On February 17, 2022 Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) reported positive interim results from AROHIF21001, a Phase 1b dose-finding clinical study of ARO-HIF2, the company’s investigational RNA interference (RNAi) therapeutic being developed as a treatment for patients with clear cell renal cell carcinoma (ccRCC) (Press release, Arrowhead Pharmaceuticals, FEB 17, 2022, View Source [SID1234608237]). The data presented provide initial proof of target engagement based on reductions in hypoxia inducible factor-2 alpha (HIF2α) expression, as well as an acceptable safety profile in response to escalating doses of ARO-HIF2. The data are being presented by James Brugarolas, M.D., Ph.D, Professor at University of Texas Southwestern Medical Center and investigator in the study, in a poster presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU), being held February 17-19, 2022, in San Francisco, CA and online.

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Presentation Details:

Title: Initial results from the phase 1 study of ARO-HIF2 to silence HIF2-alpha in patients with advanced ccRCC (AROHIF21001)
Authors: James Brugarolas, et al.
Session: Poster Session C: Renal Cell Cancer; Adrenal, Penile, Urethral, and Testicular Cancers
Abstract Number: 339
Poster Number: F9

Key results from AROHIF21001 as of December 1, 2021 data cut:

Pharmacodynamics and Efficacy

Tumoral expression of HIF2α protein was assessed via immunohistochemistry
Among patients with evaluable biopsy, 9/14 showed reductions in HIF2α protein
Responders in Cohort 1 (225 mg, n=3), Cohort 2 (525 mg, n=4), and Cohort 3 (1050 mg, n=2) achieved mean reductions of HIF2α protein of -45%, -57%, and -80%, respectively
Tumoral expression of HIF2α messenger RNA (mRNA) was assessed by quantitative polymerase chain reaction (qPCR)
Among patients with evaluable biopsy, 9/9 showed reductions in HIF2α mRNA
Cohort 1, Cohort 2, and Cohort 3 achieved mean reductions of HIF2α mRNA of -38%, -28%, and -44%, respectively
Efficacy was assessed by Response Evaluation Criteria in Solid Tumors (RECIST)
Disease control rate (complete response + partial response + stable disease) was 39% (10 of 26) across all cohorts
Objective response (complete response + partial response) was 8% (2 of 26), with one patient in Cohort 2 and one patient in Cohort 3 achieving a partial response
Safety

ARO-HIF2 was generally well-tolerated in patients. Anemia and hypoxia, frequently reported on-target adverse events (AEs) with small molecule HIF2α inhibitors, were reported in 12% of patients
Five serious AEs in 5 patients were reported by investigators as possibly drug related, including myocarditis (in a patient with a history of TKI induced cardiomyopathy), demyelinating neuropathy (in a patient with autoimmune sequelae due to checkpoint inhibitors), chronic inflammatory demyelinating polyradiculoneuropathy (in a patient with distant history of checkpoint inhibitor use), hypoxia (in a patient with a pulmonary infiltrate), and acute hypoxemic respiratory failure (in a patient with progressive lung metastatic disease)
A copy of the presentation materials with full data may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website.

AROHIF21001 (NCT04169711) is a Phase 1b dose-finding clinical study in patients with advanced ccRCC to evaluate the safety of ARO-HIF2 and to determine the recommended Phase 2 dose. Secondary objectives include the assessment of pharmacokinetics and preliminary efficacy, based on Response Evaluation Criteria in Solid Tumors (RECIST). Exploratory objectives for AROHIF21001 are post-dose tumoral expression of HIF genes in response to treatment with ARO-HIF2, change in Karnofsky Performance Status (KPS), correlation of tumor response based on RECIST with tumor HIF2α gene expression and tumor integrin expression, correlation of integrin expression with changes in HIF gene expression, evaluation of serum biomarkers of ARO-HIF2 activity, correlation of RCC-related gene expression to ARO-HIF2 activity, and evaluation of plasma and urine metabolites.

On February 17, 2022 XOMA Corporation (Nasdaq: XOMA), a biotechnology royalty aggregator playing a distinctive role in helping companies achieve their goal of improving human health, reported its Chief Executive Officer, Jim Neal, will present at the Aegis Capital Corp Virtual Conference on February 24, 2022 at 11:00 AM ET (Press release, Xoma, FEB 17, 2022, View Source [SID1234608236]). The conference will be held from February 23-25, 2022, from 8:30 AM until 5:30 PM ET daily, and can be viewed at https://bit.ly/3BoscUs.

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XOMA’s presentation will be available by request to Aegis during the conference. The presentation can also be accessed by visiting the investor relations section of the Company’s website at www.xoma.com. A replay of the presentation will be available and archived on the site for 90 days after the event.

On February 17, 2022 Ribon Therapeutics, a clinical stage biotechnology company developing therapeutics targeting stress support pathways, reported that the Board of Directors has appointed Prakash Raman, Ph.D., as President, Chief Executive Officer and member of the Board of Directors (Press release, Ribon Therapeutics, FEB 17, 2022, View Source [SID1234608235]). Dr. Raman has succeeded Victoria Richon, Ph.D., in these roles. Dr. Richon will remain actively involved in the Company as an R&D advisor to the Board of Directors and Chair of the Scientific Advisory Board, where she will work closely with Dr. Raman and executive leadership to advance Ribon’s scientific activities.

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"Since joining Ribon in 2015 as founding President, Vicky has built an exceptional research and development organization that has created a novel pipeline of first-in-class drugs in clinical development," said Jodie Morrison, Chair of the Board of Directors of Ribon Therapeutics. "The Board is excited to welcome Prakash, whose scientific background and strong business acumen are an excellent complement to our executive management team. This leadership transition allows Ribon to enhance its focus on its pipeline capabilities, business development and strategic growth plans while enabling Vicky to continue to contribute to the advancement of our innovative science as R&D Advisor to the Board of Directors and Chair of our Scientific Advisory Board. On behalf of the Board of Directors, I sincerely thank Vicky for her many contributions to the Company."

"It was only several years ago that the role of NAD+-utilizing enzymes in stress support pathways in cancer and inflammatory disease was considered an emerging science and not well understood," said Dr. Raman. "Under Vicky’s leadership, Ribon has advanced this family of enzymes to the clinic, where initial data have demonstrated PARP7, an NAD+-utilizing monoPARP, inhibition and early signs of antitumor activity in patients, a remarkable achievement. I am honored to join such a strong scientific organization with great potential for transforming the lives of patients with high unmet needs through the application of truly innovative science. I look forward to a collaborative and productive relationship with Vicky and the organization at Ribon to shepherd the company through its next phase of growth."

"I am pleased to welcome Prakash to Ribon at this important time for the Company," said Dr. Richon. "Prakash has the experience and skill set to carry the business forward toward our goal of bringing novel medicine to patients with cancer and inflammation. I look forward to a strong collaboration with the team in my role as SAB Chair as we work together to achieve our Company’s mission."

Dr. Raman brings to Ribon decades of biopharmaceutical business development and executive leadership experience, blending his scientific background, program and portfolio management and strong business development experience. Prior to joining Ribon, he served as Senior Partner, Chief Business Development Officer at Flagship Pioneering, where he leveraged the platforms and assets in Flagship’s network to generate opportunities for significant value creation. Prior to Flagship, Dr. Raman spent nearly fourteen years at Novartis, most recently as Vice President, Global Head of Novartis Institutes for Biomedical Research (NIBR) Business Development and Licensing (BD&L). During his time at Novartis, Dr. Raman was instrumental in forging key collaborations in immuno-oncology, executing many out-licensing opportunities and guiding the acquisitions of Advanced Accelerator Applications, Endocyte, IFM Tre and Selexys. In addition, he has led cross-functional drug discovery and early development project teams that successfully progressed compounds to clinical testing in patients. Prior to Novartis, Dr. Raman spent six years as a Senior Scientist at Millennium Pharmaceuticals and two years as a post-doctoral fellow at The Scripps Research Institute. He completed his undergraduate work at the Indian Institute of Technology, Bombay, and received his Ph.D. in Organic and Medicinal Chemistry from the University of Wisconsin-Madison.

Ribon, named a "Fierce 15" Biotech Company by Fierce Biotech in 2021, is pioneering the discovery and development of first-in-class precision therapies targeting stress support pathways in cancer and inflammation for patients with limited options. By leveraging its proprietary BEACON+ platform, the Company is building a pipeline of selective, small molecule inhibitors to numerous NAD+-utilizing enzymes. Ribon’s lead program is RBN-2397, a PARP7 inhibitor in clinical development for the treatment of cancer. The expansion portion of the RBN-2397 Phase 1 trial is currently underway in a number of defined patient cohorts, including squamous cell carcinoma of the lung (SCCL). Ribon is also advancing a second clinical candidate, RBN-3143, a potent and selective PARP14 inhibitor for the treatment of patients with inflammatory diseases.

On February 17, 2022 RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported a business update for the fourth quarter of 2021, including certain estimated unaudited preliminary financial data (Press release, RedHill Biopharma, FEB 17, 2022, View Source [SID1234608234]).

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Dror Ben-Asher, RedHill’s Chief Executive Officer, said: "Strong sales growth momentum in the face of the persistent pandemic environment, coupled with strengthening our salesforce through internal realignment to include 120 customer-facing sales professionals, disciplined cost-control measures and the potential addition of products synergistic to our existing commercial basket, are planned to bring us closer to commercial operations profitability in 2022. In parallel, our compact R&D team continues to display tremendous creativity and drive in progressing RedHill’s robust late clinical-stage pipeline. In particular, extensive discussions are ongoing with regulators in multiple countries regarding potential pathways to approval of orally-administered opaganib, likely the first novel oral drug candidate to have shown an improvement in viral clearance in severe hospitalized COVID-19 patients."

The Company intends to announce its audited fourth quarter and full year 2021 results in the coming weeks. The preliminary financial data ranges described herein have not been audited and are subject to adjustment based on the Company’s completion of year-end financial close processes.

On February 17, 2022 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage biopharmaceutical company utilizing proprietary genetic engineering platform technologies to create cell and gene therapeutics with the capacity to cure, reported interim results from its Phase 1 clinical trial of P-PSMA-101, the Company’s solid tumor autologous CAR-T product candidate to treat patients with metastatic castrate-resistant prostate cancer (mCRPC) (Press release, Poseida Therapeutics, FEB 17, 2022, View Source [SID1234608233]). These data are being presented today at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) in a poster presentation entitled, "Phase 1 Study of P-PSMA-101 CAR-T Cells in Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC)." The presentation (Abstract 98/Poster E9) will be available on demand through the Symposium’s virtual platform and during Poster Session A: Prostate Cancer today at 2:30 pm ET at ASCO (Free ASCO Whitepaper) GU, which is taking place in San Francisco and virtually February 17-19, 2022.

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"The results being presented at ASCO (Free ASCO Whitepaper) GU continue to reinforce the potential for a CAR-T product to effectively treat solid tumor indications like prostate cancer," said Mark Gergen, Chief Executive Officer of Poseida Therapeutics. "We are excited by the initial responses seen even at the lowest doses and will continue to evaluate additional dosing regimens as we treat patients. We are also encouraged by the durable responses observed to date and look forward providing additional updates on this program as the trial progresses."

Of the 17 patients treated thus far, 14 were treated and evaluable at the cutoff date of December 31, 2021. Six patients were treated in the 0.25X106 cells/kg cohort (an average of about 22M cells), seven patients were treated in the 0.75X106 cells/kg cohort (an average of about 61M cells), and one patient was treated in the 2.0X106 cells/kg cohort (112M cells). All patients received a lymphodepletion regimen consisting of 30 mg/m2 fludarabine + 300 mg/m2 cyclophosphamide, prior to a single infusion of P-PSMA-101. Patients were heavily pre-treated, having received an average of seven prior lines of therapy with a median time since diagnosis of 6.4 years.

"The responses we have seen in this trial are impressive and speak to the innovative nature and potential of Poseida’s CAR-T cell therapy platform," said Susan F. Slovin, M.D., Ph.D., with Memorial Sloan Kettering Cancer Center, an investigator who is presenting at the Symposium. "This interim update on the P-PSMA-101 trial shows the exceptional efficacy of this novel anti-PSMA CAR-T cell product. Thus far, at very low doses P-PSMA-101 has shown to produce a robust and durable anti-tumor response in heavily pretreated patients with mCRPC, including one pathologic complete response."

Efficacy

Standard responses were measured as per Prostate Cancer Working Group 3 (PCWG3) criteria including PSA, bone scans/CT, and exploratory biomarkers and novel tumor-targeted PET imaging (PSMA-PET, FDG). PET imaging was dependent on institutional availability.

Key findings included:

10/14 (71%) patients demonstrated measurable declines in PSA levels

5/14 (36%) patients showed a decline in PSA levels of 50% or more

One patient demonstrated evidence of complete tumor elimination and remains in a durable response of greater than ten months at the time of this presentation

Clinical evidence confirmed by biopsy in several patients that the TSCM nature of the product resulted in trafficking of CAR-T cells to the bone, important in a bone-avid disease like prostate cancer

Safety and Tolerability

P-PSMA-101 demonstrated an acceptable safety and tolerability profile and most treatment-emergent adverse events in the trial were managed with early treatment. Six patients experienced grade 1/2 cytokine release syndrome (CRS), with two patients experiencing grade 3 or higher, including the previously reported case of Macrophage Activation Syndrome (MAS) exacerbated by patient non-compliance. Immune effector cell-associated neurotoxicity syndrome (ICANS) was experienced in two patients, both of which were manageable when treated rapidly with anti-cytokine agents and/or steroids. Common reported adverse events included headache, fatigue, chills and blurred vision but were overall well-tolerated.

The Phase 1 trial is an open label, multi-center, 3+3 dose-escalating study designed to assess the safety of P-PSMA-101 in up to 60 adult subjects with mCRPC. The primary objectives of this study are to determine the safety, efficacy, and maximum tolerated dose of P-PSMA-101. Additional information about the study is available at www.clinicaltrials.gov using identifier: NCT04249947.