On November 4, 2021 TG Therapeutics, Inc. (NASDAQ: TGTX), reported the release of six abstracts that will be presented at the upcoming 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting and exposition, to be held December 11 – 14, 2021, virtually and also live at the Georgia World Congress Center in Atlanta, Georgia (Press release, TG Therapeutics, NOV 4, 2021, View Source [SID1234594399]). Abstracts are now publicly available online via the ASH (Free ASH Whitepaper) meeting website at www.hematology.org.

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Michael S. Weiss, Chairman and Chief Executive Officer, stated, "We are looking forward to a live ASH (Free ASH Whitepaper) annual meeting this year where we will be sharing six presentations, including three oral presentations. Specifically, we are pleased to share new data from the UNITY-NHL Phase 2b trial showing the U2 combination in patients with relapsed or refractory marginal zone lymphoma and diffuse large b-cell lymphoma. We are also excited to share two novel analyses from the UNITY-CLL Phase 3 trial. One highlighting the outcomes of U2 treated patients who had comorbidities or required certain concomitant medications, both of which represent areas of high unmet need as these patients may be poor candidates for BTK therapy. The other presentation sharing the efficacy and safety of U2 by CLL pre-treatment status, that is, comparing the treatment naïve cohort with the previously treated cohort. Finally, we will also share two presentations from studies evaluating U2 triplet regimens with a BTK, namely TG-1701 and ibrutinib. We believe these presentations showcase the strength of our combination B-cell platform, which has the potential to produce multiple product opportunities in the future."

ASH Presentation Details:

Oral Presentations:
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

Session Date/Time: Saturday, December 11, 2021 / 10:00 AM ET
Session Name: 623. Mantle Cell, Follicular, and Other B-Cell Lymphomas: Clinical and Epidemiological: Targeted Therapy in Low Grade Lymphoma
Room: Georgia World Congress Center, A411-A412
Lead Author: Julio Chavez, MD, MS, Moffitt Cancer Center, Tampa, FL
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)

Session Date/Time: Sunday, December 12, 2021 / 5:30 PM ET
Session Name: 626. Aggressive Lymphomas Prospective Therapeutic Trials: Novel Agents and Combinations
Room: Georgia World Congress Center, Thomas Murphy Ballroom 1-2
Lead Author: John Burke, MD, Rocky Mountain Cancer Centers / US Oncology Research, Aurora, CO
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

Session Date/Time: Sunday, December 12, 2021 / 10:30 AM ET
Session Name: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological I
Room: Georgia World Congress Center, B401-B402
Lead Author: Lindsey E. Roeker, MD, CLL Program, Leukemia Service, Division of Hematologic Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY
Poster Presentations:
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

Date/Time: Saturday, December 11, 2021 / 5:30 PM – 7:30 PM ET
Session Name: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster I
Location: Georgia World Congress Center, Hall B5
Lead Author: Chan Y. Cheah, MBBS, DMSc, Linear Clinical Research, Nedlands, Australia; Medical School, University of Western Australia, Perth, Australia; and Department of Haematology, Sir Charles Gairdner Hospital, Perth, Australia
Poster Presentation Title: Favorable Outcomes for Patients Treated with U2 with Co-Morbidities or Concomitant Medications: A Retrospective Analysis of Unity-CLL Phase 3 Trial

Date: Monday, December 13, 2021 / 6:00 PM – 8:00 PM
Session Name: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster III
Location: Georgia World Congress Center, Hall B5
Lead Author: Javier Pinilla-Ibarz, MD, Lymphoma Section Head, Director of Immunotherapy, Malignant Hematology Division at the H. Lee Moffitt Cancer Center in Tampa, Florida
Poster Presentation Title: Efficacy and Safety of Ublituximab in Combination with Umbralisib (U2) in Patients with Chronic Lymphocytic Leukemia (CLL) By Treatment Status: A Sub-Analysis of the Phase 3 Unity-CLL Study

Date/Time: Monday, December 13, 2021 / 6:00 PM – 8:00 PM
Session Name: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster III
Location: Georgia World Congress Center, Hall B5
Lead Author: Ryan Jacobs, MD, Department of Hematology, Lymphoma Division, Assistant Professor of Medicine, Levine Cancer Institute/Atrium Health, Charlotte, NC
Abstracts are now publicly available via the ASH (Free ASH Whitepaper) meeting website at www.hematology.org. Final presentations will be accessible at the above dates/times via the publications page of TG corporate website at View Source

On November 4, 2021 Seagen Inc. (Nasdaq:SGEN) reported that new data for ADCETRIS (brentuximab vedotin), including five oral presentations, will be featured at the upcoming 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place December 11-14, 2021 (Press release, Seagen, NOV 4, 2021, View Source [SID1234594398]). Data presentations will include updated safety and efficacy results from clinical trials examining the potential of ADCETRIS with novel combinations in patients with advanced stage classical Hodgkin lymphoma (HL), in patients with newly diagnosed CD30-expressing peripheral T-cell lymphoma (PTCL) and in patients with other histologies.

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"We look forward to sharing new data for the continued development of ADCETRIS in combination with other therapies across patient populations," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "Additionally, initial results will be presented from our SEA-BCMA program in patients with relapsed/refractory multiple myeloma."

ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL and expressed on the surface of several types of PTCL. ADCETRIS is approved in more than 75 countries for relapsed or refractory HL and systemic anaplastic large cell lymphoma (sALCL).

Presentations of Company-Sponsored ADCETRIS Trials:

Abstract Title

Abstract #

Presentation

Lead Author

The ECHELON-2 Trial: 5-Year Exploratory Subgroup Analyses of a Randomized, Double-Blind, Phase 3 Study of Brentuximab Vedotin and CHP (A+CHP) vs CHOP in Frontline Treatment of Pts with CD30-Positive Peripheral T-Cell Lymphoma

#135

Oral presentation /
Saturday, Dec. 11,
12:00 – 1:30 p.m. EST

S. Horwitz

Classical Hodgkin Lymphoma: Real-World Observations from Physicians, Patients, and Caregivers on the Disease and Its Treatment (CONNECT): Observations of Physicians on Treatment and Interim PET-Adapted Regimens

#1390

Poster presentation /
Saturday, Dec. 11,
5:30 – 7:30 p.m. EST

S. Parsons

Classical Hodgkin Lymphoma: Real-World Observations from Physicians, Patients, and Caregivers on the Disease and Its Treatment (CONNECT)—a Cross-Sectional Survey of Patients with Stage III or IV Classical Hodgkin Lymphoma Compared By Age

#1966

Poster presentation /
Saturday, Dec. 11,
5:30 – 7:30 p.m. EST

D. Flora

Pharmacodynamics of SEA-BCMA, a Nonfucosylated Antibody Targeting BCMA, in Patients with Relapsed/Refractory Multiple Myeloma

#1197

Poster presentation /
Saturday, Dec. 11,
5:30 – 7:30 p.m. EST

D. Taft

Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine (AN+AD) for advanced stage classic Hodgkin lymphoma: preliminary results from the single-arm phase 2 study (SGN35-027 Part B)

#2454

Poster presentation /
Sunday, Dec. 12,
6:00 – 8:00 p.m. EST

H. Lee

An Oncology Simulation Model to Estimate 10-Year Progression-Free Survival and Overall Survival Based on the 5-Year Update from the Echelon-2 Trial in Frontline Patients with Peripheral T-Cell Lymphoma: A United States Perspective

#2440

Poster presentation /
Sunday, Dec. 12,
6:00 – 8:00 p.m. EST

T. Phillips

Classical Hodgkin Lymphoma: Real-World Observations from Physicians, Patients, and Caregivers on the Disease and Its Treatment (CONNECT): Physician First-Line Treatment Preferences for Stage III or IV Classical Hodgkin Lymphoma

#2467

Poster presentation /
Sunday, Dec. 12,
6:00 – 8:00 p.m. EST

A. Evens

An Oncology Simulation Model to Estimate 10-Year Progression-Free Survival and Overall Survival Based on the 5-Year Update from the Echelon-2 Trial in Frontline Patients with Peripheral T-Cell Lymphoma: A United States Perspective

#2466

Poster presentation /
Sunday, Dec. 12,
6:00 – 8:00 p.m. EST

J. Burke

SEA-BCMA, an investigational nonfucosylated monoclonal antibody: interim results of a phase 1 study in relapsed/refractory multiple myeloma patients (SGNBCMA-001)

#2740

Poster presentation /
Sunday, Dec. 12,
6:00 – 8:00 p.m. EST

J. Hoffman

Trials-In-Progress

Brentuximab Vedotin in Combination with Nivolumab, Doxorubicin, and Dacarbazine in Newly Diagnosed Patients with Advanced Stage Hodgkin Lymphoma (SGN35-027, Trial in Progress)

#1369

Poster presentation /
Saturday, Dec. 11,
5:30 – 7:30 p.m. EST

I. Flinn

Brentuximab Vedotin in Combination with Lenalidomide and Rituximab in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (ECHELON-3, Trial in Progress)

#3564

Poster presentation /
Monday, Dec. 13,
6:00 – 8:00 p.m. EST

N. Bartlett

Frontline Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin and Prednisone in Patients With Peripheral T Cell Lymphoma With Less Than 10% CD30 Expression (SGN35 032, Trial in Progress)

#1401

Poster presentation /
Saturday, Dec. 11,
5:30 – 7:30 p.m. EST

D. Jagadeesh

Presentations of Investigator-Sponsored and Cooperative Group ADCETRIS Trials:

Abstract Title

Abstract #

Presentation

Lead Author

Brentuximab vedotin Plus Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (CHEP-BV) Followed by BV Consolidation in Patients with CD30-Expressing Peripheral T-cell Lymphomas

#133

Oral presentation /
Saturday, Dec. 11,
12:00 – 1:30 p.m. EST

A. Herrera

The Eatl-001 Trial: Results of a Phase 2 Study of Brentuximab vedotin and CHP Followed By Consolidation with High-Dose Therapy – Autologous Stem-Cell Transplantation (HDTASCT) in the Frontline Treatment of Patients with Enteropathy-Associated T-Cell Lymphoma

#136

Oral presentation /
Saturday, Dec. 11,
12:00 – 1:30 p.m. EST

D. Sibon

Interim results of a multicenter pilot study evaluating brentuximab vedotin with cyclophosphamide, doxorubicin, etoposide, and prednisone (BV-CHEP) for the treatment of aggressive adult T-cell leukemia/lymphoma

#1395

Poster presentation /

Saturday, Dec. 11,
5:30 – 7:30 p.m. EST

C. Dittus

Pacific: A Phase II Study of Brentuximab vedotin and Nivolumab Alone and then Combined with Rituximab, Cyclophosphamide, Doxorubicin and Prednisone for Patients with Untreated Primary Mediastinal Large B-Cell Lymphoma

#1408

Poster presentation /
Saturday, Dec. 11,
5:30 – 7:30 p.m. EST

R. Steiner

Brentuximab vedotin plus ESHAP (BRESHAP) versus ESHAP as salvage strategy for patients with primary refractory or relapsed classical Hodgkin’s Lymphoma. Preliminary results from the BRESELIBET prospective clinical

#2459

Poster presentation /
Sunday, Dec. 12,
6:00 – 8:00 p.m. EST

A. Sureda

Effect of Brentuximab Vedotin Addition to Chemotherapy and Prognostic Factors in 718 Patients with Relapsed/Refractory Hodgkin Lymphoma

#879

Oral presentation /
Monday, Dec. 13,
6:15 – 7:45 p.m. EST

J. Driessen

The Evolution of Children’s Oncology Group Hodgkin Lymphoma Trials: Predicted Impact on Late Cardiac Toxicity

#81

Oral presentation /
Monday, Dec. 13,
6:15 – 7:45 p.m. EST

A. Lo

On November 4, 2021 Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported a topline summary of the presentations planned for today’s 2021 R&D Day virtual event, which begins at 11:00 AM ET (Press release, Precigen, NOV 4, 2021, View Source [SID1234594397]). Participants may register and access the live webcast through Precigen’s investor relations website in the Events & Presentations section.

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Today’s event will showcase clinical progress for Precigen’s UltraCAR-T platform, including PRGN-3005 UltraCAR-T, PRGN-3006 UltraCAR-T, PRGN-3007 UltraCAR-T and the AdenoVerse immunotherapy platform, including PRGN-2009 off-the-shelf (OTS) AdenoVerse Immunotherapy, and PRGN-2012 OTS AdenoVerse Immunotherapy. Presentations will be made by Precigen executives and clinical trial investigators, including:

Helen Sabzevari, PhD, President and CEO of Precigen;
Mary L. (Nora) Disis, MD, University of Washington (UW) Professor of Medicine, Director of UW Center for Translational Medicine, Professor in the Clinical Research Division at the Fred Hutchinson Cancer Research Center and a lead investigator for the PRGN-3005 clinical trial;
David Sallman, MD, Assistant Member in the Department of Malignant Hematology at the H. Lee Moffitt Cancer Center & Research Institute and a lead investigator for the PRGN-3006 clinical trial;
James L. Gulley, MD, PhD, FACP, Branch Chief and Director of the Medical Oncology Service at the National Institutes of Health (NIH) and a lead investigator for the PRGN-2009 clinical trial; and
Clint T. Allen, MD, Principal Investigator with the Section on Translational Tumor Immunology at the NIH and a lead investigator for the PRGN-2012 clinical trial.
"Today’s R&D Day highlights the most significant clinical data presented for the UltraCAR-T and AdenoVerse platforms to date," said Helen Sabzevari, PhD, President and CEO of Precigen, "and we are highly encouraged by the initial results we are seeing across assets in both platforms. With UltraCAR-T, initial data for PRGN-3005 and PRGN-3006 continue to demonstrate favorable safety profiles, dose-dependent expansion, and durable persistence. The very encouraging clinical responses in relapsed or refractory AML patients treated with PRGN-3006 at the two lowest dose levels in the lymphodepletion cohort, which are administered at significantly lower doses than competing approaches, highlight the potential of the UltraCAR-T platform. Our AdenoVerse immunotherapy platform is equally impressive with initial data for PRGN-2009 and PRGN-2012 showing antigen-specific immune responses, low neutralizing antibody responses, and favorable safety profiles highlighting the potential for repeat administrations. Preliminary data for PRGN-2009 show encouraging objective responses and suggest an attractive opportunity for potential combination of PRGN-2009 with checkpoint inhibitors in multiple HPV-associated cancers. Finally, preliminary data for PRGN-2012 show encouraging clinical responses in RRP patients, including a reduction in surgical interventions following PRGN-2012 treatment. We are on track to pursue potentially registrational trials for therapeutic candidates in both the UltraCAR-T and AdenoVerse platforms upon dose confirmation and expansion."

PRGN-3006 UltraCAR-T

Overview: PRGN-3006 is an investigational multigenic, autologous chimeric antigen receptor T cell (CAR-T) therapy engineered to simultaneously express a chimeric antigen receptor (CAR) specifically targeting CD33, membrane bound IL-15 (mbIL15), and a kill switch. PRGN-3006 UltraCAR-T is under evaluation in a Phase 1/1b clinical trial for the treatment of patients with r/r AML or higher-risk myelodysplastic syndromes (MDS). Trial subjects receive the PRGN-3006 infusion either without prior lymphodepletion (Cohort 1) or following lymphodepleting chemotherapy (Cohort 2). PRGN-3006 UltraCAR-T has been granted Orphan Drug Designation in patients with AML by the US Food and Drug Administration (US FDA).
Enrollment: Enrollment in Dose Level 4 of the non-lymphodepletion cohort and Dose Level 3 of the lymphodepletion cohort of the Phase 1 dose escalation trial is ongoing concurrently.
Dosing: As of the July 25, 2021 data cut-off, 15 r/r AML patients were treated in the non-lymphodepletion cohort (N=9) and the lymphodepletion cohort (N=6). Patients were heavily pre-treated with a median of 4 (range: 1 to 6) and 3 (range: 1 to 7) prior regimens in the non-lymphodepletion and the lymphodepletion cohorts, respectively. Additionally, 33% and 50% of the patients had failed prior allogeneic hematopoietic stem cell transplant (allo-HSCT) in the non-lymphodepletion and the lymphodepletion cohorts, respectively. Patients received a single PRGN-3006 administration at one of the following dose levels:

Safety data: Data from the first three dose levels in Cohort 1 (non-lymphodepletion) and the first two dose levels in Cohort 2 (lymphodepletion) show that PRGN-3006 was well-tolerated with no dose-limiting toxicities (DLTs) and no neurotoxicity. Only one transient Grade 3 cytokine release syndrome (CRS) was reported (DL1, Cohort 1), which resolved in less than 24 hours with tocilizumab and dexamethasone. Remaining cases of CRS were Grade 1 or 2 that either required no specific intervention or resolved following standard CRS management.
Clinical activity: Dose-dependent expansion and persistence in both the non-lymphodepletion and the lymphodepletion cohorts was observed.
An ORR of 50% (3 out of 6) was reported in the lymphodepletion cohort (Cohort 2) in patients treated at the two lowest dose levels. This included an ORR of 33% (1 out of 3) at Dose Level 1 and 67% (2 out of 3) at Dose Level 2.
Objective responses included one partial response (PR) in a patient with extramedullary AML, one complete response with incomplete hematologic recovery (CRi) which was bridged to allo-HSCT, and one complete response with hematologic recovery (CRh).
Upcoming presentation: An abstract for the PRGN-3006 Phase 1 trial (Abstract# 825) titled, "Phase 1/1b Safety Study of PRGN-3006 UltraCAR-T in Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes," was selected for oral presentation at the 63rd ASH (Free ASH Whitepaper) Annual Meeting and Exposition on December 13, 2021 at 5:00 PM ET.
PRGN-3005 UltraCAR-T

Overview: PRGN-3005 UltraCAR-T is an investigational multigenic, autologous CAR-T cell therapy engineered to express a CAR specifically targeting the unshed portion of MUC16, which is highly expressed on ovarian tumors with limited normal tissue expression, mbIL15, and a kill switch. PRGN-3005 UltraCAR-T is under evaluation in a Phase 1/1b clinical trial for the treatment of patients with advanced, recurrent platinum resistant ovarian cancer. Trial subjects receive PRGN-3005 either via intraperitoneal (IP) (Arm A) or intravenous (IV) (Arm B) infusion.
Enrollment: Doses are currently being administered without lymphodepletion. Dose escalation in the IP arm and IV arm is ongoing concurrently.
Dosing: Ten heavily pretreated, advanced, platinum resistant ovarian cancer patients with aggressive disease were treated with a single IP infusion of PRGN-3005 without prior lymphodepletion at one of the following dose levels:

Manufacturing: Precigen’s UltraPorator system has enabled escalation to higher doses, as evidenced by the successful infusion of greater than 320 million UltraCAR-T cells, through the decentralized UltraCAR-T manufacturing process.
Safety data: New data continue to show a favorable safety profile with no DLTs, no neurotoxicity, and no CRS reported.
Clinical activity: Data show dose-dependent expansion and persistence in the peripheral blood for more than 3 months after PRGN-3005 treatment without lymphodepletion, and clinical activity as evidenced by a decrease or stabilization of total target tumor burden at the first restaging in a majority of patients.
Next steps: Complete dose escalation in the IP and IV arms and, subsequently, incorporate lymphodepletion prior to PRGN-3005 infusion, which was cleared by the US FDA. Additionally, based on the favorable safety profile, the potential for repeat dosing is being evaluated.
PRGN-3007 Next Generation UltraCAR-T with Intrinsic PD-1 Inhibition

Overview: PRGN-3007, based on the next generation of UltraCAR-T platform, is an investigational multigenic, autologous CAR-T cell therapy engineered to simultaneously express a CAR targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), mbIL15, a kill switch, and a novel mechanism for the intrinsic blockade of PD-1 gene expression. ROR1 is aberrantly expressed in multiple hematological and solid tumors with minimal expression in healthy adult tissues.
Trial design: As recently announced, the US FDA cleared the investigational new drug (IND) application to initiate a Phase 1/1b open-label trial designed to evaluate the safety and efficacy of PRGN-3007 in patients with advanced ROR1+ hematological (Arm 1) and solid (Arm 2) tumors. The target patient population for Arm 1 includes r/r chronic lymphocytic leukemia (CLL), r/r mantle cell leukemia (MCL), r/r acute lymphoblastic leukemia (ALL), and r/r diffuse large B-cell lymphoma (DLBCL). The target patient population for Arm 2 includes locally advanced unresectable or metastatic histologically confirmed triple negative breast cancer (TNBC). The trial will enroll in two parts: an initial 3+3 dose escalation in each arm followed by a dose expansion at the maximum tolerated dose. Arm 1 and Arm 2 will enroll in parallel.
Preclinical data: An abstract highlighting PRGN-3007 preclinical data (Abstract# 1694) titled, "Preclinical evaluation of PRGN-3007, a non-viral, multigenic, autologous ROR1 UltraCAR-T cell therapy with novel mechanism of intrinsic PD-1 blockade for treatment of hematological and solid cancers," will be presented as a poster presentation at the 63rd ASH (Free ASH Whitepaper) Annual Meeting and Exposition.
PRGN-2012 OTS AdenoVerse Immunotherapy

Overview: PRGN-2012 is an investigational OTS AdenoVerse immunotherapy designed to elicit immune responses directed against cells infected with HPV 6 or HPV 11 for treatment of recurrent respiratory papillomatosis (RRP). PRGN-2012 is currently under evaluation in a Phase 1 clinical trial under a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI). The Phase 1 trial is designed to follow 3+3 dose escalation of PRGN-2012 as an adjuvant immunotherapy following standard-of-care surgical removal of visible papillomas in adult patients with RRP. PRGN-2012 has been granted Orphan Drug Designation in patients with RRP by the US FDA.
Enrollment: Enrollment in the Phase 1 dose escalation portion of the trial is complete and enrollment in the expansion cohort is ongoing.
Dosing: Six patients have been enrolled in the Phase 1 dose escalation arm at one of the following dose levels with patients receiving four PRGN-2012 administrations (on days 1, 15, 43 and 85) via subcutaneous injection:
Additionally, 8 patients have been enrolled in the Phase 1 dose expansion arm to receive four PRGN-2012 administrations (on days 1, 15, 43 and 85) at 5 x 1011 vp/dose via subcutaneous injection.
Baseline patient characteristics (N=14) included an average of 51 lifetime surgeries (range: 9 to > 800), and an average of 5.5 surgeries (range: 2 to 9) in the last 2 months before enrolling in the trial.

Dose Level 1: 1 x 1011 viral particles (vp)/dose; N=3
Dose Level 2: 5 x 1011 vp/dose; N=3
Safety data: Repeated administrations of PRGN-2012 were well-tolerated with no DLTs and no treatment-related adverse events greater than Grade 2. The lack of a significant neutralizing antibody response over time with subsequent additional vaccinations highlights the ability to deliver repeated administrations of PRGN-2012, a differentiating feature of the AdenoVerse platform.
Clinical activity: Preliminary data from three RRP patient case studies demonstrate very encouraging clinical activity of PRGN-2012 with reduction or elimination in the need for surgical interventions at the most recent follow-up, up to 12 weeks after PRGN-2012 treatment, compared to the recent history of surgical interventions for these patients before enrolling in the trial.
PRGN-2009 OTS AdenoVerse Immunotherapy

Overview: PRGN-2009 is an OTS investigational immunotherapy utilizing the AdenoVerse platform that has been designed to activate the immune system to recognize and target HPV-positive solid tumors. PRGN-2009 is currently under evaluation in a Phase 1/2 clinical trial under a CRADA with the NCI. The Phase 1 trial is evaluating safety and response of PRGN-2009 as monotherapy (Arm A) and in combination with bintrafusp alfa (Arm B) in previously treated patients with recurrent or metastatic HPV-associated cancers.
Enrollment: Enrollment in the Phase 1 monotherapy dose escalation arm is complete and enrollment in the Phase 1 combination arm is ongoing. In addition, enrollment in the monotherapy arm of the Phase 2 trial, which evaluates PRGN-2009 as a neoadjuvant therapy for newly diagnosed oropharyngeal or sinonasal squamous cell cancer patients (OPSCC) is ongoing.
Dosing: Six patients (all with prior anti-PD-1/PD-L1 treatment) have been treated in the Phase 1 monotherapy dose escalation arm at one of the following dose levels with patients receiving three PRGN-2009 administrations (on days 1, 15 and 29), followed by PRGN-2009 administration once every 4 weeks for up to 1 year:
Additionally, 6 patients (all with prior anti-PD-1/PD-L1 treatment) were treated in the Phase 1 combination arm with patients receiving three PRGN-2009 administrations (5 x 1011 vp/dose on days 1, 15 and 29) in combination with bintrafusp alfa (1200 mg) once every 2 weeks, followed by PRGN-2009 administration once every 4 weeks in combination with bintrafusp alfa administrations once every 2 weeks for up to 1 year. Five patients with at least one post-treatment scan were evaluable for disease response.

Dose Level 1: 1 x 1011 vp/dose; N=3
Dose Level 2: 5 x 1011 vp/dose; N=3
Safety data: Phase 1 data show that repeated administrations of PRGN-2009 demonstrated a favorable safety profile as monotherapy and in combination therapy with no DLTs. The lack of a significant neutralizing antibody response over time with subsequent additional vaccinations highlights the ability to deliver repeated administrations of PRGN-2009.
Clinical activity: Patient case studies show encouraging increases in the HPV16 and/or HPV18-specific immune response with repeated administrations of PRGN-2009.
In the Phase 1 monotherapy arm, a DCR of 50% (3 out of 6 with stable disease (SD)) at the first restaging was observed. This includes a patient with durable (>1 year) SD who has received 16 PRGN-2009 monotherapy administrations.
In the Phase 1 combination therapy arm, an ORR of 40% (2 out of 5) per RECIST v1.1 was observed. Objective responses included one ongoing CR at approximately 6 months after treatment initiation and one ongoing PR at approximately 7 months after treatment initiation. Additionally, a DCR of 60% (3 out of 5) at first restaging was observed.

On November 4, 2021, Keros Therapeutics, Inc. (the "Company") updated its corporate presentation (Presentation, Keros Therapeutics, NOV 4, 2021, View Source [SID1234594396])

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On November 4, 2021 Syndax Pharmaceuticals, Inc. (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that updated data from both of its ongoing SNDX-5613 and axatilimab programs will be featured during oral sessions at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held December 11-14, 2021 (Press release, Syndax, NOV 4, 2021, View Source [SID1234594395]). SNDX-5613 is the Company’s highly selective oral menin inhibitor. Axatilimab is Syndax’s anti-CSF-1R monoclonal antibody.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"We are pleased to share that both our innovative pipeline programs will be highlighted during oral presentation sessions at the upcoming ASH (Free ASH Whitepaper) Annual Meeting," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "For SNDX-5613, updated data from the Phase 1 portion of AUGMENT-101 continue to demonstrate robust clinical activity and a well-tolerated safety profile in heavily pretreated patients with mixed lineage leukemia rearranged (MLLr) or nucleophosmin (NPM1c) mutations."

"We are also excited to share updates from the Phase 1/2 trial of axatilimab for the treatment of chronic graft-versus-host disease (cGVHD). With additional patients and longer follow up, we have observed a high rate of durable responses and multiorgan clinical benefit in patients refractory to multiple therapeutic agents. We are encouraged by the continued trend we are seeing, notably in those treated in the 1 mg/kg Phase 2 expansion cohort, and look forward to presenting additional updated data for both programs in December."

SNDX-5613

A copy of the abstract published today can be viewed here. The oral presentation will include updated Phase 1 data from additional patients as of a more recent cutoff date, as well as further details on durability and complete response (CR) or CR with partial hematologic recovery (CRh) rate and mutational status.

The abstract highlights data from the Phase 1 portion of the Company’s Phase 1/2 AUGMENT-101 trial of SNDX-5613 in patients with MLLr and NPM1c mutant relapsed/refractory (R/R) acute leukemias as of a June 29, 2021 data cutoff date. Of the 45 patients with MLLr or mNPM1 mutant leukemia who received at least one dose of SNDX-5613, the composite complete response (CRc: CR+CRh+CRp+CRi/MLFS) rate was 44% (n=20/45), with 14 of the 20 (70%) patients with a CRc showing no evidence of minimal residual disease (MRD-). The CR/CRh rate in this population was 22% (n=10/45). At the time of the data cut for the abstract, the median follow up was only 3.2 months and the median duration of response for patients achieving a CR/CRh was 5.2 months. Thirteen patients remained on treatment as of the data cutoff date. SNDX-5613 was generally safe and well-tolerated, with no study discontinuations due to treatment-related adverse events.

Oral Presentation Details:

Title: Safety and Efficacy of Menin Inhibition in Patients (Pts) with MLL-Rearranged and NPM1 Mutant Acute Leukemia: A Phase (Ph) 1, First-in-Human Study of SNDX-5613 (AUGMENT 101)
Presenter: Eytan Stein, M.D.
Session Name: 616: Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Targeted Therapies and Novel Therapies Session
Session Date: Monday, December 13, 2021
Session Time: 2:45 – 4:15 p.m. ET
Presentation Time: 3:15 p.m. ET
Abstract/Publication Number: 699
Axatilimab

A copy of the abstract published today can be viewed here. The oral presentation will include additional follow up on all patients enrolled.

The abstract published today highlights data from 40 patients treated in the Company’s Phase 1/2 trial of axatilimab in patients with cGVHD as of a June 28, 2021 data cutoff date. A total of 38 patients were evaluable for response and demonstrated an overall response rate (ORR) of 66% (25/38). Thirty-two patients were treated at two of the doses being tested in the Company’s ongoing AGAVE-201 global pivotal study, and 30 were evaluable for response at the time of the data cutoff. A best ORR (CR+partial response) of 75% (18/24) at 1mg/kg every two weeks and 50% (3/6) at 3mg/kg every four weeks was observed, with responses noted across organ systems including difficult to treat manifestations such as lung, skin, and joints and fascia. Axatilimab was generally safe and well-tolerated. Enrollment is ongoing in the pivotal Phase 2 AGAVE-201 trial of axatilimab in patients with cGVHD, with topline data expected in 2023.

Oral Presentation Details:

Title: Safety, Tolerability, and Efficacy of Axatilimab, a CSF-1R Humanized Antibody, for Chronic Graft-Versus-Host Disease after 2 or More Lines of Systemic Treatment
Presenter: Stephanie Lee, M.D, M.P.H.
Session Name: 722: Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Treatment of Acute and Chronic Graft vs. Host Disease
Session Date: Saturday, December 11, 2021
Session Time: 2:00 – 3:30 p.m. ET
Presentation Time: 3:00 p.m. ET
Abstract/Publication Number: 263
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 Axatilimab

Axatilimab is an investigational monoclonal antibody that targets colony stimulating factor-1 receptor, or CSF-1R, a cell surface protein thought to control the survival and function of monocytes and macrophages. In pre-clinical models, inhibition of signaling through the CSF-1 receptor has been shown to reduce the number of disease-mediating macrophages along with their monocyte precursors, which has been shown to play a key role in the fibrotic disease process underlying diseases, such as chronic graft-versus-host disease (cGVHD) and idiopathic pulmonary fibrosis (IPF). Axatilimab data has demonstrated deep, durable responses and multiorgan clinical benefit in patients with cGVHD refractory to multiple therapeutic agents, and is currently being evaluated in the global pivotal Phase 2 AGAVE-201 trial in patients with cGVHD. Axatilimab was granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of patients with cGVHD and IPF. In September 2021, Syndax and Incyte entered into an exclusive worldwide collaboration and license agreement to develop and commercialize axatilimab. Axatilimab is being developed under an exclusive worldwide license from UCB entered into between Syndax and UCB in 2016.