On November 26, 2018 Bayer reported that the U.S. Food and Drug Administration (FDA) has approved Vitrakvi (larotrectinib), the first ever oral TRK inhibitor, for the treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment.1,2 This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR) (Press release, Bayer, NOV 26, 2018, View Source [SID1234531623]). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Vitrakvi is the first treatment to receive a tumor-agnostic indication at the time of initial FDA approval. In clinical trials of patients with TRK fusion cancer, Vitrakvi demonstrated an ORR of 75 percent (N=55) (95% CI, 61%, 85%), including a 22 percent complete response (CR) rate.2

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"The FDA approval of larotrectinib marks an important milestone in how we treat cancers that have an NTRK gene fusion – a rare driver of cancer. I have seen firsthand how treatment with larotrectinib, which is designed specifically for this oncogenic driver, can deliver clinically meaningful responses in patients with TRK fusion cancer, regardless of patient age or tumor type," said David Hyman, M.D., chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center and a global principal investigator for a larotrectinib clinical trial. "We now have the first therapy approved for this genomic alteration, regardless of cancer type."

NTRK gene fusions are genomic alterations that result in constitutively-activated chimeric TRK fusion proteins that can act as an oncogenic driver, promoting cell proliferation and survival in tumor cell lines.2 Vitrakvi, developed by Bayer and Loxo Oncology, Inc., is a CNS active TRK inhibitor designed to inhibit these proteins.2 TRK fusions can be found in many types of solid tumors and affect both children and adults.1 In the clinical trials that were the basis for this approval, Vitrakvi showed clinical benefit across numerous unique tumor types, including lung, thyroid, melanoma, GIST, colon, soft tissue sarcoma, salivary gland and infantile fibrosarcoma.2

"Today’s approval of Vitrakvi is the culmination of years of hard work and research by many people to bring the first ever treatment to patients with TRK fusion cancer. TRK fusions are rare, but occur across many different tumor types. In this era of precision medicine, we are delivering on Bayer’s commitment to advance the future of cancer care while providing value for patients and physicians," said Robert LaCaze, member of the executive committee of Bayer’s Pharmaceuticals Division and head of the Oncology Strategic Business Unit at Bayer. "It is very rewarding to provide a therapy specifically for patients with advanced solid tumors harboring an NTRK gene fusion."

Vitrakvi (larotrectinib) has warnings and precautions of neurotoxicity, hepatotoxicity and embryo-fetal toxicity.2 The most common adverse events observed in more than 20 percent of patients, regardless of attribution, were increased ALT, increased AST, anemia, fatigue, nausea, dizziness, cough, vomiting, constipation, and diarrhea.2 The majority of adverse events occurring in greater than or equal to 10 percent of patients were grade 1 or 2.2

TRK fusion cancer occurs across a broad range of tumor types with varying frequency in both adult and pediatric patients.1 It is diagnosed through the identification of NTRK gene fusions using specific tests, including those that employ next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH).2 Patients eligible for treatment with Vitrakvi should be selected based on the presence of an NTRK gene fusion in their tumor.2

"We are grateful to the investigators, research teams and patients who contributed to and participated in the larotrectinib clinical trials that supported this approval," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. "The approval of Vitrakvi is a testament to the relentless prioritization of biology in the drug development process. It is now even more critical to screen patients of all ages with advanced solid tumors for actionable genomic insights that could benefit their care or aid in their referral to clinical trials."

The FDA reviewed Vitrakvi under Priority Review, which is reserved for medicines that could provide significant improvements in the safety or effectiveness of the treatment for serious conditions. The FDA previously granted Vitrakvi Breakthrough Therapy Designation, Rare Pediatric Disease Designation and Orphan Drug Designation.

"We welcome the FDA approval of Vitrakvi and the innovations in genomic testing that make such precision medicine a reality," said Andrea Stern Ferris, president and chief executive officer of the LUNGevity Foundation. "We’re seeing scientific advancements, like genomic testing capable of detecting an NTRK gene fusion, beginning to transform the treatment of cancer and provide new options for patients."

Vitrakvi will be available in oral capsules as well as a liquid formulation for adults and children.2 For more information, visit www.vitrakvi.com.

Bayer to Provide Comprehensive Value and Access Programs
Bayer is committed to ensuring that patients in the U.S. who are prescribed Vitrakvi are able to access the medication and receive the support they may need. As part of this commitment, Bayer is providing two comprehensive programs, the Vitrakvi Commitment ProgramTM and the TRAK AssistTM patient support program.

The Vitrakvi Commitment Program will refund the cost of Vitrakvi to payers, patients and third-party organizations paying on behalf of patients, in the event eligible patients do not experience clinical benefit within 90 days of treatment initiation. Eligible patients include those who have tested positive for an NTRK gene fusion, have not received clinical benefit within 90 days of treatment initiation, and received Vitrakvi from an in-network specialty pharmacy.

The TRAK AssistTM patient support program provides comprehensive reimbursement support and patient assistance services. For more information and eligibility requirements, please call 1-844-634-TRAK (8725).

The Bayer US Patient Assistance Foundation, a charitable organization that helps eligible patients get their Bayer prescription medicine at no cost, is an additional resource for patients in need of financial assistance.

"Express Scripts applauds Bayer for its thoughtful approach to patient access. The Vitrakvi Commitment Program represents a significant advance to patient access," said Steve Miller, M.D., chief medical officer, Express Scripts. "We look forward to working together to help those who will benefit from this medicine have affordable access to it."

Clinical Trial Results
The FDA approval of Vitrakvi (larotrectinib) is based on pooled data across the Phase I adult trial, Phase II NAVIGATE trial and Phase I/II pediatric SCOUT trial (N=55).2 In pooled study results, Vitrakvi demonstrated an overall response rate (ORR) of 75 percent (95% CI, 61%, 85%) by blinded independent review committee (with 22 percent of patients achieving a complete response and 53 percent of patients achieving a partial response) across various tumor types, including soft tissue sarcoma, salivary gland, infantile fibrosarcoma, thyroid, lung, melanoma, colon, GIST, cholangiocarcinoma, appendix, breast and pancreas.2 Seventy-three percent of responding patients (N=41) had a duration of response (DOR) lasting six months or greater at the time of data cut-off.2 Median DOR (range 1.6+, 33.2+) and progression-free survival (PFS) had not been reached at the time of analysis.2,3 Median time to response was 1.84 months.3 In the safety database (N=176), which included patients with and without an NTRK gene fusion, the majority of adverse events (AEs) reported in greater than or equal to 10 percent of patients were grade 1 or 2.2 AEs of any grade observed in more than 20 percent of patients, regardless of attribution, included increased ALT (45%), increased AST (45%), anemia (42%), fatigue (37%), nausea (29%), dizziness (28%), cough (26%), vomiting (26%), constipation (23%), and diarrhea (22%).2 In October 2018, updated efficacy and safety data on larotrectinib were presented at the ESMO (Free ESMO Whitepaper) 2018 Congress (European Society for Medical Oncology).

Vitrakvi will be available in the U.S. market immediately. Bayer submitted a Marketing Authorization Application (MAA) in the European Union in August 2018.

For additional information about the larotrectinib clinical trials, please refer to www.clinicaltrials.gov or visit www.loxooncologytrials.com.

About Vitrakvi (larotrectinib)
Vitrakvi is an oral TRK inhibitor for the treatment of adult and pediatric patients with solid tumors with an NTRK gene fusion without a known acquired resistance mutation that are either metastatic or where surgical resection will likely result in severe morbidity, and have no satisfactory alternative treatments or have progressed following treatment.2 This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Research suggests that the NTRK genes can become abnormally fused to other genes, producing a TRK fusion protein that can lead to the growth and survival of solid tumors in various sites of the body.1,2

In November 2017, Bayer and Loxo Oncology entered into an exclusive global collaboration for the development and commercialization of the TRK inhibitors larotrectinib and LOXO-195. Bayer and Loxo Oncology are jointly developing the two products with Loxo Oncology leading the ongoing clinical studies as well as the filing in the U.S., and Bayer leading ex-U.S. regulatory activities and worldwide commercial activities. In the U.S., Bayer and Loxo Oncology will co-promote the products.

Larotrectinib has not been approved by the European Medicines Agency.

About TRK Fusion Cancer
TRK fusion cancer occurs when an NTRK gene fuses with another unrelated gene, producing an altered TRK protein.2 The altered protein, or TRK fusion protein, becomes constitutively active or overexpressed, triggering a signaling cascade.2 These TRK fusion proteins act as oncogenic drivers promoting cell growth and survival, leading to TRK fusion cancer, regardless of where it originates in the body.2 TRK fusion cancer is not limited to certain types of tissues and can occur in any part of the body.1 TRK fusion cancer occurs in various adult and pediatric solid tumors with varying frequency, including lung, thyroid, GI cancers (colon, cholangiocarcinoma, pancreatic and appendiceal), sarcoma, CNS cancers (glioma and glioblastoma), salivary gland cancers (mammary analogue secretory carcinoma) and pediatric cancers (infantile fibrosarcoma and soft tissue sarcoma).1,2

Important Safety Information

Neurotoxicity: Among the 176 patients who received VITRAKVI, neurologic adverse reactions of any grade occurred in 53% of patients, including Grade 3 and Grade 4 neurologic adverse reactions in 6% and 0.6% of patients, respectively. The majority (65%) of neurological adverse reactions occurred within the first three months of treatment (range 1 day to 2.2 years). Grade 3 neurologic adverse reactions included delirium (2%), dysarthria (1%), dizziness (1%), gait disturbance (1%), and paresthesia (1%). Grade 4 encephalopathy (0.6%) occurred in a single patient. Neurologic adverse reactions leading to dose modification included dizziness (3%), gait disturbance (1%), delirium (1%), memory impairment (1%), and tremor (1%).2

Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dose when resumed.2

Hepatotoxicity: Among the 176 patients who received VITRAKVI, increased transaminases of any grade occurred in 45%, including Grade 3 increased AST or ALT in 6% of patients. One patient (0.6%) experienced Grade 4 increased ALT. The median time to onset of increased AST was 2 months (range: 1 month to 2.6 years). The median time to onset of increased ALT was 2 months (range: 1 month to 1.1 years). Increased AST and ALT leading to dose modifications occurred in 4% and 6% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 2% of patients.2

Monitor liver tests, including ALT and AST, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed.2

Embryo-Fetal Toxicity: VITRAKVI can cause fetal harm when administered to a pregnant woman. Larotrectinib resulted in malformations in rats and rabbits at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily.2

Advise women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment and for 1 week after the final dose of VITRAKVI.2

Most Common Adverse Reactions (≥20%): The most common adverse reactions (≥20%) were: increased ALT (45%), increased AST (45%), anemia (42%), fatigue (37%), nausea (29%), dizziness (28%), cough (26%), vomiting (26%), constipation (23%), and diarrhea (22%).2

Drug Interactions: Avoid coadministration of VITRAKVI with strong CYP3A4 inhibitors (including grapefruit or grapefruit juice), strong CYP3A4 inducers (including St. John’s wort), or sensitive CYP3A4 substrates. If coadministration of strong CYP3A4 inhibitors or inducers cannot be avoided, modify the VITRAKVI dose as recommended. If coadministration of sensitive CYP3A4 substrates cannot be avoided, monitor patients for increased adverse reactions of these drugs.2

On November 26, 2018 Aptose Biosciences Inc. (NASDAQ: APTO, TSX: APS), a clinical-stage company developing highly differentiated therapeutics targeting the underlying mechanisms of cancer, reported that dosing has commenced in the first patient in its Phase 1b clinical study of APTO-253 in patients with relapsed or refractory hematologic malignancies (Press release, Aptose Biosciences, NOV 26, 2018, View Source [SID1234531640]). APTO-253 is the only known clinical-stage molecule that can directly inhibit expression of the MYC oncogene, shown to reprogram survival signaling pathways in cells and thereby transform cells and contribute to drug resistance in many malignancies, including acute myeloid leukemia (AML).

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"We are pleased to announce the successful re-initiation of patient dosing in our clinical trial with APTO-253, our first-in-class inhibitor of the MYC oncogene that has the potential to benefit a large patient population across various therapeutic areas, and we look forward to providing updates moving forward," commented William G. Rice, Ph.D., Chairman, President and CEO. "As the clinical protocol requires only one patient at each of the two lowest dose levels, we have and will continue to carefully select patients for those first two dose levels. Relapsed/refractory AML patients tend to be acutely sick, and we seek to complete those two lower dose levels with a favorable tolerability profile. Indeed, we hope this thoughtful approach will allow expeditious escalation to higher dose levels and may provide greater benefit to the AML patients."

About the APTO-253 Clinical Trial

The Phase 1b, multicenter, open-label, dose-escalation clinical trial of APTO-253 is designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamic responses and establish the recommended Phase 2 dose and efficacy of APTO-253 as a single agent. APTO-253 will be administered once weekly, over a 28-day cycle. The study is expected to enroll up to 20 patients with relapsed or refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) patients. The study is designed to then transition, as appropriate, to single-agent expansion cohorts in AML and MDS, followed by combination studies. More information can be found at www.clinicaltrials.gov.

About APTO-253

APTO-253 is a clinical-stage, small molecule, targeted therapeutic agent that inhibits expression of the MYC oncogene, leading to cell cycle arrest and programmed cell death (apoptosis) in human-derived solid tumor and hematologic cancer cells. The MYC oncogene is overexpressed in hematologic cancers, including acute myeloid leukemia (AML). Aptose researchers have reported the ability of APTO-253 to induce cell death, or apoptosis, in multiple blood cancer cell lines including AML, as well as in vitro synergy with various classes of conventional approved and investigational therapies for AML or myelodysplastic syndromes (MDS). New findings reveal that APTO-253 might also serve certain solid tumor patients with BRCA1/2 mutations, but without causing toxicity to the normal bone marrow functions.

On November 23, 2018 The Mundipharma network of independent associated companies reported that the European Commission (EC) has granted approval for the use of Pelmeg (pegfilgrastim) as a treatment for reduction in the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes).1 (Press release, Mundipharma, NOV 23, 2018, View Source [SID1234531587])

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The EC’s decision follows a recommendation from the Committee for Medicinal Products for Human Use (CHMP) that was based on a robust regulatory submission of key biosimilarity data from analytical, biofunctional and clinical study comparisons for Pelmeg.2 In all cases it demonstrated comparable pharmacodynamics, pharmacokinetics, and immunogenicity to its reference product Neulasta.3,4,5 The information submitted, and conclusions reached, were comprehensive enough to extrapolate the indication for Neulasta across to Pelmeg.2 As such, it is indicated in the exact same way as subcutaneous (pre-filled syringe) Neulasta.

"We hope this approval will significantly improve the lives of people who are affected by chemotherapy induced neutropenia and febrile neutropenia. The availability of this biosimilar represents an important opportunity to reduce healthcare costs while increasing access to an effective treatment option," said Philippe Bastide, Head of Biosimilars, Mundipharma International.

Pelmeg is the fourth biosimilar medicine to be commercialised by the Mundipharma network. It was developed by Cinfa Biotech which was acquired by the Mundipharma network and announced in October 2018. The acquisition of Cinfa Biotech provides Mundipharma with global reach and expanded development capabilities.

▼ This medicinal product is subject to additional monitoring.

Notes to editors

About the clinical data

A comprehensive analytical, biofunctional, preclinical and clinical comparability programme has demonstrated a high degree of similarity between Pelmeg and Neulasta. Its biosimilarity has been studied in healthy volunteers who have no comorbidities, require no co-medication and are immunocompetent.3,4,5

The Pelmeg data:

Confirmed biosimilarity to Neulasta in sensitive clinical study settings
Demonstrated pharmacokinetic comparability to Neulasta at the clinical dose of 6 mg
Demonstrated pharmacodynamic comparability to Neulasta at the clinical dose of 6 mg and at the reduced dose of 3 mg
Did not show any clinically meaningful differences in the safety and immunogenicity profile compared to Neulasta
About Pelmeg

Pelmeg is a pegfilgrastim biosimilar.6 Pegfilgrastim is a pegylated version of granulocyte-colony stimulating factor (G-CSF) that works by stimulating the bone marrow to produce more neutrophils, thereby reducing the incidence of febrile neutropenia. It is administered as a subcutaneous injection once per chemotherapy cycle, at least 24 hours after cytotoxic chemotherapy.6

About neutropenia and febrile neutropenia

People taking chemotherapy for cancer are at risk of dangerously low levels of a type of white blood cell called a neutrophil. Neutrophils play an important role in the immune system guarding against infection. Febrile neutropenia is a low level of neutrophils in the blood accompanied by a fever.7

On November 23, 2018 Tiziana Life Sciences plc (Nasdaq: TLSA / AIM: TILS) (the "Company" or "Tiziana"), a UK biotechnology company that focuses on the discovery and development of novel molecules to treat human disease in oncology and immunology, reported the closing of its underwritten, registered public offering in the United States (the "Offering") of 442,910 American Depositary Shares ("ADSs"), representing 4,429,100 new ordinary shares of nominal value £0.03 each in the capital of the Company ("Ordinary Shares") at a price of $9.90 per ADS, for aggregate gross proceeds of approximately £3.42 million (or $4.39 million at a GBP1 : US$1.2839 exchange rate), before deducting underwriting discounts and commissions (Press release, Tiziana Life Sciences, NOV 23, 2018, View Source [SID1234531588]). Each ADS offered represents 10 Ordinary Shares. All ADSs sold in the Offering will be offered by the Company.

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In addition, Tiziana has granted the underwriter a 30-day option to purchase up to an additional 66,437 ADSs on the same terms and conditions (the "Option"). The number of Ordinary Shares represented by ADSs comprised in the Offering (including by way of the exercise of the Option) will be within existing shareholder authorities.

The ADSs began trading on the Nasdaq Global Market ("Nasdaq") under the ticker "TLSA" on 20 November 2018.

Laidlaw & Company (UK) Ltd. acted as the sole book-running manager in respect of the Offering.

Following Admission, the issued share capital of the Company will be 136,409,818 Ordinary Shares (or 137,074,183 Ordinary Shares if the underwriters exercise the Option in full) and this figure may be used by shareholders as a denominator for the calculations by which they will determine if they are required to notify their interest in, or change to their interest, the Company, under the Disclosure Guidance and Transparency Rules published by the UK Financial Conduct Authority. There are no Ordinary Shares held in treasury. Each Ordinary Share entitles the holder to a single vote at general meetings of the Company.

The Offering was made only by means of a prospectus, which, for the avoidance of doubt, did not constitute a "prospectus" for the purposes of the Prospectus Directive (as defined below) and was not been reviewed by any competent authority in any Member State (as defined below).

Copies of the final prospectus and accompanying prospectus relating to and describing the terms of the Offering may be obtained from Laidlaw & Company Ltd., Attention: Syndicate Department, 521 Fifth Avenue, New York, NY 10175, by telephone at +01 (0)212 953 4917 or by email at [email protected]. Electronic copies of the final prospectus supplement and accompanying prospectus are also available on the website of the US Securities and Exchange Commission (the "SEC") at www.sec.gov.

A registration statement relating to these securities was declared effective by the SEC on 19 November 2018.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy securities, nor shall there be any sale of, these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

For readers in the European Economic Area

In any member state in the European Economic Area (each, a "Member State") that has implemented the Prospectus Directive (as defined below), this announcement is only addressed to and directed at qualified investors in that Member State within the meaning of the Prospectus Directive. The term "Prospectus Directive" means Directive 2003/71/EC (and amendments thereto, including Directive 2010/73/EU, to the extent implemented in each relevant Member State), together with any relevant implementing measure in the relevant Member State.

For readers in the United Kingdom

This announcement, in so far as it constitutes an invitation or inducement to enter into investment activity (within the meaning of section 21 of the Financial Services and Markets Act 2000, as amended) in connection with the securities which are the subject of the Offering described in this announcement or otherwise, is being directed only at (i) persons who are outside the United Kingdom or (ii) persons who have professional experience in matters relating to investments who fall within Article 19(5) ("Investment professionals") of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005, as amended (the "Order") or (iii) certain high value persons and entities who fall within Article 49(2)(a) to (d) ("High net worth companies, unincorporated associations etc.") of the Order; or (iv) any other person to whom it may lawfully be communicated (all such persons in (i) to (iv) together being referred to as "relevant persons"). The ADSs offered in the Offering are only available to, and any invitation, offer or agreement to subscribe, purchase or otherwise acquire such ADSs will be engaged in only with relevant persons. Any person who is not a relevant person should not act or rely on this announcement or any of its contents.

For distributors

Solely for the purposes of the product governance requirements contained within: (a) EU Directive 2014/65/EU on markets in financial instruments, as amended ("MiFID II"); (b) Articles 9 and 10 of Commission Delegated Directive (EU) 2017/593 supplementing MiFID II; and (c) local implementing measures (together, the "MiFID II Product Governance Requirements"), and disclaiming all and any liability, whether arising in tort, contract or otherwise, which any "manufacturer" (for the purposes of the MiFID II Product Governance Requirements) may otherwise have with respect thereto, the ADSs have been subject to a product approval process, which has determined that such securities are: (i) compatible with an end target market of retail investors and investors who meet the criteria of professional clients and eligible counterparties, each as defined in MiFID II; and (ii) eligible for distribution through all distribution channels as are permitted by MiFID II (the "Target Market Assessment").

Notwithstanding the Target Market Assessment, "distributors" (for the purposes of the MiFID II Product Governance Requirements) should note that: the price of ADSs may decline and investors could lose all or part of their investment; the ADSs offer no guaranteed income and no capital protection; and an investment in ADSs is compatible only with investors who do not need a guaranteed income or capital protection, who (either alone or in conjunction with an appropriate financial or other adviser) are capable of evaluating the merits and risks of such an investment and who have sufficient resources to be able to bear any losses that may result therefrom. The Target Market Assessment is without prejudice to the requirements of any contractual, legal or regulatory selling restrictions in relation to the Offering.

For the avoidance of doubt, the Target Market Assessment does not constitute: (a) an assessment of suitability or appropriateness for the purposes of MiFID II; or (b) a recommendation to any investor or group of investors to invest in, or purchase, or take any other action whatsoever with respect to ADSs.

On November 23, 2018 Kancera AB (publ) reported that unique blockers of the Fractal System have been patented. From the patented blockers, Kancera intends to further develop a new drug candidate, which is estimated to take about 12 months (Press release, Kancera, NOV 23, 2018, View Source;releaseID=1593528 [SID1234531596]).

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• Kancera provided an operational update for the Fractalkine project as follows •Research results show that blockade of the Fractal system can be expected to protect both heart and kidney function in inflammation

• Clinical studies focusing on cardiovascular inflammation of myocardial infarction are expected to start in the first half of 2019

• Kancera’s research in cancer continues with a focus on lymphoma (biomarker study scheduled for completion in the fourth quarter of 2018) and ovarian cancer (EU-funded preclinical research), while the Vinnova-funded study of neuroblastoma has been reported and completed.

• Kancera announced that the company is reorganizing to focus on Fractalkine projects.

• Kancera announced that results of cooperation with Karolinska Institutet were published in the journal Nature Communications under the title "Targeting PFKFB3 radiosensitizes cancer cells and suppresses homologous recombination".

SIGNIFICANT EVENTS AFTER THE END OF THE THIRD QUARTER

• Kancera has reported that the company has registered a patent application (EP18205819.8) for a third series of novel substances that selectively inhibit the enzyme HDAC6 for the treatment of inflammation and cancer

.• In the framework of EU research program Horizon 2020, Kancera has been awarded a research grant of a total of approximately 250,000 Euro for funding a doctoral student in order to explore the role of the Fractalkine system in the development of pain in arthritis.

• Kancera has announced that terms have been developed for shareholders’ investment decisions in the company by Global Corporate Finance Inc. (GCF), New York. The investment, which covers a maximum of SEK 60 million over 30 months, is intended to take place in tranches (rounds) of which Kancera determines the timing.

• Kancera hereby provides a status update for the Fractalkine project:

New effect study in animal model of myocardial infarction showed that lower doses than expected give a significant cardiovascular effectssww
Preliminary results from the GLP toxicology study showed that the calculated effective dose of KAND567 was safe (final results from this study are expected in January).
Phase 0 study in lymphoma patients will be completed in December and the analyzes are expected to be completed in January 2019
STATEMENT FROM THE CEO

In the Fractalkine project, we have strengthened our patent protection against competition and conducted a series of studies aimed at both preparing for Phase IIa cardiovascular patients and evaluating the possibility of an effect on blood cancer (lymphoma).

The protection has been further strengthened after our patenting of a new series of Fractalkine blockers that allow for the development of several independent products within the project.

Prior to the cardiac study in humans, the choice of intravenous dosing with KAND567 has been evaluated for efficacy and safety. The effect has been evaluated in a disease model of myocardial infarction and safety in a toxicological GLP study. The efficacy study showed that lower doses than expected provide a significant heart-protecting effect. Preliminary results from the toxicology study provide evidence pointing towards the safety of the calculated effective dose of KAND567 (final results from this study are expected in January). The next step in the preparation is the start of manufacturing KAND567 for intravenous treatment in clinical trials, which will occur within a few weeks. This means that the application for authorization for implementation of Fas Ib is planned to be submitted to the Medical Products Agency during the first quarter and completed during the second quarter of 2019 and that the corresponding Phase IIa application is scheduled for submission during the second quarter.

In May, we started a biomarker study (Phase 0) in lymphoma patients together with partners at Karolinska Hospital and the Institute. The aim of the study is to investigate whether there are groups of lymphoma patients in which the Fractalkine system is activated and possibly pervasive in the disease. Recruitment of patients has proceeded at a high rate in parallel with immunological analysis of blood samples. This means that sample collection can be completed in December and be analyzed in January. The results will determine whether continued evaluation of the role of the Fractalkine system in cancer continues toward lymphoma or focuses on the EU-funded solid tumor research project.

Interest in how Fractalkine affects various diseases in humans increases with continuous research progress, in the field of dementia and nerve pain amongst others. This has resulted in an invitation to participate in a further EU-funded research project with European research groups and pharmaceutical companies with the above focus. Kancera has participated in the application for this now approved EU project, starting in the spring of 2019.

The fact that Kancera is developing in the right direction we believe also forms the basis for the interest from the family-owned company GC Finance to invest in the company. The intention is to use capital injection from GC F (to be decided by an extraordinary general meeting) to expand to evaluate additional indications for the portfolio of Fractalkine blockers, expand clinical studies and for operations.