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Moleculin Presents Clinical Trial Data Demonstrating a Median Reduction of 56% in Skin Cancer Lesions

On February 18, 2020 Moleculin Biotech, Inc., (Nasdaq: MBRX) (Moleculin or the Company), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors, reported the final data from its CTCL clinical trial of WP1220 for the treatment of cutaneous T-cell lymphoma (CTCL), which was published and presented by Dr. M. Sokolowska-Wojdylo in conjunction with the 4th Annual World Congress of Cutaneous Lymphomas in Barcelona, Spain on February 13, 2020 (Press release, Moleculin, FEB 18, 2020, View Source [SID1234554415]). The final results supported the safety of topical WP1220 and demonstrated a median improvement in the Composite Assessment of Index Lesion Severity (CAILS) score of 56% in treated (index) lesions for patients completing the study.

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Moleculin Biotech, Inc. is a clinical stage pharmaceutical company focused on the development of a broad portfolio of oncology drug candidates for the treatment of highly resistant tumors. (PRNewsfoto/Moleculin Biotech, Inc.)

"WP1220 is part of our p-STAT3 inhibitor drug portfolio. Late last year, we announced the preliminary results of this proof of concept Phase 1 trial. For years, p-STAT3 (the activated form of STAT3) has been considered an ‘undruggable’ target because of the difficulty of reaching and affecting this cell-signaling protein," commented Walter Klemp, Moleculin’s Chairman and CEO. "We are pleased to conclude this trial and demonstrate a therapeutic effect from a p-STAT3 inhibitor which could be considered a significant breakthrough in cancer research."

Introduction & Objectives: Mycosis Fungoides or MF, the most common variant of CTCL, is a disease with symptomatic, disfiguring skin lesions. STAT3, an oncogenic transcription factor, has been identified as a critical regulator of MF, whereby the activation of STAT3 through phosphorylation (p-STAT3) has been linked to tumor proliferation and suppression of immune responses. WP1220, a synthetic compound, potently inhibits the activity of p-STAT3 and the growth of CTCL cell lines. This Phase 1b study was designed to demonstrate the safety and efficacy of WP1220 after topical treatment of MF.

Results: Of 5 subjects enrolled, 9 lesions were assessed according to the CAILS scoring system. The only adverse event (AE) was mild contact dermatitis in one subject felt not to be related to the drug. 4 of the 5 subjects had significant improvement in CAILS scores on index lesions, with a median reduction of 56% (range 25%-94%). Improvement was noted within 7 days of treatment initiation and maintained 1 month after discontinuation. Independent dermatologic review based on photographic documentation was conducted and corroborated these findings.

Conclusions: WP1220, an inhibitor of p-STAT3, shows safety and significant efficacy in MF after topical treatment. We believe this is the first demonstration in humans that inhibition of p-STAT3 with topical therapy has efficacy in CTCL. A larger Phase 2 study is now being planned.

Karyopharm to Participate at 9th Annual SVB Leerink Global Healthcare Conference

On February 18, 2020 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), an oncology-focused pharmaceutical company, reported that Michael Kauffman, MD, PhD, Chief Executive Officer, reported that it will participate in a fireside chat at the 9th Annual SVB Leerink Global Healthcare Conference on Tuesday, February 25, 2020 at 11:30 a.m. ET in NYC (Press release, Karyopharm, FEB 18, 2020, View Source [SID1234554414]).

A live webcast of the fireside chat can be accessed on the "Events & Presentations" in the Investor section of the Company’s website, View Source A replay of the webcast will be archived on the Company’s website for 90 days following the fireside chat.

HOOKIPA Pharma to Present at SVB Leerink 9th Annual Global Healthcare Conference

On February 18, 2020 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics targeting infectious diseases and cancers based on its proprietary arenavirus platform, reported that HOOKIPA’s management team will present and host one-on-one meetings at the SVB Leerink 9th Annual Global Healthcare Conference, taking place February 25 – 27, 2020 in New York (Press release, Hookipa Pharma, FEB 18, 2020, View Source [SID1234554413]):

Presentation: Tuesday, February 25, 2020 at 10:00 a.m. ET, Lotte New York Palace, Room Kennedy I
A live audio webcast of the presentation held at the SVB Leerink Healthcare Conference will be available within the Investors & Media section of HOOKIPA’s website at View Source An archived replay will be accessible for 30 days following the event.

Analysis of RNA sequences and modifications by mass spectrometry published in Nature Communications

On February 17, 2020 STORM Therapeutics, the biotechnology company focused on the discovery of small molecule therapies modulating RNA epigenetics, reported that it has published a scientific paper in the peer reviewed journal Nature Communications (Press release, STORM Therapeutics, FEB 17, 2020, View Source [SID1234561052]).

The paper is entitled: ‘A computational platform for high-throughput analysis of RNA sequences and modifications by mass spectrometry’ and showcases breakthrough analysis of RNA sequences and modification using STORM’s mass spectrometry. The work, which was carried out in collaboration with the University of Cambridge, University of Tübingen, Germany, and the University of Pennsylvania, US describes a novel algorithm that allows the quantitative analysis of RNA modifications in the context of their RNA sequence using mass spectrometry. See link to paper: View Source, DOI: 10.1038/s41467-020-14665-7

Dr Oliver Rausch, CSO of STORM Therapeutics, said: "STORM is a pioneer in RNA epigenetics and we are very pleased to see the publication of this paper in Nature Communications, validating the use of STORM’s algorithm, created to extend the use of mass spectrometric data to RNA epigenetics in order to boost the discovery power of teams investigating the role of RNA modifications in disease."

The study describes a novel computational algorithm named Nucleic Acid Search Engine (NASE) that allows sequencing of RNA molecules by mass spectrometry including positional identification of chemical modifications on the RNA molecules. In particular, the algorithm enables the mapping of RNA fragmentation patterns obtained by mass spectrometry to RNA sequence databases, thus identifying the originating RNA molecules

Dr Hendrik Weisser, Principal Scientist at STORM and senior author on the paper commented: "I am delighted to see the publication of this new algorithm in a world leading journal. Our algorithm represents a novel approach for characterizing modifications on many different RNA species. Unbiased quantitative analysis of RNA modification on specific RNAs is one of the key challenges in the novel field of RNA Epigenetics and resources like NASE are critical to rapid innovation and advancement in the discovery of RNA modifications. By making this approach available publicly we are providing a new tool to the community that will accelerate overall progress in the field."

Targeting turncoat immune cells to treat cancer

On February 17, 2020 A Ludwig Cancer Research reported that study has identified a mechanism by which regulatory T cells, which suppress immune responses, adapt their metabolism to thrive in the harsh microenvironment of the tumor (Press release, Ludwig Institute For Cancer Research, FEB 17, 2020, View Source [SID1234554428]). This mechanism, the study finds, is exclusively engaged by regulatory T cells (Tregs) that reside in tumors and could be disrupted to selectively target such Tregs and boost the effects of cancer immunotherapy.

"It has long been known that the Tregs found in tumors protect cancer cells from immune attack, so countering Tregs would be an important strategy for cancer immunotherapy," says Ping-Chih Ho, associate member of the Lausanne Branch of the Ludwig Institute for Cancer Research, who led the study. "But a major hurdle to such interventions is that the systemic suppression of Treg activity can cause severe autoimmune reactions. We have discovered a potential approach to overcoming that problem, one that selectively targets Tregs in tumors and could therefore prevent such adverse effects."

Tregs play a critical role in healthy tissues, where they prevent autoimmune disease and aid wound-healing. But, when recruited into tumors, Tregs also thwart anti-cancer immune responses—and immunotherapy. The current study, published in Nature Immunology, identifies a protein that drives the metabolic adaptations of intratumoral Tregs. The researchers show in a mouse model of melanoma that targeting that protein with an antibody significantly boosts the efficacy of immunotherapy without causing autoimmune side effects.

The cores of tumors are often acidic and starved of oxygen and vital nutrients, which forces resident cells to adapt their metabolism to survive. Ho and graduate student Haiping Wang suspected those adaptations might also reveal vulnerabilities unique to intratumoral Tregs. To find those vulnerabilities, they analyzed a dataset of Treg gene expression in breast tumors and blood compiled a few years ago by the laboratory of Ludwig MSK Director Alexander Rudensky.

They found that those and other intratumoral Tregs expressed high levels of genes involved in lipid uptake and metabolism—particularly CD36, a receptor involved in lipid import. An analysis of Tregs from human melanoma patients conducted by Ludwig Memorial Sloan Kettering (MSK) researchers Taha Merghoub and Jedd Wolchok yielded similar results.

To explore the role of CD36 in intratumoral Tregs, the researchers generated mice that lacked the CD36 gene only in their Treg cells and engrafted them with melanoma. "We found that the tumor burden was reduced in CD36-deficient mice," says Wang, "and the number and functionality of Tregs declined only within tumors, not in the other, healthy tissues of the mice."

CD36 deficiency induced in intratumoral Tregs a form of cell suicide known as apoptosis that was driven by a decline in the health and number of mitochondria—the power generators of cells. Further study revealed that CD36 fuels the activity of PPARβ, a protein essential to the genesis and function of mitochondria.

Treating mice bearing melanoma tumors with an antibody to CD36 resulted in a decline of intratumoral Tregs that was not seen in genetically identical control mice. When this antibody was combined with an immunotherapy known as PD-1 blockade, which stimulates a T cell attack on cancer cells, tumor growth slowed significantly, prolonging the survival of the mice.

"By targeting CD36 with an antibody, we don’t just create trouble for intratumoral Tregs, we also create trouble for the tumor’s ability to maintain an immunosuppressive microenvironment and hamper immunotherapy," says Ho.

Ho’s lab is now working to translate these findings into a potential cancer therapy while exploring how CD36-targeting might be combined with other interventions to more extensively disable Tregs selectively within tumors. They are also exploring which other types of solid tumors harbor Tregs that are dependent on CD36 for survival.

This study was supported by Ludwig Cancer Research, the Swiss Cancer Foundation, the Swiss Institute for Experimental Cancer Research, the European Research Council, the Cancer Research Institute, the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), the US National Institutes of Health, the Research Foundation—Flanders, the Swiss Cancer Research Foundation, Swim Across America, the Parker Institute for Cancer Immunotherapy and the Breast Cancer Research Foundation.