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AACR Meeting Brief: H3 Biomedicine, Checkmate, Deciphera and More

The following is a roundup of presentations and findings from multiple companies participating in the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) in Chicago (Press release, BioSpace, APR 17, 2018, View Source [SID1234525435]).

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H3 Biomedicine Inc. – Working with Foundation Medicine, H3 Biomedicine unveiled novel findings from a comprehensive genomic analysis of 6,235 patients across 15 hematologic malignancies at AACR (Free AACR Whitepaper). The results include the first-ever observance of recurrent RNA splicing factor mutations in non-Hodgkin’s lymphoma and multiple myeloma, the company said. In its announcement, H3 said the findings demonstrate the "continued emergence of splicing factor mutations as a hallmark of dozens of hematologic and solid tumor cancers, their potential role in tumor formation and growth, and, thus, the opportunity to advance a new class of therapies."
Checkmate Pharmaceuticals – Data from an ongoing Phase Ib trial shows that Checkmate’s Toll-like receptor 9 CMP-001 combined with Merck’s Keytruda demonstrated "deep and durable clinical responses" in patients with advanced melanoma who are resistant to prior anti-PD-1 checkpoint inhibition. Data shows that the combination therapy brought about the systemic regression of "non-injected cutaneous, nodal, hepatic, and splenic metastases in patients who had progressed on a median of two prior therapies."

Deciphera Pharmaceuticals – Cambridge, Mass.-based Deciphera unveiled preclinical data that showed DCC-2618, a KIT and PDGFRα kinase switch control inhibitor, inhibited primary and secondary KIT mutations and primary PDGFRα mutations in gastrointestinal stromal tumors (GIST) and systemic mastocytosis. Deciphera said in comparison to other approved compounds, DCC-2618 demonstrated the "broadest profile of inhibition" in the preclinical study.
NewLink Genetics – In a poster presentation at AACR (Free AACR Whitepaper) NewLink showed that indoximod has a unique method of action in modulating AhR-driven transcription of genes. The company said the different mechanism of action may contribute to antitumor immune responses in the IDO pathway, as well as independent of that IDO pathway. The company said indoximod regulates the "differentiation of helper T cells toward an immuno-stimulatory helper function and downregulates genes that control the differentiation of T cells into immuno-suppressive regulatory T cells in an AhR dependent manner."

Torque – Preclinical data presented by Torque at AACR (Free AACR Whitepaper) shows the company’s Deep-Primed IL-15 and Deep-Primed IL-12 cellular therapy programs demonstrated superior activity compared to systemically administered IL-15 and IL-12. Torque’s Deep-Primed therapeutics use material engineering to anchor immune-stimulatory drugs directly to the surface of multi-targeted, antigen-primed T cells. This allows the activation of the adaptive and innate immune system with pharmacologic control in the tumor microenvironment, according to the company.
Laboratory for Advanced Medicine – With a push to advance early cancer diagnostics California-based Laboratory for Advanced Medicine revealed data that demonstrates the utility of circulating tumor DNA (ctDNA) methylation markers in the diagnosis, surveillance and prognosis of Hepatocellular Carcinoma. In an AACR (Free AACR Whitepaper) presentation, the company said the findings support that "ctDNA carrying cancer-specific genetic and epigenetic aberrations may enable a non-invasive liquid biopsy for the diagnosis and monitoring of cancer."
PharmaMar – New data presented by PharmaMar at AACR (Free AACR Whitepaper) showed that plitidepsin interacts with and inhibits PKR on the eEF1A2 enzyme. Plitidepsin inhibits this interaction obtaining the induction of cell death, the company announced. PharmaMar said through the bonding to eEF1A2, plitidepsin annuls the oncogenic properties of its target.

Sanofi to Sell its Generic Division to Advent for $2.4 Billion

On April 17, 2018 Paris-based Sanofi has reported that agreed to sell its generics division, Zentiva, to Advent International (Press release, BioSpace, APR 17, 2018, View Source [SID1234525434]).

The deal is expected to wrap by the end of this year. Advent, a private equity firm, will acquire the company for 1.9 billion euros, or about $2.4 billion (U.S.).

Reuters notes, "Sanofi has been reshaping its business in recent months, spending more than $16 billion to buy biotech company Ablynx and U.S. hemophilia specialist Bioverativ, but also selling off some assets. This week, it sold some brands to Charterhouse Capital Partners’ Cooper-Vemedia drugs manufacturing arm for 158 million euros."
"Zentiva is a robust business with a highly talented workforce and we believe it has demonstrated its potential for growth," said Olivier Brandicourt, Sanofi’s chief executive officer, in a statement. "Following a comprehensive review of strategic options for our generics unit in Europe, we have determined that transferring this business to Advent is the best option to ensure its long-term success."

This specific sale planning began in October 2017. However, it has been up for grabs for some time, including plans made in November 2015. Sanofi had spent much of the year prior to restructuring Zentiva as a stand-alone company in order to be sold. In February, Reuters reported that the short list of potential buyers included Carlyle, BC Partners and a consortium of Blackstone and Nordic Capital. Two pharma companies were also on the list, Brazilian company EMS and India’s Torrent Pharma.

Since at least 2015, Sanofi has been restructuring as part of a new strategy. This included spinning off its animal health unit, Merial, and the European generics business. In mid-December 2015, Sanofi and Germany-based Boehringer Ingelheim GmbH announced plans to exchange business units. The intention was for Sanofi to swap Merial with Boehringer Ingelheim’s consumer healthcare business. Boehringer Ingelheim’s consumer healthcare business in China was not part of that deal.

The sale of Zentiva was delayed partly to decide which parts of the division to sell. Some of the rationale behind the sale is related to distributor consolidation. Distributors buy generic versions to sell to patients, and once merged, they have more leverage to negotiate lower prices. For the last three years, there has been significant consolidation of generics distributors worldwide.

Zentiva does business in 50 markets, particularly in Eastern Europe—the Czech Republic, Slovakia and Romania. Its portfolio of generic drugs includes products for cardiovascular indications and gastrointestinal drugs, in addition to versions of ibuprofen and leflunomide.
Jerome Schupp, fund manager at Geneva-based Prime Partners, which currently does not hold Sanofi shares, told Reuters, "The sale price is decent, but nothing that extraordinary. Sanofi will probably re-invest the proceeds in looking to make pharma or biotech acquisitions. They are looking to strengthen their pipeline, which is a bit weak at the moment."

The news follows yesterday’s announcement that Shire was selling its oncology business to France’s Servier for $2.4 billion. And Japan’s Takeda Pharmaceuticals announced several weeks ago its interest in buying Shire. Under UK acquisition laws, Takeda has until April 25 to announce an official bid. Shire’s market value is about $47 billion.
Pfizer has also been trying to unload its consumer healthcare business. Most recently, GlaxoSmithKline walked away from the deal, as had Reckitt Benckiser Group. The Pfizer business unit is valued at about $15 to $20 billion.

AACR Meeting Brief: Compugen, Bayer, Tarveda, Alligator and Others

Now in its fourth day, the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018 held in Chicago, has had plenty of news, much of it preclinical or early-clinical data (Press release, BioSpace, APR 17, 2018, View Source [SID1234525433]). Here’s a roundup of some of the top stories.

Compugen and Bayer AG presented efficacy data of BAY 1905254 in cancer immunotherapy. The compound is a first-in-class antibody candidate that targets ILDR2, a novel immune checkpoint discovered by Israeli company Compugen. Bayer expects to move it into human trials sometime this year.

"ILDR2 is a completely new immune checkpoint that we discovered through our computational discovery capabilities," said Anat Cohen-Dayag, Compugen’s president and chief executive officer, in a statement. "This immune checkpoint, together with the discovery of TIGIT and PVRIG, clearly demonstrate the power and value of Compugen’s predictive discovery capabilities in the discovery of new drug targets and pathways, enabling the development of first-in-class product opportunities."
Sierra Oncology, based in Vancouver, presented data for its Checkpoint kinase 1 (Chk1) inhibitor SRA737, as a monotherapy and in combination with a poly ADP-ribose polymerase inhibitor (PARPi) like Tesaro’s Zejula (niraparib). It is being evaluated in an ongoing Phase I/II trial in replication stress-driven cancer. It also plans to initiate a Phase Ib/II trial in metastatic castration-resistant prostate cancer in the fourth quarter.

Tarveda Therapeutics, headquartered in Watertown, Massachusetts, presented preclinical data related to PEN-866. PEN-866 is a miniature drug conjugate to treat patients with solid tumor types that are sensitive to topoisomerase 1 inhibitors like SN-38, which is PEN-866’s payload. It is being evaluated in models of ovarian cancer, lung cancer and colorectal cancer. PEN-866 utilizes the activation of Heat Shock Protein 90 (HSP90) in tumors in order to accumulate and release its payload.

Lycera Corp., located in New York and Ann Arbor, Michigan, released clinical findings from the Phase I part of its Phase I/IIa ARGON trial of the company’s novel immuno-oncology candidate, LYC-55716. LYC-55716 is a first-in-class oral, selective retinoic acid-related orphan receptor-gamma (RORgamma) agonist that reprograms the immune system in solid tumor patients. In the 32 patients enrolled in six dosing cohorts, the drug was well tolerated and no dose-limiting toxicities were seen.
"The promising safety results and early signals of efficacy with LYC-55716 as a monotherapy are very encouraging," said Judy Wang, associate director of Drug Development, Florida Cancer Specialists and Sarah Cannon Research Institute, in a statement. "We are very pleased to be participating in the development of this novel immunotherapeutic, and are actively enrolling patients with advanced solid tumor cancers in the Phase IIa portion of the study."

Lund, Sweden’s Alligator Bioscience presented preclinical data on its immune activating antibody ATOR-1015. ATOR-1015 is a first-in-class bispecific tumor-directed antibody that targets CTLA-4 and OX40. The data shows the compound localizes to the tumor and activates the immune system in the surrounding area, which confirms the drug’s mechanism of action. It is designed mostly for a combo-therapy with PD-1 blocking antibody.
"The results presented in Chicago confirm that our CTLA-4 bispecific antibody ATOR-1015 selectively activates the immune system in the tumor area," said Per Norlen, Alligator’s chief executive officer, in a statement. "This offers great potential for an improved benefit/risk profile for cancer patients. We are more and more excited about the significant prospects for this unique compound, particularly in combination with PD-1 blockers, and are looking forward to initiate clinical development later in the year."
CBT Pharmaceuticals, based in Pleasonton, California, a U.S. and China-based biopharmaceutical company, presented preclinical in-vivo data and animal safety pharmacology studies of CBT-102. This compound is a multi-targeted kinase inhibitor that targets VEGFR, PDGFR, MAPK, B-RAF, C-RAF, C-KIT and CSF1R. It showed tumor regression in 52 patient-derived xenograft models, including non-small cell lung, colorectal, gastric, and hepatocellular carcinoma.
"We are highly encouraged by the preclinical safety and efficacy data of CBT-102," said Sanjeef Redkar, president and chief executive officer of CBT Pharma, in a statement. "Based on this data set, we plan to advance CBT-102 into GLP toxicology studies in 2018 with an aim to enter the clinic in early 2019 in combination with other agents in our portfolio."

Aptose Presents Preclinical Data on APTO-253 at 2018 AACR Annual Meeting

On April 17, 2018 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) reported the presentation of preclinical data exploring the mechanism of action of APTO-253, the company’s clinical stage product candidate (Press release, Aptose Biosciences, APR 17, 2018, View Source;p=RssLanding&cat=news&id=2343016 [SID1234525432]). The data, demonstrating heightened sensitivity of BRCA1 or BRCA2 mutated cancer cells to APTO-253, were presented in a poster Tuesday, April 17 at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 14-18, in Chicago, IL.

The poster, entitled APTO-253 is a new addition to the repertoire of drugs that can exploit DNA BRCA1/2 deficiency, explored the mechanism of action of APTO-253, a small molecule with anti-proliferative activity against cell lines derived from a wide range of human malignancies. This study investigated the mechanism of action of APTO-253 to identify synthetic lethal interactions that can guide combination drug studies.

The research team found that APTO-253 stabilizes certain quadruplex DNA structures, causes DNA damage, and exhibits synthetic lethality comparable to olaparib – an FDA-approved targeted therapy that acts against cancers in people with hereditary BRCA1 or BRCA1 mutations, including some ovarian, breast and prostate cancers – albeit through a different mechanism. Unlike other drugs for which loss of this DNA repair function results in hypersensitivity, APTO-253 does not produce myelosuppression even at the maximum tolerated dose. The observations reported also identify γH2AX as a potential biomarker of clinical effect and open the window to more detailed studies of how APTO-253 promotes DNA damage and how it might be used clinically to treat patients with tumors harboring deficiencies in DNA repair.

The presentation will be published in the AACR (Free AACR Whitepaper) Conference Proceedings. The poster can also be accessed here or at the Publications & Presentations section of the Aptose website, www.aptose.com.
"We have clarified the mechanism of APTO-253 during the past year or so, including its mechanism to inhibit expression of the MYC gene, an oncogene that promotes tumor growth and resistance to drugs in AML and other cancers," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "AML remains our primary focus for APTO-253, and we hope to re-initiate dosing of AML patients with APTO-253 in an open phase Ib trial during the 2nd quarter of 2018. In the current presentation at AACR (Free AACR Whitepaper), we report that cancer cells deficient in the BRCA1/2 DNA repair functions are hyper-sensitive to APTO-253, analogous to the FDA-approved PARP inhibitor olaparib, but acting through a different mechanism. The findings reveal potential new solid tumor indications for APTO-253. Importantly, APTO-253 does not produce myelosuppression even at the maximum tolerated dose, which significantly distinguishes it from other cancer chemotherapies."

About APTO-253
APTO-253 is a clinical-stage small molecule targeted therapeutic agent that inhibits expression of the c-Myc oncogene, leading to cell cycle arrest and programmed cell death (apoptosis) in human-derived solid tumor and hematologic cancer cells, without causing general myelosuppression of the healthy bone marrow. The c-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.

Apexian Pharmaceuticals to present two poster sessions at AACR meeting in Chicago – April 14-18, 2018

On April 17, 2018 Apexian Pharmaceuticals, a clinical-stage biotechnology company focused on developing safe and effective therapy for patients with high unmet medical needs, reported that it will present two key poster sessions at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Meeting, which will be held at McCormick Place in Chicago, Illinois from April 14 – 18, 2018 (Press release, Apexian Pharmaceuticals, APR 17, 2018, View Source [SID1234525431]). Dr. Mark Kelley, Apexian’s Chief Scientific Officer, along with the research team will available at the posters session. The company will present two posters on combination therapy of APX3330 in pancreatic cancer and APE1 signaling pathway.

The titles and locations for these sessions are:
"Combination Therapy in PDAC Involving Blockade of the APE1/Ref-1 Signaling Pathway: An Investigation into Drug Synthetic Lethality and Anti-Neuropathy Therapeutic Approach"
Session Date and Time: Tuesday, April 17, 2018 from 1:00 – 5:00 PM
Location: McCormick Place South, Exhibit Hall A, Poster Section 37
"APE1/Ref-1 Redox Signaling Regulates HIF1a-mediated CA9 Expression in Hypoxic Pancreatic Cancer Cells: Combination Treatment in Patient-derived Pancreatic Tumor Models"
Session Date and Time: Monday, April 16, 2018 from 1:00 – 5:00 PM
Location: McCormick Place South, Exhibit Hall A, Poster Section 41
The poster sessions will add significant new information gathered on the effectiveness of Apexian’s lead clinical candidate, APX3330, and the ongoing research on the APE1/Ref-1 target.