On November 2, 2023 Wugen, Inc., a clinical-stage biotechnology company developing allogeneic, off-the-shelf cell therapies for the treatment of hematological and solid tumor malignancies, reported that it will be presenting four abstracts, now available online, at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition Dec. 9-12 (Press release, Wugen, NOV 2, 2023, View Source [SID1234636804]).

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In an oral presentation, Armin Ghobadi, M.D., from Washington University in St. Louis, will share data from study WU-CART-007 1001, "A Phase 1/2 dose-escalation and dose-expansion study of the safety and efficacy of anti-CD7 allogeneic CAR-T cells (WU-CART-007) in patients with relapsed or refractory T-cell Acute Lymphoblastic Leukemia (T ALL)/Lymphoblastic Lymphoma (LBL)."

In a second oral presentation, Sergio Rutella, M.D., Ph.D., from Nottingham University in the U.K. will present pre-clinical findings for WU-NK-101, a cytokine-reprogrammed, expanded, cryopreserved, off-the-shelf, un-engineered memory-like NK cell product derived from peripheral blood mononuclear cells (PBMCs).

The Wugen oral and poster presentation schedule at ASH (Free ASH Whitepaper) is below. The meeting will take place at the Marriott Marquis in San Diego and virtually. Access the full schedule here.

Oral Presentations

Title: Phase 1/2 Dose-Escalation/Dose-Expansion Study of Anti-CD7 Allogeneic CAR-T Cells (WU-CART-007) in Relapsed or Refractory (R/R) T-Cell Acute Lymphoblastic Leukemia/ Lymphoblastic Lymphoma (T-ALL/LBL)

Presenter: Armin Ghobadi, M.D., Washington University, St. Louis, MO

Presentation time/location: Monday, Dec. 11, 10:45 a.m. PT; Room 6CF

Session: #704, Cellular Immunotherapies: Early Phase and Investigational Therapies: Novel Approaches to Enhance Cellular Therapies and Immune Responses in Leukemias and Lymphomas, 10:30 a.m.- 12 p.m. PT

Title: WU-NK-101 (W-NK), a Memory-like (ML) NK Cell, Intrinsically Overcomes Factors Restricting Adoptive Cell Therapy (ACT) in Acute Myeloid Leukemia (AML)

Presenter: Sergio Rutella, M.D., Ph.D., Nottingham Trent University, Nottingham, UK

Presentation time/location: Sunday, Dec. 10; 10:15 a.m. PT; Room 6A

Session: #703, Cellular Immunotherapies: Basic and Translational: Novel Approaches for Next Generation Cellular Immunotherapies, 9:30-11 a.m. PT

Poster Presentations

Title: Adoptively Infused Memory-like Natural Killer Cells Impact Adaptive Immune Responses in Patients with Acute Myeloid Leukemia

Presenter: Sergio Rutella, M.D., Ph.D., Nottingham Trent University, Nottingham, UK

Presentation time/location: Monday, Dec. 11; 6-8 p.m. PT; Halls G-H

Title: WU-NK-101 (W-NK), a Memory-like (ML) NK cell, Naturally Overcomes Tumor Microenvironment (TME) Metabolic Challenges, Retaining Anti-tumor Potency

Presenter: Nupur Bhatnagar, Ph.D., Metafora Biosystems, Paris, France

Presentation time/location: Monday, Dec. 11; 6-8 p.m. PT; Halls G-H

About WU-CART-007

WU-CART-007 is an allogeneic, off-the-shelf, fratricide-resistant CD7-targeted CAR-T cell therapy engineered to overcome the technological challenges of harnessing CAR-T cells to treat CD7+ hematological malignancies. Wugen is deploying CRISPR/Cas9 gene editing technology to delete CD7 and the T-cell receptor alpha constant (TRAC), preventing CAR-T cell fratricide and mitigating the risk of graft-versus-host-disease (GvHD). WU-CART-007 is manufactured using healthy donor-derived T-cells to eliminate the risk of malignant cell contamination historically observed in the autologous CAR-T setting. WU-CART-007 is currently being evaluated in a global Phase 1/2 clinical trial for the treatment of relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (LBL). Additional information is available on clinicaltrials.gov, identifier NCT# 04984356. WU-CART-007 has received Orphan Drug, Fast Track, and Rare Pediatric Disease Designations from the U.S. Food and Drug Administration for the treatment of R/R T-ALL/LBL.

About WU-NK-101

WU-NK-101 is a novel immunotherapy harnessing the power of memory natural killer (NK) cells to treat liquid and solid tumors. Memory NK cells are hyper-functional, long-lasting immune cells that exhibit enhanced anti-tumor activity and a cytokine-induced memory-like (CIML) phenotype. This rare cell population has a superior phenotype, proliferation capacity, and metabolic fitness, making it better suited for cancer therapy than other NK cell therapies. Wugen is applying its proprietary MonetaTM platform to advance WU-NK-101 as a commercially scalable, off-the-shelf cell therapy for cancer. WU-NK-101 is currently in development for acute myelogenous leukemia (AML). Wugen is planning to initiate solid tumor studies of WU-NK-101 in combination with cetuximab. Studies of WU-NK-101 to date have shown promising robust in vivo activity in various tumor indications, retention of anti-cancer activity in TME, resistance to immune suppression, and enhanced activity with checkpoint inhibitors. WU-NK-101 has received Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of AML.

About the MonetaTM Platform

Wugen’s proprietary MonetaTM manufacturing platform is a robust, efficient, scalable process to generate off-the-shelf memory natural killer (NK) cell therapies with enhanced anti-tumor functionality. The MonetaTM platform uses cytokine fusion complexes for streamlined and consistent manufacturing, is free of feeder cells for enhanced safety, and integrates cryopreservation to allow convenient dosing options for cancer patients.

On November 2, 2023 Vor Bio (Nasdaq: VOR), a clinical-stage cell and genome engineering company, reported that preclinical and clinical data supporting the Company’s novel platform and approach for treating acute myeloid leukemia (AML), will be presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, being held from December 9-12, 2023, in San Diego, CA (Press release, Vor BioPharma, NOV 2, 2023, View Source [SID1234636802]).

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"These three oral and two poster presentations represent further preclinical and clinical validation of our platform and reflect the significant progress we continue to make as we develop truly novel next generation transplants that have the potential to improve the lives of patients with blood cancers," said Dr. Robert Ang, Vor Bio’s President and Chief Executive Officer.

VBP101 Clinical Data Update

An abstract providing a clinical update from the VBP101 clinical trial (NCT048499910), a Phase 1/2a multicenter, open-label, first-in-human study of trem-cel (VOR33) in patients with AML, was accepted by ASH (Free ASH Whitepaper) for oral presentation. This data supports robust neutrophil engraftment of trem-cel and provides evidence of hematologic protection from MylotargTM, a CD33-targeted antibody drug conjugate.

An updated data release from VBP101 is expected by the Relapse After Transplant and Cellular Therapy (HSCT²) conference taking place November 10-11, 2023.

CD33CART Study Clinical Data Update

The Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) released data providing a clinical update on a Phase 1/2 study of CD33CART (NCT03971799)1, an autologous CAR-T therapy targeting CD33 (also referred to as VCAR33AUTO) which uses the same CAR-T construct as VCAR33ALLO. Nineteen pediatric and young adult patients with relapsed/refractory AML with a median age of 16 years were infused in the Phase 1 portion of the study. This data shows that as of the cutoff date of June 1, 2023, 2 of 5 (40%) evaluable patients treated at the highest dose level (DL4, 1 x 107 CAR+ cells/kg) achieved complete remission. Transient CD33CART expansion was detected in 11 (58%) subjects across all doses tested and in all 6 (100%) subjects evaluated at DL4, as of the cutoff date. Four out of 19 evauable patients treated had cytokine release syndrome (CRS) ≥ Grade 3. The study is being led by Nirali Shah, MD, MHSc, Head, Hematologic Malignancies Section, Pediatric Oncology Branch, National Cancer Institute and Richard Aplenc, MD, PhD, MSCE, Professor of Pediatrics, Children’s Hospital of Philadelphia (CHOP). This abstract was accepted by ASH (Free ASH Whitepaper) for oral presentation.

Sarah K. Tasian, MD, is a co-investigator on the PTCTC-supported clinical trial and led the preclinical testing and translation of CD33CART with Terry Fry, MD, at the University of Colorado.

Dr. Tasian commented: "The interim results from our CD33 CAR T cell immunotherapy clinical trial are very encouraging. CD33CART is clearly an active therapy based upon our data to date, and the expansion phase of the study will provide additional critical safety and efficacy data. Our results provide a compelling foundation for Vor Bio’s approach using the same construct for their VBP301 study."

Vor Bio’s VCAR33ALLO uses the same CAR-T construct used in CD33CART. However, VCAR33ALLO uses a potentially superior T cell source from healthy transplant donors, which the Company believes are likely to have a more stem-like phenotype and greater potential for expansion, persistence, and anti-leukemic activity compared to a product derived from autologous sources.

Additional ASH (Free ASH Whitepaper) Presentations

The Company also released data from a single cell analysis studying molecular signatures from 28 AML patients in various stages of AML progression. This data is the most comprehensive analysis to date on AML profiling. This abstract was accepted by ASH (Free ASH Whitepaper) for oral presentation.

The preclinical collaboration between Vor Bio and Janssen yielded in vitro and in vivo xenotransplant data demonstrating that CD33-deleted allografts were synergistic with Janssen’s CD33 directed immunotherapy candidate (JNJ-67571244), and maintained robust on-target cytotoxicity while reducing production of inflammatory cytokines associated with CRS. This abstract was accepted by ASH (Free ASH Whitepaper) for poster presentation.

Lastly, a trial-in-progress poster will be presented on the Company’s VBP301 clinical trial, a Phase 1/2 multicenter, open-label, first-in-human study of VCAR33ALLO in patients with relapsed or refractory AML after allogeneic stem cell transplantation. This abstract was accepted by ASH (Free ASH Whitepaper) for poster presentation.

Full details of the ASH (Free ASH Whitepaper) 2023 presentations are as follows:

Vor Bio Clinical Abstracts

Abstract Title: Trem-cel, a CRISPR/Cas9 Gene-Edited Allograft Lacking CD33, Shows Rapid Primary Engraftment with CD33-Negative Hematopoiesis in Patients with High-Risk Acute Myeloid Leukemia (AML) and Avoids Hematopoietic Toxicity During Gemtuzumab Ozogamicin (GO) Maintenance Post-Hematopoietic Cell Transplant (HCT)

Format: Oral presentation

Session Name: Gene Therapies: New Approaches from Bench to Bedside

Session date and time: Sunday, December 10, 2023, 10:00 AM PST

Abstract Title: Phase 1/2 Study of Donor-Derived Anti-CD33 Chimeric Antigen Receptor Expressing T Cells (VCAR33) in Patients with Relapsed or Refractory Acute Myeloid Leukemia after Allogeneic Hematopoietic Cell Transplantation

Format: Trial in Progress Poster, #483

Session Name: Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster III

Session date and time: Monday, December 11, 2023, 6:00 PM – 8:00 PM PST

PTCTC Clinical Abstract

Abstract Title: CD33 CAR T-cells (CD33CART) for Children and Young Adults with Relapsed/Refractory AML: Dose-Escalation Results from a Phase I Multicenter Trial

Format: Oral presentation

Session Name: Cellular Immunotherapies: Early Phase and Investigational Therapies: Novel Approaches to Enhance Cellular Therapies and Immune Responses in Leukemias and Lymphomas

Session date and time: Monday, December 11, 2023, 11:00 AM PST

Vor Bio Preclinical Abstracts

Abstract Title: Multimodal Atlas of Paired Diagnosis and Relapse AML Samples Enables Novel Therapeutic Targeting of Surface Antigens

Format: Oral presentation

Session Name: Acute Myeloid Leukemias: Biomarkers, Molecular Markers and Minimal Residual Disease in Diagnosis and Prognosis: Biomarkers and Therapeutics

Session date and time: Saturday, December 9, 2023, 2:15 PM PST

Abstract Summary: The most comprehensive single cell AML atlas known to date (More than 450,000 cells from 28 AML patients) was generated to identify potential differences in molecular signatures in AML tumor types at multiple stages of AML progression. This extensive AML profiling offers deep insight into cell surface changes during disease progression and reveals the potential for multi-targeted treatment strategies.

Abstract Title: CD33-Deleted Hematopoietic Cells (trem-cel) are Protected from CD33xCD3 Bispecific Antibody Treatment and Produce Significantly Reduced Levels of Inflammatory Cytokines in Preclinical Studies

Format: Poster, #3425

Session Name: Experimental Transplantation: Basic and Translational: Poster II

Session date and time: Sunday, December 10, 2023, 6:00 PM – 8:00 PM PST

Abstract Summary: Preclinical proof-of-concept data resulting from the Company’s strategic collaboration with Janssen, demonstrated that the CD33 deleted hematopoietic compartment was protected from Janssen’s CD33 directed immunotherapy (JNJ-67571244) both in cytotoxicity assays and xenotransplantation studies, with reduction of inflammatory cytokines associated with CRS. These findings may enable the development of a next-generation AML treatment strategy by pairing a trem-cel transplant with a subsequent CD33-directed bispecific compound that could enhance the safety and effectiveness of the treatment while decreasing the harmful effect on the bone marrow.

Conference Call & Webcast Information

Members of the Vor Bio management team, joined by Sarah K. Tasian, MD, will conduct a live conference call and webcast to discuss the abstracts, today at 9:30 AM ET.

On November 2, 2023 Vincerx Pharma, Inc. (Nasdaq: VINC)("Vincerx"), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported that it will present three posters related to VIP943 (NCT06034275), VIP924 (in preclinical studies), and enitociclib (in collaboration with University of Calgary) at the 65th American Society for Hematology Meeting (ASH) (Free ASH Whitepaper), taking place in San Diego California from December 9 to 12, 2023 (Press release, Vincerx Pharma, NOV 2, 2023, View Source [SID1234636801]).

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"The three ASH (Free ASH Whitepaper) 2023 posters highlight the strong scientific foundation for Vincerx’s programs. We look forward to providing new data on the robust preclinical activity of our lead antibody-drug conjugate (ADC), VIP943, which recently began enrolling patients with relapsed/refractory acute myeloid leukemia (R/R AML), myelodysplastic syndrome (MDS), and B-cell acute lymphoblastic leukemia (B-cell ALL)," said Ahmed Hamdy, M.D., Chief Executive Officer of Vincerx. "In addition, we are pleased to share preclinical data related to the activity of VIP924, a first-in-class CXCR5 ADC for the treatment of B-cell malignancies. Also, in collaboration with University of Calgary, we show enitociclib’s preclinical activity in pediatric leukemia."

Poster Presentation Information:

Title: Selectivity and Safety of VIP943: A Novel CD123-Targeting Antibody-Drug Conjugate (ADC) Using a Proprietary Linker and Payload Class
Session Name: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster I
Session Date: Saturday, December 9, 2023
Presentation Time: 5:30 PM – 7:30 PM, Pacific Standard Time
Location: San Diego Convention Center, Halls G-H
Publication Number: 1435
Presented by Beatrix Stelte-Ludwig, Vincerx Pharma

Title: Comparison of the CXCR5-Antibody Drug Conjugate (ADC; VIP924) to a CD19-ADC and a CD79b-ADC in a Humanized Rec-1 Mantle Cell Lymphoma (MCL) Mouse Model
Session Name: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster II
Session Date: Sunday, December 10, 2023
Presentation Time: 6:00 PM – 8:00 PM, Pacific Standard Time
Location: San Diego Convention Center, Halls G-H
Publication Number: 2809
Presented by Tibor Schomber, Vincerx Pharma

Title: Targeting CDK9 in KMT2A-Rearranged Infant Leukemia: Evidence for Activity and Drug Synergy with Enitociclib
Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster III
Session Date: Monday, December 11, 2023
Presentation Time: 6:00 PM – 8:00 PM, Pacific Standard Time
Location: San Diego Convention Center, Halls G-H
Publication Number: 4293
Presented by Ritul Sharma, University of Calgary

On November 2, 2023 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel products for serious rare and ultrarare genetic diseases, reported its financial results for the quarter ended September 30, 2023 and provided its financial guidance for the year (Press release, Ultragenyx Pharmaceutical, NOV 2, 2023, View Source [SID1234636799]).

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"We’re in a strong financial position due to growing demand for our commercial products, completion of our recent offering, and our disciplined expense and portfolio management," said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. "We’ve also made significant progress on our key clinical programs and highlighted new, interim data from UX143 for osteogenesis imperfecta, GTX-102 for Angelman syndrome, and UX701 for Wilson Disease at our Analyst Day in October demonstrating promising therapeutic potential in these larger indications with further updates to come in 2024."

Third Quarter 2023 Selected Financial Data Tables and Financial Results

Revenues (dollars in thousands), (unaudited)
Three Months Ended September 30, Nine Months Ended September 30,
2023
2022
2023
2022
Crysvita
Product sales $ 19,200 $ 13,184 $ 57,318 $ 34,980
Royalty revenue 35,160 — 64,221 —
Non-cash royalty revenue 20,543 5,373 42,695 15,634
Revenue in profit-share territory — 51,348 69,705 148,121
Total Crysvita revenue 74,903 69,905 233,939 198,735
Dojolvi 16,553 13,274 47,347 39,200
Mepsevii 5,633 6,045 22,552 15,839
Evkeeza 963 — 1,540 —
Daiichi Sankyo — 1,479 1,479 6,207
Total revenues $ 98,052 $ 90,703 $ 306,857 $ 259,981

Total Revenues
Ultragenyx reported $98.1 million in total revenue for the third quarter 2023, which represents 8% growth compared to the third quarter 2022. Third quarter 2023 Crysvita product sales, primarily in Latin America, were $19.2 million, which represents 46% growth compared to the same period in 2022 and 14% growth over the second quarter 2023. Third quarter 2023 also includes Crysvita royalty and non-cash royalty revenue in North America of $50.2 million, which was impacted by a decrease in channel inventory related to Kyowa Kirin Co., Ltd.’s (KKC) change from Ultragenyx labeled product to KKC’s labeled product as part of the transition of North America commercialization responsibilities for Crysvita from Ultragenyx to KKC. This one-time change occurred in the third quarter 2023, and the Company expects Crysvita channel inventories to increase to more normal levels at the end of the year. Third quarter 2023 non-cash royalty revenue in Europe was $5.5 million.

Selected Financial Data (dollars in thousands, except per share amounts), (unaudited)
Three Months Ended September 30, Nine Months Ended September 30,
2023 2022 2023 2022
Total revenues $ 98,052 $ 90,703 $ 306,857 $ 259,981
Operating expense:
Cost of sales 10,987 8,631 33,158 23,001
Research and development 157,245 237,297 487,892 534,981
Selling, general and administrative 74,917 69,841 232,966 205,290
Total operating expense 243,149 315,769 754,016 763,272
Net loss $ (159,649 ) $ (245,106 ) $ (483,449 ) $ (555,588 )
Net loss per share, basic and diluted $ (2.23 ) $ (3.50 ) $ (6.81 ) $ (7.96 )

Operating Expenses
Total operating expenses for the third quarter of 2023 were $243.1 million, including non-cash stock-based compensation of $34.9 million. In 2023, annual operating expenses are expected to decrease compared to 2022, as the company manages headcount and increases operational leverage while executing on its high-value programs.

Net Loss
For the third quarter of 2023, Ultragenyx reported net loss of $159.6 million, or $2.23 per share basic and diluted, compared with a net loss for the third quarter of 2022 of $245.1 million, or $3.50 per share, basic and diluted.

Cash, Cash Equivalents and Marketable Debt Securities
Cash, cash equivalents, and marketable debt securities were $524.2 million as of September 30, 2023. This excludes net proceeds of $326.5 million from an underwritten public offering of common stock and pre-funded warrants that closed in October 2023.

2023 Financial Guidance
For the full year 2023, the company expects:

Total revenue in the range of $425 million to $450 million
Crysvita revenue in the range of $325 million to $340 million. This includes all regions where Ultragenyx will recognize revenue, including the royalties in Europe, which have been ongoing, and the royalties in North America, which began in April 2023.
Dojolvi revenue in the range of $65 million to $75 million
Net Cash Used in Operations to be around $425 million
Recent Updates and Clinical Milestones

UX143 (setrusumab) monoclonal antibody for Osteogenesis Imperfecta (OI): Phase 2 demonstrated 67% reduction in annualized fracture rate and continuous improvements in bone mineral density
At the American Society of Bone and Mineral Research 2023 Annual Meeting (ASBMR), interim data from the Phase 2 portion of the Phase 2/3 Orbit study were presented that demonstrated treatment with setrusumab significantly reduced incidence of fractures in patients with OI with at least 6 months of follow-up and continued to demonstrate ongoing and meaningful improvements in lumbar spine bone mineral density (BMD). As of the cut-off date on August 4, 2023 and following at least six months of treatment with setrusumab, the annualized fracture rate across all 24 patients in the Phase 2 portion of the study was reduced by 67%. The median annualized fracture rate of 0.72 in the two years prior to treatment was reduced to 0.00 (n=24, p=0.042) during the mean treatment duration period of nine months. As of the data cut-off, there were no treatment-related serious adverse events (SAEs) observed in the study. Additional longer-term Phase 2 data are expected in 2024.

Patients are being dosed in the late-stage clinical trials, Orbit and Cosmic, which evaluate setrusumab in pediatric and young adult patients with OI. The Phase 3 portion of the Orbit study is targeting to enroll up to 195 patients at more than 50 sites across 12 countries. The Phase 3 Cosmic study is an active-controlled study evaluating the effect of setrusumab compared to intravenous bisphosphonate (IV-BP) therapy on annualized total fracture rate in patients aged 2 to <5 years. Cosmic is targeting to enroll approximately 65 patients at more than 20 global sites.

GTX-102 antisense oligonucleotide for Angelman syndrome: data from extension cohorts in Phase 1/2 study showed clinically meaningful improvements in multiple domains
In October 2023, interim data from the extension cohorts (Cohorts 4-7) in the ongoing Phase 1/2 for GTX-102 in Angelman syndrome were presented at an Analyst Day event. The data showed improvements across multiple domains compared to natural history data, where available, and clinical changes were associated with quantitative changes in EEG. Long-term data showed patients who stopped and restarted treatment reacquired previously gained developmental skills when they were re-dosed with the current regimen. As of the data cut-off, there have been no additional treatment-related SAEs, including lower extremity weakness, since November 2022.

Globally, sites are dosing patients in the expansion cohorts (Cohorts A-E), which will evaluate the same safety, pharmacokinetic, and efficacy measures as the extension cohorts. Data from at least 20 patients enrolled in the expansion cohorts, who have been on therapy for six months or more, are currently expected in the first half of 2024.

UX701 AAV gene therapy for Wilson Disease: Stage 1 of pivotal clinical study dosing patients; expect Stage 1 enrollment completion around the end of the year
In October 2023, interim data from the first dose cohort (5.0 x 10^12 GC/kg) in the ongoing Cyprus2+ study for UX701 in Wilson disease were presented at an Analyst Day event. The company announced four out of five patients in Cohort 1 had reductions in urinary copper and were tapering off of chelators and/or zinc therapy, including two of three earlier treated patients in the cohort that are now completely off standard of care therapy. As of the data cut-off, UX701 had been generally well-tolerated with no treatment-related SAEs.

Dosing in the second of three dose escalation cohorts in the pivotal study has been completed. The data safety monitoring board (DSMB) is scheduled to meet and will review the available safety data from Cohort 2 before making a recommendation on escalating to Cohort 3 of Stage 1 in this study. Stage 1 is currently on track to complete enrollment around the end of the year and these data are expected in the first half of 2024. During this stage, the safety and efficacy of UX701 will be evaluated and a dose will be selected for further evaluation in the pivotal, randomized, placebo-controlled stage of the study.

DTX401 AAV gene therapy for Glycogen Storage Disease Type Ia (GSDIa): Dosing in Phase 3 study complete
In May 2023, Ultragenyx announced the last patient had been dosed in the Phase 3 study. The 48-week study has fully enrolled patients eight years of age and older, randomized 1:1 to DTX401 or placebo. The primary endpoint is the reduction in oral glucose replacement with cornstarch while maintaining glucose control. Phase 3 data are expected in the first half of 2024.

DTX301 AAV gene therapy for Ornithine Transcarbamylase (OTC) Deficiency: Phase 3 study dosing patients
Ultragenyx is randomizing and dosing patients in the ongoing Phase 3 study. The pivotal, 64-week study will include approximately 50 patients, randomized 1:1 to DTX301 or placebo. The primary endpoints are response as measured by removal of ammonia-scavenger medications and protein-restricted diet and change in 24-hour ammonia levels. Enrollment is currently expected to be completed in the first half of 2024.

Conference Call and Webcast Information

Ultragenyx will host a conference call today, Thursday, November 2, 2023, at 2 p.m. PT/5 p.m. ET to discuss the third quarter 2023 financial results and provide a corporate update. The live and replayed webcast of the call will be available through the company’s website at View Source To participate in the live call, please register by clicking on the following link (View Source), and you will be provided with dial-in details. The replay of the call will be available for one year.

On November 2, 2023 Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported its financial results for the quarter ended September 30, 2023, and provided a business update (Press release, Syndax, NOV 2, 2023, View Source [SID1234636798]).

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"Syndax continues to make excellent progress against our key milestones and corporate priorities and is well positioned to potentially launch two first- and best-in-class blockbuster therapies in 2024," said Michael A. Metzger, Chief Executive Officer. "We are also pleased to announce final Phase 1 mNPM1 data with a 36% CR/CRh rate, which demonstrates revumenib’s ability as a monotherapy with excellent safety and tolerability to drive patients with mNPM1 AML to durable MRD negative remissions. We recently shared topline pivotal data for revumenib in R/R KMT2Ar acute leukemia, our second positive pivotal result over the past few months. We look forward to providing additional monotherapy and combination data, which further highlight the compelling clinical profile and utility of each asset, next month at the ASH (Free ASH Whitepaper) Annual Meeting."

New Data Announcement

The Company announced today positive data from the Phase 1 portion of the AUGMENT-101 trial of revumenib in a total of 14 patients with relapsed or refractory (R/R) mutant nucleophosmin (mNPM1) acute myeloid leukemia (AML) who met the recommended Phase 2 dose (RP2D) criteria. The final dataset includes three additional patients that were enrolled in the Phase 1 trial to complete the pharmacokinetic characterization of revumenib. In this analysis, the overall response rate (ORR)1 was 50% (7/14) with a complete remission (CR) or a CR with partial hematological recovery (CRh) rate of 36% (5/14); 100% (5/5) of CR/CRh patients were minimal residual disease (MRD) negative. 43% (3/7) of responders proceeded to transplant, all after achieving a CR or CRh. 60% (3/5) of CR/CRh patients maintained a response beyond six months. At the time of the analysis, four patients remained in response, with two patients in response over twenty-two months. Revumenib was well tolerated, and the safety profile was consistent with what was previously reported in the AUGMENT-101 trial. There were no Grade 4 or 5 QTc prolongation or greater than Grade 2 differentiation syndrome events, and no patients discontinued due to treatment-related adverse events (TREAs).

Recent Pipeline Progress and Anticipated Milestones

Revumenib

In October 2023, the Company announced positive topline data from the pivotal AUGMENT-101 trial of revumenib, Syndax’s first-in-class menin inhibitor, in patients with R/R KMT2A-rearranged (KMT2Ar) acute leukemia. The trial met its primary endpoint at the protocol-defined interim analysis stage with a CR/CRh rate of 23% (13/57; 95% confidence interval [CI]: [12.7, 35.8, one-sided p-value = 0.0036]) in the pooled KMT2Ar acute leukemia cohort. The CR/CRh rate in patients with KMT2Ar AML was 24.5% (12/49). 39% (14/36) of patients who achieved a CR/CRh underwent hematopoietic stem cell transplant (HSCT); eight of whom went to transplant prior to achieving CR/CRh and therefore, were not included in the reported CR/CRh rate. The CR/CRh responses in both the overall population and the AML subset were durable with a 6.4-month (95% CI: 3.4, NR) median duration as of the July 2023 data cut-off, with 46% (6/13) remaining in response. MRD status was assessed in 10 of the 13 patients who achieved a CR/CRh, 70% (7/10) of whom were MRD negative. Revumenib was well tolerated, and the overall safety profile was consistent with the Company’s previously reported data. TRAEs leading to dose reductions and treatment discontinuation were low. Based on the Independent Data Monitoring Committee (IDMC) recommendation, the Company stopped the trial to further accrual in the KMT2Ar cohorts.

The AUGMENT-101 pivotal data will be presented at the upcoming 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on Sunday, December 10, 2023. Of note, the abstract for this session only includes data from the Phase 1 portion of the AUGMENT-101 trial, however the presentation will describe the pivotal dataset.

The Company announced today that it has initiated a New Drug Application (NDA) for revumenib for the treatment of R/R KMT2Ar acute leukemia under the FDA’s Real-time Oncology Review (RTOR) program. RTOR provides a more efficient review process for oncology drugs to ensure that safe and effective treatments are available to patients as early as possible. The Company expects to complete the NDA submission by year-end 2023.

The AUGMENT-101 pivotal trial is enrolling patients with mNPM1 AML which could support a second indication in acute leukemia for revumenib. The Company expects to complete enrollment of the cohort in late 1Q24 or early 2Q24 and report topline data in 4Q24.

The Company also announced data from patients in the AUGMENT-101 trial who received revumenib as post-transplant maintenance, including patients who have been treated with revumenib maintenance for over a year, resulting in long-term responses and conversion to MRD negative status. The data will be presented at the upcoming ASH (Free ASH Whitepaper) Annual Meeting on Monday, December 11, 2023. A copy of the abstract is available on the ASH (Free ASH Whitepaper) website at www.hematology.org.

The Company has several trials of revumenib ongoing across the treatment landscape in mNPM1 and KMT2Ar acute leukemias that include the following:

BEAT-AML: Evaluating the combination of revumenib with venetoclax and azacitidine in front-line AML patients, being conducted as part of the Leukemia & Lymphoma Society’s Beat AML Master Clinical Trial. The Company expects to present preliminary safety and efficacy data in 4Q23.

SAVE: Evaluating the all-oral combination of revumenib with venetoclax and decitabine/cedazuridine in R/R AML or mixed phenotype acute leukemias. The trial is being conducted by investigators from the MD Anderson Cancer Center. Early results from the trial will be featured in an oral presentation at the ASH (Free ASH Whitepaper) Annual Meeting on Saturday, December 9, 2023. A copy of the abstract is available on the ASH (Free ASH Whitepaper) website at www.hematology.org.

AUGMENT-102: Evaluating the combination of revumenib with chemotherapy in patients with R/R acute leukemias. The Company expects to provide an update on initial safety data along with the RP2D from the trial in 4Q23.

INTERCEPT: Evaluating revumenib as a monotherapy in patients with AML who are minimal residual disease-positive following initial treatment as part of the INTERCEPT AML Master Clinical Trial.

The Company plans to initiate a trial of revumenib with 7+3 cytarabine and daunorubicin chemotherapy followed by maintenance treatment in newly diagnosed patients with mNPM1 or KMT2Ar acute leukemias in late 4Q23 or early 1Q24.

A proof-of-concept clinical trial of revumenib in patients with unresectable metastatic microsatellite stable colorectal cancer is enrolling patients, and the Company expects to provide an update on the Phase 1 trial in 1Q24.
Axatilimab

In July 2023, the Company and its partner, Incyte, announced positive topline data from the pivotal AGAVE-201 trial of axatilimab, Syndax’s anti-CSF-1R antibody, in patients with chronic graft-versus-host disease (cGVHD) following two or more prior lines of therapy. All three dose cohorts, 0.3 mg/kg every two weeks, 1.0 mg/kg every two weeks and 3.0 mg/kg every four weeks, met the primary endpoint. The ORR within the first six months of treatment at the 0.3 mg/kg dose was 74%, and 60% of these patients were still responding at one year. Furthermore, axatilimab was generally well tolerated, and the most common adverse events were consistent with on-target effects and prior trials. Syndax and Incyte expect to submit a Biologics License Application (BLA) filing by year-end 2023.

The pivotal AGAVE-201 trial results will be featured at the plenary session at the ASH (Free ASH Whitepaper) Annual Meeting on Sunday, December 10, 2023. A copy of the abstract is available on the ASH (Free ASH Whitepaper) website at www.hematology.org.

The Company expects to initiate a randomized, double-blind and placebo-controlled Phase 2 trial that assesses the efficacy, safety and tolerability of axatilimab in patients with idiopathic pulmonary fibrosis (IPF) by year-end 2023.

Incyte and Syndax expect to initiate a trial assessing axatilimab in combination with ruxolitinib in cGVHD in mid-2024.
Third Quarter 2023 Financial Results

As of September 30, 2023, Syndax had cash, cash equivalents, short and long-term investments of $379.3 million and 69.9 million common shares and prefunded warrants outstanding.

Third quarter 2023 research and development expenses increased to $39.1 million from $26.9 million for the comparable prior year period. The increase in research and development expenses was primarily due to increased employee-related expenses and professional fees as well as increased clinical and manufacturing expenses.

Third quarter 2023 general and administrative expenses increased to $17.3 million from $8.2 million for the comparable prior year period. The increase is primarily due to employee-related expenses and professional fees.

For the three months ended September 30, 2023, Syndax reported a net loss attributable to common stockholders of $51.1 million, or $0.73 per share, compared to a net loss attributable to common stockholders of $35.4 million, or $0.58 per share, for the comparable prior year period.

Financial Update and Guidance

For the full year of 2023, the Company expects research and development expenses to be $160 to $165 million and total operating expenses to be $225 to $230 million. This is a reduction from prior guidance of $160 to $175 million for research and development expenses and $225 to $240 million for total operating expenses.

Conference Call and Webcast

In connection with the earnings release, Syndax’s management team will host a conference call and live audio webcast at 4:30 p.m. ET today, Thursday, November 2, 2023.

The live audio webcast and accompanying slides may be accessed through the Events & Presentations page in the Investors section of the Company’s website. Alternatively, the conference call may be accessed through the following:

Conference ID: SNDX3Q23
Domestic Dial-in Number: 800-590-8290
International Dial-in Number: 240-690-8800
Live webcast: https://www.veracast.com/webcasts/syndax/events/SNDX3Q23.cfm

For those unable to participate in the conference call or webcast, a replay will be available on the Investors section of the Company’s website at www.syndax.com approximately 24 hours after the conference call and will be available for 90 days following the call.