On December 12, 2021 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that updated initial safety and efficacy findings from the Phase 1b/2 study of IMGN632 in combination with Vidaza (azacitidine) and Venclexta (venetoclax) in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) were presented in an oral session at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, ImmunoGen, DEC 12, 2021, View Source [SID1234596824]). Data for IMGN632 in frontline patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) were also presented in a poster session at the conference.

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"The unmet need in AML remains large, as patients typically have low survival rates despite initial response," said Naval Daver, MD, Associate Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. "Together, the observed anti-leukemia activity and tolerability of IMGN632 in the relapsed/refractory setting are compelling and support the continued evaluation of this triplet in AML patients. I look forward to the next steps for IMGN632 in combination with azacitidine and venetoclax, with preparations for Phase 2 expansion cohorts already underway in both the relapsed and frontline AML settings."

IMGN632 TRIPLET DATA IN AML

Title (Abstract #372): "Safety and Efficacy from a Phase 1b/2 Study of IMGN632 in Combination with Azacitidine and Venetoclax for Patients with CD123-Positive Acute Myeloid Leukemia"
Oral Session: 616
Session Date: Sunday, December 12, 2021
Session Time: 9:30 am – 11:00 am

Updated key findings from the Phase 1b/2 study of IMGN632 in combination with azacitidine and venetoclax include:

Safety

IMGN632 was administered to 51 patients at 15 mcg/kg or 45 mcg/kg, azacitidine at 50-75 mg/m2 for 7 days, and venetoclax at 400 mg daily for 8-21 days per 28-day cycle.
IMGN632 continued to display a manageable safety profile in R/R AML patients.
The most common treatment emergent adverse events all grades [grade 3+ events] seen in >20% of patients were infusion-related reactions (33% [2%]), febrile neutropenia (31% [26%]), dyspnea (28% [8%]), fatigue (28% [0%]), hypophosphatemia (26% [2%]), diarrhea (22% [0%]), hypokalemia (22% [2%]), nausea (22% [0%]), vomiting (22% [0%]), and pneumonia (20% [16%]).
No tumor lysis syndrome, veno-occlusive disease, capillary leak, or cytokine release were reported.
Efficacy

Responses were seen across all cohorts/doses and schedules (efficacy evaluable population, n=46). The objective response rate (ORR) was 48%, with a composite complete remission (CCR) rate of 30% (4 CR, 8 CRh, 1 CRp, 1 CRi).
Higher intensity cohorts (n=29) were associated with higher response rates including an ORR of 59% and a CCR rate of 38% (4 CR, 6 CRh, 1 CRp).
Significant activity was also observed in the FLT3 mutant subset (n=9), with ORR and CCR rates of 89% and 78%, respectively.
Enrollment continues at the putative recommended Phase 2 dose (IMGN632 45 mcg/kg IV on day 7, azacitidine 50 or 75 mg/m2 on days 1-7, and venetoclax 400 mg on days 1-14).
"These data reinforce the potential of IMGN632 as a new therapy for patients with relapsed/refractory AML. We are very encouraged by the manageable safety profile and 38% composite complete remission rate seen in the higher intensity cohorts," said Anna Berkenblit, MD, Senior Vice President and Chief Medical Officer of ImmunoGen. "We look forward to further exploring the safety and efficacy of this triplet in Phase 2 expansion cohorts planned for next year. We believe IMGN632 also has the potential to become a best-in-class monotherapy treatment option for patients with BPDCN. Based on the results seen in three frontline patients, we continue to enroll patients in our pivotal study, CADENZA, and look forward to sharing top-line data in the second half of 2022."

IMGN632 MONOTHERAPY IN FRONTLINE BPDCN

Poster Presentation, Abstract #1284

IMGN632, administered as a brief outpatient infusion, was evaluated as monotherapy in frontline BPDCN patients. Three patients received IMGN632 prior to commencement of the enrolling pivotal cohort and achieved a clinical complete remission (CRc). IMGN632 in these three frontline BPDCN patients was associated with a favorable safety profile and limited grade 3+ TEAEs. Enrollment continues in the pivotal frontline and R/R cohorts.

Additional information can be found at www.hematology.org, including abstracts.

ABOUT IMGN632

IMGN632 is a CD123-targeting ADC in clinical development for hematological malignancies, including blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML), and other CD123+ hematologic malignancies. IMGN632 is currently being evaluated in multiple cohorts, including monotherapy for patients with BPDCN and minimal residual disease positive (MRD+) AML and in combinations with Vidaza (azacitidine) and Venclexta (venetoclax) for patients with relapsed/refractory AML. IMGN632 uses one of ImmunoGen’s novel indolinobenzodiazepine (IGN) payloads, which alkylate DNA and cause single strand breaks without crosslinking. IGNs are designed to have high potency against tumor cells, while demonstrating less toxicity to normal marrow progenitors than other DNA-targeting payloads. The FDA granted IMGN632 Breakthrough Therapy Designation in relapsed/refractory BPDCN.

ABOUT ACUTE MYELOID LEUKEMIA (AML)

AML is a cancer of the bone marrow cells that produce white blood cells. It causes the marrow to increasingly generate abnormal, immature white blood cells (blasts) that do not mature into effective infection-fighting cells. The blasts quickly fill the bone marrow, impacting the production of normal platelets and red blood cells. The resulting deficiencies in normal blood cells leave the patient vulnerable to infections, bleeding problems, and anemia. It is estimated that, in the U.S. alone, more than 20,000 people will be diagnosed with AML this year and more than 11,000 will die from the disease.

ABOUT BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM (BPDCN)

BPDCN is a rare form of blood cancer that has features of both leukemia and lymphoma, with characteristic skin lesions, lymph node involvement, and frequent spread to the bone marrow. This aggressive cancer requires intense treatment often followed by stem cell transplant. Despite the approval of a CD123-targeting therapy, the unmet need remains high for patients, both in the frontline and in the relapsed/refractory setting.

ABOUT CD123

CD123, the interleukin-3 alpha chain, is expressed on multiple myeloid and lymphoid cancers including AML, BPDCN, ALL, chronic myeloid leukemia, and myeloproliferative neoplasms. With limited expression on normal hematopoietic cells, rapid internalization, and expression on AML leukemia stem cells, CD123 is a validated therapeutic target, with the approval of a CD123-targeting therapy for BPDCN.

On December 12, 2021 Sana Biotechnology, Inc. (NASDAQ: SANA), a company focused on creating and delivering engineered cells as medicines, reported that data at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place from Saturday, December 11 to Tuesday, December 14, 2021, which highlighted further progress with key technologies supporting Sana’s in vivo and ex vivo CAR T cell programs (Press release, Sana Biotechnology, DEC 12, 2021, View Source [SID1234596821]).

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"The data presented at ASH (Free ASH Whitepaper) showcase the progress we are making with Sana’s CAR T cell programs," said Terry Fry, M.D., Sana’s Head of T Cell Therapeutics. "The hypoimmune and fusogen technologies are designed to address significant challenges that lead to sub-optimal patient outcomes and prevent widespread utilization of cell and gene therapies, including cell persistence and cell-specific delivery. We continue to move these potential therapies toward clinical trials in patients, with a goal of filing two INDs as early as next year."

On Saturday, December 11, Sonja Schrepfer, M.D., Ph.D., Sana’s Head of Hypoimmune Platform, presented a poster (Abstract 1690) titled "Engineered hypoimmune allogeneic CAR T cells exhibit innate and adaptive immune evasion even after sensitization in humanized mice and retain potent anti-tumor activity." Data demonstrated continued progress with Sana’s hypoimmune allogeneic CAR T cell platform, showing in murine models that these gene-modified CAR T cells targeting CD19 can evade both the innate and adaptive immune systems without any evidence of a change in their ability to eliminate leukemia. This immune evasion was present in naïve subjects as well as in sensitized subjects that had previously rejected non-hypoimmune CAR T cells. In the study, the hypoimmune allogeneic CD19 CAR T cells did not induce activation of the adaptive immune system, T cells or B cells, in the treated subjects (p<0.0001 when compared to non-modified CD19 CAR T cells), and also evaded the subjects’ innate immune responses. These findings are an important step toward the possibility of "off-the-shelf" allogeneic CD19 CAR T cells that persist without immunosuppression, including in patients that have previously been treated with a CAR T therapy.

On Sunday, December 12, Terry Fry, M.D., presented a poster (Abstract 2769) titled "In vivo delivery of a CD20 CAR using a CD8-targeted fusosome in Southern pig-tail macaques (M. nemestrina) results in B cell depletion." The presentation outlined the potential to deliver a CAR gene to make CAR T cells in vivo. B cell depletion in these healthy non-human primates is used as a surrogate marker for an anti-tumor effect against B cell malignancies such as leukemia and lymphoma. Following the infusion of the CD8a-targeted fusosome carrying the gene for an anti-CD20 CAR into macaques, B cells were meaningfully reduced in 4 of 6 animals after 7 to 10 days. Scientists found the anti-CD20 CAR transcripts via measurements of mRNA expression in spleen cells isolated from treated animals; conversely, no expression was detected in tissues from control animals. Subjects in this study received no lymphodepleting chemotherapy. Additionally, the fusosome treatment was well-tolerated in all animals with no evidence of adverse effects. These findings suggest that the fusosome technology represents a novel therapeutic opportunity to treat patients with B cell malignancies, with the potential for in vivo delivery of the CAR gene to CD8 T cells.

On Sunday, December 12, Sana Scientist Christie Ciarlo, Ph.D., presented a poster (Abstract 2942) titled "CD4-targeted fusosomes are capable of transducing resting T helper cells to generate highly potent CAR T cells." The presentation highlighted the ability of select fusosomes to effectively target the correct cells and to deliver an integrating CAR payload that can develop CAR T cells in vivo. CD4-targeted CD19 CAR fusosomes efficiently transduced activated T cells (34% ± 1.5% CD4+CAR+; 0.54 ± 0.18 c/dg) and resting T cells (20% ± 0.5% CD4+CAR+; 0.28 ± 0.14 c/dg). The data showed that these fusosomes were specific to certain T cells based on their functionality and also that they could deliver their payloads to helper T cells without activation, opening up new potential pathways for in vivo cell therapies. Investigators concluded that targeting the CD4 co-receptor through in vivo delivery of a genetic payload can produce potent and functional CAR T cells, with the potential to target certain cancers.

On December 12, 2021 MorphoSys AG (FSE: MOR; NASDAQ: MOR) reported the latest data from the ongoing MANIFEST study, an open-label, Phase 2 clinical trial of pelabresib, an investigational BET inhibitor, in patients with myelofibrosis, a rare bone marrow cancer for which only limited treatment options are available (Press release, MorphoSys, DEC 12, 2021, View Source [SID1234596820]). These latest results, which included more patients and longer-term follow-up than previously reported data, suggest the potential of pelabresib in the treatment of myelofibrosis. These findings were presented during poster and oral sessions at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH 2021), held December 11 – 14, 2021 in Atlanta, Georgia and virtually.

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"These data reconfirm previously published results and reinforce the role pelabresib may play, if approved, in overcoming some of the challenges we face in treating myelofibrosis," said Malte Peters, M.D., MorphoSys Chief Research and Development Officer. "We are further exploring the effectiveness and safety of pelabresib as a first-line treatment for myelofibrosis in MANIFEST-2, an ongoing Phase 3 study. The latest results reaffirm our confidence in the MANIFEST-2 study, and we look forward to sharing findings from this trial once they become available."

At ASH (Free ASH Whitepaper) 2021, the latest data evaluating pelabresib as a first-line combination with ruxolitinib – the current standard of care – for patients with myelofibrosis who had not previously been treated with a JAK inhibitor (JAK inhibitor-naïve) were presented. As of September 10, 2021, the data cut-off, a total of 84 JAK inhibitor-naïve patients have been enrolled and received the combination. The data showed 68 percent (n=57) of patients treated with the combination achieved a >=35 percent reduction in spleen volume (SVR35) from baseline at week 24 and 60 percent (n=47) maintained SVR35 at week 48. Most patients also saw their symptoms reduced, with 56 percent (n=46) achieving >=50 percent reduction in total symptom score (TSS50) from baseline at week 24. At the time of the data cut-off, 53 patients (63 percent of the 84 patients) were still on treatment. No new safety signals were identified in the study. The most common hematologic adverse events were thrombocytopenia (12 percent, grade 3/4) and anemia (34 percent, grade 3/4). Non-hematological events included dyspnea (5 percent, grade 3) and respiratory tract infections (8 percent, grade 3/4).

Additionally, analyses from an exploratory endpoint presented at ASH (Free ASH Whitepaper) 2021 showed a reduction of megakaryocyte clustering in bone marrow and correlation with spleen volume reduction. Megakaryocytes are the cells in the bone marrow responsible for making platelets, and the clustering of these cells are one of the signs of myelofibrosis. The exploratory data, which require further evaluation, suggest the potential pelabresib may have in changing the course of myelofibrosis treatment, if approved.

"In my opinion, a challenge in treating myelofibrosis is knowing that despite available treatment options the disease will ultimately progress in the majority of patients diagnosed," said Srdan Verstovsek, M.D., Ph.D., professor of medicine and hematologist-oncologist at the MD Anderson Cancer Center and a MANIFEST investigator. "Identifying new, first-line treatment options will improve physicians’ ability to better manage the disease from the time of diagnosis. These latest data, although early in the investigational process, suggest that by combining pelabresib and ruxolitinib, we may have the potential to enhance the current standard of care in the first-line treatment of myelofibrosis."

Additional data from Arm 1 of the MANIFEST study were also presented in an oral presentation at ASH (Free ASH Whitepaper) 2021. In Arm 1, pelabresib is being evaluated as a monotherapy in patients with advanced myelofibrosis who are ineligible to receive, intolerant of, or refractory to JAK inhibitors, a population with very limited therapeutic options. Patients were divided into two cohorts, transfusion-dependent (TD) and non-transfusion-dependent (non-TD). For the TD cohort, the primary endpoint was conversion to transfusion independence (TI) for 12 consecutive weeks. In the non-TD cohort, the primary endpoint was SVR35 at week 24. At week 24, 11 percent (n=7) of patients reached SVR35. In addition, we observed 31 percent of patients had a spleen volume reduction of 25 percent or more (n=20) at week 24. Across all cohorts, 28 percent (n=18) of patients achieved TSS50. No new safety signals were identified in the study. The most common hematologic adverse events were thrombocytopenia (23 percent, grade 3/4) and anemia (15 percent, grade 3). Non-hematological events included diarrhea (6 percent, grade 3) and respiratory tract infections (5 percent, grade 3).

About Pelabresib
Pelabresib (CPI-0610) is an investigational selective small-molecule designed to promote anti-tumor activity by inhibiting the function of bromodomain and extra-terminal domain (BET) proteins to decrease the expression of abnormally expressed genes in cancer. Pelabresib is currently being investigated as a treatment for myelofibrosis and has not yet been evaluated or approved by any regulatory authorities.

About MANIFEST
MANIFEST is an open-label, Phase 2 clinical trial of pelabresib (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 Pharmaceuticals, an affiliate of MorphoSys, is evaluating pelabresib 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 Pharmaceuticals is also evaluating pelabresib 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 suboptimal response to ruxolitinib or MF progression (Arm 2). Patients in Arms 1 and 2 are being stratified based on transfusion-dependent (TD) status. The primary endpoint for the patients in cohorts 1A and 2A, who were TD at baseline, is conversion to transfusion independence for 12 consecutive weeks. The primary endpoint for 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.

On December 12, 2021 ALX Oncology Holdings Inc., ("ALX Oncology") (Nasdaq: ALXO), a clinical-stage immuno-oncology company developing therapies to block the CD47 checkpoint pathway, reported the presentation of initial clinical data from its ongoing trial evaluating evorpacept in combination with azacitidine for the treatment of patients with previously untreated higher-risk ("HR") or relapsed or refractory ("r/r") myelodysplastic syndrome ("MDS"). The new results, shared in a poster at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) ("ASH") Annual Meeting [Abstract #2601], show that the combination of evorpacept and azacitidine is active and well tolerated (Press release, ALX Oncology, DEC 12, 2021, View Source [SID1234596819]). As of October 25, 2021, 22 patients with either previously untreated HR or r/r MDS have been treated with evorpacept in the Phase 1 dose escalation part of the study, administered at 20 mg/kg or 30 mg/kg once every 2 weeks ("Q2W") or 60 mg/kg once every 4 weeks ("Q4W") together with standard dosing of azacitidine. Median follow-up is 3.4 months, and accrual is ongoing.

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Evorpacept in combination with azacitidine was well tolerated (N=22) with no dose limiting toxicities, no observed treatment related serious adverse events, and a maximum administered dose of 60 mg/kg Q4W.
In 6 previously untreated HR MDS response-evaluable patients, 3 patients achieved an objective response ("OR") (2 complete response ("CR"), 1 marrow CR), and 2 patients achieved stable disease ("SD"). Two out of 4 transfusion dependent patients achieved transfusion independence on study.
Among 5 previously untreated HR MDS patients with TP53 mutation and complex cytogenetic abnormalities, 3 achieved an OR (2 CR and 1 marrow CR).
Five of 9 patients with response-evaluable relapsed or refractory MDS that had progressed upon prior hypomethylating agents achieved an OR (5 marrow CRs). In addition, 2 patients achieved SD.
"Evorpacept’s preliminary clinical activity seen in patients with a difficult to treat subset of MDS including disease with TP53 mutation, poor risk cytogenetics, and progression on prior hypomethylating agent regimens, is encouraging," said Guillermo Garcia-Manero M.D., Professor, Department of Leukemia, at MD Anderson Cancer Center, Houston, TX. "Additionally, evorpacept’s favorable initial tolerability profile in combination with azacitidine suggests it may be safely added without worsening cytopenias, which is particularly notable for this patient population."

"The initial tolerability and activity of evorpacept seen in ASPEN-02 further support CD47 as a relevant therapeutic target in patients with MDS," said Sophia Randolph M.D., Ph.D., Chief Medical Officer, ALX Oncology. "Evaluation of evorpacept in our myeloid malignancy program including studies in both MDS and acute myeloid leukemia is built on a strong scientific rationale and we are pleased to now also see initial clinical data supporting its role in enhancing the innate immune anti-cancer response."

Conference Call on December 13th at 8:00 a.m. EST

ALX Oncology will host a conference call on Monday, December 13, 2021 at 8:00 a.m. EST to further discuss the initial MDS data from ASPEN-02. In addition to ALX Oncology’s executive management team, Dr. Guillermo Garcia-Manero, Professor, Department of Leukemia, at MD Anderson Cancer Center, Houston, TX will be featured on the call to discuss the emerging clinical data in MDS patients.

To access the conference call, please dial (844) 467-7655 (U.S./Canada) or (409) 983-9840 (international) at least 10 minutes prior to the start time and refer to conference ID 7598031. Presentation slides will be available to download under "News & Events" (see "Events") in the Investors section of the ALX Oncology website at www.alxoncology.com.

On December 11, 2021 Servier, a growing leader in oncology committed to bringing the promise of tomorrow to the patients we serve, reported Phase 3 data demonstrating that TIBSOVO (ivosidenib tablets) in combination with the chemotherapy azacitidine significantly improved event-free survival (EFS) and overall survival (OS) compared to azacitidine plus placebo in adults with previously untreated IDH1-mutated acute myeloid leukemia (AML) who are not candidates for intensive chemotherapy (Press release, Servier, DEC 11, 2021, View Source [SID1234596887]). These data from the global AGILE study will be presented in an oral session on Monday, December 13, 2021 from 2:45 – 4:15 PM ET, Abstract #697 and featured in the official press program during the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

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Treatment with TIBSOVO in combination with azacitidine demonstrated a statistically significant improvement in EFS (hazard ratio [HR] = 0.33, 95% CI 0.16, 0.69, 1-sided P = 0.0011 1,2). In addition, the combination of TIBSOVO with azacitidine showed a statistically significant improvement in OS (HR = 0.44 [95% CI 0.27, 0.73]; 1-sided P = 0.0005), with a median OS of 24.0 months in the ivosidenib + azacitidine arm vs 7.9 months in the placebo + azacitidine arm.

"These significant findings from the AGILE Phase 3 study for TIBSOVO bolster our growing body of evidence supporting the rationale to target IDH1 mutations early in blood cancers like acute myeloid leukemia," said Susan Pandya, M.D., Vice President Clinical Development & Head of Cancer Metabolism Global Development Oncology & Immuno-Oncology, Servier Pharmaceuticals. "Up to 10 percent of patients with AML have mutations in the IDH1 enzyme, and current treatment options are limited, especially for those who are newly diagnosed and are not eligible for intensive chemotherapy."

Additional Study Results
Investigators reported on results of key secondary endpoints of the AGILE trial including:

Complete remission (CR) rate was 47.2% (n=34/72) for TIBSOVO in combination with azacitidine vs. 14.9% (n=11/74) for placebo plus azacitidine (p < 0.0001).
CR + complete remission with partial hematologic recovery rate (CR + CRh rate) was 52.8% (n=38/72) for TIBSOVO in combination with azacitidine vs. 17.6% (n=13/74) for placebo plus azacitidine (p < 0.0001).
Objective response rate (ORR) was 62.5% (n=45/72) for TIBSOVO in combination with azacitidine vs. 18.9% (n=14/74) for placebo plus azacitidine (p < 0.0001).
"We are excited about the potential to bring a new treatment option to patients with previously untreated IDH1-mutated AML. This further extends the significant clinical benefit for patients with acute myeloid leukemia and IDH1 mutations," said Patrick Therasse, M.D., Ph.D., Vice President, Head of Late Stage and Life Cycle Management in Oncology and Immuno-Oncology Therapeutic Area, Servier Group.

Acute myeloid leukemia is a rapidly progressing type of cancer, and the prognosis is often poor," said Stephane De Botton, M.D. Ph.D., Principle Investigator and Head of Multidisciplinary Hematology Committee at the Institut Gustave Roussy, Villejuif, France. "Our goal with treatment is to prolong overall survival, and the impressive clinical benefit following treatment with TIBSOVO in combination with azacitidine is incredibly promising for these patients with previously untreated IDH1-mutated acute myeloid leukemia."

Common all-grade adverse events (AEs) occurring in more than 20 percent of patients receiving TIBSOVO in combination with azacitidine vs. placebo plus azacitidine were nausea (42.3% vs. 38.4%), vomiting (40.8% vs 26.0%), diarrhea (35.2% vs 35.6%), pyrexia (33.8% vs 39.7%), anemia (31.0% vs 28.8%), febrile neutropenia (28.2% vs 34.2%), thrombocytopenia (28.2% vs 20.5%), neutropenia (28.2% vs 16.4%), constipation (26.8% vs 52.1%) and pneumonia (23.9% vs 31.5%).

The AGILE study has halted further enrollment due to compelling efficacy data for TIBSOVO.

Servier is in discussions with regulatory health authorities regarding submissions to expand the currently approved indications for TIBSOVO.

TIBSOVO[*] is currently approved in the U.S. as monotherapy for the treatment of adults with IDH1-mutant relapsed or refractory acute myeloid leukemia (AML), and for adults with newly diagnosed IDH1-mutant AML who are ≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy. Recently, TIBSOVO was approved as a first and only targeted therapy for patients with previously treated IDH1-mutated cholangiocarcinoma.

About NCT03173248 AGILE Phase 3 AML Trial
The AGILE trial is a global, Phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial designed to evaluate the efficacy and safety of TIBSOVO in combination with azacitidine compared with placebo in combination with azacitidine, in adults with previously untreated IDH1-mutated acute myeloid leukemia (AML) who are not candidates for intensive chemotherapy (≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy). The study’s primary endpoint is EFS, defined as the time from randomization until treatment failure, relapse from remission, or death from any cause, whichever occurs first. Treatment failure is defined as failure to achieve complete remission (CR) by Week 24.

Other key secondary endpoints included complete remission rate (CR rate), defined as the proportion of participants who achieve a CR; overall survival (OS), defined as the time from date of randomization to the date of death due to any cause; CR and complete remission with partial hematologic recovery (CRh) rate, defined as the proportion of participants who achieve a CR or CRh; and objective response rate (ORR), defined as the rate of CR, CR with incomplete hematologic recovery (CRi) (including CR with incomplete platelet recovery [CRp]), partial remission (PR), and morphologic leukemia-free state (MLFS).

About Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow marked by rapid disease progression and is the most common acute leukemia affecting adults with approximately 20,000 new cases in the U.S., and 43,000 cases in Europe each year3,4. The majority of patients with AML eventually relapse. Relapsed or refractory AML has a poor prognosis5. The five-year survival rate is approximately 27%3. For 6 to 10 percent of AML patients, the mutated IDH1 enzyme blocks normal blood stem cell differentiation, contributing to the genesis of acute leukemia6.