On March 22, 2022 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported the discontinuation of ORIC-101 and also reported financial results and operational updates for the quarter and year ended December 31, 2021 (Press release, ORIC Pharmaceuticals, MAR 22, 2022, View Source [SID1234610602]). The company conducted planned interim analyses of two Phase 1b studies and concluded that ORIC-101 did not demonstrate sufficient clinical activity to warrant further development.

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"We are disappointed in the outcome of the ORIC-101 studies in combination with nab-paclitaxel in various solid tumors and in combination with enzalutamide in metastatic prostate cancer, two late-line patient populations for whom limited treatment options exist today. We believe both studies were well designed, allowing us to thoroughly and efficiently answer an important clinical question. With this decision to discontinue ORIC-101 development, we would like to thank the investigators, site staff, the ORIC team, and most importantly, patients and families who participated in the trials," said Pratik S. Multani, MD, chief medical officer.

"We’ve always been committed to rapid, data driven decision making and allocating resources efficiently and prudently," said Jacob M. Chacko, MD, chief executive officer, "We intentionally built a diverse pipeline of differentiated programs, 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. We expect to report initial data from each study in the first half of 2023. As a result of the ORIC-101 discontinuation, we project our cash runway to extend into the second half of 2024, well beyond the planned initial data disclosures from these three clinical programs."

Fourth Quarter 2021 and Other Recent Highlights

ORIC-101: Glucocorticoid Receptor Antagonist

Based on interim analyses from the two Phase 1b studies, ORIC-101 did not demonstrate sufficient clinical activity and, therefore, the company has discontinued further development.

The dose expansion portion of the Phase 1b clinical trial of ORIC-101 in combination with enzalutamide enrolled 28 patients at the recommended phase 2 dose (RP2D) with metastatic prostate cancer progressing on enzalutamide. The RP2D was well tolerated with a safety profile consistent with previously reported results. ORIC-101 in combination with enzalutamide did not translate into a meaningful clinical benefit, with a median progression-free survival (PFS) in the target patient population of 3.7 months.

The dose expansion portion of the Phase 1b clinical trial of ORIC-101 in combination with nab-paclitaxel enrolled 61 patients at the RP2D across four cohorts: pancreatic ductal adenocarcinoma (PDAC), ovarian cancer, triple negative breast cancer (TNBC), and other advanced solid tumors. The RP2D was well tolerated with a safety profile consistent with previously reported results. There were no objective responses in the PDAC cohort (n=21) and there was one confirmed partial response in the ovarian cancer cohort (n=13). There was no meaningful clinical benefit based on median PFS across all cohorts (PDAC: 1.9 months, and ovarian cancer: 2.2 months).

ORIC-533: CD73 Inhibitor
ORIC-533 is a highly potent, orally bioavailable small molecule inhibitor of CD73 and has demonstrated more potent adenosine inhibition in preclinical studies compared to an antibody approach and other small molecule inhibitors of the adenosine pathway.

Ex vivo human data supporting the therapeutic potential of single agent ORIC-533 in multiple myeloma were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting.
Single agent activity in an autologous bone marrow mononuclear assay system from multiple myeloma patients showed CD73 inhibition compared favorably to approved therapies for the treatment of multiple myeloma, including lenalidomide, bortezomib and daratumumab.
A Phase 1b trial with ORIC-533 as a single agent in multiple myeloma is enrolling patients and initial data are expected to be reported 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.

Compelling brain exposure and antitumor activity of ORIC-114 in preclinical studies of HER2-positive breast cancer were presented at AACR (Free AACR Whitepaper)-NCI-EORTC.
Head-to-head data in an EGFR exon 20 NSCLC xenograft model were disclosed demonstrating good tolerability and improved efficacy, including a 90% complete response rate, with ORIC-114 versus multiple clinical stage exon 20 inhibitors.
The Clinical Trial Application (CTA) for ORIC-114 was filed in the fourth quarter of 2021 and was cleared by the regulatory authorities of the Republic of Korea in the first quarter of 2022.
A Phase 1b trial with ORIC-114 as a single agent has been initiated and will enroll patients with advanced solid tumors with EGFR or HER2 exon 20 alterations or HER2 amplification and will allow 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.

The IND for ORIC-944 was cleared by the FDA in the fourth quarter of 2021.
A Phase 1b trial with ORIC-944 as a single agent will enroll patients with metastatic prostate cancer. 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. Breast cancer models as well as other tumor models with this TRIM37 amplification have a key tumor dependency on PLK4 and our therapeutic approach is to selectively inhibit this enzyme.

Corporate
In November 2021, the company appointed Angie You, PhD, to its board of directors. Dr. You was most recently CEO of Amunix Pharmaceuticals, which was acquired by Sanofi, and brings broad experience spanning venture capital, business development and public company leadership roles.

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
Fourth Quarter and Full year 2021 Financial Results

Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments totaled $280.4 million as of December 31, 2021, and with the discontinuation of ORIC-101, the company expects its cash runway to be extended into the second half of 2024.

R&D Expenses: Research and development (R&D) expenses were $16.7 million for the three months ended December 31, 2021, compared to $12.1 million for the three months ended December 31, 2020, an increase of $4.6 million. For the year ended December 31, 2021, R&D expenses were $56.9 million compared to $35.9 million for the same period of 2020, an increase of $20.9 million. The increases for the 2021 periods were primarily driven by an increase in external expenses related to the advancement of ORIC-101, ORIC-533 and our other product candidates, as well as higher personnel costs, including additional non-cash stock-based compensation of $0.7 million and $2.9 million for the three and twelve months ended December 31, 2021, as compared to the same periods in 2020, respectively.

G&A Expenses: General and administrative (G&A) expenses were $6.1 million for the three months ended December 31, 2021, compared to $4.3 million for the three months ended December 31, 2020, an increase of $1.8 million. For the year ended December 31, 2021, G&A expenses were $22.0 million compared to $13.4 million for the same period in 2020, an increase of $8.6 million. These increases were primarily due to higher personnel costs, including additional non-cash stock-based compensation of $1.1 million and $4.6 million for the three and twelve months ended December 31, 2021, as compared to the same periods in 2020, respectively, and higher costs related to operating as a public company.
Webcast and Conference Call

ORIC will host a conference call and webcast today at 5:00 p.m. ET. To participate in the conference call, please dial (833) 651-0991 (domestic) or (918) 922-6080 (international) and refer to conference ID 8637367. A live webcast and audio archive of the conference call will be available through the investor section of the company’s website at www.oricpharma.com. The webcast will be available for replay for 90 days following the presentation.

On March 22, 2022 TCR2 Therapeutics Inc. (Nasdaq: TCRR), a clinical-stage cell therapy company with a pipeline of novel T cell therapies for cancer patients suffering from solid tumors, reported financial results for the fourth quarter ended December 31, 2021 and provided a corporate update (Press release, TCR2 Therapeutics, MAR 22, 2022, View Source [SID1234610601]).

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"Consistent execution throughout the last year has positioned TCR2 for a series of important readouts as we accelerate our clinical progress in 2022," said Garry Menzel, Ph.D., President and Chief Executive Officer of TCR2 Therapeutics. "We were able to successfully conclude the dose escalation portion of our ongoing gavo-cel Phase 1/2 clinical trial with the identification of a RP2D and submit a protocol amendment with the FDA for the upcoming Phase 2 clinical trial. We also submitted an IND with the FDA for our first enhanced TRuC-T cell that incorporates a PD-1:CD28 switch. In the meantime, we have been identifying new clinical trial sites and expanding manufacturing capacity for the reproducible process used by Miltenyi and ElevateBio to support our clinical trials. In addition to the clinical readouts from gavo-cel and TC-510, we will continue to provide updates on the innovations in our rapidly growing pipeline, most immediately with a preclinical data presentation on our allogeneic TRuC targeting mesothelin at the AACR (Free AACR Whitepaper) Annual Meeting in April."

Recent Developments

Gavo-cel:

•TCR2 announced the submission of a protocol amendment to the US Food and Drug Administration (FDA) in the first quarter of 2022 for the gavo-cel Phase 2 expansion cohort, including the amendment to treat patients with gavo-cel in combination with Opdivo and/or Yervoy which forms the basis of the Company’s clinical trial collaboration with Bristol Myers Squibb.

TC-510:

•TCR2 announced the submission of an Investigational New Drug (IND) to the FDA in the first quarter of 2022 for TC-510, the Company’s first enhanced TRuC-T cell targeting mesothelin with a PD-1:CD28 chimeric switch receptor.
Pipeline:

•TCR2 announced it will present a poster at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 featuring new preclinical data on an allogeneic (off-the-shelf) TRuC-T cell, taking place on April 8-13, 2022 in New Orleans, Louisiana. In preclinical studies, this allogeneic product candidate without an enhancement demonstrated improved anti-tumor efficacy associated with enhanced persistence and increased antigen sensitivity in vivo compared to donor-matched autologous TRuC-T cells targeting mesothelin. Furthermore, allogeneic TRuC-T cells generated with an additional knockout of Beta-2-microglobulin (B2M) maintained their potency.
•TCR2 announced a strategic research collaboration agreement with Arbor Biotechnologies focused on the further development of a defined set of allogeneic TRuC-T cell therapies. The collaboration leverages Arbor’s proprietary CRISPR gene-editing technology, which is tailored to address the underlying pathology of genetic diseases and TCR2’s first-in-class TRuC platform, which has demonstrated clinical activity in multiple treatment-refractory mesothelin-expressing solid tumor indications with gavo-cel.

Corporate:

•TCR2 announced the appointment of experienced biotech executive Rosemary Harrison, Ph.D., as Chief Business and Strategy Officer where she will be responsible for supporting a range of activities including commercial strategy, operational planning, corporate partnerships and long-term growth opportunities.

Anticipated Milestones

•Gavo-cel:
oPresent the expanded and complete Phase 1 dataset for gavo-cel in the second quarter of 2022.
oInitiate the Phase 2 expansion cohort of the ongoing gavo-cel Phase 1/2 clinical trial in the first half of 2022.
oProvide an initial update from at least one of the Phase 2 expansion cohorts of the ongoing gavo-cel Phase 1/2 clinical trial in the second half of 2022.
•TC-510:
oReport initial safety, efficacy and translational data from at least one of the Phase 1 dose escalation cohorts of the TC-510 Phase 1/2 clinical trial in the second half of 2022.
•Pipeline:
Initiate IND-enabling studies for TC-520, an enhanced CD70 targeting TRuC-T cell program, in 2022.
oSelect a lead candidate for its allogeneic program in 2022.
•Manufacturing:
oProduction of clinical trial material to commence at ElevateBio BaseCamp as capacity is increased in anticipation of demand from the Phase 2 expansion trial of gavo-cel in 2022.

Financial Highlights

•Cash Position: TCR2 ended the fourth quarter of 2021 with $265.6 million in cash, cash equivalents, and investments compared to $228.0 million as of December 31, 2020. Net cash used in operations was $23.3 million for the fourth quarter of 2021 compared to $13.5 million for the fourth quarter of 2020. TCR2 projects net cash use of $115-125 million for 2022. We expect cash on hand to support operations into 2024.

•R&D Expenses: Research and development expenses were $22.4 million for the fourth quarter of 2021 compared to $14.3 million for the fourth quarter of 2020. The research and development expenses for the fourth quarter of 2021 include restructuring costs of $3.7 million and are partially offset by a $2 million settlement from a vendor due to a commercial dispute. The remaining increase in R&D expenses was primarily due to an increase in headcount and manufacturing facilities.

•G&A Expenses: General and administrative expenses were $5.2 million for the fourth quarter of 2021 compared to $4.3 million for the fourth quarter of 2020. The increase in general and administrative expenses was primarily due to an increase in personnel costs.

•Net Loss: Net loss was $27.7 million for the fourth quarter of 2021 compared to $18.5 million for the fourth quarter of 2020.

On March 22, 2022 Propanc Biopharma, Inc. (OTCQB: PPCB) ("Propanc" or the "Company"), a biopharmaceutical company developing novel cancer treatments for patients suffering from recurring and metastatic cancer, reported that a Notice of Allowance has been received from the US Patent and Trademark Office (USPTO) for claims involving a novel method to treat cancer stem cells (CSC’s) (Press release, Propanc, MAR 22, 2022, View Source [SID1234610600]). The allowed US patent protects proprietary claims capturing methods and uses for pancreatic proenzymes to treat cancer by specifically targeting and eradicating CSCs.

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CSCs represent only a small fraction of the cell population within a tumor and can remain dormant for periods of time, thereby evading standard treatment approaches like radiation and chemotherapy that target dividing cells. Therefore, a priority for improving treatment and reducing risk of relapse is to develop a strategy that targets CSC eradication, whilst leaving healthy cells alone. This continues to be a specific area of focus as the Company’s lead product candidate, PRP, advances to a First-In-Human study for the treatment of patients with late-stage solid tumors.

The allowed patent, citing the novel CSC treatment method, is currently one of 4 patent families, consisting of 65 patents either in force, or pending in global jurisdictions. It is the first allowed by the USPTO covering a method of minimizing the progression of cancer in a patient by administering a therapeutically effective amount of two proenzymes, trypsinogen and chymotrypsinogen, thereby preventing metastatic cancer in the patient by targeting and eradicating CSCs from solid tumors.

"The allowance of this patent by the USPTO is a significant step for our intellectual property portfolio in the biggest global healthcare market in the world and confirms our claims cover a novel therapeutic approach for the treatment and prevention of metastatic cancer, which is the main cause of patient death for sufferers," said James Nathanielsz, Propanc’s Chief Executive Officer. "It is especially important to continue to expand and grow our intellectual property portfolio, as we advance further along the drug development pathway. Additional patent applications are anticipated and we are excited about the growth and commercial potential of our portfolio with the goal of creating significant, long term shareholder value."

A point of difference from other CSC therapies is the ability of the Company’s technology to differentiate cancer stem cells back towards exhibiting normal behavior, so they become benign and die naturally, rather than directly killing CSCs. This means that CSCs are selectively targeted based on the proteins they express, which healthy cells do not, resulting in leaving healthy stem cells alone. Therefore, based on scientific evidence to date, PRP is considered less toxic compared to standard treatment approaches. PRP is a mixture of two proenzymes, trypsinogen and chymotrypsinogen from bovine pancreas administered by intravenous injection. A synergistic ratio of 1:6 inhibits growth of most tumor cells. Examples include kidney, ovarian, breast, brain, prostate, colorectal, lung liver, uterine and skin cancers.

On March 22, 2022 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a clinical stage biotechnology company developing the next generation of therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, reported its financial results for the year ended December 31, 2021 and provided a business update (Press release, Phio Pharmaceuticals, MAR 22, 2022, View Source [SID1234610599]).

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"Over the past year, we have made significant progress moving towards the initiation of our first-in-human clinical studies for our lead program, PH-762, in 2022. Currently, we are on track to start enrolling patients in the first of these trials, a Phase 1b study of PH-762 in advanced melanoma, in the coming weeks," said Dr. Gerrit Dispersyn, President and CEO of Phio. "I am proud of the Phio team’s execution of our preclinical program for PH-762, which has generated a steady stream of positive data and supported our regulatory strategy. These studies were conducted during the second year of the ongoing global pandemic, which has proven to be a difficult period of time for the team, yet we incurred only minor delays to our original timelines. I believe the achievement of these milestones within the stated timeframes speak to the strength of our team and the assets in our pipeline, as well as our INTASYL platform. We look forward to continuing to deliver on our current development pipeline in 2022 as our business fulfills its transition into a clinical stage company."

Quarter in Review and Recent Corporate Updates

Granted clinical trial authorization (CTA) by the French National Agency for the Safety of Medicines and Health Products to proceed with a first-in-human clinical trial for PH-762 to treat patients with melanoma at the Gustave Roussy Institute, one of the largest cancer centers in Europe.
Presented new data in an in vivo hepatocarcinoma model that show PH-762 administered locally cleared untreated distal tumors, which indicates a systemic immune response.
Initiated efficacy animal studies with INTASYL-based antiviral compounds against SARS-CoV-2 infection, the virus that causes COVID-19, following collection of positive results from in vitro studies under this development program.
Upcoming Pipeline Milestones for 2022

Expect to start patient enrollment in a Phase 1b clinical study to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of PH-762 in a neoadjuvant setting in subjects with advanced melanoma in the first quarter of 2022.
Expect to initiate a first-in-human clinical study on the use of PH-762 in tumor infiltrating lymphocytes (TILs) in adoptive cell therapy (ACT) in patients with advanced melanoma in the second quarter of 2022.
Scheduled to present new study data regarding PH-894, a BRD4-targeting, self-delivering RNAi, at the AACR (Free AACR Whitepaper) Annual Meeting 2022, which is being held in New Orleans, Louisiana, from April 8-13, 2022.
Expect to finalize IND-enabling studies for PH-894 in the second half of 2022.
Additional data publications on the Company’s pipeline programs.
Financial Results

Cash Position

At December 31, 2021, the Company had cash of $24.1 million as compared with $14.2 million at December 31, 2020. The Company expects its current cash will be sufficient to fund currently planned operations to the second quarter of 2023.

Research and Development Expenses

Research and development expenses were approximately $8.9 million for the year ended December 31, 2021, compared to approximately $3.7 million for the year ended December 31, 2020. The increase in research and development expenses was primarily due to manufacturing costs for the Company’s PH-762 and PH-894 INTASYL compounds, fees for the required preclinical studies in support of the Company’s clinical trials for PH-762 and CRO and consulting related costs to support the initiation of the Company’s clinical trials as compared to the same period in the prior year.

General and Administrative Expenses

General and administrative expenses were approximately $4.6 million for the year ended December 31, 2021, compared to approximately $5.1 million for the year ended December 31, 2020. The decrease in general and administrative expenses was primarily due to a decrease in patent and legal fees partially offset by increases in the use of an outside consultant to support business development activities and corporate insurance premiums.

Net Loss

Net loss was $13.3 million, or $1.04 per share, for the year ended December 31, 2021, compared with $8.8 million, or $1.92 per share, for the year ended December 31, 2020. The increase in net loss was primarily attributable to the increase in research and development expenses related to the Company’s manufacturing of its INTASYL compounds and preclinical activities in preparation for the start of its clinical trial with PH-762, as described above. The change in net loss per share was primarily due to an increase in the number of shares outstanding as a result of the Company’s capital raise activities as compared to the prior year period.

On March 22, 2022 Philochem, a subsidiary of the Philogen Group, and Bracco Imaging reported that they have entered into a license and collaboration agreement to develop and commercialize a small organic molecule for imaging applications, with proven ability to selectively detect a variety of metastatic solid tumors in cancer patients, paving the way for a new approach to tumor diagnosis (Press release, Philogen, MAR 22, 2022, View Source(003).pdf [SID1234610598]).

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Philogen and Bracco share an Italian heritage and operate globally in the pharmaceutical and biotech sectors. Bracco and Philochem will pioneer the development of cutting-edge technologies for the discovery and optimization of small molecule ligands that enable unprecedented specificity and sensitivity for the imaging of solid tumors.

Prof. Dr. Dario Neri, Member of the Board of Philochem and CEO of the Philogen Group, commented: "We are extremely pleased to establish a new collaboration with Bracco Imaging, a leading global company in the image diagnostics field. This new collaboration will focus on the development and commercialization of a small molecule for imaging applications, which promises to improve the diagnosis, staging and monitoring of response-to-treatment for cancer patients. Both companies are committed to the development of the product and making it available to patients who may benefit from it."

"We are very excited about this collaboration with Philochem, a leader in the discovery and development of novel pharmaceutical and biopharmaceutical products. It demonstrates Bracco’s commitment to long-term value creation in medical imaging. Over the years, Bracco has built a portfolio of leading products across all imaging modalities and is continuing to invest in innovation to shape the future of precision imaging and improve people’s lives", commented Fulvio Renoldi Bracco, Vice-Chairman & CEO of Bracco Imaging.