Curis Profile
Curis, Inc. operates as a biotechnology company. The company focuses on the development of first-in-class and innovative therapeutics for the treatment of cancer.
The company engages in the discovery and development of innovative drug candidates for the treatment of human cancers.
Product Development Programs
The company is seeking to develop and commercialize innovative drug candidates to treat cancer. The company’s product development initiatives are being pursued using its internal resources or through its collaborations. The company conducts its research and development programs both internally and through strategic collaborations.
Emavusertib
Emavusertib, the company’s lead clinical stage drug candidate, is an orally available small molecule drug candidate that is designed to inhibit the Interlukin-1 receptor associated kinase 4, or IRAK4 kinase, which is an important transducer of toll-like receptor or certain interleukin receptor signaling pathways. These signaling pathways are shown to be involved in certain human cancers and inflammatory diseases.
Emavusertib is a potent inhibitor of IRAK4 in biochemical and cell-based assays, as well as in an in vivo tumor model of diffuse large B cell lymphoma that harbors mutation in the IRAK4 pathway. Lead compounds from this program were also shown to be effective in an in vivo preclinical model of acute inflammation, suggesting that emavusertib and other program compounds have the potential for use in the treatment of cancer and inflammatory diseases. Emavusertib has been shown to be active in in vivo xenograft models of human lymphoma, and demonstrates activity in ex-vivo models of acute myeloid leukemia, or AML, and high-risk myelodysplastic syndromes, or hrMDS. In April 2021, emavusertib was granted Orphan Drug Designation for the treatment of AML and hrMDS by the U.S. Food and Drug Administration, or FDA.
Emavusertib is undergoing testing in a Phase 1/2 open-label, single arm dose escalating and expansion trial in patients with relapsed or refractory, or R/R, AML, and hrMDS, also known as the TakeAim Leukemia Phase 1/2 study. The company is also conducting a separate Phase 1/2 open-label dose escalating clinical trial in patients with relapsed or refractory hematologic malignancies, such as non-Hodgkin lymphomas, or NHL, including those with Myeloid Differentiation Primary Response Protein 88, or MYD88, alterations, also known as the TakeAim Lymphoma Phase 1/2 study.
In April 2022, the FDA placed partial clinical holds on the company’s TakeAim Leukemia Phase 1/2 study and TakeAim Lymphoma Phase 1/2 study after it reported the death of a patient with R/R AML in the TakeAim Leukemia Phase 1/2 study. In August 2022, the FDA lifted the partial clinical hold on the TakeAim Lymphoma Phase 1/2 study. The partial clinical hold was lifted following agreement with the FDA on its strategy for rhabdomyolysis identification and management, as well as on the enrollment of at least nine additional patients at the 200mg dose level. In addition, the company has agreed to enroll at least six additional patients at the 100mg dose level of emavusertib in combination with ibrutinib. In August 2022, the FDA notified the company that it could resume enrollment of additional patients in the monotherapy dose finding phase (Phase 1a) of the TakeAim Leukemia Phase 1/2 study, in which it has agreed to enroll at least nine additional patients at the 200mg dose level. The partial clinical hold remains in place for the monotherapy expansion phase (Phase 2a) and the combination therapy phase (Phase 1b) of emavusertib with azacitidine or venetoclax of the study until Phase 1a is complete and the FDA approves proceeding to the next phases of the study.
In June 2022, the company provided initial preliminary clinical data for patients in the combination portion of the TakeAim Lymphoma Phase 1/2 study, and it presented initial clinical data for patients from the TakeAim Leukemia Phase 1/2 study in both January and December 2022.
Erivedge
Erivedge is an orally bioavailable small molecule which is designed to selectively inhibit the Hedgehog signaling pathway by targeting a protein called Smoothened. Erivedge is FDA approved for the treatment of adults with metastatic basal cell carcinoma, or with locally BCC that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation and is being developed under a collaboration agreement with Genentech Inc., a member of the Roche Group. Genentech and F. Hoffmann-La Roche Ltd, or Roche, are responsible for the clinical development and global commercialization of Erivedge. Erivedge is marketed and sold in the U.S. by Genentech and in the European Union, Australia and several other countries by Roche.
Other programs
In November 2022, the company announced that it is concentrating its resources to further advance the development of emavusertib. Resources have been reallocated to the emavusertib programs and resources dedicated to all other pipeline programs have been reduced. Deprioritization of other programs enabled a reduction of approximately 30% of its workforce and is expected to extend its cash runway into 2025. In connection with this reprioritization, the following programs have been deprioritized.
CI-8993
CI-8993 is a human IgG1 kappa monoclonal antibody directed against the VISTA protein. VISTA shares homology with other immune checkpoint proteins, including PD-1 and PD-L1, and is an important negative regulator in the immune suppression induced by cancer. Recent studies suggest VISTA is strongly upregulated in response to treatment with other cancer immunotherapy agents. VISTA is strongly expressed in several tumor types, including pancreatic cancer, mesothelioma, and prostate cancer. VISTA creates an immune blocking signal that is independent of, and complementary to, PD-1 and CTLA-4.
CI-8993 was originally developed as part of a license and collaboration agreement between ImmuNext and Janssen Biotech, Inc., or Janssen. In 2016, Janssen initiated clinical development of CI-8993 in a Phase 1 study evaluating safety, pharmacokinetics and pharmacodynamics of ascending doses 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. Janssen opted to close the study and ImmuNext regained control of the asset.
In September 2020, the company began enrollment in its Phase 1 trial of CI-8993 in patients with R/R solid tumors. The company has an option to license CI-8993 from ImmuNext. To date, it has escalated the dose of CI-8993 to 1mg/kg in its Phase 1 study and has not yet reached the maximum tolerated dose. The company is continuing to monitor patients.
Fimepinostat
Fimepinostat was invented by the company’s scientists and is an oral, dual inhibitor of HDAC and PI3K enzymes. The company conducted Phase 1 and Phase 2 fimepinostat monotherapy clinical studies in R/R DLBCL (3rd line or later) and as a Phase 1 combination study with fimepinostat and venetoclax in DLBCL patients. In the monotherapy study, the company observed durable complete and partial responses. In its combination study, the company observed no significant drug-drug interaction. The company is evaluating strategic alternatives for fimepinostat.
The company is party to an agreement with The Leukemia and Lymphoma Society, or LLS, dated November 2011, and as amended in August 2015.
CA-170
CA-170 is an oral small molecule drug candidate that is designed to selectively target VISTA and PDL1 immune checkpoint proteins, both of which independently function as negative regulators of immune activation. The company conducted a Phase 1 trial of CA-170 in patients with solid tumors and lymphomas. The company’s collaboration partner, Aurigene Discovery Technologies Limited, or Aurigene, is conducting a Phase 2b/3 randomized study evaluating CA-170 in combination with chemoradiation.
CA-327
CA-327 is an oral small molecule drug candidate that is designed to selectively target PD-L1 and TIM3 immune checkpoint proteins, both of which independently function as negative regulators of immune activation. CA-327 has demonstrated anti-tumor activity in multiple syngeneic mouse tumor models in an immune-dependent manner.
Collaborations and License Agreements
Aurigene
In January 2015, the company entered into an exclusive collaboration agreement with Aurigene for the discovery, development and commercialization of small molecule compounds in the areas of immuno-oncology and selected precision oncology targets. Under the collaboration agreement, Aurigene granted the company an option to obtain exclusive, royalty-bearing licenses to relevant Aurigene technology to develop, manufacture and commercialize products containing certain of such compounds anywhere in the world, except for India and Russia, which are territories retained by Aurigene.
In September 2016, the company and Aurigene entered into an amendment to the collaboration agreement. In February 2020, the company and Aurigene further amended its collaboration agreement. Under the terms of the amended agreement, Aurigene will fund and conduct a Phase 2b/3 randomized study evaluating CA-170, in combination with chemoradiation, in approximately 240 patients with nsNSCLC. In turn, Aurigene has rights to develop and commercialize CA-170 in Asia, in addition to its existing rights in India and Russia, based on the terms of the original agreement. The company retains U.S., European Union, and rest of world rights to CA-170, and are entitled to receive royalty payments on potential future sales of CA-170 in Asia.
As of December 31, 2022, the company had exercised its option to license the following four programs under the collaboration:
IRAK4 Program - a precision oncology program of small molecule inhibitors of IRAK4. The development candidate is emavusertib.
PD1/VISTA Program - an immuno-oncology program of small molecule antagonists of PD1 and VISTA immune checkpoint pathways. The development candidate is CA-170.
PD1/TIM3 Program - an immuno-oncology program of small molecule antagonists of PD1 and TIM3 immune checkpoint pathways. The development candidate is CA-327.
The company exercised its option to license a fourth program, which is an immuno-oncology program.
For each of its licensed programs, the company obligated to use commercially reasonable efforts to develop, obtain regulatory approval for, and commercialize at least one product in each of the U.S., specified countries in the European Union and Japan, and Aurigene is obligated to use commercially reasonable efforts to perform its obligations under the development plan for such licensed program in an expeditious manner.
ImmuNext
In January 2020, the company entered into an option and license agreement with ImmuNext, or the ImmuNext Agreement. Under the terms of the ImmuNext Agreement, the company agreed to engage in a collaborative effort with ImmuNext, and to conduct a Phase 1 clinical trial of CI-8993. In exchange, ImmuNext granted the company an exclusive option, exercisable until the earlier of (a) January 2024 and (b) 90 days after database lock for the first Phase 1 trial in which the endpoints are satisfied, or the Option Period, to obtain an exclusive, worldwide license to develop and commercialize certain VISTA antagonizing compounds and products containing these compounds in the field of oncology.
Genentech
In 2003, the company entered into a collaborative research, development and license agreement with Genentech, which it refers to as the collaboration agreement.
Under the terms of its collaboration agreement with Genentech, the company granted Genentech an exclusive, global, royalty-bearing license, with the right to sublicense, to make, use, sell and import molecules capable of inhibiting the Hedgehog signaling pathway (including small molecules, proteins and antibodies) for human therapeutic applications, including cancer therapy. Genentech subsequently granted a sublicense to Roche for non-U.S. rights to Erivedge other than in Japan where such rights are held by Chugai. Genentech and Roche are responsible for worldwide clinical development, regulatory affairs, manufacturing and supply, formulation, and sales and marketing.
Transactions Related to Erivedge Royalties
In March 2019, the company and Curis Royalty entered into a royalty interest purchase agreement, referred to as the Oberland Purchase Agreement, with TPC Investments I LP and TPC Investments II LP, referred to as the Purchasers, each of which is a Delaware limited partnership managed by Oberland Capital Management, LLC, and Lind SA LLC, referred to as the Agent, a Delaware limited liability company managed by Oberland Capital Management, LLC, as collateral agent for the Purchasers, for the purpose of providing operating cash flow and extinguishing a previous credit agreement.
Intellectual Property
In the U.S., as of December 31, 2022, the company had 70 issued or allowed patents expiring on various dates between 2023 and 2039, as well as numerous pending patent applications. The company has foreign counterpart patent filings for most of its U.S. issued patents and patent applications. These patents and patent applications are directed to various inventions, including compositions of matter, methods of making and using these compositions for multiple applications, methods for drug screening and discovery, developmental biological processes, and patents which relate to its proprietary technologies.
Emavusertib, CA-170, CA-327 and other Aurigene Collaboration Programs: In conjunction with the October 2015 exercise of options to license the PD-L1/VISTA and IRAK-4 programs, the October 2016 exercise of the company’s option to license the PD-L1/TIM3 program under its collaboration with Aurigene, and the March 2018 exercise of its option to the fourth program in immuno-oncology, the company obtained world-wide (except for India and Russia) exclusive licenses to the Aurigene intellectual property relevant to the program. The portfolio consists of U.S. and foreign filings which cover various genera of compounds from each program and methods of use thereof. As of December 31, 2022, there are 15 issued or allowed U.S. patents expiring between 2033 and 2038 included in such filings.
CI-8993: Under its ImmuNext Agreement as of December 31, 2022, there are 13 issued or allowed U.S. patents expiring on various dates between 2025 and 2037, which relate to anti-VISTA antibodies, including CI-8993. In addition, there are foreign patent applications filed corresponding to many of the aforementioned U.S. filings that could provide additional patent protection for anti-VISTA antibody products, including CI-8993.
Fimepinostat and other Targeted Drug Candidates: As of December 31, 2022, the company had 27 issued or allowed U.S. patents that expire on various dates between 2027 and 2039, including patents covering the composition of matter for fimepinostat, which expires in 2032. The company also has several U.S. and foreign utility patent applications directed to its novel small molecules. The company’s patents and patent applications cover compositions of matter, methods of manufacturing these molecules, formulations, and methods of using these molecules to treat a variety of therapeutic indications. The company intends to continue to file additional U.S. and foreign applications as the programs progress.
Erivedge and the Hedgehog Signaling Pathway: As of December 31, 2022, the company had 15 issued U.S. patents expiring on various dates between 2023 and 2036, which relate to the Hedgehog signaling pathway, including patents covering Erivedge’s composition of matter, which expire in 2028. The company’s patents and patent applications cover proteins, and certain small molecule agonists and inhibitors of the Hedgehog signaling pathway, drug screening and discovery methods, as well as methods of using Hedgehog proteins, antibodies or small molecules to activate or inhibit the Hedgehog signaling pathway for a variety of therapeutic indications or diagnostic uses. In addition, the company has filed foreign patent applications corresponding to many of the aforementioned the U.S. filings that could provide additional patent protection for products that activate or inhibit the Hedgehog signaling pathway.
The company’s academic and research institution collaborators have certain rights to publish data and information regarding their discoveries to which it has rights. The company is party to various license agreements that give it rights to commercialize various technologies, particularly its Hedgehog signaling pathway technologies, and to use technologies in its research and development processes.
Research and Development
The company’s research and development expenses were $43.3million for the year ended December 31, 2022.
Sales and Marketing
The company must build infrastructure related to product sales, marketing and distribution or make arrangements with third parties to perform these services.
Competition
Licensed Programs Under Aurigene Collaboration: The company is aware of multiple other companies that are developing IRAK4 inhibitors for oncology indications, including: Emmaus Life Sciences, Inc./Kainos Medicine, Inc. (KM-10544), Kurome Therapeutics (IRAK1/4 asset), Kymera Therapeutics, Inc. (KT-413 and KT-474), and Rigel Pharmaceuticals, Inc. (R289). VISTA (V-domain Ig Suppressor of T-cell Activation) is a novel immuno-oncology target. The company is aware that Hummingbird Bioscience Pte Ltd (HMBD-002), Pierre Fabre SA (W0180), and Kineta Inc. (KVA12123) have active clinical-stage programs and multiple other companies have preclinical developments, including Apexigen Inc. (APX-201), PharmAbcine Inc. (PMC-309), Sensei Biotherapeutics, Inc. (SNS-101), and Suzhou Stainwei Biotech Inc. (mAb-5). The company is also aware of multiple other companies developing drugs to target TIM3, including Novartis AG, Incyte Corporation, TESARO, Inc., Bristol-Myers Squibb Company, Eli Lilly and Company, and others.
Licensed Programs Under ImmuNext Collaboration: The company is aware that Hummingbird Bioscience Pte Ltd (HMBD-002), Pierre Fabre SA (W0180), and Kineta, Inc. (KVA12123), has active clinical-stage programs and multiple other companies have preclinical development programs, including Apexigen Inc. (APX-201), PharmAbcine Inc. (PMC-309), Sensei Biotherapeutics, Inc. (SNS-101), and Suzhou Stainwei Biotech Inc. (mAb-5).
Erivedge: The company is aware of several other biotechnology and pharmaceutical companies that have drug development programs relating to compounds that modulate the Hedgehog signaling pathway, including Exelixis, Inc./Bristol-Myers Squibb Company (BMS-833923 / XL139), PellePharm Inc. (patidegib), and Senhwa Biosciences Inc. (silmitasertib / CX-4945). Furthermore, glasdegib (Daurismo) is marketed by Pfizer Inc. for the treatment of newly diagnosed adult AML patients for whom intensive chemotherapy is not an option, and sonidegib (Odomzo) is marketed by Sun Pharmaceutical Industries Ltd., for the treatment of adults with locally advanced BCC.
History
Curis, Inc. was founded in 2000 as a Delaware corporation. The company was incorporated in 2000.
