On November 28, 2022 Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) reported financial results for its fiscal year ended September 30, 2022 (Press release, Arrowhead Research Corporation, NOV 28, 2022, View Source [SID1234624492]). The company is hosting a conference call today, November 28, 2022, at 4:30 p.m. ET to discuss the results.

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Conference Call and Webcast Details
Investors may access a live audio webcast on the Company’s website at View Source A replay of the webcast will be available approximately two hours after the conclusion of the call.
For analysts that wish to participate in the conference call, please register at https://register.vevent.com/register/BI9d277550044a4f44bfc335d52e38d268. Once registered, you will receive the dial-in number and a personalized PIN code that will be required to access the call.
Selected Recent Events
•Presented interim data on the cardiometabolic pipeline in three late-breaking oral presentations at the American Heart Association (AHA) Scientific Sessions 2022 and at a virtual analyst and investor event. Key results included the following:
◦ARO-APOC3, an investigational RNAi therapeutic targeting apolipoprotein C-III (APOC3) being developed as a treatment for patients with cardiovascular disease, severe hypertriglyceridemia (SHTG), and familial chylomicronemia syndrome (FCS), decreased triglycerides by 86%, and non-HDL-C by 45% while increasing HDL-C by 99% in patients with severe hypertriglyceridemia
◦ARO-ANG3, investigational RNAi therapeutic designed to silence the hepatic expression of angiopoietin-like protein 3 (ANGPTL3) being developed as a treatment for patients heterozygous and homozygous familial hypercholesterolemia (HeFH and HoFH), decreased triglycerides by 59%, LDL-C by 32%, and was associated with a relative reduction in liver fat fraction in patients with mixed dyslipidemia
◦Olpasiran, which was originally developed by Arrowhead using its proprietary Targeted RNAi Molecule (TRiM) platform and licensed to Amgen in 2016 and is designed to lower levels of lipoprotein(a) (Lp(a)), a genetically-determined independent risk factor for cardiovascular disease, reduced Lp(a) levels by more than 95% in patients with established atherosclerotic cardiovascular disease. These data were simultaneously published in the New England Journal of Medicine (NEJM)

•Reached full enrollment for Phase 2 studies of cardiometabolic candidates ARO-APOC3 and ARO-ANG3, including SHASTA-2, MUIR, ARCHES-2, and GATEWAY
•Strengthened the balance sheet with the sale of Arrowhead’s royalty interest in olpasiran to Royalty Pharma for:
◦$250 million in cash upfront
◦Up to $160 million in additional payments contingent on the achievement of certain clinical, regulatory, and sales milestones
◦Retained rights to $400 million in development, regulatory, and sales milestone payments potentially due from Amgen from the 2016 out licensing agreement
•Initiated Phase 1/2a clinical studies for two new investigational medicines designed to treat various muco-obstructive and inflammatory pulmonary conditions
◦ARO-MUC5AC, an investigational RNAi therapeutic designed to inhibit the production of mucin 5AC (MUC5AC)
◦ARO-RAGE, an investigational RNAi therapeutic designed to inhibit the production of Receptor for Advanced Glycation End products (RAGE)
•Initiated a Phase 1/2a clinical trial of ARO-MMP7, an investigational RNAi therapeutic designed to reduce expression of matrix metalloproteinase 7 (MMP7) as a potential treatment for idiopathic pulmonary fibrosis (IPF), with dosing to begin soon

On November 28, 2022 Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the "Company"), a clinical-stage macrophage reprogramming immunotherapy company, reported that the U.S. Food & Drug Administration (FDA) has cleared an Investigational New Drug (IND) application to study Allocetra in patients with advanced solid malignancies (Press release, Enlivex Therapeutics, NOV 28, 2022, View Source [SID1234624490]). The FDA’s Phase I/II clearance follows a recent announcement by the Company that the first patient has been dosed in a Phase I/II multi-center clinical trial in Israel designed to evaluate the safety, tolerability and preliminary efficacy of Allocetra stand-alone, and in combination with a PD1 checkpoint inhibitor, in patients with advanced solid tumors.

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Oren Hershkovitz, Ph.D., Chief Executive Officer of Enlivex, stated "We are pleased with the FDA’s regulatory clearance for our IND. The formal initiation of clinical development of AllocetraTM for oncology indications in the United States represents a significant milestone for Enlivex. We believe that AllocetraTM has the potential to provide a paradigm shift in the treatment of advanced solid tumors, and we look forward to observing safety and potential indication of effect in patients, who we expect to enroll in several open-label Company-sponsored and investigator-initiated oncology trials during 2023."

ABOUT ALLOCETRA

Allocetra is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as "unmet medical needs", as a stand-alone therapy or in combination with leading therapeutic agents.

On November 28, 2022 Cimeio Therapeutics, a biotechnology company developing a novel approach to cell therapies, reported the U.S. Patent Office has issued a key patent covering the company’s Shielded-Cell & Immunotherapy Pairs (SCIP) platform (Press release, Cimeio Therapeutics, NOV 28, 2022, https://www.cimeio.com/2022/11/28/cimeio-therapeutics-announces-issuance-of-key-patent-covering-cell-therapy-platform/?utm_source=rss&utm_medium=rss&utm_campaign=cimeio-therapeutics-announces-issuance-of-key-patent-covering-cell-therapy-platform [SID1234624489]).

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U.S. Patent No. 11,499,168 covers a method for in vivo selective depletion of edited primary hematopoietic cells or non-edited primary hematopoietic cells. This method was first discovered and developed in the lab of company founder Lukas Jeker, M.D., Ph.D., at the University of Basel, and is exclusively licensed to Cimeio.

"This comprehensive intellectual property provides broad protection for our platform," said Cimeio CEO Thomas Fuchs. "We believe this patent, along with those we’ve filed for our target antigen and immunotherapy portfolio, cements us as a leader in the emerging field of cell shielding and will enable the broad development of our SCIP platform."

Cimeio uses genome editing to insert novel protein variants into hematopoietic stem cells or other types of cells, allowing the cells to maintain their function while making them resistant to paired immunotherapy depletion. Cimeio’s platform has effectively shielded cells from depletion mediated by antibodies, T-cell engagers, ADCs, and CAR-T cells in preclinical studies.

The company is advancing its first programs towards clinical development for genetic and malignant hematologic diseases. As previously disclosed, two posters for the company’s pipeline programs will be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) meeting in December 2022 in New Orleans.

On November 28, 2022 Ikena Oncology, Inc. (Nasdaq: IKNA, "Ikena"), a targeted oncology company forging new territory in patient-directed cancer treatment, reported a next-generation mitogen-activated protein kinase (MEK)-RAF complex inhibitor, IK-595, has been nominated as the company’s first development candidate in the RAS pathway (Press release, Ikena Oncology, NOV 28, 2022, View Source [SID1234624488]).

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The RAS pathway is implicated in at least half a million new cancer diagnosis each year in the United States alone. Ikena aims to target the pathway on multiple levels, including preventing known resistance mechanisms to achieve deep and sustained responses. Ikena’s new development candidate, IK-595, traps MEK and RAF in an inactive complex, more completely inhibiting RAS signals than existing inhibitors. IK-595’s ability to complex CRAF, in particular, prevents a well-recognized signaling bypass mechanism that cancer cells employ to drive therapeutic resistance to other drugs in this class. In addition, trapping CRAF in an inactive complex prevents the kinase independent anti-apoptotic function in RAS and RAF mutant cancers, a mechanism that cannot be addressed with first generation MEK inhibitors or pan-RAF inhibitors. IK-595 is being developed as an oral therapy, with a half-life enabling a pharmacokinetic profile potentially superior to other drugs, with the goal of developing an optimal therapeutic window for patients. The company plans to submit an investigational new drug application (IND) for IK-595 to the US Food & Drug Administration (FDA) in the second half of 2023.

"I am thrilled to announce this addition to our pipeline, one that adds to our holistic approach to the Hippo & RAS oncosignaling network. IK-595 inhibits multiple nodes of MEK-RAF signaling, including avoiding known mechanisms of resistance," said Mark Manfredi, PhD, Ikena’s Chief Executive Officer. "The industry’s excitement about MEK inhibition stems from its great potential as a target, but the challenges of CRAF bypass and achieving optimal target inhibition have kept first generation treatments from meeting the full potential of the target. We are hopeful that our MEK-RAF trapping approach with an optimized therapeutic window can make IK-595 a game-changing candidate for multiple indications in the RAS space."

Development Highlights, Corporate Updates, and Upcoming Milestones

Advancing new development candidate, IK-595, through IND-enabling studies, targeting MEK-RAF through novel mechanisms aiming to address existing gaps in the MEK inhibitor space
Preclinical differentiation data planned for presentation in the first half of 2023
IND targeted in the second half of 2023
Progressing novel, paralog-selective transcriptional enhanced associate domain (TEAD) inhibitor, IK-930, in the clinic and further defining differentiation profile from panTEAD inhibition
Monotherapy program progressing as planned, advanced through multiple dose escalation cohorts
Preclinical data on differentiation and advantages of paralog selectivity planned for presentation in first half of 2023
Initiation of osimertinib combination cohort clinical program expected in first half of 2023
Initial clinical data from IK-930 monotherapy program expected in second half of 2023
Following a portfolio review, discontinuing the internal clinical development of the EP4 antagonist IK-007 and exploring strategic alternatives for this program
Clinical data from IK-007 in microsatellite stable colorectal cancer (MSS-CRC) will be presented in a poster at 2022 European Society for Medical Oncology Immuno-Oncology Congress
Portfolio reprioritization and streamlining of discovery and clinical activities contribute to extension of cash runway into 2025
Runway does not include any potential licensing revenue from the aryl hydrocarbon receptor (AHR) antagonist IK-175 program, currently in development in collaboration with Bristol Myers Squibb and eligible for opt-in through early 2024
"Ikena has a strong track record of internal drug discovery and development that has built our robust clinical and early-stage pipeline," said Jotin Marango, MD, PhD, Chief Financial Officer and Head of Corporate Development of Ikena. "Our goal is to continue our leadership in targeted oncology by discovering and advancing best-in-class candidates like IK-930 and IK-595, therapies designed to address the needs of specific patient populations while at the same time building value for our shareholders."

On November 28, 2022 Evotec’s partner Exscientia plc (Nasdaq: EXAI) reported clinical trial application ("CTA") approval of a Phase I/II trial of EXS-21546, an A2a receptor antagonist, co-invented and developed through a collaboration between Exscientia and Evotec (Press release, Evotec, NOV 28, 2022, View Source [SID1234624487]). The approval enables site activation in the first European country.

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The Phase I/II trial will evaluate safety, efficacy, pharmacokinetics and pharmacodynamics of EXS-21546 in combination with anti-PD-1 therapy in up to 110 patients with immunotherapy relapsed or refractory renal cell carcinoma ("RCC") and non-small cell lung cancer ("NSCLC"). The molecule was identified in 9 months after testing 163 compounds and is one of the first AI designed drugs in the industry to enter the clinic. In June 2022, Exscientia reported topline data from a healthy volunteer study which confirmed Exscientia’s target product profile design, including potency, high receptor selectivity and expected low brain exposure with no CNS adverse events reported.

Exscientia intends to expand to additional tumour types, including breast cancer, in future trials after assessment of EXS-21546 activity and validation of its selection biomarkers.

Exscientia will lead further clinical development of the molecule and Evotec will retain co-ownership rights throughout clinical development.