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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"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.

On November 4, 2021 IGM Biosciences, Inc. (Nasdaq: IGMS), a clinical-stage biotechnology company focused on creating and developing engineered IgM antibodies, reported its financial results for the third quarter ended September 30, 2021 and provided an update on recent developments (Press release, IGM Biosciences, NOV 4, 2021, View Source [SID1234594394]).

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"IGM continues to validate and expand the IgM platform through the clinical development of IGM-2323, our CD20 x CD3 T cell engager IgM antibody for the treatment of B cell proliferative diseases, IGM-8444, our Death Receptor 5 (DR5) agonist IgM antibody for the treatment of solid and hematologic cancers, and the establishment of our infectious diseases and autoimmunity and inflammation business units," said Fred Schwarzer, Chief Executive Officer of IGM Biosciences. "We plan to continue to expand our clinical development efforts, and by the end of 2022 we expect to be actively pursuing the clinical development of four oncology product candidates, led by two Phase 2 clinical studies of IGM-2323."

"We are encouraged by the emerging data from the clinical testing of IGM-2323 in our most fully explored titration dose cohort, 100 mg, where we have seen multiple complete responses in both diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), and we look forward to sharing the initial data from this 100 mg dose cohort at our American Society of Hematology (ASH) (Free ASH Whitepaper) presentation in December," said Chris Takimoto, M.D., Ph.D., F.A.C.P., Chief Medical Officer of IGM Biosciences. "While the number of patients we have treated at 100 mg is relatively small, we believe that the planned Phase 2 expansion studies could potentially provide the basis for accelerated review and approval. As a first step, consistent with the spirit of the U.S. Food and Drug Administration’s (FDA) Project Optimus, we plan to test doses of 100 mg and 300 mg in two separate randomized ‘pick the winner’ Phase 2 studies of 30 patients at each dose level, one in DLBCL and one in FL. We plan to then expand the Phase 2 studies at the optimal dose, while including the prior data from that dose for purposes of potential registration. While our safety profile at 600 mg and 1000 mg is consistent with lower doses and very encouraging, we do not plan to continue to explore doses higher than 300 mg for purposes of greater efficacy in either DLBCL or FL."

Pipeline Updates

IGM-2323 (CD20 x CD3)

Plans to initiate potentially registrational Phase 2 study. IGM reported plans to commence two potentially registrational Phase 2 studies to assess the safety and efficacy of two doses of IGM-2323, 100 mg and 300 mg, in patients with DLBCL and FL, one Phase 2 study in DLBCL and one Phase 2 study in FL. Each Phase 2 multicenter, open-label study will take place in two stages. In the first stage, cohorts of 30 patients at each dose level (100 mg and 300 mg) will be randomized in a ‘pick the winner’ design in both DLBCL and FL, respectively. The optimal dose arm in each Phase 2 clinical trial will then be expanded to additional patients in the second stage, potentially providing the basis for accelerated review and approval of IGM-2323, assuming the clinical data support that expansion.
Data from Phase 1 trial evaluating IGM-2323 selected for oral presentation at 2021 ASH (Free ASH Whitepaper) Annual Meeting and Exposition, being held virtually and in-person in Atlanta, Georgia, December 11-14, 2021. The results will be presented on Saturday, December 11, 2021, at 1:15 p.m. ET, in an oral presentation titled "A Phase 1 Dose Escalation Study of IGM-2323, a Novel Anti-CD20 x Anti-CD3 IgM T Cell Engager (TCE) in Patients with Advanced B-Cell Malignancies." In the ASH (Free ASH Whitepaper) oral presentation, IGM plans to present additional safety and efficacy data collected subsequent to the April 30, 2021 data cut-off for the ASH (Free ASH Whitepaper) abstract, which was released online today in Blood, ASH (Free ASH Whitepaper)’s official journal.
As described in the abstract released today, as of April 30, 2021, 29 patients had been enrolled in the Phase 1 study of IGM-2323: 12 at 5 fixed dose levels (0.5, 2.5, 10, 20, 100 mg) and 17 at 5 dose titration levels (100, 200, 300, 600, and 1000 mg). All 29 patients received at least one dose and were evaluable for safety. There were no dose limiting toxicities (DLTs) and no neurotoxicity adverse events (AEs). No patients discontinued due to an AE. Of the 29 patients evaluable for safety, 6 patients had cytokine release syndrome (CRS), primarily Grade 1. As previously described, there were only two higher grade CRS events as of April 30, 2021, one Grade 2 and one Grade 3. As previously described, the Grade 3 patient had been treated with an experimental CAR-T and had high baseline circulating B-cells. Of the 11 evaluable patients treated in the titration dose cohorts, as of the April 30, 2021 data cut-off, there were 5 responses, 3 complete responses and 2 partial responses.

IGM-8444 (DR5)

Clinical development of IGM-8444 advances. IGM continues to advance the clinical development of IGM-8444, the Company’s IgM DR5 agonist, in an open-label, multicenter, Phase I study of IGM-8444 as a single agent and in combination in subjects with relapsed and/or refractory solid and hematologic cancers.
Every two-week monotherapy dose escalation cohort successfully completed. IGM announced that it has successfully cleared its highest single-agent dose escalation cohort (10 mg/kg Q2W) with no DLTs and no clinically significant liver toxicity observed to date.
Second FOLFIRI dose cohort successfully completed. IGM also announced that it has cleared the second of four planned FOLFIRI combination dose escalation cohorts (1.0 mg/kg Q2W) with no DLTs and no clinically significant liver toxicity observed to date. IGM is currently enrolling patients in the third of four planned FOLFIRI combination dose escalation cohorts (3.0 mg/kg Q2W).
No acute or chronic clinically significant liver toxicity or clinically significant anti-drug antibodies observed to date. IGM also announced today that there have been no DLTs and no clinically significant liver toxicities observed to date in the 32 patients treated with IGM-8444, of whom 11 remain on treatment. Importantly, 7 patients have been on treatment for 5 or more months without showing signs of any chronic toxicities to date. No patient has discontinued treatment for drug related safety reasons, and no clinically significant anti-drug antibodies have been observed to date.
First patient dosed in combination with birinapant. IGM announced that it has treated its first patient in a combination clinical study of IGM-8444 with birinapant, a SMAC mimetic which binds to and degrades inhibitors of apoptosis proteins (IAPs) leading to apoptotic cell death in tumors. The combination of these two apoptotic agents, IGM-8444 and birinapant, has shown strong synergy in preclinical testing, and IGM has acquired exclusive worldwide rights to manufacture, develop and commercialize birinapant. The first patient in this combination cohort was successfully treated with no clinically significant adverse events observed to date. IGM is currently enrolling additional patients in this first birinapant dose cohort. IGM is also preparing to enroll patients with chronic lymphocytic leukemia/small lymphocytic lymphoma in a venetoclax-IGM-8444 combination cohort.
Markers of on-target biological activity observed. Signs of biological activity consistent with the activation of DR5 by a DR5 agonist have been observed in some patients, both in circulating biomarkers and histological tumor samples.
"IGM-8444’s toxicity profile to date, which has not shown any clinically significant liver toxicity, differentiates it from some of the second generation DR5 agonists that have struggled to progress in the clinic due to liver toxicity," said Dr. Takimoto. "Importantly, we believe this safety profile will be critical to successful combinations with other drugs, which we believe represent by far the most exciting and promising uses of DR5 agonists for the treatment of multiple solid and hematologic cancers. For this reason, our clinical development focus continues to be on combinations of IGM-8444 with standard of care and novel agents, such as FOLFIRI, venetoclax and birinapant."

IGM-6268 (COVID-19)

IGM-6268 for the treatment and prevention of COVID-19 expected to advance into the clinic in the fourth quarter. IGM-6268 is an IgM version of an anti-SARS-CoV-2 IgG monoclonal antibody and is being developed as an intranasally administered agent for the treatment and prevention of COVID-19. It is expected to start clinical development by the end of 2021, initially in healthy volunteers.
IGM-7354 (IL-15 x PD-L1)

Phase 1 clinical testing expected to initiate in 2022. IGM plans to initiate a Phase 1 study of IGM-7354, the Company’s IL‑15 x PD‑L1 bispecific IgM antibody, in solid tumors in 2022.
IGM-2644 (CD38 x CD3)

Phase 1 clinical testing expected to initiate in 2022. IGM announced today that it plans to initiate a Phase 1 study of IGM-2644, the Company’s CD38 x CD3 bispecific IgM antibody, in multiple myeloma in 2022.
"We believe the safety and efficacy profile that we have observed to date in the clinical development of IGM-2323, our T cell engaging IgM antibody targeting CD20 on lymphoma cells, is very encouraging with respect to the future clinical development of IGM-2644, our T cell engaging IgM antibody targeting CD38 on multiple myeloma cells, as it has shown similar preclinical safety and efficacy features to those we observed with IGM-2323," said Bruce Keyt, Ph.D., Chief Scientific Officer of IGM Biosciences. "We hope to file an investigational new drug (IND) application with the FDA and begin the Phase 1 clinical development of IGM-2644 next year."

Corporate Updates

Announced leadership appointments and formation of IGM Infectious Diseases and IGM Autoimmunity and Inflammation business units. The new business units will utilize and build upon IGM’s platform technology to create and develop novel IgM and IgA antibodies to address infectious diseases, autoimmunity and inflammation. To lead the IGM Autoimmunity and Inflammation business unit, IGM announced the appointment of Mary Beth Harler, M.D., as President. To lead the IGM Infectious Diseases business unit, IGM announced the appointments of John Shiver, Ph.D. and Tong-Ming Fu, M.D., Ph.D., as Chief Strategy Officer and Chief Scientific Officer, respectively.
Third Quarter 2021 Financial Results

Cash and Investments: Cash and investments as of September 30, 2021 were $265.6 million, compared to $366.3 million as of December 31, 2020.
Research and Development (R&D) Expenses: For the third quarter of 2021, R&D expenses were $34.2 million, compared to $15.8 million for the same period in 2020.
General and Administrative (G&A) Expenses: For the third quarter of 2021, G&A expenses were $10.0 million, compared to $4.7 million for the same period in 2020.
Net Loss: For the third quarter of 2021, net loss was $44.2 million, or a loss of $1.32 per share, compared to a net loss of $20.3 million, or a loss of $0.66 per share, for the same period in 2020.
2021 Financial Guidance

IGM reiterates its previously issued financial guidance expecting full year GAAP operating expenses to be between $175 million and $185 million including estimated non-cash stock-based compensation expense of approximately $25 million. IGM expects to end 2021 with a balance of over $200 million in cash and investments.

On November 4, 2021 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported that, based on feedback from the U.S. Food and Drug Administration ("FDA") at a recent Type B meeting, where the Company provided the FDA with additional detailed data and the statistical analysis plan, the Company has requested a pre-BLA meeting for omburtamab for the treatment of pediatric patients with CNS/leptomeningeal metastasis from neuroblastoma (Press release, Y-mAbs Therapeutics, NOV 4, 2021, View Source [SID1234594393]). The Company believes the pre-BLA meeting will be held in January 2022, and pending a positive meeting, the Company aims to initiate resubmission of the omburtamab BLA shortly thereafter.

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"We are very pleased to be aligned with the FDA on the next step towards the resubmission of the omburtamab BLA, and believe that, if approved, omburtamab will be of significant benefit to children with CNS/leptomeningeal metastasis from neuroblastoma, who are currently facing a significant unmet medical need," stated Thomas Gad, founder, Chairman and President.

Dr. Claus Moller, Chief Executive Officer, continued, "We are reconfirming our anticipated timeline for resubmission of the omburtamab BLA, as we believe we are still positioned to complete the submission during the course of the first quarter 2022, potentially allowing for FDA approval of omburtamab in the fourth quarter 2022."

Researchers at Memorial Sloan Kettering Cancer Center ("MSK") developed omburtamab, which is exclusively licensed by MSK to Y-mAbs. As a result of this licensing arrangement, MSK has institutional financial interests in the compound.