On May 9, 2022 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported financial results and operational updates for the quarter ended March 31, 2022 (Press release, ORIC Pharmaceuticals, MAY 9, 2022, View Source [SID1234613925]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We continue to make steady progress in advancing our pipeline of novel oncology candidates," said Jacob M. Chacko, MD, chief executive officer, "We expect to report initial data from our three ongoing studies in the first half of 2023, which includes our Phase 1b single agent trials for ORIC-533, our orally bioavailable CD73 inhibitor, ORIC-114, our brain penetrant EGFR/HER2 inhibitor, and ORIC-944, our embryonic ectoderm development (EED) inhibitor."

First Quarter 2022 and Other Recent Highlights

Preclinical Data Presented at AACR (Free AACR Whitepaper): In April 2022, ORIC disclosed new preclinical data in three poster presentations and one oral presentation at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

ORIC-533: Oral Small Molecule CD73 Inhibitor

ORIC-533 is a highly potent, orally bioavailable small molecule inhibitor of CD73 that has demonstrated more potent adenosine inhibition in preclinical studies compared to an antibody approach and other small molecule inhibitors of the adenosine pathway. In preclinical studies, ORIC-533 overcame immune suppression and triggered significant lysis and cell death of multiple myeloma cells in an assay comprised of autologous bone marrow microenvironment. A Phase 1b trial with ORIC-533 as a single agent in multiple myeloma is enrolling patients, and the company expects to report initial Phase 1b data from this trial in the first half of 2023.

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. In preclinical studies, ORIC-114 achieved tumor regressions in an EGFR exon 20 NSCLC model with superior efficacy relative to CLN-081 and demonstrated greater anti-tumor activity compared to mobocertinib (TAK-788) in an intracranial NSCLC model. A Phase 1b trial with ORIC-114 as a

single agent is enrolling patients with advanced solid tumors with EGFR or HER2 exon 20 alterations or HER2 amplification and allows for patients with CNS metastases that are either treated or untreated but asymptomatic. The company expects to report initial Phase 1b data from this trial in the first half of 2023.

ORIC-944: PRC2 Inhibitor

ORIC-944 is a potent and selective allosteric inhibitor of polycomb repressive complex 2 (PRC2) that targets its regulatory embryonic ectoderm development (EED) subunit and has demonstrated single agent efficacy in multiple enzalutamide-resistant prostate cancer models in preclinical studies. A Phase 1b trial with ORIC-944 as a single agent is enrolling patients with metastatic prostate cancer, and the company expects to report initial Phase 1b data from this trial in the first half of 2023.

PLK4 Inhibitor Program

In March, the company announced a small molecule therapeutic program intended to address a mechanism of innate resistance found in a subset of breast cancers, specifically a synthetic lethal interaction of polo-like kinase 4 (PLK4) inhibition in tumors bearing a TRIM37 DNA amplification. ORIC discovered novel, potent, orally bioavailable small molecule inhibitors of PLK4 that are highly selective and achieved strong anti-tumor activity of TRIM37 high xenograft tumors, with corresponding pharmacodynamic effects and no body weight loss. The PLK4 inhibitor program is currently in lead optimization.

Anticipated Program Milestones

ORIC anticipates the following upcoming milestones:

•ORIC-533: Initial Phase 1b data in 1H 2023
•ORIC-114: Initial Phase 1b data in 1H 2023
•ORIC-944: Initial Phase 1b data in 1H 2023

First Quarter 2022 Financial Results

Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments totaled $256.2 million as of March 31, 2022, which the company expects will fund its current operating plan into the second half of 2024.

R&D Expenses: Research and development (R&D) expenses were $16.8 million for the three months ended March 31, 2022, compared to $11.7 million for the same period in 2021, an increase of $5.1 million. The increase was primarily driven by an increase in external expenses related to the advancement of ORIC-533, ORIC-114, ORIC-944 and our other product candidates of $4.6 million, offset by a decrease in ORIC-101 costs of $0.7 million due to the discontinuation of the program in the first quarter of 2022. Higher internal expenses related to higher personnel costs, including additional non-cash stock-based compensation of $0.5 million, also contributed to the increase in research and development expenses.

G&A Expenses: General and administrative (G&A) expenses were $6.4 million for the three months ended March 31, 2022, compared to $4.9 million for the same period in 2021, an increase of $1.6 million. The increase was primarily due to higher personnel costs, including additional non-cash stock-based compensation of $0.7 million.

On May 9, 2022 Foghorn Therapeutics Inc. (Nasdaq: FHTX), a clinical stage biotechnology company pioneering a new class of medicines that modulate gene expression through selectively targeting the chromatin regulatory system, reported a corporate update in conjunction with the Company’s 10-Q filing for the quarter ended March 31, 2022 (Press release, Foghorn Therapeutics, MAY 9, 2022, View Source [SID1234613942]). With an initial focus in oncology, Foghorn’s Gene Traffic Control Platform and resulting broad pipeline has the potential to transform the lives of people suffering from a wide spectrum of diseases.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"With $424.7 million in cash on the balance sheet, Foghorn is well capitalized, to execute on its strategy of developing precision medicines targeting the chromatin regulatory system. This quarter, we continued to advance our robust pipeline that includes clinical and pre-clinical programs evaluating targeted protein degraders, enzymatic inhibitors and transcription factor disruptors for diverse cancers," said Foghorn CEO Adrian Gottschalk. "Specifically, we continue to enroll patients and dose escalate in our Phase 1 clinical studies of FHD-286 and FHD-609 and look forward to disclosing initial clinical data."

Key First Quarter 2022 Updates

FHD-286 Update. Foghorn expects to provide initial Phase 1 clinical data for FHD-286, an inhibitor of BRG1/BRM, in metastatic uveal melanoma (mUM), relapsed and/or refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), in the second half of 2022.

FHD-609 Update. Enrollment is continuing in the Phase 1 clinical study of FHD-609, a potent and selective heterobifunctional protein degrader of BRD9, initially being developed for the treatment of synovial sarcoma with initial data expected in 2023.

2022 AACR (Free AACR Whitepaper) Annual Meeting. Presented preclinical data supporting the clinical development and mechanistic understanding of FHD-286’s anti-tumor activity in AML demonstrated by tumor inhibition in different cancer cell types, synergistic activity with combination medicines, including chemotherapy and other targeted therapies, and mutation agnostic responses in AML patient derived bone marrow samples.

BRM-selective Progress. Foghorn is advancing its BRM-selective programs in collaboration with Loxo Oncology at Lilly, with the BRM-selective inhibitor program in lead optimization and the protein degrader program in hit-to-lead stage. Foghorn is leading discovery and early research activities, and Lilly is leading development and commercialization activities with participation from Foghorn. U.S. economics will be shared equally, and Foghorn is eligible to receive royalties on ex-U.S. sales in the low double-digit to twenties range based on revenue levels.
Pipeline Advancement. Foghorn continued to advance its broad therapeutic pipeline of which the majority are wholly owned including protein degraders, enzymatic inhibitors and transcription factor disruptors targeting cancers impacted by breakdowns in the chromatin regulatory system.

Strong Balance Sheet and Cash Runway. As of March 31, 2022, the Company had $424.7 million in cash, cash equivalents and marketable securities.
About FHD-286

FHD-286 is a highly potent, selective, allosteric and orally available, small-molecule, enzymatic inhibitor of BRG1 and BRM, two highly similar proteins that are the ATPases, or the catalytic engines across all forms of the BAF complex, one of the key regulators of the chromatin regulatory system. In preclinical studies, FHD-286 has shown anti-tumor activity across a broad range of malignancies including both hematologic and solid tumors. To learn more about these studies please visit ClinicalTrials.gov. (Link here for metastatic uveal melanoma and here for AML and MDS).

About AML

Adult acute myeloid leukemia (AML) is a cancer of the blood and bone marrow and the most common type of acute leukemia in adults. AML is a diverse disease associated with multiple genetic mutations. It is diagnosed in about 20,000 people every year in the United States.

About Uveal Melanoma

Uveal (intraocular) melanoma (UM) is a rare eye cancer that forms from cells that make melanin in the iris, ciliary body, and choroid. It is the most common eye cancer in adults. It is diagnosed in about 2,000 adults every year in the United States and occurs most often in lightly pigmented individuals with a median age of 55 years. However, it can occur in all races and at any age. UM metastasizes in approximately 50% of cases, leading to very poor prognosis.

About FHD-609

FHD-609 is a potent, selective, intravenously administered protein degrader of BRD9, a component of the ncBAF complex. Preclinical studies have demonstrated tumor growth inhibition in synovial sarcoma, a cancer genetically dependent on BRD9. To learn more about the first-in-human clinical trial of FHD-609 in synovial sarcoma, please visit ClinicalTrials.gov.

About Synovial Sarcoma

Synovial sarcoma is a rare, often aggressive soft tissue sarcoma that originates from different types of soft tissue, including muscle or ligaments. Synovial sarcoma can occur at any age but is most common among adolescents and young adults. It represents around 5-10% of all soft tissue sarcomas, with ~800 new cases each year in the United States. Surgery remains the most effective treatment for synovial sarcoma, and there are limited therapeutic treatment options.

On May 9, 2022 Twist Bioscience Corporation (NASDAQ: TWST), a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, reported it has entered into a research collaboration and exclusive option license agreement with Astellas Pharma Inc (Press release, Twist Bioscience, MAY 9, 2022, View Source [SID1234613958]). Under the terms of the agreement, the companies will jointly conduct research activities to identify and optimize proprietary Twist antagonist antibodies, targeting an undisclosed checkpoint inhibitor pathway in the tumor microenvironment (TME), as potential therapeutic development candidates. Ligands in this pathway are found in relatively high concentrations in the tumor microenvironment. Blocking the receptor’s activation has the potential to markedly enhance anti-tumor immunity with other Astellas therapies including chimeric antigen receptor-based (CAR) technologies combined with Universal Donor Cells. Astellas will have the exclusive option to license any development candidates generated as part of the collaboration.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Our robust antibody discovery and optimization capabilities uniquely position us to develop antibodies with high affinity and specificity for historically difficult targets, such as those mediating immune suppression in the TME," said Emily M. Leproust, Ph.D., CEO and co-founder of Twist Bioscience. "This out-licensing agreement validates the capabilities of Twist-generated antibodies to enable the discovery and advancement of next generation therapies. As the first out-licensing agreement for Twist Biopharma, this deal will serve as an initial base that we intend to build on as we pursue increasingly larger and later stage out-licensing opportunities with additional partners and targets."

Targeting this pathway with antibody therapeutics is a novel approach with no antibodies in clinical development. Developing next-generation checkpoint inhibitor immunotherapies using new modalities is promising as an innovative healthcare solution. Through this collaboration we expect to stimulate a highly specific and targeted attack on cancer cells by optimizing these development candidates, and leveraging Astellas’ flexible convertibleCAR cell therapy technology.

Under the terms of the agreement, Twist will receive an upfront payment from Astellas as well as an additional payment upon the exercise of the licensing option. Twist will receive payments connected to success-based clinical milestones as well as royalty payments on product sales for each licensed product. Astellas will be responsible for the development, manufacturing and commercialization of any licensed products.

On May 9, 2022 Enara Bio, a biotechnology company advancing novel T-cell receptor (TCR) directed immunotherapies against unconventional, shared, cancer-specific antigens, reported that three abstracts from the Company and its academic collaborators have been selected for presentation at the 12th International CD1-MR1 European Molecular Biology Organization (EMBO) Meeting, which will be held in Gothenberg, Sweden, 22-26 May 2022 (Press release, Enara Bio, MAY 9, 2022, View Source [SID1234613975]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The three abstracts cover pioneering research being conducted by Enara Bio in collaboration with leading immunology and MR1 research groups at Monash University and the University of Oxford towards the identification and validation of cancer-specific MR1 ligands and the development of MR1-targeted T-cell receptor cell therapies (TCR-T).

MR1 is an unconventional antigen-presenting molecule that presents metabolites to the immune system in the context of cancer and infection. The monomorphic nature of MR1 strongly suggests that therapies based on MR1-displayed antigens could be effective across the entire human population. These unique properties make MR1 a promising target for off-the-shelf, HLA-independent, TCR-based immunotherapies for solid tumors.

The first presentation, from Enara scientists, highlights the progress the Company is making with its lead autologous MR1-targeting TCR-T program. The two other presentations, led by scientists from Jamie Rossjohn’s and Tony Purcell’s groups at the Monash Biomedicine Discovery Institute (BDI), and Nicola Ternette’s group at the University of Oxford’s Nuffield Department of Medicine, describe novel immunopeptidomic and metabolomic methods to identify and characterize the cancer-specific MR1 ligandome.

Joe Dukes, Vice President, Head of Research at Enara Bio, commented: "We are very pleased to be presenting important abstracts at the upcoming CD1-MR1 EMBO meeting, which showcase the continued developments we are making in partnership with our world-class collaborators to advance the next generation of cancer immunotherapies designed to treat a broad patient population. We have made remarkable progress in our mission to characterize unconventional immunotherapy targets, such as ligands presented by MR1, which we hope will enable development of a pipeline of product candidates that can be advanced into clinical development."

Details of the poster presentations (which will be available on the Company website at the time of the meeting) are as follows:

Enara Bio

– Abstract Title: A novel TCR-T cell therapy targeting a cancer-specific antigen presented by monomorphic MR1 to overcome the challenge of HLA restricted TCR therapies.
– Presenter: Dr. Jonathan Silk

Monash University

– Abstract Title: Design and testing of cleavable constructs for identification and functional validation of MR1 ligands.
– Presenter: Dr. Patricia Illing

The University of Oxford

– Abstract Title: Development of a metabolomics-based MR1 ligand discovery platform using proteomics instrumentation
– Presenter: Dr. Thierry Schmidlin

On May 9, 2022 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported that it will release first quarter 2022 financial results before the market open on Monday, May 16, 2022 (Press release, Hookipa Pharma, MAY 9, 2022, View Source [SID1234613877]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Company will not be conducting a conference call in conjunction with this earnings release.