On December 12, 2017 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and Puma Biotechnology, Inc. (Nasdaq: PBYI) reported a preclinical research collaboration with Memorial Sloan Kettering Cancer Center (MSK) to explore the combination of Daiichi Sankyo’s investigational antibody drug conjugate DS-8201 and Puma Biotechnology’s irreversible pan-HER tyrosine kinase inhibitor neratinib (NERLYNX) in HER2-mutated or HER2-positive solid tumors (Press release, Puma Biotechnology, DEC 12, 2017, http://investor.pumabiotechnology.com/press-release/daiichi-sankyo-and-puma-biotechnology-announce-research-collaboration-major-cancer-cen [SID1234522597]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

A team of scientists led by Maurizio Scaltriti, PhD, and in collaboration with a team of clinical investigators led by Bob Li, MD, will use isogenic models and established patient-derived xenograft models to assess the susceptibility of HER2-mutated or HER2-positive cancers to DS-8201, neratinib and other HER2-targeting therapies, elucidate mechanisms of action and resistance of these various tumor types, and evaluate the potential for synergistic combinations. Daiichi Sankyo and Puma Biotechnology will co-sponsor the research.

"Since early clinical data suggest that DS-8201 may have activity beyond breast and gastric cancers, the archetype HER2-driven tumors, we are interested in studying this asset on a molecular level as well as in combination with other HER2-targeting agents," said Tom Held, Vice President, Global Head, Antibody Drug Conjugate Task Force, Daiichi Sankyo. "In this collaboration, we are examining whether combining DS-8201 and neratinib, with its specific covalent binding to the HER2 receptor and associated increased internalization, is a rational combination therapy strategy to pursue. We are excited to join forces with Memorial Sloan Kettering and Puma to advance the understanding of combining HER2-targeted therapies to potentially treat various forms of HER2-mutated cancer."

"We are pleased to enter into this research collaboration with Memorial Sloan Kettering and Daiichi Sankyo to explore the combination of neratinib and DS-8201," said Alan Auerbach, Puma’s Chief Executive Officer and President. "Combination therapy with agents that address different and complementary pathways, with neratinib targeting the HER2 kinase and DS-8201 providing an innovative targeted delivery of a potent cytotoxic, represents an intriguing approach to the treatment of HER2 mutated tumors and helps to maximize the potential for both agents in treating cancers with a HER2 mutation."

About DS-8201

DS-8201 is the lead product in the ADC Franchise of the Daiichi Sankyo Cancer Enterprise. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary ADC technology, DS-8201 is a smart chemotherapy comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

DS-8201 is currently in phase 2 clinical development for HER2-positive unresectable and/or metastatic breast cancer resistant or refractory to T-DM1 (DESTINY-Breast01), phase 2 development for HER2-positive advanced gastric resistent or refractory to trastuzumab (DESTINY-Gastric01) and phase 1 development for other HER2-expressing advanced/unresectable or metastatic solid tumors.

DS-8201 has been granted Breakthrough Therapy designation for the treatment of patients with HER2-positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1), and Fast Track designation for the treatment of HER2-positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2-targeted therapies including T-DM1 by the U.S. Food and Drug Administration (FDA). DS-8201 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About NERLYNX (neratinib)

Neratinib was approved by the FDA in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX (neratinib) tablets.

Important Safety Information (ISI)
NERLYNX (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated for the extended adjuvant treatment of adult patients with early-stage HER2 overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS:

Diarrhea: Aggressively manage diarrhea occurring despite recommended prophylaxis with additional antidiarrheals, fluids, and electrolytes as clinically indicated. Withhold NERLYNX in patients experiencing severe and/or persistent diarrhea. Permanently discontinue NERLYNX in patients experiencing Grade 4 diarrhea or Grade ≥ 2 diarrhea that occurs after maximal dose reduction.
Hepatotoxicity: Monitor liver function tests monthly for the first 3 months of treatment, then every 3 months while on treatment and as clinically indicated. Withhold NERLYNX in patients experiencing Grade 3 liver abnormalities and permanently discontinue NERLYNX in patients experiencing Grade 4 liver abnormalities.
Embryo-Fetal Toxicity: NERLYNX can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.
ADVERSE REACTIONS: The most common adverse reactions (≥ 5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, epistaxis, weight decreased and urinary tract infection.

To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at 1-844-NERLYNX (1-844-637-5969) and www.NERLYNX.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

DRUG INTERACTIONS:

Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors (PPI) and H2-receptor antagonists. Separate NERLYNX by 3 hours after antacid dosing.
Strong or moderate CYP3A4 inhibitors: Avoid concomitant use.
Strong or moderate CYP3A4 inducers: Avoid concomitant use.
P-glycoprotein (P-gp) substrates: Monitor for adverse reactions of narrow therapeutic agents that are P-gp substrates when used concomitantly with NERLYNX.
USE IN SPECIFIC POPULATIONS:

Lactation: Advise women not to breastfeed.
Please see Full Prescribing Information for additional safety information.

The recommended dose of NERLYNX is 240 mg (six 40 mg tablets) given orally once daily with food, continuously for one year. Antidiarrheal prophylaxis should be initiated with the first dose of NERLYNX and continued during the first 2 months (56 days) of treatment and as needed thereafter.

To help ensure patients have access to NERLYNX, Puma has implemented the Puma Patient Lynx support program to assist patients and healthcare providers with reimbursement support and referrals to resources that can help with financial assistance. More information on the Puma Patient Lynx program can be found at www.NERLYNX.com or 1-855-816-5421.

About Puma Biotechnology

Puma Biotechnology, Inc. is a biopharmaceutical company with a focus on the development and commercialization of innovative products to enhance cancer care. Puma in-licenses the global development and commercialization rights to three drug candidates — PB272 (neratinib (oral)), PB272 (neratinib (intravenous)) and PB357. NERLYNX (neratinib) is approved for commercial use by prescription in the United States as extended adjuvant therapy for early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy and is marketed as NERLYNX. Neratinib is a potent irreversible tyrosine kinase inhibitor that blocks signal transduction through the epidermal growth factor receptors, HER1, HER2 and HER4. Currently, Puma is primarily focused on the commercialization of NERLYNX and the continued development of its other advanced drug candidates directed at the treatment of HER2-positive breast cancer. Puma believes that NERLYNX has clinical application in the potential treatment of several other cancers that over-express or have a mutation in HER2. Further information about Puma Biotechnology can be found at www.pumabiotechnology.com

About Daiichi Sankyo Cancer Enterprise

The vision of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking in order to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by our Antibody Drug Conjugate (ADC) and Acute Myeloid Leukemia (AML) Franchises, our cancer pipeline includes more than 20 small molecules, monoclonal antibodies and ADCs stemming from our powerful research engines: our two laboratories for biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. Compounds in development include: quizartinib, an oral FLT3 inhibitor, for newly-diagnosed and relapsed or refractory AML with FLT3-ITD mutations; DS-8201, an ADC for HER2-expressing breast and gastric cancer, and other HER2-expressing solid tumors; and pexidartinib, an oral CSF-1R inhibitor, for tenosynovial giant cell tumor (TGCT), which is also being explored in a range of solid tumors in combination with the anti-PD1 immunotherapy pembrolizumab. For more information, please visit: www.DSCancerEnterprise.com.

On December 12, 2017 Repros Therapeutics Inc. (NASDAQ: RPRX) ("Repros" or the "Company") reported that it has entered into a definitive agreement under which Allergan plc ("Allergan"), through a subsidiary, will acquire Repros for a cash payment of $0.67 per share (Press release, Repros Therapeutics, DEC 12, 2017, View Source [SID1234522585]). The Company’s Board of Directors has unanimously approved the transaction.

Under the terms of the merger agreement, a subsidiary of Allergan will commence a cash tender offer to purchase all of the outstanding shares of Repros common stock for $0.67 per share. The closing of the tender offer is subject to customary closing conditions, including the tender of a majority of the outstanding shares of Repros common stock. The merger agreement contemplates that Allergan, through its subsidiary, will acquire any shares of Repros that are not tendered into the offer through a second-step merger, which will be completed as soon as practicable following the closing of the tender offer. Pending approvals, Repros anticipates the transaction will close during the first quarter of 2018.

Stifel, Nicolaus & Company, Incorporated is serving as exclusive financial advisor to Repros, and Morgan, Lewis & Bockius LLP is serving as Repros’ legal counsel. Covington & Burling LLP is serving as Allergan’s legal counsel.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On December 12, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported the first results from the pivotal phase III MURANO study evaluating Venclexta/Venclyxto (venetoclax) plus MabThera/Rituxan (rituximab) compared to bendamustine plus MabThera/Rituxan (BR) for the treatment of people with relapsed or refractory chronic lymphocytic leukaemia (CLL) (Press release, Hoffmann-La Roche, DEC 12, 2017, View Source [SID1234522580]). The results showed that a fixed duration of treatment with Venclexta/Venclyxto plus MabThera/Rituxan significantly reduced the risk of disease progression or death (progression-free survival; PFS, as assessed by investigator) by 83% compared with BR (HR=0.17; 95% CI 0.11-0.25; p<0.0001). No new safety signals were observed. Venclexta/Venclyxto is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the United States and commercialised by AbbVie outside of the United States.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The MURANO study results indicate that Venclexta/Venclyxto plus MabThera/Rituxan has the potential to provide an important new chemotherapy-free option for people with previously treated chronic lymphocytic leukaemia," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We are particularly encouraged by the magnitude of benefit observed across key efficacy measures compared to a current standard of care, and we look forward to discussing these results with health authorities."

Results from the study were featured in the official press programme of the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta on Monday, 11 December, and will be presented during the Late-Breaking Abstracts Session on Tuesday, 12 December, at 7.45am EST by John F. Seymour, MD, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia (Abstract #LBA-2).

Data from the MURANO study will be submitted to global health authorities, including the US Food and Drug Administration (FDA), which has granted Breakthrough Therapy Designation for Venclexta in combination with Rituxan for the treatment of relapsed or refractory CLL based on promising results from the phase Ib M13-365 study.

Venclexta was granted accelerated approval by the FDA in April 2016 for the treatment of people with CLL with 17p deletion, as detected by an FDA approved test, who have received at least one prior therapy. The MURANO study is part of the company’s commitment in the United States to convert the current accelerated approval of Venclexta to a full approval.

A robust clinical development programme for Venclexta/Venclyxto is ongoing, and additional results across multiple blood cancers including acute myeloid leukaemia (AML) and multiple myeloma (MM) were also presented at the ASH (Free ASH Whitepaper) Annual Meeting.

About the MURANO Study
MURANO (NCT02005471) is a phase III open-label, international, multicentre, randomised study evaluating the efficacy and safety of Venclexta/Venclyxto in combination with MabThera/Rituxan compared to bendamustine in combination with MabThera/Rituxan (BR). All treatments were of fixed duration. The study included 389 patients with relapsed or refractory chronic lymphocytic leukaemia (CLL) who had been previously treated with at least one, but not more than three, lines of therapy. Patients were randomly assigned in a 1:1 ratio to receive either Venclexta/Venclyxto plus MabThera/Rituxan (Arm A) or BR (Arm B). The primary endpoint of the study is investigator-assessed progression-free survival (PFS). Secondary endpoints include PFS assessed by independent review committee (IRC), overall response rate (ORR), complete response rate (with or without complete blood count recovery, CR/CRi), overall survival (OS), minimal residual disease (MRD) status, duration of response, event-free survival and time to next CLL treatment.

The results showed:

Patients in the study who received Venclexta/Venclyxto plus MabThera/Rituxan lived significantly longer without their disease worsening (PFS, as assessed by investigator) compared to those who received BR (HR=0.17; 95% CI, 0.11-0.25; p<0.0001; median PFS: not reached vs. 17.0 months, respectively).
At two years, 84.9% of patients in the Venclexta/Venclyxto plus MabThera/Rituxan arm had not experienced disease progression, compared to 36.3% of patients in the BR arm.
Consistent benefit was observed in all patient subgroups for Venclexta/Venclyxto plus MabThera/Rituxan compared to BR, including high-risk and low-risk groups.
IRC assessment was consistent; as assessed by IRC, Venclexta/Venclyxto plus MabThera/Rituxan reduced the risk of disease progression or death by 81% compared to BR (HR=0.19; 95% CI 0.13, 0.28; p<0.0001).
Clinical benefit observed for Venclexta/Venclyxto plus MabThera/Rituxan compared to BR was consistent across key secondary endpoints, including OS (HR=0.48, 95% CI 0.25-0.90; medians not yet reached), ORR as assessed by investigator (93.3% vs. 67.7%), CR/CRi as assessed by investigator (26.8% vs. 8.2%). These results were not statistically significant. In addition, higher rates of MRD-negativity at any time were observed with Venclexta/Venclyxto plus MabThera/Rituxan compared to BR (83.5% vs. 23.1%). MRD negativity was defined as less than one CLL cell in 10,000 leukocytes.
No new safety signals were observed with the treatment combination of Venclexta/Venclyxto plus MabThera/Rituxan. The most common Grade 3-4 adverse events with Venclexta/Venclyxto plus MabThera/Rituxan compared to BR, respectively, were low white blood cell count (57.7% vs. 38.8%), low red blood cell count (10.8% vs. 13.8%), low platelet count (5.7% vs. 10.1%), low white blood cell count with fever (3.6% vs. 9.6%), pneumonia (5.2% vs. 8.0%) and infusion reactions (1.5% vs. 5.3%).
About Venclexta/Venclyxto
Venclexta/Venclyxto is a small molecule designed to selectively bind and inhibit the BCL-2 protein, which plays an important role in a process called apoptosis (programmed cell death). Overexpression of the BCL-2 protein in CLL has been associated with resistance to certain therapies. It is believed that blocking BCL-2 may restore the signalling system that tells cells, including cancer cells, to self-destruct. Venclexta/Venclyxto is being developed by Roche and AbbVie. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the United States and commercialised by AbbVie outside of the United States.

Together, the companies are committed to further research with Venclexta/Venclyxto, which is currently being evaluated in phase III clinical trials for the treatment of CLL, along with studies in several other types of cancers. In the United States, Venclexta has been granted four breakthrough therapy designations by the FDA: in combination with Rituxan for people with relapsed or refractory CLL, as a monotherapy for people with relapsed or refractory CLL with 17p deletion; in combination with hypomethylating agents (azacitidine or decitabine) for people with untreated acute myeloid leukaemia (AML) ineligible for intensive chemotherapy, and in combination with low-dose cytarabine (LDAC) for people with untreated AML ineligible for intensive chemotherapy.

About Chronic Lymphocytic Leukaemia
Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in the Western world.1 CLL mainly affects men and the median age at diagnosis is about 70 years.2 Worldwide, the incidence of all leukaemias is estimated to be over 350,0001 and CLL is estimated to affect around one-third of all people newly diagnosed with leukaemia.3

About Roche in haematology
For more than 20 years, Roche has been developing medicines that redefine treatment in haematology. Today, we are investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. In addition to approved medicines MabThera /Rituxan (rituximab), Gazyva/Gazyvaro (obinutuzumab), and Venclexta / Venclyxto (venetoclax) in collaboration with AbbVie, Roche’s pipeline of investigational haematology medicines includes Tecentriq (atezolizumab), an anti-CD79b antibody drug conjugate (polatuzumab vedotin/RG7596) and a small molecule antagonist of MDM2 (idasanutlin/RG7388). Roche’s dedication to developing novel molecules in haematology expands beyond malignancy, with the development of Hemlibra (emicizumab), a bispecific monoclonal antibody for the treatment of haemophilia A.

On December 12, 2017 Immutep Limited (ASX: IMM; NASDAQ: IMMP) (Immutep or the Company), reported update on the Company’s two ongoing clinical trials with eftilagimod alpha (LAG-3Ig or IMP321). Immutep is pleased to advise that clinical studies of eftilagimod alpha are progressing well (Press release, Prima Biomed, DEC 12, 2017, View Source [SID1234522623]).
In line with previous guidance, the third cohort of TACTI-mel (Two ACTive Immunotherapeutics in melanoma), the Company’s Australian melanoma clinical trial, has now been fully recruited. The sixth and last patient of that cohort received their first treatment yesterday, bringing the total number of patients recruited for the trial to 18.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The patients eligible to participate in the TACTI-mel Phase 1 clinical trial are those with unresectable or metastatic melanoma who have either had a suboptimal response or had disease progression with pembrolizumab (KEYTRUDA) monotherapy as a first-line of treatment. These patients are dosed with eftilagimod alpha in combination with pembrolizumab. To date, no dose limiting toxicity has been observed in any patient at any dose level. Data shows the combination to be safe and well tolerated. Data from all three cohorts is expected in H1 2018.

AIPAC (Active Immunotherapy PAClitaxel), the Company’s European clinical trial started recruitment of the randomized part of the study in January 2017. In addition to centres in Belgium and the Netherlands, competent authorities’ approvals have been received and patient recruitment has also now commenced in Poland, Hungary, United Kingdom and Germany, with France following in due course. In total, 29 out of 34 clinical sites have been activated with the outstanding site activations expected to occur in early 2018. The study is expected to be fully recruited by mid-2018.

As announced earlier in June, data from the open-label safety run-in cohort of 15 patients, who received 6mg and 30mg doses of eftilagimod alpha in combination with paclitaxel, were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL, USA. Final results received in December 2017 confirm the data presented at ASCO (Free ASCO Whitepaper). Data shows that the combination of eftilagimod alpha plus weekly paclitaxel in patients with metastatic breast cancer is safe and well tolerated, leading to an overall response rate of 47% in the safety run-in. Pharmacodynamic parameters on primary and secondary target cells confirmed the proof of principle in patients.

Eftilagimod alpha Partnering Update
Immutep’s Chinese partner for eftilagimod alpha, EOC Pharma, an oncology focused affiliate of Eddingpharm, applied in the first quarter of 2017 for an Investigational New Drug (IND) in China, in preparation before starting clinical trials. Recent positive changes in the Chinese regulatory environment are likely to speed up development of eftilagimod alpha in China.

CYTLIMIC, the Japanese NEC spin off with which Immutep has a collaboration agreement, presented a poster at ASCO (Free ASCO Whitepaper) (View Source) which showed the results of their T-cell based therapeutic cancer vaccine with eftilagimod alpha as a vaccine adjuvant. A new material transfer agreement with CYTLIMIC regarding their purchase of additional vials of eftilagimod alpha from Immutep was concluded in September 2017.

1
LOGO
IMP761 Update
IMP761 is the first humanized antibody which acts as an agonist to one of the three immune checkpoint molecules targeted in oncology, namely CTLA-4, PD-1 and LAG-3. Consequently, Immutep is the first company to translate the vast amount of clinical data and biologic knowledge from oncology to the field of auto-immune diseases. The preclinical development of our agonist anti-LAG-3 antibody has now been successfully advanced following an extensive cross-reactivity study on a series of 30 FDA-approved human tissues sections, a prerequisite before entering the clinic.

On December 12, 2017 CEL-SCI Corporation (NYSE American: CVM) reported that no further patient enrollment is required in the pivotal Phase 3 head and neck cancer study of its investigational immunotherapy Multikine* (Leukocyte Interleukin, Injection). The accrual and treatment phases of this Phase 3 study are complete (Press release, Cel-Sci, DEC 12, 2017, View Source [SID1234522593]). All of the 928 enrolled patients in the study are being followed-up as required by the study protocol.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

CEL-SCI recently announced that the study’s Independent Data Monitoring Committee (IDMC) completed its most recent review of the data from all 928 patients enrolled in the study, and recommended continuing the study as there was no evidence of any significant safety questions.

The primary endpoint of the study, a 10% improvement in overall survival of the Multikine treatment regimen plus Standard of Care (SOC) vs. Standard of Care alone, will be determined after a total of 298 deaths have occurred in these two main comparator arms of the study and have been recorded in the study database. The last patient was enrolled in the study in September 2016. Approximately 135 patients were enrolled in the study from 2011 to 2013, about 195 were enrolled in 2014, about 340 in 2015, and about 260 in 2016. The study protocol assumed an overall survival rate of about 55% at 3 years for the SOC treatment group alone.

IDMCs are committees commonly used by sponsors of clinical trials to protect the interests of the patients and the integrity of the study data in ongoing trials, especially when the trials involve patients with life threatening diseases, and when, as in cancer clinical trials, they extend over long periods of time.