 patients will be enrolled in each cohort of the two-part study, starting with 200 mg BID, which was demonstrated to be well-tolerated, capable of achieving relevant levels of drug exposure and has demonstrated signs of biologic activity in Curis’s ongoing Phase 1 study of CA-4948 for the treatment of patients with relapsed or refractory non-Hodgkin’s lymphoma. The primary objective of the study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for CA-4948 based on safety and tolerability, dose-limiting toxicities (DLT), and any biologic activity, pharmacokinetic and pharmacodynamic findings from the study trial population. Additional objectives include characterization of CA-4948’s pharmacokinetic parameters, and biomarker correlations. As of November 23, 2020, 4 AML patients and 3 high-risk MDS patients had been enrolled in the first 2 study cohorts and no DLTs had been observed. The data being reported from this ongoing trial are preliminary and subject to change.
Key findings include:
| • | Marrow blast reductions observed in all evaluable patients (6 patients). |
|---|---|
| • | 6 of 7 patients enrolled remain on study. |
| --- | --- |
| • | Patients enrolled experienced a median of 3 prior lines of treatment (range<br>1-4). |
| --- | --- |
| • | Two patients experienced a marrow complete response, one with blast count going from 23% pretreatment to 1% on<br>treatment, and the other going from 11% pretreatment to 2% on treatment. |
| --- | --- |
| • | No DLTs observed in 7 DLT-evaluable patients in the 200 mg BID and 300 mg BID cohorts. |
| --- | --- |
| • | Enrollment has begun in the 400 mg BID cohort. |
| --- | --- |
Webcast Event Information
Curis management will host a virtual KOL event today, 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 https://www.curis.com/.
About Curis, Inc.
Curis is a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer. In 2015, Curis entered into a collaboration with Aurigene in the areas of immuno-oncology and precision oncology. As part of this collaboration, Curis has exclusive licenses to oral small molecule antagonists of immune checkpoints including the VISTA/PDL1 antagonist CA-170, and the TIM3/PDL1 antagonist CA-327, as well as the IRAK4 kinase inhibitor, CA-4948. CA-4948 is currently undergoing testing in a Phase 1 trial in patients with non-Hodgkin’s lymphoma and in a Phase 1 trial in patients with acute myeloid leukemia and myelodysplastic syndromes. In addition, Curis is engaged in a collaboration with ImmuNext for development of CI-8993, a monoclonal anti-VISTA antibody, which is currently undergoing testing in a Phase 1a/1b trial in patients with solid tumors. Curis is also party to a collaboration with Genentech, a member of the Roche Group, under which Genentech and Roche are commercializing Erivedge^®^ for the treatment of advanced basal cell carcinoma. For more information, visit Curis’ website at www.curis.com.
Forward-Looking Statements:
This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, including, without limitation, statements regarding any expectations of the potential for the Company’s proprietary drug candidate CA-4948, including with respect to the activity and tolerability of CA-4948, future studies with respect to CA-4948, the potential advantages and benefits of CA-4948 and small molecule checkpoint antagonists, statements with respect to the timing of the Company’s studies, including enrollment and reporting of data, and the Company’s plans to advance its development programs. Forward-looking statements may contain the words “believes,” “expects,” “anticipates,” “plans,” “intends,” “seeks,” “estimates,” “assumes,” “will,” “may,” “could” or similar expressions. These forward-looking statements are not guarantees of future performance and involve risks, uncertainties, assumptions and other important factors that may cause actual results to be materially different from those indicated by such forward-looking statements. For example, Curis may experience adverse results, delays and/or failures in its drug development programs and may not be able to successfully advance the development of its drug candidates in the time frames it projects, if at all. Curis’s drug candidates may fail to demonstrate sufficient safety and efficacy in clinical studies and/or may never receive regulatory approval. Favorable results seen in preclinical studies and early clinical trials of Curis’s drug candidates may not be replicated in later trials. There can be no guarantee that Curis’s collaborations with Aurigene and ImmuNext will continue for their full terms and receive sufficient financing and other resources, or that the parties will successfully discover, develop or commercialize drug candidates under the collaborations. Regulatory authorities may delay or restrict Genentech’s and/or Roche’s ability to continue to develop or commercialize Erivedge in BCC. Erivedge may not merit further development in disease indications other than BCC. Competing drugs may be developed that
are superior to Erivedge. Curis faces risks relating to the transfer and encumbrance of certain royalty and royalty-related payments on commercial sales of Erivedge, which could have a material adverse effect on its business, financial condition and stock price. Based on its available cash resources, Curis does not have sufficient cash on hand to support current operations for the next 12 months. If it is not able to obtain sufficient funding, it will be forced to delay, reduce in scope or eliminate some of its research and development programs, including related clinical trials and operating expenses, potentially delaying the time to market for, or preventing the marketing of, any of its product candidates, which could adversely affect its ability to continue operations and pursue its business strategies. Curis faces substantial competition. Curis also faces the risk of potential adverse decisions made by the FDA and other regulatory authorities, investigational review boards, and publication review bodies. Curis may not obtain or maintain necessary patent protection and could become involved in expensive and time-consuming patent proceedings. Unstable market and economic conditions, natural disasters, public health crises, political crises and other events outside of Curis’s control could significantly disrupt its operations or the operations of third parties on which Curis depends. For example, the COVID-19 pandemic may result in closures of third-party facilities, impact clinical trial enrollment or impact sales of Erivedge. The extent to which the COVID-19 pandemic may impact Curis’s business is uncertain. Other important factors that may cause or contribute to actual results being materially different from those indicated by forward-looking statements include the factors set forth under the caption “Risk Factors” in Curis’s most recent Form 10-K and Form 10-Q and the factors that are discussed in other filings that Curis periodically makes with the Securities and Exchange Commission (“SEC”). In addition, any forward-looking statements represent the views of Curis only as of today and should not be relied upon as representing Curis’s views as of any subsequent date. Curis disclaims any intention or obligation to update any of the forward-looking statements after the date of this press release whether as a result of new information, future events or otherwise, except as may be required by law.
Contacts
Investor Relations
Stephanie Ascher
Stern Investor Relations, Inc.
(212) 362-1200
stephanie.ascher@sternir.com