Arvinas Expands Strategic License Agreement with Genentech

On November 15, 2017 Arvinas LLC, a private biotechnology company creating a new class of drugs based on protein degradation, reported it has expanded its ongoing license agreement with Genentech, a member of the Roche Group, for the development of new therapeutics using Arvinas’ novel PROTAC technology (Press release, Arvinas, NOV 15, 2017, View Source [SID1234558785]). The multi-year strategic license agreement, initiated in October 2015, will encompass additional disease targets and expand the collaboration.

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Under the revised terms of the agreement, Arvinas is eligible to receive development and commercialization milestone payments in excess of $650 million based on achievement of certain predetermined milestones. In addition, Arvinas is eligible to receive tiered-royalties on sales of products resulting from the license agreement. Full financial terms have not been disclosed.

"Genentech’s decision to expand our original agreement to include additional disease targets shows the promise seen in our first two years together and further supports our targeted protein degradation platform as a novel drug modality to treat a broad array of diseases," said John Houston, Ph.D., President and Chief Executive Officer of Arvinas. "This expansion also supports our initial decision to work with Genentech in 2015 and we look forward to this growing collaboration."

The PROTAC Platform offers potential improvements over traditional small molecule inhibitors using the ubiquitin and proteasome system within a cell to degrade disease causing proteins. By removing target proteins directly rather than inhibiting them, PROTACs can provide multiple advantages over small molecule inhibitors, which can require high systemic exposure to achieve sufficient inhibition, often resulting in toxic side effects and eventual drug resistance.

Invitae Completes Acquisition of CombiMatrix, Becoming a Leader in Family and Reproductive Health Genetic Information Services

On November 15, 2017 Invitae Corporation (NYSE: NVTA), one of the fastest growing genetic information companies, reported it has completed its acquisition of CombiMatrix, which specializes in providing genetic information for prenatal diagnosis, miscarriage analysis and diagnosis of pediatric developmental disorders, establishing Invitae as a new leader in family and reproductive genetic health services (Press release, CombiMatrix, NOV 15, 2017, View Source [SID1234522094]).

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Invitae’s (NVTA) mission is to bring comprehensive genetic information into mainstream medical practice to improve the quality of healthcare for billions of people. www.invitae.com (PRNewsFoto/Invitae Corporation)

"With the addition of CombiMatrix to Invitae, we have completed our entry into prenatal and perinatal genetics, currently the second-largest category of genetic testing services. Our integrated offering will build on the expertise and technologies developed by CombiMatrix to offer customers the most comprehensive offering from a single provider in the category," said Sean George, chief executive officer of Invitae. "Invitae’s platform now delivers comprehensive genetic information services that support the use of genetics in mainstream medical care throughout all stages of life."

CombiMatrix leverages cytogenomic and cytogenetic technologies such as single nucleotide polymorphism chromosomal microarray analysis and next generation sequencing, supported by long-standing expertise in technically challenging sample types, to provide in-depth answers for patients and clinicians addressing complex reproductive health questions.

"Access to actionable genetic information is essential for monitoring pregnancies, particularly for women going through IVF or facing recurrent miscarriages," said Robert Nussbaum, MD, chief medical officer of Invitae. "Our integrated platform and world-class expertise can provide genetic information that helps women and their clinicians with some of the most important decisions of their lives today, even as we continue to advance the understanding of the role genetics plays in having healthy pregnancies."

In connection with the closing, Invitae issued approximately $21.2 million in shares of its common stock to former CombiMatrix securityholders, or approximately 2.7 million shares. Together with the approximately 1.7 million shares of Invitae common stock underlying CombiMatrix Series F warrants assumed in the Merger, the transaction has a total enterprise value of approximately $34.9 million.

The acquisition of CombiMatrix complements Invitae’s recent acquisition of another reproductive genetics company, Good Start Genetics, to establish a category-leading menu with the breadth and depth needed to provide comprehensive support for women, their partners and clinicians to use genetic information when considering their reproductive health options, from carrier screening to preimplantation genetic screening and diagnosis to newborn diagnostics.

Transaction Details

At the closing of the Merger, Invitae issued shares of its common stock to (i) CombiMatrix’s common stockholders, at an exchange ratio of 0.8692 of a share of Invitae common stock (the "Merger Exchange Ratio") for each share of CombiMatrix common stock outstanding immediately prior to the Merger, (ii) CombiMatrix’s Series F preferred stockholders, at the Merger Exchange Ratio for each share of CombiMatrix common stock underlying Series F preferred stock outstanding immediately prior to the Merger, (iii) holders of outstanding and unexercised in-the-money CombiMatrix stock options, which were fully accelerated to the extent of any applicable vesting period and converted into the right to receive a number of shares of Invitae common stock adjusted for the Merger Exchange Ratio and reduced by the aggregate exercise price, and (iv) holders of outstanding and unsettled CombiMatrix restricted stock units ("RSUs"), which were fully accelerated to the extent of any applicable vesting period and converted into the right to receive a number of shares of Invitae common stock adjusted for the Merger Exchange Ratio. No fractional shares were issued in connection with the Merger and Invitae will pay cash in lieu of any such fractional shares. The Merger Exchange Ratio was determined through arm’s-length negotiations between Invitae and CombiMatrix.

In addition, at the closing of the Merger, (a) all outstanding and unexercised out-of-the money CombiMatrix stock options were cancelled and terminated without the right to receive any consideration, (b) all CombiMatrix Series D Warrants and Series F Warrants outstanding and unexercised immediately prior to the closing of the Merger were assumed by Invitae and converted into warrants to purchase the number of shares of Invitae common stock determined by multiplying the number of shares of CombiMatrix common stock subject to such warrants by the Merger Exchange Ratio, and with the exercise price adjusted by dividing the per share exercise price of the CombiMatrix common stock subject to such warrants by the Merger Exchange Ratio, and (c) certain entitlements under CombiMatrix’s executive compensation transaction bonus plan (the "Transaction Bonus Plan") were paid in shares of Invitae common stock or RSUs to be settled in shares of Invitae common stock. All outstanding and unexercised CombiMatrix Series A, Series B, Series C, Series E, and PIPE warrants were repurchased by CombiMatrix prior to closing pursuant to that certain CombiMatrix Common Stock Purchase Warrants Repurchase Agreement dated July 11, 2016.

Invitae’s previously announced offer to exchange each outstanding Series F warrant (the "CombiMatrix Series F warrants") to acquire one share of common stock of CombiMatrix for 0.3056 of a share of Invitae common stock (the "Exchange Offer") expired at 12:00 midnight (one minute after 11:59 p.m.), New York City time, on November 13, 2017. Because the minimum tender condition of 90% was not achieved in the Exchange Offer, Invitae did not accept any of the CombiMatrix Series F warrants that were tendered in the Exchange Offer prior to its expiration. Accordingly, any CombiMatrix Series F warrants that were tendered will be promptly returned to the holder by the exchange agent.

Invitae issued an aggregate of 2,726,324 shares of its common stock and 214,976 RSUs in connection with the Merger (including shares and RSUs issued pursuant to the Transaction Bonus Plan). Immediately after the Merger, (i) there were approximately 52.9 million shares of Invitae common outstanding, (ii) the former CombiMatrix securityholders and executives owned approximately 8.6% of the fully-diluted common stock of the combined company, and (iii) Invitae securityholders, whose shares of Invitae capital stock remain outstanding after the Merger, owned approximately 91.4% of the fully-diluted common stock of the combined company.

Upon completion of the Merger, CombiMatrix became a wholly owned subsidiary of Invitae. As a result, the CombiMatrix common stock and Series F warrants will cease trading on the Nasdaq Capital Market and will be delisted.

About Invitae’s Family and Reproductive Health Genetic Services

Invitae’s reproductive genetics products, which include CombiPGS, CombiPGD and CombiSNP from CombiMatrix and Good Start Genetics’ GeneVu, EmbryVu and VeriYou, provide affordable and accessible genetic information to help people have healthy families. Good Start Genetics became part of Invitae in August 2017.

Our Science

Istari Oncology’s second technology platform consists of a series of ADCs for a variety of oncology targets (Company Web Page, Istari Oncology, NOV 15, 2017, View Source [SID1234522093]). These select, highly specific, monoclonal antibodies are presently conjugated with PE-38 toxin to maximize the killing effect.
We believe our platform overcomes some of the challenges associated with other ADCs because it is based on genetic linkage, which provides more stability than chemical linkers, making it is easier to manufacture. The FDA granted our ADC conjugate, D2C7-IT, Orphan Drug designation in 2016.
Beyond the various PE-38 toxins, our technology could be linked with other therapeutic agents for different targets. Toxins used in construction of immunotoxins are typically derived from bacteria, fungi, and plants. These agents and linkers potentially provide another platform for additional pipeline therapeutics. Possible tumor targets include solid, nonlymphoid tumors.

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LabCorp Announces New Expanded Use for PD-L1 Test with Bristol-Myers Squibb’s OPDIVO®

On November 15, 2017 LabCorp (NYSE: LH) a leading global life sciences company, reported the U.S. availability of the PD-L1 IHC 28-8 pharmDx assay as a complementary diagnostic for two newly approved indications in connection with the use of Bristol-Myers Squibb’s OPDIVO (nivolumab) to treat patients with metastatic urothelial carcinoma, also referred to as bladder cancer, and squamous cell carcinoma of the head and neck (Press release, LabCorp, NOV 15, 2017, View Source;p=RssLanding&cat=news&id=2317135 [SID1234522109]). The PD-L1 IHC 28-8 pharmDx assay was developed by Agilent’s Dako pathology division. While OPDIVO is approved for these indications without use of the test, the test provides physicians with important information about those patients who are most likely to respond positively to OPDIVO. LabCorp’s Center for Molecular Biology and Pathology laboratory performed testing for the clinical studies that supported approval of the new indications for the assay.

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The PD-L1 IHC 28-8 pharmDx assay was previously approved for use as a complementary diagnostic with OPDIVO to treat certain patients with non-squamous non-small cell lung cancer (NSCLC) and melanoma. LabCorp’s central clinical trials laboratory was the sole provider of testing to support the clinical trial for the 2015 approval of the non-squamous NSCLC treatment indication, reflecting how the combined capabilities of LabCorp’s clinical laboratory infrastructure and Covance’s central clinical trials laboratory provide integrated support for clinical trials.

"The expanded use of this PD-L1 test as a complementary diagnostic for two new cancer indications, as well as our collaboration in the studies that supported regulatory approval, demonstrate the unique solutions that only LabCorp can provide for the development and commercialization of new tests and therapies, particularly complementary and companion diagnostics," said David P. King, chairman and chief executive officer of LabCorp. "The combined expertise of LabCorp Diagnostics and Covance Drug Development makes us the industry leader in precision medicine, including the exciting area of immuno-oncology. With our extensive experience performing this test, physicians can have high confidence that the results we deliver will help them identify the most appropriate treatment for their patients and will improve the delivery of care."

The PD-L1 IHC 28-8 pharmDx assay is approved for use with patients diagnosed with advanced or metastatic bladder cancer, or recurrent or metastatic squamous cell carcinoma of the head and neck, whose cancers have returned or progressed after prior treatment with platinum-based chemotherapy. OPDIVO is an immunotherapy that helps the immune systems of certain individuals detect and kill cancer cells. The PD-L1 IHC 28-8 pharmDx assay identifies a tumor’s expression of the PD-L1 protein, which may be associated with an increased likelihood of positive immune system response to treatment with OPDIVO; however, OPDIVO is approved for use regardless of PD-L1 status.

Squamous cell carcinoma of the head and neck is the most common form of head and neck cancer, and urothelial carcinoma is the most common type of bladder cancer, accounting for approximately 90 percent of diagnoses. These cancers are often difficult to treat using traditional therapies, and immunotherapies like OPDIVO offer the hope of enhanced survival for appropriate patients.

The PD-L1 IHC 28-8 pharmDx assay is available from LabCorp and its Integrated Oncology specialty laboratory.

OPDIVO is a registered trademark of Bristol-Myers Squibb Company.

EFTILAGIMOD ALPHA (LAG-3Ig or IMP321) PRE-IND MEETING WITH THE FDA

On November 15, 2017 Prima BioMed Ltd (ASX: PRR; NASDAQ: PBMD) ("Prima") reported that it held a Pre-Investigational New Drug Application (pre-IND) meeting with the U.S. Food and Drug Administration (FDA) in November to discuss the regulatory pathway for the development of Eftilagimod Alpha (LAG-3Ig or IMP 321) in the United States (Press release, Prima Biomed, NOV 15, 2017, View Source [SID1234522106]).

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The FDA addressed Prima’s questions related to preclinical, nonclinical, and clinical data and design of clinical trials of Eftilagimod Alpha in a chemo-immunotherapy setting and in an immuno-oncology combination trial. Prima intends to file an investigational new drug application (IND) in the first half of calendar year 2018. After having successfully started clinical development of Eftilagimod Alpha in Australia and Europe, an IND would provide Prima with the opportunity to commence clinical studies and regulatory interactions in the United States.
"The U.S. is the largest pharmaceutical market in the world, so the pre-IND meeting regarding Eftilagimod Alpha was an important milestone. Our meeting with the FDA was very productive and their guidance will be most valuable in assessing the appropriate U.S. clinical and regulatory strategies for Eftilagimod Alpha," said Marc Voigt, Prima’s Chief Executive Officer.