On December 18, 2019 The Jackson Laboratory (JAX) reported that it has received $2.5 million from The Mark Foundation for Cancer Research to study in mice the influence of host genetics on response to immunotherapy (Press release, The Mark Foundation For Cancer Research, DEC 18, 2019, View Source [SID1234553264]). The goal of this project is to generate insights that will empower future decisions about the best treatments for cancer patients based on their genetic backgrounds.

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Immunotherapy, which uses the body’s own immune system to fight cancer, is one of the most promising approaches to cancer treatment today, and expanding its effectiveness to a wider population of patients is a high priority for researchers across the globe.

The project, "Dissecting the Genetic Control of Response to Immune Checkpoint Inhibitors in Cancer," has major implications for how oncologists may be able to predict whether their patients will respond positively to immunotherapy before prescribing a treatment regimen.

A unique opportunity

Immunotherapy has resulted in some remarkable outcomes for patients whose cancers would have otherwise been fatal. Nonetheless, the overall efficacy rates for this class of treatment are not high, and many patients experience serious or even life-threatening side effects. The determination of which patients will respond well to immunotherapy is still uncertain. Probing factors that may influence response to immunotherapy, such as the personal genetics of each individual, tumor characteristics, and the cross-talk among these profiles is a critical step toward designing immune therapies that will have broader impact.

JAX President and CEO Edison T. Liu, MD and Associate Professor Laura Reinholdt, PhD, co-principal investigators of the study, will use genetically diverse JAX mouse models to untangle the relationship between genetics and response to immunotherapies.

"This research may one day allow doctors to use genetic sequencing to predict patient response to immunotherapy, as well as help scientists develop more effective anti-cancer drugs that fight tumors by activating an immune response," said Liu. "We are so grateful to The Mark Foundation for enabling this extraordinary opportunity, which we hope will have a significant impact on patients and the field of immunotherapy," said Liu.

The mission of The Mark Foundation for Cancer Research is to support scientists tackling the toughest challenges in cancer research. Multi-disciplinary groups such as the JAX team, which brings together experts in genetics, bioinformatics, mouse models, and immunology, are well positioned to take on these challenges. By funding this type of collaborative project, The Mark Foundation ensures that the right expertise is brought to bear on a substantial unmet need, ultimately accelerating cancer research to the benefit of patients.

"This project addresses critical limitations in cancer research. First, most mouse models for studying therapeutic response lack the genetic diversity that exists in the human population, often leading to disappointment when treatments that show promise in these models are deployed broadly in patients. Second, the biology of how genetics impact tumor response is not well understood due to a lack of adequate experimental systems for uncovering new knowledge", said Michele Cleary, PhD, CEO of The Mark Foundation. "Solving both of these issues requires the type of complex and nuanced work in mouse genetics for which JAX is world-renowned."

The power of genetic diversity

The grant to the Jackson Laboratory research team, which also includes Assistant Professor Chih-Hao "Lucas" Chang, PhD, Associate Research Scientist John P. Graham, PhD, Professor Karolina Palucka, MD, PhD, and Research Scientist Daniel Skelly, PhD, will examine four different tumor lines: a melanoma tumor, a triple-negative breast cancer tumor, and two types of colon cancer tumors. The tumor types were chosen to represent a wide range of responses to immunotherapy. For example, melanoma tumors tend to respond quite well to immunotherapy, whereas triple-negative breast cancer tumors typically do not.

The scientists will use JAX’s genetically diverse mouse strains in their studies, which will allow them to identify the genetic differences that underlie the variation in response to immunotherapy. Such an approach is inordinately difficult to achieve in human clinical trials.

"The increasing adoption of genetically diverse mice in biomedical research is really a paradigm shift driven by new technologies and biological resources, and by the recognition that an inbred mouse strain only represents one genome," said Reinholdt.

"This project is providing a unique opportunity to harness natural genetic variation in laboratory mice to more accurately model the biological complexity of cancer treatment response. The power of these genetically diverse mouse strains is that they facilitate genetic discovery and they provide tractable in vivo systems for dissecting molecular pathways, which are essential for the identification of biomarkers and potentially new therapeutic targets."

The research team plans to map the genetic differences found in the mice to specific genetic variants in humans. Ultimately, they hope that doctors will be able to test and determine a given individual’s likely response to immunotherapy to help guide the selection of a treatment regimen.

On December 18, 2019 The lOR Institute of Oncology Research reported that new grant awarded to the Tumor Biology and Experimental Therapeutics Group (Press release, The lOR Institute of Oncology Research, DEC 18, 2019, View Source [SID1234553216]).

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The project Nanoparticle-based delivery and combinatorial therapies for cancer funded by SNSF in the context of the European COST action on Cancer Nanomedicine (CA17140) aims at developing new nanoparticle-based medicine for precision therapy of advanced prostate cancer.

The project involves scientific partners in Turkey (Prof. Rana Sanyal, Department of Chemistry, Center for Life Sciences and Technologies Bogazici University, Istanbul, View Source) and in France (Maria Eugenia Riveiro, CSO Early Drug Development Group, www.e2dg.com).

On December 18, 2019 Vaccitech Ltd reported that its strategic collaboration with the Ludwig Institute for Cancer Research (Ludwig), Vaccitech Oncology Limited (VOLT), has entered into a clinical partnership with Cancer Research UK to develop VOLT’s VTP-600 immunotherapy as a treatment option for patients with non-small cell lung cancer (NSCLC) (Press release, Vaccitech, DEC 18, 2019, View Source [SID1234553211]).

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VTP-600 is a cancer immunotherapy comprised of Vaccitech’s proprietary heterologous prime-boost T cell induction platform; ChAdOx1 and Modified Vaccinia Ankara (MVA). The two viral vectors are engineered to express the tumour-associated antigens MAGE-A3 and NY-ESO-1, previously discovered and clinically validated by Ludwig. MAGE-A3 and NY-ESO-1 are aberrantly expressed by tumour cells and elicit strong immune responses. The VTP-600 therapeutic vaccine is administered intramuscularly and designed to stimulate the immune system to produce sustained cytotoxic CD8+ T cells specific for cancers that highly express the antigens, which include NSCLC. To maximise therapeutic benefit, VTP-600 can be administered selectively to patients whose tumours express MAGE-A3 alone, and those which also express NY-ESO-1. This novel design may help boost an optimal, highly specific, anti-tumour immune response to destroy cancer cells.

Cancer Research UK’s Centre for Drug Development (CDD) will sponsor and manage a Phase I/IIa clinical trial of VTP-600 in combination with current standard of care and first-line treatment (chemotherapy and anti-PD-1) in approximately 80 patients with NSCLC. The trial is anticipated to begin in Q4 2020 across multiple clinical sites in the UK. VOLT holds an option to licence the results of the trial in order to undertake further clinical development and commercialisation of VTP-600.

Vaccitech’s CEO, Bill Enright, said: "We are delighted to enter into a clinical development partnership with two of the world’s most prestigious cancer research institutions. We believe that this partnership is an important validation of our prime boost platform’s utility in oncology as well as infectious disease."

Jonathan Skipper, Executive Vice President for Technology Development, Ludwig Institute for Cancer Research, commented, "Previous clinical trials of experimental cancer vaccines targeting MAGE and NY-ESO antigens have demonstrated that these antigens are highly specific to cancer and capable of eliciting strong immune responses. We believe that Vaccitech’s highly effective T cell induction platform should provide a potent immunotherapeutic that, in combination with checkpoint blockade, is capable of inducing sustained levels of cancer antigen-specific CD8+ T cells and the desired therapeutic effect in patients."

Dr Nigel Blackburn, Cancer Research UK’s director of drug development, said: "This partnership with VOLT is an important step to help accelerate this promising immunotherapy and could help more people survive lung cancer, which remains very hard to treat. This novel approach using a modified adenovirus to prime the immune system and alert it to the presence of cancer cells could offer a completely new way to treat the disease."

On December 18, 2019 Selecta Biosciences, Inc. (the "Company") reported that it has entered into a Securities Purchase Agreement (the "Purchase Agreement") with the purchasers named therein (the "Investors"), including certain members of the board of directors of the company (Filing, 8-K, Selecta Biosciences, DEC 18, 2019, View Source [SID1234552606]).

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Pursuant to the Purchase Agreement, the Company agreed to sell (i) an aggregate of 37,634,883 shares of its common stock (the "Shares"), par value $0.0001 per share (the "Common Stock"), at a purchase price equal to $1.46 per share, which was equal to the most recent consolidated closing bid price on the Nasdaq Global Market on December 18, 2019, (ii) warrants to purchase an aggregate of 22,988,501 shares of Common Stock (the "Common Warrants"), at a purchase price equal to at $0.125 per share underlying each Common Warrant , and (iii) pre-funded warrants to purchase an aggregate of 8,342,128 shares of Common Stock (the "Pre-Funded Warrants" and, together with the Common Warrants, the "Warrants"), at a purchase price equal to at $1.46 per share underlying each Pre-Funded Warrant, to the Investors for aggregate gross proceeds of approximately $70.0 million (collectively, the "Offering"). The closing of the Offering occurred on December 23, 2019.

Each Common Warrant has an exercise price per share of Common Stock equal to $1.46 per share. Each Pre-Funded Warrant has an exercise price per share of Common Stock equal to $0.0001 per share. The exercise price and the number of shares of Common Stock issuable upon exercise of each Warrant is subject to appropriate adjustments in the event of certain stock dividends and distributions, stock splits, stock combinations, reclassifications or similar events affecting the Common Stock. In addition, in certain circumstances, upon a fundamental transaction, a holder of Warrants will be entitled to receive, upon exercise of the Warrants, the kind and amount of securities, cash or other property that such holder would have received had they exercised the Warrants immediately prior to the fundamental transaction; provided, however, that in the event of a fundamental transaction where the consideration consists solely of cash, solely of marketable securities or a combination thereof, each Warrant will be deemed to be exercised in full in a cashless exercise effective immediately prior to and contingent upon the consummation of such fundamental transaction. Each Warrant is exercisable from the date of issuance and has a term of five years.

The Company may not effect the exercise of certain Common Warrants, and the applicable holder will not be entitled to exercise any portion of any such Common Warrant, which, upon giving effect to such exercise, would cause the aggregate number of shares of Common Stock beneficially owned by the holder of the Common Warrant (together with its affiliates) to exceed 4.999% or 9.999%, as applicable, of the number of shares of Common Stock outstanding immediately after giving effect to the exercise, as such percentage ownership is determined in accordance with the terms of the Common Warrants. However, any holder may increase or decrease such percentage to any other percentage not in excess of 19.99% upon at least 61 days’ prior notice from the holder to the Company subject to the terms of the Common Warrants.

On December 23, 2019, in connection with the Purchase Agreement, the Company entered into a Registration Rights Agreement (the "Registration Rights Agreement") with the Investors. Pursuant to the Registration Rights Agreement, the Company agreed to prepare and file a registration statement with the Securities and Exchange Commission (the "SEC") within 45 days after the closing of the Offering for purposes of registering the resale of the Shares, shares of Common Stock issuable upon exercise of the Warrants, and any shares of Common Stock issued as a dividend or other distribution with respect to the Shares or shares of Common Stock issuable upon exercise of the Warrants. The Company agreed to use its reasonable best efforts to cause this registration statement to be declared effective by the SEC within 90 days after the closing of the Offering (or within 120 days if the SEC reviews the registration statement).

The Company has also agreed, among other things, to indemnify the Investors, their officers, directors, members, employees and agents, successors and assigns under the registration statement from certain liabilities and to pay all fees and expenses (excluding any legal fees of the selling holder(s), and any underwriting discounts and selling commissions) incident to the Company’s obligations under the Registration Rights Agreement

The Offering is exempt from registration pursuant to Section 4(a)(2) of the Securities Act and Regulation D promulgated thereunder, as a transaction by an issuer not involving a public offering. The Investors have acquired the securities for investment only and not with a view to or for sale in connection with any distribution thereof, and appropriate legends have been affixed to the securities issued in this transaction.

On December 18, 2019 Medivir AB (Nasdaq Stockholm: MVIR) reported that the first patient has been enrolled and is being dosed with remetinostat gel 1% in an investigator-initiated phase II clinical study in patients with squamous cell carcinoma (SCC) (Press release, Medivir, DEC 18, 2019, View Source [SID1234552489]). This clinical study is conducted at the Stanford University School of Medicine in California, USA under the leadership of the principal investigator, Dr Kavita Sarin. Medivir is providing remetinostat drug supply for this study, and has full access to, and the rights to use, all clinical data after the study is complete.

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The primary objective of the study is to assess the effects of topical remetinostat on biopsy-proven SCC and SCC in situ tumors and could establish that remetinostat has the potential for use in other skin-associated cancers in addition to MF-CTCL. Further details of the study can be found at www.clinicaltrials.gov, reference number NCT03875859.

"This study together with the ongoing study in basal cell carcinoma explore the potential of remetinostat to be used in multiple conditions beyond cutaneous T-cell lymphoma," said Dr. Uli Hacksell, CEO of Medivir. He continues, "We are eagerly looking forward to the results from these studies."

About squamous cell carcinoma

Squamous cell carcinoma (SCC) is the second most common form of cancer in humans occurring in the skin. Surgery is standard of care and there are currently no marketed products approved for the treatment of SCC. There is a need for efficacious and safe treatments when surgery is impractical, e.g. multiple lesions and/or difficult treatment sites.

About remetinostat

Remetinostat is a histone deacetylase (HDAC) inhibitor. The unique design of remetinostat enables topical application, making it active only in the skin. As soon as it reaches the blood stream, it is degraded, avoiding the side effects associated with orally administered HDAC inhibitors. The effect of remetinostat on basal cell carcinoma is investigated in an ongoing phase II study.