On April 12, 2021 Instil Bio, Inc. ("Instil") (Nasdaq: TIL), a clinical-stage biopharmaceutical company focused on developing tumor infiltrating lymphocyte, or TIL, therapies for the treatment of patients with cancer, reported that clinical data from a compassionate use program for the treatment of metastatic melanoma at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) virtual meeting April 10 – 15, 2021 (Press release, Instil Bio, APR 12, 2021, View Source [SID1234583990]). The presentation abstract and additional information is available on the AACR (Free AACR Whitepaper) conference web site at www.aacr.org.

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"Despite the recent advances in immunotherapy for solid tumors, many patients do not receive clinical benefit or experience relapse after an initial remission," said Robert Hawkins, MBBS FRCP, PhD, Chief Strategy Advisor to Instil and presenting study author. "In this compassionate use setting in which patients had exhausted all other available therapies, a one-time treatment with TILs was able to induce a remission in more than half of the treated patients."

"This presentation highlights the potential for ITIL-168 to produce deep and durable remissions in patients with advanced melanoma," said Bronson Crouch, Chief Executive Officer of Instil. "We eagerly anticipate beginning a global Phase 2 clinical trial investigating ITIL-168 for the treatment of advanced melanoma later this year."

In this compassionate use program, 21 patients with stage IV cutaneous melanoma were treated between 2011 and 2019 at the Christie Hospital in Manchester, United Kingdom with TILs manufactured by Instil. All TIL products were generated in Instil’s company-operated, in-house manufacturing facilities in Manchester.

Among the 21 patients, 14 (67%) achieved an objective response, with four (19%) achieving a complete response. All complete responders remained in remission at the time of data cutoff with those remissions ranging in duration from 30 months to over 80 months from TIL infusion. With a median duration of follow-up of 52.2 months, the median overall survival was 21.3 months with nearly half of patients experiencing long term survival. Side effects of treatment were largely transient, self-limited and generally attributable to the lymphodepleting chemotherapy regimen and post-TIL IL-2 treatment.

The company plans to submit these results for peer-reviewed publication in 2021.

Instil expects to begin a Phase 2 trial of ITIL-168 in advanced melanoma patients in the second half of 2021. The company anticipates obtaining topline safety and efficacy data in 2023, which could support the submission of a BLA to the FDA in 2023 and a Marketing Authorization Application to the European Medicines Agency in 2024.

Poster Information:

Title: Clinical Feasibility and Treatment Outcomes with Unselected Autologous Tumor Infiltrating Lymphocyte Therapy in Patients with Advanced Cutaneous Melanoma

Session Type: E-Poster Session

Session Title: Adoptive Cell Therapy

Abstract Number: LB150

About ITIL-168

ITIL-168 is an investigational, autologous cell therapy made from tumor infiltrating lymphocytes, or TILs. ITIL-168 is manufactured with Instil’s proprietary, optimized, and scalable manufacturing process, which has been designed to capture and preserve the maximum diversity of each patient’s TILs; the manufacturing process also offers significant scheduling flexibility for patients and physicians at the time of both tumor resection and TIL treatment. Instil plans to investigate ITIL-168 in a global phase 2 trial in advanced melanoma in 2021 and additional solid tumor indications in Phase 1 clinical trials beginning in 2022.

On April 12, 2021 Genmab A/S (Nasdaq: GMAB) reported the initiation of a share buy-back program to mitigate dilution from warrant exercises and to honor our commitments under our Restricted Stock Units program (Press release, Genmab, APR 12, 2021, View Source [SID1234577893]).

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The share buy-back program is expected to be completed no later than June 30, 2021 and comprises up to 200,000 shares.

The following transactions were executed under the program from April 5, 2021 to April 9, 2021:

Details of each transaction are included as an appendix to this announcement.

Following these transactions, Genmab holds 208,977 shares as treasury shares, corresponding to 0.32% of the total share capital and voting rights.

The share buy-back program is undertaken in accordance with Regulation (EU) No. 596/2014 (‘MAR’) and the Commission Delegated Regulation (EU) 2016/1052, also referred to as the "Safe Harbour Regulation." Further details on the terms of the share buy-back program can be found in our company announcement no. 11 dated February 23, 2021.

On April 12, 2021 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of resistance in cancer, reported four preclinical poster presentations at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) virtual annual meeting (Press release, ORIC Pharmaceuticals, APR 12, 2021, View Source [SID1234577910]).

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ORIC-101: Glucocorticoid Receptor (GR) Antagonist
ORIC-101 is a potent and selective GR antagonist, with two distinct mechanisms of action being evaluated in two Phase 1b trials in combination with: (1) Abraxane (nab-paclitaxel) in advanced or metastatic solid tumors and (2) Xtandi (enzalutamide) in metastatic prostate cancer.

Key findings of the presentation:

GR upregulation and activation, an established resistance mechanism for antiandrogens, may drive resistance when antiandrogens are combined with AKT inhibitors.
ORIC-101 was able to overcome this resistance and restore antitumor activity in preclinical prostate cancer cell lines.
Poster Presentation:

GR antagonist ORIC-101 overcomes GR-mediated resistance to the combination of AR and AKT inhibition in preclinical prostate cancer cell lines (Abstract 1420)
ORIC-533: CD73 Inhibitor
ORIC-533 is a highly potent, orally bioavailable CD73 inhibitor and has demonstrated greater potency in preclinical studies compared to an antibody approach and other small molecule CD73 inhibitors.

Key findings of the presentation:

Nanomolar concentrations of ORIC-533 efficiently rescued cytotoxic T-cell function in the presence of high AMP concentrations, reflective of levels observed in tumors.
Inhibitors of adenosine receptors A2A or A2A/B were only able to rescue CD8+ T-cell function in the context of low micromolar AMP, thus may be ineffective in tumors with moderate or high AMP and adenosine levels.
ORIC-533 has potential best-in-class properties in reversing immunosuppression in tumors.
Poster Presentation:

Blocking adenosine production with ORIC-533, a CD73 inhibitor with best-in-class properties, reverses immunosuppression in high-AMP environments (Abstract LB-163)
ORIC-944: PRC2 Inhibitor
ORIC-944 is a potent and selective allosteric inhibitor of polycomb repressive complex 2 (PRC2) and targets its regulatory embryonic ectoderm development (EED) subunit.

Key findings of the presentation:

ORIC-944 has potential best-in-class drug properties compared to first generation PRC2 inhibitors, including a clean CYP profile.
ORIC-944 demonstrated superior activity compared to an EZH2 inhibitor in an in vivo DLBCL model.
ORIC-944 demonstrated strong tumor growth inhibition as a single agent with once daily dosing in both enzalutamide-responsive and enzalutamide-resistant in vivo prostate cancer models.
Poster Presentation:

ORIC-944, a potent and selective allosteric PRC2 inhibitor, demonstrates robust in vivo activity in prostate cancer models (Abstract 1131).
ORIC-114: EGFR/HER2 Inhibitor
ORIC-114 is a brain penetrant, orally bioavailable, irreversible inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations.

Key findings of the presentation:

ORIC-114 is highly selective for the EGFR family of receptors with superior kinome selectivity compared to other exon 20 inhibitors.
ORIC-114 demonstrated low nanomolar potency across exon 20 insertion variants in biochemical and cell-based assays.
Significant tumor regression was observed in multiple EGFR exon 20 patient-derived xenograft models using once daily oral administration of ORIC-114.
ORIC-114 displayed superior brain exposure relative to other compounds targeting exon 20 insertion mutations, and greater activity compared to other EGFR inhibitors in an intracranial NSCLC EGFR mutant xenograft model.
Poster Presentation:

ORIC-114, a brain penetrant, orally bioavailable, irreversible inhibitor selectively targets EGFR and HER2 exon20 insertion mutants and regresses intracranial NSCLC xenograft tumors (Abstract 1466).

On April 12, 2021 FairJourney Biologics S.A (FJB) and IONTAS Limited (IONTAS), leaders in the discovery and optimisation of VHH fully human antibodies, reported a collaboration with global immunology company, argenx to harness IONTAS’ proprietary mammalian display technology (Press release, FairJourney Biologics, APR 12, 2021, View Source [SID1234577927]). The goal of the collaboration is to explore diverse panels of novel antibody candidates, with the potential to advance select candidates into the argenx discovery pipeline.

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Under the terms of the agreement, FJB and IONTAS will provide argenx with access to IONTAS’ novel mammalian display technology, which can generate abundant therapeutic antibody leads, selecting for key attributes that may address the novel targets or pathways that argenx is exploring. The agreement will also provide a dedicated full-time FJB/IONTAS team assigned to the project.

FJB/IONTAS and argenx have highly complementary capabilities for identification of potential next-generation antibody candidates, including argenx’s pipeline of investigational immunology therapies aimed at improving the lives of people living with severe autoimmune diseases and cancer. Through its Immunology Innovation Program, argenx collaborates with leading researchers to translate immunology breakthroughs in disease biology into differentiated therapeutic antibodies.

Dr António Parada, CEO at FairJourney Biologics and IONTAS commented: "We have gained considerable experience in antibody discovery through mammalian display for use in generating therapeutics with specific properties.

Additionally, we continue to make improvements to the technology that will allow more diverse applications. We look forward to growing our relationship with argenx and applying our deep knowledge and experience to generate a diverse set of antibodies for potential immunological application."

For further information on mammalian display technology, please visit: fjb.pt/_mammalian-display/

On April 12, 2021 Treovir, an immuno-oncology company that is developing and plans to commercialize G207 for recurrent glioblastoma in children, reported that G207, an oncolytic HSV immunotherapy, was well tolerated with evidence of clinical effectiveness in a phase 1 study of 12 pediatric patients with recurrent high-grade glioma (Press release, Treovir, APR 12, 2021, View Source [SID1234577943]). Data from the phase 1 study (NCT02457845) are being presented by Gregory Friedman, M.D., professor in the Department of Pediatrics at the University of Alabama at Birmingham, during Week 1 of the virtual AACR (Free AACR Whitepaper) Annual Meeting 2021, held April 10-15. Data from this trial have been published in the New England Journal of Medicine.

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In the Phase 1 dose-escalation study, 12 pediatric patients 7 to 18 years of age with progressive high-grade glioma received an infusion of G207 alone or G207 in combination with radiation. No dose-limiting toxic effects or serious adverse events were attributed to G207 by the investigators and only 20 grade 1 adverse events were possibly related to G207. Radiographic, neuropathological, or clinical responses were seen in 11 patients. The median overall survival was 12.2 months (95% confidence interval, 8.0 to 16.4). The overall survival rate was more than double the typical survival rate for children with high-grade glioma. Some 36 percent of the patients thus far have survived longer than 18 months, surpassing the expected survival for newly diagnosed children with high-grade glioma. Additionally, G207 markedly increased the number of tumor-infiltrating lymphocytes for at least nine months after infusion effectively turning immunologically "cold" tumors "hot".

Gregory Friedman, M.D., Principal Investigator of the study, said, "This is the first study utilizing delivery of a viral immunotherapy directly into brain tumors in children and the results indicate that G207 can be delivered safely into tumors located in all areas of the cerebrum in children. The key findings thus far are that the approach is safe and well tolerated, and the preliminary evidence of efficacy is very promising."

G207 is an oncolytic HSV engineered to infect only tumor cells. When infused into a tumor, the virus enters the tumor cells and replicates and kills the cells. In the process, G207 releases viral progeny that infect and kill nearby tumor cells. Furthermore, as demonstrated in the Phase 1 study for the first time, G207 induces a strong local immune response to harness the body’s immune system to further fight against the tumor cells.

"We are enthusiastic that the Phase 1 results appear to support the use of G207 as a safe and potentially effective therapy to treat pediatric high-grade gliomas," said Michael Christini, CEO of Treovir. "There are no approved therapies to treat these types of lethal tumors and it is our goal to develop G207 for glioma and other childhood brain cancers."

In collaboration with Dr. Friedman and the Pediatric Brain Tumor Consortium, Treovir is in the late stages of planning its Phase 2 clinical trial for G207 in recurrent high grade glioma (NCT 04482933). The Phase 2 trial is expected to start later in 2021. Additionally, G207 is being studied at UAB and Children’s of Alabama in recurrent pediatric brain tumors, including medulloblastoma, which arise in the cerebellum, the most common location for pediatric tumors to arise. (NCT 03911388)

"It is our goal that the Phase 2 study will support market approval of G207 to treat pediatric recurrent high-grade gliomas and our company’s mission is clear: We want to commercialize G207 and provide hope to the children and families who currently have no effective therapeutic options," stated Mr. Christini.

Brain tumors are the most common solid tumor in children, and aggressive types like glioblastoma have an extremely low survival rate: as low as 10% five years after diagnosis. Malignant high-grade glioma accounts for 8 to 10% of pediatric brain tumors and survival rates have not improved in 30 years. The median life expectancy of recurrent high-grade glioma is only 5.6 months.

The study was supported by the US FDA Orphan Products Clinical Trials Grants Program, Cannonball Kids’ Cancer Foundation, the Rally Foundation for Childhood Cancer Research, Hyundai Hope on Wheels, St. Baldrick’s Foundation, and the Kaul Pediatric Research Institute. Dr. Friedman has no financial or equity interest in Treovir and was not paid by Treovir for the Phase 1 study.