On February 20, 2018 Immune Therapeutics, Inc. (OTCQB:IMUN) ("Immune" "IMUN" or the "Company"), a clinical late stage biopharmaceutical company focused on the development of two immunomodulating therapies (IRT-103 "Lodonal" and IRT-101 "MENK") for the treatment of autoimmune diseases, inflammatory diseases, cancer and HIV/AIDs, reported the company has shipped its initial order of Lodonal to AHAR Pharma in Nigeria (Press release, Immune Therapeutics, FEB 20, 2018, View Source [SID1234524071]).

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In addition, IMUN has received both trademark and patent approval from the Federal Republic of Nigeria giving the Company ironclad protection of its ideas, inventions, designs, and trade secrets while also ensuring IMUN legal rights are not infringed upon.

Immune Therapeutics shipped 100,000 capsules of Lodonal fulfilling the initial purchase order for $195,000 with AHAR Pharma, Immune’s agent and distributor in Nigeria. Since the company’s shipment has recently cleared customs, it is now available via AHAR in Nigeria.

The company has received a Certificate of Patent Approval for Lodonal NG/P/2017/602 and Certificate of Registration of Design (Trademark, Name, Box Design) NG/D.2017/603.

CEO Noreen Griffin states, "The initial Lodonal order to Nigeria is just the beginning for us with many more to come based on our strong relationship with AHAR and our ability to expand our reach in the African country through a number of potential sub-distributors for sales and marketing."

"While we are focused on an aggressive marketing strategy of Lodonal in Nigeria it is vital for us to register and protect our intellectual property rights there as well especially due to the fact that we are a non-Nigerian business desiring to take a slice of the almost 200 Million strong import-dependent domestic market which Nigeria represents. We also believe it forestalls potential pirating and counterfeiting of our products as well."

"Immune and AHAR are currently completing the necessary regulatory paperwork for presentation to the National Agency for Food and Drug Administration and Control (NAFDAC) for the approval of Lodonal for a number of additional indications."

Griffin said she believes the company will be ready to submit to NAFDAC in Q1 of 2018.

The company plans to meet this month with AHAR, GB Pharma and Fidson HealthCare as a follow up to their initial meeting in October, 2017. The companies plan to further discuss the potential for the transfer of distributorship from AHAR to Fidson. Under a potential new agreement, AHAR would remain Immune’s agent in Nigeria.

On February 20, 2018 Heat Biologics, Inc. ("Heat") (Nasdaq: HTBX), a biopharmaceutical company developing drugs designed to activate a patient’s immune system against cancer, reported that it has received a recommendation by the Independent Data Monitoring Committee (DMC) to continue patient enrollment of its ongoing Phase 2 Clinical Trial for HS-110 and nivolumab for the treatment of advanced non-small cell lung cancer (NSCLC) (Press release, Heat Biologics, FEB 20, 2018, View Source [SID1234524070]).

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The recommendation follows the first of several planned DMC meetings that took place on Wednesday, Feb. 14, 2018, to discuss the continued development of the trial.

"We believe that the continued advisement from an independent, unbiased committee of expert clinicians will help guide us to select the most appropriate patient population to include in a registrational trial for NSCLC," said CEO of Heat, Jeff Wolf. "We look forward to expanding enrollment to additional patient cohorts who may benefit from our therapy."

To-date, 35 adenocarcinoma patients with no prior history with checkpoint inhibitors have been treated with the HS-110/nivolumab combination. Further enrollment is expected to also include patients with squamous cell histology as well as those who have relapsed after checkpoint inhibitor therapy.

Heat will be hosting an analyst and investor event in New York City on February 28, 2018, at 8 a.m. ET, to discuss data generated from the first 35 patients enrolled in this trial. Event details and webcast information to be provided prior to the event.

On February 20, 2018 H3 Biomedicine Inc., a clinical stage biopharmaceutical company specializing in the discovery and development of next generation cancer therapies using its data molecular science and precision chemistry product engine, reported publication of the discovery and preclinical characterization of H3B-8800, its oral, first-in-class modulator of the SF3b spliceosome complex (Press release, H3 Biomedicine, FEB 20, 2018, View Source [SID1234524068]). The publication highlights the significant anti-tumor activity of H3B-8800 in several in vivo models, including patient-derived xenografts (PDX) of hematological malignancies with recurrent mutations in RNA splicing factor genes that comprise the spliceosome. The H3B-8800 data generated by H3 Biomedicine scientists and collaborators appear in the most recent issue of Nature Medicine and can be accessed online at nature.com/nm. (Seiler M. et al, "H3B-8800, a novel oral splicing modulator, induces lethality in spliceosome-mutant cancers").

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RNA splicing is the biological process by which pre-cursor messenger RNA (pre-mRNA) is edited into a mature mRNA. Splicing factors are proteins that carry out the editing process which is catalyzed by the core spliceosome complex. Mutations in genes encoding for certain of these RNA splicing factors that form the spliceosome are among the most common mutations found in patients with Acute Myeloid Leukemia (AML), Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) and Chronic Lymphocytic Leukemia (CLL), and occur in subsets of patients with solid tumors.

Despite the high prevalence of these mutations in cancer, no known spliceosome mutation-targeting cancer therapies are approved currently. Based on these promising preclinical data, H3 Biomedicine is a leader in this emerging area of drug discovery, and is currently evaluating H3B-8800 in a Phase 1 clinical trial for patients with AML, MDS and CMML identified by certain splicing factor mutations, and expects to present initial clinical data from this ongoing study in 2018. In 2017, H3B-8800 was granted orphan drug designation for AML and CMML.

"The significant anti-tumor activity shown in this publication demonstrates preclinical proof-of-concept of H3B-8800 in several hematological cancers of high unmet medical need," said Peter Smith, Ph.D., Chief Scientific Officer of H3 Biomedicine, Inc. "No therapies currently exist to affect mutations in the spliceosome in cancers, and H3B-8800 is the first known investigational therapy to modulate and target cancer cells with mutated genes in this complex. The discovery of H3B-8800 highlights the power of the H3 Biomedicine product engine to create highly differentiated investigational therapies to address molecular traits driving cancers in subsets of patients."

The Nature Medicine publication outlines the discovery process led by H3 Biomedicine scientists to create and characterize a highly potent and selective, oral, first-in-class modulator of the SF3b complex to target cancer cells with mutations in RNA splicing factor genes. Data highlights of the publication include:

Dose-dependent anti-leukemic efficacy and splicing modulation of H3B-8800 in a cell line xenograft model of SF3B1-mutant leukemia and significant anti-tumor activity in an SF3B1-mutant AML PDX model;
Anti-leukemic efficacy of H3B-8800 in mice with SRSF2-mutant CMML in which ten-day treatment with H3B-8800 substantially reduced leukemic burden in peripheral blood, spleen and liver;
Differential anti-tumor efficacy in in vitro and in vivo models with mutant genes in the spliceosome compared to wild-type or normal genes in the complex; and
In mechanism of action studies, H3B-8800 was shown to exploit a synthetic lethality imposed by aberrant splicing leading to differential cell killing in tumor cells harboring spliceosome mutations whereas normal cells were substantially less affected. This phenomenon is not shared by other small molecule spliceosome modulators.
H3B-8800 is one of three investigational therapies of H3 Biomedicine in clinical trials. The two additional investigational therapies include:

H3B-6545, an oral, first-in-class ESR1 covalent antagonist targeting wild-type and mutant estrogen receptor in endocrine-therapy resistant metastatic breast cancer patients; and
H3B-6527, an oral, potent and highly selective small molecule covalent inhibitor of FGFR4 for treatment of hepatocellular carcinoma (HCC) patients with overexpression of FGF19.
Portions of the work described in the Nature Medicine publication were originally presented at the 2016 American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting by lead author Silvia Buonamici, Ph. D., Executive Director, Target Biology and Translational Research, H3 Biomedicine.

About H3B-8800
H3B-8800 is a potent, selective, and orally bioavailable small molecule modulator of wild-type and mutant SF3b complex, a key component of the spliceosome. Recurrent heterozygous mutations in several core members (SF3B1, U2AF1, SRSF2, ZRSR2) of the spliceosome have been identified in both hematological malignancies, including myelodysplastic syndrome, acute myelogenous leukemia and chronic lymphocytic leukemia, as well as solid tumors such as skin, lung, breast and pancreatic cancers. Preclinical data indicates that H3B-8800 modulates RNA splicing and shows preferential antitumor activity in a range of spliceosome mutant cancer models. H3 is conducting initial clinical development in patients with hematological malignancies (including MDS, AML, and CMML) that may carry mutations in the core spliceosome genes to assess the safety and preliminary efficacy of H3B-8800.

On February 20, 2018 Myriad Genetics, Inc. (NASDAQ:MYGN) reported that the National Comprehensive Cancer Network (NCCN) has updated its medical guidelines for prostate cancer treatment to broadly include biomarker testing in prostate cancer (Press release, Myriad Genetics, FEB 20, 2018, View Source [SID1234524056]). The changes to the guidelines include new language supporting Prolaris as standard of care in treatment decision making for patients with low and favorable-intermediate risk prostate cancer. Additionally, the new guidelines support an expansion of hereditary cancer testing for prostate cancer to include all patients with a family history regardless of Gleason score along with all patients with metastatic disease, and new recommendations supporting testing for homologous recombination deficiency (HRD) in patients with metastatic prostate cancer.

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"We view this significant update in guidelines as a clear indication of the increasing importance of molecular biomarkers in guiding prostate cancer care and Myriad is uniquely positioned with its broad portfolio of tests to address these clinical needs," said Nicole Lambert, general manager, Urology. "These new guidelines are critical in our efforts to broaden insurance coverage and increase patient access to Myriad’s entire portfolio of prostate cancer molecular diagnostic tests."

Below are the key updates from the guidelines:

Prolaris: now standard of care for 110,000 patients per year identified as low or favorable-intermediate risk patients.
myRisk Hereditary Cancer: now recommended for approximately 70,000 prostate cancer patients per year including all patients with metastatic prostate cancer and those with a family history of cancer regardless of Gleason score.
myChoice HRD: now recommended for 20,000 patients per year with metastatic prostate cancer to identify tumors with homologous recombination deficiency (HRD) so that these patients can be considered for targeted therapies.
About Prolaris
Prolaris is a novel 46-gene RNA-expression test that directly measures tumor cell growth characteristics for stratifying the risk of disease progression in patients with prostate cancer. Prolaris provides a quantitative measure of the RNA expression levels of genes involved in the progression of tumor growth. Low gene expression is associated with a low risk of disease progression in men who may be candidates for active surveillance and high gene expression is associated with a higher risk of disease progression in patients who may benefit from additional therapy. For more information visit: www.prolaris.com.

About Myriad myRisk Hereditary Cancer
The Myriad myRisk Hereditary Cancer test uses an extensive number of sophisticated technologies and proprietary algorithms to evaluate 28 clinically significant genes associated with the development of eight hereditary cancers including: breast, colon, ovarian, endometrial, pancreatic, prostate and gastric cancers and melanoma. The myRisk Hereditary Cancer test offers physicians several distinct advantages over other commercial tests, including unsurpassed lab accuracy, industry leading variant classification, a medical management tool and exceptional customer service.

Men with prostate cancer can take the Hereditary Cancer Quiz to find out if they might be at risk for an inherited mutation and therefore eligible for myRisk Hereditary Cancer test.

About myChoice HRD
Myriad’s myChoice HRD is the most comprehensive homologous recombination deficiency test, enabling physicians to identify tumors that have lost the ability to repair double-stranded DNA breaks, resulting in increased susceptibility to DNA-damaging drugs such as platinum drugs or PARP inhibitors. The myChoice HRD test is a composite of three proprietary technologies (loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions).

Positive myChoice HRD scores, reflective of DNA repair deficiencies, are prevalent in all breast cancer subtypes, ovarian cancer and most other major cancers. It is estimated that 1.4 million people in the United States and Europe who are diagnosed with cancers annually may be candidates for treatment with DNA-damaging agents. Learn more: View Source

On February 20, 2018 Kancera AB (publ) hereby reports results from a Phase I study in healthy subjects with the immunoregulating drug candidate KAND567 (Press release, Kancera, FEB 20, 2018, View Source;releaseID=1434356 [SID1234524054]). The study shows that KAND567 is safe and well-tolerated up to 500 mg twice daily for 7 days. The plasma levels achieved with KAND567 at that dose are five to ten times higher than the calculated effective level for therapeutic effect in humans. Upon further increase of the dose, a reversible increase in markers for liver effects was noted. The results also showed that KAND567 blocks the Fractalkine system by reducing the number of Fractalkine receptors on the surface of immune cells. Furthermore, results are reported from three preclinical disease models showing cardiovascular protection properties of KAND567. The company is now evaluating the conditions for continued clinical development of KAND567 against cancer and inflammatory cardiovascular injuries, e.g. in connection with infarction.

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Design
The study was a randomized, double-blind, placebo-controlled Phase I study in healthy subjects aimed at studying safety, tolerability and pharmacokinetic properties (uptake, plasma concentrations and excretion) of KAND567. In a first part of the study, KAND567 was given in increasing single doses (8 – 2500 mg) to groups of healthy subjects where a group received KAND567 with and without food on different occasions. In the second part of the study, KAND567 was given in increasing doses up to 7 days (300 – 800 mg twice a day). In total, 82 subjects have been included in the study, 62 of which received active substance and 20 placebo.

Results
Results from the single dose part of the study showed that KAND567 was safe and tolerable in single doses up to 2500 mg as no clinically relevant side effects were noted. The results also show that KAND567 is absorbed efficiently from the intestine to the blood independent of food, and that KAND567 stays in the blood long enough in humans to allow dosage one to two times a day.

In the multiple dose part of the study, KAND567 proved safe and well-tolerated at doses up to 500 mg twice a day (total 1000 mg) for 7 days. This dose is five to ten times higher than the calculated effective dose in humans. Dose-limiting side effects at 800 mg twice a day (total 1600 mg) included gastric side effects in the form of diarrhea and a clinically relevant increase in markers for hepatic impairment, which returned to normal level after the end of treatment. No other clinically relevant side effects of KAND567 were noted.

In the multiple dose part of the study, the effect of KAND567 on the Fractalkine system in the immune cells of the blood was also studied. After 7 days of treatment with KAND567 (300 mg, twice daily), the number of Fractalkine receptors on the cell surface significantly decreased in specific immune cells such as NK cells, T cells and monocytes. These findings, along with in vitro findings showing that KAND567 in whole blood blocks the Fractalkine signal in human immune cells at low concentrations, show that KAND567 blocks the Fractalkine system through two co-operating mechanisms.

"It is encouraging that the results of the Phase I study show that KAND567 blocks the Fractalkine system as hoped and the drug candidate is well tolerated in doses up to levels that are five to ten times above the calculated effective dose," says Thomas Olin, CEO Kancera.

"We will now continue to deepen our understanding of how KAND567 affects the liver in relation to the desired pharmacological effects to develop a clinical development plan for both chronic and acute treatment of inflammatory diseases and cancer, eg lymphoma. There is support for the benefits of short-term treatment with KAND567 against, for example, myocardial infarction, giving the project additional opportunities because of the good safety margin we have seen in short term treatment, "says Thomas Olin.

Strategy for continued evaluation and development of KAND567
In parallel with in-depth studies of efficacy and safety for KAND567, Kancera AB has started preparations for a possible clinical development program to study the effect of KAND567 in the treatment of lymphoma (blood cancer) and cardiovascular disease. This focus has the potential to result in two products; a tablet for oral longer-term treatment of lymphoma and a product for short term treatment following myocardial infarction.

The focus on lymphoma and inflammation of the heart vessels is based on the following results.

Lymphoma (a form of blood cancer)

In 2017, results were published that support the correlation of the Fractalkine system in immune cells with an aggressive disease in lymphoma and suggest that a blockade of the Fractalkine system could inhibit the disease (1). In view of these results, as well as Kancera AB’s results from the clinical Phase I study, which show that KAND567 affects the identified immune cells, Kancera AB has initiated a collaboration with Karolinska Institutet. The collaboration aims to prepare for a clinical study by evaluating biomarkers for the Fractalkine system in blood and cancer tissue and the effect of KAND567 on these biomarkers (in isolated blood from the patients), which may provide information on which patients could benefit clinically from treatment with KAND567.

Inflammation of the blood vessels, for example in myocardial infarction

In three preclinical animal models, KAND567 has shown cardiovascular protective anti-inflammatory properties by significantly reducing infarct size (internal report), stabilizing vascular plaque (internal report) that can cause infarction and reversing relapse (restenosis) after widening of the coronary artery with so-called vessel stents (2). These studies were carried out when the project was owned by AstraZeneca. Publications of independent research groups also support blocking of the Fractalkine system to protect the heart in the context of myocardial infarction (in animal models) (3) and that the Fractalkine system is an independent risk marker and driving factor behind the inflammation of the blood vessels and the heart muscle after a heart attack in humans (4). Together, these results provide support for KAND567 as a drug candidate for the treatment of vascular disease. The results also provide information on appropriate biomarkers for the identification of patients who could benefit from such treatment.

Oncotarget. 2017 Nov 3; 8(54): 92289–92299
Biomaterials. 2015 Nov;69:22-9
Exp Physiol. 100.7. 2015: 805–817
J Clin Invest. 2015 Aug 3; 125(8): 3063–3076
About the Fractalkine project
KAND567 is an orally available small molecule that blocks CX3CR1, the Fractalkine receptor. Fractalkine is an immunomodulating factor, known as a chemokine, which transmits signals via the CX3CR1 receptor, thereby controlling the function of immune cells and cancer cells. The amount of Fractalkine and its receptor CX3CR1 has been shown to be elevated in several cancers, inflammatory diseases and in heart disease.

Kancera AB’s drug candidate KAND567 is the most advanced small molecule drug candidate against CX3CR1 and has been shown to be effective against inflammation, pain and cardiovascular disease in several preclinical disease models.