On March 22, 2018 Array BioPharma Inc. (Nasdaq: ARRY) reported that detailed results of its pivotal Phase 3 COLUMBUS trial for the treatment of patients with BRAF-mutant advanced, unresectable or metastatic melanoma were published in The Lancet Oncology (Press release, Array BioPharma, MAR 22, 2018, View Source;p=RssLanding&cat=news&id=2339334 [SID1234524945]). In the analysis of the primary endpoint, the median progression-free survival (mPFS) for patients treated with the combination of encorafenib, 450 mg daily, plus binimetinib, 45 mg twice daily (COMBO450) was 14.9 months versus 7.3 months for patients treated with vemurafenib, 960 mg twice daily [hazard ratio (HR) 0.54, 95% CI 0.41–0.71; p<0.0001].

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The manuscript entitled "Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial," was published online on March 21, 2018. Array previously announced top line results from this study in September 2016.

"A median progression-free survival of nearly 15 months with the combination of encorafenib and binimetinib is clinically meaningful for patients with advanced BRAF-mutant metastatic melanoma," said Keith T. Flaherty, M.D., Director of the Termeer Center for Targeted Therapy, Massachusetts General Hospital Cancer Center and Professor of Medicine, Harvard Medical School. "Further, a median overall survival of 33.6 months, compared to 16.9 months with vemurafenib monotherapy (HR of 0.61, 95% CI 0.47-0.79, p<0.001), a secondary endpoint not included in this publication, was recently announced. This further supplements the published data and shows that the combination of encorafenib and binimetinib may become a promising new therapy for patients with advanced BRAF-mutant metastatic melanoma."

As previously reported, the combination of encorafenib and binimetinib was generally well-tolerated. The median duration of treatment was 51.2 weeks (27.1-79.7) for encorafenib and 50.6 weeks (26.1-79.7) for binimetinib. The median dose intensity was 100% (93-100) of planned doses of encorafenib and 99.6% (80-100) of planned doses of binimetinib. The most common Grade 3/4 adverse events (AEs) seen in more than 5% of patients were increased gamma-glutamyltransferase (GGT) 9% (18/192 patients), increased creatine phosphokinase 7% (13), and hypertension 6% (11) in the encorafenib plus binimetinib group.

The U.S. Food and Drug Administration (FDA) is currently reviewing the New Drug Applications to support use of the combination of encorafenib and binimetinib for the treatment of patients with BRAF-mutant advanced, unresectable or metastatic melanoma. The FDA set a target action date under the Prescription Drug User Fee Act (PDUFA) of June 30, 2018 for both applications. In addition, the European Medicines Agency (EMA), as well as the Swiss Medicines Agency (Swissmedic) and the Australian Therapeutic Goods Administration (TGA), are reviewing the Marketing Authorization Applications for encorafenib and binimetinib.

An update from the COLUMBUS trial will be presented at an upcoming medical congress.

About Melanoma
Metastatic melanoma is the most serious and life-threatening type of skin cancer and is associated with low survival rates. [1, 2] There are about 200,000 new cases of melanoma diagnosed worldwide each year, approximately half of which have BRAF mutations, a key target in the treatment of metastatic melanoma. [1, 3, 4]

About COLUMBUS
The COLUMBUS trial, (NCT01909453), is a two-part, international, randomized, open label Phase 3 trial evaluating the efficacy and safety of the combination of encorafenib and binimetinib compared to vemurafenib and encorafenib monotherapy in 921 patients with locally advanced, unresectable or metastatic melanoma with BRAFV600 mutation. Prior immunotherapy treatment was allowed. Over 200 sites across North America, Europe, South America, Africa, Asia and Australia participated in the trial. Patients were randomized into two parts:

In Part 1, 577 patients were randomized 1:1:1 to receive COMBO450, encorafenib, 300 mg daily (ENCO 300), or vemurafenib, 960 mg twice daily alone. The dose of encorafenib in the combination arm is 50% higher than the single agent maximum tolerated dose of 300 mg. A higher dose of encorafenib was possible due to improved tolerability when combined with binimetinib. The primary endpoint for the COLUMBUS trial was an mPFS comparison of the COMBO450 arm versus vemurafenib. mPFS is determined based on tumor assessment (RECIST version 1.1 criteria) by a Blinded Independent Central Review (BICR). Secondary endpoints include a comparison of the mPFS of COMBO450 arm to that of ENCO300 and a comparison of overall survival (OS) in patients treated in the COMBO450 arm to that of vemurafenib alone. Results from Part 1 of the COLUMBUS trial previously presented at the 2016 Society for Melanoma Research Annual Congress, showed that COMBO450 more than doubled mPFS in patients with advanced BRAF-mutant melanoma, with a mPFS of 14.9 months compared with 7.3 months observed with vemurafenib [HR 0.54, (95% CI 0.41-0.71, p<0.0001)]. In the secondary mPFS comparison of COMBO450 to ENCO300, ENCO300 demonstrated a mPFS of 9.6 months [HR 0.75, (95% CI 0.56-1.00, p=0.051)].
In Part 2, 344 patients were randomized 3:1 to receive encorafenib 300 mg plus binimetinib 45 mg twice daily (COMBO300) or ENCO300. Part 2 was designed to provide additional data to help evaluate the contribution of binimetinib to the combination of encorafenib and binimetinib.
As the secondary endpoint comparison of mPFS between the COMBO450 arm and ENCO300 arm in Part 1 did not achieve statistical significance, the protocol specified analysis of OS is descriptive.

About Encorafenib and Binimetinib
BRAF and MEK are key protein kinases in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Research has shown this pathway regulates several key cellular activities including proliferation, differentiation, survival and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers including melanoma and colorectal cancer. Encorafenib is a late-stage small molecule BRAF inhibitor and binimetinib is a late-stage small molecule MEK inhibitor, both of which target key enzymes in this pathway. Encorafenib and binimetinib are being studied in clinical trials in advanced cancer patients, including the Phase 3 BEACON CRC trial and the Phase 3 COLUMBUS trial.

Array BioPharma has exclusive rights to encorafenib and binimetinib in the U.S. and Canada. Array has granted Ono Pharmaceutical exclusive rights to commercialize both products in Japan and South Korea and Pierre Fabre exclusive rights to commercialize both products in all other countries, including Europe, Asia and Latin America. Encorafenib and binimetinib are investigational medicines and are not currently approved in any country.

On March 22, 2018 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or the "Company") reported the initiation of patient dosing in the new cohort of the TACTI-mel (Two ACTive Immunotherapies in melanoma) Phase 1 clinical trial (Press release, Immutep, MAR 22, 2018, View Source [SID1234524958]). This clinical study is evaluating the combination of Immutep’s lead immunotherapy product candidate eftilagimod alpha ("efti" or "IMP321") with pembrolizumab (KEYTRUDA) in unresectable or metastatic melanoma patients in Australia.

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The additional cohort consists of six patients that will receive 30 mg of efti in combination with pembrolizumab starting at cycle one of pembrolizumab. Patients will be treated for up to 12 months. Yesterday the first patient in this cohort received their first dose of the two drugs. Safety assessment is the main objective of this study.

"This additional cohort of the ongoing TACTI-mel clinical trial is very important to the clinical development of efti, especially in the light of our new collaboration study announced on 12th of March 2018, as we are now dosing efti at cycle one in combination with KEYTRUDA with the highest dose and for a 12-month duration," said Dr. Frédéric Triebel, Immutep’s Chief Scientific Officer and Chief Medical Officer. "We look forward to presenting additional data from the TACTI-mel study during the middle of this calendar year as we hope it will further support our hypothesis that combining an antigen-presenting cell activator (efti) with a checkpoint inhibitor (KEYTRUDA) results in a therapeutic synergy and a potential benefit over checkpoint inhibitor monotherapy."

About TACTI-mel

The ongoing TACTI-mel Phase I clinical trial is a multi-centre, open-label, dosing escalating (1, 6 or 30 mg of efti) study evaluating the combination of efti with pembrolizumab (for 6 months, starting at cycle 5) in unresectable or metastatic melanoma patients that have had either a suboptimal response or had disease progression with pemobrolizumab monotherapy. Each cohort of the study is comprised of six patients. As previously reported in December 2017, the last patient of the third cohort (30 mg) has been dosed, bringing the total number of patients recruited and dosed in the trial to 18. Preliminary data from the 1 and 6 mg cohorts were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2017 Annual Meeting in November 2017. As reported at SITC (Free SITC Whitepaper), anti-tumour activity (tumour reduction) was observed in 7/12 patients (58%) in the first two cohorts of the study. Prior to treatment with efti, all of these patients had either a suboptimal response or had disease progression when treated with pembrolizumab monotherapy. The TACTI-mel trial was expanded with the addition of a new cohort in February 2018.

About Eftilagimod Alpha

Eftilagimod alpha ("efti" or "IMP321"), a LAG-3Ig fusion protein, is a MHC class II agonist that activates antigen-presenting cells ("APCs") such as dendritic cells and monocytes (primary target cells) and then CD8 T-cells (secondary target cells). The activation of the dendritic cell network and the subsequent T cell recruitment at the tumour site with efti may lead to stronger anti-tumor CD8 T cell responses than observed

LOGO

with checkpoint inhibitor monotherapy, as in the case of the TACTI-mel (Two ACTive Immunotherapies in melanoma) Phase I clinical trial (clinicaltrials.gov identifier NCT02676869). In combination with chemotherapy, the activation of the APC network with efti the day after injection of a single agent chemotherapy may lead to stronger cytotoxic cellular responses associated with an improved long-term Th1 (IFN-g) immune status, both parameters being essential for a potent immune response against the tumour, as in the case of the AIPAC (Active Immunotherapy PAClitaxel) Phase IIb clinical trial (clinicaltrials.gov identifier NCT02614833).

On March 22, 2018-Triumvira Immunologics, a privately held biopharmaceutical company developing a novel platform for engineering T cells to attack cancers, reported that it will present at the 25th BioCentury Future Leaders conference at the Millennium Broadway Hotel & Conference Center in New York City (Press release, , 22 22, 2018, View Source [SID1234524954]). Chief Executive Officer and President, Paul Lammers, M.D., M.Sc. will be presenting on March 23 from 8:45-9:00am ET in Presentation Room 508.

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President & CEO of Triumvira Immunologics, Paul Lammers will be presenting at BioCentury’s Future Leaders conference in New York on March 23

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Dr. Lammers will provide an overview of Triumvira and the improvements the company is making over current therapies with its novel immuno-oncology platform T Cell-Antigen Coupler (TAC). Dr. Lammers will also be giving updates on Triumvira’s lead drug, CD19 TAC#921, which is targeted to enter clinical development in Q1 2019 – Phase 1/2 in patients with relapsing/refractory diffuse large B-cell lymphoma (DLBCL).

The Future Leaders conference offers Wall Street and pharma executives the opportunity to assess private and public companies with healthy financial profiles, poised to deliver on milestones that could lead to the next tier of valuations.

On March 22, 2018 Caladrius Biosciences, Inc. (Nasdaq: CLBS) ("Caladrius" or the "Company"), a development-stage biopharmaceutical company with multiple technology platforms targeting autoimmune and select cardiovascular indications, reported that financial results for the three and twelve months ended December 31, 2017 and provides a business update (Press release, Caladrius Biosciences, MAR 22, 2018, View Source [SID1234524949]).

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Highlights of the 2017 fourth quarter and recent weeks include:

Completed enrollment in The Sanford Project: T-Rex Study;

Dosed first patient in Phase 2 clinical trial in Japan with Caladrius’ proprietary CD34 cell therapy (CLBS12) for the treatment of no-option critical limb ischemia ("CLI");

Acquired from Shire plc (LSE: SHP, Nasdaq: SHPG) an exclusive worldwide license to data and regulatory filings from a late stage CD34 cell therapy program for the treatment of chronic myocardial ischemia targeting refractory angina ("RfA"); and

Reported results from the predetermined interim analysis in The Sanford Project: T-Rex Study, which concluded the treatment to be well-tolerated and non-futile for therapeutic effect.

Management Commentary

"The past months have been especially productive as we made much progress advancing and expanding our clinical development pipeline," stated David J. Mazzo, Ph.D., President and Chief Executive Officer of Caladrius.
"We were particularly pleased to acquire the late-stage asset from Shire’s CD34 cell therapy program for the treatment of refractory angina. In addition to adding a potentially late-stage product candidate that is complementary to our current pipeline in ischemic repair, this program represents a large potential commercial opportunity as refractory angina afflicts approximately one million people in the U.S. alone, with an incidence rate of 50,000 to 100,000 annually.1
"Our active clinical programs continue to progress well and we were delighted to complete enrollment in our landmark Phase 2 T-Rex study in children and adolescents with recent onset type 1 diabetes. We subsequently reported the conclusions of the independent statisticians for the predetermined interim analysis that the therapy continues to be well tolerated and was deemed non-futile as determined by pre-defined futility criteria for therapeutic effect. This analysis was triggered by 50% of the targeted total number of patients completing six months of follow-up. We look forward to completing and reporting the 12-month follow-up on all 110 patients in early 2019 as the complete data set will inform the next steps in our development plan.

1 Global Cardiology Science & Practice: April 30, 2015
"We believe that we have an exciting year ahead as we plan to advance a number of key clinical programs in cardiovascular indications such as CLI, coronary microvascular dysfunction and RfA and as we near the completion of the T-Rex study in type 1 diabetes. We continue to build on our recent accomplishments and hope to attain a number of value-creating inflection points throughout the balance of the year and beyond," Dr. Mazzo continued.

Fourth Quarter Financial Highlights

Note: Effective with the sale of PCT to Hitachi in the second quarter of 2017, all PCT-related activities and gain on sale results will be reported as discontinued operations. All remaining operations will be reported as continuing operations. In addition, all prior year comparative financial results will restate PCT operations as discontinued operations.
Research and development (R&D) expenses for the fourth quarter of 2017 of $4.7 million increased 45% compared with $3.2 million in the fourth quarter of 2016, as the Company focused its R&D efforts on the ongoing Phase 2 T-Rex Study and preparations for other pipeline programs, including the initiation of our CLI clinical program in Japan. Caladrius’ clinical development programs are supported, in part, by grants and collaborations.
General and administrative (G&A) expenses for the fourth quarter of 2017 increased 17% to $2.7 million, compared with $2.3 million in the fourth quarter of 2016.
The net loss from continuing operations for the fourth quarter of 2017 was $4.0 million, and included a non-cash tax benefit of $3.2 million, compared with $5.7 million for the comparable 2016 period. The non-cash tax benefit in 2017 is principally offset by non-cash tax expense reported in discontinued operations.
Income from discontinued operations for the fourth quarter of 2017 was $1.1 million, which represented a non-cash income tax adjustment on gain on the sale of PCT to Hitachi in the second quarter of 2017.
Net loss per share from continuing operations attributable to Caladrius common stockholders for the fourth quarter of 2017 was $0.40 per share compared to net loss per share of $0.69 for the same period in 2016.

2017 Financial Highlights

R&D expenses for 2017 decreased 5% to $15.8 million compared with $16.7 million for the 2016 year. G&A expenses decreased 8% to $11.8 million for 2017 compared with $12.8 million for the 2016 year. 2017 included $1.9 million of equity compensation expense related to the acceleration of employee equity stock and option award vesting triggered by the sale of the Company’s PCT subsidiary to Hitachi.
The net loss from continuing operations for the twelve months ended December 31, 2017 was $16.2 million, compared with the net loss from continuing operations of $31.3 million for the same period of
2016. The continuing operations net loss includes a non-cash tax benefit of $11.5 million, which is substantially offset by a non-cash tax expense reported in discontinued operations.
Income from discontinued operations during 2017 was $38.4 million, which includes a $41.2 million gain on the sale of PCT (net of $10.5 million taxes), compared with a loss from discontinued operations of
$2.1 million in the same period in 2016.

Net loss per share from continuing operations attributable to Caladrius common stockholders for the twelve months ended December 31, 2017 was $1.78 per share compared to a net loss per share of $4.74 for the same period in 2016.

Balance Sheet Highlights

As of December 31, 2017, Caladrius had cash, cash equivalents, restricted cash and marketable securities of $60.1 million compared with $7.1 million as of December 31, 2016. During 2017, the Company received gross proceeds of $79.4 million from the sale of PCT and $5.7 million in proceeds from stock issuance.
Based on existing programs and projections, the Company is confident its cash balances and additional grant funding, along with continued disciplined expense management, will allow it to fund its current business plan

beyond 2019.

Conference Call

Caladrius’ management will host a conference call for the investment community beginning today at 4:30 p.m. Eastern Time to review financial results, provide a Company update and answer questions.
Shareholders and other interested parties may participate in the conference call by dialing 866-595- 8403 (U.S.) or 706-758-9979 (international) and providing conference ID 8668599. The call will also be broadcast live on the Company’s website at www.caladrius.com/events.
For those unable to participate in the live conference call or webcast, a replay will be available beginning March 22, 2018 two hours after the close of the conference call. To access the replay, dial (855) 859- 2056 or (404) 537-3406. The replay passcode is: 8668599.

The webcast will be archived on the Company’s website for 90 days.

On March 22, 2018 Atara Biotherapeutics, Inc. (Nasdaq:ATRA), a leading off-the-shelf T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported that Chris Haqq, M.D., Ph.D., the Company’s Executive Vice President of Research and Development and Chief Scientific Officer, will participate in three upcoming immuno-oncology conferences (Press release, Atara Biotherapeutics, MAR 22, 2018, View Source [SID1234524946]):

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Guggenheim Healthcare Talk: Disruptive Technologies in Immune-Oncology

Fireside chat on Tuesday, March 27th, 2018 at 2:00 p.m. EDT. The conference will be held at Convene, 101 Park Avenue in New York, NY.
Jefferies Immuno-Oncology Cell Therapy Summit

Fireside chat on Tuesday, April 3rd, 2018 at 7:30 a.m. EDT. The conference will be held at the Boston Harbor Hotel in Boston, MA.
William Blair 8th Annual Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper)

Panel discussion titled "Allogenic Platforms" on Wednesday, April 4th, 2018 at 10:40 a.m. EDT. The conference will be held at the Apella Event Space Alexandria Center in New York, NY.