Taiho Pharmaceutical and Cullinan Oncology Establish Collaboration to Develop TAS6417, Novel EGFR Tyrosine Kinase Inhibitor

On February 5, 2019 Taiho Pharmaceutical Co., Ltd. and Cullinan Oncology, LLC reported on February 5 an agreement to develop TAS6417, a novel EGFR (epidermal growth factor receptor) tyrosine kinase inhibitor discovered by Taiho Pharmaceutical (Press release, Taiho, FEB 5, 2019, View Source [SID1234533083]).

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Under the terms of the agreement, Taiho Pharmaceutical will grant an exclusive, global license ex-Japan for the development and commercialization of TAS6417 to Cullinan Pearl, a newly formed USbased company under the Cullinan Oncology umbrella. Taiho Pharmaceutical will receive an upfront payment, regulatory and sales milestones, as well as royalties based on net sales. Taiho Ventures, LLC, a strategic corporate venture arm of Taiho Pharmaceutical, alongside Cullinan Oncology, will provide funding for Cullinan Pearl’s Series A.

"The Taiho’s drug research team created a unique molecule targeting EGFR Exon 20 insertion mutation using proprietary drug discovery platform technology. This alliance, one of the first of its kind at Taiho Pharmaceutical, allows our organization to optimize its R&D resource allocation and accelerate global development by accessing external talent and resources. We are pleased to partner with Cullinan Oncology and its experienced management team in bringing this novel treatment to NSCLC patients," said Teruhiro Utsugi, Managing Director of Taiho Pharmaceutical.

Cullinan Pearl will utilize Cullinan Oncology’s shared service platform to develop TAS6417, which relies on a central management team and a network of integrated collaborators to help drive the development of preclinical and clinical assets.

"We are excited to partner with Taiho Pharmaceutical and Taiho Ventures in exploring the utility of this novel drug in a patient population with limited options to date. We are thankful for Taiho’s trust in our team’s ability to execute the clinical development of this exciting asset," stated Owen Hughes, CEO of Cullinan Oncology.

About TAS6417

TAS6417 is an orally available tyrosine kinase inhibitor designed to target activating mutations in EGFR. The molecule was engineered to inhibit EGFR variants with exon 20 insertion mutations, while sparing wild-type EGFR. TAS6417 is a clinical candidate for NSCLC driven by EGFR exon 20 insertion mutations and is expected to be a novel therapeutic option for the patients with highly unmet medical needs

GSK and Merck KGaA, Darmstadt, Germany announce global alliance to jointly develop and commercialise M7824, a novel immunotherapy with potential in multiple difficult-to-treat cancers

On February 5, 2019 GlaxoSmithKline plc (LSE/NYSE: GSK) and Merck KGaA, Darmstadt, Germany reported that they have entered into a global strategic alliance to jointly develop and commercialise M7824 (bintrafusp alfa*). M7824 is an investigational bifunctional fusion protein immunotherapy that is currently in clinical development, including potential registration studies, for multiple difficult-to-treat cancers (Press release, GlaxoSmithKline, FEB 5, 2019, View Source [SID1234533081]). This includes a Phase II trial to investigate M7824 compared with pembrolizumab as a first-line treatment in patients with PD-L1 expressing advanced non-small cell lung cancer (NSCLC).

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M7824 is designed to simultaneously target two immuno-suppressive pathways, transforming growth factor-β (TGF-β) trap and an anti-programmed cell death ligand-1 (PD-L1), that are commonly used by cancer cells to evade the immune system. Bifunctional antibodies aim to increase efficacy above and beyond that achieved with individual therapies or combinations of individual therapies.1 M7824 has the potential to offer new ways to fight difficult-to-treat cancers beyond the established PD-1/PD-L1 class. In addition to use as a single agent, M7824 is also being considered for use in combination with other assets from the pipelines of both companies.

Dr Hal Barron, Chief Scientific Officer and President R&D, GSK, said: "Despite recent medical advances, many patients with difficult-to-treat cancers don’t currently benefit from immuno-oncology therapies leaving them with limited treatment options. M7824 brings together two different biological functions in a single molecule and we have observed encouraging clinical results in treating certain cancer patients, particularly those people with non-small cell lung cancer. I’m excited by the potential impact this first-in-class immunotherapy could have on the lives of cancer patients."

Dr Belén Garijo, Member of the Executive Board and CEO Healthcare of Merck KGaA, Darmstadt, Germany said: "Our bifunctional fusion protein M7824 has the potential to bring new answers to patients living with cancer. Together with GSK we aim to drive a paradigm shift in the treatment of cancer as the leader in this novel class of immunotherapies. GSK clearly emerged as the ideal partner due to their strong commitment to oncology, and the complementary talent and capabilities they will bring to our alliance. We now look forward to harnessing the full potential of M7824 across a broad range of cancer indications as we continue to advance our oncology portfolio."

Merck KGaA, Darmstadt, Germany will receive an upfront payment of €300 million (£260 million) and is eligible for potential development milestone payments of up to €500 million (£440 million) triggered by data from the M7824 lung cancer programme. Merck KGaA, Darmstadt, Germany will also be eligible for further payments upon successfully achieving future approval and commercial milestones of up to €2.9 billion (£2.5 billion). The total potential deal value is up to €3.7 billion (£3.2 billion). Both companies will jointly conduct development and commercialisation with all profits and costs from the collaboration being shared equally on a global basis.

For GSK, this alliance is a further step in the company’s priority to strengthen its pharmaceuticals pipeline. This follows the company’s recent acquisition of TESARO, an oncology-focused company based in Waltham, Massachusetts. GSK’s approach to oncology is focused on innovation in the areas of immuno-oncology, cell therapy, cancer epigenetics and, most recently, genetic medicine.

This alliance reflects Merck KGaA, Darmstadt, Germany’s strategic approach to oncology R&D, identifying those opportunities that can progress the company’s highly promising clinical stage assets as efficiently and rapidly as possible, whether through internal expertise and capabilities or external collaborations.

With this alliance, both companies have the leadership position in this new class of immunotherapies, specifically leveraging TGF-β biology.

*Bintrafusp alfa is the proposed International Nonproprietary Name (INN) for the bifunctional immunotherapy M7824. Bintrafusp alfa is currently under clinical investigation and not approved for any use anywhere in the world.

About M7824 (also now known as bintrafusp alfa)
M7824 is an investigational bifunctional immunotherapy that is designed to combine a TGF-β trap with the anti-PD-L1 mechanism in one fusion protein. M7824 is designed to combine co-localised blocking of the two immuno-suppressive pathways – targeting both pathways aims to control tumour growth by potentially restoring and enhancing anti-tumour responses. M7824 is currently in Phase I studies for solid tumours, as well as a randomised Phase II trial to investigate M7824 compared with pembrolizumab as a first-line treatment in patients with PD-L1 expressing advanced NSCLC. The multicentre, randomised, open-label, controlled study is evaluating the safety and efficacy of M7824 versus pembrolizumab as a monotherapy treatment.

To-date, nearly 700 patients have been treated with M7824 across more than 10 tumour types in Phase I studies. Encouraging data from the ongoing Phase I studies indicates M7824’s potential safety and clinical anti-tumour activity across multiple types of difficult-to-treat cancers, including advanced NSCLC, human papillomavirus-associated cancers, biliary tract cancer (BTC) and gastric cancer. In addition, in pre-clinical studies M7824 demonstrated superior anti-tumour activity, compared with anti-PD-L1 alone or with anti-PD-L1 and TGF-β trap when co-administered. In total, eight high priority immuno-oncology clinical development studies are ongoing or expected to commence in 2019, including studies in non-small cell lung and biliary tract cancers.

Leap Therapeutics Announces Closing of Public Offering and Full Exercise of Underwriters’ Option to Purchase Additional Securities

On February 5, 2019 Leap Therapeutics, Inc. (Nasdaq: LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported the closing of an underwritten public offering of 6,571,428 shares of its common stock and warrants to purchase up to 6,571,428 shares of its common stock, as well as an additional 985,714 shares of its common stock and warrants to purchase up to 985,714 shares of its common stock pursuant to the full exercise of the underwriters’ option to purchase additional securities (Press release, Leap Therapeutics, FEB 5, 2019, View Source [SID1234533078]). Total gross proceeds to Leap from this offering were approximately $13,225,000, before deducting underwriting discounts and offering expenses payable by Leap, and excluding any proceeds Leap may receive upon exercise of the warrants.

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Raymond James & Associates, Inc. and Ladenburg Thalmann acted as book-running managers for the offering.

The shares were offered pursuant to an effective shelf registration statement on Form S-3 (File No. 333-223419) that was previously filed by Leap with the Securities and Exchange Commission (the "SEC") on March 2, 2018 and was declared effective by the SEC on March 16, 2018. A prospectus supplement and the related prospectus have been filed with the SEC and are available, for free, on the SEC’s website at View Source Copies of the prospectus supplement and the accompanying prospectus may be obtained from: Raymond James & Associates, Inc., Attention: Equity Syndicate, 880 Carillon Parkway, St. Petersburg, Florida 33716, or by telephone at (800) 248-8863, or e-mail at [email protected]; or from Ladenburg Thalmann, 277 Park Ave, 26th Floor, New York, NY 10172, or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

Neurocrine Biosciences Reports Fourth Quarter and Year-End 2018 Financial Results

On February 5, 2019 Neurocrine Biosciences, Inc. (NASDAQ: NBIX) reported its financial results for the quarter ended December 31, 2018 and provided an update on the launch of INGREZZA (valbenazine) and its clinical development programs (Press release, Neurocrine Biosciences, FEB 5, 2019, View Source [SID1234533077]).

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"We are extremely proud of what we have accomplished since INGREZZA was approved in 2017 and the impact INGREZZA is having on the lives of many patients with tardive dyskinesia. Our field sales team expansion and educational efforts position us to further help patients struggling with tardive dyskinesia," said Kevin Gorman, Ph.D., Chief Executive Officer of Neurocrine Biosciences. "Beyond INGREZZA, we are gearing up to file an NDA for opicapone to treat Parkinson’s disease and anticipating the Phase IIa data readout for our congenital adrenal hyperplasia program. And now, our pipeline includes the collaboration programs with Voyager in Parkinson’s disease and Friedreich’s ataxia. These efforts, along with AbbVie’s anticipated mid-year NDA submission for elagolix in uterine fibroids, put Neurocrine in an exciting position to have the potential of three approved drugs in four indications in 2020 with a robust and highly diversified pipeline."

Financial Results

Total revenue was $131.5 million for the fourth quarter of 2018, compared to $94.5 million for the same period in 2017. For the year ended December 31, 2018, total revenue was $451.2 million, compared to $161.6 million for the same period in 2017.

Total revenues were comprised of the following (unaudited, in thousands):

Three Months Ended

December 31,

Year Ended

December 31,

2018

2017

2018

2017

Revenues:

INGREZZA product sales, net

$ 130,326

$ 64,517

$ 409,608

$ 116,626

Collaboration revenue

1,166

30,000

41,632

45,000

Total revenue

$ 131,492

$ 94,517

$ 451,240

$ 161,626

INGREZZA was made available for commercial distribution on May 1, 2017 and ORILISSA (elagolix) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of endometriosis with associated moderate to severe pain during the third quarter of 2018, with AbbVie sales beginning in August 2018. With the FDA approval of ORILISSA, the Company recognized a $40 million event-based milestone as revenue under the Company’s collaboration agreement with AbbVie during the third quarter of 2018. Total revenue for 2017 was inclusive of milestone revenue of $45 million recognized pursuant to the Company’s collaboration agreements with AbbVie and Mitsubishi Tanabe Pharma Corporation (MTPC).

The Company reported net income of $18.1 million, or $0.19 diluted net income per share, for the fourth quarter of 2018, compared to $6.9 million, or $0.07 diluted net income per share, for the same period in 2017. For the year ended December 31, 2018, the Company reported net income of $21.1 million, or $0.22 diluted net income per share, compared to a net loss of $142.5 million, or $1.62 net loss per share, for the same period in 2017. The increase in net income across both periods is primarily due to increased INGREZZA net product sales.

Research and development (R&D) expenses increased to $39.1 million for the fourth quarter of 2018, from $25.6 million for the same period in 2017. For the year ended December 31, 2018, R&D expenses increased to $160.5 million from $121.8 million for the same period in 2017. The increase in R&D expenses across both periods is primarily due to advancement of the Company’s clinical programs, including congenital adrenal hyperplasia (CAH), a vesicular monoamine transporter 2 (VMAT2) inhibitor, and a first-in-class central nervous system (CNS) compound, as well as activities to prepare for the Company’s intended opicapone new drug application (NDA) submission in the second quarter of 2019.

Sales, general and administrative (SG&A) expenses increased to $69.0 million for the fourth quarter of 2018, from $56.3 million for same period in 2017. For the year ended December 31, 2018, SG&A expenses increased to $248.9 million from $169.9 million for the same period in 2017. The increase in SG&A expenses across both periods is primarily due to the hiring of the Company’s sales force, including the third quarter 2018 sales force expansion, and commercialization activities for INGREZZA, which launched in the third quarter of 2017.

The Company’s balance sheet at December 31, 2018, reflected total assets of $993.2 million, including cash and investments of $866.9 million, compared to total assets of $817.6 million at December 31, 2017.

2019 Financial Guidance

Revenue milestones under the AbbVie agreement for 2019 are expected to be $20 million contingent on FDA’s acceptance of the NDA submission of elagolix for uterine fibroids. Ongoing SG&A and R&D expenses for 2019, excluding upfront expenses associated with the recently announced Voyager Therapeutics collaboration, should approximate $550 to $600 million. The 2019 anticipated expenses include an estimated $80 million of share-based compensation expense. The increase in expenses is largely attributable to the Voyager collaboration’s ongoing program costs, increased investment in INGREZZA patient education, sales and marketing activities, opicapone NDA submission and increased R&D pipeline activities.

Pipeline Highlights

INGREZZA (valbenazine) Update

INGREZZA received FDA approval on April 11, 2017, becoming the first medicine approved in the United States for the treatment of adults with tardive dyskinesia.

In March 2015, the Company announced that it had entered into an exclusive collaboration and licensing agreement for the development and commercialization of INGREZZA in Japan and other select Asian markets with MTPC. In 2017, MTPC initiated a pivotal trial of INGREZZA in Japan for the treatment of tardive dyskinesia.

ORILISSA (elagolix) Update

On July 24, 2018, AbbVie, in collaboration with Neurocrine, announced FDA approval and in October 2018 Health Canada approval for ORILISSA for the management of endometriosis with associated moderate to severe pain. The FDA granted priority review to ORILISSA. The FDA grants priority review designation to medicines that, if approved, would provide a significant improvement in the safety or effectiveness of treatment of a serious condition. AbbVie began commercialization of ORILISSA in the United States in August 2018.

AbbVie provided positive top-line efficacy data from two Phase III studies in women with uterine fibroids in the first quarter of 2018 and from the associated six-month safety extension during the third quarter of 2018. The ELARIS UF-I and UF-II studies of elagolix met all primary and ranked secondary endpoints at month six. These replicate Phase III studies were randomized, parallel, double-blind, placebo-controlled clinical trials evaluating elagolix alone or in combination with low-dose hormone (add-back) therapy in women with heavy uterine bleeding associated with uterine fibroids. The studies enrolled approximately 400 patients each for an initial six-month placebo-controlled dosing period. At the end of the six months of placebo-controlled evaluation, patients were eligible to enter an additional six-month safety extension study. The primary efficacy endpoint of the study was an assessment of the change in menstrual blood loss utilizing the alkaline hematin method comparing baseline to month six. Additional secondary efficacy endpoints were evaluated including the change in fibroid volume and hemoglobin. Bone mineral density was assessed via dual-energy x-ray absorptiometry (DEXA) scan at baseline at the conclusion of dosing and at six months post-dosing. Results from these studies will form the basis for an anticipated NDA submission to the FDA for the approval of elagolix in the treatment of uterine fibroids in the middle of 2019.

Opicapone Update

In February 2017, the Company entered into an exclusive licensing agreement with BIAL – Portela & CA, S.A. (BIAL) for the development and commercialization of opicapone in the United States and Canada. Opicapone is a once-daily, oral, peripherally-acting, highly-selective catechol-O-methyltransferase inhibitor, being developed as an adjunct therapy to preparations of levodopa/DOPA decarboxylase inhibitors for adult patients with Parkinson’s disease and motor fluctuations. The Company met with the FDA in January 2018 and based upon the BIPARK-I and BIPARK-II pivotal Phase III studies conducted by BIAL, the FDA did not require additional Phase III trials to form an NDA submission. The Company is in the process of preparing for an NDA submission which it anticipates will occur during the second quarter of 2019.

CAH Program (NBI-74788) Update

In the second quarter of 2017, the Company successfully completed the Phase I investigational new drug (IND)-opening study of NBI-74788 in healthy volunteer participants. The study was a randomized, open-label, two-period crossover study to evaluate the pharmacokinetics, the effect of food on pharmacokinetics, and the safety of NBI-74788 in a total of 16 healthy adults.

The Company began a Phase II proof-of-concept study examining the pharmacokinetics, pharmacodynamics, and safety of NBI-74788 in adult males and females with classic 21-hydroxylase deficiency CAH in November of 2017. This study will evaluate the safety and tolerability of NBI-74788 in patients with CAH together with the relationship between exposure and specific steroid hormone levels in these patients. Initial results from this trial are expected during the first quarter of 2019.

New VMAT2 Inhibitor

The Company has filed an IND and completed dosing in the single ascending dose portion of a Phase I study designed to assess initial safety, tolerability and pharmacokinetics of a novel, internally discovered VMAT2 inhibitor. This compound has the potential to be used in the treatment of several neurology and/or psychiatry disorders. The multiple dosing portion of this Phase I study is ongoing and is expected to be completed during the first half of 2019.

New CNS Compound

The Company has filed an IND and completed dosing in a Phase I single ascending dose study for an internally discovered first-in-class CNS compound with potential use in the treatment of several neurology and/or psychiatry disorders. The study is a randomized, double-blind, single ascending dose study to evaluate the safety, tolerability, and pharmacokinetic profile of the compound in healthy participants. The Company is currently analyzing the data from this study to inform the design of future clinical studies for the program.

Voyager Collaboration

Neurocrine Biosciences formed a strategic collaboration with Voyager Therapeutics focused on the development and commercialization of Voyager’s gene therapy programs, VY-AADC for Parkinson’s disease and VY-FXN01 for Friedreich’s ataxia, as well as rights to two programs to be determined. This collaboration combines Neurocrine Biosciences’ expertise in neuroscience, drug development and commercialization with Voyager’s innovative gene therapy programs targeting severe neurological diseases. This transaction is anticipated to close in the first quarter subject to standard Hart-Scott-Rodino waiting periods.

Conference Call and Webcast Today at 4:30 PM Eastern Time

Neurocrine will hold a live conference call and webcast today at 4:30 p.m. Eastern Time (1:30 p.m. Pacific Time). Participants can access the live conference call by dialing 877-876-9174 (US) or 785-424-1669 (International) using the conference ID: NBIX. The webcast can also be accessed on Neurocrine’s website under Investors at www.neurocrine.com. A replay of the webcast will be available on the website approximately one hour after the conclusion of the event and will be archived for approximately one month.

About INGREZZA (valbenazine) Capsules
INGREZZA, a selective VMAT2 inhibitor, is the first FDA-approved product indicated for the treatment of adults with tardive dyskinesia, a condition associated with uncontrollable, abnormal and repetitive movements of the face, torso, and/or other body parts.

INGREZZA is thought to work by reducing the amount of dopamine released in a region of the brain that controls movement and motor function, helping to regulate nerve signaling in adults with tardive dyskinesia. VMAT2 is a protein in the brain that packages neurotransmitters, such as dopamine, for transport and release from presynaptic neurons. INGREZZA, developed in Neurocrine’s laboratories, is novel in that it selectively inhibits VMAT2 with no appreciable binding affinity for VMAT1, dopaminergic (including D2), serotonergic, adrenergic, histaminergic, or muscarinic receptors. Additionally, INGREZZA can be taken for the treatment of tardive dyskinesia as one capsule, once-daily, together with psychiatric medications such as antipsychotics or antidepressants.

Important Safety Information

Contraindications
INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA. Rash, urticaria, and reactions consistent with angioedema (e.g., swelling of the face, lips, and mouth) have been reported.

Warnings & Precautions
Somnolence
INGREZZA can cause somnolence. Patients should not perform activities requiring mental alertness such as operating a motor vehicle or operating hazardous machinery until they know how they will be affected by INGREZZA.

QT Prolongation
INGREZZA may prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing. INGREZZA should be avoided in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. For patients at increased risk of a prolonged QT interval, assess the QT interval before increasing the dosage.

Adverse Reactions
The most common adverse reaction (≥5% and twice the rate of placebo) is somnolence. Other adverse reactions (≥2% and >placebo) include: anticholinergic effects, balance disorders/falls, headache, akathisia, vomiting, nausea, and arthralgia.

Sensei Biotherapeutics to Present at BIO CEO & Investor Conference

On February 5, 2019 Sensei Biotherapeutics, Inc., a clinical-stage biopharmaceutical company developing precision immuno-oncology therapies, reported that John Celebi, President and Chief Executive Officer of Sensei Biotherapeutics, will present a company overview at the BIO CEO & Investor Conference on Monday, February 11, 2019, at 3:45 p.m. ET in New York, NY (Press release, Sensei Biotherapeutics, FEB 5, 2019, View Source [SID1234533076]).

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