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CrystalGenomics to co-develop immuno-oncology combination therapy with US firm

On April 25, 2019 CrystalGenomics, a Korean biopharmaceutical company reported it has signed a co-development agreement with U.S.-based CBT Pharmaceuticals for an investigational combination therapy of CG200745 and CBT-501 across a variety of solid tumors with high unmet medical needs (Press release, CrystalGenomics, APR 25, 2018, View Source;year=2018&no=263708 [SID1234539164]).

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CG200745 from CrystalGenomics is a novel pan-HDAC inhibitor currently in Phase II clinical study for pancreatic cancer and Phase Ib for myelodysplastic syndrome in Korea.

CBT-501 from CBT Pharmaceuticals is a novel IgG4 humanized monoclonal antibody against the Programmable Death-1 (PD-1) membrane receptor on immune cells. CBT-501 is under evaluation in two Phase I trials designed to evaluate the safety and efficacy in patients with advanced solid tumors, recurrent or refractory to standard of care therapies.

Under the exclusive agreement, the duo will be responsible for the co-development and global commercialization of the combination of CG200745 and CBT-501 in multiple tumor types, including hepatocarcinoma correlated with poor prognosis.

Immune checkpoint inhibitors such as the programmed death receptor-1 (PD-1) have been proven effective but many patients do not respond due to resistance. Recent reports suggest immune enhancing effects of HDAC inhibitors, in addition to their direct anti-tumor properties, making CG200745 a good candidate for combination therapy with CBT-501, according to CBT Pharmaceuticals.

Shares of Kosdaq-listed CrystalGenomics finished Wednesday down 2.8 percent at 26,000 won ($24.06).
By Shin Chan-ok and Minu Kim

Calithera Biosciences Announces CB-839 Abstracts Accepted for Presentation at ASCO 2018

On April 25, 2019 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, reported that three abstracts describing CB-839, the Company’s novel, orally bioavailable glutaminase inhibitor, will be presented at the 54th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), which is being held from June 1 to June 7, 2018 in Chicago, Illinois (Press release, Calithera Biosciences, APR 25, 2018, View Source [SID1234535240]).

Calithera’s collaborators will present the following results:

Phase I clinical trial of the glutaminase inhibitor CB-839 plus capecitabine in patients with advanced solid tumors Abstract #2562 Presenter: Jennifer R. Eads, M.D., Case Comprehensive Cancer Center
Date: June 4, 2018
Poster Display: 8:00 a.m.-11:30 a.m. CT, Hall
A Developmental Therapeutics–Clinical Pharmacology and Experimental Therapeutics Funding for this study was provided in part by Stand Up To Cancer1. Calithera and clinical collaborators will present two trials-in-progress abstracts, which describe the design of ongoing studies.

CANTATA: A randomized phase 2 study of CB-839 in combination with cabozantinib vs. placebo with cabozantinib in patients with advanced metastatic renal cell carcinoma.
Abstract #TPS4601 Presenter: Nizar M. Tannir, M.D., MD Anderson Cancer Center
Date: June 2, 2018
Poster Display: 8:00 a.m.-11:30 a.m. CT, Hall A Genitourinary (Non-Prostate) Cancer

Novel PET/CT imaging biomarkers of CB-839 in combination with panitumumab and irinotecan in patients with metastatic and refractory RAS wildtype colorectal cancer: A phase I/II study Abstract #TPS3616 Presenter: Satya Das, M.D., Vanderbilt University Cancer Center Date: June 3, 2018 Poster Display: 8:00 a.m.-11:30 a.m. CT, Hall A Gastrointestinal (Colorectal) Cancer About CB-839 Calithera’s lead product candidate, CB-839, is a potent, selective, reversible and orally bioavailable inhibitor of glutaminase. CB-839’s onco-metabolism activity takes advantage of the unique metabolic requirements of tumor cells and cancer-fighting immune cells such as cytotoxic T-cells. It is currently being evaluated in Phase 2 clinical trials in multiple tumor types, in combination with standard of care agents.

Takeda notes statement by Shire plc regarding revised proposal and extension of PUSU deadline to May 8, 2018

On April 25, 2018 Takeda Pharmaceutical Company Limited ("Takeda") reported the statement made by Shire plc ("Shire") confirming that it has received a revised proposal from Takeda regarding a possible offer for Shire (Press release, Takeda, APR 25, 2018, View Source [SID1234525760]).

Takeda confirms that the revised proposal comprises 0.839 new Takeda shares and US$30.33 in cash for each Shire ordinary share (the "Revised Proposal").

Based on Takeda’s share price of ¥4,923 and the exchange rates of £:¥ of 1:151.51 and £:US$ of 1:1.3945 as at the close of business on April 23, 2018, the Revised Proposal implies an equivalent value of approximately £49 per Shire ordinary share, comprising the equivalent of:

£27.26 in new Takeda shares; and
£21.75 in cash.
On this basis the Revised Proposal is equivalent to a value of approximately £46 billion for the entire issued and to be issued share capital of Shire. Shire shareholders would also be entitled to any dividends announced, declared, made or paid by Shire in the ordinary course prior to completion of the possible transaction.

Takeda and its Board have remained disciplined with respect to the terms of the Revised Proposal and Takeda intends to maintain its well-established dividend policy and investment grade credit rating.

At completion, Shire shareholders would own approximately 50 percent of the enlarged Takeda and the new Takeda shares will be listed in Japan and in the US through an ADR program.

The Board of Shire has indicated to Takeda that it would be willing to recommend the Revised Proposal to Shire shareholders, subject to satisfactory resolution of the other terms of the possible offer, including completion of reciprocal due diligence by Shire on Takeda. Accordingly, the Board of Shire will engage in discussions with Takeda in relation to these terms.

The making of any firm offer by Takeda would be subject to the following matters:

agreement of certain other terms of the Revised Proposal;
satisfactory completion of a confirmatory due diligence review by Takeda;
the unanimous and unconditional recommendation of the Board of Shire; and
final approval by the Board of Takeda.
Takeda reserves the right to waive in whole or in part any of the pre-conditions to making a firm offer set out in this announcement.

With the consent of the Panel on Takeovers and Mergers (the "Takeover Panel"), the Board of Shire has agreed to an extension of the relevant deadline under Rule 2.6(c) of the Code until 5.00 p.m. (London time) on May 8, 2018 to enable the parties to conclude their ongoing discussions. This deadline may be extended further with the consent of the Takeover Panel, at Shire’s request, in accordance with Rule 2.6(c) of the Code.

Takeda reserves the following rights in respect of the Revised Proposal:

to make an offer for Shire at any time on less favorable terms or to vary the mix of consideration:
with the agreement or recommendation of the Board of Shire;
if a third party announces a firm intention to make an offer for Shire which, at the date Takeda announces a firm intention to make an offer for Shire, is valued at a lower price than contemplated by the terms of the Revised Proposal; or
following the announcement by Shire of a whitewash transaction pursuant to the Code; and
in the event that any dividend and/or other form of capital return or distribution is announced, declared, made or paid by Shire otherwise than in the ordinary course, to reduce any offer by the amount of such dividend and/or other form of capital return or distribution.
There can be no certainty that any firm offer for Shire will be made.

GSK delivers Q1 sales of £7.2 billion, -2% AER, +4% CER
Total EPS 11.2p, -48% AER, -33% CER; Adjusted EPS 24.6p, -2% AER, +11% CER
Significant currency impact in the quarter reflecting movements in Sterling

On April 25, 2018 GlaxoSmithKline reported financial highlights for the first quarter of 2018 (Press release, GlaxoSmithKline, APR 25, 2018, View Source [SID1234525740]).

• CER sales growth across all 3 businesses. Pharmaceuticals sales £4.0 billion -4% AER, +2% CER;
Vaccines £1.2 billion +7% AER, +13% CER; Consumer Healthcare £2.0 billion -3% AER, +2% CER
• Adjusted Group operating margin of 26.6%, down 0.2 percentage points AER, up 1.3 percentage points
CER. Pharmaceuticals 33.2%; Vaccines 27.4%; Consumer Healthcare 19.4%
• Total EPS 11.2p, -48% AER, -33% CER, reflecting revaluation of Consumer Healthcare business
following agreement to acquire full ownership
• Adjusted EPS 24.6p, -2% AER, +11% CER driven by continued operating and financial efficiencies
• Q1 free cash flow £324 million -50% primarily reflecting impact of £317 million Vaccine sales milestone
payment to Novartis
• 19p dividend declared for quarter. Continue to expect 80p for FY 2018
• Guidance for CER growth in Adjusted EPS for 2018 maintained
Novartis transaction
• Agreement reached with Novartis to acquire full ownership of Consumer Healthcare business for
$13 billion, subject to shareholder approval
Product and pipeline highlights
• Sales of Ellipta Respiratory products, £386 million +25% AER, +34% CER and Nucala £104 million
+76% AER, +86% CER. Landmark IMPACT data for Trelegy Ellipta published in NEJM. sNDA
approved in US and data submitted to European Medicines Agency to support expanded label.
OSMO study demonstrating Nucala improves asthma control in severe eosinophilic asthma patients
uncontrolled on Xolair presented at AAAAI
• Continued growth from dolutegravir-based HIV products, including new 2 drug regimen Juluca, with
sales of £964 million +15% AER, +23% CER. Positive CHMP opinion received for Juluca in Europe
• Shingrix sales of £110 million; approved in Europe and Japan (23 March)

Emma Walmsley, Chief Executive Officer, GSK said:
"GSK has continued to make good progress in the first quarter with sales growth on a CER basis across all
three businesses. We are strongly focused on commercial execution with encouraging starts for our most
recent new product launches, Shingrix, Trelegy and Juluca. This performance combined with continued cost
discipline has driven a further improvement in the Group’s Adjusted operating margin at CER. We also agreed
to acquire full ownership of the Consumer Healthcare business during the quarter, delivering on one of our key
capital allocation priorities. This will help improve future cash generation and support capital planning for the
Group’s main priority to strengthen the Pharmaceuticals business and R&D pipeline.

2018 guidance
The Group expects to make continued progress in 2018, although the expectation for Adjusted EPS growth
is impacted by a number of factors including, in particular, uncertainties relating to the timing and extent of
potential generic competition to Advair in the US.
In the event that no substitutable generic competitor to Advair is introduced to the US market in 2018, the
Group continues to expect 2018 Adjusted EPS growth of 4 to 7% at CER. In the first quarter, the Group has
made continued progress, with encouraging performances from new launches, Shingrix, Trelegy and Juluca
and other new products, as well as agreeing the buyout of Novartis’ shareholding in the Consumer Healthcare
Joint Venture, subject to shareholder approval. However, the Group has also seen increased pricing and
competitive pressures in the US inhaled respiratory market in the first quarter, and GSK now expects a decline
in 2018 US Advair sales of around 30% at CER.
In the event of a mid-year introduction of a substitutable generic competitor to Advair in the US, the Group
expects full year 2018 US Advair sales of around £750 million at CER (US$1.30/£1), with Adjusted EPS
flat to down 3% at CER.
The effective tax rate for 2018 is expected to be approximately 19-20% of Adjusted profits after the impact
of US tax reform which is expected to benefit the Group effective tax rate by two to three percentage points.
GSK is not able to give guidance for Total results as it cannot reliably forecast certain material elements of
our Total results such as the future fair value movements on contingent consideration and put options. It
should be noted that contingent consideration cash payments are made each quarter primarily to Shionogi by
ViiV Healthcare which reduce the balance sheet liability and are hence not recorded in the income statement.
An explanation of the acquisition-related arrangements with ViiV Healthcare, including details of cash
payments to Shionogi, is set out on page 37.
If exchange rates were to hold at the closing rates on 31 March 2018 ($1.40/£1, €1.14/£1 and Yen 149/£1)
for the rest of 2018, the estimated negative impact on full-year 2018 Sterling turnover growth would be around
5% and if exchange gains or losses were recognised at the same level as in 2017, the estimated negative
impact on 2018 Sterling Adjusted EPS growth would be around 8%

Sarah Cannon Development Innovations Collaborates with Pivotal on Immuno-Oncology Trials

On April 25, 2018 Sarah Cannon Development Innovations reported a new strategic collaboration with Pivotal to expand access to novel immunotherapies in early phase clinical trials in Europe (Press release, Sarah Cannon Research Institute, APR 25, 2018, View Source [SID1234525708]). In late 2016, Sarah Cannon and Boehringer Ingelheim announced a strategic collaboration for a joint clinical development program in the U.S. for immune checkpoint inhibitors for the treatment of multiple difficult-to-treat cancers. Through Sarah Cannon´s collaboration with Pivotal, a European Contract Research Organization (CRO), patients in Europe will have greater access to innovative cancer therapies.

"The combined expertise in drug development and clinical research excellence of Pivotal and Sarah Cannon will enable us to accelerate research and provide access to novel investigational agents," said Lourdes Huarte, PharmD, MBA, VP Regulatory and Clinical Operations, Pivotal. "We look forward to collaborating with these experts to impact the lives of people facing cancer throughout Europe."

Through Sarah Cannon Development Innovations, a full-service, oncology-focused CRO, Sarah Cannon provides comprehensive clinical development services and operational delivery of Boehringer Ingelheim’s early stage development programs. With Pivotal’s expertise as a European CRO, the organization will facilitate rapid patient enrollment into clinical trials across selected sites in Europe.

"The collaboration with Pivotal to expand clinical research access in Europe further advances Sarah Cannon’s mission to bring the latest therapies to patients close to home," said Dawn Sauro, President of Sarah Cannon Development Innovations. "Working together with Boehringer Ingelheim over the last two years has further accelerated drug development in immunotherapies that will continue to impact patients around the world."

The expansion of Boehringer Ingelheim and Sarah Cannon’s joint clinical development program with the incorporation of Pivotal’s deep knowledge of the European populations in the clinical trials field will address a critical need for many cancer patients. Immunotherapy is showing very promising results for patients with unmet medical needs such as melanoma and metastatic non-small-cell lung cancer among others. Immunotherapy has shown impressive response rates compared to standard chemotherapy, improving progression-free survival in this population with some patients experiencing long-lasting responses. This therapeutic approach is becoming available for more cancer populations, but despite these advances, there are still many cancer patients with unmet needs. The current trial program by Boehringer Ingelheim supported by Sarah Cannon as CRO, and to which Sarah Cannon expands the reach by collaborating with Pivotal, is focused on the clinical development of BI 754091 (anti- PD-1) and BI 754111 (anti-LAG- 3) monoclonal antibodies, immune checkpoint inhibitors that mobilize the patient’s immune system to defeat cancer.

"As part of our dedication to transforming the lives of cancer patients, we are pleased to see that Sarah Cannon expands its reach by collaborating with Pivotal to help speed development of novel immunotherapies," said Mehdi Shahidi, Global Medical Head Oncology, Boehringer Ingelheim. "The power of partnerships, such as the one Sarah Cannon and Pivotal are embarking on, brings together the best minds and capabilities to accelerate this dynamic area of research. This is in line with our goal to transform the lives of patients and help win the fight against cancer."

About Pivotal

Pivotal was founded in 2001 by Dr. Ibrahim Farr on the principle that strategic medical advice and support should be the backbone of all clinical trials. After working for over two decades in the pharmaceutical industry, Dr. Farr recognized the need for a medium-sized CRO with a solid internal medical franchise that could act not only as the "doers" but also as the "co-thinkers" for their clients, through its strategic scientific advice. To date, we are the trusted advisor and counselor for many companies to deliver maximum value in their drug development programmes. We are a leading privately-held European CRO and, since inception, we have experienced a fast and steady organic growth in Europe.

Pivotal clients’ portfolio spans major pharmaceutical, biotechnological, medical device and nutrition companies, and we have long-standing relations with over 188 clients. Pivotal has extensive experience across major therapeutic areas and phases I to IV. Our highly customized teams bring to each client a combination of broad industry knowledge and operational excellence, to offer our clients fresh perspectives and breakthrough business insights. Additionally, we have built a strong oncology, innovative therapies, rare diseases and early phases hub that enables us to tackle our customers most difficult challenges, turning recommendations into concrete actions. By remaining true to our core principles and values, our vision is to become our client’s preferred outsourcing solution partner.

For more information, please visit www.pivotal.es.