On June 12, 2020 ALX Oncology Holdings Inc., a clinical-stage immuno-oncology company developing therapies that block the CD47 checkpoint pathway, reported preliminary results from the fully enrolled ALX148 plus rituximab combination cohort of the Phase 1 clinical program at the 25th Annual Congress of EHA (Free EHA Whitepaper) [abstract #EP1247] (Press release, ALX Oncology, JUN 12, 2020, View Source [SID1234561060]). As of April 1, 2020, 33 patients with relapsed or refractory non-Hodgkin Lymphoma (NHL) were administered ALX148 at 10 or 15 mg/kg once per week (QW) in combination with a standard rituximab regimen. The following key results were observed in response-evaluable subjects:

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ALX148 in combination with a standard regimen of rituximab is well tolerated with no maximum tolerated dose reached. The maximum administered dose is 15 mg/kg QW (molar equivalent to 30 mg/kg QW an antibody) with no exposure-dependent cytopenia observed across the exposure range evaluated.
ALX148 10mg/kg plus rituximab (n=22): In all subjects, an overall objective response rate (ORR) of 40.9% and median progression-free survival (mPFS) of 7.4 months were observed.
In patients with aggressive NHL (n=15) an ORR of 33.3% and median duration of response (mDOR) of 5.6 months were observed.
In patients with indolent NHL (n=7) an ORR of 57.1% was observed and mDOR was not reached.
Three patients achieved complete response.
ALX148 15mg/kg plus rituximab (n=11): In all subjects, an ORR of 54.6% was observed and mPFS was not reached.
In patients with aggressive NHL (n=7) an ORR of 42.9% was observed and mDOR was not reached.
In patients with indolent NHL (n=4) an ORR of 75% was observed and mDOR was not reached.
Two patients achieved complete response.
ALX148 demonstrates linear pharmacokinetics at 10 mg/kg and 15 mg/kg QW with near complete peripheral CD47 target occupancy in combination with rituximab at both dose levels.
"With no exposure-dependent cytopenias observed, and a greater response rate observed in the higher dosing cohort of heavily pre-treated subjects with NHL, we believe this study provides compelling evidence for the potential of ALX148 in treating hematologic malignancies," said Sophia Randolph, M.D., Ph.D., Chief Medical Officer of ALX Oncology. "The higher ALX148 exposure levels observed in subjects with objective responses is encouraging evidence for the pharmacologic activity of ALX148 and supports higher dose administration in future trials for patients with cancer."

On June 12, 2020 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) has approved an expanded indication for GARDASIL 9 for the prevention of oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58 (Press release, Merck & Co, JUN 12, 2020, View Source [SID1234561059]). The oropharyngeal and head and neck cancer indication is approved under accelerated approval based on effectiveness in preventing HPV-related anogenital disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. The trial is currently underway.

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"At Merck, working to help prevent certain HPV-related cancers has been a priority for more than two decades," said Dr. Alain Luxembourg, director, clinical research, Merck Research Laboratories. "Today’s approval for the prevention of HPV-related oropharyngeal and other head and neck cancers represents an important step in Merck’s mission to help reduce the number of men and women affected by certain HPV-related cancers."

GARDASIL 9 is a vaccine indicated in females 9 through 45 years of age for the prevention of cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by human papillomavirus (HPV) Types 16, 18, 31, 33, 45, 52, and 58; cervical, vulvar, vaginal, and anal precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

GARDASIL 9 is indicated in males 9 through 45 years of age for the prevention of anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58; anal precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

GARDASIL9 (Human Papillomavirus 9-valent Vaccine, Recombinant) is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL 9 or GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant].

Both men and women can be at risk for HPV-attributable oropharyngeal cancer; however, this cancer affects men five times more than women.1 For most people, HPV clears on its own. But, for those who don’t clear the virus, it can cause certain cancers. Oropharyngeal cancer can arise as a result of HPV infection in the oropharynx, which includes the soft palate, side and back wall of the throat, tonsils, and back one-third of the tongue. According to a recent model published by the U.S. Centers for Disease Control and Prevention (CDC), HPV-attributable oropharyngeal cancer has surpassed cervical cancer as the most prevalent type of HPV-related cancer in the U.S.1

1 The CDC analyzed data from the U.S. Cancer Statistics (USCS) to assess the incidence of HPV-associated cancers and to estimate the annual number of cancers caused by HPV, overall and by state, during 2012 to 2016.

The estimated number of HPV-attributable cancers was calculated by multiplying the average number of HPV-associated cancers by the percentage of HPV-attributable cancers diagnosed from 1993 to 2005, before HPV vaccination was available in the U.S.

The detection of HPV DNA in an HPV study is not enough to determine that HPV caused the cancer.

Not all cervical and oropharyngeal cancers are caused by HPV.

Important Information About GARDASIL 9

GARDASIL 9 does not eliminate the necessity for vaccine recipients to undergo screening for cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers as recommended by a healthcare provider.

GARDASIL 9 has not been demonstrated to provide protection against diseases caused by:

HPV types not covered by the vaccine
HPV types to which a person has previously been exposed through sexual activity
Not all vulvar, vaginal, anal, oropharyngeal and other head and neck cancers are caused by HPV, and GARDASIL 9 protects only against those vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58.

GARDASIL9 (Human Papillomavirus 9-valent Vaccine, Recombinant) is not a treatment for external genital lesions; cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers; or cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), or anal intraepithelial neoplasia (AIN).

Vaccination with GARDASIL 9 may not result in protection in all vaccine recipients.

Select Safety Information for GARDASIL 9

GARDASIL 9 is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL 9 or GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant].

Because vaccinees may develop syncope, sometimes resulting in falling with injury, observation for 15 minutes after administration is recommended. Syncope, sometimes associated with tonic-clonic movements and other seizure-like activity, has been reported following HPV vaccination. When syncope is associated with tonic-clonic movements, the activity is usually transient and typically responds to restoring cerebral perfusion.

Safety and effectiveness of GARDASIL 9 have not been established in pregnant women.

The most common (≥10%) local and systemic adverse reactions in females were injection-site pain, swelling, erythema, and headache. The most common (≥10%) local and systemic reactions in males were injection-site pain, swelling, and erythema.

The duration of immunity of GARDASIL 9 has not been established.

Dosage and Administration for GARDASIL 9

GARDASIL 9 should be administered intramuscularly in the deltoid or anterolateral area of the thigh.

For individuals 9 through 14 years of age, GARDASIL 9 can be administered using a 2-dose or 3-dose schedule. For the 2-dose schedule, the second dose should be administered 6-12 months after the first dose. If the second dose is administered less than 5 months after the first dose, a third dose should be given at least 4 months after the second dose. For the 3-dose schedule, GARDASIL 9 should be administered at 0, 2 months, and 6 months.
For individuals 15 through 45 years of age, GARDASIL 9 is administered using a 3-dose schedule at 0, 2 months, and 6 months.
About HPV and HPV-related Cancers and Diseases

According to the CDC, an estimated 14 million new HPV infections occur every year in the United States. HPV is so common that 80% of people who are sexually active get HPV at some point in their life. For most people, HPV clears on its own; but for those who don’t clear the virus, it could cause certain cancers and diseases. There is no way to know which people who have HPV will develop cancer or other health problems. GARDASIL9 (Human Papillomavirus 9-valent Vaccine, Recombinant) helps protect against seven HPV types that cause the majority of HPV-related cancers in the United States. Persistent HPV infection can also lead to pre-cancerous lesions that may require additional follow-up procedures. With the exception of cervical cancer, there is no routinely recommended screening for the detection of HPV-related cancers.

On June 12, 2020 Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") reported that it prepaid in full its outstanding term loans on June 12, 2020 (Press release, Sorrento Therapeutics, JUN 12, 2020, View Source [SID1234561058]).

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The prepaid debt, comprised of an initial $100 million term loan and an additional $20 million term loan from certain funds affiliated with Oaktree Capital Management, L.P., was obtained pursuant to a Term Loan Agreement entered into in November 2018.

On June 12, 2020 Aura Biosciences, a clinical-stage biopharmaceutical company developing a novel class of tumor targeted therapies for initial application in primary tumors such as choroidal melanoma, reported the virtual presentation of updated clinical data from its ongoing Phase 1b/2 clinical trial evaluating the safety and efficacy of light-activated AU-011, the Company’s lead product candidate for the first line treatment of primary choroidal melanoma, as part of the Association for Research in Vision and Ophthalmology (ARVO) 2020 Annual Meeting (Press release, Aura Biosciences, JUN 12, 2020, View Source [SID1234561036]).

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"The clinical data presented this year at ARVO show that AU-011 has a favorable preliminary safety profile, controls tumor growth rate, and preserves vision in the vast majority of patients, including those at high risk for vision loss with tumors close to the fovea or optic nerve," said Prithvi Mruthyunjaya, MD, MHS, Associate Professor of Ophthalmology and Director, Ocular Oncology Service, Byers Eye Institute at Stanford University, and presenter of the abstract. "We believe these data support further clinical investigation in pivotal studies."

Updated Results from the Phase 1b/2 Study Evaluating AU-011

This open-label, multicenter trial is designed to investigate single and multiple ascending doses of light-activated AU-011, administered via intravitreal injection, in adult subjects with clinically diagnosed primary choroidal melanoma. The updated data demonstrate that multiple administrations of light-activated AU-011 were generally well-tolerated. Among the patients evaluated for safety (n=56), the most common treatment-related adverse events (AEs) were expected and included vitreous inflammation, anterior chamber inflammation and increase in intraocular pressure; all were manageable with standard-of-care treatments and the majority resolved without clinical sequelae. There were two treatment-related serious AEs (vision loss; 3.6%). Tumor control and vision preservation data continue to be supportive of the planned pivotal study.

Expanding Development of AU-011 to Include Suprachoroidal Administration

In addition to intravitreal administration, Aura is also planning to investigate AU-011 using the suprachoroidal (SC) route of administration. Aura believes that delivering AU-011 into the suprachoroidal space (SCS) within the eye, has the potential to maximize bioavailability at the tumor site and could allow for the treatment of a wider range of tumor sizes (small to medium size tumors), and therefore, a larger number of patients. The Company is partnered with Clearside Biomedical for use of Clearside’s SCS Microinjector for administration of AU-011 into the SCS. Preclinical research regarding the ocular distribution and efficacy in a rabbit model of AU-011 using the SC administration is also being presented as part of the ARVO 2020 virtual program. The data showed excellent distribution of AU-011 in the SCS and complete necrosis of tumors following laser activation in a rabbit model of choroidal melanoma. Further preclinical studies are currently ongoing and Aura expects to initiate a Phase 2 clinical study evaluating SC delivery of AU-011 during the third quarter of 2020.

Cadmus Rich, MD, MBA Chief Medical Officer and Head of Research and Development at Aura Biosciences commented, "The suprachoroidal delivery route is exciting because it offers certain potential advantages over intravitreal injection, including high bioavailability of drug to the posterior segment of the eye where the choroidal melanoma is located and minimal exposure of non-targeted tissues which, based on preclinical toxicology studies, may lead to less intraocular inflammation and an improved safety profile. We believe that the SC administration of AU-011 will ultimately allow us to treat a larger number of patients with choroidal melanoma. We look forward to initiating a first-in-human Phase 2 study to assess this additional route of administration this year."

Details for the ARVO 2020 presentation is as follows:

Title: An Ongoing Phase 1b/2 Open-Label Clinical Trial to Evaluate the Safety and Efficacy of AU-011 for the Treatment of Choroidal Melanoma – Study Update

Presenter: Prithvi Mruthyunjaya, Stanford University

Abstract #: 4025

Session: Uveal melanoma

URL: View Source

Title: Ocular distribution and efficacy after suprachoroidal injection of AU-011 for treatment of ocular melanoma

Presenter: Anneli Savinainen, Aura Biosciences

Abstract #: 3615

Session: Uveal melanoma – Advances in Therapy

URL: View Source

The presentations can be accessed by ARVO members on the ARVOLearn website. The presentations can also be accessed by visiting the "Presentations" section of "News and Publications" page of the Aura Biosciences website.

About Choroidal Melanoma

Choroidal melanoma is a rare and aggressive type of eye cancer. Choroidal melanoma is the most common primary intraocular tumor in adults and develops in the uveal tract of the eye. No targeted therapies are available at present, and current radiotherapy treatments can be associated with severe visual loss and other long-term sequelae such as dry eye, glaucoma, cataracts and radiation retinopathy. The most common current treatment is plaque radiotherapy, which involves surgical placement of a radiation device on the exterior of the eye over the tumor. The alternative is enucleation, or total surgical removal of the eye. Choroidal melanoma metastasizes in approximately 50 percent of cases with liver involvement in 80-90% of cases and, unfortunately, metastatic disease is universally fatal (source: OMF). There is a very high unmet need for a new vision sparing targeted therapy that could enable early treatment intervention for this life-threatening rare disease given the lack of approved therapies, and the comorbidities of radioactive treatment options.

About Light-Activated AU-011

AU-011 is a first-in-class targeted therapy in development for the treatment of primary choroidal melanoma. The therapy consists of proprietary viral-like particle bioconjugates (VPB) that are activated with an ophthalmic laser. The VPBs bind selectively to unique receptors on cancer cells in the eye and are derived from technology originally pioneered by Dr. John Schiller of the Center for Cancer Research at the National Cancer Institute (NCI), recipient of the 2017 Lasker-DeBakey Award. Upon activation with an ophthalmic laser, the drug rapidly and specifically disrupts the cell membrane of tumor cells while sparing key eye structures, which may allow for the potential of preserving patients’ vision and reducing other long-term complications of radiation treatment. AU-011 can be delivered using equipment commonly found in an ophthalmologist’s office and does not require a surgical procedure, pointing to a potentially less invasive, more convenient therapy for patients and physicians. AU-011 for the treatment of choroidal melanoma has been granted orphan drug and fast track designations by the U.S. Food and Drug Administration and is currently in clinical development.

On June 12, 2020 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a Phase 3 stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, with an initial focus on myelodysplastic syndromes (MDS), reported updated aggregated baseline genomic data from HMA-failure patients screened for the INSPIRE trial were presented in an e-poster at the virtual 25th Annual EHA (Free EHA Whitepaper) Congress (Press release, Onconova, JUN 12, 2020, View Source [SID1234561035]).

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"There are more than 45 driver mutations that have been identified in higher-risk (HR) MDS patients. To our knowledge, this mutational analysis from the INSPIRE trial is among the largest such datasets to be collected," said Steven M. Fruchtman, M.D., President and Chief Executive Officer.

The on-demand presentation will be available on the EHA (Free EHA Whitepaper) website as of Friday, June 12 at 8:30 a.m. CEST, and will be accessible until October 15, 2020.

Abstract #EP829. "Mutations in RAS Pathway Genes Correlate with Type of Failure to Azacitidine: Genomic Analysis at Randomization onto the Inspire Trial."

As an exploratory endpoint, bone marrow samples were collected at baseline, months 2, 4 and 6, and every 6 months thereafter, as well as at the end of treatment, for mutational analysis. Genomic DNA was extracted and deep sequencing of 295 genes will be performed on these samples following analysis of the primary endpoint. In total, 55 different mutations were identified at baseline, with the median number of mutations per patient at 3.

"RAS pathway mutations were observed more frequently in patients that progressed on HMA therapy than those that failed HMA therapy completely. Understanding the association between RAS mutations and prognoses in this MDS setting appears to be informative to the potential role of RAS-targeting agents such as rigosertib," said Richard C. Woodman, M.D., Chief Medical Officer.