First-in-Human Dose-Escalation Study of Cyclin-Dependent Kinase 9 Inhibitor VIP152 in Patients with Advanced Malignancies Shows Early Signs of Clinical Efficacy

Cyclin-dependent kinases (CDK) belong to a family of serine/threonine kinases that associate with an activating cyclin regulatory subunit (1). Cell-cycle CDKs (CDK1, CDK2, CDK4, and CDK6) are required for regulation of cell division, while non–cell-cycle CDKs (e.g., CDK7 and CDK9) regulate gene transcription (2–4). With deregulated CDK activity, cell-cycle checkpoint function is lost and anti-apoptotic protein expression increased, important hallmarks of the underlying pathology of cancer (5). Clinical trials of nonselective CDK inhibitors, often referred to as “pan-CDK” inhibitors [e.g., flavopiridol (alvocidib) and seliciclib], have generated suboptimal clinical trial results, particularly with regard to therapeutic window (1, 5); however, the importance of increased selectivity in CDK inhibitors, absence of off-target activity, and optimization of patient selection are now widely accepted.

Interaction of CDK9 with cyclin T1, one of several binding partners, results in formation of the positive transcription elongation factor b (PTEFb) complex essential to mRNA elongation—a key target to address transcriptional addiction in cancer (1, 6). Selective PTEFb inhibition is of interest for tumor types exhibiting increased PTEFb activity (7) or addiction to transcription of short-lived RNAs encoding for anti-apoptotic and pro-survival proteins; for example, MYC, myeloid cell leukemia 1 protein (MCL1), and cyclin D1 (1, 2, 8, 9). Effective PTEFb inhibition with atuveciclib, the first selective CDK9 inhibitor to enter the clinic, reduces expression of MYC and MCL1, causing growth inhibition and apoptosis in tumor cells (10, 11). However, phase I clinical trials with oral atuveciclib were unsuccessful in obtaining a therapeutic window, despite evaluating various doses and schedules (12, 13).

To fully explore future treatment options using selective CDK9 inhibitors, a follow-up program was initiated to maximize the therapeutic index. A highly potent and selective CDK9 inhibitor with a short half-life (t_1/2) was envisaged to enable defined periods of acute and sufficient CDK9 inhibition, obtaining the desired antitumor effect without reducing the therapeutic window. Starting from atuveciclib, lead optimization efforts aiming at identifying intravenous applicable CDK9 inhibitors with an improved therapeutic index led to the discovery of the highly potent and selective clinical candidate VIP152 (previously BAY 1251152; ref. 14). In a comprehensive survey of CDK inhibitor selectivity, VIP152 was the most potent and functionally selective CDK9 inhibitor (15). In human xenograft tumor models of acute myeloid leukemia (AML), VIP152 exhibited marked single agent in vivo antitumor efficacy and excellent tolerability across various dosing schedules, including once weekly dosing (14).

Here, we report the results of the first-in-human phase I study of VIP152 (ClinicalTrials.gov identifier: NCT02635672), characterizing its safety/tolerability, pharmacokinetics, pharmacodynamics, MTD, and preliminary antitumor activity in patients with solid tumors or aggressive NHL.

Adult patients with solid tumors or aggressive NHL that were refractory to or had exhausted all available therapies were eligible. Inclusion criteria included: Eastern Cooperative Oncology Group performance status ≤ 2, hemoglobin ≥ 9.0 g/dL independent of transfusion, absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, platelet count ≥ 100 × 10⁹/L (solid tumors) or ≥ 75 × 10⁹/L (NHL), and adequate renal and hepatic function.

Major exclusion criteria included: clinically significant cardiac disease or abnormality including uncontrolled hypertension or QTC > 470 ms; active infection; uncontrolled seizure or bleeding disorder; history of organ allograft other than bone marrow transplant; new or progressive central nervous system metastases; major surgery or anticancer therapy, including radiotherapy, mAbs, and experimental treatments ≤ 4 weeks of starting therapy; growth factor support ≤ 3 weeks of starting therapy (was allowed before first dose for NHL); use of strong CYP3A inhibitors or inducers ≤ 7 days of starting therapy or during therapy; and history of previous cancer ≤ 3 years before entry (except cervical cancer in situ, non-melanoma skin cancers, superficial bladder tumors).

This phase I study was conducted at four centers in the United States and Spain in accordance with Good Clinical Practice guidelines, provided by the International Conference on Harmonization and principles of the Declaration of Helsinki. The Institutional Review Boards or ethics committees at each participating site approved the study, and all patients provided written informed consent before enrollment.

All patients received a 30-minute intravenous, once weekly infusion of VIP152 at 5 (n = 3), 10 (n = 3), 15 (n = 4), 22.5 (n = 9) or 30 mg (n = 18) in 21-day cycles until disease progression, unacceptable toxicity, or patient or investigator decision to end therapy. The protocol allowed some patients to remain on therapy after progression at the discretion of the investigator. For patients treated at the MTD or in the expansion cohorts, GCSF and other hematopoietic growth factors were allowed for the management of acute toxicity, such as febrile neutropenia, when clinically indicated or at the investigator's discretion. Dose escalation continued until the MTD was determined on the basis of protocol-defined dose-limiting toxicity (DLTs) delineated as ANC < 0.5 × 10⁹/L for ≥ 7 days, febrile neutropenia, platelet count < 25 × 10⁹/L at any time or platelet count < 50 × 10⁹/L for ≥ 7 days or platelet count < 50 × 10⁹/L at any time associated with grade ≥ 3 bleeding, any grade ≥ 3 non-hematologic toxicity, excluding suboptimally treated nausea, vomiting, and diarrhea, optimally treated nausea, vomiting, or diarrhea grade ≥ 3 persisting for > 72 hours, missing ≥ 1 study drug doses due to any drug-related toxicity except suboptimally treated nausea, vomiting, or diarrhea, and any study drug–related deaths. Dose escalation was guided by Bayesian adaptive modeling, targeting a DLT rate of 20% (16, 17). DLT assessment period was 1 cycle (21 days). At the MTD, an expansion cohort was opened to enroll patients with high-grade B-cell lymphoma with MYC and BCL2/BCL6 translocations (HGL; ref. 18) based on preclinical efficacy of VIP152 in HGL (19) as well as the complete remission observed in a patient with HGL from the dose escalation.

Adverse events (AE) were monitored throughout the study, and toxicities were assessed using NCI Common Toxicity Criteria for grading AEs (version 4.03; ref. 20) and Medical Dictionary for Regulatory Activities for AE terminology. Physical examinations and vital signs were done on days 1, 2, 4, 8 and 15 of cycle 1 and at every weekly visit thereafter. Blood samples for hematology and serum chemistry were taken on days 1, 2, 3, 4, 8, 11, 15, 18 of cycle 1 and at every weekly visit thereafter. Solid tumor assessments were done by CT scan or MRI at the end of cycle 2 and every two cycles thereafter. PET-CT was used for tumor assessments for fluorodeoxyglucose-avid lymphomas (e.g., HGL). Radiologic assessments for patients with HGL were done within 7 days of the start of each odd cycle during year 1, every 12 weeks during year 2, and every 6 months during year 3. Tumor response and progression were evaluated on the basis of the response evaluation criteria in solid tumors (RECIST 1.1; refs. 21, 22) and NHL (Lugano Classification; ref. 23).

Plasma samples for pharmacokinetic assessments were collected at predose, 0.25, 0.5, 0.67, 1, 2, 4, 6, 8, 24, 48, 72, and 168 hours after the start of infusion on days 1 and 15. Pharmacokinetic parameters were assessed by noncompartmental methods and expressed as geometric means. VIP152 was quantified in plasma using a validated liquid chromatography coupled to mass spectrometry assay. The calibration range for the assay was from 0.200 to 400 μg/L. The assay's interbatch precision was between 1.2% and 6.4% and the interbatch accuracy was between 90.0% and 96.7% of nominal VIP152 concentrations.

Extraction of total (intracellular) RNA from whole blood collected in PAXgene Blood RNA tubes for pharmacodynamic mRNA analysis of target genes at cycle 1 day 1 (C1D1): predose and 0.5 (end of infusion), 1, 2, 4, 6, 8, 24 (C1D2) and 48 (C1D3) hours after start of infusion, C1D8: predose and 0.5 (end of infusion) and 2 hours after start of infusion, C1D15: predose and 0.5 (end of infusion), 1 2, 4, 6, and 8 hours after start of infusion.

RNA isolation was prepared with PAXgene Blood RNA Kit (PreAnalytix, QIAGEN), cDNA synthesis with the High Capacity RNA-to-cDNA Kit (Applied Biosystems, Thermo Fisher Scientific) and the qPCR with TaqMan reagents for MYC, MCL1, and proliferating cell nuclear antigen (PCNA), including glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and hypoxanthine phosphoribosyltransferase 1 (HPRT1) housekeeping genes (Applied Biosystems, Thermo Fisher Scientific).

This was a dose-escalation trial designed to determine the MTD of VIP152 and to characterize AEs and DLTs. The safety population was all patients who received ≥ 1 VIP152 dose. The MTD evaluable population included all patients who completed cycle 1 or who experienced DLT in cycle 1. Patients who discontinued during cycle 1 of therapy due to any reason other than DLT and patients not experiencing a DLT who were administered less than three infusions (100%) of study drug during cycle 1 were replaced to ensure up to 4 evaluable patients per cohort. Also, all patients who received at least one dose of VIP152 were evaluated during dose-escalation meetings and taken into account by the sponsor and investigators when determining the MTD. The MTD was determined utilizing a modified continual reassessment method targeting a DLT rate of 20% during cycle 1 (24). However, the final decision on the MTD was based on the assessment all available safety and tolerability data from all cohorts, including safety data beyond cycle 1 to capture potential delayed toxicities. The stopping rules were any of the following conditions:

• (i) MTD precisely estimated: coefficient of variation of MTD, calculated as the interquartile range over the median, was <40%.

• (ii) Probability was >80% that the DLT rate was <20% at maximum possible dose level.

• (iii) Probability was <20% that the DLT rate was <20% at the first dose level (5 mg).

Best tumor response was summarized using descriptive statistics and graphically displayed using a waterfall plot. Duration of response (DOR) was defined as time from the date of the first tumor response to the date of disease progression determined by the investigator or death due to any cause. Patients not experiencing death or progression were censored at the last on-treatment tumor assessment date. Response for patients with HGL was assessed by investigators per the Lugano Classification (23).

Clinical trial data will be uploaded to clinicaltrials.gov and data may be shared with external parties upon request to the corresponding author.

From February 2016 to September 2018, 53 patients were enrolled—of whom 1 withdrew consent during screening, 1 had an AE during screening, and 14 did not meet entry criteria, with the remaining 37 patients receiving ≥ 1 VIP152 dose. Baseline disease and treatment characteristics are listed in Table 1. Median age was 62 years (range, 28–84 years). Approximately two-thirds of the patients were women. Most patients had advanced disease (86% stage IV), and all had received ≥ 2 prior therapies. Five cohorts were treated at 5 (n = 3), 10 (n = 3), 15 (n = 4), 22.5 (n = 9), or 30 mg (n = 12) once weekly on 21-day cycles. In addition, at the time of the data cutoff, the HGL expansion cohort had enrolled 6 subjects at 30 mg. Median number of cycles received was 2 with an average number of six cycles (range, 1–64).

The MTD for VIP152 was defined as 30 mg based on collective safety data according to the model-based dose–response analysis. DLT was grade 3/4 neutropenia, including one case of grade 3 febrile neutropenia (Table 2). Six patients (n = 3 at 30 mg; n = 3 at 22.5 mg) required dose reductions for neutropenia. No other AEs led to dose reduction. Eight patients required dose interruptions (most skipped only one dose) due to neutropenia. Seven patients (n = 2 at 22.5 mg; n = 5 at 30 mg) received GCSF, most often in the first cycle.

The most common treatment-emergent AEs observed in the study (Table 3) were typically grade 1/2 in severity; grade 3/4 events were infrequent and independent of dose, except for neutropenia (Fig. 1). Neutropenia appeared dose dependent with reductions in absolute neutrophil count in each cohort (Fig. 1) correlating with VIP152 drug exposures (Fig. 2A–C; Supplementary Table S1). Of the most common AEs, grade 3/4 AEs occurring in ≥ 2 patients were neutropenia (22%), anemia (11%), abdominal pain (8%), increased blood alkaline phosphatase (8%), and hyponatremia (8%). Grade 3/4 AEs did not appear to increase with time on treatment (Supplementary Fig. S1). No deaths or serious AEs related to treatment were observed. No tumor lysis syndrome occurred in any patients. No patients withdrew from study drug due to an AE. Most patients (86%) withdrew due to disease progression (Fig. 3A). Two deaths occurred because of disease progression: 1 patient on study for 16 days died 9 days after last dose, and 1 patient on study for 87 days died 37 days after the last dose. Two grade 5 AEs occurred, related to clinical disease progression: sepsis 40 days after last dose (on study for 15 days) and hepatorenal syndrome 12 days after last dose (received one VIP152 dose).

After 30-minute intravenous infusion of VIP152, maximum concentrations (C_max) were typically observed near the end of infusion (Supplementary Table S1). Mean t_1/2 ranged from 3 to 6 hours. VIP152 exposures [C_max and area under the plasma concentration vs. time curve (AUC)] were approximately dose proportional, though an overlap in concentrations occurred between the 22.5- and 30-mg doses, likely due to patient variability (Fig. 2; Supplementary Table S1). After the first dose, mean plasma clearance (CL) was low, ranging from 8.26 to 16.1 L/hour over the dose range evaluated and mean volume of distribution at steady-state (V_ss) ranged from 46 to 61 L. CL and V_ss showed no obvious dose dependence. At 30 mg, which was declared as the MTD, day 1 AUC was 2,780 μg·hours/L, which exceeds the predicted minimum therapeutic exposure based on MOLM-13 xenograft studies in rats (Fig. 2C; Supplementary Table S1). VIP152 pharmacokinetics was comparable after single dose (C1D1) and multiple doses (C1D15), with no evidence of significant accumulation or alteration in general pharmacokinetic properties (Fig. 2A and B; Supplementary Table S1). The pharmacokinetics of patients with HGL (n = 7) given 30 mg of VIP152 were comparable with other patients assessed at the same dose level in this study. Relevant unbound pharmacokinetic parameters are shown in Supplementary Table S2.

For all doses, downregulation of MYC, MCL1, and PCNA mRNA levels compared with baseline were detected (Fig. 2D; Supplementary Fig. S2). Downregulation was dose and time dependent with maximal pathway inhibition achieved at the two highest dose levels (22.5 and 30 mg). The highest degree of downregulation was achieved at 0.5 to 4 hours postdose for MYC, 1 to 2 hours postdose for MCL1, and 1 to 4 hours postdose for PCNA. These results were consistent regardless of dosing day.

Of 30 patients with solid tumors treated in the dose escalation, disease control (stable disease) was observed in 7 patients (23%), 5 of whom received either 22.5 or 30 mg (Fig. 3A). Change in aggregate tumor size for evaluable patients is shown in Fig. 3B. Durable disease control was observed in individual patients with pancreatic cancer and salivary gland cancer (9.5 and 16.8 months of treatment, respectively). Of 7 patients with HGL treated with VIP152 30 mg once weekly, 2 patients had complete metabolic remissions (CMR); both achieved CMR after 10 cycles (Fig. 3A). When treatment ended because of the COVID pandemic (i.e., patients had been in long remission and did not want to risk COVID infection at the hospital), both were still in CMR. One had been receiving treatment for 3.7 years and the other for 2.3 years; as submission of this article, both remain in remission (Supplementary Fig. S3 provides additional clinical features).

Previously atuveciclib, an orally administered, highly selective, first-in-class CDK9 inhibitor, was evaluated in two clinical studies, one involving patients with advanced malignancies refractory to or having exhausted standard therapies, the second in patients with advanced AML (12, 13). Both studies demonstrated rapid absorption of atuveciclib, t_1/2 of 2.5–4.1 hours after single and multiple administrations, respectively, and a high incidence of acute, rapid-onset neutropenia leading to DLTs. Despite schedule modification to allow for intermittent (3 days on/4 days off) dosing and prophylactic GCSF in one of the studies, neutropenia and febrile neutropenia were still observed and neither study was able to establish a therapeutic window for atuveciclib, suggesting alternative administration methods are warranted to optimize transcriptional elongation inhibition while minimizing acute hematologic toxicity. To improve the therapeutic index of atuveciclib, a follow-up program was initiated to identify a new generation of highly potent and selective CDK9 inhibitors, like VIP152, amenable to once weekly intravenous administration to produce an “oncogenic shock”-like disruption of oncogene transcription followed by a time without target inhibition, allowing for the circulating neutrophil recovery (25).

In this phase I first-in-human study, once weekly intravenous monotherapy with VIP152 was well tolerated with manageable AEs, favorable pharmacokinetics, and preliminary antitumor activity in heavily pretreated adult patients with solid tumors or aggressive NHL. VIP152 demonstrated a favorable safety profile up to and including the MTD, determined to be 30 mg i.v. once weekly in 21-day cycles. The DLT was grade 3/4 neutropenia. Overall, VIP152 monotherapy demonstrated an acceptable therapeutic window with preliminary evidence of efficacy in various tumor types.

VIP152 pharmacokinetics revealed a profile with the intended characteristics, including high systemic exposure due to low CL, short t_1/2 (geometric mean, 3–6 hours), and exposure at the MTD above the minimum predicted therapeutic exposure. In addition, no evidence of accumulation or change in pharmacokinetics was observed after multiple doses, and maximum pathway modulation is achieved at the two highest doses after the first dose and after the third dose, demonstrating consistent pathway modulation of short half-life mRNA transcripts such as MYC, MCL1, and PCNA.

Overall, VIP152 monotherapy was well tolerated at all dose levels evaluated; the most commonly reported AEs consisted of low-grade gastrointestinal symptoms. The grade 3/4 AE incidence was low and independent of dose, except for neutropenia, which was also the DLT observed at the 30-mg dose. In contrast to the clinical experience with atuveciclib, no subjects withdrew consent due to treatment-related AEs and no treatment-related serious AEs were reported, indicating that VIP152 monotherapy has an encouraging safety profile.

Although DLTs of neutropenia were reported at the 22.5- and 30-mg doses, the impact of VIP152 on neutrophils was an anticipated on-target effect owing to neutrophil kinetics and the role of MCL1 in neutrophil survival. Dose reductions for neutropenia were required in 6 patients (16%); however, no patients withdrew from the study due to neutropenia, which was successfully managed using GCSF in the first cycle. Median neutrophil counts revealed a transient reduction, mostly within the normal range, with overall neutrophil counts after the initial VIP152 dose followed by a return to near or above the lower limit of the normal range during subsequent cycles at the highest doses.

Treatment with VIP152 monotherapy in patients with solid tumors, who were not selected for MYC overexpression or translocation, resulted in disease control in 7 patients, providing evidence of clinical activity. Of these, 2 were particularly notable: a patient with pancreatic cancer, who was refractory to last treatment (paclitaxel/gemcitabine), achieved prolonged disease stabilization lasting 9.5 months, and a patient with salivary cancer, who had received palliative therapy before study entry, achieved prolonged disease stabilization lasting 16.8 months. In both instances, VIP152 treatment was well tolerated. Given their poor prognosis, the prolonged disease stabilization is encouraging.

HGL is an aggressive high-grade form of NHL characterized by translocations involving MYC and BCL2 or BCL6. Currently, no specific therapies are approved for HGL, and multiple retrospective studies have reported median overall survival < 2 years (26–31)—highlighting the unmet need for effective treatments for this patient population. Two of 7 patients with HGL (29%) who received VIP152 monotherapy achieved CMR, as assessed by the Lugano criteria. Of note, the remissions occurred after 7 months of therapy, highlighting the importance of long-term tolerability. Remarkably, the patients were still in CMR when they withdrew consent after 2.3 and 3.7 years, respectively, of treatment and remained in remission as of this writing. The observed on- and off-treatment DOR not only exceeds each patient's response to prior therapies; it also exceeds available data for current therapies in this patient population (32).

Initial clinical evaluation of VIP152 monotherapy has demonstrated that once weekly intravenous dosing with this highly selective and potent CDK9 inhibitor is able to overcome the acute toxicity that limited clinical development of the oral CDK9 inhibitor, atuveciclib, without sacrificing the oncogenic shock needed for clinical efficacy. The pharmacokinetic profile of VIP152 displays intended characteristics of low CL and a short t_1/2 allowing for potent, yet transient, CDK9 inhibition in the hours immediately after dosing followed by VIP152 elimination and neutrophil recovery before the subsequent dose. Expression of PTEFb-regulated genes, such as MYC, is consistently modulated after each dose and maximum pathway inhibition is achieved at the two highest VIP152 dose levels, indicating their biologic activity. Tumor-based pharmacodynamic studies are required to confirm these whole blood findings.

Overall, VIP152 monotherapy demonstrated an acceptable therapeutic window and a favorable safety profile along with evidence of clinical benefit in patients with advanced hematologic and solid tumors. Given the favorable safety and efficacy profile of VIP152, further clinical evaluation is underway in MYC- and MCL1-driven malignancies (NCT02635672/NCT04978779).

J.R. Diamond reports grants from Bayer during the conduct of the study as well as grants from Adlai Norte, Takeda, Merck, AstraZeneca, Astellas, AbbVie, BMS, Deciphera, and Bayer; grants and other support from Gilead; and other support from OnKure outside the submitted work. V. Boni reports other support from Bayer during the conduct of the study as well as personal fees from Puma Biotechnology, Ideaya Biosciences, Loxo Therapeutics, CytomX Therapeutics, Guidepoint, and Oncoart outside the submitted work; in addition, V. Boni is employed as Director of Clinical Cancer Research, NEXT Madrid, University Hospital QuirónSalud Pozuelo. E. Lim reports other support from Pfizer outside the submitted work. G. Nowakowski reports other support from Bayer during the conduct of the study as well as grants from BMS, Incyte, and Roche; personal fees from Kite, AbbVie, Ryvu, Kryopharm, and Kymera; and grants and other support from Morphosys outside the submitted work. R. Cordoba reports grants from Pfizer and personal fees from Roche, Janssen, AbbVie, Gilead, BMS, Takeda, AstraZeneca, and Incyte outside the submitted work. D. Morillo reports personal fees from Janssen, Takeda, AbbVie, and Gilead during the conduct of the study. R. Valencia reports personal fees from Bayer Pharmaceuticals during the conduct of the study. O. Boix reports personal fees from Bayer AG during the conduct of the study as well as other support from and stock ownership in Bayer outside the submitted work; in addition, O. Boix is an employee of Bayer AG. M.M. Frigault reports other support from Vincerx Pharma and AstraZeneca outside the submitted work. J.M. Greer reports other support from Gilead Sciences and Annexon Biosciences outside the submitted work. A.M. Hamdy reports grants and personal fees from Vincerx during the conduct of the study as well as personal fees from Vincerx outside the submitted work; in addition, A.M. Hamdy has a patent for dosing schedule of CDK9 pending, and executive management. X. Huang reports other support from Vincerx Pharma outside the submitted work. R. Izumi reports other support from Vincerx Pharma, Acerta Pharma, and AstraZeneca outside the submitted work; in addition, R. Izumi has a patent for VIP152 pending. H. Wong reports other support from Vincerx during the conduct of the study; in addition, H. Wong is an employee of the University of British Columbia. V. Moreno reports other support from Bayer during the conduct of the study as well as personal fees from Roche, Bayer, BMS, Janssen, and Basilea outside the submitted work. No disclosures were reported by the other authors.

J.R. Diamond: Data curation, investigation, writing–review and editing. V. Boni: Data curation, investigation, writing–review and editing. E. Lim: Investigation, writing–review and editing. G. Nowakowski: Data curation, investigation, writing–review and editing. R. Cordoba: Data curation, investigation, writing–review and editing. D. Morillo: Data curation, investigation, writing–review and editing. R. Valencia: Conceptualization, data curation, supervision, writing–review and editing. I. Genvresse: Data curation, supervision, writing–review and editing. C. Merz: Data curation, investigation, writing–review and editing. O. Boix: Data curation, formal analysis, writing–review and editing. M.M. Frigault: Data curation, formal analysis, writing–original draft. J.M. Greer: Data curation, writing–original draft. A.M. Hamdy: Data curation, writing–review and editing. X. Huang: Data curation, formal analysis, writing–review and editing. R. Izumi: Data curation, writing–original draft. H. Wong: Data curation, formal analysis, writing–original draft. V. Moreno: Data curation, supervision, investigation, writing–review and editing.

The authors wish to thank all the investigators and coordinators at each clinical site; the patients who participated in this trial and their families; and the Bayer study team who designed and conducted this study, including John Lettieri and Stuart Ince. Medical writing assistance, funded by Vincerx Pharma, was provided by Laurie Orloski of InSeption Group.

This clinical study was funded by Bayer Pharma AG. Medical writing support was funded by Vincerx Pharma, Inc.

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