Background:
Non-Hodgkin lymphomas are blood cancers that can be difficult to treat. They can also return after treatment. Examples include diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL). More effective treatments are needed for these diseases.
Objective:
To test the safety of a study drug (VIP152) in combination with other drugs used to treat people with aggressive blood cancers.
Eligibility:
People aged 18 years or older diagnosed with DLBCL, PTCL, or related blood cancers. The cancers must have either not responded to treatment or returned after treatment.
Design:
Participants will undergo screening. They will have a physical exam with scans and blood and urine tests. They will have imaging scans and tests of their heart function. They may also provide a bone marrow aspiration or biopsy.
Participants may provide a saliva sample for DNA testing.
Participants will receive study treatment in cycles. Each cycle is 21 days.
Participants will take two drugs by mouth at home once a day on days 1-10 of each cycle.
On days 2 and 9 they will come to the clinic to receive VIP152. This drug will be administered through a small plastic tube with a needle placed in a vein.
On day 11, participants will receive a fourth medication as an injection under the skin. They will rest and recover on days 12-21.
Screening tests will be repeated periodically throughout the study period.
Treatment will continue for up to 24 cycles.
Participants will have follow-up visits for up to 5 years.

Start Date05 Apr 2023

Sponsor / Collaborator

National Cancer Institute

NCT04978779 / TerminatedPhase 1

An Open-label, Multicenter Phase 1/1b Study to Characterize Safety, Tolerability, Preliminary Antitumor Activity, Pharmacokinetics, and Pharmacodynamics of VIP152 Monotherapy or Combination Therapy in Subjects With High-risk Chronic Lymphocytic Leukemia or Richter Syndrome

Determine the safety, tolerability, pharmacokinetics, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of VIP152 as monotherapy or in combination with a BTKi in patients with Chronic Lymphocytic Leukemia (CLL) or Richter Syndrome

Start Date16 Dec 2021

Sponsor / Collaborator

Vincerx Pharma, Inc.

NCT02745743 / CompletedPhase 1

An Open-label, Multicenter Phase I Study to Characterize the Safety, Tolerability, Preliminary Anti-tumor Activity, Pharmacokinetics and Maximum Tolerated Dose of BAY1251152 in Patients With Advanced Hematological Malignancies

The purpose of this study is to identify the most appropriate dose that can be safely administered and that can have an effect on blood cancer cells. Once that safe dose is identified, additional patients will be asked to join the study to further evaluate the safety and effectiveness of the study drug. The study will also investigate the pharmacokinetics (study of what the body does to the drug), as well as pharmacodynamics (study of what the drug does to the body), which may provide information about the effects of BAY 1251152. The study will also measure some biological markers (markers of biological activity in your body) that can be used to predict the response and safety of the proposed treatment.

Start Date17 Jun 2016

Sponsor / Collaborator

Bayer AG

100 Clinical Results associated with Enitociclib

100 Translational Medicine associated with Enitociclib

100 Patents (Medical) associated with Enitociclib

Literatures (Medical) associated with Enitociclib

01 Nov 2024·Bioorganic & Medicinal Chemistry Letters

Discovery and preclinical profile of YK-2168, a differentiated selective CDK9 inhibitor in clinical development

Article

Author: Ding, Charles Z. ; Zhu, Zhenzhen ; Ding, Charles Z ; Xu, Zhaobing ; Chen, Shuhui ; Zhou, Wang ; Zhu, Xingxun ; Xia, Li ; Li, Wei ; Jiang, Wen ; Li, Qi ; Xia, Yuanfeng ; Gao, Xiao ; Chen, Yadong ; Liu, Yingchun ; Hu, Lihong

Emerging clinical evidence indicates that selective CDK9 inhibition may provide clinical benefits in the management of certain cancers. Many CDK9 selective inhibitors have entered clinical developments, and are being investigated. No clear winner has emerged because of unforeseen toxicity often observed in clinic with these agents. Therefore, a novel agent with differentiated profiles is still desirable. Herein, we report our design, syntheses of a novel azaindole series of selective CDK9 inhibitors. SAR studies led to a preclinical candidate YK-2168. YK2168 exhibited improved CDK9 selectivity over AZD4573 and BAY1251152; also showed differentiated intravenous PK profile and remarkable solid tumor efficacy in a mouse gastric cancer SNU16 CDX model in preclinical studies. YK-2168 is currently in clinical development in China (CTR20212900).

31 Dec 2023·Cancer Biology & Therapy

Targeting CDK9 with selective inhibitors or degraders in tumor therapy: an overview of recent developments

Review

Author: Liu, Yi ; Shen, Lisong ; Chen, Hui ; Xiao, Lanshu

As a catalytic subunit of the positive transcription elongation factor b (P-TEFb), cyclin-dependent kinase 9 (CDK9) has been demonstrated to contribute to carcinogenesis. This review focuses on the development of selective CDK9 inhibitors and proteolysis-targeting chimera (PROTAC) degraders. Twenty selective CDK9 inhibitors and degraders are introduced along with their structures, IC50 values, in vitro and in vivo experiments, mechanisms underlying their inhibitory effects, and combination regimens. NVP-2, MC180295, fadraciclib, KB-0742, LZT-106, and 21e have been developed mainly for treating solid tumors, and most of them work only on certain genotypes of solid tumors. Only VIP152 has been proven to benefit the patients with advanced high-grade lymphoma (HGL) and solid tumors in clinical trials. Continued efforts to explore the molecular mechanisms underlying the inhibitory effects, and to identify suitable tumor genotypes and combination treatment strategies, are crucial to demonstrate the efficacy of selective CDK9 inhibitors and degraders in tumor therapy.

09 Nov 2023·Cancer Research Communications

Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription

Article

Author: Frigault, Melanie M ; Izumi, Raquel ; Hamdy, Ahmed ; Huang, Xin ; Johnson, Amy J ; Stelte-Ludwig, Beatrix ; Wong, Harvey ; Mithal, Arushi ; Mandava, Vinay ; Birkett, Joseph

AbstractDouble-hit diffuse large B-cell lymphoma (DH-DLBCL) is an aggressive, and often refractory, type of B-cell non–Hodgkin lymphoma (NHL) characterized by rearrangements in MYC and BCL2. Cyclin-dependent kinase 9 (CDK9) regulates transcriptional elongation and activation of transcription factors, including MYC, making it a potential targeted approach for the treatment of MYC+ lymphomas. Enitociclib is a well-tolerated and clinically active CDK9 inhibitor leading to complete metabolic remissions in 2 of 7 patients with DH-DLBCL treated with once weekly 30 mg intravenous administration. Herein, we investigate the pharmacodynamic effect of CDK9 inhibition in preclinical models and in blood samples from patients [DH-DLBCL (n = 10) and MYC+ NHL (n = 5)] treated with 30 mg i.v. once weekly enitociclib. Enitociclib shows significant regulation of RNA polymerase II Ser2 phosphorylation in a MYC-amplified SU-DHL-4 cell line and depletion of MYC and antiapoptosis protein MCL1 in SU-DHL-4 and MYC-overexpressing SU-DHL-10 cell lines in vitro. Tumor growth inhibition reaching 0.5% of control treated SU-DHL-10 xenografts is achieved in vivo and MYC and MCL1 depletion as well as evidence of apoptosis activation after enitociclib treatment is demonstrated. An unbiased analysis of the genes affected by CDK9 inhibition in both cell lines demonstrates that RNA polymerase II and transcription pathways are primarily affected and novel enitociclib targets such as PHF23 and TP53RK are discovered. These findings are recapitulated in blood samples from enitociclib-treated patients; while MYC downregulation is most robust with enitociclib treatment, other CDK9-regulated targets may be MYC independent delivering a transcriptional downregulation via RNA polymerase II.Significance:MYC+ lymphomas are refractory to standard of care and novel treatments that downregulate MYC are needed. The utility of enitociclib, a selective CDK9 inhibitor in this patient population, is demonstrated in preclinical models and patients. Enitociclib inhibits RNA polymerase II function conferring a transcriptional shift and depletion of MYC and MCL1. Enitociclib intermittent dosing downregulates transcription factors including MYC, providing a therapeutic window for durable responses in patients with MYC+ lymphoma.

News (Medical) associated with Enitociclib

12 Nov 2024

·www.globenewswire.com

Vincerx Pharma Reports Third Quarter 2024 Financial Results

Continued enrollment and dose escalation in Phase 1 study of VIP943, a potentially best-in-class anti-CD123 antibody-drug conjugate (ADC); additional data expected by early 2025 Completed Phase 1 dose-escalation studies of small molecule drug-conjugate (SMDC), VIP236, and CDK9 inhibitor, enitociclib, and identified the maximum tolerated dose Expected cash runway into early 2025 PALO ALTO, Calif., Nov. 12, 2024 (GLOBE NEWSWIRE) -- Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, today reported financial results for the third quarter of 2024 and provided an overview of its clinical programs and anticipated milestones. “As we direct our efforts and resources toward our ADC technologies and programs, we are committed to advancing VIP943 based on the encouraging safety, efficacy, and tolerability results observed to date. We look forward to presenting additional data from patients at efficacious dose cohorts by early next year,” said Ahmed Hamdy, M.D., Chief Executive Officer. “Securing the funding necessary to advance our programs remains a priority. Alongside exploring financing options, we remain focused on strategic partnerships, particularly as pharmaceutical companies intensify their search for truly differentiated and transformative technologies.” THIRD QUARTER 2024 CLINICAL PROGRAM HIGHLIGHTS AND ANTICIPATED MILESTONES VIP943 VIP943 is a novel CD123-targeted ADC developed with the Company’s next-generation VersAptx platform.VIP943 has shown promising safety, efficacy, and tolerability in an ongoing Phase 1 dose-escalation study for patients with relapsed/refractory acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and B-cell acute lymphoblastic leukemia (B-ALL) (NCT06034275). In October, the Company reported two complete responses in this Phase 1 study: one out of four patients with relapsed AML in the 1 mg/kg dose cohort achieved complete remission with incomplete hematologic recovery (CRi), and one out of one patient with higher-risk MDS in the 1.3 mg/kg dose cohort achieved complete remission with limited count recovery (CRL).VIP943 has shown effective target engagement and elimination of CD123+ malignant cells, with pharmacodynamic data demonstrating decreases in CD123+ blasts after dosing. Preliminary pharmacokinetic data indicates minimal payload release (≤1% in plasma), signifying a stable linker.Given the favorable safety and tolerability observed for VIP943, the Company continues dose escalation to assess potential for additional efficacy. Enrollment in the once-weekly and twice-weekly (as an induction therapy) dosing schedules is ongoing.Vincerx expects to share additional Phase 1 study data for VIP943 by early 2025. Enitociclib Enitociclib is a highly selective CDK9 inhibitor designed to block the activation of RNA polymerase II, leading to inhibition of oncogenes, including MYC and MCL1.Enitociclib is currently in a Phase 1 dose-escalation study (NTC05371054) evaluating the combination of enitociclib, venetoclax, and prednisone in diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL). This study is being conducted in collaboration with the National Institutes of Health (NIH). As of September 2024, the study reported four partial responses (PRs) in seven patients (57% overall response rate), including one patient with double hit lymphoma (DH-DLBCL) and three patients with PTCL.Enitociclib has successfully completed its Phase 1 dose-escalation study as a monotherapy (NCT02635672), enrolling 63 patients across dose-escalation and expansion cohorts. The treatment demonstrated a favorable safety profile, dose-proportional pharmacokinetics, and on-target pharmacodynamic activity. Clinical benefits included durable complete metabolic remissions in two patients with DH-DLBCL, lasting 3.7 and 2.3 years, with both remissions continuing more than two years after treatment cessation. In addition, a transformed follicular (tFL) patient achieved a PR with a 63% tumor reduction after nearly two years, a meaningful outcome given the historically poor prognosis of tFL. Furthermore, 13 patients with solid tumors achieved stable disease as their best response, including five ovarian cancer patients—indicating a promising path for future combination studies in this indication.The Company is actively focused on finding a strategic partner to continue the development of this asset. VIP236 VIP236 is a αVβ3 SMDC conjugated to an optimized camptothecin (CPT) payload developed with the Company’s VersAptx platform.VIP236 has completed its Phase 1 dose-escalation study (NCT05712889), identifying the maximum tolerated dose that could be utilized in future studies. As reported in October, a total of 29 patients were enrolled in the Phase 1 study, resulting in a 45% disease control rate. The drug demonstrated a favorable safety profile, distinguishing itself from other CPTs by showing no instances of common dose-limiting side effects such as life-threatening diarrhea, severe stomatitis/mucositis, or interstitial lung disease.The Company intends to identify a partner to champion VIP236 through further development. THIRD QUARTER 2024 FINANCIAL RESULTS Vincerx had approximately $10.1 million in cash, cash equivalents, and marketable securities as of September 30, 2024, as compared to approximately $16.3 million as of June 30, 2024. Based on its current business plans and assumptions, Vincerx believes its available capital will be sufficient to meet its operating requirements into early 2025.Research and development expenses for the third quarter ended September 30, 2024, were approximately $3.9 million, as compared to approximately $6.1 million for the same period in 2023. This decrease is primarily the result of decreases in research services of approximately $2.4 million and personnel-related expenses of approximately $0.8 million, offset by an increase in clinical-related expenses of approximately $0.9 million.General and administrative expenses for the third quarter ended September 30, 2024, were approximately $3.9 million, as compared to approximately $3.5 million for the same period in 2023. This increase was due to a $0.5 million increase in professional services, partially offset by a decrease in personnel-related expenses of $0.1 million.For the third quarter ended September 30, 2024, Vincerx reported a net loss of approximately $7.8 million, or $0.17 per share. For the third quarter ended September 30, 2023, Vincerx reported a net loss of approximately $9.0 million, or $0.42 per share. About Vincerx Pharma, Inc.Vincerx Pharma, Inc. is a clinical-stage biopharmaceutical company committed to developing differentiated and novel therapies to address the unmet medical needs of patients with cancer. Vincerx has assembled a seasoned management team with a proven track record of successful oncology drug development, approvals, and value creation. Vincerx’s diverse pipeline consists of the next-generation ADC VIP943, currently in Phase 1; SMDC VIP236, which has completed its Phase 1; CDK9 inhibitor enitociclib, which has completed a Phase 1 monotherapy study and continues in a Phase 1 study in collaboration with the NIH; preclinical ADC VIP924; and VersAptx, a versatile, next-generation bioconjugation platform. Vincerx is based in Palo Alto, California, and has a research subsidiary in Monheim, Germany. For more information, please visit www.vincerx.com and follow Vincerx on LinkedIn. Forward-Looking StatementThis press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the Securities Act), and Section 21E of the Securities Exchange Act of 1934, as amended, that are intended to be covered by the “safe harbor” created by those sections. Forward-looking statements, which are based on certain assumptions and describe future plans, strategies, expectations and events, can generally be identified by the use of forward-looking terms such as “believe,” “expect,” “may,” “will,” “should,” “would,” “could,” “suggest,” “seek,” “intend,” “plan,” “goal,” “potential,” “on-target,” “on track,” “project,” “estimate,” “anticipate,” or other comparable terms. All statements other than statements of historical facts included in this press release are forward-looking statements. Forward-looking statements include, but are not limited to, Vincerx’s business model, cash runway, pipeline, strategy, timeline, product candidates and attributes, and preclinical and clinical development, timing, and results. Forward-looking statements are neither historical facts nor assurances of future performance or events. Instead, they are based only on current beliefs, expectations, and assumptions regarding future business developments, future plans and strategies, projections, anticipated events and trends, the economy, and other future conditions. Forward-looking statements are subject to inherent uncertainties, risks, and changes in circumstances that are difficult to predict, many of which are outside Vincerx’s control.Actual results, conditions, and events may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause actual results, conditions, and events to differ materially from those indicated in the forward-looking statements include, but are not limited to, Vincerx’s capital requirements, availability and uses of capital, ability to raise additional capital and cash runway; risks associated with preclinical or clinical development and studies; failure to realize the benefits of Vincerx’s license agreement with Bayer; risks related to the timing of expected business and product development milestones; changes in the assumptions underlying Vincerx’s expectations regarding its future business or business model; Vincerx’s ability to successfully develop and commercialize product candidates; general economic, financial, legal, political, and business conditions; and the risks and uncertainties set forth in the Form 10-Q for the quarter ended June 30, 2024 and subsequent reports filed with the Securities and Exchange Commission by Vincerx. Forward-looking statements speak only as of the date hereof, and Vincerx disclaims any obligation to update any forward-looking statements. Vincerx, the Vincerx logo, and VersAptx are our trademarks. ContactsGabriela JairalaVincerx Pharma, Inc.gabriela.jairala@vincerx.com Totyana SimienInizio Evoke Commstotyana.simien@inizioevoke.com Vincerx Pharma, Inc. Condensed Consolidated Balance Sheets (in thousands) September 30, 2024 December 31, 2023 (unaudited) ASSETS Current assets: Cash and cash equivalents$2,942 $12,782 Short-term marketable securities 7,144 - Prepaid expenses 283 51 Grant receivable 1,063 1,044 Other current assets 316 856 Total current assets 11,748 14,733 Right-of-use assets 1,431 2,201 Property, plant and equipment, net 85 125 Other assets 1,683 1,158 Total assets$ 14,947 $ 18,217 LIABILITIES AND STOCKHOLDERS' EQUITY Current liabilities Accounts payable$1,963 $2,497 Accrued expenses 1,724 1,755 Lease liability 1,274 1,162 Common stock warrant liabilities 463 191 Total current liabilities 5,424 5,605 Lease liability, net of current portion 365 1,340 Other noncurrent liabilities 50 50 Total liabilities 5,839 6,995 Total stockholders' equity 9,108 11,222 Total liabilities and stockholders' equity$ 14,947 $ 18,217 Vincerx Pharma, Inc.Condensed Consolidated Statements of Operations(unaudited)(in thousands, except per share amounts) For the three months ended For the nine months ended September 30, September 30, 2024 2023 2024 2023 Operating expenses: General and administrative$3,885 $3,508 $10,419 $11,816 Research and development 3,908 6,101 12,218 25,260 Total operating expenses 7,793 9,609 22,637 37,076 Loss from operations (7,793) (9,609) (22,637) (37,076) Other income (expense) Change in fair value of warrant liabilities (331) 112 (272) 12 Interest income 154 260 410 1,053 Other income (expense) 127 230 419 804 Total other income (expense) (50) 602 557 1,869 Net loss $ (7,843) $ (9,007) $ (22,080) $ (35,207) Net loss per common share, basic and diluted$(0.17) $(0.42) $(0.63) $(1.66) Weighted average common shares outstanding, basic and diluted 45,672 21,345 35,175 21,269

Phase 1Clinical ResultFinancial StatementADC

09 Oct 2024

·www.globenewswire.com

Vincerx Reports Positive Initial Clinical Data from Ongoing VIP943 Phase 1 Dose-Escalation Study and Provides Pipeline and Corporate Updates

VIP943 demonstrates promising safety and tolerability and achieves two complete responses to date in Phase 1 dose-escalation study, reinforcing the program’s potential and validating the VersAptx™ Platform technology Vincerx focusing resources on continued development of VIP943 Expected cash runway into early 2025 Management to host webcast and Q&A today at 5:00 PM EDT to review pipeline and corporate updates, followed by commentary from key opinion leader Dr. M. Yair Levy Oct. 07, 2024 -- Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, announced two complete responses in the ongoing first-in-human, Phase 1 dose-escalation study of VIP943, the Company’s next-generation antibody-drug conjugate (ADC) being evaluated in relapsed/refractory acute myeloid leukemia (AML), higher-risk myelodysplastic syndrome (HR-MDS), and B-cell acute lymphoblastic leukemia (B-ALL). The Company also provided pipeline and corporate updates. The ongoing Phase 1 dose-escalation study of VIP943 has enrolled 22 patients to date across several escalating dose cohorts (0.2 to 1.3 mg/kg once weekly). These 22 patients represent a ‘hard-to-treat’ salvage population, which rarely responds to monotherapy. Nine patients (six AML; three HR-MDS) have received at least three doses of an efficacious dose of VIP943 (i.e., ≥1.0 mg/kg). Of these nine patients, four (44%) remain on study. So far, one patient with relapsed AML has achieved complete remission with incomplete hematologic improvement (CRi) and one patient with HR-MDS has achieved complete remission with limited count recovery (CRL) based on international consensus response criteria. These response criteria are widely recognized as an approvable benchmark in AML and MDS studies, further underscoring the significance of these early results. “We are excited by the emerging data from our Phase 1 study of VIP943, showing clinical responses in difficult-to-treat patients," said Ahmed Hamdy, M.D., Chief Executive Officer of Vincerx. "We believe these promising clinical responses highlight the potential of VIP943 as a best-in-class therapy for CD123+ hematologic malignancies and validate our VersAptx platform’s ability to create safer, more effective bioconjugates by overcoming the challenges of historical ADCs.” As of August 2024, VIP943 has shown favorable safety and tolerability, with no dose-limiting toxicities reported in 22 patients. Serious adverse events (SAEs) have been consistent with expectations for this patient population. The most common SAEs included pneumonia (three patients, 14%), and cellulitis and febrile neutropenia (two patients each, 9%). Only one patient (5%) experienced a drug-related SAE (Grade 3 diarrhea). Target engagement (i.e., receptor occupancy) has been demonstrated by binding of VIP943 to CD123+ peripheral blood blasts from patients with AML from the Phase 1 study. Maximal receptor occupancy of 84% was achieved in the highest dose cohort (1.3 mg/kg). Across all the cohorts, receptor occupancy was retained for less than 96 hours. Concurrent decreases in CD123+ peripheral blood blasts were also observed after dosing. These pharmacodynamic (PD) markers show that VIP943 is binding to and eliminating CD123+ malignant cells. Preliminary pharmacokinetic (PK) data continues to show low release of payload (≤1% in plasma). The half-life of VIP943 is less than 96 hours, and no accumulation occurs with repeat dosing. These PK and PD results have prompted evaluation of twice weekly dosing of VIP943 as a potential “induction” regimen. Enrollment in the once weekly and twice weekly dosing cohorts is ongoing. Dr. Hamdy continued, “Our initial clinical results demonstrate that VersAptx is a next-generation platform that overcomes key challenges associated with traditional ADCs. The PK profile shows that our linker is stable, cleaving exclusively inside cells without extracellular degradation. Our PD results coupled with clinical responses confirm the payload effectively kills cancer cells in peripheral blood and bone marrow without harming nearby healthy tissue. This innovative design with proof-of-concept in Phase 1 reinforces our confidence in VersAptx as a transformative platform for ADC development.” The company anticipates providing another data update on the ongoing Phase 1 VIP943 study by the end of the year. Dr. M. Yair Levy, Director of Hematologic Malignancies Research at Texas Oncology added, "Although this is still early data, VIP943 is clearly differentiated from other ADCs, particularly with its favorable safety profile. We’re not seeing neutropenia as a dose-limiting toxicity, which is encouraging and may allow the drug to move into earlier lines of therapy in combination. I look forward to the continued development of VIP943 and its potential to improve treatment options for patients with CD123+ malignancies.” VIP236 is Vincerx’s first-in-class small molecule drug conjugate (SMDC) being evaluated in an ongoing first-in-human, Phase 1 dose-escalation study as a monotherapy in patients with advanced solid tumors. As of September 2024, 29 patients have been enrolled. Of these patients, 20 were evaluable per-protocol for response from the every 2- or 3-week schedule; nine of 20 patients had stable disease for a disease control rate of 45%. In addition, one of these subjects has been on treatment for over 300 days and four additional patients were on study for more than 120 days, demonstrating promising monotherapy duration of response in patients with advanced cancer. VIP236 continued to show a favorable safety and tolerability profile in these 29 patients, with no instances of the dose-limiting side effects commonly associated with camptothecins, such as life-threatening diarrhea, severe stomatitis/mucositis, or interstitial lung disease. These results support the potential role of VIP236 as a strong combination agent for the treatment of advanced cancers. Considering the promising VIP236 clinical data, the Company intends to pursue a strategic partner to champion its future development for the benefit of patients. “We've made significant progress in identifying an effective dose and schedule. We believe it is now crucial to study VIP236 in the right patient population, which could include triple-negative breast cancer and gastric cancer, where camptothecins are used, especially in combination with other anticancer agents,” added Dr. Hamdy. By transitioning VIP236 to a partnering asset, the Company plans to streamline its operations and focus its efforts on the continued development of its lead ADC, VIP943. Enitociclib, a highly selective CDK9 inhibitor, is currently being evaluated in a Phase 1 dose-escalation study in combination with venetoclax and prednisone for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL), in collaboration with the National Institutes of Health (NIH). As of September 2024, the study reported four partial responses (PRs) in seven patients (57% overall response rate), including one patient with double hit lymphoma (DH-DLBCL) and three patients with PTCL. All responses occurred in patients considered refractory by SCHOLAR-1 criteria and included one patient with prior CAR-T therapy. The study is currently enrolling in the third dose level (enitociclib 30 mg [efficacious dose] and venetoclax 600 mg) with two patients enrolled to date. Additionally, in a separate Phase 1 study of enitociclib as a monotherapy (30 mg), one patient with transformed follicular lymphoma achieved a metabolic PR. As of September 2024, this patient remains on enitociclib monotherapy after more than 26 months. Overall, these clinical results continue to show the promising safety, tolerability, and efficacy of enitociclib for the treatment of relapsed/refractory lymphoma. The Company is actively focused on finding a strategic partner to continue the development of this asset. VIP236, the first-in-class SMDC from the VersAptx Platform, consists of an αvβ3 integrin binder, a neutrophil elastase linker cleaved in the tumor microenvironment, and a camptothecin payload optimized for high permeability and low active efflux. VIP236 was designed to deliver its payload to advanced/metastatic solid tumors that express αvβ3. VIP236 is being evaluated in a first-in-human, Phase 1 dose escalation study in patients with advanced malignancies (NCT05712889). VIP943, the first ADC from the VersAptx platform, consists of an anti-CD123 antibody, a unique linker cleaved intracellularly by legumain, and a novel kinesin spindle protein inhibitor (KSPi) payload enhanced with Vincerx’s CellTrapper™ technology. Vincerx’s proprietary effector chemistry (linker + payload) was designed to reduce non-specific release of the payload and ensure payload accumulation in cancer cells versus healthy cells. The increased therapeutic index has the potential to address challenges associated with many ADCs by improving efficacy and reducing severe toxicities. VIP943 is being evaluated in a Phase 1 dose-escalation trial in patients with relapsed/refractory AML, HR-MDS, and B-ALL who have exhausted standard therapeutic options (NCT06034275). Enitociclib, a highly selective CDK9 inhibitor, is currently being evaluated in a Phase 1 dose-escalation study (NCT05371054) in combination with venetoclax and prednisone for DLBCL and PTCL, in collaboration with the NIH. Enitociclib has demonstrated favorable safety and PK, with significant clinical benefits across various indications, including durable complete metabolic remissions in patients with double-hit (DH)-DLBCL and stable disease in solid tumors, notably in ovarian cancer, suggesting promising potential for future combination studies. VersAptx is a versatile and adaptable next-generation bioconjugation platform. The modular nature of this innovative platform allows the combination of different targeting, linker, and payload technologies to develop bespoke bioconjugates that address different cancer biologies. With this platform, (i) antibodies and small molecules can be used to target different tumor antigens, (ii) linkers can be designed to reduce non-specific release of the payload, cleave intracellularly or extracellularly, and conjugate to single or multiple payloads, and (iii) payloads can be designed with reduced permeability using our CellTrapper technology to ensure accumulation in cancer cells or to be permeable for release in the tumor microenvironment. The VersAptx platform allows the development of bioconjugates designed to address the safety and efficacy challenges of historical ADCs. Vincerx Pharma, Inc. is a clinical-stage biopharmaceutical company committed to developing differentiated and novel therapies to address the unmet medical needs of patients with cancer. Vincerx has assembled a seasoned management team with a proven track record of successful oncology drug development, approvals, and value creation. Vincerx’s diverse pipeline consists of the next-generation antibody-drug conjugate, VIP943, in Phase 1; small molecule-drug conjugate, VIP236, in Phase 1; preclinical antibody-drug conjugate, VIP924; CDK9 inhibitor, enitociclib, in an NIH-sponsored Phase 1; and VersAptx, its versatile and adaptable, next-generation bioconjugation platform. The content above comes from the network. if any infringement, please contact us to modify.

Clinical ResultADC

08 Oct 2024

·endpts.com

Scholar Rock aims to raise $275M; Vincerx to reshuffle pipeline focus

Plus, news about Vicore: Scholar Rock seeks $275M in stock sale: After announcing the success of a pivotal clinical trial for its muscle-targeted spinal muscular atrophy treatment, Scholar Rock’s shares $SRRK skyrocketed over 300% on Monday. The biotech is now seeking $275 million via a public offering. It plans to put the money towards funding the commercialization of its SMA therapy apitegromab, among other uses. — Lei Lei Wu Vincerx reprioritizes its pipeline: The Palo Alto, CA-based biotech said it will partner off its advanced solid tumor candidate, VIP236, and instead focus resources on continued development of VIP943 for acute myeloid leukemia. Vincerx is also looking for a partner for its diffuse large B cell lymphoma asset, called enitociclib. The company has a cash runway through early next year. Its stock $VINC was down about 19% on Tuesday morning. — Ayisha Sharma Vicore raises SEK 100M in share sale: The biotech issued more than 11 million new shares for SEK 9 apiece, securing the equivalent of $9.6 million. The proceeds are expected to help the drugmaker fund an expanded Phase 2b test of its idiopathic pulmonary fibrosis drug candidate, buloxibutid, and get ready for registrational development. — Ayisha Sharma

Phase 2IPOPhase 1

100 Deals associated with Enitociclib

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diffuse Large B-Cell Lymphoma	Phase 2	US	Vincerx Pharma, Inc.	07 Jun 2022
Hematologic Neoplasms	Phase 2	US	Bayer AG	17 Jun 2016
Hematologic Neoplasms	Phase 2	DE	Bayer AG	17 Jun 2016
Hematologic Neoplasms	Phase 2	GB	Bayer AG	17 Jun 2016
Hematologic Neoplasms	Phase 2	ES	Bayer AG	17 Jun 2016
Recurrent Non-Hodgkin Lymphoma	Phase 1	PL	Vincerx Pharma, Inc.	16 Dec 2021
Advanced cancer	Phase 1	US	Vincerx Pharma, Inc.	10 Feb 2016
Advanced cancer	Phase 1	ES	Vincerx Pharma, Inc.	10 Feb 2016
Advanced cancer	Phase 1	CL	Vincerx Pharma, Inc.	10 Feb 2016
Peripheral T-Cell Lymphoma	Phase 1	US	Vincerx Pharma, Inc.	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05371054 (Corporate Publications) Manual	Phase 1/2	Peripheral T-Cell Lymphoma \| Diffuse Large B-Cell Lymphoma \| Non-Hodgkin Lymphoma	-	ENITOCICLIB+VENETOCLAX+PREDNISONE (PTCL)	(obmuqoikvg) = nffhndtquk zjjjkdinyx (cyhpzallrn )	Positive	07 Jan 2024
NCT05371054 (Corporate Publications) Manual	Phase 1/2		-	ENITOCICLIB+VENETOCLAX+PREDNISONE (DH-DLBCL)	(obmuqoikvg) = omrxmkriuk zjjjkdinyx (cyhpzallrn )	Positive	07 Jan 2024
NCT05371054 \| NCT04978779 (Pubmed)	Not Applicable	Lymphoma MYC+ \| BCL2 \| MCL1	-	Enitociclib 30 mg	qhzkyglabz(ujecueyhjm) = hrfaguudmn vjoathpkun (clgyhhrdks )	-	09 Nov 2023
NCT02635672 \| NCT04978779 (VNC-152-102, ASH2022) Manual	Phase 1	Chronic Lymphocytic Leukemia \| Non-Hodgkin Lymphoma	17	Enitociclib	(bxlvoqluat) = anemia (12% Gr 2, 18% Gr 3), neutropenia/neutrophil count decrease (18% Gr 2, 6% Gr 3, 12% Gr 4) managed with G-CSF support, and platelet count decrease (6% each Gr 1, 2, 3 and 12% Gr 4) ntjrywjaab (cjmywdnpio ) View more	Positive	15 Nov 2022
NCT02635672 \| NCT04978779 (AACR2022)	Phase 1	-	-	VIP152	jnecedvlzc(adesaxheow) = lpnltopuop ryeugqgpre (uhebyjukme )	-	15 Jun 2022
NCT02635672 \| NCT04978779 (EHA2022)	Phase 1	Lymphoma	-	VIP152	kpzujzcjdf(zqdlqokycp) = VIP152 does not prolong QTc interval after single or multiple doses (5-30 mg) gugeczwzky (vgkfaesrue )	-	12 May 2022
NCT02635672 (Pubmed \| Clin Cancer Res)	Phase 1	Advanced cancer	-	VIP152	rkrfysyqtz(aulauuosrm) = 75.7% jtlkucyfpu (zxrgyvpyfj ) View more	Positive	19 Jan 2022
NCT02635672 \| NCT02745743 (AACR2017)	Phase 1	Neoplasms	21	BAY 1251152	mzvplqdaye(mdhfnbpqsa) = hbewkslvbf mhsmjitdfv (dxnusdwrhu ) View more	-	01 Jul 2017

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