Deciphera Pharmaceuticals Stock

Deciphera Pharmaceuticals, Inc. operates as a biopharmaceutical company.

The company focuses on discovering, developing, and commercializing important new medicines to improve the lives of people with cancer. Leveraging the company’s proprietary switch-control kinase inhibitor platform and deep expertise in kinase biology, the company designs kinase inhibitors to target the switch pocket region of the kinase with the goal of developing potentially transformative medicines. Through the company’s patient-inspired approach, the company seeks to develop a broad portfolio of innovative medicines to improve treatment outcomes.

QINLOCK, the company’s switch-control tyrosine kinase inhibitor, was discovered using the company’s proprietary drug discovery platform and designed for the treatment of GIST. QINLOCK is approved in Australia, Canada, China, the European Union (EU), Hong Kong, Iceland, Israel, Liechtenstein, Macau, New Zealand, Norway, Singapore, Switzerland, Taiwan, the U.K., and the U.S. for the treatment of fourth-line GIST. The company wholly owns QINLOCK and all of the company’s drug candidates with the exception of a development and commercialization out-license agreement for QINLOCK in Greater China. In addition to QINLOCK, the company has developed a robust pipeline of novel drug candidates using the company’s switch-control kinase inhibitor platform, including vimseltinib and DCC-3116.

Strategy

The principal components of the company’s strategy include:

With respect to QINLOCK,

Build on the company’s successful commercialization in fourth-line GIST in the U.S., where the company is the standard of care;

Continue the company’s geographic expansion in fourth-line GIST in European and international markets, while working to provide access to QINLOCK to eligible patients in other countries around the world through other channels; and

Expand the market opportunity for QINLOCK through the company’s pivotal Phase 3 INSIGHT study in second-line GIST patients with mutations in KIT exon 11 and 17/18.

With respect to vimseltinib,

Rapidly seek approval, and continue commercial preparations, for vimseltinib as a potential therapy for the treatment of TGCT, and leverage potential synergies and experience the company has gained from QINLOCK towards this second drug candidate to prepare for a potential launch, if approved; and

Initiate a Phase 2 study of vimseltinib for the potential treatment of chronic graft-versus-host disease (cGVHD), subject to the U.S. Food and Drug Administration (FDA) feedback.

Develop DCC-3116, the company’s inhibitor of ULK kinase, which is being studied in a Phase 1/2 study for the potential treatment of advanced or metastatic solid tumors with mutations in the RAS/MAPK pathway and select a recommended Phase 2 dose for potential expansion cohort(s) to maximize the potential of DCC-3116, subject to favorable data.

Develop DCC-3084, the company’s pan-RAF inhibitor, for which the company submitted an IND to FDA in the fourth quarter of 2023 and plans to initiate a Phase 1 study in the first half of 2024.

Develop DCC-3009, the company’s next generation KIT inhibitor, for which the company plans to submit an IND to the FDA in the first half of 2024 and initiate a Phase 1 study in the second half of 2024, each subject to FDA feedback.

Continue to advance the company’s discovery efforts using its switch-control kinase inhibitor platform.

Evaluate strategic opportunities to accelerate development timelines and maximize the commercial potential of the company’s drug candidates.

Foster a values-based culture that embraces diversity and advances the company’s patient-focused mission.

Approach: Switch-Control Kinase Inhibitors

The company created its diverse pipeline of clinical-stage drug candidates entirely in house using the company’s proprietary switch-control kinase inhibitor platform. The company developed its platform based on its deep insight into the biology of kinases, which are regulated by control of their shape, or conformation. The transformation of a kinase from an inactive to an activated state is dependent upon the interaction of one region of the kinase called the activation switch with another region called the switch pocket. This activation switch mechanism is common among kinases. Some kinases also can be activated if the activity of an inhibitory switch that ordinarily blocks the ability of the activation switch to interact with the switch pocket is diminished or lost. While the interaction between the activation switch and the switch pocket is common among kinases, the molecular structure of the activation switch and the switch pocket varies among kinases. The company takes advantage of this variation to design molecules that inhibit a specific kinase or kinases. An extension of the company’s platform has been shown to enable the design of switch-control inhibitors for serine/threonine kinases that utilize kinase regions other than the activation loop for switch regulation/activation, including the C-helix, P-loop, or catalytic amino acid residues. This expanded platform enables the design of switch-control inhibitors that bind a kinase in either a Type II state (DFG-out) or a Type I state (DFG-in).

The company’s proprietary switch-control kinase inhibitor platform includes a library of drug-like, switch-control kinase compounds. The company has determined and assessed more than 200 co-crystal structures where the company’s compounds are bound into the switch regions of specific kinases. The company use this information to identify and optimize candidate molecules. By directly targeting the switch pocket or other regions that control switch regulation/activation, the company can design inhibitors that will be broadly active against the target kinase, covering both wild-type and many or all of the known mutant or amplified forms, or spectrum-selective towards several chosen kinases.

Using the company’s switch-control kinase inhibitor platform, the company has developed a diverse pipeline of differentiated, orally administered drug candidates that include the company’s approved drug, QINLOCK, and two clinical-stage agents, vimseltinib and DCC-3116, and ongoing research-stage programs, including the company’s pan-RAF inhibitor, DCC-3084, and the company’s next generation KIT inhibitor, DCC-3009. The company’s switch-control kinase inhibitors are designed to interact at a molecular level that is distinct from other kinase inhibitors and are designed to generate higher and more durable rates of response. The company’s drug candidates may contribute to higher activity than available kinase inhibitors.

Drug and Drug Candidates

The company is leveraging its proprietary switch-control kinase inhibitor platform to develop a pipeline of highly selective, potent small molecule drug candidates that are designed to directly inhibit kinases implicated in the growth and spread of tumors. The company’s platform allows the company to rapidly identify new drug candidates to enter preclinical development. The company wholly owns QINLOCK and all of its drug candidates with the exception of a development and commercialization out-license agreement for QINLOCK in Greater China. The company’s research-stage programs are also wholly-owned.

QINLOCK: A Kinase Inhibitor of KIT and PDGFRA for GIST

QINLOCK is an orally administered switch-control kinase inhibitor developed for the treatment of GIST and is approved in twelve territories for the treatment of fourth-line advanced GIST. While approved kinase inhibitors control certain initiating and drug resistance-causing mutations in KIT and PDGFRA, the kinases that drive disease progression in most GIST patients, these approved drugs fail to inhibit all known mutations. The company designed QINLOCK to improve the treatment of GIST patients by inhibiting the full spectrum of the known mutations in KIT and PDGFRA. QINLOCK is a KIT and PDGFRA switch-control kinase inhibitor that blocks initiating and resistance KIT mutations in exons 9, 11, 13, 14, 17, and 18 known to be present in GIST patients. QINLOCK similarly inhibits the primary initiating PDGFRA mutations occurring in exons 12 and 18 and also inhibits wild-type PDGFRA that is subject to amplification in cancers.

Following the Phase 3 INVICTUS study of QINLOCK in fourth-line GIST which met its primary endpoint of improved progression-free survival (PFS) versus placebo, on May 15, 2020, QINLOCK was approved by the FDA for the treatment of adult patients with advanced GIST who have received prior treatment with three or more kinase inhibitors, including imatinib. Following FDA approval of QINLOCK, in May 2020, the company commenced sales and marketing of QINLOCK in the U.S.

In 2020, QINLOCK was also approved for the treatment of fourth-line GIST in Canada and Australia. In November 2020, the company entered into exclusive distribution agreements for QINLOCK in Canada, Israel, Australia, New Zealand, Singapore, Malaysia, and Brunei. In November 2021, the company announced that the European Commission (EC) approved QINLOCK in the EU for the treatment of adult patients with GIST who have received prior treatment with three or more kinase inhibitors, including imatinib. The EC decision is applicable to all 27 EU member states plus Iceland, Norway, and Liechtenstein. In 2021, QINLOCK was also approved for the treatment of fourth-line GIST in Switzerland and the U.K. QINLOCK was approved for the treatment of fourth-line GIST in New Zealand in 2022 and Israel, Macau, and Singapore in 2023. In January 2024, the company entered into an exclusive distribution agreement for QINLOCK in Poland, the Czech Republic, Greece, Republic of Cyprus, Malta, Hungary, Romania, Slovenia, Bulgaria, Slovakia, Croatia, Estonia, Lithuania, and Latvia as member states of the EU (Central and Eastern Europe or CEE).

In June 2019, the company entered into a license agreement with Zai Lab (Shanghai) Co. Ltd. (Zai) (such agreement, the Zai License Agreement) pursuant to which the company granted Zai exclusive rights to develop and commercialize QINLOCK, including certain follow-on compounds (the Licensed Products) in Greater China. QINLOCK was approved for the treatment of adult patients with advanced GIST who have received prior treatment with three or more kinase inhibitors, including imatinib by the China National Medical Products Administration (China NMPA) and the Taiwan Food and Drug Administration in 2021 and the Macau Institute for Pharmaceutical Supervision and Administration in 2023. In 2021, the Hong Kong Department of Health approved QINLOCK in Hong Kong for the treatment of adult patients with advanced GIST who have received prior treatment with imatinib, sunitinib, and regorafenib.

In November 2021, the company announced top-line data from INTRIGUE, the company’s Phase 3 study of QINLOCK for the treatment of second-line GIST. The INTRIGUE study did not meet the primary endpoint of improved PFS compared with the standard of care sunitinib. The Phase 3 INTRIGUE study is an interventional, randomized, global, multicenter, open-label study to evaluate the efficacy and safety of QINLOCK compared to sunitinib in patients with GIST previously treated with imatinib.

In January 2023, the company announced findings from an exploratory circulating tumor DNA (ctDNA) analysis from the Phase 3 INTRIGUE study demonstrating substantial clinical benefit of QINLOCK in second-line GIST patients with mutations in KIT exon 11 and 17/18. In August 2023, the company opened the first sites for enrollment in the INSIGHT study of QINLOCK versus sunitinib in this patient population. In 2024, the company plan to continue to enroll the INSIGHT pivotal Phase 3 study in second-line GIST patients with mutations in KIT exon 11 and 17/18.

In March 2023, the company announced that QINLOCK has been included in the latest National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology as a preferred regimen for second-line GIST patients intolerant to sunitinib. The company also announced that the FDA granted Breakthrough Therapy Designation (BTD) for QINLOCK for the treatment of adult patients with unresectable or metastatic GIST who received prior treatment with imatinib, and who harbor a KIT exon 11 mutation and co-occurring KIT exon 17 and/or 18 mutations.

Following QINLOCK’s EC approval in fourth-line GIST in November 2021, the company has focused its direct commercial efforts in key European markets. The company launched QINLOCK in Germany in 2022 and Italy in 2023, and have conducted the post-approval paid access program (AP2) program in France since 2022. In 2024, the company plans to continue the geographic expansion of QINLOCK with planned commercial launches following conclusion of pricing and reimbursement negotiations in additional European and international markets. The company also plans to provide access to QINLOCK to fourth-line GIST patients in additional countries through other channels with distribution arrangements.

Vimseltinib: CSF1R Kinase Inhibitor for TGCT

Vimseltinib is an investigational, orally administered, potent, and highly-selective switch-control kinase inhibitor of CSF1R. Vimseltinib was designed to selectively bind to the CSF1R switch pocket. It has greater than 100-fold selectivity for CSF1R over the closely related kinases FLT3, KIT, PDGFRA, PDGFRB, and VEGFR2 and has an even greater selectivity for CSF1R over approximately 300 other human kinases tested. This high selectivity for inhibition of CSF1R is attributed to vimseltinib binding into a unique selectivity region of the CSF1R activation switch that is not available in closely related kinases. Vimseltinib inhibits CSF1R signaling in cellular assays, as well as blocks macrophage-mediated tumor cell migration, osteoclast differentiation, and proliferation of a CSF1R-dependent cell line.

The company is studying vimseltinib in the pivotal Phase 3 study in patients with TGCT. The MOTION study is a two-part, randomized, double-blind, placebo-controlled study of vimseltinib to assess the efficacy and safety in patients with TGCT who are not amenable to surgery. In October 2023, the company announced positive top-line data from the MOTION study. The company will continue to engage with regulatory authorities and expect to submit a New Drug Application (NDA) to the FDA in the second quarter of 2024 and a marketing authorization application (MAA) with the European Medicines Agency (EMA) in the third quarter of 2024 for vimseltinib for the treatment of patients with TGCT.

The company is also conducting an international, multicenter, ongoing open-label Phase 1/2 study designed to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of vimseltinib in patients with solid tumors and TGCT. In the Phase 2 expansion portion of the study, Cohort A includes TGCT patients with no prior anti-CSF1/CSF1R (previous therapy with imatinib or nilotinib is allowed) and Cohort B includes patients with prior anti-CSF1/CSF1R (previous therapy with imatinib or nilotinib alone is not allowed). In October 2023, the company provided updated data from the company’s Phase 1/2 study of vimseltinib in TGCT patients. The data demonstrated strong clinical benefit with best ORR of 72% (Phase 1) and 64% (Phase 2 Cohort A), an increasing median treatment duration of 25.1 months (Phase 1) and 21.0 months (Phase 2 Cohort A), and a favorable long-term safety profile with no evidence of cholestatic hepatotoxicity.

In November 2021, the company announced that vimseltinib had been granted fast track designation by the FDA for the treatment of patients with TGCT who are not amenable to surgery.

In January 2023, the company plans to initiate a Phase 2 study of vimseltinib for the potential treatment of cGVHD in the fourth quarter of 2024, subject to FDA feedback.

DCC-3116: ULK Kinase Inhibitor for RTK/RAS/MAPK Driven Cancers

DCC-3116 is a potential first-in-class investigational, orally administered, potent, and highly selective switch-control inhibitor of the ULK kinase. DCC-3116 is designed to inhibit autophagy, a key tumor survival mechanism in cancer cells, by inhibiting the ULK kinases, which have been shown to be the initiating factors that activate autophagy. DCC-3116, in combination with RTK/RAS/MAP kinase signaling pathway inhibition has the potential to change the treatment of RTK/RAS/MAPK driven cancers, if approved.

DCC-3116 is being studied in a Phase 1/2 study designed to evaluate the safety, tolerability, clinical activity, PK, and PD of DCC-3116 as a single agent and in combination with sotorasib in patients with advanced or metastatic solid tumors with KRASG12C mutations, and QINLOCK, the company’s FDA-approved KIT inhibitor, in patients with GIST. The clinical development plan for DCC-3116 will focus on combination strategies for patients with documented RAS and RAF cancer mutations, which utilize autophagy for tumor growth, survival, and as a resistance mechanism to inhibitors of RTK, RAS, and MAP kinases. In 2024, the company plans to select a recommended Phase 2 dose for potential expansion cohort(s), subject to favorable data.

In April 2023, the company presented preclinical data on new clinical combinations with DCC-3116 at the American Association for Cancer (AACR) Annual Meeting 2023, including preclinical models in combination with QINLOCK in GIST.

In August 2023, the company announced the completion of the single agent DCC-3116 dose escalation portion of the Phase 1/2 study (n=28). The company also provided updated data on the PK characteristics of single agent DCC-3116. In addition, the company provided an update on the ongoing Phase 1/2 study in combination with trametinib, binimetinib, and sotorasib. In August 2023, the company also opened the first site for enrollment in two new combinations evaluating DCC-3116 in combination cohorts with QINLOCK in patients with GIST and in combination with encorafenib and cetuximab in patients with colorectal cancer.

In January 2024, the company was prioritizing the development of DCC-3116 in combination with sotorasib and with QINLOCK and discontinued development of the DCC-3116 cohorts in combination with trametinib in patients with advanced or metastatic solid tumors with RAS, NF1, or RAF mutations; binimetinib in patients with advanced or metastatic solid tumors with RAS, NF1, or RAF mutations; and encorafenib and cetuximab in patients with colorectal cancer. As a result, the company also terminated the clinical trial collaboration and supply agreement with Pfizer Inc. (Pfizer) for the dose escalation study evaluating DCC-3116 in combination with encorafenib and cetuximab in patients with colorectal cancer prior to enrollment in any clinical studies.

Preclinical Pipeline

The company is making a focused investment in its next generation of research programs, which are designed to provide first-in-class or best-in-class treatments using the company’s proprietary switch-control inhibitor platform, which includes DCC-3084 and DCC-3009.

DCC-3084

DCC-3084 is a potential best-in-class RAF inhibitor that is designed to broadly inhibit Class I, II, and III BRAF mutations, BRAF fusions, and BRAF/CRAF heterodimers. DCC-3084 is a potent and selective inhibitor of both BRAF and CRAF kinases and has been shown to target aberrant signaling mechanisms, including RAF signaling through monomers, homodimers, and heterodimers. DCC-3084 exhibits high permeability, good central nervous system penetrance, and tumor tissue accumulation. Strong preclinical efficacy in cancer models driven by RAF or RAS mutations support exploration of single agent and combination opportunities.

In April 2023, the company presented preclinical data for DCC-3084 at the AACR Annual Meeting 2023, which demonstrated its ability to target the relevant aberrant signaling mechanisms, including inhibition of BRAF monomers, BRAF homodimers, and BRAF/CRAF heterodimers. To facilitate tumor access, DCC-3084 possesses desirable pharmaceutical properties, including high permeability, CNS penetration, and good solubility at gastric pH. In addition, DCC-3084's optimal properties include a long residency time on RAF kinases, low cellular efflux, and drug-transporter inhibition. Together, the preclinical data on DCC-3084 supports single agent use in tumors driven by RAF and RAS mutations with even deeper responses observed in combination with MEK inhibitors.

In the fourth quarter of 2023, the company submitted an IND application to the FDA for DCC-3084 and expect to initiate the Phase 1 study of DCC-3084 in the first half of 2024.

DCC-3009

DCC-3009 is a potential best-in-class next generation KIT inhibitor that is designed to inhibit the broad spectrum of known primary and secondary drug resistant mutations in GIST, spanning KIT exons 9, 11, 13, 14, 17, and 18. Drug-resistant GIST is a complex cancer that has a diverse spectrum of KIT mutations that arise in response to treatment with tyrosine kinase inhibitors. Many patients harbor multiple different drug-resistant mutations in tumors and/or metastatic tumor sites. There remains an unmet medical need for a pan-KIT inhibitor that can broadly and potently inhibit the spectrum of KIT mutations that drive GIST. To potentially achieve this, the company focused on making a drug that can inhibit the spectrum of KIT mutations found in GIST across exons 9, 11, 13, 14, 17, and 18, as well as PDGFRA mutations, while maintaining very high selectivity versus the rest of the kinome.

In April 2023, the company presented preclinical data for DCC-3009 at the AACR Annual Meeting 2023, which demonstrated that treatment with DCC-3009 exhibited tumor regressions in multiple drug-resistant preclinical GIST models. DCC-3009 has suitable pharmaceutical and absorption, distribution, metabolism, and excretion (ADME) properties for oral administration, high kinase selectivity, and free drug levels in preclinical models that enable pharmaceutically active exposures needed to suppress the broad spectrum of KIT mutations in GIST.

The company expects to submit an IND application to the FDA for DCC-3009 in the first half of 2024 and initiates a Phase 1 study of DCC-3009 in the second half of 2024, each subject to FDA feedback.

Out-License of QINLOCK in Greater China

In June 2019, the company entered into the Zai License Agreement, pursuant to which the company granted Zai exclusive rights to develop and commercialize the Licensed Products in Greater China, also referred to as the Territory. The company retains exclusive rights to, among other things, develop, manufacture, and commercialize the Licensed Products outside the Territory.

In February 2020, the company entered into a Supply Agreement (the Zai Supply Agreement) with Zai, as required by terms in the Zai License Agreement, pursuant to which the company will supply the Licensed Products to Zai for use in the Territory for clinical trials, as well as commercial inventory, if QINLOCK obtained regulatory approval in the Territory.

Commercial Operations

For QINLOCK, the company has established its own commercial and marketing organization in the U.S. and the company has built a targeted infrastructure to commercialize QINLOCK in key European markets, and plan to provide access to QINLOCK in additional countries through other channels with distribution arrangements. In addition, the company has entered into distributor arrangements in certain countries, including Australia, Canada, and CEE; and may in the future enter into additional select distributor arrangements to offer QINLOCK to geographies where the company does not intend to distribute QINLOCK on the company’s own, or to selectively establish partnerships, such as the Zai license for Greater China described above, in other markets outside the U.S. The company continuously assesses its expansion initiatives and look to strategically utilize all available channels to commercialize QINLOCK globally. In the U.S., the company has built a specialist sales force to target physicians who treat GIST, including key opinion leaders at academic centers of excellence, as well as to call on community oncologists and sarcoma doctors with eligible GIST patients. The company’s sales force is supported by sales management, internal sales support, an internal marketing group, and distribution support. Additionally, the company’s commercial team manages relationships with key accounts, such as managed care organizations, group purchasing organizations, hospital systems, physician group networks, and government accounts.

For vimseltinib, the company has begun pre-launch planning in patients with TGCT, and if approved, will leverage the potential synergies and experience the company has gained from QINLOCK as GIST and TGCT have significant overlap in the key opinion leaders and treating physicians.

In addition, the company will consider entering into relationships with strategic partners that enable the expansion of the ongoing clinical development and/or licenses for development and commercialization or distribution in geographies where the company does not intend to distribute QINLOCK on the company’s own, while retaining significant value for the company’s shareholders. These pharmaceutical company partnerships could focus on specific patient populations and their caregivers, on regional development, or on distribution and sales.

Intellectual Property

With regard to QINLOCK (ripretinib), as of January 31, 2024, the company owned twenty-two issued U.S. patents with composition of matter and, method of use, and drug product claims. Of these, one issued U.S. patent is expected to expire in 2030, one issued U.S. patent is expected to expire in 2034 (inclusive of patent term extension), one issued U.S. patent is expected to expire in 2034, eighteen are expected to expire in 2040, and one is expected to expire in 2042. In addition, the company owns related patents in Europe, Australia, South America, and Asia that are expected to expire between 2032 and 2040. In addition, the company owns twenty-two pending U.S. applications, and related pending applications in Europe, Australia, South America, and Asia, as well as one pending Patent Cooperation Treaty (PCT) patent applications directed to various methods of use, including uses for indications other than GIST, and drug product of QINLOCK (ripretinib). If one or more patents claiming priority to these patent applications is granted, it is expected to expire between 2037 and 2042.

With regard to vimseltinib, as of January 31, 2024, the company owned three issued U.S. patents with composition of matter and method of use claims. The issued U.S. patents are expected to expire between 2034 and 2040. In addition, the company owns one pending U.S. application which, if granted, is expected to expire in 2039, and related patents and pending applications in Australia, Canada, Asia, Europe and South America that are expected to expire between 2034 and 2039. Further, the company owns one pending PCT application. If one or more patents claiming priority to this PCT application is granted, it is expected to expire in 2043. The company also owns four pending U.S. provisional applications. If one or more patents claiming priority to these provisional applications is granted, it is expected to expire in 2044.

With regard to DCC-3116, as of January 31, 2024, the company owned three issued U.S. patents with composition of matter claims and method of use claims that are expected to expire in 2040. The company owns five pending U.S. applications which, if granted, are expected to expire between 2040 and 2043. In addition, the company owns related pending applications in Australia, Canada, Asia, Africa, Middle East, Europe, and South America. The company also owns two pending PCT applications. If one or more patents claiming priority to these PCT applications is granted, it is expected to expire in 2043.

With regard to the company’s early-stage research programs, as of January 31, 2024, the company owned six pending U.S. applications which, if granted, are expected to expire between 2041 and 2042. The company owns six pending U.S. provisional applications. If one or more patents claiming priority to these provisional applications is granted, are expected to expire in 2044. The company has five pending PCT applications. In addition, the company owns a related pending application in Europe. If one or more patents claiming priority to these PCT applications is granted, it is expected to expire between 2041 and 2043.

Trademarks

The Deciphera logo and the QINLOCK word mark and logo are registered trademarks and the Deciphera word mark is a trademark of Deciphera Pharmaceuticals, LLC.

Government Regulation

The company’s drug candidates must be approved by the FDA through the NDA process before they may be legally marketed in the U.S.

History

Deciphera Pharmaceuticals, Inc. was founded in 2003. The company, a Delaware corporation, was incorporated in 2017.