On March 12, 2021 AVEO Oncology (Nasdaq: AVEO) reported that it has entered into a clinical trial collaboration and supply agreement with Bristol Myers Squibb to evaluate FOTIVDA (tivozanib) in combination with OPDIVO (nivolumab), Bristol Myers Squibb’s anti-PD-1 therapy, in the pivotal Phase 3 TiNivo-2 trial in patients with advanced relapsed or refractory renal cell carcinoma (RCC) following prior immunotherapy exposure (Press release, AVEO, MAR 12, 2021, View Source [SID1234576596]). FOTIVDA is an oral, next-generation vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) approved for the treatment of adult patients with relapsed or refractory advanced RCC following two or more prior systemic therapies.

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The randomized, open-label, controlled TiNivo-2 Phase 3 trial is expected to enroll approximately 326 patients with advanced RCC who have progressed following prior immunotherapy treatment. The study plans to enroll across clinical sites in the United States, Europe, and Latin America. Patients will be randomized 1:1 to receive either FOTIVDA (1.34 mg/QD for 21 days followed by 7 days off treatment) in combination with OPDIVO (480 mg every 4 weeks) or FOTIVDA alone. The TiNivo-2 study’s primary endpoint will assess progression free survival (PFS), with key secondary endpoints to include overall survival, overall response rate and duration of response, and safety.

"With the recent U.S. FDA approval of FOTIVDA in the relapsed/refractory RCC setting, I look forward to further exploring FOTIVDA’s immunomodulatory effects and differentiated tolerability profile in combination with OPDIVO," said Toni Choueiri, M.D., Director, Lank Center for Genitourinary Oncology; Director, Kidney Cancer Center; Jerome and Nancy Kohlberg Chair and Professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute. "This combination was first explored in the Phase 1/2 TiNivo study, where it demonstrated favorable tolerability and prolonged PFS using the combination of FOTIVDA and OPDIVO in both treatment naïve and previously treated patients with advanced RCC. The TiNivo-2 Phase 3 study is expected to further our understanding of the activity and tolerability of this combination following prior immunotherapy."

"The advanced RCC treatment landscape has seen significant benefit from the introduction of immunotherapy-VEGF TKI combinations in earlier-line treatment, and we believe that this benefit could extend to the relapsed/refractory setting with an effective, well-tolerated combination," said Michael Bailey, president and chief executive officer of AVEO. "On the heels of the recent U.S. FDA approval of FOTIVDA as monotherapy for the treatment of adult patients with relapsed or refractory advanced RCC following two or more prior systemic therapies, we are keenly interested in exploring its full potential in the combination setting. Working with our clinical collaborators and Bristol Myers Squibb, our goal is to advance this trial as expeditiously as possible."

Bristol Myers Squibb will provide OPDIVO clinical drug supply for the study. AVEO will serve as the study sponsor and will be responsible for costs associated with the trial execution.

OPDIVO is a registered trademark of Bristol Myers Squibb.

About FOTIVDA (tivozanib)

FOTIVDA (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021 for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner EUSA Pharma (UK) Limited for the treatment of adult patients with advanced RCC. FOTIVDA has been shown to significantly reduce regulatory T-cell production in preclinical models1. FOTIVDA was discovered by Kyowa Kirin.

INDICATIONS

FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hypertension and Hypertensive Crisis: Control blood pressure prior to initiating FOTIVDA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the FOTIVDA dose.

Cardiac Failure: Monitor for signs or symptoms of cardiac failure throughout treatment with FOTIVDA.

Cardiac Ischemia and Arterial Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe arterial thromboembolic events, such as myocardial infarction and stroke.

Venous Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe venous thromboembolic events.

Hemorrhagic Events: Closely monitor patients who are at risk for or who have a history of bleeding.

Proteinuria: Monitor throughout treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment with FOTIVDA.

Thyroid Dysfunction: Monitor before initiation and throughout treatment with FOTIVDA.

Risk of Impaired Wound Healing: Withhold FOTIVDA for at least 24 days before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue FOTIVDA if signs or symptoms of RPLS occur.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

Allergic Reactions to Tartrazine: The 0.89 mg capsule of FOTIVDA contains FD&C Yellow No.5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis, and the most common Grade 3 or 4 laboratory abnormalities (≥5%) were sodium decreased, lipase increased, and phosphate decreased.

DRUG INTERACTIONS

Strong CYP3A4 Inducers: Avoid coadministration of FOTIVDA with strong CYP3A4 inducers.

USE IN SPECIFIC POPULATIONS

Lactation: Advise not to breastfeed.

Females and Males of Reproductive Potential: Can impair fertility.

Hepatic Impairment: Adjust dosage in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.

On March 12, 2021 Anixa Biosciences, Inc. (NASDAQ: ANIX), a biotechnology company focused on the treatment and prevention of cancer and infectious diseases, reported hat the European Patent Office has issued and published the first European patent for its novel ovarian cancer vaccine technology (Press release, Anixa Biosciences, MAR 12, 2021, View Source [SID1234576577]). This technology was invented and developed at Cleveland Clinic and Anixa is the worldwide licensee.

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The patent is titled, "Ovarian Cancer Vaccines," and the inventors are Drs. Vincent K. Tuohy, Suparna Mazumder, and Justin M. Johnson, all of Cleveland Clinic.

Dr. Amit Kumar, President and CEO of Anixa Biosciences, stated, "We are pleased that the European Patent Office (EPO) has issued this patent. This ovarian cancer vaccine has the potential to eliminate one of the deadliest malignancies in women. Ovarian cancer is often diagnosed after it has reached Stage 3 or 4, and when it is difficult to effectively treat. Five-year survival statistics for ovarian cancer are poor, so if this vaccine is able to eliminate the onset of ovarian cancer, the impact for women and for our healthcare system will be tremendous."

"The ovarian cancer vaccine targets a protein (the Extracellular Domain of the Anti-Mullerian Hormone Receptor 2, AMHR2-ED) that is expressed only in the ovaries and only in pre-menopausal women. After menopause, the target protein disappears and is only seen again when ovarian cancer cells arise. Our vaccine targets the AMHR2-ED and trains the immune system to destroy these cancer cells as they arise," said Dr. Vincent Tuohy of the Department of Inflammation and Immunity at Cleveland Clinic’s Lerner Research Institute. "We are looking forward to our continued alliance with Anixa Biosciences to further develop this technology."

On March 12, 2021 Onco360, the nation’s largest independent Oncology Pharmacy, reported that it has been selected by AVEO Oncology to be a specialty pharmacy partner for FOTIVDA (tivozanib), a new oral treatment for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies (Press release, Onco360, MAR 12, 2021, View Source [SID1234576597]).

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"Onco360 is excited to be selected as a specialty pharmacy provider for FOTIVDA patients," said Benito Fernandez, Chief Commercial Officer, Onco360. "The recent approval of FOTIVDA unlocks a new therapy option for treatment-experienced patients with previously treated advanced RCC who have limited treatment options. As a provider of this key treatment, Onco360 can support the highly specialized needs of RCC patients and their physicians across the US."

Renal cell carcinoma (RCC) is the most common type of kidney cancer1, which is among the 10 most common cancers in both men and women.2 According to the American Cancer Society 2020 statistics, approximately 73,750 new cases of kidney cancer will be diagnosed and about 14,830 people will die from this disease.2 Local therapies are often used to treat RCC in earlier stages; however, RCC patients are typically asymptomatic until disease progression and require systemic and targeted treatments at diagnosis.3 Targeted drugs used to treat advanced kidney cancer or metastatic RCC work by blocking angiogenesis and/or important proteins in cancer cells that help them grow and survive.4 Agents that target the vascular endothelial growth factor (VEGF) pathway have shown significant antitumor activity in RCC but are associated with adverse events and side effects that commonly result in high rates of dose interruptions and reductions.5 A more potent, highly selective inhibitor of VEGF receptors may improve efficacy and tolerability, and thus meet an unmet need for efficacious agents with differentiated safety profiles for RCC patients.6

FOTIVDA is manufactured by AVEO Oncology, an oncology-focused biopharmaceutical company committed to delivering medicines that provide a better life for cancer patients. The FDA’s approval of FOTIVDA, for the treatment of adult patients with relapsed or refractory advanced RCC following two or more prior systemic therapies, is based on AVEO’s pivotal Phase 3 study, TIVO-3, comparing FOTIVDA to sorafenib in relapsed or refractory advanced RCC following two or more prior systemic therapies. The study met its primary endpoint of progression free survival (PFS), demonstrating a reduction in the risk of progression or death on treatment by 27% and a 44% improvement in median PFS compared to sorafenib (PFS hazard ratio of 0.73, p=0.02). Median PFS was 5.6 months for FOTIVDA compared to 3.9 months for sorafenib. The application is also supported by three additional trials in RCC and includes safety data from over 1,000 clinical trial subjects. For full prescribing information, visit FOTIVDA.com.

On March 12, 2021 TallacTherapeutics reported AACR (Free AACR Whitepaper) 2021 presentation on preclinical data for TAC-001, the lead program from our novel Toll-like Receptor Agonist Antibody Conjugate (TRAAC) platform (Press release, Tallac Therapeutics, MAR 12, 2021, View Source [SID1234579806]). "TAC-001, a toll-like receptor 9 (TLR9) agonist antibody conjugate targeting B cells, promotes anti-tumor immunity and favorable safety profile following systemic administration in preclinical models"

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On March 12, 2021 Inhibrx, Inc. (Nasdaq: INBX), a biotechnology company with four clinical programs in development, reported financial results for the fourth quarter and fiscal year 2020, and announced results from the single agent dose escalation of the Phase 1 study of INBRX-105 (Press release, Inhibrx, MAR 12, 2021, View Source [SID1234576582]).

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Mark Lappe, Inhibrx’s CEO commented, "2020 was a transformative year for Inhibrx. We made substantive advances in our four clinical programs across oncology and orphan disease, continued to progress our pre-clinical pipeline, and successfully completed an initial public offering."

Phase 1 Dose Escalation Results for INBRX-105

INBRX-105 is a precisely engineered multi-specific therapeutic candidate based on our single domain antibody (sdAb) platform that is designed to agonize 4-1BB selectively in the presence of programmed death ligand 1 (PD-L1), a protein that is typically found in the tumor microenvironment and lymphoid tissues.

The study is a first-in-human, multicenter, open-label, non-randomized, Phase 1 trial in patients with locally advanced or metastatic solid tumors. The trial is designed to determine the safety profile and identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose of INBRX-105 administered as a single agent or in combination with Keytruda (pembrolizumab), a programmed death receptor-1 (PD-1) checkpoint inhibitor. Single agent dose escalation was completed with a total of 32 patients enrolled. We observed dose-limiting toxicities, which were consistent with immune related adverse events (for example, hepatitis, arthritis and myalgia/hyperthyroidism) at several dose levels and determined the 1 mg/kg dose level as the MTD of INBRX-105. Patients were not pre-screened for PD-L1 expression. Eight out of 18 evaluable patients (44%) receiving INBRX-105 at dose levels equal to or greater than 0.1 mg/kg achieved stable disease, with the greatest reduction in tumor volume observed to be 20% by RECISTv1.1. The longest duration on treatment with INBRX-105 was 41 weeks, or approximately nine and a half months. Notably, seven patients with stable disease tested positive for PD-L1 expression, with a minimum of 1% positivity as determined by immunohistochemistry (Range 1 to 95%), and the results of one patient are pending. Four of these eight patients were refractory to or progressed on prior PD-1 checkpoint inhibitors.

We expect to achieve the maximal therapeutic benefit of INBRX-105 in combination with PD-1 checkpoint blockade. In our preclinical studies we observed that acute exposure to PD-L1 dependent 4-1BB agonism was sufficient to derive maximal anti-tumor activity when co-dosed with another PD-1 blocking agent at a target saturating dose. As such, a dose escalation cohort of INBRX-105 in combination with Keytruda is targeted to initiate enrollment during the second quarter of 2021 and we expect to announce initial data during the fourth quarter of 2021.

Financial Results

Cash and Cash Equivalents. Cash and cash equivalents totaled $128.7 million as of December 31, 2020, compared to $11.5 million as of December 31, 2019. Cash and cash equivalents totaled $111.3 million as of February 28, 2021.
R&D Expense. Research and development expense was $17.7 million during the fourth quarter of 2020, as compared to $12.3 million during the fourth quarter of 2019. Research and development expense was $73.5 million during the fiscal year 2020, as compared to $47.9 million during the fiscal year 2019. These increases were primarily due to an increase in contract manufacturing expense for scale-up activities performed by Inhibrx’s contract development and manufacturing organization partners for its INBRX-109 and INBRX-101 programs. Additionally, clinical research organization costs increased due to the progression of its Phase 1 trials.
G&A Expense. General and administrative, or G&A, expense was $2.2 million during the fourth quarter of 2020, as compared to $1.7 million during the fourth quarter of 2019. G&A expense was $6.8 million during the fiscal year 2020, as compared to $6.3 million during the fiscal year 2019. These increases were primarily due to increases in Inhibrx’s personnel-related expenses due to increased headcount and increased rent expense under its amended building lease.
Net Loss. Net loss was $17.6 million during the fourth quarter of 2020, or a net loss per share of $0.47, as compared to a net loss of $16.3 million during the fourth quarter of 2019, or a net loss per share of $0.90. Net loss was $76.1 million during the fiscal year 2020, or a net loss per share of $3.01, as compared to a net loss of $51.4 million during the fiscal year 2019, or a net loss per share of $2.83.
Inhibrx Corporate Presentation

Inhibrx has also updated its corporate presentation which is available on the "Investors" section of its website at www.inhibrx.com.

About the Inhibrx sdAb Platform

Inhibrx utilizes diverse methods of protein engineering in the construction of therapeutic candidates that can address the specific requirements of complex target and disease biology. A key tool for this effort is the Inhibrx proprietary sdAb platform, which enables the development of therapeutic candidates with attributes superior to other monoclonal antibody and fusion protein approaches. This platform allows the combination of multiple binding units in a single molecule, enabling the creation of therapeutic candidates with defined valency or multiple specificities that can achieve enhanced cell signaling or conditional activation. An additional benefit of this platform is that these optimized, multi-functional entities can be manufactured using the established processes that are commonly used to produce therapeutic proteins.