1stOncology™: Cancer Intelligence Service – Page 16082 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

AACR Meeting Brief: Sosei, Verseon, Rgenix, Xencor and others

The 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) is being held in Chicago. Here’s a roundup of some of company news (Press release, BioSpace, APR 18, 2018, View Source [SID1234525504]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

Tokyo, Japan and London-based Sosei Group released new preclinical data for AZD4635, a selective, orally available, small molecule adenosine A2A receptor antagonist. It was discovered by the company’s subsidiary Heptares Therapeutics. AstraZeneca licensed the global rights to the compound in 2016. The drug is now in a Phase I trial as a monotherapy and in combination with AstraZeneca’s Imfinzi (durvalumab) in solid tumors.

Verseon Corporation, headquartered in Fremont, California, presented preclinical data for its tubulin inhibitors in cancer, including cancer cells that showed multidrug resistance. The company utilizes a computer-driven drug discovery platform with a comprehensive chemistry and biology workflow to design new drug candidates. "We are very encouraged by these preclinical results," said Mohan Siviraja, associate director of Biology for Verseon, in a statement. "Multidrug resistance is one of the main reasons why chemotherapies fail. The insensitivity of our compounds to the major transporters and to the overexpression of beta-III tubulin may help us address the need for a more effective, precise therapy."

Rgenix, based in New York, released preclinical data of its RGX-202 in colorectal cancer and other cancers. The compound inhibits SLC6a8, a creatine transporter important to tumor metabolism. The drug was studied alone and in combination with standard chemotherapy agents, such as 5-FU. "The data presented today is just a snapshot of our preclinical progress on our research of RGX-202," said Masoud Tavozoie, Rgenix’ chief executive officer, in a statement. "These data show the strong potential for RGX-202 and support further research of the compound. With these data, we are building a strong foundation for future clinical development of RGX-202, which, with regulatory approval, would diversify our clinical pipeline."

Roswell Park Comprehensive Cancer Center scientists in Chicago have identified epigenetic markers in the breast cancer tumors of African-American women and women of European descent. Christine Ambrosone, professor of Oncology and senior vice president of Population Sciences and chair of Cancer Prevention & Control at Roswell, were interested in epigenetic changes, the ways in which genes are turned on or off in response to environment and other factors. Lead author of the study, Matthew Buas, assistant professor of Oncology in the Roswell Department of Cancer Prevention and Control, said in a statement, "Our findings suggest that epigenetic differences between African-American women and women of European ancestry are important in breast cancer pathogenesis, and may underlie observed differences in the incidence of breast cancer subtypes by race."

Xencor, headquartered in Monrovia, California, presented preclinical data on XmAb24306, an IL15/IL15 receptor alpha complex fused to a bispecific XmAb Fc domain for the treatment of several different cancers. The data showed the complex improved the duration and magnitude of T and NK cell proliferation in vitro and in vivo.

"The plug and play nature of our XmAb technology provides tremendous opportunity to build a suite of tumor microenvironment activators with tunable potency and sustained activity, which have the potential for improved performance over current approaches," said Bassil Dahiyat, president and chief executive officer of Xencor, in a statement. The company expects to file an IND in 2019.

CytRx, based in Los Angeles, presented three posters about its albumin binding ultra high potency Linker Activated Drug Release (LADR) drug candidates, LADR-7, LADR-8, LADR-9 and LADR-10. The technology allows drugs to molecularly bind to albumin in the bloodstream and controls its release at the tumor site. Felix Kratz, the company’s vice president of Drug Discovery, stated, "This technology allows for the delivery of higher doses of drug directly to the tumor, while avoiding much of the off-target toxicity observed with the parent molecules."

MabVax Therapeutics, located in San Diego, presented three posters about its antibody development programs. Paul Maffuid, MabVax’ executive vice president of Research and Development, stated, "We successfully shared the significant progress we have made through these clinical and preclinical studies that continue to establish our growing body of data supporting the development of MVT-1075 for the treatment of pancreatic cancer and other CA19-9 cancers, MVT-2163 as a immunoPET imaging agent, and our most advanced research program focused on the Tn and sTn cancer antigen targets."

InteRNA Technologies, based in Utrecht, Netherlands, presented proof-of-concept data on INT-1B3. INT-1B3 is a lipid nanoparticle formulation of microRNA 193a-3p mimic that can be delivered to cancer cells. MicroRNA 193a-3p is a known tumor suppressor for several cancers. "Overall these data strongly support the unique potential of microRNAs, and INT-1B3 in specific, as a novel therapeutic modality in cancer that acts as a ‘combination treatment in one drug,’" said Roel Schaapveld, InteRNA’s chief executive officer, in a statement. "It is an important milestone for InteRNA because it validates our microRNA platform and demonstrates the focus and commitment of the team over the last years."

Eli Lilly Shows Off More Verzenio Data at AACR

Nearly two months after Eli Lilly secured an expanded approval indication for its cancer drug Verzenio, the company unveiled final data from the MONARCH 3 trial that won the latest nod from the U.S. Food and Drug Administration for the treatment of some breast cancer patients (Press release, BioSpace, APR 18, 2018, View Source [SID1234525503]).

During a presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in Chicago this weekend Lilly revealed that Verzenio (abemaciclib), a cyclin-dependent kinase inhibitor, provided even longer progression-free survival than originally believed. Last fall Eli Lilly released interim-data from the MONARCH 3 trial that showed PFS was estimated at 14 months. Now though data shows Verzenio in combination with an aromatase inhibitor (AI) provides progression-free survival of 28 months.

"That’s a significant prolongation in progression-free survival that is important for the lives of patients," Levi Garraway, senior vice president of global development and medical affairs at Eli Lilly told BioSpace in an exclusive interview. "We’ve been happy with the news that this gives women with breast cancer one more option."

In February the FDA gave approval for the treatment of postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. That approval marked the third time the FDA gave the drug the green light since its first regulatory win in September 2017.

By adding abemaciclib to endocrine therapy as part of a treatment regimen, Eli Lilly said the program demonstrated improved progression-free survival in patients with HR+/HER2-negative breast cancer. In patients with measurable disease, the objective response rate was 55.4 percent in the abemaciclib arm and 40.2 percent in the placebo arm, according to data.

Within the MONARCH 2 and MONARCH 3 clinical trial subgroup populations, researchers at Eli Lilly identified certain clinical characteristics of the disease that typically confer a less favorable prognosis. Eli Lilly believes this information may help clinicians optimize treatment decisions, including the use of CDK4 & 6 inhibitors, and potentially provide the groundwork for more individualized therapy.

During the conference Garraway said he engaged with several doctors about the use of cyclin-dependent kinases inhibitors in the treatment of breast cancer. He said the response they have seen from prescribers is positive, which indicates there is a path for cyclin-dependent kinases inhibitors.

"These doctors, they’ve been seeing some positive moves and are gaining confidence in its (Verzenio) use," Garraway said.

With the success that Eli Lilly has had with Verzenio, the company now aims to determine if it can be used as a treatment in other types of breast cancer, as well as other cancer indications. Currently, the company has Verzenio in a study in the high-risk adjuvant breast cancer setting, as well as an ongoing Phase II study in Her2+ breast cancer. Garraway said data from the mid-stage trial is expected by the end of the year. While Garraway did not provide many details on the Phase II study, He said it was designed so that if the data readout is strong enough there is a chance Eli Lilly could seek regulatory approval on that data alone. But, he quickly noted that it depends on whether or not there is a large enough of an effect from the treatment for the company to go into regulatory discussions as opposed to a Phase III study.

"There’s a biological rationale for the testing and we’re looking forward to seeing the results later this year," Garraway said.

For potential uses outside of breast cancer Garraway would not disclose what areas the company is exploring with Verzenio, he said the company has identified some areas "that are worth the investment."

Not related to Eli Lilly’s presentations at AACR (Free AACR Whitepaper), this morning the company announced a partnership with Boehringer Ingelheim and the University of Oxford to investigate the effects of Jardiance on the progression of kidney disease and the occurrence of cardiovascular death, in adults with established chronic kidney disease with and without diabetes. The primary outcome of the study is to assess the effect of Jardiance on time to clinically relevant kidney disease progression or cardiovascular death.

1Q2018 Earnings Call Highlights Abbott’s $7.4 Billion In Sales

On April 18, 2018 Abbott reported financial results for the first quarter ending March 31, 2018. Key takeaways from this morning’s earnings call include (Press release, BioSpace, APR 18, 2018, View Source [SID1234525502]):

First-quarter reported sales growth of 16.7 percent
First-quarter organic sales growth of 6.9 percent
First-quarter adjusted earnings per share from continuing operations of 59 cents, at the upper end of the previous guidance range
Several recently launched products contributing to strong growth
"We’re off to a strong start to the year as we forecasted," said Miles D. White, chairman and chief executive officer. "We’re particularly pleased with the continued strong growth in medical devices and improving performance in our nutrition business."

The company’s adjusted income rose to 59 cents per share on $7.39 billion in sales for its first quarter, beating Zacks Investment Research estimates of 58 cents on $7.26 billion in sales. Last year at this time, Abbott shares were trading at 48 cents with $6.34 billion in sales.

An infographic from the company highlights an increase of 6.9 percent in worldwide organic sales led by successes in nutrition, diagnostics, established pharmaceuticals and medical devices.

"Back in January I commented that we were entering the year with strong momentum which has continued as we forecasted," White added during the earnings call. "The strong growth we are achieving is a direct result of the steps we have taken to position the company in the most attractive areas of health care as well as the outstanding productivity of our new product pipeline."

Despite the company’s upbeat attitude about its Q1 earnings, shares dipped 3.5 percent early Wednesday on pharmaceutical sales that lagged behind Wall Street’s expectations by nearly 4 percent.

Revenue from established pharmaceuticals fell short by $56 million, RBC Capital Markets wrote in a note to clients. Also, Evercore noted the $1.04 billion in sales for that unit missed the consensus by 3.6 percent.

Medical device sales had the best organic growth in Q1, rising 9.4 percent to $2.74 billion. That beat the consensus for $2.67 billion, Evercore noted. Diagnostics also performed well, rising 5.5 percent organically to $1.84 billion in sales to top the consensus by $69 million.

"For the full year 2018, we continue to forecast organic sales growth of 6 percent to 7 percent," said Chief Financial Officer Brian Yoor. "In addition, we continue to expect rapid diagnostics to contribute sales of a little more than $2 billion."

With a forecasted adjusted gross margin ratio of around 59 percent of sales, Yoor said that research and development investments will be adjusted to around 7.5 percent of sales, and selling, general and administrative expenses adjusted above 30.5 percent of sales."

Worldwide, nutrition sales were $1.76 billion, up 4.7 percent organically and topping guidance for low single-digit growth. Both adult and pediatric segments performed well, growing a respective 4.3 percent and 5.1 percent on an organic basis.

But, White cautioned, nutrition is a highly competitive business in a branded space. "I give our U.S. team a lot of credit for how well they’ve done in the pediatric and adult (nutrition) space. It’s extremely competitive and it’s competitive in both pediatric and adult. And we will see from time-to-time a competitor tries false advertising or other things to take momentary share. But I think overall, we’ve not only sustained our position, but steadily grown it, from a share standpoint."

For the year, Abbott reaffirmed its adjusted profit target of $2.80 to $2.90 a share. Analysts modeled adjusted earnings of $2.87 per share and $30.91 billion in sales. Abbott also sees second-quarter adjusted income coming in at 70 to 72 cents per share.

Astellas Announces Sale of Certain Agensys Research Facilities to Kite, a Gilead Company

On April 18, 2018 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, "Astellas" ) and Kite, a Gilead Company (Nasdaq: GILD, President and CEO: John Milligan, "Kite"), reported that an agreement has been completed for the transfer of certain Agensys research facilities in Santa Monica, California, USA, to Kite (Press release, Astellas Pharma US, APR 18, 2018, View Source [SID1234525501]). The asset transfer was completed on April 12, 2018. Additional financial information or further deal terms are not being disclosed.

Astellas is a pharmaceutical company dedicated to improving the health of people around the world. (PRNewsFoto/Astellas Pharma Inc.)

The facilities transfer is part of the wind-down process of the Agensys research operations, as announced by Astellas on July 27, 2017. Additional wind-down activities were completed in the first quarter of calendar year 2018, following the Company’s decision to further refine its oncology strategy by expanding its investment in the research of new technologies and modalities and reducing its focus on Antibody-Drug Conjugate (ADC) research, which was the core focus of work conducted at Agensys. Astellas will continue certain clinical trials and collaborations on some ADC programs that have been in progress at Agensys, including its collaboration with Seattle Genetics, Inc.

TRILLIUM THERAPEUTICS REPORTS TTI-622 PRECLINICAL DATA AT
THE 2018 AACR ANNUAL MEETING

On April 18, 2018 Trillium Therapeutics Inc. (Nasdaq/TSX: TRIL), a clinical-stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported that preclinical data from its TTI-622 (SIRPa-IgG4 Fc) immune checkpoint inhibitor program were presented at the 109th Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Trillium Therapeutics, APR 18, 2018, View Source [SID1234525500]).

TTI-622 (SIRPa-IgG4 Fc) is the second SIRPaFc decoy receptor that Trillium is advancing into the clinic. It consists of the CD47-binding domain of human SIRPa linked to an IgG4 Fc region and is being developed primarily for combination therapy.

The data presented at AACR (Free AACR Whitepaper) demonstrate that TTI-622 induces the phagocytosis of a broad panel of tumor cells derived from patients with both hematological and solid tumors. As a monotherapy, TTI-622 treatment resulted in decreased tumor growth and improved survival in a B cell lymphoma xenograft model, and enhanced the efficacy of cetuximab (anti-EGFR) and daratumumab (anti-CD38) antibodies in solid and hematological xenograft models, respectively. Unlike CD47-blocking antibodies, TTI-622 bound minimally to human erythrocytes and did not induce hemagglutination in vitro.

"The preclinical data presented at AACR (Free AACR Whitepaper) reinforce our confidence in this target and provide a solid foundation for initiating a clinical program with TTI-622," said Dr. Niclas Stiernholm, President and CEO of Trillium Therapeutics. This second SIRPaFc decoy receptor complements TTI-621, and allows us to evaluate the effects of CD47 blockade using different levels of Fc receptor engagement. Importantly, we believe the minimal binding of TTI-622 to human red blood cells distinguishes this agent from other IgG4-based CD47 targeted therapies."

A two-part, multicenter, open-label, phase 1a/1b study of TTI-622 in patients with advanced relapsed or refractory lymphoma or multiple myeloma is being initiated, with the first patient expected to be dosed in Q2 2018. In the phase 1a dose-escalation study, patients will be enrolled in sequential dose cohorts to receive TTI-622 once weekly to characterize safety, tolerability, pharmacokinetics, and to determine the maximum tolerated dose. In the phase 1b study, patients will be treated with TTI-622 in combination with rituximab, a PD-1 inhibitor or a proteasome inhibitor-containing regimen.