On November 3, 2023 Pierre Fabre Laboratories reported an expanded global partnership with Atara Biotherapeutics, a leader in T-cell immunotherapy, leveraging its novel allogeneic Epstein-Barr virus (EBV) T-cell platform, for EBVALLO (tabelecleucel) a monotherapy already registered in the EU for the treatment of adult and pediatric patients two years of age and older with relapsed or refractory Epstein–Barr virus positive post–transplant lymphoproliferative disease (EBV+ PTLD) who have received at least one prior therapy (Press release, Pierre Fabre, NOV 3, 2023, View Source [SID1234636921]). EBV+ PTLD is a rare, acute, and potentially deadly hematologic malignancy that occurs after transplantation when patient T-cell immune responses are compromised by immunosuppression.

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This geographical expansion of the licensing rights encompasses the USA, Canada and all remaining territories. Pierre Fabre Laboratories already acquired the rights for Europe in October 2021 and EBVALLO was approved by EMA in December 2022. EBVALLO is, as of today, commercialized in Germany and Austria.

"Since EBVALLO’s marketing authorization in Europe less than a year ago, patients have already been treated in Germany, or have benefited from the treatment through the Early Access Program in place in other European countries" said Eric Ducournau, CEO of Pierre Fabre Laboratories. "We are now eager to progress on the upcoming FDA milestones in the next months and ensure American patients diagnosed with EBV+ PTLD can access this novel therapy".

"We are proud to expand our global EBVALLO partnership with Pierre Fabre Laboratories, who is committed to deliver this first-of-its kind treatment to patients in need across the globe" said Pascal Touchon, President and Chief Executive Officer of Atara.

According to the expanded Global EBVALLO Partnership between Pierre Fabre Laboratories and Atara Biotherapeutics:

Atara will receive up to $640M and significant double-digit tiered royalties on net sales from Pierre Fabre Laboratories. In addition, Pierre Fabre Laboratories has agreed to reimburse Atara for expected EBVALLO global development costs through transfer of the BLA (Biologics License Application) approval by the FDA in the US and purchase current and future EBVALLO inventory through the BLA transfer date.
Near-term payments to Atara include:
Approximately $30M in cash up front and initial inventory purchase at closing
Approximately $30M in cash up front and initial inventory purchase at closing
$100M in potential regulatory milestones through BLA approval
Substantially all EBVALLO manufacturing, clinical, and regulatory activities are planned to transition from Atara to Pierre Fabre Laboratories at the time of BLA approval transfer

Atara expects to submit the EBVALLO PTLD BLA in Q2 2024
The closing of the transaction, subject to expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and other customary closing conditions, is expected to occur in December 2023.

"Pierre Fabre Laboratories have made oncology their top priority in Medical Care. Since 2019, we have almost tripled our revenues in this therapeutic field, and we expect to pass the 500M€ bar this year. This expansion of our partnership with Atara will allow us to make a first step in the US, by far the largest oncology market in the world, and to reach even more patients in need for innovative treatments" added Eric Ducournau, CEO of Pierre Fabre Laboratories.

About EBVALLO and EBV+ PTLD
EBVALLO (tabelecleucel) is an allogeneic, EBV-specific T-cell immunotherapy which targets and eliminates EBV-infected cells in an HLA-restricted manner. EBV+ PTLD is a rare, acute, and potentially deadly hematologic malignancy that occurs after transplantation when patient T-cell immune responses are compromised by immunosuppression. It can impact patients who have undergone solid organ transplant (SOT) or allogeneic HCT. Poor median survival of 0.7 months and 4.1 months for HCT and SOT, respectively, is reported in EBV+ PTLD patients for whom standard of care failed, underscoring the significant need for new therapeutic options.

EBVALLO has orphan designation in Europe. Orphan designation is reserved for medicines treating life-threatening or chronically debilitating diseases that are rare (affecting not more than five in 10,000 people in the EU).

On November 3, 2023 Sumitomo Pharma America, Inc. (SMPA) reported preliminary clinical data for investigational agents TP-3654, a selective oral PIM1 kinase inhibitor, and DSP-5336, an inhibitor of the menin and mixed-lineage leukemia (MLL) protein interaction (Press release, Sumitomo Pharmaceuticals, NOV 3, 2023, View Source [SID1234636920]). These data will be presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, held December 9-12 in San Diego, Calif.

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Preliminary results from the ongoing Phase 1/2 study of TP-3654 monotherapy in patients with relapsed or refractory myelofibrosis who were previously treated with or ineligible for a JAK inhibitor will be presented in an oral presentation at ASH (Free ASH Whitepaper). In this study, oral TP-3654 was well-tolerated with limited myelosuppressive adverse events. TP-3654 exhibited early signs of clinical activity including spleen volume reduction, total symptom score improvement, and correlating cytokine reductions.

SMPA will also present a poster on preliminary clinical data from the ongoing Phase 1/2 first-in-human study of oral DSP-5336, in patients with relapsed or refractory acute leukemia. Preliminary data showed that DSP-5336 was well-tolerated with no dose limiting toxicities, including no observed cardiac signals. Target pharmacodynamic changes were observed with treatment, including rapid decreases in genes commonly expressed in leukemia (HOXA9, MEIS1, and PBX3). These changes were seen particularly in patients with acute myeloid leukemia characterized by a KMT2A (MLL) gene rearrangement or a mutation in the NPM1 gene.

"We are encouraged by the early signs of clinical activity shown in the preliminary results from the TP-3654 and DSP-5336 Phase 1/2 trials. We look forward to sharing the data and having important scientific engagement involving both agents at the annual ASH (Free ASH Whitepaper) meeting in December," said Jatin Shah, M.D., Chief Oncology Development Officer, SMPA. "Improving patient outcomes and developing new oncological treatments is a primary focus for SMPA and we remain committed to exploring the potential of our diverse research pipeline."

Abstract Title

Detail

Lead Author

Phase 1/2 Study of TP-3654, a Selective PIM1 Kinase Inhibitor: Preliminary Data Showed Clinical Activity and Cytokine Reductions in Relapsed/Refractory Myelofibrosis Patients

Session Name: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Myelofibrosis: New Therapeutic Frontiers

Session Date:

Sunday, December 10

Session Time: 4:30 p.m. – 6:00 p.m. PST

Presentation Time:

4:45 p.m. PST

Location: Marriott Marquis San Diego Marina, Pacific Ballroom Salons 21-22

Oral Podium Presentation

Lindsay A.M. Rein, M.D.

Phase 1/2 First-in-Human Study of the Menin-MLL Inhibitor DSP-5336 in Patients with Relapsed or Refractory Acute Leukemia

Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II

Session Date:

Sunday, December 10

Presentation Time:

6:00 p.m. – 8:00 p.m. PST

Location: San Diego Convention Center, Halls G-H

Poster Presentation

Naval Daver, M.D.

About TP-3654
TP-3654 is an oral investigational inhibitor of PIM1 kinase, which has shown potential antitumor and antifibrotic activity through multiple pathways, including induction of apoptosis in preclinical models.1,2 TP-3654 was observed to inhibit proliferation and increase apoptosis in murine and human hematopoietic cells expressing the clinically relevant JAK2V617F mutation.2 TP-3654 alone and in combination with ruxolitinib showed white blood cell and neutrophil count normalization, and also reduced spleen size and bone marrow fibrosis in JAK2V617F and MPLW515L murine models of myelofibrosis.2 The safety and efficacy of TP-3654 is currently being clinically evaluated in a Phase 1/2 study in patients with intermediate and high-risk myelofibrosis (NCT04176198). The U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for TP-3654 for the indication of myelofibrosis in May 2022.

About DSP-5336
DSP-5336 is an investigational small molecule inhibitor of the menin and mixed-lineage leukemia (MLL) protein interaction. Menin is a scaffold nuclear protein that plays various key roles in biological pathways, including cell growth regulation, cell cycle control, genomic stability, bone development, and hematopoiesis.3,4 In preclinical studies, DSP-5336 has shown selective growth inhibition in human acute leukemia cell lines with KMT2A (MLL) rearrangements or NPM1 mutations.3,5 The safety and efficacy of DSP-5336 is currently being clinically evaluated in a Phase 1/2 dose escalation/dose expansion study in patients with relapsed or refractory acute leukemia (NCT04988555). The FDA granted Orphan Drug Designation for DSP-5336 for the indication of acute myeloid leukemia in June 2022.

On November 3, 2023 Hopewell Therapeutics, a biotechnology company with a tissue targeted lipid nanoparticle (ttLNP) platform harnessing unique ionizable lipid chemistry, reported that it will have both an oral and a poster presentation on preclinical data from the Company’s Oncology programs at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting, being held November 1 – 5, 2023, in San Diego, California (Press release, Hopewell Therapeutics, NOV 3, 2023, View Source [SID1234636919]).

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Details of the presentations are as follows:

Poster Presentation

Title: Tissue-targeted lipid nanoparticle delivery for mRNA encoding bispecific T-cell engager demonstrated potent antitumor effects on both hematological malignancies and solid tumors
Presenter: Xin Kai, Ph.D., Director of Discovery Biology, Hopewell Therapeutics
Abstract Number: 1358
Date and Time: Saturday, November 4th, 2023, from 9:00 a.m.– 8:30 p.m. PDT
Location: Exhibit Halls A and B1 – San Diego Convention Center

Oral Presentation

Title: Tissue-targeted lipid nanoparticle delivery for mRNA encoding bispecific T-cell engager demonstrated potent antitumor effects on both hematological malignancies and solid tumors
Presenter: Xin Kai, Ph.D., Director of Discovery Biology, Hopewell Therapeutics
Abstract Number: 1358
Session: 205b | Rapid-Oral Abstract-Clinical
Date and Time: Saturday, November 4th, 2023, at 12:40 p.m. PDT
Location: Ground Level – Exhibit Hall C – San Diego Convention Center

Posters will be available here at the start of the scientific session.

On November 3, 2023 Immunitas Therapeutics ("Immunitas"), a clinical stage precision immunotherapy company committed to discovering and developing novel, differentiated therapeutics for patients with cancer, reported the first proof-of-concept data on its second program, a myeloid and B cell modulating anti CLEC2D-Toll-like receptor 9 (TLR9) agonist conjugate, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 38th Annual Meeting (SITC 2023), held November 1-5 in San Diego, California (Press release, Immunitas Therapeutics, NOV 3, 2023, https://www.prnewswire.com/news-releases/immunitas-therapeutics-presents-new-data-for-tlr9-agonist-conjugate-at-the-society-for-immunotherapy-of-cancer-2023-annual-meeting-301976730.html [SID1234636918]).

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CLEC2D is a C-type lectin-like protein that is broadly expressed on a subset of immune cells and is naturally internalized by myeloid and B cells. Upon internalization, it can act as a vehicle to deliver histone/DNA complexes to endosomal TLR9, stimulating inflammatory responses. Harnessing this CLEC2D-mediated internalization offers a compelling immunotherapy approach of delivering CpG to TLR9 that can stimulate inflammatory responses with the potential to improve recruitment of functional T and NK cells into tumor tissues.

"The inability to induce adequate responses in tumors with poor T and NK cell infiltration has limited the clinical impact of existing immunotherapies. At Immunitas, we prioritize targeting novel biological pathways with first-in-class molecules that have potential to show monotherapy efficacy in early clinical development. This program leverages our specialized knowledge of the CD161-CLEC2D pathway, and we are excited to be progressing a therapeutic with demonstrated potential to address the challenge of poor T and NK cell infiltration and truly benefit patients who lack immunotherapy options," said Amanda Wagner, President and Chief Executive Officer of Immunitas Therapeutics. "We are pleased to have our team present this data demonstrating in vitro proof-of-concept for our anti-CLEC2D antibody conjugated to a CpG oligonucleotide."

The presented data showed that treatment with Immunitas’ anti CLEC2D-TLR9 agonist immune stimulating antibody complex (ISAC) induced pro-inflammatory responses in THP1-TLR9 reporter cell lines and dramatically increased production of IFN-α, a critical cytokine for induction of anti-tumor T cells, in human plasmacytoid dendritic cells. Treatment of CLEC2D-expressing B cells with the ISAC molecule resulted in sustained B cell proliferation and upregulation of co-stimulatory molecules, enabling stronger induction of T cell immune responses.

The results further confirmed that CLEC2D is expressed on tumor-associated macrophages (TAMs)—macrophages that strongly contribute to the immunosuppression in tumor microenvironments and can also directly promote tumor cell growth. Treatment of TAMs with Immunitas’ anti CLEC2D-TLR9 agonist ISAC reversed TAM-mediated suppression of T cell proliferation and activation, indicating that TLR9 agonism can reprogram TAMs towards an inflammatory state. Studies in human peripheral blood mononuclear cells (PBMCs) has demonstrated that treatment with the anti CLEC2D-TLR9 agonist ISAC did not trigger release of inflammatory cytokines, providing a preliminary indication of safety.

The presentation will be available on the Immunitas website following the meeting.

Presentation Details for SITC (Free SITC Whitepaper) 2023
Title: Anti CLEC2D-TLR9 agonist conjugate binds to and internalizes CLEC2D on myeloid cells, plasmacytoid DCs and B cells leading to robust TLR pathway activation and inflammatory cytokine production
Abstract Number: 1131
Date/Time: Friday, November 3, 2023, 9:00am – 7:00pm PDT

About CLEC2D
CLEC2D is a C-type lectin-like protein broadly expressed on a subset of immune cells and tumor cells. It is also the ligand for CD161, target for Immunitas’ lead investigational candidate, IMT-009. Additionally, CLEC2D naturally internalizes in TLR9 expressing myeloid and B cells. Building on this biology, Immunitas is developing a novel anti CLEC2D-TLR9 agonist immune stimulating antibody complex (ISAC) comprising a fully human anti-CLEC2D antibody conjugated to a CpG oligonucleotide. This CLEC2D-TLR9-ISAC molecule is capable of triggering TLR9 pathway activation in myeloid cells, B cells, and plasmacytoid dendritic cells and enabling induction of sustained T cell immunity. Harnessing this biology offers a compelling immunotherapy approach that stimulates inflammatory responses that may improve recruitment of functional T and NK cells in tumors with otherwise poor T cell infiltration.

On November 3, 2023 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system cancers, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to rhenium (186Re) obisbemeda for the treatment of breast cancer with leptomeningeal metastases (LM) (Press release, PLUS THERAPEUTICS, NOV 3, 2023, View Source [SID1234636917]).

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ODD status is granted by the FDA to an investigational drug or biological product intended to prevent, diagnose or treat a rare diseases or condition affecting fewer than 200,000 people in the United States. Companies granted ODD are eligible for certain benefits, including assistance in the drug development process, tax credits for clinical costs, exemptions from certain FDA fees and 7 years of post-approval marketing exclusivity.

"Receiving Orphan Drug Designation from the FDA is important validation of our radiotherapeutic candidate for breast cancer patients with LM who currently have no FDA-approved treatment options," said Marc H. Hedrick M.D., President and Chief Executive Officer of Plus Therapeutics. "LM is a rapidly progressing and fatal complication of several cancers, including breast cancer, and incidence continues to rise. ODD status, together with the previously granted Fast Track designation, underscores the significant and urgent need for new treatment options for LM. We believe rhenium (186Re) obisbemeda has the potential to address this unmet need, and we look forward to continued progress of our ReSPECT-LM program."

Rhenium (186Re) obisbemeda is currently being evaluated in the ReSPECT-LM Phase 1/2a dose escalation clinical trial. Cohort 4 of the ReSPECT-LM trial recently completed enrollment, and the Company anticipates moving into Cohort 5 following standard safety review. Updates on the ReSPECT-LM trial will be presented at the Society for Neuro-Oncology Annual Meeting November 15-19, 2023. In addition to ODD, the FDA previously granted rhenium (186Re) obisbemeda Fast Track designation for the treatment of LM.

About Leptomeningeal Metastases (LM)

LM is a rare complication of cancer in which the primary cancer spreads to the cerebrospinal fluid (CSF) and leptomeninges surrounding the brain and spinal cord. All malignancies originating from solid tumors, primary brain tumors, or hematological malignancies have this LM complication potential with breast cancer as the most common cancer linked to LM, with 3-5% of breast cancer patients developing LM. Additionally, lung cancer, GI cancers and melanoma can also spread to the CSF and result in LM. LM occurs in approximately 5% of people with cancer and is usually terminal with 1-year and 2-year survival of just 7% and 3%, respectively. The incidence of LM is on the rise, partly because cancer patients are living longer and partly because many standard chemotherapies cannot reach sufficient concentrations in the spinal fluid to kill the tumor cells, yet there are no FDA-approved therapies specifically for LM patients, who often succumb to this complication within weeks to several months, if untreated.

About Rhenium (186Re) obisbemeda

Rhenium (186Re) obisbemeda is a novel injectable radiotherapy specifically formulated to deliver highly targeted high dose radiation in CNS tumors in a safe, effective and convenient manner to optimize patient outcomes. Rhenium (186Re) obisbemeda has the potential to reduce risks and improve outcomes for CNS cancer patients, versus currently approved therapies, with a more targeted and potent radiation dose. Rhenium-186 is an ideal radioisotope for CNS therapeutic applications due to its short half-life, beta energy for destroying cancerous tissue and gamma energy for live imaging. Rhenium (186Re) obisbemeda is being evaluated for the treatment of recurrent glioblastoma and leptomeningeal metastases in the ReSPECT-GBM and ReSPECT-LM clinical trials. ReSPECT-GBM is supported by an award from the National Cancer Institute (NCI), part of the U.S. National Institutes of Health (NIH), and ReSPECT-LM is funded by a three-year $17.6M grant by the Cancer Prevention & Research Institute of Texas (CPRIT).