On December 13, 2021 Sutro Biopharma, Inc. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation cancer and autoimmune therapeutics, reported that its research collaborators at the Fred Hutchinson Cancer Research Center presented nonclinical data of STRO-002 and STRO-001 in two oral presentations at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH 2021) in Atlanta, Georgia (Press release, Sutro Biopharma, DEC 13, 2021, View Source [SID1234596951]). The research was conducted by investigators from the laboratory of Soheil Meshinchi, M.D., Ph.D., Professor, Clinical Research Division at Fred Hutchinson Cancer Research Center and Professor, Division of Pediatric Hematology-Oncology at the University of Washington School of Medicine.

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Dr. Meshinchi commented, "Using a computational approach, we have identified FOLR1, or FolRα, as an actionable target for high-risk pediatric AML; and CD74 as an actionable target in adult and pediatric AML and ALL. We further demonstrated that STR0-002 effectively targets a high-risk AML subtype and STRO-001 effectively targets AML and ALL cells that express CD74, providing promising nonclinical data for possible treatment options."

Nonclinical data was presented by Quy Le, Ph.D., Staff Scientist, Meshinchi Lab, Fred Hutchinson Cancer Research Center on Sutro’s folate receptor alpha (FOLR1 or FolRα) -targeting antibody-drug conjugate (ADC), STRO-002, as a potential therapeutic in a rare pediatric acute myeloid leukemia (AML) subtype expressing FolRα. RNA-sequencing data demonstrated that FOLR1 is uniquely expressed in CBFA2T3-GLIS2 fusion (CBF/GLIS) AML and absent in other AML subtypes and normal hematopoietic cell populations. Data from an AML cell line engineered to express FOLR1 and CBF/GLIS-transduced cord blood hematopoietic stem/progenitor cells (CB HSPCs) demonstrated high cytotoxicity of STRO-002. In FOLR1 positive and CBF/GLIS-transduced CB HSPCs xenograft models, STRO-002 demonstrated potent activity that led to complete leukemia clearance.

Nonclinical data was also presented by Quy Le, Ph.D., Staff Scientist, Meshinchi Lab, Fred Hutchinson Cancer Research Center on Sutro’s CD74-targeting ADC, STRO-001, as a potential therapeutic in AML and acute lymphoblastic leukemia (ALL). Data from AML and ALL cell lines, as well as from nonclinical xenograft models, demonstrated robust in vitro and in vivo cytotoxicity of STRO-001 on cells expressing high- to -moderate levels of CD74, with no cytotoxicity observed in cells without CD74 expression. Potent anti-leukemia activity was also demonstrated in three primary AML patient samples with varied CD74 expression levels.

Dr. Arturo Molina, Sutro’s Chief Medical Officer added, "These nonclinical data presented by collaborators at Fred Hutchinson Cancer Research Center demonstrates the potential of targeted ADCs as therapeutics for AML and ALL. These data provide additional validation for an FolRα- and CD74-antigen directed approach, as our clinical studies for STRO-002 in ovarian and endometrial cancers and STRO-001 in B cell malignancies, respectively, continue to enroll patients."

On December 13, 2021 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a precision oncology company targeting virus-associated malignancies, reported that final data from its Phase 1b/2 trial of Nana-val in relapsed/refractory (R/R) EBV+ lymphoma (VT3996-201) were presented in an oral presentation at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting by Bradley Haverkos, M.D., Associate Professor at the University of Colorado School of Medicine (Press release, Viracta Therapeutics, DEC 13, 2021, View Source [SID1234596948]). Nana-val was well tolerated and continues to demonstrate promising activity with complete responses observed across multiple EBV+ lymphoma subtypes and a median duration of response of 10.4 months.

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Key data and conclusions from the ASH (Free ASH Whitepaper) presentation:

As of the October 28, 2021, data cutoff, 55 patients were enrolled. Patients had a median age of 60 (range 19-84) and had a median of two prior therapies. 75% (41/55) were refractory to their last therapy, and 96% (53/55) had exhausted all standard therapies (per Investigator).

Nana-val was generally well tolerated with reversible low-grade toxicities. The most commonly observed treatment emergent adverse events were reversible cytopenias, low grade creatinine elevations, and gastrointestinal symptoms.

Efficacy in evaluable patient (n=43):

Across all lymphoma subtypes: ORR = 40% (17/43); CR = 19% (8/43); Clinical Benefit Rate (CBR) [(CR+ partial response (PR) + stable disease (SD) ≥6 months] = 56% (24/43)
T/NK-NHL: ORR = 60% (9/15); CR = 27% (4/15); CBR = 67% (10/15)
Extranodal NK/T-Cell Lymphoma (ENKTL): ORR = 63% (5/8); CR = 13% (1/8); CBR = 63% (5/8)
Peripheral T-cell lymphoma (PTCL)/ Angioimmunoblastic T-cell lymphoma (AITL): ORR = 67% (4/6); CR = 50% (3/6); CBR = 83% (5/6)
DLBCL: ORR = 67% (4/6); CR = 33% (2/6); CBR = 83% (5/6)
Both DLBCL complete responses were in patients refractory to first line R-CHOP
IA-LPD: ORR = 50% (3/6); CR = 33% (2/6); CBR = 50% (3/6)
Durable responses:

Median DoR was 10.4 months
Three patients achieved responses with durations >2 years
"EBV is easily detectable and can be associated with a number of lymphoma subtypes, having a negative impact on clinical outcomes such as survival," said Dr. Haverkos, lead investigator of the VT3996-201 study. "The clinical safety and efficacy profile demonstrated thus far in this refractory patient population is very encouraging and underscores the utility of this unique EBV-targeted approach."

"Clinicians and key opinion leaders have shown a high level of enthusiasm for our potentially registration-enabling NAVAL-1 study, which we believe underscores the strength of the clinical dataset supporting the trial and the urgency of the unmet need in EBV-associated cancers. We expect this enthusiasm to be further bolstered following this oral presentation at ASH (Free ASH Whitepaper), which has provided us with the opportunity to broadly discuss the final Phase 1b/2 results with the clinical community," said Ivor Royston, M.D., President and Chief Executive Officer of Viracta. "We are encouraged by the final Phase 1b/2 data, as the response rates and median durations observed in the B- and T-cell lymphoma subtypes compare favorably to those seen in other single arm R/R lymphoma studies that have led to accelerated approvals and demonstrate Nana-val’s potential to provide meaningful clinical benefit to patients who currently lack effective treatment options. We look forward to the continued evaluation of this promising combination therapy in NAVAL-1 and anticipate providing further clinical program updates in 2022."

A copy of the ASH (Free ASH Whitepaper) presentation will be available by visiting the Events and Webcasts page of the Viracta website following the conference’s conclusion.

About Nana-Val (Nanatinostat and Valganciclovir)

Nanatinostat (VRx-3996) is an orally available histone deacetylase (HDAC) inhibitor being developed by Viracta. Nanatinostat is selective for specific isoforms of Class I HDACs, which is key to inducing viral genes that are epigenetically silenced in EBV-associated malignancies. Nanatinostat is currently being investigated in combination with the antiviral agent valganciclovir as an all-oral combination therapy, Nana-Val, in various subtypes of EBV-associated malignancies. Ongoing trials include a registration-enabling global, multicenter, open-label Phase 2 basket trial in multiple subtypes of relapsed/refractory EBV+ lymphoma (NAVAL-1) as well as a multinational Phase 1b/2 trial in patients with EBV+ recurrent or metastatic nasopharyngeal carcinoma and other EBV+ solid tumors.

About EBV-Associated Cancers

Approximately 95% of the world’s adult population is infected with Epstein-Barr virus (EBV). Infections are commonly asymptomatic or associated with mononucleosis. Following infection, the virus remains latent in a small subset of lymphatic cells for the duration of the patient’s life. Cells containing latent virus are increasingly susceptible to malignant transformation. Patients who are immunocompromised are at an increased risk of developing EBV+ lymphomas. EBV is estimated to be associated with approximately 2% of the global cancer burden and is also associated with a variety of solid tumors, including nasopharyngeal carcinoma and gastric cancer.

On December 13, 2021 TG Therapeutics, Inc. (NASDAQ: TGTX), reported four data presentations, including three oral presentations and one poster presentation, evaluating the combination of ublituximab, the Company’s investigational anti-CD20 monoclonal antibody and UKONIQ (umbralisib), the Company’s inhibitor of PI3K-delta and CKI-epsilon, (U2), as well as U2-based triple combination therapies, including U2 plus TG’s investigational BTK inhibitor TG-1701 (Press release, TG Therapeutics, DEC 13, 2021, View Source [SID1234596946]). Data presentations occurred this past weekend during the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting and exposition. Presentation highlights are included below.

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Michael S. Weiss, Chairman and Chief Executive Officer of TG Therapeutics stated, "We are excited to have showcased four presentations this past weekend, including three oral presentations, during the live ASH (Free ASH Whitepaper) annual meeting. It was also gratifying to learn that two of our oral presentations, U2 in relapsed or refractory MZL and U2 as an add-on to Ibrutinib to create a time-limited therapy, were chosen for highlights of ASH (Free ASH Whitepaper). We believe these presentations further demonstrate the potential for U2 to enhance patient care and complement current standard of care for patients with B-cell malignancies."

PRESENTATION HIGHLIGHTS

Oral Presentation Title: The Combination of Umbralisib Plus Ublituximab Is Active in Patients with Relapsed or Refractory Marginal Zone Lymphoma (MZL): Results from the Phase 2 Global Unity-NHL Trial

A total of 72 relapsed/refractory (R/R) marginal zone lymphoma (MZL) patients were enrolled in the ublituximab plus umbralisib (U2) cohort of the UNITY-NHL.
Patients had a median of 2 prior lines of therapy (range 1 – 9), with 25% refractory to their immediate prior therapy
Overall Response Rate (ORR) by independent review committee (IRC) was 70%, with 21% complete response (CR) rate (n=71),
Median duration of response (DOR) was not reached at a median follow up of 20 months.
Grade 3/4 AEs of clinical interest included diarrhea (13%), neutropenia (18%), ALT/AST increased (15%) and non-infectious colitis (2.8%).
Oral Presentation Title: Efficacy and Safety of Umbralisib, Ublituximab (U2), and U2 Plus Bendamustine in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

A total of 226 patients were treated within the DLBCL cohort of the UNITY-NHL trial. 30 patients received umbralisib monotherapy, 66 patients received ublituximab plus umbralisib or U2, and 130 patients received U2 plus bendamustine.
IRC assessed response rates:
43% ORR and 17% CR for U2 plus bendamustine triple combination (n=130)
32% ORR and 11% CR for U2 double combination (n=66)
13% ORR and 3% CR for umbralisib monotherapy (n=30)
IRC assessed median duration of response (DOR) was 3 months for umbralisib monotherapy, 28 months for U2 combination, and 8 months for U2 plus bendamustine
Both U2 and U2 + bendamustine demonstrated a manageable safety profile. Grade 3/4 AEs of special interest occurring in the U2 group (n=66) included ALT/AST increased (12%), non-infectious colitis (2%), diarrhea (2%), neutropenia (11%) and pneumonitis (2%). Grade 3/4 AEs of special interest occurring in the U2 plus bendamustine group (n=130) included ALT/AST increased (5%), non-infectious colitis (2%), diarrhea (7%), neutropenia (27%), pneumonitis (1%) and rash (2%).
Oral Presentation Title: A Phase 2 Study Evaluating the Addition of Ublituximab and Umbralisib (U2) to Ibrutinib in Patients with Chronic Lymphocytic Leukemia (CLL): A Minimal Residual Disease (MRD)-Driven, Time-Limited Approach-Limited Approach

This study utilized an "add-on" approach, where the combination of umbralisib and ublituximab (U2) was added to therapy in patients who were on ibrutinib for greater than 6 months and had detectable minimum residual disease (MRD)
Patients who achieve undetectable MRD (uMRD) or those who completed 24 cycles of therapy with detectable MRD stop all therapy and enter a period of treatment-free observation (TFO). Patients with clinical progression during TFO are eligible for re-treatment with the U2 + ibrutinib combination.
28 patients with chronic lymphocytic leukemia (CLL) were enrolled, with 27 evaluable for efficacy. Patients were on ibrutinib for a median of 21 months (range 7-67) prior to study entry.
77% of evaluable patients achieved uMRD, with a median time to first uMRD of 7.4 months
Grade 3/4 AEs included diarrhea (4%), hypertension (7%), ALT/AST increased (4%) and COVID-19 (4%).
Poster Presentation Title: The Selective Bruton Tyrosine Kinase (BTK) Inhibitor TG-1701 As Monotherapy and in Combination with Ublituximab and Umbralisib (U2) in Patients with B-Cell Malignancies

A total of 135 patients with R/R CLL or B-cell lymphoma were included in this presentation, with patients receiving 200 mg of TG-1701 in a dose-expansion cohort (n=61), 300 mg of TG-1701 in a CLL dose-expansion cohort (n=20), TG-1701 in combination with U2 in a dose escalation cohort (TG-1701 doses ranging from 100 – 300 mg once daily and umbralisib at either 600 mg or 800mg) (n=21), and a triple combination expansion cohort of 100mg of TG-1701 plus U2 (400 mg of umbralisib) (n=33).
Efficacy Overall Response Rate (ORR) and Complete Response (CR) Outcomes:
100% ORR observed in the CLL 300 mg QD TG-1701 monotherapy expansion cohort at a median follow up of 13.8 months (n=19)
95% ORR observed in the CLL 200 mg QD TG-1701 monotherapy expansion cohort at a median follow up of 20 months (n=20)
86% ORR, including 19% CR rate, observed in the 1701+U2 dose escalation cohort (using doses of 100 mg to 300 mg QD of TG-1701) at a median follow up of 20.2 months (n=21)
83% ORR, including 6% CR rate, observed in the 1701+U2 dose expansion cohort (using 100 mg QD of TG-1701 and 400 mg QD of umbralisib) at a median follow up of 2.7 months (n=18)
Grade 3/4 AEs occurring in patients treated with 200 mg QD of TG-1701 (n=61) and 300 mg QD of TG-1701 (n=20), respectively, included neutropenia (8%, 20%), ALT increased (3%, 5%), AST increased (2%, 5%) and anemia (5%, 0%). Grade 3/4 AEs occurring in patients treated with the triple combination in the U2 plus TG-1701 expansion cohort (100 mg QD TG-1701 plus 400 mg QD of umbralisib; n=19) and U2 plus TG-1701 escalation cohort (100 mg to 300 mg QD; n=21), respectively, included neutropenia (16%, 19%), ALT increased (5%, 19%), AST increased (5%, 14%).
At the time of data cut-off, no patients had discontinued treatment due to a treatment-related adverse event across all cohorts.
The above referenced presentations are now available on the Publications page of the Company’s corporate website at View Source

On December 13, 2021 Targovax ASA reported that its CEO, Erik Digman Wiklund, is invited to present at DNB’s Nordic Healthcare Conference (Press release, Targovax, DEC 13, 2021, View Source [SID1234596944]).

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DNB’s 12th Nordic Healthcare Conference:
Date: 16 December 2021
Presenter: Erik Digman Wiklund (CEO)
Time: 09:50 CET

On December 13, 2021 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported updated positive data from the Phase 1 dose escalation portion of the AUGMENT-101 trial of SNDX-5613 in patients with mutant nucleophosmin (mNPM1) or mixed lineage leukemia rearranged (MLLr) relapsed/refractory (R/R) acute leukemias (Press release, Syndax, DEC 13, 2021, View Source [SID1234596942]). SNDX-5613 is the Company’s highly selective oral menin inhibitor . The data are being featured during an oral session at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on Monday, December 13, 2021 at 3:15 p.m. ET.

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"Patients with relapsed or refractory leukemia harboring NPM1 mutations or MLL-rearrangements face a particularly poor prognosis," said Eytan M. Stein, M.D., Assistant Attending Physician and Director, Program for Drug Development in Leukemia, Department of Medicine at Memorial Sloan Kettering Cancer Center, and the trial’s principal investigator. "Data being reported today show highly encouraging clinical activity and favorable tolerability across a heavily pretreated population. In addition to very high MRD negative rates in those patients achieving complete response (CR) or CR with partial hematologic recovery (CRh), we are also seeing response durations greater than six months."

"The updated data presented today at ASH (Free ASH Whitepaper) from our ongoing AUGMENT-101 trial strongly support the potential of SNDX-5613 to serve as a best-in-class treatment option for patients with NPM1 or MLLr leukemia, which together represents approximately 40% of all acute leukemias," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "We are also very pleased that discussions with the U.S. Food and Drug Administration (FDA) have confirmed that the ongoing Phase 2 AUGMENT-101 trial may potentially serve as the basis for regulatory filings in each of its three indication-specific cohorts of NPM1 mutant acute myeloid leukemia (AML), MLLr AML, and MLLr acute lymphoblastic leukemia (ALL), and that patients will be able to restart treatment with SNDX-5613 following a stem cell transplant."

Dr. Morrison continued, "We also remain focused on executing on our strategy to expand into earlier lines of therapy and pediatric populations, and we look forward to initiating the BEAT AML trial in frontline MLLr and mNPM1 AML in combination with venetoclax and azacitidine, the INTERCEPT trial in AML patients with MRD positive disease, and the AUGMENT-102 trial in combination with chemotherapy in adult and pediatric relapsed/refractory MLLr and mNPM1 acute leukemia patients."

As of an October 18, 2021 data cutoff date, a total of 59 patients with a median of four prior therapies, including 42% who received a prior stem cell transplant and 59% who received prior venetoclax, were dosed in the Phase 1 portion of the trial. Across evaluable patients with mNPM1 (n=13) or MLLr (n=38) acute leukemia who received at least one dose of SNDX-5613, the overall response rate1 (ORR) was 55%, with a CR/CRh rate of 24% and nine patients proceeding to stem cell transplant (two patients achieving a CR with incomplete platelet recovery [CRp] with no evidence of minimal residual disease [MRD], and seven patients who achieved MRD- CR or CRh). The ORR in evaluable patients harboring an NPM1 mutation was 38% (5/13), with a CR/CRh rate of 23% (3/13). The ORR in evaluable patients harboring an MLL-rearrangement was 61% (23/38), with a CR/CRh rate of 24% (9/38).

The overall MRD negative rate was 31% (16/51). Among those patients who achieved CR/CRh, 92% (11/12) were MRD negative, including 100% (3/3) of NPM1 patients and 89% (8/9) of MLLr patients. Median time to response for patients achieving a CR/CRh was two months. Median duration of response (DOR) was not reached, inclusive of patients who received stem cell transplant, and 6/12 patients who achieved CR/CRh had a duration of response greater than six months.

SNDX-5613 was well-tolerated, with no discontinuations due to treatment-related adverse events observed in heavily pretreated patients. The only dose limiting toxicity observed was Grade 3 QT prolongation, which occurred in 7% (3/43) of patients treated at the four doses that met the study’s pre-defined recommended Phase 2 dose criteria. Differentiation syndrome was reported in 14% of patients (8/59) with all cases being Grade 1 or 2 and readily managed with standard therapies.

As data from the Phase 1 portion of the trial have continued to mature, the results have demonstrated consistent and compelling anti-leukemic activity with favorable tolerability in patients with both R/R MLLr and NPM1 acute leukemias. The following table summarizes select efficacy and safety data that has been presented by the Company throughout 2021.

Best Response in Response Evaluable Patients

April ’21

May ’21

Dec ’21

n = 31 (%)

n = 31 (%)

n = 51 (%)

Overall Response Rate* (ORR)

15/31 (48%)

15/31 (48%)

28/51 (55%)

CR/CRh

5 (16%)

7 (23%)

12 (24%)

CRp

5 (16%)

4 (13%)

7 (14%)

CRi/MLFS

5 (16%)

4 (13%)

9 (18%)

Received HSCT

4

4

9

MLLr ORR

13/24 (54%)

13/24 (54%)

23/38 (61%)

mNPM1 ORR

2/7 (29%)

2/7 (29%)

5/13 (38%)

≥Gr3 QTc prolonged (all doses)

14%

14%

12%

≥Gr3 QTc prolonged (RP2D doses)

9%

9%

7%

* Overall Response Rate = CR + CRh + CRp + CRi + MLFS

The Phase 2 portion of AUGMENT-101, which will assess 163 mg every 12 hours of SNDX-5613 in patients receiving concomitant strong CYP3A4 inhibitor treatment, is currently underway. A total of 64 adult and up to ten pediatric patients will be enrolled across each of the following three distinct trial populations: patients with NPM1 mutant AML, patients with MLLr AML, and patients with MLLr ALL. Discussions with the FDA have confirmed that AUGMENT-101 may potentially serve as the basis for regulatory filings in each of the three distinct trials. The primary endpoint for each of the three trials will be efficacy as measured by complete remission rate (CR + CRh), with key secondary endpoints including DOR and overall survival.

A copy of today’s presentation will be available in the Publications and Meeting Presentations section of Syndax’s website.

About SNDX-5613

SNDX-5613 is a potent, selective, small molecule inhibitor of the menin-MLL binding interaction that is being developed for the treatment of mixed lineage leukemia rearranged (MLLr) acute leukemias including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), and NPM1 mutant AML. In preclinical models of MLLr acute leukemias, SNDX-5613 demonstrated robust, dose-dependent inhibition of tumor growth, resulting in a marked survival benefit. Menin-MLL interaction inhibitors have also demonstrated robust treatment benefit in multiple preclinical models of NPM1 mutant AML, which represents the most frequent genetic abnormality in adult AML. SNDX-5613 is currently being evaluated in the Company’s AUGMENT-101 Phase 1/2 open-label clinical trial for the treatment of relapsed/refractory (R/R) acute leukemias. SNDX-5613 was granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of patients with AML, and Fast Track designation for the treatment of adult and pediatric patients with relapsed or refractory acute leukemias harboring a mixed lineage leukemia rearranged MLLr or NPM1 mutation.

About Mixed Lineage Leukemia Rearranged Acute Leukemias

Rearrangements of the MLL gene give rise to mixed lineage leukemia rearranged (MLLr) acute leukemias known to have a poor prognosis, with less than 25% of adult patients surviving past five years. MLL rearrangements produce fusion proteins that require interaction with the protein called menin to drive leukemic cancer growth. Disruption of the menin-MLLr interaction has been shown to halt the growth of MLLr leukemic cells. MLLr leukemias, which are routinely diagnosed through currently available cytogenetic or molecular diagnostic techniques, occur in approximately 80% of infant acute leukemias and up to 10% of all acute leukemias. There are currently no approved therapies indicated for MLLr leukemias.

About NPM1 Mutant Acute Myeloid Leukemia

NPM1 mutant acute myeloid leukemia (AML), which is distinguished by point mutations in the NPM1 gene that drive the leukemic phenotype, is the most common type of cytogenetically normal adult AML and represents approximately 30% of all adult AML cases. This subtype of AML has a five-year overall survival rate of approximately 50%. Similar to mixed lineage leukemia rearranged (MLLr) leukemias, NPM1 mutant AML is highly dependent on the expression of specific developmental genes shown to be negatively impacted by inhibitors of the menin-MLL interaction. NPM1 mutant AML is routinely diagnosed through currently available screening techniques. There are currently no approved therapies indicated for NPM1 mutant AML.