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): January 6, 2022
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,<br> <br>Lexington, MA | 02421 | |
| --- | --- | |
| (Address of principal executive offices) | (Zip Code) |
Registrant’s telephone number, including area code: (617) 503-6500
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) |
| --- | --- |
| ☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
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| ☐ | 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.
Curis, Inc. (“Curis” or the “Company”) will present the updates described in Item 8.01 of this Current Report on Form 8-K on a conference call to be held on January 6, 2022. A copy of this 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.
On January 6, 2022, the Company issued a press release announcing updated clinical data from its ongoing open label Phase 1/2 dose escalation and expansion study of CA-4948, a novel, small molecule IRAK-4 inhibitor, as a monotherapy in patients with relapsed or refractory (“R/R”) acute myeloid leukemia or high risk myelodysplastic syndromes, as well as initial safety, pharmacokinetic and pharmacodynamic data from its Phase 1 dose escalation study of CI-8993, a monoclonal antibody targeting VISTA for patients with R/R solid tumors.
The full text of the press release issued in connection with this announcement is attached as Exhibit 99.2 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 U.S. Private Securities Litigation Reform Act of 1995, including, without limitation, any statements concerning expectations of the potential for Curis’s proprietary drug candidates CA-4948 and CI-8993, including with respect to the potency, anti-cancer activity, durability and tolerability of CA-4948 and CI-8993; future studies with respect to CA-4948 and CI-8993; the potential advantages and benefits of CA-4948, CI-8993 and checkpoint inhibitors over other therapies; Curis’s plans to advance its development programs for CA-4948 and CI-8993, including with respect to anticipated results, clinical trials, regulatory and commercialization plans and timelines; and statements of assumptions underlying any of the foregoing. Forward-looking statements may contain the words “believes,” “expects,” “anticipates,” “plans,” “intends,” “seeks,” “estimates,” “assumes,” “predicts,” “projects,” “targets,” “will,” “may,” “would,” “could,” “should,” “continue,” “potential,” “focus,” “strategy,” “mission,” 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 cause unexpected toxicities, fail to demonstrate sufficient safety and efficacy in clinical studies and/or may never achieve the requisite regulatory approvals needed for commercialization. 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 the collaboration agreements with Aurigene Discovery Technologies Limited and ImmuNext, Inc., or the Cooperative Research and Development Agreement with the National Cancer Institute, will continue for their full terms, that Curis or its collaborators will each maintain the financial and other resources necessary to continue financing their respective portions of the research, development and commercialization costs, or that the parties will successfully discover, develop or commercialize drug candidates under the collaborations. Regulatory authorities may determine to delay or restrict the ability of Genentech Inc. (“Genentech”), a member of the Roche Group (“Roche”), and/or Roche’s ability to continue to develop or commercialize Erivedge® in advanced basal cell carcinoma (“BCC”). Erivedge may not demonstrate sufficient or any activity to merit its further development in disease indications other than BCC. Competing drugs may be developed that are superior to Erivedge. In connection with its agreement with entities managed by Oberland Capital Management, LLC, Curis faces risks relating to the transfer and encumbrance of certain royalty and royalty-related payments on commercial sales of Erivedge, including the risk that, in the event of a default by Curis or its wholly-owned subsidiary, Curis could lose all retained rights to future royalty and royalty-related payments, Curis could be required to repurchase such future royalty and royalty-related payments at a price that is a multiple of the payments it has received, and its ability to enter into future arrangements may be
inhibited, all of which could have a material adverse effect on its business, financial condition and stock price. Curis will require substantial additional capital to fund its business. 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 business prospects and its ability to continue operations, and would have a negative impact on its financial condition and its ability to pursue its business strategies. Curis faces substantial competition. Curis and its collaborators face 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 litigation and interference 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, and could adversely impact Curis’s operating results and its ability to raise capital. For example, the COVID-19 pandemic may result in closures of third-party facilities, impact enrollment in clinical trials or impact sales of Erivedge by Genentech and/or Roche. The extent to which the COVID-19 pandemic may impact Curis’s business or operating results 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 captions “Risk Factor Summary” and “Risk Factors” in Curis’s most recent Annual Report on Form 10-K and Quarterly Report on 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 the date of this Current Report on 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 Current Report on 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.
| (d) | Exhibits. |
|---|---|
| Exhibit No. | Description |
| --- | --- |
| 99.1 | Presentation |
| 99.2 | Press Release dated January 6, 2022 |
| 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: January 6, 2022 | By: | /s/ JAMES E. DENTZER |
| James E. Dentzer<br> <br>President and Chief Executive Officer |
EX-99.1
CA-4948 & CI-8993 Clinical Data Update January 2022 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, expectations of the potential for Company’s proprietary drug candidates CA-4948 and CI-8993, including with respect to the potency, anti-cancer activity, durability and tolerability of CA-4948 and CI-8993; future studies with respect to CA-4948 and CI-8993; the potential advantages and benefits of CA-4948, CI-8993 and checkpoint inhibitors over other therapies; and the Company’s plans to advance its development programs for CA-4948 and CI-8993, including with respect to anticipated results, clinical trials, regulatory and commercialization plans and timelines. 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.
Today’s Participants James Dentzer President & Chief Executive Officer at Curis Robert Martell, MD, PhD Head of R&D at Curis Daniel DeAngelo, MD, PhDChief, Division of Leukemia at Dana-Farber Cancer Institute
Introductory Remarks Clinical update on CA-4948 (IRAK4) and CI-8993 (VISTA) CA-4948 addresses a novel target (IRAK4) and: (1) demonstrates clear anti-cancer activity as an oral single agent (2) is active in genetically-defined populations that can be identified and enrolled (3) has the added potential benefit of also hitting FLT3 CI-8993 addresses a novel target (VISTA) and: (1) has successfully cleared dose level where Janssen observed dose-limiting toxicity (DLT) (2) with pharmacodynamic effects suggesting multiple anti-cancer mechanisms are being activated
CA-4948: First-in-class IRAK4 Inhibitor Targeting Specific Genetic Populations in R/R AML and high-risk MDS (MDS)
Biology and CA-4948 Role of IRAK4 in AML/MDS (normal vs. oncogenic activity) 1. Smith et al. Nat Cell Biol 2019. 2. Guillamot et al. Nat Cell Biol 2019. constitutive activation MYD88 IRAK1 IRAK4-S Myddosome IRAK1 IRAK4-L MYD88 Malignant Heme Cell2 Spliceosome Spliceosome Normal Heme Cell1 Spliceosome Mutation CA-4948 CA-4948 Leukemia1 (AML, MDS) NF-κB MAPK (normal immune signaling) IRAK4-L activity leads to NF-κB IRAK4-S activity leads to MAPK Specific genetic mutations (SF3B1, U2AF1) in the spliceosome drive overexpression of IRAK4-L IRAK4-L then causes constitutive activation of the myddosome, leading to overactivity of NF-κB
CA-4948 is the Leading IRAK4 Inhibitor in Development for Cancer Targeted design offers added potential benefit of also hitting FLT3 CA-4948 Kinase Interaction Map % Inhibition at 0.1 nM Illustration reproduced courtesy of Cell Signaling Technology CA-4948 binds specifically and with high affinity to IRAK4 CA-4948 “fingerprint” illustrates unique molecular signature specifically engineered to hit key oncogenic targets Target Kd nM IRAK1 12,000 IRAK2 >20,000 IRAK3 8,500 IRAK4 23 DYRK1A 25 FLT3 wt FLT3 (D835H) 31 5 FLT3 (D835V) 44 FLT3 (D835Y) 3 FLT3 (ITD) 8 FLT3 (K663Q) 47 FLT3 (N841I) 16 Haspin (GSG2) 32 CLK1 10 CLK2 20 CLK3 >20,000 CLK4 14 TrkA 130 CA-4948 Binding Affinity DiscoverX Kinase Panel (378 kinases screened) Dual targeting of IRAK4 and FLT3 confers a potential efficacy advantage vs. other IRAK4 inhibitors and expands potential to additional genetic populations
Clinical Study Overview Phase 1/2 Study in AML and MDS
CA-4948 in AML and MDS Study Objectives 1ᵒ: Determine maximum tolerated dose Determine recommended Phase 2 dose 2ᵒ:Pharmacokinetic (PK) profile Preliminary anti-cancer activity Study Population Relapsed/Refractory AML or high-risk MDS ECOG performance Status of ≤ 2 Age ≥ 18 years Dosing Oral, Twice Daily (BID) Dosing 28-day cycles Open-label, single arm, Phase 1/2 dose escalation and expansion study Data extraction date: Dec 16, 2021 1. These are non-targeted patients, due to lack of Spliceosome or FLT3 mutation, this population will be addressed in the combination therapy study; 2. One patient was not response evaluable because of discontinuation due to patient decision; 3. Two AML patients have both a spliceosome and FLT3 mutation and are included in both populations (there are 13 total evaluable patients with Spliceosome or FLT3 mutation) Dose Escalation: 200/300/400/500 mg BID Dose Expansion: 300 mg BID 49 Total Patients Treated 43 Patients Started Treatment prior to September 30, 2021 AML Spliceosome2,3 (n=6) MDS Spliceosome (n=7) AML FLT33 (n=3) Jan 2022 Safety Update Jan 2022 Efficacy Update AML/MDS w/o targeted mutations1 (n=29)
Well-Tolerated and Manageable AE Profile for CA-4948 in AML/MDS with No Cumulative Toxicities Observed No Grade 4 or 5 TRAEs reported; all AEs were manageable Data extraction date: Dec 16, 2021. 1. Data for the two patients that have escalated from 300 mg BID to 400 mg BID were included in the 400 mg BID dose group. Grade 3+ Treatment-Related Adverse Event 200 mg BID (N = 3) 300 mg BID (N = 26) 400 mg BID (N = 17) 500 mg BID (N = 3) Preferred Term n (%) n (%) n (%) n (%) Number of patients having grade 3+ treatment-related AEs 1 (33.3) 6 (23.1) 6 (35.3) 2 (66.7) Alanine aminotransferase increased 1 (33.3) 0 0 0 Blood creatine phosphokinase increased 0 1 (3.8) 0 0 Dizziness 1 (33.3) 0 0 0 Dyspnoea 0 0 1 (5.9) 0 Enterobacter infection 0 0 1 (5.9) 0 Fatigue 0 0 1 (5.9) 0 Gastrointestinal haemorrhage 0 1 (3.8) 0 0 Hypophosphataemia 0 1 (3.8) 0 0 Hypotension 0 1 (3.8) 0 0 Lipase increased 0 2 (7.7) 0 0 Platelet count decreased 0 1 (3.8) 0 0 Presyncope 0 0 1 (5.9) 0 Rhabdomyolysis 0 1 (3.8) 2 (11.8) 1 (33.3) Syncope 0 0 0 1 (33.3) No dose-limiting myelosuppression reported, which is a life-threatening problem characteristic of many cancer treatments, making CA-4948 favorable for combinations Well-tolerated and manageable AE profile with no cumulative toxicities reported Recommended Phase 2 Dose
Clinical Data Overview: Three Targeted Patient Populations (1) AML Spliceosome, (2) MDS Spliceosome, (3) AML FLT3
Heavily Pretreated Patient Population Baseline Characteristics of AML/MDS Subsets AML Spliceosome1 (n=6) MDS Spliceosome (n=7) AML FLT31 (n=3) Female n (%) : Male n (%) 0 (0) : 6 (100) 5 (71) : 2 (29) 0 (0) : 3 (100) Age (yrs): median (range) 76 (60, 84) 74 (61, 80) 80 (78, 87) ECOG: n 0/1/2 0/4/2 2/5/0 0/1/2 Median platelets (103/mm3) (range) 28 (21, 80) 16 (7, 146) 21 (9, 23) Median ANC (103/mm3) (range) 0.23 (0, 3.3) 1.85 (0.15, 11.0) 0.05 (0, 0.11) Median lines of prior therapy (range) 2.5 (1, 4) 2 (1, 4) 2 (1, 4) Risk Category (ELN): Favorable / Intermediate / Adverse 0/3/3 NA 0/1/2 IPSS-R: Low / Intermediate / High / Very High NA 0/0/2/5 NA Prior therapy, n (%) HMA2 6 (100) 7 (100) 3 (100) Chemotherapy3 3 (50) 0 (0) 1 (33) Venetoclax 4 (67) 1 (14) 3 (100) Data extraction date: Dec 16, 2021. 1. Two AML patients have both a spliceosome and FLT3 mutation and are included in both populations (there are 13 total evaluable patients with Spliceosome or FLT3 mutation); 2. HMA includes azacitidine, decitabine, and guadecitabine; 3. Chemotherapy includes cytarabine. Patient demographics indicate older population with poor prognosis; all patients received prior hypomethylating agent (HMA) therapy
Encouraging Clinical Activity in R/R AML/MDS Patient Populations CA-4948 shows activity as a monotherapy in patients with Spliceosome and FLT3 mutations Population #1: AML Spliceosome Patients1 CR/CRh Rate 2/5(40%) CR 1/5(20%) CRh 1/5(20%) Population #2: MDS Spliceosome Patients Objective Response Rate (ORR) 4/7(57%) CR 0/7(0%) mCR 4/7(57%) Population #3: AML FLT3 Patients1 CR/CRh Rate 1/3(33%) CR 1/3(33%) CRh 0/3(0%) Data extraction date: Dec 16, 2021. 1. Two AML patients have both a spliceosome and FLT3 mutation and are included in both populations (there are 13 total evaluable patients with Spliceosome or FLT3 mutation). Response criteria per 2017 ELN Criteria for AML and Modified IWG Criteria for MDS: CR=Complete Remission CRh=CR with partial hematologic recovery mCR=marrow CR The CR and CRh patients are both MRD-negative 1 mCR patient went to Stem Cell Transplant (SCT) FLT3 mutation eradicated in 2 out of 3 patients Best Response Efficacy
Clinical Data: R/R AML Patients with Spliceosome Mutation Patient Population #1
Unmet Need for R/R AML Patients with Spliceosome Mutation Spliceosome mutations occur in ~10% of AML patients1 These mutations create a chronic inflammatory marrow microenvironment2, which impairs hematologic recovery3 Ability to achieve CR is impaired in patients with U2AF1/SF3B1 mutation4 There are no effective therapies for patients R/R to Ven/HMA: no unified standard of care No approved targeted therapies and no unified standard of care for these patients 1. DiNardo et al, Hematology Am Soc 2016; 2. Smith et al. Nat Cell Biol 2019; 3. Trowbridge JEM 2021. Ochi Cancers 2021. Hou, Oncotarget 2016; 4. Hou, Oncotarget 2016; 5. Maiti et al. Haemtologica 2021 Opportunity to meaningfully improve outcomes in R/R AML patients with spliceosome mutations Intensive Elderly / Non-Intensive Induction Chemo SCT Ven/HMA Ven/HMA No Effective Therapies (mOS 2–4 months5) Salvage chemo SCT Salvage chemo
Initial CA-4948 Data Compare Favorably to Existing Therapies Potential to meaningfully improve outcomes in R/R AML patients with spliceosome mutation 1. CancerMPact Treatment Architecture U.S. AML, Cerner Enviza, www.cancermpact.com, accessed January 3, 2022. Excludes Investigational Therapies; 2. Product Package Insert; 3. Ritchie et al, Leuk Lymphoma 2013; 4. Itzykson et al, Leuk Res 2014; 5. Frikha et al, Bulletin du Cancer 1996; 6. Gemtuzumab ozogamicin is only approved for patients with newly-diagnosed CD33-positive AML or R/R CD33-positive AML Azacitidine2,4 LoDAC5 HMA Chemotherapy 17% CR/CRi rate Myelosuppressive IV or SC Administration ~13% ORR Myelosuppressive and Black Box Warning IV Administration Most Commonly Used in R/R AML with Wild Type FLT3/IDH1 Decitabine2,3 HMA ~16% CR rate Myelosuppressive IV Administration >6 months on CA-4948 for patients with CR/CRh CA-4948 40% CR/CRh rate (2 of 5 patients) No dose-limiting myelosuppression Oral Administration Gemtuzumab Ozogamicin2,6 Monoclonal Anti-CD33 Antibody (ADC) ~26% CR Myelosuppressive and Black Box Warning IV Administration IRAK4 Inhibitor Initial CA-4948 data compare favorably vs. historical responses with mainstay treatments for R/R AML patients with wild type FLT3/IDH
Encouraging Clinical Activity in R/R AML Patients with Spliceosome Mutation Achieved 40% CR/CRh rate, with treatment duration >6 months to date in responding patients CA-4948 achieved CR/CRh responses, despite transformed AML being historically highly resistant to treatment CR CRh Dx Dose (BID) Risk Category (ELN) Baseline Molecular Mutations Prior Therapies Duration on CA-4948 (mos) Blasts Baseline Blasts Best Response % Change # Lines Therapy sAML 300 mg Intermediate RUNX1, WT1, SF3B1 1 decitabine 7 23 0 -100% (CRh) sAML 300 mg Intermediate U2AF1, FLT3, BCOR, WT1 1 decitabine/venetoclax 6+ 39 4 -90% (CR) AML 300 mg Intermediate U2AF1, NRAS 4 cytarabine/idarubicin, decitabine/venetoclax, fludarabine/cyclophosphamide/methotrexate, azacitidine 2.5 33 16 -52% AML 300 mg Adverse FLT3, SF3B1, NRAS, PTPN11, RAD21, RUNX1, TET2, GATA, STAT3 4 cytarabine/daunorubicin, decitabine, decitabine/venetoclax, gilteritinib 2.6 95 77 -19% sAML 400 mg Adverse SF3B1, DNMT3A, P53 1 azacitidine/venetoclax 2 20 23 15% Data extraction date: Dec 16, 2021; “+” in Duration of Treatment indicates the patient remains on treatment as of the date of data extraction. 1. Two AML patients have both a spliceosome and FLT3 mutation and are included in both populations (there are 13 total evaluable patients with Spliceosome or FLT3 mutation).
Clinical Data: R/R MDS Patients with Spliceosome Mutation Patient Population #2
Spliceosome Mutations Common in MDS Spliceosome mutations (U2AF1/SF3B1) are the most prominent mutations in MDS, accounting for ~30% of all MDS patients1 These mutations create a chronic inflammatory marrow microenvironment2, which impairs hematologic recovery3 There are no effective therapies for patients R/R to HMA: chemotherapy is standard of care Large unmet need for R/R MDS patients with spliceosome mutation 1. Ochi Cancers 2021.; 2. Smith et al. Nat Cell Biol 2019.; 3. Trowbridge JEM 2021. Ochi Cancers 2021.; 4. Jabbour et al Cancer 2010; Prebet et al., JCO 2011; Duong et al, Clin Lymphoma Myeloma Leuk, 2013. Current standard of care offers limited therapeutic benefit to patients SCT Eligible Not SCT Eligible HMA SCT HMA No Effective Therapies (mOS 4–6 months4)
Clear Unmet Need in Relapsed/Refractory MDS Current standard of care offers little therapeutic benefit to patients 1. CancerMPact Treatment Architecture U.S. AML, Cerner Enviza, www.cancermpact.com, accessed January 3, 2022. Excludes Investigational Therapies; 2. Prébet et al, JCO 2011.; 3. Product Package Insert.; 4. Jabbour et al Cancer 2010; Prébet et al., JCO 2011; Duong et al, Clin Lymphoma Myeloma Leuk, 2013. Chemotherapy2 Decitabine3 Azacitidine3 CA-4948 Chemotherapy HMA HMA IRAK4 Inhibitor ~8% ORR Myelosuppressive and Black Box Warning IV Administration 2nd line response data unavailable Myelosuppressive IV Administration 2nd line response data unavailable Myelosuppressive IV or SC Administration 57% mCR rate (4 of 7 patients, incl. 1 that went to SCT) No dose-limiting myelosuppression Oral Administration Initial CA-4948 data compared favorably vs. historical responses with the mainstay treatment for R/R MDS patients In MDS post-HMA mOS is 4–6 months4; clear unmet need for these patients Most Commonly Used Therapies in R/R MDS1
Dx Dose (BID) IPSS-R Baseline Molecular Mutations Prior Therapies Duration on CA-4948 (mos) Blasts Baseline Blasts Best Response % Change # Lines Therapy MDS 200 mg Very High Risk U2AF1 ,ASXL1, NF1, PHF6, GFI1, KDM6A, TET2 1 azacitidine 5.7 11 2 -82% (mCR) MDS 300 mg Very High Risk U2AF1, DNMT3A, BCOR, STAG2, BCORL1, ETV6, SETBP1 1 magrolimab/azacitidine 3.3+ 12 5 -58% (mCR) MDS 400 mg Very High Risk SF3B1, RUNX1, NFE2 2 lenalidomide, guadecitabine 4.3 7 3 -57% (mCR) MDS 300 mg High Risk SF3B1, DNMT3A, ASXL1, TET2, EZH2 2 azacitidine, canakinumab 0.9 8 4 -50% (mCR) MDS 300 mg High Risk U2AF1, ASXL1 4 lenalidomide, azacitidine, cyclosporine, decitabine 5.3+ 3 2 -33% MDS 300 mg Very High Risk SF3B1, ASXL1, NF1, SH2B3, RUNX1, PHF6, CBL, GFI1, EZH2 3 ipilimumab/azacitidine, quizartinib/azacitidine, azacitidine/venetoclax/ pevonedistat 1.6 8 9 13% MDS 400 mg Very High Risk U2AF1, ASXL1, BCOR, DNMTA, GATA2, SETBP1 1 azacitidine 1.2 9 62 >100% Encouraging Clinical Activity in R/R MDS Patients with Spliceosome Mutation Marrow blast reduction achieved in 5 of 7 patients, including 4 marrow CRs Consistent tumor burden reduction in targeted population with limited options (went to SCT) Data extraction date: Dec 16, 2021; “+” in Duration of Treatment indicates the patient remains on treatment as of the date of data extraction. Patient went to SCT
Clinical Data: R/R AML Patients with FLT3 Mutation Patient Population #3
IRAK4 Signaling Drives Resistance to FLT3 Inhibitors IRAK4 inhibition is synergistic with, and prevents adaptive resistance to, FLT3 inhibition IRAK4 activity increases after quizartinib treatment of MLL-AF9 FLT3-ITD cells IRAK4 activity also shown to increase in patients during gilteritinib treatment IRAK and FLT3 inhibition is synergistically cytotoxic Viability of MLL-AF9;FLT3-ITD cells treated for 3 days with DMSO (vehicle control), quizartinib (0.5 μM), IRAK-Inh (10 μM), or quizartinib and IRAK-Inh Mice die if treated with quizartinib, but survive if treated with IRAK/FLT3 inhibitor (1481) Leukemia-free survival of NRGS mice xenografted with AML-019 Source: Melgar, Sci Transl Med. 2019.
CA-4948 May Address Unmet Need in R/R AML Patients with FLT3 Mutation No approved therapies for patients R/R to FLT3 inhibitors 1. CancerMPact Treatment Architecture U.S. AML, Cerner Enviza, www.cancermpact.com, accessed January 3, 2022. Excludes Investigational Therapies; 2. Product Package Insert; 3. Perl et al NEJM 2019; 4. Gemtuzumab ozogamicin is only approved for patients with CD33-positive AML; 5. Saygin, et al. J Hematol Oncol. 2017; 6. Melgar, Sci Transl Med. 2019 Gilteritinib2,3 Azacitidine2 CA-4948 FLT3 Inhibitor HMA IRAK4 Inhibitor ~12% CR No dose-limiting myelosuppression Oral Administration 2nd line response data unavailable Myelosuppressive IV or SC Administration 33% CR (1 of 3 patients) No dose-limiting myelosuppression Oral Administration IRAK4/FLT3 inhibition may improve efficacy in R/R AML patients with FLT3 mutation5 Decitabine2 HMA 2nd line response data unavailable Myelosuppressive IV Administration Gemtuzumab Ozogamicin2,4 Monoclonal Anti-CD33 Antibody (ADC) ~26% CR Myelosuppressive and Black Box Warning IV Administration Most Commonly Used Therapies in R/R AML Patients with FLT3 Mutation1 Dual inhibition of IRAK4 and FLT3 may lead to increased efficacy, as signaling through IRAK4 drives resistance to FLT3 inhibitors6 ~30% of AML patients have FLT3 mutation5
Encouraging Clinical Activity in R/R AML Patients with FLT3 Mutation Achieving disease modification in heavily pretreated patients with CA-4948 monotherapy Significant marrow blast reduction and FLT3 mutation eradicated in 2 out of 3 patients Data extraction date: Dec 16, 2021; “+” in Duration of Treatment indicates the patient remains on treatment as of the date of data extraction. 1. Two AML patients have both a spliceosome and FLT3 mutation and are included in both populations (there are 13 total evaluable patients with Spliceosome or FLT3 mutation). Dx Dose (BID) Risk Category (ELN) Baseline Molecular Mutations Prior Therapies Duration on CA-4948 (mos) Blasts Baseline Blasts Best Response % Change # Lines Therapy AML 400 mg Adverse FLT3 (eradicated at C3D1), ASXL1, BCOR, CEBPA (eradicated at C3D1), CSF3R, EZH2, NRAS, RUNX1 (X3), STAG2, TET2(X2,1) (eradicated at C3D1) 2 decitabine/venetoclax, gilteritinib (refractory to gilteritinib) 5.1 60 5 -92% sAML 300 mg Intermediate FLT3 (eradicated at C4D1), BCOR (eradicated at C4D1), U2AF1 (decreased to 1.3 VAF at C4D1), WT1 (eradicated at C4D1) 1 decitabine/venetoclax 6.2+ 39 4 -90% (CR) AML 300 mg Adverse FLT3, SF3B1, NRAS, PTPN11, RAD21, RUNX1, TET2, GATA, STAT3 4 cytarabine/daunorubicin, decitabine/PCM-075, decitabine/venetoclax, gilteritinib 2.6 95 77 -19%
Summary CA-4948 in Three Targeted Patient Populations
Comments from Clinical Investigator, Daniel DeAngelo, MD, PhD Encouraging clinical activity in patients with R/R disease, all of whom had prior HMA treatment 4 out of 5 patients with spliceosome-mutated AML achieved blast reduction 2 patients achieved CR/CRh with significant hematologic improvement, including 1 full CR 5 out of 7 patients with spliceosome-mutated MDS achieved blast reduction 4 patients achieved marrow CR, 1 of whom proceeded to Stem Cell Transplant All 3 patients with FLT3-mutated AML achieved blast reduction 2 patients achieved eradication of FLT3 mutation, including 1 full CR Manageable Toxicity/Safety Profile Oral drug with a well-tolerated and manageable safety profile Supports further development, both as a single agent and in combination therapy Chief, Division of Leukemia at Dana-Farber Cancer Institute
CA-4948 Has Potential to Address Clear Unmet Need in AML and MDS First-in-class IRAK4 inhibitor targets specific genetic populations in AML and MDS Next Steps in Expansion Monotherapy: Spliceosome mutation Monotherapy: FLT3 mutation Combination: CA-4948 + azacitidine Combination: CA-4948 + venetoclax Plan to discuss potential for a rapid registrational path with FDA in 1H 2022 CA-4948 addresses a novel target (IRAK4) and: (1) demonstrates clear anti-cancer activity as an oral single agent (2) is active in genetically-defined populations that can be identified and enrolled (3) has the added potential benefit of also hitting FLT3 Well-tolerated and manageable safety profile may provide advantage to existing standard of care therapies as a single agent, and also suggests CA-4948 may be a favorable candidate for addition to combination therapy regimens Dual targeting of IRAK4 and FLT3 may prevent adaptive resistance to current FLT3 inhibitors1 1. Melgar, Sci Transl Med. 2019
CI-8993: First-in-class VISTA Antagonist Novel Immune Checkpoint Inhibitor for Solid Tumors
Anti-cancer Mechanisms of Checkpoint Inhibitors Role of VISTA may go beyond other checkpoint inhibitors Target VISTA (CI-8993) þ þ þ þ þ PD-1 (Pembro, Nivo, etc.) þ ý ý ý þ PD-L1 (Atezo, Durva, etc.) ý ý ý ý þ CTLA-4 (Ipi) ý ý ý ý þ TIM3 þ ý ý ý þ LAG3 ý ý ý ý þ OX40 ý ý ý ý þ TIGIT ý ý ý ý þ We believe VISTA inhibition has potential for broad application in many tumor types in monotherapy and in combination with existing checkpoint inhibitors Checkpoint Inhibitors Approved in Multiple Malignancies: Melanoma Lung Carcinoma Renal Cell Carcinoma Head & Neck Squamous Cell Carcinoma Lymphoma Hepatocellular Carcinoma Merkel Cell Carcinoma Gastric/Gastroesophageal Adenocarcinoma Cervical Carcinoma Cutaneous Squamous Cell Carcinoma Breast Carcinoma Esophageal Carcinoma Uterine Carcinoma Urothelial Carcinoma Genomic Alterations (e.g., MSI-high) Sources: Curis & ImmuNext internal data, Curis 2021 VISTA Symposium.
Incorporated Learnings from CI-8993 Prior Clinical Study CI-8993 is the first anti-VISTA monoclonal antibody (IgG1κ) to be studied in clinical trials Janssen initiated a Ph1 study in 2016 and enrolled 12 patients1 Transient Cytokine Release Syndrome (CRS) observed in several patients at 0.15mg/kg Transient grade 3 CRS-associated encephalopathy observed at 0.3mg/kg, after which Janssen halted the study Pharmacodynamic activity (cytokine release) observed in initial clinical study CI-8993 Protocol Designed to Manage Expected CRS CRS is likely an on-target effect; indicates drug is hitting the target and inducing immune response NCCN guidelines were issued in 2018; oncology community now familiar with managing CRS Desensitizing step-dose of CI-8993, and pre/post-infusion medication, administered to mitigate CRS 1. ClinicalTrials.gov, Trial #NCT02671955
CI-8993 Clinical Plan: Phase 1 Dose Escalation Study On-going clinical study to determine safety Patient Population Patients with advanced refractory solid tumors (includes mesothelioma, melanoma, NSCLC, TNBC) Treatment Bi-weekly dosing Plan to mitigate potential toxicities by co-medication and step dosing (desensitization) Objectives Safety, PK/PD, tolerability during dose escalation Anti-cancer activity during expansion Continue dose escalation until RP2D is identified Higher Doses 0.6 mg/kg (current dose) 0.3 mg/kg 0.15 mg/kg Phase 1 Dose Escalation Study Design NSCLC: Non-Small Cell Lung Cancer; TNBC: Triple Negative Breast Cancer
CI-8993 Has Demonstrated Favorable Safety Profile Successfully managed expected CRS at all levels dosed to date Data extraction date: Dec 11, 2021. One additional patient experienced grade 2 treatment-related AE after receiving step dose and chose not to proceed to full dose. CI-8993 has successfully cleared dose level where Janssen observed DLT All Grades Treatment-Related Adverse Events Occurring in 2+ Patients 0.15 mg/kg (N = 7) 0.3 mg/kg (N = 5) Preferred Term n (%) n (%) Number of patients having any grade treatment-related AEs 4 (57.1) 4 (80.0) Headache 3 (42.9) 1 (20.0) Chills 2 (28.6) 1 (20.0) Alanine aminotransferase increased 1 (14.3) 1 (20.0) Fatigue 2 (28.6) 0 Hypotension 0 2 (40.0) Grade 3+ Treatment-Related Adverse Events 0.15 mg/kg (N = 7) 0.3 mg/kg (N = 5) Preferred Term n (%) n (%) Number of patients having grade 3+ treatment-related AEs 0 1 (20.0) Leukopenia 0 1 (20.0)
CI-8993 Has Demonstrated Favorable PK Profile CI-8993 mean plasma concentration vs. time profile following IV administration at full dose 3.5-fold 1.5-fold 9.8-fold 8.0-fold 78.4-fold Cmax Levels Log-Mean ± SE CI-8993 Plasma Concentration (ng/mL) 100,000 1,000,000 10,000 1,000 100 10 1 Saturation kinetics in Cmax data (“sink effect”) suggest potential for broad bioavailability at higher dose levels Plasma Concentration
Pharmacodynamic Effects of CI-8993 in Patients CI-8993 affects multiple anticancer mechanisms supporting VISTA potential Decreased recruitment of MDSCs Decreased CXCR2 on granulocytes 1 2 NK Cell Activation Decreased CD16 on NK cells Baseline Pre-1st Dose Post-1st Dose Pre-3rd Dose Baseline Pre-1st Dose Post-1st Dose Pre-3rd Dose Baseline Pre-1st Dose Post-1st Dose Pre-3rd Dose Baseline Pre-1st Dose Post-1st Dose Pre-3rd Dose Cohort 1 Cohort 2 Cohort 1 Cohort 2 Similar finding for CCR2 on monocytes CI-8993 reduces MDSCs (↓CXCR2 and ↓CCR2); MDSCs suppress anti-tumor immunity and impair efficacy of other checkpoint inhibitors CI-8993 activates NK cells (↓CD16 signifies NK activation); activated NK cells exert an important anti-tumor function via the innate immune system
Pharmacodynamic Effects of CI-8993 in Patients CI-8993 affects multiple anticancer mechanisms supporting VISTA potential Enhanced Antigen Presentation Increased HLA-DR on Monocytes 4 5 Release of T-Cell Activating Factors Increased Secretion of IP10 Similar finding for MIP1a Baseline Pre-1st Dose Post-1st Dose Pre-3rd Dose Baseline Pre-1st Dose Post-1st Dose Pre-3rd Dose Baseline Post-Infusion 4h Post-Infusion 2h Post-Infusion 24h Post-Infusion Baseline Pre-Infusion 2h Post-Infusion Post-Infusion 4h Post-Infusion 24h Post-Infusion CI-8993 enhances antigen presentation (↑HLA-DR); antigen presentation allows the immune system to recognize the tumor and attack it CI-8993 increases T-cell factors (↑IP10 and ↑MIP1α); these stimulate T-cell expansion and transformation into effector T-cells Cohort 1 Cohort 2 Cohort 1 Cohort 2
CI-8993 Cleared Initial Safety Hurdle First-in-class CI-8993 has potential for broad applicability in immune checkpoint therapy Encouraging initial safety data appears to demonstrate effectiveness of procedures implemented to manage expected CRS Pharmacokinetic profile of CI-8993 exhibits saturation kinetics, suggesting potential to overcome “sink effect” Pharmacodynamic effects of CI-8993 in patients suggest multiple anti-cancer mechanisms may be activated Next Steps in Dose Escalation Continue dose-escalation for signs of anti-cancer activity and determination of RP2D
Closing Comments
Initial clinical data demonstrate clear anti-cancer activity with a single, oral agent in specific genetic populations of AML/MDS Initial safety data appear to demonstrate that expected immune effects (cytokine release) can be managed, and early PK/PD data show that anti-cancer mechanisms are being activated Closing Remarks & Next Steps Clinical update on CA-4948 (IRAK4) and CI-8993 (VISTA) Next Steps Plan to discuss potential for a rapid registrational path with FDA in 2022 Next Steps Continue dose-escalation for signs of anti-cancer activity and determination of RP2D CA-4948 CI-8993
Q&A
EX-99.2
Exhibit 99.2
PRESS RELEASE
Curis Announces Updated Data with Additional Encouraging Clinical Activity in Phase 1/2 Study ofCA-4948 Monotherapy in Targeted Patients with Relapsed or Refractory AML and MDS; and Initial Clinical Data from Phase 1 Study of CI-8993 in Patients with Relapsed orRefractory Solid Tumors
40% CR/CRh rate (complete remission and complete remission with partial hematologic recovery) in R/R AMLpatients with U2AF1 or SF3B1 spliceosome mutation treated with CA-4948
57% ORR (objectiveresponse rate) observed in R/R MDS patients with U2AF1 or SF3B1 spliceosome mutation treated with CA-4948
Added potential benefit of FLT3 inhibition highlighted by significant marrow blast reduction and eradication of FLT3 mutation in 2 out of 3R/R AML patients with FLT3 mutation at baseline following treatment with CA-4948
Promisinginitial safety data of CI-8993 highlights effectiveness of procedures implemented to manage expected cytokine release syndrome and enable dose escalation past 0.3 mg/kg
Pharmacodynamic data provide early indication that targeting VISTA with CI-8993 may activatemultiple anti-cancer mechanisms
Management to host conference call today at 8:00 a.m. ET
LEXINGTON, Mass., January 6, 2022 /PRNewswire/ — Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, today announced positive updated clinical data from the ongoing open label Phase 1/2 dose escalation and expansion study of CA-4948, a novel, small molecule IRAK-4 inhibitor, as a monotherapy in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) or high risk myelodysplastic syndromes (MDS) as well as initial safety, pharmacokinetic and pharmacodynamic data from the Phase 1 dose escalation study of CI-8993, a monoclonal antibody targeting VISTA for patients with R/R solid tumors.
“These data continue to build on what we believe to be a compelling profile for CA-4948, showing its activity as a monotherapy in a targeted population of patients living with R/R AML/MDS, for whom prior lines of therapy have been unsuccessful,” said James Dentzer, President and Chief Executive Officer of Curis. “We are especially pleased that these results demonstrate both a favorable safety profile and improved anti-cancer activity compared with standard of care therapies for these patients. Furthermore, we have been able to successfully identify and enroll these patients using existing genetic diagnostic panels. We remain on track to enroll additional patients with a spliceosome mutation to prepare for potential discussions with the U.S. Food and Drug Administration (FDA) in the first half of 2022 regarding the potential for a rapid registrational path forward for CA-4948 as a monotherapy in genetically-defined patient populations.”
“We are also encouraged by the safety data from the CI-8993 trial, which we believe demonstrate that the procedures we implemented to manage the expected cytokine release effect have been successful – and have allowed us to escalate patient dosing up to and beyond 0.3 mg/kg,” he continued. “We have recently begun dosing at 0.6 mg/kg; and look forward to providing another update on our progress in the second half of 2022. We are thrilled to have achieved this key safety and dose escalation milestone, as it brings us one step closer to providing anti-VISTA therapy for patients living with solid tumors.”
Phase 1/2 monotherapy study of CA-4948 in R/R AML/MDS
Well Tolerated and Manageable Safety Profile at 300 mg BID Dose Level
As of December 16, 2021, 49 total patients had been administered CA-4948 in the R/R AML/MDS study across 200mg, 300mg, 400mg, and 500mg dose cohorts. The safety profile observed to date showed the following key findings:
| • | CA-4948 was well-tolerated across multiple dose levels, including at the<br>Recommended Phase 2 Dose of 300 mg BID |
|---|---|
| • | Treatment-related adverse events were reversible and manageable |
| --- | --- |
| • | No dose-limiting myelosuppression |
| --- | --- |
| • | No cumulative toxicities observed |
| --- | --- |
| • | No grade 4 or 5 treatment-related adverse events |
| --- | --- |
We believe these attributes of CA-4948’s emerging safety profile may provide an advantage compared to current standard of care therapies in monotherapy and could also make CA-4948 an attractive candidate for addition to combination therapy regimens.
In Expanded Data Set, Findings Support Earlier Data Presented in June 2021
Previous data presented by Curis at the European Hematology Association in June 2021, highlighted preliminary efficacy data of CA-4948 in R/R AML/MDS patients whose disease is characterized by spliceosome or FLT3 mutation. It is this genetically-defined subset of AML/MDS that is specifically targeted by CA-4948 and therefore represents the patients most
likely to benefit from treatment with CA-4948 in monotherapy. Today’s clinical data update provides an expanded data set for this genetically-defined patient population and further support the rationale for seeking a discussion with FDA in the first half of 2022 to discuss the potential for a rapid registrational path forward for CA-4948 as a monotherapy in genetically-defined patient populations.
In order to assess preliminary efficacy for these patients on study, Curis presented data on patients that had enrolled as of September 30, 2021, which allowed the opportunity for at least 2 disease assessments, to determine marrow response. Based on this criterion, there were 12 evaluable patients with a U2AF1 or SF3B1 spliceosome mutation (7 MDS; 5 AML) and 3 evaluable patients with a FLT3 mutation. There were 13 total evaluable patients; two AML patients presented with both a spliceosome mutation and FLT3 mutation and are therefore included in both subpopulations. These patients had experienced a median of 2 prior lines of therapy (range 1-4), and all patients had prior hypomethylating agent (HMA) treatment.
In patients with spliceosome-mutated R/R AML, key findings included:
| • | CR/CRh rate of 40% (2 out of 5 patients) |
|---|---|
| • | Both patients who achieved CR/CRh have been on study > 6 months and achieved negative MRD (minimal residual<br>disease) status |
| --- | --- |
| • | Consistent tumor burden reduction observed, 3 out of 5 patients with elevated blast counts achieving ³ 50% reduction in blast counts |
| --- | --- |
In patients with spliceosome-mutated R/R MDS, key findings included:
| • | Objective response rate of 57% (4 out of 7 patients) |
|---|---|
| • | One of the patients who achieved a marrow CR (mCR) proceeded to stem cell transplant after 1 cycle<br> |
| --- | --- |
| • | Consistent tumor burden reduction observed, with 4 out of 7 patients achieving<br>³ 50% reduction in blast counts |
| --- | --- |
In patients with a FLT3 mutated R/R AML, key findings included:
| • | CR rate of 33% (1 out of 3 patients) |
|---|---|
| • | 2 out of 3 patients showed eradication of FLT3 mutation following treatment, indicating potential to modify the<br>disease |
| --- | --- |
| • | Consistent tumor burden reduction observed; with 2 out of 3 patients with elevated blast counts achieving ³ 50% reduction in blast counts |
| --- | --- |
We believe the data suggest a favorable safety and anti-cancer activity profile compared to standard of care therapies for these patient populations.
Enrollment in the study of CA-4948 in R/R AML/MDS is on-going, and Curis looks forward to potential discussions with the FDA in the first half of 2022 regarding the potential for a rapid registrational path forward for CA-4948 as a monotherapy in genetically-defined patient populations. Curis expects to provide additional data from the R/R AML/MDS study at a medical meeting in 2022.
Phase 1 monotherapy study of CI-8993 in R/R solid tumors
Promising Safety Profile – No DLTs
Based on 13 patients treated in the first two dose cohorts of 0.15mg/kg and 0.3mg/kg, we believe CI-8993 has shown a promising safety profile to date, with no dose-limiting toxicities observed.
Following the implementation of safety measures including step dosing and co-medication, the trial has successfully dose escalated through the 0.15 mg/kg and 0.3 mg/kg cohorts, the dose level at which Janssen discontinued a prior study after a patient experienced a reversible grade 3 treatment-related adverse event.
The current study of CI-8993 in patients with solid tumors is currently enrolling at 0.6 mg/kg.
Encouraging PK/PD Activity
In the prior Janssen study, CI-8993 had demonstrated that, at low doses, a “sink effect” limited the amount of CI-8993 that could be detected in the circulation of patients. In the current Curis study, CI-8993 has shown non-linear increases in pharmacokinetic (PK) exposure at each dose level and exhibits saturation kinetics, indicating the potential to overcome this sink effect as we increase dose. These findings suggest the potential for broad bioavailability at higher dose levels. The pharmacodynamic (PD) effects of CI-8993 in patients observed to date suggest the possibility that CI-8993 can activate multiple anti-cancer immune mechanisms, including mechanisms that are not addressed by currently approved checkpoint inhibitors. Curis intends to further explore this PK/PD relationship at higher dose levels, as the study continues.
Curis expects to report expanded safety and tolerability data, along with initial PK, PD and anti-cancer data from the trial in the second half of 2022.
Conference Call Information
Curis management will host a conference call today, January 6, 2022, at 8:00 a.m. ET, to discuss these results with Dr. Daniel DeAngelo, Chief, Division of Leukemia at Dana-Farber Cancer Institute.
To access the live conference call, please dial 1-888-346-6389 from the United States or 1-412-317-5252 from other locations, shortly before 8:00 a.m. ET. The conference call can also be accessed on the Curis website at www.curis.com in the Investors section.
About CA-4948
CA-4948 is an IRAK4 kinase inhibitor and IRAK4 plays an essential role in the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways, which 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. The overexpression of IRAK4-L is believed to be driven by a variety of factors, including specific spliceosome mutation such as SF3B1 and U2AF1. In addition to inhibiting IRAK4, CA-4948 was also designed to inhibit FLT3, a known oncologic driver, which may provide additional benefit in patients with AML and MDS.
About CI-8993
CI-8993 is a monoclonal IgG1K antibody with active Fc, designed to antagonize the V-domain Ig suppressor of T-cell activation (VISTA) signaling pathway. VISTA is a novel negative checkpoint ligand expressed on myeloid cells and T cells that is homologous to PD-1/PD-L1. VISTA enhances T cell quiescence and myeloid derived immune suppressor cells (MDSCs). CI-8993 relieves negative regulation by hematopoietic cells and enhances protective anti-tumor immunity. Preclinically, VISTA monoclonal antibody treatment increased the number of tumor-specific T cells in the periphery, and enhanced the infiltration, proliferation and effector function of tumor-reactive T cells within the tumor microenvironment (TME). VISTA blockade alters the suppressive feature of the TME by decreasing the presence of monocytic and granulocytic MDSCs and increasing the presence of activated dendritic cells (DCs) within the TME leading to enhanced T cell mediated immunity. VISTA monoclonal antibody administration as a monotherapy has been shown to suppress the growth of both transplantable and inducible melanoma in preclinical models. CI-8993 was originally developed as part of a license and collaboration agreement between ImmuNext and Janssen Biotech, Inc (Janssen). In 2016, Janssen initiated clinical development of CI-8993 in a Phase 1 study of CI-8993 in patients with advanced solid tumors. The study enrolled 12 patients, in which one patient experienced dose-limiting side effects related to cytokine release syndrome. Afterwards, Janssen opted to close the study and ImmuNext regained control of the asset. Curis is engaged in a collaboration with ImmuNext for the development of CI-8993.
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 1/2 trial in patients with non-Hodgkin’s lymphoma both as a monotherapy and in combination with BTK inhibitor ibrutinib. Curis is also evaluating CA-4948 in a Phase 1/2 trial in patients with acute myeloid leukemia and myelodysplastic syndromes, for which it has received Orphan Drug Designation from the U.S. Food and Drug Administration. 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 1 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’s website at www.curis.com.
Cautionary Note Regarding 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, any statements concerning expectations of the potential for Curis’s proprietary drug candidates CA-4948 and CI-8993, including with respect to the potency, anti-cancer activity, durability and tolerability of CA-4948 and CI-8993; future studies with respect to CA-4948 and CI-8993; the potential advantages and benefits of CA-4948, CI-8993 and checkpoint inhibitors over other therapies; and Curis’s plans to advance its development programs for CA-4948 and CI-8993, including with respect to anticipated results, clinical trials, regulatory and commercialization plans and timelines; and statements of assumptions underlying any of the foregoing. Forward-looking statements may contain the words “believes,” “expects,” “anticipates,” “plans,” “intends,” “seeks,” “estimates,” “assumes,” “predicts,” “projects,” “targets,” “will,” “may,” “would,” “could,” “should,” “continue,” “potential,” “focus,” “strategy,” “mission,” 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 cause unexpected toxicities, fail to demonstrate sufficient safety and efficacy in clinical studies and/or may never achieve the requisite regulatory approvals needed for commercialization. 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 the collaboration agreements with Aurigene and ImmuNext, or the CRADA with National Cancer Institute, will continue for their full terms, , that Curis or its collaborators will each maintain the financial and other resources necessary to continue financing their respective portions of the research, development and commercialization costs, or that the parties will successfully discover, develop or commercialize drug candidates under the collaborations. Regulatory authorities may determine to delay or restrict Genentech’s and/or Roche’s ability to continue to develop or commercialize Erivedge in BCC. Erivedge may not demonstrate sufficient or any activity to merit its further development in disease indications other than BCC. Competing drugs may be developed that are superior to Erivedge. In connection with its agreement with Oberland Capital, Curis faces risks relating to the transfer and encumbrance of certain royalty and royalty-related payments on commercial sales of Erivedge, including the risk that, in the event of a default by Curis or its wholly-owned subsidiary, Curis could lose all retained rights to future royalty and royalty-related payments, Curis could be required to repurchase such future royalty and royalty-related payments at a price that is a multiple of the payments it has received, and its ability to enter into future arrangements may be inhibited, all of which could have a material adverse effect on its business, financial condition and stock price. Curis will require substantial additional capital
to fund its business. 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 business prospects and its ability to continue operations, and would have a negative impact on its financial condition and its ability to pursue its business strategies. Curis faces substantial competition. Curis and its collaborators face 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 litigation and interference 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, and could adversely impact Curis’s operating results and its ability to raise capital. For example, the COVID-19 pandemic may result in closures of third-party facilities, impact enrollment in clinical trials or impact sales of Erivedge by Genentech and/or Roche. The extent to which the COVID-19 pandemic may impact Curis’s business or operating results 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 captions “Risk Factor Summary” and “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 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.
For further information:
Elif McDonald
VP, Investor Relations and Corporate Communications
Curis, Inc.
617-503-6583
emcdonald@curis.com