On November 3, 2023 Integral Molecular, a leading biotech company specializing in antibody discovery against undruggable protein targets reported multispecific molecules targeting GPRC5D, BCMA, and CD3 this week during the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) conference in San Diego (Press release, Integral Molecular, NOV 3, 2023, View Source [SID1234636887]).

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Recent clinical data demonstrate that combination therapy of T cell engaging molecules individually targeting GPRC5D and BCMA on tumor cells offers unprecedented therapeutic benefits in relapsed/refractory multiple myeloma patients. A trispecific antibody that simultaneously engages these molecules while activating T cells is expected to provide comparable and additional benefits as a monotherapy.

Integral Molecular’s oncology drug discovery program has yielded a panel of high affinity bispecific and trispecific molecules targeting GPRC5D, a GPCR target with complex structural biology. The molecules show picomolar cell-killing activity and are highly selective for their targets.

"For decades we have navigated the complexities of molecules like GPRC5D, successfully discovering antibodies against even the most challenging targets," said Joseph Rucker, PhD, VP of R&D at Integral Molecular. "In just a few short months we were able to simultaneously target GPRC5D and BCMA, and we expect to rapidly advance this molecule into preclinical studies."

The company leveraged its MPS antibody discovery platform to discover and engineer antibodies for this program. MPS is unique from other platforms in the use of RNA, DNA, and virus-like particles (VLPs, or Lipoparticles) to present properly folded membrane proteins, and the use of divergent species (chickens) to generate diverse antibody responses.

Dr. Rucker will present the company’s bi- and trispecific GPRC5D antibodies in a poster during the SITC (Free SITC Whitepaper) 2023 conference. GPRC5D and other antibody assets from Integral Molecular are available for licensing.

On November 3, 2023 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported that several abstracts, including one oral presentation, have been selected for the 65th ASH (Free ASH Whitepaper) (American Society of Hematology) Annual Meeting and Exposition, taking place December 9-12, 2023 in San Diego, California (Press release, Innate Pharma, NOV 3, 2023, View Source [SID1234636886]).

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Lacutamab in patients with T-cell Lymphomas

Abstract details from the TELLOMAK Phase 2 Trial in Patients with Advanced Sézary syndrome include:
The oral presentation will highlight the results from Cohort 1, designed to evaluate safety and efficacy of single agent lacutamab in 56 patients with relapsed/refractory Sézary syndrome after at least two prior systemic therapies including mogamulizumab. At the data cut-off of May 1, 2023, with a global confirmed Objective Response Rate (ORR) of 37.5% (n=21; 95% CI 26.0-50.6) including 2 Complete Responses (CRs), confirmed ORR in skin of 46.4% (n=26; 95% CI 34.0-59.3) including 5 CRs and confirmed ORR in blood of 48.2% (n=27; 95% CI 35.7-61.0) including 15 CRs, data confirm that lacutamab monotherapy shows promising clinical activity in a heavily pre-treated relapsed/refractory population previously treated with a median of 6 prior lines (range 2-15), including mogamulizumab, and an overall favorable safety profile. Clinical Benefit Rate (CBR, defined as CR+PR+SD) was 87.5 % (n=49; 95% CI 76.4-93.8). Median PFS was 8.0 months (95% CI 4.7, 21.2). Continued evaluation of this promising new targeted treatment option for patients with Sezary Syndrome is warranted.

Preliminary Monotherapy Clinical Data and Pre-Clinical Combinability Data in Patients with Peripheral T-Cell Lymphoma (PTCL):
The poster will display preclinical combination data supporting anti-tumor activity and rationale for the exploration of lacutamab in combination with approved and novel therapies in patients with PTCL. Preliminary monotherapy data from an ongoing Phase 1b study in PTCL is also presented.

SAR443579/IPH6101 in patients with relapsed or refractory acute myeloid leukemia (R/R AML), B-cell acute lymphoblastic leukemia (B-ALL) or high-risk myelodysplasia (HR-MDS) (from a Joint Research Collaboration with Sanofi)

A presentation from the Sanofi oncology pipeline at ASH (Free ASH Whitepaper) includes updated efficacy and safety results from an open-label, first-in-human, dose-escalation study of an investigational CD123 targeting Natural Killer Cell Engager (NKCE). Results investigating SAR443579 as a monotherapy for the treatment of blood cancers with high unmet needs, including relapsed or refractory acute myeloid leukemia, B-cell acute lymphoblastic leukemia and high-risk myelodysplasia show data across all dose levels tested. Observed clinical remissions will also be presented. Abstract details include:

As of July 5, 2023, 43 patients (42 R/R AML and 1 HR-MDS) across 8 Dose Levels (DLs) at 10 – 6000 μg/kg/dose were included. Patients had received a median of 2.0 (1.0 – 10.0) prior lines of treatment with 13 patients (30.2%) reporting prior hematopoiectic stell cell transplantation and 36 patients (83.7%) with prior exposure to venetoclax. In DLs with a highest dose of 1000 μg/kg QW, 5/15 (33.3%) patients achieved a CR (4 CR / 1 CRi) as of the cut-off date. Data from PK/PD and in vitro mechanistic analyses studying dose-response relations will also be presented. SAR443579 was well tolerated up to doses of 6000 μg/kg QW with observed clinical benefit in patients with R/R AML. The results are consistent with the predicted favorable safety profile.

ASH abstract details:

Lacutamab

Oral Presentation

Publication Number: 185
Title: Lacutamab in Patients with Relapsed and Refractory Sézary Syndrome: Results from the Tellomak Phase 2 Trial
Session Name: 624. Hodgkin Lymphomas and T/NK Cell Lymphomas: Clinical and Epidemiological: Topics in T Cell, Sezary and Hodgkin Lymphomas
Session Date and Time: Saturday, December 9, 2023 3:00 PM
Presenter: Prof Porcu
Room: Manchester Grand Hyatt San Diego, Grand Hall B
Poster session

Publication Number: 3072
Title: Strategies to Develop Anti-KIR Mab Lacutamab in Patients with Peripheral T-Cell Lymphoma: Preliminary Monotherapy Clinical Data and Pre-Clinical Combinability Data
Session Name: 624. Hodgkin Lymphomas and T/NK cell Lymphomas: Clinical and Epidemiological: Poster II
Session Date: Sunday, December 10, 2023
Presentation Time: 6:00 PM – 8:00 PM
Location: San Diego Convention Center, Halls G-H
SAR443579 / IPH6101 (Sanofi collaboration)

Publication Number: 3474
Title: First-in-Human Study of the CD123 NK Cell Engager SAR443579 in Relapsed or Refractory Acute Myeloid Leukemia, B-Cell Acute Lymphoblastic Leukemia or High Risk-Myelodysplasia: Updated Safety, Efficacy, Pharmacokinetics and Pharmacodynamics
Session Name: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster II
Session Date: Sunday, December 10, 2023
Presentation Time: 6:00 PM-8:00 PM
Location: San Diego Convention Center, Halls G-H

On November 3, 2023 IN8bio, Inc. (Nasdaq: INAB), a leading clinical-stage biopharmaceutical company focused on innovative gamma-delta T cell therapies, reported new positive preclinical data from its induced pluripotent stem cell (iPSC) gamma-delta T cell platform at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 38th Annual Meeting (Abstract #: 637 in Exhibit Halls A and B1) (Press release, In8bio, NOV 3, 2023, View Source [SID1234636885]). The data represents a significant advance in the development of the INB-500 iPSC program towards the development of allogeneic gamma-delta T cell therapies.

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"Our deep understanding of gamma-delta T cell biology allows for significant ex vivo expansion capabilities," said William Ho, Co-founder and CEO. "We have successfully developed and utilized a robust serum and feeder-free process for generating iPSC derived gamma-delta T cells, representing an important step towards developing a truly allogeneic ‘off-the-shelf’ gamma-delta T cell source for therapeutic development."

The presented data underscores the platform’s ability to reprogram donor cells into iPSCs, expand them, and guide their differentiation into gamma-delta T cells through IN8bio’s proprietary process, which can be scaled for full GMP manufacturing. Notably, the platform enables the differentiation into both Vd1+ and Vd2+ cell subtypes using cell-type specific processes. The iPSC-derived gamma-delta T cells underwent comprehensive characterization, encompassing morphological analysis, cell surface markers and functional assessment via tumor cell killing assays. Key findings include:

iVd1+ gamma-delta T cells expressed the cell markers expected of innate gamma-delta T cells, including a strong capacity for cytokine release, indicating that the cells possess an effector phenotype.
To date, hundreds of millions of iVd1+ gamma-delta T cells have been produced from single iPSC clones at a low passage number.
The cells demonstrated robust cytotoxic activity across a variety of cancer cell lines, including ovarian, glioblastoma (GBM), acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) cell lines, potentially providing an allogeneic platform for a broad range of cancers.
Cryopreservation did not impact the cells with the Vd1+ gamma-delta T cells showing comparable cytotoxicity to fresh cells, which allows them to be expanded and banked for potential on-demand clinical use.
"High concentrations of gamma-delta T cells in both peripheral blood and in solid tumor infiltrates are associated with improved survival outcomes in both hematopoietic and solid cancers," said Lawrence Lamb, PhD, Co-founder and Chief Scientific Officer. "iPSC-derived gamma-delta cells could address existing challenges, including donor sourcing and limitations of sufficient cell numbers to sustain a therapeutic effect particularly in solid tumors. iPSCs, with their nearly unlimited self-renewal capacity, multi-lineage differentiation potential, and relative ease of generic engineering offer the possibility of therapeutic cell production for patients across a wide range of cancers."

On November 3, 2023 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported updated Phase 1 clinical, biomarker and translational data on HB-200 as a monotherapy in heavily pretreated patients with recurrent/metastatic Human Papillomavirus 16-positive (HPV16+) head and neck cancer (Press release, Hookipa Pharma, NOV 3, 2023, View Source [SID1234636884]). The data show HB-200 monotherapy induced robust, high-quality and durable tumor-specific T cell responses, which showed a trend of clinical benefit measured by a 44 percent disease control rate in a difficult-to-treat patient population. The data were presented in a poster presentation (abstract #679) at the 2023 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting.

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"The data presented at SITC (Free SITC Whitepaper) expand the body of evidence that HB-200 monotherapy has the ability to induce targeted T cells necessary for tumor control, which can translate into tumor shrinkage and encouraging clinical activity, especially in a difficult-to-treat population," said Joern Aldag, Chief Executive Officer at HOOKIPA. "As the data have matured, we have consistently delivered best-in-class T cell activation, and we continue to see the durability and functionality of tumor-specific T cells induced by HB-200. We look forward to sharing continued analyses of HB-200 across all arms of our trial in the future."

HB-200 Phase 1 biomarker results (NCT04180215)
As of March 31, 2023, 93 patients with HPV16+ recurrent/metastatic cancer were treated in the Phase 1 trial of HB-200. The goal of the trial was to determine the recommended dose for further evaluation in a Phase 2 study. All patients were heavily pretreated with a median of 3 prior therapies (range 1-11).

Biomarker and translational data results
HB-200 demonstrated a robust increase in tumor-specific CD8+ T cells in all evaluable patients with HPV16+ head and neck cancers. These results are from intracellular staining of blood samples from 35 patients across all four dose levels tested in Phase 1. An analysis of 29 of these patients—treated at either the recommended phase 2 dose (RP2D) or RP2D-1—showed that T cell increases were rapid and sustained for at least 8 months, and T cell function improved over time with repeat dosing. Quantity and quality of T cells are considered important for tumor infiltration and subsequent tumor control.

Importantly, paired biopsy data suggest an association between the induction of robust, high-quality, tumor-specific T cells after HB-200 treatment and best overall response. Paired biopsy data from 13 heavily pretreated patients show that patients who achieved disease control after treatment with HB-200 monotherapy generally had greater CD8+ T cell infiltration in tumors and the tumor microenvironment compared to patients with a best overall response of disease progression.

Additional Phase 1 data
The poster presentation also includes updated clinical activity and safety data from the Phase 1 study. As of the August 7 data cut-off, there were 27 evaluable patients with HPV16+ head and neck cancers who received HB-200 at the at RP2D or RP2D-1. Among these difficult-to-treat patients, HB-200 demonstrated a 44 percent disease control rate, with 1 confirmed partial response and 11 patients with stable disease. While overall survival is still maturing, median overall survival is approximately 13 months, with a median follow-up period of 6.3 months.

Phase 1 data also consistently demonstrate that HB-200 was generally well tolerated among 93 patients treated across all dose-level cohorts. Treatment-related adverse events grade 3 or above were reported in 11.8 percent of patients (n=11), while those leading to treatment discontinuation were reported in only 2.2 percent of patients (n=2). This favorable tolerability profile highlights the potential of HB-200—and arenaviral immunotherapies in general—to be safely combined with other immunotherapies.

Data presentation details:

Title: Characterization of tumor-specific CD8+ T cell responses in patients with recurrent/metastatic HPV16-positive head and neck cancer receiving HB-200 monotherapy as second or later-line treatment in a Phase 1 study
Presenter: Dr. Winston Wong, Head and Neck Oncologist at Memorial Sloan Kettering Cancer Center and a trial investigator
Abstract: 679
About HB-200
HB-200 is HOOKIPA’s lead oncology candidate engineered with the company’s proprietary replicating arenaviral vector platform. It comprises two single-vector compounds with arenaviral backbones based on lymphocytic choriomeningitis virus and pichinde virus. Both express the same transgene encoding an E7E6 fusion protein derived from HPV16. HB-200 is an alternating 2-vector immunotherapy designed to further focus the immune response against the encoded antigen. HB-200 in combination with pembrolizumab received Fast Track Designation from the U.S. Food and Drug Administration for the treatment of 1st-line recurrent/metastatic HPV16+ head and neck cancers.

About the HB-200 trial (NCT04180215)
This Phase 1/2 clinical trial is an open-label trial evaluating HB-200 for the treatment of advanced HPV16+ cancers. Phase 1 assessed various dose levels, regimen, and modes of administration in a post-standard of care setting. Based on safety and tolerability, initial anti-tumor activity and T cell response data, HB-200 advanced for further development in Phase 2. The Phase 2 part of the trial is open label with primary endpoints of efficacy based on objective response and disease control rate as defined by RECIST 1.1 and iRECIST. The trial is evaluating HB-200 in combination with pembrolizumab in the 1st-line and 2nd-line plus settings, as well as HB-200 alone in the post-standard of care setting.

About Human Papillomavirus-driven Cancers
Human Papillomavirus, or HPV, is a common viral infection estimated to cause about 5 percent of the worldwide cancer burden. This includes up to 60 percent of head and neck, 89 percent of cervical, 78 percent of vaginal, 88 percent of anal, 67 percent of vulvar and 50 percent of penile cancers.

While there are numerous HPV types associated with cancer, HPV16 is the most common cause of cancer. Most HPV infections are cleared from the body with no lasting consequences. However, in some cases, HPV DNA becomes integrated into chromosomal DNA. When host cells take up this DNA, they express the HPV E6 and E7 proteins. This uptake can potentially lead to cancer since expression of these proteins leads to alterations in cell cycle control, which in turn predisposes these cells to become cancerous.

On November 3, 2023 GlycoMimetics, Inc. (Nasdaq: GLYC), a late clinical-stage biotechnology company discovering and developing glycobiology-based therapies for cancers and inflammatory diseases, reported its financial results and highlights for the third quarter ended September 30, 2023. Cash and cash equivalents as of September 30, 2023 were $49.4 million (Press release, GlycoMimetics, NOV 3, 2023, View Source [SID1234636883]).

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"We look ahead to 2024 with anticipation and excitement. Topline results for our pivotal Phase 3 study of uproleselan in relapsed/refractory AML remain on track by the end of Q2 and together with our potential NDA filing before the end of 2024 represent a transformational opportunity for patients, clinicians, and our company," said Harout Semerjian, Chief Executive Officer of GlycoMimetics. "Our progress toward these important milestones, along with the upcoming presentation of independent data on uproleselan at ASH (Free ASH Whitepaper) and the expected initial results of our Phase 1a GMI-1687 study by end of Q1 2024, demonstrate our ability and ambition to deliver our development strategy and move closer to becoming a commercial stage company."

Operational Highlights

Uproleselan

In Q2, GlycoMimetics announced U.S. Food and Drug Administration (FDA) clearance of a protocol amendment to the company’s pivotal Phase 3 study of uproleselan for R/R AML. This amendment provides for a time-based analysis of the primary endpoint of overall survival after a defined cutoff date, if the 295 survival events of the originally planned event-driven analysis have not been observed by that date. With the addition of the time-based analysis, the company expects topline results by the end of Q2 2024.
The National Cancer Institute (NCI) Alliance for Clinical Trials in Oncology will conduct a planned interim analysis of event-free survival in 267 patients randomized to its Phase 2/3 clinical trial (NCI protocol A041701) evaluating uproleselan in newly diagnosed older adults with AML who are fit for chemotherapy. Enrollment of the Phase 2 portion of the study was completed in December of 2021. The company reiterates that when available, it will share these results.
The company agreed with the European Medicines Agency on a Pediatric Investigational Plan (PIP), which followed the prior agreement with the FDA in Q2 2023 on an initial Pediatric Study Plan (iPSP). The PIP and iPSP each include a deferral for study completion, and a waiver for children less than 28 days of age. As part of the pediatric plans, an NCI sponsored Phase 1/2 pediatric trial is currently being conducted by the Children’s Oncology Group Pediatric Early Phase Clinical Trials Network. The Phase 1/2 dose escalation study (NCI protocol PEPN2113) evaluates the safety and preliminary activity of uproleselan plus fludarabine and high dose cytarabine in pediatric AML patients after two or more prior therapies. The first patient in the Phase 1 portion of the study has been dosed with an expected enrollment of 18 patients.
Updated clinical data from an investigator-initiated trial studying the use of uproleselan in combination with chemotherapy for patients with treated secondary AML has been accepted for poster presentation at the ASH (Free ASH Whitepaper) Annual Meeting in December. Investigators at MD Anderson Cancer Center are conducting the Phase 1b/2 clinical trial to evaluate safety, tolerability, and preliminary efficacy of uproleselan added to cladribine and low dose cytarabine in patients with this difficult to treat subset of AML.
GMI-1687

In August, GlycoMimetics initiated a Phase 1a double-blind, single-center, randomized, placebo-controlled, sequential, single ascending dose trial in healthy adult volunteers. It is expected to enroll approximately 40 subjects. Eligible subjects will receive a single dose of GMI-1687 or placebo (6:2 ratio) via subcutaneous injection. Safety, tolerability, and pharmacokinetics of up to five dose levels (3.3, 10, 20, 40, and 80 mg) will be evaluated. GMI-1687 is a highly potent E-selectin antagonist that has potential application in inflammatory diseases with initial focus on sickle cell disease. Initial results are expected by the end of Q1 2024.
Third Quarter 2023 Financial Results:

Cash position: As of September 30, 2023, GlycoMimetics had cash and cash equivalents of $49.4 million as compared to $47.9 million as of December 31, 2022.
R&D Expenses: The company’s research and development expenses increased to $5.3 million for the quarter ended September 30, 2023, as compared to $4.9 million for the same period in 2022. The increased expenses were primarily due to the clinical development costs related to the Phase 1a trial of GMI-1687 in healthy adult volunteers, which was initiated in August 2023; the increase was partially offset by decreased personnel-related and stock-based compensation costs due to a lower number of personnel than in the prior year.
G&A Expenses: The company’s general and administrative expenses increased to $4.5 million for the quarter ended September 30, 2023, as compared to $3.8 million for the same period in 2022. The increased expenses were primarily due to higher personnel-related expenses and higher professional fees as the company advances uproleselan and prepares for potential regulatory filing and commercialization.
Shares Outstanding: Shares of common stock outstanding as of September 30, 2023 were 64,368,843.
The company will host a conference call and webcast today at 8:30 a.m. ET. To access the call by phone, please go to this registration link, and you will be provided with dial in details. Participants are encouraged to connect 15 minutes in advance of the scheduled start time.

A live webcast of the call will be available on the "Investors" tab on the GlycoMimetics website. A webcast replay will be available for 30 days following the call.

About Uproleselan

Discovered and developed by GlycoMimetics, uproleselan is an investigational, first-in-class E-selectin antagonist. Uproleselan (yoo’ pro le’se lan), currently in a broad development program including a late-stage Phase 3 trial in acute myeloid leukemia (AML), has received Breakthrough Therapy and Fast Track designations from the FDA and Breakthrough Therapy designation from the Chinese National Medical Products Administration for the treatment of adult AML patients with relapsed or refractory disease. Uproleselan is designed to block E-selectin binding and stimulation of myeloid cells. E-selectin is expressed on the surface of blood vessels, and its binding to myeloid cells confers a pro-survival effect. Uproleselan is intended to enable a novel approach to disrupting established mechanisms of leukemic cell resistance.

About GMI-1687

Discovered and developed by GlycoMimetics, GMI-1687 is a highly potent E-selectin antagonist that has been shown in animal models to be fully bioavailable following subcutaneous administration. This second-generation compound is currently being studied in a Phase 1a double-blind, single-center, randomized, placebo-controlled, sequential, single ascending dose trial in healthy adult volunteers. GMI-1687 is believed to have potential application in inflammatory diseases, and the company’s initial development focus is treatment of sickle cell disease (SCD). E-selectin is believed to play a major role in vaso-occlusive crisis (VOC), the vascular clots and blockages that cause pain crises in people living with SCD. Administration of GMI-1687 via subcutaneous injection, if successfully developed in the clinic, may enable the drug to address current challenges of IV therapies for SCD as well as offer a potential point-of-care treatment option at the onset of VOC.