On May 20, 2021 NeoImmuneTech, Inc. (KOSDAQ: 950220), a clinical-stage T cell-focused biopharmaceutical company, reported that new data from two clinical trials evaluating the company’s lead asset NT-I7 (efineptakin alfa) will be presented during poster sessions at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, to be held in a virtual platform June 4-8, 2021 (Press release, NeoImmuneTech, MAY 20, 2021, View Source [SID1234580386]). The data come from clinical studies evaluating NT-I7, a novel long-acting human IL-7, 1. in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) as a treatment for advanced solid tumors, and 2. given concurrently with adjuvant chemotherapy in patients with high-grade gliomas.

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Details related to the poster presentations are as follows:

Title: Safety, Pharmacokinetics, Pharmacodynamics Profiles and Preliminary Antitumor Activity of Phase 1b/2a Study of NT-I7, a Long-Acting Interleukin-7, plus Pembrolizumab in Patients with Advanced Solid Tumors: The Phase 1b Data Report
Lead Author: Aung Naing, MD, The University of Texas MD Anderson Cancer Center
Abstract Number: 2594
Poster Session: Developmental Therapeutics—Immunotherapy, on demand starting at 9:00am ET, June 4, 2021

Title: A phase I/II study to evaluate the safety and efficacy of a novel long-acting interleukin-7, NT-I7, for patients with newly diagnosed high-grade gliomas after chemoradiotherapy: the interim result of the phase I data
Lead Author: Jian Li Campian, MD, PhD, Washington University School of Medicine in St. Louis/Siteman Cancer Center
Abstract Number: 2040
Poster Session: Central Nervous System Tumors, on demand starting at 9:00am ET, June 4, 2021

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., USA.

About NT-I7

NT-I7 (efineptakin alfa) is the only clinical-stage long-acting human IL-7, and is being developed for oncologic and immunologic indications, in which T cell amplification and enhanced functionality may provide clinical benefit. IL-7 is a fundamental cytokine for naïve and memory T cell development and for sustaining immune response to chronic antigens (as in cancer) or foreign antigens (as in infectious diseases). In clinical trials to date, NT-I7 has exhibited favorable PK/PD and safety profiles, both as a monotherapy and in combination with other anticancer treatments. NT-I7 is being studied in multiple clinical trials in solid tumors and as a vaccine adjuvant. Studies are being planned for testing in hematologic malignancies, additional solid tumors and other immunology-focused indications.

On May 20, 2021 Xilio Therapeutics, a biotechnology company developing tumor-selective immuno-oncology therapies for patients with cancer, reported the presentation of data from preclinical studies of XTX202, its tumor-selective interleukin-2 (IL-2) product candidate, demonstrating selective anti-tumor activity and favorable tolerability with no systemic toxicity observed (Press release, Xilio Therapeutics, MAY 20, 2021, View Source [SID1234580385]). The data will be reported in a poster entitled "XTX202, a protein-engineered IL-2, exhibits tumor-selective activity in mice without peripheral toxicities in non-human primates" at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The poster will be made available on the ASCO (Free ASCO Whitepaper) Annual Meeting website at the start of the meeting on June 4, 2021 at 9am ET.

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Xilio is leveraging its proprietary platform to engineer novel molecules that are designed to be activated in the tumor microenvironment (TME) and have the potential to result in localized, tumor-selective clinical activity without dose-limiting toxicities. XTX202, Xilio’s lead cytokine product candidate, is an engineered form of IL-2 that is masked with a protein domain to prevent binding activity until cleaved off by TME-associated proteases.

"The power of IL-2 to activate the immune system as a cancer therapeutic is promising, but utility of IL-2 agents has historically been greatly reduced due to toxicities," said Rónán O’Hagan, Ph.D., chief scientific officer of Xilio. "We have engineered XTX202 to overcome those challenges, with key features designed to ensure it is released and activated locally within the TME, where it selectively binds to IL-2 receptors on immune cells. We are excited to present these data which, for the first time, demonstrate selective tumor-inhibition and favorable tolerability of XTX202 in preclinical models. With these data, we plan to complete IND-enabling studies and submit an IND application in the second half of 2021 to evaluate XTX202 in patients with solid tumors."

Data reported in the poster are from preclinical studies in both mouse and non-human primate (NHP) models, including comparisons between XTX202 and XTX200, a non-masked, parent version of XTX202, as well as aldesleukin, a synthetic form of IL-2 approved for certain cancer indications by the U.S. Food and Drug Administration. Key data include:

XTX202, in its masked form, did not bind to IL-2 receptors, and matrix metalloproteinase (MMP) activation of XTX202 restored full binding to IL-2 receptor beta that is found on immune activating CD8 T cells and natural killer cells, illustrating the tight, protease-dependent control of IL-2 activity conferred by XTX202.
XTX202 was engineered to eliminate binding to IL-2Ra in order to enhance immune activation by CD8 T cells and NK cells, and to minimize immune suppression by regulatory T cells. No binding to IL-2Ra was detectable even after MMP-dependent activation of XTX202.
XTX202 inhibited tumor growth in syngeneic mouse models as a single agent with no evidence of toxicity or peripheral immune activation, thus demonstrating tumor selective activity.
XTX202 matched the tumor growth inhibition activity of aldesleukin and the non-masked control XTX200, without activation of immune response outside the TME, thereby avoiding the body weight loss in mice that was associated with doses of XTX200 or aldesleukin required for tumor growth inhibition.
XTX202 was well-tolerated in repeat dose studies in NHPs at doses up to 30 mg/kg.
XTX202 is estimated to have a greater than 100-fold improvement in therapeutic index compared to aldesleukin.

On May 20, 2021 GammaDelta Therapeutics ("GammaDelta"), a company focussed on exploiting the unique properties of gamma delta (γδ) T cells for immunotherapy, reported the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for the Company’s allogeneic variable delta 1 (Vδ1) gamma-delta (γδ) T cell therapy, GDX012, to be investigated as a treatment for haematological malignancies (Press release, GammaDelta Therapeutics, MAY 20, 2021, View Source [SID1234580384]). The FDA also granted orphan drug designation to allogeneic Vδ1 γδ T cell therapy (GDX012) for the treatment of Acute Myeloid Leukaemia (AML).

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Dr. Paolo Paoletti, CEO of GammaDelta Therapeutics, commented: "The clearance of our IND application for GDX012 marks an important step for our company in establishing a portfolio of innovative allogeneic cell therapies. The unique properties of Vδ1 γδ T cells will be evaluated for the first time in a clinical study for patients with AML. This important milestone results from our efforts to establish a robust pipeline of cellular immunotherapies derived from our proprietary platforms and processes for the isolation and expansion of Vδ1 γδ T cells from both blood and tissues for targeting haematological malignancies and solid tumours."

GammaDelta plans to initiate a Phase 1 clinical trial for patients with measurable residual disease (MRD) positive AML. Expected to begin later in 2021 as a multicentre study in the US, the trial will evaluate safety, tolerability and anti-leukemic activity of GDX012. GammaDelta Therapeutics is advancing its novel T cell platform under an ongoing collaboration with Takeda Pharmaceutical Company Limited ("Takeda") formed in 2017.

Dr. Michael Koslowski, Head of R&D and Chief Medical Officer of GammaDelta Therapeutics, said: "Although progress has been made in the treatment of AML, the median overall five-year survival rate for patients diagnosed with AML remains under 30 percent. With the development of GDX012 we are aiming to change the treatment paradigm for AML and potentially other haematologic malignancies. The unique biological characteristics of Vδ1 γδ T cells offer a first-in-class Vδ1 γδ T cell therapy for AML, where the development of cell therapies has been historically limited due to the lack of specific targets."

Dr. Chris Arendt, Oncology Therapeutic Area Unit Head of Takeda, commented: "The progression of GammaDelta Therapeutics’ platform technology underscores the potential of γδ T cells and the power of the innate immune system. Through collaboration with pioneers like GammaDelta Therapeutics, we hope to advance next-generation cell therapies and to maximise off-the-shelf treatments in the battle against hard-to-treat cancers."

GammaDelta has developed proprietary technologies to generate both blood-and tissue-derived allogeneic immunotherapies based on Vδ1 γδ T cells for the treatment of haematologic malignancies and solid tumours. Both platforms have enabled the creation of highly active and selective non-engineered and genetically engineered allogeneic cell therapies, which demonstrate cellular activity and tumour cell killing capacity. Vδ1 γδ T cells are a unique subset of T cells that specifically recognise and are activated by molecular patterns of dysregulation on cancer cells. The non-MHC-restricted activity of Vδ1 γδ T cells makes them a unique cell type for the development of fully allogeneic, "off-the-shelf" cell therapies.

On May 20, 2021 Crescendo Biologics Ltd (Crescendo), a clinical stage immuno-oncology company developing novel, targeted T cell enhancing therapeutics, reported that the first patient has entered the POTENTIA trial, a Phase 1, open-label, monotherapy study of CB307, the most advanced Humabody in Crescendo’s portfolio of T cell enhancers (Press release, Crescendo Biologics, MAY 20, 2021, View Source [SID1234580383]).

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CB307 is a unique, half-life extended Humabody targeting prostate-specific membrane antigen (PSMA) and the potent co-stimulatory molecule CD137 (4-1BB). Monospecific monoclonal antibodies against CD137 have been shown to enhance T cell activity in clinical studies as a cancer therapy, and CB307 is designed to enable potent, conditional and tumour-specific T cell activation whilst avoiding systemic toxicity.

The POTENTIA trial is a Phase 1, multi-centre, non-randomised study of CB307 in patients with advanced and/or metastatic PSMA-positive solid tumours. The study is designed to recruit up to 50 patients across dose escalation and expansion cohorts. The primary endpoint of the trial is to assess the safety and tolerability of CB307 and to determine the maximum tolerated dose.

Additional endpoints include initial evaluation of clinical efficacy, and the trial also includes a comprehensive panel of pharmacokinetic and other translational endpoints. Initial data from the dose escalation part of the trial are expected to be presented at a medical conference in 2022.

More information about the POTENTIA trial can be found on clinicaltrials.gov via NCT04839991 and in the poster recently presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in April 2021.

Dr Kenji Hashimoto, Chief Medical Officer of Crescendo Biologics, said: "Recent clinical data have provided important validation for both PSMA and CD137 as therapeutic targets. We are therefore delighted to have initiated the CB307 clinical programme with our investigators. CB307 is a unique immuno-oncology therapy which we believe has potential to bring significant benefit to people suffering from hard-to-treat cancers."

Theodora Harold, Chief Executive Officer of Crescendo Biologics, added: "The initiation of the POTENTIA trial is an important milestone for Crescendo as it marks the beginning of clinical development of the first product candidate in our proprietary pipeline of T cell enhancing Humabody therapeutics. We have reached this point thanks to the dedication and focus of the Crescendo team, and we look forward to applying the data emerging from this trial to guide future clinical programmes."

On May 20, 2021 TRACON Pharmaceuticals (NASDAQ: TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted cancer therapeutics and utilizing a cost efficient, CRO-independent product development platform to partner with ex-U.S. companies to develop and commercialize innovative products in the U.S., reported the presentation of two abstracts at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 annual meeting, being held virtually June 4-8, 2021 (Press release, Tracon Pharmaceuticals, MAY 20, 2021, View Source [SID1234580380]).

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Poster Presentation:
Abstract Title: ENVASARC: A Pivotal Trial of Envafolimab, and Envafolimab in Combination with Ipilimumab, in Patients with Advanced or Metastatic Undifferentiated Pleomorphic Sarcoma or Myxofibrosarcoma who have Progressed on Prior Chemotherapy
Abstract Number: TPS11581
Poster Session: Sarcoma
Session Start: June 4, 2021 9:00AM EDT

Poster Discussion Session:
Abstract Title: Preliminary safety, pharmacokinetics (PK), pharmacodynamics (PD) and clinical efficacy of Uliledlimab (TJ004309), a differentiated CD73 antibody, in combination with atezolizumab in patients with advanced cancer
Abstract Number: 2511
Poster Session: Development Therapeutics-Immunotherapy
Session Start: June 4, 2021 9:00AM EDT
The posters will be available on the publications page of the company’s website following presentation.

About Envafolimab

Envafolimab (KN035), a novel, single-domain antibody against PD-L1, is the first subcutaneously injected PD-(L)1 inhibitor to be studied in pivotal trials. Envafolimab is currently being studied in the ENVASARC Phase 2 pivotal trial in the U.S. sponsored by TRACON, has been studied in a completed Phase 2 pivotal trial as a single agent in MSI-H/dMMR advanced solid tumor patients in China and is being studied in an ongoing Phase 3 pivotal trial in combination with gemcitabine and oxaliplatin in advanced biliary tract cancer patients in China, with both Chinese trials sponsored by 3D Medicines. TRACON’s partners Alphamab Oncology and 3D Medicines submitted an NDA to the NMPA in China for envafolimab in MSI-H/dMMR cancer that was accepted for review in December 2020 and granted priority review in January 2021. In the Phase 2 MSI-H/dMMR advanced solid tumor trial, the confirmed objective response rate (ORR) by blinded independent central review in MSI-H/dMMR colorectal cancer (CRC) patients treated with envafolimab who failed a fluoropyrimidine, oxaliplatin and irinotecan was 32%, which was similar to the 28% confirmed ORR reported in the Opdivo package insert in MSI-H/dMMR CRC patients who failed a fluoropyrimidine, oxaliplatin, and irinotecan and the 33% confirmed ORR reported for Keytruda in MSI-H/dMMR CRC patients who failed a fluoropyrimidine, oxaliplatin and irinotecan in cohort A of the KEYNOTE-164 clinical trial.

About ENVASARC (NCT04480502)

The ENVASARC pivotal trial is a multi-center, open label, randomized, non-comparative, parallel cohort study at approximately 25 top cancer centers in the United States that began dosing in December 2020. TRACON expects the trial to enroll 160 patients with UPS or MFS who have progressed following one or two lines of prior treatment and have not received an immune checkpoint inhibitor, with 80 patients enrolled into cohort A of treatment with single agent envafolimab and 80 patients enrolled in cohort B of treatment with envafolimab and Yervoy. The primary endpoint is ORR by blinded independent central review with duration of response a key secondary endpoint.

About TJ004309

TJ004309 is a novel, humanized antibody against CD73, an ecto-enzyme expressed on stromal cells and tumors that converts extracellular adenosine monophosphate (AMP) to adenosine, which is highly immunosuppressive. TJ004309 is currently being studied in an ongoing Phase 1 trial to assess safety and preliminary efficacy as a single agent and when combined with the PD-L1 checkpoint inhibitor Tecentriq in patients with advanced solid tumors.