On June 12, 2020 Imago BioSciences reported the presentation of data at the 2020 Virtual European Hematology Association (EHA) (Free EHA Whitepaper) meeting relating to the clinical trial of bomedemstat (IMG-7289) for the treatment of advanced myelofibrosis (Press release, Imago BioSciences, JUN 12, 2020, View Source [SID1234561031]). The abstract published online in May included an analysis of data from 34 patients. The presentation today as a poster reflects a more extensive analysis of a larger patient population based on a later data cutoff.

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"The poster enumerates spleen volume reductions and improvements in Total Symptom Scores in a majority of patients. Additionally, there were improvements in hemoglobin with patients transitioning from transfusion-dependence to transfusion-independence and bone marrow fibrosis improvements," said Kristen Petitt, MD, Assistant Professor of Medicine at the University of Michigan, Rogel Cancer Center, in Ann Arbor. "In this ongoing study, the preliminary data indicate that bomedemstat has significant clinical activity as monotherapy in a myelofibrosis patient population with advanced disease and no therapeutic alternatives."

Data Highlights

Bomedemstat (IMG-7289) monotherapy in intermediate-2 /high-risk patients with myelofibrosis who have become intolerant or resistant to a JAK inhibitor

Of evaluable patients at 24 weeks:
83% had spleen volume reductions
86% demonstrated reductions in Total Symptom Scores (TSS)
70% of patients had stable or improved hemoglobin
71% of patients had a stable or improved BM fibrosis score
>90% of patients with elevated circulating inflammatory cytokines showed significant reductions
Safety

Bomedemstat (IMG-7289) in patients with myelofibrosis was generally well tolerated. No dose-limiting toxicities were observed, and a maximum tolerated dose was not identified.

There were 723 adverse events (AEs) reported, of which 215 were attributed to bomedemstat. Only four SAEs — painful splenomegaly, heart failure, headache, rectal bleeding (all Grade 3) — were deemed by the Investigator to be related to bomedemstat. There were no Grade 5 events related to bomedemstat.

The most common treatment-emergent AEs deemed related to bomedemstat was dysgeusia (33%).

For further details, please see the 2020 EHA (Free EHA Whitepaper) abstract and poster on Imago’s website at www.imagobio.com.

Poster Presentation

TITLE: A PHASE 2 STUDY OF BOMEDEMSTAT (IMG-7289), A LYSINE-SPECIFIC DEMETHYLASE-1 (LSD1) INHIBITOR, FOR THE TREATMENT OF MYELOFIBROSIS (MF)

Session: Myeloproliferative Neoplasms—Clinical

Date and Time: June 12, 2020, 8:30 AM CEST/2:30 AM EDT

About Bomedemstat (IMG-7289)

Bomedemstat is being evaluated in an open-label Phase 2 clinical trial (www.myelofibrosisclinicalstudy.com) for the treatment of myelofibrosis (MF), a bone marrow cancer that interferes with the production of blood cells. The endpoints include spleen volume reduction and symptom improvement at 12 and 24 weeks of treatment. Bomedemstat is used as monotherapy in patients who are resistant to, intolerant of, or ineligible for ruxolitinib.

Bomedemstat is a small molecule developed by Imago BioSciences that inhibits lysine-specific demethylase 1 (LSD1 or KDM1A), an enzyme shown to be vital in cancer stem/progenitor cells, particularly neoplastic bone marrow cells. In non-clinical studies, IMG-7289 demonstrated robust in vivo anti-tumor efficacy across a range of myeloid malignancies as a single agent and in combination with other chemotherapeutic agents. Bomedemstat (IMG-7289) is an investigational agent currently being evaluated in ongoing clinical trials (ClinicalTrials.gov Identifier: NCT03136185 and NCT04254978). Bomedemstat has FDA Orphan Drug and Fast Track Designation for the treatment of myelofibrosis, essential thrombocythemia and acute myeloid leukemia.

On June 12, 2020 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, and Royalty Pharma reported that Agios has sold its tiered, sales-based royalty rights on worldwide net sales of Bristol Myers Squibb’s IDHIFA (enasidenib), as well as its rights to receive up to $55 million in outstanding regulatory milestone payments from Bristol Myers Squibb, to Royalty Pharma for $255 million (Press release, Agios Pharmaceuticals, JUN 12, 2020, View Source [SID1234561030]). Agios will continue to co-promote IDHIFA and receive reimbursement from Bristol Myers Squibb for this co-promotion under its 2010 collaboration agreement with Celgene, a wholly owned subsidiary of Bristol Myers Squibb. Agios also retains the right to receive a $25 million payment upon achievement of a specified ex-U.S. commercial milestone event. IDHIFA is an oral, targeted therapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation.

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"It is an exciting time at Agios with multiple ongoing mid- and late-stage trials in each of our core therapeutic focus areas that we believe have the potential to make a meaningful difference in patients’ lives. This non-dilutive funding provides us with additional financial flexibility as we continue to invest in advancing our robust clinical pipeline, including mitapivat across three rare disease indications and our IDH inhibitors in solid tumors and novel combination approaches for AML," said Jackie Fouse, Ph.D., chief executive officer of Agios. "Royalty Pharma, a pioneer in this space, is an industry leader in identifying promising late-stage and commercial therapies, and we are pleased with their recognition of IDH inhibition as an important therapeutic approach for hematologic malignancies."

"IDHIFA is an innovative, targeted treatment that has benefited numerous AML patients who may otherwise have had few other treatment options," said Pablo Legorreta, founder and chief executive officer of Royalty Pharma. "We are delighted to partner with Agios, a biotechnology company that stands out for its strong scientific foundation and a track record of successful development of multiple innovative targeted therapies. The proceeds that Agios will receive today will help further their mission and fund their exciting pipeline that will drive the next phase of the company’s growth."

Cowen served as financing advisor to Agios and Wilmer Hale served as legal advisor to Agios. Goodwin Procter LLP, Dechert LLP and Maiwald Patentanwalts- und Rechtsanwaltsgesellschaft mbH acted as legal advisors to Royalty Pharma on the transaction.

About the Agios/Celgene IDH Program
In 2010, Agios and Celgene Corporation, now a wholly owned subsidiary of Bristol Myers Squibb, entered into a collaboration agreement focused on cancer metabolism. Under the terms of the agreement, Celgene has worldwide development and commercialization rights for IDHIFA (enasidenib). Celgene and Agios are currently co-commercializing IDHIFA in the U.S., and Agios continues to conduct certain clinical development activities within the IDHIFA development program. Agios is eligible to receive a $25 million payment upon achievement of a specified ex-U.S. commercial milestone event, as well as reimbursement for costs incurred for its co-commercialization efforts and development activities.

On June 12, 2020 Sierra Oncology, Inc. (NASDAQ: SRRA), a late-stage drug development company focused on the registration and commercialization of momelotinib, a JAK1, JAK2 & ACVR1 inhibitor with a potentially differentiated therapeutic profile for the treatment of myelofibrosis, reported that Long-Term Safety and Dose Intensity data for momelotinib are being presented today in two posters at the 25th European Hematology Association (EHA) (Free EHA Whitepaper) Virtual Congress (Press release, Sierra Oncology, JUN 12, 2020, View Source [SID1234561029]).

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More than 820 patients with myelofibrosis have received momelotinib during its development, including a number of patients who remain on treatment since the start of the original Phase 2 studies initiated a decade ago. One of these patients will reach a major milestone this week, having received momelotinib therapy for 10 years, highlighting the relevance of the long-term dosing and safety data for momelotinib being presented this week at EHA (Free EHA Whitepaper). The data presented at EHA (Free EHA Whitepaper) draw from more than 550 patients across the two previously conducted SIMPLIFY Phase 3 studies and their subsequent ongoing extended treatment periods. More than 90 SIMPLIFY-1 and SIMPLIFY-2 patients continued to receive momelotinib for 3.5 years or longer.

"Consistent with prior data, and reflecting momelotinib’s differentiated pharmacological profile, our new long-term safety analyses continue to show a rapid and sustained increase in hemoglobin levels during momelotinib therapy, in contrast to the significant decrease in hemoglobin for patients receiving ruxolitinib. Patients treated with momelotinib also experienced significantly higher mean platelet counts compared to those receiving ruxolitinib. Importantly, patients who switched from ruxolitinib to momelotinib also achieved a sustained improvement in both hemoglobin and platelets," said Prof. Claire Harrison, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom. "In addition to an absence of significant rates of high-grade hematological toxicities, long-term tolerability was favorable with no new safety signals or evidence of cumulative toxicity. Notably, this was achieved with most patients receiving full-dose momelotinib."

"Momelotinib’s safety profile and durable anemia benefits facilitated sustained dose intensity across the continuum of JAK inhibitor naïve and previously JAK inhibitor treated myelofibrosis patients. While the starting doses for ruxolitinib were often attenuated due to low platelets, further reductions in dose intensity were also commonly required for ruxolitinib. In contrast, momelotinib was initiated at full dose for all subjects enrolled to the SIMPLIFY studies and high dose intensity was maintained in the majority over extended durations," said Dr. Vikas Gupta, Princess Margaret Cancer Centre, Toronto, Canada. "The ability to safely dose momelotinib sustainably at high dose intensity likely facilitates its ability to durably control the cardinal features of myelofibrosis, namely anemia, constitutional symptoms, and splenomegaly. Furthermore, patients who switch from ruxolitinib to momelotinib saw an immediate and sustained improvement in dose intensity, suggesting a link to the corresponding improvements in hemoglobin and platelets noted by Prof. Harrison. These data suggest that momelotinib may be an optimal therapy in myelofibrosis patients, in particular those experiencing hematological toxicity and disease-related myelosuppression, which are significant unmet needs in this disease."

The SIMPLIFY-1 trial was conducted in JAKi-naïve myelofibrosis patients (n=432) randomized 1:1 to momelotinib or ruxolitinib for 24 weeks. The SIMPLIFY-2 trial was conducted in prior ruxolitinib-treated myelofibrosis patients with hematological toxicity (n=156) randomized 2:1 to momelotinib or best available therapy (consisting of ruxolitinib in 88% of patients) for 24 weeks. All patients were then subsequently allowed to receive momelotinib for an extended treatment period including those who did not receive momelotinib initially, as they were eligible to cross-over to momelotinib at the end of the 24-week randomized treatment period in both studies.

About the Posters:
Please visit www.sierraoncology.com to view Prof. Harrison and Dr. Gupta present the momelotinib Long-Term Safety and Dose Intensity posters. Both e-posters are available through the on-demand EHA (Free EHA Whitepaper) Virtual Congress platform at View Source

Title: Long term Safety of Momelotinib in JAKi Naïve and Previously JAKi Treated Intermediate/High Risk Myelofibrosis Patients
Lead Author: Prof. Claire Harrison, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom
Session Title: Myeloproliferative neoplasms – Clinical
Poster No.: EP1113

Title: Momelotinib Dose-Intensity is Maintained in JAKi Naïve and Previously JAKi Treated Intermediate/High Risk Myelofibrosis Patients
Lead Author: Dr. Vikas Gupta, Princess Margaret Cancer Centre, Toronto, ON, Canada
Session Title: Myeloproliferative neoplasms – Clinical
Poster No.: EP1103

On June 12, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported updated data on one of its investigational CD20xCD3 T-cell engaging bispecific antibodies, glofitamab (formerly known as CD20-TCB), in people with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) (Press release, Hoffmann-La Roche, JUN 12, 2020, View Source [SID1234561027]). Updated results from the phase I dose-escalation NP30179 study [NCT03075696] of glofitamab, administered via intravenous infusion for a fixed-duration of up to 12 21-day cycles, showed durable complete responses (CRs) in heavily pre-treated patients who had received a median of three prior lines of therapy. These data feature in an oral presentation (abstract #S241) at the European Hematology Association (EHA) (Free EHA Whitepaper) 25th Annual Congress Virtual Edition, taking place from 11-14 June 2020.

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"Non-Hodgkin lymphomas such as diffuse large B-cell lymphoma may present considerable treatment challenges, especially cases involving multiple relapses," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "We’re encouraged by these early results which support the potential of glofitamab for patients who have failed multiple prior lines of therapy and need new treatment options urgently."

Updated efficacy data from the ≥0.6mg and ≥10mg cohorts showed high response rates across NHL subtypes.

In the ≥0.6mg cohorts, the investigator-assessed CR rate was 30.9% (38/123) for patients with aggressive NHL and the investigator-assessed overall response rate (ORR) was 45.5% (56/123). For patients with indolent NHL, the investigator-assessed CR rate was 52.2% (12/23) and the investigator-assessed ORR was 65.2% (15/23).
In the ≥10mg cohorts, the investigator-assessed CR rate was 34.1% (29/85) for patients with aggressive NHL and the investigator-assessed ORR was 49.4% (42/85). For patients with indolent NHL, the investigator-assessed CR rate was 50.0% (9/18) and the investigator-assessed ORR was 66.7% (12/18).
CRs also appeared durable. Of the patients achieving a CR in the ≥0.6mg cohorts, 72.7% (24/33) with aggressive NHL and 81.8% (9/11) with indolent NHL maintained their CR by the data cut-off date (17 April 2020). Median duration of CR was not reached in either group after a median follow-up of 10.2 months.
The safety profile of glofitamab was consistent with its mechanism of action. Common adverse events (AEs) occurring in over 15% of participants in the ≥0.6mg cohorts (n=156) were cytokine release syndrome (CRS; n=88, 56.4%), neutropenia (n=48, 30.8%), pyrexia (n=47, 30.1%), anaemia (n=35, 22.4%) and thrombocytopenia (n=26, 16.7%). The majority of CRS events were low grade (Grade 1-2), were associated with the first cycle, and were manageable.

A robust clinical development programme for glofitamab is ongoing, investigating the molecule alone and in combination with other Roche and non-Roche molecules. Combination regimens include studies with Polivy (polatuzumab vedotin), Tecentriq (atezolizumab), MabThera/Rituxan (rituximab) and Gazyva/Gazyvaro (obinutuzumab) in NHL and other blood cancers, across a variety of settings and tumour types, including earlier treatment lines, to identify where glofitamab may be able to provide benefit over current treatment options.

About glofitamab
Glofitamab is an investigational CD20xCD3 T-cell engaging bispecific antibody designed to target CD20 on the surface of B-cells and CD3 on the surface of T-cells. This dual targeting activates and redirects a patient’s existing T-cells to engage and eliminate target B-cells by releasing cytotoxic proteins into the B-cells. Glofitamab is based on a novel structural format which we call ‘2:1’, which refers to the structure of the antibody. It is engineered to have two ‘Fab’ regions which bind to CD20, and one ‘Fab’ region which binds to CD3. A robust clinical development programme for glofitamab is ongoing, investigating the molecule as a monotherapy and in combination with other medicines, for the treatment of people with CD20-positive B-cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma and follicular lymphoma, and other blood cancers.

About the NP30179 study
The NP30179 study [NCT03075696] is a phase I/Ib, multicentre, open-label, dose-escalation study, evaluating the efficacy, safety, tolerability and pharmacokinetics of glofitamab. In this study, glofitamab is assessed as a single agent and in combination with Gazyva/Gazyvaro (obinutuzumab), following pre-treatment with a one-time, fixed dose of Gazyva/Gazyvaro, in people with relapsed or refractory B-cell non-Hodgkin lymphoma. Outcome measures include overall response rate, complete response rate per Lugano 2014 criteria, maximum tolerated dose, and tolerability.

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for over 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera/Rituxan (rituximab), Gazyva/Gazyvaro (obinutuzumab), Polivy (polatuzumab vedotin), Venclexta/Venclyxto (venetoclax) in collaboration with AbbVie, and Hemlibra (emicizumab). Our pipeline of investigational haematology medicines includes idasanutlin, a small molecule which inhibits the interaction of MDM2 with p53; T-cell engaging bispecific antibodies, glofitamab and mosunetuzumab, targeting both CD20 and CD3, Tecentriq (atezolizumab), a monoclonal antibody designed to bind with PD-L1; and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.

On June 12, 2020 Constellation Pharmaceuticals, Inc. (Nasdaq: CNST) reported that three posters relating to the MANIFEST clinical trial of CPI-0610 in myelofibrosis (MF) were published online in association with the European Hematology Association (EHA) (Free EHA Whitepaper) annual meeting (Press release, Constellation Pharmaceuticals, JUN 12, 2020, View Source [SID1234561026]). The data in these posters are based on a data cutoff of April 17, 2020, and reflect an analysis of clinical activity in 51 first-line (1L) and 73 second-line (2L) patients.

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"I’m encouraged that the initial signals of activity with CPI-0610, such as spleen and symptom responses, that were presented last December at ASH (Free ASH Whitepaper) continue to be observed in a larger dataset presented in these EHA (Free EHA Whitepaper) posters," said Claire Harrison, D.M. (Oxon.), Professor of Haematology and a MANIFEST investigator. "In addition, we continue to see signals of disease modification, such as increases in hemoglobin, conversions of transfusion-dependent patients to transfusion independence, and bone marrow fibrosis improvements. If corroborated in further testing, these data suggest that CPI-0610 could potentially change the treatment paradigm in MF."

"We are excited about the emerging profile of CPI-0610," said Jigar Raythatha, Chief Executive Officer of Constellation Pharmaceuticals. "Our goal is to drive CPI-0610 to registration and to transform the standard of care in myelofibrosis and potentially other hematologic diseases."

Data Highlights

Arm 3 (1L) – CPI-0610 + ruxolitinib in JAK-inhibitor-naïve patients

37 of 51 evaluable patients (73%) achieved a 35% reduction in spleen volume (SVR35) at 12 weeks and had a median spleen volume reduction of 51%
19 of 30 evaluable patients (63%) achieved SVR35 at 24 weeks (the primary endpoint for Arm 3) and had a median spleen volume reduction of 53%
17 of 29 evaluable patients (59%) achieved a 50% improvement in Total Symptom Score (TSS50) at 24 weeks and had a median TSS improvement of 64%
No evidence of correlation between SVR35 response and baseline risk status, platelet count, or spleen volume
Arm 1 (2L) – CPI-0610 monotherapy in JAK-inhibitor-experienced or -ineligible patients

3 of 14 (21%) evaluable transfusion-dependent (TD) patients converted to transfusion independence (TI), the primary endpoint for cohort 1A
5 of 21 (24%) evaluable non-TD patients achieved SVR35 (the primary endpoint for cohort 1B) and 9 of 19 (47%) evaluable non-TD patients achieved TSS50 at 24 weeks
11 of 19 (58%) non-TD patients on treatment for at least 12 weeks without any transfusions achieved a ≥1.5 g/dL mean increase in hemoglobin
Arm 2 (2L) – CPI-0610 + ruxolitinib in ruxolitinib-experienced patients

11 of 32 (34%) evaluable TD patients converted to TI, the primary endpoint for cohort 2A
4 of 18 (22%) evaluable non-TD patients achieved SVR35 (the primary endpoint for cohort 2B) and 7 of 19 (37%) evaluable non-TD patients achieved TSS50 at 24 weeks
Safety

CPI-0610 in MANIFEST, both as monotherapy and in combination with ruxolitinib and in both JAK-inhibitor-naïve and JAK-inhibitor-experienced and -ineligible patients, was generally well tolerated.

Among the most common treatment-emergent adverse events (TEAEs) for CPI-0610 monotherapy in 43 safety-evaluable patients in Arm 1, those that were Grade 3 were thrombocytopenia (14.0%), anemia (9.3%), diarrhea (4.7%), and respiratory tract infection (2.3%). Six patients discontinued treatment because of TEAEs. There were no Grade 4 or Grade 5 TEAEs.

Among the most common TEAEs in 70 safety-evaluable patients in Arm 2, those that were Grade 3 were thrombocytopenia (22.9%), anemia (7.1%), fatigue (5.7%), diarrhea (4.3%), respiratory tract infections (4.3%), nausea (2.9%), and abdominal pain (1.4%). Grade 4 TEAEs included thrombocytopenia (1.4%) and anemia (1.4%). Seven patients discontinued treatment due to TEAEs, including four Grade 5 TEAEs, which were acute kidney injury, traumatic subdural hematoma, brain stem hemorrhage (no concomitant thrombocytopenia), and disease progression.

Among the most common TEAEs in 64 safety-evaluable patients in Arm 3, those that were Grade 3 were anemia (15.6%), respiratory tract infections (3.1%), and thrombocytopenia (1.6%). Grade 4 TEAEs included thrombocytopenia (3.1%), anemia (1.6%), and respiratory tract infection (1.6%). Four patients discontinued treatment due to TEAEs, including two Grade 5 TEAEs, each due to multi-organ failure due to sepsis.

For further details, please see the EHA (Free EHA Whitepaper) poster presentations here.

EHA Poster Presentations

TITLE: CPI-0610, A Bromodomain and Extraterminal Domain Protein (BET) Inhibitor, in Combination with Ruxolitinib, in JAK Inhibitor Treatment Naive Myelofibrosis Patients: Update of MANIFEST Phase 2 Study (Presentation Code: EP1084)

TITLE: CPI-0610, A Bromodomain and Extraterminal Domain Protein (BET) Inhibitor, as Monotherapy in Advanced Myelofibrosis Patients Refractory / Intolerant to JAK Inhibitor: Update from Phase 2 MANIFEST Study (Presentation Code: EP1091)

TITLE: CPI-0610, Bromodomain and Extraterminal Domain Protein (BET) Inhibitor, as "Add-on" to Ruxolitinib (Rux), in Advanced Myelofibrosis Patients with Suboptimal Response: Update of MANIFEST Phase 2 Study (Presentation Code: EP1083)

Session: Myeloproliferative Neoplasms—Clinical

Date and Time: June 12, 2020, 8:30 AM CEST/2:30 AM EDT

Investor Event

Constellation will host a virtual analyst/investor event and conference call on June 12 at 8:00 AM EDT to discuss the data from these three posters relating to the MANIFEST clinical trial for CPI-0610 being presented at the European Hematology Association (EHA) (Free EHA Whitepaper) meeting. The agenda of the event will include:

An overview of myelofibrosis (MF) and the potential impact of Constellation’s BET inhibitor CPI-0610 in treating MF
A review of the data from the MANIFEST clinical trial presented in the EHA (Free EHA Whitepaper) posters
A live question-and-answer session
The event will be webcast live and can be accessed on the Investor Relations section of Constellation’s website at View Source To participate in the live question-and-answer session, please dial (877) 473-2077 (domestic) or (661) 378-9662 (international) and refer to conference ID 6275774.

EZH2 Program Prioritization

Constellation reported that it plans to prioritize further clinical development of its next-generation EZH2 inhibitor CPI-0209. The decision is based on a recent data cut and review of ProSTAR, the ongoing Phase 1b/2 clinical study evaluating CPI-1205, a small-molecule inhibitor of EZH2, combined with enzalutamide or abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC). The data did not demonstrate the definitive signal of activity necessary to advance the program into pivotal studies in mCRPC. A full data set from ProSTAR will be presented at a future medical meeting.

"We thank the patients and investigators who participated in ProSTAR," said Jigar Raythatha. "While we are disappointed with the outcome of this study, we remain committed to EZH2 as an important cancer target and will apply the learnings from ProSTAR to our second-generation EZH2 inhibitor, CPI-0209. We believe the deeper and more durable target engagement as well as the improved metabolic properties that CPI-0209 demonstrated in preclinical studies give it the potential to be a best-in-class EZH2 inhibitor for use in a broad range of cancer types. CPI-0209 is progressing through the dose escalation portion of a phase 1/2 clinical trial, and we expect to determine a recommended Phase 2 dose later in the year."

About MANIFEST

MANIFEST is an open-label Phase 2 clinical trial of CPI-0610 in patients with myelofibrosis (MF), a rare cancer of the bone marrow that disrupts the body’s normal production of blood cells. Constellation is evaluating CPI-0610 in combination with ruxolitinib in JAK-inhibitor-naïve MF patients (Arm 3), with a primary endpoint of the proportion of patients with a ≥35% spleen volume reduction from baseline (SVR35) after 24 weeks of treatment. Constellation is also evaluating CPI-0610, either as a monotherapy in patients who are resistant to, intolerant of, or ineligible for ruxolitinib and no longer on the drug (Arm 1), or as add-on therapy in combination with ruxolitinib in patients with a sub-optimal response to ruxolitinib or MF progression (Arm 2). Patients in Arms 1 and 2 are being stratified based on TD status. The primary endpoint for the patients in cohorts 1A and 2A, who were TD at baseline, is conversion to TI for 12 consecutive weeks. The primary endpoint for the patients in cohorts 1B and 2B, who were not TD at baseline, is the proportion of patients with a ≥35% spleen volume reduction from baseline after 24 weeks of treatment.

About ProSTAR

ProSTAR is an open-label Phase 1b/2 clinical trial of CPI-1205, a potent and highly selective small-molecule EZH2 inhibitor, in patients with metastatic castration-resistant prostate cancer (mCRPC) in the second-line setting. The ProSTAR study is evaluating CPI-1205 in combination with either enzalutamide or abiraterone/prednisone ("abiraterone"), which are androgen receptor signaling (ARS) inhibitors, in mCRPC patients who experienced disease progression while receiving the other ARS inhibitor.