On April 12, 2021 Celldex Therapeutics, Inc. (Nasdaq:CLDX) reported the presentation of promising data from the Company’s growing bispecific platform at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 being held April 10th – 15th (Press release, Celldex Therapeutics, APR 12, 2021, View Source [SID1234577983]). The Company described the discovery and characterization of ILT4 inhibitory monoclonal antibodies (mAbs) for engineering bispecific antibodies (bsAbs) that revert myeloid cell suppression by antagonizing ILT4 and activate T-cell responses through PD-(L)1 inhibition (poster # 1865). Based on the results reported today, Celldex is developing clinical bispecific candidates that co-target ILT4 and PD-(L)1.

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Expression of ILT4 in several tumor types is associated with poor outcome. In preclinical models, antagonist antibodies to ILT4 have demonstrated immune enhancing and antitumor effects. More recently, in early clinical studies, combination approaches that combine co-targeting of ILT4 and checkpoint blockade have demonstrated clinical activity and safety, including in patients refractory to checkpoint inhibition therapy. The data Celldex presented at AACR (Free AACR Whitepaper) describe novel humanized antibodies with high affinity and specificity to ILT4 that effectively block immune suppression in macrophages. Candidate bispecific antibodies matched with either PD-L1 or PD-1 antibodies resulted in molecules that retained all the properties of the parental antibodies and simultaneously blocked the inhibitory signals from both ILT4 and PD-1. The data provide proof of concept for development of clinical candidates.

"Celldex continues to draw upon our deep antibody experience to build best-in-class bispecific antibodies to more effectively control antitumor immunity," said Tibor Keler, Ph.D., Executive Vice President and Chief Scientific Officer of Celldex Therapeutics. "The ILT4/PD-(L)1 approach combines two critical checkpoint pathways into one molecule, which may provide advantages from a development perspective and the potential for greater activity than the combination of the individual antibodies. We look forward to completing this work and selecting a lead candidate for advancement."

Celldex’s deep antibody experience and in-house manufacturing capabilities support efficient development of bispecific antibody targets. Targets are selected based on new science as well as their compatibility to be used in bispecific antibody formats with existing Celldex antibody programs. CDX-527, which combines CD27 activation and PD-1 blockade, was the first candidate to enter the clinic from the platform and is currently enrolling patients in a Phase 1 dose escalation study. Celldex is also exploring important targets controlling inflammation and auto-immune pathways.

On April 12, 2021 BriaCell Therapeutics Corp. (Nasdaq: BCTX, BCTXW) (TSX-V:BCT) ("BriaCell" or the "Company"), a clinical-stage biotechnology company specializing in targeted immunotherapies for advanced breast cancer, reported the presentation of results from clinical studies with its lead product candidate, Bria-IMT, summarized in a poster session held at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021, a virtual meeting, held over two weeks (Week 1: April 10-15; Week 2: May 17-21) (Press release, BriaCell Therapeutics, APR 12, 2021, View Source [SID1234578327]).

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The findings indicate disease control in advanced breast cancer patients, including stable disease (SD), partial responses (PR) or complete responses (CR). Disease control was especially noted in patients with Grade I/II (i.e. well or moderately differentiated) tumors or those that matched Bria-IMT at 2 or more HLA alleles. Patients with low or undetectable levels of circulating cancer cells were more likely to benefit from therapy.

Patients were treated with the Bria-IMT regimen alone (i.e. monotherapy study) or the Bria-IMT regimen in combination with immune checkpoint inhibitors, including pembrolizumab (KEYTRUDA; manufactured by Merck & Co., Inc.), and, more recently, Incyte’s retifanlimab (INCMGA00012, under a corporate collaboration with Incyte Corporation). Dr. Bill Williams, BriaCell’s President & CEO, presented the results of the clinical and pathological analysis. The patient data summarized and discussed belong to previously disclosed patients (i.e., no incremental numbers enrolled).

Details and results on the poster presentation are summarized below:

Poster Title: Predictors of response to a modified whole tumor cell immunotherapy in patients with advanced breast cancer from two phase I/IIa trials

Analysis and Discussion:

• The Bria-IMT regimen with or without checkpoint inhibitors is able to induce an effective immune response and disease control in heavily pre-treated advanced breast cancer patients. The patients were all heavily pretreated and failed multiple prior regimens.
• Delayed Type Hypersensitivity (DTH) to Bria-IMT analysis identified a group with significantly higher rates of disease control and progression-free survival (8 months) in both monotherapy and combination therapy studies suggesting a robust immune response is predictive of clinical benefit in these patients.
• Highest levels of disease control and PFS was observed in patients who matched Bria-IMT at 2 or more HLA alleles in the monotherapy study but not in the combination therapy study supporting our strategy to develop Bria-OTS, an off-the-shelf personalized immunotherapy for advanced breast cancer.
• Patients with Grade I/II tumors (median of 8 prior therapy regimens) were more likely to respond with disease control (67%) and longer progression free survival. The response was more pronounced in the patients in the combination therapy study suggesting additive or synergistic effects of checkpoint inhibitors when combined with the Bria-IMT regimen. Bria-IMT, with a molecular signature most closely related to Grade I/II tumors, may result in disease control and clinical benefit especially in this subset of patients.

A copy of the poster is posted at the following: View Source

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).