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.

https://bit.ly/2JgNMyk

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.

https://bit.ly/2Lmk1wO

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.

https://wb.md/2LVKhPE

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.”

https://bit.ly/2Jg2qGe

#ASCO18: Merck Keytruda ‘alone bests chemo’ in advanced lung cancer

Patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab (Keytruda) had a greater median survival than patients treated with standard chemotherapy, even if the former had low levels of PD-L1, researchers reported here.

Depending on the percentage of PD-L1 expression in the tumor, survival was between 4 and 8 months longer for patients treated with immunotherapy alone versus those treated with chemotherapy, according to Gilberto Lopes, MD, MBA, of the Sylvester Comprehensive Cancer Center at the University of Miami, and colleagues.

The benefit in overall survival (OS) was accomplished without an increase in adverse events (62.7% with pembrolizumab vs 89.9% with chemo), Lopes said at a press conference at American Society of Clinical Oncology (ASCO) annual meeting.

Serious adverse events were seen in 17.8% of the patients on pembrolizumab and in 41% of patients on chemotherapy, he added.

“Given the overall efficacy and safety profile, pembrolizumab monotherapy is a standard-of-care first-line therapy for PD-L1 expressing, locally advanced or metastatic, squamous or nonsquamous non-small-cell lung cancer,” Lopes said.

Pembrolizumab currently has FDA approval for NSCLC patients with a PD-L1 level of ≥50% based on results of the phase III KEYNOTE-024 trial. Lopes suggested the current study’s findings would expand the population of patients with NSCLC who could be treated with immunotherapy, rather than chemotherapy, in the first-line setting.

The patient population for the KEYNOTE-042 trial consisted of those with previously untreated advanced/metastatic NSCLC, without sensitizing EGFR or ALK alterations, and a PD-L1 tumor proportion score (TPS) ≥1%.

ASCO expert John Heymach, MD, of the MD Anderson Cancer Center in Houston, said the study results are part of “a new era in treatment” and that immunotherapy is pushing the use of chemotherapy to the back burner for many cancer patients. He said about 75% of NSCLC patients with advanced disease would be eligible to receive pembrolizumab, or other target agents, in lieu of chemotherapy as a first-line treatment.

“Immunotherapy with pembrolizumab alone benefits a much larger number of patients than we had previously thought,” Heymach said. “This is yet another promising result with immunotherapy in lung cancer that brings new momentum to the treatment of this notoriously difficult disease.”

Eligible patients were randomized 1:1 to ≤35 cycles of pembrolizumab 200 mg Q3W, or investigator’s choice of ≤6 cycles of paclitaxel plus carboplatin or pemetrexed plus carboplatin with optional pemetrexed maintenance in nonsquamous disease only.

Randomization was stratified by region (east Asia vs non-east Asia), ECOG performance status (0 vs 1), histology (squamous vs nonsquamous), and TPS (≥50% vs 1-49%).

Lopes said that 299 patients with PD-L1 expression of ≥50% who were assigned pembrolizumab achieved a median OS of 20.0 months versus median OS of 12.2 months for 300 patients who received chemotherapy (hazard ratio 0.69, P=0.003).

Of the 413 patients who had a PD-L1 expression of ≥20% treated with pembrolizumab, the median OS was 17.7 months versus median OS 13 months for the 405 patients assigned to chemotherapy (P=0.002).

The 637 patients who had a PD-L1 level of ≥1% who were assigned to receive pembrolizumab achieved a median OS of 16.7 months compared with a median OS 12.1 months for 637 patients assigned to receive placebo (P=0.0018).

“These data confirm and potentially extend the role of [pembrolizumab] monotherapy as a standard first-line treatment for PD-L1–expressing advanced/metastatic NSCLC,” the authors concluded, adding that the external data monitoring committee recommended continuing the trial to evaluate progression-free survival.

The trial was supported by Merck. Some co-authors are company employees.

Lopes disclosed relevant relationships with Merck Sharp & Dohme, EMD Serono, and AstraZeneca. Co-authors disclosed multiple relevant relationships with industry.

Heymach disclosed relevant relationships with Abbvie, ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Genentech, Medivation, Novartis, OncoMed, Synta, Bio-Tree and Cardinal Spine.

• Primary Source

  American Society of Clinical Oncology

  Source Reference: Lopes G, et al “Pembrolizumab versus platinum-based chemotherapy as first-line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score ≥ 1%: Open-label, phase 3 KEYNOTE-042 study” ASCO 2018; Abstract LBA4.

https://bit.ly/2HiM8e2

Gilead-licensed experimental therapy reported eliminating woman’s cancer

Researchers at the U.S. National Cancer Institute grew copies of rare cells custom-made by the immune system from inside tumors and infused them back into a 49-year-old woman whose cancerous tumors were growing despite seven types of chemotherapy and hormonal therapy, reported Bloomberg. The experimental immune cell therapy, which has since been licensed to Gilead Sciences, left the woman cancer-free and also shrank hard-to-treat tumors in six other patients with colon and cervical cancers, according to a report about the study, the results of which were published Monday in the scientific journal Nature Medicine. In late morning trading, Gilead shares are up 1.6% to $69.42

https://bit.ly/2M0F4Ga

Supreme Court throws out illegal immigrant teen abortion ruling

The U.S. Supreme Court on Monday threw out a lower court ruling that let a pregnant illegal immigrant minor held in federal immigration custody to obtain an abortion last year at age 17 over the objections of President Donald Trump’s administration.

The action by the justices provided a legal victory to Trump’s administration even though the teenager already has had the abortion because it eliminated a precedent at the federal appeals court level that could have applied in similar circumstances in which detained minors sought abortions.

In the unsigned opinion with no dissents, the justices threw out the appeals court decision on the grounds that the dispute became moot once the unnamed teenager had the abortion.

The justices, however, declined to take up the administration’s request for disciplinary action against the American Civil Liberties Union lawyers who represented the girl, who underwent an abortion in Texas last October. The administration had accused the ACLU lawyers of misleading the Justice Department over when she would have the abortion.

The court also allowed litigation to continue in lower courts concerning other detained immigrants in detention in a similar situation.

The high court said that it takes misconduct allegations against lawyers seriously but said “not all communication breakdowns constitute misconduct.”

The ACLU, which has filed a range of lawsuits against the administration, sued in Washington in October, seeking a decision on obtaining abortions that would be binding in any future cases that arise.

A 1973 Supreme Court ruling legalized abortion nationwide. One of the issues raised by the case is whether illegal immigrant women have the same right to an abortion as American citizens and legal residents.

The girl at the center of the legal fight had an abortion on Oct. 25, the day after a U.S. appeals court ruled against the Trump administration’s objections.

The Justice Department has said it was preparing to appeal that ruling to the Supreme Court when it learned she had already had the abortion early that morning.

While the case was pending at the Supreme Court, litigation continued in lower courts.

On March 30, a federal judge in Washington issued an injunction that prevents the administration from impeding access to abortion by detained immigrant minors. U.S. District Judge Tanya Chutkan also certified a class action of similar minors to challenge the administration’s policy.

https://reut.rs/2LWmvmF