On April 27, 2017 Myriad Genetics, Inc. (NASDAQ: MYGN) and Clovis Oncology, Inc. (NASDAQ:CLVS) reported a companion diagnostic collaboration to support a post-marketing regulatory commitment related to Clovis’ PARP inhibitor, Rubraca (Press release, Myriad Genetics, APR 27, 2017, View Source [SID1234518718]). Financial terms of the deal were not disclosed.

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Under the agreement, Myriad will submit a supplementary premarket approval (sPMA) application under its existing PMA for BRACAnalysis CDx to include Rubraca. The Myriad sPMA submission will fulfill a post-approval regulatory commitment by Clovis Oncology to the Food and Drug Administration (FDA) for Rubraca. In December 2016, Rubraca was approved for women with advanced ovarian cancer who have been treated with two or more chemotherapies and whose tumors have a deleterious BRCA mutation as identified by an FDA-approved companion diagnostic test. The companion diagnostic test approved with Rubraca does not discriminate between germline and somatic mutations. Knowledge of germline status is important to provide patients appropriate counseling.

"BRACAnalysis CDx is the only germline companion diagnostic test approved by the FDA to identify patients with BRCA1/2 mutations, and we are excited to support Clovis’ clinical development program and help identify patients who are most likely to benefit from rucaparib," said Mark C. Capone, president and CEO, Myriad Genetics. "This agreement further solidifies Myriad’s leadership role in developing best-in-class companion diagnostics for use with PARP inhibitors and supports our goal of being the worldwide leader in personalized medicine."

"This partnership with Myriad Genetics not only enables us to fulfill our post-marketing commitment to the FDA, but will enhance the companion diagnostic information already available to physicians and patients, providing a robust toolkit for personalizing treatment of patients with BRCA1/2 mutations," said Patrick J. Mahaffy, president and CEO, Clovis Oncology.

About Rubraca (rucaparib)
Rubraca is a PARP inhibitor indicated as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer, who have been treated with two or more chemotherapies, and selected for therapy based on an FDA-approved companion diagnostic for Rubraca. The indication for Rubraca is approved under the FDA’s accelerated approval program based on objective response rate and duration of response, and is based on results from two multicenter, single-arm, open-label clinical trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Please visit rubraca.com for more information. About BRACAnalysis CDx BRACAnalysis CDx is an in vitro diagnostic device intended for the qualitative detection and classification of variants in the protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes using genomic DNA obtained from whole blood specimens collected in EDTA. Single nucleotide variants and small insertions and deletions (indels) are identified by polymerase chain reaction (PCR) and Sanger sequencing. Large deletions and duplications in BRCA1 and BRCA2 are detected using multiplex PCR. BRACAnalysis CDx was reviewed and approved by the FDA in December 2014 for use as a companion diagnostic to aid in identifying ovarian cancer patients eligible for treatment with AstraZeneca’s PARP inhibitor, olaparib. This assay is for professional use only and is to be performed only at Myriad Genetic Laboratories, a single laboratory site located at 320 Wakara Way, Salt Lake City, UT 84108.

MediciNova has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

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On April 26, 2017 Silvergate Pharmaceuticals, Inc. (www.silvergatepharma.com), leaders in the development and commercialization of innovative and safe medicines for children, reported that the United States Food and Drug Administration (FDA) approved XATMEP (methotrexate) Oral Solution, the first and only FDA-approved methotrexate oral solution (Press release, Silvergate Pharmaceuticals, APR 26, 2017, View Source [SID1234625387]). XATMEP is indicated for the treatment of acute lymphoblastic leukemia (ALL) and polyarticular juvenile idiopathic arthritis (pJIA) in pediatric patients.

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"XATMEP is an exciting product in that it provides an FDA-approved, ready-to-use oral solution of methotrexate for children without the need for needles, crushing of tablets or compounding into a liquid formulation," said Frank Segrave, President & CEO, Silvergate Pharmaceuticals, Inc. "As a company, we continue to focus on pediatric medications that are safe, effective, and readily available."

XATMEP (methotrexate) Oral Solution, 2.5 mg/mL, is a ready-to-use product that requires no preparation, facilitating accuracy and ease of dispensing at the pharmacy. XATMEP is manufactured under CGMPs in accordance with FDA regulations. It eliminates the need for needles, crushing or splitting tablets or for compounding tablets into a liquid formulation. It requires refrigeration but may be stored at room temperature for 60 days after dispensing. XATMEP is available through an extensive network of pharmacies and a qualified mail-order service. For additional information on how to obtain XATMEP, please call 1-855-379-0382.

INDICATIONS

XATMEP is a folate analog metabolic inhibitor indicated for the:

management of pediatric patients with active polyarticular juvenile idiopathic arthritis (pJIA) who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full dose non-steroidal anti-inflammatory agents (NSAIDs).
treatment of pediatric patients with acute lymphoblastic leukemia (ALL) as part of a multi-phase, combination chemotherapy maintenance regimen.
About XATMEP

XATMEP (methotrexate) Oral Solution was developed, primarily, to meet the need for a ready-to-use, 2.5 mg/mL, methotrexate oral solution for the treatment of pediatric patients for the indications stated above. Currently, there is no FDA-approved, ready-to-use oral liquid formulation of methotrexate for use by pediatric patients requiring body surface area (BSA) dosing (mg/m2) or who have difficulty swallowing or cannot consume tablets, or those with needle-phobia. Silvergate Pharmaceuticals, Inc.’s XATMEP (methotrexate) Oral Solution resolves these unmet medical needs in pediatric patients.

IMPORTANT SAFETY INFORMATION

XATMEP includes a BOXED WARNING: SEVERE TOXIC REACTIONS, INCLUDING EMBRYO-FETAL TOXICITY

See full prescribing information for complete boxed warning.

Methotrexate can cause severe or fatal toxicities. Monitor closely and modify dose or discontinue for the following toxicities: bone marrow suppression (5.1), infection (5.2), renal (5.3), gastrointestinal (5.4), hepatic (5.5), pulmonary (5.6), hypersensitivity and dermatologic (5.7).
Methotrexate can cause embryo-fetal toxicity and fetal death. Use in polyarticular juvenile idiopathic arthritis is contraindicated in pregnancy (4). Consider the benefits and risks of XATMEP and risks to the fetus when prescribing XATMEP to a pregnant patient with a neoplastic disease. Advise patients to use effective contraception during and after treatment with XATMEP (5.9, 8.1, 8.3).
ADDITIONAL IMPORTANT SAFETY INFORMATION

XATMEP is contraindicated in patients who are hypersensitive to methotrexate.
XATMEP is contraindicated in patients who are pregnant or nursing.
Warnings and Precautions:

Monitor closely and modify dose or discontinue XATMEP as appropriate.

Methotrexate can cause the following severe, life-threatening or fatal adverse reactions:

Bone marrow suppression: pancytopenia, anemia, leukopenia, neutropenia, and thrombocytopenia.
Serious infections: bacterial, fungal, or viral infections, including Pneumocystis jiroveci pneumonia, invasive fungal, hepatitis B reactivation, tuberculosis, Herpes zoster and cytomegalovirus infections.
Renal toxicity and renal impairment, including acute renal failure.
Gastrointestinal toxicity: diarrhea, stomatitis, vomiting, hemorrhagic enteritis, fatal intestinal perforation. Unexpected severe and fatal gastrointestinal toxicity can occur with concomitant us of NSAIDs.
Hepatic toxicity: severe and potentially irreversible hepatotoxicity, including fibrosis, cirrhosis, and fatal liver failure.
Pulmonary toxicity: acute or chronic interstitial pneumonitis and irreversible or fatal cases at all dose levels.
Hypersensitivity: anaphylaxis.
Dermatologic reactions: toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, skin necrosis, erythema multiforme. Radiation dermatitis and "sunburn" may be recalled.
Secondary malignancies: lymphoproliferative disease has been reported with low-dose oral methotrexate which regressed when methotrexate is withdrawn.
Embryo-fetal toxicity and fetal death: Consider the risks and benefits of XATMEP and risks to the fetus when prescribing to a pregnant patient with a neoplastic disease. XATMEP is contraindicated in non-neoplastic disease.
Immunizations may be ineffective when given during XATMEP therapy.
Immunization with live virus vaccines is not recommended during XATMEP therapy.
Effects on reproduction: Methotrexate can cause impairment of fertility, oligospermia, and menstrual dysfunction. Effective contraception should be practiced by patients of reproductive potential while receiving XATMEP therapy, and for 3 and 6 months afterwards for males and females, respectively.
Third-space accumulation: Evacuate significant third-space accumulation prior to methotrexate administrations.
Concomitant radiation therapy increases the risk of soft tissue necrosis and osteonecrosis associated with methotrexate.
Closely monitor laboratory parameters for hematology, renal function and liver function. Increase monitoring during initial dosing, dose changes and during periods of increased risk of elevated methotrexate blood levels (e.g., dehydration).
Improper dosing: Once weekly dosing is appropriate. Fatal toxicity has been reported with daily dosing. An accurate millimeter measuring device should be used.
Advise women not to breastfeed.
Adverse Reactions: See full prescribing information for additional adverse reactions.

Most common adverse reactions are ulcerative stomatitis, leukopenia, nausea, abdominal distress, and elevated liver function tests.

Other frequently reported reactions are malaise, fatigue, chills and fever, dizziness, and decreased risk to infection.

Drug Interactions:

Oral antibiotics: Hematologic and gastrointestinal toxicity may increase.
Hepatotoxins: May increase hepatoxicity.
Probenecid: Consider alternative drugs as may increase methotrexate exposure.
Theophylline: May reduce theophylline clearance.
To report SUSPECTED ADVERSE REACTIONS, contact Silvergate Pharmaceuticals at 1-855-379-0383, or FDA at 1-800-FDA-1088 or www.fda.gov/MedWatch.

Please see accompanying full Prescribing Information, including the complete BOXED WARNING.

About Silvergate Pharmaceuticals, Inc.
Headquartered near Denver, Colorado, Silvergate Pharmaceuticals, Inc., is a privately held pharmaceutical company dedicated to leading the way in the development and commercialization of innovative pediatric medications that are safe, effective, and readily available.

Silvergate Pharmaceuticals is committed to filling the unmet needs of children, developing innovative medications that will help improve the quality of care and outcomes for pediatric patients. For more information, please visit View Source

Reference: XATMEP [prescribing information]. Greenwood Village, CO: Silvergate Pharmaceuticals, Inc.; 2017.

On April 25, 2017 Tessa Therapeutics, an immunotherapy company dedicated to revolutionizing the treatment of cancer, and Vyriad, an oncolytic virotherapy company using engineered viruses to destroy tumors and boost the antitumor immune response, reported a collaboration that will enable Tessa and Vyriad to investigate T cell and oncolytic virus combination therapies (Press release, Vyriad, APR 25, 2017, View Source [SID1234527874]). The combination of these two therapies is highly synergistic and has the potential to target a wide range of solid tumors with increased efficacy.

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Tessa and Vyriad have signed a collaboration agreement to combinae Tessa’s HPV-specific T cells with Vyriad’s vesicular stomatitis virus (VSV) for the treatment of HPV-associated cancers such as cervical as well as head and neck cancers. Tessa is currently employing its HPV-specific T Cell technology in an FDA Phase I trial targeting these cancers, and aims to commence Phase II trials in 2017/2018. Vyriad is currently testing its oncolytic VSV technology in FDA Phase I trials. Additionally, Vyriad plans to clinically test a virus that has been engineered to drive proliferation of HPV-specific T cells in early 2018.

Whilst oncolytic viruses are known for their ability to specifically infect and destroy tumors, Vyriad’s oncolytic viruses have been engineered to express antigens to improve the immune response against the tumor. This increased antigen expression is expected to significantly enhance the efficacy of Tessa’s VSTs by improving their ability to recognize, target, and destroy cancer cells, thus making the combination of both treatments highly synergistic. Furthermore, oncolytic viruses can be engineered to express viral tumor antigens in nonvirus associated cancers, hence widening the potential range of cancers that can be targeted by Tessa’s VST-based treatments.

Andrew Khoo, co-founder and CEO of Tessa Therapeutics, commented on the partnership "We are constantly looking for ways to expand the efficacy and potential applications of our cancer treatments to benefit as many patients as possible. The combination of VSTs with oncolytic viruses is a novel approach that is entirely aligned with our philosophy of redirecting the body’s highly effective anti-viral immune response to target and destroy solid tumors."

Dr Stephen Russell, co-Founder, President and CEO of Vyriad, said "Through this partnership, Tessa and Vyriad can build on each company’s expertise to develop treatments that are more potent with broader applications. The use of engineered viruses, together with VSTs, is highly synergistic and has the potential to benefit a greater range of patients in areas of significant unmet medical need."

On April 25, 2017 Circle Pharma , Inc. reported that it has completed an expansion of its Series A financing, with new investors WI Harper Group, Elements Partners, LLC, Whitesun Healthcare Ventures Limited and LifeForce Capital joining the round (Press release, Circle Pharma, APR 25, 2017, View Source [SID1234635668]). Mission Bay Capital led Circle’s Series A, with Pfizer Inc. (NYSE:PFE), ShangPharma Investment Group, Ltd. and a syndicated group of individual investors subscribing at the initial close. With this subsequent closing, a total of approximately $6.5M of shares of Circle’s Series A Preferred Stock has been issued in the Series A financing.

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"We are gratified to have this new group of high-caliber investors joining our first equity financing," said David J. Earp, J.D., Ph.D., Circle’s president and CEO. "The funds will support Circle’s platform development and our therapeutic pipeline, which is focused on intracellular protein-protein interactions that are key drivers in oncogenic pathways. This is an exciting time for Circle. We are adding new targets to our pipeline, including MCL1 and the substrate binding site of cyclinA / cdk2, both of which are important oncology targets that have proven challenging for small molecule drug development. Our chemistry process development work has recently successfully achieved key steps required for a more highly automated synthesis platform. Finally, with support from Pfizer, we are building a physical library of macrocycles which are predicted to have optimized permeability. This library will complement our rational design/virtual library screening approach. We will begin synthesis of the physical library shortly, enabling us to deliver it to Pfizer, and potentially other collaborators, for screening use later this year. We are especially delighted to welcome James Lu to our board in connection with this expanded Series A investment. He brings deep experience building high-growth, global companies both as an investor and in management roles."

Mr. Lu is a Managing Director of WI Harper, a cross border venture capital firm investing in leading healthcare and technology startups in the U.S. and China. Previously, Mr. Lu co-founded and was a General Partner of iD Ventures America (formerly Acer Technology Ventures), which managed several funds that were early investors in companies such as iRobot (NASDAQ:IRBT); Harmonix Music (acquired by MTV/Viacom (NYSE:VIA)); and Monolithic Power Systems (NASDAQ:MPWR). In prior roles, Mr. Lu was General Counsel of the Acer Group and earlier was a corporate and commercial attorney with the McCutchen law firm in San Francisco and a banker at JP Morgan in New York. Mr. Lu graduated with a BA from Yale College, an MBA from Harvard Business School and a JD from UC Berkeley School of Law.

Peter Liu, Founder and Chairman of WI Harper Group commented, "We are seeing excellent opportunities for investing in ground-breaking life science companies that are advancing new technologies and addressing unsolved problems. Circle Pharma is one such company; we are pleased to participate in their Series A financing and look forward to building a strong relationship with the management team and the other investors."

"Completion of Circle’s Series A financing strengthens Circle’s investor base and brings additional depth on the technical side, relations with strategic partners and, with WI Harper and Elements, connections to activities and initiatives outside of the U.S., and especially in key Asia markets," said Douglas Crawford, Ph.D., managing director of Mission Bay Capital.

About Macrocyclic Peptides
Macrocyclic peptides have the potential to allow drug developers to address the large proportion of known therapeutic targets (estimated at up to 80%) that are considered undruggable with conventional small molecule or biologic modalities. In particular, there is great interest in developing macrocycles to modulate protein-protein interactions, which play a role in almost all disease conditions, including cancer, fibrosis, inflammation and infection. However, the development of macrocyclic therapeutics has been limited by the need for a greater understanding of how to develop macrocycles with appropriate pharmacokinetics, cell permeability and oral bioavailability. Circle is applying its ability to design potent macrocycles with intrinsic cell permeability and drug-like characteristics to unlock access to challenging, high value therapeutic targets that have been out of reach to other approaches.