Search This Blog

Monday, June 4, 2018

Bayer launches $7 billion cash call to fund Monsanto deal


Bayer launched a 6 billion euros ($7 billion/5.24 billion pounds) rights issue on Sunday, a cornerstone of the financing package for its planned $62.5 billion takeover of seeds maker Monsanto.

Bayer last week won U.S. approval for the Monsanto takeover, clearing a major hurdle for a deal that will create by far the largest seeds and pesticides maker.
The cash call is smaller than initially envisaged by Bayer because Monsanto reduced its debt while the antitrust review dragged on.
Also, Bayer raised 4.5 billion euros more from selling down its stake in plastics maker Covestro than initially expected.
The German drugmaker also grossed 7.6 billion euros in proceeds from selling assets to BASF, as the antitrust reviews were stricter than anticipated, but that did not cut the need to raise money via a share issue because future cash flows to service debts would also be lower.
When the merger was agreed in September 2016, Bayer said it would raise $19 billion worth of fresh equity capital for the takeover deal, parts of which was covered by issuing 4 billion euros in mandatory convertible notes in November 2016.
Bayer has said it would close the transaction very soon, which it needs to do because Monsanto could withdraw from the takeover agreement and seek a higher price after June 14.
Bayer is set to close the transaction on June 7, according to a media report on Sunday.
Bayer will create an agricultural supplies giant with sales of about 20 billion euros, based on 2017 figures, when taking into account the divestments.
At current foreign exchange rates, that compares to about 12.4 billion euros at DowDuPont Corteva Agriscience unit, 11 billion euros at ChemChina’s Syngenta and 7.9 billion at BASF, including businesses to be acquired.

#ASCO18: Sanofi, Regeneron skin cancer med trial results ‘strong’


The New England Journal of Medicine published pivotal data from two trials evaluating cemiplimab in advanced cutaneous squamous cell carcinoma. The results were also presented at the 2018 American Society of Clinical Oncology Annual Meeting. Advanced CSCC, the deadliest nonmelanoma skin cancer, encompasses both patients with metastatic CSCC and those with locally advanced CSCC who are not candidates for surgery; there is currently no approved treatment for these patients. Cemiplimab is an investigational human monoclonal antibody targeting the immune checkpoint PD-1. “The strong results seen with cemiplimab are noteworthy given that advanced CSCC is a very serious condition that currently has no approved treatments once surgery is no longer an option,” said Michael R. Migden, M.D., co-lead author and Associate Professor in the Departments of Dermatology and Head and Neck Surgery at The University of Texas MD Anderson Cancer Center. “Advanced CSCC tumors were shown to be responsive to cemiplimab in both metastatic and locally advanced patients, with the results being clinically meaningful and consistent between the Phase 1 and Phase 2 trials.” Cemiplimab is being jointly developed by Sanofi (SNY) and Regeneron (REGN) under a global collaboration agreement.

#ASCO18: Cytomx safety seems improved in early data: Jefferies


CytomX early data point to some safety differentiation, says Jefferies. Jefferies analyst Biren Amin said he thinks some investors may have sought a better efficacy profile from CX-072. However, he notes that the Yervoy combo data provided at ASCO are in the dose-escalation phase and are in heavily pretreated patients, adding that safety seems improved with the CX-072 plus ipi combo. Amin has a Buy rating and $40 price target on CytomX shares, which are down $5.58, or 22%, to $19.96 in afternoon trading

Stanford spinout Forty Seven arrives at #ASCO18 with promising data, $115M IPO


Here’s a neat trick for up-and-coming oncology biotechs to consider.
Execs for Forty Seven, the CD47 star founded by Stanford’s legendary Irv Weissman, filed for a $115 million IPO on Friday and then — instead of hunkering down for the quiet period — promptly flew out to Chicago to tout a promising set of proof-of-concept data for their lead drug at ASCO.
Forty Seven has preliminary data on 22 patients taking 5F9, with an impressive initial snapshot of early data for the small group. Fifteen of the patients suffer from treatment resistant diffuse large B-cell lymphoma (DLBCL) and the other 7 have follicular lymphoma. In DLBCL investigators tracked an objective response rate of 40% with a third achieving a complete response; in follicular lymphoma the ORR was 71% with 43% achieving a CR.
It’s still too early to set a median rate on the duration of response, but the researchers say that just 1 of the 22 saw their cancer progress after 6 months.
5F9 is an antibody that targets the popular CD47 receptor targets, which has inspired a slate of development efforts. Hitting that target is intended to scramble the “don’t-eat-me” signal that cancer cells rely on to avoid being chewed up by macrophages. And the Menlo Park, CA-based biotech has 6 studies underway in solid tumors, acute myeloid leukemia, non-Hodgkin’s lymphoma and colorectal carcinoma.
The biotech plans to push its studies ahead as a mono therapy as well as in combinations with PD-1/PD-L1 and CTLA-4 checkpoint inhibitors, starting with Genentech’s Tecentriq.

Forty Seven has an interesting past. The 78-year-old Weissman was able to wrangle substantial support for his early research work on CD47 from the California Institute for Regenerative Medicine, even launching early human studies — a rare feat in academic circles. Weissman and former CIRM chief Alan Trounson enjoyed a tight relationship, which extended to Trounson’s appointment to the board of another startup that Weissman had helped found — StemCells —shortly after his departure from the agency. And Forty Seven is still getting money from CIRM under its latest $19 million grant.
So far the company has raised $149 million and spent $84 million of that, according to the S-1.
Mark McCamish, a Novartis vet who enjoyed a $3.7 million pay package last year, is the CEO. He also has 3.6% of the stock. Lightspeed Ventures Partners and Sutter Hill Partners each control 16.8% of the stock, followed by Clarus at 15.8%. And Weissman has retained a hefty 9.5% of the equity, which could soon be worth a small fortune.
Forty Seven includes the following companies on its list of rivals in the field: Celgene Corporation, Trillium Therapeutics, Alexo Therapeutics, Arch Therapeutics, Surface Oncology, Novimmune, OSE Immunotherapeutics and Aurigene Discovery Technologies.

Vaxart reports Phase 2 defeat for a legacy antiviral from Aviragen


When Vaxart picked Aviragen Therapeutics for the reverse merger that got it on the Nasdaq, the South San Francisco biotech highlighted a Phase II treatment for condyloma caused by HPV as particularly interesting among the antiviral programs it was inheriting. Seven months later, Vaxart is finding out the drug, like many of Aviragen’s previous therapies, might be a failure after all.

Vaxart reports today that teslexivir (BTA074) has flunked the primary efficacy endpoint: complete clearance of baseline condyloma, or small bumps on genitals, by week 16. In a double blind trial evaluating the teslexivir 5% gel in 218 patients, only 30.6% of the drug arm — not a statistically significant difference from 23.3% in the placebo group — completely cleared baseline condyloma by week 16.
The news sent Vaxart’s stock $VXRT down 18.7% in pre-market trading, despite the company’s efforts to shine what positive light they had on the data.
Some of the patients who cleared all condyloma within the predetermined period have entered a three-month follow-up period to assess the recurrence efficacy endpoints. That’s part of the secondary efficacy endpoints, which include various assessments of clearance, time to clearance, and wart area reduction for both baseline warts and post-baseline emergent warts.
The company attempted to salvage the situation with a preliminary subgroup analysis of female patients and those with large condylomas, while noting neither of the results are significant. Female patients on teslexivir saw a 37.5% clearance rate versus 23.3% among those on placebo; for patients with large condylomas, the numbers were 30.0% (drug) and 15.4% (placebo).
“While this trial did not achieve the primary efficacy endpoint, we were pleased with the benign safety profile and positive efficacy trends in certain patient subpopulations,” said CEO Wouter Latour in a statement. “We are currently in the follow-up phase of the study and data collection should continue for a few more weeks. During this period, we will conduct further analysis of the results, which should inform us about the future steps with the teslexivir program. In the meantime, we will continue to focus on the advancement of our oral vaccine platform through the clinic.”
Under the leadership of new CMO David Taylor, Vaxart is marching onward with its signature oral vaccines intended to replace the injectables in use. It had a positive Phase II readout in January for its prophylactic influenza pill, and is hoping to do the same with a norovirus program.

AI Detects Polyps Better Than Colonoscopists


High-performing colonoscopists can identify 20% more polyps with artificial intelligence (AI) than without, a new study indicates.
Some gastroenterologists have expressed concern, worrying that they will be put out of work, “but I don’t see that happening,” said William Karnes, MD, from UC Irvine Health in California.
“I see what we’re doing with AI as primarily a way to make the colonoscopists’s job easier, giving more time to our patients and less time to paperwork,” he explained.
When Karnes and his colleagues applied a video-based machine-learning model to about 4100 images with polyps and 4500 without, the accuracy rate for polyp detection was 96%, he reported here at Digestive Disease Week 2018.
Four colonoscopists with career adenoma detection rates of at least 50% then examined the videos with and without the AI video overlay.
The researchers hope that the use of AI will ultimately lead to fewer cases of interval colorectal cancer, because 50% to 80% are the result of missed polyps.
“This was basically a feasibility study to try to mimic what happens during a colonoscopy, using some deidentified videos from older studies, to see whether AI enhanced our ability to see polyps,” Karnes told Medscape Medical News.
“When I saw the first overlay on video, I thought, ‘this is so cool’,” he told Medscape Medical News. “I was actually blown away.”
The 8641 images used in the study were considered diverse and balanced, and included all portions of the colon plus random features, such as debris and diverticuli. The machine-learning model, which incorporated a so-called convolutional neural network, operated at a processing speed exceeding that required for live video.
Using the AI polyp detection technique, the four colonoscopists were tasked with identifying all polyps in nine colonoscopy videos. Karnes, who has performed more than 20,000 colonoscopies, was the only one of the four to review machine-learning-overlaid videos, and he determined the uniqueness of each polyp and the confidence level — low to high — of true polyp presence.
This limitation could create potential bias, he acknowledged, but it will be remedied in upcoming clinical trials.
I was actually blown away.
Karnes compared the AI overlay video with a video stream brought into a small gaming computer. Before sending the video to the monitor, an algorithm assessed each frame to determine if a polyp was present and, if so, placed a box around the polyp.
“So we’re seeing, in real time, the original video along with a little green box if a polyp is present,” he explained.

High Performance

No unique polyps were missed with the machine-learning model. In fact, with the machine-overlaid videos, the number of unique polyps detected increased from 36 to 45. Confidence was high for three of the additional nine polyps detected, and low for six.
The AI model produced a false-positive rate of only 7%, and a negative predictive value of 99.5%, Karnes reported. This means that gastroenterologists using this technology might not have to wait for pathology results.
“When combined with accurate optical pathology, AI may eventually bring us to real-time measures of adenoma detection rate,” he said.
The technology, when used by gastroenterologists during colonoscopy, will likely prompt more careful inspection and the detection of additional polyps, Karnes noted. Multiple centers are already lined up to conduct primarily randomized clinical trials on the technique, he said, and data are expected to accrue quickly thereafter.
AI is already being used in other facets of colonoscopy. It can assess the thoroughness of bowel prep, for example, and monitor when the scope is placed inside and removed from the colon.
After conversations with practicing gastroenterologists, Karnes said he believes most will be “very eager” to try this technique.
AI approaches to polyp detection are “what’s going to happen,” said Daniel Stonewall Anderson, MD, from Kaiser Permanente in San Diego, who is president of the California Colorectal Cancer Coalition. However, he noted, the results “seem very, very early.”
“The AI looking at the images will eventually help us,” he told Medscape Medical News. “It is interesting that removing these tiny polyps that would never mean anything [in terms of cancer development] would come to mean something because they’re an index of quality. It means we’re looking well.”
Karnes is a cofounder of DocBot, a spinoff of this study that might eventually lead to profits for the University of California, Irvine. Anderson has disclosed no relevant financial relationships.
Digestive Disease Week (DDW) 2018: Presentation 133. Presented June 2, 2018.

Siemens Healthineers says FDA clears Biograph Vision PET/CT system


The FDA has cleared the Biograph Vision, a new positron emission tomography/computed tomography system from Siemens Healthineers that “delivers a new level of precision in PET/CT imaging.”