On January 4, 2019 Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, reported "2020 Blueprint," a two-year strategy to launch Blueprint Medicines’ global commercial business (Press release, Blueprint Medicines, JAN 4, 2019, View Source [SID1234532460]). Under this strategy, by the end of 2020, the company expects to have two marketed products and at least four additional marketing applications pending in the United States and Europe. In addition, Blueprint Medicines reported recent milestones and key goals through 2020 across its differentiated portfolio of investigational precision therapies.

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"Our vision is to rapidly evolve Blueprint Medicines into the leading global precision therapy company, with a robust scientific platform reproducibly designing innovative compounds and an effective and nimble commercial organization delivering a portfolio of important medicines to patients worldwide," said Jeff Albers, Chief Executive Officer of Blueprint Medicines. "As we enter the new year, we are at the precipice of this transformation with the planned submission of our first new drug application for our lead therapeutic candidate avapritinib and growing momentum in building our commercial capabilities. Combined with seven ongoing or planned registration-enabling clinical trials for avapritinib and BLU-667, we believe Blueprint Medicines is well-positioned to quickly capitalize on this first potential regulatory approval and realize our goal of becoming a portfolio-based commercial-stage company."

"2020 Blueprint" Global Business Strategy

The "2020 Blueprint" strategy establishes a path to transform Blueprint Medicines into a global commercial enterprise focused on delivering a portfolio of precision therapies to patients with cancer and rare diseases. Under this strategy, Blueprint Medicines anticipates achieving the following by the end of 2020:

2 marketed products in the United States and 1 marketed product in Europe
4 additional marketing applications pending in the United States and Europe
6 therapeutic candidates in global clinical development
8 research programs that leverage strategic areas of focus
"Our ‘2020 Blueprint’ strategy extends to our ongoing research efforts, where we are advancing multiple programs designed to complement our scientific and clinical expertise and planned commercial profile," said Marion Dorsch, Ph.D., Chief Scientific Officer of Blueprint Medicines. "Under this strategy, we have three research areas of focus: franchise opportunities in gastrointestinal stromal tumors, systemic mastocytosis and lung cancer where we believe our understanding of mutational drivers gives us an advantage; cancer immunotherapy under our ongoing collaboration with Roche; and novel genetic drivers that we characterize and target with our differentiated scientific platform."

Recent Portfolio Milestones and Key Goals through 2020

RECENT MILESTONES:

Blueprint Medicines today announced:

Top-line results from the Phase 1 NAVIGATOR clinical trial of avapritinib in patients with advanced gastrointestinal stromal tumors (GIST), as of a data cutoff date of November 16, 2018. These data will be used to support the submission of a planned new drug application (NDA) to the U.S. Food and Drug Administration (FDA) in the first half of 2019 for the treatment of patients with PDGFRA Exon 18 mutant GIST, which primarily includes PDGFRα D842V GIST, and fourth-line GIST. The primary endpoints for registration are objective response rate (ORR) and duration of response (DOR) based on central radiology and modified Response Evaluation Criteria in Solid Tumors version 1.1 (mRECIST 1.1) criteria.
In 43 patients with PDGFRA Exon 18 mutant GIST treated with a starting dose of 300 or 400 mg once daily (QD), the ORR was 86 percent (one response pending confirmation). Median DOR was not reached.
In 111 patients with fourth-line GIST treated with a starting dose of 300 or 400 mg QD, the ORR was 22 percent (one response pending confirmation). Median DOR was 10.2 months.
Top-line safety results were consistent with those previously reported. Avapritinib was well-tolerated, and most adverse events (AEs) reported by investigators were Grade 1 or 2. Across all doses (n=237), only 23 patients (9.7 percent) discontinued treatment with avapritinib due to treatment-related AEs.
Two registration-enabling clinical trials for avapritinib in systemic mastocytosis (SM) are now underway. The first clinical site recently opened for the Phase 2 PIONEER clinical trial for patients with indolent and smoldering SM, and initial patient screening for this trial is anticipated in January 2019. In addition, patient dosing has been initiated in the Phase 2 PATHFINDER clinical trial for patients with advanced SM.
As part of the collaboration with CStone Pharmaceuticals, the China National Medicinal Products Administration has approved an investigational new drug (IND) application for the ongoing global Phase 1 trial of BLU-554 in advanced hepatocellular carcinoma. The companies expect to initiate patient enrollment in the trial by the middle of 2019.
The FDA has cleared an IND application for BLU-782, a selective ALK2 inhibitor in development for patients with fibrodysplasia ossificans progressiva (FOP), and the company plans to initiate a Phase 1 clinical trial in healthy volunteers in the first quarter of 2019.
KEY GOALS:

Blueprint Medicines reported the following key goals and anticipated milestones through 2020:

Avapritinib: advanced gastrointestinal stromal tumors

Submit an NDA to the FDA for PDGFRA Exon 18 mutant GIST and fourth-line GIST in the first half of 2019.
Present additional data from the Phase 1 NAVIGATOR trial in the first half of 2019.
Complete enrollment of the Phase 3 VOYAGER trial in third- or fourth-line GIST in the second half of 2019.
Initiate the Phase 3 COMPASS-2L precision medicine trial in second-line GIST in the second half of 2019.
Submit an NDA to the FDA for third-line GIST in 2020.
Avapritinib: systemic mastocytosis

Present updated data from the Phase 1 EXPLORER trial in advanced SM in the first half of 2019.
Present initial data from the Phase 2 PIONEER trial in indolent and smoldering SM in the second half of 2019.
Complete enrollment of the Phase 2 PATHFINDER trial in advanced SM in the second half of 2019.
Submit an NDA to the FDA for advanced SM in 2020.
BLU-667: RET-altered non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and other solid tumors

Present updated data from the Phase 1 ARROW trial in RET-altered cancers in the first half of 2019.
Complete enrollment of previously treated NSCLC and MTC cohorts in the Phase 1 ARROW trial in the first half of 2019.
Initiate a Phase 3 trial in first-line RET-fusion NSCLC in the second half of 2019.
Initiate a Phase 2 combination trial of BLU-667 and osimertinib in treatment-resistant, EGFR-mutant NSCLC harboring an acquired RET alteration in the second half of 2019.
Submit an NDA to the FDA for second-line RET-fusion NSCLC and second-line RET-mutant MTC in the first half of 2020.
BLU-554: advanced hepatocellular carcinoma

Enroll the first patient in China in the ongoing global Phase 1 trial of BLU-554 under the collaboration with CStone Pharmaceuticals by the middle of 2019.
Initiate a Phase 1 combination trial of BLU-554 and CS-1001, CStone Pharmaceuticals’ anti-PD-L1 inhibitor, in China in the second half of 2019.
BLU-782: fibrodysplasia ossificans progressiva

Initiate a Phase 1 trial in healthy volunteers in the first quarter of 2019.
Initiate a Phase 2 trial in patients with FOP in the first half of 2020.
Research portfolio

Provide an update on the company’s robust and diverse research portfolio, including disclosure of up to two new targets, at a Blueprint Medicines Research and Development day in 2019.
Nominate at least one new wholly-owned discovery program in 2019.

On January 4, 2019 Arvinas, Inc. (Nasdaq: ARVN), a biotechnology company creating a new class of drugs based on targeted protein degradation, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s investigational new drug application (IND) for ARV-110, an oral androgen receptor (AR) PROTAC protein degrader, for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) (Press release, Arvinas, JAN 4, 2019, View Source [SID1234532476]). Arvinas expects to begin enrollment of a Phase 1 clinical trial for ARV-110 in the first quarter of this year.

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"This IND clearance is a key step forward for Arvinas and for the field of protein degradation," said John Houston, Ph.D., President and CEO of Arvinas. "Our PROTAC platform has demonstrated exciting promise in preclinical studies and represents an entirely new approach to treating patients with mCRPC and many other diseases. We hope ARV-110 will deliver a much-needed new therapeutic option for patients, and we expect to dose our first patient in the first quarter of 2019."

ARV-110 was developed using Arvinas’ proprietary technology platform – PROTAC (proteolysis-targeting chimera) protein degraders – that uses small molecules to harness the body’s own natural protein recycling system (the ubiquitin proteasome system) to selectively and efficiently remove disease-causing proteins. ARV-110 is a PROTAC protein degrader specifically designed to target and degrade AR, and has demonstrated activity in preclinical models of AR overexpression and AR mutations, which are both common resistance mechanisms to current standard-of-care agents in men with prostate cancer. The Phase 1 study will investigate the safety and tolerability of ARV-110 in patients with mCRPC who have progressed on at least two standard of care treatment regimens and includes exploratory measures of efficacy.

On January 4, 2019 Immunocore Limited, a leading T Cell Receptor (TCR) biotechnology company, reported that Bahija Jallal has been appointed as Chief Executive Officer and Director of the Board (Press release, Immunocore, JAN 4, 2019, View Source [SID1234532461]).

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With more than 25 years of international leadership experience within the pharmaceutical industry, Bahija joins Immunocore from AstraZeneca, where she is President of MedImmune, its global biologics research and development arm, and a member of the senior executive team reporting to the CEO.

Since joining MedImmune in 2006, Bahija has overseen the development of several new medicines, including Imfinzi, Fasenra, Lumoxiti, Siliq and FluMist Quadrivalent. Under Bahija’s leadership, MedImmune has significantly boosted its pipeline, expanding from 40 to more than 130 molecules in research and development targeting cancer; respiratory, inflammation, and autoimmunity; cardiovascular, renal and metabolic; and infectious diseases. Bahija has fostered an entrepreneurial culture that resulted in hundreds of patent applications and significant growth in the publication of MedImmune science in high impact journals. She forged industry-first collaborations and led efforts to acquire four independent biotech, big data and technology companies. Bahija also laid the foundation for the creation of an inflammation and autoimmunity carve out as an independent biotech.

Bahija has authored more than 70 peer-reviewed publications and holds more than 15 patents. She serves on the Board of Anthem, Inc. in Indianapolis, Indiana and on the Board of Trustees of the Johns Hopkins University in Baltimore, Maryland. She is a member of the Government-University-Industry Research Roundtable (GUIRR) of the National Science Foundation and is the immediate past President of the board of the Association of Women in Science. In 2017, Bahija was named Woman of the Year by the Healthcare Businesswomen’s Association.

Sir John Bell, Chairman of Immunocore, said: "Bahija is the ideal candidate to lead Immunocore at this transformational point in its development. A champion for science and diversity, Bahija is a highly seasoned pharmaceutical executive with considerable experience in biologics R&D and immuno-oncology. Her appointment will significantly strengthen Immunocore as we advance our lead candidate, IMCgp100, towards commercialisation, and our growing pipeline of TCR candidates through clinical development. I would like to extend my thanks also to Andrew Hotchkiss, who has been a highly capable interim CEO of Immunocore, for his support."

"I am excited to have the opportunity to head Immunocore, the leader in cutting-edge TCR bispecifics," said Bahija Jallal, incoming Chief Executive Officer of Immunocore. "With its strong platform, with potential to be applicable in multiple therapy areas, Immunocore has successfully translated its innovative science into the clinic with ongoing pivotal trials in uveal melanoma and clinical and pre-clinical stage programs in other disease areas. I am looking forward to helping the company, and its talented employees, bring innovative T cell receptor-based medicines to patients."

On January 4, 2019 Mersana Therapeutics, Inc., (NASDAQ:MRSN) a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody drug conjugates (ADCs) targeting cancers in areas of high unmet need, reported that after a strategic evaluation the Company will prioritize its resources to focus on the advancement of XMT-1536, a first-in-class ADC candidate targeting NaPi2b. As a result, Mersana and its partner, Takeda, plan to terminate the co-development collaboration for XMT-1522. Mersana will work with investigators to ensure that patients benefitting from XMT-1522 will continue to have access to the therapy as needed.

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"While still in early clinical development, we are encouraged with the safety, tolerability, and activity of XMT-1536 as well as the pace at which the current study is advancing. For this reason, we have decided to focus our resources on advancing XMT-1536, our first-in-class ADC candidate targeting NaPi2b, a clinically validated ADC target broadly expressed in ovarian and non-small cell lung cancer (NSCLC) adenocarcinoma, for which there remains a significant unmet medical need," said Anna Protopapas, President and CEO, Mersana Therapeutics. "We have made the difficult decision to terminate the further development of XMT-1522 despite a favorable emerging profile of efficacy and tolerability due to the competitive environment for HER2-targeted therapies."

"Looking forward, we’re very enthusiastic about our clinical progress with XMT-1536 and the expansion of our clinical pipeline," said Dirk Huebner, M.D., Chief Medical Officer, Mersana Therapeutics. "On behalf of the Company and our partner Takeda we want to thank the patients and their families for their participation in the study, as well as the investigators and our team for their diligent work on the clinical development of XMT-1522. We are committed to leveraging our proprietary ADC platforms to generate a differentiated pipeline of ADCs."

Update on XMT-1536

· XMT-1536 is a first-in-class ADC against a clinically validated target. Ovarian and non-small cell lung cancer (NSCLC) adenocarcinoma express NaPi2b and remain areas of significant unmet need. XMT-1536 has the potential to play a significant role in the treatment of these diseases.

· The data to date from the ongoing XMT-1536 dose escalation study indicate that the trial has reached clinically relevant dose levels but has not yet reached a maximum tolerated dose. The once-every-three-week regimen has been fully explored. The once-every-four-week schedule is currently being evaluated. The 20 mg/m2 dose cohort has been shown to be well tolerated and the 30 mg/m2 is currently being evaluated.

· As of December 31, 2018, the dose escalation study of XMT-1536, in multiple tumor types, includes eight heavily pretreated and evaluable ovarian cancer patients treated at clinically relevant doses. These patients are unselected for NaPi2b expression and had 3 to 11 (median 6) prior regimens in the platinum resistant or refractory setting. Of these eight patients, two achieved a partial response and the remaining six achieved stable disease. The higher dose levels currently being evaluated, as well as additional patient enrollment, provide the opportunity to further define and optimize the profile of XMT-1536.

Mersana Therapeutics 2019 Corporate Goals

XMT-1536

· The Company expects to select a dose for use in its Phase 1 expansion studies and to initiate enrollment of patients in the expansion cohorts in the first half of 2019. The expansion cohorts will focus on platinum-resistant ovarian cancer and NSCLC adenocarcinoma. The Company also plans to utilize its proprietary and validated immunohistochemistry assay to retrospectively determine NaPi2b expression to determine whether a companion diagnostic would facilitate the clinical development of XMT-1536.

· The Company plans to report Phase 1 dose escalation data in the first half of 2019.

Pipeline Expansion

· The Company expects to disclose its next clinical candidate in the second half of 2019 and is targeting the filing of an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) in the first half of 2020.

Research and Discovery

· Mersana continues to build a pipeline of promising ADCs across a variety of tumor types with significant unmet need, leveraging its three proprietary ADC platforms (Dolaflexin, Dolasynthen, and Alkymer).

· The Company is applying its expertise in ADCs to optimize and validate Immunosynthen, a new platform designed to allow systemic delivery of a potent immunostimulatory molecule to provide optimal efficacy and tolerability.

· Mersana plans to disclose the progress of these research and discovery efforts at scientific meetings throughout the year.

Corporate Developments

· The Company is proactively evaluating the potential for strategic collaborations that maximize the value of each of its pipeline candidates and platforms.

· Mersana is focused on the continued recruitment and retention of top talent, while maintaining a culture of scientific excellence, focused execution, and patient needs.

Upcoming Events

· The Company will provide further details during its presentation at the 37th Annual J.P. Morgan Healthcare Conference in San Francisco, CA on Wednesday, January 9, 2019 at 3:00 pm PT.

On January 4, 2019 Ribon Therapeutics, a biotechnology company developing first-in-class therapeutics targeting novel enzyme families activated under cellular stress conditions, reported the closing of a $65 million Series B financing (Press release, Ribon Therapeutics, JAN 4, 2019, View Source [SID1234532462]). Proceeds will be used to advance lead programs from the company’s growing pipeline into clinical testing, including small molecule monoPARP inhibitors.

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The financing was led by the Novartis Venture Fund, with participation from new investors JJDC and Celgene Corporation, as well as existing investors, The Column Group, Deerfield Management, U.S. Venture Partners, Osage University Partners, Takeda Ventures and Euclidean Capital.

"We are delighted to have the support of such a distinguished group of investors who share our commitment to bringing novel therapies to cancer patients and excitement for the therapeutic potential of modulating cellular stress responses," said Victoria Richon, Ph.D., President and Chief Executive Officer, Ribon Therapeutics. "Leveraging landmark discoveries made by our scientific founders, which ushered in a better understanding of the molecular action and biological function of novel enzyme classes beginning with monoPARPs, we are applying our expertise in drug discovery to develop novel and effective treatments for defined patient populations with limited therapeutic options."

Targeting MonoPARPs

MonoPARPs are key regulators of stress responses that enable cancer cells to survive and also evade immune detection, and emerging science has linked their activity with disease development. Ribon has built an integrated technology platform to interrogate monoPARPs to develop first-in-class, small molecule therapeutics. The company’s initial focus is in oncology, however, the 12 distinct monoPARPs function across a variety of stress responses relevant to disease development in cancer, inflammatory diseases and neurodegenerative diseases, giving Ribon’s approach broad utility. The focus of Ribon’s lead program is on advancing the science of PARP7 inhibitors for the treatment of cancer, beginning with squamous cell carcinoma of the lung.

"We have been following Victoria and her team for more than a year and are impressed by Ribon’s tremendous progress and ability to execute," said Anja Koenig, Head of the Novartis Venture Fund, who will be joining the Ribon board of directors as part of the Series B financing along with an investor from JJDC. "Ribon has developed a novel platform with the flexibility and rigor to investigate and exploit new targets providing the opportunity to build a diverse and attractive pipeline of first-in-class therapeutics."